bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adult-Onset Cancer Predisposition Syndromes in Children and Adolescents—To Test or not to Test?
Authors: Kratz Christian P. , Lupo Philip J. , Zelley Kristin , Schienda Jaclyn , Nichols Kim E. , Stewart Douglas R. , Malkin David , Brodeur Garrett M. , Maxwell Kara , Plon Sharon E. , Walsh Michael F. 
Published: February 2024

Abstract
With the increasing use of comprehensive germline genetic testing of children and adolescents with cancer, it has become evident that pathogenic variants (PV) in adult-onset cancer predisposition genes (aoCPG) underlying adult-onset cancer predisposition syndromes, such as Lynch syndrome or hereditary breast and ovarian cancer, are enriched and reported in 1% to 2% of children and adolescents with cancer. However, the causal relationship between PVs in aoCPGs and childhood cancer is still under investigation. The best-studied examples include heterozygous PVs in mismatch repair genes associated with Lynch syndrome in children with mismatch repair deficient high-grade glioma, heterozygous PVs in BARD1 in childhood neuroblastoma, and heterozygous PVs in BRCA2 in children with rhabdomyosarcoma. The low penetrance for pediatric cancers is considered to result from a combination of the low baseline risk of cancer in childhood and the report of only a modest relative risk of disease in childhood. Therefore, we do not advise that healthy children empirically be tested for PVs in an aoCPG before adulthood outside a research study. However, germline panel testing is increasingly being performed in children and adolescents with cancer, and exome and genome sequencing may be offered more commonly in this population in the future. The precise pediatric cancer risks and spectra associated with PVs in aoCPGs, underlying cellular mechanisms and somatic mutational signatures, as well as treatment response, second neoplasm risks, and psycho-oncological aspects require further research.
Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer
Authors: Neeb Antje , Figueiredo Ines , Bogdan Denisa , Cato Laura , Stober Jutta , Jiménez-Vacas Juan M. , Gourain Victor , Lee Irene I. , Seeger Rebecca , Muhle-Goll Claudia , Gurel Bora , Welti Jonathan , Nava Rodrigues Daniel , Rekowski Jan , Qiu Xintao , Jiang Yija , Di Micco Patrizio , Mateos Borja , Bielskutė Stasė , Riisnaes Ruth , Ferreira Ana , Miranda Susana , Crespo Mateus , Buroni Lorenzo , Ning Jian , Carreira Suzanne , Bräse Stefan , Jung Nicole , Gräßle Simone , Swain Amanda , Salvatella Xavier , Plymate Stephen R. , Al-Lazikani Bissan , Long Henry W. , Yuan Wei , Brown Myles , Cato Andrew C.B. , de Bono Johann S. , Sharp Adam 
Published: February 2024

Abstract
Therapies that abrogate persistent androgen receptor (AR) signaling in castration-resistant prostate cancer (CRPC) remain an unmet clinical need. The N-terminal domain of the AR that drives transcriptional activity in CRPC remains a challenging therapeutic target. Herein we demonstrate that BCL-2–associated athanogene-1 (BAG-1) mRNA is highly expressed and associates with signaling pathways, including AR signaling, that are implicated in the development and progression of CRPC. In addition, interrogation of geometric and physiochemical properties of the BAG domain of BAG-1 isoforms identifies it to be a tractable but challenging drug target. Furthermore, through BAG-1 isoform mouse knockout studies, we confirm that BAG-1 isoforms regulate hormone physiology and that therapies targeting the BAG domain will be associated with limited “on-target” toxicity. Importantly, the postulated inhibitor of BAG-1 isoforms, Thio-2, suppressed AR signaling and other important pathways implicated in the development and progression of CRPC to reduce the growth of treatment-resistant prostate cancer cell lines and patient-derived models. However, the mechanism by which Thio-2 elicits the observed phenotype needs further elucidation as the genomic abrogation of BAG-1 isoforms was unable to recapitulate the Thio-2–mediated phenotype. Overall, these data support the interrogation of related compounds with improved drug-like properties as a novel therapeutic approach in CRPC, and further highlight the clinical potential of treatments that block persistent AR signaling which are currently undergoing clinical evaluation in CRPC.
Maternal Dietary Patterns During Pregnancy Are Linked to Hypertensive Disorders of Pregnancy Among a Predominantly Low‐Income US Hispanic/Latina Pregnancy Cohort
Authors: Maldonado Luis E. , Bastain Theresa M. , Toledo‐Corral Claudia M. , Dunton Genevieve F. , Habre Rima , Eckel Sandrah P. , Yang Tingyu , Grubbs Brendan H. , Chavez Thomas , Al‐Marayati Laila A. , Breton Carrie V. , Farzan Shohreh F. 
Published: February 2024

Background
Diet during pregnancy may be a potential intervention for preventing hypertensive disorders of pregnancy that disproportionally burdens Hispanic/Latina women.

Methods and Results

The MADRES (Maternal And Developmental Risks from Environmental and Social stressors) study (n=451) is a prospective pregnancy cohort of predominantly low‐income Hispanic/Latina women in Los Angeles, California, who completed up to 2 staff‐administered 24‐hour dietary recalls in the third trimester of pregnancy. Hypertensive disorders of pregnancy were abstracted from medical records and based on a physician's diagnosis or systolic or diastolic blood pressure (≥140 or ≥90 mm Hg, respectively) at ≥2 consecutive prenatal visits. Using multivariable logistic regression, we evaluated associations of 2 previously derived dietary patterns in this population (solid fats, refined grains, and cheese and vegetables, oils, and fruit) and the Healthy Eating Index 2015 with (1) gestational hypertension, (2) preeclampsia, and (3) any hypertensive disorder of pregnancy (either gestational hypertension or preeclampsia). In separate models, we additionally tested interactions with prepregnancy body mass index. Comparing highest‐to‐lowest quartiles, the solid fats, refined grains, and cheese dietary pattern was associated with an increased odds of any hypertensive disorder of pregnancy (odds ratio [OR], 3.99 [95% CI, 1.44–11.0];
P
trend
=0.014) and preeclampsia (OR, 4.10 [95% CI, 1.25–13.5];
P
trend
=0.036), whereas the vegetables, oils, and fruit pattern was associated with reduced odds of preeclampsia (OR, 0.32 [95% CI, 0.10–0.99];
P
trend
=0.041). Among the overweight prepregnancy body mass index category, inverse associations of vegetables, oils, and fruit and Healthy Eating Index 2015 with preeclampsia were more pronounced (both
P
interactions
=0.017). Healthy Eating Index 2015 findings were generally nonsignificant.

Conclusions
While the solid fats, refined grains, and cheese diet was strongly associated with preeclampsia during pregnancy, findings suggest the vegetables, oils, and fruit diet may be more relevant than Healthy Eating Index 2015 for preventing preeclampsia among low‐income Hispanic/Latina women.
Sex Differences in the Epidemiology of Intracerebral Hemorrhage Over 10 Years in a Population‐Based Stroke Registry
Authors: Foschi Matteo , D’Anna Lucio , Gabriele Claudia , Conversi Francesco , Gabriele Francesca , De Santis Federica , Orlandi Berardino , De Santis Federico , Ornello Raffaele , Sacco Simona 
Published: February 2024

Background
We investigated incidence and outcome of spontaneous intracerebral hemorrhage (ICH) in a population‐based stroke registry and provided data to inform on the figures of the disease in women and in men.

Methods and Results

Our prospective population‐based registry included patients with first‐ever ICH occurring from January 2011 to December 2020. Incidence rates were standardized to the 2011 Italian and European population, and incidence rate ratios were calculated. Multivariate hazard ratios for 30‐day and 1‐year fatality were estimated with Cox regression, including components of the ICH score and sex. We included 748 first‐ever ICHs (41.3% women). Women were significantly older than men at ICH onset (78.9±12.6 versus 73.2±13.6 years;
P
<0.001) and showed higher clinical severity on presentation (median National Institutes of Health Stroke Scale score, 11 [interquartile range, 6–20] versus 9 [interquartile range, 4–15], respectively;
P
=0.016). The crude annual incidence rate was 20.2 (95% CI, 18.0–22.6) per 100 000 person‐years in women and 30.2 (95% CI, 27.4–33.2) per 100 000 person‐years in men); incidence was lower in women versus men (incidence rate ratio, 0.67 [95% CI, 0.58–0.78];
P
<0.001) and did not change over time in both sexes (
P
for trend=0.073 and 0.904, respectively). Unadjusted comparison showed higher 1‐year case‐fatality rates in women versus men (48.5% versus 40.1%;
P
=0.026). After adjusting for components of the ICH score, female sex lost significance as a predictor of mortality.

Conclusions
We found lower ICH incidence in women than in men. However, women showed a higher 1‐year case‐fatality rate versus men, which was likely related to older age at ICH onset and higher clinical severity. Identification of factors explaining the reported differences is important to develop targeted interventions.
Sex Differences in the Relationship Between Schizophrenia and the Development of Cardiovascular Disease
Authors: Komuro Jin , Kaneko Hidehiro , Suzuki Yuta , Okada Akira , Fujiu Katsuhito , Takeda Norifumi , Jo Taisuke , Morita Hiroyuki , Senoo Keitaro , Node Koichi , Yasunaga Hideo , Ieda Masaki , Komuro Issei 
Published: February 2024

Background
There are few data on sex differences in the association between schizophrenia and the development of cardiovascular disease (CVD). We sought to clarify the relationship of schizophrenia with the risk of developing CVDs and to explore the potential modification effect of sex differences.

Methods and Results

We conducted a retrospective analysis using the JMDC Claims Database between 2005 and 2022. The study population included 4 124 508 individuals aged 18 to 75 years without a history of CVD or renal replacement therapy. The primary end point is defined as a composite end point that includes myocardial infarction, angina pectoris, stroke, heart failure, atrial fibrillation, and pulmonary thromboembolism. During a mean follow‐up of 1288±1001 days, we observed 182 158 composite end points. We found a significant relationship of schizophrenia with a greater risk of developing composite CVD events in both men and women, with a stronger association observed in women. The hazard ratio for the composite end point was 1.63 (95% CI, 1.52–1.74) in women and 1.42 (95% CI, 1.33–1.52) in men after multivariable adjustment (
P
for interaction=0.0049). This sex‐specific difference in the association between schizophrenia and incident CVD was consistent for angina pectoris, heart failure, and atrial fibrillation.

Conclusions
Our analysis using a large‐scale epidemiologic cohort demonstrated that the association between schizophrenia and subsequent CVD events was more pronounced in women than in men, suggesting the clinical importance of addressing schizophrenia and tailoring the CVD prevention strategy based on sex‐specific factors.
Posttraumatic Stress Disorder Is Associated With Elevated Risk of Incident Stroke and Transient Ischemic Attack in Women Veterans
Authors: Ebrahimi Ramin , Dennis Paul A. , Alvarez Carlos A. , Shroyer A. Laurie , Beckham Jean C. , Sumner Jennifer A. 
Published: February 2024

Background
Posttraumatic stress disorder (PTSD) has been associated with ischemic heart disease in women veterans, but evidence for associations with other cardiovascular disorders remains limited in this population. This retrospective longitudinal cohort study evaluated the association of PTSD with incident stroke/transient ischemic attack (TIA) in women veterans.

Methods and Results
Veterans Health Administration electronic health records were used to identify women veterans aged ≥18 years engaged with Veterans Health Administration health care from January 1, 2000 to December 31, 2019. We identified women veterans with and without PTSD without a history of stroke or TIA at start of follow‐up. Propensity score matching was used to match groups on age, race or ethnicity, traditional cardiovascular risk factors, female‐specific risk factors, a range of mental and physical health conditions, and number of prior health care visits. PTSD, stroke, TIA, and risk factors used in propensity score matching were based on diagnostic codes. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for associations of PTSD with an incident stroke/TIA composite. Subanalyses considered stroke and TIA separately, plus age‐ and race‐ or ethnicity‐stratified analyses were carried out.

The analytic sample included 208 092 women veterans (104 046 with and 104 046 without PTSD). PTSD was associated with a greater rate of developing stroke/TIA (HR, 1.33 [95% CI, 1.25–1.42],
P
<0.001). This elevated risk was especially pronounced in women <50 years old and in Hispanic/Latina women.

Conclusions
Findings indicate a strong association of PTSD with incident stroke/TIA in women veterans. Research is needed to determine whether addressing PTSD and its downstream consequences can offset this risk.
Validating GOES Radar Estimation via Machine Learning to Inform NWP (GREMLIN) Product over CONUS
Authors: Lee Yoonjin , Hilburn Kyle 
Published: February 2024

Abstract
Geostationary Operational Environmental Satellites (GOES) Radar Estimation via Machine Learning to Inform NWP (GREMLIN) is a machine learning model that outputs composite reflectivity using GOES-R Series Advanced Baseline Imager (ABI) and Geostationary Lightning Mapper (GLM) input data. GREMLIN is useful for observing severe weather and initializing convection for short-term forecasts, especially over regions without ground-based radars. This study expands the evaluation of GREMLIN’s accuracy against the Multi-Radar Multi-Sensor (MRMS) System to the entire contiguous United States (CONUS) for the entire annual cycle. Regional and temporal variation of validation metrics are examined over CONUS by season, day of year, and time of day. Since GREMLIN was trained with data in spring and summer, root-mean-square difference (RMSD) and bias are lowest in the order of summer, spring, fall, and winter. In summer, diurnal patterns of RMSD follow those of precipitation occurrence. Winter has the highest RMSD because of cold surfaces mistaken as precipitating clouds, but some of these errors can be removed by applying the ABI clear-sky mask product and correcting biases using a lookup table. In GREMLIN, strong echoes are closely related to the existence of lightning and corresponding low brightness temperatures, which result in different error distributions over different regions of CONUS. This leads to negative biases in cold seasons over Washington State, lower 30-dBZ critical success index caused by high misses over the Northeast, and higher false alarms over Florida that are due to higher frequency of lightning.
Radar Characteristics of Supercell Thunderstorms Traversing the Appalachian Mountains
Authors: McKeown Katherine E. , Davenport Casey E. , Eastin Matthew D. , Purpura Sarah M. , Riggin Roger R. 
Published: February 2024

Abstract
The evolution of supercell thunderstorms traversing complex terrain is not well understood and remains a short-term forecast challenge across the Appalachian Mountains of the eastern United States. Although case studies have been conducted, there has been no large multicase observational analysis focusing on the central and southern Appalachians. To address this gap, we analyzed 62 isolated warm-season supercells that occurred in this region. Each supercell was categorized as either crossing (∼40%) or noncrossing (∼60%) based on their maintenance of supercellular structure while traversing prominent terrain. The structural evolution of each storm was analyzed via operationally relevant parameters extracted from WSR-88D radar data. The most significant differences in radar-observed structure among storm categories were associated with the mesocyclone; crossing storms exhibited stronger, wider, and deeper mesocyclones, along with more prominent and persistent hook echoes. Crossing storms also moved faster. Among the supercells that crossed the most prominent peaks and ridges, significant increases in base reflectivity, vertically integrated liquid, echo tops, and mesocyclone intensity/depth were observed, in conjunction with more frequent large hail and tornado reports, as the storms ascended windward slopes. Then, as the supercells descended leeward slopes, significant increases in mesocyclone depth and tornado frequency were observed. Such results reinforce the notion that supercell evolution can be modulated substantially by passage through and over complex terrain.

Significance Statement
Understanding of thunderstorm evolution and severe weather production in regions of complex terrain remains limited, particularly for storms with rotating updrafts known as supercell thunderstorms. This study provides a systematic analysis of numerous warm season supercell storms that moved through the central and southern Appalachian Mountains. We focus on operationally relevant radar characteristics and differences among storms that maintain supercellular structure as they traverse the terrain (crossing) versus those that do not (noncrossing). Our results identify radar characteristics useful in distinguishing between crossing and noncrossing storms, along with typical supercell evolution and severe weather production as storms cross the more prominent peaks and ridges of the central and southern Appalachian Mountains.
Positive Affect and Physical Activity Associations in Women and Their Spouses
Authors: Forster Anna K. , Richards Elizabeth A. , Franks Melissa M. , Foli Karen J. , Hass Zachary 
Published: February 2024

Background: Only 21% of U.S. women meet the recommended physical activity guidelines, placing them at increased risk for long-term conditions such as heart disease and diabetes. Physical activity is influenced by individual and interpersonal factors (e.g., romantic partners). Individual factors, such as positive affect, are associated with lower mortality risk and improved health behaviors. Objectives: This secondary data analysis, guided by Fredrickson’s Broaden and Build Theory, aims to examine the relationship between positive affect of married women (n = 115 couples) and their physical activity behavior on the same- and next- day, while also considering their spouses’ positive affect. Methods: Two population average models assessed the relationship of calm and happy (positive affect) to physical activity. Physical activity was assessed as the sum of the minutes of moderate-to-vigorous physical activity (MVPA) over the prior 24 hours. Covariates of age, baseline activity frequency, education, marital quality, and race/ethnicity were also included. Results: Women’s happiness ( β = 0.15, p < .005), not calmness ( β = −0.03, p = .60), was found to have a significant association with same-day MVPA. Spouses’ happiness ( β = 0.11, p = .045) was significantly associated with women’s next-day MVPA while their calmness ( β = −0.04, p = .44) was not. Conclusions: The results of this study support that incorporating positive affect could be valuable for improving physical activity behaviors. Spouse reports provide additional context to consider in physical activity promotion research.
Wheel profile optimization for intercity EMUs based on the Gaussian function correction method
Authors: Hou Maorui , Qi Yayun , Chi Changxin , Ao Peng , Liu Hua 
Published: February 2024

Intercity EMUs are prone to wheel flange wear and tread wear due to the high operating speed and many small radius curved tracks. The problems caused by wheel wear have seriously affected the safety of high-speed railway operations in China. In this paper, based on the original LMA wheel profile, the Gaussian function correction (GFC) method is proposed to design the wheel profile. The GFC method mainly changes the root region of the wheel flange, to enhance the curve passing performance and reduce wheel wear of the vehicle. The optimal profile is optimized by the Kriging surrogate model (KSM) and the whale optimization algorithm (WOA). The wheel-rail contact characteristics, dynamic characteristics and the wheel wear of the wheel profiles before and after optimization are simulated and analyzed. The results show that the equivalent conicity of the optimized profile is reduced; the critical speed is increased by 9.3 km/h, the lateral ride index and comfort index of the vehicle are further reduced. The curve passing performance is also improved, the wheel-rail wear of the optimized profile is further reduced and the maximum wear depth of the wheels before and after optimization is 43.4e-9m and 34.1e-9m on the curved track with a radius of 500m, which is reduced by 21.43%. This method provides a reference and basis for wheel profile design and profile re-profiling of intercity EMUs.
Comparative Evaluation of Safety and Economic Burden Due to Topical Steroid Misuse in Patients with Self-medication and Prescribed Medication
Authors: Besra Laxman , Tripathy Ratikanta , Srivastava Vartika , Gaba Sakshi , Padhee Sourav 
Published: February 2024

Introduction Topical corticosteroids are currently the primary drugs to treat several dermatological disorders. But they are misused for various indications such as acne, pigmentation, fungal infection, and pruritus, and many times as a cosmetic or a skin cream for any type of rash. This study is performed to compare the magnitude of adverse events between practitioner-prescribed and self-prescribed groups of patients. In addition, this study also focuses on the demographic and educational status of patients where topical steroids are most widely misused. Materials and Methods It is a cross-sectional, hospital-based observational study conducted in the Department of Dermatology in collaboration with the Department of Pharmacology, KIMS, Bhubaneswar. A total of 134 patients were enrolled after getting the informed consent for the study, and assessed based on their topical steroid misuse and their adverse effects. Results The present study showed that steroid misuse was most common between 20 and 30 years of age group patients with low educational status. The most commonly applied steroid was clobetasol followed by mometasone and steroid abuse was more common in self-prescribed patients than physician-prescribed patients. The economic burden was more in the case of people using steroid cream only or steroid + anti-fungal creams because they have to be applied over a large body surface area. Incidence of adverse effects was observed more in self-prescribed patients and with low educational status. Conclusion This study highlights the fact that self-medication increases the incidence of adverse reactions and economic burden on the patients. Continuous education of patients and strict regulations regarding over-the-counter sales of steroids may help decrease the incidence of steroid misuse.