bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes After Central Wedge Labiaplasty Performed Under General Versus Local Anesthesia
Authors: Nwaoz Basil , Sinnott Catherine J. , Kuruvilla Annet , Natoli Noel B.
Published: April 2021

Purpose

Interest in labiaplasty as a way to alter and improve genital appearance has been on the rise. Labiaplasty procedures can be performed in the office setting under local anesthesia. However, these procedures are often performed under general anesthesia for patient comfort and to facilitate the operative technique and to potentially improve outcomes. Outcomes after labiaplasty performed under general anesthesia as compared with that performed under local anesthesia in the office setting have not been well-defined. This article aimed to compare outcomes after central wedge labiaplasty performed under general anesthesia versus that performed under local anesthesia.

Methods

A retrospective chart review identified patients who underwent central wedge labiaplasty performed by a single surgeon from 2011 to 2019. Demographic, clinical, and operative information were reviewed and recorded. Outcomes were assessed by evaluating postoperative complications and the need for revision surgery.

Results

Thirty-two women with a mean age of 32.8 ± 11.2 years and a mean body mass index of 22.0 ± 3.5 kg/m2 underwent central wedge or extended central wedge labiaplasty during the study period. Ten (31.2%) labiaplasties were performed under local anesthesia in an office setting, and 22 (68.8%) were performed under general anesthesia. Demographic, clinical, and operative characteristics were comparable between labiaplasties performed under local anesthesia and those performed under general anesthesia. Postoperative asymmetry and wound dehiscence were the most common complications. Outcomes after labiaplasty performed under general anesthesia were comparable to those performed under local anesthesia, with regard to asymmetry (27.3% vs 10.0%; P = 0.387), dehiscence (27.3% vs 40.0%; P = 0.683), scarring (4.5% vs 0.0%; P = 1.000), and the need for revision surgery (31.8% vs 40.0%; P = 0.703), respectively. There were no cases of infection, hematoma, decreased sensation, or dyspareunia.

Conclusions

Postoperative asymmetry and dehiscence were the most common complications after labiaplasty performed under general or local anesthesia. Outcomes after labiaplasty performed under general anesthesia were comparable to those performed under local anesthesia. Further studies are needed to assess outcomes after labiaplasty performed under general anesthesia versus that performed under local anesthesia.
Trends in Peripheral Nerve Epidemiology and Reconstruction
Authors: Bellaire Christopher P. , Inglesby Dani C. , Marayati Naoum Fares , Warburton Andrew J. , Melamed Eitan
Published: April 2021

Background

Peripheral nerve injuries (PNIs) are most commonly treated with direct nerve repair procedures or nerve autografts. However, recent advancements in synthetic and vein conduits have led to their increased utilization. The present study quantifies the incidence of these procedures over time and geography and identifies differences in complication rates, illustrating the current epidemiologic climate regarding conduit use for PNI repair.

Methods

A query was conducted using the State Ambulatory Surgery and Services Databases data from 2006 to 2011 in both Florida and California for patients undergoing nerve repair, nerve grafting, synthetic conduits, and vein conduits. Patient zip code data were analyzed to determine the geographic distribution of various types of repair. In addition, text-mining algorithms were used to identify trends in PNI-related publications.

Results

In the 6-year period investigated, direct nerve repair was the most frequently used procedure for PNIs. However, the utilization of direct repairs declined significantly from 2006 to 2011. Synthetic and vein conduits demonstrated a significant increase over the same period. There were significantly higher rates of complications for autologous grafts (3.3%), vein conduits (3.5%), and synthetic conduits (2.4%), as compared with direct nerve repairs (1.4%). There was a nonsignificant difference in infection rates between these types of nerve repair.

Conclusions

From an epidemiologic perspective, both graft and synthetic conduit-based PNI repairs are increasing in prevalence both in clinical practice and in the academic literature. This will likely continue in the future with the development of advancements in biologic and synthetic nerve conduit PNI repair options.
Three-Dimensional Computed Tomography Reconstruction and Measurement of Nasal End Deformity in Complete Unilateral Cleft Lip and Palate
Authors: Wang Binqing , Xu Meng , Yin Ningbei , Wang Yongqian , Song Tao
Published: April 2021

Background

The repair of nasal deformities secondary to cleft lip and palate is complex and requires reliable preoperative nasal 3-dimensional assessment. This study explored nasal end (defined as the lower third of the external nasal and vestibular parts of the nasal cavity) deformities secondary to unilateral complete cleft lip and palate.

Methods

Three-dimensional nasal end morphometric measurements were obtained from 48 patients who had undergone Millard cleft lip repair and reached skeletal maturity (cleft group) and from 36 age- and ethnicity-matched normal subjects (control group). For the cleft group, paired t tests and 1-way analysis of covariance were used to evaluate the internal and external morphological characteristics of the cleft and noncleft sides of the nasal end, and correlation analysis was done to evaluate the relationship between cleft-side measurements.

Results

In the cleft group, the cleft side showed significantly smaller nasal vestibular volume and skin area, nostril area, nasal column length, and nostril height and greater nostril base length and nasal alar length than the noncleft side (all P < 0.05). Controlling for sex, there were significant differences in the nasal vestibular volume and skin area, internal nasal valve area, long nostril diameter, nostril base length, columella length, nostril height, and nasal alar length between the cleft and control groups (all P < 0.05). On the cleft side, the area of the skin lining of the nasal vestibule positively correlated with the alar length (r = 0.67, P < 0.05).

Conclusions

Three-dimensional nasal end reconstruction provides a more detailed preoperative nasal end morphological evaluation than previously available techniques.

Level of Evidence

Level III, case-control study
High-Pressure Injection Injuries of the Hand
Authors: Nichols Georgina , Gallegos Jose , Tavana M. Lance , Armstrong Milton B. , Herrera Fernando A.
Published: April 2021

Introduction

The incidence of high-pressure injection injuries of the hand is low. Although the occurrence is rare, the precarious progression of the injury exacts prompt surgical evaluation in order to avoid complications and amputation. The current study was devised in order to make comparisons to the current data, in addition to supplementing the literature with observations regarding clinical course and management.

Methods

A multisurgeon, retrospective chart review from a single institution was performed. Inclusion criteria included cases involving a high-pressure injection injury to the hand that underwent surgical management. Patient demographics, injury details, and hospital course were all reviewed and recorded.

Results

This retrospective review identified 20 cases meeting criteria, all of which involved males. The average age at time of injury was 39.7 years (range, 21–71 years). The incidence of injection injuries over a 10-year time period was 2.1 cases per year. The nondominant hand was injured in 11 cases (63%). The most common site of injury was the index finger with 11 recorded incidents (55%). Other reported locations included the metacarpal (40%) and small finger (5%). Occupational data included 10 construction workers, 5 painters, and 2 cleaning crew members, and 3 had nonmanual occupations. Paint was the most commonly injected substance with 17 reported cases (85%). On average, the delay until surgery was observed to be 21.9 hours (n = 16). Only 1 patient underwent surgery at 6 hours after surgery. The average number of procedures performed was 1.8 (range, 1–4). Hospitalization duration was on average 3.9 days (range, 1–9 days), and the average follow-up length was 69 days (range, 7–112 days). There were no identified cases that necessitated amputation.

Conclusions

This form of injury most commonly affects male, middle-aged laborers. Our study found very low amputation rates when compared with the current literature, despite observing longer delays to surgery according to current recommendations. Limited comparisons can be made from data regarding clinical course and management because of the small sample size of the current study and the limited published data. This indicates a need for further exploration and collection of data involving parameters such as clinical course and management.
Neutralization of SARS-CoV-2 variants by convalescent and vaccinated serum
Authors: Bates Timothy A. , Leier Hans C. , Lyski Zoe L. , McBride Savannah K. , Coulter Felicity J. , Weinstein Jules B. , Goodman James R. , Lu Zhengchun , Siegel Sarah A. R. , Sullivan Peter , Strnad Matt , Brunton Amanda E. , Lee David X. , Curlin Marcel E. , Messer William B. , Tafesse Fikadu G.
Published: April 2021

We tested human sera from large, demographically balanced cohorts of BNT162b2 vaccine recipients (n=51) and COVID-19 patients (n=44) for neutralizing antibodies against SARS-CoV-2 variants B.1.1.7 and B.1.351. Although the effect is more pronounced in the vaccine cohort, both B.1.1.7 and B.1.351 show significantly reduced levels of neutralization by vaccinated and convalescent sera. Age is negatively correlated with neutralization in vaccinee, and levels of variant-specific RBD antibodies are proportional to neutralizing activities.
Using Machine Learning to Classify Schizophrenia Based on Retinal Images
Authors: Joseph Diana , Lai Adriann , Silverstein Steven , Ramchandran Rajeev , Bernal Edgar A.
Published: April 2021

VII.

Objectives

Thinning of retinal layers has been documented in patients with chronic schizophrenia using standard metrics of optical coherence tomography (OCT) devices. We demonstrate the effectiveness of machine learning (ML) techniques to differentiate between schizophrenia patients and healthy controls using OCT images.

Methods

Features extracted from a convolutional neural network (CNN) designed to segment retinal layers from OCT images represented abstracted data from the OCT images of 14 first episode (FEP) and 18 chronic schizophrenia patients, and their respective 20 and 18 age-matched controls. The abstracted data and OCT machine metrics were used separately to train support vector classification (SVC) models to differentiate between control and schizophrenia samples and test them.

Results

SVCs operating on OCT machine metrics did not classify unseen samples of FEP schizophrenia patients and controls with performance better than chance, while those looking at chronic schizophrenia did, paralleling results obtained using parametric statistics. In contrast, SVCs operating on OCT image data extracted from the CNN classified unseen samples from both populations with performance greater than chance.

Conclusion

These results suggest that ML techniques can detect patterns in patients with FEP schizophrenia with greater performance using features extracted from OCT images than metrics provided by OCT machines.
Using flexible carbon fiber insoles for 1st metatarsophalangeal arthritis lead to pain reduction and high compliance rate: A Randomized Controlled Trial
Authors: Sornsakrin Pongpanot , Bhimani Rohan , Vrolyk Michael Drew , Lubberts Bart , Guss Daniel , DiGiovanni Christopher W , Waryasz Gregory
Published: April 2021

Introduction

Shoe modification and orthotics play an important role in non-operative management for 1st metatarsophalangeal (MTP) arthritis. However, compliance can be low due to pain and discomfort. We hypothesized that patients who wear a flexible carbon fiber insole for 1st metatarsophalangeal arthritis will report reduced pain, and higher physical function and compliance rate when compared with a rigid Morton’s extension insole.

Methods

Four males and nine females (mean age of 56 years; range 35-79) diagnosed with 1st metatarsophalangeal arthritis were included in this randomized controlled trial. Participants randomly received either bilateral flexible carbon fiber insoles (VKTRY®) (n=7) or unilateral Morton’s extension insole (n=6). Outcome measures included patient compliance, comfort rate, and Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires Global Health, pain interference, v1.0 pain intensity, v2.0 Physical Function, and v1.0 Depression. Participants filled out questionnaires at baseline and at two, six, and twelve weeks follow-up.

Results

Compared to Morton’s extension insole, use of flexible carbon fiber insole led to reduction of pain interference score at 6 and 12 weeks (median ⍰ −9.5 vs 0.0 p=0.015; and median ⍰ −15.1 vs −2.3 p=0.015, respectively), as well as reduction of pain intensity score at 6 and 12 weeks (median ⍰ −11.9 vs −2.3 p=0.018; and median ⍰ −11.9 vs −2.3 p=0.010, respectively). The compliance rate in flexible carbon fiber insole group was 100% at 2, 6 and 12 weeks, compared to 83%, 83% and 50% in the Morton group. In addition, patients wearing carbon fiber insoles experienced higher comfort levels (p-values ranging from <0.001 to p=0.007). There were no differences between the comparison groups at 2, 6, and 12 weeks in terms of the global health, physical function, and depression scores.

Conclusion

Patients diagnosed with 1st metatarsophalangeal arthritis may benefit from wearing flexible carbon fiber insoles, compared to commonly used rigid orthotic insoles, such as the Morton’s extension. This insert can be used safely for nonoperative treatment of hallux rigidus and is another option for nonoperative treatment.

LEVEL OF EVIDENCE

Level I, randomized clinical trial.
Cost-Effectiveness Threshold for Healthcare and Safety: Justification and Quantification
Authors: Yanovskiy Moshe , Levy Ori Nissim , Shaki Yair Y. , Zigdon Avi , Socol Yehoshua
Published: April 2021

Every public expenditure, including saving lives or extending life expectancy of particular persons (target population), has unwanted but unavoidable side effects of statistical shortening of life expectancy of the general public. Therefore, cost-effectiveness analysis in making decisions regarding health and safety is an ethical necessity. We report here cost-effectiveness estimation based on comparison of three independent methods: (1) by analyzing salaries in risky occupations, (2) by assuming that people value their lives twice more than the wealth they earn, and (3) by comparing with the U.S. current legal practice. To the best of our knowledge, nobody applied method (2) to cost-effectiveness analysis. Our result is that the cost-effectiveness threshold for the developed countries is about US$60,000 ± 25,000 per life-year (LY), or about 1.0 ± 0.4 GDP (gross domestic product) per capita per LY. Therefore, a sum of not higher than US$85,000 (1.4 GDP per capita) is statistically sufficient to “purchase” an additional year of life – or, alternatively, to “rob” one year of life if taken away. So, 140% GDP per capita per life-year should be considered as the upper limit of prudent expenditure on healthcare and safety. The result is in excellent correspondence with the existing healthcare policies.

Highlights

Safety consumes resources; resources are limited

Therefore, excessive safety expenditure claims more life than it saves

Prudent safety expenditure is up to 140% GDP per capita per life-year
Exploring the genetic overlap of suicide-related behaviors and substance use disorders
Authors: Colbert Sarah M.C. , Hatoum Alexander S. , Shabalin Andrey , Coon Hilary , Nelson Elliot C. , Agrawal Arpana , Docherty Anna R. , Johnson Emma C.
Published: April 2021

Background

Suicide-related behaviors are heterogeneous and transdiagnostic, and may demonstrate varying levels of genetic overlap with different substance use disorders (SUDs).

Methods

We used linkage disequilibrium score regression, genomic structural equation models, and Mendelian Randomization to examine the genetic relationships between several SUDs and suicide-related behaviors. Our analyses incorporated summary statistics from the largest genome-wide association studies (GWAS) of problematic alcohol use (PAU), the Fagerström Test for Nicotine Dependence (FTND), cannabis use disorder (CUD), and opioid use disorder (OUD; Ns ranging from 46,213-435,563) and GWAS of ever self-harmed, suicide attempt, and suicide death (Ns ranging from 18,223-117,733). We also accounted for genetic liability to depression (N=500,199) and risk tolerance (N=315,894).

Results

Suicide-related behaviors were significantly genetically correlated with each other and each SUD, but there was little evidence of causal relationships between the traits. Simultaneously correlating a common SUD factor with each specific suicide indicator while controlling for depression and risk tolerance revealed significant, positive genetic correlations between the SUD factor and suicide-related behaviors (rg = 0.26-0.45, se=0.08-0.09). In the model, depression’s association with suicide death (β = 0.42, se = 0.06) was weaker compared to ever-self harmed and suicide attempt (β = 0.58, se=0.05 and β = 0.50, se=0.06, respectively).

Discussion

We identify a general level of genetic overlap between SUDs and suicide-related behaviors which is independent of depression and risk tolerance. Additionally, our findings suggest that genetic and behavioral contributions to suicide death may somewhat differ from non-lethal suicide-related behaviors.
mRNA vaccination compared to infection elicits an IgG-predominant response with greater SARS-CoV-2 specificity and similar decrease in variant spike recognition
Authors: Röltgen Katharina , Nielsen Sandra C. A. , Arunachalam Prabhu S. , Yang Fan , Hoh Ramona A. , Wirz Oliver F. , Lee Alexandra S. , Gao Fei , Mallajosyula Vamsee , Li Chunfeng , Haraguchi Emily , Shoura Massa J. , Wilbur James L. , Wohlstadter Jacob N. , Davis Mark M. , Pinsky Benjamin A. , Sigal George B. , Pulendran Bali , Nadeau Kari C. , Boyd Scott D.
Published: April 2021

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, new vaccine strategies including lipid nanoparticle delivery of antigen encoding RNA have been deployed globally. The BioNTech/Pfizer mRNA vaccine BNT162b2 encoding SARS-CoV-2 spike protein shows 95% efficacy in preventing disease, but it is unclear how the antibody responses to vaccination differ from those generated by infection. Here we compare the magnitude and breadth of antibodies targeting SARS-CoV-2, SARS-CoV-2 variants of concern, and endemic coronaviruses, in vaccinees and infected patients. We find that vaccination differs from infection in the dominance of IgG over IgM and IgA responses, with IgG reaching levels similar to those of severely ill COVID-19 patients and shows decreased breadth of the antibody response targeting endemic coronaviruses. Viral variants of concern from B.1.1.7 to P.1 to B.1.351 form a remarkably consistent hierarchy of progressively decreasing antibody recognition by both vaccinees and infected patients exposed to Wuhan-Hu-1 antigens.
Detecting Pathogen-Associated RNA via Piecewise Isothermal Testing achieving Sample-to-Result Integration
Authors: Banerjee Saptarshi , Biswas Sujay Kumar , Kedia Nandita , Sarkar Rakesh , De Aratrika , Mitra Suvrotoa , Roy Subhanita , Bandopadhyay Aditya , Banerjee Indranath , Goswami Ritobrata , Dutta Shanta , Chawla-Sarkar Mamta , Chakraborty Suman , Mondal Arindam
Published: April 2021

We report a novel piece-wise isothermal nucleic acid test (PINAT) for diagnosing pathogen-associated RNA that embeds an exclusive DNA-mediated specific probing reaction with the backbone of an isothermal reverse-transcription cum amplification protocol as a unified single-step procedure. This single step sample-to-result test method has been seamlessly integrated in an inexpensive, scalable, pre-programmable and portable instrument, resulting in a generic platform technology for detecting nucleic acid from a wide variety of pathogens. The test exhibited high sensitivity and specificity of detection when assessed using 200 double-blind patient samples for detecting SARS-CoV-2 infection conducted by the Indian Council of Medical Research (ICMR), reporting a positive and negative percent agreement of 94.6% and 98% respectively. We also established its efficacy in detecting influenza-A infection, performing the diagnosis at the point of collection with uncompromised detection rigor. The envisaged trade-off between advanced laboratory-based procedures with the elegance of common rapid tests renders the innovation to be ideal for deployment in resource-limited settings towards catering the needs of the underserved.
Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals
Authors: Kustin Talia , Harel Noam , Finkel Uriah , Perchik Shay , Harari Sheri , Tahor Maayan , Caspi Itamar , Levy Rachel , Leschinsky Michael , Dror Shifra Ken , Bergerzon Galit , Gadban Hala , Gadban Faten , Eliassian Eti , Shimron Orit , Saleh Loulou , Ben-Zvi Haim , Amichay Doron , Ben-Dor Anat , Sagas Dana , Strauss Merav , Avni Yonat Shemer , Huppert Amit , Kepten Eldad , Balicer Ran D. , Nezer Doron , Ben-Shachar Shay , Stern Adi
Published: April 2021

The SARS-CoV-2 pandemic has been raging for over a year, creating global detrimental impact. The BNT162b2 mRNA vaccine has demonstrated high protection levels, yet apprehension exists that several variants of concerns (VOCs) can surmount the immune defenses generated by the vaccines. Neutralization assays have revealed some reduction in neutralization of VOCs B.1.1.7 and B.1.351, but the relevance of these assays in real life remains unclear. We performed a case-control study that examined the distribution of SARS-CoV-2 variants observed in infections of vaccinated individuals (“breakthrough cases”) and matched infections of unvaccinated individuals. We hypothesized that if there is lower vaccine effectiveness against one of the VOCs, its proportion among the breakthrough cases should be higher than among unvaccinated cases. Our results show that vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1). Those who tested positive between two weeks after the first dose and one week after the second dose, were disproportionally infected by B.1.1.7 (odds ratio of 26:10), suggesting reduced vaccine effectiveness against both VOCs at particular time windows following vaccination. Nevertheless, the B.1.351 incidence in Israel to-date remains low and vaccine effectiveness remains high among those fully vaccinated. These results overall suggest that vaccine breakthrough infection may be more frequent with both VOCs, yet a combination of mass-vaccination with two doses coupled with non-pharmaceutical interventions control and contain their spread.
Utility of Automated Data-adaptive Propensity Score Method for Confounding by Indication in Comparative Effectiveness Study in Real World Medicare and Registry Data
Authors: Kumamaru Hiraku , Jalbert Jessica J. , Nguyen Louis L. , Williams Lauren A , Miyata Hiroaki , Setoguchi Soko
Published: April 2021

Background

Confounding by indication is a serious threat to comparative studies using real world data. We assessed the utility of automated data-adaptive analytic approach for confounding adjustment when both claims and clinical registry data are available.

Methods

We used a comparative study example of carotid artery stenting (CAS) vs. carotid endarterectomy (CEA) in 2005-2008 when CAS was only indicated for patients with high surgical risk. We included Medicare beneficiaries linked to the Society for Vascular Surgery’s Vascular Registry >65 years old undergoing CAS/CEA. We compared hazard ratios (HRs) for death while adjusting for confounding by combining various 1) Propensity score (PS) modeling strategies (investigator-specified [IS-PS] vs. automated data-adaptive [ada-PS]); 2) data sources (claims-only, registry-only and claims-plus-registry); and 3) PS adjustment approaches (matching vs. quintiles-adjustment with/without trimming). An HR of 1.0 was a benchmark effect estimate based on CREST trial.

Results

The cohort included 1,999 CAS and 3,255 CEA patients (mean age 76). CAS patients were more likely symptomatic and at high surgical risk, and experienced higher mortality (crude HR=1.82 for CAS vs. CEA). HRs from PS-quintile adjustment without trimming were 1.48 and 1.52 for claims-only IS-PS and ada-PS, 1.51 and 1.42 for registry-only IS-PS and ada-PS, and 1.34 and 1.23 for claims-plus-registry IS-PS and ada-PS, respectively. Estimates from other PS adjustment approaches showed similar patterns.

Conclusions

In a comparative effectiveness study of CAS vs. CEA with severe confounding by indication, ada-PS performed better than IS-PS in general, but both claims and registry data were needed to adequately control for bias.
The demographic and geographic impact of the COVID pandemic in Bulgaria and Eastern Europe in 2020
Authors: Rangachev Antoni , Marinov Georgi K. , Mladenov Mladen
Published: April 2021

Background

The COVID-19 pandemic followed a unique trajectory in Eastern Europe compared to other heavily affected regions, with most countries there only experiencing a major surge of cases and deaths towards the end of 2020 after a relatively uneventful first half of the year. However, the consequences of that surge have not received as much attention as the situation in Western countries. Bulgaria, even though it has been one of the most heavily affected countries, has been one of those neglected cases.

Methods

We use mortality and mobility data from Eurostat, official governmental and other sources to examine the development and impact of the COVID-19 pandemic in Bulgaria and other European countries.

Results

We find a very high level of excess mortality in Eastern European countries measured by several metrics including excess mortality rate (EMR), P-scores and potential years of life lost. By the last metric Eastern Europe emerges as the hardest hit region by the pandemic in Europe in 2020. With a record EMR at ∼0.25% and a strikingly large and mostly unique to it mortality rate in the working age demographics, Bulgaria emerges as one of the most affected countries in Eastern Europe. The high excess mortality in Bulgaria correlates with insufficient intensity of testing and with delayed imposition of “lockdown” measures. We also find major geographic and demographic disparities within the country, with considerably lower mortality observed in major cities relative to more remote areas (likely due to disparities in the availability of medical resources). Analysis of the course of the epidemic revealed that individual mobility measures were predictive of the eventual decline in cases and deaths. However, while mobility declined as a result of the imposition of a lockdown, it already trended downwards before such measures were introduced, which resulted in a reduction of deaths independent of the effect of restrictions.

Conclusions

Large excess mortality and high numbers of potential years of life lost are observed as a result of the COVID pandemic in Bulgaria, as well as in several other countries in Eastern Europe. Significant delays in the imposition of stringent mobility-reducing measures combined with a lack of medical resources likely caused a substantial loss of life, including in the working age population.
Postoperative morbidity after liver resection- A Systemic review, meta-analysis, and metaregression of factors affecting them
Authors: Vasavada Bhavin , Patel Hardik
Published: April 2021

Aim of the study

This systemic review and meta-analysis aimed to analyze post-operative morbidity after liver resection, and also study various factors associated with mortality via metaregression analysis.

Material and Methods

PubMed, Cochrane Library, Embase, google scholar, web of science with keywords like ‘liver resection”; “mortality”;” hepatectomy”. Weighted percentage post-operative morbidities were analyzed. Meta-analysis and meta-regression were done by the DerSimonian-Liard random effect model. Heterogeneity was assessed using the Higgins I2 test. Publication bias was assessed using a funnel plot. Funnel plot asymmetry was evaluated by Egger’s test. Morbidity was defined as any postoperative morbidity mentioned.

Results

A total of 46 studies was included in the final analysis. Total 45771 patients underwent liver resections. 16111 patients experienced complications during the postoperative period. Weighted post-operative morbidity was 30.2% (95 % C.I. 24.8-35.7%). Heterogeneity was high with I2 99.46% and p-value <0.01. On univariate analysis, major liver resections were significantly associated with heterogeneity. (p=0.024). However, residual heterogeneity was still high with I2 98.62%, p<0.001. So, multifactor metaregression analysis major hepatectomy (p<0.001), Open hepatectomy (p=0.001), cirrhotic liver (p=0.002), age (p<0.001), blood loss (p<0.001), and colorectal metastasis (p<0.001) independently associated with postoperative morbidity. Residual heterogeneity was moderate I2= 39.9% and nonsignificant p=0.189.

Conclusion

Liver resection is associated with high postoperative morbidity and various factors like major hepatectomy, Open hepatectomy, cirrhotic liver, blood loss, and colorectal metastasis were associated with morbidity and responsible for heterogeneity across the studies.
Machine Learning based COVID-19 Diagnosis from Blood Tests with Robustness to Domain Shifts
Authors: Roland Theresa , Böck Carl , Tschoellitsch Thomas , Maletzky Alexander , Hochreiter Sepp , Meier Jens , Klambauer Günter
Published: April 2021

We investigate machine learning models that identify COVID-19 positive patients and estimate the mortality risk based on routinely acquired blood tests in a hospital setting. However, during pandemics or new outbreaks, disease and testing characteristics change, thus we face domain shifts. Domain shifts can be caused, e.g., by changes in the disease prevalence (spreading or tested population), by refined RT-PCR testing procedures (taking samples, laboratory), or by virus mutations. Therefore, machine learning models for diagnosing COVID-19 or other diseases may not be reliable and degrade in performance over time. To countermand this effect, we propose methods that first identify domain shifts and then reverse their negative effects on the model performance. Frequent re-training and reassessment, as well as stronger weighting of more recent samples, keeps model performance and credibility at a high level over time. Our diagnosis models are constructed and tested on large-scale data sets, steadily adapt to observed domain shifts, and maintain high ROC AUC values along pandemics.
Living Shorelines Achieve Functional Equivalence to Natural Fringe Marshes across Multiple Ecological Metrics
Authors: Isdell Robert E. , Bilkovic Donna Marie , Guthrie Amanda G. , Mitchell Molly M. , Chambers Randolph M. , Leu Matthias , Hershner Carlton
Published: April 2021

Nature-based features provide a welcome class of adaptations to promote ecological resilience in the face of climate change. Along coastlines, living shorelines are among the preferred adaptation strategies to both reduce erosion and provide ecological functions. As an alternative to shoreline armoring, living shorelines are viewed favorably among coastal managers, wetlands boards, and some private property owners, but they have yet to undergo a thorough examination of how their levels of ecosystem functions compare to their closest natural counterpart: fringing marshes. Here, we provide a synthesis of results from a multi-year, large-spatial-scale study in which we compared numerous ecological metrics measured in thirteen pairs of living shorelines and natural fringing marshes throughout coastal Virginia, USA. Overall, we found that living shorelines were functionally equivalent to natural marshes in nearly all measured aspects, except for a lag in sediment composition. These data support the prioritization of living shorelines as a coastal adaptation strategy.
Pathological changes induced by Alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice
Authors: Lam Suzanne , Hérard Anne-Sophie , Boluda Susana , Petit Fanny , Eddarkaoui Sabiha , Cambon Karine ,   The Brainbank Neuro-CEB Neuropathology Network, Picq Jean-Luc , Buée Luc , Duyckaerts Charles , Haïk Stéphane , Dhenain Marc
Published: April 2021

Alzheimer’s disease (AD) is characterized by intracerebral accumulations of extracellular amyloid-β (Aβ) plaques and intracellular tau pathology that spread in the brain. Tau lesions occur in the form of neuropil threads, neurofibrillary tangles, and neuritic plaquesi.e.tau aggregates within neurites surrounding Aβ deposits. The cascade of events linking these lesions and synaptic or memory impairments are still debated. Intracerebral infusion of human AD brain extracts in Aβ plaque-bearing mice that do not overexpress pathological tau proteins induces tau pathologies following heterotopic seeding of mouse tau protein. There is however little information regarding the downstream events including synaptic or cognitive repercussions of tau pathology induction in these models. In the current study, human AD brain extracts (ADbe) and control-brain extracts (Ctrlbe) were infused in the hippocampus of Aβ plaque-bearing APPswe/PS1dE9mice. Memory, synaptic density, as well as Aβ plaque and tau aggregate loads, microgliosis, astrogliosis at the inoculation site and in connected regions (perirhinal/entorhinal cortex) were evaluated 4 and 8 months post-inoculation. ADbeinoculation induced memory deficit. It increased deposition of Aβ plaques close to the inoculation site. Tau pathology was also induced in ADbe-inoculated mice. Neuropil threads and neurofibrillary tangles occurred next to the inoculation site and spread to connected regions notably the perirhinal/entorhinal cortex. Neuritic plaque pathology was detected in both ADbe- and Ctrlbe- inoculated animals but ADbeinoculation increased the severity close and at distance of the inoculation site. Finally, ADbeinoculation reduced synaptic density close to the inoculation site and in connected regions as the perirhinal/entorhinal cortex. Synaptic impairments were correlated with increased severity of neuritic plaques but not of other tau lesions or Aβ lesions, which suggests that neuritic plaques are a culprit for synaptic loss. Synaptic density was also associated with microglial load.

Graphical abstract
New distributional opportunities with niche innovation in Eurasian snowfinches
Authors: Cobos Marlon E , Cheng Yalin , Song Gang , Lei Fumin , Peterson A. Townsend
Published: April 2021

This study explores the evolutionary history of ecological niche characters in the Eurasian snowfinch lineage. Specifically, we use new analytical approaches to reconstruct ecological niche evolution, taking uncertainty in knowledge of the ecological niche limits into account. We found an overall pattern of niche conservatism in relation to both temperature and precipitation characteristics of niches, but for one dramatic niche evolution event, inMontifringilla nivalis. Interestingly, this species is also that which has by far the broadest geographic distribution among snowfinches. We conclude that an evolutionary change in niche characteristics perhaps withinM. nivalis(i.e., present in some and not all of its populations) made possible the broad, westward range expansion of that species, thus changing the distributional potential of the snowfinch lineage dramatically.
Characterising contact in disease outbreaks via a network model of spatial-temporal proximity
Authors: Myall Ashleigh , Peach Robert L. , Wan Yu , Mookerjee Siddharth , Jauneikaite Elita , Bolt Frankie , Price James , Davies Frances , Weiße Andrea Y. , Holmes Alison , Barahona Mauricio
Published: April 2021

Contact tracing is a key tool in epidemiology to identify and control outbreaks of infectious diseases. Existing contact tracing methodologies produce contact maps of individuals based on a binary definition of contact which can be hampered by missing data and indirect contacts. Here, we present a Spatial-temporal Epidemiological Proximity (StEP) model to recover contact maps in disease outbreaks based on movement data. The StEP model accounts for imperfect data by considering probabilistic contacts between individuals based on spatial-temporal proximity of their movement trajectories, creating a robust movement network despite possible missing data and unseen transmission routes. Using real-world data we showcase the potential of StEP for contact tracing with outbreaks of multidrug-resistant bacteria and COVID-19 in a large hospital group in London, UK. In addition to the core structure of contacts that can be recovered using traditional methods of contact tracing, the StEP model reveals missing contacts that connect seemingly separate outbreaks. Comparison with genomic data further confirmed that these recovered contacts indeed improve characterisation of disease transmission and so highlights how the StEP framework can inform effective strategies of infection control and prevention.
Statistical Design and Analysis of Diagnostic Tests for Mutating Viruses
Authors: Han Yang , Sun Yujia , Hsu Jason C. , House Thomas , Gent Nick , Hall Ian
Published: April 2021

As the SARS-CoV-2 virus mutates, mutations harboured in patients become increasingly diverse. Patients classified into two strains may have overlapping non-variant-defining mutations.

Mutation calling by sequencing is relative to a reference genome. As SARS-CoV-2 mutates, tracking emerging mutant strains may become increasingly problematic if the reference genome remains Wuhan-Hu-1, because the comparison then becomes indirect: current dominant strain relative to Wuhan-Hu-1 versus emerging strain relative to Wuhan-Hu-1.

The original Thermo Fisher’s TaqPath PCR test, on which the UK has standardized national testing of SARS-CoV-2 primarily, targets Wuhan-Hu-1. PCR targets appear readily updated, as TaqPath 2.0 now targets both currently known and future SARS-CoV-2 mutations, probing the N gene and ORF1ab but not the S gene, with 8 probes instead of the original 3 probes. Going forward, our statistical method can more directly compare current wildtype versus emerging mutants, since our new method can use any pair of probes updated to probe the current wildtype and anticipated mutations.

The fact that patients harbour mixtures of mutations allows our statistical methods to potentially catch emerging mutants. Given a PCR test which targets the current dominant strain (current wildtype), our statistical method can potentially directly differentiate the current wildtype from an emerging strain.
Metabolic and muscle-derived serum biomarkers define CHCHD10-linked late-onset spinal muscular atrophy
Authors: Järvilehto Julius , Harjuhaahto Sandra , Palu Edouard , Auranen Mari , Kvist Jouni , Zetterberg Henrik , Koskivuori Johanna , Lehtonen Marko , Saukkonen Anna Maija , Jokela Manu , Ylikallio Emil , Tyynismaa Henna
Published: April 2021

Objective

To characterize serum biomarkers in mitochondrial CHCHD10-linked spinal muscular atrophy Jokela type (SMAJ) for disease monitoring and for understanding of pathogenic mechanisms.

Methods

We collected serum samples from a cohort of 49 SMAJ patients, all carriers of the heterozygous c.197G>T p.G66V variant inCHCHD10. As controls, we used age- and sex-matched serum samples obtained from Helsinki Biobank. Neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were measured with Single molecule array (Simoa), and fibroblast growth factor 21 (FGF-21) and growth differentiation factor 15 (GDF-15) with enzyme-linked immunosorbent assay. For nontargeted serum metabolite profiling, samples were analyzed with liquid chromatography–high resolution mass spectrometry. Disease severity was evaluated retrospectively by calculating a symptom-based score.

Results

Axon degeneration marker NfL was unexpectedly not altered in the serum of SMAJ patients, whereas astrocytic activation marker GFAP was slightly decreased. Creatine kinase was elevated in most patients, in particular males. We identified six metabolites that were significantly altered in SMAJ patients’ serum compared to controls: increased creatine and pyruvate, and decreased creatinine, taurine, N-acetyl-carnosine and succinate. Creatine correlated with disease severity. Altered pyruvate and succinate indicated a metabolic response to mitochondrial dysfunction, however, lactate or mitochondrial myopathy markers FGF-21 or GDF-15 were not changed.

Conclusions

Biomarkers of muscle mass and damage are altered in SMAJ serum, indicating a role for skeletal muscle in disease pathogenesis in addition to neurogenic damage. Despite the minimal mitochondrial pathology in skeletal muscle, signs of a metabolic shift can be detected in the serum of SMAJ patients.
Improved diagnosis of SARS-CoV-2 by using Nucleoprotein and Spike protein fragment 2 in quantitative dual ELISA tests
Authors: Verissimo Carolina De M. , O’Brien Carol , López Corrales Jesús , Dorey Amber , Cwiklinski Krystyna , Lalor Richard , Doyle Jack M. , Field Stephen , Masterson Claire , Martinez Eduardo Ribes , Hughes Gerry , Bergin Colm , Walshe Kieran , McNicholas Bairbre , Laffey John G. , Dalton John P. , Kerr Colm , Doyle Sean
Published: April 2021

The novel Coronavirus, SARS-CoV-2, is the causative agent of the 2020 worldwide coronavirus pandemic. Antibody testing is useful for diagnosing historic infections of a disease in a population. These tests are also a helpful epidemiological tool for predicting how the virus spreads in a community, relating antibody levels to immunity and for assessing herd immunity. In the present study, SARS-CoV-2 viral proteins were recombinantly produced and used to analyse serum from individuals previously exposed, or not, to SARS-CoV-2. The nucleocapsid (Npro) and Spike subunit 2 (S2Frag) proteins were identified as highly immunogenic, although responses to the former were generally greater. These two proteins were used to develop two quantitative ELISA assays that when used in combination resulted in a highly reliable diagnostic test. Npro and S2Frag-ELISAs could detect at least 10% more true positive COVID-19 cases than the commercially available ARCHITECT test (Abbott). Moreover, our quantitative ELISAs also show that specific antibodies to SARS-CoV-2 proteins tend to wane rapidly even in patients that had developed severe disease. As antibody tests complement COVID-19 diagnosis and determine population-level surveillance during this pandemic, the alternative diagnostic we present in this study could play a role in controlling the spread of the virus.
Evaluating and optimizing COVID-19 vaccination policies: a case study of Sweden
Authors: Sjödin Henrik , Rocklöv Joacim , Britton Tom
Published: April 2021

We evaluate the efficiency of vaccination scenarios for COVID-19 by analysing a data-driven mathematical model. Healthcare demand and incidence are investigated for different scenarios of transmission and vaccination schemes. Our results suggest that reducing the transmission rate affected by invading virus strains, seasonality and the level of prevention, is most important. Second to this is timely vaccine deliveries and expeditious vaccination management. Postponing vaccination of antibody-positive individuals reduces also the disease burden, and once risk groups have been vaccinated, it is best to continue vaccinating in a descending age order.
GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme
Authors: Sherpa Dawafuti , Chrustowicz Jakub , Qiao Shuai , Langlois Christine R. , Hehl Laura A. , Gottemukkala Karthik Varma , Hansen Fynn M. , Karayel Ozge , von Gronau Susanne , Prabu J. Rajan , Mann Matthias , Alpi Arno F. , Schulman Brenda A.
Published: April 2021

To achieve precise cellular regulation, E3 ubiquitin ligases must be configured to match substrate quaternary structures. Here, by studying the yeast GID complex, mutation of which isGlucose-InducedDegradation deficient, we discover supramolecular chelate assembly as an E3 ligase strategy for targeting an oligomeric substrate. Cryo EM structures show that to bind the tetrameric substrate fructose-1,6-bisphosphatase (Fbp1), two otherwise functional GID E3s assemble into a 20-protein Chelator-GIDSR4, which resembles an organometallic supramolecular chelate. The Chelator-GIDSR4assembly avidly binds multiple Fbp1 degrons and positions Fbp1 so that its protomers are simultaneously ubiquitylated at lysines near its allosteric and substrate binding sites. Significantly, key structural and biochemical features -including capacity for supramolecular assembly - are preserved in the human ortholog, the CTLH E3. Based on our integrative structural, biochemical and cell biological data, we propose that higher-order E3 ligase assembly generally underlies multipronged targeting, capable of simultaneously incapacitating multiple protomers and functionalities of oligomeric substrates.
Invasive grass litter suppresses native species and promotes disease
Authors: Benitez Liliana , Kendig Amy E. , Adhikari Ashish , Clay Keith , Harmon Philip F. , Holt Robert D. , Goss Erica M. , Flory S. Luke
Published: April 2021

Plant litter can alter ecosystems and promote plant invasions by changing resource acquisition, depositing toxins, and transmitting microorganisms to living plants. Transmission of microorganisms from invasive litter to live plants may gain importance as invasive plants accumulate pathogens over time since introduction. It is unclear, however, if invasive plant litter affects native plant communities by promoting disease.Microstegium vimineumis an invasive grass that suppresses native populations, in part through litter production, and has accumulated leaf spot diseases since its introduction to the U.S. In a greenhouse experiment, we evaluated howM. vimineumlitter and accumulated pathogens mediated resource competition with the native grassElymus virginicus. Resource competition reduced biomass of both species and liveM. vimineumincreased disease incidence on the native species.Microstegium vimineumlitter also promoted disease on the native species, suppressed establishment of both species, and reduced biomass ofM. vimineum. Nonetheless, interference competition from litter had a stronger negative effect on the native species, increasing the relative abundance ofM. vimineum. Altogether, invasive grass litter suppressed both species, ultimately favoring the invasive species in competition, and increased disease incidence on the native species.