bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term safety and influence on growth in patients receiving sirolimus: a pooled analysis
Authors: Wang Yang-Yang , Zou Li-Ping , Xu Kai-Feng , Xu Wen-Shuai , Zhang Meng-Na , Lu Qian , Tian Xin-Lun , Pang Ling-Yu , He Wen , Wang Qiu-Hong , Gao Yang , Liu Li-Ying , Chen Xiao-Qiao , Ma Shu-Fang , Chen Hui-Min , Dun Shuo , Yang Xiao-Yan , Luo Xiao-Mei , Huang Lu-Lu , Li Yu-Fen 
Published: August 2024

Abstract
Background
Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients.

Methods
This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded.

Results
Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217).

Conclusions
Sirolimus’s long-term administration is not associated with adverse effects on children’s physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration.

Trial registration
Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892.
Severe and invasive bacterial infections in infants aged less than 90 days with and without SARS-CoV-2 infection
Authors: Brigadoi Giulia , Tirelli Francesca , Rossin Sara , Casotto Veronica , Riello Francesca , Gallinaro Giulia , Donà Daniele , Bressan Silvia , Da Dalt Liviana 
Published: August 2024

Abstract
Background
Fever in children represents one of the most common causes of medical evaluation. Infants younger than 90 days of age are at higher risk of severe and invasive bacterial infections (SBI and IBI). However, clinical signs and symptoms of viral and bacterial infections in young infants are frequently similar, and several studies have shown that the risk of SBIs remains non-negligible even in the presence of a positive point-of-care viral test. Our study aims to evaluate whether the proportion of SBIs and IBIs in febrile infants younger than 90 days during the COVID-19 pandemic was higher than that in the pre-pandemic period, and to describe the proportion of SBIs and IBIs in infants with and without SARS-CoV-2 infection.

Methods
This was a retrospective single-center cohort study conducted at the Children's Hospital of the University of Padua in Italy, involving febrile young infants evaluated in the Pediatric Emergency Department (PED) and admitted to Pediatric Acute Care Unit (PACU) between March 2017 to December 2022. Infants admitted before the COVID-19 pandemic were compared to infants admitted during the pandemic period and SARS-CoV-2 positive patients to the negative ones.

Results
442 febrile infants younger than 90 days were evaluated in Padua PED and admitted to the wards. The proportion of SBIs and IBIS did not significantly change over the study periods, ranging between 10.8% and 32.6% (p = 0.117) and between 0% and 7.6%, respectively (p = 0.367). The proportion of infants with a diagnosis of SBIs and IBIs was higher in the SARS-CoV-2 negative group (30.3% and 8.2%, respectively) compared to the positive group (8.5% and 2.8%, respectively) (p < 0.0001). The most common diagnosis in both groups was UTI, mainly caused by E. coli. A similar proportion of blood and urine cultures were performed, whereas lumbar puncture was more frequently performed in SARS-CoV-2 negative infants (40.2% vs 16.9%, p = 0.001).

Conclusions
Although the risk of concomitant serious bacterial infection with SARS-CoV-2 is low, it remains non-negligible. Therefore, even in SARS-CoV-2-positive febrile infants, we suggest that the approach to screening for SBIs remains cautious.
Bone stress injuries in athletics (track and field) championships: findings from a prospective injury surveillance conducted across 24 international championships with 29,147 registered athletes
Authors: Hoenig Tim , Tenforde Adam S. , Hollander Karsten , Junge Astrid , Branco Pedro , Vinther Anders , Edouard Pascal 
Published: August 2024

Abstract
Background
Athletics (track and field) athletes are prone to develop bone stress injuries (BSIs) but epidemiological data on BSIs from top-level sports events are scarce.

Objective
To describe the incidence and characteristics of BSIs during 24 international athletics championships held from 2007 to 2023.

Methods
BSI-related data were prospectively collected during 24 international athletics championships, including the Olympic Games (n = 3), World Outdoor Championships (n = 4), European Outdoor Championships (n = 6), World Indoor Championships (n = 3) and European Indoor Championships (n = 8). Descriptive and comparative statistics were used to assess the epidemiological characteristics of BSIs.

Results
BSIs accounted for 1.5% of all reported injuries (n = 36; 1.2 per 1000 registered athletes (95%CI 0.8 to 1.6)). No significant difference of BSI incidence was detected between female (2.0 per 1000 athletes (95%CI: 0.9 to 2.3)) and male athletes (0.9 per 1000 athletes (95%CI: 0.4 to 1.4)) (relative risk (RR) = 1.73, 95%CI: 0.88 to 3.40). BSI incidence was significantly higher during outdoor championships (1.6 per 1000 registered athletes (95%CI: 1.0 to 2.1)) as compared to indoor championships (0.2 per 1000 registered athletes (95%CI: 0.0 to 0.5)) (RR = 10.4, 95%CI: 1.43 to 76.0). Most BSIs were sustained in the foot (n = 50%) or leg (n = 33%). BSIs were reported in athletes participating in endurance disciplines (52.8%) or in explosive disciplines (47.2%).

Conclusions
BSIs represent a small portion of injuries sustained during international athletics championships. Collective results suggest that injury rates are higher in outdoor competitions as compared to indoor competitions. The most common injury locations comprise the foot and leg.

Clinical Trial Number
Not applicable.
Right-to-left shunt due to iatrogenic atrial septal defect manifested by aorto-caval fistula: a case report
Authors: Kimura Takuya , Okada Takuya , Obata Norihiko , Motoyama Yasushi , Nagae Masaharu 
Published: August 2024

Abstract
Background
An aorto-caval fistula is a rare but critical complication of abdominal aortic aneurysm (AAA) rupture, leading to high-output heart failure and increased venous pressure. The anesthetic management of such cases, particularly when complicated by an intraoperative right-to-left shunt, is seldom reported.

Case presentation
A 71-year-old man with a history of atrial fibrillation and catheter ablation presented with heart failure and abdominal pain, leading to cardiac arrest. Imaging revealed an AAA rupture into the inferior vena cava. During emergency surgery, severe venous bleeding was managed using intra-aortic balloon occlusion (IABO). Transesophageal echocardiography (TEE) identified a right-to-left shunt due to an iatrogenic atrial septal defect.

Conclusion
Early TEE recognition and timely IABO intervention were crucial in managing this complex case, underscoring the importance of these techniques in similar emergency scenarios.
Association between serotonin transporter gene polymorphism and obsessive–compulsive disorder in the Egyptian population
Authors: Mehrez Sara , Neamatallah Mustafa Ahmed , Gomaa Zeinab , El-Gilany Abdel-Hady , Shahda Mohammed , Elsaied Hiam F 
Published: August 2024

Abstract
Background
Obsessive–compulsive disorder (OCD) is a debilitating disorder that has multifactorial etiology including genetic, neurobiological, cognitive, and environmental influences. Genetic studies have focused on the genes of the serotonin system. This study aimed to look for the possible relation between the polymorphism in the promotor region of the serotonin transporter gene and obsessive–compulsive disorder in the Egyptian population.

Results
This study included 94 OCD patients and 116 healthy control individuals. Blood samples were collected from all participants for DNA extraction and genotyping. The assessment of patients was done by application of the structured clinical interview according to DSM-V, the dimensional Yale-Brown Obsessive–Compulsive Scale. There was an association between serotonin transporter gene polymorphism and OCD development. The carriage of the short allele was a risk factor for having OCD.

Conclusion
Obsessive–compulsive disorder is associated with serotonin transporter gene polymorphism. This will contribute to considering the genetic information of patients for the prediction of best drug response and tolerability by personalizing the choice of treatment.
Middle ear-acquired cholesteatoma diagnosis based on CT scan image mining using supervised machine learning models
Authors: Ouattassi Naouar , Maaroufi Mustapha , Slaoui Hajar , Benateya Andaloussi Taha , Zarghili Arsalane , El Amine El Alami Mohamed Nouredine 
Published: August 2024

Abstract
Background
Distinguishing between middle ear cholesteatoma and chronic suppurative otitis media (CSOM) is an ongoing challenge. While temporal bone computed tomography (CT) scan is highly accurate for diagnosing middle ear conditions, its specificity in discerning between cholesteatoma and CSOM is only moderate. To address this issue, we utilized trained machine learning models to enhance the specificity of temporal bone CT scan in diagnosing middle ear cholesteatoma. Our database consisted of temporal bone CT scan native images from 122 patients diagnosed with middle ear cholesteatoma and a control group of 115 patients diagnosed with CSOM, with both groups labeled based on surgical findings. We preprocessed the native images to isolate the region of interest and then utilized the Inception V3 convolutional neural network for image embedding into data vectors. Classification was performed using machine learning models including support vector machine (SVM), k-nearest neighbors (k-NN), random forest, and neural network. Statistical metrics employed to interpret the results included classification accuracy, precision, recall, F1 score, confusion matrix, area under the receiver operating characteristic curve (AUC), and FreeViz diagram.

Results
Our training dataset comprised 5390 images, and the testing dataset included 125 different images. The neural network, k-NN, and SVM models demonstrated significantly higher relevance in terms of classification accuracy, precision, and recall compared to the random forest model. For instance, the F1 scores were 0.974, 0.987, and 0.897, respectively, for the former three models, in contrast to 0.661 for the random forest model.

Conclusion
The performance metrics of the presented trained machine learning models hold promising prospects as potentially clinically useful aids.
Sex Differences in “Life’s Essential 8” Cardiovascular Health and Type 2 Diabetes Mellitus Risk Across Menopause Stages
Authors: Cheng Wenke , Geng Shanshan , Li Yukun , Chen Rundong , Du Zhongyan 
Published: August 2024

Abstract

Context
Existing guidelines often lack sex-specific prevention strategies for type 2 diabetes mellitus (T2DM). Life’s Essential 8 (LE8) highlights the role of health behaviors in influencing cardiovascular health (CVH). Due to inherent sex differences, the impact of CVH on T2DM risk may vary between men and women, especially across menopausal stages.

Objective
The purpose of this paper is to explore sex-based differences in CVH and the incidence of T2DM among women at different menopausal stages and men.

Methods
A prospective cohort study was conducted, involving 126 818 participants without preexisting T2DM from the UK Biobank. CVH was assessed using the LE8. Absolute risks (ARs) and hazard ratios (HRs) were separately employed to assess the association between increased CVH and T2DM risk. The accelerated failure time model assessed the effect of CVH on the time to T2DM onset.

Results
Over a mean follow-up of 168 months, 4315 cases of T2DM were documented. In men, each 1-point increase in CVH was associated with a 0.268% decrease in AR and a 6.4% decrease in HR for T2DM. In premenopausal, perimenopausal, and postmenopausal women, each unit increase in CVH resulted in a 0.105%, 0.180%, and 0.166% decrease in AR and a 7.7%, 5.2%, and 6.4% decrease in HR of T2DM. The adjusted median time to T2DM onset was delayed by 12.46, 9.83, 11.5, and 21.43 months in the highest quintile of men, premenopausal, perimenopausal, and postmenopausal women, respectively, compared with the lowest CVH quintile.

Conclusion
As CVH improved, the reduction in AR for T2DM was more prominent in men than in women. HR trends for CVH and T2DM were similar in men and postmenopausal women. Increased CVH delayed the onset of T2MD both in men and women, with the most significant delay observed in postmenopausal women.
Shaping the Skeleton: Impact of GnRH Analogue and Sex Hormone Therapy on Skeletal Dimensions in Transgender Individuals
Authors: Boogers Lidewij Sophia , Sikma Boukje Teatske , Bouman Mark-Bram , van Trotsenburg Adrianus Sarinus Paulus , den Heijer Martin , Wiepjes Chantal Maria , Hannema Sabine Elisabeth 
Published: August 2024

Abstract

Context
Skeletal dimensions vary between sexes. Men typically have broader shoulders and women a wider pelvis. Whether gender-affirming hormone therapy (GAHT) with or without prior puberty suppression (PS) alters these dimensions in transgender individuals remains unclear.

Objective
To investigate impact of PS and GAHT on skeletal dimensions.

Methods
This retrospective cross-sectional study, conducted at a gender identity clinic, included transgender individuals assigned male at birth (AMAB) and assigned female at birth (AFAB) who underwent dual-energy x-ray absorptiometry (DXA) scanning between ages 18 and 28 years and who were divided into 4 groups: Early PS (Tanner G/B2-3) + GAHT, Late PS (Tanner G/B4-5) + GAHT, GAHT-only, and untreated. Shoulder and pelvis dimensions measured by DXA were compared between groups, with adjustment for height.

Results
A total of 121 individuals AMAB and 122 AFAB were included. Only individuals AMAB who underwent early PS had smaller shoulders compared to untreated individuals AMAB (−1.3 cm; 95% CI −2.1; −0.5). In individuals AMAB from both the Early and Late PS groups, pelvic inlet, pubic symphysis width, and interischial distance were greater compared to untreated individuals AMAB, resulting in dimensions comparable to untreated individuals AFAB. Only in Early PS AFAB was pelvic inlet width smaller compared to untreated individuals AFAB (−1.0 cm; 95% CI −1.5; −0.6), and comparable to untreated individuals AMAB.

Conclusion
The study results suggest that skeletal dimensions are only altered by GAHT if endogenous puberty has not yet been completed at start of PS. These findings enhance our understanding of hormonal effects on the skeleton and may hold clinical relevance for body image as well as for forensic anthropology. Future research should evaluate clinical implications for surgical or obstetrical outcomes in transgender individuals.
The association of manganese levels with red cell distribution width: A population-based study
Authors: Dai Guanmian , Sun Huanhuan , Lan Yanli , Jiang Jinhong , Fang Bingmu 
Published: August 2024

Objectives
Experimental and acute exposure studies imply that manganese affects red blood cell production. Nevertheless, the association between environmental exposure and red blood cell distribution width (RDW) has yet to be explored. This research sought to assess the correlation between blood manganese levels and RDW within the general population of the United States.

Materials and methods
Employing weighted multiple linear regression models, data from the 2011–2018 National Health and Nutrition Examination Survey (NHANES) were utilized to assess the correlation between manganese levels in the blood and RDW. Restricted cubic spline plots and two-piecewise linear regression models were also employed.

Result
The analysis included a total of 15882 participants in which we determined an independent positive relationship between blood manganese levels and RDW among participants(β = 0.079, P<0.001). Moreover, we identified a J-shaped association between blood manganese levels and RDW in total participants (inflection point for blood manganese: 7.32 ug/L) and distinct subgroups following adjusted covariates. Women exhibited a more pronounced association, even after controlling for adjusted covariates.

Conclusions
We determined a J-shaped relationship between blood manganese levels and RDW with an inflection point at 7.32 ug/L for blood manganese. Nevertheless, fundamental research and large sample prospective studies are needed to determine the extent to which blood manganese levels correlate with RDW.
Second breast cancer following negative breast MRI: Analysis by interval from surgery and risk factors
Authors: Joo Yohan , Kim Min Jung , Yoon Jung Hyun , Rho Miribi , Park Vivian Youngjean 
Published: August 2024

Objectives
This study aims to compare outcomes following a negative surveillance MRI study by surgery-MRI interval and investigate factors associated with second breast cancers in women with a personal history of breast cancer (PHBC).

Methods
This retrospective study included 1552 consecutive women (mean age, 53 years) with a PHBC and a negative prevalence surveillance breast MRI result between August 2014 and December 2016. The incidence and characteristics of second breast cancers were reviewed and compared according to surgery-MRI interval (< 3 years vs ≥ 3 years). Logistic regression analysis was used to investigate associations with clinical-pathologic characteristics.

Results
Twenty-five second breast cancers occurred after negative MRI. The incidence of second breast cancers or local-regional recurrence did not significantly differ by surgery-MRI interval. The median intervals between MRI to second breast cancer detection showed no significant difference between the two groups (surgery-MRI interval <3 years vs. ≥ 3 years). Two node-positive second breast cancers were detected in the group with <3 years interval. BRCA mutation status, receipt of breast-conserving surgery, and adjuvant chemotherapy (all p < .05) were significant factors associated with the development of second breast cancers.

Conclusion
Outcomes following a negative surveillance MRI did not differ by surgery-MRI interval. BRCA mutation status, receipt of breast-conserving surgery and adjuvant chemotherapy were independently associated with the risk of developing second breast cancers after negative surveillance MRI.
Barriers to the uptake of eye care services: A cross-sectional survey from rural and urban communities
Authors: Owusu-Afriyie Bismark , Peter Nancy , Ivihi Felix , Kopil Issac , Gende Theresa 
Published: August 2024

Purpose
To explore the barriers to the uptake of eye care services in urban and rural communities in Papua New Guinea.

Methods
This was a population-based cross-sectional descriptive study and involved multi-stage sampling. Communities were randomly selected from each of the three clusters of Madang District for free eye care outreaches from June to September 2022. A structured questionnaire was used to collect data from the outreach patients. The study excluded attendees who refused to consent. Responses were rated from 1 (not a barrier) to 10 (a very strong barrier). The p-value significance was set at ≤ 0.05.

Results
The majority of the 972 participants (60.2%) were from rural communities. The mean age of participants was 40.82 ± 13.14 years. Almost two-thirds of the participants (61.4%) never had an eye examination before this study was conducted. All the participants reported that time constraint, insufficient income, good vision in the fellow eye, not considering their eye conditions as serious issues and cultural beliefs were personal barriers to accessing eye care services. Provider-related challenges included long waiting periods at eye clinics and fear of procedure complications. There were differences in barriers with respect to the participants’ demographic clusters.

Conclusion
There are major personal- and service-related barriers to eye care services in Madang. These barriers could be overcome through strategic human resource development, health education, school screening programs, and establishing eye care centres in the communities to improve the uptake of eye care services in Madang and more widely across the country.
COVID-19 in nursing homes: Geographic diffusion and regional risk factors from January 1 to July 26, 2020 of the pandemic
Authors: Grady Sue C. , Pavan Amanda , Qiong Zhang , Rachael Portelli , Ligmann-Zielinska Arika 
Published: August 2024

Background
COVID-19 deaths in nursing homes accounted for 30.2% of all COVID-19 deaths in the United States during the early weeks (1-January to 26-July, 2020) of the pandemic. This study presents the geographic diffusion of COVID-19 cases and deaths in nursing homes during this time period, while also providing explanation of regional risk factors.

Methods and findings
Nursing home COVID-19 data on confirmed cases (n = 173,452) and deaths (n = 46,173) were obtained from the Centers for Medicare and Medicaid Services. Weekly COVID-19 case counts were spatially smoothed to identify nursing homes in areas of high COVID-19 infection. Bivariate spatial autocorrelation was used to visualize High vs. Low-case counts and related deaths. Zero-inflated negative binomial models were estimated within Health and Human Service (HHS) Regions at three-week intervals to evaluate facility and area-level risk factors. The first reported nursing home resident to die of COVID-19 was in the state of Washington on 28-February, 2020. By 24-May, 2020 there were simultaneous epicenters in the Northeast (HHS Regions 1 and 2) and Midwest (HHS Region 5) with diffusion into the South (HHS Regions 4 and 6) from 15-June to 5-July, 2020. The case-fatality rate was highest from 25-May to 14-June, 2020 (30.9 deaths per 1000 residents); thereafter declining to 24.1 (15-June to 5-July, 2020) and 19.4 (6-July to 26-July, 2020) (overall case-fatality rate 1-January to 26-July = 26.6). Statistically significant risk factors for COVID-19 deaths were admission of patients with COVID-19 into nursing homes, staff confirmed infections and nursing shortages. COVID-19 deaths were likely to occur in nursing homes in high minority and non-English speaking neighborhoods and neighborhoods with a high proportion of households with disabilities.

Conclusions
Enhanced communication between HHS regional administrators about “lessons learned” could provide receiving state health departments with timely information to inform clinical practice to prevent premature death in nursing homes in future pandemics.