bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral Cavity Fluid as an Alternative Postmortem Matrix
Authors: Cox Joseph , Morris Kylea , Miller Autumn C. , Champion Jana L. , Reisinger Amy J. , Pandey Maneesha , Kraner James C. , Arroyo-Mora Luis E. 
Published: July 2023

Abstract
In postmortem toxicology analysis, a variety of specimens consisting of fluids and tissues are often collected, each with an intrinsic value. Oral cavity fluid (OCF) is emerging as an alternative matrix in forensic toxicology for contributing to a diagnosis in postmortem cases; especially when blood is limited or not available. The aim of this study was to assess the analytical results obtained from OCF and compare them with blood, urine, and other traditional matrices collected from the same postmortem subjects. Of the 62 decedents studied (including 1 stillborn, 1 charred, and 3 decomposed subjects), 56 had quantifiable drugs and metabolites data in the OCF, blood, and urine. Notable findings were benzoylecgonine (24 cases), ethyl sulfate (23 cases), acetaminophen (21 cases), morphine (21 cases), naloxone (21 cases), gabapentin (20 cases), fentanyl (17 cases), and 6-acetylmorphine (15 cases), which were detected more frequently in OCF than in blood (heart, femoral, or body cavity) or urine. This study suggests that OCF is a suitable matrix for detecting and quantifying analytes in postmortem subjects compared with traditional matrices, particularly when other matrices are limited or difficult to collect because of body condition or putrefaction.
The Role of Autopsy in Quality Assurance
Authors: Miller Catherine R. , Johnston Robert D. , Blake Brooke H. , Aronson Judith F. 
Published: July 2023

Abstract
Hospital autopsies frequently reveal errors in diagnosis that could have affected the patient's clinical outcome. The aims of this study were (1) to investigate the ability of autopsy at our institution to elucidate unrecognized antemortem diagnoses and (2) to pilot a method for tabulating diagnostic discrepancies on a prospective basis. The study sample consisted of 296 cases from our hybrid hospital/forensic autopsy service during the period 2016 to 2018. Discrepancies in autopsy and clinical diagnosis were reported by pathologists at the time of autopsy report generation using a standard form. The rates of major discrepancies between autopsy and clinical diagnoses were 37.5% for in-hospital cases and 25% for patients who died outside our hospital (P < 0.05). The most common discrepant category was infection. The overall rates of discrepant causes of death were 14% (in hospital) and 8% (out of hospital) (ns). Overall percentages of cases with major diagnostic discrepancies were higher in our study than have been previously reported. It is possible that the nature of our patient population plays a role in this result. This study describes an important prospective reporting tool that will allow us to track rates of medical errors and improve diagnosis and treatment of the critically ill.
Biodistribution and Internal Dosimetry of 68Ga-DOTA-IBA PET Imaging for Patients With Bone Metastases
Authors: Yang Jian , Deng Jia , Fan Dongmei , Chen Gefei , Lu Zhonglin , Liu Hanxiang , Mok Greta S.P. , Chen Yue 
Published: July 2023

PurposeWe have developed a new pharmaceutical, ibandronic acid (IBA), and preliminarily demonstrated that it is an efficient bisphosphonate for the diagnosis and treatment of bone metastases. This study aims to examine the biodistribution and internal dosimetry of the diagnostic68Ga-DOTA-IBA in patients.Patients and Methods68Ga-DOTA-IBA was intravenously injected based on 1.81–2.57 MBq/Kg into 8 patients with bone metastases. Each patient underwent 4 sequential static whole-body PET scans at 0.1, 0.45, 0.8, and 1.8 hours after injection. The acquisition time for each scan was 20 minutes with 10 bed positions. Image registrations and volume of interest delineation were first performed on Hermes, whereas percentage injected activity (%IA), absorbed dose, and effective dose were measured for source organs, using OLINDA/EXM v2.0. Dosimetrics for the bladder was based on a bladder voiding model.ResultsNo adverse effects were observed on all patients. After the injection,68Ga-DOTA-IBA rapidly accumulated in bone metastases and cleared from nonbone tissues, as indicated by visual analysis and %IA measured on the sequential scans. High activity uptake was presented in the expected target organs, that is, bone, red marrow, and the drug-excretion organs such as kidneys and bladder. The mean total body effective dose is 0.022 ± 0.002 mSv/MBq.Conclusions68Ga-DOTA-IBA has high bone affinity and is promising in the diagnosis of bone metastases. Dosimetric results show that the absorbed doses for critical organs and total body are within the safety limit and with high bone retention. It also has the potential to be used in177Lu-therapy as a theranostic pair.
Mortality, Survival, and Readmissions During a 12-Month Follow-Up After Hip Fracture: Inpatient Rehabilitation Versus Home Rehabilitation
Authors: Ben Natan Merav , Masarwa Rawan , Yonai Yaniv , Finkel Binyamin , Berkovich Yaron 
Published: July 2023

Abstract

Purpose
This study compared readmissions, survival, and mortality during a 12-month follow-up period of inpatient rehabilitation and home rehabilitation for older persons who had experienced a hip fracture.

Methods
This work was retrospective cohort research. Between January 1 and December 30, 2019, the medical records of 280 elderly patients who were admitted to a hospital with a hip fracture were analyzed. Of these patients, 74.3% received inpatient rehabilitation, whereas 25.7% received home rehabilitation.

Results
In terms of readmissions and death, there were no appreciable differences between the inpatient rehabilitation and home rehabilitation groups. The patients in the inpatient rehabilitation group were older; more likely to need assistance with activities of daily living; and were taking, on average, more prescription drugs on a daily basis than those in the home rehabilitation group.

Conclusions and Clinical Relevance
In conclusion, as better outcomes were expected for the home rehabilitation group, which on average included less complicated patients, our findings suggest that the home rehabilitation pathway may not be a good alternative to the inpatient rehabilitation pathway.
Supportive care for chimeric antigen receptor T-cell patients
Authors: Springell Deborah , O’Reilly Maeve , Roddie Claire 
Published: July 2023

Purpose of review
The purpose of this review is to provide clear guidance to health professionals delivering chimeric antigen receptor T-cell (CAR-T) therapy on the best supportive management throughout the CAR-T pathway, from referral to long-term follow-up, including psychosocial aspects.

Recent findings
CAR-T therapy has changed the treatment landscape for relapsed/refractory (r/r) B-cell malignancy. Approximately 40% of r/r B-cell leukaemia/lymphoma patients receiving CD19-targeted CAR-T therapy achieve durable remission following a single dose. The field is rapidly expanding to encompass new CAR-T products for indications such as multiple myeloma, mantle cell lymphoma and follicular lymphoma, and the number of patients eligible to receive CAR-T therapy is likely to continue to grow exponentially. CAR-T therapy is logistically challenging to deliver, with involvement of many stakeholders. In many cases, CAR-T therapy requires an extended inpatient hospital admission, particularly in older, comorbid patients, and is associated with potentially severe immune side effects. Further, CAR-T therapy can lead to protracted cytopenias that can last for several months accompanied by a susceptibility to infection.

Summary
For the reasons listed above, standardised, comprehensive supportive care is critically important to ensure that CAR-T therapy is delivered as safely as possible and that patients are fully informed of the risks and benefits, as well as the requirement for extended hospital admission and follow-up, to fully realise the potential of this transformative treatment modality.
Neural subspaces of imagined movements in parietal cortex remain stable over several years in humans
Authors: Bashford L , Rosenthal I , Kellis S , Bjånes D , Pejsa K , Brunton BW , Andersen RA 
Published: July 2023

AbstractA crucial goal in brain-machine interfacing is long-term stability of neural decoding performance, ideally without regular retraining. Here we demonstrate stable neural decoding over several years in two human participants, achieved by latent subspace alignment of multi-unit intracortical recordings in posterior parietal cortex. These results can be practically applied to significantly expand the longevity and generalizability of future movement decoding devices.
Antibacterial mechanism of inosine againstAlicyclobacillus acidoterrestris
Authors: Liu Xiaoxue , Wu Youzhi , Ran Junjian , Jiao Lingxia , Sun Linjun , Ye Fuzhou 
Published: July 2023

AbstractInosine could potentially become a novel antibacterial agent againstA. acidoterrestrisas low-dose of inosine can preventA. acidoterrestriscontamination. However, until now the antibacterial mechanism of inosine targetingA. acidoterrestrisis still unknown. In this study, to unravel the mechanism of inosine againstA. acidoterrestrispuzzle, the effects of inosine on bacterial surface hydrophobicity, intracellular protein content, cell membrane damage extent and permeability of theA. acidoterrestriswere investigated. The results showed that inosine can effectively inhibit the growth and reproduction ofA. acidoterrestrisby destroying the integrity of cell membrane and increasing its permeability, causing the leakage of intracellular nutrients. Furthermore, the interaction networks of inosine target proteins were analyzed. The interaction networks further revealed that damage of bacterial cell membrane might be relevant to inosine’s effect on bacterial DNA replication and cell energy metabolism through regulating nucleotide synthesis and metabolism and the activity of translation initiation factors. Finally, the antibacterial mechanism of inosine againstA. acidoterrestriswas proposed.
Barley cultivars shape the abundance, phenotype, genotype and gene expression of their associated microbiota by differential root exudate secretion
Authors: Pacheco-Moreno Alba , Bollmann-Giolai Anita , Chandra Govind , Brett Paul , Davies Jack , Thornton Owen , Poole Philip , Ramachandran Vinoy , Brown James K.M. , Nicholson Paul , Ridout Chris , DeVos Sarah , Malone Jacob G. 
Published: July 2023

AbstractPlant associated microbes play vital roles in promoting plant growth and health, with plants secreting root exudates into the rhizosphere to attract beneficial microbes. Exudate composition defines the nature of microbial recruitment, with different plant species attracting distinct microbiota to enable optimal adaptation to the soil environment. To more closely examine the relationship between plant genotype and microbial recruitment, we analysed the rhizosphere microbiomes of landrace (Chevallier) and modern (NFC Tipple) barley cultivars. Distinct differences were observed between the plant-associated microbiomes of the two cultivars, with the plant-growth promoting rhizobacterial genusPseudomonassubstantially more abundant in the Tipple rhizosphere. Striking differences were also observed between the phenotypes of recruitedPseudomonaspopulations, alongside distinct genotypic clustering by cultivar. Cultivar-drivenPseudomonasselection was driven by root exudate composition, with the greater abundance of hexose sugars secreted from Tipple roots attracting microbes better adapted to growth on these metabolites, and vice versa. Cultivar-driven selection also operates at the molecular level, with both gene expression and the abundance of ecologically relevant loci differing between Tipple and ChevallierPseudomonasisolates. Finally, cultivar-driven selection is important for plant health, with both cultivars showing a distinct preference for microbes selected by their genetic siblings in rhizosphere transplantation assays.
SARS-CoV-2 Nsp1 regulates translation start site fidelity to promote infection
Authors: Aviner Ranen , Lidsky Peter V , Xiao Yinghong , Tasseto Michel , Zhang Lichao , McAlpine Patrick L , Elias Joshua , Frydman Judith , Andino Raul 
Published: July 2023

AbstractA better mechanistic understanding of virus-host interactions can help reveal vulnerabilities and identify opportunities for therapeutic interventions. Of particular interest are essential interactions that enable production of viral proteins, as those could target an early step in the virus lifecycle. Here, we use subcellular proteomics, ribosome profiling analyses and reporter assays to detect changes in polysome composition and protein synthesis during SARS-CoV-2 (CoV2) infection. We identify specific translation factors and molecular chaperones whose inhibition impairs infectious particle production without major toxicity to the host. We find that CoV2 non-structural protein Nsp1 selectively enhances virus translation through functional interactions with initiation factor EIF1A. When EIF1A is depleted, more ribosomes initiate translation from an upstream CUG start codon, inhibiting translation of non-structural genes and reducing viral titers. Together, our work describes multiple dependencies of CoV2 on host biosynthetic networks and identifies druggable targets for potential antiviral development.
Validation of Dried Blood Spots for Capturing Hepatitis C Virus Diversity for Genomic Surveillance
Authors: Tully Damien C. , Power Karen A. , Sarette Jacklyn , Stopka Thomas J. , Friedmann Peter D. , Korthuis P. Todd , Cooper Hannah , Young April M. , Seal David W. , Westergaard Ryan P. , Allen Todd M. 
Published: July 2023

ABSTRACTDried blood spots (DBS) have emerged as a promising alternative to traditional venous blood for HCV testing. However, their capacity to accurately reflect the genetic diversity of HCV remains poorly understood. We employed deep sequencing and advanced phylogenetic analyses on paired plasma and DBS samples to evaluate the suitability of DBS for genomic surveillance. Results demonstrated that DBS captured equivalent viral diversity compared to plasma with no phylogenetic discordance observed. The ability of DBS to accurately reflect the profile of viral genetic diversity suggests it may be a promising avenue for future surveillance efforts to curb HCV outbreaks.
The efficacy of CB-103, a first-in-class transcriptional Notch inhibitor, in preclinical models of breast cancer
Authors: Vigolo Michele , Urech Charlotte , Lamy Sebastien , Monticone Giulia , Zabaleta Jovanny , Hossain Fokhrul , Wyczechowska Dorota , Valle Luis Del , O’Regan Ruth , Miele Lucio , Lehal Rajwinder , Majumder Samarpan 
Published: July 2023

AbstractBackgroundNotch signaling has been shown to mediate treatment resistance and support cancer stem cells (CSCs) in endocrine-resistant estrogen receptor positive (ER+) and triple negative breast cancers (TNBCs). The clinical development of GSIs, first generation Notch inhibitors, has been hindered by lack of Notch specificity and dose-limiting toxicity. Here we describe the safety and efficacy of a first-in-class, clinical stage, orally available small molecule pan-Notch inhibitor, CB-103. Due to its unique mode of action, CB-103 doesn’t induce GI toxicities noted with GSIs. There is a critical need for effective, safe, targeted therapies for patients with endocrine-refractory metastatic breast cancer. Recently approved targeted therapies for TNBC are only effective for a subset of patients. Moreover, GSI-resistant, constitutively activating Notch1 or Notch2 mutations are observed in ∼10% of TNBC. Our study elucidating the synergy of CB-103 with fulvestrant and paclitaxel in preclinical models of both hormone-refractory ER+ BC and TNBC respectively provides a novel and unique opportunity to address major unmet therapeutic needs.MethodsCB-103 was screened in combination with a panel of anti-neoplastic drugs. We evaluated the anti-tumor activity of CB-103 with fulvestrant in ESR1-mutant (Y537S), endocrine-resistant BC xenografts. In the same model, we examined anti-CSC activity in mammosphere formation assays for CB-103 alone or in combination with fulvestrant or palbociclib. We also evaluated the effect of CB-103 plus paclitaxel on primary tumors and CSC in GSI-resistant TNBC model HCC1187. Comparisons between groups were performed with two-sided unpaired Student’st-test. One-way or two-way ANOVA followed by Tukey’s post analysis was performed to analyze in vivo efficacy study results.ResultsCB-103 showed synergism with fulvestrant in ER+ cells and with paclitaxel in TNBC cells. CB-103 combined with fulvestrant or paclitaxel potently inhibited mammosphere formation in both models. Combination of CB-103 and fulvestrant significantly reduced tumor volume in an ESR1-mutant, endocrine-resistant BC model. In a GSI-resistant TNBC model, CB-103 plus paclitaxel significantly delayed tumor growth compared to paclitaxel alone.ConclusionsOur data indicate that CB-103 is an attractive candidate for clinical investigation in endocrine resistant, recurrent breast cancers with biomarker-confirmed Notch activity in combination with SERDs and/or CDKis and in TNBCs with biomarker-confirmed Notch activity in combination with taxane-containing chemotherapy regimens.
Pseudospatial transcriptional gradient analysis of hypothalamic ependymal cells: towards a new tanycyte classification
Authors: Brunner M. , Lopez-Rodriguez D. , Messina A. , Thorens B. , Santoni F , Langlet F. 
Published: July 2023

ABSTRACTThe ependyma lining the third ventricle (3V) in the mediobasal hypothalamus is recognized as a critical player in controlling energy balance and glucose homeostasis. Its molecularly distinct cell types, including diverse tanycyte subpopulations and typical ependymal cells, confer a high functional heterogeneity. The study of gene expression profiles and dynamics of ependymal cells has the potential to uncover fundamental mechanisms and pathways involved in metabolic regulation.Here, we cataloged 5481 hypothalamic ependymocytes using FACS-assisted single-cell RNA sequencing from fed, 12h-fasted, and 24h-fasted adult male mice. First, standard clustering analysis revealed the limitation of the current characterization regarding the different ependymal cell subpopulations along the 3V. Indeed, while typical ependymal cells and β2-tanycytes are sharply defined at the molecular level, other subpopulations (i.e., β1-, α2-, and α1 tanycytes) display fuzzy boundaries and very few specific markers. Moreover, we observed that 12h- and 24h-fasting dynamically modulate gene expression, increasing tanycyte subgroup heterogeneity. Secondly, pseudospatial trajectory analysis based on peculiar UMAP neuroanatomical distribution improved the identification of tanycyte markers, distinguishing specificversusoverlapping features and better segregating tanycyte specificversusstandard functions. Intriguingly, we discovered numerous functions related to tanycyte-neuron and tanycyte-synapse interactions with modulation by energy balance. Finally, combining pseudospatial analysis and gene regulatory network inference, we observed that fasting dynamically shifts patterns in gene expression and transcription activity along the 3V, creating a metabolic and functional switch for some subpopulations.Altogether, this data provides a mechanism through which energy status leads to distinct cell type-specific responses along the 3V and gives new insights into molecular diversity underlying tanycyte classification.
Accelerated matrix-vector multiplications for matrices involving genotype covariates with applications in genomic prediction
Authors: Freudenberg Alexander , Vandenplas Jeremie , Schlather Martin , Pook Torsten , Evans Ross , ten Napel Jan 
Published: July 2023

AbstractIn the last decade, a number of methods have been suggested to deal with large amounts of genetic data in genomic predictions. Yet, steadily growing population sizes and the suboptimal use of computational resources are pushing the practical application of these approaches to their limits. As an extension to the C/CUDA librarymiraculix, we have developed tailored solutions for the computation of genotype matrix multiplications which is a critical bottleneck in the empirical evaluation of many statistical models. We demonstrate the benefits of our solutions at the example of single-step models which make repeated use of this kind of multiplication. Targeting modern Nvidia®GPUs as well as a broad range of CPU architectures, our implementation significantly reduces the time required for the estimation of breeding values in large population sizes.miraculixis released under the Apache 2.0 license and is freely available athttps://github.com/alexfreudenberg/miraculix.
Codon usage bias study of the Vitamin D receptor (VDR) gene of Multiple Sclerosis and Diabetes-1 patients
Authors: Barik Sushanta Kumar , Turuk Jyotirmayee , Giri Sidhartha , Pati Sanghamitra 
Published: July 2023

AbstractObjectiveThe codon bias usage study of the 33 Vitamin D Receptor (VDR) genes of the Multiple sclerosis and Diabetes-1 patients were characterized.MethodsVarious computational tools such as clustal-W, Codon adaptation index calculation (CAI cal), Effective number of codons (ENC), Relative Synonymous Codon Usage, Codon usage frequency, Nucleotide substation rate calculation, Relative codon deoptimization index, Grand average hydropathicity, Sequence Manipulation Suite software’s were used to find out the codon usage pattern of the VDR genes in both group of patients.ResultsThe base compositions, nucleotide substation rates, codon adaptation index, hydrophobic nature of the amino acids of VDR gene of both group of patients were analysed.ConclusionThe analysis of the synonymous codon usage pattern of the genes would helpful in the heterologous expression of the VDR genes leads to codon optimizations in Multiple Sclerosis and Diabetes-1 patients. The codon usage bias analysis of the VDR gene of the Multiple sclerosis and Diabetes-1 patients through computational approach determined the pattern of VDR gene expression and evolution during the acquiring of the disease in the patients.
SpaceANOVA: Spatial co-occurrence analysis of cell types in multiplex imaging data using point process and functional ANOVA
Authors: Seal Souvik , Neelon Brian , Angel Peggi , O’Quinn Elizabeth C. , Hill Elizabeth , Vu Thao , Ghosh Debashis , Mehta Anand , Wallace Kristin , Alekseyenko Alexander V. 
Published: July 2023

AbstractMotivationMultiplex imaging platforms have enabled the identification of the spatial organization of different types of cells in complex tissue or tumor microenvironment (TME). Exploring the potential variations in the spatial co-occurrence or co-localization of different cell types across distinct tissue or disease classes can provide significant pathological insights, paving the way for intervention strategies. However, the existing methods in this context either rely on stringent statistical assumptions or suffer from a lack of generalizability.ResultsWe present a highly powerful method to study differential spatial co-occurrence of cell types across multiple tissue or disease groups, based on the theories of the Poisson point process (PPP) and functional analysis of variance (FANOVA). Notably, the method accommodates multiple images per subject and addresses the problem of missing tissue regions, commonly encountered in such a context due to the complex nature of the data-collection procedure. We demonstrate the superior statistical power and robustness of the method in comparison to existing approaches through realistic simulation studies. Furthermore, we apply the method to three real datasets on different diseases collected using different imaging platforms. In particular, one of these datasets reveals novel insights into the spatial characteristics of various types of precursor lesions associated with colorectal cancer.AvailabilityThe associatedRpackage can be found here,https://github.com/sealx017/SpaceANOVA.Contactsealso@musc.eduSupplementary informationThe supplementary material is attached.