bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stacked mutations in wheat homologues of rice SEMI-DWARF1 confer a novel semi-dwarf phenotype
Authors: Ndreca Barbora , Huttly Alison , Bibi Sajida , Bayon Carlos , Lund George , Ham Joshua , Alarcón-Reverte Rocío , Addy John , Tarkowská Danuše , Pearce Stephen , Hedden Peter , Thomas Stephen G. , Phillips Andrew L. 
Published: May 2024

Abstract
Background
Semi-dwarfing alleles are used widely in cereals to confer improved lodging resistance and assimilate partitioning. The most widely deployed semi-dwarfing alleles in rice and barley encode the gibberellin (GA)-biosynthetic enzyme GA 20-OXIDASE2 (GA20OX2). The hexaploid wheat genome carries three homoeologous copies of GA20OX2, and because of functional redundancy, loss-of-function alleles of a single homoeologue would not be selected in wheat breeding programmes.
Instead, approximately 70% of wheat cultivars carry gain-of-function mutations in REDUCED HEIGHT 1 (RHT1) genes that encode negative growth regulators and are degraded in response to GA. Semi-dwarf Rht-B1b or Rht-D1b alleles encode proteins that are insensitive to GA-mediated degradation. However, because RHT1 is expressed ubiquitously these alleles have pleiotropic effects that confer undesirable traits in some environments.

Results
We have applied reverse genetics to combine loss-of-function alleles in all three homoeologues of wheat GA20OX2 and its paralogue GA20OX1 and evaluated their performance in three years of field trials. ga20ox1 mutants exhibited a mild height reduction (approximately 3%) suggesting GA20OX1 plays a minor role in stem elongation in wheat. ga20ox2 mutants have reduced GA1 content and are 12–32% shorter than their wild-type segregants, comparable to the effect of the Rht-D1b ‘Green Revolution’ allele. The ga20ox2 mutants showed no significant negative effects on yield components in the spring wheat variety ‘Cadenza’.

Conclusions
Our study demonstrates that chemical mutagenesis can expand genetic variation in polyploid crops to uncover novel alleles despite the difficulty in identifying appropriate mutations for some target genes and the negative effects of background mutations. Field experiments demonstrate that mutations in GA20OX2 reduce height in wheat, but it will be necessary to evaluate the effect of these alleles in different genetic backgrounds and environments to determine their value in wheat breeding as alternative semi-dwarfing alleles.
Weibull parametric model for survival analysis in women with endometrial cancer using clinical and T2-weighted MRI radiomic features
Authors: Li Xingfeng , Marcus Diana , Russell James , Aboagye Eric O. , Ellis Laura Burney , Sheeka Alexander , Park Won-Ho Edward , Bharwani Nishat , Ghaem-Maghami Sadaf , Rockall Andrea G. 
Published: May 2024

AbstractBackgroundSemiparametric survival analysis such as the Cox proportional hazards (CPH) regression model is commonly employed in endometrial cancer (EC) study. Although this method does not need to know the baseline hazard function, it cannot estimate event time ratio (ETR) which measures relative increase or decrease in survival time. To estimate ETR, the Weibull parametric model needs to be applied. The objective of this study is to develop and evaluate the Weibull parametric model for EC patients’ survival analysis.MethodsTraining (n = 411) and testing (n = 80) datasets from EC patients were retrospectively collected to investigate this problem. To determine the optimal CPH model from the training dataset, a bi-level model selection with minimax concave penalty was applied to select clinical and radiomic features which were obtained from T2-weighted MRI images. After the CPH model was built, model diagnostic was carried out to evaluate the proportional hazard assumption with Schoenfeld test. Survival data were fitted into a Weibull model and hazard ratio (HR) and ETR were calculated from the model. Brier score and time-dependent area under the receiver operating characteristic curve (AUC) were compared between CPH and Weibull models. Goodness of the fit was measured with Kolmogorov-Smirnov (KS) statistic.ResultsAlthough the proportional hazard assumption holds for fitting EC survival data, the linearity of the model assumption is suspicious as there are trends in the age and cancer grade predictors. The result also showed that there was a significant relation between the EC survival data and the Weibull distribution. Finally, it showed that Weibull model has a larger AUC value than CPH model in general, and it also has smaller Brier score value for EC survival prediction using both training and testing datasets, suggesting that it is more accurate to use the Weibull model for EC survival analysis.ConclusionsThe Weibull parametric model for EC survival analysis allows simultaneous characterization of the treatment effect in terms of the hazard ratio and the event time ratio (ETR), which is likely to be better understood. This method can be extended to study progression free survival and disease specific survival.Trial registrationClinicalTrials.gov NCT03543215,https://clinicaltrials.gov/, date of registration: 30th June 2017.
Safety analysis of Oseltamivir and Baloxavir Marboxil after market approval: a pharmacovigilance study based on the FDA adverse event reporting system
Authors: Li Yunsong , Wang Xiaoling , Liao Yufang , Zeng Yanbin , Lin Wanlong , Zhuang Wei 
Published: May 2024

Abstract
Background and objectives
Amidst limited influenza treatment options, evaluating the safety of Oseltamivir and Baloxavir Marboxil is crucial, particularly given their comparable efficacy. This study investigates post-market safety profiles, exploring adverse events (AEs) and their drug associations to provide essential clinical references.

Methods
A meticulous analysis of FDA Adverse Event Reporting System (FAERS) data spanning the first quarter of 2004 to the fourth quarter of 2022 was conducted. Using data mining techniques like reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multiple Gamma Poisson Shrinkage, AEs related to Oseltamivir and Baloxavir Marboxil were examined. Venn analysis compared and selected specific AEs associated with each drug.

Results
Incorporating 15,104 Oseltamivir cases and 1,594 Baloxavir Marboxil cases, Wain analysis unveiled 21 common AEs across neurological, psychiatric, gastrointestinal, dermatological, respiratory, and infectious domains. Oseltamivir exhibited 221 significantly specific AEs, including appendicolith [ROR (95% CI), 459.53 (340.88 ∼ 619.47)], acne infantile [ROR (95% CI, 368.65 (118.89 ∼ 1143.09)], acute macular neuroretinopathy [ROR (95% CI), 294.92 (97.88 ∼ 888.64)], proctitis [ROR (95% CI), 245.74 (101.47 ∼ 595.31)], and Purpura senile [ROR (95% CI), 154.02 (81.96 ∼ 289.43)]. designated adverse events (DMEs) associated with Oseltamivir included fulminant hepatitis [ROR (95% CI), 12.12 (8.30-17.72), n=27], ventricular fibrillation [ROR (95% CI), 7.68 (6.01–9.83), n=64], toxic epidermal necrolysis [ROR (95% CI), 7.21 (5.74–9.05), n=75]. Baloxavir Marboxil exhibited 34 specific AEs, including Melaena [ROR (95% CI), 21.34 (14.15–32.18), n = 23], cystitis haemorrhagic [ROR (95% CI), 20.22 (7.57-54.00), n = 4], ileus paralytic [ROR (95% CI), 18.57 (5.98–57.71), n = 3], and haemorrhagic diathesis [ROR (95% CI), 16.86 (5.43–52.40)), n = 3]. DMEs associated with Baloxavir Marboxil included rhabdomyolysis [ROR (95% CI), 15.50 (10.53 ∼ 22.80), n = 26].

Conclusion
Monitoring fulminant hepatitis during Oseltamivir treatment, especially in patients with liver-related diseases, is crucial. Oseltamivir’s potential to induce abnormal behavior, especially in adolescents, necessitates special attention. Baloxavir Marboxil, with lower hepatic toxicity, emerges as a potential alternative for patients with liver diseases. During Baloxavir Marboxil treatment, focused attention on the occurrence of rhabdomyolysis is advised, necessitating timely monitoring of relevant indicators for those with clinical manifestations. The comprehensive data aims to provide valuable insights for clinicians and healthcare practitioners, facilitating an understanding of the safety profiles of these influenza treatments in real-world scenarios.
Improvement effects of transplanting pancreatic islet that previously incubated with biomaterials on the diabetic nephropathy in STZ- diabetic rats
Authors: Nemati Marzieh , Hosseinzadeh Zahra , Nemati Fatemeh , Koohpeyma Farhad 
Published: May 2024

Abstract
Background
Islet transplantation is an effective treatment for diabetes or even its complications. Aim of this study is to investigate efficacy of biomaterial treated islet transplantation on treating diabetic nephropathy.

Methods
Male rats were randomly divided into 6 groups; Control, diabetic control, diabetic transplanted with untreated islets, with platelet rich plasma treated islets, with pancreatic islets homogenate treated islets, or with these biomaterials combination treated islets. Islets cultured with biomaterials and transplanted to diabetic rats. After 60 days, biochemical, oxidative stress, and stereological parameters were assessed.

Results
Serum albumin and BUN concentration, decreased and increased respectively, Oxidative stress of kidney impaired, kidney weight, volume of kidney, cortex, medulla, glomerulus, proximal and distal tubules, collecting ducts, vessels, inflammatory, necrotic and fibrotic tissue in diabetic group increased compared to control group (p < 0.001). In treated groups, especially pancreatic islets homogenate treated islets transplanting animals, there was significant changes in kidney weight, and volume of kidney, proximal and distal tubules, Henle’s loop and collecting ducts compared with diabetic group (p = 0.013 to p < 0.001). Combination treated islets animals showed significant increase in vessel volume compared to diabetic group (p < 0.001). Necrotic and fibrotic tissue significantly decreased in islets treated than untreated islet animals, it was higher in pancreatic islets homogenate, and combination treated islets groups (p = 0.001).

Conclusions
Biomaterials treated islets transplanting could improve diabetic nephropathy. Improvement of oxidative stress followed by controlling glucose level, and effects of growth factors presenting in biomaterials can be considered as capable underlying mechanism of ameliorating inflammatory, necrotic and fibrotic tissue volume.
Delivering the diagnosis of multiple system atrophy: a multicenter survey on Japanese neurologists’ perspectives
Authors: Yoshitake Miki , Sugiyama Atsuhiko , Shimohata Takayoshi , Araki Nobuyuki , Suzuki Masahide , Shibuya Kazumoto , Nagashima Kengo , Hattori Nobutaka , Kuwabara Satoshi 
Published: May 2024

Abstract
Background
Multiple system atrophy (MSA) is a progressive, incurable, life-threatening neurodegenerative disease uniquely characterized by the risk of sudden death, which makes diagnosis delivery challenging for neurologists. Empirical studies on breaking a diagnosis of MSA are scarce, with no guidelines currently established. This study aimed to investigate neurologists’ current practices and experiences in delivering the diagnosis of MSA.

Methods
We conducted a multicenter online survey and employed a mixed-methods (quantitative and qualitative) study design in which responses to open-ended questions were analyzed qualitatively using critical incident technique.

Results
Among the 194 neurologists surveyed, 166 opened the survey (response rate = 85.6%), of whom 144 respondents across various Japanese regions completed the survey. Accordingly, 92.3% and 82.8% of the participating neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, respectively. Factors independently associated with difficulties in diagnosis delivery included explaining the importance of the family decision making process in life-prolonging treatment, perceived difficulties in delivering information regarding the risk of sudden death, and perceived difficulties in differential diagnosis of MSA.

Conclusions
Our findings showed that the majority of neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, which could have been associated with the difficulty of breaking the diagnosis of MSA. Difficulty in conveying bad news in MSA are caused by various factors, such as empathic burden on neurologists caused by the progressive and incurable nature of MSA, the need to explain complex and important details, including the importance of the family decision-making process in life-prolonging treatment, difficulty of MSA diagnosis, and communication barriers posed by mental status and cognitive impairment in patients or their family members. Neurologists consider various factors in explaining the risk of sudden death (e.g., patient’s personality, mental state, and degree of acceptance and understanding) and adjust their manner of communication, such as limiting their communication on such matters or avoiding the use of the term “sudden death” in the early stages of the disease. Although neurologists endeavor to meet the basic standards of good practice, there is room for the multiple aspects for improvement.
Relationship between static and dynamic balance in 4-to-5-year-old preschoolers: a cross-sectional study
Authors: Liu Ruqiang , Yang Juan , Xi Feifei , Xu Zichun 
Published: May 2024

Abstract
Background
Balance is crucial for physical development in preschool children. Exploring the relationship between different types of balance can help understand early physical development in children. Currently, research is mostly focused on the relationship between different types of balance in the adult population and lacks exploration of the preschool population. The aim of this study explored the relationship between static and dynamic balance in preschool children aged 4 to 5 years.

Methods
A total of 128 preschool children between the ages of 4 to 5 years were selected. The following tests were conducted as they wore inertial sensors detecting their centers of mass (COM): T1, standing with eyes open; T2, standing with eyes closed; T3, standing with eyes open on foam; T4, standing with eyes closed on foam; and T5, walking on the balance beam. Static balance was measured by the angular velocity modulus (ω−T1–ω−T4) of the shaking COM, as well as the pitch angle (θ−T1–θ−T4) and roll angle (φ−T1–φ−T4) indicators in T1–T4 testing. Dynamic balance was measured by the time (t) and angular velocity modulus (ω−T5), as well as the pitch angle (θ−T5) and roll angle (φ−T5) indicators in the T5 test. The Pearson product-moment correlation coefficient was used to test the correlation between static and dynamic balance indicators.

Results
There is no correlation between ω−T1–ω−T4 and t (P > 0.05), while ω−T1–ω−T4 and ω−T5 (r = 0.19–0.27, P < 0.05) and ω−T1–ω−T4 and θ−T5, φ−T5 (r = 0.18–0.33, P < 0.05) were weakly correlated. There is no correlation between θ−T1–θ−T4, φ−T1–φ−T4 and t (P > 0.05), while θ−T1–θ−T4, φ−T1–φ−T4, and θ−T5, φ−T5 were weakly correlated (r = 0.01–0.28, P < 0.05).

Conclusions
The relationship between static and dynamic balance in preschool children aged 4–5 years is weak. Static and dynamic balance in children needs to be intervened separately for the development of children.
Effects of an early transfer from incubator to a warming crib in very low birthweight preterm infants
Authors: Greve Sandra , Bruns Nora , Dathe Anne-Kathrin , Schuendeln Michael M. , Felderhoff-Mueser Ursula , Stein Anja 
Published: May 2024

Abstract
Purpose
Very low birth weight infants are cared for postnatally in the incubator because of adverse consequences of hypothermia. Data on the optimal weight of transfer to a warming crib are rare. The aim of this study was to determine the course of temperature and body weight during a standardized transfer to a warming crib at a set weight.

Methods
Prospective intervention study in very low birthweight infants who were transferred from the incubator to a warming crib at a current weight between 1500 g and 1650 g.

Results
No infant had to be transferred back to an incubator. Length of hospital stay was equal compared to a historical cohort from the two years directly before the intervention. The intervention group showed an increase in the volume fed orally on the day after transfer to the warming crib, although this did not translate into an earlier discontinuation of gavage feedings. Compared to the historical group, infants in the intervention group could be transferred to an unheated crib at an earlier postmenstrual age and weight.

Conclusions
Early transfer from the incubator to a warming crib between 1500 g and 1650 g is feasible and not associated with adverse short-term events or outcomes.

Trial registration
DRKS-IDDRKS00031832.
Multiple obesity indices suggest a close relationship between obesity and constipation: evidence from NHANES
Authors: Xiang Nengjun , Xu Lulu , Qian Haihua , Zhang Dan 
Published: May 2024

Abstract
Objective
This study aims to investigate the relationship between obesity and constipation among American adults.

Methods
Our study leveraged data from the National Health and Nutrition Examination Survey (NHANES). This comprehensive approach enabled us to summarize the weighted prevalence rates of obesity in adults. To further deepen our understanding, we employed a variety of analytical methods. These included multivariable logistic regression, subgroup analysis and restricted cubic splines. Through these methodologies, we were able to effectively evaluate the correlation between various obesity indicators and constipation, offering new insights into this complex relationship.

Results
The weighted prevalence of constipation stands at 9.42%. Notably, an increased risk of constipation is linked with a BMI (body mass index) exceeding 28 kg/m2, WSR (waist-stature ratio) that is either between 58.3 and 64.8 or above 64.8, as well as a LAP (lipid accumulation products) ranging from 50.8 to 90.1. In contrast, a reduced risk of constipation is associated with WWI (weight-adjusted-waist index) that falls between 0.015 and 0.020, exceeds 0.020, and without the presence of central obesity (P < 0.05). Restricted cubic spline analysis, a significant non-linear relationship was discerned between BMI, WSR, and LAP in relation to constipation.

Conclusions
This pioneering large-scale study explores the relationship between various obesity indices and constipation. It reveals that reducing the BMI, WSR, LAP and waist circumference can decrease the risk of constipation. Conversely, a higher value of WWI correlates with a lower constipation risk, and this remains true even after adjusting for a wide range of variables.
Hepatitis B virus infection among illegal drug users in Enugu State, Nigeria: prevalence, immune status, and related risk factors
Authors: Orabueze Ibuchukwu N , Ike Anthony C , Aniche Oluchi M , Nwafia Ifeyinwa N , Ebede Samuel O 
Published: May 2024

Abstract
Introduction
Hepatitis B virus infection poses a global health challenge, particularly in low- and middle-income African countries. Illicit drug use exacerbates the problem, with drug users having a higher HBV infection risk and maintaining a quiet transmission pool. This study aimed to determine HBV infection prevalence, immune status, and risk factors among illegal drug users in Enugu State, Nigeria.

Materials and methods
A cross-sectional study was conducted in Enugu State, using privileged access interviewer methods to enroll drug users. Pre-tested structured questionnaires were administered after informed consent was obtained. Blood samples were tested for HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb using immunochromatographic rapid test kits. Statistical analysis was performed using SPSS version 25.

Results
One hundred drug users were recruited into the study. Overall, 7% of the drug users had HBV infection. 61% were found to be susceptible to HBV infection, 15% showed serological evidence of immunity from HBV vaccination and 1% developed natural immunity from HBV exposure. Significant risk factors for HBV infection were age less than 20 years, young age (≤ 20 years) at drug initiation, being single, injecting drugs more than or equal to 20 times per month and injecting with used syringes.

Conclusion
This study shows high intermediate endemicity of HBV infection among drug users, low vaccination uptake, and high susceptibility to HBV infection. This calls for the urgent inclusion of drug users in national HBV vaccination campaigns and the adoption of the World Health Organization’s recommendations on the prevention of viral hepatitis among people who inject drugs.
Diabetes, life course and childhood socioeconomic conditions: an empirical assessment for Mexico
Authors: Gonzalez-Samano Marina , Villarreal Hector J. 
Published: May 2024

Abstract
Background
Demographic and epidemiological dynamics characterized by lower fertility rates and longer life expectancy, as well as higher prevalence of non-communicable diseases such as diabetes, represent important challenges for policy makers around the World. We investigate the risk factors that influence the diagnosis of diabetes in the Mexican population aged 50 years and over, including childhood poverty.

Results
This work employs a probabilistic regression model with information from the Mexican Health and Aging Study (MHAS) of 2012 and 2018. Our results are consistent with the existing literature and should raise strong concerns. The findings suggest that risk factors that favor the diagnosis of diabetes in adulthood are: age, family antecedents of diabetes, obesity, and socioeconomic conditions during both adulthood and childhood.

Conclusions
Poverty conditions before the age 10, with inter-temporal poverty implications, are associated with a higher probability of being diagnosed with diabetes when older and pose extraordinary policy challenges.
Short-term and long-term outcomes after robotic radical surgery for rectal gastrointestinal stromal tumor
Authors: Maeda Chikara , Yamaoka Yusuke , Shiomi Akio , Kagawa Hiroyasu , Hino Hitoshi , Manabe Shoichi , Kai Chen , Nanishi Kenji 
Published: May 2024

Abstract
Background
The optimal approach for ensuring both complete resection and preservation of anal function in rectal gastrointestinal stromal tumor (GIST) remains unknown. The aim of this study was to clarify short-term and long-term outcomes after robotic radical surgery for rectal GIST.

Methods
A total of 13 patients who underwent robotic radical surgery for rectal GIST between December 2011 and April 2022 were included. All robotic procedures were performed using a systematic approach. A supplemental video of robotic radical surgery for rectal GIST is attached. The short-term outcome was the incidence of postoperative complications during the first 30 days after surgery. Surgical outcomes were retrieved from a prospective database. Long-term outcomes, including overall survival and recurrence-free survival, were determined in all patients.

Results
Median distance from the tumor to the anal verge was 4.0 cm. Surgical margins were negative in all patients. Two patients underwent neoadjuvant imatinib therapy. All patients underwent sphincter-preserving surgery. None underwent conversion to open or laparoscopic surgery. The incidence of postoperative Clavien-Dindo grade II and grade ≥ III complications was 7.7% and 0%, respectively. The median postoperative hospital stay was 7 days. Twelve patients (92.3%) underwent stoma closure within 5 months of the initial surgery. Median follow-up time was 76 months. The 5-year overall survival and recurrence-free survival rates were both 100%. None of the patients had recurrence.

Conclusion
Short-term and long-term outcomes after radical robotic surgery for rectal GIST were favorable. Robotic surgery might be a useful surgical approach for rectal GIST.