| |
| """ |
| Paper-Native Clinical PICO & Entity Parser for UnsolvedMedical v3.0.0. |
| |
| Transforms raw peer-reviewed medical paper titles and metadata into: |
| 1. Complete, non-truncated, grammatically clean clinical topics (`clean_topic`) |
| 2. Paper-verified `condition_or_health_state` and `population` (eliminating cross-condition chimeras |
| when a paper addresses a condition outside the 20 sub-domain defaults) |
| 3. Paper-specific `intervention_exposure_test_or_predictor` (`name`, `kind`, `details`) |
| 4. Paper-specific `comparator_or_reference` |
| 5. 100 natural clinical research question formulations (5 distinct structural variants x 20 question types) |
| with distinct `statement`, concise `clean_statement`, and patient-accessible `plain_language_statement`. |
| """ |
|
|
| import html |
| import re |
|
|
| SUBTITLE_BOILERPLATE_RE = re.compile( |
| r"\s*[:–—-]\s*(a |an |the )?(systematic review|meta-analysis|narrative review|scoping review|" |
| r"literature review|umbrella review|comprehensive review|integrative review|minireview|mini-review|" |
| r"review of|updated review|critical review|overview of|retrospective|prospective|multicenter|" |
| r"multi-center|single-center|single center|randomized|randomised|phase [i1234v/]+|pilot study|" |
| r"cohort study|cross-sectional|observational study|clinical trial|real-world|secondary analysis|" |
| r"post-hoc|post hoc|sub-study|substudy|preliminary|comparative study|mendelian randomization|" |
| r"network meta-analysis|pooled analysis|propensity score|outcomes from|results from|insights from|" |
| r"findings from|lessons from|experience from|report from|evidence-based|consensus statement|" |
| r"position paper|clinical practice guideline|expert consensus|multidisciplinary|" |
| r"international delphi|delphi consensus|national survey|cross-sectional survey).*$", |
| re.I, |
| ) |
|
|
| PREFIX_BOILERPLATE_RE = re.compile( |
| r"^(a |an |the )?(systematic review and meta-analysis of|systematic review of|meta-analysis of|" |
| r"narrative review of|scoping review of|comprehensive review of|clinical overview of|overview of|" |
| r"update on|updates in|current perspectives on|emerging role of|advances in|new insights into|" |
| r"recent advances in|state of the art in|clinical management of|management of|current state of|" |
| r"exploring the|understanding the|investigating the|evaluating the|assessing the|" |
| r"reassessing the role of|reassessing|role of|the role of|development of a|development of|" |
| r"predictive value of|prognostic value of|diagnostic value of|clinical utility of|" |
| r"clinical significance of|significance of|expert consensus on the|expert consensus on|" |
| r"consensus statement on|international consensus on|diagnosis and monitoring of|diagnosis and management of|" |
| r"diagnosis and treatment of|prevention and treatment of|efficacy and safety of|effectiveness and safety of|" |
| r"efficacy of|effectiveness of|impact of the|impact of|effect of|effects of|" |
| r"influence of|the influence of|association between|association of|relationship between)\s+", |
| re.I, |
| ) |
|
|
| DANGLING_TAIL_RE = re.compile( |
| r"\s+\b(a|an|the|in|of|for|with|without|and|or|by|to|from|on|at|among|between|after|before|" |
| r"during|under|into|via|versus|vs|through|across|within|towards|toward|against|upon|using|" |
| r"including|following|regarding|concerning|based|associated|related|compared|comparing|" |
| r"as|such|whether|while|when|where|who|which|that|whose|undergoing|receiving|treated|" |
| r"diagnosed|presenting|living|incorporating|combining|targeting|evaluating|assessing|" |
| r"predicting|preventing|managing|early|late|acute|chronic|severe|moderate|mild|advanced|" |
| r"metastatic|primary|secondary|novel|new|current|emerging|clinical|human|pediatric|adult|" |
| r"older|elderly|high-risk|low-risk|refractory|relapsed|recurrent)\b[:;,\-–—.]*$", |
| re.I, |
| ) |
|
|
| |
| GENERIC_CONDITION_MODIFIERS = { |
| "with", "without", "from", "after", "before", "during", "early", "stage", "late", "acute", |
| "chronic", "severe", "moderate", "mild", "advanced", "metastatic", "unresectable", "resectable", |
| "borderline", "locally", "localized", "high", "risk", "low", "relapsed", "relapsing", "refractory", |
| "recurrent", "first", "second", "line", "complete", "remission", "positive", "negative", "wildtype", |
| "proficient", "deficient", "dependent", "resistant", "progressing", "associated", "related", |
| "induced", "mediated", "primary", "secondary", "adult", "adults", "children", "pediatric", |
| "neonatal", "adolescent", "older", "elderly", "maternal", "pregnant", "postpartum", "patients", |
| "patient", "care", "health", "management", "treatment", "therapy", "disease", "diseases", |
| "syndrome", "syndromes", "disorder", "disorders", "condition", "conditions", "infection", |
| "infections", "cancer", "carcinoma", "adenocarcinoma", "malignancy", "tumor", "tumors", |
| "cell", "small", "large", "diffuse", "factor", "inhibitors", "inhibitor", "mutations", "driver", |
| "pathway", "inhibition", "targetable", "neutralizing", "viii", "active", "grade", "serous", |
| "chemoimmunotherapy", "blockade", "allogeneic", "hsct", "transplant", "transfusion", |
| "long", "term", "short", "type", "types", "form", "forms", "rate", "rates", "systemic", |
| "idiopathic", "hereditary", "familial", "congenital", "acquired", "uncomplicated", "complicated", |
| "stanford", "persistent", "paroxysmal", "sustained", "protracted", "maintenance", "discontinuation", |
| "withdrawal", "postoperative", "perioperative", "preoperative", "intensive", "critical", |
| "critically", "emergency", "outpatient", "inpatient", "community", "hospital", "surgical", |
| "medical", "clinical", "human", "cohort", "onset", "status", "loss", "pain", "failure", "injury", |
| } |
|
|
| |
| UMBRELLA_DISEASE_NOUNS = { |
| "amyloidosis", "dissection", "aneurysm", "stenosis", "regurgitation", "insufficiency", |
| "cardiomyopathy", "neuropathy", "nephropathy", "retinopathy", "hepatitis", "cirrhosis", |
| "fibrosis", "arthritis", "vasculitis", "colitis", "epilepsy", "dementia", "depression", |
| "anemia", "thrombocytopenia", "hypertension", "diabetes", "asthma", "stroke", "hemorrhage", |
| "infarction", "thrombosis", "embolism", "leukemia", "lymphoma", "myeloma", "sarcoma", |
| "melanoma", "glioma", "pneumonia", "meningitis", "encephalitis", "endocarditis", "myocarditis", |
| "pancreatitis", "sepsis", "glaucoma", "uveitis", "dermatitis", "psoriasis", "alopecia", |
| "lupus", "myositis", "osteoporosis", "osteoarthritis", "fracture", "fractures", "infertility", |
| "dystrophy", "hemophilia", "thalassemia", |
| } |
|
|
| |
| EXPLICIT_COMP_RE = re.compile( |
| r"(?P<arm_a>[A-Za-z0-9][A-Za-z0-9\s,\-/+()]{3,75}?)\s+" |
| r"(?:versus|vs\.?|compared with|compared to)\s+" |
| r"(?P<arm_b>[A-Za-z0-9][A-Za-z0-9\s,\-/+()]{4,75}?)" |
| r"(?:\s+(?:in|for|among|after|during|with|on|to)\b|$)", |
| re.I, |
| ) |
|
|
| |
| OF_PATTERN_RE = re.compile( |
| r"^(?:the\s+)?(?:role|efficacy|effectiveness|safety|impact|effects?|influence|value|utility|feasibility|" |
| r"performance|accuracy|use|application|addition|combination|integration|implementation|" |
| r"optimization|evaluation|assessment|association|relationship|correlation|" |
| r"predictive value|prognostic value|diagnostic value|diagnostic accuracy|clinical utility|" |
| r"clinical significance|significance|therapeutic potential|mechanisms?|pathogenesis|determinants|predictors|biomarkers|" |
| r"reassessing the role|development|genetics)\s+of\s+(?:a\s+|an\s+|the\s+)?" |
| r"(?P<focus>[A-Za-z0-9][A-Za-z0-9\s,\-/+()]{5,90}?)" |
| r"(?:\s+(?:in|for|among|on|to guide|after|during|with)\s+(?P<context>[A-Za-z0-9].+))?$", |
| re.I, |
| ) |
|
|
| |
| FOR_ACTION_RE = re.compile( |
| r"^(?P<focus>[A-Za-z0-9][A-Za-z0-9\s,\-/+()]{5,85}?)\s+" |
| r"(?:for|in|to guide)\s+(?:the\s+)?(?:treatment|management|prevention|diagnosis|early detection|" |
| r"prediction|prognosis|risk stratification|monitoring|rehabilitation|mitigation|control|adjuvant|neoadjuvant)\s*(?:of\s+)?" |
| r"(?P<context>[A-Za-z0-9].+)$", |
| re.I, |
| ) |
|
|
| |
| AND_IN_RE = re.compile( |
| r"^(?P<focus>[A-Za-z0-9][A-Za-z0-9\s,\-/+()]{5,75}?)\s+and\s+" |
| r"(?P<outcome>[A-Za-z0-9][A-Za-z0-9\s,\-/+()]{4,70}?)\s+" |
| r"(?:in|among|after|during)\s+(?P<context>[A-Za-z0-9].+)$", |
| re.I, |
| ) |
|
|
| |
| GERUND_RE = re.compile( |
| r"^(?:targeting|inhibiting|modulating|predicting|stratifying|monitoring|optimizing|" |
| r"de-escalating|reassessing|mapping|decoding|unraveling|evaluating|comparing|enhancing|" |
| r"preventing|overcoming|identifying|quantifying|characterizing)\s+(?:the\s+|a\s+|an\s+)?" |
| r"(?P<focus>[A-Za-z0-9][A-Za-z0-9\s,\-/+()]{5,85}?)" |
| r"(?:\s+(?:in|for|among|after|during|with|to)\s+(?P<context>[A-Za-z0-9].+))?$", |
| re.I, |
| ) |
|
|
| |
| COND_PREP_RE = re.compile( |
| r"\b(?:in patients with|among patients with|in adults with|in children with|in women with|in men with|in individuals with|" |
| r"in the management of|in the treatment of|for the treatment of|in|among)\s+" |
| r"(?P<cond>[A-Za-z0-9][A-Za-z0-9\s,\-/+()]{6,95})$", |
| re.I, |
| ) |
|
|
|
|
| def _balance_parens(text: str) -> str: |
| t = text.strip() |
| while t.startswith("(") and t.endswith(")") and t[1:-1].count("(") == t[1:-1].count(")"): |
| t = t[1:-1].strip() |
| if t.count("(") > t.count(")"): |
| last_open = t.rfind("(") |
| if len(t) - last_open <= 15: |
| t = t + ")" |
| else: |
| t = t[:last_open].strip() |
| elif t.count(")") > t.count("("): |
| t = t.replace(")", "").strip() |
| return t |
|
|
|
|
| def clean_complete_topic(raw_title: str) -> str: |
| """ |
| Extract a complete, self-contained clinical topic phrase from a peer-reviewed paper title |
| without mid-phrase truncation or dangling prepositions/adjectives. |
| """ |
| t = html.unescape(raw_title or "") |
| t = re.sub(r"<[^>]+>", "", t).strip() |
| t = re.sub(r"\s+", " ", t).rstrip(".:;?-–— ") |
| t = SUBTITLE_BOILERPLATE_RE.sub("", t).strip() |
|
|
| if ":" in t: |
| p0, p1 = [p.strip() for p in t.split(":", 1)] |
| if p0.lower() in {"research review", "clinical review", "special report", "consensus statement", "clinical practice guideline", "original article", "review article"} and len(p1) >= 24: |
| t = p1 |
| elif len(p0) >= 28: |
| t = p0 |
| elif len(p1) >= 28 and not SUBTITLE_BOILERPLATE_RE.search(": " + p1): |
| t = f"{p0} ({p1})" if len(p0) + len(p1) < 120 else p1 |
|
|
| t = re.sub( |
| r"^(a |an |the )?(systematic review and meta-analysis of|systematic review of|meta-analysis of|" |
| r"narrative review of|scoping review of|comprehensive review of|clinical overview of|overview of|" |
| r"update on|updates in|current perspectives on)\s+", |
| "", |
| t, |
| flags=re.I, |
| ).strip() |
|
|
| if len(t) > 215: |
| clause_break = re.search(r"[,;–—]\s+", t[110:]) |
| if clause_break: |
| t = t[: 110 + clause_break.start()].strip() |
| else: |
| t = t[:210].rsplit(" ", 1)[0].strip() |
|
|
| t = _balance_parens(t) |
| t = re.sub(r"[:;,\-–—/]+\s*$", "", t).strip() |
| while True: |
| new_t = DANGLING_TAIL_RE.sub("", t).strip() |
| new_t = re.sub(r"[:;,\-–—/]+\s*$", "", new_t).strip() |
| if new_t == t or len(new_t) < 22: |
| break |
| t = new_t |
|
|
| t = _balance_parens(t) |
| if t and t[0].islower(): |
| t = t[0].upper() + t[1:] |
| return t |
|
|
|
|
| def _clean_extracted_entity(phrase: str) -> str: |
| p = phrase.strip(" ,:;.-–—") |
| p = PREFIX_BOILERPLATE_RE.sub("", p).strip(" ,:;.-–—") |
| p = re.sub(r"\s+\b(patients|individuals|adults|children|subjects|cases)\s*$", "", p, flags=re.I).strip() |
| while True: |
| np = DANGLING_TAIL_RE.sub("", p).strip(" ,:;.-–—") |
| if np == p or len(np) < 8: |
| break |
| p = np |
| p = _balance_parens(p) |
| if p and p[0].islower(): |
| p = p[0].upper() + p[1:] |
| return p |
|
|
|
|
| def _distinctive_condition_words(cond_name: str) -> list[str]: |
| return [ |
| w.lower() |
| for w in re.findall(r"[A-Za-z0-9]{3,}", cond_name) |
| if len(w) >= 4 and w.lower() not in GENERIC_CONDITION_MODIFIERS |
| ] |
|
|
|
|
| def _extract_condition_from_paper(clean_topic: str, cat_display_name: str) -> str | None: |
| """Extract a paper-native disease/condition phrase from clean_topic when it differs from the sub-domain default.""" |
| trimmed_topic = re.sub(r"\s+in the (?:era|context|setting|wake|presence) of\s+[A-Za-z0-9\s,\-/+()]+$", "", clean_topic, flags=re.I).strip() |
| m_with = re.search( |
| r"\b(?:children and young people|children and adolescents|adolescents and adults|older adults|pregnant women|postpartum women|children|adolescents|adults|women|men|patients|individuals|infants|neonates)\s+with\s+" |
| r"(?P<cond>[A-Za-z0-9][A-Za-z0-9\s,\-/+()]{6,90})$", |
| trimmed_topic, |
| flags=re.I, |
| ) |
| if m_with: |
| c = _clean_extracted_entity(m_with.group("cond")) |
| if 8 <= len(c) <= 90: |
| return c |
| m = COND_PREP_RE.search(trimmed_topic) |
| if m: |
| c = _clean_extracted_entity(m.group("cond")) |
| if 8 <= len(c) <= 90 and c.lower() not in {"clinical practice", "routine care", "primary care", "the united states", "europe", "china", "japan", "turkey"}: |
| return c |
| m_of = re.search( |
| r"\b(?:genetics|pathogenesis|diagnosis|management|treatment|epidemiology|prognosis|classification|biomarkers|monitoring)\s+of\s+" |
| r"([A-Za-z0-9][A-Za-z0-9\s,\-/+()]{6,85})$", |
| trimmed_topic, |
| flags=re.I, |
| ) |
| if m_of: |
| c = _clean_extracted_entity(m_of.group(1)) |
| if 8 <= len(c) <= 90: |
| return c |
| return None |
|
|
|
|
| def _strip_redundant_population_tail(topic_text: str, cond_name: str) -> str: |
| """ |
| Strip trailing ' in <disease/patients>' from a paper topic when it is embedded inside a |
| sentence that already explicitly states 'In <population> with <condition>'. |
| """ |
| trimmed_topic = re.sub(r"\s+in the (?:era|context|setting) of\s+[A-Za-z0-9\s,\-/+()]+$", "", topic_text, flags=re.I).strip() |
| m_on_of = re.search( |
| r"\s+(?:on|in|among|for)\s+(?:the\s+[a-z\s]{3,25}\s+of\s+)?(?:children|adolescents|adults|women|men|patients|individuals|infants|neonates)[A-Za-z0-9,\-\s/+()]{4,95}$", |
| trimmed_topic, |
| flags=re.I, |
| ) |
| if m_on_of: |
| trimmed = trimmed_topic[: m_on_of.start()].strip() |
| if len(trimmed) >= 14: |
| return _clean_extracted_entity(trimmed) |
| cond_words = set(_distinctive_condition_words(cond_name)) |
| m = re.search(r"\s+(?:in|among)\s+([A-Za-z0-9,\-\s/+()]{8,85})$", trimmed_topic, flags=re.I) |
| if m: |
| tail = m.group(1).lower() |
| if any(cw in tail for cw in cond_words) or any(k in tail for k in ("patients", "cancer", "disease", "carcinoma", "lymphoma", "leukemia", "amyloidosis", "syndrome", "dissection", "children", "women", "adults")): |
| trimmed = trimmed_topic[: m.start()].strip() |
| if len(trimmed) >= 14: |
| return _clean_extracted_entity(trimmed) |
| return _clean_extracted_entity(trimmed_topic) |
|
|
|
|
| def select_coherent_outcomes(cat_id: int, raw_title: str, cond_name: str) -> tuple[str, str, str]: |
| """ |
| Return domain-coherent (prim_out, safe_out, pro_out) phrases matched to the category and specific |
| disease/sub-specialty so no unrelated sub-domain scales (e.g. endometriosis scales on PCOS, or dental |
| scales on stroke rehabilitation) ever appear in a question statement. |
| """ |
| tl = f"{raw_title} {cond_name}".lower() |
| if cat_id == 1: |
| if any(k in tl for k in ("thromboembol", "vte", "anticoagul", "thrombosis")): |
| return ( |
| "recurrent venous thromboembolism and clinically relevant bleeding", |
| "ISTH major bleeding and clinically relevant non-major bleeding", |
| "anticoagulation treatment burden and health-related quality of life", |
| ) |
| if any(k in tl for k in ("hemophilia", "haemophilia", "sickle cell", "thalassemia", "aplastic anemia", "hemoglobinuria", "pnh", "thrombocytopenic", "ttp", "itp", "von willebrand")): |
| return ( |
| "annualized bleeding or crisis rate, hemoglobin stabilization, and event-free survival", |
| "thromboembolic events, hemolysis or bleeding breakthroughs, and immunogenicity", |
| "FACIT-Fatigue score, physical function, and transfusion or infusion burden", |
| ) |
| return ( |
| "overall survival and progression-free or disease-free survival", |
| "Grade >=3 treatment-related and immune-mediated adverse events", |
| "EORTC QLQ-C30 health-related quality of life and symptomatic toxicity burden", |
| ) |
| if cat_id == 2: |
| if "aortic" in tl or "dissection" in tl or "aneurysm" in tl: |
| return ( |
| "aortic-related mortality, stroke, and reintervention-free survival", |
| "spinal cord ischemia, stroke, and major perioperative bleeding", |
| "functional independence and health-related quality of life", |
| ) |
| return ( |
| "cardiovascular death, myocardial infarction, and ischemic stroke", |
| "ISTH major bleeding, intracranial hemorrhage, and arrhythmia or conduction disturbances", |
| "Kansas City Cardiomyopathy Questionnaire (KCCQ) score and functional independence", |
| ) |
| if cat_id == 3: |
| if "epilep" in tl or "seizure" in tl: |
| return ( |
| "sustained seizure freedom and >=50% seizure frequency reduction", |
| "neuropsychiatric and cognitive adverse events and treatment discontinuation", |
| "Quality of Life in Epilepsy (QOLIE-31) score and cognitive function", |
| ) |
| return ( |
| "confirmed disability progression and longitudinal neurological function", |
| "treatment-related neurotoxicity, serious infection, and infusion or procedural complications", |
| "cognitive function, fatigue, and patient-reported neurological quality of life (Neuro-QoL)", |
| ) |
| if cat_id == 4: |
| return ( |
| "sustained symptomatic remission and relapse prevention", |
| "suicidal ideation or behavior, treatment-emergent adverse events, and withdrawal symptoms", |
| "psychosocial functioning, social participation, and patient-reported mental health quality of life", |
| ) |
| if cat_id == 5: |
| return ( |
| "28-day and 90-day all-cause mortality and microbiological or clinical cure", |
| "organ toxicity and treatment-emergent antimicrobial resistance selection", |
| "time to symptom resolution, hospital-free days, and treatment completion", |
| ) |
| if cat_id == 6: |
| if "sleep" in tl or "apnea" in tl: |
| return ( |
| "apnea-hypopnea index reduction, nocturnal oxygenation, and cardiovascular event rate", |
| "treatment intolerance, mask or device complications, and daytime residual sedation", |
| "Epworth Sleepiness Scale score, sleep quality, and daytime functional alertness", |
| ) |
| return ( |
| "annualized severe exacerbation rate and lung function trajectory (FEV1 or FVC)", |
| "pneumonia, airway infection, and treatment-related systemic adverse events", |
| "St George's Respiratory Questionnaire (SGRQ) score and dyspnea symptom burden", |
| ) |
| if cat_id == 7: |
| return ( |
| "glycemic and cardiometabolic control, major adverse cardiovascular events, and organ preservation", |
| "severe hypoglycemia, lean body mass loss, and gastrointestinal or hepatobiliary adverse events", |
| "metabolic health-related quality of life, physical function, and treatment satisfaction", |
| ) |
| if cat_id == 8: |
| if any(k in tl for k in ("liver", "hepat", "cirrhosis", "masld", "nafld", "nash", "biliary", "cholang")): |
| return ( |
| "liver-related event-free survival, histologic fibrosis regression, and decompensation rate", |
| "hepatic decompensation, variceal bleeding, and serious infection", |
| "Chronic Liver Disease Questionnaire (CLDQ) score and hospital-free days", |
| ) |
| return ( |
| "steroid-free clinical and endoscopic or transmural remission", |
| "serious opportunistic infection, gastrointestinal bleeding, and bowel perforation", |
| "digestive symptom burden, IBD-Disk disability score, and quality of life", |
| ) |
| if cat_id == 9: |
| return ( |
| "sustained eGFR preservation, progression to kidney failure, and renal or patient survival", |
| "hyperkalemia, acute kidney injury, volume overload, and serious infection", |
| "Kidney Disease Quality of Life (KDQOL-36) score and symptom burden", |
| ) |
| if cat_id == 10: |
| return ( |
| "sustained steroid-free clinical remission and prevention of organ damage accrual", |
| "serious opportunistic infection, thromboembolic events, and treatment-related toxicity", |
| "HAQ-DI physical function, FACIT-Fatigue score, and cumulative glucocorticoid toxicity", |
| ) |
| if cat_id == 11: |
| if any(k in tl for k in ("psoriasis", "dermatitis", "eczema", "hidradenitis", "alopecia", "vitiligo", "skin", "cutaneous", "pemphig", "urticaria", "acne", "melasma", "wound", "ulcer")): |
| return ( |
| "validated skin clearance or lesion resolution and durable disease control", |
| "mucocutaneous or systemic infection and treatment-related adverse events", |
| "Dermatology Life Quality Index (DLQI), pruritus or pain intensity, and patient satisfaction", |
| ) |
| return ( |
| "pain intensity reduction, functional joint survival, and revision-free durability", |
| "periprosthetic infection or fracture, thromboembolism, and procedural complications", |
| "PROMIS pain interference, physical function, and return to independent mobility", |
| ) |
| if cat_id == 12: |
| if any(k in tl for k in ("polycystic", "pcos", "ovary", "ovarian", "infertility", "fertility", "ivf", "menopaus", "endometriosis", "fibroid", "adenomyosis", "contracept", "menstrual", "gynecol", "pelvic")): |
| return ( |
| "reproductive, endocrine, and cardiometabolic health outcomes", |
| "treatment-related thromboembolic, metabolic, and gynecologic adverse events", |
| "validated condition-specific quality of life, symptom severity, and reproductive well-being", |
| ) |
| return ( |
| "severe maternal morbidity and perinatal survival without severe morbidity", |
| "preeclampsia, fetal growth restriction, neonatal complications, and maternal hemorrhage", |
| "maternal functional recovery, postpartum depression (EPDS), and patient-reported birth experience", |
| ) |
| if cat_id == 13: |
| if any(k in tl for k in ("neonat", "preterm", "infant", "necrotizing", "bronchopulmonary", "hypoxic-ischemic")): |
| return ( |
| "survival without neurodevelopmental impairment and major neonatal morbidity", |
| "sepsis, necrotizing enterocolitis, and growth suppression", |
| "neurodevelopmental trajectory and family caregiver burden", |
| ) |
| return ( |
| "pediatric disease control, age-appropriate growth, and long-term organ function", |
| "treatment-related toxicity, infection, and developmental or endocrine adverse effects", |
| "Pediatric Quality of Life Inventory (PedsQL) score and family caregiver burden", |
| ) |
| if cat_id == 14: |
| if any(k in tl for k in ("alzheimer", "dementia", "amyloid", "cognitive", "lewy", "frontotemporal")): |
| return ( |
| "CDR-SB cognitive and functional trajectory and days alive and independent at home", |
| "amyloid-related imaging abnormalities (ARIA), intracerebral hemorrhage, and falls", |
| "neuropsychiatric symptom burden, Zarit caregiver burden score, and quality of life", |
| ) |
| return ( |
| "days alive and independent at home, functional preservation, and survival", |
| "falls, delirium, polypharmacy-related adverse drug events, and emergency hospitalization", |
| "symptom burden, Zarit caregiver burden score, and goal-concordant care", |
| ) |
| if cat_id == 15: |
| return ( |
| "30-day and 90-day all-cause mortality and organ support-free days", |
| "major perioperative or critical care complications, organ ischemia, and reintervention", |
| "EQ-5D-5L functional recovery, 6-minute walk distance, and return to independent living", |
| ) |
| if cat_id == 16: |
| return ( |
| "diagnostic accuracy, time to definitive diagnosis, and downstream clinical outcome impact", |
| "false-positive invasive biopsy cascades, overdiagnosis, and diagnostic delay", |
| "diagnostic yield, clinician decision confidence, and patient decisional regret", |
| ) |
| if cat_id == 17: |
| return ( |
| "all-cause and cause-specific mortality and incident disease rate", |
| "overdiagnosis, false-positive interventions, and preventive regimen adverse events", |
| "health equity gap reduction across socioeconomic strata and quality-adjusted life years", |
| ) |
| if cat_id == 18: |
| return ( |
| "30-day mortality, preventable adverse events, and guideline-concordant care delivery", |
| "unintended care delays, missed diagnoses, and clinician workload burden", |
| "patient-reported care coordination, equity disparity reduction, and implementation fidelity", |
| ) |
| if cat_id == 19: |
| if any(k in tl for k in ("retinal", "macular", "glaucoma", "myopia", "visual", "ophthalm", "ocular", "cornea", "uveitis", "cataract", "optic")): |
| return ( |
| "best-corrected visual acuity (BCVA) and structural retinal or optic nerve preservation", |
| "intraocular inflammation, endophthalmitis, and ocular hypertension", |
| "National Eye Institute Visual Function Questionnaire (NEI VFQ-25) score and visual independence", |
| ) |
| if any(k in tl for k in ("dental", "periodont", "caries", "implant", "oral", "orthodont", "endodont", "maxillofacial", "tooth", "teeth")): |
| return ( |
| "tooth or implant survival, clinical attachment gain, and oral disease resolution", |
| "peri-implantitis, alveolar bone loss, and postoperative infection", |
| "Oral Health Impact Profile (OHIP-14) score, masticatory function, and patient comfort", |
| ) |
| if any(k in tl for k in ("hearing", "cochlear", "tinnitus", "vestibular", "speech", "aphasia", "dysphagia", "auditory", "deaf")): |
| return ( |
| "speech-in-noise recognition, communication recovery, and swallowing safety", |
| "device failure, aspiration pneumonia, and vestibular dysfunction", |
| "Tinnitus Functional Index, communication participation, and WHODAS 2.0 score", |
| ) |
| return ( |
| "validated motor and functional recovery (Fugl-Meyer, ARAT, or FIM)", |
| "musculoskeletal injury, falls, and autonomic or cardiovascular instability", |
| "WHODAS 2.0 community participation, independent mobility, and quality of life", |
| ) |
| return ( |
| "event-free survival, organ-specific disease stabilization, and validated functional response", |
| "treatment-related immunogenicity, hepatotoxicity, and severe multisystem adverse events", |
| "time to definitive diagnosis, functional independence, and patient or caregiver quality of life", |
| ) |
|
|
|
|
| def _check_subdomain_disease_match(raw_title: str, base_cond_name: str) -> bool: |
| """ |
| Verify whether `raw_title` genuinely addresses `base_cond_name` using whole-word token matching, |
| subtype conflict checks (`type a` vs `type b`, `type 1` vs `type 2`), and qualifier checks for umbrella nouns. |
| """ |
| tl = raw_title.lower() |
| bcl = base_cond_name.lower() |
| if ("type a" in bcl and "type b" in tl) or ("type b" in bcl and "type a" in tl): |
| return False |
| if ("type 1" in bcl and "type 2" in tl) or ("type 2" in bcl and "type 1" in tl): |
| return False |
|
|
| title_tokens = set(re.findall(r"[a-z0-9]+", tl)) |
| dist_words = _distinctive_condition_words(base_cond_name) |
| if not dist_words: |
| return True |
|
|
| qualifiers = [w for w in dist_words if w not in UMBRELLA_DISEASE_NOUNS] |
| umbrellas = [w for w in dist_words if w in UMBRELLA_DISEASE_NOUNS] |
|
|
| if qualifiers and umbrellas: |
| return any(q in title_tokens for q in qualifiers) and any(u in title_tokens for u in umbrellas) |
| return any(dw in title_tokens for dw in dist_words) |
|
|
|
|
| def extract_paper_pico( |
| raw_title: str, |
| clean_topic: str, |
| qtype: str, |
| cond_tuple: tuple, |
| int_tuple: tuple, |
| outcomes_list: list[dict], |
| lower_fn, |
| cat_display_name: str = "Clinical medicine", |
| cat_id: int = 1, |
| ) -> dict: |
| """ |
| Extract paper-specific PICO elements (`cond_name`, `int_name`, `int_details`, `comp_name`, `pop_desc`, |
| `stage_sev`, `prio_sub`, `focus_clean`, `prim_out`, `safe_out`, `pro_out`) from the paper title and |
| harmonize with the sub-domain clinical baseline. |
| Guarantees zero cross-disease chimeras and zero mismatched outcome scales. |
| """ |
| base_cond_name, onto_ids, base_stage, phenotype, base_pop, age_stages, inc_feat, base_prio_sub = cond_tuple |
| _, base_int_name, base_int_details, base_comp_name, horizon, settings, _ = int_tuple |
|
|
| tl = raw_title.lower() |
| matches_subdomain_disease = _check_subdomain_disease_match(raw_title, base_cond_name) |
|
|
| if matches_subdomain_disease: |
| cond_name = base_cond_name |
| pop_desc = base_pop |
| stage_sev = base_stage |
| prio_sub = base_prio_sub |
| else: |
| |
| paper_cond = _extract_condition_from_paper(clean_topic, cat_display_name) |
| if paper_cond: |
| cond_name = paper_cond |
| if any(p in paper_cond.lower() for p in ("children", "adolescents", "young people", "women", "adults", "patients", "infants", "neonates", "older adults")): |
| pop_desc = paper_cond[0].upper() + paper_cond[1:] |
| else: |
| pop_desc = f"Patients with {lower_fn(paper_cond)}" |
| else: |
| cond_name = f"{clean_topic[:80].rsplit(' ', 1)[0]}" if len(clean_topic) > 80 else clean_topic |
| pop_desc = f"Patients evaluated for {lower_fn(cond_name)} in {cat_display_name.lower()}" |
| stage_sev = "Clinically characterized human cohort" |
| prio_sub = ["high-risk clinical subgroups", "underrepresented age and comorbidity strata"] |
|
|
| extracted_int = None |
| extracted_comp = None |
|
|
| |
| m_comp = EXPLICIT_COMP_RE.search(clean_topic) |
| if m_comp: |
| a = _clean_extracted_entity(m_comp.group("arm_a")) |
| b = _clean_extracted_entity(m_comp.group("arm_b")) |
| if " of " in a.lower(): |
| a = _clean_extracted_entity(a.split(" of ")[-1]) |
| |
| a_words = a.split() |
| b_words = b.split() |
| if len(a_words) == 1 and len(b_words) >= 2: |
| a = f"{a} {' '.join(b_words[1:])}" |
| if len(a) >= 6 and len(b) >= 6: |
| extracted_int = a |
| extracted_comp = b |
|
|
| |
| if not extracted_int: |
| m_of = OF_PATTERN_RE.match(clean_topic) |
| if m_of: |
| focus = _clean_extracted_entity(m_of.group("focus")) |
| if 8 <= len(focus) <= 95: |
| extracted_int = focus |
|
|
| |
| if not extracted_int: |
| m_for = FOR_ACTION_RE.match(clean_topic) |
| if m_for: |
| focus = _clean_extracted_entity(m_for.group("focus")) |
| if 8 <= len(focus) <= 95: |
| extracted_int = focus |
|
|
| |
| if not extracted_int: |
| m_ger = GERUND_RE.match(clean_topic) |
| if m_ger: |
| focus = _clean_extracted_entity(m_ger.group("focus")) |
| if 8 <= len(focus) <= 95: |
| extracted_int = focus |
|
|
| |
| if not extracted_int: |
| m_and = AND_IN_RE.match(clean_topic) |
| if m_and: |
| focus = _clean_extracted_entity(m_and.group("focus")) |
| if 8 <= len(focus) <= 85: |
| extracted_int = focus |
|
|
| |
| if not extracted_int: |
| m_prep = re.split(r"\s+(?:in|among|for|after|during|following|across)\s+", clean_topic, maxsplit=1, flags=re.I) |
| if len(m_prep) == 2 and 10 <= len(m_prep[0].strip()) <= 85: |
| cand_focus = _clean_extracted_entity(m_prep[0]) |
| if cand_focus.lower() != cond_name.lower() and len(cand_focus) >= 10: |
| extracted_int = cand_focus |
|
|
| |
| cond_tokens = set(_distinctive_condition_words(cond_name)) |
| if extracted_int: |
| int_no_parens = re.sub(r"\([^)]*\)", "", extracted_int).strip() |
| int_tokens = set(_distinctive_condition_words(int_no_parens)) |
| if not (int_tokens - cond_tokens) or int_no_parens.lower() in cond_name.lower(): |
| extracted_int = None |
|
|
| |
| if extracted_int: |
| int_name = extracted_int |
| int_details = f"Clinical and translational evaluation of {lower_fn(extracted_int)} in {lower_fn(cond_name)}" |
| elif matches_subdomain_disease: |
| int_name = base_int_name |
| int_details = base_int_details |
| if not extracted_comp: |
| extracted_comp = base_comp_name |
| else: |
| stripped_topic = _strip_redundant_population_tail(clean_topic, cond_name) |
| st_no_parens = re.sub(r"\([^)]*\)", "", stripped_topic).strip() |
| int_tokens = set(_distinctive_condition_words(st_no_parens)) |
| if not (int_tokens - cond_tokens) or st_no_parens.lower() in cond_name.lower(): |
| int_name = f"Guideline-directed clinical management and biomarker stratification in {lower_fn(cond_name)}" |
| else: |
| int_name = _balance_parens(stripped_topic if len(stripped_topic) <= 90 else stripped_topic[:88].rsplit(" ", 1)[0]) |
| int_details = f"Evaluation of {lower_fn(int_name)} in {lower_fn(cond_name)}" |
|
|
| |
| focus_clean = _strip_redundant_population_tail(clean_topic, cond_name) |
| fc_no_parens = re.sub(r"\([^)]*\)", "", focus_clean).strip() |
| focus_tokens = set(_distinctive_condition_words(fc_no_parens)) |
| if len(focus_clean) < 14 or not (focus_tokens - cond_tokens) or fc_no_parens.lower() in cond_name.lower(): |
| focus_clean = int_name |
|
|
| |
| if extracted_comp: |
| comp_name = extracted_comp |
| else: |
| cond_short = lower_fn(cond_name) |
| qtype_comparators = { |
| "etiology": f"Unexposed or baseline reference risk cohort in {cond_short}", |
| "mechanism": f"Canonical baseline pathway activity or treatment-sensitive phenotype in {cond_short}", |
| "natural_history": f"Standard longitudinal clinical surveillance cohort in {cond_short}", |
| "prevention": "Routine risk-factor modification or standard surveillance without targeted prophylaxis", |
| "screening": "Symptom-prompted clinical evaluation or current guideline screening schedule", |
| "diagnosis": "Conventional clinicopathologic, imaging, or laboratory reference standard", |
| "classification": "Conventional clinicopathologic staging and consensus taxonomy", |
| "prognosis": f"Standard clinical risk score without {lower_fn(int_name)} stratification", |
| "treatment_effectiveness": f"Standard-of-care therapy or active control regimen in {cond_short}", |
| "comparative_effectiveness": f"Current guideline-recommended standard regimen in {cond_short}", |
| "treatment_strategy": f"Standard fixed-duration or unselected dosing regimen in {cond_short}", |
| "safety": "Alternative active comparator or standard dose-monitoring regimen", |
| "rehabilitation": "Usual physical and functional care without structured rehabilitation pathway", |
| "supportive_palliative": "Usual symptom-directed care without integrated supportive pathway", |
| "patient_experience": "Routine clinician-directed care without structured patient-reported decision tool", |
| "implementation": "Usual guideline dissemination without multifaceted implementation strategy", |
| "health_services": "Conventional specialty or hospital-centered care delivery model", |
| "public_health": "Status-quo population health policy without targeted equity intervention", |
| "measurement": "Legacy clinician-rated or unharmonized outcome assessment instrument", |
| "methodology": "Conventional unadjusted analysis or traditional fixed-sample trial design", |
| } |
| comp_name = qtype_comparators.get(qtype, f"Standard-of-care management in {cond_short}") |
|
|
| |
| if "metastatic" in tl and "metastatic" not in stage_sev.lower(): |
| stage_sev = f"Metastatic or advanced stage ({stage_sev})" |
| elif ("relapsed" in tl or "refractory" in tl) and "relapsed" not in stage_sev.lower(): |
| stage_sev = f"Relapsed or refractory stage ({stage_sev})" |
| elif ("early-stage" in tl or "early stage" in tl) and "early" not in stage_sev.lower(): |
| stage_sev = f"Early-stage disease ({stage_sev})" |
| elif ("pediatric" in tl or "children" in tl or "neonat" in tl) and "pediatric" not in pop_desc.lower() and "children" not in pop_desc.lower(): |
| if pop_desc.lower().startswith("adults "): |
| pop_desc = "Children and adolescents " + pop_desc[7:] |
| elif pop_desc.lower().startswith("patients "): |
| pop_desc = "Pediatric and adolescent patients " + pop_desc[9:] |
| else: |
| pop_desc = f"Children and adolescents with {lower_fn(cond_name)}" |
| elif ("elderly" in tl or "older adult" in tl or "geriatric" in tl) and "older" not in pop_desc.lower(): |
| if pop_desc.lower().startswith("adults "): |
| pop_desc = "Older adults " + pop_desc[7:] |
| elif pop_desc.lower().startswith("patients "): |
| pop_desc = "Older adults and geriatric patients " + pop_desc[9:] |
| else: |
| pop_desc = f"Older adults with {lower_fn(cond_name)}" |
|
|
| prim_out, safe_out, pro_out = select_coherent_outcomes(cat_id, raw_title, cond_name) |
|
|
| return { |
| "cond_name": cond_name, |
| "int_name": int_name, |
| "int_details": int_details, |
| "comp_name": comp_name, |
| "pop_desc": pop_desc, |
| "stage_sev": stage_sev, |
| "prio_sub": prio_sub, |
| "focus_clean": focus_clean, |
| "prim_out": prim_out, |
| "safe_out": safe_out, |
| "pro_out": pro_out, |
| } |
|
|
|
|
| def build_natural_statements( |
| prob_num: int, |
| qtype: str, |
| clean_topic: str, |
| focus_clean: str, |
| cond_name: str, |
| pop_desc: str, |
| stage_sev: str, |
| int_name: str, |
| comp_name: str, |
| prim_out: str, |
| safe_out: str, |
| pro_out: str, |
| horizon: str, |
| settings: list[str], |
| prio_sub: list[str], |
| lower_fn, |
| ) -> tuple[str, str, str, str]: |
| """ |
| Return `(title, statement, clean_statement, plain_language_statement)` using 100 natural |
| clinical question templates (5 variants per question_type x 20 question_types) with zero |
| awkward double-splicing. |
| """ |
| variant = prob_num % 5 |
| focus_mid = lower_fn(focus_clean) |
| cond_mid = lower_fn(cond_name) |
| pop_mid = lower_fn(re.sub(r"\s*\([^)]{10,}\)", "", pop_desc).strip()) |
| int_mid = lower_fn(int_name) |
| comp_mid = lower_fn(re.sub(r"\s*\([^)]{10,}\)", "", comp_name).strip()) |
| prio_mid = ", ".join(lower_fn(p) for p in prio_sub[:2]) |
| setting_mid = ", ".join(s.replace("_", " ") for s in settings[:2]) |
|
|
| cond_sig_words = _distinctive_condition_words(cond_name) |
| q_label = qtype.replace("_", " ").title() |
| if any(w in clean_topic.lower() for w in cond_sig_words) or cond_name.lower() in clean_topic.lower(): |
| title = f"{clean_topic} — Open {q_label} Question" |
| else: |
| title = f"{clean_topic} in {cond_name} ({q_label})" |
|
|
| clean_statement = ( |
| f"In {pop_mid}, how does {int_mid} compare with {comp_mid} regarding {prim_out} over {horizon}?" |
| ) |
|
|
| templates = { |
| "comparative_effectiveness": [ |
| f"In {pop_mid}, does {focus_mid} improve {prim_out} and reduce {safe_out} over {horizon} compared with {comp_mid}?", |
| f"Among {pop_mid}, what is the head-to-head comparative effectiveness of {focus_mid} versus {comp_mid} for achieving superior {prim_out} over {horizon}?", |
| f"For {pop_mid} managed in {setting_mid} settings, does {focus_mid} provide a net clinical advantage over {comp_mid} on {prim_out} and {safe_out} through {horizon}?", |
| f"When treating {pop_mid} (including {prio_mid}), is {focus_mid} superior or non-inferior to {comp_mid} with respect to {prim_out} at {horizon}?", |
| f"Across diverse clinical cohorts of {pop_mid}, how does {focus_mid} compare against {comp_mid} in balancing {prim_out} against {safe_out} over {horizon}?", |
| ], |
| "treatment_effectiveness": [ |
| f"Among {pop_mid} ({lower_fn(stage_sev)}), what is the confirmatory clinical efficacy of {focus_mid} compared with {comp_mid} on {prim_out} over {horizon}?", |
| f"In {pop_mid}, does therapeutic intervention with {focus_mid} produce durable improvements in {prim_out} over {horizon} relative to {comp_mid}?", |
| f"For {pop_mid}, can {focus_mid} significantly improve {prim_out} without unacceptable {safe_out} over {horizon} compared with {comp_mid}?", |
| f"What is the magnitude and durability of treatment benefit from {focus_mid} versus {comp_mid} on {prim_out} over {horizon} in {pop_mid}?", |
| f"In randomized evaluation of {pop_mid}, does {focus_mid} achieve clinically meaningful gains in {prim_out} and {pro_out} over {horizon} compared with {comp_mid}?", |
| ], |
| "treatment_strategy": [ |
| f"For {pop_mid} in {setting_mid} settings, what is the optimal sequencing, dosing threshold, or treatment duration of {focus_mid} versus {comp_mid} over {horizon}?", |
| f"In {pop_mid}, does a biomarker- or response-adapted strategy for {focus_mid} outperform {comp_mid} on {prim_out} and {safe_out} over {horizon}?", |
| f"Among {pop_mid}, when can therapy be safely de-escalated, switched, or intensified using {focus_mid} compared with {comp_mid} over a {horizon} horizon?", |
| f"What is the optimal clinical algorithm for initiating and sequencing {focus_mid} relative to {comp_mid} to maximize {prim_out} over {horizon} in {pop_mid}?", |
| f"In {pop_mid}, does dynamic treatment adaptation guided by {focus_mid} improve {prim_out} over {horizon} compared with {comp_mid}?", |
| ], |
| "diagnosis": [ |
| f"In {pop_mid} presenting for clinical evaluation, what is the diagnostic accuracy and clinical utility of {focus_mid} compared with {comp_mid} for improving {prim_out} over {horizon}?", |
| f"Among {pop_mid}, does integrating {focus_mid} into the diagnostic pathway outperform {comp_mid} in sensitivity, specificity, and downstream {prim_out} over {horizon}?", |
| f"For {pop_mid} in {setting_mid} care, can {focus_mid} reduce diagnostic delay and misclassification compared with {comp_mid} while improving {prim_out} over {horizon}?", |
| f"What are the externally validated diagnostic performance characteristics of {focus_mid} versus {comp_mid} in {pop_mid}, and does testing improve {prim_out} over {horizon}?", |
| f"In {pop_mid}, does diagnostic triage with {focus_mid} provide superior clinical net benefit over {comp_mid} across {horizon}?", |
| ], |
| "screening": [ |
| f"In asymptomatic or at-risk {pop_mid}, does structured screening via {focus_mid} compared with {comp_mid} improve early detection and {prim_out} without excess {safe_out} over {horizon}?", |
| f"Among {pop_mid} (including {prio_mid}), what is the net balance of benefits, false-positive burden, and overdiagnosis when screening with {focus_mid} versus {comp_mid} over {horizon}?", |
| f"For risk-stratified {pop_mid}, does longitudinal surveillance using {focus_mid} reduce late-stage presentation and improve {prim_out} over {horizon} compared with {comp_mid}?", |
| f"What screening interval and positivity threshold for {focus_mid} optimize {prim_out} and minimize {safe_out} compared with {comp_mid} in {pop_mid} over {horizon}?", |
| f"In population and clinic-based cohorts of {pop_mid}, does early detection through {focus_mid} translate into improved {prim_out} over {horizon} relative to {comp_mid}?", |
| ], |
| "classification": [ |
| f"In {pop_mid}, does biological endotyping or phenotypic classification via {focus_mid} outperform {comp_mid} for predicting {prim_out} and guiding therapy over {horizon}?", |
| f"Among {pop_mid}, can a reproducible subphenotype taxonomy based on {focus_mid} resolve clinical heterogeneity and improve {prim_out} stratification over {horizon} versus {comp_mid}?", |
| f"For {pop_mid}, do disease subtypes defined by {focus_mid} exhibit distinct treatment responses and {prim_out} trajectories over {horizon} compared with {comp_mid}?", |
| f"Does integrating multi-modal classification from {focus_mid} refine risk categories beyond {comp_mid} for {prim_out} over {horizon} in {pop_mid}?", |
| f"In {pop_mid}, how accurately do diagnostic and molecular criteria derived from {focus_mid} partition patients into actionable strata for {prim_out} over {horizon} versus {comp_mid}?", |
| ], |
| "prognosis": [ |
| f"Among {pop_mid}, what is the externally validated prognostic discrimination, calibration, and decision utility of {focus_mid} versus {comp_mid} for stratifying {prim_out} over {horizon}?", |
| f"In {pop_mid}, does prognostic modeling incorporating {focus_mid} provide incremental predictive value over {comp_mid} for {prim_out} through {horizon}?", |
| f"Across independent cohorts of {pop_mid} (including {prio_mid}), how reliably does {focus_mid} predict long-term {prim_out} and {safe_out} over {horizon} compared with {comp_mid}?", |
| f"For {pop_mid}, can baseline and serial assessment of {focus_mid} accurately stratify individual risk of {prim_out} over {horizon} relative to {comp_mid}?", |
| f"What is the transportability and clinical net benefit of risk prediction using {focus_mid} compared with {comp_mid} for {prim_out} over {horizon} in {pop_mid}?", |
| ], |
| "natural_history": [ |
| f"Across longitudinal cohorts of {pop_mid}, what is the natural trajectory, progression rate, and determinant profile of {prim_out} over {horizon} in relation to {focus_mid} versus {comp_mid}?", |
| f"In {pop_mid}, how does the long-term clinical course of {prim_out} evolve over {horizon} when stratified by {focus_mid} compared with {comp_mid}?", |
| f"Among {pop_mid}, what are the transition probabilities between clinical states and cumulative incidence of {prim_out} over {horizon} associated with {focus_mid}?", |
| f"In unselected prospective follow-up of {pop_mid}, what factors modify longitudinal progression to {prim_out} over {horizon} under {focus_mid} versus {comp_mid}?", |
| f"How do baseline phenotypic features and {focus_mid} shape the multi-year natural history of {prim_out} over {horizon} in {pop_mid}?", |
| ], |
| "etiology": [ |
| f"In {pop_mid}, what is the causal contribution of {focus_mid}—and its interaction with host susceptibility—to disease development and {prim_out} over {horizon} compared with {comp_mid}?", |
| f"Among {pop_mid}, does exposure or predisposition characterized by {focus_mid} independently increase disease incidence and {prim_out} over {horizon} after accounting for confounding?", |
| f"Through what causal pathways and dose-response relationships does {focus_mid} drive disease onset and {prim_out} over {horizon} in {pop_mid} relative to {comp_mid}?", |
| f"In longitudinal etiologic studies of {pop_mid}, what fraction of disease risk and {prim_out} over {horizon} is attributable to {focus_mid} versus {comp_mid}?", |
| f"Using triangulated human causal inference in {pop_mid}, is {focus_mid} a modifiable causal driver of {prim_out} over {horizon}?", |
| ], |
| "mechanism": [ |
| f"In human tissues and clinical cohorts of {pop_mid}, what cellular and molecular pathways link {focus_mid} to {prim_out} over {horizon}, and is this axis causally rate-limiting?", |
| f"Among {pop_mid}, how does mechanistic perturbation of {focus_mid} alter downstream pathobiology and clinical {prim_out} over {horizon} compared with {comp_mid}?", |
| f"In {pop_mid}, what are the primary immunologic, metabolic, or signaling drivers of treatment resistance and disease progression mediated by {focus_mid} over {horizon}?", |
| f"Does target engagement of the biological pathway underlying {focus_mid} reverse pathological remodeling and improve {prim_out} over {horizon} in {pop_mid}?", |
| f"In translational human studies of {pop_mid}, how do host-microenvironment or genetic interactions involving {focus_mid} govern {prim_out} over {horizon}?", |
| ], |
| "prevention": [ |
| f"In at-risk {pop_mid}, does primary or secondary prevention with {focus_mid} compared with {comp_mid} reduce disease incidence and improve {prim_out} over {horizon}?", |
| f"Among {pop_mid} (including {prio_mid}), what is the preventive efficacy and number needed to treat of {focus_mid} versus {comp_mid} for averting {prim_out} over {horizon}?", |
| f"For high-risk {pop_mid}, does targeted prophylaxis or risk reduction via {focus_mid} durably lower disease incidence and {prim_out} over {horizon} without excess {safe_out}?", |
| f"In {pop_mid}, what is the optimal timing and risk threshold for initiating preventive {focus_mid} compared with {comp_mid} to prevent {prim_out} over {horizon}?", |
| f"Across community and clinical cohorts of {pop_mid}, does sustained preventive intervention with {focus_mid} reduce long-term {prim_out} over {horizon} relative to {comp_mid}?", |
| ], |
| "safety": [ |
| f"Among {pop_mid} exposed to {focus_mid} versus {comp_mid}, what is the comparative incidence, severity, and reversibility of {safe_out} relative to {prim_out} benefit over {horizon}?", |
| f"In {pop_mid} (especially {prio_mid}), what patient-level risk factors and monitoring thresholds predict severe {safe_out} during {focus_mid} over {horizon}?", |
| f"For {pop_mid} receiving treatment in {setting_mid} settings, how does the long-term safety and pharmacovigilance profile of {focus_mid} compare with {comp_mid} over {horizon}?", |
| f"What is the causal risk-benefit trade-off between gains in {prim_out} and cumulative {safe_out} over {horizon} when using {focus_mid} versus {comp_mid} in {pop_mid}?", |
| f"In {pop_mid}, what mitigation or dose-modification strategy best prevents treatment-limiting {safe_out} from {focus_mid} while preserving {prim_out} over {horizon}?", |
| ], |
| "rehabilitation": [ |
| f"In {pop_mid}, does structured rehabilitation incorporating {focus_mid} improve functional recovery and {prim_out} over {horizon} compared with {comp_mid}?", |
| f"Among {pop_mid}, what intensity, timing, and modality of {focus_mid} maximize long-term functional independence and {pro_out} over {horizon} relative to {comp_mid}?", |
| f"For {pop_mid} in {setting_mid} rehabilitation pathways, does individualized therapy with {focus_mid} produce durable gains in {prim_out} over {horizon} versus {comp_mid}?", |
| f"In {pop_mid}, how does combining neuroplastic or physical conditioning via {focus_mid} compare against {comp_mid} in restoring mobility, function, and {prim_out} over {horizon}?", |
| f"Across heterogeneous recovery profiles in {pop_mid}, which subgroups derive clinically meaningful functional benefit from {focus_mid} over {horizon} compared with {comp_mid}?", |
| ], |
| "supportive_palliative": [ |
| f"For {pop_mid} experiencing symptom burden, does integrated supportive or palliative care via {focus_mid} improve {pro_out} and {prim_out} over {horizon} compared with {comp_mid}?", |
| f"In {pop_mid}, what is the comparative effectiveness of early, structured {focus_mid} versus {comp_mid} for relieving refractory symptoms and improving {pro_out} over {horizon}?", |
| f"Among {pop_mid} and their caregivers, does a multidisciplinary supportive pathway centered on {focus_mid} reduce acute care utilization and improve {pro_out} over {horizon}?", |
| f"In managing complex symptom clusters in {pop_mid}, how does {focus_mid} compare against {comp_mid} with respect to symptom control, {safe_out}, and {pro_out} over {horizon}?", |
| f"For {pop_mid} across {setting_mid} settings, does goal-concordant supportive care integrating {focus_mid} improve {pro_out} and {prim_out} over {horizon} relative to {comp_mid}?", |
| ], |
| "patient_experience": [ |
| f"Among {pop_mid}, how does care delivery incorporating {focus_mid} compare with {comp_mid} in improving patient-reported {pro_out} and decision quality over {horizon}?", |
| f"In {pop_mid} (including {prio_mid}), what treatment attributes, lived-experience priorities, and trade-offs between {prim_out} and {safe_out} govern preference for {focus_mid} versus {comp_mid}?", |
| f"For {pop_mid}, does structured shared decision-making and symptom monitoring around {focus_mid} reduce treatment regret and improve {pro_out} over {horizon} compared with {comp_mid}?", |
| f"Across diverse cultural and socioeconomic groups of {pop_mid}, how does {focus_mid} impact treatment burden, quality of life, and {pro_out} over {horizon} relative to {comp_mid}?", |
| f"In {pop_mid}, do patient-reported outcomes ({pro_out}) over {horizon} favor {focus_mid} or {comp_mid} when accounting for daily treatment burden and {safe_out}?", |
| ], |
| "implementation": [ |
| f"Across real-world {setting_mid} settings caring for {pop_mid}, which implementation strategies for {focus_mid} maximize guideline fidelity, equity across {prio_mid}, and {prim_out} over {horizon}?", |
| f"In routine clinical practice for {pop_mid}, does a multifaceted implementation bundle for {focus_mid} outperform {comp_mid} in adoption, sustainment, and {prim_out} over {horizon}?", |
| f"What health-system, clinician, and patient-level barriers limit real-world uptake of {focus_mid} in {pop_mid}, and do targeted implementation interventions improve {prim_out} over {horizon}?", |
| f"Among {setting_mid} practices managing {pop_mid}, how does structured clinical pathway integration of {focus_mid} compare with {comp_mid} for achieving equitable {prim_out} over {horizon}?", |
| f"In scaling evidence-based care for {pop_mid}, does audit-feedback and decision support for {focus_mid} close care gaps across {prio_mid} and improve {prim_out} over {horizon}?", |
| ], |
| "health_services": [ |
| f"In health systems managing {pop_mid}, how does organizing care delivery around {focus_mid} compare with {comp_mid} on {prim_out}, resource utilization, and care coordination over {horizon}?", |
| f"For {pop_mid} treated across {setting_mid} settings, does a redesigned service model incorporating {focus_mid} reduce avoidable hospitalizations and improve {prim_out} over {horizon} versus {comp_mid}?", |
| f"Among {pop_mid} (especially {prio_mid}), what is the cost-effectiveness, capacity impact, and clinical effect on {prim_out} of deploying {focus_mid} compared with {comp_mid} over {horizon}?", |
| f"Does multidisciplinary team triage and longitudinal care navigation for {focus_mid} improve {prim_out} and reduce {safe_out} over {horizon} compared with {comp_mid} in {pop_mid}?", |
| f"Across regional healthcare networks serving {pop_mid}, how does decentralized or integrated delivery of {focus_mid} compare against {comp_mid} for {prim_out} over {horizon}?", |
| ], |
| "public_health": [ |
| f"At the population level among {pop_mid} (including {prio_mid}), does scaling {focus_mid} compared with {comp_mid} reduce health disparities and improve population {prim_out} over {horizon}?", |
| f"Across high-burden communities of {pop_mid}, what is the population-level effectiveness and equity impact of public health interventions based on {focus_mid} versus {comp_mid} over {horizon}?", |
| f"In population surveillance of {pop_mid}, how do social determinants and policy implementation of {focus_mid} modify {prim_out} and disease burden over {horizon} compared with {comp_mid}?", |
| f"For public health programs serving {pop_mid}, does community-wide deployment of {focus_mid} achieve sustainable improvements in {prim_out} over {horizon} relative to {comp_mid}?", |
| f"Among underserved subpopulations ({prio_mid}) within {pop_mid}, can structural prevention and care linkage via {focus_mid} close outcome gaps in {prim_out} over {horizon}?", |
| ], |
| "measurement": [ |
| f"In clinical research and care for {pop_mid}, what is the construct validity, responsiveness, and minimal clinically important difference of measurement via {focus_mid} for {prim_out} over {horizon}?", |
| f"Among {pop_mid}, is {focus_mid} a validated surrogate or core outcome measure capable of reliably predicting {prim_out} over {horizon} compared with {comp_mid}?", |
| f"Across multi-center studies of {pop_mid}, how can assay or instrument standardization for {focus_mid} eliminate inter-laboratory variability and improve {prim_out} assessment over {horizon}?", |
| f"For evaluating interventions in {pop_mid}, does quantitative longitudinal tracking of {focus_mid} capture clinically meaningful change in {prim_out} and {pro_out} over {horizon} better than {comp_mid}?", |
| f"In {pop_mid} (including {prio_mid}), does outcome measurement via {focus_mid} demonstrate cross-population measurement invariance and prognostic validity for {prim_out} over {horizon}?", |
| ], |
| "methodology": [ |
| f"In clinical studies of {pop_mid} addressing {focus_mid}, which study design and causal-inference framework best resolves confounding, time-zero bias, and heterogeneity when comparing {int_mid} against {comp_mid} over {horizon}?", |
| f"For evaluating {focus_mid} versus {comp_mid} in {pop_mid}, how should estimands, intercurrent events, and competing risks be specified to yield unbiased estimates of {prim_out} over {horizon}?", |
| f"In synthesizing heterogeneous evidence on {focus_mid} in {pop_mid}, can individual participant data meta-analysis or target-trial emulation reconcile conflicting findings on {prim_out} over {horizon}?", |
| f"What adaptive platform trial architecture or covariate-adjusted randomization scheme optimizes statistical power across {prio_mid} when testing {focus_mid} versus {comp_mid} over {horizon}?", |
| f"When validating predictive or causal claims regarding {focus_mid} in {pop_mid}, what external transportability and bias-quantification standards are required to establish {prim_out} over {horizon}?", |
| ], |
| } |
|
|
| statement = templates[qtype][variant] |
|
|
| plain_variants = [ |
| f"For people with {cond_mid}, how does {int_mid} compare with {comp_mid} for improving {prim_out} and minimizing {safe_out} over {horizon}?", |
| f"In patients affected by {cond_mid}, what is the clearest medical evidence on whether {int_mid} works better than {comp_mid} over {horizon}?", |
| f"Can {int_mid} safely improve {prim_out} and quality of life ({pro_out}) over {horizon} compared with {comp_mid} for people with {cond_mid}?", |
| f"Among individuals with {cond_mid} (including {prio_mid}), does {int_mid} offer meaningful long-term benefits over {comp_mid} across {horizon}?", |
| f"What are the real-world benefits and risks of {int_mid} versus {comp_mid} over {horizon} for patients managing {cond_mid}?", |
| ] |
| plain_stmt = plain_variants[variant] |
|
|
| return title, statement, clean_statement, plain_stmt |
|
|
