bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Reported Sensory Gating and Stress-Related Hypertension
Authors: Peters Rosalind M. , El-Masri Maher , Cassidy-Bushrow Andrea E.
Published: April 2020

Background

Increasing evidence views hypertension as a stress-induced disorder. Stressors must be “gated” by the brain before any inflammatory or immune processes that contribute to hypertension are initiated. No studies were found that examined sensory gating in relation to hypertension.

Objectives

The aim of the study was to determine if disturbances in self-reported sensory gating could differentiate normotensive from hypertensive young adults.

Methods

A nonmatched, case–control design was used. We administered an online survey to 163 young adult participants. Participants were predominantly female, in their mid-20s, well educated, and approximately evenly distributed by race and hypertension status. The Sensory Gating Inventory (SGI) measured gating disturbances.

Results

The mean SGI scores were significantly higher among persons diagnosed with hypertension, reflecting a moderate effect size of sensory gating. After adjusting for confounders, however, the normotensive and hypertensive groups were not significantly different on their SGI scores.

Discussion

With an observed moderate effect size of 0.35, but low power, more research is warranted regarding the role of gating disturbances in the development of stress-induced hypertension. Clinically, the SGI may be important for screening patients who would benefit from ambulatory blood pressure monitoring to identify persons with masked hypertension.
Evaluation of Text Message Reminders to Encourage Retesting for Chlamydia and Gonorrhea Among Female Patients at the Municipal Sexually Transmitted Disease Clinic in Seattle, Washington
Authors: Unutzer Anna , Dombrowski Julia C. , Katz David A. , Barbee Lindley A. , Golden Matthew R. , Khosropour Christine M.
Published: April 2020

Background

United States guidelines recommend retesting for chlamydia (CT) and gonorrhea (GC) approximately 3 months after treatment, but adherence to these guidelines is poor.

Methods

In May 2016, the municipal sexually transmitted disease (STD) Clinic in Seattle, WA, integrated opt-in short message system (SMS) (text message) retesting reminders for female patients into our clinic's routine electronic intake. Women were asked if they wanted to receive an SMS reminder for retesting for GC/CT in 3 months. We used Fisher exact tests to compare the proportion who returned to the clinic for retesting and the proportion who retested GC/CT positive 3 to 6 months after their initial diagnosis. We used sexually transmitted disease surveillance data to ascertain repeat GC/CT diagnoses.

Results

From May 2016 to December 2017, 743 (36%) of 2067 women opted to receive an SMS reminder. Overall, 95 of these women tested positive for GC or CT and provided a valid phone number; 31 (33%) had opted into SMS reminders. The percentage of women who returned to the clinic 3 to 6 months after their initial GC/CT diagnosis did not significantly differ for women who did and did not opt in to receive SMS reminders (23% vs 9%; P = 0.11). Repeat GC/CT diagnosis 3 to 6 months after the initial GC/CT diagnosis was not significantly different between women who did and did not opt in (7% vs 3%; P = 0.58).

Conclusions

Uptake of automated SMS reminders among women was low, and most women who received reminders did not return for retesting. Despite this, SMS reminders integrated into an existing clinic infrastructure may somewhat increase retesting among women with GC/CT.
The Early Effects of COVID-19 on Plastic Surgery Residency Training: The University of Washington Experience
Authors: Cho Daniel Y. , Yu Jenny L. , Um Grace T. , Beck Christina M. , Vedder Nicholas B. , Friedrich Jeffrey B.
Published: April 2020

Plastic surgeons have the unique perspective of working with all types of patients and care teams from almost all specialties in surgery and medicine, which creates unique challenges in times of distress. As the initial epicenter of coronavirus disease 2019 cases in the United States, the University of Washington program was required to rapidly develop strategies to deal with the escalating crisis. All aspects of the program were affected, including the need to triage the urgency of plastic surgery care, safe staffing of plastic surgery teams, and the role of plastic surgery in the greater hospital community. In addition, as a residency training program, limiting the impact of resident education and maintaining a sense of community and connection among members of the program developed into important considerations. The authors hope that the narrative of their experience will provide insight into the decisions made in the University of Washington health care system but also remind others that they are not alone in dealing with the challenges of this pandemic.
Intestinal Oxygenation and Survival After Surgery for Necrotizing Enterocolitis
Authors: Kuik Sara J. , van der Heide Martin , Bruggink Janneke L. M. , Bos Arend F. , Verhagen A. A. Eduard , Kooi Elisabeth M. W. , Hulscher Jan B. F.
Published: April 2020

Objective:

To assess whether regional intestinal oxygen saturation (rintSO2) and regional cerebral oxygen saturation (rcSO2) measurements aid in estimating survival of preterm infants after surgery for NEC.

Summary of Background Data:

Predicting survival after surgery for NEC is difficult yet of the utmost importance for counseling parents.

Methods:

We retrospectively studied prospectively collected data of preterm infants with surgical NEC who had available rintSO2 and rcSO2 values measured via near-infrared spectroscopy 0–24 hours preoperatively. We calculated mean rintSO2 and rcSO2 for 60–120 minutes for each infant. We analyzed whether preoperative rintSO2 and rcSO2 differed between survivors and non-survivors, determined cut-off points, and assessed the added value to clinical variables.

Results:

We included 22 infants, median gestational age 26.9 weeks [interquartile range (IQR): 26.3–28.4], median birth weight 1088 g [IQR: 730–1178]. Eleven infants died postoperatively. Preoperative rintSO2, but not rcSO2, was higher in survivors than in non-survivors [median: 63% (IQR: 42–68) vs 29% (IQR: 21–43), P < 0.01), with odds ratio for survival 4.1 (95% confidence interval, 1.2–13.9, P = 0.02) per 10% higher rintSO2. All infants with rintSO2 values of >53% survived, whereas all infants with rintSO2 <35% died. Median C-reactive protein [138 mg/L (IQR: 83–179) vs 73 mg/L (IQR: 12–98), P < 0.01), lactate [1.1 mmol/L (IQR: 1.0–1.6) vs 4.6 mmol/L (IQR: 2.8–8.0), P < 0.01], and fraction of inspired oxygen [25% (IQR: 21–31) vs 42% (IQR: 30–80), P < 0.01] differed between survivors and non-survivors. Only rintSO2 remained significant in the multiple regression model.

Conclusions:

Measuring rintSO2, but not rcSO2, seems of added value to clinical variables in estimating survival of preterm infants after surgery for NEC. This may help clinicians in deciding whether surgery is feasible and to better counsel parents about their infants’ chances of survival.
Breakthrough cancer pain in 2020
Authors: Løhre Erik T. , Thronæs Morten , Klepstad Pål
Published: April 2020

Purpose of review

An overview on breakthrough cancer pain (BTCP), including inherent limitations of the terminology, assessment, clinical presentation, and treatment options.

Recent findings

The estimated prevalence of BTCP is dependent on the defined cutoffs for controlled background pain and the magnitude of the pain flare. In addition, pain flares outside the definition of BTCP are prevalent. In the 11th Revision of the International Classification of Diseases, the temporal characteristics of cancer pain are described as continuous background pain and intermittent episodic pain. BTCP should be assessed by validated methods, and the patient perspective should be included. The pain may be related to neoplastic destruction of bone, viscera, or nerve tissue and is characterized by rapid onset, high intensity, and short duration. Treatment directed towards painful metastases must be considered. Due to pharmacological properties mirroring the pain characteristics, transmucosal fentanyl formulations are important for the treatment of BTCP. Oral immediate release opioids can be used for slow-onset or predictable BTCP. For more difficult pain conditions, parenteral, or even intrathecal pain medication, may be indicated.

All clinically relevant episodic pains must be adequately treated in accordance with the patient's preferences. Transmucosal fentanyl formulations are effective for BTCP.
Innate lymphoid cells in treatment-induced gastrointestinal pathogenesis
Authors: Omar Saïd Z. , Blom Bianca , Hazenberg Mette D.
Published: April 2020

Purpose of review

Tissue injury often occurs as collateral damage after chemotherapy and radiotherapy and is associated with significant comorbidity and mortality. The arsenal of options to prevent tissue injury other than dose reduction is limited, and treatment is mostly aimed at symptom relief and prevention of complications, such as bacterial translocation and malnourishment. Novel approaches directed at prevention and early repair of damaged tissues are highly anticipated.

Recent findings

Innate lymphoid cells (ILC) are important in tissue homeostasis and wound healing. Most knowledge of ILC is based on studies in mice, and the contribution of ILC to repair therapy-induced tissue damage in humans is relatively understudied. A picture is nevertheless emerging, suggesting that ILC have several means to maintain tissue homeostasis. Subsets of ILC produce, for example, interleukin (IL)-22 or amphiregulin (AREG) that induce epithelial tissue repair and the release of microbiome modulating proteins. In addition, ILC have immune-regulatory capacities given that adoptive transfer of ILC in a mouse model of graft versus host disease (GvHD) attenuated tissue inflammation.

ILC are important in tissue maintenance and damage repair and as such have the potential to be developed as (adoptive) therapy to prevent and repair therapy-induced tissue damage.
How soon is too soon?: Optimal timing of split-thickness skin graft following polyglactin 910 mesh closure of the open abdomen
Authors: Lewis Richard H. , Sharpe John P. , Croce Martin A. , Fabian Timothy C. , Magnotti Louis J.
Published: April 2020

BACKGROUND

Various management strategies exist for the abdomen that will not close. At our institution, these patients are managed with polyglactin 910 mesh followed 14 days later (LATE) by split-thickness skin graft (STSG) or, in some cases, earlier (EARLY, <14 days), if the wound is judged to be adequately granulated. The purpose of this study was to evaluate the impact of STSG timing for wounds felt ready for grafting on STSG failure.

METHODS

Consecutive patients over a 3-year period managed with polyglactin 910 mesh followed by STSG were identified. Patient characteristics, severity of injury and shock, time to STSG, and outcomes, including STSG failure, were recorded and compared. Multivariable logistic regression analysis was performed to identify predictors of graft failure.

RESULTS

Sixty-one patients were identified: 31 EARLY and 30 LATE. There was no difference in severity of injury or shock between the groups. Split-thickness skin graft failure occurred in 11 patients (9 EARLY vs. 2 LATE, p < 0.0001). Time to STSG was significantly less in patients with graft failure (11 days vs. 15 days, p = 0.012). In fact, after adjusting for age, injury severity, severity of shock, and time to STSG, multivariable logistic regression identified EARLY STSG (odds ratio, 1.4; 95% confidence interval, 1.1–1.8, p = 0.020) as the only independent predictor of graft failure.

CONCLUSION

Appearance of the open abdomen can be misleading during the first 2 weeks following polyglactin 910 mesh placement. EARLY STSG was the only modifiable risk factor associated with graft failure. Thus, for optimal results, STSG should be delayed at least 14 days after polyglactin 910 mesh placement.

LEVEL OF EVIDENCE

Prognostic study, level IV.
One-Leg Standing and Y-Balance Test Performance in Elderly Fallers and Nonfallers
Authors: Park Kyue-nam , Yang Mi , Yoo Tae-gi , Kim Si-hyun
Published: April 2020

Background:

Falls are one of the severe causes of injury and death in older adults.

Objectives:

The aims of this study were to compare the 1-leg standing time and Y-balance test score between older adults with and without a history of falls, and to examine the association between 1-leg standing and Y-balance test performance in older adults.

Design:

A cross-sectional study.

Methods:

Twelve older adults who had fallen in the past year and 27 who had not experienced falls participated. One-leg standing and Y-balance tests were used to assess balance.

Results:

There were no significant differences in 1-leg standing time or Y-balance test distance and percentage scores between fallers and nonfallers. One-leg standing showed a fair correlation with Y-balance test in excursion distance of posterolateral reach and scores of the posteromedial and posterolateral reach.

Conclusions:

One-leg standing and Y-balance tests are useful and easy-to-apply tools for assessing balance, and a significant correlation between performance on the 2 tests was demonstrated in the older adults in this study. However, additional evaluation with 1-leg standing and Y-balance test may be needed to identify differences in balance and fall risk between older fallers and nonfallers.
Change in Estimated GFR and Risk of Allograft Failure in Patients Diagnosed With Late Active Antibody-mediated Rejection Following Kidney Transplantation
Authors: Irish William , Nickerson Peter , Astor Brad C. , Chong Edward , Wiebe Chris , Moreso Francesc , Seron Daniel , Crespo Marta , Gache Larry , Djamali Arjang
Published: April 2020

Background.

There are challenges in designing adequate, well-controlled studies of patients with active antibody-mediated rejection (AMR) after kidney transplantation (KTx).

Methods.

We assessed the functional relationship between change in estimated glomerular filtration rate (eGFR) following the diagnosis of AMR and the risk of subsequent death-censored graft failure using the joint modeling framework. We included recipients of solitary KTx between 1995 and 2013 at 4 transplant centers diagnosed with biopsy-proven active AMR at least 1 year post-KTx, who had a minimum of 3-year follow-up.

Results.

A total of 91 patients across participating centers were included in the analysis. Of the 91 patients, n = 54 patients (59%) met the death-censored graft failure endpoint and n = 62 patients (68%) met the all-cause graft failure composite endpoint. Kaplan-Meier death-censored graft survival rates at 12, 36, and 60 months postdiagnosis of AMR pooled across centers were 88.9%, 58.9%, and 36.4%, respectively. Spaghetti plots indicated a linear trend in the change in eGFR, especially in the first 12 months postdiagnosis of active AMR. A significant change in eGFR was observed within the first 12 months postdiagnosis of active AMR, getting worse by a factor of −0.757 mL/min/1.73 m2 per month during the 12-month analysis period (a delta of −9.084 mL/min/1.73 m2 at 1 y). Notably, an extrapolated 30% improvement in the slope of eGFR in the first 12 months was associated with a 10% improvement in death-censored graft failure at 5 years.

Conclusions.

If prospectively validated, this study may inform the design of pivotal clinical trials for therapies for late AMR.
E-health and multiple sclerosis
Authors: Matthews Paul M. , Block Valerie J. , Leocani Letizia
Published: April 2020

Purpose of review

To outline recent applications of e-health data and digital tools for improving the care and management of healthcare for people with multiple sclerosis.

Recent findings

The digitization of most clinical data, along with developments in communication technologies, miniaturization of sensors and computational advances are enabling aggregation and clinically meaningful analyses of real-world data from patient registries, digital patient-reported outcomes and electronic health records (EHR). These data are allowing more confident descriptions of prognoses for multiple sclerosis patients and the long-term relative benefits and safety of disease-modifying treatments (DMT). Registries allow detailed, multiple sclerosis-specific data to be shared between clinicians more easily, provide data needed to improve the impact of DMT and, with EHR, characterize clinically relevant interactions between multiple sclerosis and other diseases. Wearable sensors provide continuous, long-term measures of performance dynamics in relevant ecological settings. In conjunction with telemedicine and online apps, they promise a major expansion of the scope for patients to manage aspects of their own care. Advances in disease understanding, decision support and self-management using these Big Data are being accelerated by machine learning and artificial intelligence.

Both health professionals and patients can employ e-health approaches and tools for development of a more patient-centred learning health system.
Psychiatric Symptoms Related to the COVID-19 Pandemic
Authors: Rohde Christopher , Jefsen Oskar Hougaard , Nørremark Bettina , Aalkjær Danielsen Andreas , Østergaard Søren Dinesen
Published: April 2020

The COVID-19 pandemic and the consequential societal changes are likely to have major health consequences way beyond those caused by the virus infection. One of the medical fields that may experience significant consequences of the pandemic is that of psychiatry. Importantly, individuals who already live with mental disorders may be particularly vulnerable to the psychological stress associated with the pandemic. However, data on how the COVID-19 pandemic affects this group of people is largely absent from the literature.

Here, we report data from a quality development project conducted at the psychiatric services of the Central Denmark Region (CDR), which has a catchment area of approximately 1.3 million people covered by five psychiatric hospitals providing inpatient and outpatient treatment of all types of mental disorders. Based on a manual screening of all clinical notes from the period from February 1st to March 23rd 2020 that contained at least one of the following words: corona, COVID, virus, epidemic, pandemic, and contaminate/contamination (including compound words), we found 1357 notes from 918 adult patients that described pandemic-related psychopathology (symptoms that appeared to be caused/deteriorated by the pandemic and/or its societal consequences).

To our knowledge, this is the first investigation of COVID-19 pandemic-related psychopathology from a large psychiatric treatment setting. The results clearly suggest that this phenomenon exists among individuals with mental illness. However, as the data from this investigation stems from standard clinical practice where the patients were not systematically assessed for pandemic-related psychopathology, we cannot speak to its overall prevalence. Nevertheless, we believe that our findings underline the necessity of taking urgent action to mitigate the negative effects of the COVID-19 pandemic on patients with mental disorders. A low-cost intervention would be to simply discuss the ongoing pandemic and its societal consequences with patients seeking care in psychiatric settings - as this may lead to relief of pandemic-related symptoms via general comforting, and clarification of misunderstandings/false beliefs regarding the pandemic.
A single-cell atlas of the peripheral immune response to severe COVID-19
Authors: Wilk Aaron J. , Rustagi Arjun , Zhao Nancy Q. , Roque Jonasel , Martinez-Colon Giovanny J. , McKechnie Julia L. , Ivison Geoffrey T. , Ranganath Thanmayi , Vergara Rosemary , Hollis Taylor , Simpson Laura J. , Grant Philip , Subramanian Aruna , Rogers Angela J. , Blish Catherine A.
Published: April 2020

There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2. Here, we apply single-cell RNA sequencing (scRNA-seq) to peripheral blood mononuclear cells (PBMCs) of 7 patients hospitalized with confirmed COVID-19 and 6 healthy controls. We identify substantial reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene (ISG) signature, HLA class II downregulation, and a novel B cell-derived granulocyte population appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines, suggesting that circulating leukocytes do not significantly contribute to the potential COVID-19 cytokine storm. Collectively, we provide the most thorough cell atlas to date of the peripheral immune response to severe COVID-19.
Trends of SARS-Cov-2 infection in 67 countries: Role of climate zone, temperature, humidity and curve behavior of cumulative frequency on duplication time
Authors: Berumen Jaime , Schmulson Max , Guerrero Guadalupe , Barrera Elizabeth , Larriva-Sahd Jorge , Olaiz Gustavo , Garcia-Leyva Rebeca , Wong Chew Rosa María , Betancourt-Cravioto Miguel , Gallardo Héctor , Fajardo-Dolci Germán , Tapia-Conyer Roberto
Published: April 2020

Objective

To analyze the role of temperature, humidity, date of first case diagnosed (DFC) and the behavior of the growth-curve of cumulative frequency (CF) [number of days to rise (DCS) and reach the first 100 cases (D100), and the difference between them (ΔDD)] with the doubling time (Td) of Covid-19 cases in 67 countries grouped by climate zone.

Design

Retrospective incident case study.

Setting

WHO based register of cumulative incidence of Covid-19 cases.

Participants

1,706,914 subjects diagnosed between 12-29-2019 and 4-15-2020.

Exposures

SARS-Cov-2 virus, ambient humidity, temperature and climate areas (temperate, tropical/subtropical).

Main outcome measures

Comparison of DCS, D100, ΔDD, DFC, humidity, temperature, Td for the first (Td10) and second (Td20) ten days of the CF growth-curve between countries according to climate zone, and identification of factors involved in Td, as well as predictors of CF using lineal regression models.

Results

Td10 and Td20 were ≥3 days longer in tropical/subtropical vs. temperate areas (2.8±1.2 vs. 5.7±3.4; p=1.41E-05 and 4.6±1.8 vs. 8.6±4.2; p=9.7E-05, respectively). The factors involved in Td10 (DFC and ΔDD) were different than those in Td20 (Td10 and climate areas). After D100, the fastest growth-curves during the first 10 days, were associated with Td10<2 and Td10<3 in temperate and tropical/subtropical countries, respectively. The fold change Td20/Td10 >2 was associated with earlier flattening of the growth-curve. In multivariate models, Td10, DFC and ambient temperature were negatively related with CF and explained 44.7% (r2 = 0.447) of CF variability at day 20 of the growth-curve, while Td20 and DFC were negatively related with CF and explained 63.8% (r2 = 0.638) of CF variability towards day 30 of the growth-curve.

Conclusions

The larger Td in tropical/subtropical countries is positively related to DFC and temperature. Td and environmental factors explain 64% of CF variability in the best of cases. Therefore, other factors, such as pandemic containment measures, would explain the remaining variability.
Identification of super-transmitters of SARS-CoV-2
Authors: Yang Xuemei , Dong Ning , Chan Edward Wai-Chi , Chen Sheng
Published: April 2020

A newly emerged coronavirus, SARS-CoV-2, caused severe outbreaks of pneumonia in China in December 2019 and has since spread to various countries around the world. To probe the origin and transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences of viruses available in the GISAID platform as of March 05, 2020. A substantial number of earliest sequences reported in Wuhan in December 2019, including those of viruses recovered from the Huanan Seafood Market (HNSM), the site of the initial outbreak, were genetically diverse, suggesting that viruses of multiple sources were involved in the original outbreak. The viruses were subsequently disseminated to different parts of China and other countries, with diverse mutational profiles being recorded in strains recovered subsequently. Interestingly, four genetic clusters defined as Super-transmitters (STs) were found to become dominant and were responsible for the major outbreaks in various countries. Among the four clusters, ST1 is widely disseminated in Asia and the US and mainly responsible for outbreaks in the states of Washington and California in the US as well as those in South Korea at the end of February and early March, whereas ST4 contributed to the pandemic in Europe. Each ST cluster carried a signature mutation profile which allowed us to trace the origin and transmission patterns of specific viruses in different parts of the world. Using the signature mutations as markers of STs, we further analysed 1539 genome sequences reported after February 29, 2020. We found that around 90% of these genomes belonged to STs with ST4 being the dominant one and their contribution to pandemic in different continents were also depicted. The identification of these super-transmitters provides insight into the control of further transmission of SARS-CoV-2.
Impact of control strategies on COVID-19 pandemic and the SIR model based forecasting in Bangladesh
Authors: Rahman Mohammad Mahmudur , Ahmed Asif , Hossain Khondoker Moazzem , Haque Tasnima , Hussain Anowar
Published: April 2020

Background

COVID-19 is transmitting worldwide drastically and infected nearly two and half million of people so far. Till date 2144 cases of COVID-19 is confirmed in Bangladesh till 18th April though the stage-3/4 transmission is not validated yet.

Methods

To project the final infection numbers in Bangladesh we used the SIR mathematical model. Confirmed cases of infection data were obtained from Institute of Epidemiology, Disease Control and Research (IEDCR) of Bangladesh

Results

The confirmed cases in Bangladesh follow our SIR model prediction cases. By the end of April the predicted cases of infection will be 17450 to 21616 depending on the control strategies. Due to large population and socio-economic characteristics, we assumed 60% social distancing and lockdown can be possible. Assuming that, the predicated final size of infections will be 3782558 on the 92th day from the first infections and steadily decrease to zero infection after 193 days

Conclusion

To estimate the impact of social distancing we assumed eight different scenarios, the predicted results confirmed the positive impact of this type of control strategies suggesting that by strict social distancing and lockdown, COVID-19 infection can be under control and then the infection cases will steadily decrease down to zero.
Dynamics of Transmission and Control of COVID-19: A Real-time Estimation Using the Kalman Filter
Authors: Marioli Francisco Arroyo , Bullano Francisco , Rondón-Moreno Carlos
Published: April 2020

The COVID-19 pandemic has become the center of attention for both researchers and authorities. In this paper, we propose and test a methodology to estimate the daily effective reproduction number (ℛt) through the lens of the Kalman Filter and Bayesian estimation. Moreover, we apply our method to data from the current COVID-19 pandemic in China, Italy, Japan, and South Korea. We correlate our findings with the implementation of control measures in each of these countries. Our results show that China, Italy, and South Korea have been able to reduce ℛt over time. We find significant heterogeneity in the way ℛt decreases across countries. For instance, China reduced ℛt from its peak to below one in 19 days, while South Korea achieved the same reduction in 12 days. In contrast, it has taken Italy almost a month to reach similar levels. We hypothesize this is related to how strict, enforceable, and comprehensive are the implemented policies.
Community and Socioeconomic Factors Associated with COVID-19 in the United States: Zip code level cross sectional analysis
Authors: Guha Avirup , Bonsu Janice M. , Dey Amit Kumar , Addison Daniel
Published: April 2020

Background

Multiple reports have pointed towards involvement of community and socioeconomic characteristics of people in the United States may be associated with COVID-19 cases and deaths.

Methods

In this study, zip-code level data from 5 major metropolitan areas, was utilized to study the effect of multiple demographic & socioeconomic factors – including race, age, income, chronic disease comorbidity, population density, number of people per household on number of positive cases and ensuing death. Adjusted linear regression analysis using 13 to 16 such variables was performed.

Results

Overall, 442 zip codes reporting 93,170 positive COVID-19 cases and 138 zip codes reporting mortality ranging from 0 to 25 were included in this study. A multivariable linear regression model noted that 1% increase in the proportion of residents above the age of 65 years, proportion of African American residents, proportion of females, persons per household and population density of the zip code increased the proportion of positive cases by 0.77%, 0.23%, 1.64%, 1.83% and 0.46% respectively (P<0.01) with only population density remaining significant in zip codes with greater than median number of cases. In zips with greater than median number of deaths, no community/socio-economic factor contributed significantly to death.

Conclusion

This study gives early signals of gender, and racial inequalities while providing overwhelming evidence of how population density may contribute to an increase in the number of positive cases of COVID-19.
Fruit bromelain derived peptides destabilize growth of amyloidal fibrils
Authors: Das Sromona , Dutta Sangita , Paidi Ramesh K , Biswas Subhas C , Halder Umesh C , Bhattacharyya Debasish
Published: April 2020

β-Amyloid deposition as fibrillar plaques in brain is the primary cause of Alzheimer’s disease. We report potency of cysteine protease ‘fruit bromelain’ from pineapple in destabilising Aβ fibrils. Bromelain peptide pool (Mw<500 Da) obtained mimicking human alimentary tract digestion inhibited fibrillation from monomeric and oligomeric states of A and irreversibly dissociated preformed fibrils into small oligomers of varied sizes. Time kinetics was followed by Thioflavin-T assay and microscopic imaging. Synthetic bromelain peptides corresponding to Aβ sticky region found using ClustalW analysis revealed specificity of peptides in destabilisation of amyloidal structures. Spectra of different molecular states of Aβ obtained from application of 8-anilino-1-naphthalenesulfonic acid, circular dichroism and Fourier-Transformed Infrared spectroscopy collectively indicated interaction dependent structural change. Probable mechanism for fibril dissociation was thus predicted. Peptides relieved Aβ cytotoxicity on pheochromcytoma cells and dissociated plaques in AD-type rats prepared by bilateral intracerebroventricular administration of Aβ in rat brain cortex. Pineapple being a phytoceutical, its efficiency to disaggregate amyloid bodies warrant further investigation.

GRAPHICAL ABSTRACT
Tissue accumulation and the effects of long-term dietary copper contamination on osmoregulation in the mudflat fiddler crabMinuca rapax(Crustacea, Ocypodidae)
Authors: Capparelli MV , McNamara JC , Grosell MG
Published: April 2020

We examined copper accumulation in the hemolymph, gills and hepatopancreas, and hemolymph osmolality, Na+and Cl-concentrations, together with gill Na+/K+-ATPase and carbonic anhydrase activities, after dietary copper delivery (0, 100 or 500 µg Cu/g) for 12 days in a fiddler crab,Minuca rapax. In contaminated crabs, copper concentration decreased in the hemolymph and hepatopancreas, but increased in the gills. Hemolymph osmolality and gill Na+/K+-ATPase activity increased while hemolymph [Na+] and [Cl-] and gill carbonic anhydrase activity decreased. Excretion likely accounts for the decreased hemolymph and hepatopancreas copper titers. Dietary copper clearly affects osmoregulatory ability and hemolymph Na+and Cl-regulation inM. rapax. Gill copper accumulation decreased carbonic anhydrase activity, suggesting that dietary copper affects acid-base balance. Elevated gill Na+/K+-ATPase activity appears to compensate for the ion-regulatory disturbance. These effects of dietary copper illustrate likely impacts on semi-terrestrial species that feed on metal contaminated sediments.
Neural markers of vulnerability to anxiety outcomes following traumatic brain injury
Authors: Popovitz Juliana , Mysore Shreesh P. , Adwanikar Hita
Published: April 2020

Anxiety outcomes following traumatic brain injury (TBI) are complex, and the underlying neural mechanisms are poorly understood. Here, we developed a multidimensional behavioral profiling approach to investigate anxiety-like outcomes in mice that takes into account individual variability. Departing from the tradition of comparing outcomes in TBI versus sham groups, we identified animals within the TBI group that are vulnerable to anxiety dysfunction by applying dimensionality reduction, clustering and post-hoc validation to behavioral data obtained from multiple assays for anxiety at several post-injury timepoints. These vulnerable animals expressed distinct molecular profiles in the corticolimbic network, with downregulation in GABA and glutamate, and upregulation in NPY markers. Indeed, among vulnerable animals, not resilient or sham controls, severity of anxiety outcomes correlated strongly with expression of molecular markers. Our results establish a foundational approach, with predictive power, for reliably identifying maladaptive anxiety outcomes following TBI and uncovering neural signatures of vulnerability to anxiety.
A Thermodynamic Interpretation of the Stimulated Raman Spectroscopic Signature of an Action Potential in a Single Neuron
Authors: Shrivastava Shamit , Lee Hyeon Jeong , Cheng Ji-Xin
Published: April 2020

It has previously been suggested that the plasma membrane condenses and melts reversibly during an action potential in a neuron, analogous to an acoustic wave travelling in the compressive membrane region. If true it has fundamental consequences for our understanding of the regulation of biological functions during an action potential. It has long been known that the electrical dipoles in the neuronal membrane reorient during an action potential, observed through a variety of optical methods. However, this information has been insufficient to confirm if and how the collective thermodynamic state of the neuronal membrane changes during an action potential. Here, we show that hyperspectral stimulated Raman spectroscopy (SRS) can resolve the thermodynamic state of the neuronal membranes in a single neuron during an action potential. These measurements indicate that the system becomes ordered and compressed during the de-polarisation phase and disordered and expanded during hyper polarisation Therefore, the observation is consistent with the acoustic hypothesis and SRS provides a powerful tool to not only further validate the hypothesis in future, but also explore the role of membrane thermodynamics during an action potential.
A preliminary study on the reproductive toxicity of GS-5734 on male mice
Authors: Fan Jing , Luo Jiao , Zhao Depeng , Deng Tianqin , Weng Yuanbo , Sun Yangyang , Li Xuemei
Published: April 2020

The authors have withdrawn their manuscript given that some conclusions need more research and data support. In addition, they intend to improve the experimental design to make the research more rigorous. If you have any questions, please contact the corresponding author.
Reference-free andde novoIdentification of Circular RNAs
Authors: Qin Yangmei , Xu Tingting , Lin Wenbo , Jia Qingjie , He Qiushun , Liu Ke , Du Juan , Chen Linshan , Yang Xiaozhen , Du Fei , Li Mengjun , Chen Min , Tao Tao , Ji Zhi-Liang
Published: April 2020

Background

Early studies have unveiled multiple regulatory functions of circular RNAs (circRNAs); however, accurate detection and quantification of circRNAs, especially in understudied organisms, is unsolved yet.

Results

In this study, we developed a new reference-free method, namely Cirit, tode novodetect circRNAs with sequence support from the next generation sequencing (NGS) transcriptome. The Cirit showed remarkable performance in accurate detection and quantification of circRNAs via comparing with current methods from different aspects. Using Cirit, we detected 28,813 nonredundant human circRNAs from 91 transcriptome datasets, as well as 2,385 circRNAs from four understudied organisms. Subsequent analyses found that the majority of human circRNAs expressed spatiotemporally; only a very small portion of circRNAs were back-splice junction (BSJ)-consistent (maximally 5.17%) or sequence-consistent (under 2%). Furthermore, circRNA genesis were relatively flexible that only about 60% of human circRNAs used the canonical GT-AG pattern for back-splice. The inconsistent expression of circRNAs challenges their roles as precise transcriptional regulators.

Conclusions

In summary, the reference-free method provides a straightforward and universal way for reliable circRNA research. It will largely boost the successful rate in designing highly specific probes to monitor circRNA behavior in cell. In particular, it brings circRNA research to the organisms that have no genome or draft genome.
Allosteric HSP70 inhibitors perturb mitochondrial proteostasis and overcome proteasome inhibitor resistance in multiple myeloma
Authors: Ferguson Ian D. , Lin Yu-Hsiu T. , Lam Christine , Shao Hao , Hale Martina , Tharp Kevin M. , Mariano Margarette C. , Steri Veronica , Wang Donghui , Phojanokong Paul , Tuomivaara Sami T. , Hann Byron , Driessen Christoph , Van Ness Brian , Gestwicki Jason E. , Wiita Arun P.
Published: April 2020

Proteasome inhibitor (PI) resistance remains a central challenge in multiple myeloma. To identify pathways mediating resistance, we first map proteasome-associated genetic co-dependencies. We identify cytosolic heat shock protein 70 (HSP70) chaperones as potential targets, consistent with proposed mechanisms of myeloma tumor cells overcoming PI-induced stress. These results lead us to explore allosteric HSP70 inhibitors (JG compounds) as myeloma therapeutics. We show these compounds exhibit increased efficacy against acquired and intrinsic PI-resistant myeloma models, unlike HSP90 inhibition. Surprisingly, shotgun and pulsed-SILAC proteomics reveal that JGs overcome PI resistance not via the expected mechanism of inhibiting cytosolic HSP70s, but instead through mitochondrial-localized HSP70, HSPA9, destabilizing the 55S mitoribosome. Analysis of myeloma patient data further supports strong effects of global proteostasis capacity, and particularlyHSPA9expression, on PI response. Our results characterize dynamics of myeloma proteostasis networks under therapeutic pressure while motivating further investigation of HSPA9 as a specific vulnerability in PI-resistant disease.
Negative feedback may suppress variation to improve collective foraging performance
Authors: Reina Andreagiovanni , Marshall James A. R.
Published: April 2020

Social insect colonies use negative as well as positive feedback signals to regulate foraging behaviour. In ants and bees individual foragers have been observed to use negative pheromones or mechano-auditory signals to indicate that forage sources are not ideal, for example being unrewarded, crowded, or dangerous. Here we propose an additional function for negative feedback signals during foraging, variance reduction. We show that while on average populations will converge to desired distributions over forage patches both with and without negative feedback signals, in small populations negative feedback reduces variation around the target distribution compared to the use of positive feedback alone. Our results are independent of the nature of the target distribution, providing it can be achieved by foragers collecting only local information. Since robustness is a key aim for biological systems, and deviation from target foraging distributions may be costly, we argue that this could be a further important and hitherto overlooked reason that negative feedback signals are used by foraging social insects.
Membrane estrogen receptor (GPER) and follicle-stimulating hormone receptor heteromeric complexes promote human ovarian follicle survival
Authors: Casarini Livio , Lazzaretti Clara , Paradiso Elia , Limoncella Silvia , Riccetti Laura , Sperduti Samantha , Melli Beatrice , Marcozzi Serena , Anzivino Claudia , Sayers Niamh S. , Czapinski Jakub , Brigante Giulia , Potì Francesco , Marca Antonio La , De Pascali Francesco , Reiter Eric , Falbo Angela , Daolio Jessica , Villani Maria Teresa , Lispi Monica , Orlando Giovanna , Klinger Francesca G. , Fanelli Francesca , Rivero-Müller Adolfo , Hanyaloglu Aylin C. , Simoni Manuela
Published: April 2020

Classically, follicle stimulating hormone receptor (FSHR) driven cAMP-mediated signaling boosts human ovarian follicle growth and would be essential for oocyte maturation. However, contradictingin vitrosuggest a different view on physiological and clinical significance of FSHR-mediated cAMP signaling. We found that the G protein coupled estrogen receptor (GPER) heteromerizes with FSHR, reprogramming cAMP/death signals into proliferative stimuli fundamental for sustaining oocyte survival. In human granulosa cells, survival signals are effectively delivered upon equal expression levels of both receptors, while they are missing at high FSHR:GPER ratio, which negatively impacts follicle maturation and strongly correlates with FSH responsiveness of patients undergoing controlled ovarian stimulation. Consistent with high FSHR expression levels during follicular selection, cell viability is dramatically reduced in FSHR overexpressing cells due to preferential coupling to the Gαs protein/cAMP pathway. In contrast, FSHR/GPER heteromer formation resulted in FSH-triggered anti-apoptotic/proliferative signaling delivered via the Gβγ dimer while heteromer impairment or GPER-associated Gαs inhibitory protein complexes resulted in cell death. GPER-depleted granulosa cells have an amplified FSH-dependent decrease in cell viability and steroidogenesis, consistent with the requirement of estrogen signaling for successful oocyte growth. Therefore, our findings indicate how oocyte maturation depends on the capability of GPER to shape FSHR selective signals, indicating hormone receptor heteromers may be a marker of cell proliferation.

One Sentence Summary

FSHR/GPER heteromers block cAMP-dependent selection of ovarian follicles and target tumor growth and poor FSH-response in women.
Circadian Rhythms of Perineuronal Net Composition
Authors: Pantazopoulos Harry , Gisabella Barbara , Rexrode Lindsay , Benefield David , Yildiz Emrah , Seltzer Phoebe , Valeri Jake , Chelini Gabriele , Reich Anna , Ardelt Magdalena , Berretta Sabina
Published: April 2020

Perineuronal Nets (PNNs) are extracellular matrix (ECM) structures that envelop neurons and regulate synaptic functions. Long thought to be stable structures, PNNs have been recently shown to respond dynamically during learning, potentially regulating the formation of new synapses. We postulated that PNNs vary during sleep, a period of active synaptic modification. Notably, PNN components are cleaved by matrix proteases such as the protease cathepsin-S. This protease is diurnally expressed in the mouse cortex, coinciding with dendritic spine density rhythms. Thus, cathepsin-S may contribute to PNN remodeling during sleep, mediating synaptic reorganization. These studies were designed to test the hypothesis that PNN numbers vary in a diurnal manner in the rodent and human brain, as well as in a circadian manner in the rodent brain, and that these rhythms are disrupted by sleep deprivation. In mice, we observed diurnal and circadian rhythms of PNNs labeled with the lectin wisteria floribunda agglutinin (WFA+PNNs) in several brain regions involved in emotional memory processing. Sleep deprivation prevented the daytime decrease of WFA+ PNNs and enhances fear memory extinction. Diurnal rhythms of cathepsin-S expression in microglia were observed in the same brain regions, opposite to PNN rhythms. Finally, incubation of mouse sections with cathepsin-S eliminated PNN labeling. In humans, WFA+PNNs showed a diurnal rhythm in the amygdala and thalamic reticular nucleus (TRN). Our results demonstrate that PNNs vary in a circadian manner and this is disrupted by sleep deprivation. We suggest that rhythmic modification of PNNs may contribute to memory consolidation during sleep.
FastSK: Fast Sequence Analysis with Gapped String Kernels
Authors: Blakely Derrick , Collins Eamon , Singh Ritambhara , Norton Andrew , Lanchantin Jack , Qi Yanjun
Published: April 2020

Gappedk-mer kernels with Support Vector Machines (gkm-SVMs) have achieved strong predictive performance on regulatory DNA sequences on modestly-sized training sets. However, existing gkm-SVM algorithms suffer from slow kernel computation time, as they depend exponentially on the sub-sequence feature-length, number of mismatch positions, and the task’s alphabet size. In this work, we introduce a fast and scalable algorithm for calculating gappedk-mer string kernels. Our method, named FastSK, uses a simplified kernel formulation that decomposes the kernel calculation into a set of independent counting operations over the possible mismatch positions. This simplified decomposition allows us to devise a fast Monte Carlo approximation that rapidly converges. FastSK can scale to much greater feature lengths, allows us to consider more mismatches, and is performant on a variety of sequence analysis tasks. On 10 DNA transcription factor binding site (TFBS) prediction datasets, FastSK consistently matches or outperforms the state-of-the-art gkmSVM-2.0 algorithms in AUC, while achieving average speedups in kernel computation of ∼100× and speedups of ∼800× for large feature lengths. We further show that FastSK outperforms character-level recurrent and convolutional neural networks across all 10 TFBS tasks. We then extend FastSK to 7 English-language medical named entity recognition datasets and 10 protein remote homology detection datasets. FastSK consistently matches or outperforms these baselines. Our algorithm is available as a Python package and as C++ source code1.