bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival With Continuous Outpatient Intravenous Inotrope Therapy in the Modern Era
Authors: Mody Behram P. , Khan Mohammed Hasan , Zaid Syed , Ahn Chul , Lloji Amanda , Aronow Wilbert S. , Gupta Chhaya A. , Levine Avi , Gass Alan L. , Cooper Howard A. , Lanier Gregg M.
Published: October 2020

Background:

To describe baseline characteristics and outcomes in the largest known registry of advanced heart failure (HF) patients receiving continuous outpatient intravenous inotrope therapy. Studies evaluating the use of outpatient inotropes for palliation or as a bridge to advanced therapies were performed before current guideline directed medical and device therapy (GDMDT). There are limited data on the modern experience using outpatient inotrope (OI) therapy.

Study Question:

We aimed to study current use and outcomes of OI.

Study Design:

Retrospective database analysis.

Measures and Outcomes:

From 2015 to 2017, 1540 advanced HF patients in a largess nationwide registry received OI with either milrinone or dobutamine. Baseline characteristics of 1149 patients data were retrospectively reviewed. Unadjusted Kaplan–Meier survival estimates censored at the time of transplant or mechanical circulatory support were reported.

Results:

Of 1149 patients, more patients were treated with milrinone than dobutamine (64.6% vs. 35.4%). Regardless of the indication for OI, estimated 1 and 2-years survival was 61.8% and 41.6%, respectively. Milrinone use was associated with a greater 1-year survival than dobutamine (70.7% vs. 46.2%, P < 0.0001). The superiority of milrinone over dobutamine extended to all indications for OI, including bridge to transplant (85.9% vs. 71.3%, P < 0.0001), bridge to mechanical support (91.4% vs. 71%, P = 0.001), and palliation (73.6% vs. 63.3%, P < 0.001). After adjusting for indication, age, gender and weight, milrinone was associated with lower mortality than dobutamine (HR 0.50, 95% CI 0.39–0.64, P < 0.0001).

Conclusions:

In the largest dataset of HF patients receiving OI, survival on OI for palliation in the current era of GDMDT is significantly higher than previously reported. Compared with dobutamine, milrinone was associated with improved survival in all cohorts.
Microcirculatory, Endothelial, and Inflammatory Responses in Critically Ill Patients With COVID-19 Are Distinct From Those Seen in Septic Shock: A Case Control Study
Authors: Hutchings Sam D. , Watchorn James , Trovato Francesca , Napoli Salvatore , Mujib Salma F. , Hopkins Philip , McPhail Mark
Published: October 2020

Critically ill patients with COVID-19 infection frequently exhibit a hyperinflammatory response and develop organ failures; however, the underlying mechanisms are unclear. We investigated the microcirculatory, endothelial, and inflammatory responses in critically ill COVID-19 patients and compared them to a group of patients with septic shock in a prospective observational case control study. Thirty critically ill patients with COVID-19 were compared to 33 patients with septic shock.

Measurements of sublingual microcirculatory flow using Incident Dark Field video-microscopy and serial measurements of IL-6 and Syndecan-1 levels were performed. COVID-19 patients had significantly less vasoactive drug requirement and lower plasma lactate than those with septic shock. Microcirculatory flow was significantly worse in septic patients than those with COVID-19 (MFI 2.6 vs 2.9 p 0.02, PPV 88 vs 97% P < 0.001). IL-6 was higher in patients with septic shock than COVID-19 (1653 vs 253 pg/mL, P 0.03). IL-6 levels in COVID 19 patients were not elevated compared to healthy controls except on the day of ICU admission. Syndecan-1 levels were not different between the two pathological groups. Compared to patients with undifferentiated septic shock an overt shock state with tissue hypoperfusion does not appear typical of COVID-19 infection. There was no evidence of significant sublingual microcirculatory impairment, widespread endothelial injury or marked inflammatory cytokine release in this group of critically ill COVID-19 patients.
Toward Monocyte HLA-DR Bedside Monitoring: A Proof-of-Concept Study
Authors: Bourgoin Pénélope , Taspinar Ramazan , Gossez Morgane , Venet Fabienne , Delwarde Benjamin , Rimmelé Thomas , Morange Pierre-Emmanuel , Malergue Fabrice , Monneret Guillaume
Published: October 2020

Objectives:

Decreased expression of human leukocyte antigen-DR on monocytes (mHLA-DR) is recognized as the most appropriate marker for the monitoring of immune alterations in septic patients and critically ill subjects. Its measurement has been established for years by flow cytometry, but remains under-used due to pre-analytical constraints. The objectives of the present work were to develop a rapid and robust one-step protocol.

Methods:

A novel, simplified protocol has been developed to measure mHLA-DR in whole blood using flow cytometry. It is a one-step procedure that includes red cell lysis, antibodies, and fixative reagents. It has been compared to the standardized routine protocol in two consecutive cohorts of septic shock patients (n = 37). Finally, the protocol was applied to a few subjects in point-of-care settings, by collecting capillary blood from fingerpricks.

Results:

Strong correlation was observed between the one-step method and routine protocol in 24 patients. After testing several stabilizing agents, the procedure was further optimized by adding a low-dose formaldehyde to the stain and lyse solution. This improved method was tested in a second cohort of 13 patients, and again strongly correlated to the routine protocol. Finally, the fingerprick and venous puncture samples were shown to provide similar results.

Conclusions:

The present work demonstrates the feasibility of a bedside protocol for flow cytometry measurement of mHLA-DR in critically ill subjects. This helps overcome pre-analytical constraints previously identified, which have limited wider use of this biomarker in intensive care units. In addition, preliminary results from fingerprick samples are promising.
Vulpeculin: a novel and abundant lipocalin in the urine of the common brushtail possum,
Trichosurus vulpecula
Authors: Loxley Grace M. , Hooks David O. , Antonopoulos Aristotelis , Dell Anne , Haslam Stuart M. , Linklater Wayne L. , Hurst Jane L. , Beynon Robert J.
Published: October 2020

Lipocalins are a family of secreted proteins. They are capable of binding small lipophilic compounds and have been extensively studied for their role in chemosignalling in rodent urine. Urine of the common brushtail possum (
Trichosurus vulpecula
) contains a prominent glycoprotein of 20 kDa, expressed in both sexes. We have isolated this protein and determined its primary sequence by mass spectrometry, including the use of metabolic labelling to resolve the leucine/isoleucine isobaric ambiguity. The protein sequence was identified as a lipocalin, and phylogenetic analysis grouped the protein with other marsupial lipocalin sequences in a phylogenetic clade distinct from established cross-species lipocalin sub-families. The pattern of expression in possum urine and the similarity in sequence and structure to other lipocalins suggests this protein may have a role in brushtail possum chemosignalling.
Neuroinflammation characterizes the earliest changes in Alzheimer’s disease pathology and associated subjective cognitive impairment in adult hydrocephalus biopsies
Authors: Huang Wenrui , Bartosch Anne Marie , Xiao Harrison , Flowers Xena , Leskinen Sandra , Tomljanovic Zeljko , Iodice Gail , Boyett Deborah , Spinazzi Eleonora , Menon Vilas , McGovern Robert A. , McKhann Guy M. , Teich Andrew F.
Published: October 2020

In an effort to better characterize the transcriptomic changes that accompany early Alzheimer’s disease (AD) pathology in living patients and correlate with contemporaneous cognitive data, we performed RNA-seq on 106 cortical biopsies that were taken during shunt placement for adult onset hydrocephalus with varying degrees of comorbid AD pathology. A restricted set of genes correlate with AD pathology in these biopsies, and co-expression network analysis demonstrates an evolution from microglial homeostasis to a disease-associated microglial phenotype in conjunction with increasing AD pathologic burden, along with a subset of additional astrocytic and neuronal genes that accompany these changes. Further analysis demonstrates that these correlations are driven by patients that report mild cognitive symptoms, despite similar levels of β-amyloid and tau pathology in comparison to patients who report no cognitive symptoms. Interestingly, downregulation of homeostatic genes and upregulation of disease-associated genes also correlate with microglial plaque invasion and an activated microglial morphology, and this change is not sensitive to cognitive status, suggesting that an initial microglial response to AD pathology is eventually maladaptive. Taken together, these findings highlight a restricted set of microglial and non-microglial genes and suggest that early AD pathology is largely characterized by a loss of homeostatic genes and an activated microglial phenotype that continues to evolve in conjunction with accumulating AD pathology in the setting of subjective cognitive decline.
Prevalence of Function-Limiting Late Effects in Hodgkin Lymphoma Survivors
Authors: Enam Nabela , Chou Kathy , Stubblefield Michael D.
Published: October 2020

Objective

To define the prevalence of neuromuscular, musculoskeletal, pain, visceral, oncologic and other late effects impacting function and quality of life in Hodgkin lymphoma(HL) survivors presenting to an outpatient cancer rehabilitation clinic.

Design

A retrospective cohort analysis.

Setting

Outpatient cancer rehabilitation clinic.

Participants

One hundred consecutive HL survivors.

Interventions

None.

Main Outcome Measures

The prevalence of neuromuscular, musculoskeletal, pain, visceral, oncologic and other late effects contributing to functional impairment and disability in HL survivors.

Results

Among the 100 HL survivors, 43% received chemotherapy, 94% radiation therapy, and 38% a combination of chemotherapy and radiation for initial treatment. Nearly all HL survivors were diagnosed with myelopathy (83%), radiculo-plexopathy (93%), mononeuropathy (95%) and localized myopathy (93%). Musculoskeletal sequelae were extremely common and included dropped head syndrome (83%), cervicalgia (79%), shoulder girdle dysfunction (73%), and dysphagia (42%). Visceral disorders were also common and included cardiovascular (70%), pulmonary (44%), endocrine (63%), gastrointestinal (29%), and genitourinary (11%) dysfunction. Lymphedema affected 21% of survivors and 30% had a history of a secondary malignancy. Pain (71%), fatigue (45%), and dyspnea (43%) were major function-limiting impairments. Nearly all (95%) of survivors were referred to at least one therapy discipline including physical therapy, occupational therapy, speech and language pathology and/or lymphedema therapy.

Conclusion

Neuromuscular, musculoskeletal, pain, visceral, oncologic and other late effectsare extremely common in HL survivors seeking physiatric evaluation. Multiple function-limiting disorders can co-exist in HL survivors with the potential to severely compromise function and quality of life. Safe and effective rehabilitation may depend on the physiatrist’s ability to identify, evaluate and manage the multitude of complex and often interrelated functional late effects seen in HL survivors.
Decoupling sleep and brain size in childhood: An investigation of genetic covariation in the ABCD study
Authors: Hernandez Leanna M. , Kim Minsoo , Hernandez Cristian , Thompson Wesley , Fan Chun Chieh , Galván Adriana , Dapretto Mirella , Bookheimer Susan Y. , Fuligni Andrew , Gandal Michael
Published: October 2020

Background

Childhood sleep problems are common and among the most frequent and impairing comorbidities of childhood psychiatric disorders. However, little is known about the genetic architecture of childhood sleep and potential etiological links between sleep, brain morphology, and pediatric-onset psychiatric symptoms.

Methods

Using data from the Adolescent Brain and Cognitive Development Study (NPhenotype=4,428 for discovery/replication, NGenetics=4,728, age: 9-10), we assessed phenotypic relationships, heritability, and genetic correlation between childhood sleep disturbances (SDs: insomnia, arousal, breathing, somnolence, hyperhidrosis, sleep-wake transitions), brain size (surface area [SA], cortical thickness, volume), and dimensional psychopathology.

Results

SDs showed widespread positive associations with multiple domains of childhood psychopathology; however, only insomnia showed replicable associations with smaller brain SA. Among the SDs assessed, only insomnia showed significant SNP-based heritability (h2SNP=0.15, p<0.05), and showed substantial genetic correlations with externalizing symptoms and attention-deficit hyperactivity disorder (ADHD; rG’s>0.80, p’s<0.05), suggesting significant pleiotropy across these complex childhood traits. We find no evidence of genetic correlation between childhood insomnia and brain size. Polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of adult insomnia and adult brain size did not predict childhood insomnia; instead, PRS trained using ADHD GWAS predicted decreased SA at baseline, as well as insomnia and externalizing symptoms longitudinally.

Conclusions

These findings demonstrate a distinct genetic architecture underlying childhood insomnia and brain size and indicate that childhood insomnia should be considered along the dimensional axis of externalizing traits. Uncovering shared and unique genetic risk across childhood traits may inform our understanding of the developmental origins of comorbid psychiatric disorders.
COVID-19 Outbreaks in Refugee Camps
Authors: Hernandez-Suarez Carlos , Verme Paolo , Radyakin Sergiy , Efren-Murillo
Published: October 2020

1

We built a mathematical model for SARS-CoV-2 transmission and analyze it using both a deterministic and a stochastic approach. We used this model to project the burden of the disease in refugee camps characterized by peculiar demographic characteristics and a high level of deprivation, including lack of medical facilities and personnel, as well as limited possibility to implement containment and quarantine measures. Most of the parameters in our model were adapted from published literature but we used our own estimates of the basic reproduction number, R0 as well as the lethality by age group and gender. We projected the burden in terms of number of infections, number of deaths and number of bed-days in hospitalization and intensive care, among others. We conclude that the harsh conditions of refugee camps combined with a high share of young people leads to a relatively mild scenario for the burden of the disease.
Pooled Saliva Specimens for SARS-CoV-2 Testing
Authors: Barat Bidisha , Das Sanchita , De Giorgi Valeria , Henderson David K. , Kopka Stacy , Lau Anna F. , Miller Tracey , Moriarty Theresa , Palmore Tara N. , Sawney Shari , Spalding Chris , Tanjutco Patricia , Wortmann Glenn , Zelazny Adrian M. , Frank Karen M.
Published: October 2020

We evaluated saliva (SAL) specimens for SARS-CoV-2 RT-PCR testing by comparison of 459 prospectively paired nasopharyngeal (NP) or mid-turbinate (MT) swabs from 449 individuals with the aim of using saliva for asymptomatic screening. Samples were collected in a drive-through car line for symptomatic individuals (N=380) and in the emergency department (ED) (N=69). The percent positive and negative agreement of saliva compared to nasopharyngeal swab were 81.1% (95% CI: 65.8% – 90.5%) and 99.8% (95% CI: 98.7% – 100%), respectively. The sensitivity increased to 90.0% (95% CI: 74.4% – 96.5%) when considering only samples with moderate to high viral load (Cycle threshold (Ct) for the NP <=34). Pools of five saliva specimens were also evaluated on three platforms: bioMérieux NucliSENS easyMAG with ABI 7500Fast (CDC assay), Hologic Panther Fusion, and Roche COBAS 6800. The median loss of signal upon pooling was 2-4 Ct values across the platforms. The sensitivity of detecting a positive specimen in a pool compared with testing individually was 100%, 93%, and 95% for CDC 2019-nCoV Real-Time RT-PCR, Panther Fusion® SARS-CoV-2 assay, and cobas® SARS-CoV-2 test respectively, with decreased sample detection trending with lower viral load. We conclude that although pooled saliva testing, as collected in this study, is not quite as sensitive as NP/MT testing, saliva testing is adequate to detect individuals with higher viral loads in an asymptomatic screening program, does not require swabs or viral transport media for collection, and may help to improve voluntary screening compliance for those individuals averse to various forms of nasal collections.
Poor metabolic health increases COVID-19-related mortality in the UK Biobank sample
Authors: Morys Filip , Dagher Alain
Published: October 2020

Previous studies link obesity, components of metabolic health, such as hypertension or inflammation, to increased hospitalisations and death rates of patients with COVID-19. Here, in two overlapping samples of over 1,000 individuals from the UK Biobank we investigate whether metabolic health as measured by waist circumference, dyslipidaemia, hypertension, diabetes, and systemic inflammation is related to increased COVID-19 infection and mortality rates. Using logistic regression and controlling for confounding variables such as socioeconomic status, age, sex or ethnicity, we find that individuals with worse metabolic health (measured on average eleven years prior to 2020) have an increased risk for COVID-19-related death (adjusted odds ratio: 1.67). We also find that specific factors contributing to increased mortality are increased serum glucose levels, systolic blood pressure and waist circumference.
Role of Statins in the Primary Prevention of Atherosclerotic Cardiovascular Disease and Mortality in the Population with Mean Cholesterol in the Near-Optimal to Borderline High Range: A Systematic Review and Meta-Analysis
Authors: Singh Bishnu M. , Lamichhane Hari K. , Srivatsa Sanjay S. , Adhikari Prabhat , Kshetri Bikash J. , Khatiwada Sijan , Shrestha Dhan B.
Published: October 2020

Objective

The objective of this meta-analysis was to analyze the benefits and harms of treating the population with statins in those having mean low-density lipoprotein cholesterol (LDL-C) in the near-optimal (100 to 129 mg/dl) to borderline high (130 to 159 mg/dl) range and free of cardiovascular disease (CVD). Methods: We searched PubMed, PubMed Central, Cochrane Library, and Google Scholar databases for randomized controlled trials (RCTs) published between 1994 and July 2020. We included RCTs with greater than 90% of participants free of CVD. Two reviewers independently screened the articles using the Covidence software, assessed the methodological quality using the risk of bias 2 tool, and analyzed the data using the RevMan 5.4 software. Results: Eleven trials were included. Statin therapy was associated with a decreased risk of myocardial infarction (RR=0.56, 95% CI: 0.47 to 0.67), major cerebrovascular events (RR=0.78, 95% CI: 0.63 to 0.96), major coronary events (RR=0.67, 95% CI: 0.57 to 0.80), composite cardiovascular outcome (RR=0.71, 95% CI: 0.62 to 0.82), revascularizations (RR=0.65, 95% CI: 0.57 to 0.74), angina (RR=0.76, 95% CI: 0.63 to 0.92) and hospitalization for cardiovascular causes (RR=0.74, 95% CI: 0.64 to 0.86). There was no benefit associated with statin therapy for cardiovascular mortality and coronary heart disease mortality. All-cause mortality benefit with statin therapy was seen in the population with diabetes and increased risk of CVD. Statin therapy was associated with no significant increased risk of myalgia, creatine kinase elevation, rhabdomyolysis, myopathy, incidence of any cancer, incidence of diabetes, withdrawal of the drug due to adverse events, serious adverse events, fatal cancer, and liver enzyme abnormalities. Conclusion: Statin therapy was associated with a reduced risk of cardiovascular disease and procedures without increased risk of harm in populations with mean LDL-C near-optimal to the borderline high range without prior atherosclerotic cardiovascular disease.
SMORASO-DT : A hybrid machine learning classification model to classify individuals based on working memory load in mental arithmetic task
Authors: Shivabalan K R , Deb Brototo , Goel Shivam , Arivan R
Published: October 2020

Nonlinear dynamics and chaos theory are being widely used nowadays in neuroscience to characterize complex systems within which the change of the output is not proportional to the change applied at the input. Such nonlinear systems compared to linear systems, often appear chaotic, unpredictable, or counterintuitive, however, yet their behaviour is not mapped out as random. Thus, hidden potential of the dynamical properties of the physiological phenomenon can be detected by these approaches especially to elucidate the complex human brain activity gathered from the electroencephalographic (EEG) signals. As it is known, brain is a chaotic dynamical system and its generated EEG signals are generally chaotic because, with respect to time, the amplitude changes continuously. A reliable and non-invasive measurement of memory load, to measure continuously while performing a cognitive task, is highly desirable to assess cognitive functions, crucial for prevention of decision-making errors. Such measurements help to keep up the efficiency and productivity in task completion, work performance, and to avoid cognitive overload, especially at high mental or physical workload places like traffic control, military operations, and rescue commands. In this work, we have measured the linear and nonlinear dynamics of the EEG signals in subjects undergoing mental arithmetic task. Further, we have also differentiated the subjects who can perform a mental task good or bad, and developed a hybrid machine learning model, the SMORASO-DT (SMOte + Random forest + lASso-Decision Tree), to differentiate good and bad performers during n-back task state with an accuracy rate of 78%.
Implementation of a Computing Pipeline for Evaluating the Extensibility of Boolean Networks’ Structure and Function
Authors: Segretain Rémi , Ivanov Sergiu , Trilling Laurent , Glade Nicolas
Published: October 2020

Formal interaction networks are well suited for representing complex biological systems and have been used to model signalling pathways, gene regulatory networks, interaction within ecosystems, etc. In this paper, we introduce Sign Boolean Networks (SBNs), which are a uniform variant of Threshold Boolean Networks (TBFs). We continue the study of the complexity of SBNs and build a new framework for evaluating their ability to extend,i.e. the potential to gain new functions by addition of nodes, while also maintaining the original functions. We describe our software implementation of this framework and show some first results. These results seem to confirm the conjecture that networks of moderate complexity are the most able to grow, because they are not too simple, but also not too constrained, like the highly complex ones. Biological Regulation, Biological Networks, Sign Boolean Networks, Complexity, Extensibility, Network Growth
Exploring heteroaromatic rings as a replacement for the labile amide of antiplasmodial pantothenamides
Authors: Guan Jinming , Spry Christina , Tjhin Erick T. , Yang Penghui , Kittikool Tanakorn , Howieson Vanessa M. , Ling Harriet , Starrs Lora , Burgio Gaetan , Saliba Kevin J. , Auclair Karine
Published: October 2020

ThePlasmodiumparasites that cause malaria are adept at developing resistance to antimalarial drugs, necessitating the search for new antiplasmodials. Although several amide analogs of pantothenate (pantothenamides) show potent antiplasmodial activity, hydrolysis by pantetheinases (or vanins) present in blood rapidly inactivates them. We report herein the facile synthesis and biological activity of a small library of pantothenamide analogs in which the labile amide group is replaced with a variety of heteroaromatic rings. Several of the new analogs display antiplasmodial activity in the nanomolar range againstP. falciparumand/orP. knowlesiin the presence of pantetheinase. A previously reported triazole and an isoxazole derivative presented here were further characterized and found to possess high selectivity indices, medium or high Caco-2 permeability, and medium or low microsomal clearancein vitro. Although we show here that the two compounds fail to suppress proliferation ofP. berghei in vivo, pharmacokinetic and contact time data presented provide a benchmark for the compound profile required to achieve antiplasmodial activity in mice and should facilitate lead optimization.
Impact of pre-existing T cell immunity to SARS-CoV-2 in uninfected individuals with COVID-19 mortality in different countries
Authors: Glinsky Gennadi V.
Published: October 2020

Several recent studies identified SARS-CoV-2 reactive T cells in people without exposure to the virus. However, pathophysiological implications of these findings remain unknown. Here, the potential impact of pre-existing T cell reactivity against SARS-CoV-2 in uninfected individuals on markedly different COVID-19 mortality levels in different countries has been investigated. The inverse correlation is documented between the prevalence of pre-existing SARS-CoV-2 reactive T cells in people without exposure to the virus and COVID-19 mortality rates in different countries. In countries with similar levels of pre-existing SARS-CoV-2 cross-reactive T cells in uninfected individuals, differences in COVID-19 mortality appear linked with the extend and consistency of implementations of social measures designed to limit the transmission of SARS-CoV-2 (lockdown; physical distancing; mask wearing). Collectively, these observations support the model that the level of pre-existing SARS-CoV-2 reactive T cells is one of the important determinants of the innate herd immunity against COVID-19. Together with the consistent social measures directed to limit the virus spread, high levels of pre-existing SARS-CoV-2 reactive T cells appear significant determinants diminishing the COVID-19 mortality. Observations reported in this contribution should have significant impact on definitions of the herd immunity threshold required to effectively stop the pandemic in different countries across the globe.
Fractal and inertia moment analysis of SARS CoV-2 proliferation through replication
Authors: Raj Vimal , Sreejyothi S , Swapna M S , Sankararaman S
Published: October 2020

The present work proposes a surrogate method for understanding and analyzing the replication of SARS CoV-2 through fractal and inertia moment (IM) analysis of cell culture images at different stages. The fractal analysis of images of cell culture, calculated by the box-counting and power spectral density methods, reflect the stages of virus infection, leading to the replication of the virus RNA and damaging the host cell. The linear increase of IM value reveals not only the proliferation of SARS CoV-2 by replication but also damage to the host cell with time. Thus, the work shows the possibility of fractal analysis and IM measurement for understanding the dynamics of the virus infection.
The effect of face mask mandates during the COVID-19 pandemic on the rate of mask use in the United States
Authors: Maloney Michael J.
Published: October 2020

As COVID-19 continues to spread throughout the United States, there has been a search for policies to prevent individual infections, to slow the spread of the virus in general, and to mitigate the economic impact of the pandemic. Masks have proven to be a cost-effective measure in all regards, and as such some state governments have begun to mandate their use. However, while the efficacy of masks has been demonstrated, the efficacy of public policies which mandate the use of masks has not been demonstrated. This paper compares the rates of mask use in counties as defined by state policy. It finds that state mandates are strongly correlated with higher rates of mask use, and that mandating use by all individuals in public spaces is more effective than a less comprehensive mandate for mask use by all public facing employees.
Lysophosphatidic acid and lysophosphatidylcholine levels in serum samples of patients with major depressive disorder
Authors: Bari Sumaia , Sultana Sharmin , Daria Sohel , Proma Maliha Afrin , Islam Md. Rabiul , Haque Md. Ahsanul
Published: October 2020

Major depressive disorder (MDD) is a heterogeneous condition featured with a continuous low mood, feeling of sadness, lack of interest to perform daily activities. Many factors including genetic, physiological, biological, social, and environmental are thought to be connected with the pathophysiology of depression. Several previous studies failed to identify the favorable biomarkers for MDD. Lysophosphatidic acid (LPA) and lysophosphatidylcholine (LPC)showed important roles in the regulation of emotion among experimental animals. The current study aimed to measure the serum levels of LPA and LPC in MDD patients and healthy controls (HCs) to explore their roles and relationship with depression. This case-control study enrolled 53 MDD patients and 50 healthy controls (HCs). The patients were recruited from the department of psychiatry, Bangabandhu Sheikh Mujib Medical University whereas the controls was from different locations of Dhaka city. Both the cases and controls were strictly matched by gender, age, and body mass index. A qualified psychiatrist diagnosed patients and evaluated controls based on the diagnostic and statistical manual of mental disorders, 5th edition. The severity of depression in MDD patients was measured by using the Hamilton depression rating scale (Ham-D). Enzyme-linked immunosorbent assay kits were used to measure serum levels LPA and LPC. We found no alterations of these parameters in serum levels of MDD patients compared to HCs. A significant positive correlation was found between serum LPA and LPC levels in MDD patients. Moreover, the present study showed no significant associations between target markers and either diagnosis of depression or Ham-D scores, or management of depression. The present study suggests that LPA and LPC levels probably would not serve as potential biomarkers of MDD. Thus, further studies with large and more homogeneous populations are recommended to explore the exact relationship between targeted serum lipids and major depression.
Higher levels of serum IL-1β and TNF-α are associated with an increased probability of major depressive disorder
Authors: Das Rajesh , Zaman Emon Md. Prova , Shahriar Mohammad , Nahar Zabun , Ashraful Islam Sardar Mohammad , Bhuiyan Mohiuddin Ahmed , Islam Sheikh Nazrul , Islam Md. Rabiul
Published: October 2020

Major depressive disorder (MDD) is a serious psychiatric disorder but there are no reliable risk assessment tools for this condition. The actual reason for affecting depression is still controversial. It is assumed that the dysregulated cytokines are produced due to the hyperactivation of the immune system in depression. We aimed to evaluate the possible alteration and the role of serum interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in MDD patients. The diagnostic and statistical manual of mental disorders, 5th edition was used to diagnose patients and evaluation of healthy controls (HCs). The severity of depression was measured by the Hamilton depression rating scale (Ham-D). Serum IL-1β and TNF-α levels were quantified by enzyme-linked immunosorbent assay kits. Increased levels of serum IL-1β and TNF-α were observed in MDD patients compared to HCs. These higher levels of peripheral markers were positively correlated with the severity of depression. Moreover, females with higher Ham-D scores showed greater serum IL-1β and TNF-α levels compared to males. Good predictive values were detected for both serum IL-1β and TNF-α levels by receiver operating characteristic analysis. Therefore, the elevated levels of serum IL-1β and TNF-α might be used as risk assessment indicators for MDD.
Rationale and prognosis of repurposed drugs with risk stratification of COVID-19 patients requiring Oxygen supplementation: A systematic review and meta-analysis
Authors: Elangovan Esther Jebarani , Kumar Vanitha Shyamili , Kathiravan Adhithyan , Mallampalli Raghav , Thomas Tiju , Subramaniyam Gnanasambandam
Published: October 2020

Background

The rising number of trials on repurposed dugs in COVID-19 has led to duplication and a need for curation of available outcomes from treatments that have been followed across the world. We have conducted a systematic review and meta-analysis that focus on evaluating the clinical outcomes of repurposed interventions against COVID-19.

Methods

Random effects model was adopted to estimate overall treatment effect and heterogeneity. Meta- regression was performed to study the correlation between comorbid conditions and non- invasive or invasive ventilation requirement.

Results

Twenty-nine articles met our eligibility criteria. In subgroup analysis, Tocilizumab was highly significant with lower mortality rate (OR 27.50; 95%CI [5.39-140.24]) of severe COVID-19 patients. Hydroxychloroquine and Lopinavir-ritonavir was found to be inefficacious in severe patients (OR 0.64; 95%CI [0.47-0.86] and 1.40 [0.71-2.76]). Dexamethasone had marginal effect on overall mortality rate (OR 1.19; 95%CI [1.05-1.35]). The meta-regression shows a positive correlation between prevalence of patients on Tocilizumab in non invasive support and hypertension condition (P = 0.02), whereas a negative correlation was identified with patients having lung disease (P = 0.03).

Conclusion

Overall, our study confirmed that tocilizumab may probably reduce the mortality rate (<10%) of severe COVID-19 patients than other interventions. Further, reduce the risk of requiring non- invasive ventilator support in patients with comorbid condition of lung disease. Hydroxychloroquine and Lopinavir-ritonavir has no clinical benefits in severe COVID-19. A high quality evidence is required to evaluate the usage of Serpin + Favipiravir combination in severe or critical COVID-19.
Digital re-classification of equivocal dysplastic urothelial lesions using morphologic and immunohistologic analysis
Authors: Vrabie Camelia D , Gangal Marius
Published: October 2020

A precise diagnostic of precursor dysplastic urothelial lesions is critical for patients but it can be a challenge for pathologists. Multiple immunohistologic markers (panel) improve ambiguous diagnostics but results are subjective, with a high degree of observational variability. Our research objective was to evaluate how a classification algorithm may help morphology diagnostic. Data coming from 45 unequivocal cases of flat urothelial lesions (“training set”: 20 carcinomas in situ, 8 dysplastic and 17 reactive lesions) were used as ground truth in training a random tree classification algorithm. 50 “atypia of unknown significance” diagnostics (diagnostic set) were digitally re-classified based on morphological and immunohistochemical features as possible carcinoma in situ (20), dysplastic (17) and reactive atypia cases (13). The main sorting criterium was morphologic (nuclear area). A four-markers panel was used for a precise classification (74% correctly classified, 93% accuracy, 76% precision, averaged ROC=0.828). 3 cases were “false negative”. The performance of the immunohistologic panel was evaluated based on a stain index, calculated for CD20, p53, Ki67 and observed for CD44. Within training set, the immunohistologic performance was high. In the diagnostic set both the percentage of high stain index for each marker and the percentage of cases with 2-3 strong markers were low, explaining the initial high number of equivocal cases. In conclusion, digital analysis of morphologic and immunohistologic features may bring clarification in classification of equivocal urothelial lesions. Computational pathology supports diagnostic process as it can measure features and handle data in a precise, reproducible and objective way. In our proof of concept study, a low number of cases and the (deliberate) absence of clinical data were main limitations. Validation of the method on a high number of cases, use of genomics and clinical data are essential for improving the reliability of machine learning classification
Intra-county modeling of COVID-19 infection with human mobility: assessing spatial heterogeneity with business traffic, age and race
Authors: Hou Xiao , Gao Song , Li Qin , Kang Yuhao , Chen Nan , Chen Kaiping , Rao Jinmeng , Ellenberg Jordan S. , Patz Jonathan A.
Published: October 2020

The novel coronavirus disease (COVID-19) pandemic is a global threat presenting health, economic and social challenges that continue to escalate. Meta-population epidemic modeling studies in the susceptible-exposed-infectious-removed (SEIR) style have played important roles in informing public health and shaping policy making to mitigate the spread of COVID-19. These models typically rely on a key assumption on the homogeneity of the population. This assumption certainly cannot be expected to hold true in real situations; various geographic, socioeconomic and cultural environments affect the behaviors that drive the spread of COVID-19 in different communities. What’s more, variation of intra-county environments creates spatial heterogeneity of transmission in different sub-regions. To address this issue, we develop a new human mobility flow-augmented stochastic SEIR-style epidemic modeling framework with the ability to distinguish different regions and their corresponding behavior. This new modeling framework is then combined with data assimilation and machine learning techniques to reconstruct the historical growth trajectories of COVID-19 confirmed cases in two counties in Wisconsin. The associations between the spread of COVID-19 and human mobility, business foot-traffic, race & ethnicity, and age-group are then investigated. The results reveal that in a college town (Dane County) the most important heterogeneity is spatial, while in a large city area (Milwaukee County) ethnic heterogeneity becomes more apparent. Scenario studies further indicate a strong response of the spread rate on various reopening policies, which suggests that policymakers may need to take these heterogeneities into account very carefully when designing policies for mitigating the spread of COVID-19 and reopening.
New targets acquired: improving locus recovery from the Angiosperms353 probe set
Authors: McLay Todd G.B. , Birch Joanne L. , Gunn Bee F. , Ning Weixuan , Tate Jennifer A. , Nauheimer Lars , Joyce Elizabeth M. , Simpson Lalita , Weigner Nick , Schmidt-Lebuhn Alexander N. , Baker William J. , Forest Félix , Jackson Chris J.
Published: October 2020

Universal target enrichment kits maximise utility across wide evolutionary breadth while minimising the number of baits required to create a cost-efficient kit. Locus assembly requires a target reference, but the taxonomic breadth of the kit means that target references files can be phylogenetically sparse. The Angiosperms353 kit has been successfully used to capture loci throughout angiosperms but includes sequence information from 6–18 taxa per locus. Consequently, reads sequenced from on-target DNA molecules may fail to map to references, resulting in fewer on-target reads for assembly, reducing locus recovery. We expanded the Angiosperms353 target file, incorporating sequences from 566 transcriptomes to produce a ‘mega353’ target file, with each gene represented by 17–373 taxa. This mega353 file is a drop-in replacement for the original Angiosperms353 file in HybPiper analyses. We provide tools to subsample the file based on user-selected taxon groups, and to incorporate other transcriptome or protein-coding gene datasets. Compared to the default Angiosperms353 file, the mega353 file increased the percentage of on-target reads by an average of 31%, increased loci recovery at 75% length by 61.9%, and increased the total length of the concatenated loci by 30%. The mega353 file and associated scripts are available at:https://github.com/chrisjackson-pellicle/NewTargets
Integrative identification by Hi-C revealed distinct advanced structural variations in Lung Adenocarcinoma tissue
Authors: Zhang Li , Song Tingting , Yao Menglin , Yang Ying , Liu Zhiqiang , Li Weimin
Published: October 2020

Advanced three-dimensional structure variations of chromatin in large genome fragments, such as conversion of A/B compartment, topologically associated domains (TADs) and chromatin loops are related closely to occurrence of malignant tumors. However, the structural characteristics of lung cancer still remain uncovered. In this study, we used high-throughput chromosome (HiC) confirmation capture to detect 2 non-smoking female lung adenocarcinoma (LUAD) tumor and paired normal tissues. The results indicated that significant chromatin variations were detected in tumor tissues compared with normal tissues. At compartment scale, the main conversion type of compartment is A→B in tumor tissues, which concentrated mainly on chromosome 3 (33.6%). Total of 216 tumor-specific TADs were identified in tumor tissues, which distributed mainly in chr1 (19), chr2 (15) and chr3(17). Finally we observed 41 distinct enhancer-promoter loops in tumor tissue, which associated closely to tumor-related pathways including MAPK, PI3K-AKT, Ras, Wnt and Ras1. The most important observation in this study was that we identified 5 important genes (SYT16, NCEH1, NXPE3, MB21D2, andDZIP1L), which were detected in both A→B compartment, TADs and chromatin loops. Four of these genes (NCEH1, NXPE3, MB21D2, andDZIP1L) located on q arm of chromosome 3, which also revealed the importance of chr3 in occurrence of structural variations in LUAD.
Harnessing machine learning to unravel protein degradation inEscherichia coli
Authors: Nagar Natan , Ecker Noa , Loewenthal Gil , Avram Oren , Ben-Meir Daniella , Biran Dvora , Ron Eliora , Pupko Tal
Published: October 2020

Degradation of intracellular proteins in Gram-negative bacteria regulates various cellular processes and serves as a quality control mechanism by eliminating damaged proteins. To understand what causes the proteolytic machinery of the cell to degrade some proteins while sparing others, we employed a quantitative pulsed-SILAC (Stable Isotope Labeling with Amino acids in Cell culture) method followed by mass spectrometry analysis to determine the half-lives for the proteome of exponentially growingEscherichia coli, under standard conditions. We developed a likelihood-based statistical test to find actively degraded proteins, and identified dozens of novel proteins that are fast-degrading. Finally, we used structural, physicochemical and protein-protein interaction network descriptors to train a machine-learning classifier to discriminate fast-degrading proteins from the rest of the proteome. Our combined computational-experimental approach provides means for proteomic-based discovery of fast degrading proteins in bacteria and the elucidation of the factors determining protein half-lives and have implications for protein engineering. Moreover, as rapidly degraded proteins may play an important role in pathogenesis, our findings could identify new potential antibacterial drug targets.
The impact of the COVID-19 pandemic on families in Germany
Authors: Brandstetter Susanne , Poulain Tanja , Vogel Mandy , Meigen Christof , Melter Michael , Seelbach-Göbel Birgit , Apfelbacher Christian , Kiess Wieland , Kabesch Michael , Körner Antje ,   the KUNO Kids study group
Published: October 2020

Objective

To assess the impact of the COVID-19 pandemic on families with young children in two population-based childhood cohorts with a low and moderate COVID-19 prevalence, respectively.

Methods

A cross-sectional study using online questionnaires in families from LIFE Child (n=306, Leipzig) and KUNO Kids (n=612, Regensburg) was performed at the end of the German lock-down period. Outcomes were parent-reported impact of the COVID-19 pandemic on family life, concerns and trust in political measures.

Results

Most families were concerned about the COVID-19 pandemic and lock-down measures, with major concerns directed towards the economic situation (>70%), the health of close-ones (37%), but less towards their own health (<10%). Many concerns, seeking information and approval of federal measures were more pronounced in the more affected region. Approval of lockdown measures and concerns about economic recession were related to regional differences and not significantly dependent on educational status or being personally affected by the disease.

Conclusion

Regional differences in approval of lockdown measures were observed and thus, measures to specifically support families according to the regional impact of the COVID-19 pandemic are needed.
Impact of ‘never use’ abbreviations (Error Prone Abbreviations-EPA’s) list on incidence of EPAs in inpatient medical prescriptions in apex tertiary care public hospital in India
Authors: Thachaparambil Arif , Kausar Mohammad , Mahesh R , Sharma DK
Published: October 2020

Background

Abbreviations are commonly used in medical records to save time and space but use in prescriptions can be a reason for communication failures and preventable harm during healthcare delivery. Nearly 5% of medication errors can be attributable to abbreviation use. Prescriptions need to be clear so that nurses and pharmacists can correctly interpret intentions of doctors. For patient safety, hospitals should implement a process for uniform use of approved abbreviations, such as through use of an approved list or never-use list of abbreviations and symbols.

Local Problem

In the hospital under study, there was no system of avoiding error prone abbreviations while prescribing to prevent medical errors. Hence, an interventional study was done to quantify and reduce incidence of error prone abbreviations.

Methods

The study design was pre-post interventional / quasi-experimental design to assess the impact of never use list and standardized abbreviations. The study was conducted after ethical approval from Institute Ethics Committee. Pre intervention data was collected by a retrospective closed in-patient medical record review. Post interventional incidence of error prone abbreviations was determined and the effectiveness of the same was assessed by using statistical analysis.

Intervention

An approved ‘Never use’ list and standardized abbreviations were developed and poster copies were affixed in inpatient wards, doctors were educated and poster pamphlets were also distributed.

Results

Incidence of error abbreviations in inpatient prescription were 47.5% and ‘Never Use’ list of abbreviation led to a statistically significant reduction of error-prone abbreviation by 8.2% from 47.5% to 43.6% (P\0.006)

Conclusion

‘Never Use’ lists are effective in reducing incidence of common error-prone abbreviations and discipline wise variation is observed. Adoption of such lists is highly recommended. The lists should be comprehensive, regularly updated and educational interventions should be comprehensive and integration into patient medical charts and pocket friendly flash cards may be provided for better outcomes. Enforcing a policy to prohibit the use of EPAs while prescribing will also be helpful.