bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nine-weeks versus one-year trastuzumab for early-stage HER2+ breast cancer: 10-year update of the Short-HER phase III randomized trial.
Authors: Conte Pier Franco , Bisagni Giancarlo , Piacentini Federico , Sarti Samanta , Minichillo Santino , Anselmi Elisa , Aieta Michele , Gebbia Vittorio , Schirone A , Musolino Antonino , Garrone Ornelia , Beano A , Rimanti Anita , Giotta Francesco , Turletti Anna , Dieci Maria Vittoria , Vicini Roberto , Balduzzi Sara , D'Amico R , Guarneri Valentina 
Published: June 2023

LBA637 Background: The ShortHER trial is a phase III non-inferiority, randomized trial comparing 9 weeks (short arm) versus 1 year (long arm) of adjuvant trastuzumab combined with chemotherapy in HER2+ eBC patients. The first primary end point of the study was the event-driven analysis of disease-free survival which was achieved in 2017, presented at ASCO 2017 and published in Annals of Oncology in 2018. The HR was 1.13 (90% CI 0.89-1.42) and the non-inferiority could not be claimed as the upper border of CI crossed the upper limit of 1.29 chosen as non-inferiority margin. According to a pre-planned Bayesian analysis, the probability that the short arm was not inferior to the standard one was 80%. Methods: 1254 HER2+ early breast cancer patients were stratified according to nodal status and randomized. Median age was 55 years (range 25-78); 672 (54%) patients were node negative, 383 (30%) with 1-3 positive nodes, 198 (16%) 4 or more positive nodes. At the time of the event-driven analysis, median follow up was 6 years, 200 DFS events and 78 deaths were reported. Here we report the overall survival,+ which was the second co-primary end point, updated DFS and outcomes according to nodal status. Results: Median follow-up is now 9 years, 248 DFS events and 116 deaths have been reported. The 10 year DFS is 77% in the long arm and 78% in the short arm (HR 1.06; 90% CI 0.86-1.31). The 10-year OS is 89% in the long arm and 88% in the short arm (HR 1.15; 90% CI 0.85-1.56). The DFS and OS data overall and by nodal status are summarized in the table below. Conclusions: At a median follow-up of 9 years, the ShortHER trial shows that 1 year trastuzumab is still the standard treatment for HER2+ eBC patients as non-inferiority cannot be claimed in terms of DFS or OS. Numerically however, the differences for the patients at low risk (N0) or intermediate risk (N 1-3) is negligible and patients with 4 or more positive lymph nodes have a clear benefit with 1 year trastuzumab. I. This long-term date can reassure clinicians if, for any reason a patient at low/intermediate risk has to stop trastuzumab and, more important, might facilitate access to a far less expensive treatment to the thousands of patients worldwide who cannot afford the cost of one year of trastuzumab. Clinical trial information: NCT00629278 . [Table: see text]
Beta-Blocker Use Is Associated With Worse Relapse-Free Survival in Patients With Head and Neck Cancer
Authors: Chen Hannah Y. , Zhao Weilu , Na'ara Shorook , Gleber-Netto Frederico O. , Xie Tongxin , Ali Shahrukh , Thompson Zachary M. , Buell Jane , Stafford Haleigh , Nagarajan Priyadharsini , Davies Michael , Wong Michael K. , Migden Michael R. , Sharma Padmanee , Myers Jeffrey N. , Gross Neil D. , Amit Moran 
Published: June 2023

PURPOSE Although beta-blockers (BBs) have been hypothesized to exert a beneficial effect on cancer survival through inhibition of beta-adrenergic signaling pathways, clinical data on this issue have been inconsistent. We investigated the impact of BBs on survival outcomes and efficacy of immunotherapy in patients with head and neck squamous cell carcinoma (HNSCC), non–small-cell lung cancer (NSCLC), melanoma, or squamous cell carcinoma of the skin (skin SCC), independent of comorbidity status or cancer treatment regimen. METHODS Patients (N = 4,192) younger than 65 years with HNSCC, NSCLC, melanoma, or skin SCC treated at MD Anderson Cancer Center from 2010 to 2021 were included. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were calculated. Kaplan-Meier and multivariate analyses adjusting for age, sex, TNM staging, comorbidities, and treatment modalities were performed to assess the effect of BBs on survival outcomes. RESULTS In patients with HNSCC (n = 682), BB use was associated with worse OS and DFS (OS: adjusted hazard ratio [aHR], 1.67; 95% CI, 1.06 to 2.62; P = .027; DFS: aHR, 1.67; 95% CI, 1.06 to 2.63; P = .027), with DSS trending to significance (DSS: aHR, 1.52; 95% CI, 0.96 to 2.41; P = .072). Negative effects of BBs were not observed in the patients with NSCLC (n = 2,037), melanoma (n = 1,331), or skin SCC (n = 123). Furthermore, decreased response to cancer treatment was observed in patients with HNSCC with BB use (aHR, 2.47; 95% CI, 1.14 to 5.38; P = .022). CONCLUSION The effect of BBs on cancer survival outcomes is heterogeneous and varies according to cancer type and immunotherapy status. In this study, BB intake was associated with worse DSS and DFS in patients with head and neck cancer not treated with immunotherapy, but not in patients with NSCLC or skin cancer.
Gift or Weapon? Reproductive Decision, the Phenomenology of Pregnancy, and Alien Language in Denis Villeneuve's Arrival
Authors: Morgenstern Naomi 
Published: June 2023

Abstract
This essay analyzes Denis Villeneuve's 2016 film, Arrival, and elucidates its strikingly original meditation on the ethics of reproduction and the relationships between and among embodied maternal subjectivity, language, and temporality. Drawing on deconstructive theories of language and relationality as well as on the writing of scholars working at the intersection of reproductive biology and feminist philosophy, the essay argues that Arrival uses some of the generic features of science fiction cinema (alien encounter and time travel) to articulate a feminist and posthumanist philosophy of relation and care. Focusing on the film's language of risk, danger, contamination, and even social disintegration, Arrival prompts us to consider how a particularly suggestive account of the maternal-fetal relationship, and of the process of fostering and becoming a relationally determined being, simultaneously engages with the fraught question of reproductive choice and reproductive justice in our contemporary moment. Meditating on the film's visual, sonic, and conceptual representations of the “placental wall” and of the “parasitical” structure of pregnancy, the essay shows how Arrival parallels feminist readings of the materiality of pregnancy that deconstruct the self-possessed or “virile” subject of patriarchal individualism.
Gastrostomy Sequence With Ventriculoperitoneal Shunting—Does It Matter?
Authors: Khalid Syed I. , Deysher Daniel , Khilwani Harsh , Mirpuri Pranav , Thomson Kyle , Maynard Marquis , Mehta Ankit I. 
Published: June 2023

BACKGROUND:
Neurological injury requiring ventriculoperitoneal shunt (VPS) placement often necessitates gastrostomy for nutritional support. The sequence of these procedures is debated over concerns for shunt infection and displacement requiring revisional surgery as a consequence of gastrostomy.

OBJECTIVE:
To determine the optimal sequence of VPS shunt and gastrostomy tube placement in adults.

METHODS:
In an all-payer database, adult patients undergoing gastrostomy and VPS placement were identified within 15 days between January 2010 and October 2021. Patients were categorized as receiving gastrostomy before, on the same day as, or after shunt placement. The primary outcomes of this study were rates of revision and infection. All outcomes were evaluated within 30 months after index shunting.

RESULTS:
In total, 3015 patients were identified as undergoing VPS and gastrostomy procedures within 15 days. After a 1:1:1 match, 1080 patient records were analyzed. Revision rates at 30 months were significantly lower among patients who received VPS and gastrostomy procedures on the same day compared with gastrostomy after VPS (odds ratio [OR] 0.61, 95% CI 0.39-0.96). In addition, patients who received gastrostomy before VPS compared with those after had lower revision rates (OR 0.61, 95% CI 0.39-0.96) and infection (OR 0.46, 95% CI 0.21-0.99). No significant differences were noted in mechanical complication or shunt displacement rates.

CONCLUSION:
Patients requiring VPS and gastrostomy may benefit from undergoing both procedures concurrently or with gastrostomy before VPS placement, secondary to lower revision rates. Patients undergoing gastrostomy before VPS have the added benefit of decreased infection rates.
DNA methylation dynamic in male rat germ cells during gametogenesis
Authors: El Omri-Charai Rhizlane , Gilbert Isabelle , Prunier Julien , Desmarais Rebecka , Ghinet Mariana Gabriela , Robert Claude , Boissonneault Guylain , Delbes Géraldine 
Published: June 2023

ABSTRACT
In mammals, a near complete resetting of DNA methylation (DNAme) is observed during germline establishment. This wave of epigenetic reprogramming is sensitive to the environment, which could impair the establishment of an optimal state of the gamete epigenome, hence proper embryo development. Yet, we lack a comprehensive understanding of DNAme dynamics during spermatogenesis, especially in rats, the model of choice for toxicological studies. Using a combination of cell sorting and DNA methyl-seq capture, we generated a stage-specific mapping of DNAme in nine populations of differentiating germ cells from perinatal life to spermiogenesis. DNAme was found to reach its lowest level at gestational day 18, the last demethylated coding regions being associated with negative regulation of cell movement. The following de novo DNAme displayed three different kinetics with common and distinct genomic enrichments, suggesting a non-random process. DNAme variations were also detected at key steps of chromatin remodeling during spermiogenesis, revealing potential sensitivity. These methylome datasets for coding sequences during normal spermatogenesis in rat provide an essential reference for studying epigenetic-related effects of disease or environmental factors on the male germline.
Muscle force–length dynamics during walking over obstacles indicates delayed recovery and a shift towards more ‘strut-like’ function in birds with proprioceptive deficit
Authors: Schwaner M. Janneke , Gordon Joanne C. , Biewener Andrew A. , Daley Monica A. 
Published: June 2023

ABSTRACT
Recent studies of in vivo muscle function in guinea fowl revealed that distal leg muscles rapidly modulate force and work to stabilize running in uneven terrain. Previous studies focused on running only, and it remains unclear how muscular mechanisms for stability differ between walking and running. Here, we investigated in vivo function of the lateral gastrocnemius (LG) during walking over obstacles. We compared muscle function in birds with intact (iLG) versus self-reinnervated LG (rLG). Self-reinnervation results in proprioceptive feedback deficit due to loss of monosynaptic stretch reflex. We tested the hypothesis that proprioceptive deficit results in decreased modulation of EMG activity in response to obstacle contact, and a delayed obstacle recovery compared with that for iLG. We found that total myoelectric intensity (Etot) of iLG increased by 68% in obstacle strides (S 0) compared with level terrain, suggesting a substantial reflex-mediated response. In contrast, Etot of rLG increased by 31% in S 0 strides compared with level walking, but also increased by 43% in the first post-obstacle (S +1) stride. In iLG, muscle force and work differed significantly from level walking only in the S 0 stride, indicating a single-stride recovery. In rLG, force increased in S 0, S +1 and S +2 compared with level walking, indicating three-stride obstacle recovery. Interestingly, rLG showed little variation in work output and shortening velocity in obstacle terrain, indicating a shift towards near-isometric strut-like function. Reinnervated birds also adopted a more crouched posture across level and obstacle terrains compared with intact birds. These findings suggest gait-specific control mechanisms in walking and running.
Efficacy and safety of mizoribine in comparison with cyclophosphamide for treatment of lupus nephritis: Protocol for a multi-center, open-label, randomized controlled trial
Authors: Dong Zheyi , Zhou Jianhui , Wang Yong , Sun Shiren , He Yani , Ni Zhaohui , Lin Hongli , Sun Xuefeng , Zhang Li , Chen Xiangmei 
Published: June 2023

Background: Monthly intravenous cyclophosphamide (IVCY) is a widely accepted induction therapy for lupus nephritis (LN) because this regimen balances the time needed for renal remission with the risk of adverse events. However, IVCY is associated with numerous severe toxicities. Mizoribine (MZR) was originally used as an antibiotic against Candida albicans, but researchers found it had strong immunosuppressive activity in various animal models. Previous clinical trials also examined the efficacy of MZR as an immunosuppressant, and it has been used for treatment of LN in Japan since 1990. We will conduct a phase 3 study in China to evaluate the efficacy and safety of oral MZR in comparison with standard IVCY in patients with LN. Methods: This study will be a multi-center, randomized, controlled, open-label clinical trial that consists of a screening period (seven days) followed by a treatment period (52 weeks). After screening, all eligible subjects will be randomized to an MZR or IVCY group in a 1:1 ratio. Then, subjects will initially receive methylprednisolone pulse therapy (0.5 g/day) for three days, followed by the study drug (MZR or CY) with oral corticosteroid therapy from visit two (day four). The efficacy and safety of oral MZR in comparison with standard IVCY will be determined. Discussion: This paper describes the protocol of a multi-center, open-label, randomized controlled trial that compares the efficacy and safety of MZR with IVCY for treatment of LN. The results may help determine whether LN should be considered an indication for this drug in China. Trial registration: ClinicalTrials.gov register, NCT02256150. Registered 2014-10-01. The protocol version number is 1.3 (2016-08-30).
Sociodemographic and clinical characteristics of hospital admissions for COVID-19: A retrospective cohort of patients in two hospitals in the south of Brazil
Authors: Jesus Edna Ribeiro de , Boell Julia Estela Willrich , Reckziegel Juliana Cristina Lessmann , Vaz Rafael Sittoni , Goulart Marco Aurélio , Peluso Flávia Marin , Nogueira Tiago da Cruz , Ávila Márcio Costa Silveira de , Malkiewiez Michelle Mariah , Schmidt Catiele Raquel , Weissenberg Vanessa Cruz Corrêa , Piccolin Millena Maria , Charão Junior Walmiro Martins , Lorenzini Elisiane 
Published: June 2023

Background: This database aims to present the sociodemographic and clinical profile of a cohort of 799 patients hospitalized with coronavirus disease 2019 (COVID-19) in two hospitals in southern Brazil. Methods: Data were collected, retrospectively, from November 2020 to January 2021, from the medical records of all hospital admissions that occurred from 1 April 2020 to 31 December 2020. The analysis of these data can contribute to the definition of the clinical and sociodemographic profile of patients with COVID-19. Data description: This dataset covers 799 patients hospitalized for COVID-19, characterized by the following sociodemographic variables: sex, age group, race, marital status and paid work. The sex variable was collected as sex assigned at birth from medical records data. Clinical variables included: admission to clinical ward, hospitalization in the Intensive Care Unit, COVID-19 diagnosis, number of times hospitalized due to COVID, hospitalization time in days and risk classification protocol. Other clinical variables include: pulmonary impairment; patients ventilation pattern; high-flow oxygen mask; pulmonary thromboembolism; cardiovascular disease; pulmonary sepsis; influenza exam results. Other health problems: diabetes, systemic arterial hypertension, chronic obstructive pulmonary disease, obesity, tabaco smoking, asthma, chronic kidney disease, overweight, vascular accident, sedentary lifestyle, HIV/AIDS, cancer, Alzheimer's disease, Parkinson's disease. Conclusions: The analysis of these data can contribute to the definition of the clinical and sociodemographic profile of patients with COVID-19. Thus, a great social impact is demonstrated when databases are published. Open data accelerates the research process, facilitates reuse and enriches datasets, in addition to optimizing the application of public resources, that is, enabling more use of the same investment.
Serum calprotectin as a marker of neonatal sepsis: a hospital-based cross-sectional diagnostic study
Authors: Ramineni Pardha , Kamath Sowmini Padmanabh , Manjrekar Poornima , Kamath Padmanabh , Mithra Prasanna , Kulkarni Vaman 
Published: June 2023

Background: Despite significant advances in neonatal care, neonatal sepsis remains a major contributor to mortality, morbidity, and protracted hospitalization. The development of early possible diagnostic indicators for newborn sepsis is critical. Since calprotectin participates in major biological processes, it could be a diagnostic marker for infection/inflammation. This study aimed to estimate serum calprotectin in neonates with clinical sepsis. In addition, we compared serum calprotectin with standard sepsis markers and serum procalcitonin to evaluate its diagnostic accuracy. Methods: A hospital-based cross-sectional diagnostic study of neonates identified with clinical sepsis using standard criteria was carried out. We compared estimated serum calprotectin levels to serum procalcitonin levels and conventional sepsis markers (leucocyte count, blood culture, immature to total neutrophil ratio, and C- reactive protein). We used SPSS version 25 to analyze the data. To examine diagnostic accuracy and determine a cut-off value for serum calprotectin, we used the receiver operating characteristics (ROC) curve. Results: Of the 83 subjects included, 36.5% (30/83) had blood culture positive status, the median value of serum calprotectin being 0.93 ng/ml (0.67 to 1.3). Respiratory, cardiovascular, and gastrointestinal instabilities were present in 67.5% (56/83), 59% (49/83), and 50.1% (42/83) cases, respectively. The presence of positive and negative blood cultures did not significantly affect sepsis parameters (p=0.09). On ROC, calprotectin was not predictive for blood culture positivity (sensitivity: 50%; specificity: 44% at 0.83 ng/ml of serum calprotectin) and C-reactive protein (CRP) levels (sensitivity: 57%; specificity: 67% at serum calprotectin levels of 0.89 ng/ml). However, compared with serum procalcitonin, serum calprotectin at 1.2 ng/ml had sensitivity and specificity of 60% and 73%, respectively. Conclusions: Serum calprotectin did not show a distinct advantage over the existing sepsis markers. Serum calprotectin level at 1.2 ng/ml had a sensitivity and specificity of 60% and 73%, respectively, compared to serum procalcitonin in detecting neonatal sepsis.
Discordant results among major histocompatibility complex binding affinity prediction tools
Authors: Nguyen Austin , Nellore Abhinav , Thompson Reid F. 
Published: June 2023

Background: Human leukocyte antigen (HLA) alleles are critical components of the immune system’s ability to recognize and eliminate tumors and infections. A large number of machine learning-based major histocompatibility complex (MHC) binding affinity (BA) prediction tools have been developed and are widely used for both investigational and therapeutic applications, so it is important to explore differences in tool outputs. Methods: We examined predictions of four popular tools (netMHCpan, HLAthena, MHCflurry, and MHCnuggets) across a range of possible peptide sources (human, viral, and randomly generated) and MHC class I alleles. Results: We uncovered inconsistencies in predictions of BA, allele promiscuity and the relationship between physical properties of peptides by source and BA predictions, as well as quality of training data. We found amount of training data does not explain inconsistencies between tools and yet for all tools, predicted binding quantities are similar between human and viral proteomes. Lastly, we find peptide physical properties are associated with allele-specific binding predictions. Conclusions: Our work raises fundamental questions about the fidelity of peptide-MHC binding prediction tools and their real-world implications. The real-world use of these prediction tools for theoretical binding of peptides to alleles is worrying, as the range of allele promiscuity is substantial yet does not differentiate between potential foreign versus self-antigens. Evaluating more viruses – as well as bacteria, fungi, and other pathogens – and linking these analyses with metrics such as evolutionary distance may give greater insight into the relationship between HLA evolution and disease.
Evidence of the Unintended Labor Scheduling Implications of the Minimum Wage
Authors: Yu Qiuping , Mankad Shawn , Shunko Masha 
Published: June 2023

Problem definition: The effect of the minimum wage is an important yet controversial topic that has received attention for decades. Our study is the first to take an operational lens and empirically study the impact of the minimum wage on firms’ scheduling practices. Methodology/results: Using a highly granular data set from a chain of fashion retail stores, we estimate that a $1 increase in the minimum wage, although having a negligible impact on the total labor hours used by the stores, leads to a 27.7% increase in the number of workers scheduled per week, but a 19.4% reduction in weekly hours per worker. For an average store in California, these changes translate into four extra workers and five fewer hours per worker per week. Such scheduling adjustment not only reduces the total wage compensation per worker but also reduces workers’ eligibility for benefits. We also show that the minimum wage increase reduces the consistency of weekly and daily schedules for workers. For example, the absolute (relative) deviation in weekly hours worked by each worker increases by up to 32.9% (6.6%) and by up to 9.7% (2.1%) in daily hours, as the minimum wage increases by $1. Managerial implications: Our study empirically identifies and highlights a new operational mechanism through which increasing the minimum wage may negatively impact worker welfare. Our further analysis suggests that the combination of the reduced hours, lower eligibility for benefits, and less consistent schedules (that resulted from the minimum wage increase) may substantially hurt worker welfare, even when the overall employment at the stores stay unchanged. By better understanding the intrinsic tradeoff of firms’ scheduling decisions, policy makers can better design minimum wage policies that will truly benefit workers. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2023.1212 .