bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor steatosis and glutamine synthetase expression in patients with advanced hepatocellular carcinoma receiving atezolizumab plus bevacizumab therapy
Authors: Kurebayashi Yutaka , Tsujikawa Hanako , Sugimoto Katsutoshi , Yunaiyama Daisuke , Araki Yoichi , Saito Kazuhiro , Takahashi Hiroshi , Kakegawa Tatsuya , Wada Takuya , Tomita Yusuke , Abe Masakazu , Yoshimasu Yu , Takeuchi Hirohito , Hirata Taiki , Sakamaki Kentaro , Kakimi Kazuhiro , Nagao Toshitaka , Itoi Takao , Sakamoto Michiie 
Published: June 2023

AbstractAimThe anti‐programmed death‐ligand 1 antibody atezolizumab and vascular endothelial growth factor‐neutralizing antibody bevacizumab in combination (Atezo + Bev) have become the first‐line therapy in advanced hepatocellular carcinoma (HCC). Distinct types of tumor immune microenvironment (TIME) and their associations with specific molecular subclasses and driver gene mutations have been identified in HCC; however, these insights are mainly based on surgically resected early‐stage tumors. The current study aimed to reveal the biology and TIME of advanced HCC and their significance in predicting clinical outcomes of Atezo + Bev therapy.MethodsThirty‐three patients with advanced HCC who were scheduled for treatment with Atezo + Bev therapy were included in this study. Pretreatment tumor biopsy, pre‐ and posttreatment diffusion‐weighted magnetic resonance imaging (MRI) with nine b values (0–1500 s/mm2), and other clinicopathologic factors were analyzed.ResultsCompared with resectable HCC, advanced HCC was characterized by higher proliferative activity, a higher frequency of Wnt/β‐catenin‐activated HCC, and lower lymphocytic infiltration. Prognostically, two metabolism‐related factors, histopathologically determined tumor steatosis and/or glutamine synthetase (GS) expression, and MRI‐determined tumor steatosis, were the most significant prognostic indicators for progression‐free survival (PFS) and overall survival after Atezo + Bev therapy. Furthermore, changes in the pre‐ and posttreatment true diffusion coefficients on MRI, which might reflect changes in TIME after treatment, were significantly associated with better PFS.ConclusionsThe biology and TIME of HCC were strikingly different in advanced HCC compared with those of surgically resected HCC. Two metabolism‐related factors, pathologically determined tumor steatosis and/or GS expression, and MRI‐determined tumor steatosis, were found to be the most significant prognostic indicators for Atezo + Bev therapy in advanced HCC.
Reciprocity, Vulnerability, and the Moral Significance of Herd Immunity
Authors: Bernstein Justin , Navin Mark 
Published: June 2023

ABSTRACTThis article proposes a novel defense of vaccine mandates: such policies are justifiable because they protect the capabilities of individuals who cannot cultivate individual immunity against infection. We begin by considering a nearby argument that has recently enjoyed popularity, which claims individuals have an enforceable obligation to get vaccinated because they have benefited from community protection (often referred to as ‘herd immunity’), and thus they ought to do their fair share in sustaining that public good by getting vaccinated. We object, however, that this kind of argument misstates the ethical basis for vaccine mandates because community protection primarily protects unvaccinated people. We contend that the duty to vaccinate is not fundamentally an obligation to make a fair contribution to a public good from which vaccinated people benefit, but a duty to protect the wellbeing of otherwise vulnerable third parties. We flesh out our view by drawing on Martha Nussbaum's capabilities approach.
The molecular and clinical role of Tensin 1/2/3 in cancer
Authors: Mainsiouw Laurensius , Ryan Matthew Edward , Hafizi Sassan , Fleming Jason C. 
Published: June 2023

AbstractTensin 1 was originally described as a focal adhesion adaptor protein, playing a role in extracellular matrix and cytoskeletal interactions. Three other Tensin proteins were subsequently discovered, and the family was grouped as Tensin. It is now recognized that these proteins interact with multiple cell signalling cascades that are implicated in tumorigenesis. To understand the role of Tensin 1–3 in neoplasia, current molecular evidence is categorized by the hallmarks of cancer model. Additionally, clinical data involving Tensin 1–3 are reviewed to investigate the correlation between cellular effects and clinical phenotype. Tensin proteins commonly interact with the tumour suppressor, DLC1. The ability of Tensin to promote tumour progression is directly correlated with DLC1 expression. Members of the Tensin family appear to have tumour subtype‐dependent effects on oncogenesis; despite numerous data evidencing a tumour suppressor role for Tensin 2, association of Tensins 1–3 with an oncogenic role notably in colorectal carcinoma and pancreatic ductal adenocarcinoma is of potential clinical relevance. The complex interplay between these focal adhesion adaptor proteins and signalling pathways are discussed to provide an up to date review of their role in cancer biology.
Trends in healthy days at home for Medicare beneficiaries using the emergency department
Authors: Burke Laura G. , Burke Ryan C. , Duggan Ciara E. , Figueroa Jose F. , Orav E. John , Marcantonio Edward R. 
Published: June 2023

AbstractBackgroundOlder adults, particularly those with Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD), have high rates of emergency department (ED) visits and are at risk for poor outcomes. How best to measure quality of care for this population has been debated. Healthy Days at Home (HDAH) is a broad outcome measure reflecting mortality and time spent in facility‐based healthcare settings versus home. We examined trends in 30‐day HDAH for Medicare beneficiaries after visiting the ED and compared trends by AD/ADRD status.MethodsWe identified all ED visits among a national 20% sample of Medicare beneficiaries ages 68 and older from 2012 to 2018. For each visit, we calculated 30‐day HDAH by subtracting mortality days and days spent in facility‐based healthcare settings within 30 days of an ED visit. We calculated adjusted rates of HDAH using linear regression, accounting for hospital random effects, visit diagnosis, and patient characteristics. We compared rates of HDAH among beneficiaries with and without AD/ADRD, including accounting for nursing home (NH) residency status.ResultsWe found fewer adjusted 30‐day HDAH after ED visits among patients with AD/ADRD compared to those without AD/ADRD (21.6 vs. 23.0). This difference was driven by a greater number of mortality days, SNF days, and, to a lesser degree, hospital observation days, ED visits, and long‐term hospital days. From 2012 to 2018, individuals living with AD/ADRD had fewer HDAH each year but a greater mean annual increase over time (p < 0.001 for the interaction between year and AD/ADRD status). Being a NH resident was associated with fewer adjusted 30‐day HDAH for beneficiaries with and without AD/ADRD.ConclusionsBeneficiaries with AD/ADRD had fewer HDAH following an ED visit but saw moderately greater increases in HDAH over time compared to those without AD/ADRD. This trend was visit driven by declining mortality and utilization of inpatient and post‐acute care.
Kidney cell culture Macaca fascicularis as a candidate for vaccine development and in vitro model
Authors: Yusni Rahmat , Mariya Silmi , Saepuloh Uus , Mariya Sela S. , Darusman Huda S. 
Published: June 2023

AbstractBackgroundCell culture is the proliferation of a cell population in vitro by isolating from the original tissue or growing from existing ones. One essential source is the monkey kidney cell cultures which have an essential role in biomedical study. This is due to the significant homology between the human and macaque genomes making these useful for cultivating human viruses, especially enteroviruses, and growing vaccines.MethodsThis study developed cell cultures derived from the kidney of Macaca fascicularis (Mf) and validated its gene expression.ResultsThe primary cultures were successfully subcultured up to six passages, grew as monolayers, and exhibited epithelial‐like morphology. The cultured cells remained heterogeneous in phenotype and they expressed CD155 and CD46 as viral receptors, cell morphology (CD24, endosialin, and vWF), proliferation, also apoptosis markers (Ki67 and p53).ConclusionsThese results indicated that the cell cultures can be used as in vitro model cells for vaccine development and bioactive compound.
Lack of an association between first‐trimester concentration of mid‐regional pro‐atrial natriuretic peptide and risk of early‐onset preeclampsia <34 weeks' gestation
Authors: Mortensen Signe Milling , Ekelund Charlotte Kvist , Pedersen Berit Woetmann , Tabor Ann , Rode Line 
Published: June 2023

AbstractAimWe examined the heart failure biomarker mid‐regional pro‐atrial natriuretic peptide during the first trimester of pregnancy in relation to early‐onset preeclampsia <34 weeks.Materials and MethodsThis case–control study included 34 women with singleton pregnancies with a preeclampsia diagnosis and delivery before 34 weeks of gestation who had attended the routine first‐trimester ultrasound scan at 11–13+6 weeks of gestation between August 2010 and October 2015 at the Copenhagen University Hospital Rigshospitalet, Denmark, and 91 uncomplicated singleton pregnancies matched by time of the routine first‐trimester blood sampling at 8–13+6 weeks.Descriptive statistical analyses were performed for maternal characteristics and obstetric and medical history for the case versus the control group. Concentrations of mid‐regional pro‐atrial natriuretic peptide, placental growth factor, soluble fms‐like tyrosine kinase‐1, and pregnancy‐associated plasma protein A between early‐onset preeclampsia cases and the control group were compared using Students t‐test and the Mann–Whitney U test. Biochemical marker concentrations were converted into multiples of the expected median values after adjustment for gestational age.ResultsMid‐regional pro‐atrial natriuretic peptide levels were not significantly different between early‐onset preeclampsia cases and the control group in the first trimester of pregnancy. As expected, both placental growth factor and pregnancy‐associated plasma protein A levels were significantly lower in early‐onset preeclampsia, whereas soluble fms‐like tyrosine kinase‐1 levels were not statistically significantly different.ConclusionThe maternal first‐trimester concentration of mid‐regional pro‐atrial natriuretic peptide, a peptide with multiple biological functions including a relation to cardiovascular disease, was not significantly different in women with early‐onset preeclampsia.
Prosthodontic implications of saliva and salivary gland dysfunction
Authors: Khoury Zaid H. , Sultan Ahmed S. 
Published: June 2023

AbstractPurposeTo provide a detailed overview of the fundamentals of saliva constituents and production. The review outlines the clinical manifestations as a consequence of salivary gland dysfunction and management strategies for patients with salivary gland dysfunction. Prosthodontic implications of saliva and salivary gland dysfunction are presented.Materials and methodsEnglish‐language literature relating to saliva constituents, physiologic saliva production, clinical manifestations secondary to salivary gland dysfunction, salivary biomarkers, and management strategies were retrieved via electronic search. Relevant articles were summarized for this manuscript with a view toward providing pragmatic information.ResultsSaliva is produced by three pairs of major and minor salivary glands. The major salivary glands, namely, the parotid, submandibular, and sublingual glands, contribute approximately 90% of saliva production. Saliva contains serous and mucinous secretions produced by different types of cells within salivary glands. Parasympathetic and sympathetic fibers innervate the major salivary glands, and upon stimulation, the parasympathetic innervation increases serous secretions, while the sympathetic innervation increases protein secretion. Stimulated saliva is mainly derived from the parotid glands which are composed of serous acini, while unstimulated saliva is mainly derived from the submandibular glands which are composed of mixed seromucous acini. As major salivary glands contribute the most to salivary flow, local or systemic factors influencing those glands can disrupt saliva production resulting in clinically significant oral manifestations.ConclusionThis review provides a fundamental overview of saliva production. In addition, the review highlights the various clinical manifestations secondary to salivary gland dysfunction, explores salivary biomarkers for screening of systemic diseases, discusses management strategies for patients with salivary gland dysfunction, and outlines the prosthodontic implications of saliva and salivary gland dysfunction.
Efforts by critical access hospitals to increase health equity through greater engagement with social determinants of health
Authors: Lemont Bethany , Puro Neeraj , Franz Berkeley , Cronin Cory E. 
Published: June 2023

AbstractPurposeGreater health care engagement with social determinants of health (SDOH) is critical to improving health equity. However, no national studies have compared programs to address patient social needs among critical access hospitals (CAHs), which are lifelines for rural communities. CAHs generally have fewer resources and receive governmental support to maintain operations. This study considers the extent to which CAHs engage in community health improvement, particularly upstream SDOH, and whether organizational or community factors predict involvement.MethodsUsing descriptive statistics and Poisson regression, we compared 3 types of programs (screening, in‐house strategies, and external partnerships) to address the patient social needs between CAHs and non‐CAHs, independent of key organizational, county, and state factors.FindingsCAHs were less likely than non‐CAHs to have programs to screen patients for social needs, address unmet social needs of patients, and enact community partnerships to address SDOH. When we stratified hospitals according to whether they endorsed an equity‐focused approach as an organization, CAHs matched their non‐CAH counterparts on all 3 types of programs.ConclusionsCAHs lag relative to their urban and non‐CAH counterparts in their ability to address nonmedical needs of their patients and broader communities. While the Flex Program has shown success in offering technical assistance to rural hospitals, this program has mainly focused on traditional hospital services to address patients’ acute health care needs. Our findings suggest that organizational and policy efforts surrounding health equity could bring CAHs in line with other hospitals in terms of their ability to support rural population health.
The ripple effects of clines from coevolutionary hotspots to coldspots
Authors: Thompson John N. 
Published: June 2023

Coevolution has the potential to alter not only the ecological interactions of coevolving partners, but also their interactions with yet other species. The effects of coevolution may ripple throughout networks of interacting species, cascading across trophic levels, swamping competitors, or facilitating survival or reproduction of yet other species linked only indirectly to the coevolving partners. These ripple effects of coevolution may differ among communities, amplifying how the coevolutionary process produces geographic mosaics of traits and outcomes in interactions among species. In a From the Cover article in this issue of Molecular Ecology, Hague et al. (2022) provide a clear example, using the well‐studied interactions between Pacific newts (Taricha spp.) and their common garter snake (Thamnophis sirtalis) predators in western North America. Pacific newts harbour tetrodotoxin (TTX), which is highly toxic to vertebrate predators. In coevolutionary hotspots, extreme escalation of toxicity in the newts and resistance to toxicity in the snakes have resulted in snake populations that retain high levels of TTX. In two geographic regions, snakes in these hotspot populations have evolved bright, aposematic colours that may act as warning signals to their own vertebrate predators. The warning signals and toxin‐resistance alleles in the snake populations decrease clinally away from the coevolutionary hotpots, shaped by a geographically variable mix of selection imposed by the snakes' prey and by their own predators.
Simultaneous Nbs1 and p53 inactivation in neural progenitors triggers high‐grade gliomas
Authors: Reuss David E. , Downing Susanna M. , Camacho Cristel V. , Wang Yong‐Dong , Piro Rosario M. , Herold‐Mende Christel , Wang Zhao‐Qi , Hofmann Thomas G. , Sahm Felix , von Deimling Andreas , McKinnon Peter J. , Frappart Pierre‐Olivier 
Published: June 2023

AbstractAimsNijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder caused by hypomorphic mutations of NBS1. NBS1 is a member of the MRE11‐RAD50‐NBS1 (MRN) complex that binds to DNA double‐strand breaks and activates the DNA damage response (DDR). Nbs1 inactivation in neural progenitor cells leads to microcephaly and premature death. Interestingly, p53 homozygous deletion rescues the NBS1‐deficient phenotype allowing long‐term survival. The objective of this work was to determine whether simultaneous inactivation of Nbs1 and p53 in neural progenitors triggered brain tumorigenesis and if so in which category this tumour could be classified.MethodsWe generated a mouse model with simultaneous genetic inactivation of Nbs1 and p53 in embryonic neural stem cells and analysed the arising tumours with in‐depth molecular analyses including immunohistochemistry, array comparative genomic hybridisation (aCGH), whole exome‐sequencing and RNA‐sequencing.ResultsNBS1/P53‐deficient mice develop high‐grade gliomas (HGG) arising in the olfactory bulbs and in the cortex along the rostral migratory stream. In‐depth molecular analyses using immunohistochemistry, aCGH, whole exome‐sequencing and RNA‐sequencing revealed striking similarities to paediatric human HGG with shared features with radiation‐induced gliomas (RIGs).ConclusionsOur findings show that concomitant inactivation of Nbs1 and p53 in mice promotes HGG with RIG features. This model could be useful for preclinical studies to improve the prognosis of these deadly tumours, but it also highlights the singularity of NBS1 among the other DNA damage response proteins in the aetiology of brain tumours.
Long‐term outcomes after paediatric sepsis (LOTUS)–A protocol for an Australian cohort study
Authors: Minogue Jessicah , Schlapbach Luregn J. , Keogh Samantha , Gibbons Kristen , Long Debbie 
Published: June 2023

AbstractBackgroundGlobally, sepsis has been identified as one of the leading causes of preventable childhood mortality and morbidity. Previous studies on intensive care patients estimated that approximately 30% of children with sepsis experience some form of disability at discharge. Development of care has seen growing numbers of children treated for sepsis not requiring a PICU admission; however, outcomes in this population are yet to be understood. Further focus is required to understand sepsis survivorship across the wider population to address knowledge gaps and morbidity burden in the broader surviving population.AimsTo assess the cognitive, physical, emotional and social health of children surviving sepsis 2 years after hospital discharge.Study DesignA prospective, observational cohort study.ResultsTwo hundred and thirty‐two children will be screened, 2 years after their hospital admission, and approached for participation in this study. Children who are <18 years of age at follow‐up, treated for sepsis‐related organ dysfunction or septic shock in Queensland between October 2018 and December 2019, will be included. Children who are deceased at follow‐up, under care of the state, or require English interpreters will be excluded from participation. Data will be collected through an online follow‐up survey comprising validated caregiver‐reported questionnaires covering the four Post Intensive Care Syndrome‐paediatrics (PICS‐p) domains (cognitive, physical, emotional and social health; Manning et al. Pediatr Crit Care Med, 2018, 19, 298–300).The primary outcome is an adaptive behaviour of the participants assessed using the Vinelands‐3 tool. Secondary outcomes will include neurodevelopment, quality of life, child distress, overall function, executive function, caregiver's distress and caregiver's stress. Analysis of variance (ANOVA), Kruskal‐Wallis and Fisher's exact test/chi‐squared tests will be used for statistical analyses. No adjustments will be made for multiple comparisons but it is acknowledged that comparisons made in this study are exploratory.Relevance to Clinical PracticeWith more children surviving sepsis, there is a need for a more comprehensive assessment of patient and family outcomes to allow support structures for families leaving the hospital after sepsis. This study is expected to inform clinicians and stakeholders of patient and family well‐being after sepsis survivorship.
Canonical Rab5 GTPases are essential for pollen tube growth through style in Arabidopsis
Authors: Hao Guang‐Jiu , Li Lu‐Shen , Zhao Xin‐Ying , Ying Jun , Zhang Miao‐Miao , Cui Xue‐Chun , Sun Tiantian , Li En , Su Le‐Yan , Shen Jinbo , Zhou Xiang , Zhu Xiaoyue , Li Sha , Zhang Yan 
Published: June 2023

Summary

Pollen tubes have dynamic tubular vacuoles. Functional loss of AP‐3, a regulator of one vacuolar trafficking route, reduces pollen tube growth. However, the role of canonical Rab5 GTPases that are responsible for two other vacuolar trafficking routes in Arabidopsis pollen tubes is obscure.

By using genomic editing, confocal microscopy, pollen tube growth assays, and transmission electron microscopy, we demonstrate that functional loss of canonical Rab5s in Arabidopsis, RHA1 and ARA7, causes the failure of pollen tubes to grow through style and thus impairs male transmission.

Functional loss of canonical Rab5s compromises vacuolar trafficking of tonoplast proteins, vacuolar biogenesis, and turgor regulation. However, rha1;ara7 pollen tubes are comparable to those of wild‐type in growing through narrow passages by microfluidic assays.

We demonstrate that functional loss of canonical Rab5s compromises endocytic and secretory trafficking at the plasma membrane (PM), whereas the targeting of PM‐associated ATPases is largely unaffected. Despite that, rha1;ara7 pollen tubes contain a reduced cytosolic pH and disrupted actin microfilaments, correlating with the mis‐targeting of vacuolar ATPases (VHA). These results imply a key role of vacuoles in maintaining cytoplasmic proton homeostasis and in pollen tube penetrative growth through style.
Faith and rational deference to authority
Authors: Buchak Lara 
Published: June 2023

AbstractMany accounts of faith hold that faith is deference to an authority about what to believe or what to do. I show that this kind of faith fits into a more general account of faith, the risky‐commitment account. I further argue that it can be rational to defer to an authority even when the authority's pronouncement goes against one's own reasoning. Indeed, such deference is rational in typical cases in which individuals treat others as authorities.