bluuebunny/crossref_metadata_2025_split huggingface dataset:
High incidence of subclinical peripheral artery disease in people with HIV
Authors: Suarez-Zdunek Moises Alberto , Høgh Julie , Kirkegaard-Klitbo Ditte Marie , Jensen Anne Marie R. , Rupert Adam , Trøseid Marius , Gerstoft Jan , Nielsen Susanne D. , Knudsen Andreas D. 
Published: May 2022

Objective:
Atherosclerosis is common in people with HIV (PWH). Peripheral artery disease (PAD) is the peripheral manifestation of atherosclerosis, but little is known about the incidence of PAD in PWH. Our objective was to determine the PAD incidence in PWH and to investigate potential risk factors.

Design:
Prospective longitudinal study on PWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study cohort.

Methods:
We performed ankle-brachial index (ABI) measurements at study entry and at 2-year follow-up and included participants with normal ABI at study entry. We defined de novo PAD as ABI ≤0.9 at follow-up. Using Poisson regression adjusted for age, sex, and smoking, we investigated the role of traditional and HIV-related risk factors, including inflammatory markers.

Results:
Of 844 PWH followed for a median duration of 2.3 years, 30 (3.6%) developed de novo PAD. All cases were subclinical. Diabetes (relative risk [RR] = 4.90 [95% confidence interval [CI]: 1.99–12.1]), current CD4 count <350 cells/μl (2.66 [1.06–6.71]), longer duration of antiretroviral therapy (antiretroviral therapy [ART], 1.88 [1.06–3.33] per decade), and concentrations of high-sensitivity C-reactive protein (1.33 [1.08–1.63] per doubling) and interleukin-6 (1.38 [1.06–1.80] per doubling), were associated with de novo PAD.

Conclusions:
PWH had a high incidence of de novo subclinical PAD. Diabetes, low current CD4 count, duration of ART, and inflammatory markers were associated with de novo PAD, indicating a possible role in PAD pathogenesis in PWH.
Isoniazid preventive therapy and TB transcriptional signatures in people with HIV
Authors: Valinetz Ethan D. , Matemo Daniel , Gersh Jill K. , Joudeh Lara L. , Mendelsohn Simon C. , Scriba Thomas J. , Hatherill Mark , Kinuthia John , Wald Anna , Cangelosi Gerard A. , Barnabas Ruanne V. , Hawn Thomas R. , Horne David J. 
Published: May 2022

Objective(s):
To examine the association between isoniazid preventive therapy (IPT) or nontuberculous mycobacteria (NTM) sputum culture positivity and tuberculosis (TB) transcriptional signatures in people with HIV.

Design:
Cross-sectional study.

Methods:
We enrolled adults living with HIV who were IPT-naive or had completed IPT more than 6 months prior at HIV care clinics in western Kenya. We calculated TB signatures using gene expression data from qRT-PCR. We used multivariable linear regression to analyze the association between prior receipt of IPT or NTM sputum culture positivity with a transcriptional TB risk score, RISK6 (range 0–1). In secondary analyses, we explored the association between IPT or NTM positivity and four other TB transcriptional signatures.

Results:
Among 381 participants, 99.7% were receiving antiretroviral therapy and 86.6% had received IPT (completed median of 1.1 years prior). RISK6 scores were lower (mean difference 0.10; 95% confidence interval (CI): 0.06–0.15; P < 0.001) among participants who received IPT than those who did not. In a model that adjusted for age, sex, duration of ART, and plasma HIV RNA, the RISK6 score was 52.8% lower in those with a history of IPT (P < 0.001). No significant association between year of IPT receipt and RISK6 scores was detected. There was no association between NTM sputum culture positivity and RISK6 scores.

Conclusion:
In people with HIV, IPT was associated with significantly lower RISK6 scores compared with persons who did not receive IPT. These data support investigations of its performance as a TB preventive therapy response biomarker.
Anti-CD4 autoantibodies in immunological non-responder people living with HIV: Cause of CD4+ T-cell depletion?
Authors: Muñoz-Muela Esperanza , Trujillo-Rodríguez María , Serna-Gallego Ana , Ruiz-Mateos Ezequiel , Espinosa Nuria , Roca-Oporto Critina , Benhnia Mohamed Rafii-El-Idrissi , López-Cortés Luis F. , Gutiérrez-Valencia Alicia 
Published: May 2022

Objective:
We aimed to evaluate the anti-CD4 IgG role in the poor immune recovery of immunological nonresponder people with HIV (INR).

Design:
INR display low CD4+ T-cell increase despite long-term undetectable viremia. Among other factors, autologous anti-CD4 IgG-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells has been proposed to cause CD4+ T-cell depletion.

Methods:
Plasma anti-CD4 IgG levels were quantified and purified by chromatography columns for the subsequent use in a coculture of CD4+ T and NK cells. We analyzed NK cell degranulation markers (CD107a, perforin and granzyme B) and IFN-γ release, and CD4+ T-cell death. Binding affinity of anti-CD4 IgG for CD4+ T cells was also assessed.

Results:
A total of 168 individuals were enrolled (INR, 56; immunological responders, 40; treatment-naive, 39; and healthy controls, 33). The highest anti-CD4 IgG levels were found in treatment-naive PWH, followed by participants on treatment. There were no correlations between anti-CD4 IgG levels and CD4+ T-cell counts. In a 15-participant subgroup (naive, immunological responders, and INR), anti-CD4 IgG induced a slight NK-cell expression of degranulation markers and IFN-γ; however, the percentage of CD4+ T-cell death was negligible. Consistently, no significant changes in NK cell polyfunctionality were observed. In addition, purified anti-CD4 IgG showed scarce binding affinity for CD4+ T cells. These results were similar in all analyzed participant groups.

Conclusion:
Our results suggest that autologous anti-CD4 IgG neither trigger CD4+ T-cell death by ADCC nor are responsible for CD4+ lymphocyte depletion in INR.

Video abstract:

http://links.lww.com/QAD/C518.
Joint Report on Terminology for Cosmetic Gynecology
Authors:   Developed by the Joint Writing Group of the International Urogynecological Association and the American Urogynecologic Society. Individual writing group members are noted in the Acknowledgment section.
Published: May 2022

Introduction and hypothesis
The current terminology used to describe cosmetic gynecologic procedures includes many nondescriptive, trademarked, or informal names, which contributes to substantial ambiguity about their aims and specific techniques. The development of clear, uniform descriptive terminology for cosmetic gynecology is needed for patients, researchers, and practitioners across multiple specialties.

Methods
This document was developed from a collaboration of selected members from the International Urogynecological Association (IUGA) and the American Urogynecologic Society (AUGS). Wide-ranging literature reviews were performed to identify the breadth of currently used terms and tools for measuring efficacy and safety. After extensive internal review the adoption of each definition was ratified by group consensus.

Results
A terminology report for elective cosmetic gynecology procedures, anatomical classification, outcome metrics, and reporting of complications has been developed. This document seeks to provide clear descriptive guidance for patients, researchers, and practitioners across multiple specialties. This document will be subject to internal review by IUGA and AUGS to incorporate and adopt evidence-based changes in the field.

Conclusions
A consensus-based document establishing clear terminology for cosmetic gynecology procedures has been created. Use of these terms should be encouraged to provide clarity to patients seeking these procedures and to facilitate future research to establish the safety and efficacy of these procedures.
Targeting de novo loss of function variants in constrained disease genes improves diagnostic rates in the 100,000 Genomes Project
Authors: Seaby Eleanor G. , Thomas N. Simon , Webb Amy , Brittain Helen , Taylor Tavares Ana Lisa ,   Genomics England Consortium, Baralle Diana , Rehm Heidi L. , O’Donnell-Luria Anne , Ennis Sarah 
Published: May 2022

AbstractWhole genome sequencing was first offered clinically in the UK through the 100,000 Genomes Project (100KGP); however, data analysis was time and resource intensive with 3 million variants found per patient. Consequently, analysis was restricted to predefined gene panels associated with the patient’s phenotype. However, panels rely on clearly characterised phenotypes and risk missing diagnostic variants outside of the panel(s) applied. We propose a complementary method to rapidly identify diagnostic variants, including those missed by 100KGP methods.The Loss-of-function Observed/Expected Upper-bound Fraction (LOEUF) score quantifies gene constraint, with low scores correlated with haploinsufficiency. We applied DeNovoLOEUF, a filtering strategy to sequencing data from 13,949 rare disease trios in the 100KGP, by filtering for rare, de novo, single nucleotide loss-of-function variants in OMIM disease genes with a LOEUF score <0.2. We conducted our analysis prospectively in 2019 and compared our findings with the corresponding diagnostic reports as returned in 2019 and again in 2021.324/336 (96%) of the variants identified through DeNovoLOEUF were classified as diagnostic or partially diagnostic. We identified 39 diagnoses that were “missed” by 100KGP standard analyses, which are now being returned to patients. We have demonstrated a highly specific and rapid method with a 96% positive predictive value that has good concordance with standard analysis, low false positive rate, and can identify additional diagnoses. Globally, as more patients are being offered genome sequencing, we anticipate that DeNovoLOEUF will rapidly identify new diagnoses and facilitate iterative analyses when new disease genes are discovered.
Immunoglobulins genes in Neoceratodus forsteri and Protopterus annectens explain the origin of the immunoglobulins of the animals that passed ashore
Authors: Mirete-Bachiller Serafin , Gambón-Deza Francisco 
Published: May 2022

AbstractSarcopterygii fish have great evolutionary interest since tetrapods and animals that came ashore arose from them. Within immunology, they can teach us about the emergence of Immunoglobulins D, A/X, and Y already present in amphibians. We have studied the genes of the immunoglobulins in the fish Sarcopterygii Neoceratodus forsteri and Protopterus annectens. In the first fish, we find that several loci for the constant chains of immunoglobulins are distributed in 4 chromosomes. We have found four genes for IgM, a gene for IgW and a gene for IgN. In the second, we find one locus with genes for IgN and IgM and another with one gene for IgW. With these sequences, together with those obtained in other publications, we have been able to study the possible evolution and emergence of immunoglobulin classes. We conclude that there are two evolutionary lines, one focused on IgM and very conservative, and the other focused on IgW, which allows high variability. The W line gave rise to the IgD of 11 domains of reptiles. IgA and IgY are unique since they arose from recombination between the two evolutionary lines. The W line gave origin to the CH1 and CH2 domains, and the M line gave the CH3 and CH4 domains.
Vitamin D constrains inflammation by modulating the expression of key genes on Chr17q12-21.1
Authors: Kılıç Ayşe , Halu Arda , Marzio Margherita De , Maiorino Enrico , Duvall Melody G. , Brueggemann Thayse , Quintero Joselyn J. Rojas , Chase Robert , Mirzakhani Hooman , Sungur Ayse Özge , Koepke Janine , Nakano Taiji , Peh Hong Yong , Krishnamoorthy Nandini , Abdulnour Raja-Elie , Georgopoulos Katia , Litonjua Augusto A. , Demay Marie B. , Renz Harald , Levy Bruce D. , Weiss Scott T. 
Published: May 2022

AbstractVitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (1). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D mediated immunoregulation. Here we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases (2–4). We demonstrate increased vitamin D receptor (VDR) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of theIkzf3encoded protein Aiolos to suppress IL-2-signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders.One Sentence SummaryVitamin D regulates two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, that are associated with autoimmune and chronic inflammatory diseases.
Comparing the Effect of Helical-centerline Stent Placement on Blood Flow Velocity with a Straight Stent
Authors: Kohata Yutaro , Anzai Hitomi , Ohta Makoto 
Published: May 2022

AbstractStent treatment can be used to treat blood vessel stenosis in a less invasive manner, but re-stenosis is a concern. Because a helical-stent configuration has been thought to reduce the amount of intimal hyperplasia, the helical stent is considered clinically effective. The effects of the helical stent on blood flow velocity, however, have not been studied. In this study, we estimated flow velocities before and after helical stenting using time-intensity-curve (TIC) from angiography images and compared them with straight stenting velocities. As a result, in all cases (N = 3), the velocity reduction was less with helical stenting than with straight stenting. Based on angiography images, this flow estimation method can estimate patient-specific blood flow velocity in situ even in a presence of a stent.
Exploring the utility of ssDNA aptamers directed against snake venom toxins as new therapeutics for tropical snakebite envenoming
Authors: Alomran Nessrin , Chinnappan Raja , Alsolaiss Jaffer , Casewell Nicholas R. , Zourob Mohammed 
Published: May 2022

AbstractSnakebite is a neglected tropical disease that causes considerable death and disability in the tropical world. Although snakebite can cause a variety of pathologies in victims, haemotoxic effects are particularly common and are typically characterised by haemorrhage and/or venom-induced consumption coagulopathy. Antivenoms are the mainstay therapy for treating the toxic effects of snakebite, but despite saving thousands of lives annually, these therapies are associated with limited cross-snake species efficacy due to venom variation, which ultimately restricts their therapeutic utility to particular geographical regions. In this study, we sought to explore the potential of ssDNA aptamers as toxin-specific inhibitory alternatives to antibodies. As a proof of principle model, we selected snake venom serine protease toxins, which are responsible for contributing to venom-induced coagulopathy following snakebite envenoming, as our target. Using SELEX technology, we selected ssDNA aptamers against recombinantly expressed versions of the fibrinogenolytic SVSPs Ancrod from the venom of Calloselasma rhodostoma and Batroxobin from Bothrops atrox. From the resulting pool of specific ssDNA aptamers directed against each target, we identified candidates that exhibited low nanomolar binding affinities to their targets. Downstream ALISA, fibrinogenolysis, and coagulation profiling experiments demonstrated that the candidate aptamers were able to recognise native and recombinant SVSP toxins and inhibit toxin- and venom-induced prolongation of plasma clotting times and consumption of fibrinogen, with inhibitory potencies highly comparable to commercial polyvalent antivenoms. Our findings demonstrate that rationally selected toxin-specific aptamers can exhibit broad in vitro cross-reactivity against toxins found in different snake venoms and are capable of inhibiting toxins in pathologically relevant in vitro and ex vivo models of venom activity. These data highlight the potential utility of ssDNA aptamers as novel toxin-inhibiting therapeutics of value for tackling snakebite envenoming.
BOA: A Partitioned View of Genome Assembly
Authors: Ghosh Priyanka , An Xiaojing , Keppler Patrick , Kurt Sureyya Emre , Çatalyürek Ümit V. , Krishnamoorthy Sriram , Sadayappan P. , Rajam Aravind Sukumaran , Kalyanaraman Ananth 
Published: May 2022

AbstractDe novo genome assembly is a fundamental problem in computational molecular biology that aims to reconstruct an unknown genome sequence from a set of short DNA sequences (or reads) obtained from the genome. High throughput sequencers could generate several billions of such short reads in a single run. However, the relative ordering of the reads along the target genome is not known a priori. This lack of information is one of the main contributors to the increased complexity of the assembly process. Typically, state-of-the-art approaches produce an ordering of the reads toward the end of the assembly process, making it rather too late to benefit from the ordering information. In this paper, with the dual objective of improving assembly quality as well as exposing a high degree of parallelism for assemblers, we present a partitioning-based approach. Our framework—which we call BOA (for bucket-order-assemble)—uses a bucketing alongside graph- and hypergraph-based partitioning techniques to produce a partial ordering of the reads. This partial ordering enables us to divide the read set into disjoint blocks that can be independently assembled in parallel using any state-of-the-art serial assembler of choice. We tested the BOA framework on a variety of genomes. Experimental results show that the hypergraph variant of our approach, Hyper-BOA, consistently improves both the overall assembly quality and performance. For the inputs tested, the Hyper-BOA framework consistently improves the N50 values of the popular standalone MEGAHIT assembler by an average of 1.70× and up to 2.13×; while the largest alignment length improves 1.47× on average and up to 1.94×. The time to solution also consistently improves between 3-4× for the system sizes tested.
Social Regulation of Egg Size Plasticity in the Honey Bee is Mediated by Cytoskeleton Organizer Rho1
Authors: Han Bin , Wei Qiaohong , Amiri Esmaeil , Hu Han , Meng Lifeng , Strand Micheline K. , Tarpy David R. , Xu Shufa , Li Jianke , Rueppell Olav 
Published: May 2022

AbstractEgg size plasticity represents an adaptive reproductive strategy in numerous organisms, including the honey bee, Apis mellifera. However, the proximate causation of this plasticity and egg size in general is unknown. We show that honey bee queens predictably and reversibly adjust egg size in response to their colony size and that this plasticity is an active response to the queens’ perception of colony size instead of a consequence of egg laying rate. The egg size increase involves changes of 290 ovarian proteins, mostly related to increased energy metabolism, protein transport, and cytoskeleton functions. Spatio-temporal expression analysis of the small GTPase Rho1 indicates its central role in egg size regulation, which we confirm by RNAi-mediated gene knock-down and expression analyses. The molecular adjustments that promote maternal investment of honey bee queens in response to their social environment thus reveal a novel mechanism of egg size regulation.
Selectivity for food in human ventral visual cortex
Authors: Jain Nidhi , Wang Aria , Henderson Margaret M. , Lin Ruogu , Prince Jacob S. , Tarr Michael J. , Wehbe Leila 
Published: May 2022

AbstractVisual cortex contains regions of selectivity for domains of ecological importance. Food is an evolutionarily critical category whose visual heterogeneity may make the identification of selectivity more challenging. We investigate neural responsiveness to food using natural images combined with large-scale human fMRI. Leveraging the improved sensitivity of modern designs and statistical analyses, we identify two food-selective regions in the ventral visual cortex. Our results are robust across 8 subjects from the Natural Scenes Dataset (NSD), multiple independent image sets and multiple analysis methods. We then test our findings of food selectivity in an fMRI “localizer” using grayscale food images. These independent results confirm the existence of food selectivity in ventral visual cortex and help illuminate why earlier studies may have failed to do so. Our identification of food-selective regions stands alongside prior findings of functional selectivity and adds to our understanding of the organization of knowledge within the human visual system.
A crescendo of competent coding (c3) contains the Standard Genetic Code
Authors: Yarus Michael 
Published: May 2022

AbstractThe Standard Genetic Code (SGC) can arise by fusion of partial codes evolved in different individuals, perhaps for differing prior tasks. Such code fragments can be unified into an SGC after later evolution of accurate third-position Crick wobble. Late wobble advent fills in the coding table, leaving only later development of final translational initiation and termination in separate domains of life. This code fusion mechanism is computationally implemented here. C3 fusion before late Crick wobble (c3-lCw) is tested for its ability to evolve the SGC. Compared with the previously-studied evolution of isolated coding tables, or with increasing numbers of similar, but non-fusing codes, code fusions reach the SGC sooner, work in a smaller population, and present more accurate and more complete codes more frequently. Notably, a crescendo of SGC-like codes is exposed to selection for an extended period. c3-lCw also effectively suppresses varied disordered assignments, unifying the coding table. Such codes approach the SGC, making its selection seem likely. Given unexceptional conditions, ≈ 1 of 22 c3-lCw environments evolves codes with ≥ 20 assignments and ≤ 3 differences from the SGC, including some with assignments identical to the SGC.
Machine learning enables accurate prediction of breast cancer five-year survival using somatic genomic variants
Authors: Jiang Xiaosen , Zhang Laizhi , Cao Guangshuo , Li Jia , Bai Yong 
Published: May 2022

AbstractBreast cancer is one of the most common cancers, accounting for about 30% of female cancers and a mortality rate of 15%. The 5-year survival rate is most commonly used to assess cancer progression and guide clinical practice. We used the CatBoost model to systematically construct a five-year mortality risk prediction model based on two independent data sets (BRCA_METABRIC, BRCA_TCGA). The model input data are the somatic genomic variants (copy number variation, SNP locus, cumulative mutation number of genes) and phenotype data of cancer samples. The optimal model combined all the above characteristics, and the AUC reached 0.70 in an independent external data set. At the same time, we also conducted a biological analysis of the characteristics of the model and found some potential biomarkers (TP53, DNAH11, MAP3K1, PHF20L1, etc.). The results of model risk stratification can be used as a guide for the prognosis of breast cancer.