bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of human milk samples obtained pre- and post-influenza vaccination reveals a poor boosting of seasonally-relevant, hemagglutinin-specific antibodies
Authors: Yang Xiaoqi , DeCarlo Claire , Fox Alisa , Pineda Nicole , Powell Rebecca L.R. 
Published: February 2023

AbstractInfluenza (flu) vaccination prevented over 100,000 hospitalizations and 7000 deaths from flu over the 2019-2020 season in the USA [1]. Infants <6 months are the most likely to die from flu, though flu vaccines are only licensed for infants >6□months old. Therefore, it is recommended that flu vaccination occur during pregnancy, as this reduces severe complications; however, vaccination rates are suboptimal, and vaccination is also recommended postpartum [2-6]. For breast/chest-fed infants, the vaccine is believed to elicit protective and robust seasonally-specific milk antibody (Ab) [4, 7]. Few comprehensive studies exist examining Ab responses in milk after vaccination, with none measuring secretory Ab (sAb). Determining whether sAbs are elicited is critical, as this Ab class is highly stable in milk and mucosae [8, 9]. In the present study, our aim was to determine to what extent specific Ab titers in the milk of lactating people were boosted after seasonal influenza vaccination. Over the 2019-2020 and 2020-2021 seasons, milk was obtained pre- and post-vaccination and assessed for specific IgA, IgG, and sAb against relevant hemagglutinin (HA) antigens by a Luminex immunoassay. IgA and sAb were not found to be significantly boosted, while only IgG titers against B/Phuket/3073/2013, included in vaccines since 2015, exhibited an increase. Across the 7 immunogens examined, as many as 54% of samples exhibited no sAb boost. No significant differences for IgA, sAb, or IgG boosting were measured between seasonally-matched versus mismatched milk groups, indicating boosting was not seasonally-specific. No correlations between IgA and sAb increases were found for 6/8 HA antigens. No boost in IgG-or IgA-mediated neutralization post vaccination was observed. This study highlights the critical need to redesign influenza vaccines with the lactating population in mind, wherein the aim should be to elicit a potent seasonally-specific sAb response in milk. As such, this population must be included in clinical studies.
An Expert-guided Hierarchical Graph Attention Network for Post-traumatic Stress Disorder Highly-associative Genetic Biomarkers Identification
Authors: Zhang Qi , Han Yang , Lam Jacqueline CK , Bai Ruiqiao , Gozes Illana , Li Victor OK 
Published: February 2023

AbstractPost-traumatic Stress Disorder (PTSD) is a common debilitating mental disorder, that occurs in some individuals following extremely traumatic events. Traditional identification of Genetic Markers (GM) for PTSD is mainly based on a statistical clinical approach by comparing PTSD patients with normal controls. However, these statistical studies present limitations, often generating inconsistent results. Few studies have yet examined thoroughly the role of somatic mutations, PTSD disease pathways and their relationships. Capitalizing on deep learning techniques, we have developed a novel hierarchical graph attention network to identify highly correlational GM (HGMs) of PTSD. The network presents the following novelties: First, both a hierarchical graph structure and a graph attention mechanism have been integrated into a model to develop a graph attention network (GAtN) model. Second, domain-specific knowledge, including somatic mutations, genes, PTSD pathways and their correlations have been incorporated into the graph structures. Third, 12 somatic mutations having high or moderate impacts on proteins or genes have been identified as the potential HGMs for PTSD. Fourth, our study is carefully guided by prominent PTSD literature or clinical experts of the field; any high saliency HGMs generated from our model are further verified by existing PTSD-related authoritative medical journals. Our study illustrates the utility and significance of a hybrid approach, integrating both AI and expert-guided/domain-specific knowledge for thorough identification of biomarkers of PTSD, while building on the nature of convergence and divergence of PTSD pathways. Our expert-guided AI-driven methodology can be extended to other pathological-based HGM identification studies; it will transform the methodology of biomarker identification for different life-threatening diseases to speed up the complex lengthy procedures of new biomarkers identification.
The emergence of SARS-CoV-2 lineages and associated antibody responses among asymptomatic individuals in a large university community
Authors: Merling Marlena R. , Williams Amanda , Mahfooz Najmus , Ruane-Foster Marisa , Smith Jacob , Jahnes Jeff , Ayers Leona W. , Bazan Jose A. , Norris Alison , Norris Turner Abigail , Oglesbee Michael , Faith Seth A. , Quam Mikkel B. , Robinson Richard T. 
Published: February 2023

ABSTRACTSARS-CoV-2 (CoV2) infected, asymptomatic individuals are an important contributor to COVID transmission. CoV2-specific immunoglobulin (Ig)—as generated by the immune system following infection or vaccination—has helped limit CoV2 transmission from asymptomatic individuals to susceptible populations (e.g. elderly). Here, we describe the relationships between COVID incidence and CoV2 lineage, viral load, saliva Ig levels (CoV2-specific IgM, IgA and IgG) and inhibitory capacity in asymptomatic individuals between Jan 2021 and May 2022. These data were generated as part of a large university COVID monitoring program and demonstrate that COVID incidence among asymptomatic individuals occurred in waves which mirrored those in surrounding regions, with saliva CoV2 viral loads becoming progressively higher in our community until vaccine mandates were established. Among the unvaccinated, infection with each CoV2 lineage (pre-Omicron) resulted in saliva Spike-specific IgM, IgA and IgG responses, the latter increasing significantly post-infection and being more pronounced than N-specific IgG responses. Vaccination resulted in significantly higher Spike-specific IgG levels compared to unvaccinated infected individuals, and uninfected vaccinees’ saliva was more capable of inhibiting Spike function. Vaccinees with breakthrough Delta infections had Spike-specific IgG levels comparable to those of uninfected vaccinees; however, their ability to inhibit Spike binding was diminished. These data demonstrate that COVID vaccines achieved hoped-for effects in our community, including the generation of mucosal antibodies that inhibit Spike and lower community viral loads, and suggest breakthrough Delta infections were not due to an absence of vaccine-elicited Ig, but instead limited Spike binding activity in the face of high community viral loads.
Does engagement in HIV care affect screening, diagnosis, and control of noncommunicable diseases in sub-Saharan Africa? A systematic review and meta-analysis
Authors: Kileel Emma M , Zheng Amy , Bor Jacob , Fox Matthew P , Crowther Nigel J , George Jaya A , Khoza Siyabonga , Rosen Sydney , Venter Willem DF , Raal Frederick , Hibberd Patricia , Brennan Alana T 
Published: February 2023

AbstractObjectiveLow- and middle-income countries are facing a growing burden of noncommunicable diseases (NCDs). Providing HIV treatment may also provide opportunities to increase access to NCD services in under-resourced environments. We sought to investigate whether reported use of antiretroviral therapy (ART) was associated with increased screening, diagnosis, treatment, and/or control of diabetes, hypertension, chronic kidney disease, or cardiovascular disease among people living with HIV (PLWH) in sub-Saharan Africa (SSA).DesignSystematic review and meta-analysis.MethodsWe searched 10 electronic literature databases for studies published between 01 January 2011 and 31 December 2022 using a comprehensive search strategy. We sought studies reporting on screening, diagnosis, treatment, and/or control of NCDs of interest by ART use among non-pregnant adults with HIV>16 years of age in SSA. Random effects models were used to calculate summary odds ratios (ORs) of the risk of diagnosis by ART status and corresponding 95% confidence intervals (95% CIs), where appropriate.ResultsTwenty-six studies, describing 13,570 PLWH in SSA, 61% of whom were receiving ART, were included. ART use was associated with a small but imprecise increase in the odds of diabetes diagnosis (OR: 1.07; 95% CI: 0.71, 1.60) and an increase in the odds of hypertension diagnosis (OR: 2.10, 95% CI: 1.42, 3.09). We found minimal data on the association between ART use and screening, treatment, or control of NCDs.ConclusionDespite a potentially higher NCD risk among PLWH and regional efforts to integrate NCD and HIV care, evidence to support effective care integration models is lacking.
Association of Inflammation Biomarkers with Food Cravings and Appetite Changes Across the Menstrual Cycle
Authors: Agarwal Khushbu , Franks Alexis T. , Zhang Xuemin , Schisterman Enrique , Mumford Sunni L. , Joseph Paule V. 
Published: February 2023

AbstractBackgroundPremenstrual symptoms, including food cravings, are often a regular complaint among menstruating women. However, existing evidence regarding the biological mechanisms by which these food cravings occur remains unclear. Inflammation may play an essential role in the occurence of these food cravings before menstruation.PurposeThe purpose of the present study was to examine the associations between inflammatory markers and the risk of moderate/severe food cravings while accounting for changes in hormone levels and stress across the menstrual cycle.MethodsThe BioCycle Study followed women (n=259) aged 18-44 for two menstrual cycles. Food cravings (via questionnaire) were assessed up to four times per cycle. Each assessment corresponded to menses and mid-follicular, ovulation, and luteal phases of the menstrual cycle. A wide range of cytokine and chemokine levels (hsCRP, GCSF, GMCSF, IL-4, IL-6, RANTES, MIP1B, etc.) were assessed in blood samples collected at up to 8 visits per cycle, with visits timed using fertility monitors. Cravings for chocolate, sweets, salty, and other foods, and changes in appetite were determined to estimate the odds of moderate or severe cravings. Associations between inflammatory markers and risk of reporting a moderate/severe craving symptom at each cycle visit was determined using weighted generalized linear models (e.g., marginal structural models). Models were adjusted for age, BMI, and race, as well as time-varying covariates such as estradiol, stress, leptin, and total energy intake, and accounted for repeated measures (i.e., multiple cycles per woman). Both inflammatory markers and reports of cravings were modeled to account for variation at each visit.ResultsAn association between higher inflammatory biomarkers such as hsCRP, GCSF, GMCSF, IL-4, IL-6, RANTES, MIP1B, and increased risk of moderate/severe cravings were identified across the menstrual cycle |all risk ratio>0.8, all CIs range>0.7-0.9|. hsCRP retained statistical significance after false discovery rate correction with chocolate, sweet, and salty cravings, while GCSF, GMCSF, IL-6, and RANTES retained significance with chocolate and sweet cravings only.ConclusionThe results suggest a potential role of inflammation in food cravings and appetite changes across the menstrual cycle.
COVID-19 diagnostic testing underestimated cases amongst females in Pakistan
Authors: Ghanchi Najia Karim , Masood Kiran Iqbal , Nasir Asghar , Islam Nazneen , Ansar Zeeshan , Hasan Zahra 
Published: February 2023

AbstractObjectivesUnderstanding the impact of COVID-19 largely depended on information from PCR based diagnostic testing of SARS-CoV-2. It was recognized early in the pandemic that testing rates varied greatly between high and low income countries. Whilst total numbers of tests conducted are noted, little attention has been made to differences that may be due to gender and we examined this in the context of Pakistan.MethodsWe conducted a retrospective cross-sectional analysis of respiratory specimens received for SARS-CoV-2 by PCR at Aga Khan University Hospital, Karachi, Pakistan between February 2020 and February 2022. Data was analysed in six monthly intervals; P-I, February to July 2020; P-II, August 2020 to January 2021; P-III, February to July 2021 and August 2021 until February 2022.ResultsA total of 470,047 PCR tests were conducted. The proportion of tests conducted for females was, 35% in P-I; 40% in P-II; 44% in P-III and 46% in P-III. 21% of specimens were positive for SARS-CoV-2, only 9% of these specimens were from females. The greatest numbers of tests were conducted in males aged 31 to 45 years followed by those aged 16-30 years. The fewest tests were conducted in children aged under 15 years. The highest percentage of PCR positive tests was found in those ages 60 years and above. Compared for gender SARS-CoV-2 positivity rates were comparable across the study period.ConclusionsCOVID-19 data from Pakistan indicates that there are larger numbers of males as compared with females who were affected by this disease. Our results show that this may be due to a gender bias in the demographics of testing. This was especially true in the early pandemic period, leading to under-surveillance and -reporting of COVID-19 cases in females especially, in those of younger and older age groups.Strengths and limitations of this studywe stratified PCR testing based on gender and provide information on diagnostic trendswe found COVID-19 rates were comparable between females and malesFewer samples from females were received particularly, in 2020 with an increase by 2022it proposes the importance of examine the total samples tested in any case before drawing conclusions based on results of laboratory reports.LimitationsThis study was from one private healthcare system and cannot completely reflect nationwide trends to limited access to testing and also stigma related to the COVID-19.
DLK-dependent axonal mitochondrial fission drives degeneration following axotomy
Authors: Gómez-Deza Jorge , Nebiyou Matthew , Alkaslasi Mor R. , Nadal-Nicolás Francisco M. , Somasundaran Preethi , Slavutsky Anastasia L. , Ward Michael E. , Li Wei , Watkins Trent A. , Le Pichon Claire E. 
Published: February 2023

AbstractCurrently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we developed a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma. We demonstrated that this apoptotic wave is locally initiated in the axon by dual leucine zipper kinase (DLK). We found that mitochondrial fission and resultant cell death are entirely dependent on phosphorylation of dynamin related protein 1 (DRP1) downstream of DLK, revealing a new mechanism by which DLK can drive apoptosis. Importantly, we show that CRISPR mediatedDrp1depletion protected mouse retinal ganglion neurons from degeneration after optic nerve crush. Our results provide a powerful platform for studying degeneration of human neurons, pinpoint key early events in damage related neural death and new focus for therapeutic intervention.
Spatially resolved multiomics of human cardiac niches
Authors: Kanemaru Kazumasa , Cranley James , Muraro Daniele , Miranda Antonio M.A. , Pett Jan Patrick , Litvinukova Monika , Kumasaka Natsuhiko , Ho Siew Yen , Polanski Krzysztof , Richardson Laura , Mach Lukas , Dabrowska Monika , Richoz Nathan , Barnett Sam N. , Perera Shani , Wilbrey-Clark Anna , Talavera-López Carlos , Mulas Ilaria , Mahbubani Krishnaa T. , Bolt Liam , Mamanova Lira , Tuck Liz , Wang Lu , Huang Margaret M. , Prete Martin , Pritchard Sophie , Dark John , Saeb-Parsy Kourosh , Patel Minal , Clatworthy Menna R. , Hübner Norbert , Chowdhury Rasheda A. , Noseda Michela , Teichmann Sarah A. 
Published: February 2023

AbstractA cell’s function is defined by its intrinsic characteristics and its niche: the tissue microenvironment in which it dwells. Here, we combine single-cell and spatial transcriptomic data to discover cellular niches within eight regions of the human heart. We map cells to micro-anatomic locations and integrate knowledge-based and unsupervised structural annotations. For the first time, we profile the cells of the human cardiac conduction system, revealing their distinctive repertoire of ion channels, G-protein coupled receptors, and cell interactions using a customCellPhoneDB.orgmodule. We show that the sinoatrial node is compartmentalised, with a core of pacemaker cells, fibroblasts and glial cells supporting paracrine glutamatergic signalling. We introduce a druggable target prediction tool, drug2cell, which leverages single-cell profiles and drug-target interactions, providing unexpected mechanistic insights into the chronotropic effects of drugs, including GLP-1 analogues. In the epicardium, we show enrichment of both IgG+ and IgA+ plasma cells forming immune niches which may contribute to infection defence. We define a ventricular myocardial-stress niche enriched for activated fibroblasts and stressed cardiomyocytes, cell states that are expanded in cardiomyopathies. Overall, we provide new clarity to cardiac electro-anatomy and immunology, and our suite of computational approaches can be deployed to other tissues and organs.
Programmable peroxidase-assisted signal amplification enables flexible detection of nucleic acid targets in cellular and histopathological specimens
Authors: Attar Sahar , Browning Valentino E. , Liu Yuzhen , Nichols Eva K. , Tsue Ashley F. , Shechner David M. , Shendure Jay , Lieberman Joshua A. , Akilesh Shreeram , Beliveau Brian J. 
Published: February 2023

AbstractIn situhybridization (ISH) is a powerful tool for investigating the spatial arrangement of nucleic acid targets in fixed samples. ISH is typically visualized using fluorophores to allow high sensitivity and multiplexing or with colorimetric labels to facilitate co-visualization with histopathological stains. Both approaches benefit from signal amplification, which makes target detection effective, rapid, and compatible with a broad range of optical systems. Here, we introduce a unified technical platform, termed ‘pSABER’, for the amplification of ISH signals in cell and tissue systems. pSABER decorates thein situtarget with concatemeric binding sites for a horseradish peroxidase-conjugated oligonucleotide which can then catalyze the massive localized deposition of fluorescent or colorimetric substrates. We demonstrate that pSABER effectively labels DNA and RNA targets, works robustly in cultured cells and challenging formalin fixed paraffin embedded (FFPE) specimens. Furthermore, pSABER can achieve 25-fold signal amplification over conventional signal amplification by exchange reaction (SABER) and can be serially multiplexed using solution exchange. Therefore, by linking nucleic acid detection to robust signal amplification capable of diverse readouts, pSABER will have broad utility in research and clinical settings.
Spectral signatures of cross-modal attentional control in the adolescent brain and their link with physical activity and aerobic fitness levels
Authors: Hernández Doris , Kujala Jan , Heinilä Erkka , Ruotsalainen Ilona , Lapinkero Hanna-Maija , Syväoja Heidi , Parkkonen Lauri , Tammelin Tuija H. , Parviainen Tiina 
Published: February 2023

AbstractTop–down attentional control seems to increase and suppress the activity of sensory cortices for relevant stimuli and to suppress activity for irrelevant ones. Higher physical activity (PA) and aerobic fitness (AF) levels have been associated with improved attention, but most studies have focused on unimodal tasks (e.g., visual stimuli only). The impact of higher PA or AF levels on the ability of developing brains to focus on certain stimuli while ignoring distractions remains unknown. The aim of this study was to examine the neural processes in visual and auditory sensory cortices during a cross-modal attention–allocation task using magnetoencephalography in 13–16-year-old adolescents (n= 51). During continuous and simultaneous visual (15 Hz) and auditory (40 Hz) noise-tagging stimulation, participants attended to either visual or auditory targets appearing on their left or right sides. High and low PA groups were formed based on seven-day accelerometer measurements, and high and low AF groups were determined based on the 20-m shuttle-run test. Steady-state (evoked) responses to the visual stimulus were observed in all the adolescents in the primary visual cortex, but some did not show responses in the primary auditory cortices to the auditory stimulus. The adolescents with auditory-tag-driven signals in the left temporal cortex were older than those who did not show responses. Visual cortices showed enhanced visual-tag-related activity with attention, but there was no cross-modal effect, perhaps due to the developmental effect observed in the temporal areas. The visual-tag-related responses in the occipital cortex were enhanced in the higher-PA group, irrespective of task demands. In summary, sensory cortices are unequally involved in cross-modal attention in the adolescent brain. This involvement seems to be enhanced by attention. Higher PA seems to be associated with a specific visual engagement benefit in the adolescent brain.Highlights- Visual and auditory cortices’ engagement differs in cross-modal processing in adolescence.- Adolescents with responses in the left temporal cortex are older than those without responses.- Physical activity, but not aerobic fitness, is associated with visual engagement benefits in the adolescent brain.
Production of antigenically stable enterovirus A71 virus-like particles inPichia pastorisas a vaccine candidate
Authors: Kingston Natalie J , Snowden Joseph S , Martyna Agnieszka , Shegdar Mona , Grehan Keith , Tedcastle Alison , Pegg Elaine , Fox Helen , Macadam Andrew J , Martin Javier , Hogle James M , Rowlands David J , Stonehouse Nicola J 
Published: February 2023

AbstractEnterovirus A71 (EVA71) causes widespread disease in young children with occasional fatal consequences. In common with other picornaviruses, both empty capsids (ECs) and infectious virions are produced during the viral lifecycle. While initially antigenically indistinguishable from virions, ECs readily convert to an expanded conformation at moderate temperatures. In the closely related poliovirus, these conformational changes result in loss of antigenic sites required to elicit protective immune responses. Whether this is true for EVA71 remains to be determined and is the subject of this investigation.We previously reported the selection of a thermally resistant EVA71 genogroup B2 population using successive rounds of heating and passage. The mutations found in the structural protein-coding region of the selected population conferred increased thermal stability to both virions and naturally produced ECs. Here, we introduced these mutations into a recombinant expression system to produce stabilised virus-like particles (VLPs) inPichia pastoris.The stabilised VLPs retain the native virion-like antigenic conformation as determined by reactivity with a specific antibody. Structural studies suggest multiple potential mechanisms of antigenic stabilisation, however, unlike poliovirus, both native and expanded EVA71 particles elicited antibodies able to directly neutralise virusin vitro. Therefore, the anti-EVA71 neutralising antibodies are elicited by sites which are not canonically associated with the native conformation, but whether antigenic sites specific to the native conformation provide additional protective responsesin vivoremains unclear. VLPs are likely to provide cheaper and safer alternatives for vaccine production and these data show that VLP vaccines are comparable with inactivated virus vaccines at inducing neutralising antibodies.