bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction modelling the impact of onset to treatment time on the modified Rankin Scale score at 90 days for patients with acute ischaemic stroke
Authors: Ennab Vogel Nicklas , Tatlisumak Turgut , Wester Per , Lyth Johan , Levin Lars-Åke 
Published: August 2022

IntroductionShortening the time from stroke onset to treatment increases the effectiveness of endovascular stroke therapies.AimThis study aimed to predict the modified Rankin Scale score at 90 days post-stroke (mRS-90d score) in patients with acute ischaemic stroke (AIS) with respect to four types of treatment: conservative therapy (CVT), intravenous thrombolysis only (IVT), mechanical thrombectomy only (MT) and pretreatment with IVT before MT (IVT+MT).Patients and methodsThis nationwide observational study included 124 484 confirmed cases of acute stroke in Sweden over 6 years (2012–2017). The associations between onset-to-treatment time (OTT), patient age and hospital admission National Institutes of Health Stroke Scale (NIHSS) score with the five-levelled mRS-90d score were retrospectively studied. A generalised linear model (GLM) was fitted to predict the mRS-90d scores for each patient group.ResultsThe fitted GLM for CVT patients is a function of age and NIHSS score. For IVT, MT and IVT+MT patients, GLMs additionally employed OTT variables. By reducing the mean OTTs by 15 min, the number needed-to-treat (NNT) for one patient to make a favourable one-step shift in the mRS was 30 for IVT, 48 for MT and 21 for IVT+MT.Discussion and conclusionThis study demonstrates linear associations of mRS-90d score with OTT for IVT, MT and IVT+MT, and shows in absolute effects measures that OTT reductions for IVT and/or MT produces substantial health gains for patients with AIS. Even moderate OTT reductions led to sharp drops in the NNT.
Sequencing of theZMYND15gene in a cohort of infertile Chinese men reveals novel mutations in patients with teratozoospermia
Authors: Wen Yuting , Wang Xiang , Zheng Rui , Dai Siyu , Li Jinhui , Yang Yihong , Shen Ying 
Published: August 2022

BackgroundThe information ofZMYND15in human reproduction is very limited, resulting in the unclear link betweenZMYND15variants and male infertility.MethodsWhole exome sequencing and Sanger sequencing to identify the potential pathogenic variation ofZMYND15in infertile men, Papanicolaou staining and electron microscopy to investigate the spermatozoa morphology, western blotting and immunofluorescence staining to confirm the pathogenicity of the identified variants, and proteomic analysis and coimmunoprecipitation to clarify the potential molecular mechanism.ResultsA total of 31ZMYND15variants were identified in 227 infertile patients. Three deleterious biallelic variants, including a novel compound heterozygous variant of c.1105delG (p.A369Qfs*15) and c.1853T>C (p.F618S), a new homozygous splicing mutation of c.1297+5G>A and a reported homozygous nonsense mutation of c.1209T>A (p.Y403*), were detected in three affected individuals with oligoasthenoteratozoospermia, showing a biallelic pathogenic mutation frequency of 1.3% (3/227). No biallelic pathogenic mutation was found in 692 fertile men. Morphology analysis showed abnormalities in sperm morphology in the patients harbouringZMYND15mutations. Western blotting and immunofluorescence staining confirmed the nearly absent ZMYND15 expression in the sperm of the patients. Mechanistically, ZMYND15 might regulate spermatogenesis by interacting with key molecules involved in sperm development, such as DPY19L2, AKAP4 and FSIP2, and might also mediate the expression of the autophagy-associated protein SPATA33 to maintain sperm individualisation and unnecessary cytoplasm removal.ConclusionOur findings broaden the variant and phenotype spectrum ofZMYND15in male infertility, and reveal the potential signalling pathway of ZMYND15 regulating spermatogenesis, finally confirming the essential role ofZMYND15in human fertility.
Poziotinib Inhibits HER2-Mutant–Driven Therapeutic Resistance and Multiorgan Metastasis in Breast Cancer
Authors: Kalra Rashi , Chen Ching Hui , Wang Junkai , Salam Ahmad Bin , Dobrolecki Lacey E. , Lewis Alaina , Sallas Christina , Yates Clayton C. , Gutierrez Carolina , Karanam Balasubramanyam , Anurag Meenakshi , Lim Bora , Ellis Matthew J. , Kavuri Shyam M. 
Published: August 2022

Abstract

The pan-HER tyrosine kinase inhibitor (TKI) neratinib is therapeutically active against metastatic breast cancers harboring activating HER2 mutations, but responses are variable and often not durable. Here we demonstrate that recurrent HER2 mutations have differential effects on endocrine therapy responsiveness, metastasis, and pan-HER TKI therapeutic sensitivity. The prevalence and prognostic significance may also depend on whether the HER2 mutant has arisen in the context of lobular versus ductal histology. The most highly recurrent HER2 mutant, L755S, was particularly resistant to neratinib but sensitive to the pan-HER TKI poziotinib, alone or in combination with fulvestrant. Poziotinib reduced tumor growth, diminished multiorgan metastasis, and inhibited mTOR activation more effectively than neratinib. Similar therapeutic effects of poziotinib were observed in both an engineered HER2L755S MCF7 model and a patient-derived xenograft harboring a HER2G778_P780dup mutation. Overall, these findings support the need for clinical evaluation of poziotinib for the treatment of HER2-mutant metastatic breast cancer.

Significance:
Evaluation of the functional impact of HER2 mutations on therapy-induced resistance and metastasis identifies robust antitumor activity of poziotinib and supports the clinical evaluation of poziotinib in ER+ HER2 mutant breast cancer.
Leveraging Therapy-Specific Polygenic Risk Scores to Predict Restrictive Lung Defects in Childhood Cancer Survivors
Authors: Im Cindy , Yuan Yan , Austin Eric D. , Stokes Dennis C. , Krasin Matthew J. , Davidoff Andrew M. , Sapkota Yadav , Wang Zhaoming , Ness Kirsten K. , Wilson Carmen L. , Armstrong Gregory T. , Hudson Melissa M. , Robison Leslie L. , Mulrooney Daniel A. , Yasui Yutaka 
Published: August 2022

Abstract

Therapy-related pulmonary complications are among the leading causes of morbidity among long-term survivors of childhood cancer. Restrictive ventilatory defects (RVD) are prevalent, with risks increasing after exposures to chest radiotherapy and radiomimetic chemotherapies. Using whole-genome sequencing data from 1,728 childhood cancer survivors in the St. Jude Lifetime Cohort Study, we developed and validated a composite RVD risk prediction model that integrates clinical profiles and polygenic risk scores (PRS), including both published lung phenotype PRSs and a novel survivor-specific pharmaco/radiogenomic PRS (surPRS) for RVD risk reflecting gene-by-treatment (GxT) interaction effects. Overall, this new therapy-specific polygenic risk prediction model showed multiple indicators for superior discriminatory accuracy in an independent data set. The surPRS was significantly associated with RVD risk in both training (OR = 1.60, P = 3.7 × 10−10) and validation (OR = 1.44, P = 8.5 × 10−4) data sets. The composite model featuring the surPRS showed the best discriminatory accuracy (AUC = 0.81; 95% CI, 0.76–0.87), a significant improvement (P = 9.0 × 10−3) over clinical risk scores only (AUC = 0.78; 95% CI: 0.72–0.83). The odds of RVD in survivors in the highest quintile of composite model-predicted risk was ∼20-fold higher than those with median predicted risk or less (OR = 20.01, P = 2.2 × 10−16), exceeding the comparable estimate considering nongenetic risk factors only (OR = 9.20, P = 7.4 × 10−11). Inclusion of genetic predictors also selectively improved risk stratification for pulmonary complications across at-risk primary cancer diagnoses (AUCclinical = 0.72; AUCcomposite = 0.80, P = 0.012). Overall, this PRS approach that leverages GxT interaction effects supports late effects risk prediction among childhood cancer survivors.

Significance:
This study develops a therapy-specific polygenic risk prediction model to more precisely identify childhood cancer survivors at high risk for pulmonary complications, which could help improve risk stratification for other late effects.
Obesity and Breast Cancer Metastasis across Genomic Subtypes
Authors: Olsson Linnea T. , Walens Andrea , Hamilton Alina M. , Benefield Halei C. , Fleming Jodie M. , Carey Lisa A. , Hursting Stephen D. , Williams Kevin P. , Troester Melissa A. 
Published: August 2022

Abstract

Background:
Obese women have higher risk of aggressive breast tumors and distant metastasis. However, obesity has rarely been assessed in association with metastasis in diverse populations.

Methods:
In the Carolina Breast Cancer Study Phase 3 (2008–2013), waist-to-hip ratio (WHR), body mass index (BMI), and molecular subtype [PAM50 risk-of-recurrence (ROR) score] were assessed. Obesity measures were evaluated in association with metastasis within five years of diagnosis, overall and stratified by race and ROR score. Absolute risk of metastasis and risk differences between strata were calculated using the Kaplan–Meier estimator, adjusted for age, grade, stage, race, and ER status. Relative frequency of metastatic site and multiplicity were estimated in association with obesity using generalized linear models.

Results:
High-WHR was associated with higher risk of metastasis (5-year risk difference, RD, 4.3%; 95% confidence interval, 2.2–6.5). It was also associated with multiple metastases and metastases at all sites except brain. The 5-year risk of metastasis differed by race (11.2% and 6.9% in Black and non-Black, respectively) and ROR score (19.5% vs. 6.6% in high vs. low-to-intermediate ROR-PT). Non-Black women and those with low-to-intermediate ROR scores had similar risk in high- and low-WHR strata. However, among Black women and those with high ROR, risk of metastasis was elevated among high-WHR (RDBlack/non-Black = 4.6%, RDHigh/Low-Int = 3.1%). Patterns of metastasis were similar by BMI.

Conclusions:
WHR is associated with metastatic risk, particularly among Black women and those with high-risk tumors.

Impact:
Understanding how risk factors for metastasis interact may help in tailoring care plans and surveillance among patients with breast cancer.
New record of a rare copepod, Metridia bicornuta Davis, 1949 (Calanoida, Metridinidae) for the South China Sea
Authors: Feng Y. Z. , Liu Z. S. , Wang C. S. 
Published: August 2022

Abstract
The genus Metridia Boeck, 1864 is widely distributed in the global ocean, but only 9 species of Metridia have been recorded from the China seas. Here we report the rare copepod Metridia bicornuta Davis, 1949 for the first time for the South China Sea. One specimen was collected from the southern basin of the South China Sea (13°0.21′N 113°0.21′E) at depths of 500-800 m. Females of this species differ from those of congeneric species by the following features: (i) Prosome 1.5 times as long as urosome; (ii) forehead with lateral points projecting on both sides; (iii) genital somite 1.8 times as long as the second somite; (iv) distal segment of fifth swimming leg (P5) with a small outer marginal spine and 3 subequal robust terminal setae. This finding expands the known global distribution of M. bicornuta, and increases the number of copepod species in the China seas.
Analysis of changes in biochemical composition in the body of juvenile Portunus trituberculatus during overwintering (Brachyura, Portunidae)
Authors: Wan Litao , Zhang Dongxu , Xu Wenjun , Wu Xugan , He Jie 
Published: August 2022

Abstract
This study analysed the composition and content of nutrients in the muscle and hepatopancreas of juvenile Portunus trituberculatus cultured in a pond at the beginning, middle and end of overwintering, so as to understand the nutrient metabolic patterns in the body of P. trituberculatus during overwintering. The results showed that the muscle index (MY) of P. trituberculatus changed little during overwintering, but the hepatosomatic index (HSI) decreased significantly (7.88% at the beginning of overwintering and only 6.23% at the end of overwintering). The total carbohydrate, crude lipid and crude protein in the muscle and hepatopancreas of juvenile P. trituberculatus decreased to different degrees throughout the overwintering period, in particular, the decrease in total carbohydrate was approximately 50% and the decrease in crude lipid was around 30%. In terms of fatty acid composition, the total saturated fatty acids (ΣSFAs) in the muscle of juvenile P. trituberculatus slightly decreasing, the monounsaturated fatty acid content (ΣMUFAs) slightly increasing, while the total polyunsaturated fatty acids (ΣPUFAs) remained basically unchanged. In contrast, the content of fatty acids in the hepatopancreas changed greatly, and the ΣSFAs decreased significantly (), which was 44.2% at the beginning of overwintering and only 24.02% at the end. The ΣMUFAs decreased only at the end of overwintering, while the ΣPUFAs increased significantly (), reaching 7.62% at the beginning of overwintering, 18.59% at the middle and 32.83% at the end of overwintering. In general, the energy material of juvenile P. trituberculatus was mainly derived from the hepatopancreas throughout the overwintering period, and it mainly utilized carbohydrates and crude lipids in the body and was highly selective in the oxidative utilization of fatty acids, mainly utilizing SFAs for oxidative energy supply, while PUFAs, HUFAs, EPA and DHA were selectively retained.
The Grammarian Cannot Wait: Thackeray, Muraoka, and the Analysis of Septuagint Syntax
Authors: Evans Trevor 
Published: August 2022

Abstract
This article deals with the question of the nature of and scholarly approaches to studying Greek syntax in the Septuagint. The concrete point of departure is the publication of A Syntax of Septuagint Greek by T. Muraoka (Leuven: Peeters, 2016). The author discusses Muraoka’s work, while touching upon general trends in Septuagint scholarship, and reviews the book in a detailed manner. The author’s theoretical considerations are illustrated by two case studies that demonstrate the problems associated with Muraoka’s approach to syntax in the Septuagint. By way of conclusion, the author reflects on future directions in research on the Septuagint and its language usage.
Healthcare, Healthcare Resource Allocation, and Rationing: Pragmatist Reflections
Authors: Taye Belayneh , Assefa Andebet Hailu 
Published: August 2022

Abstract
This article approaches the ethical dilemma of healthcare allocation and rationing from the perspective of pragmatist ethics, mainly following John Dewey’s ethics. The moral dilemma of healthcare allocation arises whenever we allocate limited resources, and rationing is a necessary option for distributing available resources. In a broader sense, the moral problems of healthcare allocation also encompass the issue of access to primary healthcare, especially for low-income sections of communities. In this sense, allocation always entails rationing – denying service to someone for the benefit of others. Such aspects of allocation and rationing and the relational aspect of disease and health make the problem morally controversial, which makes it difficult to agree on a principle or principles of allocation and rationing applicable across different contexts. Hence, this paper argues that moral challenges of healthcare rationing ought not to be addressed through the appeal to principles, but rather through deliberation that embraces a more pragmatic and democratic approach to negotiating health resource allocation and rationing. However, this does not mean that moral principles and values are insignificant in healthcare allocation.
Double root translocation: Early experience on performance of translocated aortic and pulmonary root
Authors: Agarwal Vijay , Vaidyanathan Swaminathan 
Published: August 2022

Aim Transposition of great arteries with ventricular septal defect and pulmonary stenosis is a complex congenital cardiac malformation with varied treatment options. Double root translocation is one of the described techniques with several advantages over other techniques. Our goal of this study is to report our early experiences on the performance of translocated aortic and pulmonary root. Methods From 2016 to 2019, a total of 12 patients (seven boys and five girls) aged from one year to three years underwent double root translocation. All our patients were diagnosed with dextro-transposition of the great arteries (d-TGA)/double-outlet right ventricle (DORV), ventricular septal defect (VSD), and pulmonary stenosis (PS). One patient (8.33%) presented with (IL 2R CX), remaining 11 patients (91.66%) had (IL CX 2R) as their coronary pattern. Mean follow-up period was two years (1–3 years). Results At six months follow up, one patient died due to severe MR, one patient had severe TR and was taken back for surgery after two weeks post-surgery. Three patients had trivial aortic regurgitation (AR) and nine had no AR, two patients had trivial mitral regurgitation (MR) and 10 had no MR 11 patients had post-operative sinus rhythm and were in NYHA class 1. One patient with a complete heart block was supported with extracorporeal membrane oxygenator followed by tracheostomy. Redo TV repair was done in one patient. Peritoneal dialysis was accomplished in two patients. Conclusions Double root translocation is a good alternative surgical treatment for TGA/DORV, VSD, and PS, where the pulmonary valve is small, but the leaflets are usable. Although the operation is technically demanding, our early follow-up on translocated root performance shows promising outcomes.
Dynamic modulation of inhibition ability following repeated exposures to morphine in macaque monkey
Authors: Ghasemian Sadegh , Vardanjani Marzieh M , Sheibani Vahid , Mansouri Farshad A 
Published: August 2022

Background: Deficits in cognitive control, particularly inhibition ability, play crucial roles in susceptibility, progress, and relapse to opioid addiction. However, it is unclear when and how such deficits develop and interact with repeated exposures to prescribed opioids. Aim: Using macaque monkey ( Macaca mulatta), as an animal model with high translational merits in cognitive neuroscience, we tried to delineate alterations of inhibition ability in the course of repeated exposures to morphine. Methods: Monkeys were trained to perform stop-signal task and then we closely monitored their inhibition ability before exposure, after initial exposure, and following repeated exposures to morphine when they experienced abstinent periods. We also assessed morphine-induced conditioned place preference (CPP) in these monkeys to monitor the long-lasting effects of morphine on other behaviors. Results: Compared to the baseline level, monkeys’ inhibition ability was significantly enhanced after initial exposure to morphine (early phase); however, it became significantly attenuated after repeated exposures (late phase). These alterations occurred while monkeys consistently expressed the morphine-induced CPP over the course of morphine exposure. Conclusions: Our findings indicate that repeated and scheduled exposures to morphine, which is akin to its clinical and recreational use, lead to dynamic alterations in primates’ cognitive control depending on the extent of exposure. Enhancement of inhibition after limited exposure might provide opportunities to intervene and prevent the progress and culmination of opioid addiction, which is characterized by disinhibited drug-seeking and consumption.
Is psychedelic use associated with cancer?: Interrogating a half-century-old claim using contemporary population-level data
Authors: Barnett Brian S , Ziegler Kathleen , Doblin Rick , Carlo Andrew D 
Published: August 2022

Background: In 1967, concerns about the carcinogenic potential of psychedelics arose after a study reported chromosomal damage in human leukocytes following in vitro lysergic acid (LSD) exposure. Worries were further heightened by subsequent reports of leukemia and other cancers in LSD users. Additional investigations of psychedelics’ effects on chromosomes were published over the next decade, with the majority suggesting these concerns were unfounded. However, the relationship between psychedelics and cancer has been explored only minimally from an epidemiological perspective. Aims: To determine whether associations exist between psychedelic use and either lifetime cancer or hematologic cancer diagnoses. Methods: We analyzed data from adult participants in the 2015–2019 administrations of the National Survey on Drug Use and Health for associations between lifetime use of psychedelics and lifetime diagnosis of either any cancer or hematologic cancer. Results: We identified no associations between lifetime psychedelic use and either lifetime cancer diagnosis or hematologic cancer diagnosis. Sub-analyses of lifetime lysergamide, phenethylamine, and tryptamine use also revealed no associations with lifetime cancer or hematologic cancer diagnosis. Conclusions: While laboratory studies and case reports from the 1960s and 1970s generated concerns about psychedelics’ carcinogenic potential, this analysis of recent epidemiological data does not support an association between psychedelic use and development of cancer in general or hematologic cancer. Important study limitations to consider include a lack of information about psychedelic dosage, number of lifetime psychedelic exposures, and the temporal relationship between psychedelic use and cancer diagnosis.
Effect of age on presentation and outcome in renal colic
Authors: Golomb Dor , Shemesh Amit , Goldberg Hanan , Shalom Ben , Hen Eyal , Barkai Eyal , Atamna Fahed , Abu Nijmeh Haitham , Cooper Amir , Raz Orit 
Published: August 2022

Objectives: To examine the age-related differences in the presentation, management, and outcomes of patients admitted to the emergency department (ED) with ureteral stones. Patients and methods: A retrospective analysis of all patients who visited the ED at a single institution that were found to have a ureteral stone on CT. Clinical, laboratory, and imaging parameters were collected, including outcomes. Patients were subdivided into age groups: 18–30, 31–50, 51–70, and >70 years. Results: Between January 2018 and December 2020, 778 patients were admitted to the ED with a ureteral stone. About 78% (609) were males and 22% (169) were females. The mean ages were 49.4 (SD 14.4) and 51.6 (SD 15.7) in males and females, respectively ( p = 0.08). Patients in the 36–50 age group, had significantly higher visual analogue scale (VAS) scores ( p < 0.0001). Patients older than 70 years old presented with significantly higher serum creatinine levels ( p < 0.0001), C-reactive protein (CRP) ( p < 0.001) and leukocyte levels ( p = 0.002). These patients were also found to have significantly larger stones (mean size of 6.2 mm (SD 4.8) ( p < 0.0001)) and underwent percutaneous nephrolithotripsy (PCNL) in significantly higher numbers (56.3% vs 43.8%, ( p < 0.0001)). Less than half of the patients older than 50 years were given medical expulsive therapy (MET) with alpha-blockers, compared to more than 50% in the other age groups ( p = 0.002). Spontaneous stone expulsion was noted in 70.2% of the 18–35-year group, 62.4% of the 36–50-year-old group, 51.8% of the 51–70-year-old group, and 37% of the >70-year-old group ( p < 0.0001). The ED re-admission rates at 7 and 30 days were not significantly different among all age groups. Conclusions: Our data suggests that older patients presented with larger stones, elevated inflammatory markers and creatinine and were more likely to require surgical intervention. The spontaneous stone expulsion rate was inversely associated with age.