bluuebunny/crossref_metadata_2025_split huggingface dataset:
MYB12 spatiotemporally represses TMO5/LHW-mediated transcription in the Arabidopsis root meristem
Authors: Wybouw Brecht , Arents Helena E. , Yang Baojun , Nolf Jonah , Smet Wouter , Vandorpe Michael , Van Damme Daniël , Glanc Matouš , De Rybel Bert 
Published: March 2022

AbstractTranscriptional networks are crucial to integrate various internal and external signals into optimal responses during plant growth and development. Primary root vasculature patterning and proliferation are controlled by a network centred around the basic Helix-Loop-Helix transcription factor complex formed by TARGET OF MONOPTEROS 5 (TMO5) and LONESOME HIGHWAY (LHW), which control cell proliferation and orientation by modulating cytokinin response and other downstream factors. Despite recent progress, many aspects of the TMO5/LHW pathway are not fully understood. In particular, the upstream regulators of TMO5/LHW activity remain unknown. Here, using a forward genetic approach to identify new factors of the TMO5/LHW pathway, we discovered a novel function of the MYB-type transcription factor MYB12. MYB12 physically interacts with TMO5 and dampens the TMO5/LHW-mediated induction of direct target gene expression as well as the periclinal/radial cell divisions. The expression ofMYB12is activated by the cytokinin response, downstream of TMO5/LHW, resulting in a novel MYB12-mediated negative feedback loop that restricts TMO5/LHW activity to ensure optimal cell proliferation rates during root vascular development.
Rare Variants in Inborn Errors of Immunity Genes Associated with Covid-19 Severity
Authors: Liu Panhong , Fang Mingyan , Luo Yuxue , Zheng Fang , Jin Yan , Cheng Fanjun , Zhu Huanhuan , Jin Xin 
Published: March 2022

AbstractCovid-19 is a contagious disease caused by SARS-CoV-2, a novel severe acute respiratory syndrome coronavirus. Common variants and networks underlying host genetic mechanisms have been extensively studied to identify disease-associated genetic factors. However, there are few studies about the rare variants, typically inborn errors of immunity, in understanding the host genetics behind Covid-19 infection, especially in the Chinese population. To fill this gap, we investigate likely-deleterious missense and high-confidence predicted loss-of-function variants by (a) performing gene- and pathway-level association analyses, (b) examining known genes involved in type I interferon signaling and others previously reported in Covid-19 disease, and (c) identifying candidate genes with accumulating mutations and their potential protein-protein interactions with known genes. Based on our analyses, several putative genes and pathways are uncovered and worth further investigation, for example, genes IL12RB1, TBK1, and TLR3, and pathways Tuberculosis (hsa:05152), Primary Immunodeficiency (hsa:05340), and Influenza A (hsa:05164). These regions generally play an essential role in regulating antiviral innate immunity responses to foreign pathogens and in responding to many inflammatory diseases. We believe that to some extent, as an acute inflammatory disease, Covid-19 is also affected by these inborn errors of immunity. We hope that the identification of these rare genetic factors will provide new insights into the genetic architecture of Covid-19.
SHERLOCK4HAT: a CRISPR-based tool kit for diagnosis of Human African Trypanosomiasis
Authors: Sima Núria , Dujeancourt-Henry Annick , Perlaza Blanca Liliana , Ungeheuer Marie-Noelle , Rotureau Brice , Glover Lucy 
Published: March 2022

AbstractElimination of Human African Trypanosomiasis (HAT) requires highly specific and sensitive tools for both diagnostic at point of care and epidemiological surveys. We have adapted SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the detection of trypanosome nucleic acids. Our SHERLOCK4HAT diagnostic tool kit, using 7SLRNA, TgSGP and SRA targets, distinguishes between Trypanosoma brucei (T. b.) brucei, T. b. gambiense (g) and T. b. rhodesiense (r) without cross-reactivity and with sensitivity between 0.01 and 0.1 parasite/µL. SHERLOCK4HAT can accurately detect a trypanosome infection in cryo-banked patient buffy coats, with 85.1% sensitivity and 98.4% specificity for gHAT, and 100% sensitivity and 94.1% specificity for rHAT. Our SHERLOCK4HAT diagnostic showed 85.6% correlation with a reference standard qPCR in gHAT patients, 96.2% correlation in rHAT patients, discriminates between r/gHAT with 100% accuracy and is compatible with lateral flow assay readout for use at the point of care.
The development of the Supplemental Nutrition Assistance Program enrollment accessibility (SNAP-Access) score
Authors: Samuel Laura J. , Xiao Emily , Cerilli Caroline , Sweeney Fiona , Campanile Jessica , Milki Nubaira , Smith Jared , Zhu Jiafeng , Yenokyan Gayane , Gherman Adi , Varadaraj Varshini , Swenor Bonnielin K. 
Published: March 2022

ABSTRACTBackgroundThe Supplemental Nutrition Assistance Program (SNAP) is a federally funded public benefit providing critical food assistance to millions of Americans. However, it is typically administered by states, creating potential variation in accessibility and transparency of information about enrollment for people with disabilities.ObjectiveTo create a method to assess the accessibility and transparency of information about the disability-inclusive process and practices of SNAP enrollmentMethodsData was collected from SNAP landing and enrollment webpages from all 50 U.S. states, the District of Columbia, and New York City from June-August 2021. Based on key principles of universal design and accessibility, scores were determined for each SNAP program across three areas: flexibility in the enrollment process (6 points), efficiency of finding information about enrollment on SNAP websites (6 points), and the accessibility of SNAP webpages (6 points). Total scores were the sum of these sub-categories (18 points maximum).ResultsOf the 52 SNAP programs assessed, mean scores were 10.66 (SD=2.51) for the total score, 2.67 (SD=0.91) for flexibility in the enrollment process, 3.32 (SD=1.19) for efficiency of finding information about enrollment on SNAP websites, and 4.67 (SD=1.72) for the accessibility of SNAP webpage. A total of 0 SNAP programs received the maximum score (6 points) on flexibility, 2 programs the maximum on efficiency, and 31 programs the maximum on accessibility.ConclusionsWe found differences in the accessibility, flexibility, and efficiency of SNAP program enrollment information available on SNAP websites and outline much room for improvement across all three of these areas.
Deciphering the heterogeneous niche in the tumor progression of hepatocellular carcinoma: a Spatial single-cell landscape and multi-omics atlas analysis
Authors: Ye Jiazhou , Lin Yan , Liao Zhiling , Gao Xing , Lu Cheng , Lu Lu , Huang Julu , Huang Xi , Bai Tao , Chen Jie , Wang Xiaobo , Luo Min , Xie Mingzhi , Wu Feixiang , Wu Guobin , Ma Liang , Xiang Bangde , Li Yongqiang , Yu Hongping , Luo Xiaoling , Liang Rong 
Published: March 2022

AbstractHepatocellular carcinoma (HCC) is an invasive disease which is characteristic with highly heterogeneous molecular phenotype, rich blood supply, and unique immune niche, therefore it is of great significance to explore the tumor heterogeneous niche and clonal evolution progress of these malignant cells. Based on the advance in single-cell technology, spatial transcriptome technology, and Oxford nanopore technology, this study innovatively reconstructed and delineated the heterogeneity of the HCC tumor niche and its tumor progression pattern. Our results showed that the copy number variation (CNV) of cells in cancer lesions and liver cirrhosis lesions of the same patient is basically the same and is mainly regulated by transcription factors such as TP53, HOXA7, FOXN3, and PPARG, suggests that malignant cells of common origin gradually evolve into different lesions in a very rare numbers of different CNVs, which are mainly regulated by expression patterns and mediate the heterogeneity between the tumor and cirrhosis lesions. Angiogenesis-related genes (SREBF1, ZNF585A, and HOXB5) may mediate communication between HCC subpopulations and endothelial cells via exosomes, thereby contributing to the angiogenic niche before HCC metastasis. In addition, numerous CNVs were found in patients with early recurrent HCC, and these mutated genes is the potential niche genes for the early tumor recurrence. In summary, this study provides a general transcriptional landscape of the ecological structure of HCC, systematically maps the molecular, cellular, and spatial composition of different HCC cell niches, and provides a scientific and theoretical basis at the molecular and cellular levels for personalized and accurate treatment strategies for HCC.
Seroneutralization of Omicron BA.1 and BA.2 in patients receiving anti-SARS-CoV-2 monoclonal antibodies
Authors: Bruel Timothée , Hadjadj Jérôme , Maes Piet , Planas Delphine , Seve Aymeric , Staropoli Isabelle , Guivel-Benhassine Florence , Porrot Françoise , Bolland William-Henry , Nguyen Yann , Casadevall Marion , Charre Caroline , Péré Hélène , Veyer David , Prot Matthieu , Baidaliuk Artem , Cuypers Lize , Planchais Cyril , Mouquet Hugo , Baele Guy , Mouthon Luc , Hocqueloux Laurent , Simon-Loriere Etienne , André Emmanuel , Terrier Benjamin , Prazuck Thierry , Schwartz Olivier 
Published: March 2022

AbstractThe SARS-CoV-2 Omicron BA.1 variant has been supplanted in many countries by the BA.2 sub-lineage. BA.2 differs from BA.1 by about 21 mutations in its spike. Human anti-spike monoclonal antibodies (mAbs) are used for prevention or treatment of COVID-19. However, the capacity of therapeutic mAbs to neutralize BA.1 and BA.2 remains poorly characterized. Here, we first compared the sensitivity of BA.1 and BA.2 to neutralization by 9 therapeutic mAbs. In contrast to BA.1, BA.2 was sensitive to Cilgavimab, partly inhibited by Imdevimab and resistant to Adintrevimab and Sotrovimab. Two combinations of mAbs, Ronapreve (Casirivimab + Imdevimab) and Evusheld (Cilgavimab + Tixagevimab), are indicated as a pre-exposure prophylaxis in immunocompromised persons at risk of severe disease. We analyzed sera from 29 such individuals, up to one month after administration of Ronapreve and/or Evusheld. After treatment, all individuals displayed elevated antibody levels in their sera and neutralized Delta with high titers. Ronapreve recipients did not neutralize BA.1 and weakly impaired BA.2. With Evusheld, neutralization of BA.1 and BA.2 was detected in 19 and 29 out of 29 patients, respectively. As compared to Delta, titers were more severely decreased against BA.1 (344-fold) than BA.2 (9-fold). We further report 4 breakthrough Omicron infections among the 29 participants. Therefore, BA.1 and BA.2 exhibit noticeable differences in their sensitivity to therapeutic mAbs. Anti-Omicron activity of Ronapreve, and to a lesser extent that of Evusheld, is reduced in patients’ sera, a phenomenon associated with decreased clinical efficacy.
The effect of focused muscle contraction therapy on chronic pain and Brodmann Area activity in former National Football League players
Authors: Cohen Neli , Hachaj Greg , Rubio Jose , Kastelz Alexandra , Hachaj Marcin , Zierfuss Dan , Osman Maab , Tsiampas Pete , Fernhall Bo , Velis Effrossyni Votta , Benedetti Enrico , Bartholomew Amelia 
Published: March 2022

AbstractNFL players have a traumatic injury rate approaching 100%; chronic pain with decreased concentration occur commonly. This study examined the role of a novel focused muscle contraction therapy for the treatment of chronic pain and identified its impact on brain activity. Chronic pain was assessed by numerical score, neuropathic component, and impact on daily activities in 8 retired players. Brain activity was characterized by QEEG with low-resolution electromagnetic tomography analysis and functional measures of visual and auditory attention. Focused muscle contraction muscle therapy administered twice weekly for 6 months was tapered to twice monthly by 12 months. Brodmann Areas (BA) 4 and 9, known to associate with chronic pain, showed values outside the clinically normal range; mean pain duration was 16.5 ± 12.9 years. At 6 months, 5/8 subjects reported pain scores of 0. High beta wave activity was seen in BA 19, 21, 29, 30, and 39, affecting auditory, visual, and body perceptions. Clinically relevant improvements were observed in auditory attention and visual stamina. Pain relief was sustained through 18 months of follow-up. Focused muscle contraction therapy appears to redirect brain activity to new areas of activity which are associated with long-lasting relief of chronic pain and its detriments. This study was registered with clinicaltrial.gov #NCT04822311.
Evidence for SARS-CoV-2 Delta and Omicron co-infections and recombination
Authors: Bolze Alexandre , Basler Tracy , White Simon , Rossi Andrew Dei , Wyman Dana , Roychoudhury Pavitra , Greninger Alexander L. , Hayashibara Kathleen , Beatty Mark , Shah Seema , Stous Sarah , Kil Eric , Dai Hang , Cassens Tyler , Tsan Kevin , Nguyen Jason , Ramirez Jimmy , Carter Scotty , Cirulli Elizabeth T. , Barrett Kelly Schiabor , Washington Nicole L. , Belda-Ferre Pedro , Jacobs Sharoni , Sandoval Efren , Becker David , Lu James T. , Isaksson Magnus , Lee William , Luo Shishi 
Published: March 2022

AbstractBetween November 2021 and February 2022, SARS-CoV-2 Delta and Omicron variants co-circulated in the United States, allowing for co-infections and possible recombination events. We sequenced 29,719 positive samples during this period and analyzed the presence and fraction of reads supporting mutations specific to either the Delta or Omicron variant. We identified 18 co-infections, one of which displayed evidence of a low Delta-Omicron recombinant viral population. We also identified two independent cases of infection by a Delta-Omicron recombinant virus, where 100% of the viral RNA came from one clonal recombinant. In the three cases, the 5’-end of the viral genome was from the Delta genome, and the 3’-end from Omicron including the majority of the spike protein gene, though the breakpoints were different. Delta-Omicron recombinant viruses were rare, and there is currently no evidence that Delta-Omicron recombinant viruses are more transmissible between hosts compared to the circulating Omicron lineages.
Knowledge, attitudes, and positions of religious leaders towards female genital mutilation: A cross-sectional study from the Kurdistan Region of Iraq
Authors: Mahmood Kazhan I. , Shabu Sherzad A. , M-Amen Karwan , Saleh Abubakir M. , Ahmed Hamdia , Mzori Barzhang Q. , Shabila Nazar P. 
Published: March 2022

AbstractBackgroundUnderstanding the perspectives of the key players in the community regarding female genital cutting (FGC) is very important for directing preventive programs. Religious leaders help shape community behaviors, which is highly pertinent in the case of FGC as it is frequently perceived to be a religious requirement. This study assesses religious leaders’ knowledge, attitudes, and positions towards FGC in the Kurdistan Region of Iraq.MethodsThis cross-sectional study was conducted in the Kurdistan Region of Iraq. It included a purposive sample of 147 local religious leaders (khateebs) representing the three governorates of Erbil, Sulaimaniyah, and Duhok. A self-administered questionnaire was used to collect data about the religious leaders’ knowledge, attitude, and position towards FGC.ResultsThe participants identified reduction of the sexual desire of women as the main benefit (37%) and risk (24%) of FGC. Cultural tradition and religious requirements were the main reasons for practicing FGC. About 59% of the religious leaders stated that people ask for their advice on FGC. Around 14% of the participants supported performing FGC, compared to 39.1% who opposed it. Religious (73.9%) and cultural (26.1%) rationales were the main reasons given for supporting FGC. Being a cultural practice and having harmful effects (53.5%) and lack of clear religious evidence (46.6%) were the main reasons for being against FGC. Around 52% of the participants recommended banning FGC by law, while 43.5% did not support banning it. A statistically significant association (P=0.015) was found between religious leaders’ residence and their position on performing FGC. More than 46% of those residing in Duhok were against performing FGC, compared to lower proportions in Erbil (38.8%) and Sulaimaniyah (30%).ConclusionA conclusive decision concerning FGC banning needs to be made by religious authorities to advise people to avoid the practice. Health awareness activities incorporating FGC risks should be carried out to enlighten religious leaders at different levels of religious positions. Further research exploring perspectives of religious authorities concerning religious leaders’ inconclusive judgments about FGC is deemed necessary.
Afucosylation of HLA-specific IgG1 as a potential predictor of antibody pathogenicity in kidney transplantation
Authors: Bharadwaj Pranay , Shrestha Sweta , Pongracz Tamas , Concetta Catalano , Sharma Shilpee , Le Moine Alain , de Haan Noortje , Murakami Naoka , Riella Leonardo V. , Holovska Vanda , Wuhrer Manfred , Marchant Arnaud , Ackerman Margaret E. 
Published: March 2022

SummaryAntibody-mediated rejection (AMR) is the leading cause of graft failure. While donor-specific antibodies (DSA) are associated with a higher risk of AMR, not all patients with DSA develop rejection suggesting that the characteristics of alloantibodies that determine their pathogenicity remain undefined. Using human leukocyte antigen (HLA)-A2-specific antibodies as a model, we applied systems serology tools to investigate qualitative features of immunoglobulin G (IgG) alloantibodies including Fc-glycosylation patterns and FcγR binding properties. The levels of afucosylation of anti-A2 antibodies were elevated in all seropositive patients and were significantly higher in AMR patients, suggesting potential cytotoxicity via FcγRIII-mediated mechanisms. Afucosylation of both glycoengineered monoclonal and naturally glycovariant polyclonal serum IgG specific to HLA-A2 exhibited potentiated binding to, slower dissociation from, and enhanced signaling through FcγRIII, a receptor widely expressed on innate effector cells. Collectively, these results suggest that afucosylated DSA may be a biomarker of AMR and could contribute to its pathogenesis.
Graphical Abstract.Potential influence of HLA-A2-specific IgG1 afucosylation, FcγRIIIa binding and activation on ADCC and graft rejection.Illustration created with https://BioRender.com.
FHIR “Profiliferation”: A Data Science Approach
Authors: Kramer Mark A. 
Published: March 2022

AbstractProfiling is a mechanism for shaping Fast Healthcare Interoperability Resources (FHIR) for particular use cases. “Profiliferation” (profile + proliferation) is a coinage referring to the explosive growth in the number of FHIR profiles over the past few years. By reviewing a broad sample of almost 3000 FHIR profiles from 125 implementation guides, it was determined that just two items, Observation and Extension, accounted for half the profiles. FHIR’s 80/20 rule was determined to be closer to 65/35, revealing that FHIR is more dependent on profiling than initially intended. Use of the Observation resource was inconsistent, hinting that the resource is either poorly designed, or that users lack proper guidance. Better management of reusable items and certain changes in FHIR and profiling practices could improve the consistency of FHIR artifacts and reduce unnecessary and potentially incompatible profiles.
Disentangling the effect of measures, variants and vaccines on SARS-CoV-2 Infections in England: A dynamic intensity model
Authors: Boldea Otilia , Cornea-Madeira Adriana , Madeira Joao 
Published: March 2022

AbstractIn this paper, we estimate the path of daily SARS-CoV-2 infections in England from the beginning of the pandemic until the end of 2021. We employ a dynamic intensity model, where the mean intensity conditional on the past depends both on past intensity of infections and past realised infections. The model parameters are time-varying and we employ a multiplicative specification along with logistic transition functions to disentangle the time-varying effects of non-pharmaceutical policy interventions, of different variants and of protection (waning) of vaccines/boosters. We show that earlier interventions and vaccinations are key to containing an infection wave. We consider several scenarios that account for more infectious variants and different protection levels of vaccines/boosters. These scenarios show that, as vaccine protection wanes, containing a new wave in infections and an associated increase in hospitalisations in the near future will require further booster campaigns and/or non-pharmaceutical interventions.
Long COVID and its associated factors among COVID survivors in the community from a middle-income country – an online cross-sectional study
Authors: Moy Foong Ming , Hairi Noran Naqiah , Jian Lim Eugene Ri , Bulgiba Awang 
Published: March 2022

IntroductionPatients with COVID-19 usually recover and return to normal health, however some patients may have symptoms that last for weeks or even months after recovery. This persistent state of ill health is known as Long COVID if it continues for more than 12 weeks and are not explained by an alternative diagnosis. Long Covid has been overlooked in low and middle income countries. Therefore, we conducted an online survey among the COVID-19 survivors in the community to explore their Long COVID symptoms, factors associated with Long COVID and how Long COVID affected their work.MethodsThis was a cross sectional study conducted from July to September 2021, during the implementation of a nationwide movement control order (MCO). Data was collected using the REDCap electronic data capture tool. The questionnaire was distributed in social and news media. The questionnaire covers information such as socio-demographic characteristics, existing comorbidities, self-perception on health, information on the acute COVID-19 condition and treatment received, symptoms and duration of post-COVID condition and effects on occupation. Results: A total of 732 COVID-19 survivors responded. There were slightly more females (58.7%), younger and more highly educated respondents. More than half of them were overweight or obese and about two third were free of comorbidities. Among these respondents, about 56% were without or with mild symptoms during their acute COVID-19 conditions. A total of 21.1% of the respondents reported to experience Long COVID. The most commonly reported symptoms for Long COVID were fatigue, brain fog, depression, anxiety, insomnia, arthralgia or myalgia. Females had 58% higher odds (95% CI: 1.02, 2.45) of experiencing Long COVID. Patients with moderate and severe levels of acute COVID-19 symptoms had OR of 3.01 (95% CI: 1.21, 7.47) and 3.62 (95% CI: 1.31, 10.03) respectively for Long COVID.ConclusionThis study provides additional insight on the symptoms and duration of post-COVID symptoms as well as the associated factors with Long COVID among COVID-19 survivors in Malaysia. Recognition of Long COVID and its associated factors is important in planning prevention, rehabilitation, clinical management to improve recovery and long-term COVID-19 outcomes.