bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between allergic rhinitis and hypertension risk: A bidirectional 2-sample mendelian randomization study
Authors: Zhang Yanhua , Li Xia , Song Zhizhou , Yang Youdong
Published: December 2023

Previous studies have suggested a potential association between allergic rhinitis (AR) and hypertension, but the genetic basis remains unclear. In this study, we aimed to explore the genetic correlation and potential causal association between AR and hypertension. Using a large-scale genome-wide association study (GWAS) public database, we conducted meticulous screening to acquire the most up-to-date GWAS data on single nucleotide polymorphisms (SNPs) relevant to AR and hypertension, with a significance threshold of P < 5 × 10-8. Then, we investigated the causal association between AR and hypertension through mendelian randomization (MR) analysis. We also performed reverse MR analysis to assess the possibility of reverse causality. Sensitivity analyses encompassed various factors, including horizontal pleiotropy, heterogeneity testing, and stepwise exclusion sensitivity checks. To investigate the causal relationship between AR and hypertension, we utilize the odds ratio (OR) and 95% confidence interval (CI) as our evaluative metric. This study leveraged a database comprising 112583 samples for AR and 461880 samples for hypertension. After meticulous screening, we identified 32 SNPs as instrumental variables. By employing the aforementioned 2-sample Mendelian randomization approaches, the estimated causal effects showed striking concordance. A discernible causal association between AR and hypertension was found using the IVW method (OR = 0.91, 95% CI: 0.86–0.98, P = .008), with horizontal pleiotropy and heterogeneity tests supporting the validity of our MR study. MR-Egger regression findings provided reassurance against bias stemming from genetic pleiotropy (intercept = -0.0006802, P = .6947). Interestingly, “leave-one-out” analysis yielded no evidence of nonspecific SNP influences, further consolidating our findings. Moreover, our reverse MR analysis yielded no indication of reverse causality from hypertension to AR, effectively discounting any influence from the latter on the former. Our study found evidence of a causal association between AR and hypertension in individuals of European ancestry. It demonstrated that AR reduced the risk of hypertension, suggesting a protective effect on hypertension due to the negative correlation with AR.
Primary adenomatoid tumor of the adrenal gland: A case report and literature review
Authors: Qi Hong-Feng , Chen Li-Qian , Yang Mai-Qing , Li Xiu-Feng , Zhang Hai-Ning , Zhang Ke-Xin , Xu Hong-Tao
Published: December 2023

Rationale:

Adenomatoid tumors are rare benign tumors, mainly involving the reproductive tract, such as the epididymis in men and the uterus and fallopian tubes in women. However, a few cases can occur outside the reproductive tract. Herein, we report a rare case of a primary adenomatoid tumor of the adrenal gland.

Patient concerns:

A 50-year-old man underwent ultrasound examination and was found to have a right adrenal mass without elevated blood pressure, weakness after fatigue, frequent nocturnal urination urgency, pain, or a history of hematuria. The patient’s general health was normal. Computed tomography revealed a polycystic mixed-density lesion in the right adrenal region, approximately 7.3 × 4.5 cm in size.

Diagnoses:

Based on the clinical information, morphological features, and immunohistochemistry results, a pathological diagnosis of primary adenomatoid tumor of the adrenal gland was made.

Intervention:

Excision of the right adrenal gland and tumor through the 11 ribs.

Outcomes:

The patient’s postoperative course was uneventful.

Lessons:

Preventing misdiagnosis adenomatoid tumors with other types of adrenal gland tumors or metastatic tumors is imperative. Morphological and immunohistochemical features can help diagnose primary adenomatoid tumors of the adrenal gland.
Do emergency medicine health care workers rate triage level of chest pain differently based upon appearance in simulated patients?
Authors: Coisy Fabien , Olivier Guillaume , Ageron François-Xavier , Guillermou Hugo , Roussel Mélanie , Balen Frédéric , Grau-Mercier Laura , Bobbia Xavier
Published: December 2023

Background and importance

There seems to be evidence of gender and ethnic bias in the early management of acute coronary syndrome. However, whether these differences are related to less severe severity assessment or to less intensive management despite the same severity assessment has not yet been established.

Objective

To show whether viewing an image with characters of different gender appearance or ethnic background changes the prioritization decision in the emergency triage area.

Methods

The responders were offered a standardized clinical case in an emergency triage area. The associated image was randomized among eight standardized images of people presenting with chest pain and differing in gender and ethnic appearance (White, Black, North African and southeast Asian appearance).

Outcome measures and analysis

Each person was asked to respond to a single clinical case, in which the priority level [from 1 (requiring immediate treatment) to 5 (able to wait up to 2 h)] was assessed visually. Priority classes 1 and 2 for vital emergencies and classes 3–5 for nonvital emergencies were grouped together for analysis.

Results

Among the 1563 respondents [mean age, 36 ± 10 years; 867 (55%) women], 777 (50%) were emergency physicians, 180 (11%) emergency medicine residents and 606 (39%) nurses. The priority levels for all responses were 1–5 : 180 (11%), 686 (44%), 539 (34%), 131 (9%) and 27 (2%). There was a higher reported priority in male compared to female [62% vs. 49%, difference 13% (95% confidence interval; CI 8–18%)]. Compared to White people, there was a lower reported priority for Black simulated patients [47% vs. 58%, difference −11% (95% CI −18% to −4%)] but not people of southeast Asian [55% vs. 58%, difference −3% (95% CI −10–5%)] and North African [61% vs. 58%, difference 3% (95% CI −4–10%)] appearance.

Conclusion

In this study, the visualization of simulated patients with different characteristics modified the prioritization decision. Compared to White patients, Black patients were less likely to receive emergency treatment. The same was true for women compared with men.
Assessment of performance and confidence level of simulation based clinical examination of respiratory system in undergraduate medical students of a medical college: a comparative cross-sectional study
Authors: Rajaure Yesha Shree , Thapa Bikalp , Budhathoki Lee , Rana Shavana R.L. , Neupane Rajendra , Karki Parag
Published: December 2023

Introduction:

Students in the preclinical phase have adequate clinical exposure to normal physiological findings of clinical examinations performed in healthy peers but do not have exposure to pathological findings other than theoretical knowledge, which is challenging for students during the clinical phase of curricula in examining actual patients. Simulation based medical education (SBME) has recently emerged to address this gap. This study aimed to assess performance and confidence level of simulation based clinical examination of respiratory system in preclinical undergraduate medical students of a medical college.

Methods:

A comparative cross-sectional study was conducted in the Department of Human Physiology of Medical College. All second year medical students using purposive sampling were taken. Students were divided into three groups and subdivided into six subgroups and each subgroup carried out examination in either healthy subjects or both healthy subjects and manikin. Predesigned proforma was used for assessment of students and the clinical examination process was invigilated by certified physiologists.

Results:

Students who received both simulation and conventional tutoring methods were able to accurately identify all lung sounds better as compared to those with conventional tutoring with the percentage difference being maximum in identifying vesicular (29 vs 6), stridor (28 vs 6), and bronchial (25 vs 6) breath sounds and least in identifying coarse crackles (3 vs 2). Majority (39 out of 41) of the students receiving SBME of respiratory system were satisfied with the simulation based practice and 34 of those students were even confident on clinical examination.

Conclusion:

SBME increases performance status and confidence level in medical students. A practical curriculum can be planned to incorporate simulation based clinical examination in preclinical medical students in practical sessions.
Healthy Behaviors Among Non-Hispanic Black and Hispanic People Affected by Cancer During the Posttreatment Survivorship
Authors: Seven Memnun , Moraitis Ann Marie , Hammer Marilyn J. , Pearlman Jessica , Reid Allecia E. , Sturgeon Susan R. , Wenzel Jennifer
Published: December 2023

Background

There are disparities in health behaviors across racial and ethnic groups. However, limited studies focus on cancer survivors’ experiences developing and maintaining healthy behaviors, particularly in non-Hispanic Black (NHB) and Hispanic people.

Objective

This study aimed to understand the experiences of NHB and Hispanic people affected by cancer in developing and maintaining positive health behaviors beyond a cancer diagnosis.

Methods

The data were collected in a mixed-method study through semistructured interviews with 29 NHB and Hispanic cancer survivors between June and October 2022. Conventional content analysis was used.

Results

The lived experiences of cancer survivors were narrated in 3 themes: impact of a cancer diagnosis on oneself, facilitators and barriers to health and health behaviors, and utilization of available sources for health. Facilitators and barriers to health and health behaviors were further explored as biological (eg, symptoms, comorbidities), behavioral (eg, help-seeking behavior, sleep pattern), physical/built (eg, available sources, neighborhood), and sociocultural environment (eg, income, transportation, knowledge, culture, upbringing, household and community composition, social and family network), and healthcare system–related factors (eg, insurance coverage, personal preferences, perceived discrimination, and stigma).

Conclusion

Non-Hispanic Black and Hispanic people, specifically those living in disadvantaged neighborhoods with limited sources or where they feel discriminated and stereotyped, those with limited income and transportation, and those with physical, social, or mental health problems, seemed to have challenges prioritizing health behaviors and maintaining healthy living.

Implications for Practice

Biological, behavioral, and psychosocial determinants of health behaviors should be addressed through multilevel collaborations among different levels of partners.
Association Between Estimated Geocoded Residential Maternal Exposure to Lithium in Drinking Water and Risk for Autism Spectrum Disorder in Offspring in Denmark
Authors: Liew Zeyan , Meng Qi , Yan Qi , Schullehner Jörg , Hansen Birgitte , Kristiansen Søren Munch , Voutchkova Denitza D. , Olsen Jørn , Ersbøll Annette Kjær , Ketzel Matthias , Raaschou-Nielsen Ole , Ritz Beate R.
Published: December 2023

(Abstracted from JAMA Pediatr 2023;177(6):617–624)

Lithium is an element that is common in trace amounts, whereas larger quantities are often used as a mood-stabilizing medication for bipolar disorders. The mechanism of action of lithium in the brain is unknown, but there are many theories; one postulated mechanism of action of lithium overlaps with neurodevelopment and autism.
Second Victim Symptoms and Desired Support Strategies Among Italian Health Care Workers in Friuli-Venezia Giulia: Cross-Sectional Survey and Latent Profile Analysis
Authors: Scarpis Enrico , Beorchia Yvonne , Moretti Valentina , Favero Beatrice , Farneti Federico , Cocconi Roberto , Quattrin Rosanna , Castriotta Luigi
Published: December 2023

Background and Objective

The second victim (SV) phenomenon concerns health care workers (HCWs) whose involvement in a medical error, as well as non-error patient safety events, has affected their well-being. Its prevalence ranges from 10% to 75% and can predispose HCWs to burnout, increasing the probability of committing errors. The primary aim of our study was to determine the prevalence of HCWs involved in an adverse patient safety event in Friuli Venezia Giulia Region (Italy). The secondary aims were to use latent profile analysis to identify profiles of SVs and factors influencing profile membership, and to evaluate the relationship between the severity of symptoms and desired support options.

Methods

A cross-sectional survey through the Italian version of the Second Victim Experience and Support Tool tool was conducted in 5 local health authorities. Descriptive statistics were conducted for all variables. Associations and correlations were assessed with statistical tests, as appropriate. Latent profile analysis was based on the scores of dimensions measuring SVs’ symptoms. Factors affecting profile membership were assessed through multinomial logistic regression.

Results

A total of 733 HCWs participated. Of them, 305 (41.6%) experienced at least 1 adverse event. Among dimensions measuring SVs’ symptoms, psychological distress had the highest percentage of agreement (30.2%). Three latent profiles were identified: mild (58.7%), moderate (24.3%), and severe (17.0%) symptoms. Severe symptoms profile was positively associated with the agreement for extraoccupational support and negatively associated with the agreement for organizational support. A respected colleague with whom to discuss the details of the incident (78.7%) and free counseling outside of work (71.2%) were the support options most desired by HCWs. The severity of symptoms was directly associated with the desire for support strategies.

Conclusions

The prevalence of HCWs involved in adverse events is consistent with the literature. Three latent profiles have been identified according to SV symptoms, and the higher the severity of symptoms, the greater the reliance on extraoccupational support.
Brief Report: Relationship Between Adiposity and Biomarkers of Aging and Frailty Among Adults Aging With HIV
Authors: Oliveira Vitor H. F. , Willig Amanda L. , Horvat Davey Christine , Buford Thomas W. , Menezes Prema , Cachay Edward , Crane Heidi M. , Burkholder Greer A. , Gripshover Barbara M. , Fleming Julia G. , Cleveland John D. , Webel Allison R.
Published: December 2023

Background:

This study examined the relationships among adiposity, handgrip, physical function, inflammation (ie, senescence-associated secretory phenotype chemokines as biomarkers of aging and frailty), and sex hormones in aging people with HIV.

Methods:

This cross-sectional exploratory study included 150 people with HIV aged ≥40 years (67.3% of participants were male). Our measures included (1) body mass index and waist circumference as measures of adiposity; (2) handgrip as a measure of muscle strength; (3) short physical performance battery as a measure of physical function; (4) interleukin-6, tumor necrosis factor alpha receptor II, high sensitivity C-reactive protein, C-X-C motif chemokine 10, and C-X3-C motif chemokine ligand 1 also known as fractalkine as senescence-associated secretory phenotype chemokines; and (5) free testosterone, estradiol, sex hormone–binding globulin, and dehydroepiandrosterone as sex hormones. Quantile regression analyses were used to identify relationships among inflammatory markers and hormones with age, adiposity, handgrip, and physical function.

Results:

Overall, 74% (n = 111) of participants were classified as overweight or obese and 53.3% (n = 80) presented with abdominal obesity. After controlling for age and sex, body mass index was positively associated with estradiol (β = 0.043, P < 0.01), and waist circumference was positively associated with high sensitivity C-reactive protein (β = 2.151, P < 0.01). After controlling for sex, age was positively associated with C-X-C motif chemokine 10 (β = 0.024, P = 0.03) and tumor necrosis factor alpha receptor II (β = 2.205, P = 0.01). After controlling for age and sex, short physical performance battery was negatively associated with dehydroepiandrosterone (β = −0.004, P = 0.01); no statistically significant associations were observed for handgrip.

Conclusion:

Adiposity levels and aging were associated with inflammation (ie, C-X-C motif chemokine 10, tumor necrosis factor alpha receptor II, and high sensitivity C-reactive protein) among people with HIV aged 40 years and older.
Antimicrobial Prophylaxis with Ampicillin-sulbactam Compared with Cefazolin for Esophagectomy
Authors: Hirano Yuki , Konishi Takaaki , Kaneko Hidehiro , Itoh Hidetaka , Matsuda Satoru , Kawakubo Hirofumi , Uda Kazuaki , Matsui Hiroki , Fushimi Kiyohide , Daiko Hiroyuki , Itano Osamu , Yasunaga Hideo , Kitagawa Yuko
Published: December 2023

Objective:

To assess the effect of antimicrobial prophylaxis with ampicillin-sulbactam (ABPC/SBT) compared with cefazolin (CEZ) on the short-term outcomes after esophagectomy.

Summary Background Data:

CEZ is widely used for antimicrobial prophylaxis in esophagectomy without procedure-specific evidence, whereas ABPC/SBT is preferred in some hospitals to target both aerobic and anaerobic oral bacteria.

Methods:

Data of patients who underwent esophagectomy for cancer between July 2010 and March 2019 were extracted from a nationwide Japanese inpatient database. Overlap propensity score weighting was conducted to compare the short-term outcomes [including surgical site infection (SSI), anastomotic leakage, and respiratory failure] between antimicrobial prophylaxis with CEZ and ABPC/SBT, after adjusting for potential confounders. Sensitivity analyses were also performed using propensity score matching and instrumental variable analyses.

Results:

Among 17,772 eligible patients, 16,077 (90.5%) and 1695 (9.5%) patients were administered CEZ and ABPC/SBT, respectively. SSI, anastomotic leakage, and respiratory failure occurred in 2971 (16.7%), 2604 (14.7%), and 2754 patients (15.5%), respectively. After overlap weighting, ABPC/SBT was significantly associated with a reduction in SSI [odds ratio 0.51 (95% confidence interval 0.43–0.60)], anastomotic leakage [0.51 (0.43–0.61)], and respiratory failure [0.66 (0.57–0.77)]. ABPC/SBT was also associated with reduced respiratory complications, postoperative length of stay, and total hospitalization costs. The proportion of Clostridioides difficile colitis and noninfectious complications did not differ between the groups. Propensity score matching and instrumental variable analyses demonstrated equivalent results.

Conclusions:

The administration of ABPC/SBT as antimicrobial prophylaxis for esophagectomy was associated with better short-term postoperative outcomes compared to CEZ.
Mitigating Health Disparities in Transplantation Requires Equity, Not Equality
Authors: Reed Rhiannon D. , Locke Jayme E.
Published: December 2023

Despite decades of research and evidence-based mitigation strategies, disparities in access to transplantation persist for all organ types and in all stages of the transplant process. Although some strategies have shown promise for alleviating disparities, others have fallen short of the equity goal by providing the same tools and resources to all rather than tailoring the tools and resources to one’s circumstances. Innovative solutions that engage all stakeholders are needed to achieve equity regardless of race, sex, age, socioeconomic status, or geography. Mitigation of disparities is paramount to ensure fair and equitable access for those with end-stage disease and to preserve the trust of the public, upon whom we rely for their willingness to donate organs. In this overview, we present a summary of recent literature demonstrating persistent disparities by stage in the transplant process, along with policies and interventions that have been implemented to combat these disparities and hypotheses for why some strategies have been more effective than others. We conclude with future directions that have been proposed by experts in the field and how these suggested strategies may help us finally arrive at equity in transplantation.
Incidence of Acute Rejection Compared With Endomyocardial Biopsy Complications for Heart Transplant Patients in the Contemporary Era
Authors: Cusi Vincenzo , Vaida Florin , Wettersten Nicholas , Rodgers Nicholas , Tada Yuko , Gerding Bryn , Urey Marcus Anthony , Greenberg Barry , Adler Eric D. , Kim Paul J.
Published: December 2023

Background.

The reference standard of detecting acute rejection (AR) in adult heart transplant (HTx) patients is an endomyocardial biopsy (EMB). The majority of EMBs are performed in asymptomatic patients. However, the incidence of treated AR compared with EMB complications has not been compared in the contemporary era (2010–current).

Methods.

The authors retrospectively analyzed 2769 EMBs obtained in 326 consecutive HTx patients between August 2019 and August 2022. Variables included surveillance versus for-cause indication, recipient and donor characteristics, EMB procedural data and pathological grades, treatment for AR, and clinical outcomes.

Results.

The overall EMB complications rate was 1.6%. EMBs performed within 1 mo after HTx compared with after 1 mo from HTx showed significantly increased complications (OR, 12.74, P < 0.001). The treated AR rate was 14.2% in the for-cause EMBs and 1.2% in the surveillance EMBs. We found the incidence of AR versus EMB complications was significantly lower in the surveillance compared with the for-cause EMB group (OR, 0.05, P < 0.001). We also found the incidence of EMB complications was higher than treated AR in surveillance EMBs.

Conclusions.

The yield of surveillance EMBs has declined in the contemporary era, with a higher incidence of EMB complications compared with detected AR. The risk of EMB complications was highest within 1 mo after HTx. Surveillance EMB protocols in the contemporary era may need to be reevaluated.
Modifications of long-term heart rate variability produced in an experimental model of diet-induced metabolic syndrome
Authors: Lozano W. M. , Ortiz-Guzmán J. E. , Arias-Mutis O. , Bizy A. , Genovés P. , Such-Miquel L. , Alberola A. , Chorro F. J. , Zarzoso M. , Calvo C. J.
Published: December 2023

Metabolic syndrome (MetS) has been linked to a higher prevalence of cardiac arrhythmias, the most frequent being atrial fibrillation, but the mechanisms are not well understood. One possible underlying mechanism may be an abnormal modulation of autonomic nervous system activity, which can be quantified by analysing heart rate variability (HRV). Our aim was to investigate the modifications of long-term HRV in an experimental model of diet-induced MetS to identify the early changes in HRV and the link between autonomic dysregulation and MetS components. NZW rabbits were randomly assigned to control (n= 10) or MetS (n= 10) groups, fed 28 weeks with high-fat, high-sucrose diet. 24-hour recordings were used to analyse HRV at week 28 using time-domain, frequency-domain and nonlinear analyses. Time-domain analysis showed a decrease in RR interval and triangular index (Ti). In the frequency domain, we found a decrease in the low frequency band. Nonlinear analyses showed a decrease in DFA-α1 and DFA-α2 (detrended fluctuations analysis) and maximum multiscale entropy. The strongest association between HRV parameters and markers of MetS was found between Ti and mean arterial pressure, and Ti and left atrial diameter, which could point towards the initial changes induced by the autonomic imbalance in MetS.
Evaluating pro-arrhythmogenic effects of the T634S-hERG mutation: insights from a simulation study
Authors: Hu Wei , Zhang Wenfeng , Zhang Kevin , Al-Moubarak Ehab , Zhang Yihong , Harmer Stephen C. , Hancox Jules C. , Zhang Henggui
Published: December 2023

A mutation to serine of a conserved threonine (T634S) in the hERG K
+
channel S6 pore region has been identified as a variant of uncertain significance, showing a loss-of-function effect. However, its potential consequences for ventricular excitation and arrhythmogenesis have not been reported. This study evaluated possible functional effects of the T634S-hERG mutation on ventricular excitation and arrhythmogenesis by using multi-scale computer models of the human ventricle. A Markov chain model of the rapid delayed rectifier potassium current (I
Kr
) was reconstructed for wild-type and T634S-hERG mutant conditions and incorporated into the ten Tusscher
et al
. models of human ventricles at cell and tissue (1D, 2D and 3D) levels. Possible functional impacts of the T634S-hERG mutation were evaluated by its effects on action potential durations (APDs) and their rate-dependence (APDr) at the cell level; and on the QT interval of pseudo-ECGs, tissue vulnerability to unidirectional conduction block (VW), spiral wave dynamics and repolarization dispersion at the tissue level. It was found that the T634S-hERG mutation prolonged cellular APDs, steepened APDr, prolonged the QT interval, increased VW, destablized re-entry and augmented repolarization dispersion across the ventricle. Collectively, these results imply potential pro-arrhythmic effects of the T634S-hERG mutation, consistent with LQT2.
Mechanisms of pulmonary arterial hypertension-induced atrial fibrillation: insights from multi-scale models of the human atria
Authors: Bai Jieyun , Lo Andy , Kennelly James , Sharma Roshan , Zhao Na , Trew Mark L. , Zhao Jichao
Published: December 2023

This study aimed to use multi-scale atrial models to investigate pulmonary arterial hypertension (PAH)-induced atrial fibrillation mechanisms. The results of our computer simulations revealed that, at the single-cell level, PAH-induced remodelling led to a prolonged action potential (AP) (ΔAPD: 49.6 ms in the right atria (RA) versus 41.6 ms in the left atria (LA)) and an increased calcium transient (CaT) (ΔCaT: 7.5 × 10
−2
µM in the RA versus 0.9 × 10
−3
µM in the LA). Moreover, heterogeneous remodelling increased susceptibility to afterdepolarizations, particularly in the RA. At the tissue level, we observed a significant reduction in conduction velocity (CV) (ΔCV: −0.5 m s
–1
in the RA versus −0.05 m s
–1
in the LA), leading to a shortened wavelength in the RA, but not in the LA. Additionally, afterdepolarizations in the RA contributed to enhanced repolarization dispersion and facilitated unidirectional conduction block. Furthermore, the increased fibrosis in the RA amplified the likelihood of excitation wave breakdown and the occurrence of sustained re-entries. Our results indicated that the RA is characterized by increased susceptibility to afterdepolarizations, slow conduction, reduced wavelength and upregulated fibrosis. These findings shed light on the underlying factors that may promote atrial fibrillation in patients with PAH.
Pirfenidone increases transverse tubule length in the infarcted rat myocardium
Authors: Moammer Hussam , Bai Jizhong , Jones Timothy L. M. , Ward Marie , Barrett Caroyln , Crossman David J.
Published: December 2023

Transverse (t)-tubule remodelling is a prominent feature of heart failure with reduced ejection fraction (HFrEF). In our previous research, we identified an increased amount of collagen within the t-tubules of HFrEF patients, suggesting fibrosis could contribute to the remodelling of t-tubules. In this research, we tested this hypothesis in a rodent model of myocardial infarction induced heart failure that was treated with the anti-fibrotic pirfenidone. Confocal microscopy demonstrated loss of t-tubules within the border zone region of the infarct. This was documented as a reduction in t-tubule frequency, area, length, and transverse elements. Eight weeks of pirfenidone treatment was able to significantly increase the area and length of the t-tubules within the border zone. Echocardiography showed no improvement with pirfenidone treatment. Surprisingly, pirfenidone significantly increased the thickness of the t-tubules in the remote left ventricle of heart failure animals. Dilation of t-tubules is a common feature in heart failure suggesting this may negatively impact function but there was no functional loss associated with pirfenidone treatment. However, due to the relatively short duration of treatment compared to that used clinically, the impact of long-term treatment on t-tubule structure should be investigated in future studies.
Analyzing morphological alternations of vessels in multiple Sclerosis using SLO images of the eyes
Authors: Soltanipour Asieh , Arian Roya , Aghababaei Ali , Kafieh Raheleh , Ashtari Fereshteh
Published: December 2023

Background

Our purpose was to investigate the most relevant and discriminating clinical feature set of Scanning laser ophthalmoscopy (SLO) images, which could differentiate multiple sclerosis (MS) and healthy control (HC) patients.

Methods

In this work, SLO images were used for the first time to measure the most valuable manual and clinical features from some retinal structures, optic disc, cup and blood vessels, for MS and HC classifications. For this, first an age-matching algorithm along with a subject-wise k-fold cross-validation data splitting approach were applied for construction of training, validation and test dataset, minimizing the risk of model overestimation. Then, it was needed to segment the retinal structures from the SLO images, and due to the lack of ground truth for our SLO images, we took advantage of a previously proposed deep learning algorithm for anatomical segmentation using color fundus images. But owing to different imaging modalities of SLO images, we also used two stages of pre-processing and post-processing to obtain accurate results for the segmentation step. Following that, a set of manual and clinical features was measured from the segmented optic disc, cup and vessels to gain a better comprehension of the features playing an important role in classification of MS and HC images. Finally, three simple machine learning models were applied to evaluate the measured features and the most valuable and effective features were computed.

Results

The measured feature set from the segmented optic disc, cup and blood vessels resulted in a mean accuracy (ACC) of 83%, sensitivity (SE) of 79%, specificity (SP) of 85%, and AUROC of 84%, when testing on validation data by using a XGBoost classifier model. Furthermore, horizontally disc location, fractal dimension and intensity variation of blood vessels were selected as the most important and effective features for MS and HC classification.

Conclusion

The location of optic disc, fractal dimension and vessel intensity, the ratio between intensity of vessels to intensity of he whole SLO image, were selected as three most valuable features for MS and HC classification. Regarding the optic disc location, we found out the used SLO images had been captured with two different imaging techniques. So, this feature could not be trusted as the most important feature. Two other features were confirmed by one expert as clinically distinguishing features for MS and HC classification.
Expanding the phenotypic spectrum of TRAF7 syndrome: report of eleven new cases and literature review
Authors: Palma-Milla Carmen , Prat-Planas Aina , Soengas-Gonda Emma , Centeno-Pla Mónica , Sánchez-Pozo Jaime , Lazaro-Rodriguez Irene , Quesada-Espinosa Juan F. , Arteche-Lopez Ana , Olival Jonathan , Pacio-Miguez Marta , Palomares-Bralo María , Santos-Simarro Fernando , Cancho-Candela Ramón , Vázquez-López María , Seidel Veronica , Martinez-Monseny Antonio F , Casas-Alba Didac , Grinberg Daniel , Balcells Susanna , Serrano Mercedes , Rabionet Raquel , Martin Miguel A. , Urreizti Roser
Published: December 2023

TRAF7 syndrome, a multisystemic neurodevelopmental disorder caused by germline missense variants in theTRAF7gene, exhibits heterogeneous clinical presentations. We present a detailed description of eleven new TRAF7 syndrome cases, featuring eight distinct variants, including a novel one. Phenotypic analysis and a comprehensive review of the 58 previously reported cases outline consistent clinical presentations, emphasizing dysmorphic features, developmental delay, endocrine manifestations, and cardiac defects. In this enlarged collection, novelties include a wider range of cognitive dysfunction, with some individuals exhibiting normal development despite early psychomotor delay. Communication challenges, particularly in expressive language, are prevalent, necessitating alternative communication methods. Autistic traits, notably rigidity, are observed in the cohort. Also, worth highlighting are hearing loss, sleep disturbances, and endocrine anomalies, including growth deficiency. Cardiac defects, frequently severe, pose early-life complications. Facial features, including arched eyebrows, contribute to the distinct gestalt. A novel missense variant, p.(Arg653Leu), further underscores the complex relationship between germlineTRAF7variants and somatic changes linked to meningiomas. Our comprehensive analysis expands the phenotypic spectrum, emphasizing the need for oncological evaluations and proposing an evidence-based schedule for clinical management. This study contributes to a better understanding of TRAF7 syndrome, offering insights for improved diagnosis, intervention, and patient care.

Key Message

TRAF7 syndrome, a complex neurodevelopmental disorder, exhibits variable cognitive outcomes, complex behavioral presentation and clinical complications emphasizing the need for tailored interventions and follow-up.
NHANES-GPT: Large Language Models (LLMs) and the Future of Biostatistics
Authors: Titus Alexander J.
Published: December 2023

Background

Large Language Models (LLMs) like ChatGPT have significant potential in biomedicine and health, particularly in biostatistics, where they can lower barriers to complex data analysis for novices and experts alike. However, concerns regarding data accuracy and model-generated hallucinations necessitate strategies for independent verification.

Objective

This study, using NHANES data as a representative case study, demonstrates how ChatGPT can assist clinicians, students, and trained biostatisticians in conducting analyses and illustrates a method to independently verify the information provided by ChatGPT, addressing concerns about data accuracy.

Methods

The study employed ChatGPT to guide the analysis of obesity and diabetes trends in the NHANES dataset from 2005-2006 to 2017-2018. The process included data preparation, logistic regression modeling, and iterative refinement of analyses with confounding variables. Verification of ChatGPT’s recommendations was conducted through direct statistical data analysis and cross-referencing with established statistical methodologies.

Results

ChatGPT effectively guided the statistical analysis process, simplifying the interpretation of NHANES data. Initial models indicated increasing trends in obesity and diabetes prevalence in the U.S.. Adjusted models, controlling for confounders such as age, gender, and socioeconomic status, provided nuanced insights, confirming the general trends but also highlighting the influence of these factors.

Conclusions

ChatGPT can facilitate biostatistical analyses in healthcare research, making statistical methods more accessible. The study also underscores the importance of independent verification mechanisms to ensure the accuracy of LLM-assisted analyses. This approach can be pivotal in harnessing the potential of LLMs while maintaining rigorous standards of data accuracy and reliability in biomedical research.
Safe and reliable transport of prediction models to new healthcare settings without the need to collect new labeled data
Authors: Tuwani Rudraksh , Beam Andrew
Published: December 2023

How can practitioners and clinicians know if a prediction model trained at a different institution can be safely used on their patient population? There is a large body of evidence showing that small changes in the distribution of the covariates used by prediction models may cause them to fail when deployed to new settings. This specific kind of dataset shift, known as covariate shift, is a central challenge to implementing existing prediction models in new healthcare environments. One solution is to collect additional labels in the target population and then fine tune the prediction model to adapt it to the characteristics of the new healthcare setting, which is often referred to as localization. However, collecting new labels can be expensive and time-consuming. To address these issues, we recast the core problem of model transportation in terms of uncertainty quantification, which allows one to know when a model trained in one setting may be safely used in a new healthcare environment of interest. Using methods from conformal prediction, we show how to transport models safely between different settings in the presence of covariate shift, even when all one has access to are covariates from the new setting of interest (e.g. no new labels). Using this approach, the model returns a prediction set that quantifies its uncertainty and is guaranteed to contain the correct label with a user-specified probability (e.g. 90%), a property that is also known as coverage. We show that a weighted conformal inference procedure based on density ratio estimation between the source and target populations can produce prediction sets with the correct level of coverage on real-world data. This allows users to know if a model’s predictions can be trusted on their population without the need to collect new labeled data.
Interictal intracranial EEG asymmetry lateralizes temporal lobe epilepsy
Authors: Conrad Erin C. , Lucas Alfredo , Ojemann William K.S. , Aguila Carlos A. , Mojena Marissa , LaRocque Joshua J. , Pattnaik Akash R. , Gallagher Ryan , Greenblatt Adam , Tranquille Ashley , Parashos Alexandra , Gleichgerrcht Ezequiel , Bonilha Leonardo , Litt Brian , Sinha Saurabh , Ungar Lyle , Davis Kathryn A.
Published: December 2023

Patients with drug-resistant temporal lobe epilepsy often undergo intracranial EEG recording to capture multiple seizures in order to lateralize the seizure onset zone. This process is associated with morbidity and often ends in postoperative seizure recurrence. Abundant interictal (between-seizure) data is captured during this process, but these data currently play a small role in surgical planning. Our objective was to predict the laterality of the seizure onset zone using interictal (between-seizure) intracranial EEG data in patients with temporal lobe epilepsy. We performed a retrospective cohort study (single-center study for model development; two-center study for model validation). We studied patients with temporal lobe epilepsy undergoing intracranial EEG at the University of Pennsylvania (internal cohort) and the Medical University of South Carolina (external cohort) between 2015 and 2022. We developed a logistic regression model to predict seizure onset zone laterality using interictal EEG. We compared the concordance between the model-predicted seizure onset zone laterality and the side of surgery between patients with good and poor surgical outcomes. 47 patients (30 women; ages 20-69; 20 left-sided, 10 right-sided, and 17 bilateral seizure onsets) were analyzed for model development and internal validation. 19 patients (10 women; ages 23-73; 5 left-sided, 10 right-sided, 4 bilateral) were analyzed for external validation. The internal cohort cross-validated area under the curve for a model trained using spike rates was 0.83 for a model predicting left-sided seizure onset and 0.68 for a model predicting right-sided seizure onset. Balanced accuracies in the external cohort were 79.3% and 78.9% for the left- and right-sided predictions, respectively. The predicted concordance between the laterality of the seizure onset zone and the side of surgery was higher in patients with good surgical outcome. In conclusion, interictal EEG signatures are distinct across seizure onset zone lateralities. Left-sided seizure onsets are easier to distinguish than right-sided onsets. A model trained on spike rates accurately identifies patients with left-sided seizure onset zones and predicts surgical outcome.
Machine learning models for blood pressure phenotypes combining multiple polygenic risk scores
Authors: Hrytsenko Yana , Shea Benjamin , Elgart Michael , Kurniansyah Nuzulul , Lyons Genevieve , Morrison Alanna C. , Carson April P. , Haring Bernhard , Mitchel Braxton D. , Psaty Bruce M. , Jaeger Byron C. , Gu C Charles , Kooperberg Charles , Levy Daniel , Lloyd-Jones Donald , Choi Eunhee , Brody Jennifer A , Smith Jennifer A , Rotter Jerome I. , Moll Matthew , Fornage Myriam , Simon Noah , Castaldi Peter , Casanova Ramon , Chung Ren-Hua , Kaplan Robert , Loos Ruth J.F. , Kardia Sharon L. R. , Rich Stephen S. , Redline Susan , Kelly Tanika , O’Connor Timothy , Zhao Wei , Kim Wonji , Guo Xiuqing , Chen Yii Der Ida ,   the Trans-Omics in Precision Medicine Consortium, Sofer Tamar
Published: December 2023

We construct non-linear machine learning (ML) prediction models for systolic and diastolic blood pressure (SBP, DBP) using demographic and clinical variables and polygenic risk scores (PRSs). We developed a two-model ensemble, consisting of a baseline model, where prediction is based on demographic and clinical variables only, and a genetic model, where we also include PRSs. We evaluate the use of a linear versus a non-linear model at both the baseline and the genetic model levels and assess the improvement in performance when incorporating multiple PRSs. We report the ensemble model’s performance as percentage variance explained (PVE) on a held-out test dataset. A non-linear baseline model improved the PVEs from 28.1% to 30.1% (SBP) and 14.3% to 17.4% (DBP) compared with a linear baseline model. Including seven PRSs in the genetic model computed based on the largest available GWAS of SBP/DBP improved the genetic model PVE from 4.8% to 5.1% (SBP) and 4.7% to 5% (DBP) compared to using a single PRS. Adding additional 14 PRSs computed based on two independent GWASs further increased the genetic model PVE to 6.3% (SBP) and 5.7% (DBP). PVE differed across self-reported race/ethnicity groups, with primarily all non-White groups benefitting from the inclusion of additional PRSs.
County-level Socio-Environmental Factors and Obesity Prevalence in the United States
Authors: Salerno Pedro R.V.O. , Qian Alice , Dong Weichuan , Deo Salil , Nasir Khurram , Rajagopalan Sanjay , Al-Kindi Sadeer
Published: December 2023

Aims

There are substantial geographical variations in obesity prevalence. Sociodemographic and environmental determinants of health (SEDH), understood as upstream determinants of obesogenic behaviors, may be contributing to this disparity. Thus, we investigated high-risk SEDH potentially associated with adult obesity in American counties using machine learning (ML) techniques.

Materials and methods

We performed a cross-sectional analysis of county-level adult obesity prevalence (≥30 kg/m2) in the U.S. using data from the Diabetes Surveillance System 2017. We harvested 49 county-level SEDH factors that were used by a Classification and Regression Trees (CART) model to identify county-level clusters. CART was validated using a “hold-out” set of counties and variable importance was evaluated using Random Forest.

Results

Overall, we analyzed 2,752 counties in the U.S identifying a national median obesity prevalence of 34.1% (IQR, 30.2, 37.7). CART identified 11 clusters with a 60.8% relative increase in prevalence across the spectrum. Additionally, 7 key SEDH variables were identified by CART to guide the categorization of clusters, includingPhysically Inactive(%),Diabetes, Severe Housing Problems(%),Food Insecurity(%),Uninsured(%),Population over 65 years(%), andNon-Hispanic Black(%).

Conclusion

There is significant county-level geographical variation in obesity prevalence in the United States which can in part be explained by complex SEDH factors. The use of ML techniques to analyze these factors can provide valuable insights into the importance of these upstream determinants of obesity and, therefore, aid in the development of geo-specific strategic interventions and optimize resource allocation to help battle the obesity pandemic.

Article Highlights

Why did we undertake this study?To improve the understanding of the association between complex sociodemographic and environmental determinants of health (SEDH) and obesity prevalence in the U.S.

What is the specific question(s) we wanted to answer?What are the SEDH associated with obesity prevalence?

What did we find?Seven key SEDH variables were identified by CART to guide the categorization of clusters, includingPhysically Inactive(%),Diabetes, Severe Housing Problems(%),Food Insecurity(%),Uninsured(%),Population over 65 years(%), andNon-Hispanic Black(%).

What are the implications of our findings?Our study shows the importance of SEDH for the regional variation of obesity prevalence and aids in the development of geo-specific strategies to reduce disparities.
Genetic analysis of cognitive preservation in the midwestern Amish reveals a novel locus on chromosome 2
Authors: Main Leighanne R , Song Yeunjoo E , Lynn Audrey , Laux Renee A , Miskimen Kristy L , Osterman Michael D , Cuccaro Michael L , Ogrocki Paula K , Lerner Alan J , Vance Jeffery M , Fuzzell M Denise , Fuzzell Sarada L , Hochstetler Sherri D , Dorfsman Daniel A , Caywood Laura J , Prough Michael B , Adams Larry D , Clouse Jason E , Herington Sharlene D , Scott William K , Pericak-Vance Margaret A , Haines Jonathan L
Published: December 2023

INTRODUCTION

Alzheimer disease (AD) remains a debilitating condition with limited treatments and additional therapeutic targets needed. Identifying AD protective genetic loci may identify new targets and accelerate identification of therapeutic treatments. We examined a founder population to identify loci associated with cognitive preservation into advanced age.

METHODS

Genome-wide association and linkage analyses were performed on 946 examined and sampled Amish individuals, aged 76-95, who were either cognitively unimpaired (CU) or impaired (CI).

RESULTS

12 SNPs demonstrated suggestive association (P≤5x10-4) with cognitive preservation. Genetic linkage analyses identified >100 significant (LOD≥3.3) SNPs, some which overlapped with the association results. Only one locus on chromosome 2 retained significance across multiple analyses.

DISCUSSION

A novel significant result for cognitive preservation on chromosome 2 includes the genesLRRTM4andCTNNA2. Additionally, the lead SNP, rs1402906, impacts the POU3F2 transcription factor binding affinity, which regulatesLRRTM4andCTNNA2.
Characterisation of tomato (Solanum lycopersiconMill.) genotypes for morphological and disease resistance traits through cluster analysis
Authors: Tejaswini Uppuluri , Parashivamurthy  , Siddaraju R. , Vishwanath K. , Ramanappa T. M. , Srinivasappa K. N. , Nagaraju N.
Published: December 2023

The characterisation of germplasm is very important for the seed material (breeding) and development of improved varieties. The seed material is collected from the M/s. Noble Seeds Pvt. Ltd., Yelhanka few of them are resistant to ToLCV, where Ty gene background is inserted, five genotypes are non-resistant to ToLCV and one check ArkaVikas (susceptible to ToLCV) conducted the research at Kestur Village Doddballapura duringKharif, 2021 andKharif, 2022. The genotypes were morphologically characterised according to DUS guidelines(PPV&FRA). The 20 qualitative and 22 quantitative traits were characterised, out of which 25 traits were observed with variations. Multivariate cluster analysis were assessed for which two clusters (A and B) were formed and for each two, two more sub-clusters (C and D) were observed. The 66.67 % of 30 genotypes (20) are clustered under the Cluster E (15 genotypes), 5 genotypes are considered under the Cluster C, 3 genotypes under the Cluster D and only 2 genotypes are classified under F cluster. The distance in terms of variations is high between the NBLTM-22 and NBLTM-11. And nearing the distance closer and less variations are observed. By this we can say that minimum the distance between the clusters maximum of similarity between the genotypes for the traits.