bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all prior infected and vaccinated individuals
Authors: Naranbhai Vivek , Nathan Anusha , Kaseke Clarety , Berrios Cristhian , Khatri Ashok , Choi Shawn , Getz Matthew A. , Tano-Menka Rhoda , Ofoman Onosereme , Gayton Alton , Senjobe Fernando , Denis Kerri J. St , Lam Evan C. , Garcia-Beltran Wilfredo F. , Balazs Alejandro B. , Walker Bruce D. , Iafrate A. John , Gaiha Gaurav D. 
Published: January 2022

ABSTRACTThe SARS-CoV-2 Omicron variant (B.1.1.529) contains mutations that mediate escape from infection and vaccine-induced antibody responses, although the extent to which these substitutions in spike and non-spike proteins affect T cell recognition is unknown. Here we show that T cell responses in individuals with prior infection, vaccination, both prior infection and vaccination, and boosted vaccination are largely preserved to Omicron spike and non-spike proteins. However, we also identify a subset of individuals (∼21%) with a >50% reduction in T cell reactivity to the Omicron spike. Evaluation of functional CD4+and CD8+memory T cell responses confirmed these findings and reveal that reduced recognition to Omicron spike is primarily observed within the CD8+T cell compartment. Booster vaccination substantially enhanced T cell responses to Omicron spike. In contrast to neutralizing immunity, these findings suggest preservation of T cell responses to the Omicron variant, although with reduced reactivity in some individuals.
Modern lineages of Mycobacterium tuberculosis were recently introduced in western India and demonstrate increased transmissibility
Authors: Dixit Avika , Kagal Anju , Ektefaie Yasha , Freschi Luca , Karyakarte Rajesh , Lokhande Rahul , Groschel Matthias , Tornheim Jeffrey A , Gupte Nikhil , Pradhan Neeta N , Paradkar Mandar S , Deshmukh Sona , Kadam Dileep , Schito Marco , Engelthaler David M. , Gupta Amita , Golub Jonathan , Mave Vidya , Farhat Maha 
Published: January 2022

AbstractBackgroundMycobacterium tuberculosis (Mtb) transmissibility may vary between lineages (or variants) and this may contribute to the slow decline of tuberculosis (TB) incidence. The objective of our study was to compare transmissibility across four major lineages (L1-4) of Mtb among participants from two cohort studies in Pune, India.MethodsWe performed whole-genome sequencing (WGS) of Mtb sputum culture-positive isolates from participants in two prospective cohort studies of adults with pulmonary TB seeking care at public treatment centers in Pune, Maharashtra. We performed genotypic susceptibility prediction for both first- and second-line drugs using a previously validated random forest model. We used single nucleotide substitutions (SNS) and maximum likelihood estimation to build isolate phylogenies by lineage. We used Bayesian molecular dating to estimate ancestral node ages and compared tree characteristics using a two-sample Kolmogorov-Smirnov (KS) test.ResultsOf the 642 isolates from distinct study participants that underwent WGS, 612 met sequence quality criteria. The median age of the 612 participants was 31 years (IQR 24.4-44.2), the majority were male (64.7%) and sputum smear-positive (83.3%), and 6.7% had co-infection with HIV. Most isolates belonged to L3 (44.6%). The majority (61.1%) of multidrug-resistant isolates (MDR, resistant to isoniazid and rifampin) belonged to L2 (P < 0.001 [Fisher’s Exact]). There was no significant difference in host characteristics between participants infected with the four major lineages. In phylogenetic analysis, we measured shorter terminal branch lengths in the L2 tree compared to L1 and L3 trees indicating less time elapsing between transmission and sampling and higher transmissibility (median branch lengths: L2 - 3.3, L3 - 7.8, p <0.001). Branching times for L2 and L4 were more recent than L1 and L3 indicating recent introduction into the region (p < 0.01 [KS test]).ConclusionModern Mtb lineages (L2 and L4) were more recently introduced in western India, compared to older lineages (L1 and L3). L2 shows a higher frequency of drug-resistance and higher transmissibility. Our findings highlight the need for contact tracing around cases of TB due to L2, and heightened surveillance of TB antibiotic resistance in India.
Statistical learning in patients in the minimally conscious state
Authors: Xu Chuan , Gao Jian , Gao Jiaxin , Li Lingling , He Fangping , Yu Jie , Ling Yi , Li Hangcheng , Li Jingqi , Melloni Lucia , Luo Benyan , Ding Nai 
Published: January 2022

AbstractWhen listening to an unknown language, listeners could learn the transitional probability between syllables and group frequently co-occurred syllables into a whole unit. Such statistical learning ability has been demonstrated for both pre-verbal infants and adults, even during passive listening. Here, we investigated whether statistical learning occurred in patients in minimally conscious state (MCS) and patients emerged from the minimally conscious state (EMCS) using electroencephalography (EEG). We presented to participants an isochronous sequence of syllables, which were composed of either 2-word real phrases or 2-word artificial phrases that were defined by the transitional probability between words. An inter-trial phase coherence (ITPC) analysis revealed that the phrase-rate EEG response was weakened in EMCS patients compared with healthy individuals, and was even more severely weakened in MCS patients. Although weak, the phrase-rate response or its harmonics remained statistically significant in MCS patients, suggesting that the statistical learning ability was preserved in MCS patients. The word-rate response was also weakened with a decreased level of consciousness. The harmonics of the word-rate response, however, were more salient in MCS than EMCS patients in the alpha and beta bands. Together with previous studies, the current results suggest that MCS patients retain residual learning ability, which can potentially be harnessed to induce neural plasticity, and that different frequency bands are differentially related to the consciousness level.
Breast milk exposure is associated with cortical maturation in preterm infants
Authors: Sullivan Gemma , Vaher Kadi , Blesa Manuel , Galdi Paola , Stoye David Q. , Quigley Alan J. , Thrippleton Michael J. , Bastin Mark E. , Boardman James P. 
Published: January 2022

AbstractObjectiveBreast milk exposure is associated with improved neurocognitive outcomes following preterm birth but the neural substrates linking nutrition with outcome are uncertain. By combining nutritional data with brain MRI, we tested the hypothesis that high versus low breast milk exposure in preterm infants during neonatal care results in a cortical morphology that more closely resembles that of infants born at term.MethodsWe studied 135 preterm (mean gestational age 30+2 weeks, range 22+1 to 32+6) and 77 term-born infants (mean gestational age 39+4 weeks, range 36+3 to 42+1). Nutritional data was collected from birth until hospital discharge to identify the proportion of days preterm infants received exclusive breast milk. Structural and diffusion MRI were performed at term-equivalent age. Cortical indices (volume, thickness, surface area, gyrification index, sulcal depth, curvature) and water diffusion parameters (fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity, neurite density index, orientation dispersion index) were compared between preterm infants who received exclusive breast milk for <75% of inpatient days (n=68), preterm infants who received exclusive breast milk for ≥75% of inpatient days (n=67) and term-born controls (n=77).ResultsHigh breast milk exposure was associated with reduced cortical gray matter volume (d=0.47, p=0.014), thickness (d=0.42, p=0.039) and radial diffusivity (d=0.38, p=0.039), and increased fractional anisotropy (d=0.38, p=0.037) after adjustment for age at MRI.InterpretationHigh versus low breast milk exposure in the weeks following preterm birth is associated with a cortical imaging phenotype that more closely resembles the brain morphology of healthy infants born at term.
Estimation of causal effects of a time-varying exposure at multiple time points through Multivariable Mendelian randomization
Authors: Sanderson Eleanor , Richardson Tom G , Morris Tim T , Tilling Kate , Smith George Davey 
Published: January 2022

AbstractMendelian Randomisation (MR) is a powerful tool in epidemiology to estimate the causal effect of an exposure on an outcome in the presence of unobserved confounding, by utilising genetic variants as instrumental variables (IVs) for the exposure. The effects obtained from MR studies are often interpreted as the lifetime effect of the exposure in question. However, the causal effects of many exposures are thought to vary throughout an individual’s lifetime and there may be periods during which an exposure has more of an effect on a particular outcome. Multivariable MR (MVMR) is an extension of MR that allows for multiple, potentially highly related, exposures to be included in an MR estimation. MVMR estimates the direct effect of each exposure on the outcome conditional on all of the other exposures included in the estimation. We explore the use of MVMR to estimate the direct effect of a single exposure at different time points in an individual’s lifetime on an outcome. We use simulations to illustrate the interpretation of the results from such analyses and the key assumptions required. We show that causal effects at different time periods can be estimated through MVMR when the association between the genetic variants used as instruments and the exposure measured at those time periods varies, however this estimation will not necessarily identify exact time periods over which an exposure has the most effect on the outcome. We illustrate the method through estimation of the causal effects of childhood and adult BMI on smoking behaviour.
Validation of a novel fluorescent lateral flow assay for rapid qualitative and quantitative assessment of total anti-SARS-CoV-2 S-RBD binding antibody units (BAU) from plasma or fingerstick whole-blood of COVID-19 vaccinees
Authors: Younes Nadin , Al-Sadeq Duaa W. , Shurrab Farah M. , Zidan Hadeel T. , Abou-Saleh Haissam , Halawa Bushra Y. Abo , AlHamaydeh Fatima M. , Elsharafi Amira E. , Daas Hanin I. , Thomas Swapna , Aboalmaaly Sahar , Farsi Afra Al , Al-Buainain Reeham , Ataelmannan Samar , Paul Jiji , Al Saadi Amana Salih , Yassine Hadi M. , Majdalawieh Amin F. , Ismail Ahmed , Abu-Raddad Laith J. , Nasrallah Gheyath K. 
Published: January 2022

AbstractBackgroundLimited commercial LFA assays are available to provide a reliable quantitative measurement of the total binding antibody units (BAU/mL) against the receptor-binding domain of the SARS-CoV-2 spike protein (S-RBD).AimTo evaluate the performance of FinecareTM2019-nCoV S-RBD LFA and its fluorescent reader (FinecareTM-FIA Meter) against the following reference methods (i) The FDA-approved Genscript surrogate virus-neutralizing assay (sVNT), and (ii) three highly performing automated immunoassays: BioMérieux VIDAS®3, Ortho VITROS®, and Mindray CL-900i®.MethodsPlasma from 488 vaccinees were tested by all aforementioned assays. Fingerstick whole-blood samples from 156 vaccinees were also tested by FinecareTM.Results and conclusionsFinecareTM showed 100% specificity as none of the pre-pandemic samples tested positive. Equivalent FinecareTM results were observed among the samples taken from fingerstick or plasma (Pearson correlationr=0.9, p<0.0001), suggesting that fingerstick samples are sufficient to quantitate the S-RBD BAU/mL. A moderate correlation was observed between FinecareTM and sVNT (r=0.5, p<0.0001), indicating that FinecareTM can be used for rapid prediction of the neutralization antibody post-vaccination. FinecareTM BAU results showed strong correlation with VIDAS®3 (r=0.6, p<0.0001), and moderate correlation with VITROS® (r=0.5, p<0.0001), and CL-900i® (r=0.4, p<0.0001), suggesting that FinecareTM be used as a surrogate for the advanced automated assays to measure S-RBD BAU/mL.
Heterologous immunization with inactivated vaccine followed by mRNA booster elicits strong humoral and cellular immune responses against the SARS-CoV-2 Omicron variant
Authors: Zuo Fanglei , Abolhassani Hassan , Du Likun , Piralla Antonio , Bertoglio Federico , de Campos-Mata Leire , Wan Hui , Schubert Maren , Wang Yating , Sun Rui , Cassaniti Irene , Vlachiotis Stelios , Kumagai-Braesch Makiko , Andréll Juni , Zhang Zhaoxia , Xue Yintong , Wenzel Esther Veronika , Calzolai Luigi , Varani Luca , Rezaei Nima , Chavoshzadeh Zahra , Baldanti Fausto , Hust Michael , Hammarström Lennart , Marcotte Harold , Pan-Hammarström Qiang 
Published: January 2022

AbstractBackgroundThere has been an unprecedented global effort to produce safe and effective vaccines against SARS-CoV-2. However, production challenges, supply shortages and unequal global reach, together with an increased number of breakthrough infections due to waning of immunity and the emergence of new variants of concern (VOC), have prolonged the pandemic. To boost the immune response, several heterologous vaccination regimes have been tested and have shown increased antibody responses compared to homologous vaccination. Here we evaluated the effect of mRNA vaccine booster on immunogenicity in individuals who had been vaccinated with two doses of inactivated vaccines.MethodsThe levels of specific antibodies against the receptor-binding domain (RBD) of the spike protein from wild-type virus and the Beta, Delta and Omicron variants were measured in healthy individuals who had received two doses of homologous inactivated (BBIBP-CorV or CoronoVac) or mRNA (BNT162b2 or mRNA-1273) vaccines, and in donors who were given an mRNA vaccine boost after two doses of either vaccine. Pre-vaccinated healthy donors, or individuals who had been infected and subsequently received the mRNA vaccine were also included as controls. In addition, specific memory B and T cell responses were measured in a subset of samples.ResultsA booster dose of an mRNA vaccine significantly increased the level of specific antibodies that bind to the RBD domain of the wild-type (6-fold) and VOCs including Delta (8-fold) and Omicron (14-fold), in individuals who had previously received two doses of inactivated vaccines. The level of specific antibodies in the heterologous vaccination group was furthermore similar to that in individuals receiving a third dose of homologous mRNA vaccines or boosted with mRNA vaccine after natural infection. Moreover, this heterologous vaccination regime significantly enhanced the specific memory B and T cell responses.ConclusionsHeterologous prime-boost immunization with inactivated vaccine followed by an mRNA vaccine boost markedly increased the levels of specific antibodies and B and T cell responses and may thus increase protection against emerging SARS-CoV-2 variants including Omicron.
Containment of a multi-index B.1.1.7 outbreak on a university campus through a genomically-informed public health response
Authors: Martin Emily T. , Lauring Adam S. , Montgomery JoLynn P. , Valesano Andrew L. , Eisenberg Marisa C. , Sheen Danielle , Nord Jennifer , Ernst Robert D. , Mortenson Lindsey Y. , Valdez Riccardo , Niknafs Yashar , Conway Darryl , Rifat Sami F. , Bagdasarian Natasha , Lyon-Callo Sarah , Collins Jim , Blankenship Heather , Soehnlen Marty , Marquez Juan 
Published: January 2022

AbstractThe first cluster of SARS-CoV-2 cases with lineage B.1.1.7 in the state of Michigan was identified through intensive university-led surveillance sampling and targeted sequencing. A collaborative investigation and response was conducted by the local and state health departments, and the campus and athletic medicine COVID-19 response teams, using S-gene target failure screening and rapid genomic sequencing to inform containment strategies. A total of 50 cases of B.1.1.7-lineage SARS-CoV-2 were identified in this outbreak, which was due to three coincident introductions of B.1.1.7-lineage SARS-CoV-2, all of which were genetically distinct from lineages which later circulated in the broader community. This investigation demonstrates the successful implementation of a genomically-informed outbreak response which can be extended to university campuses and other settings at high risk for rapid emergence of new variants.
Timing of Breakthrough Infection Risk After Vaccination Against SARS-CoV-2
Authors: Fisman David N. , Lee Nelson , Tuite Ashleigh R. 
Published: January 2022

AbstractBackgroundProvision of safe and effective vaccines has been a remarkable public health achievement during the SARS-CoV-2 pandemic. The effectiveness and durability of protection of the first two doses of SARS-CoV-2 vaccines is an important area for study, as are questions related to optimal dose combinations and dosing intervals.MethodsWe performed a case-cohort study to generate real-world evidence on efficacy of first and second dose of SARS-CoV-2 vaccines, using a population-based case line list and vaccination database for the province of Ontario, Canada between December 2020 and October 2021. Risk of infection after vaccination was evaluated in all laboratory-confirmed vaccinated SARS-CoV-2 cases, and a 2% sample of vaccinated controls, evaluated using survival analytic methods, including construction of Cox proportional hazards models. Vaccination status was treated as a time-varying covariate.ResultsFirst and second doses of SARS-CoV-2 vaccine markedly reduced risk of infection (first dose efficacy 68%, 95% CI 67% to 69%; second dose efficacy 88%, 95% CI 87 to 88%). In multivariable models, extended dosing intervals were associated with lowest risk of breakthrough infection (HR for redosing 0.64 (95% CI 0.61 to 0.67) at 6-8 weeks). Heterologous vaccine schedules that mixed viral vector vaccine first doses with mRNA second doses were significantly more effective than mRNA only vaccines. Risk of infection largely vanished during the time period 4-6 months after the second vaccine dose, but rose markedly thereafter.InterpretationA case-cohort design provided an efficient means to identify strong protective effects associated with SARS-CoV-2 vaccination, particularly after the second dose of vaccine. However, this effect appeared to wane once more than 6 months had elapsed since vaccination. Heterologous vaccination and extended dosing intervals improved the durability of immune response.
Engineered collagen-targeting therapeutics reverse lung and kidney fibrosis in mice
Authors: White Michael JV , Raczy Michal M , Budina Erica , Yuba Eiji , Solanki Ani , Shim Ha-Na , Zhang Zheng Jenny , Gray Laura T , Cao Shijie , Alpar Aaron T. , Hubbell Jeffrey A 
Published: January 2022

AbstractFibrotic diseases are involved in 45% of deaths in the United States. In particular, fibrosis of the kidney and lung are major public health concerns due to their high prevalence and lack of existing treatment options. Here, we harness the pathophysiological features of fibrotic diseases, namely leaky vasculature and aberrant extracellular matrix (ECM) protein deposition (i.e. collagen), to target an anti-fibrotic biologic and a small molecule drug to disease sites of fibrosis, thus improving their therapeutic potential in mouse models of lung and kidney fibrosis. First, we identify and validate collagen-targeting drug delivery systems that preferentially accumulate in the diseased organs: von Willebrand Factor’s A3 domain (VWF-A3) and decorin-derived collagen-binding peptide-conjugated micelles (CBP-micelles). We then engineer and recombinantly express novel candidate biologic therapies based on the anti-inflammatory cytokine IL-10: A3-IL-10 and A3-Serum Albumin-IL-10 (A3-SA-IL-10). Simultaneously, we stably encapsulate the potential anti-fibrotic water-insoluble drug, rapamycin, in CBP-micelles. We show that these novel formulations of therapeutics bind to collagen in vitro and that their efficacy in mouse models of lung and kidney fibrosis is improved, compared to free, untargeted drugs. Our results demonstrate that collagen-targeted anti-fibrotic drugs may be next generation therapies of high clinical potential.
Texture-like representation of objects in human visual cortex
Authors: Jagadeesh Akshay V. , Gardner Justin L. 
Published: January 2022

AbstractThe human visual ability to recognize objects and scenes is widely thought to rely on representations in category-selective regions of visual cortex. These representations could support object vision by specifically representing objects, or, more simply, by representing complex visual features regardless of the particular spatial arrangement needed to constitute real world objects. That is, by representing visual textures. To discriminate between these hypotheses, we leveraged an image synthesis approach that, unlike previous methods, provides independent control over the complexity and spatial arrangement of visual features. We found that human observers could easily detect a natural object among synthetic images with similar complex features that were spatially scrambled. However, observer models built from BOLD responses from category-selective regions, as well as a model of macaque inferotemporal cortex and Imagenet-trained deep convolutional neural networks, were all unable to identify the real object. This inability was not due to a lack of signal-to-noise, as all of these observer models could predict human performance in image categorization tasks. How then might these texture-like representations in category-selective regions support object perception? An image-specific readout from category-selective cortex yielded a representation that was more selective for natural feature arrangement, showing that the information necessary for object discrimination is available. Thus, our results suggest that the role of human category-selective visual cortex is not to explicitly encode objects but rather to provide a basis set of texture-like features that can be infinitely reconfigured to flexibly learn and identify new object categories.Significance StatementVirtually indistinguishable metamers of visual textures, such as wood grain, can be synthesized by matching complex features regardless of their spatial arrangement (1–3). However, humans are not fooled by such synthetic images of scrambled objects. Thus, category-selective regions of human visual cortex might be expected to exhibit representational geometry preferentially sensitive to natural objects. Contrarily, we demonstrate that observer models based on category-selective regions, models of macaque inferotemporal cortex and Imagenet-trained deep convolutional neural networks do not preferentially represent natural images, even while they are able to discriminate image categories. This suggests the need to reconceptualize the role of category-selective cortex as representing a basis set of complex texture-like features, useful for a myriad of visual behaviors.