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Blinding
BLIND
It was impossible to blind the operator and the operator was not involved in either the distribution or evaluation processes. Furthermore, all patients were unaware of which group they were in. Throughout the follow-up times, the assessor carried out each evaluation step while being entirely unaware of the treatment pr...
PMC10704731
Criteria for patient selection
PMC10704731
Preoperative measures
For all patients, panoramic radiographs were taken to assess the mesiodistal width, the amount of bone above the apex and the root angulation PRF Group PRF preparation
PMC10704731
Surgical procedures
STERILE, CLOT
Following administration of local anesthesia (Mepivacaine HCL 2% with Levonordefrin 1:20,000. Alexandria Co. for Pharmaceuiticals and Chemical Ind., Alexandria, Egypt.), a three-line incision was made, and the mucoperiosteal flap was reflected. Atraumatic extraction of the tooth/root was then initiated by using a perio...
PMC10704731
Postoperative care
For seven days, 500 mg of Amoxicillin (Emox, Egyption Int. Pharmaceutical Industries Co., E.I.P.I.C.O., A.R.E.) was used as an oral antibiotic every six hours. A non-steriodal analgesic and anti-inflammatory medication called Diclofenac Potassium 50 mg tablets (Oflam, Mepha Pharma Egypt S.A.E.) was prescribed. Patients...
PMC10704731
Second stage surgery
Six months later, a second stage surgery was carried out. The surgical cover screw was exposed and replaced by a healing abutment for 15 days.
PMC10704731
Prosthetic rehabilitation
To create a working cast, an impression was made using an impression post and a laboratory analogue. Then the functional abutment replaced the healing abutment. Final restoration was made from porcelain fused to metal and cemented to the functional abutment.
PMC10704731
Evaluation
Every patient was seen on a regular basis for evaluation immediate, 6 and 18 months postoperative.
PMC10704731
A. Clinical evaluation
PMC10704731
1. Implant stability
At the time of implant placement, 6 months and 18 months postoperative, implant stability was measured. RFA was used to measure implant stability with an Osstell Mentor device. The outcomes were presented as ISQ.
PMC10704731
2. Peri-implant pocket depth
A graduated probe was used to measure the distance between the base of the pocket and the gingival margin. The probe was introduced until its blunt edge made contact with the base of the pocket in a straight line with the implant's vertical axis. Around each implant, the pocket depth was measured at 4 different sites (...
PMC10704731
B. Radiographic evaluation
CBCT was used to provide radiographic evaluation immediately, 6, and 18 months postoperative. All CBCT scans were performed in the same radiology centre (Planmeca, ProMax® 3D Max, Helsinki, Finland) using the same parameters (89 kVp, 24 s, 10 mA and field of view 6 cm × 8 cm). For image processing and reconstruction, O...
PMC10704731
1. Radiographic assessment of marginal bone loss
bone loss
CREST, BONE LOSS
The implant was utilized as a reference for the measurement of marginal bone loss (MBL) from the cross-sectional view by adjusting panoramic long axis in its center and bisecting it (showing the buccolingual dimensions).At the crest of the buccal plate of bone and ending at the apical level of the implant, a line was d...
PMC10704731
2. Radiographic assessment of changes in buccal bone thickness
bone loss
CREST, BONE LOSS
A perpendicular horizontal measurement was taken from the implant crest to the buccal bone plate immediately postoperative. This measurement acts as a baseline. A similar measurement was taken 18 months postoperative and subtracted from baseline value to determine horizontal bone loss.
PMC10704731
Statistical analysis
SPSS software, version 25 was used to analyze the data (SPSS Inc., PASW statistics for windows version 25. Chicago: SPSS Inc.). Quantitative data were described using mean ± standard deviation for normally distributed data after testing normality using Shapiro Wilk test. To compare more than two independent groups, the...
PMC10704731
Results
PMC10704731
Demographic data
This study involved 19 female patients and 17 male patients who received 36 dental implants to replace non-restorable maxillary anterior and premolar teeth (esthetic zone) by immediate implant. The average age was 33 years (range from 19 to 47 years). The distribution of replaced teeth was 20 maxillary central incisor,...
PMC10704731
Comparison of implant stability between the study groups
Implant stability was evaluated using ISQ at surgery, 6 months and 18 months postoperative without statistical difference at surgery (ISQ at different time intervalsThe *statistically significant
PMC10704731
Evaluation of the peri-implant pocket depth
The peri-implant pocket depth's mean values were all within acceptable ranges (2.5-4 mm). Between the study groups, there was no statistically significant difference at 6 months and at 18 months (Peri-implant pocket depth at different time intervalsThe
PMC10704731
Assessment of changes in buccal bone thickness
BONE LOSS
Bone loss changes was evaluated according to each material. Regarding buccal bone thickness changes, there was a significant difference between PRF Group (Group 1) and the other Groups (Group 2 and Group 3) after 18 months postoperative (Changes of buccal bone thickness after 18 monthsThe Similar superscripted letters ...
PMC10704731
Discussion
tooth replacement, infection, periodontium, bone loss
BONE LOSS, EPITHELIAL DOWNGROWTH, INFECTION, SCARRING, CREST
Immediate implant placement has highly predictable means of tooth replacement and shows high success rate [The area from the upper 1Before implant placement, the dimensions of the socket must be evaluated to establish the length and diameter of the implant. To obtain primary stability, the drilling extended 3–4 mm apic...
PMC10704731
Conclusion
bone loss
BONE LOSS
This study demonstrated that the use of Xenograft and Alloplastic β-tricalcium phosphate as filling materials in conjunction with immediate implant have superior results regarding buccal bone loss and buccal bone thickness over use of PRF as a filling material.
PMC10704731
Authors’ contributions
All authors substantially contributed to the study design, drafting and revising the research, approving the submitted manuscript’s final version, and accuracy of work.
PMC10704731
Funding
Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB). The authors received no funding for this research.
PMC10704731
Availability of data and materials
The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
PMC10704731
Declarations
PMC10704731
Ethics approval and consent to participate
The Institutional Review Board (IRB) of the Faculty of Dentistry, Mansoura University, Mansoura, Egypt, approved the current study in compliance with the seventh revision of the Helsinki Declaration in 2013 (A0103023OS). All of the participants gave their written informed consent.
PMC10704731
Consent for publication
Not applicable.
PMC10704731
Competing interests
The authors declare no competing interests.
PMC10704731
References
PMC10704731
Aims
hypoglycemia, hyper-insulinemia
HYPOGLYCEMIA, TYPE 1 DIABETES, EVENT
Edited by: Yanshan Dai, Bristol Myers Squibb, United StatesReviewed by: Shihao Hu, Janssen Pharmaceuticals, Inc., United States; Yue Chen, Cedars Sinai Medical Center, United States; Siyan Chen, Sanofi U.S., United StatesNon-severe hypoglycemia (NS-H) is challenging for people living with type 1 diabetes (PWT1D) and of...
PMC10272543
Methods
This is a randomized, four-way, crossover study involving PWT1D, testing NS-H treatment outcomes with 16 g vs. 32 g CHO at two plasma glucose (PG) ranges: A: 3.0–3.5 mmol/L and B: <3.0 mmol/L. Across all study arms, participants consumed an additional 16 g of CHO if PG was still <3.0 mmol/L at 15 min and <4.0 mmol/L at...
PMC10272543
Results
Participants (
PMC10272543
Conclusions
hyper-insulinemia
NS-H, in the context of hyper-insulinemia, is difficult to treat in PWT1D. Initial consumption of 32 g of CHO revealed some advantages at the 3.0–3.5 mmol/L range. This was not reproduced at lower PG ranges since participants needed additional CHO regardless of the amount of initial consumption.
PMC10272543
Clinical trial registration
PMC10272543
Introduction
hypoglycemia
HYPOGLYCEMIA, TYPE 1 DIABETES
People living with type 1 diabetes (PWT1D) are faced with increased risks of hypoglycemia and its negative impacts when trying to achieve optimal glucose management (Recent studies and review reports have questioned the 15 g/15 min rule and have required extensive research studies to investigate the most efficient trea...
PMC10272543
Methodology
PMC10272543
Study design
hypoglycemia
HYPOGLYCEMIA
This is an open-label, randomized, four-way, crossover study investigating 16 g vs. 32 g of CHO to correct insulin-induced NS-H at two hypoglycemia ranges, 3.0–3.5 mmol/L and <3.0 mmol/L, in PWT1D.
PMC10272543
Study subjects
abnormal blood panel, hypoglycemic episodes, anemia, T1D, cardiac rhythm abnormality
EVENT, ANEMIA, COMPLICATIONS
Eligible subjects were adults (≥18 years of old) with a clinical diagnosis of T1D for at least 1 year, treated with either multiple daily insulin injections (MDI) or continuous subcutaneous insulin injection (CSII) and a glycated hemoglobin HbA1c ≤ 89 mmol/mol (≤10%). Exclusion criteria included clinically significant ...
PMC10272543
Study procedures
hypoglycemia
HYPOGLYCEMIA, BLOOD, NOCTURNAL HYPOGLYCEMIA
Participants installed a glucose sensor (Dexcom G4 or G5 Platinum, Dexcom, USA) 24–48 h before study visits and installation training was offered for those unfamiliar with the technology. At least 6-day intervals separated study visits. The day before each study visit, participants had to refrain from exercise and alco...
PMC10272543
Statistical analysis
hypoglycemia, hypoglycemic
HYPOGLYCEMIA, EVENT
We conducted analyses separately for each hypoglycemia range to compare the effect of initial treatment of NS-H with 16 g vs. 32 g CHO. The primary outcome was the change in PG at 15 min (Delta-PG-15) after CHO consumption. Secondary outcomes are listed in the Finally, all hypoglycemic event data (
PMC10272543
Results
hypoglycemia
HYPOGLYCEMIA, REGRESSION
Participants included in the analysis (Baseline characteristics of the participants.Trial flowchart.Plasma glucose profiling for each of the four trial arms is shown in Plasma glucose profiles starting at 60 min before hypoglycemia treatment level was reached until 60 min after CHO consumption for the four trial arms.W...
PMC10272543
Discussion
hypoglycemia
HYPOGLYCEMIA, SECONDARY, SPONTANEOUS HYPOGLYCEMIA
For insulin-induced NS-H, an initial CHO intake of 32 g compared to 16 g of CHO at the 3.0–3.5 mmol/L hypoglycemic range showed some benefits. This resonates with real-life practices of PWT1D who consumed averages of 32 g of CHO (In our study, an increase in PG at 15 min post-treatment with 16 g of CHO was similar to t...
PMC10272543
Data availability statement
The data analyzed in this study is subject to the following licenses/restrictions: Granular data can be made available upon direct request to the senior author. Requests to access these datasets should be directed to
PMC10272543
Ethics statement
The studies involving human participants were reviewed and approved by the Ethics committee at Montreal Clinical Research Institute. The patients/participants provided their written informed consent to participate in this study.
PMC10272543
Author contributions
NT, VG, VM, and RR-L designed the study. NT, VP, and DB conducted data collection. NT and AS conducted data analysis. NT, A-SB, VG, RC, and RR-L helped in data interpretation. NT drafted the manuscript, which was critically revised by VP, VG, A-SB, AS, DB, RC, and RR-L. All authors revised the final draft and approved ...
PMC10272543
Acknowledgments
hypoglycemic
We thank all the participants in our clinical trials for their valuable time and acceptance for repeated induced hypoglycemic episodes, and the nurses and clinical research personnel at the Montreal Clinical Research Institute for their invaluable work and efforts.
PMC10272543
Conflict of interest
Nordisk, and Sanofi.
TYPE 2 DIABETES
RR-L has received research grants from Astra-Zeneca, Eli Lilly, Merck, Novo-Nordisk, and Sanofi-Aventis. He has been a consultant or member of advisory panels of Abbott, Amgen, Astra-Zeneca, Boehringer, Carlina Technology, Eli Lilly, Janssen, Medtronic, Merck, Neomed, Novo-Nordisk, Roche, Sanofi-Aventis, and Takeda. He...
PMC10272543
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or ...
PMC10272543
References
PMC10272543
Abstract
PMC10067030
Purpose
This study aimed to compare the prognostic value of multiple lymph node metastasis (LNM) indicators and to develop optimal prognostic nomograms for bladder cancer (BC) patients.
PMC10067030
Methods
tumor, TCGA, Cancer
REGRESSION, TUMOR, CANCER
BC patients were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015, and randomly partitioned into training and internal validation cohorts. Genomic and clinical data were collected from The Cancer Genome Atlas (TCGA) as external validation cohort. The predictive efficie...
PMC10067030
Results
tumor, TCGA
TUMOR
Totally, 10,093 and 107 BC patients were screened from the SEER and TCGA databases. N classification, positive lymph nodes (PLNs), lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) were all independent predictors for OS and CSS. The filtered models containing LODDS had minimal Akaike Information Crite...
PMC10067030
Conclusions
tumor
TUMOR, METASTASIS
LODDS demonstrated superior prognostic performance over N classification, PLN and LNR for OS and CSS of BC patients. The nomograms incorporating LODDS provided appropriate prediction of BC, which could contribute to the tumor assessment and clinical decision‐making.LODDS had better predictive accuracy than other lymph ...
PMC10067030
INTRODUCTION
Bladder cancer
BLADDER CANCER, MALIGNANT TUMOR OF URINARY TRACT
Bladder cancer (BC) is the most common malignant tumor of urinary tract.In recent years, several LN prognostic factors were proposed to estimate the prognosis of BC patients, including the positive lymph nodes (PLNs) and the lymph node ratio (LNR).The present study aimed to compare the prognostic values among different...
PMC10067030
METHODS
PMC10067030
Data source
tumor, Cancer
TUMOR, CANCER
We collected patients from the SEER database (SEER*Stat version 8.3.9.2) of the National Cancer Institute (NCI) program, which is one of the most representative tumor databases and covers approximately 28% of the US population.
PMC10067030
Study population
Cancer, tumor, primary bladder cancer
CANCER, TUMOR, BLADDER
Patients diagnosed with primary bladder cancer (ICD‐O‐3/WHO 2008: “Urinary Bladder”) between 2004 and 2015 were enrolled into the study. The exclusion criteria for data extraction were (1) patients aged <20 years or ≥ 80 years at diagnosis; (2) patients with no surgery or undergoing local resection; (3) patients with n...
PMC10067030
Measurement of variables
tumor, death, Low‐, TCGA, tumors
TUMOR, TUMORS, SECONDARY
We collected variables of patients including age at diagnosis, gender, T/N/M classification, tumor grade, the amount of regional ELNs and PLNs, survival time and status. The tumor stage was based on the sixth edition of AJCC staging system, which was adapted to SEER‐derived patients diagnosed from 2004 to 2015. Low‐ an...
PMC10067030
Independence of
REGRESSION
We selected the clinicopathological predictors with univariable Cox regression analyses through “survival” R package for OS and CSS in training cohort. To further assess the predictive values, each LN status factor (including N classification, PLN, LNR and LODDS) was integrated into multivariate regression models toget...
PMC10067030
Comparison of predictive performance among
Backward stepwise selection (via “MASS” R package) was utilized into the above models using Akaike Information Criterion (AIC) as the stopping rule, respectively.
PMC10067030
Construction and validation of nomograms
TCGA
Variables included in the filtered models with the highest accuracy were integrated to develop nomograms for predicting OS and CSS in training cohort (via “rms” R package), respectively. The efficiency of nomograms was evaluated by bootstrapped C‐indexes, time‐dependent AUCs and calibration plots in training, internal ...
PMC10067030
Survival risk classifiers established by nomograms
REGRESSION
The multivariate Cox regression formulas of the nomograms for OS and CSS formed in training cohort were applied into patients in three cohorts using “nomogramFormula” R package. All patients were divided into high‐ and low‐risk groups according to the total points calculated via “survminer” R package. The Kaplan–Meier ...
PMC10067030
Functional enrichment
TCGA
Differential expression genes (DEGs) from TCGA were searched for by comparing high‐ and low‐risk groups with the threshold of |log fold change| >1 and
PMC10067030
Estimation of tumor immune infiltration
tumor, TCGA
TUMOR
To estimate the tumor microenvironment (TME), the stromal and immune scores of each sample in TCGA cohort were analyzed through the “estimate” R package.
PMC10067030
Statistical analysis
Continuous variables with non‐normal distribution were reported as median with interquartile range (IQR) and categorical variables were presented as frequencies with percentages. Statistical significance was achieved with a two‐sided
PMC10067030
RESULTS
PMC10067030
Patient characteristics and survival
TCGA
BLADDER CANCER
The patients' characteristics of training, internal validation and TCGA cohorts are shown in Table Clinical and pathologic characteristics of patients with BC in three cohortsAbbreviations: BC, bladder cancer; CI, confidence interval; IQR, interquartile range; LNR, lymph node ratio; LODDS, log odds of positive lymph no...
PMC10067030
Prognostic analyses for
REGRESSION
The detailed results of the univariate Cox regression analyses in training cohort are demonstrated in Table Univariate Cox regression analyses for predicting OS and CSS in training cohortAbbreviations: CI, confidence interval; CSS, cause‐specific survival; HR, hazard ratio; LNR, lymph node ratio; LODDS, log odds of pos...
PMC10067030
Comparison of N classification,
The comparison of LN status indicators in training cohort is shown in Table Prognostic efficiency of different lymph node status indicators in training cohortAbbreviations: AIC, Akaike information criterion; AUC, area under the curve; C‐index, concordance index; LNR, lymph node ratio; LODDS, log odds of positive lymph ...
PMC10067030
Construction and validation of nomograms
TCGA, Cancer
BLADDER CANCER, CANCER
We developed nomograms based on the selected models containing LODDS in training cohort. As results, age, LODDS, T and M classification were incorporated into final nomogram for predicting OS (Figure Nomogram for OS of BC patients. (A) Prediction for 1‐, 3‐ and 5‐year OS of nomogram. Calibration plots for 1‐, 3‐ and 5‐...
PMC10067030
Survival risk classifiers based on nomograms
TCGA, Cancer
BLADDER CANCER, CANCER
To further verify the performance of nomograms, we divided patients into high‐ and low‐risk groups based on the total points calculated by nomograms for OS and CSS. The cutoff values of the total points were 100.57 for OS and 82.94 for CSS, respectively (Figure Kaplan–Meier (K‐M) analyses for BC patients classified by ...
PMC10067030
Pathway enrichment analyses
tumor, TCGA
TUMOR
After standardization among the RNA‐seq in TCGA, we extracted 78 DEGs based on the risk classifier for OS. The representative statistically enriched pathways (both GO and KEGG) were clustered together and shown with a network plot (Figure Analyses of pathway enrichment and tumor immunity of the risk classifier stratifi...
PMC10067030
The relationship between risk classifiers and tumor immunity
We investigated the TME and calculated stromal and immune scores for each BC sample based on the risk classifier for OS. The higher stromal score was observed in samples of high‐risk group (Figure 
PMC10067030
DISCUSSION
heterogeneous malignancy, bladder cancer
SOLID TUMORS, BLADDER CANCER
Despite improvement in diagnosis and surgery, bladder cancer remains a heterogeneous malignancy with poor prognosis.Considering this situation, several modified LN status factors has been proposed to predict the survival of BC, including PLN, LNR and LODDS.The N classification of AJCC staging system evaluates LN status...
PMC10067030
CONCLUSIONS
We confirmed that LODDS had better predictive accuracy compared with other LNM indicators for BC patients after surgery. Novel nomograms containing LODDS for predicting OS and CSS were established based on SEER database and successfully validated in external dataset, which could assist urologists with more accurate the...
PMC10067030
AUTHOR CONTRIBUTIONS
PMC10067030
CONFLICT OF INTEREST
The authors declared no conflicts of interest.
PMC10067030
ETHICAL APPROVAL STATEMENT
Ethical approval was not needed in this retrospective study, as all data abstracted from the public‐used databases was anonymous.
PMC10067030
Supporting information
Figure S1. Click here for additional data file. Figure S2. Click here for additional data file. Figure S3. Click here for additional data file. Table S1. Click here for additional data file. Table S2. Click here for additional data file.
PMC10067030
ACKNOWLEDGMENTS
TCGA
The authors appreciate the contributors and handlers of the SEER and TCGA databases for making these datasets publicly available.
PMC10067030
DATA AVAILABILITY STATEMENT
This article is based on available data from the SEER (
PMC10067030
REFERENCES
PMC10067030
Aims
T2DM, FM
TYPE 2 DIABETES MELLITUS
Managed by Antonio Secchi.This investigation aimed to determine the effect of different intensities of training on non-exercise physical activity (NEPA) and estimated thermogenesis (NEAT) from a 1-year exercise randomized controlled trial (RCT) in individuals with type 2 diabetes mellitus (T2DM) on non-training days. A...
PMC10063485
Methods
T2DM
Individuals with T2DM (
PMC10063485
Results
After adjustments, no time*group interactions were found for estimated NEAT in the MICT (β = − 5.33,
PMC10063485
Conclusions
FM
Both MICT and HIIT did not result in any compensatory changes in estimated NEAT and NEPA with the intervention on non-training days. Moreover, no changes in estimated NEAT and NEPA were found when categorizing our participants as low-responders and high-responders to FM and BW when compared to controls.Trial registrati...
PMC10063485
Keywords
Open access funding provided by FCT|FCCN (b-on).
PMC10063485
Introduction
Obesity, obesity, T2DM
OBESITY, OBESITY, TYPE 2 DIABETES
Obesity is an underlying risk factor for type 2 diabetes (T2DM), in which exercise alongside with medication and nutrition are the most used strategies to prevent, control, and treat this condition [An important aspect of energy balance to consider for obesity management [Characteristics of the exercise dose may influe...
PMC10063485
Methods
PMC10063485
Subjects and study design
T2DM
SECONDARY
This investigation is a secondary analysis of a 1-year randomized crossover trial conducted in individuals with T2DM that aimed to compare the effect of different exercise intensities on glycated hemoglobin as the main outcome. A total of 80 participants with T2DM completed baseline assessments and were allocated to on...
PMC10063485
Intervention protocol
The detailed protocol is described elsewhere [
PMC10063485
Anthropometry and body composition
Participants’ weight and height were measured to the nearest 0.01 kg and 0.1 cm, respectively, on an electronic scale with stadiometer (Seca, Hamburg, Germany) according to the standardized procedures [
PMC10063485
Sensor-based data
Participants were instructed to wear an accelerometer (ActiGraph, GT3X model, Fort Walton Beach, FL) on the right hip for 7 days at baseline, 6-, and 12-months (during the exercise intervention). Data were recorded at a 100 Hz frequency, and downloaded into 10 s epochs. Troiano et al. cut-points and validation criteria...
PMC10063485
Non-exercise activity thermogenesis determination
The ActiLife software and the refined 2-regression model Crouter equation [
PMC10063485
Non-exercise physical activity determination
All the activity counts were summed for each of the non-exercise days and then averaged to get the average NEPA per non-exercise day for each participant.
PMC10063485
Identifying individual exercise fat mass responders
FM loss
Currently, there are no accepted guidelines for the percent of FM loss considered to be clinically meaningful. Therefore, we considered someone who had a FM loss greater than the typical error (TE) as clinically meaningful. The TE was calculated from the standard deviation (SD) of the differences in FM over 1-year in t...
PMC10063485
Statistical analysis
FM
Descriptive statistics, including measures of central tendency (mean) and variability (standard deviation), were used to describe baseline characteristics of the control group, MICT, and HIIT. A one-way ANOVA with a Bonferroni adjustment for multiple comparisons was used to test differences in descriptive characteristi...
PMC10063485
Discussion
obese, FM, weight reduction, overweight, T2DM, weight loss
OBESE
To the best of our knowledge, this is the first experimental investigation that examined how estimated NEAT and NEPA are affected by a 1-year exercise intervention performed at different intensities in T2DM. Our results showed no compensatory decreases in NEPA and estimated NEAT on the non-exercise days following 1-yea...
PMC10063485