bluuebunny/crossref_metadata_2025_split huggingface dataset:
ScanNeo2: a comprehensive workflow for neoantigen detection and immunogenicity prediction from diverse genomic and transcriptomic alterations
Authors: Schäfer Richard A , Guo Qingxiang , Yang Rendong 
Published: October 2023

Abstract

Motivation
Neoantigens, tumor-specific protein fragments, are invaluable in cancer immunotherapy due to their ability to serve as targets for the immune system. Computational prediction of these neoantigens from sequencing data often requires multiple algorithms and sophisticated workflows, which are currently restricted to specific types of variants, such as single-nucleotide variants or insertions/deletions. Nevertheless, other sources of neoantigens are often overlooked.

Results
We introduce ScanNeo2 an improved and fully automated bioinformatics pipeline designed for high-throughput neoantigen prediction from raw sequencing data. Unlike its predecessor, ScanNeo2 integrates multiple sources of somatic variants, including canonical- and exitron-splicing, gene fusion events, and various somatic variants. Our benchmark results demonstrate that ScanNeo2 accurately identifies neoantigens, providing a comprehensive and more efficient solution for neoantigen prediction.

Availability and implementation
ScanNeo2 is freely available at https://github.com/ylab-hi/ScanNeo2/ and is accompanied by instruction and application data.
Extracellular vesicles from mouse trophoblast cells: Effects on neural progenitor cells and potential participants in the placenta–brain axis
Authors: Kinkade Jessica A , Seetharam Arun S , Sachdev Shrikesh , Bivens Nathan J , Phinney Brett S , Grigorean Gabriela , Roberts R Michael , Tuteja Geetu , Rosenfeld Cheryl S 
Published: October 2023

AbstractThe fetal brain of the mouse is thought to be dependent upon the placenta as a source of serotonin (5-hydroxytryptamine; 5-HT) and other factors. How factors reach the developing brain remains uncertain but are postulated here to be part of the cargo carried by placental extracellular vesicles (EV). We have analyzed the protein, catecholamine, and small RNA content of EV from mouse trophoblast stem cells (TSC) and TSC differentiated into parietal trophoblast giant cells (pTGC), potential primary purveyors of 5-HT. Current studies examined how exposure of mouse neural progenitor cells (NPC) to EV from either TSC or pTGC affect their transcriptome profiles. The EV from trophoblast cells contained relatively high amounts of 5-HT, as well as dopamine and norepinephrine, but there were no significant differences between EV derived from pTGC and from TSC. Content of miRNA and small nucleolar (sno)RNA, however, did differ according to EV source, and snoRNA were upregulated in EV from pTGC. The primary inferred targets of the microRNA (miRNA) from both pTGC and TSC were mRNA enriched in the fetal brain. NPC readily internalized EV, leading to changes in their transcriptome profiles. Transcripts regulated were mainly ones enriched in neural tissues. The transcripts in EV-treated NPC that demonstrated a likely complementarity with miRNA in EV were mainly up- rather than downregulated, with functions linked to neuronal processes. Our results are consistent with placenta-derived EV providing direct support for fetal brain development and being an integral part of the placenta–brain axis.
Should we enlarge the indication for kidney biopsy in diabetics? The con part
Authors: Ortiz Alberto 
Published: October 2023

ABSTRACT
Diabetes is the most common cause of chronic kidney disease (CKD), a condition found in 850 million persons and projected to become the fifth global cause of death by 2040. Research is needed that examines kidney tissue to characterize distinct phenotypes in patients with diabetes mellitus (DM) and CKD so as to identify non-invasive biomarker signatures and develop targeted therapeutic approaches. However, from a routine care point of view, kidney biopsy is likely overused in patients with CKD and DM, as most biopsy results are not expected to be associated with a therapeutic approach that differs from standard kidney protection with triple or quadruple therapy (renin–angiotensin system blockade, sodium-glucose cotransporter 2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists and glucagon-like peptide-1 receptor agonists). Moreover, expanding the kidney biopsy criteria will increase the absolute number of complications from kidney biopsies, which may reach 27 000 to 108 000 deaths of persons that would derive little benefit from kidney biopsy if all people with DM and severe CKD were biopsied globally. Finally, limited resources should be optimally allocated. The cost of one kidney biopsy can fund 7000 semiquantitative urinary albumin:creatinine ratio assessments that could identify earlier stages of the disease and allow treatment that prevents progression to a stage at which kidney biopsy may be considered.
Kidney biopsy in diabetic kidney disease. Yes, but in very selected cases
Authors: Zoccali Carmine 
Published: October 2023

ABSTRACT
The debate on kidney biopsy in diabetic kidney disease (DKD) is multifaceted. Loreto Gesualdo and colleagues argue for its broader application, claiming that biopsies can offer precise diagnostic data and guide personalized treatment plans. On the other hand, Alberto Ortiz opposes this, citing insufficient evidence, resource constraints and potential risks. He suggests that alternative diagnostic methods, such as advanced imaging techniques and serological markers, will obviate the need for biopsy in most patients. Both sides agree on the need for individualized patient care, and open discussions between healthcare providers and patients about the procedure's risks and benefits. The application of kidney biopsy in these patients needs to consider clinical evidence, practical limitations and patient preferences, and demands a balanced, case-by-case approach. Overall, this moderator believes that, although fundamental in clinical research, kidney biopsy in DKD is infrequently needed.
Organ perfusion pressure at admission and clinical outcomes in patients hospitalized for acute heart failure
Authors: Bocchino Pier Paolo , Cingolani Marco , Frea Simone , Angelini Filippo , Gallone Guglielmo , Garatti Laura , Sacco Alice , Raineri Claudia , Pidello Stefano , Morici Nuccia , De Ferrari Gaetano Maria 
Published: October 2023

Abstract

Aims
Hypoperfusion portends adverse outcomes in acute heart failure (AHF). The gradient between end-organ inflow and outflow pressures may more closely reflect hypoperfusion than mean arterial pressure (MAP) alone. The aim of this study was to investigate organ perfusion pressure (OPP), calculated as MAP minus central venous pressure (CVP), as a prognostic marker in AHF.

Methods and results
The Sodium NItroPrusside Treatment in Acute Heart Failure (SNIP)-AHF study was a multicentre retrospective cohort study of 200 consecutive patients hospitalized for AHF treated with sodium nitroprusside. Only patients with both MAP and invasive CVP data available from the SNIP-AHF cohort were included in this analysis. The primary endpoint was to assess OPP as a predictor of worsening heart failure (WHF), defined as the worsening of signs and symptoms of heart failure leading to intensification of therapy at 48 h. One hundred and forty-six patients fulfilling the inclusion criteria were included [mean age: 61.1 ± 13.5 years, 32 (21.9%) females; mean body mass index: 26.2 ± 11.7 kg/m2; mean left ventricular ejection fraction: 23.8%±11.4%, mean MAP: 80.2 ± 13.2 mmHg, and mean CVP: 14.0 ± 6.1 mmHg]. WHF occurred in 14 (9.6%) patients. At multivariable models including hemodynamic variables (OPP, shock index, and CVP), OPP at admission was the best predictor of WHF at 48 h [OR 0.91 (95% confidence interval 0.86–0.96), P-value = 0.001] with an optimal cut-off value of 67.5 mmHg (specificity 47.3%, sensitivity 100%, and AUC 0.784 ± 0.054). In multivariable models, including univariable significant parameters available at first bedside assessment, namely New York Heart Association functional class, OPP, shock index, CVP, and left ventricular end-diastolic diameter, OPP consistently and significantly predicted WHF at 48 h.

Conclusion
In this retrospective analysis on patients hospitalized for AHF treated with sodium nitroprusside, on-admission OPP significantly predicted WHF at 48 h with high sensitivity.
Macroevolutionary Origins of Comparative Development
Authors: Riahi Ideen A 
Published: October 2023

Abstract
Advances in evolutionary theories (the Extended Synthesis) demonstrate that organisms systematically modify environments in ways that influence their own and other species’ evolution. This paper utilises these theories to examine the economic consequences of human dispersal from Africa. Evidence shows that early humans’ dispersal affected the adaptability of animal species to human environments and, through this, the extinction of large mammals during Homo sapiens’ out-of-Africa migration. Empirical analyses explore the variation in extinction rates as a source of exogenous pressure for cooperation and innovation among hunter-gatherers and examine the impact of extinction on long-run development. The results indicate that extinction affects economic performance by driving continental differences in biogeography, disease environments and institutions. Eurasia’s location along the out-of-Africa migratory path provided human and animal populations with co-evolutionary foundations for domestication and agriculture, which gave Eurasians technological and institutional advantages in comparative development.
Metataxonomic analysis of milk microbiota in the bovine subclinical mastitis
Authors: Alessandri Giulia , Sangalli Elena , Facchi Mario , Fontana Federico , Mancabelli Leonardo , Donofrio Gaetano , Ventura Marco 
Published: October 2023

AbstractSubclinical mastitis is one of the most widespread diseases affecting dairy herds with detrimental effects on animal health, milk productivity, and quality. Despite its multifactorial nature, the presence of pathogenic bacteria is regarded one of the main drivers of subclinical mastitis, causing a disruption of the homeostasis of the bovine milk microbial community. However, bovine milk microbiota alterations associated with subclinical mastitis still represents a largely unexplored research area. Therefore, the species-level milk microbiota of a total of 75 milk samples, collected from both healthy and subclinical mastitis-affected cows from two different stables, was deeply profiled through an ITS, rather than a traditional, and less informative, 16S rRNA gene microbial profiling. Surprisingly, the present pilot study not only revealed that subclinical mastitis is characterized by a reduced biodiversity of the bovine milk microbiota, but also that this disease does not induce standard alterations of the milk microbial community across stables. In addition, a flow cytometry-based total bacterial cell enumeration highlighted that subclinical mastitis is accompanied by a significant increment in the number of milk microbial cells. Furthermore, the combination of the metagenomic and flow cytometry approaches allowed to identify different potential microbial marker strictly correlated with subclinical mastitis across stables.
Promoter-proximal introns impact recombinant amylase expression in Saccharomyces cerevisiae
Authors: Schwerdtfeger Kirstie S , Myburgh Marthinus W , van Zyl Willem H , Viljoen-Bloom Marinda 
Published: October 2023

Abstract
Consolidated bioprocessing (CBP) of starch requires recombinant Saccharomyces cerevisiae strains that produce raw starch-degrading enzymes and ferment the resultant sugars to ethanol in a single step. In this study, the native S. cerevisiae COX4 and RPS25A promoter-proximal introns were evaluated for enhanced expression of amylase genes (ateA, temA or temG_Opt) under the control of an S. cerevisiae promoter (ENO1P, TEF1P, TDH3P, or HXT7P). The results showed that different promoters and promoter-intron combinations differentially affected recombinant amylase production: ENO1P-COX4i and TDH3P-RPS25Ai were the best promoters for AteA, followed closely by HXT7P. The latter was also the best promoter for TemA and TemG production, followed closely by TDH3P-RPS25Ai for both these enzymes. Introducing promoter-proximal introns increased amylase activity up to 62% in Y294[ENO-COX-AteA] and Y294[TDH3-RPS-TemA], a significant improvement relative to the intron-less promoters. Strains co-expressing both an α-amylase and glucoamylase genes yielded up to 56 g/L ethanol from 20% w/v raw starch, with a higher carbon conversion observed with strains co-expressing TDH3P-RPS25Ai-temG_Opt than HXT7P-temG_Opt. The study showed that promoter-proximal introns can enhance amylase activity in S. cerevisiae and suggest that these alternative cassettes may also be considered for expression in more efficient ethanol-producing industrial yeast strains for raw starch CBP.
The reference genome and abiotic stress responses of the model perennial grass Brachypodium sylvaticum
Authors: Lei Li , Gordon Sean P , Liu Lifeng , Sade Nir , Lovell John T , Rubio Wilhelmi Maria Del Mar , Singan Vasanth , Sreedasyam Avinash , Hestrin Rachel , Phillips Jeremy , Hernandez Bryan T , Barry Kerrie , Shu Shengqiang , Jenkins Jerry , Schmutz Jeremy , Goodstein David M , Thilmony Roger , Blumwald Eduardo , Vogel John P 
Published: October 2023

Abstract
Perennial grasses are important forage crops and emerging biomass crops and have the potential to be more sustainable grain crops. However, most perennial grass crops are difficult experimental subjects due to their large size, difficult genetics, and/or their recalcitrance to transformation. Thus, a tractable model perennial grass could be used to rapidly make discoveries that can be translated to perennial grass crops. Brachypodium sylvaticum has the potential to serve as such a model because of its small size, rapid generation time, simple genetics, and transformability. Here, we provide a high-quality genome assembly and annotation for B. sylvaticum, an essential resource for a modern model system. In addition, we conducted transcriptomic studies under 4 abiotic stresses (water, heat, salt, and freezing). Our results indicate that crowns are more responsive to freezing than leaves which may help them overwinter. We observed extensive transcriptional responses with varying temporal dynamics to all abiotic stresses, including classic heat-responsive genes. These results can be used to form testable hypotheses about how perennial grasses respond to these stresses. Taken together, these results will allow B. sylvaticum to serve as a truly tractable perennial model system.
Population Genomics of the Facultatively Sexual Liverwort Marchantia polymorpha
Authors: Sandler George , Agrawal Aneil F , Wright Stephen I 
Published: October 2023

Abstract
The population genomics of facultatively sexual organisms are understudied compared with their abundance across the tree of life. We explore patterns of genetic diversity in two subspecies of the facultatively sexual liverwort Marchantia polymorpha using samples from across Southern Ontario, Canada. Despite the ease with which M. polymorpha should be able to propagate asexually, we find no evidence of strictly clonal descent among our samples and little to no signal of isolation by distance. Patterns of identity-by-descent tract sharing further showed evidence of recent recombination and close relatedness between geographically distant isolates, suggesting long distance gene flow and at least a modest frequency of sexual reproduction. However, the M. polymorpha genome contains overall very low levels of nucleotide diversity and signs of inefficient selection evidenced by a relatively high fraction of segregating deleterious variants. We interpret these patterns as possible evidence of the action of linked selection and a small effective population size due to past generations of asexual propagation. Overall, the M. polymorpha genome harbors signals of a complex history of both sexual and asexual reproduction.
What clindamycin dose should be administered by continuous infusion during combination therapy with rifampicin? A prospective population pharmacokinetics study
Authors: Mimram Léo , Magréault Sophie , Kerroumi Younes , Salmon Dominique , Kably Benjamin , Marmor Simon , Jannot Anne-Sophie , Jullien Vincent , Zeller Valérie 
Published: October 2023

Abstract

Background
Despite its important drug–drug interaction, combined clindamycin/rifampicin therapy may achieve effective plasma clindamycin concentrations, provided clindamycin is administered by continuous infusion. However, the precise clindamycin dose remains unknown.

Objectives
This study was undertaken to determine the daily clindamycin dose to be administered by continuous infusion in combination with rifampicin to achieve effective plasma clindamycin concentrations.

Patients and methods
Two plasma clindamycin concentrations were determined prospectively for 124 patients with bone-and-joint infections treated with continuously infused clindamycin. Twenty patients received clindamycin monotherapy, 19 clindamycin combined with rifampicin and 85 received clindamycin successively without and with rifampicin. A population pharmacokinetic model was developed using NONMEM 7.5. Monte Carlo simulations were run to determine which regimens obtained clindamycin concentrations of at least 3 mg/L.

Results
A linear one-compartment model with first-order elimination accurately described the data. Clindamycin distribution volume was not estimated. Mean clindamycin clearances with rifampicin and without, respectively, were 33.6 and 10.9 L/h, with 12.8% interindividual variability. The lowest daily clindamycin dose achieving plasma concentrations of at least 3 mg/L in &gt;90% of the patients, when combined with rifampicin, was 4200 mg/24 h.

Conclusions
Our results support continuous infusion of 4200 mg of clindamycin/24 h, in combination with rifampicin. This high-dose regimen requires therapeutic drug monitoring-guided dose adaptation.
Characterization of a highly virulent Avibacterium paragallinarum isolate
Authors: Mei Chen , Zhi Yan , Xu Jie , Liang Zhixuan , Zhang Xue , Hu Ge , Wang Hongjun 
Published: October 2023

Abstract
Infectious coryza (IC) is an important respiratory infectious disease in chickens. In this study, an Avibacterium paragallinarum Page serovar C strain, named ZJ-C, was isolated from a local layer flock that was routinely vaccinated with an inactivated trivalent vaccine, using reference strain Modesto as the serovar C immunogen. The pathogenicity, immunogenicity, and genetic characteristics of ZJ-C were studied. The minimum pathogenic dose of the isolate was 100 CFU, which was 1/1,000 of the dose of the serovar C reference strain Modesto. The vaccination-challenge trial in specific pathogen-free (SPF) chickens showed that the ZJ-C bacterin could provide 100% protection against challenge from both ZJ-C and Modesto strains, whereas Modesto provided 100% protection against challenge from itself, but only 70% protection against ZJ-C. Sequence analysis of the HMTp210 hypervariable region (region 2) showed that the homology of region 2 between ZJ-C and Modesto was 96.14%, whereas the homology between ZJ-C and the Kume serovar C-4 reference strain HP60 was 99.83%. Phylogenetic analysis of region 2 showed that ZJ-C was most closely related to cluster C-4, represented by HP60. The experimental data obtained in this study will help the selection of optimal vaccine strains and assist serotyping studies of Av. paragallinarum.
Assessing Risk for Complications in Acute Hematogenous Osteomyelitis in Children: Validation of 2 Predictive Scores
Authors: Sarmiento Clemente Adriana , McNeil J Chase , Hultén Kristina G , Vallejo Jesus G , Scheurer Michael E , Kaplan Sheldon L 
Published: October 2023

Abstract

Background
Acute hematogenous osteomyelitis (AHO) can be associated with severe complications which can be difficult to predict in the clinical setting. The previously published predictive acute complication score (“A-SCORE”) and chronic complication score (“C-SCORE”) show promise, however, further external validation is needed.

Methods
We performed a retrospective study of 418 children with AHO and analyzed the performance of A-SCORE (variables included bone abscess, fever after 48 h of starting antibiotics, suppurative arthritis, disseminated disease, and delayed source control) to predict risk for acute complicated course (treatment failure, prolonged admission, and/or need for ≥2 bone debridements) and C-SCORE (includes disseminated disease, bone debridement, and CRP ≥10 mg/dL at 2–4 days after starting antibiotics) to predict chronic complications (growth restriction, pathologic fracture, chronic osteomyelitis, avascular necrosis, joint deformity, and/or frozen joint).

Results
An acute complicated course occurred in 106/418 (25.4%); 51/380 (13.5%) with complete follow-up data had a chronic complication. The A-SCORE performed with similar specificity (78%) and negative predictive value (NPV) (92%), and higher sensitivity (81%) and increased area under the receiver operating curve (AUC) (0.87) in our population. The C-SCORE performed with similar sensitivity (64%) and NPV (94%) but had lower specificity (86%) and AUC (0.71) than originally reported. Other variables associated with development of complications such as tibia involvement and bacteremia ≥2 days were identified but did not result in significantly improved predictive scores.

Conclusions
Predictive A-SCORE and C-SCORE for AHO complications in children may help guide acute management and long-term follow-up decisions. Prospective studies are needed to determine their applicability.
The combination of the Song Dynasty patterns and digital technology
Authors: Hu Jia 
Published: October 2023

Abstract
The Song-era artifacts carry ideas of naturalness and moderate elegance, preserving and passing them on to future generations. The emerging digital opportunities and initiatives allow us not only to study pattern samples in detail but also to create digital equivalents that are not subject to aging or destruction. This research aims to obtain specific knowledge and situational experience regarding the digitization of Song Dynasty patterns. At the preliminary research stage, the authors performed an online survey on a popular Chinese platform. The survey confirmed the interest of a wide audience in cultural heritage (CH) objects and their preservation. The respondents noted the focus on digital sources of information and considered the documentary video format an optimal educational design. In the first stage, Song patterns were digitally processed using MATLAB version 7.0 and ACDSee. In the subsequent phase, based on the processed patterns, the authors developed an instructional video. In the third stage, the researchers assessed students’ knowledge acquired by watching a video (experimental group) or attending a lecture with a presentation based on raw patterns (control group). The results obtained before and after the intervention showed significant progress in each group. It indicated the effectiveness of the digitized images and this intervention for obtaining new knowledge and raising awareness about the Song Dynasty CH.