bluuebunny/crossref_metadata_2025 huggingface dataset:
Secondary Intention Healing After Mohs Surgical Excision as an Alternative to Surgical Repair
Authors: Liu Katherine Y. , Silvestri Brittni , Marquez Jocellie , Huston Tara L.
Published: May 2020

Background

A multitude of reconstructive options exist for patients after Mohs surgery of cutaneous neoplasms of the head and neck. Secondary intention healing is often overlooked and underused but has numerous advantages, including superior esthetic outcomes compared with surgical reconstruction for wounds that exhibit particular characteristics. The ability to predict cosmetic results based on wound characteristics can greatly help in the decision between surgical repair and secondary intention healing. Although other studies have discussed results after secondary intention healing on various areas of the head and neck, here, we specifically focus on cases of the nasal area.

Methods

We conducted a chart review of 37 patients with nasal reconstructions using secondary intention healing by a single surgeon over a 2-year period. Wound outcomes were graded as poor, acceptable, good, or excellent based on definitions found in the literature.

Results

We found that overall, the best cosmetic outcomes were associated with concave areas of the nose, such as the nasal ala and sidewall, and that superficial wounds healed better than deep wounds. Furthermore, we found that convex areas of the nose, such as the nasal tip, did not heal as well by secondary intention. However, if the wound was small and superficial enough, the wound still healed with a good to excellent cosmetic outcome.

Conclusions

Healing by secondary intention is a reasonable consideration for suitable wounds. The need for surgical scar revision is addressed, if necessary, after the wound has healed. The benefits of secondary intention healing include:

Future studies will address a larger cohort size of patients with more varied skin types and ages, as these are characteristics that can influence cosmetic outcome. Furthermore, healed wounds continue to improve in appearance over time, and it would be worthwhile to monitor patients' cosmetic outcomes over a longer follow-up period.
Availability of COVID-19 Information From National Plastic Surgery Society Web Sites
Authors: Al-Benna Sammy , Gohritz Andreas
Published: May 2020

Background

National plastic surgery society web sites are an important source of information for patients, family members, and healthcare professionals. There are currently no standardized recommendations for the information provided on web sites. The aim of this study was to assess the information available on each national plastic surgery society web site on the current pandemic of COVID-19.

Methods

A Google search was performed of United Nations member sovereign states to determine whether they had a national plastic surgery society web site and to assess its contents. The presence of COVID-19 information was recorded. Access to contact information, Facebook page, Twitter, and Instagram handles were noted.

Results

Thirty-five percent of sovereign states had plastic surgery society web sites. Twenty-two percent of national society web sites had a specific COVID-19 section. Fourteen (93%) of these 15 web sites had COVID-19–specific guidelines available for health care professionals.

Conclusions

COVID-19 information provided by national plastic surgery society web sites is sparse. Two-thirds of national plastic surgery societies do not have a web presence. The availability of COVID-19 clinical guidelines and patient information sheets on national plastic surgery society web sites is limited. This study suggests that improvement and increase in COVID-19 information provided by many national plastic surgery society web sites are needed.
Clinical Outcomes of Robotic Surgery Compared to Conventional Surgical Approaches (Laparoscopic or Open)
Authors: Muaddi Hala , Hafid Melanie El , Choi Woo Jin , Lillie Erin , de Mestral Charles , Nathens Avery , Stukel Therese A. , Karanicolas Paul J.
Published: May 2020

Objective:

Describe clinical outcomes (eg, postoperative complications, survival) after robotic surgery compared to open or laparoscopic surgery.

Background:

Robotic surgery utilization has increased over the years across a wide range of surgical procedures. However, evidence supporting improved clinical outcomes after robotic surgery is limited.

Methods:

We systematically searched MEDLINE, EMBASE, and the Cochrane Central Register of systematic reviews from inception to January 2019 for systematic reviews describing postoperative outcomes after robotic surgery. We qualitatively described patient outcomes of commonly performed robotic procedures: radical prostatectomy, hysterectomy, lobectomy, thymectomy, rectal resection, partial nephrectomy, distal gastrectomy, Roux-en-Y gastric bypass, hepatectomy, distal pancreatectomy, and cholecystectomy.

Results:

One hundred fifty-four systematic reviews included 336 studies and 18 randomized controlled trials reporting on patient outcomes after robotic compared to laparoscopic or open procedures. Data from the randomized controlled trials demonstrate that robotic-assisted radical prostatectomy offered fewer biochemical recurrence and improvement in quality of recovery and pain scores only up to 6 weeks postoperatively compared to open radical prostatectomy. When compared to laparoscopic prostatectomy, robotic surgery offered improved urinary and sexual functions. Robotic surgery for endometrial cancer had fewer conversion to open compared to laparoscopic. Otherwise, robotic surgery outcomes were similar to conventional surgical approaches for other procedures except for radical hysterectomy where minimally invasive approaches may result in patient harm compared to open approach.

Conclusion:

Robotic surgery has been widely incorporated into practise despite limited supporting evidence. More rigorous research focused on patient-important benefits is needed before further expansion of robotic surgery.
Complement 5 Inhibition Ameliorates Hepatic Ischemia/reperfusion Injury in Mice, Dominantly via the C5a-mediated Cascade
Authors: Kusakabe Jiro , Hata Koichiro , Tamaki Ichiro , Tajima Tetsuya , Miyauchi Hidetaka , Wang Yi , Nigmet Yermek , Okamura Yusuke , Kubota Toyonari , Tanaka Hirokazu , Tsuruyama Tatsuaki , Uemoto Shinji
Published: May 2020

Background.

Hepatic ischemia/reperfusion injury (IRI) is a serious complication in liver surgeries, including transplantation. Complement activation seems to be closely involved in hepatic IRI; however, no complement-targeted intervention has been clinically applied. We investigated the therapeutic potential of Complement 5 (C5)-targeted regulation in hepatic IRI.

Methods.

C5-knockout (B10D2/oSn) and their corresponding wild-type mice (WT, B10D2/nSn) were exposed to 90-minute partial (70%) hepatic ischemia/reperfusion with either anti-mouse-C5 monoclonal antibody (BB5.1) or corresponding control immunoglobulin administration 30 minutes before ischemia. C5a receptor 1 antagonist was also given to WT to identify which cascade, C5a or C5b-9, is dominant.

Results.

C5-knockout and anti-C5-Ab administration to WT both significantly reduced serum transaminase release and histopathological damages from 2 hours after reperfusion. This improvement was characterized by significantly reduced CD41+ platelet aggregation, maintained F4/80+ cells, and decreased high-mobility group box 1 release. After 6 hours of reperfusion, the infiltration of CD11+ and Ly6-G+ cells, cytokine/chemokine expression, single-stranded DNA+ cells, and cleaved caspase-3 expression were all significantly alleviated by anti-C5-Ab. C5a receptor 1 antagonist was as effective as anti-C5-Ab for reducing transaminases.

Conclusions.

Anti-C5 antibody significantly ameliorated hepatic IRI, predominantly via the C5a-mediated cascade, not only by inhibiting platelet aggregation during the early phase but also by attenuating the activation of infiltrating macrophages/neutrophils and hepatocyte apoptosis in the late phase of reperfusion. Given its efficacy, clinical availability, and controllability, C5-targeted intervention may provide a novel therapeutic strategy against hepatic IRI.
Carbamazepine-, Oxcarbazepine-, Eslicarbazepine-Associated Movement Disorder: A Literature Review
Authors: Rissardo Jamir Pitton , Caprara Ana Letícia Fornari
Published: May 2020

Background

Carbamazepine (CBZ), oxcarbazepine (OXC), and eslicarbazepine (ESL) acetate belong to the dibenzazepine family. In this context, the aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms, and management of CBZ-, OXC-, and ESL-associated movement disorders (MDs).

Review Summary

Relevant reports in 6 databases were identified and assessed by 2 reviewers without language restriction. Reports where the individuals only developed tremor or ataxia after CBZ/OXC/ESL use were not included. A total of 73 reports containing 191 individuals who developed MD associated with CBZ/OXC/ESL were identified. Were found, respectively, the following: 33 patients with myoclonus, 23 with dystonia, 14 with tics, 13 with dyskinesia, 8 with parkinsonism, and 5 with akathisia. In the group not clearly defined, there were 44 with myoclonus, 29 with dyskinesia, 20 with dystonia, 1 with incoordination, and 1 with akathisia. The mean age was 28.53 years. The most frequent sex was male in 52.77% (38/72), and the drug indication was epilepsy in 74.19% (69/93). The mean (SD) CBZ dose when the MD occurred was 692.68 (363.58) mg. The mean time until MD onset was 33.59 days, and the mean recovery period was 8.7 days. The most common form of MD management was drug withdrawal.

Conclusions

The number of cases associated with CBZ is higher than those with OXC + ESL. We believe that the study of CBZ contributes not only to the improvement of this drug but also to the knowledge about the drug-induced MD of OXC and ESL. In the literature, the description of the MD onset and recovery has been poorly reported.
Wound Healing in the Long-Term Acute Care Setting Using an Air Fluidized Therapy/Continuous Low-Pressure Therapeutic Bed
Authors: Arnold Malgorzata , Yanez Cecilia , Yanez Blanca
Published: May 2020

BACKGROUND:

We evaluated a new bed that updates the functionality of the current air fluidized therapy (AFT)/continuous low-pressure (CLP) pressure redistributing beds. This bed was evaluated in conjunction with standard wound care interventions in a long-term acute care hospital (LTACH). The AFT feature is designed to provide pressure distribution via a fluid-like medium that forces air though millions of tiny silicone beads that float the patient's body to achieve maximum immersion and envelopment. The CLP feature of the bed provides pressure distribution for the upper body. Standard wound care was provided that included debridement, topical treatments, and biophysical therapies such as negative pressure wound therapy, as indicated.

CASES:

Our multiple case series comprised 10 medically compromised patients with 25 wounds. Their mean age was 63 years, 50% were male, and the mean cumulative Braden Scale score was 12.4 out of 23, indicating a high risk for pressure injury (PI). Seven of 10 patients were incontinent of urine, 6 had fecal incontinence, and 2 had ostomies. Types of wounds treated included 2 large tissue defects from surgical excisions for the treatment of gangrene and 23 PIs. On admission, wounds had an average surface area of 139.1 cm2. The mean percentage of reduction in wound surface area was 59.3% over an average of 31.3 days of therapy. No new wounds formed during their course of care despite being at elevated risk.

CONCLUSIONS:

Findings from this multiple case series suggest that the AFT/CLP bed facilitates healing of advanced wounds in medically complex patients when included as part of a wound care program. Despite mild to high risk, no new PIs developed, and severe PIs and large tissue defects significantly improved or completely resolved. One hundred percent of surveyed staff members recommend use of the AFT/CLP bed.
Nonalcoholic fatty liver disease: implications for endocrinologists and cardiologists
Authors: Rodriguez-Araujo Gerardo
Published: May 2020

Type 2 diabetes mellitus is not just a risk factor but a progression factor for a plethora of multi-organ complications, including the liver and the vascular system. The profibrogenic-inflammatory liver disease nonalcoholic steatohepatitis affects patient’s mortality and overall cardiovascular and liver-related complications. There is an evident overlap between these diseases; therefore, there are important implications for endocrinologists, cardiologists, and hepatologists when treating these patients. In addition, as newly approved nonalcoholic steatohepatitis pharmacotherapy is expected to be available early this year, clinicians need to be able to identify patients with type 2 diabetes mellitus that are at risk of advanced liver fibrosis to establish adequate and efficient management plans to limit or avoid cardiovascular or liver-related complications. In this review, we summarize the current knowledge in the nonalcoholic steatohepatitis field with potential value for clinicians focusing on the implications of the overlap between type 2 diabetes mellitus, cardiovascular disease, and nonalcoholic steatohepatitis, the available diagnostic tools for risk stratification, management pathways, and nonalcoholic steatohepatitis pharmacotherapy, including antidiabetic and cardiovascular drugs that may be beneficial or detrimental to their patients.
A 78-year-old male with inferior ST-segment elevation on electrocardiogram, diabetic ketoacidosis and acute pancreatitis
Authors: Ho Jamie S.Y. , Mui Bryan , Sia Ching-Hui , Djohan Andie H. , Mok Shao-Feng , Chan Mark Y. , Ambhore Anand A.
Published: May 2020

A 78-year-old male presented with shortness of breath, metabolic acidosis, severe hyperglycaemia and ketonemia. Inferior ST-elevation was present on 12-lead ECG with raised troponin I, but coronary arteries were normal on emergency cardiac catheterization. Despite no previous history of diabetes mellitus and normal HbA1c levels 7 months prior, diabetic ketoacidosis (DKA) was diagnosed, complicated by subsequent shock. The underlying cause was acute pancreatic disease, supported by elevated pancreatic enzyme levels and a history of chronic heavy alcohol use. There are no previous reports, to our knowledge, of patients with acute pancreatitis presenting to the ED with secondary DKA mimicking STEMI.
Testing lags and emerging COVID-19 outbreaks in federal penitentiaries: A view from Canada
Authors: Blair Alexandra , Parnia Abtin , Siddiqi Arjumand
Published: May 2020

Objectives

To provide the first known comprehensive analysis of COVID-19 outcomes in a federal penitentiary system. We examined the following COVID-19 outcomes within federal penitentiaries in Canada and contrasted them with estimates for the overall population in the penitentiaries’ respective provincial jurisdictions: testing, prevalence, the proportion recovered, and fatality.

Methods

Data for prisons were obtained from the Correctional Service of Canada and, for the general population, from the Esri COVID-19 Canadian Outbreak Tracking Hub. Data were retrieved between March 30 and April 21, 2020, and are accurate to this date. Penitentiary-, province- and sex-specific frequency statistics for each outcome were calculated.

Results

Data on 50 of 51 penitentiaries (98%) were available. Of these, 72% of penitentiaries reported fewer tests per 1000 population than the Canadian general population average (16 tests/1000 population), and 24% of penitentiaries reported zero tests. Penitentiaries with high levels of testing were those that already had elevated COVID-19 prevalence. Five penitentiaries reported an outbreak (at least one case). Hardest hit penitentiaries were those in Quebec, Ontario, and British Columbia, with some prisons reporting COVID-19 prevalence of 30% to 40%. Of these, two were women’s prisons. Female prisoners were over-represented among cases (31% of cases overall, despite representing 5% of the total prison population).

Conclusion

Increased sentinel or universal testing may be appropriate given the confined nature of prison populations. This, along with rigorous infection prevention control practices and the potential release of prisoners, will be needed to curb current outbreaks and those likely to come.

GRAPHICAL SUMMARY

Between 20% and 57% fewer tests per 1000 population have been conducted in federal prisons in Saskatchewan, New Brunswick, Nova Scotia and Alberta than in the general population of those provinces.

Though Alberta, Manitoba, Saskatchewan, New Brunswick and Nova Scotia are reporting lower counts of COVID-19 cases, these are also the regions reporting the lowest levels of testing.

Case incidence has been highest in federal prisons in Quebec, Ontario, and British Columbia, where a total of five prisons are experiencing outbreaks (1 or more cases). These regions are those reporting the highest levels of testing – higher than the testing levels in the general population.
Contribution to COVID-19 spread modelling: A physical phenomenological dissipative formalism
Authors: Limam Oualid , Limam Mohamed
Published: May 2020

In this study, we propose an evolution law of COVID-19 transmission based first on a representation of population by a domain part of an infinite ordered lattice in which epidemic evolution is represented by a wave like free spread starting from a first case as an epicentre. Free energy of spread on a given day is defined equal to the natural logarithm of the number of infected cases. Dissipation of propagation is obtained using a postulated form of free energy built using thermodynamics of irreversible processes in analogy to isotherm wave propagation in solids and elastic damage behaviour of materials. The proposed expression of daily free energy rate leads to dissipation of propagation introducing a parameter quantifying measures taking by governments to restrict transmission. Entropy daily rate representing disorder produced in the initial system is also explicitly defined. In this context, a simple law of evolution of infected cases as function of time is given in an iterative form. The model predicts different effects on peak of infected cases Imax and epidemic period, including effects of population size N, effects of measures taking to restrict spread, effects of population density and effect of a parameter T similar to absolute temperature in thermodynamics. Different effects are presented first. The model is than applied to epidemic spread in Tunisia and compared with data registered since the report of the first confirmed case on Mar 2, 2020. It is shown that the low epidemic size in Tunisia is essentially due to a low population density and relatively strict restriction measures including lockdown and quarantine.
Awareness-driven Behavior Changes Can Shift the Shape of Epidemics Away from Peaks and Towards Plateaus, Shoulders, and Oscillations
Authors: Weitz Joshua S. , Park Sang Woo , Eksin Ceyhun , Dushoff Jonathan
Published: May 2020

The COVID-19 pandemic has caused more than 1,000,000 reported deaths globally, of which more than 200,000 have been reported in the United States as of October 1, 2020. Public health interventions have had significant impacts in reducing transmission and in averting even more deaths. Nonetheless, in many jurisdictions the decline of cases and fatalities after apparent epidemic peaks has not been rapid. Instead, the asymmetric decline in cases appears, in most cases, to be consistent with plateau- or shoulder-like phenomena – a qualitative observation reinforced by a symmetry analysis of US state-level fatality data. Here we explore a model of fatality-driven awareness in which individual protective measures increase with death rates. In this model, fast increases to the peak are often followed by plateaus, shoulders, and lag-driven oscillations. The asymmetric shape of model-predicted incidence and fatality curves are consistent with observations from many jurisdictions. Yet, in contrast to model predictions, we find that population-level mobility metrics usually increased from low early-outbreak levelsbeforepeak levels of fatalities. We show that incorporating fatigue and long-term behavior change can reconcile the apparent premature relaxation of mobility reductions and help understand when post-peak dynamics are likely to lead to a resurgence of cases.
Forecasting COVID-19 new cases in Algeria using Autoregressive fractionally integrated moving average Models (ARFIMA)
Authors: Balah Belkacem , Djeddou Messaoud
Published: May 2020

In this research, an ARFIMA model is proposed to forecast new COVID-19 cases in Algeria two weeks ahead. In the present study, public health database from Algeria health ministry has been used to build an ARFIMA model and used to forecast COVID-19 new cases in Algeria until May 11, 2020.

Background

The aim of this study is first to find the best prediction method among the two techniques used and type of memory, either short or long, of the model constructed for the daily confirmed cases in Algeria, then make forecasts of the confirmed cases in the fifteen next days.

Methods

This study was conducted based on daily new cases of COVID-19 that were collected from the official website of Algerian Ministry of Health from March 1, 2020 to April 26, 2020. Auto Regressive Integrated Moving Average (ARFIMA) model was used to predict the trend of confirmed cases. The evaluation of the fractional differentiation parameter (d) is carried out using OxMetrics 6 software.

Results

The ARFIMA model (0, 0.431779, 0) build for Algeria, has a long memory and an upward trend over the next fifteen days and which coincides with the holy month of Ramadhan.

Conclusions

The forecasted results obtained by the proposed ARFIMA model can be used as a decision support tool to manage medical efforts and facilities against the COVID-19 pandemic crisis.
Risk of secondary infection waves of COVID-19 in an insular region: the case of the Balearic Islands, Spain
Authors: Eguíluz Víctor M. , Fernández-Gracia Juan , Rodríguez Jorge P. , Pericás Juan M. , Melián Carlos
Published: May 2020

The Spanish government declared the lockdown on March 14th, 2020 to tackle the fast-spreading of COVID-19. As a consequence the Balearic Islands remained almost fully isolated due to the closing of airports and ports, These isolation measures and the home-based confinement have led to a low prevalence of COVID-19 in this region. We propose a compartmental model for the spread of COVID-19 including five compartments (Susceptible, Latent, Infected, Diseased, and Recovered), and the mobility between municipalities. The model parameters are calibrated with the temporal series of confirmed cases provided by the Spanish Ministry of Health. After calibration, the proposed model captures the trend of the official confirmed cases before and after the lockdown. We show that the estimated number of cases depends strongly on the initial dates of the local outbreak onset and the number of imported cases before the lockdown. Our estimations indicate that the population has not reached the level of herd immunization necessary to prevent future outbreaks. While the low prevalence, in comparison to mainland Spain, has prevented the saturation of the health system, this low prevalence translates into low immunization rates, therefore facilitating the propagation of new outbreaks that could lead to secondary waves of COVID-19 in the region. These findings warn about scenarios regarding after-lockdown-policies and the risk of second outbreaks, emphasize the need for widespread testing, and could potentially be extrapolated to other insular and continental regions.
Laboratory findings associated with severe illness and mortality among hospitalized individuals with coronavirus disease 2019 in Eastern Massachusetts
Authors: Castro Victor M. , McCoy Thomas H. , Perlis Roy H.
Published: May 2020

Importance

The coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented stress on health systems across the world, and reliable estimates of risk for adverse hospital outcomes are needed.

Objective

To quantify admission laboratory and comorbidity features associated with critical illness and mortality risk across 6 Eastern Massachusetts hospitals.

Design

Retrospective cohort study using hospital course, prior diagnoses, and laboratory values.

Setting

Emergency department and inpatient settings from 2 academic medical centers and 4 community hospitals.

Participants

All individuals with hospital admission and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by PCR testing across these 6 hospitals through June 5, 2020.

Exposure

Coronavirus 2 (SARS-CoV-2).

Main Outcome Measures

Severe illness defined by ICU admission, mechanical ventilation, or death.

Results

Among 2,511 hospitalized individuals who tested positive for SARS-CoV-2 (of whom 50.9% were male, 53.9% white, and 27.0% Hispanic, with mean age 62.6 years), 215 (8.6%) were admitted to the ICU, 164 (6.5%) required mechanical ventilation, and 292 (11.6%) died. L1-regression models developed in 3 of these hospitals yielded area under ROC curve (AUC) of 0.807 for severe illness and 0.847 for mortality in the 3 held-out hospitals. In total, 212/292 (78%) of the deaths occurred in the highest-risk mortality quintile.

Conclusions and Relevance

In this cohort, specific admission laboratory studies in concert with sociodemographic features and prior diagnosis facilitated risk stratification among individuals hospitalized for COVID-19.

Funding

1R56MH115187-01

Trial Registration

None

Key Points

Question

How well can sociodemographic features, laboratory values, and comorbidities of individuals hospitalized with coronavirus disease 2019 (COVID-19) in Eastern Massachusetts through June 5, 2020 predict severe illness course?

Findings

In this cohort study of 2,511 hospitalized individuals positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by PCR who were admitted to one of six hospitals, 215 (8.6%) were admitted to the ICU, 164 (6.5%) required mechanical ventilation, and 292 (11.6%) died. In a risk prediction model, 212 (78%) deaths occurred in the top mortality-risk quintile.

Meaning

Simple prediction models may assist in risk stratification among hospitalized COVID-19 patients.
MantisCOVID: Rapid X-Ray Chest Radiograph and Mortality Rate Evaluation With Artificial Intelligence For COVID-19
Authors: Yaşar Yağmur , Karli Berat Tuna , Çöteli Cem , Çöteli Mert Burkay
Published: May 2020

Abstract

The novel coronavirus pandemic has negative impacts over the health, economy and well-being of the global population. This negative effect is growing with the high spreading rate of the virus. The most critical step to prevent the spreading of the virus is pre-screening and early diagnosis of the individuals. This results in quaranteeing the patients not to effect the healthy population. COVID-19 is the name of the disease caused by the novel coronavirus. It has a high infection rate and it is urgent to diagnose many patients as we can to prevent the spread of the virus at the early stage. Rapid diagnostic tools development is urgent to save lives. MantisCOVID is a cloud-based pre-diagnosis tool to be accessed from the internet. This tool delivers a rapid screening test by analyzing the X-ray Chest Radiograph scans via Artificial Intelligence (AI) and it also evaluates the mortality rate of patients with the synthesis of the patient’s history with the machine learning methods. This study reveals the methods used over the platform and evaluation of the algorithms via open datasets.
Normalization of Cerebral Blood Flow, Neurochemicals, and White Matter Integrity After Kidney Transplantation
Authors: Lepping Rebecca J. , Montgomery Robert N. , Sharma Palash , Mahnken Jonathan D. , Vidoni Eric D. , Choi In-Young , Sarnak Mark J. , Brooks William M. , Burns Jeffrey M. , Gupta Aditi
Published: May 2020

Background

Chronic kidney disease (CKD) is associated with abnormalities in cerebral blood flow (CBF), cerebral neurochemical concentrations and white matter integrity, each of which are associated with adverse clinical consequences in the non-CKD population, and may explain the high prevalence of dementia and stroke in end stage kidney disease (ESKD). Since cognition improves after kidney transplantation (KT), we examined these brain abnormalities pre-to post-KT to identify potential reversibility in ESKD-associated brain abnormalities.

Methods

We measured the effects of KT on CBF assessed by arterial spin labeling, cerebral neurochemical concentrations (N-acetylaspartate, choline, glutamate and glutamine, myoinositol and total creatine) measured by magnetic resonance spectroscopic imaging, and white matter integrity measured by fractional anisotropy (FA) and mean diffusivity (MD) with diffusion tensor imaging. We used a linear mixed model analysis to compare longitudinal, repeated brain MRI measurements pre-KT, and 3 months and 12 months post-KT, and also compared findings with healthy controls.

Results

29 ESKD patients and 19 age-matched healthy controls participated in the study. 22 patients underwent post-KT MRI. CBF, which was higher pre-KT than in controls (p=0.003), decreased post-KT (p<0.0001) to values in controls. KT also normalized concentrations of osmotic neurochemicals choline (p<0.0001) and myo-inositol (p=0.0003) that were higher pre-KT compared to controls. Post-KT, FA increased (p=0.001) and MD decreased (p=0.0001).

Conclusions

Brain abnormalities in CKD are reversible and normalize with KT. Further studies are needed to understand the mechanisms underlying these brain abnormalities and to explore interventions to mitigate them even in patients who cannot be transplanted.

Significance statement

Kidney disease is accompanied by brain structural and physiological abnormalities and increased risk of dementia and stroke. Renal replacement therapy with dialysis does not normalize these brain abnormalities. We evaluated these brain abnormalities before and after kidney transplantation and demonstrated that unlike dialysis, kidney transplantation normalizes cerebral blood flow, neurochemical concentrations and white matter integrity. These changes persist beyond initial post-transplantation period and thus cannot be attributed to peri-procedural interventions like steroids. These results indicate reversibility of brain abnormalities in kidney disease. Further studies are needed to understand the mechanisms underlying these abnormalities and explore interventions for prevention and mitigation in patients who cannot be transplanted.
1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer
Authors: Kilgour Marisa K. , MacPherson Sarah , Zacharias Lauren , Keyes Sarah , Pauly Brenna , Allard Bertrand , Smazynski Julian , Watson Peter H. , Stagg John , Nelson Brad H. , DeBerardinis Ralph J. , Hamilton Phineas T. , Lum Julian J.
Published: May 2020

Immune regulatory metabolites are key features of the tumor microenvironment (TME), yet with a few notable exceptions, their identities remain largely unknown. We uncovered the immune regulatory metabolic states and metabolomes of sorted tumor and stromal, CD4+, and CD8+ cells from the tumor and ascites of patients with high-grade serous ovarian cancer (HGSC) using high-dimensional flow cytometry and metabolomics supplemented with single cell RNA sequencing. Flow cytometry revealed that tumor cells show a consistently greater uptake of glucose than T cells, but similar mitochondrial activity. Cells within the ascites and tumor had pervasive metabolite differences, with a striking enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared to ascites. Despite the elevated levels of MNA in T cells, the expression of nicotinamide N-methyltransferase, the gene encoding the enzyme that catalyses the transfer of a methyl group from S-adenosylmethionine to nicotinamide, was restricted to fibroblasts and tumor cells. Treatment of T cells with MNA resulted in an increase in T cell-mediated secretion of the tumor promoting cytokine tumor necrosis factor alpha. Thus, the TME-derived metabolite MNA contributes to an alternative and non-cell autonomous mechanism of immune modulation of T cells in HGSC. Collectively, uncovering the tumor-T cell metabolome may reveal metabolic vulnerabilities that can be exploited using T cell-based immunotherapies to treat human cancer.
CD8 co-receptor enhances T cell activation without any effect on initial attachment
Authors: Robert Philippe , Limozin Laurent , van der Merwe Anton , Bongrand Pierre
Published: May 2020

The scanning of surrounding tissues by T lymphocytes to detect cognate antigen is a highly demanding process that requires high rapidity, sensitivity and specificity. Co-receptors such as CD8 are known to increase detection performance, but the exact mechanism of this role remains incompletely understood. Here, we used interference reflection microscopy to image the initial spreading of 1G4 receptor transfected CD8+ and CD8− Jurkat cells dropped on surfaces exposing five cognate antigens of varying activating power, and we used a laminar flow chamber to measure the influence of CD8 on the kinetics of bond formation and rupture between cell-born T cell receptors (TCRs) and peptide-exposing major histocompatibility complex antigens (pMHCs) at the single molecule level. It is concluded that CD8 did not influence TCR-pMHC interaction during the first seconds following cell surface encounter, but it promoted the spreading responses during the first minutes, thus suggesting that CD8 was involved in early activation rather than binding. In addition, presented results were quantitatively compared with a recent report on the cell-free interaction between the same ligand-receptor couples : it is concluded that bond formation was strongly impaired by cell molecular environment, while bond rupture was comparable in both systems. Results from this and previous reports were used to propose a quantitative scheme of the strategy used by T lymphocytes to scan foreign surfaces. It is suggested that the understanding of the strategy used by cells to perform their basic functions may be a prerequisite to understand the function of molecular networks revealed by high throughput methods.
Optimizing experimental design for genome sequencing and assembly with Oxford Nanopore Technologies
Authors: Sutton John M. , Millwood Joshua D. , McCormack A. Case , Fierst Janna L.
Published: May 2020

Background

High quality reference genome sequences are the core of modern genomics. Oxford Nanopore Technologies (ONT) produces inexpensive DNA sequences in excess of 100,000 nucleotides but high error rates make sequence assembly and analysis a non-trivial problem as genome size and complexity increases. To date there has been no comprehensive attempt to generate robust experimental design for ONT genome sequencing and assembly. In this study, we simulate ONT and Illumina DNA sequence reads for the model organismsEscherichia coli,Caenorhabditis elegans,Arabidopsis thaliana,andDrosophila melanogasterand assemble with Canu, Flye, and MaSuRCA software to quantify the influence of sequencing coverage and assembly approach. Heterozygosity in outbred eukaryotes is a common problem for genome assembly. We show broad applicability of our methods using real ONT data generated for four strains of the highly heterozygous nematodeCaenorhabditis remaneiandC. latens.

Results

ONT libraries have a unique error structure and high sequence depth is necessary to assemble contiguous genome sequences.

As sequence depth increases errors accumulate and assembly statistics plateau.

High-quality assembled sequences require a combination of experimental techniques that increase sequence read length and computational protocols that reduce error through correction, read selection and ‘polishing’ with higher accuracy short sequence reads.

Our robust experimental design results in highly contiguous and accurate genome assemblies for the four strains ofC. remaneiandC. latens.

Conclusions

ONT sequencing is inexpensive and accessible but the technology’s error structure requires robust experimental design. Our quantitative results will be helpful for a broad array of researchers seeking guidance forde novoassembly projects.
Small molecule enhancers of endosome-to-cytosol import augment anti-tumour immunity
Authors: Kozik Patrycja , Gros Marine , Itzhak Daniel N. , Joannas Leonel , Magalhaes Joao G. , Alloatti Andrés , Nery Elaine Del , Borner Georg H.H. , Amigorena Sebastian
Published: May 2020

Efficient cross-presentation of antigens by dendritic cells (DCs) is critical for initiation of anti-tumour immune responses. Yet, several steps of antigen intracellular traffic during cross-presentation are incompletely understood: in particular, the molecular mechanisms and the relative importance of antigen import from endocytic compartments into the cytosol. Here, we asked whether antigen import into the cytosol is rate-limiting for cross-presentation and anti-tumour immunity. By screening 700 FDA-approved drugs, we identified 37 import enhancers. We focused on prazosin and tamoxifen, and generated proteomic organellar maps of drug-treated DCs, covering the subcellular localisations of over 2000 proteins. By combining organellar mapping, quantitative proteomics, microscopy, and bioinformatics, we conclude that import enhancers undergo lysosomal trapping leading to membrane permeation and antigen release into the cytosol. Enhancing antigen import facilitates cross-presentation of both soluble and cell-associated antigens. Systemic administration of prazosin also led to reduced growth of MC38 tumours and to a synergistic effect with checkpoint immunotherapy in a melanoma model. Thus, inefficient antigen import into the cytosol limits antigen cross-presentation, restraining the potency of anti-tumour immune responses and efficacy of checkpoint blockers.

Highlights

Quinazolamine derivatives are potent enhancers of antigen import into the cytosol

Antigen import enhancement occurs as a consequence of lysosomal trapping

Antigen import enhancers facilitate cross-presentation and synergise with PD-L1

Proteomic organellar maps of cDC1s as a tool to detect biological effects of drugs
COVID-19 SCREENING AND MONITORING OF ASYMPTOMATIC HEALTH WORKERS WITH A RAPID SEROLOGICAL TEST
Authors: Paradiso Angelo Virgilio , De Summa simona , Silvestris Nicola , Tommasi Stefania , Tufaro Antonio , De Palma Giuseppe , Larocca Angela Maria Vittoria , D'Addabbo Vincenzo , Raffaele Donata , Cafagna Vito , Garrisi Vito Michele
Published: May 2020

Background Health workers are at high risk for SARS-CoV-2 infection and, if asymptomatic, for transmitting the virus on to fragile cancer patients.
Materials and method We monitored health care workers (HCW) of our Cancer Institute with the rapid serological test Viva-DiagTM analyzing COVID-19 associated-IgG/IgM. Test were performed at time 0 and after 14 days; Rt-PCR and CLIA assays were also perfoRmed in positive Viva-DiagTM cases. 606 and 393 HCW had blood sample taken at time 0 and 14, respectively.
Results Overall, 9 HCW (1.5%) resulted not-negative at Viva-DiagTM and one of them was confirmed positive for SARS-COV2 infection at RT-PCR oropharingeal swab. At time 0, all 9 cases showed some IgM expression and only one IgG; after 14 days IgM persisted in all cases while IgG became evident in 4 ones. A parallel CLIA test was performed in 23 quaratined subjetcs and in all Viva-Diag not negative cases. CLIA confirmed a positive level of IgM in 5/13 positive Viva-Diag cases; conversely, IgG was confirmed positive at CLIA in 4/5 cases positive at Viva-Diag. These results pose the question of different performances of the two tests.
Conclusions Our study suggest that Viva-Diag assay can be of help in individualizing SARS_COV2 infected people fisrt of all in cohorts of subjetcs with high prevalence. Different performances of serological colorimetric and CLIA tools remain to be ascertained.
Contact tracing strategies for COVID-19 containment with attenuated physical distancing
Authors: Bilinski Alyssa , Mostashari Farzad , Salomon Joshua A
Published: May 2020

Contact tracing has been recommended as a critical component of containment strategies for COVID-19. We used a simple epidemic model to evaluate how contact tracing might enable modification of current physical distancing restrictions. Testing and tracing coverage need to exceed 50% in order for contact tracing to reduce transmission by at least 10%. With 90% testing and tracing as well as high isolation and quarantine efficacy, contact tracing could reduce overall transmission by >45%, which would allow for partial loosening of physical distancing measures. Benefits of contact tracing could be enhanced by testing all contacts rather than only those with symptoms and by policies to support high adherence to voluntary isolation and quarantine.
Forecasting the spread of COVID-19 in Nigeria using Box-Jenkins Modeling Procedure
Authors: Ibrahim Rauf Rauf , Oladipo Hannah Oluwakemi
Published: May 2020

Objective

This study is focused on the analysis of the spread of Covid-19 in Nigeria, applying statistical models and available data from the NCDC. We present an insight into the spread of Covid-19 in Nigeria in order to establish a suitable prediction model, which can be applied as a decision-supportive tool for assigning health interventions and mitigating the spread of the Covid-19 infection.

Methodology

Daily spread data from February 27 to April 26, 2020, were collected to construct the autoregressive integrated moving average (ARIMA) model using the R software. Stability analysis and stationarity test, parameter test, and model diagnostic were also carried out. Finally, the fitting, selection and prediction accuracy of the ARIMA model was evaluated using the AICc model selection criteria.

Results

The ARIMA (1,1,0) model was finally selected among ARIMA models based upon the parameter test and Box–Ljung test. A ten-day forecast was also made from the model, which shows a steep upward trend of the spread of the COVID-19 in Nigeria within the selected time frame.

Conclusion

Federal Government of Nigeria through the presidential task force can apply the forecasted trend of much more spread to make more informed decisions on the additional measures in place to curb the spread of the virus. Application of the model can also assist in studying the effectiveness of the lockdown on the on the spread of Covid-19 in Nigeria.
A Novel Intervention Recurrent autoencoder for real time forecasting and non-pharmaceutical intervention selection to curb the spread of Covid-19 in the world
Authors: Ge Qiyang , Hu Zixin , Li Shudi , Lin Wei , Jin Li , Xiong Momiao
Published: May 2020

As the Covid-19 pandemic soars around the world, there is urgent need to forecast the number of cases worldwide at its peak, the length of the pandemic before receding and implement public health interventions to significantly stop the spread of Covid-19. Widely used statistical and computer methods for modeling and forecasting the trajectory of Covid-19 are epidemiological models. Although these epidemiological models are useful for estimating the dynamics of transmission od epidemics, their prediction accuracies are quite low. To overcome this limitation, we formulated the real-time forecasting and evaluating multiple public health intervention problem into forecasting treatment response problem and developed recurrent neural network (RNN) for modeling the transmission dynamics of the epidemics and Counterfactual-RNN (CRNN) for evaluating and exploring public health intervention strategies to slow down the spread of Covid-19 worldwide. We applied the developed methods to the real data collected from January 22, 2020 to May 8, 2020 for real-time forecasting the confirmed cases of Covid-19 across the world.
A Novel Regulatory Role for the Circadian Clock Protein TOC1 via RNA binding
Authors: Li Yi , Chang Yong-Gang , Nagel Dawn H. , Chen Tingjian , Rugnone Matias L , LiWang Andy , Kay Steve A.
Published: May 2020

The circadian clock enables plants to predict daily changes of external signals and synchronize them with internal processes, conferring enhanced fitness and growth vigor. The first describedArabidopsiscircadian clock protein is TIMING OF CAB EXPRESSION 1 (TOC1), which functions in a transcriptional feedback loop with two myb transcription factors, CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY). Previous studies have shown that TOC1 is a DNA-binding transcriptional repressor ofCCA1andLHY. However, the DNA motifs enriched amongst TOC1 targets share weak sequence similarity and lack consensus, suggesting that TOC1 regulates the expression of its targets through a novel mechanism. Here we show that the TOC1 protein binds directly to RNA via its conserved CCT domain. Using in vitro RNA selection, we identified an RNA motif that is recognized by the TOC1-CCT domain. The TOC1-CCT domain binds to this RNA sequence with nanomolar affinity determined by quantitative electrophoretic mobility shift assays (EMSAs) and isothermal titration calorimetry (ITC). NMR experiments showed that two CCT fragments, CCT533-547and CCT550-565, use basic residues to bind the RNA motif. Mutational analysis confirmed that lysyl and arginyl residues bind to RNA in a cooperative manner. Furthermore, transiently expressed wildtype and mutant TOC1 in protoplasts demonstrated that RNA binding activity of TOC1 is required for its function as a transcriptional repressor in vivo. Our results reveal a novel regulatory mechanism for TOC1 through RNA binding, suggesting that TOC1 might play key roles as a multi-function protein.
An inhalation anaesthesia approach for neonatal mice allowing streamlined stereotactic injection in the brain
Authors: Ho Hinze , Fowle Adam , Coetzee Marisa , Greger Ingo H. , Watson Jake F.
Published: May 2020

Investigating brain function requires tools and techniques to visualise, modify and manipulate neuronal tissue. One powerful and popular method is intracerebral injection of customised viruses, allowing expression of exogenous transgenes. This technique is a standard procedure for adult mice, and is used by laboratories worldwide. Use of neonatal animals in scientific research allows investigation of developing tissues, and enables long-term study of cell populations. However, procedures on neonatal mice are more challenging, due to the lack of reliable methods and apparatus for anaesthesia of these animals. Here, we report an inhalation-based protocol for anaesthesia of neonatal (P0-2) mice, and present a custom 3D-printed apparatus for maintenance of anaesthesia during surgical procedures. This approach significantly enhances animal welfare and facilitates wider and simpler use of neonatal rodents in scientific research. Our optimised method of anaesthesia enables a rapid method of stereotactic injection in neonatal mice for transduction of brain tissue. We demonstrate this procedure for targeted labelling of specific brain regions, andin vivomodification of tissue prior to organotypic culture. This anaesthetic approach can be readily employed by any laboratory, and will enable safer use of neonatal rodents across a diverse spectrum of scientific disciplines.

Highlights

Development of inhalation-based anaesthesia for early postnatal (P0-2) mice

3D-printed mould allows anaesthetic maintenance for neonatal surgery

Improved mouse welfare through reliable neonatal inhalation anaesthesia

Rapid procedure for brain transduction of mouse litter in under 2 hours