bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of early positive end-expiratory pressure settings with ventilator-free days in patients with coronavirus disease 2019 acute respiratory distress syndrome
Authors: Valk Christel M.A. , Tsonas Anissa M. , Botta Michela , Bos Lieuwe D.J. , Pillay Janesh , Serpa Neto Ary , Schultz Marcus J. , Paulus Frederique
Published: July 2021

BACKGROUND

There is uncertainty about how much positive end-expiratory pressure (PEEP) should be used in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19).

OBJECTIVE

To investigate whether a higher PEEP strategy is superior to a lower PEEP strategy regarding the number of ventilator-free days (VFDs).

DESIGN

Multicentre observational study conducted from 1 March to 1 June 2020.

SETTING AND PATIENTS

Twenty-two ICUs in The Netherlands and 933 invasively ventilated COVID-19 ARDS patients.

INTERVENTIONS

Patients were categorised retrospectively as having received invasive ventilation with higher (n=259) or lower PEEP (n=674), based on the high and low PEEP/F
iO2 tables of the ARDS Network, and using ventilator settings and parameters in the first hour of invasive ventilation, and every 8 h thereafter at fixed time points during the first four calendar days. We also used propensity score matching to control for observed confounding factors that might influence outcomes.

MAIN OUTCOMES AND MEASURES

The primary outcome was the number of VFDs. Secondary outcomes included distant organ failures including acute kidney injury (AKI) and use of renal replacement therapy (RRT), and mortality.

RESULTS

In the unmatched cohort, the higher PEEP strategy had no association with the median [IQR] number of VFDs (2.0 [0.0 to 15.0] vs. 0.0 [0.0 to 16.0] days). The median (95% confidence interval) difference was 0.21 (−3.34 to 3.78) days, P = 0.905. In the matched cohort, the higher PEEP group had an association with a lower median number of VFDs (0.0 [0.0 to 14.0] vs. 6.0 [0.0 to 17.0] days) a median difference of −4.65 (−8.92 to −0.39) days, P = 0.032. The higher PEEP strategy had associations with higher incidence of AKI (in the matched cohort) and more use of RRT (in the unmatched and matched cohorts). The higher PEEP strategy had no association with mortality.

CONCLUSION

In COVID-19 ARDS, use of higher PEEP may be associated with a lower number of VFDs, and may increase the incidence of AKI and need for RRT.

TRIAL REGISTRATION

Practice of VENTilation in COVID-19 is registered at ClinicalTrials.gov, NCT04346342.
American Frontline Healthcare Personnel's Access to and Use of Personal Protective Equipment Early in the COVID-19 Pandemic
Authors: Rich-Edwards Janet W. , Ding Ming , Rocheleau Carissa M. , Boiano James M. , Kang Jae H. , Becene Iris , Nguyen Long H. , Chan Andrew T. , Hart Jaime E. , Chavarro Jorge E. , Lawson Christina C.
Published: July 2021

Objectives:

To quantify adequacy of personal protective equipment (PPE) for U.S. healthcare personnel (HCP) at the outset of the COVID-19 pandemic and its association with infection risk.

Methods:

March–May 2020 survey of the national Nurses’ Health Studies and the Growing Up Today study regarding self-reported PPE access, use, and reuse. COVID-19 endpoints included SARS-CoV-2 tests and COVID-19 status predicted from symptoms.

Results:

Nearly 22% of 22,232 frontline HCP interacting with COVID-19 patients reported sometimes or always lacking PPE. Fifty percent of HCP reported not needing respirators, including 13% of those working in COVID-19 units. Lack of PPE was cross-sectionally associated with two-fold or greater odds of COVID-19 among those who interacted with infected patients.

Conclusion:

These data show the need to improve the U.S. infection prevention culture of safety when confronting a novel pathogen.
Associations Between Work-Related Factors and Psychological Distress Among Construction Workers
Authors: Dennerlein Jack T. , Eyllon Mara , Garverich Suzanne , Weinstein Daniel , Manjourides Justin , Vallas Steven P. , Lincoln Alisa K.
Published: July 2021

Objective:

Identify work-related factors associated with the mental health and well-being of construction workers.

Methods:

We completed eight key informant interviews, six worker focus groups, and a survey, informed by the interviews and focus groups, of 259 construction workers on five construction sites. Negative binomial regressions examined associations between psychological distress and work-related factors including safety climate, work-to-family conflict, psychological demands, social support, harassment, and job security.

Results:

Three themes emerged from the interviews and focus groups, job demands and structure, social support and workplace relations, and job precarity. From the survey higher psychological demands, higher work-to-family conflict, lower supervisor support, higher discrimination, and higher likelihood of losing a job were associated with higher psychological distress. When combined into a single model job demands and work-to-family conflict remained significant.

Conclusions:

Work-related factors were associated with high levels of distress.
Correlation of Vital Signs and Depth of Sedation by Modified Observer’s Assessment of Alertness and Sedation (MOAA/S) Scale in Bronchoscopy
Authors: Pastis Nicholas J. , Hill Nathan T. , Yarmus Lonny B. , Schippers Frank , Imre Mihaly , Sohngen Wolfgang , Randall Ostroff , Callahan Sean P. , Silvestri Gerard A.
Published: July 2021

Background:

With complex, lengthy bronchoscopies, there is a need for safe, effective sedation. Most bronchoscopists strive for moderate sedation, though often difficult without compromising vital signs. The Modified Observer’s Assessment of Alertness and Sedation (MOAA/S) scale is a validated 6-point scale assessing responsiveness of patients coinciding with the American Society of Anesthesiologists (ASA) continuum of sedation. It is commonly used in studying bronchoscopic sedation, but depth of sedation by MOAA/S and correlation with vital signs and adverse events has not been determined.

Methods:

This study was a post hoc analysis of a prospective, double-blind, randomized trial evaluating the safety and efficacy of remimazolam. MOAA/S and corresponding vital signs were used to assess the effect of the level of sedation on vital signs and adverse events.

Results:

A total of 23,341 MOAA/S scores from 431 patients were recorded. Older and higher ASA class patients spent more time in deeper sedation (MOAA/S 0 to 1) (6% vs. 2%, P=0.01). Oxygen saturation was equal in deep sedation (MOAA/S 0 to 1) (97±3%) compared with moderate sedation (96±3%) (P=0.11). Mean systolic and diastolic blood pressures were significantly lower when comparing MOAA/S 0 to 1 to MOAA/S 5 (systolic blood pressure: 126±19 vs. 147±24 mm Hg, P<0.01; diastolic blood pressure: 68±14 vs. 84±15 mm Hg, P<0.01). There was a nonsignificant trend towards lower heart rate at deep versus moderate sedation (84±15 vs. 94±18 beats/min, P=0.07). Respiratory rate was also comparable with moderate and deep sedation (17±5 vs. 18±6 beats/min, P=0.94).

Conclusion:

There was no clinically meaningful correlation between vital signs and depth of sedation assessed by MOAA/S. Older and higher ASA class patients spend more time in deeper sedation. However, when in deep sedation, there was no difference in vital signs other than a slightly increased incidence of clinically insignificant hypotension.
Cytologic Investigations for the Diagnosis of Malignant Pleural Effusion in Non–small Cell Lung Cancer
Authors: Shojaee Samira , Roy-Chowdhuri Sinchita , Safi Javeryah , Grosu Horiana B.
Published: July 2021

Lung cancer is the current leading cause of cancer-related deaths worldwide, and malignant pleural effusion, an indicator of the advanced stage of this disease, portends a poor prognosis. Thus, making an accurate diagnosis of malignant pleural effusion is of paramount importance. During the past decade, the prognosis of patients with advanced non–small cell lung cancer has improved substantially, especially in those treated with targeted therapy and immunotherapy. The use of pleural fluid cytology should not only provide diagnoses but also aid in the selection of targeted therapies, especially when obtaining a histologic specimen is too difficult. In this evidence-based review, we address the importance of pleural fluid cytology in non–small cell lung cancer patients, from making the diagnosis to making treatment-related decisions when only pleural fluid is available.
Obsessive Thought, Compulsive Behavior, and Their Associations With Suicide Ideation and Attempts and Major Depressive Disorder
Authors: Lee Min Kang , Hong Jin Pyo , Fava Maurizio , Mischoulon David , Kim Hyewon , Park Mi Jin , Kim Eun Ji , Jeon Hong Jin
Published: July 2021

In this study, we defined obsessive thoughts (OT) as bothersome, unpleasant thoughts about oneself that keep entering the mind against one's will, and compulsive behavior (CB) as behavior that a person repeats against his or her wishes. The study included 12,532 adults selected randomly through a one-person-per-household method. Each subject selected underwent a face-to-face interview using the Korean version of the Composite International Diagnostic Interview with a questionnaire that examines lifetime suicide attempts (LSAs). Among the participants, 341 (2.74%) had OT and 639 (5.14%) had CB. The highest LSA rate was in subjects with both OT and CB, followed by those with either OT or CB; subjects with neither OT nor CB had the lowest LSA rate. In a multivariate logistic regression analysis of OT and CB, OT, ordering, and rituals of repeating words were significantly associated with LSAs. In subjects with OT and CB, those with MDD had a significantly higher risk of LSAs compared with those without, and MDD with both OT and CB showed odds of approximately 27-fold (adjusted odds ratio, 27.24; 13.29–55.82; p < 0.0001) compared with those without MDD, OT, or CB. OT and CB were associated with increased risk of LSAs, and comorbid MDD further increased LSAs.
225Ac-DOTATOC–Targeted Somatostatin Receptor α-Therapy in a Patient With Metastatic Neuroendocrine Tumor of the Thymus, Refractory to β-Radiation
Authors: Zhang Jingjing , Kulkarni Harshad R. , Baum Richard P.
Published: July 2021

Somatostatin receptor–targeted α-therapy using α-emitter 225Ac-labeled somatostatin analogs has been suggested as a treatment option in advanced metastatic neuroendocrine tumors (NETs) failing treatment with β-emitters, such as 177Lu or 90Y. Thymus NETs are rare and usually more aggressive than other neuroendocrine tumor entities. We present here a case with β-radiation refractory metastatic thymus NET, who demonstrated an excellent therapy response (molecular and morphological remission, as well as significantly improved clinical symptoms) after 225Ac-DOTATOC–targeted α-therapy, without any adverse effects during the treatment or in the follow-up period.
Mesenteric Inflammatory Myofibroblastic Tumor on 68Ga-FAPI PET/CT
Authors: Liu Huipan , Yang Xiao , Fan Dongmei , Lv Taiyong , Chen Yue
Published: July 2021

Inflammatory myofibroblastic tumor is an uncommon mesenchymal neoplasm, which can be seen in any anatomic region from the central nervous system to the gastrointestinal tract. Herein, we report the 68Ga-FAPI PET/CT findings in a 49-year-old man with mesenteric inflammatory myofibroblastic tumor.
A Cross-Sectional Analysis of American Insurance Coverage of Prominauris Otoplasty
Authors: Ha Michael , Ngaage Ledibabari M. , Badiei Beita , Onyima Chinenye , Yoon Joshua S. , Nam Arthur J. , Rada Erin M. , Rasko Yvonne M.
Published: July 2021

Background:

Prominent ears affect up to 5% of the population and can lead to social and psychological concerns at a critical time of social development. It can be addressed with an otoplasty, which is often considered a cosmetic procedure. The authors assessed insurance coverage of all indications of otoplasty and their medical necessity criteria.

Methods:

A cross-sectional analysis was conducted of 58 insurance policies for otoplasty. The insurance companies were selected based on their state enrolment and market share. A web-based search and telephone interviews were utilized to identify the policies. Medically necessary criteria were then abstracted from the publicly available policies.

Results:

Of the 58 insurance policies assessed, 25 (43%) provide coverage of otoplasty. There were 2 indications for coverage: hearing loss (n = 20, 80%) and normal approximation (n = 14, 56%), which would encompass prominent ears. Normal approximation was a covered indication for significantly fewer insurers than hearing loss (56% versus 80%, P = 0.0013). Of all the otoplasty policies which covered normal approximation, 21% (n = 3) addressed protruding ears as an etiology. Prominent ears were not included in any policies which covered hearing loss. All policies inclusive of prominent ears required a protrusion of >20 mm from the temporal surface of the head (n = 3, 100%).

Conclusions:

There is a great discrepancy in insurance coverage of otoplasty. A greater proportion of policies cover hearing loss compared to normal approximation. The authors encourage plastic surgeons to advocate for the necessity and coverage of normal approximation by insurers.
Pediatric Orthognathic Surgery: National Analysis of Perioperative Complications
Authors: Kalmar Christopher L. , Carlson Anna R. , Patel Vijay A. , Zapatero Zachary D. , Kosyk Mychajlo S. , Taylor Jesse A. , Swanson Jordan W.
Published: July 2021

Background:

Orthognathic surgery has traditionally been performed after skeletal maturity. Although these procedures are also being performed in children, the implications of earlier intervention and specific risk factors in this younger population remain unknown.

Methods:

The American College of Surgeons National Surgical Quality Improvement Program Pediatric dataset was queried for orthognathic procedures performed in 2018. Complications, readmissions, and reoperations were analyzed with appropriate statistics.

Results:

Overall adverse event rate after orthognathic surgery in pediatric patients was 7.8% (n = 22 of 281), which were associated with having any comorbidity (P < 0.001), overall respiratory comorbidities (P = 0.004), structural pulmonary abnormality (P < 0.001), developmental delay (P = 0.035), structural central nervous system abnormality (P < 0.001), and neuromuscular disorder (P = 0.035). Most common complications were excessive bleeding (2.5%), surgical site infection (1.1%), and pneumonia (0.7%). Orthognathic surgery in children below 6 years of age is associated with significantly increased adverse events (P < 0.001), including surgical site infection (P < 0.001), pneumonia (P = 0.022), readmission (P < 0.001), and reoperation (P < 0.001). Le Fort I osteotomies (P < 0.001) and bilateral sagittal split osteotomies (P = 0.009) took significantly longer for older patients in the years of permanent dentition than younger patients in the years of deciduous dentition. Single- and double-jaw procedures in pediatric patients have similarly low adverse events (P all ≥0.130). Interestingly, bilateral sagittal split osteotomies performed before 13.5 years of age were associated with a higher risk of adverse events (P = 0.012), such that these younger patients were 7.1 times more likely to experience adverse events if their procedure was performed earlier.

Conclusions:

Orthognathic surgery is relatively safe, but children in the years of deciduous dentition under 6 years of age have significantly increased risk of adverse events.
Anti-C5 Antibody Tesidolumab Reduces Early Antibody-mediated Rejection and Prolongs Survival in Renal Xenotransplantation
Authors: Adams Andrew B. , Lovasik Brendan P. , Faber David A. , Burlak Christopher , Breeden Cynthia , Estrada Jose L. , Reyes Luz M. , Vianna Rodrigo M. , Tector Matthew F. , Tector Alfred J.
Published: July 2021

Objective:

Pig-to-primate renal xenotransplantation is plagued by early antibody-mediated graft loss which precludes clinical application of renal xenotransplantation. We evaluated whether temporary complement inhibition with anti-C5 antibody Tesidolumab could minimize the impact of early antibody-mediated rejection in rhesus monkeys receiving pig kidneys receiving costimulatory blockade-based immunosuppression.

Methods:

Double (Gal and Sda) and triple xenoantigen (Gal, Sda, and SLA I) pigs were created using CRISPR/Cas. Kidneys from DKO and TKO pigs were transplanted into rhesus monkeys that had the least reactive crossmatches. Recipients received anti-C5 antibody weekly for 70 days, and T cell depletion, anti-CD154, mycophenolic acid, and steroids as baseline immunosuppression (n = 7). Control recipients did not receive anti-C5 therapy (n = 10).

Results:

Temporary anti-C5 therapy reduced early graft loss secondary to antibody-mediated rejection and improved graft survival (P < 0.01). Deleting class I MHC (SLA I) in donor pigs did not ameliorate early antibody-mediated rejection (table). Anti-C5 therapy did not allow for the use of tacrolimus instead of anti-CD154 (table), prolonging survival to a maximum of 62 days.

Conclusion:

Inhibition of the C5 complement subunit prolongs renal xenotransplant survival in a pig to non-human primate model.
Analysis of Nonbattle Deaths Among U.S. Service Members in the Deployed Environment
Authors: Le Tuan D. , Gurney Jennifer M. , Akers Kevin S. , Chung Kevin K. , Singh Karan P. , Wang Heuy-Ching , Stackle Mark E. , Pusateri Anthony E.
Published: July 2021

Objective:

Describe etiologies and trends in non-battle deaths (NBD) among deployed U.S. service members to identify areas for prevention.

Background:

Injuries in combat are categorized as battle (result of hostile action) or nonbattle related. Previous work found that one-third of injured US military personnel in Iraq and Afghanistan had nonbattle injuries and emphasized prevention. NBD have not yet been characterized.

Methods:

U.S. military casualty data for Iraq and Afghanistan from 2001 to 2014 were obtained from the Defense Casualty Analysis System (DCAS) and the Department of Defense Trauma Registry (DoDTR). Two databases were used because DoDTR does not capture prehospital deaths, while DCAS does not contain clinical details. Nonbattle injuries and NBD were identified, etiologies classified, and NBD trends were assessed using a weighted moving average and time-series analysis with autoregressive integrated moving average. Future NBD rates were forecast.

Results:

DCAS recorded 59,799 casualties; 21.0% (n = 1431) of all deaths (n = 6745) were NBD. DoDTR recorded 29,958 casualties; 11.5% (n = 206) of all deaths (n = 1788) were NBD. After early fluctuations, NBD rates for both Iraq and Afghanistan stabilized at approximately 21%. Leading causes of NBD were gunshot wounds and vehicle accidents, accounting for 66%. Approximately 25% was self-inflicted. A 24% NBD rate was forecasted from 2015 through 2025.

Conclusions:

Approximately 1 in 5 deaths were NBD. The majority were potentially preventable, including a significant proportion of self-inflicted injuries. A single comprehensive data repository would facilitate future mortality monitoring and performance improvement. These data may assist military leaders with implementing targeted safety strategies.
Risk of Myocardial Infarction, Ischemic Stroke, and Mortality in Patients Who Undergo Gastric Bypass for Obesity Compared With Nonoperated Obese Patients and Population Controls
Authors: Lundberg Christina E. , Björck Lena , Adiels Martin , Lagergren Jesper , Rosengren Annika
Published: July 2021

Objective:

The aim of this study was to estimate risks of myocardial infarction, ischemic stroke, and cardiovascular-related and all-cause mortality after Roux-en-Y gastric bypass (RYGB) for obesity compared with nonop-erated obese patients and matched nonobese population controls.

Background:

Few studies have assessed the influence of RYGB on fatal and non-fatal myocardial infarction and ischemic stroke, and the results vary between studies.

Method:

All patients aged 20 to 65 years with obesity diagnosis in the nationwide Swedish Patient Registry in 2001 to 2013 were included. These participants were divided into those who underwent RYGB within 2 years of obesity diagnosis (n = 28,204) and nonoperated (n = 40,827), and were matched for age, sex, and region with 2 nonobese population controls. Participants were followed until onset of outcome disease, death, or end of follow-up. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (95% CI).

Results:

Compared with nonoperated patients with obesity, RYGB patients had a reduced risk of myocardial infarction [HR = 0.44 (95% CI 0.28-0.63)], similar risk of ischemic stroke [HR = 0.79 (95% CI 0.54–1.14)], and decreased risks of cardiovascular-related [HR = 0.47 (95% CI 0.35–0.65)] and all-cause mortality [HR = 0.66 (95% CI 0.54–0.81)] within the first 3 years of follow-up, but not later. Compared with nonobese population controls, RYGB patients had excess risks of ischemic stroke [HR = 1.57 (95% CI 1.08–2.29)], cardiovascular-related mortality [HR = 1.82 (95% CI 1.29–2.60)], and all-cause mortality [HR = 1.42 (95% CI 1.16–1.74)], but not of myocardial infarction [HR = 1.02 (95% CI 0.72–1.46)].

Conclusion:

RYGB for obesity might not decrease the risk of ischemic stroke, but seems to decrease the risk of myocardial infarction back to population levels.
Long-term, Prolonged-release Tacrolimus-based Immunosuppression in De Novo Liver Transplant Recipients: 5-year Prospective Follow-up of Patients in the DIAMOND Study
Authors: Friman Styrbjörn , Tisone Giuseppe , Nevens Frederik , Lehner Frank , Santaniello Walter , Bechstein Wolf O. , Zhuvarel Sergey V. , Isoniemi Helena , Rummo Oleg O. , Klempnauer Jürgen , Anaokar Swapneel , Hurst Martin , Kazeem Gbenga , Undre Nasrullah , Trunečka Pavel
Published: July 2021

Background.

Immunosuppression with calcineurin inhibitors (CNIs) is reportedly associated with risk of renal impairment in liver transplant recipients. It is believed that this can be mitigated by decreasing initial exposure to CNIs or delaying CNI introduction until 3–4 d posttransplantation. The ADVAGRAF studied in combination with mycophenolate mofetil and basiliximab in liver transplantation (DIAMOND) trial evaluated different administration strategies for prolonged-release tacrolimus (PR-T).

Methods.

DIAMOND was a 24-wk, open-label, phase 3b trial in de novo liver transplant recipients randomized to: PR-T 0.2 mg/kg/d (Arm 1); PR-T 0.15–0.175 mg/kg/d plus basiliximab (Arm 2); or PR-T 0.2 mg/kg/d delayed until day 5 posttransplant plus basiliximab (Arm 3). In a 5-y follow-up, patients were maintained on an immunosuppressive regimen according to standard clinical practice (NCT02057484). Primary endpoint: graft survival (Kaplan-Meier analysis).

Results.

Follow-up study included 856 patients. Overall graft survival was 84.6% and 73.5% at 1 and 5 y post transplant, respectively. Five-year rates for Arms 1, 2, and 3 were 74.7%, 71.5%, and 74.5%, respectively. At 5 y, death-censored graft survival in the entire cohort was 74.7%. Overall graft survival in patients remaining on PR-T for ≥30 d was 79.1%. Graft survival in patients who remained on PR-T at 5 y was 87.3%. Patient survival was 86.6% at 1 y and 76.3% at 5 y, with survival rates similar in the 3 treatment arms at 5 y. Estimated glomerular filtration rate at the end of the 24-wk initial study and 5 y posttransplant was 62.1 and 61.5 mL/min/1.73 m2, respectively, and was similar between the 3 treatment arms at 5 y. Overall, 18 (2.9%) patients had ≥1 adverse drug reaction, considered possibly related to PR-T in 6 patients.

Conclusions.

In the DIAMOND study patient cohort, renal function, graft survival, and patient survival were similar between treatment arms at 5 y posttransplant.
Binasal Visual Field Defects Due to Sickle Cell Maculopathy
Authors: Kwok Jason M. , Jeeva-Patel Trishal , Margolin Edward A.
Published: July 2021

A 26-year-old African American man with sickle cell disease noticed blurry vision in both eyes after a recent complicated hospital admission for sickle cell crisis. Anterior and posterior segment examination of each eye was normal, but visual field testing revealed binasal scotomas. Optical coherence tomography of the macula demonstrated severe thinning of the temporal inner retina, suggesting previous bilateral occlusions of terminal retinal arterioles involving the temporal macula, an uncommon complication of sickle cell disease. This case is a reminder that retinal pathology should always be considered as a potential cause of unexplained visual field defects and highlights the role of macular OCT in evaluation of these patients.
Quantitative EEG as a Prognostic Tool in Suspected Anti-N-Methyl-d-Aspartate Receptor Antibody Encephalitis
Authors: Blackman Graham , Kumar Kieron , Hanrahan John G. , Dalrymple Anthony , Mullatti Nandini , Moran Nick , Valentin Antonio , Gibson Lucy , Pollak Thomas A. , David Anthony S.
Published: July 2021

Purpose:

Anti–N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a form of autoimmune encephalitis associated with EEG abnormalities. In view of the potentially severe outcomes, there is a need to develop prognostic tools to inform clinical management. The authors explored whether quantitative EEG was able to predict outcomes in patients with suspected anti-NMDAR encephalitis.

Methods:

A retrospective, observational study was conducted of patients admitted to a tertiary clinical neuroscience center with suspected anti-NMDAR encephalitis. Peak power and peak frequency within delta (<4 Hz), theta (4–8 Hz), alpha (8 - 13 Hz), and beta (13–30 Hz) frequency bands were calculated for the first clinical EEG recording. Outcome was based on the modified Rankin Scale (mRS) score at 1 year after hospital discharge. Binomial logistic regression using backward elimination was performed with peak frequency and power, anti-NMDAR Encephalitis One-Year Functional Status score, age, and interval from symptom onset to EEG entered as predictors.

Results:

Twenty patients were included (mean age 48.6 years, 70% female), of which 7 (35%) had a poor clinical outcome (mRS 2–6) at 1 year. There was no association between reported EEG abnormalities and outcome. The final logistic regression model was significant (χ2(1) = 6.35, P < 0.012) with peak frequency in the delta range (<4 Hz) the only retained predictor. The model explained 38% of the variance (Nagelkerke R
2) and correctly classified 85% of cases. Higher peak frequency in the delta range was significantly associated (P = 0.04) with an increased likelihood of poor outcome.

Conclusions:

In this exploratory study, it was found that quantitative EEG on routinely collected EEG recordings in patients with suspected anti-NMDAR encephalitis was feasible. A higher peak frequency within the delta range was associated with poorer clinical outcome and may indicate anti-NMDAR-mediated synaptic dysfunction. Quantitative EEG may have clinical utility in predicting outcomes in patients with suspected NMDAR antibody encephalitis, thereby serving as a useful adjunct to qualitative EEG assessment; however, given the small sample size, replication in a larger scale is indicated.
Pseudomonas arcuscaelestis sp. nov., isolated from rainbow trout and water
Authors: Mulet Magdalena , Duman Muhammed , Altun Soner , Saticioglu Izzet Burcin , Gomila Margarita , Matthijs Sandra , Lalucat Jorge , García-Valdés Elena
Published: July 2021

Cells of strains P66T, V1 and W15Feb18 are Gram-stain-negative short rods and motile by one polar flagellum. Strain P66Twas isolated from rainbow trout (Oncorhynchus mykiss) cultivated at a fish farm in Turkey. Strain V1 was isolated from sand of an intertidal shore on the Galicia coast in Spain and strain W15Feb18 was isolated from water collected at the Woluwe River in Belgium. Based on 16S rRNA sequence similarity values, the strains were grouped under the genusPseudomonasand thePseudomonas putidaphylogenetic group of species. The DNA G+C content ranged from 58.5 to 58.9 mol%. The strains were characterized phenotypically by the API 20NE and Biolog GEN III tests, and chemotaxonomically by their whole-cell MALDI-TOF MS protein profiles and fatty acid contents. The absence of the hydrolysis of gelatin and the assimilation of arabinose, mannose and mannitol differentiated these strains from the closest species,Pseudomonas alkylphenolica. The major fatty acid components were C16:0(29.91–31.68 %) and summed feature 3 (36.44–37.55 %). Multilocus sequence analysis with four and 83 housekeeping gene sequences and a core proteome analysis showed that these strains formed a phylogenetic cluster in theP. putidagroup of species. Genome comparisons by the average nucleotide identity based onblastand the Genome-to-Genome Distance Calculator demonstrated that the three strains belonged to the same genomic species and were distant from any known species, with similarity values lower than the thresholds established for species in the genusPseudomonas. These data permitted us to conclude that strains P66T, V1 and W15Feb18 belong to a novel species in the genusPseudomonas, for which the namePseudomonas arcuscaelestissp. nov. is proposed. The type strain is P66T(=CECT 30176T=CCUG 74872T). The other strains have been deposited in the CECT with the corresponding collection numbers: V1 (=CECT 30356) and W15Feb18 (=CECT 30355).
Generation of a Bactrian camel hepatitis E virus by a reverse genetics system
Authors: Zhang Wenjing , Ami Yasushi , Suzaki Yuriko , Doan Yen Hai , Takeda Naokazu , Muramatsu Masamichi , Li Tian-Cheng
Published: July 2021

Bactrian camel hepatitis E virus (HEV) is a novel HEV belonging to genotype 8 (HEV-8) in the Orthohepevirus A species of the genus Hepevirus in the family Hepeviridae. HEV-8 cross-transmits to cynomolgus monkeys and has a potential risk for zoonotic infection. Until now, neither a cell-culture system to grow the virus nor a reverse genetics system to generate the virus has been developed. To generate replication-competent HEV-8 and to establish a cell-culture system, we synthesized capped genomic HEV-8 RNAs by in vitro transcription and used them to transfect into PLC/PRF/5 cells. A HEV-8 strain, HEV-8M2, was recovered from the capped HEV-8 RNA–transfected cell-culture supernatants and subsequently passaged in the cells, demonstrating that PLC/PRF/5 cells were capable of supporting the replication of the HEV-8, and that a cell-culture system for HEV-8 was successfully established. In addition to PLC/PRF/5 cells, A549 and Caco-2 cells appeared to be competent for the replication, but HepG2 C3/A, Vero, Hela S3, HEp-2C, 293T and GL37 cells were incompetent. The HEV-8M2 strain was capable of infecting cynomolgus monkeys by an intravenous inoculation, indicating that HEV-8 was infectious and again carried a risk for zoonotic infection. In contrast, HEV-8 did not infect nude rats and BALB/c nude mice, suggesting that the reservoir of HEV-8 was limited. In addition, the replication of the HEV-8M2 strain was efficiently abrogated by ribavirin but not by favipiravir, suggesting that ribavirin is a drug candidate for therapeutic treatment of HEV-8-induced hepatitis. The infectious HEV-8 produced by a reverse genetics system would be useful to elucidate the mechanisms of HEV replication and the pathogenesis of type E hepatitis.
Scoping review and interpretation of Myofascial Pain/Fibromyalgia syndrome: an attempt to assemble a medical puzzle
Authors: Plaut Shiloh
Published: July 2021

Background

Myofascial Pain Syndrome (MPS) is a common, overlooked, and underdiagnosed condition and has significant burden. MPS is often dismissed by clinicians while patients remain in pain for years. MPS can evolve into fibromyalgia, however, effective treatments for both are lacking due to absence of a clear mechanism. Many studies focus on central sensitization. Therefore, the purpose of this scoping review is to systematically search cross-disciplinary empirical studies of MPS, focusing on mechanical aspects, and suggest an organic mechanism explaining how it might evolve into fibromyalgia. Hopefully, it will advance our understanding of this disease.

Methods

Systematically searched multiple phrases in MEDLINE, EMBASE, COCHRANE, PEDro, and medRxiv, majority with no time limit. Inclusion/exclusion based on title and abstract, then full text inspection. Additional literature added on relevant side topics. Review follows PRISMA-ScR guidelines. PROSPERO yet to adapt registration for scoping reviews.

Findings

799 records included. Fascia can adapt to various states by reversibly changing biomechanical and physical properties. Trigger points, tension, and pain are a hallmark of MPS. Myofibroblasts play a role in sustained myofascial tension. Tension can propagate in fascia, possibly supporting a tensegrity framework. Movement and mechanical interventions treat and prevent MPS, while living sedentarily predisposes to MPS and recurrence.

Conclusions

MPS can be seen as a pathological state of imbalance in a natural process; manifesting from the inherent properties of the fascia, triggered by a disrupted biomechanical interplay. MPS might evolve into fibromyalgia through deranged myofibroblast in connective tissue (“fascial armoring”). Movement is an underemployed requisite in modern lifestyle. Lifestyle is linked to pain and suffering. The mechanism of needling is suggested to be more mechanical than currently thought. A “global percutaneous needle fasciotomy” that respects tensegrity principles may treat MPS/fibromyalgia more effectively. “Functional-somatic syndromes” can be seen as one entity (myofibroblast-generated-tensegrity-tension), sharing a common rheuma-phycho-neurological mechanism.
First detection of SARS-CoV-2 Delta variant (B.1.617.2) in the wastewater of (Ahmedabad), India
Authors: Joshi Madhvi , Kumar Manish , Srivastava Vaibhav , Kumar Dinesh , Rathore Dalipsingh , Pandit Ramesh , Joshi Chaitanya G.
Published: July 2021

Contrary to the conventional genomic surveillance based on clinical samples (symptomatic patients), the wastewater-based genomic surveillance can identify all the variants shed by the infected individuals in the population, as it does also include RNA fragmented shredded by clinically escaped asymptomatic patients. We analyzed four samples to detect key mutations in the SARS-CoV-2 genome and track circulating variants in Ahmedabad during the first wave (Sep/ Nov 2020) and before the second wave (in Feb 2021) of COVID-19 in India. The analysis showed a total of 35 mutations in the spike protein across four samples categorized into 23 types. We noticed the presence of spike protein mutations linked to the VOC-21APR-02; B.1.617.2 lineage (Delta variant) with 57% frequency in wastewater samples of Feb 2021. The key spike protein mutations were T19R, L452R, T478K, D614G, & P681R and deletions at 22029 (6 bp), 28248 (6 bp), & 28271 (1 bp). Interestingly, these mutations were not observed in the samples of Sep and Nov 2020 but appeared before the devastating second wave of COVID-19, which started in early April 2021 in India, caused rapid transmission and deaths all over India. We found the genetic traces of the B.1.617.2 in samples of early Feb 2021 i.e., more than a month before the first clinically confirmed case of the same variant in March 2021 in Ahmedabad, Gujarat. The present study tells about the circulating variants in Ahmedabad and suggests early prediction VOCs employing the wastewater genomic surveillance approach that must be exploited at a large scale for effective COVID-19 management.

Highlights

Whole-genome sequencing of SARS-CoV-2 from the WW samples was carried out.

Variant of Concern (VoC: VOC-21APR-02; B.1.617.2) were detected in WW samples.

WBE may detect prevalent SARS-CoV-2 variants and monitor their cryptic transmission

WW genomic surveillance can aid the decision-making system for public health policies.
Pre-trial predictors of conflict response efficacy in human dorsolateral prefrontal cortex
Authors: Herman Alexander B. , Smith Elliot H. , Schevon Catherine A. , Yates Mark , McKhann Guy M. , Botvinick Matthew , Hayden Benjamin Y. , Sheth Sameer Anil
Published: July 2021

The ability to perform motor actions depends, in part, on the brain’s initial state, that is, the ensemble firing rate pattern prior to the initiation of action. We hypothesized that the same principle would apply to cognitive functions as well. To test this idea, we examined a unique set of single unit data collected in human dorsolateral prefrontal (dlPFC) cortex. Data were collected in a conflict task that interleaves Simon (motor-type) and Eriksen (flanker-type) conflict trials. In dlPFC, variability in pre-trial firing rate predicted the ability to resolve conflict, as inferred from reaction times. Ensemble patterns that predicted faster Simon reaction times overlapped slightly with those predicting Erikson performance, indicating that the two conflict types are associated with near-orthogonal initial states, and suggesting that there is a weak abstract or amodal conflict preparatory state in this region. These codes became fully orthogonalized in the response state. We interpret these results in light of the initial state hypothesis, arguing that the firing patterns in dlPFC immediately preceding the start of a task predispose it for the efficient implementation of cognitive action.
Nicotine dependence and functional connectivity of insular cortex subregions
Authors: Ghahremani Dara G. , Pochon Jean-Baptiste , Diaz Maylen Perez , Tyndale Rachel F. , Dean Andy C. , London Edythe D.
Published: July 2021

The insular cortex has been identified as a promising target in brain-based therapies for Tobacco Use Disorder, and has three major sub-regions (ventral anterior, dorsal anterior, and posterior) that serve distinct functional networks. How these subregions and associated networks contribute to nicotine dependence has not been well understood, and therefore was the subject of this study. Forty-seven individuals (24 women; 18-45 years old) who smoked cigarettes daily rated their dependence using the Fagerström Test for Nicotine Dependence (FTND), abstained from smoking overnight (~12 h), and underwent resting-state functional MRI. Correlations between dependence and resting-state functional connectivity (RSFC) of the major insular sub-regions were evaluated using whole-brain-corrected voxel-wise analyses and post-hoc region-of-interest (ROI) analyses. Dependence was analyzed both as a unitary (FTND total score) and bivariate construct – two FTND factors (“morning smoking” and “daytime smoking”). Dependence was negatively correlated with connectivity of both the right dorsal and left ventral anterior insula with the left precuneus, and with connectivity of the left posterior insula to the left putamen. In post-hoc analyses, dependence correlated negatively with connectivity between all anterior insula subregions and the left precuneus, and with bilateral posterior insula connectivity with the left posterior putamen. The latter finding was driven by “daytime smoking”. These results suggest an anterior-posterior distinction in functional insular networks associated with different dimensions of nicotine dependence, with greater dependence linked to weaker connectivity. They may inform therapeutic approaches involving brain stimulation that may elicit differential clinical outcomes depending on the insular subnetwork targeted.
A natural marmoset model of genetic generalized epilepsy
Authors: Yang Xiangyu , Chen Zhitang , Wang Ziying , He Guang , Li Zhiqiang , Shi Yongyong , Gong Neng , Zhao Binglei , Takahashi Eiki , Li Weidong
Published: July 2021

As a common neurological disease, epilepsy has been extensively studied. Efforts have been made on rodent and other animal models to reveal the pathogenic mechanisms of epilepsy and develop new drugs as treatment. However, the features of current epilepsy models cannot fully mimic different kinds of epilepsy in human, asking for non-human primates models of epilepsy. The common marmoset (Callithrix jacchus) is a New World monkey that is widely used to study brain function. Here, we show a natural marmoset model of generalized epilepsy. In this unique marmoset family, generalized epilepsy was successfully induced by handling operation in some individuals. We mapped the marmoset family with handling-sensitive epilepsy and found that epileptic marmoset had an autosomal dominant genetic predisposition. Those marmosets were more sensitive to epilepsy inducers pentylenetetrazol (PTZ). By electrocorticogram (ECoG) recording, we detected epileptic discharge in marmoset with history of seizures. However, there was no significant change in the overall structure of epileptic marmoset brain. In summary, we report a family of marmosets with generalized seizures induced by handling operation. This epileptic marmoset family provides insights to better understand the mechanism of generalized epilepsy and helps to develop new therapeutic methods.

Short summary

Despite the rodent and other animal models on epilepsy, a common neurological disease, the understanding of the pathogenic mechanisms of epilepsy and treatment are yet to be advanced., Non-human primates are good experimental animals for modelling neurological disease. Here we report a common marmoset family with generalized epilepsy induced by handling stimulation. We mapped the epileptic marmoset family and found that epilepsy had a genetic predisposition. The present report deals in detail with the phenotypes and characteristics of epileptic marmosets. This natural marmoset reflect epilepsy model will help to better understand the mechanism of epilepsy and develop new therapeutic methods.
Dissociable Multi-scale Patterns of Development in Personalized Brain Networks
Authors: Pines Adam R. , Larsen Bart , Cui Zaixu , Sydnor Valerie J. , Bertolero Maxwell A. , Adebimpe Azeez , Alexander-Bloch Aaron F. , Davatzikos Christos , Fair Damien A. , Gur Ruben C. , Gur Raquel E. , Li Hongming , Milham Michael P. , Moore Tyler M. , Murtha Kristin , Parkes Linden , Thompson-Schill Sharon L. , Shanmugan Sheila , Shinohara Russell T. , Weinstein Sarah M. , Bassett Danielle S. , Fan Yong , Satterthwaite Theodore D.
Published: July 2021

The brain is organized into networks at multiple resolutions, or scales, yet studies of functional network development typically focus on a single scale. Here, we derived personalized functional networks across 29 scales in a large sample of youths (n=693, ages 8-23 years) to identify multi-scale patterns of network re-organization related to neurocognitive development. We found that developmental shifts in inter-network coupling systematically adhered to and strengthened a functional hierarchy of cortical organization. Furthermore, we observed that scale-dependent effects were present in lower-order, unimodal networks, but not higher-order, transmodal networks. Finally, we found that network maturation had clear behavioral relevance: the development of coupling in unimodal and transmodal networks dissociably mediated the emergence of executive function. These results delineate maturation of multi-scale brain networks, which varies according to a functional hierarchy and impacts cognitive development.
Dug: A Semantic Search Engine Leveraging Peer-Reviewed Knowledge to Span Biomedical Data Repositories
Authors: Waldrop Alexander M. , Cheadle John B. , Bradford Kira , Preiss Alexander , Chew Robert , Holt Jonathan R. , Braswell Nathan , Watson Matt , Crerar Andrew , Ball Chris M. , Kebede Yaphet , Schreep Carl , Linebaugh PJ , Hiles Hannah , Boyles Rebecca , Bizon Chris , Krishnamurthy Ashok , Cox Steve
Published: July 2021

Motivation

As the number of public data resources continues to proliferate, identifying relevant datasets across heterogenous repositories is becoming critical to answering scientific questions. To help researchers navigate this data landscape, we developed Dug: a semantic search tool for biomedical datasets utilizing evidence-based relationships from curated knowledge graphs to find relevant datasets and explain why those results are returned.

Results

Developed through the National Heart, Lung, and Blood Institute’s (NHLBI) BioData Catalyst ecosystem, Dug has indexed more than 15,911 study variables from public datasets. On a manually curated search dataset, Dug’s total recall (total relevant results/total results) of 0.79 outperformed default Elasticsearch’s total recall of 0.76. When using synonyms or related concepts as search queries, Dug (0.36) far outperformed Elasticsearch (0.14) in terms of total recall with no significant loss in the precision of its top results.

Availability and Implementation

Dug is freely available at https://github.com/helxplatform/dug. An example Dug deployment is also available for use at https://search.biodatacatalyst.renci.org/.

Contact

awaldrop@rti.org or scox@renci.org
Ecological inference using data from accelerometers needs careful protocols
Authors: Garde Baptiste , Wilson Rory P. , Fell Adam , Cole Nik , Tatayah Vikash , Holton Mark D. , Rose Kayleigh A. R. , Metcalfe Richard S. , Robotka Hermina , Wikelski Martin , Tremblay Fred , Whelan Shannon , Elliott Kyle H. , Shepard Emily L. C.
Published: July 2021

Accelerometers in animal-attached tags have proven to be powerful tools in behavioural ecology, being used to determine behaviour and provide proxies for movement-based energy expenditure. Researchers are collecting and archiving data across systems, seasons and device types. However, in order to use data repositories to draw ecological inference, we need to establish the error introduced according to sensor type and position on the study animal and establish protocols for error assessment and minimization.

Using laboratory trials, we examine the absolute accuracy of tri-axial accelerometers and determine how inaccuracies impact measurements of dynamic body acceleration (DBA), as the main acceleration-based proxy for energy expenditure. We then examine how tag type and placement affect the acceleration signal in birds using (i) pigeons Columba livia flying in a wind tunnel, with tags mounted simultaneously in two positions, (ii) back- and tail-mounted tags deployed on wild kittiwakes Rissa tridactyla. Finally, we (iii) present a case study where two generations of tag were deployed using different attachment procedures on red-tailed tropicbirds Phaethon rubricauda foraging in different seasons.

Bench tests showed that individual acceleration axes required a two-level correction (representing up to 4.3% of the total value) to eliminate measurement error. This resulted in DBA differences of up to 5% between calibrated and uncalibrated tags for humans walking at different speeds. Device position was associated with greater variation in DBA, with upper- and lower back-mounted tags in pigeons varying by 9%, and tail- and back-mounted tags varying by 13% in kittiwakes. Finally, DBA varied by 25% in tropicbirds between seasons, which may be attributable to tag attachment procedures.

Accelerometer accuracy, tag placement, and attachment details critically affect the signal amplitude and thereby the ability of the system to detect biologically meaningful phenomena. We propose a simple method to calibrate accelerometers that should be used prior to deployments and archived with resulting data, suggest a way that researchers can assess accuracy in previously collected data, and caution that variable tag placement and attachment can increase sensor noise and even generate trends that have no biological meaning.