bluuebunny/crossref_metadata_2025_split huggingface dataset:
Raman spectroscopy, used transcutaneously and non-invasively from a finger, to predict COVID-19: A feasibility, proof-of-concept study
Authors: Chefitz Allen B. , Birch Thomas , Yang Yongwu , Hussain Arib 
Published: January 2023

AbstractBACKGROUNDA definitive COVID-19 infection typically is diagnosed by laboratory tests, including real-time, reverse-transcriptase Polymerase Chain Reaction (PCR)-based testing. These currently available COVID-19 tests require the patient to provide an extra-corporeal specimen and the results may not be immediate. Consequently, a variety of rapid antigen tests for COVID-19, all with a wide range of accuracy in terms of sensitivity and specificity, has proliferated (1,2). These rapid tests now represent a significantly larger proportion of all testing done for COVID-19, yet suffer from requiring a physical specimen from the nose or mouth and waiting 15 minutes for most.As a solution, we propose a non-invasive, trans-cutaneous, real-time viral detection device, based on the principles of Raman spectroscopy and machine learning. It does not require any extra-corporeal specimens and can be configured for self-administration. It can be easily used by non-experts and does not require medical training. Our approach suggests that our non-invasive, transcutaneous method may be broadly useful not only in COVID-19 diagnosis, but also in other diagnoses.METHODS160 COVID positive (+) patients and 316 COVID negative (-) patients prospectively underwent nasal PCR testing concurrently with testing using our non-invasive, transcutaneous, immediate viral detector. Both the PCR and our experimental viral detector tests were performed side-by-side on outpatients (N=389) as well as inpatients (N= 87) at Holy Name Medical Center in Teaneck, NJ between June 2021 and August, 2022. The spectroscopic data were generated using an 830nm Raman System with SpectraSoft (W2 Innovations)and then, using machine learning, processed to provide an immediate prediction. A unique patient-interface for finger insertion enabled the application of Raman spectroscopy to viral detection in humans.RESULTSThe data analysis algorithm demonstrates that there is an informative Raman spectrum output from the device, and that individual Raman peaks vary between cases and controls. Our proof-of-concept study yields encouraging results, with a specificity for COVID-19 of 0.75, and a sensitivity (including asymptomatic patients) of 0.80.CONCLUSIONSThe combination of Raman spectroscopy, artificial intelligence, and our unique patient-interface admitting only a patient finger achieved test results of 0.75 specificity and 0.80 sensitivity for COVID-19 testing in this first in human proof-of-concept study. More significantly, the predictability improved with increasing data.
Assessing treatment effect modification due to comorbidity using individual participant data from industry-sponsored drug trials
Authors: Hanlon Peter , Butterly Elaine W , Shah Anoop SV , Hannigan Laurie J , Lewsey Jim , Mair Frances S , Kent David , Guthrie Bruce , Wild Sarah H , Welton Nicky J , Dias Sofia , McAllister David A 
Published: January 2023

AbstractBackgroundPeople with comorbidities are under-represented in clinical trials. Empirical estimates of treatment effect modification by comorbidity are lacking leading to uncertainty in treatment recommendations. We aimed to produce estimates of treatment effect modification by comorbidity using individual participant data (IPD).Methods and ResultsUsing 126 industry-sponsored phase 3/4 trials across 23 index conditions, we performed a two-stage IPD meta-analysis to estimate modification of treatment effect by comorbidity. We estimated the effect of comorbidity measured in 3 ways: (i) the number of comorbidities (in addition to the index condition), (ii) presence or absence of the six commonest comorbid diseases for each index condition, and (iii) using continuous markers of underlying conditions (e.g., estimated glomerular function).Comorbidities were under-represented in trial participants and few had >2 comorbidities. We found no evidence of modification of treatment efficacy by comorbidity, for any of the 3 measures of comorbidity. This was the case for 20 conditions for which the outcome variable was continuous (e.g., change in glycosylated haemoglobin in diabetes) and for three conditions in which the outcomes were discrete events (e.g., number of headaches in migraine). Although all were null, estimates of treatment effect modification were more precise in some cases (e.g., Sodium-glucose co-transporter inhibitors for type 2 diabetes – interaction term for comorbidity count 0.004, 95% CI - 0.01 to 0.02) while for others credible intervals were wide (e.g., corticosteroids for asthma – interaction term -0.22, 95% CI -1.07 to 0.54).ConclusionFor trials included in this analysis, there was no empirical evidence of treatment effect modification by comorbidity. Our findings support the assumption that estimates of treatment efficacy are constant, at least across modest levels of comorbidity.
Antenatal Care Dropout and Associated Factors in Ethiopia: A Systematic Review and Meta-Analysis
Authors: Sisay Gizaw , Mulat Tsion 
Published: January 2023

AbstractBackgroundAntenatal care during pregnancy is one of the most important strategies for improving maternal and newborn health and preventing maternal and newborn mortality and morbidity. The prevalence and predictors of antenatal care dropout in Ethiopia were studied, and the results were inconsistent and showed considerable variation. Hence, this meta-analysis aimed at estimating the overall prevalence of antenatal care dropout and its associated factors in Ethiopia.MethodsA comprehensive search of studies published before December 30, 2022, was explored by using distinct international databases such as (PubMed, DOJA, Embase, Cochrane library, African journals online, Google scholar, web of science and the institutional repository of Ethiopian universities were used to search relevant studies. Data were extracted using Microsoft Excel, and analysis was performed using STATA version 16. A random-effects model were used to estimate the overall prevalence of antenatal care drop-out and odd ratio for determinant factors.I2Test-statistics for to assessing heterogeneity and Egger’s test for assessing publication bias were used.ResultsA total of seven studies were included for this systematic review and meta-analysis with of 11839 study participants. The overall pooled prevalence of antenatal dropout in Ethiopia was found to be 41.37% with 95% CI: (35.04, 47.70). Distance from the health care facility (AOR = 2.55, 95% CI = 1.79, 3.31), pregnancy complication signs (AOR = 2.88, 95% CI= 2.41, 3.66), place of residence (AOR= 1.59, 95% CI = 1.31, 1.87), educational level (AOR=1.79, 95%CI = 1.37, 2.21), age group(30-49) (AOR=(AOR = 0.57, 95% CI = 0.26, 0.88) were significantly associated with antenatal care dropout.ConclusionBased on this systematic review and meta-analysis, 41% of Ethiopian women dropped out of antenatal care visits before the minimum recommended visit (four times). Hence, to reduce the number of ANC dropouts it is important to counsel and educate women at their first prenatal care. Issues of urban-rural disparity and locations identified as hotspots for incomplete ANC visits require that further attention.
Estimating The Uncertain Effect of the COVID Pandemic on Drug Overdoses
Authors: Moghtaderi Ali , Zocchi Mark S. , Pines Jesse M. , Venkat Arvind , Black Bernard 
Published: January 2023

ABSTRACTObjectiveU.S. drug-related overdose deaths and Emergency Department (ED) visits rose in 2020 and again in 2021. Multiple studies and the news media attributed this rise primarily to increased drug use resulting from the societal disruptions related to the coronavirus (COVID-19) pandemic. A competing explanation is that higher overdose deaths and ED visits may instead have been a continuation of pre-pandemic trends in synthetic-opioid deaths. We assess the evidence on whether increases in overdose deaths and ED visits are likely to be causally related to the COVID-19 pandemic, increased synthetic-opioid use, or some of both.MethodsWe use national data from the Centers for Disease Control and Prevention (CDC) on rolling 12-month drug-related deaths (2015-2021); CDC data on monthly ED visits (2019-September 2020); and ED visit data across 21states from a national ED group (January 2016-June 2022). We study drug overdose deaths per 100,000 persons during the pandemic period, and ED visits for drug overdoses, compared to predicted levels based on pre-pandemic trends.ResultsMortalityNational overdose mortality increased from 21/100,000 in 2019 to 26/100,000 in 2020 and 30/100,000 in 2021. The 2020 increase is well-predicted by models that extrapolate pre-pandemic trends for rolling 12-month mortality to the pandemic period, consistent with higher mortality reflecting continuation of those trends. Placebo analyses (which assume the pandemic started earlier or later than March 2020) do not provide evidence for a change in trend in or soon after March 2020. State-level analyses of actual-minus-predicted mortality, relative to pre-pandemic trends, show no consistent pattern. The state-level results support state heterogeneity in overdose mortality trends, and do not support the pandemic being a major driver of overdose mortality.ED visitsED overdose visits rose during our sample period, reflecting a worsening opioid epidemic, but rose at similar rates during the pre-pandemic and pandemic periods.ConclusionThe causes of rising overdose mortality in 2020 and 2021 cannot be definitely determined, but the observed increases can be largely explained by a continuation of pre-pandemic trends in synthetic-opioid deaths, principally fentanyl. In contrast to prior studies, we do not find support for the pandemic having been a principal driver of rising mortality. Policymakers need to directly address the synthetic opioid epidemic, and not expect a respite as the pandemic recedes.
CONSTANS alters the circadian clock inArabidopsis thaliana
Authors: de los Reyes Pedro , Romero-Campero Francisco J , Gao He , Serrano-Bueno Gloria , Romero Jose M , Valverde Federico 
Published: January 2023

AbstractPlants are sessile organisms that have acquired highly plastic developmental strategies to adapt to the environment. Among these processes, the floral transition is essential to ensure reproductive success and is finely regulated by several internal and external genetic networks. The photoperiodic pathway, which controls the plant response to day length, is one of the most important pathways controlling flowering. InArabidopsisphotoperiodic flowering,CONSTANS(CO) is the central gene activating the expression of the florigenFLOWERING LOCUS T(FT)in the leaves at the end of a long day.COexpression is strongly regulated by the circadian clock. However, to date, no evidence has been reported regarding a feedback loop from the photoperiod pathway back to the circadian clock. Using transcriptional networks, we have identified relevant network motifs regulating the interplay between the circadian clock and the photoperiod pathway. Gene expression, chromatin immunoprecipitation experiments and phenotypic analysis allowed us to elucidate the role of CO over the circadian clock. Plants with alteredCOexpression showed a different internal clock period, measured by daily rhythmic movements in the leaves. We show that CO is able to activate key genes related to the circadian clock, such asCCA1,LHY,PRR5andGI,at the end of a long day by binding to specific sites on their promoters. Moreover, a significant number of PRR5 repressed target genes are upregulated by CO, and this could explain the phase transition promoted by CO. The CO-PRR5 complex interacts with the bZIP transcription factor HY5 and helps to localize the complex in the promoters of clock genes. Our results indicate that there may be a feedback loop in which CO communicates back to the circadian clock, feeding seasonal information to the circadian system.
Insights into the Microbial Weathering of Chinese Wooden Ancestral Halls in Guangdong Province
Authors: Liu Manchun , Su Xining , Wen Qinqing , Yang Tongshu , Lin Muyuyang , Abudureyimu Paierzhati , Lon Jerome Rumdon , Luo Jianfei 
Published: January 2023

AbstractWooden buildings are facing biodeterioration due to natural weathering. Ancestral halls are traditional Chinese wooden architecture with high artistic value. The research analyzed the microbial diversity of nine ancestral halls in Guangdong Province under subtropical monsoon climates. With amplicon sequencing, we found a common core microorganism group, includingBacillus,Pseudomonas,Paenibacillus,Acinetobacter,Toxicocladosporium,Cladosporium,Aspergillus, andEpicoccum. A total of 8 different species of bacteria and 7 different species of fungi were isolated from Chen Clan Ancestral halls, most of which were proven to be capable of degrading cellulose or lignin. The comparison between damaged and undamaged sites (whether the paint coating is flaked off) revealed similar microbial compositions but with differing abundances.FirmicutesandAscomycotadominated damaged surfaces, whileProteobacteriaandActinobacteriaprevailed in undamaged ones. Notably,Cladosporium, widely present in both sites, emerged as the primary cellulose-degrading genus. Given the similar microbial compositions between damaged and undamaged sites, it is suggested that using paint alone as the exclusive means to protect bare wood is insufficient. Apparent correlation between microorganisms on wooden surfaces and humans showed that the increase of visitor flow rates might impact the microbiota composition on cultural relics. We evaluated the effect of four representative biocides and determined the feasibility of low-concentration Isothiazolinone. This research facilitates a basic understanding of the microbial weathering of ancestral halls and add significant reference for preserving wooden structures.
Widespread distribution and evolution of poxviral entry-fusion complex proteins in giant viruses
Authors: Kao Sheng , Kao Chi-Fei , Chang Wen , Ku Chuan 
Published: January 2023

AbstractPoxviruses are known to encode a set of proteins that form an entry-fusion complex (EFC) to mediate virus entry. However, the diversity, evolution, and origin of these EFC proteins remain poorly understood. Here we identify the EFC protein homologs in poxviruses and other giant viruses of phylumNucleocytoviricota. The 11 EFC genes are present in almost all pox-viruses, with the two smallest, G3 and O3, absent inEntomopoxvirinaeand basal lineages ofChordopoxvirinae. Five of the EFC genes are further grouped into two families, A16/G9/J5 and F9/L1, which are widely distributed across other major lineages ofNucleocytoviricota, including metagenome-assembled genomes, but are generally absent in viruses infecting algae or non-amoebozoan heterotrophic protists. The A16/G9/J5 and F9/L1 families co-occur, mostly as single copies, in 93% of the non-Poxviridaegiant viruses that have at least one of them. Distribution and phylogenetic patterns suggest that both families originated in the ancestor ofNucleocytoviricota. In addition to thePoxviridaegenes, homologs from each of the otherNucleo-cytoviricotafamilies are largely clustered together, suggesting their ancient presence and vertical inheritance. Despite deep sequence divergences, we observed noticeable conservation of cysteine residues and predicted structures between EFC proteins ofPoxviridaeand other families. Overall, our study reveals widespread distribution of these EFC protein homologs beyond pox-viruses, implies the existence of a conserved membrane fusion mechanism, and sheds light on host range and ancient evolution ofNucleocytoviricota.ImportanceFusion between virus and host membranes is critical for viruses to release genetic materials and to initiate infection. Whereas most viruses use a single protein for membrane fusion, poxviruses employ a multi-protein entry-fusion complex (EFC). We report that two major families of the EFC proteins are widely distributed within the virus phylumNucleocytoviricota, which include poxviruses and other dsDNA “giant viruses” that infect animals, amoebozoans, algae, and various microbial eukaryotes. Each of these two protein families is structurally conserved, traces its origin to the root ofNucleocytoviricota, was passed down to the major subclades ofNucleocytoviricota, and is retained in most giant viruses known to infect animals and amoebozoans. The EFC proteins therefore represent a potential mechanism for virus entry in diverse giant viruses. We hypothesize that they may have facilitated the infection of an animal/amoebozoan-like host by the lastNucleocytoviricotacommon ancestor.
Gesture profiles distinguish primary progressive aphasia variants
Authors: Dresang Haley C. , Williamson Rand , Kim Hana , Hillis Argye E. , Buxbaum Laurel J. 
Published: January 2023

AbstractPrimary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by progressive language deficits. There are three main variants of PPA – semantic (svPPA), logopenic (lvPPA), and nonfluent (nfvPPA) – that can be challenging to distinguish. Limb praxis may also be affected in PPA, but it is unclear whether different variants of PPA are associated with differences in gesture production. Prior research with neurotypical individuals indicates that the left temporal lobe is a critical locus of manipulable object and hand posture representations. Moreover, when imitating gestures, individuals whose strokes include the left temporal lobe show reduced benefit of gesture meaning and disproportionate impairment in hand posture as compared to arm kinematics. We tested the hypothesis that svPPA – who typically exhibit primarily temporal lobe atrophy – would differentially show these expected patterns of gesture imitation performance. Nineteen participants with PPA completed meaningful and meaningless gesture imitation tasks, and performance was scored for hand posture and arm kinematics accuracy. Generalized logistic mixed-effect regression models controlling for dementia severity showed overall benefits from gesture meaning, and greater impairments in hand posture than arm kinematics. We also found that svPPA participants were the most impaired in gesture imitation overall. Critically, there was also a significant three-way interaction of group, meaning, and gesture component: only svPPA participants showed relative impairments of hand posture for meaningful gestures as well as meaningless gestures. Thus, unlike lvPPA and nfvPPA, the hand postures of svPPA failed to benefit from gesture meaning. This research extends prior findings on the role of the temporal lobe in hand posture representations associated with manipulable objects, and is the first to indicate that there may be distinct gesture imitation patterns as a function of PPA variant. Characterizing componential gesture deficits in PPA may help to inform differential diagnosis, compensatory communication strategies, and cognitive praxis models of PPA.
Transposon mutagenesis libraries reveal novel molecular requirements during CRISPR RNA-guided DNA integration
Authors: Walker Matt W.G. , Klompe Sanne E. , Zhang Dennis J. , Sternberg Samuel H. 
Published: January 2023

ABSTRACTCRISPR-associated transposons (CASTs) direct DNA integration downstream of target sites using the RNA-guided DNA binding activity of nuclease-deficient CRISPR-Cas systems. Transposition relies on several key protein-protein and protein-DNA interactions, but little is known about the explicit sequence requirements governing efficient transposon DNA integration activity. Here, we exploit pooled library screening and high-throughput sequencing to reveal novel sequence determinants during transposition by the Type I-FVibrio choleraeCAST system. On the donor DNA, large mutagenic libraries identified core binding sites recognized by the TnsB transposase, as well as an additional conserved region that encoded a consensus binding site for integration host factor (IHF). Remarkably, we found that VchCAST requires IHF for efficient transposition, thus revealing a novel cellular factor involved in CRISPR-associated transpososome assembly. On the target DNA, we uncovered preferred sequence motifs at the integration site that explained previously observed heterogeneity with single-base pair resolution. Finally, we exploited our library data to design modified transposon variants that enable in-frame protein tagging. Collectively, our results provide new clues about the assembly and architecture of the paired-end complex formed between TnsB and the transposon DNA, and inform the design of custom payload sequences for genome engineering applications of CAST systems.
Induction of SARS-CoV-2 N-specific CD8+T cell immunity in lungs by engineered extracellular vesicles associates with strongly impaired viral replication
Authors: Manfredi Francesco , Chiozzini Chiara , Ferrantelli Flavia , Leone Patrizia , Pugliese Katherina , Spada Massimo , Virgilio Antonio Di , Giovannelli Andrea , Valeri Mauro , Cara Andrea , Michelini Zuleika , Andreotti Mauro , Federico Maurizio 
Published: January 2023

AbstractInduction of effective immunity in lungs should be a pre-requisite for any vaccine designed to control the severe pathogenic effects generated by respiratory infectious agents. In the case of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection, vaccination is expected to associate with significant inhibition of viral replication in lungs. We recently provided evidence that the generation of endogenous extracellular vesicles (EVs) engineered for the incorporation of SARS-CoV-2 Nucleocapsid (N) protein can protect K18-hACE2 transgenic mice from the lethal intranasal infection with the ancestral Wuhan isolate. Actually, it was widely demonstrated that these transgenic mice succumb to SARS-CoV-2 intranasal infection mainly as a consequence of the viral invasiveness of central nervous system, a pathogenetic mechanism almost absent in humans. On the other hand, K18-hACE2 transgenic mice support viral replication in lungs, an event strictly mirroring the major pathogenic signature linked to the severe disease in humans. However, nothing is known about the ability of N-specific CD8+T cell immunity induced by engineered EVs in controlling viral replication in lungs. To fill the gap, we investigated the immunity generated in lungs by N-engineered EVs in terms of induction of N-specific effectors and resident memory CD8+T lymphocytes before and after virus challenge carried out three weeks and three months after boosting. At the same time points, viral replication extents in lungs were evaluated. We found that three weeks after second immunization, virus replication was reduced in mice best responding to vaccination by more than 3-logs compared to control group. The impaired viral replication matched with a reduced induction of Spike-specific CD8+T lymphocytes. The antiviral effect appeared similarly strong when the viral challenge was carried out 3 months after boosting. This inhibitory effect associated with the persistence of a N-specific CD8+T-resident memory lymphocytes in lungs of N-immunized mice. In view of the quite conserved sequence of the N protein among SARS-CoV-2 variants, these results support the idea that a vaccine strategy focused on the induction of anti-N CD8+T cell immunity in lungs has the potential to control the replication of emerging variants.