bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning the deuteron: new architectures and uncertainty quantification
Authors: Rozalén Sarmiento J. , Keeble J. W. T. , Rios A. 
Published: February 2024

AbstractWe solve the ground state of the deuteron using a variational neural network ansatz for the wavefunction in momentum space. This ansatz provides a flexible representation of both the S and the D states, with relative errors in the energy which are within fractions of a per cent of a full diagonalisation benchmark. We extend the previous work on this area in two directions. First, we study new architectures by adding more layers to the network and by exploring different connections between the states. Second, we provide a better estimate of the numerical uncertainty by taking into account the final oscillations at the end of the minimisation process. Overall, we find that the best performing architecture is the simple one-layer, state-connected network. Two-layer networks show indications of overfitting, in regions that are not probed by the fixed momentum basis where calculations are performed. In all cases, the errors associated to the model oscillations around the real minimum are larger than the stochastic initilization uncertainties.
Data Complexity: A New Perspective for Analyzing the Difficulty of Defect Prediction Tasks
Authors: Wan Xiaohui , Zheng Zheng , Qin Fangyun , Lu Xuhui 
Published: February 2024

Defect prediction is crucial for software quality assurance and has been extensively researched over recent decades. However, prior studies rarely focus on data complexity in defect prediction tasks, and even less on understanding the difficulties of these tasks from the perspective of data complexity. In this article, we conduct an empirical study to estimate the hardness of over 33,000 instances, employing a set of measures to characterize the inherent difficulty of instances and the characteristics of defect datasets. Our findings indicate that: (1) instance hardness in both classes displays a right-skewed distribution, with the defective class exhibiting a more scattered distribution; (2) class overlap is the primary factor influencing instance hardness and can be characterized through feature, structural, and instance-level overlap; (3) no universal preprocessing technique is applicable to all datasets, and it may not consistently reduce data complexity, fortunately, dataset complexity measures can help identify suitable techniques for specific datasets; (4) integrating data complexity information into the learning process can enhance an algorithm’s learning capacity. In summary, this empirical study highlights the crucial role of data complexity in defect prediction tasks, and provides a novel perspective for advancing research in defect prediction techniques.
Cadonilimab Combined with Chemotherapy with or without Bevacizumab as First-Line Treatment in Recurrent or Metastatic Cervical Cancer (COMPASSION-13): A Phase 2 Study
Authors: Lou Hanmei , Cai Hongbing , Huang Xin , Li Guiling , Wang Li , Liu Fei , Qin Wenjing , Liu Ting , Liu Wei , Wang Zhongmin Maxwell , Li Baiyong , Xia Yu , Wang Jing 
Published: February 2024

Abstract

Purpose:
Immune checkpoint inhibitors (ICI) have been a potential treatment option for patients with cervical cancer in several clinical studies. We investigated the safety and efficacy of cadonilimab, a bispecific antibody targeting PD-1 and CTLA-4, plus standard therapy for the first-line treatment of R/M CC (recurrent and/or metastatic cervical cancer).

Patients and Methods:
Eligible patients were assigned to 3 cohorts: cohort A-15 (cadonilimab 15 mg/kg every 3 weeks (Q3W) plus chemotherapy), cohort A-10 (cadonilimb 10 mg/kg Q3W plus chemotherapy), and cohort B-10 (cadonilimab 10 mg/kg Q3W plus chemotherapy and bevacizumab). They received the corresponding treatments until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. The primary objective was safety; the secondary endpoints included objective overall response (ORR), duration of response, disease control rate, progression-free survival, and overall survival. This study is registered with ClinicalTrials.gov (NCT04868708).

Results:
As of February 13, 2023, treatment-related adverse events (TRAE) occurred in 45 (100.0%) patients. Grade ≥3 TRAEs were reported in 33 (73.3%) patients. Immune-related adverse events (irAE) occurred in 29 (64.4%) patients and grade ≥3 irAEs were observed in 9 (20.0%) patients. Seven (15.6%) of 45 patients permanently discontinued cadonilimab treatment due to TRAEs. One death due to hemorrhagic shock occurred in cohort B-10. Among 44 patients who underwent at least one post-baseline tumor assessment, the ORR was 66.7% in cohort A-15, 68.8% in cohort A-10, 92.3% in cohort B-10, and 79.3% in cohorts A-10 and B-10 combined.

Conclusions:
Cadonilimab combined with standard therapy was acceptable, with encouraging antitumor activity in patients with R/M CC.
Intratumoral TREX1 Induction Promotes Immune Evasion by Limiting Type I IFN
Authors: Toufektchan Eléonore , Dananberg Alexandra , Striepen Josefine , Hickling James H. , Shim Abraham , Chen Yanyang , Nichols Ashley , Duran Paez Mercedes A. , Mohr Lisa , Bakhoum Samuel F. , Maciejowski John 
Published: February 2024

Abstract
Chromosomal instability is a hallmark of human cancer that is associated with aggressive disease characteristics. Chromosome mis-segregations help fuel natural selection, but they risk provoking a cGAS-STING immune response through the accumulation of cytosolic DNA. The mechanisms of how tumors benefit from chromosomal instability while mitigating associated risks, such as enhanced immune surveillance, are poorly understood. Here, we identify cGAS-STING–dependent upregulation of the nuclease TREX1 as an adaptive, negative feedback mechanism that promotes immune evasion through digestion of cytosolic DNA. TREX1 loss diminishes tumor growth, prolongs survival of host animals, increases tumor immune infiltration, and potentiates response to immune checkpoint blockade selectively in tumors capable of mounting a type I IFN response downstream of STING. Together, these data demonstrate that TREX1 induction shields chromosomally unstable tumors from immune surveillance by dampening type I IFN production and suggest that TREX1 inhibitors might be used to selectively target tumors that have retained the inherent ability to mount an IFN response downstream of STING.
See related article by Lim et al., p. 663
Unearthing calf burials among Asian Elephants Elephas maximus Linnaeus, 1758 (Mammalia: Proboscidea: Elephantidae) in northern Bengal, India
Authors: Kaswan Parveen , Roy Akashdeep 
Published: February 2024

Rampant environmental changes and forest destruction push elephants, both Asian and African, to explore human spaces to fulfil their dietary and ecological requirements and, consequently in shared spaces many ‘novel’ elephant behaviors come into the limelight. Elephant calf burial is reported in African literature but remains absent from the Asian context. We report calf burials by Asian Elephants in the eastern Himalayan floodplains of the northern Bengal landscape. The study area consists of fragmented forests, tea estates, agricultural lands, and military establishments. Tea estates form the majority of elephant corridors, and we explain the burial strategy of elephants in the irrigation drains of tea estates. We present five case reports of calf burials by elephants. We aimed to understand the perimortem strategy and postmortem behavior of the Asian Elephants. The major findings reflect that the carcasses were carried by trunks and legs for a distance before being buried in a ‘legs-upright-position’. We further investigated the underlying reason for calf deaths through postmortem examinations. Direct human intervention was not recorded in any of the five deaths. Through opportunistic observation, digital photography, fieldnotes, and postmortem examination reports, we suggest that the carcasses were buried in an abnormal recumbent style irrespective of the reason for the calf’s death. Through long-term observation, we further report that the elephants in this region clearly avoid the paths where carcasses were buried. We discuss and connect the literature of two distinct elephant species and also compare thanatological studies of other sentient nonhuman species.
Fortune in Exile: William Rotch, 1775–1805
Authors: Crabtree Sarah 
Published: February 2024

Abstract
Three governments in two decades (1775-1795) accused Quaker William Rotch of disloyalty, interpreting his pacifist universalism as political subversion. Yet his merchant vocation also inspired his cosmopolitanism and infuriated his opponents. Both stories are necessary for a full portrait of the man and a complete understanding of the historical moment.
Bridging New Observational Capabilities and Process-Level Simulation: Insights into Aerosol Roles in the Earth System
Authors: Mei Fan , Wang Hailong , Zhu Zihua , Zhang Damao , Zhang Qi , Fast Jerome D. , Gustafson William I. , Li Xiang-Yu , Schmid Beat , Niedek Christopher , Tomlinson Jason , Flynn Connor 
Published: February 2024

Abstract
The spatial distribution of ambient aerosol particles significantly impacts aerosol–radiation–cloud interactions, which contribute to the largest uncertainty in global anthropogenic radiative forcing estimations. However, the atmospheric boundary layer and lower free troposphere have not been adequately sampled in terms of spatiotemporal resolution, hindering a comprehensive characterization of various atmospheric processes and impeding our understanding of the Earth system. To address this research data gap, we have leveraged the development of uncrewed aerial systems (UAS) and advanced measurement techniques to obtain mesoscale spatial data on aerosol microphysical and optical properties around the U.S. Southern Great Plains (SGP) atmospheric observatory. Our study also benefits from state-of-the-art laboratory facilities that include three-dimensional molecular imaging techniques enabled by secondary ion mass spectrometry and nanogram-level chemical composition analysis via micronebulization aerosol mass spectrometry. Through our study, we have developed a framework for observation–modeling integration, enabling an examination of how various assumptions about the organic–inorganic components mixing state, inferred from chemical analysis, affect clouds and radiation in observation-constrained model simulations. By integrating observational constraints (derived from offline chemical analysis of the aerosol surface using collected samples) with in situ UAS observations, we have identified a prominent role of organic-enriched nanometer layers located at the surface of aerosol particles in determining profiles of aerosol optical and hygroscopic properties over the SGP observatory. Furthermore, we have improved the agreement between predicted clouds and ground-based cloud lidar measurements. This UAS–model–laboratory integration exemplifies how these new advanced capabilities can significantly enhance our understanding of aerosol–radiation–cloud interactions.
Anthropogenic Influence on 2022 June Extreme Rainfall over the Pearl River Basin
Authors: Liu Xinru , Jie Hang , Zou Yulin , Liu Shengjun , Hu Yamin , Liu Shuyi , Yang Dangfu , Zhao Liang , He Jian 
Published: February 2024

Abstract
According to HadGEM3 (CMIP6) models, anthropogenic forcing reduced the probability of 2022-like June mean precipitation by about 32% (15%) and increased 5-day rainfall extreme probability by about 1.8 (1.3) times.
Influence of Maternal Dietary Pattern on the Pro-Oxidant and Antioxidant Status of Mother’s Own Milk
Authors: Silva Racire Sampaio , Vasconcelos Christiane Mileib , Pessoa Iana Soares , Santos Tamires Cruz dos , Scherer Rodrigo , Endringer Denise Coutinho , Fronza Marcio 
Published: February 2024

Background: Human milk is essential for a child’s best development. However, what a mother eats while breastfeeding can directly influence the composition of mother’s milk. Research Aim: This study aimed to assess the antioxidant-oxidant profile of human milk and establish a connection between this profile and the dietary habits of the mothers. Methods: A cross-sectional study was conducted at the Hospital Infantil e Maternidade Alzir Bernardino Alves (HIMABA), located in the municipality of Vila Velha-ES, Brazil. The sample included 98 participants. All volunteers completed a structured interview and a Food Frequency Questionnaire. Approximately 5–10 ml of colostrum, transitional milk, and mature milk were manually collected. The antioxidant activity of human milk was assessed using the colorimetric method for free radical scavenging with 2,2’-azinobis-3-ethylbenzothiazoline-6-sulfonic acid. Oxidative stress was determined by measuring lipid peroxidation through malondialdehyde concentration, evaluating advanced oxidation protein products, and assessing total protein content using the Bradford method. Results: The antioxidant profile of colostrum was higher than that observed in later phases of milk, whereas pro-oxidants increased in later phases. Maternal dietary patterns influenced the pro-oxidant status of human milk. Participants with a higher daily intake of milk, dairy products, vegetable oils, olive oils, and legumes exhibited lower levels of lipid peroxidation in colostrum, transition milk, and mature milk, respectively. Conclusions: Our study highlights the vital role of a balanced maternal diet in shaping the pro-oxidant status of human milk, with implications for infant health.
Safety Profile of Selective Serotonin Reuptake Inhibitors in Real-World Settings: A Pharmacovigilance Study Based on FDA Adverse Event Reporting System
Authors: Zhao Yi , Zhang Yuzhou , Yang Lin , Zhang Kanghuai , Li Sha 
Published: February 2024

Background: Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed agents to treat depression. Considering the growth in antidepressant prescription rates, SSRI-induced adverse events (AEs) need to be comprehensively clarified. Objective: This study was to investigate safety profiles and potential AEs associated with SSRIs using the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: A retrospective pharmacovigilance analysis was conducted using the FAERS database, with Open Vigil 2.1 used for data extraction. The study included cases from the marketing date of each SSRI (ie, citalopram, escitalopram, fluoxetine, paroxetine, fluvoxamine, and sertraline) to April 30, 2023. We employed the reporting odds ratio and Bayesian confidence propagation neural network as analytical tools to assess the association between SSRIs and AEs. The Medical Dictionary for Regulatory Activities was used to standardize the definition of AEs. AE classification was achieved using system organ classes (SOCs). Results: Overall, 427 655 AE reports were identified for the 6 SSRIs, primarily associated with 25 SOCs, including psychiatric, nervous system, congenital, familial, genetic, cardiac, and reproductive disorders. Notably, sertraline ( n = 967) and fluvoxamine ( n = 169) exhibited the highest and lowest signal frequencies, respectively. All SSRIs had relatively strong signals related to congenital, psychiatric, and nervous disorders. Conclusions and relevance: Most of our findings are consistent with those reported previously, but some AEs were not previously identified. However, AEs attributed to SSRIs remain ambiguous, warranting further validation. Applying data-mining methods to the FAERS database can provide additional insights that can assist in appropriately utilizing SSRIs.
An unusual ophthalmologic finding in a patient with congenital central hypoventilation syndrome
Authors: Aguado-Casanova Víctor , Pérez-García Diana , Orejudo-Rivas Marta , Ramiro-Millán Patricia , Ibañez-Alperte Juan , Calvo-Simon Cristina , Remón Leon 
Published: February 2024

Introduction Congenital Central Hypoventilation Syndrome (CCHS) is a rare disease due to a severely impaired central control of breathing and dysfunction of the autonomic nervous system. Ophthalmologic abnormalities are common in patients with CCHS and include horizontal strabismus, pupil and iris abnormalities and ptosis. We report a unique case of CCHS in association with monocular elevation deficit (MED) in a boy diagnosed with CCHS at birth. Case description We report a case of a boy with a confirmed diagnosis of CCHS (complete sequencing of the paired-like homeobox 2b (PHOX2B) gene) after presenting little respiratory effort and cyanosis at birth. The ophthalmological examination shows an impaired elevation of the left eye, both in adduction and abduction, associated with mild and variable left ptosis. His mother has observed that the left eyelid elevates when the child feeds. A deviation in the primary gaze position or a chin-up position are not present. The funduscopic examination is normal. Given that deviation is limited to upgaze, the ptosis is mild and the patient's age, observation is decided. Conclusions Ophthalmologic abnormalities are common in patients with CCHS and include horizontal strabismus, pupil and iris abnormalities and ptosis. To the best of our knowledge, this is the first report of MED in association with CCHS. Further studies are needed to determine if an association between MED and CCHS exists or is just a casual finding in this case.
Long-term clinical outcomes in patients with multiple sclerosis who are initiating disease-modifying therapy with natalizumab compared with BRACETD first-line therapies
Authors: Butzkueven Helmut , Kalincik Tomas , Patti Francesco , Slee Mark , Weinstock-Guttman Bianca , Buzzard Katherine , Skibina Olga , Alroughani Raed , Prat Alexandre , Girard Marc , Horakova Dana , Havrdova Eva Kubala , Van der Walt Anneke , Eichau Sara , Hyde Robert , Campbell Nolan , Bodhinathan Karthik , Spelman Tim ,   MSBase Investigators
Published: February 2024

Background: Aggressive disease control soon after multiple sclerosis (MS) diagnosis may prevent irreversible neurological damage, and therefore early initiation of a high-efficacy disease-modifying therapy (DMT) is of clinical relevance. Objectives: Evaluate long-term clinical outcomes in patients with MS who initiated treatment with either natalizumab or a BRACETD therapy (interferon beta, glatiramer acetate, teriflunomide, or dimethyl fumarate). Design: This retrospective analysis utilized data from MSBase to create a matched population allowing comparison of first-line natalizumab to first-line BRACETD. Methods: This study included patients who initiated treatment either with natalizumab or a BRACETD DMT within 1 year of MS diagnosis and continued treatment for ⩾6 months, after which patients could switch DMTs or discontinue treatment. Patients had a minimum follow-up time of ⩾60 months from initiation. A subgroup analysis compared the natalizumab group to patients in the BRACETD group who escalated therapy after 6 months. Outcomes included unadjusted annualized relapse rates (ARRs), time-to-first relapse, time-to-first confirmed disability improvement (CDI), and time-to-first confirmed disability worsening (CDW). Results: After 1:1 propensity score matching, 355 BRACETD patients were matched to 355 natalizumab patients. Patients initiating natalizumab were less likely to experience a relapse over the duration of follow-up, with ARRs [95% confidence interval (CI)] of 0.080 (0.070–0.092) for natalizumab patients and 0.191 (0.178–0.205) for BRACETD patients ( p < 0.0001). A Cox regression model of time-to-first relapse showed a reduced risk of relapse for natalizumab patients [hazard ratio (95% CI) of 0.52 (0.42–0.65); p < 0.001] and a more favorable time-to-first CDI. The risk of CDW was similar between groups. The subgroup analysis showed an increased relapse risk as well as a significantly higher risk of CDW for BRACETD patients. Conclusion: Early initiation of natalizumab produced long-term benefits in relapse outcomes in comparison with BRACETD, regardless of a subsequent escalation in therapy.
Ethnomedicinal, Phytochemical, and Pharmacological Properties of Diospyros mollis Griff.: A Review
Authors: Chen Tran Van , Nghia Nguyen Trong , Nhat Truong Le Van , Khanh Linh Nguyen Hoang 
Published: February 2024

Objective/Background The genus Diospyros L. (Ebenaceae) includes about 778 species worldwide, with over 500 of them known for their significant health benefits. Among them, Diospyros mollis Griff. has been used as a tonic and treatment for many diseases related to digestive disorders and intestinal parasites. Furthermore, the fruit has also been used for dyeing silk fabrics. The purpose of this comprehensive review is to provide researchers with important information about D. mollis, particularly regarding its chemical composition and biological effects. This information can support current understanding and future studies to develop novel herbal formulations based on this species. Additionally, this review aims to compile and summarize the available literature on this species, covering its botanical, ethnomedicinal, phytochemical, and pharmacological properties reported to date. Methods The relevant information on D. mollis was collected via online electronic and databases, including Scopus, Pubmed, Web of Science, Google Scholar, ScienceDirect, Springer Link, SciFinder, and other scientific databases. Results A comprehensive review of the literature reveals that D. mollis contains various chemical constituents such as naphthalene and naphthoquinone derivatives, triterpenoids, alkaloids, sterols, glycosides, and fatty acid esters isolated from the berry, root, bark, and leaf of this species, with several pharmacological effects and other applications. Many pharmacological effects, such as hyaluronidase inhibitory, anthelmintic, and antiparasitic activities of various extracts and isolated compounds of D. mollis, are reported in this review. The review demonstrates the importance of D. mollis in the treatment of diseases, its application in fabric dyeing techniques, and its traditional use. Conclusion In conclusion, D. mollis emerges as a promising botanical resource with its rich history in traditional medicine and diverse chemical constituents, paving the way for potential future applications and innovations in the field of herbal medicine and drug development.