bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analyzing master regulators and scRNA-seq of COVID-19 patients reveals an underlying anti-SARS-CoV-2 mechanism of ZNF proteins
Authors: Qin Shijie , Xu Weijun , Wang Canbiao , Jiang Sizhu , Dai Wei , Yang Yang , Shen Jiawei , Jin Ping , Ma Fei , Xia Xinyi 
Published: March 2021

AbstractStudies have demonstrated that both mortality and severe illness rates exist significant difference in different gender COVID-19 patients, but the reasons are still very mysterious to date. Here, we firstly find that the survival outcome of female patients is better to male patients through analyzing the 3044 COVID-19 cases. Secondly, we identify many important master regulators [e.g. STAT1/STAT2 and zinc finger (ZNF) proteins], in particular female patients can express more ZNF proteins and stronger transcriptional activities than male patients in response to SARS-CoV-2 infection. Thirdly, we discover that ZNF protein activity is significantly negative correlation with the SARS-CoV-2 load of COVID-19 patients, and ZNF proteins as transcription factors can also activate their target genes to participate in anti-SARS-CoV-2 infection. Fourthly, we demonstrate that ZNF protein activity is positive correlation with the abundance of multiple immune cells of COVID-19 patients, implying that the highly ZNF protein activity might promote the abundance and the antiviral activity of multiple immune cells to effectively suppress SARS-CoV-2 infection. Taken together, our study proposes an underlying anti-SARS-COV-2 role of ZNF proteins, and differences in the amount and activity of ZNF proteins might be responsible for the distinct prognosis of different gender COVID-19 patients.
PoseFilter: a PyMOL plugin for filtering and analyzing small molecule docking in symmetric binding sites
Authors: Williams Justine C , Kalyaanamoorthy Subha 
Published: March 2021

Abstract

Summary
‘PoseFilter’ is a PyMOL plugin that assists in analyses and filtering of docked poses. PoseFilter enables automatic detection of symmetric poses from docking outputs and can be accessed using both graphical user interface and command-line options within the PyMOL program. Two methods of analyses, root mean square deviations and interaction fingerprints, are available from this plugin. The capabilities of the plugin are demonstrated using docking outputs from different oligomeric protein-ligand complexes.

Availability and implementation
The plugin can be downloaded from the GitHub page, https://github.com/skalyaanamoorthy/PoseFilter.

Supplementary information
Supplementary data are available at Bioinformatics online.
Association of intraoperative hypotension with postoperative morbidity and mortality: systematic review and meta-analysis
Authors: Wijnberge M , Schenk J , Bulle E , Vlaar A P , Maheshwari K , Hollmann M W , Binnekade J M , Geerts B F , Veelo D P 
Published: March 2021

Abstract

Background
Intraoperative hypotension, with varying definitions in literature, may be associated with postoperative complications. The aim of this meta-analysis was to assess the association of intraoperative hypotension with postoperative morbidity and mortality.

Methods
MEDLINE, Embase and Cochrane databases were searched for studies published between January 1990 and August 2018. The primary endpoints were postoperative overall morbidity and mortality. Secondary endpoints were postoperative cardiac outcomes, acute kidney injury, stroke, delirium, surgical outcomes and combined outcomes. Subgroup analyses, sensitivity analyses and a meta-regression were performed to test the robustness of the results and to explore heterogeneity.

Results
The search identified 2931 studies, of which 29 were included in the meta-analysis, consisting of 130 862 patients. Intraoperative hypotension was associated with an increased risk of morbidity (odds ratio (OR) 2.08, 95 per cent confidence interval 1.56 to 2.77) and mortality (OR 1.94, 1.32 to 2.84). In the secondary analyses, intraoperative hypotension was associated with cardiac complications (OR 2.44, 1.52 to 3.93) and acute kidney injury (OR 2.69, 1.31 to 5.55). Overall heterogeneity was high, with an I2 value of 88 per cent. When hypotension severity, outcome severity and study population variables were added to the meta-regression, heterogeneity was reduced to 50 per cent.

Conclusion
Intraoperative hypotension during non-cardiac surgery is associated with postoperative cardiac and renal morbidity, and mortality. A universally accepted standard definition of hypotension would facilitate further research into this topic.
Safety and feasibility of 2 h of normothermic machine perfusion of donor kidneys in the Eurotransplant Senior Program
Authors: Rijkse E , de Jonge J , Kimenai H J A N , Hoogduijn M J , de Bruin R W F , van den Hoogen M W F , IJzermans J N M , Minnee R C 
Published: March 2021

Abstract

Background
The 5-year graft survival rate of donor kidneys transplanted in the Eurotransplant Senior Program (ESP) is only 47 per cent. Normothermic machine perfusion (NMP) may be a new preservation technique that improves graft outcome. This pilot study aimed to assess safety and feasibility of this technique within the ESP.

Methods
Recipients were eligible for inclusion if they received a donor kidney within the ESP. Donor kidneys underwent 2 h of oxygenated NMP with a red cell-based solution at 37°C, additional to standard-of-care preservation (non-oxygenated hypothermic machine perfusion). The primary outcome was the safety and feasibility of NMP. As a secondary outcome, graft outcome was investigated and compared with that in a historical group of patients in the ESP and the contralateral kidneys.

Results
Eleven patients were included in the NMP group; the function of eight kidneys could be compared with that of the contralateral kidney. Fifty-three patients in the ESP, transplanted consecutively between 2016 and 2018, were included as controls. No adverse events were noted, especially no arterial thrombosis or primary non-function of the transplants. After 120 min of oxygenated NMP, median flow increased from 117 (i.q.r. 80–126) to 215 (170–276) ml/min (P = 0.001). The incidence of immediate function was 64 per cent in the NMP group and 40 per cent in historical controls (P = 0.144). A significant difference in graft outcome was not observed.

Discussion
This pilot study showed NMP to be safe and feasible in kidneys transplanted in the ESP. A well powered study is warranted to confirm these results and investigate the potential advantages of NMP on graft outcome.
Time trends in incidence and survival of small intestinal cancer in Sweden
Authors: Landerholm K 
Published: March 2021

Abstract

Background
Small intestinal cancer is less common than some other gastrointestinal malignancies. Tumours of different histological types and anatomical sites of origin have therefore often been described together. The aim of this study was to investigate the epidemiology for each of the four main subtypes: duodenal adenocarcinoma (D-AC), duodenal neuroendocrine tumour (D-NET), jejunoileal adenocarcinoma (J/I-AC), and jejunoileal neuroendocrine tumour (J/I-NET).

Methods
All patients with small intestinal cancer diagnosed between 1960 and 2015 were identified from the Swedish Cancer Register. The age-adjusted incidence rate with incidence rate ratios, as well as overall (OS) and net (NS) survival, were determined and temporal trends were analysed.

Results
The incidence rate was highest for J/I-NET, with 9.98 clinical diagnoses per million in 2010–2015. Clinical diagnosis of D-AC increased more than 10-fold and surpassed J/I-AC as the second most common subtype. D-NET was by far the least common subtype. Diagnosis at autopsy became less common over time, whereas clinical diagnoses increased significantly for all four subtypes. All subtypes except J/I-AC affected men more often than women. The age distribution was similar between subtypes, although patients with adenocarcinomas were slightly older. Survival was generally much better for patients with NET than for those with adenocarcinoma. Both OS and NS showed a negative association with advancing age. Survival improved only for J/I-NET from a 5-year NS of 0.69 in the 1960s to 0.81 in 2010–2015.

Conclusion
The incidence of small intestinal cancer is increasing, particularly for D-AC and in the elderly. Survival of patients with small intestinal cancer has improved only for J/I-NET over the last decades.
To what degree is late life cognitive decline driven by age-related neuropathologies?
Authors: Boyle Patricia A , Wang Tianhao , Yu Lei , Wilson Robert S , Dawe Robert , Arfanakis Konstantinos , Schneider Julie A , Bennett David A 
Published: March 2021

Abstract
The ageing brain is vulnerable to a wide array of neuropathologies. Prior work estimated that the three most studied of these, Alzheimer’s disease, infarcts, and Lewy bodies, account for ∼40% of the variation in late life cognitive decline. However, that estimate did not incorporate many other diseases that are now recognized as potent drivers of cognitive decline [e.g. limbic predominant age-related TDP-43 encephalopathy (LATE-NC), hippocampal sclerosis, other cerebrovascular conditions]. We examined the degree to which person-specific cognitive decline in old age is driven by a wide array of neuropathologies. Deceased participants (n = 1164) from two longitudinal clinical-pathological studies, the Rush Memory and Aging Project and Religious Orders Study, completed up to 24 annual evaluations including 17 cognitive performance tests and underwent brain autopsy. Neuropathological examinations provided 11 pathological indices, including markers of Alzheimer’s disease, non- Alzheimer’s disease neurodegenerative diseases (i.e. LATE-NC, hippocampal sclerosis, Lewy bodies), and cerebrovascular conditions (i.e. macroscopic infarcts, microinfarcts, cerebral amyloid angiopathy, atherosclerosis, and arteriolosclerosis). Mixed effects models examined the linear relation of pathological indices with global cognitive decline, and random change point models examined the relation of the pathological indices with the onset of terminal decline and rates of preterminal and terminal decline. Cognition declined an average of about 0.10 unit per year (estimate = −0.101, SE = 0.003, P &lt; 0.001) with considerable heterogeneity in rates of decline (variance estimate for the person-specific slope of decline was 0.0094, P &lt; 0.001). When considered separately, 10 of 11 pathological indices were associated with faster decline and accounted for between 2% and 34% of the variation in decline, respectively. When considered simultaneously, the 11 pathological indices together accounted for 43% of the variation in decline; Alzheimer’s disease-related indices accounted for 30–36% of the variation, non-Alzheimer’s disease neurodegenerative indices 4–10%, and cerebrovascular indices 3–8%. Finally, the 11 pathological indices combined accounted for less than a third of the variation in the onset of terminal decline (28%) and rates of preterminal (32%) and terminal decline (19%). Although age-related neuropathologies account for a large proportion of the variation in late life cognitive decline, considerable variation remains unexplained even after considering a wide array of neuropathologies. These findings highlight the complexity of cognitive ageing and have important implications for the ongoing effort to develop effective therapeutics and identify novel treatment targets.
Maternal Adverse Childhood Experience and Depression in Relation with Brain Network Development and Behaviors in Children: A Longitudinal Study
Authors: Zhang Han , Wong Ting-Yat , Broekman Birit F P , Chong Yap-Seng , Shek Lynette P , Gluckman Peter D , Tan Kok Hian , Meaney Michael J , Fortier Marielle V , Qiu Anqi 
Published: March 2021

Abstract
Maternal childhood maltreatment and depression increase risks for the psychopathology of the offspring. This study employed a longitudinal dataset of mother–child dyads to investigate the developmental trajectories of brain functional networks and behaviors of children in relation with maternal childhood adverse experience and depression. Maternal childhood trauma was retrospectively assessed via childhood trauma questionnaire, whereas maternal depressive symptoms were prospectively evaluated during pregnancy and after delivery (n = 518). Child brain scans were acquired at age of 4.5, 6, and 7.5 years (n = 163) and behavioral problems were measured at 7.5 years using the Child Behavior Checklist. We found the functional connectivity of the language network with the sensorimotor, frontal, and attentional networks as a function of maternal adverse experience that interacted with sex and age. Girls exposed to mothers with depressive symptoms or childhood abuse showed the increased development of the functional connectivity of the language network with the visual networks, which was associated with social problems. Girls exposed to mothers with depressive symptoms showed the slower growth of the functional connectivity of the language network with the sensorimotor networks. Our findings, in a community sample, suggest the language network organization as neuroendophenotypes for maternal childhood trauma and depression.
Age-Related Changes in Malaria Clinical Phenotypes During Infancy Are Modified by Sickle Cell Trait
Authors: Zehner Nicholas , Adrama Harriet , Kakuru Abel , Andra Teddy , Kajubi Richard , Conrad Melissa , Nankya Felistas , Clark Tamara D , Kamya Moses , Rodriguez-Barraquer Isabel , Dorsey Grant , Jagannathan Prasanna 
Published: March 2021

Abstract

Background
Infants are protected against Plasmodium falciparum malaria. Mechanisms that drive this protection remain unclear due to a poor understanding of malaria clinical phenotypes during infancy.

Methods
We enrolled a birth cohort of 678 infants in Busia, Uganda, an area of high malaria transmission. We followed infants through 12 months of age and quantified protection against parasitemia and clinical disease.

Results
Symptomatic malaria incidence increased from 1.2 to 2.6 episodes per person-year between 0 and &lt;6 months and between 6 and 12 months of age, while the monthly probability of asymptomatic parasitemia given infection decreased from 32% to 21%. Sickle cell trait (HbAS) was protective against symptomatic malaria (incidence rate ratio  = 0.57 comparing HbAS vs hemoglobin AA (HbAA); 95% confidence interval, 0.44–0.74; P &lt; .001), but age modified this relationship (Pint = &lt;0.001), with nonlinear protection that waned between 0 and 9 months of age before increasing. Increasing age was associated with higher parasite densities at the time of infection and, in infants with HbAS, a reduced ability to tolerate high parasite densities without fever.

Conclusions
Age-dependent changes in HbAS protective efficacy in infancy were accompanied by differential loss of antiparasite and antidisease protection among HbAS and HbAA infants. This provides a framework for investigating the mechanisms that underlie infant protection against malaria.

Clinical Trials Registration
NCT02793622.
Sex-specific differences in swimming, aerobic metabolism and recovery from exercise in adult coho salmon (Oncorhynchus kisutch) across ecologically relevant temperatures
Authors: Kraskura K , Hardison E A , Little A G , Dressler T , Prystay T S , Hendriks B , Farrell A P , Cooke S J , Patterson D A , Hinch S G , Eliason E J 
Published: March 2021

Abstract
Adult female Pacific salmon can have higher migration mortality rates than males, particularly at warm temperatures. However, the mechanisms underlying this phenomenon remain a mystery. Given the importance of swimming energetics on fitness, we measured critical swim speed, swimming metabolism, cost of transport, aerobic scope (absolute and factorial) and exercise recovery in adult female and male coho salmon (Oncorhynchus kisutch) held for 2 days at 3 environmentally relevant temperatures (9°C, 14°C, 18°C) in fresh water. Critical swimming performance (Ucrit) was equivalent between sexes and maximal at 14°C. Absolute aerobic scope was sex- and temperature-independent, whereas factorial aerobic scope decreased with increasing temperature in both sexes. The full cost of recovery from exhaustive exercise (excess post-exercise oxygen consumption) was higher in males compared to females. Immediately following exhaustive exercise (i.e. 1 h), recovery was impaired at 18°C for both sexes. At an intermediate time scale (i.e. 5 h), recovery in males was compromised at 14°C and 18°C compared to females. Overall, swimming, aerobic metabolism, and recovery energetics do not appear to explain the phenomenon of increased mortality rates in female coho salmon. However, our results suggest that warming temperatures compromise recovery following exhaustive exercise in both male and female salmon, which may delay migration progression and could contribute to en route mortality.
The role of phosphorylation in atrial fibrillation: a focus on mass spectrometry approaches
Authors: Safabakhsh Sina , Panwar Pankaj , Barichello Scott , Sangha Sarabjit S , Hanson Paul J , Petegem Filip Van , Laksman Zachary 
Published: March 2021

Abstract
Atrial fibrillation (AF) is the most common arrhythmia worldwide. It is associated with significant increases in morbidity in the form of stroke and heart failure, and a doubling in all-cause mortality. The pathophysiology of AF is incompletely understood, and this has contributed to a lack of effective treatments and disease-modifying therapies. An important cellular process that may explain how risk factors give rise to AF includes post-translational modification of proteins. As the most commonly occurring post-translational modification, protein phosphorylation is especially relevant. Although many methods exist for studying protein phosphorylation, a common and highly resolute technique is mass spectrometry (MS). This review will discuss recent evidence surrounding the role of protein phosphorylation in the pathogenesis of AF. MS-based technology to study phosphorylation and uses of MS in other areas of medicine such as oncology will also be presented. Based on these data, future goals and experiments will be outlined that utilize MS technology to better understand the role of phosphorylation in AF and elucidate its role in AF pathophysiology. This may ultimately allow for the development of more effective AF therapies.
Games and Sloth: Working for the Common Good in Late Medieval Flanders
Authors: Brown Andrew 
Published: March 2021

Abstract
Games, sloth and the common good are familiar subjects to scholars of late medieval Europe, yet the connections contemporaries made between them have never been properly explored. How these rhetorical ideas were aligned, how they were used and by whom, across a wide social spectrum, are the central questions in this article; and examining them reveals how malleable (and gendered) they were. Discourses on games, developed by schoolmen and other churchmen in relation to recreation, and integrated with ideas of sloth and the common good, were harnessed to serve the authority of rulers in late medieval Flanders and Burgundian lands. Yet they were also deployed to suit other agendas, especially during the troubled period of civil war from 1477 to 1492, by the rulers’ subjects—urban magistrates, elite or middling groups, but also men from lower social strata. Valuable evidence for the latter appears within the numerous pardon letters that survive from 1386 to 1500: these were specially granted by rulers to suppliants, many of whom were craftsmen, labourers and artisans. Suppliants often referred to their game-playing and recreational activities; while these cases suggest a process by which subjects were disciplined, they also show how discourses on games offered suppliants strategic room for manoeuvre.
Impact of bilateral bidirectional Glenn anastomosis on staged Fontan strategy and Fontan circulation
Authors: Imai Kenta , Hoashi Takaya , Okuda Naoki , Ohuchi Hideo , Kurosaki Kenichi , Ichikawa Hajime 
Published: March 2021

Abstract

OBJECTIVES
The aim of this study was to identify the impact of bilateral bidirectional Glenn (BBDG) anastomosis on staged Fontan strategy and late Fontan circulation.

METHODS
Of 267 patients who underwent bidirectional Glenn prior to Fontan completion between 1989 and 2013, 62 patients (23%) who underwent BBDG were enrolled in this study. Age at operation was 0.84 years (25th–75th percentile: 0.58–1.39). Thirty-three patients had heterotaxy syndrome (53%). The mean follow-up period was 12.7 ± 8.1 (max. 30.6) years.

RESULTS
The overall survival rate at 15 years was 73%. Although 49 patients (79.0%) went on to Fontan completion, 12 patients (19.4%) died without achieving it. Thrombus formation and poor development in a central pulmonary artery were not observed, but obstruction of the superior vena cava (SVC) occurred in 8 patients (13%), mainly those with right atrial isomerism (P = 0.037). SVC obstruction was not, however, a risk factor for mortality (P = 0.097) or Fontan completion (P = 0.41). The shape of BBDG anastomosis, symmetricity of pulmonary blood flow, impingement of caval blood flow returning from the superior and inferior vena cavae or coexisting interrupted inferior vena cava with azygos or hemi-azygos continuation did not affect late Fontan outcomes, such as overall survival, freedom from protein-losing enteropathy or pulmonary arterio-venous malformation rates.

CONCLUSIONS
SVC obstruction after BBDG frequently occurred, mainly in patients with right atrial isomerism; however, its direct impact on prognosis or achieving Fontan completion was not identified. Once Fontan circulation was established, the arrangement of the Fontan pathway did not affect late Fontan outcomes.
Effect of cerebrospinal fluid pressure elevation on spinal cord perfusion during aortic cross-clamping with distal aortic perfusion
Authors: Haunschild Josephina , Khachatryan Zara , von Aspern Konstantin , Herajärvi Johanna , Ossmann Susann , Naumann Jörg , Borger Michael A , Etz Christian D 
Published: March 2021

Abstract OBJECTIVESDistal aortic perfusion (DaP) is a widely accepted protective adjunct facilitating early reinstitution of visceral perfusion during extended thoracic and thoraco-abdominal aortic repair. DaP has also been suggested to secure distal inflow to the paraspinal collateral network via the hypogastric arteries and thereby reduce the risk of spinal cord ischaemia. However, an increase in cerebrospinal fluid (CSF) pressure is frequently observed during thoracoabdominal aortic aneurysm repair. The aim of this study was to evaluate the effects of DaP on regional spinal cord blood flow (SCBF) during descending aortic cross-clamping and iatrogenic elevation of cerebrospinal fluid pressure.METHODSEight juvenile pigs underwent central cannulation for cardiopulmonary bypass according to our established experimental protocol followed by aortic cross-clamping of the descending thoracic and abdominal aorta—mimicking sequential aortic clamping—with the initiation of DaP. Thereafter, CSF pressure elevation was induced by the infusion of blood plasma until baseline CSF pressure was tripled. At each time-point, microspheres of different colours were injected allowing for regional SCBF analysis.RESULTSDaP led to a pronounced hyperperfusion of the distal spinal cord [SCBF up to 480%, standard deviation (SD): 313%, compared to baseline]. However, DaP provided no or only limited additional flow to the upper and middle segments of the spinal cord (C1–Th7: 5% of baseline, SD: 5%; Th8–L2: 24%, SD: 39%), which was compensated by proximal flow only at C1–Th7 level. Furthermore, DaP could not counteract an experimental CSF pressure elevation, which led to a further decrease in regional SCBF most pronounced in the mid-thoracic spinal cord segment.CONCLUSIONSProtective DaP during thoraco-abdominal aortic repair may be associated with inadequate spinal protection particularly at the mid-thoracic spinal cord level (‘watershed area’) and result in the adverse effect of a potentially dangerous hyperperfusion of the distal spinal cord segments.