bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-omic Transcription Factors meta-analysis: an insight on TFs accessibility and expression correlation
Authors: Martini Lorenzo , Bardini Roberta , Savino Alessandro , Di Carlo Stefano 
Published: January 2024

AbstractIt is well-known how sequencing technologies propelled cellular biology research in recent years, giving an incredible insight into the basic mechanisms of cells. Single-cell RNA sequencing is at the front in this field, with Single-cell ATAC sequencing supporting it and becoming more popular. In this regard, multi-modal technologies play a crucial role, allowing the possibility to perform the mentioned sequencing modalities simultaneously on the same cells. Yet, there still needs to be a clear and dedicated way to analyze this multi-modal data. One of the current methods is to calculate the Gene Activity Matrix (GAM), which summarizes the accessibility of the genes at the genomic level, to have a more direct link with the transcriptomic data. However, this concept is not well-defined, and it is unclear how various accessible regions impact the expression of the genes. Moreover, the transcription process is highly regulated by the Transcription Factors that binds to the different DNA regions. Therefore, this work presents a continuation of the meta-analysis of Genomic-Annotated Gene Activity Matrix (GAGAM) contributions, aiming to investigate the correlation between the TFs expression and motif information in the different functional genomic regions to understand the different Transcription Factors (TFs) dynamics involved in different cell types.
The immunological profile of RC17 hESC-derived dopaminergic neural progenitor cellsin vitro: implications for the STEM-PD clinical trial
Authors: Curle Annabel J , Fazal Shaline V , Qarin Shamma , Howlett Sarah K , He Xiaoling , Barker Roger A , Jones Joanne L 
Published: January 2024

SummaryParkinson’s Disease involves the progressive loss of dopaminergic neurons (DAn), prompting clinical trials replacing cell loss with neural grafts. This includes the transplantation of pluripotent stem cell-derived DAn progenitor cells (NPC) currently under investigation in the STEM-PD trial. To determine the likelihood of immune rejection post-grafting, we characterised the immunogenicity of the STEM-PD product (RC17-hESC-derived NPCs), comparing them to human foetal ventral mesencephalic tissue (hfVM) previously tested in trials, including our own TRANSEURO trial. Despite MHC-Class I expression, upregulated by proinflammatory cytokines, no immune response to NPCs was detectedin vitro. Instead, they were immunosuppressive. Transcriptomic analysis revealed similarities between RC17-NPCs and hfVM, both strongly upregulating antigen processing and presentation pathways in response to IFNγ. Furthermore, immunosuppressant mycophenolate mofetil detrimentally affected NPC survival and differentiationin vitro. Overall, our data suggest that aggressive immunosuppression is not required following hESC-NPC transplantation and that caution should be exercised when selecting the immunosuppressive regimen.
Heparan sulfate modified proteins affect cellular processes central to neurodegeneration and modulatepresenilinfunction
Authors: Schultheis Nicholas , Connell Alyssa , Kapral Alexander , Becker Robert J. , Mueller Richard , Shah Shalini , O’Donnell Mackenzie , Roseman Matthew , Wang Weihua , Yin Fei , Weiss Ryan , Selleck Scott B. 
Published: January 2024

SummaryMutations inpresenilin-1 (PSEN1)are the most common cause of familial, early-onset Alzheimer’s disease (AD), typically producing cognitive deficits in the fourth decade. A variant ofAPOE, APOE3 Christchurch (APOE3ch), was found associated with protection from both cognitive decline and Tau accumulation in a 70-year-old bearing the disease-causingPSEN1-E280Amutation. The amino acid change in ApoE3ch is within the heparan sulfate (HS) binding domain of APOE, and purified APOEch showed dramatically reduced affinity for heparin, a highly sulfated form of HS. The physiological significance ofApoE3chis supported by studies of a mouse bearing a knock-in of this human variant and its effects on microglia reactivity and Aβ-induced Tau deposition. The studies reported here examine the function of heparan sulfate-modified proteoglycans (HSPGs) in cellular and molecular pathways affecting AD-related cell pathology in human cell lines and mouse astrocytes. The mechanisms of HSPG influences onpresenilin-dependent cell loss and pathology were evaluated inDrosophilausing knockdown of the presenilin homolog,Psn, together with partial loss of function ofsulfateless (sfl), a homolog ofNDST1, a gene specifically affecting HS sulfation. HSPG modulation of autophagy, mitochondrial function, and lipid metabolism were shown to be conserved in cultured human cell lines,Drosophila, and mouse astrocytes. RNAi ofNdst1reduced intracellular lipid levels in wild-type mouse astrocytes or those expressing humanized variants ofAPOE, APOE3, andAPOE4. RNA-sequence analysis of human cells deficient in HS synthesis demonstrated effects on the transcriptome governing lipid metabolism, autophagy, and mitochondrial biogenesis and showed significant enrichment in AD susceptibility genes identified by GWAS. Neuron-directed knockdown ofPsninDrosophilaproduced cell loss in the brain and behavioral phenotypes, both suppressed by simultaneous reductions insflmRNA levels. Abnormalities in mitochondria, liposome morphology, and autophagosome-derived structures in animals withPsnknockdown were also rescued by simultaneous reduction ofsfl. sflknockdown reversedPsn-dependent transcript changes in genes affecting lipid transport, metabolism, and monocarboxylate carriers. These findings support the direct involvement of HSPGs in AD pathogenesis.
Propofol Disrupts the Functional Core-Matrix Architecture of the Thalamus in Humans
Authors: Huang Zirui , Mashour George A. , Hudetz Anthony G. 
Published: January 2024

AbstractResearch into the role of thalamocortical circuits in anesthesia-induced unconsciousness is difficult due to anatomical and functional complexity. Prior neuroimaging studies have examined either the thalamus as a whole or focused on specific subregions, overlooking the distinct neuronal subtypes like core and matrix cells. We conducted a study of heathy volunteers and functional magnetic resonance imaging during conscious baseline, deep sedation, and recovery. We advanced the functional gradient mapping technique to delineate the functional geometry of thalamocortical circuits, within a framework of the unimodal-transmodal functional axis of the cortex. We observed a significant shift in this geometry during unconsciousness, marked by the dominance of unimodal over transmodal geometry. This alteration was closely linked to the spatial variations in the density of matrix cells within the thalamus. This research bridges cellular and systems-level understanding, highlighting the crucial role of thalamic core–matrix functional architecture in understanding the neural mechanisms of states of consciousness.
High-Resolution Laminar Identification in Macaque Primary Visual Cortex Using Neuropixels Probes
Authors: Zhang Li A. , Li Peichao , Callaway Edward M. 
Published: January 2024

AbstractLaminar electrode arrays allow simultaneous recording of activity of many cortical neurons and assignment to layers using current source density (CSD) analyses. Electrode arrays with 100-micron contact spacing have been used to estimate borders between layer 4 versus superficial or deep layers, but in macaque primary visual cortex (V1) there are far more layers, such as 4A which is only 50-100 microns thick. Neuropixels electrode arrays have 20-micron spacing, and thus could potentially discern thinner layers and more precisely identify laminar borders. Here we show that laminar distributions of CSDs lack consistency and the spatial resolution required for thin layers and accurate layer boundaries. To take full advantage of high density Neuropixels arrays, we have developed approaches based on higher resolution electrical signals and analyses, including spike waveforms and spatial spread, unit density, high-frequency action potential (AP) power spectrum, temporal power change, and coherence spectrum, that afford far higher resolution of laminar distinctions, including the ability to precisely detect the borders of even the thinnest layers of V1.
SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study (BMT CTN 2101)
Authors: Hill Joshua A. , Martens Michael J. , Young Jo-Anne H. , Bhavsar Kavita , Kou Jianqun , Chen Min , Lee Lik Wee , Baluch Aliyah , Dhodapkar Madhav V. , Nakamura Ryotaro , Peyton Kristin , Howard Dianna S. , Ibrahim Uroosa , Shahid Zainab , Armistead Paul , Westervelt Peter , McCarty John , McGuirk Joseph , Hamadani Mehdi , DeWolf Susan , Hosszu Kinga , Sharon Elad , Spahn Ashley , Toor Amir A. , Waldvogel Stephanie , Greenberger Lee M. , Auletta Jeffery J. , Horowitz Mary M. , Riches Marcie L. , Perales Miguel-Angel 
Published: January 2024

ABSTRACTBackgroundThe optimal timing of vaccination with SARS-CoV-2 vaccines after cellular therapy is incompletely understood.ObjectiveTo describe humoral and cellular responses after SARS-CoV-2 vaccination initiated <4 months versus 4-12 months after cellular therapy.DesignMulticenter prospective observational study.Setting34 centers in the United States.Participants466 allogeneic hematopoietic cell transplant (HCT; n=231), autologous HCT (n=170), or chimeric antigen receptor T cell (CAR-T cell) therapy (n=65) recipients enrolled between April 2021 and June 2022.InterventionsSARS-CoV-2 vaccination as part of routine care.MeasurementsWe obtained blood prior to and after vaccinations at up to five time points and tested for SARS-CoV-2 spike (anti-S) IgG in all participants and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains, as well as SARS-CoV-2-specific T cell receptors (TCRs), in a subgroup.ResultsAnti-S IgG and neutralizing antibody responses increased with vaccination in HCT recipients irrespective of vaccine initiation timing but were unchanged in CAR-T cell recipients initiating vaccines within 4 months. Anti-S IgG ≥2,500 U/mL was correlated with high neutralizing antibody titers and attained by the last time point in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T cell recipients, respectively. SARS-CoV-2-specific T cell responses were attained in 57%, 83%, and 58%, respectively. Humoral and cellular responses did not significantly differ among participants initiating vaccinations <4 months vs 4-12 months after cellular therapy. Pre-cellular therapy SARS-CoV-2 infection or vaccination were key predictors of post-cellular therapy anti-S IgG levels.LimitationsThe majority of participants were adults and received mRNA vaccines.ConclusionsThese data support starting mRNA SARS-CoV-2 vaccination three to four months after allogeneic HCT, autologous HCT, and CAR-T cell therapy.FundingNational Marrow Donor Program, Leukemia and Lymphoma Society, Multiple Myeloma Research Foundation, Novartis, LabCorp, American Society for Transplantation and Cellular Therapy, Adaptive Biotechnologies, and the National Institutes of Health
Mosquito and human characteristics influence natural Anopheline biting behavior andPlasmodium falciparumtransmission
Authors: Markwalter Christine F , Lapp Zena , Abel Lucy , Kimachas Emmah , Omollo Evans , Freedman Elizabeth , Chepkwony Tabitha , Amunga Mark , McCormick Tyler , Bérubé Sophie , Mangeni Judith N , Wesolowski Amy , Obala Andrew A , Taylor Steve M , O’Meara Wendy P 
Published: January 2024

AbstractThe human infectious reservoir ofPlasmodium falciparummalaria parasites is governed by the efficiency of parasite transmission during vector human contact as well as mosquito biting preferences. Understanding mosquito biting bias in a natural setting can help inform precise targeting of interventions to efficiently interrupt transmission. In a 15-month longitudinal cohort study in a high transmission setting in western Kenya, we investigated human and mosquito factors associated with differential mosquito biting by matching human DNA in single- and multi-sourceAnophelesbloodmeals to the individuals they bit. We employed risk factor analyses and econometric models of probabilistic choice to assess mosquito biting behavior with respect to both human-to-mosquito transmission and mosquito-to-human transmission. We observed thatP. falciparum-infected school-age boys accounted for 50% of bites potentially leading to onward transmission to mosquitoes and had an entomological inoculation rate 6.4x higher than any other group, that infectious mosquitoes were 2.8x more likely to bite cohort members harboringP. falciparumparasites compared to noninfectious mosquitoes, and that this preference to feed on infected people was enhanced by the presence of higher sporozoite loads in the mosquito head-thorax. Taken together, these results suggest that school-age boys disproportionately contribute to theP. falciparumtransmission cycle and thatP. falciparumsporozoites modify mosquito biting preferences to favor feeding on infected people.SignificanceThe malaria parasite transmission cycle is doubly-dependent on mosquito-human contact rates. To efficiently deploy transmission-reducing interventions, it is important to understand how mosquito biting preferences shape the human infectious reservoir. Here, we match human DNA in mosquito bloodmeals to the people they bit to quantify mosquito biting preferences and understand how mosquito characteristics shape these preferences. We observed that school-age boys were bitten the most and contributed most to onward transmission to mosquitoes. We also observed that, compared to non-infectious mosquitoes, mosquitoes harboring infectiousPlasmodium falciparumwere more likely to biteP. falciparum-infected people. These observations increase our understanding of malaria parasite transmission and evolution and provide a foundation for developing effective transmission-reducing interventions.
Associations of age at diagnosis of breast cancer with incident myocardial infarction and heart failure: a prospective cohort study
Authors: Liang Jie , Pan Yang , Zhang Wenya , Gao Darui , Wang Yongqian , Xie Wuxiang , Zheng Fanfan 
Published: January 2024

AbstractBackgroundThe associations of age at diagnosis of breast cancer with incident myocardial infarction (MI) and heart failure (HF) remain unexamined. Addressing this problem could promote understanding of the cardiovascular impact of breast cancer.MethodsData were from the UK Biobank. Information on the diagnosis of breast cancer, MI, and HF were collected at baseline and follow-ups (median=12.8 years). The propensity score matching method and Cox proportional hazards models were employed.ResultsA total of 251 277 female participants (mean age: 56.8±8.0 years), of whom 16 241 had breast cancer, were included. Among participants with breast cancer, younger age at diagnosis (per 10-year decrease) was significantly associated with elevated risks of MI (HR=1.36, 95%CI: 1.19 to 1.56,P<0.001) and HF (HR=1.31, 95% CI: 1.18 to 1.46,P<0.001). After propensity score matching, breast cancer patients with younger diagnosis ages had significantly higher risks of MI and HF than healthy controls.ConclusionYounger age at diagnosis of breast cancer was associated with higher risks of incident MI and HF, underscoring the necessity to pay additional attention to the cardiovascular health of breast cancer patients diagnosed at younger ages to conduct timely interventions to attenuate the subsequent risks of incident cardiovascular diseases.
Effects of Preanalytical Sample Collection and Handling on Comprehensive Metabolite Measurements in Human Urine Biospecimens
Authors: Braisted John , Henderson Theresa , Newman John W. , Moore Steven C. , Sampson Joshua , McClain Kathleen , Ross Sharon , Baer David J. , Mathé Ewy A. , Zanetti Krista A. 
Published: January 2024

AbstractEpidemiology studies evaluate associations between the metabolome and disease risk. Urine is a common biospecimen used for such studies due to its wide availability and non-invasive collection. Evaluating the robustness of urinary metabolomic profiles under varying preanalytical conditions is thus of interest. Here we evaluate the impact of sample handling conditions on urine metabolome profiles relative to the gold standard condition (no preservative, no refrigeration storage, single freeze thaw). Conditions tested included the use of borate or chlorhexidine preservatives, various storage and freeze/thaw cycles. We demonstrate that sample handling conditions impact metabolite levels, with borate showing the largest impact with 125 of 1,048 altered metabolites (adjusted P < 0.05). When simulating a case-control study with expected inconsistencies in sample handling, we predicted the occurrence of false positive altered metabolites to be low (< 11). Predicted false positives increased substantially (≥63) when cases were simulated to undergo alternate handling. Finally, we demonstrate that sample handling impacts on the urinary metabolome were markedly smaller than those in serum. While changes in urine metabolites incurred by sample handling are generally small, we recommend implementing consistent handling conditions and evaluating robustness of metabolite measurements for those showing significant associations with disease outcomes.
Controlling biomedical devices using pneumatic logic
Authors: Hoang Shane , Shehada Mabel , Karydis Konstantinos , Brisk Philip , Grover William H. 
Published: January 2024

AbstractMany biomedical devices are powered and controlled by electrical components. These electronics add to the cost of a device (possibly making the device too expensive for use in resource-limited or point-of-care settings) and can also render the device unsuitable for use in some environments (for example, high-humidity areas like incubators where condensation could cause electrical short circuits, ovens where electronic components may overheat, or explosive or flammable environments where electric sparks could cause serious accidents). In this work, we show that pneumatic logic can be used to power and control biomedical devices without the need for electricity or electric components. Originally developed for controlling microfluidic “lab-on-a-chip” devices, these circuits use microfluidic valves like transistors in air-powered logic “circuits.” We show that a modification to the basic valve design—adding additional air channels in parallel through the valve—creates a “high-flow” valve that is suitable for controlling a broad range of bioinstruments, not just microfluidics. As a proof-of-concept, we developed a high-flow pneumatic oscillator that uses five high-flow Boolean NOT gates arranged in a loop. Powered by a single constant vacuum source, the oscillator provides five out-of-phase pneumatic outputs that switch between vacuum and atmospheric pressure every 1.3 seconds. Additionally, a user can adjust the frequency of the oscillator by squeezing a bellows attached to one of the pneumatic outputs. We then used the pneumatic oscillator to power a low-cost 3D-printed laboratory rocker/shaker commonly used to keep blood products, cell cultures, and other heterogenous samples in suspension. Our air-powered rocker costs around $5 USD to build and performs as well as conventional electronic rockers that cost $1000 USD or more. This is the first of many biomedical devices that can be made cheaper and safer using pneumatic logic.
Prescribing pre-exposure prophylaxis (PrEP) for HIV prevention: A cross-sectional survey of General Practitioners in Australia
Authors: Wu Jason , Fairley Christopher K. , Grace Daniel , Bavinton Benjamin R. , Fraser Doug , Chan Curtis , Chow Eric P.F. , Ong Jason J. 
Published: January 2024

ABSTRACTBackgroundPre-exposure prophylaxis (PrEP) is a safe and effective medication for preventing HIV acquisition. We examined Australian general practitioners’ (GP) knowledge of PrEP efficacy, characteristics associated with ever prescribing PrEP, and barriers to prescribing.MethodsWe conducted an online cross-sectional survey of GPs working in Australia between April and October 2022. We performed univariable and multivariable logistic regression analyses to identify factors associated with: 1) the belief that PrEP was at least 80% efficacious; and 2) ever prescribed PrEP. We asked participants to rate the extent to which barriers affected their prescribing of PrEP.Results407 participants with a median age of 38 years (interquartile range 33-44). Half of the participants (50%, 205/407) identified how to correctly take PrEP, 63% (258/407) had ever prescribed PrEP, and 45% (184/407) felt confident with prescribing PrEP. Ever prescribing PrEP was associated with younger age (AOR 0.97, 95%CI: 0.94-0.99), extra training in sexual health (AOR 2.57, 95%CI: 1.54-4.29), and being a S100 Prescriber (OR 2.95, 95%CI: 1.47-5.90). The main barriers to prescribing PrEP included: ‘Difficulty identifying clients who require PrEP/relying on clients to ask for PrEP’ (76%, 310/407), ‘Lack of knowledge about PrEP’ (70%, 286/407), and ‘Lack of time’ (69%, 281/407).ConclusionLess than half of our GP respondents were confident in prescribing PrEP, and most had difficulty identifying who would require PrEP. Specific training on PrEP, which focuses on PrEP knowledge, identifying suitable clients, and making it time efficient is recommended, with GPs being remunerated for their time.
Plasticity in inhibitory networks improves pattern separation in early olfactory processing
Authors: Joshi Shruti , Haney Seth , Wang Zhenyu , Locatelli Fernando , Lei Hong , Cao Yu , Smith Brian , Bazhenov Maxim 
Published: January 2024

AbstractDistinguishing between nectar and non-nectar odors is challenging for animals due to shared compounds and varying ratios in complex mixtures. Changes in nectar production throughout the day - and potentially many times within a forager’s lifetime - add to the complexity. The honeybee olfactory system, containing fewer than 1,000 principal neurons in the early olfactory relay, the antennal lobe (AL), must learn to associate diverse volatile blends with rewards. Previous studies identified plasticity in the AL circuits, but its role in odor learning remains poorly understood. Using a biophysical computational network model, tuned by in vivo electrophysiological data, and live imaging of the honeybee’s AL, we explored the neural mechanisms and functions of plasticity in the early olfactory system. Our findings revealed that when trained with a set of rewarded and unrewarded odors, the AL inhibitory network suppresses shared chemical compounds while enhancing responses to distinct compounds. This results in improved pattern separation and a more concise neural code. Our calcium imaging data support these predictions. Analysis of a graph convolutional neural network performing an odor categorization task revealed a similar mechanism for contrast enhancement. Our study provides insights into how inhibitory plasticity in the early olfactory network reshapes the coding for efficient learning of complex odors.Significance StatementBy combining biophysical modeling, machine learning, electrophysiology and analysis of calcium imaging data, we demonstrate that associative and nonassociative plasticity in the honeybee antennal lobe (AL) the first relay of the insect olfactory system - work together to enhance the contrast between rewarded and unrewarded odors. Training the AL’s inhibitory network within specific odor environments enables the suppression of neural responses to common odor components while amplifying responses to distinctive ones. This study sheds light on the olfactory system’s ability to adapt and efficiently learn new odor-reward associations across varying environments, and it proposes innovative, energy-efficient principles applicable to artificial intelligence.