bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of programmed cell death protein 1 (PD-1) inhibitor therapy in HIV-infected patients with advanced cancer: a single-center study from China
Authors: Wu Luling , Su Jie , Yang Junyang , Gu Ling , Zhang Renfang , Liu Li , Lu Hongzhou , Chen Jun 
Published: May 2023

Abstract
Background
Anti-PD-1 antibodies have been approved for treating several cancer. However, data regarding the safety and efficacy of these agents in HIV-infected patients with cancer is lacking, because these patients are frequently omitted from clinical trials.

Objectives
The primary aim of our research is to assess the safety, activity, and long-term outcomes of PD-1 inhibitors in the treatment of HIV-infected patients with advanced cancer.

Method
We retrospectively analyzed data from HIV-infected patients with advanced cancers who were treated with PD-1 inhibitors at Shanghai Public Health Clinical Center, Shanghai, China.

Results
Fifteen HIV-infected patients (all are men; asian; median age, 44) with cancer who were treated with chemotherapy and/or combined the other oncology treatments [along with combined antiretroviral therapy (cART)] prior to Sintilimab (12 out of 15) or Nivolumab (1 out of 11) or Camrelizumab (2 out of 11) injection were identified. Eight patients responded to treatment (disease control rate 53.3%), with 1 got partial response (PR) and 7 were stable. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2 including anemia, leukopenia, hyperglycemia, granulocytopenia, and thrombocytopenia. Eight patients (53.3%) experienced treatment-related AEs (TRAEs) with grades 3/4including myelosuppression, infection, and neurological disorders. CD4+ T cell count and plasma HIV RNA remained stable throughout the treatment.

Conclusions
When used in HIV-infected patients with advanced malignancies, PD-1 inhibitors tend to have favorable efficacy, manageable side effects, and no deteriorated impacts on plasma HIV-RNA and CD4+ T cell count.
Identification of an optimal threshold to define oliguria in critically ill patients: an observational study
Authors: Bianchi Nathan Axel , Altarelli Marco , Monard Céline , Kelevina Tatiana , Chaouch Aziz , Schneider Antoine Guillaume 
Published: May 2023

Abstract
Background
The relevance of current consensus threshold to define oliguria has been challenged by small observational studies. We aimed to determine the optimal threshold to define oliguria in critically-ill patients.

Methods
Cohort study including adult patients admitted within a multi-disciplinary intensive care unit between January 1st 2010 and June 15th 2020. Patients on chronic dialysis or who declined consent were excluded. We extracted hourly urinary output (UO) measurements along with patient’s characteristics from electronic medical records and 90-day mortality from the Swiss national death registry. We randomly split our data into a training (80%) and a validation (20%) set. In the training set, we developed multivariable models to assess the relationship between 90-day mortality and the minimum average UO calculated over time windows of 3, 6, 12 and 24 h. Optimal thresholds were determined by visually identifying cut-off values for the minimum average UO below which predicted mortality increased substantially. We tested models’ discrimination and calibration on the entire validation set as well as on a subset of patients with oliguria according to proposed thresholds.

Results
Among the 15,500 patients included in this analysis (training set: 12,440, validation set: 3110), 73.0% (95% CI [72.3–73.8]) presented an episode of oliguria as defined by consensus criteria (UO < 0.5 ml/kg/h for 6 h). Our models had excellent (AUC > 85% for all time windows) discrimination and calibration. The relationship between minimum average UO and predicted 90-day mortality was nonlinear with an inflexion point at 0.2 ml/kg/h for 3 and 6 h windows and 0.3 ml/kg/h for 12 and 24 h windows. Considering a threshold of < 0.2 ml/kg/h over 6 h, the proportion of patients with an episode of oliguria decreased substantially to 24.7% (95% CI [24.0–25.4]). Contrary to consensus definition, this threshold identified a population with a higher predicted 90-day mortality.

Conclusions
The widely used cut-off for oliguria of 0.5 ml/kg/h over 6 h may be too conservative. A cut-off of 0.2 ml/kg/h over 3 or 6 h is supported by the data and should be considered in further definitions of oliguria.
CpG DNA methylation changes during epididymal sperm maturation in bulls
Authors: Capra Emanuele , Turri F. , Lazzari B. , Biffani S. , Lange Consiglio A. , Ajmone Marsan P. , Stella A. , Pizzi F. 
Published: May 2023

Abstract
Background
During epididymal transit spermatozoa acquire specific morphological features which enhance their ability to swim in a progressive manner and interact with the oocytes. At the same time, sperm cells undergo specific molecular rearrangements essential for the fertilizing sperm to drive a correct embryo development. To assess epigenetic sperm changes during epididymal maturation, the caput, corpus and cauda epididymis sperm tracts were isolated from eight bulls and characterized for different sperm quality parameters and for CpG DNA methylation using Reduced Representation Bisulfite Sequencing (RRBS) able to identify differentially methylated regions (DMRs) in higher CpG density regions.

Results
Caput sperm showed significant variation in motility and sperm kinetics variables, whereas spermatozoa collected from the corpus presented morphology variation and significant alterations in variables related to acrosome integrity. A total of 57,583 methylated regions were identified across the eight bulls, showing a significantly diverse distribution for sperm collected in the three epididymal regions. Differential methylation was observed between caput vs corpus (n = 11,434), corpus vs cauda (n = 12,372) and caput vs cauda (n = 2790). During epididymal transit a high proportion of the epigenome was remodeled, showing several regions in which methylation decreases from caput to corpus and increases from corpus to cauda.

Conclusions
Specific CpG DNA methylation changes in sperm isolated from the caput, corpus, and cauda epididymis tracts are likely to refine the sperm epigenome during sperm maturation, potentially impacting sperm fertilization ability and spatial organization of the genome during early embryo development.
Aging into tricksters: a qualitative study of women’s positioning and leadership in solar energy communities in Japan
Authors: Lazoroska Daniela 
Published: May 2023

AbstractBackgroundSince the 1960s, women’s social and political engagement in Japan has been closely tied to the roles of mothers and housewives. On the other hand, the country is undergoing considerable demographic changes and has come to be considered an aging society, where an increasing number of women are opting out of marriage and child-rearing. Drawing from qualitative research with women in managerial positions in solar energy communities, this article explores the complex maneuvers informants conducted to fulfill their goal: the expansion of renewable energy in Japan.ResultsThe empirical findings point to a new, and underexplored perspective: of aging as a catalyzer for transgressing certain norms and expectations on female behavior in the context of grassroots mobilization. Aging tends to be axiomatically represented as a time of decline, and unidirectional consumption of communal resources. I examine how transitioning from life stages centered on careers and child-rearing offers resources that my informants draw on to sustain their engagement in solar energy communities. I further examine how my informants carefully, and paradoxically, navigate gendered expectations by actively appealing to dominant narratives on women: as attentive communicators attuned to the needs of others.ConclusionsThe article provides suggestions for further diversifying Japan’s community energy landscape, such as (a) increasing awareness of inequalities through open discussion on the topic; (b) gender-inclusive quotas on boards; (c) creating peer-mentoring networks; (d) stimulating a culture of dialogue open to dissensus; (e) shifting the focus away from women needing to make behavioral changes; and (f) not idealizing how much can be achieved without generating discomfort.
Longitudinal follow-up of zearalenone and deoxynivalenol mycotoxins in breast milk in the first five months of life
Authors: Güneş Bülent , Yalçın Suzan , Yalçın Sıddika Songül 
Published: May 2023

Abstract
Objectives
There is a possibility for exposed lactating mammalians to transfer some contaminants to their milk. This study aimed to determine the levels and changes of Zearalenone (ZEN), Deoxynivalenol (DON) mycotoxins for the first five months in human milk.

Methods
Voluntary lactating mothers having infants with gestational length ≥ 37 weeks were enrolled between August 2017 and June 2018 in Şanlıurfa. Mothers and infants with chronic health problems were not included in the study. Human milk samples were taken at three different times; on enrollment (Day 6–10, visit 1), between 4 and 6 weeks postpartum (visit 2), and between 14 and 19 weeks postpartum (visit 3). Mycotoxin levels in human milk were measured utilizing Helica brand commercial kit.

Results
Nineteen voluntary mothers and their breastfed infants with three human milk samples completed the study. The mean ages of mothers and infant (± SD) were 27.4 (± 5.4) years and 7.6 (± 0.9) days on enrollment. Median levels of ZEN and DON in human milk samples were 0.39 and 16.7 ng/mL, respectively. None of the cases had a ZEN daily intake higher than 250 ng/kg bw per day. However, three fourth of the cases had DON intake higher than > 1000 ng/kg bw per day. When adjusted for infant weight for age and sex, both ZEN levels and daily intake were decreased progressively from visit 1 to visit 3 (p < 0.001). DON levels and daily intake at visit 2 were found to be significantly lower in samples of visit 3 than that taken in visit 2 (p = 0.004 and p < 0.001, respectively).

Conclusions
Breast milk monitoring study revealed that ZEN and DON mycotoxins were present in the mother-infant environment. Contamination levels changed during the lactation period.
Analysis of population structure and genetic diversity in a Southern African soybean collection based on single nucleotide polymorphism markers
Authors: Tsindi A. , Eleblu J. S. Y. , Gasura E. , Mushoriwa H. , Tongoona P. , Danquah E. Y. , Mwadzingeni L. , Zikhali M. , Ziramba E. , Mabuyaye G. , Derera J. 
Published: May 2023

AbstractSoybean is an emerging strategic crop for nutrition, food security, and livestock feed in Africa, but improvement of its productivity is hampered by low genetic diversity. There is need for broadening the tropical germplasm base through incorporation and introgression of temperate germplasm in Southern Africa breeding programs. Therefore, this study was conducted to determine the population structure and molecular diversity among 180 temperate and 30 tropical soybean accessions using single nucleotide polymorphism (SNP) markers. The results revealed very low levels of molecular diversity among the 210 lines with implications for the breeding strategy. Low fixation index (FST) value of 0.06 was observed, indicating low genetic differences among populations. This suggests high genetic exchange among different lines due to global germplasm sharing. Inference based on three tools, such as the Evanno method, silhouette plots and UPMGA phylogenetic tree showed the existence of three sub-populations. The UPMGA tree showed that the first sub-cluster is composed of three genotypes, the second cluster has two genotypes, while the rest of the genotypes constituted the third cluster. The third cluster revealed low variation among most genotypes. Negligible differences were observed among some of the lines, such as Tachiyukata and Yougestu, indicating sharing of common parental backgrounds. However large phenotypic differences were observed among the accessions suggesting that there is potential for their utilization in the breeding programs. Rapid phenotyping revealed grain yield potential ranging from one to five tons per hectare for the 200 non-genetically modified accessions. Findings from this study will inform the crossing strategy for the subtropical soybean breeding programs. Innovation strategies for improving genetic variability in the germplasm collection, such as investments in pre-breeding, increasing the geographic sources of introductions and exploitation of mutation breeding would be recommended to enhance genetic gain.
A comparative study of intestinal Pseudomonas aeruginosa in healthy individuals and ICU inpatients
Authors: Hu Yanyan , Wang Siheng , Zhang Yanyan , Wu Yuchen , Liu Congcong , Ju Xiaoyang , Zhou Hongwei , Cai Chang , Zhang Rong 
Published: May 2023

AbstractThe human intestinal tract is considered the most important reservoir of the opportunistic pathogens, including Pseudomonas aeruginosa, which is often overlooked but critical due to its antimicrobial resistance and virulence. Public health interventions to control this pathogen require a comprehensive understanding of its epidemiology and genomics. In the current study, we identified P. aeruginosa strains from 2,605 fecal samples collected between 2021 to 2022. Among these samples, 574 were from ICU inpatients in Zhejiang province, while 2,031 were obtained from healthy individuals residing in ten different provinces in China. The prevalence of P. aeruginosa intestinal carriage was found to be higher in ICU inpatients (10.28%, 95% CI: 7.79%–12.76%) than that in healthy individuals (3.99%, 81/2,031, 95% CI: 3.14%–4.84%). Similarly, the prevalence of carbapenem-resistant P. aeruginosa (CRPA) was higher in ICU inpatients (32.2%) compared to healthy individuals (7.41%). The population structure analysis of our isolates revealed a predominantly non-clonal distribution, with 41 distinct sequence types identified among 59 P. aeruginosa isolates from ICU inpatients and 38 different STs among 81 P. aeruginosa isolates from healthy individuals. These findings suggest that the individual acquisition of P. aeruginosa is more frequent than patient-to-patient transmission, as evidenced by the polyclonal population structure. Antimicrobial susceptibility testing and genome analysis indicated that P. aeruginosa strains from ICU inpatients exhibited significantly higher resistance rates to most antimicrobials and harbored a greater number of acquired resistance genes compared to strains from healthy individuals. Notably, in ICU inpatients, we identified three isolates of ST463, all of which shared the conserved Tn3-TnpR-ISKpn8-blaKPC-ISKpn6 genetic context. Additionally, five isolates carrying the qacE gene were also identified, these findings suggest that small-scale transmission events may still occur within the ICU setting, posing significant challenges for clinical management. With regard to virulence factors, we observed similar profiles between the two groups, except for phzA2, phzB2, and pilA, which were statistically higher in isolates from healthy individuals. This may be because the accumulating resistance mutations in ICU-derived P. aeruginosa are linked to a decrease in virulence.
Union Is Not a Four-Letter Word: Television and Labor in the Age of Streaming
Authors: Newman Kathy M. 
Published: May 2023

Abstract
This article considers the problem of social class in contemporary television, focusing on the last five years. The author considers the ways in which streaming platforms are increasing the range and diversity of stories that television can offer; in addition, she shifts the conversation from class, consumption, and representation to work, labor, and production, arguing that this view highlights the extent to which television is engaging with questions of labor more often than we realize.
Optimal BR signalling is required for adequate cell wall orientation in the Arabidopsis root meristem
Authors: Li Zhenni , Sela Ayala , Fridman Yulia , Garstka Lucía , Höfte Herman , Savaldi-Goldstein Sigal , Wolf Sebastian 
Published: May 2023

ABSTRACT
Plant brassinosteroid hormones (BRs) regulate growth in part through altering the properties of the cell wall, the extracellular matrix of plant cells. Conversely, feedback signalling from the wall connects the state of cell wall homeostasis to the BR receptor complex and modulates BR activity. Here, we report that both pectin-triggered cell wall signalling and impaired BR signalling result in altered cell wall orientation in the Arabidopsis root meristem. Furthermore, both depletion of endogenous BRs and exogenous supply of BRs triggered these defects. Cell wall signalling-induced alterations in the orientation of newly placed walls appear to occur late during cytokinesis, after initial positioning of the cortical division zone. Tissue-specific perturbations of BR signalling revealed that the cellular malfunction is unrelated to previously described whole organ growth defects. Thus, tissue type separates the pleiotropic effects of cell wall/BR signals and highlights their importance during cell wall placement.
The pattern of microtubules in the axonemes of Gymnosphaera albida sassaki: Evidence for 13 protofilaments
Authors: Jones W. Clifford 
Published: May 2023

ABSTRACT
The axonemes of Gymnosphaera albida radiate from a central axoplast. Their proximal ends form a shell around the axoplast. Within the shell each axoneme is enveloped by a fibrillar sheath and the microtubules are interconnected by electron-dense linkages, which sometimes appear to be double. In nearly transverse sections the microtubules and their linkages form hexagons of 2 irregular types arranged in alternating rows. The shapes of the hexagons vary from one axoneme to the next. The variation is caused largely by the inclination of the axonemes to the line of sight, but also by distortion occurring during the preparation, observation and photography of the sections. Calculations show that, of a number of likely basic patterns (as would be seen in strictly transverse section), only one is compatible with measurements made on 9 of the axonemes. This involves only one type of hexagon oriented in 2 directions to form a ‘parquet-floor’ pattern. The hexagon is bilaterally symmetrical and its 6 microtubules all have the same set of angles between their linkages, namely an unpaired angle of 138º 28’ and paired angles of 110º 46’. Because these angles are in the ratio of 5:4:4, it is deduced that the microtubules have 13 protofilaments forming their walls. Morphogenetically the lateral growth of the pattern is governed by 2 rules: (1) there must be one, and only one, direction of 2-step zig-zagging of the linkages, and (2) linkages forming opposite sides of a hexagon must be in parallel.
Vinculin Y822 is an important determinant of ligand binding
Authors: DeWane Gillian , Cronin Nicholas M. , Dawson Logan W. , Heidema Christy , DeMali Kris A. 
Published: May 2023

ABSTRACT
Vinculin is an actin-binding protein present at cell–matrix and cell–cell adhesions, which plays a critical role in bearing force experienced by cells and dissipating it onto the cytoskeleton. Recently, we identified a key tyrosine residue, Y822, whose phosphorylation plays a critical role in force transmission at cell–cell adhesions. The role of Y822 in human cancer remains unknown, even though Y822 is mutated to Y822C in uterine cancers. Here, we investigated the effect of this amino acid substitution and that of a phosphodeficient Y822F vinculin in cancer cells. We observed that the presence of the Y822C mutation led to cells that proliferate and migrate more rapidly and contained smaller focal adhesions when compared to cells with wild-type vinculin. In contrast, the presence of the Y822F mutation led to highly spread cells with larger focal adhesions and increased contractility. Furthermore, we provide evidence that Y822C vinculin forms a disulfide bond with paxillin, accounting for some of the elevated phosphorylated paxillin recruitment. Taken together, these data suggest that vinculin Y822 modulates the recruitment of ligands.
Freeze-drying methods for the scanning electron-microscopical study of the protozoon Spirostomum ambiguum and the statocyst of the cephalopod mollusc loligo vulgaris
Authors: Boyde A. , Barber V. C. 
Published: May 2023

ABSTRACT
The present study concerns methods of preparing ciliated surfaces for direct examination in the scanning electron microscope.
Air-drying methods provide good results with some ciliated structures but do not always preserve the cilia of ciliated protozoons, although the pellicle is well preserved. Air-drying is not suitable for certain epithelia because considerable shrinkage and tearing occur.
Freeze-drying methods, with or without pre-fixing, are described. These preserve the cilia in the protozoon Spirostomum in a fairly life-like position. There are some differences in the appearance of unfixed and fixed freeze-dried material—for example, the peristomial membranelles are not seen in the unfixed material. Freeze-drying again proved to be a better method of preparing the sensory epithelium lining the statocyst of the cephalopod mollusc Loligo, because it was successful in preventing the distortion due to shrinkage. The number of hair cells, their orientation, and the area covered by the cells was determined for the macula. The crista was found to be asymmetrical.
Optimisation and constraint: explaining metabolic patterns in biology
Authors: White Craig R. , Marshall Dustin J. 
Published: May 2023

ABSTRACT
Constraint-based explanations have dominated theories of size-related patterns in nature for centuries. Explanations for metabolic scaling – the way in which metabolism changes with body mass – have been based on the geometry of circulatory networks through which resources are distributed, the need to dissipate heat produced as a by-product of metabolic processes, and surface-area-to-volume constraints on the flux of nutrients or waste. As an alternative to these constraint-based approaches, we recently developed a new theory that predicts that metabolic allometry arises as a consequence of the optimisation of growth and reproduction to maximise fitness within a finite life. Our theory is free of physical geometric constraints that limit the possibilities available to evolution, and we therefore argue that metabolic allometry can be explained without the need to invoke any of the assumed constraints traditionally imposed by metabolic theories. Our findings also suggest that metabolism, growth and reproduction have co-evolved to maximise fitness (i.e. lifetime reproduction) and that the observed patterns in these fundamental characteristics of life can similarly be explained by optimisation rather than constraint. In this Centenary Commentary, we present an overview of our approach and a critique of its limitations. We propose a suite of empirical tests that we hope will move the field forward, discuss the dangers of model overparameterisation and highlight the need to remain open to non-adaptive hypotheses for the origin of biological patterns.