bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathological characteristics of primary peritoneal epithelioid mesothelioma of clear cell type
Authors: Du Xue-Mei , Wei Ya-Ping , Gao Ying , Li Zhao , Zhang Jian-Mei , Chang Hong , Li Yan
Published: March 2021

Rationale:

Primary peritoneal epithelioid mesothelioma of clear cell type is an extremely rare entity composed of clear cytoplasm. It is challenging to diagnose because of the morphological resemblance to clear cell tumor.

Patient's concerns:

A 69-year-old male patient had swollen lymph nodes in the right inguinal region for 7 months and was constipated for 1 month.

Diagnosis:

The patient was diagnosed as peritoneal epithelioid mesothelioma of clear cell type based on computed tomography scan, pathology, immunohistochemistry, special staining and whole-exome sequencing. This patient harbored VHL gene alteration in exon 1 and homologous recombination defect (with a score of 45). This finding indicated that this patient might be sensitive to platinum-based therapy and Poly ADP-ribose Polymerase (PARP) inhibitor. This patient carried no microsatellite instability, a low level of tumor mutation burden, and a high extent of intratumoral heterogeneity. Eighteen neoantigens were detected.

Interventions:

The patient received surgery-based multidisciplinary treatment by integrating cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). HIPEC was administered with docetaxel 120 mg plus cisplatin 120 mg, at 43°C, for 60 minutes. After operation, the patient received intravenous (IV) chemotherapy with docetaxel 60 mg, pemetrexed 750 mg and cisplatin 100 mg, and then intraperitoneal (IP) chemotherapy with docetaxel 40 mg. The patient received interventional therapy of hepatic artery embolization for 5 times.

Outcomes:

Regular follow-up was performed until Oct 14, 2020. The patient died 31.6 months later owing to incomplete intestinal obstruction.

Lessons:

Primary peritoneal epithelioid mesothelioma of clear cell type needs to be differentiated from a variety of clear cell tumors. This disease is characterized by specific genetic alteration. Whole-exome sequencing contributes to guide individualized therapy. CRS-HIPEC helps achieve long-term overall survival.
A case report of reversible posterior encephalopathy syndrome with intracranial hemorrhage in a child
Authors: Chen Xiaoqian , Zhu Weixue , Jiang Suhua
Published: March 2021

Introduction:

The objective is to analyze the clinical diagnosis and treatment of children with rescindable posterior encephalopathy syndrome (PRES) and intracranial hemorrhage (ICH) to improve the pediatrician's understanding of PRES combined with ICH in children.

Patient concerns and Diagnosis:

After liver transplantation, the patient developed symptoms of epilepsy and coma. Meanwhile, massive necrosis of acute cerebral infarction and small hemorrhage was observed in the left cerebellar hemisphere and left occipital lobe, respectively. The above symptoms were initially diagnosed as PRES.

Interventions and outcomes:

After adjusting the anti-rejection drug regimen, it was found that the child's neurological symptoms were relieved, and the limb motor function gradually recovered during follow-up. Imaging examination showed significant improvement on abnormal signals in brain.

Conclusion:

In general, children with PRES may further develop ICH and contribute to a poor prognosis. Early diagnosis, detection of risk factors and timely adjustment of medication regimen are the keys to prevent irreversible brain damage.
Genetic factors and the risk of drug-resistant epilepsy in young children with epilepsy and neurodevelopment disability
Authors: Lin Chien-Heng , Chou I-Ching , Hong Syuan-Yu
Published: March 2021

Drug-resistant epilepsy (DRE) affects 7% to 20% of children with epilepsy. Although some risk factors for DRE have been identified, the results have not been consistent. Moreover, data regarding the risk factors for epilepsy and its seizure outcome in the first 2 years of life are limited.

We analyzed data for children aged 0 to 2 years with epilepsy and neurodevelopmental disability from January, 2013, through December, 2017. These patients were followed up to compare the risk of DRE in patients with genetic defect (genetic group) with that without genetic defect (nongenetic group). Additionally, we conducted a meta-analysis to identify the pooled prevalence of genetic factors in children with DRE.

A total of 96 patients were enrolled. A total of 68 patients were enrolled in the nongenetic group, whereas 28 patients were enrolled in the genetic group. The overall DRE risk in the genetic group was 6.5 times (95% confidence interval [CI], 2.15–19.6; p = 0.03) higher than that in the nongenetic group. Separately, a total of 1308 DRE patients were participated in the meta-analysis. The pooled prevalence of these patients with genetic factors was 22.8% (95% CI 17.4–29.3).

The genetic defect plays a crucial role in the development of DRE in younger children with epilepsy and neurodevelopmental disability. The results can serve as a reference for further studies of epilepsy panel design and may also assist in the development of improved treatments and prevention strategies for DRE.
Lack of association between single nucleotide polymorphisms in TCF7L2 and T2DM in the Chinese Yao population
Authors: Sun Shi-Yu , Huang Run-Ze , Huang Huang , Zhang Ming-Qi , Sun Hui-Lin
Published: March 2021

Single-nucleotide polymorphisms (SNPs) in the transcription factor 7-like 2 (TCF7L2) gene have been identified to be associated with the susceptibility to type 2 diabetes mellitus (T2DM) in various populations worldwide, but the results in Chinese are conflicting, and no data are available about the Liannan Yao population. Therefore, this study aimed to investigate the association of the TCF7L2 gene polymorphisms (rs12255372, rs7903146, rs7901695, rs11196205, and rs7895340) with T2DM in the Yao population living in the rural areas in the Liannan Yao Autonomous County.

This was a case-control study of 28 subjects with T2DM or prediabetes and 52 non-T2DM controls, all from the Chinese Yao population and recruited between January 2019 and June 2020. Patients with T2DM and prediabetes were grouped as the case group. The five SNPs (rs12255372, rs7903146, rs7901695, rs11196205, and rs7895340) were examined by polymerase chain reaction and direct genomic DNA sequencing in case and control groups.

The subjects in case group were older than the controls (55±14 vs 48 ± 15 years, P = .047), had higher FBG levels (9.31 ± 5.43 vs 4.09 ± 0.81, P < .001), higher TC (5.79 ± 1.29 vs 5.13 ± 1.18 mmol/L, P = .025), and higher triglycerides (2.94 ± 2.04 vs 1.86 ± 1.39 mmol/L, P = .003). The genotypic distribution for each of the SNPs was in agreement with the Hardy-Weinberg equilibrium. There were no statistically significant differences in the distributions of genotypes or alleles at all five SNPs of the TCF7L2 gene between the case and control groups (all P > .05).

TCF7L2 SNPs were not associated with T2DM in the Liannan Yao population.
Current Evidence on the Clinical Relevance of Donor‐specific Antibodies in Paediatric Liver Transplantation
Authors: Götz Juliane K. , Kiene Hella , Goldschmidt Imeke , Junge Norman , Pfister Eva‐Doreen , Leiskau Christoph , Brown Rachel M. , Immenschuh Stephan , Baumann Ulrich
Published: March 2021

The clinical impact of donor‐specific antibodies (DSA) occurring before or after liver transplantation (LT) against donor‐human leucocyte antigen (HLA) on graft outcome is still unclear. We aim to present the current consensus based on recent paediatric LT case series. Compared to kidney transplantation, the liver seems to be less susceptible to antibody‐mediated graft damage, which is likely due to protective Kupffer cell activity. The incidence of DSA after liver transplantation is higher in children than in adults. DSA directed against HLA class II molecules, mainly DQ, occur more often. The presence of such anti‐class II DSA (DQ/DR), especially of the complement‐binding IgG3 subclass, may be associated with endothelial injury, T‐cell‐mediated rejection (TCMR), inflammation, and fibrosis. Regular DSA‐posttransplant monitoring cannot as yet be recommended in routine practice but may be useful in selected cases.
Fatty Acid-Binding Protein 1 as a Potential New Serological Marker of Liver Status in Children With Wilson Disease
Authors: Bierła Joanna Beata , Jańczyk Wojciech , Konopka Ewa , Wierzbicka-Rucińska Aldona , Więckowski Sebastian , Obrycki Łukasz , Sarnecki Jędrzej , Kanarek Ewelina , Cukrowska Bożena , Socha Piotr
Published: March 2021

Objectives:

Wilson disease (WD) is a copper metabolism disorder with toxic copper accumulation in the liver leading to liver steatosis or fibrosis. In vitro studies suggest that fatty acid-binding protein 1 (L-FABP) and lipid droplet-associated protein 5 (PLIN5) may have an impact on both processes, but knowledge about these potential biomarkers is insufficient in the case of WD. Thus, the aim of this study was to determine L-FABP and PLIN5 levels in sera of WD patients in relation to liver steatosis/fibrosis.

Methods:

The final study involved 74 WD children in whom liver steatosis (WD1 subgroup, n = 28) and fibrosis (WD2 subgroup, n = 13) were assessed with the use of transient elastography. Control groups included WD children without steatosis and fibrosis (WD0 subgroup, n = 33) and healthy children (n = 75). L-FABP and PLIN5 measurements were performed in sera with the use of the immunoenzymatic method.

Results:

L-FABP was significantly higher in the WD2 subgroup, and the correlation between L-FABP concentration and liver fibrosis was confirmed statistically by regression analysis (P = 0.04) with Pearson's coefficient r = 0.24. L-FABP was significantly correlated with alanine aminotransferase (r = 0.42) and aspartate aminotransferase (r = 0.37) activity. PLIN5 concentration was similar in all groups and was not related to steatosis and fibrosis.

Conclusions:

Our results suggest that serum L-FABP could be a novel biomarker of liver fibrosis in WD children.
Bone Health in Pediatric Patients With Crohn Disease
Authors: Rozes Sylvana , Guilmin‐Crepon Sophie , Alison Marianne , Thomas Edouard , Hugot Jean‐Pierre , Viala Jerome , Martinez‐Vinson Christine
Published: March 2021

Objective:

The aim of our study was to examine longitudinal changes in bone mineral density (BMD) of children and adolescents with Crohn disease (CD), and risk factors related to low BMD.

Patients and methods:

All patients ages from 2 to 18 years with CD who underwent dual‐energy X‐ray absorptiometry (DXA) at diagnosis and at the end of follow‐up between 1999 and 2018 were considered for inclusion in this retrospective study. Factors related to changes in BMD at diagnosis and during follow‐up were investigated.

Results:

One hundred and ninety‐three patients had the two DXA required. At diagnosis, 36 patients (18.7%) had a low BMD.

At the end of follow‐up, 31 patients (16%). One hundred and sixty‐four patients did not have the two DXA required.

In included CD, BMD values were lower in the lumbar spine (LS) than in total body less head (TBLH), as well at diagnosis (P < 0.0001) or at the end of follow‐up (P = 0.001).

At diagnosis, only growth impairment or low BMI was associated with low BMD (P < 0.0001), only cumulative dose of corticosteroid at the end of follow‐up (P = 0.01).

Conclusion:

The high prevalence of low BMD in children and adolescents with IBD highlights the importance of evaluating BMD in these patients at the time of diagnosis and throughout the course of their treatment. Special attention must be given to patients with height delay or low BMI at diagnosis. Long‐term glucocorticoid therapy is the main clinical risk factor associated with low BMD at the end of follow‐up.
Intravenous Smart Pumps During Actual Clinical Use
Authors: Giuliano Karen K. , Penoyer Daleen , Mahuren Rebecca S. , Bennett Melody
Published: March 2021

This descriptive observational study was conducted to increase understanding of medication administration practices during actual clinical use between 2 commonly used, different types of intravenous (IV) smart pumps. Compliance with manufacturer-recommended setup requirements for both primary and secondary infusions and secondary medication administration delay was compared between a head-height differential system and a cassette system. A total of 301 medication administration observations were included in this study: 102 (34%) for the linear peristaltic IV smart pump (medical–surgical: N = 51; critical care: N = 51) and 199 (66%) for the cassette pump (medical–surgical: N = 88; critical care: N = 111). Results found a 0% compliance for primary line setup and 84% compliance for secondary line setup and 1 omitted medication due to a closed clamp with the linear peristaltic system. For the cassette system, there are no head-height requirements. Two roller clamps were found to be in the closed position on initiation of the secondary infusion, but the clinician was alerted by an alarm, so no medication delays occurred. These findings support that the current system requirements for flow rate accuracy using head-height differential systems are difficult to achieve consistently at the point of care. There is a need for additional human factor designed technology to replace manual actions to improve the process of care for nurses and the safety of care for patients.
Effect of Sperm Morphology in Intrauterine Insemination: Analysis of 115 Cycles and Literature Review
Authors: Fuentes Ávila Anaïs , Blasco Sanz Ruth , Cortés Alaguero Caterina
Published: March 2021

Importance

The value of morphology as a sperm parameter remains uncertain. Many studies have addressed the importance of morphology to predict the success of intrauterine insemination (IUI), but with conflicting results.

Objective

The aims of this study were to review the current literature, to query our own clinical experience via a retrospective, descriptive study, and to determine whether the diagnosis of isolated teratozoospermia influences pregnancy rate after IUI.

Results

We identified a large number of studies addressing this question. All were retrospective and most used different criteria to assess sperm morphology. Further complicating matters, the cutoff for normal morphology decreased from 15% to 4%.

In our patient population, we found 12 cases of isolated teratozoospermia (10.43%). Only one of these produced an ongoing pregnancy and live birth. In all other cases, alteration of other sperm parameters coexisted (89.57%). These cycles produced a pregnancy rate of 13%, a nonsignficant difference. Pregnancy rates also were analyzed according to the percentage of normal morphology: 35.71% for less than 4%, 50% for 5% to 9%, and 14.29% for 10% to 14%. These rates did not differ significantly.

Conclusions and Relevance

No consistent effect of sperm morphology on pregnancy rate was found in either the published literature or our own clinical experience. Larger and prospective studies are needed to identify any subtle effects of morphology on IUI outcomes that might exist.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After participating in this activity, physicians should be better able to define features of teratozoospermia; describe pregnancy rates according to sperm morphology; determine if there are significant differences in patients' pregnancy rates for isolated teratozoospermia; and clarify whether these patients could benefit from in vitro fertilization/intracytoplasmic sperm injection.
Effect of Combined Hydrocortisone, Ascorbic Acid and Thiamine for Patients with Sepsis and Septic Shock: A Systematic Review and Meta-Analysis
Authors: Wu Tong , Hu Chang , Huang Weipeng , Xu Qiancheng , Hu Bo , Li Jianguo
Published: March 2021

Objective:

This study aims to assess the effect of HAT therapy on patients with sepsis and septic shock.

Methods:

We searched PubMed, Embase, and Cochrane Library for studies on HAT therapy published up to November 11, 2020. The primary outcome was the duration of vasopressor use. Secondary outcomes were change of Sequential Organ Failure Assessment (SOFA) score within 72 h; death within intensive care unit (ICU), hospital, and 28 or 30 days; length of stay in ICU and hospital; rate of procalcitonin (PCT) clearance and incidence of adverse events. We also used trial sequential analysis (TSA) to assess the reliability of the available evidence.

Results:

Six randomized controlled trials (RCTs) and seven observational studies enrolling 1,559 patients were included (762 were treated with HAT, and 797 were treated with hydrocortisone alone, standard care or placebo). HAT therapy was associated with significant reductions in duration of vasopressor use (mean differences [MD], −14.68, [95% CI, −24.28 to −5.08], P = 0.003) in RCTs, but not in observational studies (MD, 11.21 [95% CI, −44.93 to 67.35], P = 0.70). HAT therapy was associated with less organ dysfunction at 72 h both in RCTs (MD, −0.86 [95% CI, −1.32 to −0.40], P < 0.001) and observational studies (MD, −2.65 [95% CI, −5.29 to −0.01], P = 0.05). HAT therapy was associated with lower hospital mortality and higher PCT clearance in observational studies. Similar results for the primary outcome were found in the sensitivity analysis. TSA results suggested more trials to reach the required information size.

Conclusion:

Among patients with sepsis and septic shock, a combination therapy of hydrocortisone, ascorbic acid, and thiamine, compared with placebo, could reduce the duration of vasopressor use and SOFA scores during the first 72 h.

Trial registration:

PROSPERO registration ID for this study is CRD42020170648 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=170648).
The Influence of Alcohol on the Base Excess Parameter in Trauma Patients
Authors: Leiblein Maximilian , Sturm Ramona , Franz Niklas , Mühlenfeld Nils , Relja Borna , Lefering Rolf , Marzi Ingo , Wagner Nils
Published: March 2021

Background:

The base excess (BE) parameter can be used as an indicator of mortality. However, study results on the influence of alcohol on the validity of BE as a prognostic parameter in alcohol-intoxicated patients are controversial. Thus, this study examined the hypothesis: An increasing blood alcohol level reduces the prognostic value of the BE parameter on mortality.

Patients and Methods:

In a retrospective analysis of the multicenter database of the TraumaRegister DGU, patients from 2015 to 2017 were grouped depending on their blood alcohol level (BAL) into a BAL+ and BAL− group. The hypothesis was verified using logistic regression with an assumed significance level of 1% (P < 0.01).

Results:

Eleven thousand eight hundred eighty-nine patients were included; 9,472 patients in the BAL− group and 2,417 patients in the BAL+ group. Analysis of the BE showed lower values in the BAL+ group (BAL−: −1.8 ± 4.4 mmol/L vs. BAL+: −3.4 ± 4.6 mmol/L). There is a trend toward lower BE levels when BAL increases. Assuming a linear relationship, then BE decreases by 0.6 points per mille alcohol (95% CI: 0.5–0.7; P < 0.001). The mortality rate was significantly lower in the BAL+ group (BAL−: 11.1% vs. BAL+: 7.9%). The logistic regression analysis showed a significant beneficial influence of BAL+ on the mortality rate (OR 0.706, 95% CI 0.530–0.941, P = 0.018). To analyze whether a low BE (≤−6 mmol/L) has different prognostic effects in patients with and without alcohol, logistic regression models were calculated. However, the effect of BE ≤ −6 mmol/L was similar in both models (regression coefficients in BAL−/+ patients: 0.379/0.393).

Conclusions:

The data demonstrate an existing influence of alcohol on the BE parameter; however, this does not negatively affect the BE as a prognostic parameter at a threshold of ≤ −6 mmol/L.
Coagulation Factors Accumulate During Normothermic Liver Machine Perfusion Regardless of Donor Type and Severity of Ischemic Injury
Authors: Gilbo Nicholas , Jacquemin Marc , Nasralla David , Lazzaro Silvia , Libbrecht Louis , Lavend’homme Renaud , Peerlinck Kathelijne , Ploeg Rutger J. , Friend Peter J. , Pirenne Jacques , Monbaliu Diethard , Jochmans Ina
Published: March 2021

Background.

Coagulation factors may inform on liver function during normothermic machine perfusion (NMP). We investigated whether graft ischemic injury impairs the accumulation of anticoagulation factors during NMP of porcine and human livers.

Methods.

Dynamics of FV, FVII, FVIII, FIX, and FX during NMP and their correlation with graft injury was investigated in porcine livers with minimal (no warm ischemia, n = 5) or severe injury (60 min warm ischemia, n = 5). Next, FV, FVIII, FIX, fibrinogen, and antithrombin were measured in 35 matched human liver NMPs from the COPE trial. Correlation of these factors with outcomes was explored. Livers were categorized in to 4 groups depending on donor type and posttransplant peak aspartate aminotransferase (AST) as surrogate of minimal (peak < 500 IU/L) or moderate injury (peak > 1000 IU/L).

Results.

Factor concentrations increased significantly during NMP regardless of severity of injury. In porcine livers, factor concentrations were 2- to 6-fold lower in severely injured grafts (all P < 0.05). All factors negatively correlated with AST (coefficient range: from −0.50 to −0.93; all P < 0.05) and lactate (range: from −0.51 to −0.67; all P < 0.05). In human livers, no difference in factor accumulation rates and no correlation with other markers were observed. One graft with primary nonfunction had low rate of factor accumulation.

Conclusions.

Anticoagulation factors accumulate during NMP regardless of donor type and severity of injury. In pigs, severe ischemic injury resulted in significantly lower factor concentrations. In human livers with life-sustaining function, they do not correlate with hepatic injury. Whether low concentrations predict nonfunction in high-risk livers with severe injury requires further investigation.
Emergence of the E484K Mutation in SARS-CoV-2 Lineage B.1.1.220 in Upstate New York
Authors: Lesho Emil , Corey Brendan , Lebreton Francois , Ong Ana C. , Swierczewski Brett E. , Bennett Jason W. , Walsh Edward E. , Gann Patrick Mc
Published: March 2021

Ongoing surveillance detected a SARS-CoV-2 B.1.1.220 variant carrying the E484K substitution in four patients from a hospital network in upstate New York. Patients reported no travel history and shared no obvious epidemiological linkage. A search of online databases identified 12 additional B.1.1.220 with E484K, all of which were detected in New York since December 2020. Detailed genomic analyses suggests that the mutation has emerged independently in at least two different B.1.1.220 strains in this region.
In-person schooling and COVID-19 transmission in Canada’s three largest cities
Authors: Bignami-van Assche Simona , Boujija Yacine , Fisman David , Sandberg John
Published: March 2021

In North America and Europe, the Fall 2020 school term has coincided with the beginning of the second wave of the novel coronavirus (COVID-19) pandemic, sparking a heated debate about the role of in-person schooling for community transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This issue has immediate policy relevance for deciding how to operate schools safely as the pandemic unfolds, new variants of SARS-CoV-2 are circulating, and immunization coverage remains low. We contribute to this debate by presenting data on trends in COVID-19 weekly incidence among school-aged children 0-19 years old vis-à-vis other age groups during Fall 2020 in Canada’s three largest cities: Montréal, Toronto and Calgary. We interpret these trends in light of the different back-to-school policies and other public health measures implemented in the three cities over the observation period.

KEY POINTS

School closures are an effective measure to reduce the overall incidence of the novel coronavirus (COVID-19). Nonetheless, there is a general consensus that the decision to close schools to control the spread of COVID-19 should be used as last resort because of the negative impact on children’s development and mental health, and since they are less likely to have severe COVID-19 outcomes than adults.

Existing evidence highlights the importance of adopting appropriate mitigation strategies for limiting COVID-19 community spread when returning to in-person schooling. To understand the association between in-person schooling and COVID-19 transmission given different mitigation strategies, especially universal masking and distance learning, we compare how the second wave of COVID-19 has affected school-aged children age 0-19 years old vis-à-vis other age groups in Montréal, Toronto and Calgary during Fall 2020.

The case of Montréal attests to the negative consequences of not implementing recommended migration strategies when reopening schools, even when public health measures such as gatherings restrictions are in place to maintain low levels of community transmission. On the contrary, school measures adopted in Toronto (optional distance learning and masking mandates), have limited the role of COVID-19 transmission among school-aged children for overall community transmission. In Calgary, this effect has been smaller, likely because public health measures to limit COVID-19 community spread were not introduced until early December 2020.

Our findings have immediate policy relevance for deciding how to operate schools safely as the pandemic unfolds, new variants of SARS-CoV-2 are circulating, and immunization coverage remains low.
Determinants of COVID-19 outcomes: A systematic review
Authors: Crankson Shirley , Pokhrel Subhash , Anokye Nana Kwame
Published: March 2021

Background

The current pandemic, COVID-19, caused by a novel coronavirus SARS-CoV-2, has claimed over a million lives worldwide in a year, warranting the need for more research into the wider determinants of COVID-19 outcomes to support evidence-based policies.

Objective

This study aimed to investigate what factors determined the mortality and length of hospitalisation in individuals with COVID-19.

Data Source

This is a systematic review with data from four electronic databases: Scopus, Google Scholar, CINAHL and Web of Science.

Eligibility Criteria

Studies were included in this review if they explored determinants of COVID-19 mortality or length of hospitalisation, were written in the English Language, and had available full-text.

Study appraisal and data synthesis

The authors assessed the quality of the included studies with the Newcastle□Ottawa Scale and the Agency for Healthcare Research and Quality checklist, depending on their study design. Risk of bias in the included studies was assessed with risk of bias assessment tool for non-randomised studies. A narrative synthesis of the evidence was carried out. The review methods were informed by the Joana Briggs Institute guideline for systematic reviews.

Results

The review included 22 studies from nine countries, with participants totalling 239,830. The included studies’ quality was moderate to high. The identified determinants were categorised into demographic, biological, socioeconomic and lifestyle risk factors, based on the Dahlgren and Whitehead determinant of health model. Increasing age (ORs 1.04-20.6, 95%CIs 1.01-22.68) was the common demographic determinant of COVID-19 mortality while living with diabetes (ORs 0.50-3.2, 95%CIs −0.2-0.74) was one of the most common biological determinants of COVID-19 length of hospitalisation.

Review limitation

Meta-analysis was not conducted because of included studies’ heterogeneity.

Conclusion

COVID-19 outcomes are predicted by multiple determinants, with increasing age and living with diabetes being the most common risk factors. Population-level policies that prioritise interventions for the elderly population and the people living with diabetes may help mitigate the outbreak’s impact.

PROSPERO registration number

CRD42021237063.

Strength and limitations of this review

This is the first systematic review synthesising the evidence on determinants of COVID-19 LOS outcome.

It is also the first review to provide a comprehensive investigation of contextual determinants of COVID-19 outcomes, based on the determinants of health model; thus, presenting with crucial gaps in the literature on the determinants of COVID-19 outcomes that require urgent attention.

The review was restricted in conducting meta-analysis due to included studies’ heterogeneity.

The review focused on only papers published in the English Language; hence, other relevant papers written on other languages could have been omitted.
Co3O4/PAn Magnetic Nanoparticle-Modified Electrochemical Immunosensor for Azocyclotin
Authors: Wang Weihua , Han Zhanjiang , Xi Qian , Gao Dongla , Guo Ruicheng , Kuang Pengcheng , Li Dongliang
Published: March 2021

In the current study, for rapid detection of azocylotin residues in agricultural products, the Co3O4/PAn nanoparticles modified electrochemical immunosensor was generated successfully. Azocylotin-BSA artificial antigen coupling to the surface of the working electrode coated with the Co3O4/PAn nanoparticles thin-layer, the competitive inhibition reaction is launched between the azocylotin in the samples and the azocylotin coupled on the electrode with the azocylotin monoclonal antibodies in the test system. The antigen-antibody reaction signal conductive amplified by the coupled silver nanoparticles, and then the electrolytic current in the reaction system was detected. After establishing basic detection system, a series of optimization including the concentration of immobilized membrane optimization, electrode surface coated material composition optimization, selection of buffer, coupling antigen concentration optimization and anti-antibody label optimization will be done. Subsequently, the concentrations of azocylotin in samples of standards, orange and apple were tested, and the results indicated that this immune sensor has good sensitivity and high accuracy. The research could provide the reference for the research, development and application of sensors to realize rapid detection of pesticide residues in agricultural products.
Divergent epigenetic profiles from two differentially impacted wild populations of estuarine cordgrass (Sporobolus alterniflorus)
Authors: DeCarlo L. , Meckler F. , Hans M. , Kelemen S. , Magun H. , Noah M. , Pappajohn L. , Anderson N. , Berger R. , Berkel J. , Brooke N. , Chen L. , Chijioke O. , Dewees N. , Falkner P. , Frank J. , Holzman W. , Marino V. , Ravaschiere A. , Wang Y. , Williams A. , Williams Z. , Gentile D. , Cox R.L.
Published: March 2021

The effects of urbanization on watershed ecosystems present critical challenges to modern survival. Organisms in urbanized areas experience high rates of evolutionary change, but genetic adaptation alone cannot mitigate the rapid and severe effects of urbanization on biodiversity. Highly resilient, foundation species are key to maintaining an ecosystem’s integrity in the face of urban stressors. However, the rapid collapse and disappearance of watershed ecosystems calls into question the extent to which we can rely on such species for their services. Our research investigates the molecular mechanisms by which the foundation ecosystems provider,Sporobolus alterniflorus, adapts to life in an urbanized environment. To elucidate these mechanisms, we quantified changes in global DNA methylation (% 5-mC) as a result of acute heat stress. Specimens from two differentially impacted populations across an urban to suburban geographical transect formed the basis of this study. These two populations ofSporobolus alternifloraexhibit inverse global DNA methylation patterns when exposed to the same acute heat stress. Our findings suggest that epigenetic mechanisms, such as DNA methylation, control rapid and transient adaptation, in the form of differential stress responses, to distinct environment challenges.

Highlights for manuscript submission

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estuarine grasses native to the Bronx River, NY face stresses associated with low dissolved oxygen and urbanization

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differentially impacted populations of estuarine grasses exhibit inverse global DNA methylation profiles in response to acute heat stress

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DNA methylation may represent a mechanism by which plants transiently respond to environmental stressors, and this may represent a form of rapid adaptive evolution

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stress priming by transgenerational epigenetic modification may enhance fitness in grasses native to the heavily impacted Bronx River estuary
Dispersal across habitat boundaries: uncovering the demographic fates of populations in unsuitable habitat
Authors: Szojka Megan C. , Germain Rachel M.
Published: March 2021

Patchy landscapes are characterized by abrupt transitions among distinct habitat types, forcing species to cross habitat boundaries in order to spread. Since seed dispersal is a probabilistic process, with a kernel that decays with distance, most individuals will fail to reach new, suitable habitat. Although failed dispersers are presumed dead in population models, their demographic fates may not be so simple. If transient survival is possible within unsuitable habitat, then through time, individuals may be able to reach distant, suitable habitat, forming new populations and buffering species from extinction. In a fragmented Californian grassland, we explored the fates of individuals that crossed habitat boundaries, and if those fates differed among specialists dispersing from two habitat types: serpentine habitat patches and the invaded non-serpentine matrix. We surveyed the diversity of seedbank and adult life stages along transects that crossed boundaries between patches and the matrix. First, we considered how patch specialists might transiently survive in the matrix via seed dormancy or stepping-stone populations. Second, we investigated the dispersal of an invasive matrix specialist (Avena fatua) into patches, to assess if sink populations existed across the habitat boundary. We found that dormancy maintained populations of patch specialists deep into the matrix, as abundances of seedbanks and of adult plant communities differed with distance into the matrix. We found evidence that these dormant seeds disperse secondarily with vectors of material flows in the landscape, suggesting that they could eventually reach suitable patches even if they first land in the matrix. We found thatA. fatuawere largely absent deep in patches, where reproductive outputs plummeted and there was no evidence of a dormant seedbank. Our results not only reveal the demographic fates of individuals that land in unsuitable habitat, but that their ecological consequences differ depending on the direction by which the boundary is crossed (patch → matrix ≠ matrix → patch). Dormancy is often understood as a mechanism for persisting in face of temporal variability, but it may serve as a means of traversing unsuitable habitat in patchy systems, warranting its consideration in estimates of habitat connectivity.
Pseudomonas aeruginosareaches collective decisions via transient segregation of quorum sensing activities across cells
Authors: Jayakumar Priyanikha , Thomas Stephen A. , Brown Sam P. , Kümmerli Rolf
Published: March 2021

Bacteria engage in a cell-to-cell communication process called quorum sensing (QS) to coordinate expression of cooperative exoproducts at the group level. While population-level QS-responses are well studied, we know little about commitments of single cells to QS. Here, we use flow cytometry to track the investment ofPseudomonas aeruginosaindividuals into their intertwined Las and Rhl QS-systems. Using fluorescent reporters, we show that QS gene expression (signal synthase, receptor and exoproduct) was heterogenous and followed a gradual instead of a sharp temporal induction pattern. The simultaneous monitoring of two QS genes revealed that cells transiently segregate into low receptor (lasR) expressers that fully commit to QS, and high receptor expressers that delay QS commitment. Our mathematical model shows that such gene expression segregation could mechanistically be spurred by transcription factor limitation. In evolutionary terms, temporal segregation could serve as a QS-brake to allow for a bet-hedging strategy in unpredictable environments.
Alternative dimerization is required for activity and inhibition of the HEPN ribonuclease RnlA
Authors: Garcia-Rodriguez Gabriela , Charlier Daniel , Wilmaerts Dorien , Michiels Jan , Loris Remy
Published: March 2021

ThernlABtoxin-antitoxin operon fromEscherichia colifunctions as an anti-phage defense system. RnlA was recently identified as a member of the HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding domain) superfamily of ribonucleases. The activity of the toxin RnlA requires tight regulation by the antitoxin RnlB, the mechanism of which remains unknown. Here we show that RnlA exists in an equilibrium between two different homodimer states: an inactive resting state and an active canonical HEPN dimer. Mutants interfering with the transition between states show that canonical HEPN dimerization via the highly conserved RX4-6H motif is required for activity. The antitoxin RnlB binds the canonical HEPN dimer conformation, inhibiting RnlA by blocking access to its active site. Single-alanine substitutions mutants of the highly conserved R255, E258, R318 and H323 show that these residues are involved in catalysis and substrate binding and locate the catalytic site near the dimer interface of the canonical HEPN dimer rather than in a groove located between the HEPN domain and the preceding TBP-like domain. Overall, these findings elucidate the structural basis of the activity and inhibition of RnlA and highlight the crucial role of conformational heterogeneity in protein function.
Early life stress is associated with earlier emergence of permanent molars
Authors: McDermott Cassidy L. , Hilton Katherine , Park Anne T. , Tooley Ursula A. , Boroshok Austin L. , Mupparapu Muralidhar , Scott JoAnna M. , Bumann Erin E. , Mackey Allyson P.
Published: March 2021

Exposure to adversity can accelerate biological aging. However, existing biomarkers of early aging are either difficult to detect in individuals at scale, like epigenetic signatures, or cannot be detected until late childhood, like pubertal onset. We evaluated the hypothesis that early adversity is associated with earlier molar eruption, an easily assessed measure that has been used to track the length of childhood across primates. In a pre-registered analysis (N= 117, ages 4-7), we demonstrate that lower family income and exposure to adverse childhood experiences (ACEs) are significantly associated with earlier eruption of the first permanent molars, as rated in T2-weighted magnetic resonance images (MRI). We replicate relationships between income and molar eruption in a population-representative dataset (NHANES;N= 1,973). These findings suggest that the impact of stress on the pace of biological development is evident in early childhood, and detectable in the timing of molar eruption.
RT-QuIC detection of CWD prion seeding activity in white-tailed deer muscle tissues
Authors: Li Manci , Schwabenlander Marc D. , Rowden Gage R. , Schefers Jeremy M. , Seelig Davis , Larsen Peter A.
Published: March 2021

Chronic wasting disease (CWD) is a prion disease circulating in wild and farmed cervid populations throughout North America (United States and Canada), Europe (Finland, Norway, Sweden), and South Korea. CWD is an immediate threat to cervid heritage and the disease is causing substantial economic losses across multiple sectors. In North America, hunting and farming industries focused on the processing and consumption of white-tailed deer (WTD) venison are particularly vulnerable to CWD, as millions of WTD are consumed annually. Real-time quaking-induced conversion (RT-QuIC) is a highly sensitive assay amplifying misfolded CWD prionsin vitroand has facilitated CWD prion detection in a variety of tissues and excreta. To date, no study has comprehensively examined CWD prion content across bulk skeletal muscle tissues harvested from individual CWD infected WTD. Here, we use RT-QuIC to quantify prion-seeding activity in a variety of skeletal muscles from both wild and farmed CWD-positive WTD. We successfully detected CWD prions in muscles commonly used for consumption (e.g., backstrap, tenderloin, etc.) as well as within tongue and neck samples of WTD. Our results help to establish the utility of RT-QuIC for monitoring CWD prions in venison and suggest that the method is useful for preventing CWD prions from entering animal and human food chains. Moreover, our work indicates that CWD prions are more widely distributed across skeletal muscles of infected WTD than previously reported.
Symptomatic and Neurotrophic Effects of GABAA Receptor Positive Allosteric Modulation in a Mouse Model of Chronic Stress
Authors: Bernardo Ashley , Lee Philip , Marcotte Michael , Mian Md Yeunus , Rezvanian Sepideh , Sharmin Dishary , Kovačević Aleksandra , Savić Miroslav , Cook James M. , Sibille Etienne , Prevot Thomas D.
Published: March 2021

Chronic stress is a risk factor for Major depressive disorder (MDD), and in rodents, it recapitulates human behavioral, cellular and molecular changes. In MDD and after chronic stress, neuronal dysfunctions and deficits in GABAergic signaling are observed and responsible for symptom severity. GABA signals predominantly through GABAA receptors (GABAA-R) composed of various subunit types that relate to downstream outcomes. Activity at α2-GABAA-Rs contributes to anxiolytic properties, α5-GABAA-Rs to cognitive functions, and α1-GABAA-Rs to sedation. Therefore, a therapy aiming at increasing α2- and α5-GABAA-Rs activity, but devoid of α1-GABAA-R activity, has potential to address several symptomologies of depression while avoiding side effects. This study investigated the activity profiles and behavioral efficacy of two molecules enantiomers of each other (GL-II-73 and GL-I-54), separately and as a racemic mixture (GL-RM), and potential disease-modifying effects on neuronal morphology. Results confirm GL-I-54 and GL-II-73 exert positive allosteric modulation at the α2-, α3-, α5-GABAA-Rs and α5-containing GABAA-Rs, respectively, and have anti-depressant and pro-cognitive effects independently. Using unpredictable chronic mild stress (UCMS) in male and female mice (n=12/group), we show that acute and chronic administration of GL-RM combined the anti-depressant and pro-cognitive effects of each enantiomer, although at lower doses avoiding sedation. Morphology studies showed reversal of spine density loss caused by UCMS after chronic GL-RM treatment at apical and basal dendrites of the PFC and CA1. Together, these results support using a racemic mixture with combined α2-, α3-, α5-GABAA-R profile to reverse chronic stress-induced mood symptoms, cognitive deficits, and with anti-stress neurotrophic effects.
Genes identified in rodent studies of alcohol intake are enriched for heritability of human substance use
Authors: Huggett Spencer B. , Johnson Emma C. , Hatoum Alexander S. , Lai Dongbing , Bubier Jason A. , Chesler Elissa J. , Agrawal Arpana , Palmer Abraham A. , Edenberg Howard J , Palmer Rohan H.C.
Published: March 2021

Background

Rodent paradigms and human genome-wide association studies (GWASs) on drug use have the potential to provide biological insight into the pathophysiology of addiction.

Methods

Using GeneWeaver, we created rodent alcohol and nicotine gene-sets derived from 19 gene expression studies on alcohol and nicotine outcomes. We partitioned the SNP-heritability of these gene-sets using four large human GWASs: 1) alcoholic drinks per week, 2) problematic alcohol use, 3) cigarettes per day and 4) smoking cessation. We benchmarked our findings with curated human alcoholism and nicotine addiction gene-sets and performed specificity analyses using other rodent gene-sets (e.g., locomotor behavior) and other human GWASs (e.g., height).

Results

The rodent alcohol gene-set was enriched for heritability of drinks per week, cigarettes per day, and smoking cessation, but not problematic alcohol use. However, the rodent nicotine gene-set was not significantly associated with any of these traits. Both rodent gene-sets showed enrichment for several non-substance use GWASs, and the extent of this relationship tended to increase as a function of trait heritability. In general, larger gene-sets demonstrated more significant enrichment. Finally, when evaluating human traits with similar heritabilities, both rodent gene-sets showed greater enrichment for substance use traits.

Conclusion

Our results suggest that rodent gene expression studies can help to identify genes that capture heritability of substance use traits in humans, yet the specificity to human substance use was less than expected due to various factors such as the genetic architecture of a trait. We outline various limitations, interpretations and considerations for future research.
Adult neurogenesis mediates forgetting of multiple types of memory in the rat
Authors: Scott Gavin A. , Terstege Dylan J. , Roebuck Andrew J. , Gorzo Kelsea A. , Vu Alex P. , Howland John G. , Epp Jonathan R.
Published: March 2021

The formation and retention of hippocampus-dependent memories is impacted by neurogenesis, a process that involves the production of new neurons in the dentate gyrus of the hippocampus. Recent studies demonstrate that increasing neurogenesis after memory formation induces forgetting of previously acquired memories. Neurogenesis-induced forgetting was originally demonstrated in mice, but a recent report suggests that the same effect may be absent in rats. Although a general species difference is possible, other potential explanations for these incongruent findings are that memories which are more strongly reinforced become resilient to forgetting or that perhaps only certain types of memories are affected. Here, we investigated whether neurogenesis-induced forgetting occurs in rats using several hippocampal dependent tasks including contextual fear conditioning (CFC), the Morris Water Task (MWT), and touchscreen paired associates learning (PAL). Neurogenesis was increased following training using voluntary exercise for 4 weeks before recall of the previous memory was assessed. We show that voluntary running causes forgetting of context fear memories in a neurogenesis-dependent manner, and that neurogenesis-induced forgetting is present in rats across behavioral tasks despite differences in complexity or reliance on spatial, context, or object memories. In addition, we asked whether stronger memories are less susceptible to forgetting by varying the strength of training. Even with a very strong training protocol in the CFC task, we still observed enhanced forgetting related to increased neurogenesis. These results suggest that forgetting due to neurogenesis is a conserved mechanism that aids in the clearance of memories.

Significance Statement

Recent evidence indicates that hippocampal neurogenesis mediates forgetting of older memories and enhances encoding of new memories free of proactive interference. This evidence comes from multiple rodent species, behavioral tasks, and methods of increasing neurogenesis. However, a recent paper by (Kodali et al. 2016) found that voluntary exercise-induced neurogenesis did not cause forgetting in the Morris Water Task in rats. The results call into question whether the phenomenon is a conserved function of neurogenesis across species. In the present study, we show that voluntary running causes robust forgetting in rats in a neurogenesis-dependent manner and that the effect is present across three different behavioral tasks, confirming the existence of the phenomenon in rats and adding to the growing evidence that forgetting is a conserved function of hippocampal neurogenesis.