bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell spatial analysis of tumor immune architecture in diffuse large B cell lymphoma
Authors: Colombo Anthony , Hav Monirath , Gerdtsson Erik , Singh Mohan , Xu Alexander , Gamboa Alicia , Chen Denaly , Houldsworth Jane , Shaknovich Rita , Aoki Tomohiro , Chong Lauren , Takata Katsuyoshi , Chavez Elizabeth A , Steidl Christian , Hicks James , Kuhn Peter , Siddiqi Imran , Merchant Akil 
Published: February 2021

ABSTRACTMultiplexed immune cell profiling of the tumor microenvironment (TME) in cancer has improved our understanding of cancer immunology, but complex spatial analyses of tumor-immune interactions in lymphoma are lacking. Here we used imaging mass cytometry (IMC) on 33 cases of diffuse large B cell lymphoma (DLBCL) to characterize tumor and immune cell architecture and correlate it to clinicopathological features such as cell of origin, gene mutations, and responsiveness to chemotherapy. To understand the poor response of DLBCL to immune check point inhibitors (ICI), we compared our results to IMC data from Hodgkin lymphoma (HL), a cancer highly responsive to ICI, and observed differences in the expression of PD-L1, PD-1, and TIM-3. We created a spatial classification of tumor cells and identified sub-regions of immune activation, immune suppression, and immune exclusion within the topology of DLBCL. Finally, the spatial analysis allowed us to identify markers such as CXCR3, which are associated with penetration of immune cells into immune desert regions, with important implications for engineered cellular therapies.SIGNIFICANCEThis is the first study to integrate tumor mutational profiling, cell of origin classification, and multiplexed immuno-phenotyping of the TME into a spatial analysis of DLBCL at the single cell level. We demonstrate that, far from being histo-pathologically monotonous, DLBCL has a complex tumor architecture, and that changes in tumor topology can be correlated with clinically relevant features. This analysis identifies candidate biomarkers and therapeutic targets such as TIM-3, CCR4, and CXCR3 that are relevant for combination treatment strategies in immuno-oncology and cellular therapies such as CAR-T cells.
Optimal time to return to normality: parallel use of COVID-19 vaccines and circuit breakers
Authors: Bonsall Michael B. , Huntingford Chris , Rawson Thomas 
Published: February 2021

AbstractBy January 2020, the COVID-19 illness has caused over two million deaths. Countries have restricted disease spread through non-pharmaceutical interventions (e.g., social distancing). More severe “lockdowns” have also been required. Although lockdowns keep people safer from the virus, they substantially disrupt economies and individual well-being. Fortunately, vaccines are becoming available. Yet, vaccination programs may take several months to implement, requiring further time for individuals to develop immunity following inoculation. To prevent health services being overwhelmed it may be necessary to implement further lockdowns in conjunction with vaccination. Here, we investigate optimal approaches for vaccination under varying lockdown lengths and/or severities to prevent COVID-19-related deaths exceeding critical thresholds. We find increases in vaccination rate cause a disproportionately larger decrease in lockdowns: with vaccination, severe lockdowns can reduce infections by up to 89%. Notably, we include demographics, modelling three groups: vulnerable, front-line workers, and non-vulnerable. We investigate the sequence of vaccination. One counter-intuitive finding is that even though the vulnerable group is high risk, demographically, this is a small group (per person, vaccination occurs more slowly) so vaccinating this group first achieves limited gains in overall disease control. Better disease control occurs by vaccinating the non-vulnerable group with longer and/or more severe lockdowns.
Diagnostic performance of standard and inverted grey-scale CXR in detection of lung lesions in COVID-19 patients. A single institution study in the region of Abu Dhabi
Authors: AlHelali Abeer Ahmed , Kukkady Mohamed Ashfaque , Saeed Ghufran Aref , Elholiby Tamer Ibrahim , Mansoori Rabab Abdulrahman Al , Ahmed Luai A 
Published: February 2021

AbstractPurposeTo evaluate diagnostic performance of greyscale and inverted greyscale Chest X-ray (CXR) using Computed Tomography (CT) scan as a gold standard.MethodsIn this retrospective study, electronic medical records of 120 patients who had valid CXR and High-resolution CT (HRCT) within less than 24 hours after having a positive COVID-19 RT-PCR test during the period from May 19 th to May 23 rd 2020 in a single tertiary care center were reviewed.PA chest radiographs were presented on 2 occasions to 5 radiologists to evaluate the role and appropriateness of greyscale and inverted greyscale chest radiographs (CXR). The images were viewed on high-specification viewing systems using a primary display monitors and compared it to computed tomography (CT) findings for screening and management of suspected or confirmed COVID-19 patients.ResultsNinety-six (80%) patients had positive CT findings, 81 (67.5%) had positive grey scale CXR lesions, and 25 (20.8%) had better detection in the inverted grey scale CXR. The CXR sensitivity for COVID-19 pneumonia was 93.8% (95% CI (86.2% - 98.0%) and the specificity was 48.7% (95% CI (32.4% - 65.2%). The CXR sensitivity of detection of lung lesions was slightly higher in male (95.1% (95% CI (86.3% - 99.0%)) than female (90.0% (95% CI (68.3% - 98.8%)), while the specificity was 48.0% (95% CI (27.8% - 68.7%) and 50.0% (95% CI (23.0% - 77.0%) in males and females, respectively. However, no significant difference was detected in ROC area between men and women.ConclusionsThe sensitivity of detection of lung lesions of CXR was relatively high, particularly in men. The results of the study support the idea of considering conventional radiographs as an important diagnostic tool in suspected COVID-19 patients especially in healthcare facilities where there is no access to HRCT scans.HighlightsCXR shows high sensitivity for detecting lung lesions in HRCT confirmed COVID-19 patients.Better detection of lesions was noted in the inverted grey scale CXR in (20.8%) of cases with positive findings in standard greyscale CXR.Conventional radiographs can be used as diagnostic tools in suspected COVID-19 patients especially in healthcare facilities where there is no access to HRCT scans.
How lifestyle changes within the COVID-19 global pandemic have affected the pattern and symptoms of the menstrual cycle
Authors: Bruinvels Georgie , Goldsmith Esther , Blagrove Richard C. , Martin Dan , Shaw Laurence , Piasecki Jessica 
Published: February 2021

AbstractBackgroundThe coronavirus 2019 (COVID-19) pandemic has caused significant changes to homes, working life and stress. The purpose of this research was to investigate the implications that the COVID-19 pandemic has had on the menstrual cycle and any contributing factors to these changes.MethodsA questionnaire was completed by 749 participants, whom ranged from ‘physically active’ to elite, in their training status. The questionnaire captured detail on menstrual cycle symptoms and characteristics prior to and during the COVID-19 pandemic lockdown period, as well as lifestyle, stress, exercise and nutrition. Descriptive statistics and frequency distribution were reported and decision tree analysis performed. Statistical significance was assumed at p<0.05.ResultsFifty-two point six percent of females experienced a change in their menstrual cycle during the lockdown period. Psychosocial symptoms had changed in over half of all participants. Participants who reported increased stress/worry in family and personal health were significantly associated with changes in menstrual symptoms. Similarly, job security stress was associated with increases in bleeding time (p<0.05).ConclusionsIt is important that females and practitioners become aware of the implications of stressful environments and the possible long-term implications on fertility, particularly given the uncertainty around a second wave of the global pandemic.
Identifying Heart Failure from Electronic Health Records: A Systematic Evidence Review
Authors: Levinson Rebecca T. , Malinowski Jennifer R. , Bielinski Suzette J. , Rasmussen Luke V. , Wilson Melissa P. , Manemann Sheila M. , Wells Quinn S. , Roger Veronique L. , Wiley Laura K. 
Published: February 2021

ABSTRACTBackgroundHeart failure (HF) is a complex syndrome associated with significant morbidity, mortality, and healthcare costs. Electronic health records (EHRs) are widely used to identify patients with HF. Despite the development of many HF phenotyping algorithms, it is unclear if the characteristics of identified populations reflect the known spectrum of disease in HF patients.MethodsWe performed a systematic evidence review to assess the methods used for HF algorithm development from US based data sources and the relevant information facilitating their application to research and clinical care. We queried PubMed for articles published up to November 2021. Out of 428 studies screened, 35 articles were included for primary analysis and 23 studies using only International Classification of Diseases (ICD) codes were evaluated for secondary analysis. Results are reported descriptively.ResultsHF algorithms were most often developed at academic medical centers, though these were not evenly distributed across the US. HF and congestive HF were the most frequent labels for observed phenotypes. Diagnoses were the most common data type used to identify HF patients and echocardiography was the second most frequent. Most studies used rule-based algorithms. Validation of algorithms varied considerably with 36% of HF subtype algorithms validated and 67% of acute HF algorithms validated. Demographics of any study population were reported in 57% of algorithm studies and 70% of ICD-only studies, however fewer than half (40% of algorithm and 46% of ICD-only) of studies reported demographics of the HF population identified by their computable phenotype. Of those reporting, most identified majority (>50%) male populations, including both algorithms for HF with preserved ejection fraction identified in this study.ConclusionThere is significant heterogeneity in phenotyping algorithms used to ascertain HF from EHRs. Validation of algorithms is inconsistent and largely relies on manual review of medical records. The concentration of algorithm development at a few sites limits their generalizability to identify HF patients in other settings. Differences between the reported demographics of algorithm-identified HF populations and those expected based on HF epidemiology suggest that current algorithms do not reflect the full spectrum of HF in the general population.
Cortico-amygdalar connectivity and externalizing/internalizing behavior in children with neurodevelopmental disorders
Authors: Nakua Hajer , Hawco Colin , Forde Natalie J. , Jacobs Grace R. , Joseph Michael , Voineskos Aristotle , Wheeler Anne L. , Lai Meng-Chuan , Szatmari Peter , Kelley Elizabeth , Liu Xudong , Georgiades Stelios , Nicolson Rob , Schachar Russell , Crosbie Jennifer , Anagnostou Evdokia , Lerch Jason P. , Arnold Paul D. , Ameis Stephanie H. 
Published: February 2021

ABSTRACTBackgroundExternalizing and internalizing behaviors are common and contribute to impairment in children with neurodevelopmental disorders (NDDs). Associations between externalizing or internalizing behaviors and cortico-amygdalar connectivity have been found in children with and without clinically significant internalizing/externalizing behaviors. This study examined whether such associations are present across children with different NDDs.MethodsMulti-modal neuroimaging and behavioral data from the Province of Ontario Neurodevelopmental Disorders (POND) Network were used. POND participants aged 6-18 years with a primary diagnosis of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD), as well as typically developing children (TDC) with T1-weighted, resting-state fMRI or diffusion weighted imaging and parent-report Child Behavioral Checklist (CBCL) data available, were analyzed (n range=157-346). Associations between externalizing or internalizing behavior and cortico-amygdalar structural and functional connectivity indices were examined using linear regressions, controlling for age, gender, and image-modality specific covariates. Behavior-by-diagnosis interaction effects were also examined.ResultsNo significant linear associations (or diagnosis-by-behavior interaction effects) were found between CBCL-measured externalizing or internalizing behaviors and any of the connectivity indices examined. Post-hoc bootstrapping analyses indicated stability and reliability of these null results.ConclusionsThe current study provides evidence in favour of the absence of a shared linear relationship between internalizing or externalizing behaviors and cortico-amygdalar connectivity properties across a transdiagnostic sample of children with various NDDs and TDC. Detecting shared brain-behavior relationships in children with NDDs may benefit from the use of different methodological approaches, including incorporation of multi-dimensional behavioral data (i.e. behavioral assessments, neurocognitive tasks, task-based fMRI) or clustering approaches to delineate whether subgroups of individuals with different brain-behavior profiles are present within heterogeneous cross-disorder samples.
Hydrogen peroxide modulates lignin and silica deposits in sorghum roots
Authors: Zexer Nerya , Elbaum Rivka 
Published: February 2021

AbstractHydrated silica (SiO2·nH2O) aggregates in the root endodermis of grasses. Application of soluble silicates (Si) to roots is associated with variations in the balance of reactive oxygen species (ROS), increased tolerance to a broad range of stresses affecting ROS levels, and early lignin deposition. In sorghum (Sorghum bicolorL.), silica aggregation is patterned in an active silicification zone (ASZ) by a special type of lignin. Since lignin polymerization is mediated by ROS, we studied the formation of root lignin and silica under varied conditions of ROS by modulating hydrogen peroxide (H2O2) concentration in the growth solution. Sorghum seedlings were grown hydroponically and supplemented with Si, H2O2, and KI, a salt that catalyzes H2O2decomposition. Lignin and silica deposits in the endodermis were studied by histology, scanning electron and Raman microscopies. Cell wall composition was quantified by thermal gravimetric analysis. We found that the endodermal H2O2concentration regulated the extent of ASZ lignin deposition along the root, but not its patterning in spots. Our results show that ASZ lignin is necessary for root silica aggregation in sorghum, and that silicification is enhanced under oxidative stress as a result of increased deposition of the ASZ lignin.One sentence summaryLignin with carbonyl modifications is patterned by the activity of H2O2to nucleate silica aggregations in sorghum roots.
RIM and RIM-binding protein localize synaptic CaV2 channels to differentially regulate transmission in neuronal circuits
Authors: Jánosi Barbara , Liewald Jana F. , Yu Szi-chieh , Umbach Simon , Alcantara Ivan C. , Bergs Amelie C.F. , Schneider Martin , Shao Jiajie , Gottschalk Alexander 
Published: February 2021

AbstractAt chemical synapses, voltage-gated Ca2+-channels (VGCCs) translate electrical signals into a trigger for synaptic vesicle (SV) fusion. VGCCs and the Ca2+microdomains they elicit must be located precisely to primed SVs, to evoke rapid transmitter release. Localization is mediated by Rab3 interacting molecule (RIM) and RIM-binding proteins (RIM-BPs), which interact and bind to the C-terminus of the CaV2 VGCC α-subunit. We studied this machinery at the mixed cholinergic/GABAergic neuromuscular junction (NMJ) ofCaenorhabditis elegans. rimb-1mutants had mild synaptic defects, through loosening the anchoring of UNC-2/CaV2 and delaying the onset of SV fusion. UNC-10/RIM deletion much more severely affected transmission. Even though postsynaptic depolarization was reduced,rimb-1mutants had increased cholinergic (but reduced GABAergic) transmission, to compensate for the delayed release. This did not occur when the excitation-inhibition balance was altered by removing GABA transmission. RIMB-1 thus may differentially regulate transmission in mixed circuits. Untethering the UNC-2/CaV2 channel by removing its C-terminal PDZ ligand exacerbated therimb-1defects, and similar phenotypes resulted from acute degradation of the CaV2 β-subunit CCB-1. Therefore, untethering of the CaV2 complex is as severe as its elimination, yet does not abolish transmission, likely due to compensation by CaV1. Thus, robustness and flexibility of synaptic transmission emerges from VGCC regulation.
Kv1.1 subunits localize to cardiorespiratory brain networks in mice where their absence induces astrogliosis and microgliosis
Authors: Dhaibar Hemangini A , Hamilton Kathryn A , Glasscock Edward 
Published: February 2021

ABSTRACTCardiorespiratory collapse following a seizure is a suspected cause of sudden unexpected death in epilepsy (SUDEP), the leading cause of epilepsy-related mortality. In the commonly usedKcna1gene knockout (Kcna1−/−) mouse model of SUDEP, cardiorespiratory profiling reveals an array of aberrant breathing patterns that could contribute to risk of seizure-related mortality. However, the brain structures mediating these respiratory abnormalities remain unknown. We hypothesize that Kv1.1 deficiency in respiratory control centers of the brain contribute to respiratory dysfunction inKcna1−/−mice leading to increased SUDEP risk. Thus, in this study, we first used immunohistochemistry to map expression of Kv1.1 protein in cardiorespiratory brain regions of wild-typeKcna1+/+(WT) mice. Next, GFAP and Iba1 immunostaining was used to test for the presence of astrogliosis and microgliosis, respectively, in the cardiorespiratory centers ofKcna1−/−mice, which could be indicative of seizure-related brain injury that could impair breathing. In WT type mice, we detected Kv1.1 protein in all cardiorespiratory centers examined, including the basolateral amygdala, dorsal respiratory group, dorsal motor nucleus of vagus, nucleus ambiguus, ventral respiratory column, and pontine respiratory group, as well as chemosensory centers including the retrotrapezoid and median raphae nuclei. Extensive gliosis was observed in the same areas inKcna1−/−mice suggesting that seizure-associated brain injury could contribute to respiratory abnormalities.
Colonization at birth with human CST IV cervicovaginal microbiota alters development and increases neonatal mortality in mice
Authors: Jašarević Eldin , Hill Elizabeth M. , Kane Patrick J. , Rutt Lindsay , Gyles Trevonn , Folts Lillian , Rock Kylie D. , Howard Christopher D. , Morrison Kathleen E. , Ravel Jacques , Bale Tracy L. 
Published: February 2021

SummaryProfound racial health disparities contribute to maternal-infant morbidity and mortality. An emergent risk factor is the maternal microbiota, whereby compositional alterations impact maternal health and offspring development during pregnancy and beyond. The presence of a nonoptimal CST IV cervicovaginal microbiota, more common in Black and Hispanic women, is associated with increased risk of preterm birth and adverse birth outcomes. Through examination of the biological mechanisms by which vertical transmission of microbiota from mother to offspring influences postnatal development, we found that exposing cesarean delivered mice with CST IV cervicovaginal microbiota from pregnant women produced lasting effects on offspring metabolic, immune, and neural outcomes. We then examined how compounding effects of a typical high-risk, proinflammatoryin uteroenvironment, characterized by a maternal obesogenic state and the presence ofG. vaginalis, would affect the offspring response to CST IV microbial gut colonization. The resultant developmental immaturity, coupled with an exaggerated immune response induced by exposure to risk-associated maternal microbiota, resulted in a profound increase in neonatal mortality, supporting the critical importance of elucidating the multifactorial biological mechanisms involved in high-risk pregnancies.HighlightsGut colonization by nonoptimal human cervicovaginal microbiota had sex-specific effects on postnatal development.A high-riskin uteroenvironment increased offspring mortality risk.Heightened innate immune response associated with mortality risk.Developmental immaturity, premature birth, and exposure to CST IV contribute to increased offspring mortality risk.
Isolation andin vitroculture of primarypia matercells
Authors: Saadeh Fadi , Remsik Jan , Derderian Camille , Chi Yudan , Boire Adrienne 
Published: February 2021

AbstractThe meninges remain an unexplored area of neurobiology. These structures play host to dozens of morbid pathologies. This protocol provides a reliable way to identify and isolate pial cells from mice using robust markers of pial identity in mouse and human tissues. We describe a protocol for the extraction ofpia matercells from mice and their culture as primary cellsin vitro. Using an array of transcriptomic, histological, and flow cytometric analyses, we identified Icam1 and Slc38a2 as two novelpia matermarkersin vitroandin vivo. Our results confirm the fibroblastoid nature of pial cells and their ability to form a sheet-like layer that covers the brain parenchyma. To our knowledge, this is the first published protocol for the isolation, tissue culture, and marker identification of pial cells from mice. These findings will enable researchers in CNS barriers to describe pial cell functions in both health and disease.
Molecular mechanism underlying the non-essentiality of Bub1 for the fidelity of chromosome segregation in human cells
Authors: Chen Qinfu , Zhang Miao , Pan Xuan , Zhou Linli , Yan Haiyan , Wang Fangwei 
Published: February 2021

SUMMARYThe multi-task protein kinase Bub1 has long been considered important for chromosome alignment and spindle assembly checkpoint signaling during mitosis. However, recent studies provide surprising evidence that Bub1 may not be essential in human cells, with the underlying mechanism unknown. Here we show that Bub1 plays a redundant role with the non-essential CENP-U complex in recruiting Polo-like kinase 1 (Plk1) to the kinetochore. While disrupting either pathway of Plk1 recruitment does not affect the accuracy of whole chromosome segregation, loss of both pathways leads to a strong reduction in the kinetochore accumulation of Plk1 under a threshold level required for proper chromosome alignment and segregation. Thus, parallel recruitment of Plk1 to kinetochores by Bub1 and the CENP-U complex ensures high fidelity of mitotic chromosome segregation. This study may have implications for targeted treatment of cancer cells harboring mutations in either Bub1 or the CENP-U complex.