bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Unified Pipeline for FISH Spatial Transcriptomics
Authors: Cisar Cecilia , Keener Nicholas , Ruffalo Mathew , Paten Benedict 
Published: February 2023

AbstractIn recent years, high-throughput spatial transcriptomics has emerged as a powerful tool for investigating the spatial distribution of mRNA expression and the effects it may have on cellular function. There is a lack of standardized tools for analyzing spatial transcriptomics data, leading many groups to write their own in-house tools that are often poorly documented and not generalizable to other datasets. Currently, the only publicly available tools for extracting annotated transcript locations from raw multiplexed fluorescentin situhybridization (FISH) images are starfish, which is lacking in key areas, and MERlin, which is restricted to only MERFISH data. To address this, we have expanded and improved the starfish library and used those tools to create PIPEFISH, a semi-automated and generalizable pipeline that performs transcript annotation for FISH-based spatial transcriptomics. PIPEFISH has options for image processing, decoding, and cell segmentation, and calculates quality control metrics on the output to allow the user to assess the pipeline’s performance on their data. We used this pipeline to annotate transcript locations from three real datasets from three different common types of FISH image-based experiments: MERFISH, seqFISH, and targetedin situsequencing (ISS), and verified that the results were high quality using the internal quality metrics of the pipeline and also a comparison to a orthogonal method of measuring RNA expression in a similar tissue sample. We have made PIPEFISH publicly available through Github for anyone interested in analyzing data from FISH-based spatial transcriptomic assays.
Effect of growing regions on morphological characteristics, protein nutrition, rumen degradation and molecular structures of various whole-plant silage corn cultivars
Authors: Zhang Xinyue , Khan Nazir Ahmad , Yao Enyue , Kong Fanlin , Chen Ming , Khan Rifat Ullah , Liu Xin , Zhang Yonggen , Xin Hangshu ,   with the Lorem Ipsum Consortium
Published: February 2023

AbstractLittle information exists on the variation of morphological characteristics, nutritional value, ruminal degradability, and molecular structural makeup of diverse whole-plant silage corn (WPSC) cultivars among different growing regions. This study investigated the between-regions discrepancies in five widely used WPSC cultivars in China (FKBN, YQ889, YQ23, DK301 and ZD958) in terms of 1) morphological characteristics; 2) crude protein (CP) chemical profile; 3) Cornell Net Carbohydrate and Protein System (CNCPS) CP subfractions; 4)in situCP degradation kinetics; and 5) CP molecular structures. Our results revealed that significant difference were observed on growing region and WPSC cultivar interaction for all estimated morphological characteristics (P< 0.001), CP chemical profile (P< 0.001), CNCPS subfractions (P< 0.001) and CP molecular structural features (P< 0.05). Except ear weight (P= 0.18), all measured morphological characteristics varied among different growing regions (P< 0.001). Besides, WPSC cultivars planted in different areas had remarkably different (P< 0.01) CP chemical profiles and CNCPS subfractions. All spectral parameters of protein primary structure of WPSC differed (P< 0.05) due to the various growing regions, except amide II area (P= 0.28). Finally, the area ratio of amide I to II was negatively correlated with the contents of soluble CP (δ= -0.66;P= 0.002), CP (δ= - 0.61;P= 0.006), non-protein N (δ= -0.56;P= 0.004) and acid detergent insoluble CP (δ= - 0.43;P= 0.008), in conjunction with positively correlated with moderately degradable CP (PB1;δ= 0.58;P= 0.01). In conclusion, the current study suggested that even for the same WPSC cultivar, the morphological characteristics, protein nutritional values and rumen degradability significantly varied among different grown regions due to distinguished molecular structures.Author summaryAs the major roughage source, whole plant silage corn plays an essential role in ruminant feed industry. The quality and quantity of it largely influenced by environmental and climate conditions except genetic factors. However, there was limited information to systematically analyze whole plant silage corn from morphological characteristics, nutritional components, rumen degradation to its inherent molecular structures. Thus, this study was conducted to investigate the discrepancies of various silage-corn cultivars grown in different regions from internal structure to phenotype based novel technology - fourier transform infrared spectroscopy.
Solid Phase Synthesis of Fluorosulfate Containing Macrocycles for Chemoproteomic Workflows
Authors: Faucher Franco F. , Abegg Daniel , Ipock Phillip , Adibekian Alexander , Lovell Scott , Bogyo Matthew 
Published: February 2023

AbstractMacrocyclic peptides are attractive for chemoproteomic applications due to their modular synthesis and potential for high target selectivity. We describe a solid phase synthesis method for the efficient generation of libraries of small macrocycles that contain an electrophile and alkyne handle. The modular synthesis produces libraries that can be directly screened using simple SDS-PAGE readouts and then optimal lead molecules applied to proteomic analysis. We generated a library of 480 macrocyclic peptides containing the weakly reactive fluorosulfate (OSF) electrophile. Initial screening of a subset of the library containing each of the various diversity elements identified initial molecules of interest. The corresponding positional and confirmational isomers were then screened to select molecules that showed specific protein labeling patterns that were dependent on the probe structure. The most promising hits were applied to standard chemoproteomic workflows to identify protein targets. Our results demonstrate the feasibility of rapid, on-resin synthesis of diverse macrocyclic electrophiles to generate new classes of covalent ligands.
Tracking and curating putative SARS-CoV-2 recombinants with RIVET
Authors: Smith Kyle , Ye Cheng , Turakhia Yatish 
Published: February 2023

AbstractIdentifying and tracking recombinant strains of SARS-CoV-2 is critical to understanding the evolution of the virus and controlling its spread. But confidently identifying SARS-CoV-2 recombinants from thousands of new genome sequences that are being shared online every day is quite challenging, causing many recombinants to be missed or suffer from weeks of delay in being formally identified while undergoing expert curation. We present RIVET – a software pipeline and visual platform that takes advantage of recent algorithmic advances in recombination inference to comprehensively and sensitively search for potential SARS-CoV-2 recombinants, and organizes the relevant information in a web interface that would help greatly accelerate the process identifying and tracking recombinants.Availability and ImplementationRIVET-based web interface displaying the most updated analysis of potential SARS-CoV-2 recombinants is available athttps://rivet.ucsd.edu/. RIVET’s frontend and backend code is freely available under MIT license athttps://github.com/TurakhiaLab/rivet. All inputs necessary for running the RIVET’s backend workflow for SARS-CoV-2 are available through a public database maintained by UCSC (https://hgdownload.soe.ucsc.edu/goldenPath/wuhCor1/UShER_SARS-CoV-2/).Contactyturakhia@ucsd.edu
Barriers to access to antiretroviral therapy by people living with HIV in Indonesia during the COVID-19 pandemic: A qualitative study
Authors: Fauk Nelsensius Klau , Gesesew Hailay Abhra , Seran Alfonsa Liquory , Ward Paul Russell 
Published: February 2023

AbstractBackgroundThe coronavirus disease (COVID-19) pandemic has a significant influence on access to healthcare services. This study aimed to understand the views and experiences of people living with HIV (PLHIV) about barriers to their access to antiretroviral therapy (ART) service in Belu district, Indonesia, during the COVID-19 pandemic.MethodsThis qualitative inquiry employed in-depth interviews to collect data from 21 participants who were recruited using a snowball sampling technique. Data analysis was guided by a thematic framework analysis.ResultsThe findings showed that fear of contracting COVID-19 was a barrier that impeded participants’ access to ART service. Such fear was influenced by their awareness of their vulnerability to the infection, the possibility of unavoidable physical contact in public transport during a travelling to HIV clinic and the widespread COVID-19 infection in healthcare facilities. Lockdowns, COVID-19 restrictions and lack of information about the provision of ART service during the pandemic were also barriers that impeded their access to the service. Other barriers included the mandatory regulation for travellers to provide their COVID-19 vaccine certificate, financial difficulty, long-distance travel to the HIV clinic and a lack of public transport.ConclusionsThe findings indicate the need for dissemination of information about the provision of ART service during the pandemic and the benefits of COVID-19 vaccination for the health of PLHIV. The findings also indicate the need for new strategies to bring ART service closer to PLHIV during the pandemic such as a community-based delivery system. Future large-scale studies exploring views and experiences of PLHIV about barriers to their access to ART service during the COVID-19 pandemic and new intervention strategies are recommended.
Child Support Grant expansion and cognitive function among women in rural South Africa: findings from a natural experiment in HAALSI cohort
Authors: Chakraborty Rishika , Kobayashi Lindsay C. , Jock Janet , Wing Coady , Chen Xiwei , Phillips Meredith , Berkman Lisa , Kahn Kathleen , Kabudula Chodziwadziwa Whiteson , Rosenberg Molly 
Published: February 2023

AbstractCash transfers are a promising but understudied intervention that may protect cognitive function in adults by promoting their cognitive reserve. South Africa has a rapidly ageing population, however, less is known about the nature of association between cash transfers and cognitive function in this setting. We leveraged natural experiments from Child Support Grant (CSG) age-eligibility expansions to investigate the association between duration of CSG eligibility and cognitive function among biological mothers of child beneficiaries in South Africa. We analysed 2014/2015 baseline data from 944 women, aged 40 - 59 years with at least one CSG-eligible child, enrolled in the HAALSI cohort in Agincourt, South Africa. Duration of CSG eligibility for each mother was calculated based on the birth dates of all their children and the CSG age eligibility expansion years. Cognitive function was measured using a cognitive battery administered to the mothers at baseline interview. Linear regression was used to estimate the association between duration of CSG eligibility, dichotomized as low (≤10 years) and high (>10 years) eligibility, and cognitive function z-scores of the mothers. Our study finds that high duration of CSG eligibility, compared to low, was associated with higher cognitive function z-scores in the full sample [β: 0.15 SD; 95% CI: 0.04, 0.26; p-value = 0.01]. In mothers with one to four lifetime children, but not five or more, high duration of CSG eligibility, compared to low, was associated with higher cognitive function z-scores [β: 0.19 SD; 95% CI: 0.05, 0.34, p-value = 0.02]. Government cash transfers given to support raising children may confer substantial protective effect on cognitive function of mothers in their mid-life. Further studies are needed to understand how parity may influence this relationship. Our findings bring evidence to policymakers for designing income supplementation programmes to promote healthy cognitive ageing in low-income settings.
Sodium and Potassium Consumption in Jamaica: National Estimates and Associated Factors from the Jamaica Health and Lifestyle Survey 2016-2017
Authors: Ferguson Trevor S , Younger-Coleman Novie Om , Webster-Kerr Karen , Tulloch-Reid Marshall K. , Bennett Nadia R , Davidson Tamu , Grant Andriene S , Gordon-Johnson Kelly-Ann M. , Govia Ishtar , Soares-Wynter Suzanne , Mckenzie Joette A , Walker Evelyn , Cunningham-Myrie Colette A , Anderson Simon G , Blake Alphanso L , Ho James , Stephenson Robyn , Edwards Sharmaine E , Mcfarlane Shelly R , Spence Simone , Wilks Rainford J 
Published: February 2023

ABSTRACTObjectiveTo estimate dietary sodium and potassium consumption among Jamaicans and evaluate associations with sociodemographic and clinical characteristics.MethodsWe conducted a cross-sectional analysis of data from the Jamaica Health and Lifestyle Survey 2016-2017. Participants were non-institutionalized Jamaicans, ≥15 years. Trained staff collected sociodemographic and health data via interviewer administered questionnaires and collected spot urine samples. The Pan American Health Organization Formulae were used to estimate 24-hour urine sodium and potassium excretion. High sodium was defined as ≥2000 mg/day and low potassium as <3510 mg/day (World Health Organization criteria). Associations of these outcomes with sociodemographic and clinical characteristics were explored in sex specific multivariable ANOVA models.ResultsAnalyses included 1009 participants (368 males, 641 females; mean age 48.5 years). Mean sodium excretion was 3582 mg/day (males 3943 mg/day, females 3245 mg/day, p<0.001). Mean potassium excretion was 2052 mg/day (males 2210 mg/day, females 1904 mg/day, p=0.001). The prevalence of high sodium consumption was 66.6% (males 72.8%, female 60.7%, p<0.001) and low potassium intake was 88.8% (85.1% males, 92.3% females, p<0.001). Among males, sodium consumption was inversely associated with older age and prehypertension, but directly associated with current smoking and obesity. Among females, sodium consumption was inversely associated with hypertension, impaired fasting glucose, low GFR and high physical activity, but was directly associated with obesity.ConclusionMost Jamaican adults have diets high in sodium and low in potassium. Sodium consumption was directly associated with obesity in both men and women. Population based strategies are therefore required to address these cardiovascular risk factors.
Comparative Effectiveness of BNT162b2 and NVX-CoV2373 Vaccines in Korean Adults
Authors: Park Seon Kyeong , Choe Young June , Choe Seung Ah , Cowling Benjamin John , Hwang Ji Hae , Lee Ju Hee , Lee Kil Hun , Yi Seonju , Lee Sang Won , Kwon Geun-Yong , Jang Eun Jung , Kim Ryu Kyung , Park Young-Joon 
Published: February 2023

AbstractBackgroundVarious types of vaccines against SARS-CoV-2 have reduced the burden of coronavirus diseases 2019 (COVID-19) across the world. We conducted an observational study to evaluate the effectiveness of NVX-CoV2373 and BNT162b2 in providing protection in Korean adults.MethodsThis study was a retrospective matched cohort study to emulate a target trial of three doses of NVX-CoV2373 (N-N-N) versus three doses of BNT162b2 (B-B-B) vaccines in presumed immune-naive adults. We used data from the Korea COVID-19 Vaccine Effectiveness (K-COVE) cohort, combining all COVID-19 laboratory-confirmed cases and all COVID-19 immunization registry, between February and November 2022. We calculated 40-week risk differences and risk ratios between the two vaccines.ResultsA total of 3,019 recipients of NVX-CoV2373 vaccine and 3,027 recipients of BNT162b2 vaccine were eligible for the study. The 40-week risk ratios for recipients of the NVX-CoV2373 vaccine as compared with recipients of the BNT162b2 vaccine were 1.169 (95% CI, 1.015 to 1.347) for laboratory-confirmed SARS-CoV-2 infection, and 0.504 (95% CI, 0.126 to 2.014) for severe SARS-CoV-2 infection. Estimated risk of severe infection was 0.001 events per 1000 persons (95% CI, 0 to 0.003) for the NVX-CoV2373 vaccine and 0.002 events per 1000 persons (95% CI, 0.001 to 0.006) for BNT162b2 vaccine.ConclusionThis study identifies reduced risk of SARS-CoV-2 infection and severe infection after receipt of three doses of either NVX-CoV2373 or BNT162b2 vaccines in Korean adults. Direct, vaccine-conferred protection may be of importance among high risk persons to mitigate from serious clinical outcome from COVID-19.
Quantification of all 12 canonical ribonucleotides by real-time fluorogenicin vitrotranscription
Authors: Purhonen Janne , Kallijärvi Jukka 
Published: February 2023

ABSTRACTEnzymatic methods to quantify deoxyribonucleoside triphosphates have existed for decades. In contrast, no general enzymatic method to quantify ribonucleoside triphosphates (rNTPs), which drive almost all cellular processes and serve as precursors of RNA, exists to date. ATP can be measured with an enzymatic luminometric method employing the firefly luciferase, but the quantification of the other ribonucleoside mono-, di-, and triphosphates is still a challenge for a non-specialized laboratory and practically impossible without chromatography equipment. To allow feasible quantification of ribonucleoside phosphates in any laboratory with typical molecular biology and biochemistry tools, we developed a robust microplate assay based on real-time detection of the Broccoli aptamer duringin vitrotranscription. The assay employs the bacteriophage T7 and SP6 RNA polymerases, two oligonucleotide templates encoding the 49-nucleotide Broccoli aptamer, and a high-affinity fluorogenic aptamer-binding dye to quantify each of the four canonical rNTPs. The inclusion of nucleoside mono- and diphosphate kinases in the assay reactions enabled the quantification of the mono- and diphosphate counterparts. The assay is inherently specific and tolerates concentrated tissue and cell extracts. In summary, we describe the first chromatography-free method to quantify ATP, ADP, AMP, GTP, GDP, GMP, UTP, UDP, UMP, CTP, CDP, and CMP in biological samples.
Massive Multiplexing of Spatially Resolved Single Neuron Projections with Axonal BARseq
Authors: Yuan Li , Chen Xiaoyin , Zhan Huiqing , Gilbert Henry L. , Zador Anthony M. 
Published: February 2023

ABSTRACTNeurons in the cortex are heterogenous, sending diverse axonal projections to multiple brain regions. Unraveling the logic of these projections requires single-neuron resolution. Although a growing number of techniques have enabled high-throughput reconstruction, these techniques are typically limited to dozens or at most hundreds of neurons per brain, requiring that statistical analyses combine data from different specimens. Here we present axonal BARseq, a high-throughput approach based on reading out nucleic acid barcodes usingin situRNA sequencing, which enables analysis of even densely labeled neurons. As a proof of principle, we have mapped the long-range projections of >8000 mouse primary auditory cortex neurons from a single brain. We identified major cell types based on projection targets and axonal trajectory. The large sample size enabled us to systematically quantify the projections of intratelencephalic (IT) neurons, and revealed that individual IT neurons project to different layers in an area-dependent fashion. Axonal BARseq is a powerful technique for studying the heterogeneity of single neuronal projections at high throughput within individual brains.
Novel Evoked Synaptic Activity Potentials (ESAPs) elicited by Spinal Cord Stimulation
Authors: Sharma Mahima , Bhaskar Vividha , Yang Lillian , FallahRad Mohamad , Gebodh Nigel , Zhang Tianhe , Esteller Rosana , Martin John , Bikson Marom 
Published: February 2023

AbstractSpinal cord stimulation (SCS) evokes fast epidural Evoked Compound Action Potential (ECAPs) that represent activity of dorsal column axons, but not necessarily a spinal circuit response. Using a multimodal approach, we identified and characterized a delayed and slower potential evoked by SCS that reflects synaptic activity within the spinal cord. Anesthetized female Sprague Dawley rats were implanted with an epidural SCS lead, epidural motor cortex stimulation electrodes, an epidural spinal cord recoding lead, an intraspinal penetrating recording electrode array, and intramuscular electromyography (EMG) electrodes in the hindlimb and back. We stimulated the motor cortex or the epidural spinal cord and recorded epidural, intraspinal, and EMG responses. SCS pulses produced characteristic propagating ECAPs (composed of P1, N1, and P2 waves with latencies <2 ms) and an additional wave (“S1”) starting after the N2. We verified the S1-wave was not a stimulation artifact and was not a reflection of hindlimb/back EMG. The S1-wave has a distinct stimulation-intensity dose response and spatial profile compared to ECAPs. CNQX (a selective competitive antagonist of AMPA receptors) significantly diminished the S1-wave, but not ECAPs. Furthermore, cortical stimulation, which did not evoke ECAPs, produced epidurally detectable and CNQX-sensitive responses at the same spinal sites, confirming epidural recording of an evoked synaptic response. Finally, applying 50 Hz SCS resulted in dampening of ESAPs, but not ECAPs. Therefore, we hypothesize that the S1-wave is synaptic in origin, and we term the S1-wave type responses: Evoked Synaptic Activity Potentials (ESAPs). The identification and characterization of epidurally recorded ESAPs from the dorsal horn may elucidate SCS mechanisms.Significance StatementSpinal cord stimulation (SCS) is an established treatment for chronic pain and has applications to other disorders and neurorehabilitation. Notwithstanding decades of trials and research, questions remain about SCS mechanisms of action - and indicators thereof. Recent technological developments have enabled the detection of Evoked Compound Action Potential (ECAPs) – reflecting synchronous activity of the dorsal column axons activated by SCS. However, ECAP is not a direct measure of sensory processing in the dorsal horn. Here, we identify and characterize a novel electrophysiological signal that is evoked and detectable by epidural SCS electrodes and reflects spinal synaptic currents. This new signal, termed an Evoked Synaptic Activity Potential (ESAP), is thus a novel means with which to interrogate spinal gray matter circuits during SCS.
Diameter Dependence of Transport through Nuclear Pore Complex Mimics Studied Using Optical Nanopores
Authors: Klughammer Nils , Barth Anders , Dekker Maurice , Fragasso Alessio , Onck Patrick R. , Dekker Cees 
Published: February 2023

AbstractThe nuclear pore complex (NPC) regulates the selective transport of large biomolecules through the nuclear envelope. As a model system for nuclear transport, we construct NPC mimics by functionalizing the pore walls of freestanding palladium zero-mode waveguides with the FG-nucleoporin Nsp1. This approach enables the measurement of single-molecule translocations through individual pores using optical detection. We probe the selectivity of Nsp1-coated pores by quantitatively comparing the translocation rates of the nuclear transport receptor Kap95 to the inert probe BSA over a wide range of pore sizes from 35 nm to 160 nm. Pores below 55 ± 5 nm show significant selectivity that gradually decreases for larger pores. This finding is corroborated by coarse-grained molecular-dynamics simulations of the Nsp1 mesh within the pore, which suggest that leakage of BSA occurs by diffusion through transient openings within the dynamic mesh. Furthermore, we experimentally observe a modulation of the BSA permeation when varying the concentration of Kap95. The results demonstrate the potential of single-molecule fluorescence measurements on biomimetic NPCs to elucidate the principles of nuclear transport.