bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for the cardiodepressive effects of the plasticizer di-2-ethylhexyl phthalate
Authors: Swift Luther M , Roberts Anysja , Pressman Jenna , Guerrelli Devon , Allen Samuel , Haq Kazi T , Reisz Julie A , D’Alessandro Angelo , Posnack Nikki Gillum 
Published: October 2023

Abstract
Di-2-ethylhexyl phthalate (DEHP) is commonly used in the manufacturing of plastic materials, including intravenous bags, blood storage bags, and medical-grade tubing. DEHP can leach from plastic medical products, which can result in inadvertent patient exposure. DEHP concentrations were measured in red blood cell units stored between 7 and 42 days (17–119 μg/ml). Using these concentrations as a guide, Langendorff-perfused rat heart preparations were acutely exposed to DEHP. Sinus activity remained stable with lower doses of DEHP (25–50 μg/ml), but sinus rate declined by 43% and sinus node recovery time (SNRT) prolonged by 56.5% following 30-min exposure to 100 μg/ml DEHP. DEHP exposure also exerted a negative dromotropic response, as indicated by a 69.4% longer PR interval, 108.5% longer Wenckebach cycle length (WBCL), and increased incidence of atrioventricular (AV) uncoupling (60-min exposure). Pretreatment with doxycycline partially rescued the effects of DEHP on sinus activity, but did not ameliorate the effects on AV conduction. DEHP exposure also prolonged the ventricular action potential and effective refractory period, but had no measurable effect on intracellular calcium transient duration. Follow-up studies using human-induced pluripotent stem cell-derived cardiomyocytes confirmed that DEHP slows electrical conduction in a time (15 min–3 h) and dose-dependent manner (10–100 μg/ml). Previous studies have suggested that phthalate toxicity is specifically attributed to metabolites of DEHP, including mono-2-ethylhexylphthalate. This study demonstrates that DEHP exposure also contributes to cardiac dysfunction in a dose- and time-dependent manner. Future work is warranted to investigate the impact of DEHP (and its metabolites) on human health, with special consideration for clinical procedures that employ plastic materials.
A Comparison of Online Self-Training and Standard Bedside Training in Lung Ultrasonography for Medical Students
Authors: Jedwab Roni , Boas Stefan , Potashner Dana , Ostrovsky Daniel , Wacht Oren , Taragin Benjamin Hayatt , Gat Tomer , Dayan Roy Rafael , Fuchs Lior 
Published: October 2023

Abstract

Purpose
Point-of-care ultrasonography (POCUS) is increasingly integrated into medical education. Traditionally taught at the bedside using a hands-on approach, POCUS is limited by cost, time, faculty availability, and access to POCUS resources. With the recent transition to digitalization in medical education, the authors compare lung POCUS performance and pathology identification among medical students to examine whether using an online, self-learning lung POCUS module is noninferior to traditional bedside, faculty-led lung POCUS training.

Method
This study assessed the performance of 51 medical students from August to October 2021 on an elearning lung POCUS course with traditional bedside training and no training. POCUS students were scored on use of a simulator to identify pathologies, ability to identify lung ultrasonographic pathological clips, and scanning technique.

Results
The elearning group had a significantly higher median (interquartile range [IQR]) total test score (15/18 [10.5–16] vs. 12/18 [9–13]; P = .03) and scanning technique score (5/5 [4–5] vs. 4/5 [3–4]; P = .03) compared with the standard curriculum group. The median (IQR) accuracy in the clip segment of the examination was 7.5 of 10 (4–9) in the self-learning group and 6 of 10 (4–7) in the standard curriculum group (P = .18). The median (IQR) grade on the simulator segment of the examination was 2 of 3 (2–3) in the self-learning group and 2 of 3 (1–2) in the standard curriculum group (P = .06).

Conclusions
This study suggests that self-directed elearning of lung POCUS is at least noninferior to bedside teaching and possibly even a superior method of learning lung POCUS. This teaching method POCUS is feasible for medical students to learn lung ultrasonography and has potential to complement or augment the traditional learning process or eliminate or lessen the requirement for bedside teaching by reaching a larger audience while minimizing costs and human resources.
Population Pharmacokinetics of Topiramate in Patients with Epilepsy Using Nonparametric Modeling
Authors: Elewa Mandy , Alghanem Sarah S. , Al-Hashel Jasem , Thussu Anil , Al-Lanqawi Yousef , Matar Kamal 
Published: October 2023

Background:
Topiramate (TPM) is used for the treatment of various epileptic seizures and the prevention of migraine. This study aimed to develop a population pharmacokinetic model and identify covariates that influence TPM behavior in patients with epilepsy in Kuwait.

Methods:
Data were collected retrospectively from 108 patients (2 years old and above) with epilepsy who were treated with oral TPM and 174 TPM blood samples from 3 hospitals in Kuwait from 2009 to 2016. Data were randomly divided into 2 groups for model development and validation. The population pharmacokinetic model was built using the nonparametric modeling algorithm (Pmetrics). The model was evaluated internally through the visual predictive check method and externally using a new data set.

Results:
A 1-compartment model with first-order elimination fitted the data well. Covariates showing a significant effect on the elimination rate constant were renal function and coadministration of carbamazepine (CBZ). The mean estimated clearance was 2.11 L/h; this was 50% higher for patients coadministered with CBZ. Age and sex were essential covariates for the volume of distribution (V). The visual predictive check of the final model could predict the measured concentrations. External validation further confirmed the favorable predictive performance of the model with low bias and imprecision for predicting the concentration in a particular population.

Conclusions:
TPM elimination was increased with CBZ coadministration and was affected by renal function. Meanwhile, age and sex were the main predictors for V. The predictive performance of the final model proved to be valid internally and externally.
Sample Matrices for Mass Spectrometry–Based Adherence Monitoring: A Systematic Critical Review
Authors: Jacobs Cathy M. , Wagmann Lea , Meyer Markus R. 
Published: October 2023

Background:
Analytical monitoring of adherence using mass spectrometry (MS) plays an important role in clinical toxicology. Unambiguous detection of drugs (of abuse) and/or their metabolites in body fluids is needed to monitor intake of medication as prescribed or to monitor abstinence as a follow-up to detoxification procedures. This study focused on the advantages and disadvantages of different sample matrices used for MS-based adherence monitoring.

Methods:
Relevant articles were identified through a literature search in the PubMed database. English articles published between January 01, 2017, and December 31, 2022, were selected using the keywords “adherence assess*” or “adherence monit*” or “compliance assess*” or “compliance monit*” in combination with “mass spectrom*” in the title or abstract.

Results:
A total of 51 articles were identified, 37 of which were within the scope of this study. MS-based monitoring was shown to improve patient adherence to prescribed drugs. However, MS analysis may not be able to assess whether treatment was rigorously followed beyond the last few days before the sampling event, except when hair is the sample matrix. For medication adherence monitoring, blood-based analyses may be preferred because reference plasma concentrations are usually available, whereas for abstinence control, urine and hair samples have the advantage of extended detection windows compared with blood. Alternative sample matrices, such as dried blood samples, oral fluid, and exhaled breath, are suitable for at-home sampling; however, little information is available regarding the pharmacokinetics and reference ranges of drug (of abuse) concentrations.

Conclusions:
Each sample matrix has strengths and weaknesses, and no single sample matrix can be considered the gold standard for monitoring adherence. It is important to have sufficient information regarding the pharmacokinetics of target substances to select a sample matrix in accordance with the desired purpose.
Axillary Hidradenitis Suppurativa: A Comparison between Two Perforator Flap Reconstructive Approaches after Radical Surgical Management
Authors: Alabdulkareem Mohammad , Berkane Yanis , Le Bras Enna , Rousson Etienne , Chrelias Theodoros , Beaufils Tristan , Leclere Franck-Marie , Watier Eric , Bertheuil Nicolas 
Published: October 2023

Background:
Axillary hidradenitis suppurativa (HS) can result in significant functional impairment in both personal and professional lives. Stage 3 HS requires radical surgical treatment. Flap reconstruction allows for faster healing and better functional and aesthetic outcomes. We compared the results of thoracodorsal artery perforator (TDAP) and propeller inner arm artery perforator (IAAP) flap reconstructions after radical surgical treatment of axillary HS.

Methods:
We conducted a retrospective study that included 13 consecutive patients who underwent stage 3 axillary HS treatment between August 2015 and January 2023. Seven patients underwent reconstruction by islanded TDAP flaps, whereas six patients underwent reconstruction by propeller IAAP flaps, with one patient undergoing bilateral reconstruction. The data collected from the patient records included age, gender, smoking status, body mass index, comorbidities, operative time, defect size, flap size, hospital stay, and complications.

Results:
Although not statistically significant (P = 0.1923), a higher rate of flap complications is reported here with propeller IAAP flaps (42.86 %), whereas islanded TDAP flaps had no flap complications (0%). We found a statistically significant difference in operative time (P = 0.0006), defect size (P = 0.0064), and flap size (P = 0.0012) between the two groups. All patients exhibited satisfactory functional and aesthetic outcomes. Fourteen flaps were performed in total; only one case exhibited recurrence (7.14%).

Conclusion:
After radical surgical management, both islanded TDAP and propeller IAAP flap reconstructions offer excellent outcomes for stage 3 axillary HS. We strongly encourage our peers to consider performing perforator flaps over secondary healing for these patients with a major functional impairment.
HLA-DR genotypes in patients with systemic lupus erythematosus in Taiwan
Authors: Yen Chang-Yi , Wang Pin-Yi , Chen Kuan-Yu , Tseng Chia-Chun , Wu Cheng-Chin , Ou Tsan-Teng , Yen Jeng-Hsien 
Published: October 2023

Background:
Different human leukocyte antigen (HLA)-DR genotypes have been known to be associated with the risk of development of systemic lupus erythematosus (SLE) in different populations, although Lu et al. have reported previously that no correlation exists between the HLA-DR genotype and disease manifestation in SLE patients in Taiwan. We investigated the effects different HLA-DR genotypes had on SLE incidence in Taiwanese patients as to whether risk alleles were associated with different clinical manifestations, and the effects risk alleles had on the age of disease onset.

Methods:
Two hundred thirty-four SLE patients and 346 healthy controls were enrolled. HLA-DR genotyping was performed with the HLA FluoGene DRDQ kit for each subject. Chi-square tests and t tests were performed for statistical analysis.

Results:
HLA-DR2 was significantly more frequently found in SLE patients than in controls (odds ratio [OR] = 2.05, 95% CI, 1.44-2.92, p < 0.001). Notably, HLA-DR6 appeared to trend toward negative correlation with SLE, whereas HLA-DR8 appeared to trend toward positive correlation. HLA-DR2 patients had an earlier onset of disease as well as a higher prevalence of oral ulcer, avascular necrosis of bone, and renal involvement (lupus nephritis).

Conclusion:
HLA-DR2 was associated with SLE susceptibility in this Taiwanese population as well as lower age of disease onset and more severe clinical manifestations.
The Effects of Exercise on Telomere Length in Persons With Heart Failure
Authors: Butts Brittany , Hope Chloe , Herring Christopher , Mueller Kenneth , Gary Rebecca A. 
Published: October 2023

Background
Telomere length is reduced in persons with heart failure (HF). Inflammation is a putative mechanism contributing to telomere shortening. Although physical activity is known to increase telomere length, its effects in HF are unknown.

Objective
The aim of this study was to examine the effects of exercise on telomere length and its relationship with interleukin (IL)-1β in persons with HF.

Methods
This secondary analysis of a 3-month home-based aerobic exercise intervention measured total telomere length and IL-1β levels in persons with HF (69% with reduced ejection fraction).

Results
Total telomere length increased and plasma IL-1β levels decreased in the exercise group from baseline to 3 months. Total telomere length was negatively associated with IL-1β at baseline (r = −0.441 P = .001).

Conclusions
The association between telomere length and IL-1β suggests a relationship between inflammation and cellular aging. Moderate-intensity exercise may help maintain cellular functions. Further research is needed to examine the effects on outcomes in persons with HF.
A Comprehensive Obesity Benefit as a Guide for Employers on the Core Components of Obesity Care: Guidance From the American College of Occupational and Environmental Medicine (ACOEM) Roundtable on Obesity
Authors: Gallagher Christine , Ording Julie 
Published: October 2023

Objective
The need to confront the obesity epidemic and its impact on employers requires a serious look at how we address the treatment of obesity. This article focuses on the core components of obesity care and the need for employers to offer a comprehensive obesity benefit (COB) as part of employee insurance coverage.

Methods
In May 2022, the American College of Occupational and Environmental Medicine convened a roundtable meeting, which brought together five corporate medical directors and representatives from aerospace/defense and energy industries to learn about the disease of obesity and provide clinical insights regarding health and safety in their respective industries. The goals of the program were to provide awareness of benefits for the treatment of obesity and identify the feasibility for employers of implementing a COB for their employees. Participants learned how a comprehensive approach to covering obesity treatments is necessary, and what benefits should be offered to employees.

Results
Participants were invited to review the insurance benefits they currently offer to employees and compare them to the COB. Outcomes were limited by a lack of participation by the employers invited to participate. Participants identified actions that need to be addressed for employers to develop a more comprehensive approach to obesity care.

Conclusion
Implementing a COB can help employers increase access and utilization of comprehensive obesity care by employees.
Examining Relationships Among Leadership Behaviors, Demographic and Program Factors, and Resilience in Physical Therapy Professional Education Program Directors
Authors: Herrin Shannon 
Published: October 2023

Introduction.
Physical therapy professional education program directors (PDs) face stress associated with work roles and responsibilities, which can cause burnout and job turnover.

Review of Literature.
Burnout and turnover in physical therapy education PD positions are influenced by inexperience, insufficient compensation, decreased support, heavy workloads, difficulty hiring and retaining faculty, and internal conflict. Program directors also receive insufficient training in their roles. Individuals with greater resilience, or the ability to face adversity with positive outcomes, may be more resistant to stress, burnout, and turnover. Therefore, this study's purpose was to explore the relationships among leadership behaviors, demographic and program factors, and resilience in physical therapy PDs.

Subjects.
Of the 600 physical therapy PDs invited to participate in the study, 126 directors completed the survey (21% response rate).

Methods.
The survey included demographic questions, the Multifactor Leadership Questionnaire (MLQ-5X), and the 10-item Connor-Davidson Resilience Scale (CD-RISC-10). Correlational analyses were used to investigate relationships among leadership behaviors, demographic and program factors, and resilience.

Results.
Participants included 43 physical therapist and 82 physical therapist assistant PDs (79.4% female and 20.6% male participants; mean age, 52.0 ± 8.3 years; mean years in role, 7.3 ± 6.9 years). Mean MLQ-5X scores showed that participants primarily used transformational leadership (TFL) behaviors. The mean CD-RISC-10 score for participants was 33.06 (±4.10). Analysis revealed statistically significant positive relationships between all TFL behaviors and resilience. Exploratory regression analysis revealed that 3 leadership behaviors and one demographic factor may contribute to resilience in participants, although the proportion of variance was modest (39%).

Discussion and Conclusion.
This is the first study to offer insight regarding the relationships between leadership behaviors and resilience in physical therapy PDs. These results may help lay the foundation for future research in this area, with the goal of decreasing burnout and job turnover through increased resilience.
Metastasis-Directed Therapy for Metachronous Lung Metastases in Prostate Cancer
Authors: Mahmoud Ahmed M. , Gao Robert W. , Ahmed Mohamed E. , Orme Jacob J. , Rincón Miguel Muñiz , Harmsen William S. , Johnson Geoffrey B. , Cassivi Stephen D. , Kwon Eugene D. , Phillips Ryan M. , Andrews Jack R. , Childs Daniel S. 
Published: October 2023

Introduction:
As interest in metastasis-directed therapy (MDT) for prostate cancer (PCa) grows, exploring indications and patient selection is increasingly more important. Thus far, few studies have described long-term outcomes after surgical MDT in those with disease recurrence involving the lung. The objective of our study was to compare the cumulative incidence of cancer-related death by treatment modality in men with metachronous pulmonary metastases from PCa.

Methods:
In a single-institution retrospective study, we identified 75 men from the prospectively maintained Mayo Clinic C-11 Positron Emission Tomography Choline PCa registry with recurrent prostate cancer involving the lung but no other visceral organs. Patients were categorized into 3 groups based on treatment modalities: wedge resection ± hormonal therapy, chemohormonal therapy, and hormonal therapy alone. The risk of cancer-related death after treatment at the time of lung metastases was reported as cumulative incidence estimates. Non–cancer-related deaths were treated as a competing risk of death. A univariate Cox regression model was conducted to assess the impact of treatment modality on the risk of cancer-related death.

Results:
At the time of lung metastasis, the median age was 69.5 years, and the median (IQR) prostate-specific antigen was 4 (1.3-8.6) ng/ml. Forty-seven patients (62.7%) had hormone-sensitive disease, and 28 patients (37.3%) had hormone-resistant disease. A total of 26 patients (34.7%) were treated with wedge resection ± hormonal therapy, 27 (36%) with chemohormonal therapy, and 22 (29.3%) with hormonal therapy alone. The median (IQR) follow-up time was 50.3 (31.1-78.4) months, and 21 patients (28%) died. Patients who were treated with wedge resection ± hormonal therapy had lower rated of cancer-related death compared with those who received chemohormonal therapy (Hazard Ratio [HR]: 4.14, 95% CI: 1.01-16.96, P = .048) or hormonal therapy alone (HR: 6.37, 95% CI: 1.72-23.54, P = .005).

Conclusion:
This exploratory analysis supports the safety and feasibility of surgical metastasis-directed therapy in select patients with recurrent prostate cancer involving the lung. Favorable long-term survival provides justification for further evaluation of this approach.
Case report of a young male, with recurrent pneumothorax, hemoptysis and intrapulmonary cavitary lesions
Authors: Junping Sun , Tianyu Sun , Rentao Wang , Shengshu Li , Xiaobo Han , Xinxin Zhang , Mingyue Zhang 
Published: October 2023

Rationale:
Primary spontaneous pneumothorax (PSP) is a manifestation of Vascular Ehlers-Danlos syndrome (vEDS) caused by heterozygous mutations in the COL3A1 gene. vEDS is a rare inherited disorder with an prevalence of one in 150,000. It can causes PSP and severe fragility of connective tissues with arterial but it remains poorly defined on clinical grounds and diagnose. Through this report, we hoped to help clinicians further understand the characteristics of vEDS.

Patient concerns:
A 22-year-old man presented with recurrent pneumothorax, hemoptysis, and chest pain. Physical examination revealed remarkable hypermobility of the small joints and translucent skin with visible veins. Chest computed tomography (CT) showed pneumothorax and multiple pulmonary cavities.

Intervention and outcome:
Genomic deoxyribonucleic acid (DNA) was extracted from patients. Heterozygosity was observed in all 3 novel variants. The main variant is COL3A1, c.3256-43T > G(NM_000090.3), which represents a missense mutation in collagen type III alpha 1 that can lead to vEDS. The other 2 mutations were FLNB c.4814G > A(NM_001457.3) and TSC2 c.3145G > A (NM_000548.3). These variants were validated by Sanger sequencing of their parents. COL3A1was not detected in either of the parent strains. FLNB and TSC2 were detected in his mother.

Diagnoses:
Vascular Ehlers-Danlos syndrome.

Lessons:
Both COL3A1 and TSC2 gene mutations can cause PSP; however, to the best of our knowledge, there are no reports on these 2 gene mutations in 1 patient at the same time.