bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Case-Control Study of Prone Positioning in Awake and Nonintubated Hospitalized Coronavirus Disease 2019 Patients
Authors: Nauka Peter C. , Chekuri Sweta , Aboodi Michael , Hope Aluko A. , Gong Michelle N. , Chen Jen-Ting 
Published: February 2021

Objectives:
To determine the association between prone positioning in nonintubated patients with coronavirus disease 2019 and frequency of invasive mechanical ventilation or inhospital mortality.

Design:
A nested case-matched control analysis.

Setting:
Three hospital sites in Bronx, NY.

Patients:
Adult coronavirus disease 2019 patients admitted between March 1, 2020, and April 1, 2020. We excluded patients with do-not-intubate orders. Cases were defined by invasive mechanical ventilation or inhospital mortality. Each case was matched with two controls based on age, gender, admission date, and hospital length of stay greater than index time of matched case via risk-set sampling. The presence of nonintubated proning was identified from provider documentation.

Intervention:
Nonintubated proning documented prior to invasive mechanical ventilation or inhospital mortality for cases or prior to corresponding index time for matched controls.

Measurements and Main Results:
We included 600 patients, 41 (6.8%) underwent nonintubated proning. Cases had lower Spo2
/Fio
2 ratios prior to invasive mechanical ventilation or inhospital mortality compared with controls (case median, 97 [interquartile range, 90–290] vs control median, 404 [interquartile range, 296–452]). Although most providers (58.5%) documented immediate improvement in oxygenation status after initiating nonintubated proning, there was no difference in worst Spo2
/Fio
2 ratios before and after nonintubated proning in both case and control (case median Spo2
/Fio
2 ratio difference, 3 [interquartile range, –3 to 8] vs control median Spo2
/Fio
2 ratio difference, 0 [interquartile range, –3 to 50]). In the univariate analysis, patients who underwent nonintubated proning were 2.57 times more likely to require invasive mechanical ventilation or experience inhospital mortality (hazard ratio, 2.57; 95% CI, 1.17–5.64; p = 0.02). Following adjustment for patient level differences, we found no association between nonintubated proning and invasive mechanical ventilation or inhospital mortality (adjusted hazard ratio, 0.92; 95% CI, 0.34–2.45; p = 0.86).

Conclusions:
There was no significant association with reduced risk of invasive mechanical ventilation or inhospital mortality after adjusting for baseline severity of illness and oxygenation status.
High false-positive rate of fluorodeoxyglucose positron emission tomography to detect lymph node metastasis in microinvasive cervical cancer after conization
Authors: Kim Kidong , Kim Hayeon , Lee Hwajung , Lee Keun Ho , Lee Banghyun , Choi ChelHun , Shim Seung-Hyuk , Lee Jong-Min , Kim Miseon , Lee Jung-Yun 
Published: February 2021

AbstractWe aimed to estimate the positive predictive value of fluorodeoxyglucose positron emission tomography (FDG PET) to detect lymph node metastasis in patients with microinvasive cervical cancer who recently underwent conization. We retrospectively collected data of patients fulfilling the following criteria: 1) cervical cancer stage 1A1 (by FIGO staging revised in 1994) without invasion of the lymphovascular space diagnosed by conization from September 2008 to July 2018, 2) FDG PET within 3 months after diagnosis, 3) lymph node metastasis suspected by FDG PET, and 4) histologic confirmation or follow-up imaging study for suspected lymph node metastasis. Lymph node metastasis was suspected in 31 regions in 18 patients; however, no true metastasis was found. In conclusion, lymph node metastasis suspected by FDG PET in microinvasive cervical cancer after conization might be false positive. Lymph node dissection should not be performed for such patients.
Acceptance of COVID-19 Vaccine in Pakistan Among Health Care Workers
Authors: Malik Asmara , Malik Jahanzeb , Ishaq Uzma 
Published: February 2021

AbstractObjectiveAcceptance of the COVID-19 vaccine will impart a pivotal role in eradicating the virus. In Pakistan, health care workers (HCWs) are the first group to receive vaccination. This survey aimed at the level of acceptance to the COVID-19 vaccine and predictors of non-acceptance in HCWs.MethodThis was a cross-sectional study design and data were collected through 3rd December 2020 and February 14th, 2021. An English questionnaire was distributed through social media platforms and administration of affiliate hospitals along with snowball sampling for private hospitals.ResultsOut of 5,237 responses, 3,679 (70.2%) accepted COVID-19 vaccination and 1,284 (24.5%) wanted to delay until more data was available. Only 5.2% of HCWs rejected being vaccinated. Vaccine acceptance was more in young (76%) and female gender (63.3%) who worked in a tertiary care hospital (51.2%) and were direct patient care providers (61.3%). The reason for rejection in females was doubtful vaccine effectiveness (31.48%) while males rejected due to prior COVID-19 exposure (42.19%) and side effect profile of the vaccine (33.17%). Logistic regression analysis demonstrated age between 51-60 years, female gender, Pashtuns, those working in the specialty of medicine and allied, taking direct care of COVID-19 patients, higher education, and prior OCVID-19 infection as the predictors for acceptance or rejection of COVID-19 vaccine.ConclusionA high overall acceptance rate was observed among HCWs, favoring a successful nationwide vaccination program in Pakistan.
Impact of the Tier system on SARS-CoV-2 transmission in the UK between the first and second national lockdowns
Authors: Laydon Daniel J , Mishra Swapnil , Hinsley Wes R , Samartsidis Pantelis , Flaxman Seth , Gandy Axel , Ferguson Neil M , Bhatt Samir 
Published: February 2021

AbstractObjectiveMeasure the effects of the Tier system on the COVID-19 pandemic in the UK between the first and second national lockdowns, before the emergence of the B.1.1.7 variant of concern.DesignModelling study combining estimates of the real-time reproduction number Rt (derived from UK case, death and serological survey data) with publicly available data on regional non-pharmaceutical interventions. We fit a Bayesian hierarchical model with latent factors using these quantities, to account for broader national trends in addition to subnational effects from Tiers.SettingThe UK at Lower Tier Local Authority (LTLA) level.Primary and secondary outcome measuresReduction in real-time reproduction number Rt.ResultsNationally, transmission increased between July and late September, regional differences notwithstanding. Immediately prior to the introduction of the tier system, Rt averaged 1.3 (0.9 – 1.6) across LTLAs, but declined to an average of 1.1 (0.86 – 1.42) two weeks later. Decline in transmission was not solely attributable to Tiers. Tier 1 had negligible effects. Tiers 2 and 3 respectively reduced transmission by 6% (5%-7%) and 23% (21%-25%). 93% of LTLAs would have begun to suppress their epidemics if every LTLA had gone into Tier 3 by the second national lockdown, whereas only 29% did so in reality.ConclusionsThe relatively small effect sizes found in this analysis demonstrate that interventions at least as stringent as Tier 3 are required to suppress transmission, especially considering more transmissible variants, at least until effective vaccination is widespread or much greater population immunity has amassed.Strengths and limitations of this studyFirst study to measure effects of UK Tier system for SARS-CoV-2 control at national and regional level.Model makes minimal assumptions and is primarily data driven.Insufficient statistical power to estimate effects of individual interventions that comprise Tiers, or their interaction.Estimates show that Tiers 1 and 2 are insufficient to suppress transmission, at least until widespread population immunity has amassed. Emergence of more transmissible variants of concern unfortunately supports this conclusion.
PRESENT SITUATION OF SUICIDE IN BANGLADESH: A REVIEW
Authors: Ferdous Most. Zannatul , Alam A.S.M. Mahbubul 
Published: February 2021

ABSTRACTThe most important global cause of mortality is suicide. It is often neglected by researchers, health professionals, health policymakers, and the medical profession. This review was aimed to provide a narrative understanding of the present situation of suicide in Bangladesh based on the existing literature. We conducted a review combining articles and abstracts with full HTML and PDF format. We searched PubMed, PubMed Central, Google Scholar, ScienceDirect and BanglaJOL, google using multiple terms related to suicide without any date boundary and without any basis of types of studies, that is, all types of studies were scrutinized. Finally, 16 articles were selected for review. Report suggested that every day almost 32 people commit suicide in 2019 which was 29 and 30 in 2015 and 2017 respectively. The mortality rate of suicide found 39.6 per 100,000 in Bangladesh. The most common method is hanging followed by poisoning and jumping under the train. The most prevalent age group is age under 40 years. The rate of suicide in children is also increasing. In contrast to most Asian countries, more Bangladeshi women commit suicide than men. The mean age of male and female were 28.86 ± 11.27 years and 25.31 ± 7.70 years respectively. The most common associated factors of suicide are younger age, lower education, students, nuclear family, family history of suicide, use substance, problem in workplace, financial constraints, affair, domestic violence, divorce, and physical illness. Most of the suicidal event occurred at night, followed by morning (6 am–12 am), and evening. It’s a criminal offence in Bangladesh. The source of information is mainly police, forensic reports, media and courts. Till now there is no nationwide survey of suicide is conducted. Besides, suicide surveillance strategy is yet to be established. Suicide is a neglected and under attended public health problem in Bangladesh with few research and paucity of literature. Now nationwide survey conduction and establishment of national suicide surveillance are a time demanded step.
Naegleria’smitotic spindles are built from unique tubulins and highlight core spindle features
Authors: Velle Katrina B , Trupinić Monika , Ivec Arian , Swafford Andrew , Nolton Emily , Rice Luke , Tolić Iva M. , Fritz-Laylin Lillian K , Wadsworth Patricia 
Published: February 2021

ABSTRACTNaegleria gruberiis a unicellular eukaryote whose evolutionary distance from animals and fungi has made it useful for developing hypotheses about the last common eukaryotic ancestor.Naegleriaamoebae lack a cytoplasmic microtubule cytoskeleton and assemble microtubules only during mitosis, and thus provides a unique system to study the evolution and functional specificity of mitotic tubulins and the resulting spindle. Previous studies showed thatNaegleriaamoebae express a divergent α-tubulin during mitosis and we now show thatNaegleriaamoebae express a second mitotic α- and two mitotic β-tubulins. The mitotic tubulins are evolutionarily divergent relative to typical α- and β- tubulins, contain residues that suggest distinct microtubule properties, and may represent drug targets for the “brain-eating amoeba”Naegleria fowleri. Using quantitative light microscopy, we find thatNaegleria’s mitotic spindle is a distinctive barrel-like structure built from a ring of microtubule bundles. Similar to those of other species,Naegleria’s spindle is twisted and its length increases during mitosis suggesting that these aspects of mitosis are ancestral features. Because bundle numbers change during metaphase, we hypothesize that the initial bundles represent kinetochore fibers, and secondary bundles function as bridging fibers.
Single Unit Analysis and Wide-Field Imaging Reveal Alterations in Excitatory and Inhibitory Neurons in Glioma
Authors: Gill Brian J.A. , Khan Farhan A. , Merricks Edward M. , Goldberg Alexander R. , Wu Xiaoping , Sosunov Alexander A. , Sudhakar Tejaswi D. , Liou Jyun-you , Dovas Athanassios , McKhann Guy M. , Canoll Peter , Schevon Catherine 
Published: February 2021

AbstractSeveral studies have attributed the development of tumor-associated seizures to an excitatory-inhibitory imbalance, highlighting the importance of resolving the spatiotemporal interplay of different neuronal populations within the peritumoral microenvironment. We combined methods for microelectrode array recordings and single unit analysis during ictal events with wide-field optical mapping of pyramidal neurons in anex vivoacute slice model of diffusely infiltrating glioma in Thy1-GCaMP6f mice. This approach allowed for characterization of excitatory and inhibitory populations across an extended peritumoral cortical region. As expected, measures of excitability were increased in tumor-bearing slices compared to control. This was accompanied by marked functional alterations in single units classified as fast-spiking interneurons, including reduced firing, altered timing with respect to excitatory firing, and deficits in surround inhibition. Inhibiting mTOR with AZD8055 reversed these glioma-induced changes to excitatory and inhibitory neuronal populations, suggesting a prominent role for functional mechanisms linked to mTOR activation.
REPROGRAMMING CBX8-PRC1 FUNCTION WITH A POSITIVE ALLOSTERIC MODULATOR
Authors: Suh Junghyun L. , Bsteh Daniel , Si Yibo , Hart Bryce , Weaver Tyler M. , Pribitzer Carina , Lau Roy , Soni Shivani , Ogana Heather , Rectenwald Justin M. , Norris Jacqueline L. , Cholensky Stephanie H. , Sagum Cari , Umana Jessica D. , Li Dongxu , Hardy Brian , Bedford Mark T. , Mumenthaler Shannon M. , Lenz Heinz-Josef , Kim Yong-mi , Wang Gang Greg , Pearce Ken H. , James Lindsey I. , Kireev Dmitri B. , Musselman Catherine A. , Frye Stephen V. , Bell Oliver 
Published: February 2021

ABSTRACTCanonical targeting of Polycomb Repressive Complex 1 (PRC1) to repress developmental genes is mediated by cell type-specific, paralogous chromobox (CBX) proteins (CBX2, 4, 6, 7 and 8). Based on their central role in silencing and their misregulation associated with human disease including cancer, CBX proteins are attractive targets for small molecule chemical probe development. Here, we have used a quantitative and target-specific cellular assay to discover a potent positive allosteric modulator (PAM) of CBX8. The PAM activity of UNC7040 antagonizes H3K27me3 binding by CBX8 while increasing interactions with nucleic acids and participation in variant PRC1. We show that treatment with UNC7040 leads to efficient PRC1 chromatin eviction, loss of silencing and reduced proliferation across different cancer cell lines. Our discovery and characterization of UNC7040 not only revealed the most cellularly potent CBX8-specific chemical probe to date, but also corroborates a mechanism of polycomb regulation by non-histone lysine methylated interaction partners.
DeTOKI identifies and characterizes the dynamics of chromatin topologically associating domains in a single cell
Authors: Li Xiao , Zhang Zhihua 
Published: February 2021

AbstractThe human genome has a dynamic, well-organized hierarchical 3D architecture, including megabase-sized topologically associating domains (TAD). TADs are a key structure of the genome regulating nuclear processes, such as gene expression, DNA replication and damage repair. However, owing to a lack of proper computational tools, TADs have still not been systematically and reliably surveyed in single cells. In the present work, we developed a new algorithm todecodeTAD boundaries thatkeep chromatininteraction insulated (deTOKI) from ultra-sparse Hi-C data. By nonnegative matrix factorization, this novel algorithm seeks out for regions that insulate the genome into blocks with minimal chance of clustering. We found that deTOKI outperformed competing tools and that it reliably identified TADs with single-cell Hi-C (scHi-C) data. By applying deTOKI, we found that domain structures are prevalent in single cells. Further, although domain structures are highly dynamic between cells, TADs adhere to the ensemble, suggesting tight regulation of single-cell TADs. Finally, we found that the insulation properties of TAD boundaries have major effect on the epigenetic landscape in individual cells. In sum, deTOKI serves as a powerful tool for profiling TADs in single cells.
Host-specific gene expression as a tool for introduction success inNaupactusparthenogenetic weevils
Authors: Mackay-Smith Ava , Dornon Mary Kate , Lucier Rosalind , Okimoto Anna , de Sousa Flavia Mendonca , Rodriguero Marcela , Confalonieri Viviana , Lanteri Analia A. , Sequeira Andrea S. 
Published: February 2021

AbstractFood resource access can mediate establishment success in invasive species, and generalist herbivorous insects are thought to rely on mechanisms of transcriptional plasticity to respond to dietary variation. While asexually reproducing invasives typically have low genetic variation, the twofold reproductive capacity of asexual organisms is a marked advantage for colonization. We studied host-related transcriptional acclimation in parthenogenetic, invasive, and polyphagous weevils:Naupactus cervinusandN. leucoloma. We analyzed patterns of gene expression in three gene categories that can mediate weevil-host plant interactions through identification of suitable host plants, short-term acclimation to host plant defenses, and long-term adaptation to host plant defenses and their pathogens. This approach employed comparative transcriptomic methods to investigate differentially expressed host detection, detoxification, immune defense genes, and pathway-level gene set enrichment. Our results show that weevil gene expression responses can be host plant-specific, and that elements of that response can be transgenerational. Some host plant groups, such as legumes, appear to be more taxing as they elicit a complex gene expression response which is both strong in intensity and specific in identity. However, the weevil response to taxing host plants shares many differentially expressed genes with other stressful situations, such as host plant cultivation conditions and transition to novel host, suggesting that there is an evolutionarily favorable shared gene expression regime for responding to different types of stressful situations. Modulating gene expression in the absence of other avenues for phenotypic adaptation may be an important mechanism of successful colonization for these introduced insects.
The Mammalian Cytosolic Type 2 (R)-β-hydroxybutyrate Dehydrogenase (BDH2) is 4-oxo-L-proline Reductase (EC 1.1.1.104)
Authors: Kwiatkowski Sebastian P. , Bozko Maria , Zarod Michal , Witecka Apolonia , Jagielski Adam K. , Drozak Jakub 
Published: February 2021

AbstractThe early studies on chicken embryos revealed that exposition to 4-oxo-L-proline resulted in the explicit increase in 4-hydroxy-L-proline content in their tissues. In 1962, 4-oxo-L-proline reductase, an enzyme responsible for the reduction of 4-oxo-L-proline, was partially purified from rabbit kidneys and characterized biochemically, but only recently the molecular identity of the enzyme has been unveiled in our laboratory. The present investigation reports the purification, identification as well as biochemical characterization of 4-oxo-L-proline reductase. The enzyme was purified from rat kidneys about 280-fold. Following mass spectrometry analysis of the purified protein preparation, the mammalian cytosolic type 2 (R)-β-hydroxybutyrate dehydrogenase (BDH2) emerged as the only meaningful candidate for the reductase. Rat and human BDH2 were expressed inE. coli, purified, and shown to catalyze the reversible reduction of 4-oxo-L-proline tocis-4-hydroxy-L-proline, as confirmed by chromatographic and mass spectrometry analysis. Specificity studies carried out on both enzymes showed that 4-oxo-L-proline was the best substrate, particularly the human enzyme acted with 9400-fold higher catalytic efficiencies on 4-oxo-L-proline than on (R)-β-hydroxybutyrate. Finally, HEK293T cells efficiently metabolized 4-oxo-L-proline tocis-4-hydroxy-L-proline and simultaneously accumulatedtrans-4-hydroxy-L-proline in the culture medium, suggesting that 4-oxo-L-proline is most likely an inhibitor oftrans-4-hydroxy-L-proline metabolism in human cells. We conclude that BDH2 is mammalian 4-oxo-L-proline reductase that converts 4-oxo-L-proline tocis-4-hydroxy-L-proline, and not totrans-4-hydroxy-L-proline as currently thought, and hypothesize that the enzyme may be considered as a potential source ofcis-4-hydroxy-L-proline in mammalian tissues.
Previous estradiol treatment during midlife maintains transcriptional regulation of memory-related proteins by ERα in the hippocampus in a rat model of menopause
Authors: Baumgartner Nina E. , Black Katelyn L. , McQuillen Shannon M. , Daniel Jill M. 
Published: February 2021

AbstractPrevious midlife estradiol treatment, like continuous treatment, improves memory and results in lasting increases in hippocampal levels of estrogen receptor (ER) α and ER-dependent transcription in ovariectomized rodents. We hypothesized that previous and continuous midlife estradiol act to specifically increase levels of nuclear ERα, resulting in transcriptional regulation of proteins that mediate estrogen effects on memory. Ovariectomized middle-aged rats received estradiol or vehicle capsule implants. After 40 days, rats initially receiving vehicle received another vehicle capsule (Vehicle). Rats initially receiving estradiol received either another estradiol (Continuous Estradiol) or a vehicle (Previous Estradiol) capsule. One month later, hippocampal genes and proteins were analyzed. Continuous and previous estradiol increased levels of nuclear, but not membrane or cytosolic ERα and had no effect onEsr1. Continuous and previous estradiol impacted gene expression and/or protein levels of mediators of estrogenic action on memory including ChAT, BDNF, and PSD-95. Findings demonstrate a long-lasting role for hippocampal ERα as a transcriptional regulator of memory following termination of previous estradiol treatment in a rat model of menopause.
Arkadia-SKI/SnoN signaling cascade differentially regulates TGF-β-induced iTreg and Th17 cell differentiation
Authors: Xu Hao , Wu Lin , Nguyen Henry , Mesa Kailin R. , Raghavan Varsha , Episkopou Vasso , Littman Dan R. 
Published: February 2021

AbstractTGF-β signaling is fundamental for both Th17 and regulatory T cell (Treg) differentiation. However, these cells differ in requirements for downstream signaling components, such as various SMAD effectors, for their differentiation. To further characterize the mechanisms that distinguish TGF-β signaling requirements for Th17 and Treg cell differentiation, we investigated the role of Arkadia (RNF111), a RING type E3 ubiquitin ligase known to enhance TGF-β signaling during development. We find that Arkadia mediates the differentiation of induced-Treg (iTreg) but not Th17 cells bothin vitroandin vivo. Inactivation of Arkadia in CD4+T cells resulted in impairment of Treg cell differentiationin vitroand loss of RORγt+FOXP3+iTreg cells in the intestinal lamina propriain vivo, which increased susceptibility to microbiota-induced mucosal inflammation. Furthermore, genetic ablation of two substrates of Arkadia, the transcriptional co-repressors SKI and SnoN, rescuedin vitroandin vivoiTreg cell-differentiation of Arkadia-deficient cells. These results reveal distinct TGF-β signaling modules that govern Th17 and iTreg cell differentiation programs and that could be exploited therapeutically to selectively modulate T cell subsets in pathological settings such as autoimmunity or cancer.