bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival Comparison Between Open and Thoracoscopic Upfront Esophagectomy in Patients With Esophageal Squamous Cell Carcinoma
Authors: Wang Bing-Yen , Lin Ching-Hsiung , Wu Shiao-Chi , Chen Hui-Shan
Published: June 2021

Background:

The survival outcomes of patients with esophageal squamous cell carcinoma (ESCC) after open or thoracoscopic upfront esophagectomy remained unclear.

Objective:

The aim of this retrospective study was to compare overall survival between open and thoracoscopic esophagectomy for ESCC patients without neoadjuvant chemodatiotherapy (CRT).

Methods:

The Taiwan Cancer Registry was investigated for ESCC cases from 2008 to 2016. We enrolled 2053 ESCC patients receiving open (n = 645) or thoracoscopic (n = 1408) upfront esophagectomy. One-to-two propensity score matching between the two groups was performed. Stage-specific survival was compared before and after propensity score matching. Univariate analysis and multivariate analysis were used to identify risk factors.

Results:

After one-to-two propensity score matching, a total of 1299 ESCC patients with comparable clinic-pathologic features were identified. There were 433 patients in the open group and 866 patients in the thoracoscopic group. The 3-year overall survival of matched patients in the thoracoscopic group was better than that of matched patients in the open group (58.58% vs 47.62%, P = 0.0002). Stage-specific comparisons showed thoracoscopic esophagectomy is associated with better survival than open esophagectomy in patients with pathologic I/II ESCC. In multivariate analysis, surgical approach was still an independent prognostic factor before and after one-to-two propensity score matching.

Conclusion:

This propensity-matched study revealed that thoracoscopic esophagectomy could provide better survival than open esophagectomy in ESCC patients without neoadjuvant CRT.
Risk of Severe Maternal Morbidity After Bariatric Surgery
Authors: Auger Nathalie , Ukah U. Vivian , Monnier Maeva , Bilodeau-Bertrand Marianne , Dayan Natalie
Published: June 2021

Objective:

We assessed whether bariatric surgery before pregnancy lowers the risk of severe maternal morbidity to a level comparable to no obesity.

Summary of Background Data:

Obesity is a risk factor for severe maternal morbidity, but the potential for bariatric surgery to reduce the risk has not been studied.

Methods:

We analyzed a retrospective cohort of 2,412,075 deliveries between 1989 and 2019 in Quebec, Canada. The main exposure measures were bariatric surgery before pregnancy and obesity without bariatric surgery, compared with no obesity. The outcome was severe maternal morbidity, a composite of life-threatening pregnancy complications. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between bariatric surgery and severe maternal morbidity, adjusted for maternal characteristics.

Results:

A total of 2654 deliveries (0.1%) were in women who had bariatric surgery, and 70,041 (29.0 per 1000) were in women who had severe maternal morbidity. Risk of severe maternal morbidity was not significantly elevated for bariatric surgery (RR 1.20; 95% CI 0.98–1.46), but was greater for obesity compared with no obesity (RR 1.60; 95% CI 1.55–1.64). Bariatric surgery was not associated with morbidities such as severe preeclampsia, sepsis, and cardiac complications compared with no obesity, but obesity was associated with elevated risks of these and other severe morbidities. Bariatric surgery was associated, however, with intensive care unit admission, compared with no obesity.

Conclusions:

Pregnant women with prior bariatric surgery have similar risks as nonobese women for most types of severe maternal morbidity, except for intensive care unit admission.
Palliative and Supportive Care Consultation for Patients With Malignant Gastrointestinal Obstruction is Associated With Broad Interdisciplinary Management
Authors: Blumenthaler Alisa N. , Bruera Eduardo , Badgwell Brian D.
Published: June 2021

Objective:

The aim of this study was to assess rates of palliative care (PC) involvement in the care of patients with malignant gastrointestinal obstruction (GIO) and its influence on interdisciplinary team involvement.

Background:

Malignant GIO is an advanced oncologic diagnosis with associated poor prognosis. Data regarding PC and interdisciplinary team involvement in these patients is lacking.

Methods:

We identified consecutive surgical consultations for GIO in cancer patients at a single institution from August 2017 to July 2019. Clinical characteristics were collected. Rates of PC consultation, ACP discussion, code status change to do not resuscitate, and interdisciplinary service consultation were evaluated.

Results:

We identified 200 patients with consultations for GIO, of whom 114 (57%) had malignant GIO and were included in our study. Of these patients, 95 (83%) had stage IV disease; 68 (60%) had peritoneal metastasis, and 70 (61%) had other intra-abdominal recurrence or metastasis. PC consultation was obtained in 69 patients (61%). PC consultation was associated with higher rates of ACP discussion (64% vs 29%; P < 0.001), code status change to do not resuscitate (30% vs 2%; P < 0.001), nonsurgical procedure (46% vs 11%; P < 0.001), discharge to hospice (30% vs 7%; P < 0.001), and involvement of spiritual care (48% vs 22%; P = 0.01), social work (77% vs 42%, P < 0.001), psychology/psychiatry (42% vs 4%, P < 0.001), nutrition (86% vs 62%, P = 0.006), physical therapy (54% vs 31%, P = 0.02), and occupational therapy (42% vs 16%, P = 0.004).

Conclusions:

PC consultation benefits patients with malignant GIO by facilitating comprehensive interdisciplinary care, ACP discussions, and transition to hospice care, where appropriate. Diagnosis of malignant GIO should be a trigger for PC consultation or, in facilities with limited PC resources, consideration of deliberately broad interdisciplinary consultation.
Surgical Residents at the Forefront of the COVID-19 Pandemic
Authors: Samuel Nardin
Published: June 2021

The COVID-19 pandemic has led many of us to re-evaluate our approaches to disaster management, reflect on our experiences, and be reminded of the strong resolve for our work. This article details a resident's perspective on redeployment of surgical residents to the COVID-19 frontline setting, using the example of the COVID-19 intensive care unit. Redeployment during a pandemic brings the unique opportunity to collaborate with colleagues on the frontlines and learn alongside one another about the evolving management of this disease. During this ongoing pandemic, it is incumbent upon us as clinicians to work together in a multidisciplinary manner and reflect on ways this pandemic impacts the delivery of patient care.
Early Drain Removal is Safe in Patients With Low or Intermediate Risk of Pancreatic Fistula After Pancreaticoduodenectomy
Authors: Dai Menghua , Liu Qiaofei , Xing Cheng , Tian Xiaodong , Cao Feng , Tang Wenbo , Lv Shaocheng , Ma Yongsu , Zhang Dongxin , Kleeff Jorg , Yang Yinmo , Liu Rong , He Qiang , Li Fei , Li Guangming , Guo Junchao , Liao Quan , Zhao Yupei
Published: June 2021

Objective:

This multicenter randomized controlled trial was designed to test the hypothesis that early drain removal (EDR) could decrease the incidence of grade 2 to 4 complications for patients undoing pancreaticoduodenectomy (PD) with low or intermediate risk of postoperative pancreatic fistula (POPF).

Background:

The safety and effects of EDR on postoperative complications after PD are still controversial.

Methods:

A multicenter randomized controlled trial at 6 tertiary referral hospitals was carried out (NCT03055676). Patients who met the inclusion criteria, including drain amylase level less than 5000 U/L on postoperative day (POD) 1 and POD 3, and drain output less than 300 mL per day within 3 days after surgery, were enrolled. Patients were then randomized to the EDR group or the routine drain removal (RDR) group. In the EDR group, all drainage tubes were removed on POD3. In the RDR group, drainage tubes were removed on POD 5 or beyond. Primary outcome was the incidence of Clavien-Dindo grade 2 to 4 complications. Secondary outcomes were comprehensive complication index, grade B/C POPF, total medical expenses and postoperative in-hospital stay etc, within 90 days after surgery.

Results:

A total of 692 patients were screened, and 312 patients were eligible for randomization. Baseline characteristics were well balanced between the 2 groups and 96.8% of these 312 patients had low or intermediate risk of POPF, according to the 10-point fistula risk score. A total of 20.5% of the patients in the EDR group suffered at least 1 grade 2 to 4 complication, versus 26.3% in the RDR group (P = 0.229). Multi-variate analysis showed older age (>65 years old) and blood transfusion were independent risk factors for grade 2 to 4 complications. The rate of grade B/C POPF was low in either group (3.8% vs 6.4%, P = 0.305). The comprehensive complication index of the 2 groups was also comparable (20.9 vs 20.9, P = 0.253). Total medical expenses were not significantly different. Postoperative in-hospital stay was clinically similar (15 days vs 16 days, P = 0.010).

Conclusions:

Nearly half of the patients undergoing PD met the inclusion criteria, predicting low incidence of grade B/C POPF and major complications. EDR was safe in these patients but did not significantly decrease major complications.
Automated medical avatar animation for warfighter mission simulation
Authors: Pickle Nathan T. , Zehnbauer Timothy P. , Harrand Vincent J. , Zientara Gary P. , Zhou Xianlian , Roos Paulien E.
Published: June 2021

BACKGROUND

Virtual representations of human internal anatomy are important for military applications such as protective equipment design, injury severity prediction, thermal analysis, and physiological simulations. High-fidelity volumetric models based on imaging data are typically in static postures and difficult to use in simulations of realistic mission scenarios. This study aimed to investigate a hybrid approach to reposition medical avatars that preserves internal anatomy but allows rapid repositioning of full three-dimensional (3D) meshes.

METHODS

A software framework that accepts a medical avatar in a 3D tetrahedral mesh format representing 72 organs and tissues with an articulated skeleton was developed. The skeleton is automatically resized and associated to the avatar using rigging and skinning algorithms inspired by computer animation techniques. Military relevant motions were used for animations. A motion retargeting algorithm was implemented to apply animation to avatars of various sizes, and a motion blending algorithm was implemented to smoothly transition between movements. These algorithms were incorporated into a path generation tool that accepts initial, intermediate, and final coordinates of a multisegment action along with the specific motion for each segment to synthesize a realistic compound set of movements comprising the animation.

RESULTS

The developed pipeline for dynamic repositioning of medical avatars was demonstrated. Various complex motions were automatically animated. Retargeting was demonstrated on models of varying sizes. Movements along a path were animated to demonstrate smooth motion transitions. Animation of the full 3D avatar mesh ran in real time on a standard desktop personal computer. The repositioning algorithm successfully preserved the shape and volume of rigid structures such as bone.

CONCLUSION

The developed software leverages techniques from various disciplines to create a hybrid approach enabling real-time 3D mesh repositioning appropriate for use in simulated military missions using avatars containing a complete anatomy representation. The workflow is largely automated, enabling rapid evaluation of new mission scenarios.
Performance of a novel temporary arterial shunt in a military-relevant controlled hemorrhage swine model
Authors: Stigall Kyle S. , Sleeter Justin J. , Thomas Sarah B. , Schechtman David W. , Blough Perry E. , Rall Jason M. , Kauvar David S.
Published: June 2021

BACKGROUND

In military trauma, temporary vascular shunts restore arterial continuity until delayed vascular reconstruction, often for a period of hours. A novel US Air Force–developed trauma-specific vascular injury shunt (TS-VIS) incorporates an accessible side port for intervention or monitoring, which may improve patency under adverse hemodynamic conditions. Our objective was to evaluate TS-VIS patency in the setting of volume-limited resuscitation from hemorrhagic shock.

METHODS

Female swine (70–90 kg) underwent 30% hemorrhage and occlusion of the left external iliac artery for 30 minutes. Animals were allocated to one of three groups (n = 5 per group) by left external iliac artery treatment: Sundt shunt (SUNDT), TS-VIS with arterial pressure monitoring (TS-VIS), or TS-VIS with heparin infusion (10 μ/kg per hour, TS-VISHep). Animals were resuscitated with up to 3 U of whole blood to maintain a mean arterial pressure (MAP) of >60 mm Hg and were monitored for 6 hours. Bilateral femoral arterial flow was continuously monitored with transonic flow probes, and shunt thrombosis was defined as the absence of flow for greater than 5 minutes.

RESULTS

No intergroup differences in MAP or flow were observed at baseline or following hemorrhage. Animals were hypotensive at shunt placement (MAP, 35.5 ± 7.3 mm Hg); resuscitation raised MAP to >60 mm Hg by 26.5 ± 15.5 minutes. Shunt placement required 4.5 ± 1.8 minutes with no difference between groups. Four SUNDT thrombosed (three before 60 minutes). One SUNDT thrombosed at 240 minutes, and two TS-VIS and one TS-VISHep thrombosed between 230 and 282 minutes. Median patency was 21 minutes for SUNDT and 360 minutes for both TS-VIS groups (p = 0.04). While patent, all shunts maintained flow between 60% and 90% of contralateral.

CONCLUSION

The TS-VIS demonstrated sustained patency superior to the Sundt under adverse hemodynamic conditions. No benefit was observed by the addition of localized heparin therapy over arterial pressure monitoring by the TS-VIS side port.
Health Education Intervention for Patients Undergoing Placement of Percutaneous Nephrostomy Tube
Authors: Fernández Cacho Luis Manuel , Ayesa Arriola Rosa
Published: June 2021

PURPOSE:

The purpose of this study was to compare the economic impact (cost) of percutaneous nephrostomy (PCN) tube care in patients following an educational intervention to no intervention.

DESIGN:

A randomized controlled trial.

SUBJECTS AND SETTING:

The sample comprised 178 patients recruited between May 2017 and April 2019. The study setting was the Marqués de Valdecilla University Hospital located in Cantabria on the northern coast of Spain. Data were collected in the hospital's radiology department.

METHODS:

Participants were randomly allocated to 2 groups: an intervention group received an educational intervention that specifically addressed living with a PCN tube and a control group that received standard instruction. The intervention group received the educational intervention twice, before placement of the nephrostomy and at first tube change (6 weeks later). The main outcome variable was economic impact of the PCN, operationally defined as unscheduled or urgent visits and health care costs related to PCN tube placement.

RESULTS:

When compared to control group subjects, participants who received the educational intervention had fewer urgent (unscheduled) visits (1.9 vs 4.0; P = .004) and lower direct and indirect health care costs reflecting a savings of €5277 (approximately US $6257).

CONCLUSIONS:

The health education intervention reduced costs associated with these additional visits when compared to patients receiving standard postprocedural education.
Timing of cholecystectomy after percutaneous cholecystostomy for acute cholecystitis- A systematic review and meta-analysis
Authors: Vasavada Bhavin , Patel Hardik
Published: June 2021

Introduction

There is a controversy about the optimum timing of cholecystectomy after percutaneous cholecystostomy.

This systematic review and meta-analysis aimed to evaluate outcomes of early versus late cholecystectomy after percutaneous cholecystostomy.

Methods

The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and MOOSE guidelines. Heterogeneity was measured using Q tests and I2 statistics. The random-effects model was used. We evaluated cholecystectomy performed at different periods after percutaneous cholecystostomy within 72 hours or later, within or after one week or percutaneous cholecystostomy, within 10 days or after 10 days, less than 2 weeks or more than 2 weeks, less than 4 weeks or more than 4 weeks, less than 8 weeks or more than 8 weeks as per literature.

Results

Six studies including 18640 patients were included in the final analysis. There was no difference in overall complications within or after 72 hours cholecystectomy group, but mortality and biliary complications were significantly high in the less than 72 hours group (p=0.05 and 0.0002 respectively). There was no difference in mortality, overall complication, biliary tract complications in less than 1 week versus more than 1 week and less than 10 days versus more than 10 days group. Overall complications were significantly less in the less than 2 weeks group compared to the more than 2 weeks group. There was no difference in mortality and biliary tract complications between less than 2 weeks and more than 2 weeks group. Overall complication rate (risk ratio 0.67, p <0.0001), postoperative mortality (risk ratio 0.46, p=0.003), bile duct injury (risk ratio 0.62, p=0.01) was significantly less in earlier than 4-week group. Hospital stay was not significantly different between less than 4 weeks versus more than 4 weeks group. (Mean difference= -2.74, p=0.12). Ove all complication rates were significantly more in less than 8 weeks group. (Risk ratio 1.07, p=0.01). Hospital stay was significantly less in less than 8 weeks group. (Mean difference 0.87, p=0.01).

Conclusion

Early cholecystectomy preferably within 4 weeks after percutaneous cholecystostomy is preferable over late cholecystectomy.
Depression and Anxiety Symptoms among General Hospital Employees in need of Mental Health Treatment
Authors: Silva Nilson , Martins da Silva Anderson Sousa , Galvão Lucas Pequeno , Torales Julio , Ventriglio Antonio , Castaldelli-Maia João Mauricio , Baldassin Sergio
Published: June 2021

Background

Depression and anxiety are common and disabling mental disorders worldwide. It has been described a high prevalence of these disorders among health professionals.

Aim

This study aimed to investigate the association between occupation and depressive/anxiety symptoms, education levels, among professionals from a Brazilian General Hospital in need of mental health treatment.

Methods

This is a longitudinal twelve-years retrospective study, involving health professionals. Socio-demographic data were collected as well as two standardized scales for depression and anxiety symptoms.

Results

Data from 506 employees needing a mental health intervention have been described: mean age was 34.6 years, 46.2% of them worked in the administrative sector, 35.0% were nursing assistants, 7.5% were nursing technicians, 6.7% were nurses, and 4.5% reported other occupations. According to the ICD-10 criteria, the rates of diagnosis of depressive disorders and anxiety disorders were 60.9% and 37%, respectively.

Conclusions

The rate of depression and anxiety is higher among health professionals than the general population. Thus, specific programs of prevention based on resilience, continuing education and health promotion are needed.

Highlights

-

Although 53,9% of studied individuals did not mention any kind of areas of difficulty in the workplace, 32.8% reported difficulties with coworkers or bosses.

-

According to the ICD-10 criteria, diagnoses of depressive disorders (60.9%) and anxiety disorders (37%) were highly prevalent.

-

Nursing technicians and nursing assistants reported higher somatic cluster BDI scores than other professionals of technical staff, but they were less inclined to receive a psychiatric diagnosis.
The impact of co-circulating pathogens on SARS-CoV-2/COVID-19 surveillance: How concurrent epidemics may decrease true SARS-CoV-2 percent positivity
Authors: Kovacevic Aleksandra , Eggo Rosalind M. , Baguelin Marc , de Cellès Matthieu Domenech , Opatowski Lulla
Published: June 2021

Background

Circulation of non-SARS-CoV-2 respiratory viruses during the COVID-19 pandemic may alter quality of COVID-19 surveillance, with possible consequences for real-time analysis and delay in implementation of control measures. Here, we assess the impact of an increased circulation of other respiratory viruses on the monitoring of positivity rates of SARS-CoV-2 and interpretation of surveillance data.

Methods

Using a multi-pathogen Susceptible-Exposed-Infectious-Recovered (SEIR) transmission model formalizing co-circulation of SARS-CoV-2 and another respiratory we assess how an outbreak of secondary virus may inflate the number of SARS-CoV-2 tests and affect the interpretation of COVID-19 surveillance data. Using simulation, we assess to what extent the use of multiplex PCR tests on a subsample of symptomatic individuals can support correction of the observed SARS-CoV-2 percent positive during other virus outbreaks and improve surveillance quality.

Results

Model simulations demonstrated that a non-SARS-CoV-2 epidemic creates an artificial decrease in the observed percent positivity of SARS-CoV-2, with stronger effect during the growth phase, until the peak is reached. We estimate that performing one multiplex test for every 1,000 COVID-19 tests on symptomatic individuals could be sufficient to maintain surveillance of other respiratory viruses in the population and correct the observed SARS-CoV-2 percent positive.

Conclusions

This study highlights that co-circulating respiratory viruses can disrupt SARS-CoV-2 surveillance. Correction of the positivity rate can be achieved by using multiplex PCR, and a low number of samples is sufficient to avoid bias in SARS-CoV-2 surveillance.

COVID-19 surveillance indicators may be impacted by increased co-circulation of other respiratory viruses delaying control measure implementation. Continued surveillance through multiplex PCR testing in a subsample of the symptomatic population may play a role in fixing this problem.
COVID-19 antibody detection and assay performance using red cell agglutination
Authors: Srivastava Kshitij , West Kamille A , De Giorgi Valeria , Holbrook Michael R , Bovin Nicolai V. , Henry Stephen M , Flegel Willy A
Published: June 2021

Red cells can be labelled with peptides from the SARS-CoV-2 spike protein and used for serologic screening of SARS-CoV-2 antibodies. We evaluated 140 convalescent COVID-19 patients and 275 healthy controls using this C19-kodecyte assay. The analytical performance of the new assay was compared with a virus neutralizing assay and 2 commercial chemiluminescent antibody tests (Total assay and IgG assay, Ortho). The C19-kodecyte assay detected SARS-CoV-2 antibodies with a sensitivity of 92.8% and specificity of 96.3%, well within the minimum performance range required by FDA for EUA authorization of serologic tests. The Cohen’s kappa coefficient was 0.90 indicating an almost perfect agreement with the Total assay. The Pearson correlation coefficient was 0.20 with the neutralizing assay (0.49 with IgG, and 0.41 with Total assays). The limited correlation in assay reaction strengths suggested that the assays may detect different antibody specificities. Our easily scalable C19-kodecyte assay may vastly improve test capacity in blood typing laboratories using their routine setups for column agglutination technique.
Personal space Increases during the COVID-19 Pandemic in Response to Real and Virtual Humans
Authors: Holt Daphne J. , Zapetis Sarah , Babadi Baktash , Tootell Roger B. H.
Published: June 2021

Typically, people maintain a certain distance from others (“personal space”) during daily life, in a largely automatic, unconscious manner. However during the COVID-19 pandemic, social distancing recommendations led to deliberate expansions of personal space outside of intimate social circles. In the laboratory, personal space preferences are quite stable over repeated measurements. Here, we collected such measurements both before and during the pandemic in the same individuals, using both conventional and virtual reality-based techniques. We found that the size of personal space, and discomfort ratings in response to personal space intrusions, increased significantly during the COVID-19 pandemic, in response to both real humans and virtual “others”. Moreover, this increase in personal space requirements correlated with the perceived, not the actual, risk of being infected with COVID-19 – even in a virtual reality environment in which there was no possibility of infection. Thus, quantification of personal space may reveal some of the psychological effects of the pandemic, and subsequent progress towards recovery.
Impact of baseline SARS-CoV-2 antibody status on syndromic surveillance and the risk of subsequent Covid-19 – a prospective multicentre cohort study
Authors: Kohler Philipp , Güsewell Sabine , Seneghini Marco , Egger Thomas , Leal Onicio , Brucher Angela , Lemmenmeier Eva , Möller J. Carsten , Rieder Philip , Ruetti Markus , Stocker Reto , Vuichard-Gysin Danielle , Wiggli Benedikt , Besold Ulrike , Kuster Stefan P. , McGeer Allison , Risch Lorenz , Friedl Andrée , Vernazza Pietro , Kahlert Christian R.
Published: June 2021

Objectives

In a prospective healthcare worker (HCW) cohort, we assessed the risk of SARS-CoV-2 infection according to baseline serostatus.

Methods

Baseline serologies were performed among HCW from 23 Swiss healthcare institutions between June and September 2020, before the second COVID-19 wave. Participants answered weekly electronic questionnaires covering information about nasopharyngeal swabs (PCR/rapid antigen tests) and symptoms compatible with Coronavirus Disease 2019 (COVID-19). Screening of symptomatic staff by nasopharyngeal swabs was routinely performed in participating facilities. We compared numbers of positive nasopharyngeal tests and occurrence of COVID-19 symptoms between HCW with and without anti-nucleocapsid antibodies.

Results

A total of 4’818 HCW participated, whereof 144 (3%) were seropositive at baseline. We analysed 107’820 questionnaires with a median follow-up of 7.9 months. Median number of answered questionnaires was similar (24 vs. 23 per person, P=0.83) between those with and without positive baseline serology. Among 2’713 HCW with ≥1 SARS-CoV-2 test during follow-up, 3/67 (4.5%) seropositive individuals reported a positive result (one of whom asymptomatic), compared to 547/2646 (20.7%) seronegative participants, 12 of whom asymptomatic (risk ratio [RR] 0.22; 95% confidence interval [CI] 0.07 to 0.66). Seropositive HCWs less frequently reported impaired olfaction/taste (6/144, 4.2% vs. 588/4674, 12.6%, RR 0.33, 95%-CI: 0.15-0.73), chills (19/144, 13.2% vs. 1040/4674, 22.3%, RR 0.59, 95%-CI: 0.39-0.90), and limb/muscle pain (28/144, 19.4% vs. 1335/4674, 28.6%, RR 0.68 95%-CI: 0.49-0.95). Impaired olfaction/taste and limb/muscle pain also discriminated best between positive and negative SARS-CoV-2 results.

Conclusions

Having SARS-CoV-2 anti-nucleocapsid antibodies provides almost 80% protection against SARS-CoV-2 re-infection for a period of at least eight months.
Prevalence of uncoupling protein one genetic polymorphisms and their relationship with cardiovascular and metabolic health
Authors: Dinas Petros C. , Nintou Eleni , Vliora Maria , Sakellariou Paraskevi , Pravednikova Anna E. , Witkowicz Agata , Kachaev Zaur M. , Kerchev Victor V. , Larina Svetlana N. , Cotton James , Kowalska Anna , Gkiata Paraskevi , Bargiota Alexandra , Khachatryan Zaruhi A. , Hovhannisyan Anahit A. , Antonosyan Mariya A. , Margaryan Sona , Partyka Anna , Bogdanski Pawel , Szulinska Monika , Kregielska-Narozna Matylda , Czepczyński Rafał , Ruchała Marek , Tomkiewicz Anna , Yepiskoposyan Levon , Karabon Lidia , Shidlovskii Yulii , Metsios George S. , Flouris Andreas D.
Published: June 2021

The contribution ofUCP1single nucleotide polymorphisms (SNPs) to susceptibility for cardiometabolic pathologies (CMP) and their involvement in specific risk factors for these conditions varies across populations. We tested whetherUCP1SNPs A-3826G, A-1766G, Ala64Thr and A-112C are associated with the most common CMP (cardiovascular disease, hypertension, metabolic syndrome, and type-2 diabetes) and CMP risk factors. This case-control study included blood sample collection from 2,283 Caucasians (1,139 healthy; 1,144 CMP) across Armenia, Greece, Poland, Russia and United Kingdom for genotyping of the above-mentioned SNPs. We extended the results via a systematic review and meta-analysis, covering PubMed, Embase, and Cochrane Library databases. In Armenia the GA genotype and A allele of Ala64Thr were associated with ∼2-fold higher risk for CMP compared to the GG genotype or G allele, respectively (p<0.05). In Greece, A allele of Ala64Thr SNP decreased the risk of CMP by 39%. Healthy individuals with A-3826G GG genotype and carriers of mutant allele of A-112C and Ala64Thr had higher body mass index compared to those carrying other genotypes. In healthy Polish, higher waist-to-hip ratio (WHR) was observed in heterozygotes A-3826G compared to AA homozygotes. Heterozygosity of the A-112C and Ala64Thr SNPs was related to lower WHR in CMP individuals compared to wild type homozygotes (p<0.05). Meta-analysis in case-control studies showed no statistically significant odds ratios in different alleles across the four studied SNPs (p>0.05). Thus, we conclude that the studied SNPs could be associated with the most common CMP and their risk factors in some populations.
EFFECTIVENESS OF ACAMPROSATE FOR TINNITUS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF CLINICAL TRIALS
Authors: Person Osmar Clayton , Angélico Júnior Fernando Veiga , Santos Rodrigo Lima de Godoy , de Rezende William Marasini , Giusti Maria Fernanda , Puga Maria Eduarda dos Santos
Published: June 2021

Introduction

The effectiveness of tinnitus treatment represents a huge gap in the medical science. Acamprosate is a glutamatergic antagonist drug and GABA-agonist that could be used to control tinnitus due to its action on peripheral and central neurotransmission.

Purpose

To assess the effectiveness of acamprosate in the treatment of tinnitus.

Material and Methods

This is a systematic review and we searched for randomized clinical trials linking acamprosate to tinnitus in six databases: Cochrane - Central Register of Controlled Trials - CENTRAL (2021), PUBMED (1966-2021), EMBASE (1974-2021), IBECS (1982-2021), QINSIGHT (2021) and SCOPUS (2021). Two researchers independently extracted the data and assessed the quality of the studies.

Results

Two trials involving 121 patients were included. The methodological quality of these studies was low. Both studies evaluated as primary outcome the efficacy of acamprosate in improving tinnitus. The meta-analysis by random model resulted in no significant difference between the groups treated with acamprosate and placebo (RR = 3,69, 95% CI 0,87-15,62; p=0,08), considering tinnitus improvement. Conclusions: There is no evidence that acamprosate is effective for tinnitus treatment. We recommend new trials using rigorous methodology. Randomization and blinding should be of the highest quality, given the subjective nature of tinnitus and the strong likelihood of a placebo response. The CONSORT statement should be used in the design and reporting of future studies.
Kinematic analysis of upper body movements in adolescent with mild idiopathic scoliosis: a preliminary study
Authors: Struber Lucas , Courvoisier Aurélien , Griffet Jacques , Daniel Olivier , Moreau-Gaudry Alexandre , Cinquin Philippe , Nougier Vincent
Published: June 2021

Analysis of kinematic and postural data of adolescent idiopathic scoliosis (AIS) patients seems relevant for a better understanding of biomechanical aspects involved in AIS and its etiopathogenesis. The present project aimed at investigating kinematic differences and asymmetries in early AIS in a static task and in uniplanar trunk movements (rotations, lateral bending and forward bending). Trunk kinematics and posture were assessed using a 3D motion analysis system and a force plate. Fifteen healthy girls, fifteen AIS girls with left lumbar main curve and seventeen AIS girls with right thoracic main curve were compared. Statistical analyses were performed to investigate presumed differences between the three groups. This study showed kinematic and postural differences between mild AIS patients and controls such as static imbalance, a reduced range of motion in the frontal plane and a different kinematic strategy in lateral bending. These differences mainly occurred in the same direction whatever the type of scoliosis, and suggested that AIS patients behave similarly from a dynamic point of view.
NEWS-2 Score Assessment of Inpatient Referral during the COVID 19 Epidemic
Authors: Faure Valérie , Souris Marc , Wilmet Arnaud , Baudino Franck , Brizo Albert , Malhaire Christophe , Peccaud François-Xavier , Gonzalez Jean-Paul
Published: June 2021

Aim

To manage patients with suspected coronavirus disease (COVID-19) when they arrive at the hospital emergency department (ED), a clinical severity score is required to quickly identify patients requiring immediate hospital admission and close monitoring. The aim of this study was to evaluate, within the context of the pandemic, the performance of National Early Warning Score 2 (NEWS-2) to anticipate the admission of patients with suspected COVID-19 to a specialised emergency care unit.

Methods

This retrospective study was conducted on patients presenting at the COVID-19 entrance of the ED of the Vert-Galant private hospital (Paris, France) during the first national pandemic peak from March 20 to April 20, 2020. All patients completed a questionnaire and clinical data and vital signs were recorded. Statistical analysis and modelling were used to estimate the ability of different scores (NEWS-2, qSOFA, CRB-65) to predict hospital emergency admission and/or early COVID-19 diagnosis.

Results

NEWS-2, with a cut off value of 5, predicted hospital admission with 82% sensitivity, 98% specificity and an area under the curve (AUC) of 96%. NEWS-2 was superior to qSOFA and CRB-65 scores for predicting hospital admission of COVID-19 patients. Multilinear or logistic regression analysis of clinical data did not improve this result.

Conclusion

NEWS-2 is an excellent score to predict hospital admission of COVID-19 patients.
Does time matter in phylogeny? A perspective from the fossil record
Authors: Guenser Pauline , Warnock Rachel C.M. , Pett Walker , Donoghue Philip C.J. , Jarochowska Emilia
Published: June 2021

The role of time (i.e. taxa ages) in phylogeny has been a source of intense debate within palaeontology for decades and has not yet been resolved fully. The fossilised birth-death range process is a model that explicitly accounts for information about species through time. It presents a fresh opportunity to examine the role of stratigraphic data in phylogenetic inference of fossil taxa. Here, we apply this model in a Bayesian framework to an exemplar dataset of well-dated conodonts from the Late Devonian. We compare the results to those obtained using traditional unconstrained tree inference. We show that the combined analysis of morphology and stratigraphic data under the FBD range process reduces overall phylogenetic uncertainty, compared to unconstrained tree inference. We find that previous phylogenetic hypotheses based on parsimony and stratophenetics are closer to trees generated under the FBD range process. However, the results also highlight that irrespective of the inclusion of age data, a large amount of topological uncertainty will remain. Bayesian inference provides the most intuitive way to represent the uncertainty inherent in fossil datasets and new flexible models increase opportunities to refine hypotheses in palaeobiology.
Glioblastoma cell fate is differentially regulated by the microenvironments of the tumour bulk and infiltrative margin
Authors: Garcia-Diaz Claudia , Mereu Elisabetta , Clements Melanie P. , Pöysti Anni , Galvez-Cancino Felipe , Castillo Simon P. , Courtot Lilas , Ruiz Sara , Roncaroli Federico , Yuan Yinyin , Quezada Sergio A. , Heyn Holger , Parrinello Simona
Published: June 2021

Glioblastoma recurrence originates from invasive cells at the tumour margin that escape surgical debulking, but their biology remains poorly understood. Here we generated three somatic mouse models recapitulating the main glioblastoma driver mutations to characterise margin cells. We find that, regardless of genetics, tumours converge on a common set of neural- like cellular states. However, bulk and margin display distinct neurogenic patterns and immune microenvironments. The margin is immune-cold and preferentially follows developmental-like trajectories to produce astrocyte-like cells. In contrast, injury-like programmes dominate in the bulk, are associated with immune infiltration and generate lowly-proliferative injured neural progenitor-like (iNPCs) cells.In vivolabel-retention approaches further demonstrate that iNPCs account for a significant proportion of dormant glioblastoma cells and are induced by interferon signalling within T-cell niches. These findings indicate that tumour region is a major determinant of glioblastoma cell fate and therapeutic vulnerabilities identified in bulk may not extend to the margin residuum.
Transcranial stimulation of alpha oscillations upregulates the default mode network
Authors: Clancy Kevin J. , Andrzejewski Jeremy A. , Rosenberg Jens T. , Ding Mingzhou , Li Wen
Published: June 2021

The default mode network (DMN) is the most prominent intrinsic connectivity network, serving as a key architecture of the brain’s functional organization. Conversely, dysregulated DMN is characteristic of major neuropsychiatric disorders. However, the field still lacks mechanistic insights into the regulation of the DMN and effective interventions for DMN dysregulation. The current study approached this problem by manipulating neural synchrony, particularly, alpha (8-12 Hz) oscillations, a dominant intrinsic oscillatory activity that has been increasingly associated with the DMN in both function and physiology. Using high-definition (HD) alpha-frequency transcranial alternating current stimulation (α-tACS) to stimulate the cortical source of alpha oscillations, in combination with simultaneous EEG-fMRI, we demonstrated that α-tACS (vs. sham control) not only augmented EEG alpha oscillations but also strengthened fMRI and (source-level) alpha connectivity within the core of the DMN. Importantly, increase in alpha oscillations mediated the DMN connectivity enhancement. These findings thus identify a mechanistic link between alpha oscillations and DMN functioning. That transcranial alpha modulation can upregulate the DMN further highlights an effective non-invasive intervention to normalize DMN functioning in various disorders.

Significance Statement

In the brain’s functional organization, the default mode network (DMN) represents a key architecture, whose dysregulation is involved in a host of major neuropsychiatric disorders. However, insights into the regulation of the DMN remain scarce. Through neural synchrony, the alpha-frequency oscillation represents another key underpinning of the brain’s organization and is thought to share an inherent interdependence with the DMN. Here, we demonstrated that transcranial alternating current stimulation of alpha oscillations (α-tACS) not only augmented alpha activity but also strengthened connectivity of the DMN, with the former serving as a mediator of the latter. These findings reveal that alpha oscillations can support DMN functioning. In addition, they identify an effective non-invasive approach to regulate the DMN via α-tACS.
Anti-SARS-CoV-2 hyperimmune immunoglobulin provides potent and robust neutralization capacity and antibody-dependent cellular cytotoxicity and phagocytosis induction through N and S proteins
Authors: Díez José María , Romero Carolina , Cruz María , Vandeberg Peter , Merritt W. Keither , Pradenas Edwards , Trinité Benjamin , Blanco Julià , Clotet Bonaventura , Willis Todd , Gajardo Rodrigo
Published: June 2021

Background

Although progressive COVID-19 vaccinations provide a significant reduction of infection rate in the short-to mid-term, effective COVID-19 treatments will continue to be an urgent need.

Methods

We have functionally characterized the anti-SARS-CoV-2 hyperimmune immunoglobulin (hIG) prepared from human COVID-19 convalescent plasma. SARS-CoV-2 virus neutralization was evaluated by four different methodologies (plaque reduction, virus induced cytotoxicity, TCID50 reduction and immunofluorimetry-based methodology) performed at four different laboratories and using four geographically different SARS-CoV-2 isolates (one each from USA and Italy; two from Spain). Two of the isolates contained the D614G mutation. Neutralization capacity against the original Wuhan SARS-CoV-2 straom and variants (D614G mutant, B.1.1.7, P.1 and B.1.351 variants) was evaluated using a pseudovirus platform expressing the corresponding spike (S) protein. The capacity to induce antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) was also evaluated.

Results

All the SARS-CoV-2 isolates tested were effectively neutralized by hIG solutions. This was confirmed by all four methodologies showing potent neutralization capacity. Wild-type SARS-CoV-2 and variants were effectively neutralized as demonstrated using the pseudovirus platform. The hIG solutions had the capacity to induce ADCC and ADCP against SARS-CoV-2 N and S proteins but not the E protein. Under our experimental conditions, very low concentrations (25-100 µg IgG/mL) were required to induce both effects. Besides the S protein, we observed a clear and potent effect triggered by antibodies in the hIG solutions against the SARS-CoV-2 N protein.

Conclusions

These results show that, beyond neutralization, other IgG Fc-dependent pathways may play a role in the protection from and/or resolution of SARS-CoV-2 infection when using hIG COVID-19 products. This could be especially relevant for the treatment of more neutralization resistant SARS-CoV-2 variants of concern.
Mutations in SIX1 associated with Branchio-oto-renal Syndrome (BOR) differentially affect otic expression of putative target genes
Authors: Mehdizadeh Tanya , Majumdar Himani Datta , Ahsan Sarah , Tavares Andre , Moody Sally A.
Published: June 2021

Single nucleotide mutations inSIX1are causative in some individuals diagnosed with branchio-otic/branchio-oto-renal (BOR) syndrome. To test whether these mutations have differential effects on otic gene expression, we engineered four BOR mutations inXenopus six1and targeted mutant protein expression to the neural crest and cranial placode precursor cells in wild-type embryos. Changes in the otic expression of putative Six1 targets and/or co-factors were monitored by qRT-PCR and in situ hybridization. We found that each mutant had a different combination of effects. The V17E mutant reducedeya2, tspan13, zbtb16andpa2g4otic vesicle expression at a frequency indistinguishable from wild-type Six1, but reducedprdm1more andspry1less compared to wild-type Six1. For most of these genes, the R110W, W122R and Y129C mutants were significantly less repressive compared to wild-type Six1. Their individual effects varied according to the level at which they were expressed. The R110W, W122R and Y129C mutants also often expandedprdm1otic expression. Since previous studies showed that all four mutants are transcriptionally deficient and differ in their ability to interact with co-factors such as Eya1, we propose that altered co-factor interactions at the mutated sites differentially interfere with their ability to drive otic gene expression.
Daily transient coating of the intestine leads to weight loss and improved glucose tolerance
Authors: Lo Tammy , Lee Yuhan , Tseng Chung-Yi , Hu Yangshuo , Mantzoros Christos S. , Karp Jeffrey M. , Tavakkoli Ali
Published: June 2021

The worsening obesity epidemic has driven a parallel increase in incidence of type-2 diabetes (T2D) found in 13% of the adult US population. Roux-en-Y gastric bypass surgery (RYGB) is the golden standard surgical treatment for obesity-related T2D. However, over 70% of T2D patient do not meet the NIH criteria for surgery, and many that do, are reluctant to consider such an invasive intervention. Mechanisms behind the antidiabetic effect of RYGB are not clearly understood, but isolation of proximal bowel from nutrient exposure plays a critical role. In this study, we tested the impact of daily administration of an oral gut coating agent, LuCI (Luminal Coating of the Intestine), in controlling weight and insulin resistance. LuCI is not systemically absorbed and provides a transient coating of the proximal intestines and excludes the coated bowel from nutrient contact, thus mimicking the effects of RYGB. We demonstrate that LuCI results in weight loss and improved insulin sensitivity in a rat DIO model. LuCI also appears to replicate hormonal changes seen after RYGB, by increasing post-prandial GLP-1 and GIP levels. LuCI has the potential to replicate the metabolic benefit of surgery and be a novel therapeutic strategy for obesity associated T2D.
Principles of ecDNA random inheritance drive rapid genome change and therapy resistance in human cancers
Authors: Lange Joshua T. , Chen Celine Y. , Pichugin Yuriy , Xie Liangqi , Tang Jun , Hung King L. , Yost Kathryn E. , Shi Quanming , Erb Marcella L. , Rajkumar Utkrisht , Wu Sihan , Swanton Charles , Liu Zhe , Huang Weini , Chang Howard Y. , Bafna Vineet , Henssen Anton G. , Werner Benjamin , Mischel Paul S.
Published: June 2021

The foundational principles of Darwinian evolution are variation, selection, and identity by descent. Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumour growth, drug resistance, and shorter survival in patients1-4. Currently, the impact of non-chromosomal oncogene inheritance—random identity by descent—is not well understood. Neither is the impact of ecDNA on variation and selection. Here, integrating mathematical modeling, unbiased image analysis, CRISPR-based ecDNA tagging, and live-cell imaging, we identify a set of basic “rules” for how random ecDNA inheritance drives oncogene copy number and distribution, resulting in extensive intratumoural ecDNA copy number heterogeneity and rapid adaptation to metabolic stress and targeted cancer treatment. Observed ecDNAs obligatorily benefit host cell survival or growth and can change within a single cell cycle. In studies ranging from well-curated, patient-derived cancer cell cultures to clinical tumour samples from patients with glioblastoma and neuroblastoma treated with oncogene-targeted drugs, we show how these ecDNA inheritance “rules” can predict, a priori, some of the aggressive features of ecDNA-containing cancers. These properties are entailed by their ability to rapidly change their genomes in a way that is not possible for cancers driven by chromosomal oncogene amplification. These results shed new light on how the non-chromosomal random inheritance pattern of ecDNA underlies poor outcomes for cancer patients.