bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homologous recombination deficiency (HRD) score in aggressive prostatic adenocarcinoma with or without intraductal carcinoma of the prostate (IDC-P)
Authors: Zhu Sha , Zhao Jinge , Nie Ling , Yin Wenlian , Zhang Yaowen , Zhao Fengnian , Ni Yuchao , Zhang Xingming , Wang Zhipeng , Dai Jindong , Liu Zhenhua , Chen Junru , Zeng Yuhao , Wang Zilin , Sun Guangxi , Liang Jiayu , Zhao Xiaochen , Zhu Xudong , Tao Ronggui , Yang Jiyu , He Ben , Chen Ni , Shen Pengfei , Zeng Hao 
Published: July 2022

Abstract
Background
Intraductal carcinoma of the prostate (IDC-P) is a subtype of prostate cancer featured by poor prognosis. Previous studies suggested IDC-P could have a potentially unstable genome. Homologous recombination deficiency (HRD) score is a result-oriented method to describe the genomic instability status. This study investigates the association of HRD scores with IDC-P and other clinicopathological factors and the prognostic implication of HRD scores in an aggressive prostate cancer cohort.

Methods
This study involved 123 PCa patients, including high-risk localized (M0) and de novo metastatic (M1) diseases. HRD score is calculated based on over 10,000 single-nucleotide polymorphisms distributed across the human genome. We explored the association between HRD scores and clinicopathological characteristics, genomic alterations, and patients’ prognoses using rank-sum tests, chi-square tests, Kaplan-Meier curves, and Cox proportional hazards method.

Results
The median HRD score of this cohort is 21.0, with 65 (52.8%) patients showing HRD score≥21. Tumors with IDC-P displayed higher HRD scores than adenocarcinoma (P=0.002); other high HRD score-related factors included M1 (P =0.008) and high ISUP grades (4–5) (P=0.001). MYC mutations were associated with high HRD scores (P<0.001) in the total cohort. TP53 mutations (P=0.010) and HRR pathway mutations (P=0.028) corresponded to high HRD scores in IDC-P positive and non-IDC-P patients, respectively, but not vice versa. HRD scores higher than 21 indicated significantly worse survival in the total cohort.

Conclusions
M1, high Gleason score, and IDC-P pathology represent higher HRD scores in PCa. Tumors with IDC-P might have different driven mechanisms for high HRD scores than non-IDC-P. HRD score displayed prognostic value in this aggressive prostate cancer cohort.
Leptospirosis vaccination in dogs attending UK primary care practices: vaccine uptake and factors associated with administration
Authors: Taylor Collette , O’Neill Dan G. , Catchpole Brian , Brodbelt Dave C. 
Published: July 2022

Abstract
Background
Leptospirosis is a zoonotic disease that is found globally and affects most mammalian species. Vaccination of dogs against leptospirosis is an important approach to preventing clinical disease, or reducing disease severity, as well as reducing transmission of the infection to humans. Although it is generally considered to be a ‘core’ vaccine, there is limited information on the level of leptospirosis vaccine usage and factors associated with its usage in dogs in the UK. The study aimed to report the uptake of leptospirosis vaccination and factors associated with its usage in a cohort of dogs under primary veterinary care during a 12-month period.

Results
From a population of 905,543 dogs, 49% (95%CI 48.9–49.1%) had at least one leptospirosis vaccine administered during the 12 months of study. Adult dogs had reduced odds of receiving a leptospirosis vaccine when compared to dogs < 1 year old, with dogs > 8 years old having a greater than ten-fold reduction in odds (OR = 0.08, 95%CI 0.07–0.09). Odds of receiving a leptospirosis vaccine was increased in insured dogs when compared to uninsured dogs (OR = 1.22, 95%CI = 1.17–1.28). Neutered dogs had reduced odds of receiving a leptospirosis vaccine (OR = 0.87, 95%CI 0.83–0.91). Breed associations with receiving a leptospirosis vaccine varied. Several breeds were associated with increased odds of receiving a leptospirosis vaccine when compared to crossbreed dogs, including Border Terriers (OR = 1.49, 95%CI 1.42–1.57), Golden Retrievers (OR = 1.30, 95%CI = 1.24–1.37), Cocker Spaniels (OR = 1.27, 95%CI 1.23–1.31) and West Highland White Terriers (OR = 1.27, 95%CI 1.22–1.31). French Bulldogs (OR = 0.64, 95%CI = 0.62–0.67), Staffordshire Bull Terriers (OR = 0.79, 95%CI 0.78–0.82) and Pugs (OR = 0.91, 95%CI =0.88–0.95) had significantly reduced odds of receiving a leptospirosis vaccination during the study.

Conclusion
This work identified that almost half of the UK primary care attending population received a leptospirosis vaccine during the year. Several demographic variables were associated with leptospirosis vaccine administration, with age being particularly important. Both the proportion of uptake and factors associated with leptospirosis vaccine usage can be used as a benchmark for comparisons in the future. Additionally, an understanding of which populations have reduced odds of receiving a leptospirosis vaccine can potentially be used for initiatives to encourage owner vaccination uptake in these groups.
Exosomes-based therapy of stroke, an emerging approach toward recovery
Authors: Seyedaghamiri Fatemehsadat , Salimi Leila , Ghaznavi Dara , Sokullu Emel , Rahbarghazi Reza 
Published: July 2022

AbstractBased on clinical observations, stroke is touted as one of the specific pathological conditions, affecting an individual’s life worldwide. So far, no effective treatment has been introduced to deal with stroke post-complications. Production and release of several neurotrophic factors by different cells exert positive effects on ischemic areas following stroke. As a correlate, basic and clinical studies have focused on the development and discovery of de novo modalities to introduce these factors timely and in appropriate doses into the affected areas. Exosomes (Exo) are non-sized vesicles released from many cells during pathological and physiological conditions and participate in intercellular communication. These particles transfer several arrays of signaling molecules, like several neurotrophic factors into the acceptor cells and induce specific signaling cascades in the favor of cell bioactivity. This review aimed to highlight the emerging role of exosomes as a therapeutic approach in the regeneration of ischemic areas.
Expression of voltage-gated Ca2+ channels, Insp3Rs, and RyRs in the immature mouse ovary
Authors: Bahena-Alvarez Daniel , Millan-Aldaco Diana , Rincón-Heredia Ruth , Escamilla-Avila Nancy , Hernandez-Cruz Arturo 
Published: July 2022

Abstract
Background
The postnatal mammalian ovary undergoes a series of changes to ensure the maturation of sufficient follicles to support ovulation and fecundation over the reproductive life. It is well known that intracellular [Ca2+]i signals are necessary for ovulation, fertilization, and egg activation. However, we lack detailed knowledge of the molecular identity, cellular distribution, and functional role of Ca2+ channels expressed during folliculogenesis. In the neonatal period, ovarian maturation is controlled by protein growth factors released from the oocyte and granulosa cells. Conversely, during the early infantile period, maturation becomes gonadotropin-dependent and is controlled by granulosa and theca cells. The significance of intracellular Ca2+ signaling in folliculogenesis is supported by the observation that mice lacking the expression of Ca2+/calmodulin-dependent kinase IV in granulosa cells suffer abnormal follicular development and impaired fertility.

Results
Using immunofluorescence in frozen ovarian sections and confocal microscopy, we assessed the expression of high-voltage activated Ca2+ channel alpha subunits and InsP3 and ryanodine receptors in the postnatal period from 3 to 16 days. During the neonatal stage, oocytes from primordial and primary follicles show high expression of various Ca2+-selective channels, with granulosa and stroma cells expressing significantly less. These channels are likely involved in supporting Ca2+-dependent secretion of peptide growth factors. In contrast, during the early and late infantile periods, Ca2+ channel expression in the oocyte diminishes, increasing significantly in the granulosa and particularly in immature theca cells surrounding secondary follicles.

Conclusions
The developmental switch of Ca2+ channel expression from the oocytes to the perifollicular cells likely reflects the vanishing role of the oocytes once granulosa and theca cells take control of folliculogenesis in response to gonadotropins acting on their receptors.
Assessing the clinical utility of protein structural analysis in genomic variant classification: experiences from a diagnostic laboratory
Authors: Caswell Richard C. , Gunning Adam C. , Owens Martina M. , Ellard Sian , Wright Caroline F. 
Published: July 2022

Abstract
Background
The widespread clinical application of genome-wide sequencing has resulted in many new diagnoses for rare genetic conditions, but testing regularly identifies variants of uncertain significance (VUS). The remarkable rise in the amount of genomic data has been paralleled by a rise in the number of protein structures that are now publicly available, which may have clinical utility for the interpretation of missense and in-frame insertions or deletions.

Methods
Within a UK National Health Service genomic medicine diagnostic laboratory, we investigated the number of VUS over a 5-year period that were evaluated using protein structural analysis and how often this analysis aided variant classification.

Results
We found 99 novel missense and in-frame variants across 67 genes that were initially classified as VUS by our diagnostic laboratory using standard variant classification guidelines and for which further analysis of protein structure was requested. Evidence from protein structural analysis was used in the re-assessment of 64 variants, of which 47 were subsequently reclassified as pathogenic or likely pathogenic and 17 remained as VUS. We identified several case studies where protein structural analysis aided variant interpretation by predicting disease mechanisms that were consistent with the observed phenotypes, including loss-of-function through thermodynamic destabilisation or disruption of ligand binding, and gain-of-function through de-repression or escape from proteasomal degradation.

Conclusions
We have shown that using in silico protein structural analysis can aid classification of VUS and give insights into the mechanisms of pathogenicity. Based on our experience, we propose a generic evidence-based workflow for incorporating protein structural information into diagnostic practice to facilitate variant classification.
Grey matter changes on brain MRI in subjective cognitive decline: a systematic review
Authors: Arrondo Pablo , Elía-Zudaire Óscar , Martí-Andrés Gloria , Fernández-Seara María A. , Riverol Mario 
Published: July 2022

AbstractIntroductionPeople with subjective cognitive decline (SCD) report cognitive deterioration. However, their performance in neuropsychological evaluation falls within the normal range. The present study aims to analyse whether structural magnetic resonance imaging (MRI) reveals grey matter changes in the SCD population compared with healthy normal controls (HC).MethodsParallel systematic searches in PubMed and Web of Science databases were conducted, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Quality assessment was completed using the Newcastle-Ottawa Scale (NOS).ResultsFifty-one MRI studies were included. Thirty-five studies used a region of interest (ROI) analysis, 15 used a voxel-based morphometry (VBM) analysis and 10 studies used a cortical thickness (CTh) analysis. Ten studies combined both, VBM or CTh analysis with ROI analysis.ConclusionsMedial temporal structures, like the hippocampus or the entorhinal cortex (EC), seemed to present grey matter reduction in SCD compared with HC, but the samples and results are heterogeneous. Larger sample sizes could help to better determine if these grey matter changes are consistent in SCD subjects.
Pancreatic stone protein point-of-care testing can reduce healthcare expenditure in sepsis
Authors: Schneider John E. , Dick Katherine , Cooper Jacie T. , Chami Nadine 
Published: July 2022

Abstract
Background
Sepsis is a life-threatening organ dysfunction in response to infection. Early recognition and rapid treatment are critical to patient outcomes and cost savings, but sepsis is difficult to diagnose because of its non-specific symptoms. Biomarkers such as pancreatic stone protein (PSP) offer rapid results with greater sensitivity and specificity than standard laboratory tests.

Methods
This study developed a decision tree model to compare a rapid PSP test to standard of care in the emergency department (ED) and intensive care unit (ICU) to diagnose patients with suspected sepsis. Key model parameters included length of hospital and ICU stay, readmission due to infection, cost of sepsis testing, length of antibiotic treatment, antibiotic resistance, and clostridium difficile infections. Model inputs were determined by review of sepsis literature.

Results
The rapid PSP test was found to reduce costs by $1688 per patient in the ED and $3315 per patient in the ICU compared to standard of care. Cost reductions were primarily driven by the specificity of PSP in the ED and the sensitivity of PSP in the ICU.

Conclusions
The results of the model indicate that PSP testing is cost saving compared to standard of care in diagnosis of sepsis. The abundance of sepsis cases in the ED and ICU make these findings important in the clinical field and further support the potential of sensitive and specific markers of sepsis to not only improve patient outcomes but also reduce healthcare expenditures.
Regulatory T cells-centered regulatory networks of skeletal muscle inflammation and regeneration
Authors: Chen Ziyu , Lan HaiQiang , Liao ZhaoHong , Huang JingWen , Jian XiaoTing , Hu Jijie , Liao Hua 
Published: July 2022

AbstractAs the understanding of skeletal muscle inflammation is increasingly clarified, the role of Treg cells in the treatment of skeletal muscle diseases has attracted more attention in recent years. A consensus has been reached that the regulation of Treg cells is the key to completing the switch of inflammation and repair of skeletal muscle, whose presence directly determine the repairing quality of the injured skeletal muscle. However, the functioning process of Treg cells remains unreported, thereby making it necessary to summarize the current role of Treg cells in skeletal muscle. In this review, the characteristics, origins, and cellular kinetics of these Treg cells are firstly described; Then, the relationship between Treg cells and muscle satellite cells (MuSCs), conventional T cells (Tconv) is discussed (the former is involved in the entire repair and regeneration process, while the latter matters considerably in causing most skeletal muscle autoimmune diseases); Next, focus is placed on the control of Treg cells on the phenotypic switch of macrophages, which is the key to the switch of inflammation; Finally, factors regulating the functional process of Treg cells are analyzed, and a regulatory network centered on Treg cells is summarized. The present study summarizes the cell-mediated interactions in skeletal muscle repair over the past decade, and elucidates the central role of regulatory T cells in this process, so that other researchers can more quickly and comprehensively understand the development and direction of this very field. It is believed that the hereby proposed viewpoints and problems can provide fresh visions for the latecomers.
Protective effect of resveratrol against cadmium-induced toxicity on ovine oocyte in vitro maturation and fertilization
Authors: Piras Anna Rita , Ariu Federica , Maltana Alessio , Leoni Giovanni Giuseppe , Martino Nicola Antonio , Mastrorocco Antonella , Dell’Aquila Maria Elena , Bogliolo Luisa 
Published: July 2022

Abstract
Background
Heavy metal cadmium (Cd) is a widespread environmental contaminant with a potential toxicity that might negatively affect female reproduction and fertility. It has been reported that Cd exposure impaired the quality of oocytes and led to a defective maturation and fertilization, through oxidative stress induction. Resveratrol (Res) is a natural polyphenol with strong antioxidant properties that exhibited protective role in preventing oocyte redox homeostasis disruption and quality decline. Here, we explored whether the addition of Res to in vitro maturation (IVM) medium might act as a protection against Cd-induced toxicity on ovine oocyte maturation and fertilization. Firstly, we evaluated the effect of supplementing IVM medium with two different Res concentrations (1 and 2 μmol/L) on nuclear maturation and fertilization of oocytes matured under CdCl2 (2 μmol/L) exposure. Therefore, the concentration of 1 μmol/L Res was selected to analyse the effects of this compound on intracellular ROS levels, mitochondrial (mt) distribution and activity, chromatin configuration, cytoskeleton morphology, cortical granules (CGs) distribution and mRNA expression of genes associated with cellular response to oxidative stress (i.e. SIRT1, SOD 1, GPX1, GSR, CAT) in Cd-exposed in vitro matured oocytes.

Results
We found that 1 μmol/L Res restored the reduced oocyte meiotic competence induced by Cd exposure as well as, Res sustained oocyte ability to be normally fertilized and decreased polyspermic fertilization at both tested concentrations. Moreover, we demonstrated that 1 μmol/L Res mitigated Cd-induced alterations of oocyte cytoplasmic maturation by reducing reactive oxygen species (ROS) accumulation, preventing mt dysfunction, maintaining the correct meiotic spindle and cortical F-actin assembly and the normal cortical granule distribution as well as up-regulating SIRT1, SOD1 and GPX1 genes.

Conclusions
Taken together, our findings highlighted the beneficial influence exerted by Res in preventing Cd-induced disturbance of nuclear and cytoplasmic maturation and subsequent fertilization in ovine oocytes. Res treatment may help to establish defence strategies counteracting Cd-induced toxicity on the female gamete.
Widespread alterations in microRNA biogenesis in human Huntington’s disease putamen
Authors: Petry Serena , Keraudren Rémi , Nateghi Behnaz , Loiselle Andréanne , Pircs Karolina , Jakobsson Johan , Sephton Chantelle , Langlois Mélanie , St-Amour Isabelle , Hébert Sébastien S. 
Published: July 2022

AbstractAltered microRNA (miRNA) expression is a common feature of Huntington’s disease (HD) and could participate in disease onset and progression. However, little is known about the underlying causes of miRNA disruption in HD. We and others have previously shown that mutant Huntingtin binds to Ago2, a central component of miRNA biogenesis, and disrupts mature miRNA levels. In this study, we sought to determine if miRNA maturation per se was compromised in HD. Towards this end, we characterized major miRNA biogenesis pathway components and miRNA maturation products (pri-miRNA, pre-miRNA, and mature) in human HD (N = 41, Vonsattel grades HD2-4) and healthy control (N = 25) subjects. Notably, the striatum (putamen) and cortex (BA39) from the same individuals were analyzed in parallel. We show that Ago2, Drosha, and Dicer were strongly downregulated in human HD at the early stages of the disease. Using a panel of HD-related miRNAs (miR-10b, miR-196b, miR-132, miR-212, miR-127, miR-128), we uncovered various types of maturation defects in the HD brain, the most prominent occurring at the pre-miRNA to mature miRNA maturation step. Consistent with earlier findings, we provide evidence that alterations in autophagy could participate in miRNA maturation defects. Notably, most changes occurred in the striatum, which is more prone to HTT aggregation and neurodegeneration. Likewise, we observed no significant alterations in miRNA biogenesis in human HD cortex and blood, strengthening tissue-specific effects. Overall, these data provide important clues into the underlying mechanisms behind miRNA alterations in HD-susceptible tissues. Further investigations are now required to understand the biological, diagnostic, and therapeutic implications of miRNA/RNAi biogenesis defects in HD and related neurodegenerative disorders.
Long-chain alkenones in the Shimosa Group reveal palaeotemperatures of the Pleistocene interglacial Palaeo-Tokyo Bays
Authors: Kajita Hiroto , Nakazawa Tsutomu , Utsunomiya Masayuki , Ohkouchi Naohiko , Sato Miyako , Harada Naomi , Kawahata Hodaka 
Published: July 2022

AbstractThe Shimosa Group, a Middle- to Late-Pleistocene sedimentary succession, has been the focus of stratigraphic attention because it lies beneath the Tokyo metropolitan area of central Japan. It is also of palaeoclimatic significance because it contains important interglacial marine strata of the past 450,000 years. Because the marine strata of the Shimosa Group were formed in the shallow inner bay known as the Palaeo-Tokyo Bay, rare occurrences of planktonic foraminifera make it difficult to quantitatively reconstruct the palaeo-sea surface temperatures (SSTs). Here, we extracted long-chain alkenones (LCAs) from the core GS-UR-1 penetrating the Shimosa Group to Marine Isotope Stage (MIS) 11. We found that the alkenone unsaturation ratio appears to reflect the SST of the Palaeo-Tokyo Bay formed during the peaks of MISs 5e, 7e, 9, and 11, which was consistent with the inflowing water mass changes inferred from the benthic foraminiferal assemblages. The palaeo-SSTs during each interglacial period were 2–3 °C higher than the pre-industrial levels of Tokyo Bay and seemed to reach a level similar to that of the Holocene thermal maximum. The findings of this study demonstrate that the LCA-based proxy, which has not before been utilised in studies on the Shimosa Group, has strong potential to provide palaeoceanic and stratigraphic information.
Chorioretinal abnormalities in idiopathic intracranial hypertension: case reports
Authors: Ariello Leonardo E. , Mello Luiz Guilherme Marchesi , Pimentel Sérgio Luis Gianotti , Monteiro Mário L. R. 
Published: July 2022

Abstract
Background
Papilledema is the main ocular finding in patients with idiopathic intracranial hypertension (IIH) although several chorioretinal abnormalities may also occur and contribute to visual loss. The purpose of this paper is to describe two cases of chorioretinal abnormalities associated with idiopathic intracranial hypertension: one with choroidal folds and another with polypoidal choroidal vasculopathy, an extremely unusual ocular complication in the disease.

Case presentation
Case 1: A 47-year-old woman previous diagnosed with idiopathic intracranial hypertension treated with weight loss and acetazolamide that over the following 6 months had optic disc edema gradually resolved. The patient was follow-up for a period of 10 years and the papilledema disappeared, but choroidal folds remained unchanged. Case 2: A 61-year-old female patient was seen as a follow-up examination of a 5-year history of IIH that presented with papilledema. The patient was asymptomatic but fundoscopy evaluation revealed a yellowish white peripapillary subretinal nodular lesion temporally in OD. Multimodal imaging studies were made, and the patient was diagnosed with a rare and just recent described association of IIH and polypoidal choroidal vasculopathy.

Conclusion
Papilledema, RNFL and retinal ganglion cell loss are the most common structural complications of IIH, but chorioretinal complications are important findings and should be carefully evaluated in such patients. Awareness of such occurrence and the use of appropriated clinical and multimodal imaging studies are of great importance for its early detection, leading to proper treatment and prevention of further visual loss.