bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychiatry’s Past Can Be Psychiatry’s Future
Authors: Becker Robert E.
Published: December 2020

In the last half of the 20th century, psychiatry lost many of the conditions needed for unhindered practice. I compiled from searches of the literature the 20th century changes in the arenas of psychiatric practice and the sources of these changes. I determined how these changes are shaping 21st century health and well-being. The neglect of the severely mentally ill, first in Bedlams and now on Boulevards, reflects a wide loss of resources. Psychiatry's patients have lost a past of community-based mental health services, interdisciplinary care teams, preventive consultation with social agencies, and, with reimbursements targeted for 15-minute visits, time adequate with the physician to individualize diagnosis and treatment. With the Covid-19 and other epidemics, economic inequalities, an economic crisis, unrest over police violence, and racism, psychiatry can find in its past the resources to engage 21st century psychiatric and other problems.
Healthcare Failure Mode and Effect Analysis (HFMEA) as an Effective Mechanism in Preventing Infection Caused by Accompanying Caregivers During COVID-19—Experience of a City Medical Center in Taiwan
Authors: Tiao Chi-Hui , Tsai Ling-Chin , Chen Li-Chin , Liao Yu-Mei , Sun Li-Chen
Published: December 2020

Background and Objectives:

In response to the COVID-19 pandemic outbreak and to ensure the safety of epidemic prevention in the hospital, the hospital has established mitigation strategies in advance including risk assessment and effect analysis to control hospital visitors and accompanying persons. The study aims to assess the effectiveness of mitigation strategies implemented to effectively prevent the invasion and spread of the virus.

Method:

Conduct a status analysis in accordance with the Healthcare Failure Mode and Effect Analysis (HFMEA) 4-step model, construct a response workflow, confirm the failure mode and potential causes, perform hazard matrix analysis and decision tree analysis, and formulate risk control management measures.

Results:

For the 4 main processes and 9 subprocesses of the accompanying carers and contract caregivers entering the hospital, 26 potential failure modes and 42 potential causes of failure were analyzed. Following implementing improvement measures including strategies targeting the accompanying person, mitigation workflow failure rates decreased from 42 to 13 items, the pass rate for the maximum body temperature cutoff increased from 53.1% to 90.8%, and the compliance rate of hand washing increased from 89.5% to 100%.

Conclusion:

The HFMEA model can effectively implement preventive risk assessment and workflow management of high-risk medical procedures. The model can adjudicate the health of hospital visitors during the epidemic/pandemic, provide epidemic/pandemic education training and preventive measure health education guidance for hospital visits, and improve their epidemic prevention cognition. When combined, these strategies can prevent nosocomial infection to achieve the best anti-epidemic effect.
Synthetic Versus Biological Mesh in Laparoscopic and Open Ventral Hernia Repair (LAPSIS)
Authors: Miserez Marc , Lefering Rolf , Famiglietti Federico , Mathes Tim , Seidel Dörthe , Sauerland Stefan , Korolija Dragan , Heiss Markus , Weber Gyorgy , Agresta Ferdinando , Steup Willem-Hans , Śmietański Maciej , Ribeiro Rui , Cuccurullo Diego , Catena Fausto , Rudroff Claudia , Rosanelli Georg , Schön Fabian , Smet Bart , Wenger Frank , Saad Stefano , Naver Lars , Neugebauer Edmund
Published: December 2020

Objective:

The aim of this study was to investigate the approach (open or laparoscopic) and mesh type (synthetic or biological) in ventral hernias in a clean setting.

Summary of Background Data: The level of evidence on the optimal surgical approach and type of mesh in ventral hernia repair is still low.

Methods:

Patients with a ventral abdominal hernia (diameter 4–10 cm) were included in this double-blind randomized controlled trial across 17 hospitals in 10 European countries. According to a 2 × 2-factorial design, patients were allocated to 4 arms (open retromuscular or laparoscopic intraperitoneal, with synthetic or Surgisis Gold biological mesh). Patients and outcome assessors were blinded to mesh type used. Major postoperative complication rate (hernia recurrence, mesh infection, or reoperation) within 3 years after surgery, was the primary endpoint in the intention-to-treat population.

Results:

Between September 1st, 2005, and August 7th, 2009, 253 patients were randomized and 13 excluded. Six of 61 patients (9.8%) in the open synthetic mesh arm, 15 of 66 patients (22.7%) in the open biological mesh arm, 7 of 64 patients (10.9%) in the laparoscopic synthetic mesh arm and 17 of 62 patients (27.4%) in the laparoscopic biological mesh arm had a major complication. The use of biological mesh resulted in significantly more complications (P = 0.013), also after adjusting for hernia type, body mass index, and study site. The trial was prematurely stopped due to an unacceptable high recurrence rate in the biological mesh arms.

Conclusions:

The use of Surgisis Gold biological mesh is not recommended for noncomplex ventral hernia repair.

Trial Registration:

This trial was registered at controlled-trials.com (ISRCTN34532248).
Trends of COVID-19 (Coronavirus Disease) in GCC Countries using SEIR-PAD Dynamic Model
Authors: Sedaghat Ahmad , Abbas Oloomi Seyed Amir , Malayer Mahdi Ashtian , Mosavi Amir
Published: December 2020

Extension of SIR type models has been reported in a number of publications in mathematics community. But little is done on validation of these models to fit adequately with multiple clinical data of an infectious disease. In this paper, we introduce SEIR-PAD model to assess susceptible, exposed, infected, recovered, super-spreader, asymptomatic infected, and deceased populations. SEIR-PAD model consists of 7-set of ordinary differential equations with 8 unknown coefficients which are solved numerically in MATLAB using an optimization algorithm. Four set of COVID-19 clinical data consist of cumulative populations of infected, deceased, recovered, and susceptible are used from start of the outbreak until 23rd June 2020 to fit with SEIR-PAD model results. Results for trends of COVID-19 in GCC countries indicate that the disease may be terminated after 200 to 300 days from start of the outbreak depends on current measures and policies. SEIR-PAD model provides a robust and strong tool to predict trends of COVID-19 for better management and/or foreseeing effects of certain enforcing laws by governments, health organizations or policy makers.
Effects of photobiomodulation therapy combined with static magnetic field (PBMT-sMF) in patients with severe COVID-19 requiring intubation: a pragmatic randomized placebo-controlled trial
Authors: De Marchi Thiago , Frâncio Fabiano , Ferlito João Vitor , Weigert Renata Monteiro , de Oliveira Cristiane Aparecida , Merlo Ana Paula , Pandini Délcio Luis , Pasqual Júnior Bolivar Antônio , Giovanella Daniela Frare , Tomazoni Shaiane Silva , Pinto Leal-Junior Ernesto Cesar
Published: December 2020

Background

Photobiomodulation therapy (PBMT) when used isolated or combined with static magnetic field (PBMT-sMF) has been proven benefits on skeletal muscle increasing performance and reducing fatigue, increasing oxygen saturation, and modulating inflammatory process. However, it is unknown whether the effects observed with this therapy on respiratory muscles will be similar to the effects previously observed on skeletal muscles.

Objective

We aimed to investigate whether PBMT-sMF is able to decrease the length of stay in the intensive care unit (ICU) and to reduce the mortality rate of patients with severe COVID-19 requiring invasive mechanical ventilation, increasing the respiratory function and modulating the inflammatory process.

Methods

We conducted a prospectively registered, pragmatic, triple-blinded (patients, therapists and outcome assessors), randomized, placebo-controlled trial of PBMT-sMF in patients with severe COVID-19, requiring invasive mechanical ventilation, admitted to the ICU. Patients were randomly assigned to receive either PBMT-sMF (6 sites at the lower thorax – 189 J total, and 2 sites at the neck area – 63 J total) or placebo PBMT-sMF daily during all the ICU stay. The primary outcome was length of stay in the ICU defined by either discharge or death. The secondary outcomes were survival rate, muscle function of diaphragm, change in blood tests, change in mechanical ventilation parameters and change in arterial blood gas analysis.

Results

A total of 30 patients underwent randomization (with 15 assigned to PBMT-sMF and 15 to placebo) and were analyzed. The length of stay in the ICU for the placebo group was 23.06 days while for the PBMT-sMF group was 16.26. However, there was no statistically difference between groups for the length of stay in the ICU (mean difference - MD = - 6.80; 95% CI = - 18.71 to 5.11). Regarding the secondary outcomes were observed statistically differences in favor of PBMT-sMF for diaphragm thickness, fraction of inspired oxygen, partial pressure of oxygen/fraction of inspired oxygen ratio, C-reactive protein, lymphocytes count, and hemoglobin (p<0.05).

Conclusion

Among patients with severe COVID-19 requiring invasive mechanical ventilation, PBMT-sMF was not statistically different than placebo to the length of stay in the ICU. However, it is important to highlight that our sample size was underpowered to detect statistical differences to the primary outcome. In contrast, PBMT-sMF increased muscle function of diaphragm, improved ventilatory parameters, decreased C-reactive protein levels and hemoglobin count, and increased lymphocytes count.
Neutralising antibodies in Spike mediated SARS-CoV-2 adaptation
Authors: Kemp SA , Collier DA , Datir R , Ferreira IATM , Gayed S , Jahun A , Hosmillo M , Rees-Spear C , Mlcochova P , Lumb Ines Ushiro , Roberts David J , Chandra Anita , Temperton N ,   The CITIID-NIHR BioResource COVID-19 Collaboration,   The COVID-19 Genomics UK (COG-UK) Consortium, Sharrocks K , Blane E , Briggs JAG , van Gils MJ , Smith KGC , Bradley JR , Smith C , Doffinger R , Ceron-Gutierrez L , Barcenas-Morales G , Pollock DD , Goldstein RA , Smielewska A , Skittrall JP , Gouliouris T , Goodfellow IG , Gkrania-Klotsas E , Illingworth CJR , McCoy LE , Gupta RK
Published: December 2020

SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE2, and amino acid variation in Spike is increasingly appreciated. Given both vaccines and therapeutics are designed around Wuhan-1 Spike, this raises the theoretical possibility of virus escape, particularly in immunocompromised individuals where prolonged viral replication occurs. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences by both short and long read technologies over 23 time points spanning 101 days. Although little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days, N501Y in Spike was transiently detected at day 55 and V157L in RdRp emerged. However, following convalescent plasma we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. In vitro, the Spike escape double mutant bearing ΔH69/ΔV70 and D796H conferred decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility, but incurred an infectivity defect. The ΔH69/ΔV70 single mutant had two-fold higher infectivity compared to wild type and appeared to compensate for the reduced infectivity of D796H. Consistent with the observed mutations being outside the RBD, monoclonal antibodies targeting the RBD were not impacted by either or both mutations, but a non RBD binding monoclonal antibody was less potent against ΔH69/ΔV70 and the double mutant. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with reduced susceptibility to neutralising antibodies.
Low COVID-19 mortality in old age homes in western India: an empirical study
Authors: Panchamia Jallavi , Bhagat Bhavya , Bharati Vishakha , Joshi Anushree , Mavalankar Dileep
Published: December 2020

Objective

The study intended to understand the effect of Coronavirus disease 2019 (COVID-19) on western Indian elderly care homes. The study aimed to know the actions taken by administration of homes and challenges faced during the lockdown period.

Method

Total 44 care homes across three states of western India were contacted for data collection during the period of September-November 2020. Structured interview of the manager or owner of the elderly care homes were taken to gather required information to achieve the study objectives.

Results

Out of 44 care homes, seven care homes reported 146 case of corona virus infection and four deaths. Hence, the reported covid cases rate found to be 928 per 10,000 residents.

Discussion

Results of the study indicated that significant steps were taken by these old age care homes to stave off the infection spread among the inmates. It was observed that average 26% of the occupants were sent back to their home/relative’s home before the lockdown to decongest the care homes. Administrators adopted the new policies at care home and adhered the government guidelines. Care homes in western India seemed to have very low infection rate and very low number of deaths as compared to western world.
Interactions between hippocampal activity and striatal dopamine in people at clinical high risk for psychosis: relationship to clinical outcomes
Authors: Modinos Gemma , Richter Anja , Egerton Alice , Bonoldi Ilaria , Azis Matilda , Antoniades Mathilde , Bossong Matthijs , Crossley Nicolas , Perez Jesus , Stone James M. , Veronese Mattia , Zelaya Fernando , Grace Anthony A , Howes Oliver D , Allen Paul , McGuire Philip
Published: December 2020

Background

Preclinical models propose that the onset of psychosis involves increased hippocampal activity which drives subcortical dopaminergic dysfunction. We used multi-modal neuroimaging to examine the relationship between hippocampal regional cerebral blood flow (rCBF) and striatal dopamine synthesis capacity in people at clinical high risk (CHR) for psychosis, and investigated its association with subsequent clinical outcomes.

Methods

Ninety-five participants (67 CHR and 28 healthy controls) underwent pseudo-continuous arterial spin labelling and 18F-DOPA PET imaging at baseline. Clinical outcomes in CHR participants were determined after a median of 15 months follow-up, using the Comprehensive Assessment of At Risk Mental States (CAARMS) and the Global Assessment of Function (GAF) scale.

Results

CHR participants with a poor functional outcome (follow-up GAF<65, n=25) showed higher rCBF in the right hippocampus compared to CHRs with a good functional outcome (GAF≥65, n=25) (familywise error [FWE] p=0·026). The relationship between right hippocampal rCBF and striatal dopamine synthesis capacity was also significantly different between groups (pFWE=0·035); the association was negative in CHR with poor outcomes (pFWE=0·012), but non-significant in CHR with good outcomes. The correlation between rCBF in this right hippocampal region and striatal dopamine function also predicted a longitudinal increase in the severity of positive psychotic symptoms (p=0·041). The relationship between hippocampal rCBF and striatal dopamine did not differ in the total CHR group relative to controls.

Interpretation

These findings indicate that altered interactions between the hippocampus and the subcortical dopamine system are implicated in the pathophysiology of psychosis-related outcomes.
Factors associated with clinical severity in Emergency Department patients presenting with symptomatic SARS-CoV-2 infection
Authors: Newton Sophia , Zollinger Benjamin , Freeman Jincong , Moran Seamus , Helfand Alexandra , Authelet Kayla , McHarg Matthew , Vargas Nataly Montano , Shesser Robert , Cohen Joanna , Cummings Derek , Ma Yan , Meltzer Andrew C.
Published: December 2020

Objective

To measure the association of race, ethnicity, comorbidities, and insurance status with need for hospitalization of symptomatic Emergency Department (ED) patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.

Methods

This study is a retrospective case-series of symptomatic patients presenting to a single ED with laboratory-confirmed SARS-CoV-2 infection from March 12-August 9, 2020. We collected patient-level information regarding demographics, public insurance status (Medicare or Medicaid), comorbidities, level of care, and mortality using a structured chart review. We compared demographics and comorbidities of patients who were (1) able to convalesce at home, (2) required admission to general medical service, (3) required admission to intensive care unit (ICU), or (4) died within 30 days of the index visit. Multivariable logistic regression analyses were performed to report adjusted odds ratios (aOR) and the associated 95% confidence intervals (95% CI) with hospital admission versus ED discharge home.

Results

In total, 993 patients who presented to the ED with symptoms were included in the analysis with 370 (37.3%) patients requiring hospital admission and 70 (7.1%) patients requiring ICU care. Patients requiring admission were more likely to be Black or African American, to be Hispanic or Latino, or to have public insurance (either Medicaid or Medicare.) On multivariable logistic regression analysis comparing which patients required hospital admission, African-American race (aOR 1.4, 95% CI 0.7-2.8) and Hispanic ethnicity (aOR 1.1, 95% CI 0.5-2.0) were not associated with need for admission but, public insurance (Medicaid: aOR 3.4, 95% CI 2.2-5.4; Medicare: aOR 2.6, 95% CI 1.2-5.3; Medicaid and Medicare: aOR 3.6 95% CI 2.1-6.2) and the presence of hypertension (aOR 1.8, 95% CI 1.2-2.7), diabetes (aOR 1.6, 95% CI 1.1-2.5), obesity (aOR 1.7, 95% CI 1.1-2.5), heart failure (aOR 3.9, 95% CI 1.4-11.2), and hyperlipidemia (aOR 1.8, 95% CI 1.2-2.9) were identified as independent predictors of hospital admission.

Conclusion

Comorbidities and public insurance are predictors of more severe illness for patients with SARS-CoV-2. This study suggests that the disparities in severity seen in COVID-19 among African Americans and Hispanics are likely to be closely related to low socioeconomic status and chronic health conditions and do not reflect an independent predisposition to disease severity.
Intention of health care workers to accept COVID-19 vaccination and related factors: a systematic review and meta-analysis
Authors: Galanis Petros , Vraka Irene , Fragkou Despoina , Bilali Angeliki , Kaitelidou Daphne
Published: December 2020

Considering medical and economic burden of the coronavirus disease 2019 (COVID-19), a high COVID-19 vaccination coverage among health care workers (HCWs) is an urgent need. The aim of this systematic review and meta-analysis was to estimate the intention of HCWs to accept COVID-19 vaccination and to find out related factors. We searched PubMed, Medline, Scopus, Web of Science, ProQuest, CINAHL and medRxiv until July 14, 2021. The heterogeneity between results was very high and thus we applied a random effect model to estimate pooled effects. We performed subgroup and meta-regression analysis to identify possible resources of heterogeneity. Twenty four studies, including 39,617 HCWs met the inclusion criteria. The overall proportion of HCWs that intend to accept COVID-19 vaccination was 63.5% (95% confidence interval: 56.5-70.2%) with a wide range among studies from 27.7% to 90.1%. The following factors were associated with increased HCWs’ willingness to get vaccinated against COVID-19: male gender, older age, white HCWs, physician profession, higher education level, comorbidity among HCWs, seasonal influenza vaccination, stronger vaccine confidence, positive attitude towards a COVID-19 vaccine, fear about COVID-19, individual perceived risk about COVID-19, and contact with suspected or confirmed COVID-19 patients. The reluctance of HCWs to vaccinate against COVID-19 could diminish the trust of individuals and trigger a ripple effect in the general public. Since vaccination is a complex behavior, understanding the way that HCWs take the decision to accept or not COVID-19 vaccination will give us the opportunity to develop the appropriate interventions to increase COVID-19 vaccination uptake.

Key Messages

The overall proportion of health care workers that intent to accept COVID-19 vaccination was moderate.

Several factors affect health care workers’ willingness to get vaccinated against COVID-19.

COVID-19 vaccine hesitancy among health care workers should be eliminated to inspire the general public towards a positive attitude regarding a novel COVID-19 vaccine.
Risk of adverse outcomes with COVID-19 in the Republic of Ireland
Authors: Roe M , Wall P , Mallon P , Horgan M
Published: December 2020

Aims

To compare the risk of adverse outcomes (i.e. hospital/intensive care admission, death) in population sub-groups during two periods of the COVID-19 pandemic in the Republic of Ireland.

Methods

We analysed routinely-collected, publicly-available data on 67,900 people with laboratory confirmed COVID-19 infection between 29th Feb to 14th Nov 2020. This period encompassed two waves of infection and two corresponding national lockdowns. For two observational periods covering each wave (W1, W2), each ending 17-19 days before implementation of high-level national restrictions, we segmented the population based on age and underlying clinical conditions.

Results

The prevalence of laboratory confirmed COVID-19 was 1.4%. The risk of admission to hospital, admission to intensive care, and death was 7.2%, 0.9%, and 2.5%, respectively. Compared to younger confirmed cases, those aged ≥65 y had increased risk of hospital admission (RR 5.61), ICU admission (RR 3.56), and death (RR 60.8). W2 was associated with more cases and fewer adverse events than W1. The risk of all adverse outcomes was reduced in W2 than in W1.

Conclusions

Ongoing responses should consider the variation in risk of adverse outcomes between specific sub-groups. These findings indicate the need to sustain the prevention, identification and management of noncommunicable diseases to reduce the burden of COVID-19.
Clinical characteristics of critically ill patients with COVID-19
Authors: Bisso Indalecio Carboni , Huespe Iván , Lockhart Carolina , Massó Agustín , González Anaya Julieta , Hornos Micaela , Famiglietti Romina , Di Grazia Marcelo , Coria Pablo , Román Eduardo San , Heras Marcos Las
Published: December 2020

Objective

Describe the clinical and respiratory characteristics of critical patients with coronavirus disease 2019 (COVID-19).

Design

Observational and retrospective study over 6 months.

Setting

Intensive care unit (ICU) of a high complexity hospital in Buenos Aires, Argentina.

Patients

Patients older than 18 years with laboratory-confirmed COVID-19 by reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2 were included in the study.

Variables of interest

Demographic characteristics such as sex and age, comorbidities, laboratory results, imaging results, ventilatory mechanics data, complications, and mortality were recorded.

Results

A total of 168 critically ill patients with COVID-19 were included. 66% were men with a median age of 65 years (58-75. 79.7% had at least one comorbidity. The most frequent comorbidity was arterial hypertension, affecting 52.4% of the patients. 67.9 % required invasive mechanical ventilation (MV), and no patient was treated with non-invasive ventilation. Most of the patients in MV (73.7%) required neuromuscular blockade due to severe hypoxemia. 36% of patients were ventilated in the prone position. The length of stay in the ICU was 13 days (6-24) and the mortality in the ICU was 25%.

Conclusions

In this study of critical patients infected by SARS-CoV-2 in a high-complexity hospital, the majority were comorbid elderly men, a large percentage required invasive mechanical ventilation, and ICU mortality was 25%.
COVID-19 Test Strategy to Guide Quarantine Interval in University Student
Authors: Kolesar Jill M. , Gayheart Tyler , Poston Lance , Monday Eric , Forster Derek , Belcher Elizabeth , Jaiswal Rani , Turner J. Kirsten , Arnett Donna K. , Durbin Eric B. , Monroe Joseph , Romanelli Frank , Arnold Susanne M. , Jennings C. Darrell , Weiss Heidi , DiPaola Robert
Published: December 2020

BACKGROUND

Following COVID-19 exposure, the CDC recommends a 10-14 day quarantine for asymptomatic individuals and more recently a 7 day quarantine with a negative PCR test. We performed a university-based prospective student cohort study to determine if early PCR negativity predicts day 14 negativity.

METHODS

We enrolled 101 asymptomatic, quarantining, students, performed nasopharyngeal swabs for viral testing on days 3 or 4, 5, 7, 10 and 14 and determined the proportion of concordant negative results for each day versus day 14 with a two-sided 95% exact binomial confidence interval.

RESULTS

Overall, 14 of 90 (16%, 95% CI: 9% - 25%) tested positive while in quarantine, with 7 initial positive tests on day 3 or 4, 5 on day 5, 2 on day 7, and none on day 10 or 14. Rates of concordant negative test results are: day 5 vs. day 14 = 45/50 (90%, 95% CI: 78% - 97%); day 7 vs. day 14 = 47/52 (90%, 95% CI: 79% - 97%); day 10 vs. day 14 = 48/53 (91%, 95% CI:79% - 97%), with no evidence of different negative rates between earlier days and day 14 by McNemar’s test, p > 0.05.

CONCLUSIONS

The 16% positive rate supports the ongoing need to quarantine close contacts of COVID-19 cases, but this prospective study provides the first direct evidence that exposed asymptomatic students ages 18-44 years in a university setting are at low risk if released from quarantine at 7 days if they test negative PCR test prior to release.
Cell-fate decision of mesenchymal stem cells toward osteocyte differentiation is committed by cell condensed condition in spheroid culture
Authors: Kim Jeonghyun , Adachi Taiji
Published: December 2020

Osteocytes are mechanosensory commander cells to regulate bone remodeling throughout the lifespan. While the osteocyte is known as a terminally differentiated cell derived from mesenchymal stem cell, the detailed mechanisms of cell-fate decision toward osteocyte differentiation still remain unclear. In this study, we fabricated three-dimensional (3D) self-organized spheroids using human mesenchymal stem cells (hMSCs). Under the osteogenesis induction medium, the spheroid culture model exerted the osteocyte-likeness within 2 days compared to a conventional 2D monolayer model. By using an inhibitor of actin polymerization, we showed an involvement of actin balancing in the osteocyte differentiation in the spheroid. Notably, we represented that the cell condensed condition acquired in the 3D spheroid culture model determined a differentiation fate of MSCs to osteocytes via actin balancing. Taken together, we suggest that our self-organized spheroid model can be utilized as a newin vitromodel to represent the osteocyte differentiation process and further to recapitulate anin vitroossification process.
The hybrid nature of task-evoked activity: Inside-out neural dynamics in intracranial EEG and Deep Learning
Authors: Wolff Annemarie , Chen Liang , Tumati Shankar , Golesorkhi Mehrshad , Gomez-Pilar Javier , Hu Jie , Jiang Shize , Mao Ying , Longtin Andre , Northoff Georg
Published: December 2020

A.

The standard approach in neuroscience research infers from the external stimulus (outside) to the brain (inside) through stimulus-evoked activity. Recently challenged by Buzsáki, he advocates the reverse; an inside-out approach inferring from the brain’s activity to the neural effects of the stimulus. If so, stimulus-evoked activity should be a hybrid of internal and external components. Providing direct evidence for this hybrid nature, we measured human intracranial stereo-electroencephalography (sEEG) to investigate how prestimulus variability, i.e., standard deviation, shapes poststimulus activity through trial-to-trial variability. We first observed greater poststimulus variability quenching in trials exhibiting high prestimulus variability. Next, we found that the relative effect of the stimulus was higher in the later (300-600ms) than the earlier (0-300ms) poststimulus period. These results were extended by our Deep Learning LSTM network models at the single trial level. The accuracy to classify single trials (prestimulus low/high) increased greatly when the models were trained and tested with real trials compared to trials that exclude the effects of the prestimulus-related ongoing dynamics (corrected trials). Lastly, we replicated our findings showing that trials with high prestimulus variability in theta and alpha bands exhibits faster reaction times. Together, our results support the inside-out approach by demonstrating that stimulus-related activity is a hybrid of two factors: 1) the effects of the external stimulus itself, and 2) the effects of the ongoing dynamics spilling over from the prestimulus period, with the second, i.e., the inside, dwarfing the influence of the first, i.e., the outside.

B.

Significance Statement

Our findings signify a significant conceptual advance in the relationship between pre- and poststimulus dynamics in humans. These findings are important as they show that we miss an essential component - the impact of the ongoing dynamics - when restricting our analyses to the effects of the external stimulus alone. Consequently, these findings may be crucial to fully understand higher cognitive functions and their impairments, as can be seen in psychiatric illnesses. In addition, our Deep Learning LSTM models show a second conceptual advance: high classification accuracy of a single trial to its prestimulus state. Finally, our replicated results in an independent dataset and task showed that this relationship between pre- and poststimulus dynamics exists across tasks and is behaviorally relevant.
In-House Forecasting of Crop Latitude Adaptation through a Daylength-sensing-based Environment Adaptation Simulator (DEAS)
Authors: Qiu Leilei , Wu Qinqin , Wang Xiaoying , Zhuang Gui , Han Jiupan , Wang Hao , Shang Zhiyun , Tian Wei , Chen Zhuo , Lin Zechuan , He Hang , Hu Jie , Lv Qiming , Ren Juansheng , Xu Jun , Li Chen , Wang Xiangfeng , Li Yang , Li Shaohua , Huang Rongyu , Chen Xu , Zhang Cheng , Lu Ming , Liang Chengzhi , Qin Peng , Huang Xi , Li Shigui , Ouyang Xinhao
Published: December 2020

Global climate change necessitates the accelerated breeding of new crop varieties that can sustain yields in new environments. As a proxy for environmental adaptation, the selection of crops that can adapt to different latitudes is an appealing strategy. However, such selection currently involves a lengthy procedure that severely restricts the rapid breeding of varieties. Here, we aimed to combine molecular technologies with an in-house streamlined screening method to facilitate rapid selection for latitude adaptation. We established the Daylength-sensing-based Environment Adaptation Simulator (DEAS) to measure crop latitude adaptation via the transcriptional dynamics of florigen genes at different latitudes. We used different statistical approaches to demonstrate that DEAS predicts the florigen expression profiles in rice with high accuracy. Furthermore, we demonstrated the potential for application of DEAS in different crops. Incorporating DEAS into the breeding programs of conventional and underutilized crops could help meet the future needs for crop adaptation and promote sustainable agriculture.
Detecting de novo mitochondrial mutations in angiosperms with highly divergent evolutionary rates
Authors: Broz Amanda K. , Waneka Gus , Wu Zhiqiang , Gyorfy Matheus Fernandes , Sloan Daniel B.
Published: December 2020

Although plant mitochondrial genomes typically show low rates of sequence evolution, levels of divergence in certain angiosperm lineages suggest anomalously high mitochondrial mutation rates. However, de novo mutations have never been directly analyzed in such lineages. Recent advances in high-fidelity DNA sequencing technologies have enabled detection of mitochondrial mutations when still present at low heteroplasmic frequencies. To date, these approaches have only been performed on a single plant species (Arabidopsis thaliana). Here, we apply a high-fidelity technique (Duplex Sequencing) to multiple angiosperms from the genus Silene, which exhibits extreme heterogeneity in rates of mitochondrial sequence evolution among close relatives. Consistent with phylogenetic evidence, we found that S. latifolia maintains low mitochondrial variant frequencies that are comparable to previous measurements in Arabidopsis. Silene noctiflora also exhibited low variant frequencies despite high levels of historical sequence divergence, which supports other lines of evidence that this species has reverted to lower mitochondrial mutation rates after a past episode of acceleration. In contrast, S. conica showed much higher variant frequencies in mitochondrial (but not in plastid) DNA, consistent with an ongoing bout of elevated mitochondrial mutation rates. Moreover, we found an altered mutational spectrum in S. conica heavily biased towards AT➔GC transitions. We also observed an unusually low number of mitochondrial genome copies per cell in S. conica, potentially pointing to reduced opportunities for homologous recombination to accurately repair mismatches in this species. Overall, these results suggest that historical fluctuations in mutation rates are driving extreme variation in rates of plant mitochondrial sequence evolution.
An uncanonical transcription factor-DREB2B regulates seed vigor negatively through ABA pathway
Authors: Ali Faiza , Wei Zhenzhen , Li Yonghui , Gan Lei , Yang Zuoren , Li Fuguang , Wang Zhi
Published: December 2020

Seed vigor is an important trait for ecology, agronomy, and economy and varies with different plant species and environmental conditions. Dehydration-Responsive Element-Binding Protein 2B (DREB2B), a subgroup of the DREB transcription factor family, is well-known in drought resistance. However, the role ofDREB2Bin the regulation of seed vigor has not been identified. Here, we found thatDREB2Bis a negative regulator of seed vigor by ABA-mediated pathway in Arabidopsis with loss of function mutant and over-expressed transgenic lines. Furthermore,DREB2Bshowed epistatic and parallel toABI3simultaneously in seed vigor regulation by genetic and molecular approaches.DREB2Bhomolog gene (GhDREB2B-A09) was also identified in cotton. The expression analysis indicated that transcripts ofDREB2Bwere higher in mature dry seed, and the transgenic plants showed the conservative roles ofDREB2Bin Arabidopsis and cotton. In addition, we identified that DREB2B interacted with RADICAL-INDUCED CELL DEATH1 (RCD1) to involve seed vigor regulation together inArabidopsisand cotton with BiFC experiment and mutant phenotypic analysis. Collectively it is concluded that DREB2B interacting with RCD1 or SRO1 function at upstream of and synergistic withABI3to regulate seed vigor negatively inArabidopsisand cotton, which provides novel knowledge in the seed development study.

Highlights

DREB2B transcription is seed specific and a negative regulator of seed vigor by ABA-mediated pathway, which interacts with RCD1s, and functions synergistically with ABI3 to affecet seed germination and vigor in Arabidopsis and cotton.
Short of Breath for the Long Haul: Diaphragm Muscle Dysfunction in Survivors of Severe COVID-19 as Determined by Neuromuscular Ultrasound
Authors: Farr Ellen , Wolfe Alexis R. , Deshmukh Swati , Rydberg Leslie , Soriano Rachna , Walter James M. , Boon Andrea J. , Wolfe Lisa F. , Franz Colin K.
Published: December 2020

Many survivors from severe coronavirus disease 2019 (COVID-19) suffer from persistent dyspnea and fatigue long after resolution of the active infection. In a cohort of 25 consecutive COVID-19 survivors admitted to an inpatient rehabilitation hospital (76% male), 80% of them had at least one sonographic abnormality of diaphragm muscle structure or function.

Specifically, when compared to established normative data, 76% had reduced diaphragm thickening ratio (impaired contractility), and 20% patients had reduced diaphragm muscle thickness (atrophy). These findings support neuromuscular respiratory dysfunction as a highly prevalent underlying cause for prolonged functional impairments after hospitalization for COVID-19.
Will the COVID-19 pandemic lead to a tsunami of suicides? A Swedish nationwide analysis of historical and 2020 data
Authors: Rück Christian , Mataix-Cols David , Malki Kinda , Adler Mats , Flygare Oskar , Runeson Bo , Sidorchuk Anna
Published: December 2020

Background

Various surveys have documented a negative impact of the COVID-19 pandemic on the population’s mental health. There is widespread concern about a surge of suicides, but evidence supporting a link between global pandemics and suicide is very limited. Using historical data from the three major influenza pandemics of the 20thcentury, and recently released data from the first half of 2020, we aimed to investigate whether an association exists between influenza deaths and suicide deaths.

Methods

Annual data on influenza death rates and suicide rates were extracted from the Statistical Yearbook of Sweden from 1910-1978, covering the three 20thcentury pandemics, and from Statistics Sweden for the period from January to June of each year during 2000-2020. COVID-19 death data were available for the first half of 2020. We implemented non-linear autoregressive distributed lag (NARDL) models to explore if there is a short-term and/or long-term effect of increases and decreases in influenza death rates on suicide rates during 1910-1978. Analyses were done separately for men and women. Descriptive analyses were used for the available 2020 data.

Findings

Between 1910-1978, there was no evidence of either short-term or long-term significant associations between influenza death rates and changes in suicides. The same pattern emerged in separate analyses for men and women. Suicide rates in January-June 2020 revealed a slight decrease compared to the corresponding rates in January-June 2019 (relative decrease by −1.2% among men and −12.8% among women).

Interpretation

We found no evidence of short or long-term association between influenza death rates and suicide death rates across three 20thcentury pandemics or during the first six months of 2020 (when the first wave of COVID-19 occurred). Concerns about a substantial increase of suicides may be exaggerated. The media should be cautious when reporting news about suicides during the current pandemic.
Impaired peripheral mononuclear cell metabolism in patients at risk of developing sepsis: A cohort study
Authors: Herwanto Velma , Wang Ya , Shojaei Maryam , Khan Alamgir , Lai Kevin , Shetty Amith , Huang Stephen , Chew Tracy , Teoh Sally , Nalos Marek , Chakraborty Mandira , McLean Anthony S. , Tang Benjamin MP.
Published: December 2020

Purpose

Dysregulated immune response is a key driver of disease progression in sepsis and known to be associated with impaired cellular metabolism. This association has been studied mostly in the late stage sepsis patients. Here, we investigate whether such impairment in cellular metabolism is present in uncomplicated infection patients who do not develop sepsis.

Methods

Forty sepsis (fulfilled Sepsis-3 criteria) and 27 uncomplicated infection patients were recruited from the emergency department along with 20 healthy volunteers. Whole blood was collected for measurement of gene expression, cytokine levels and cellular metabolic functions (including mitochondrial respiration, oxidative stress and apoptosis).

Results

Our analysis revealed the impairment of mitochondrial respiration in uncomplicated infection and sepsis patients (p value <0.05), with greater degree of impairment noted in the established sepsis. The impairment was significantly correlated with increased mitochondrial oxidative stress level; the latter was increased in uncomplicated infection and more so in established sepsis patients. Further analysis revealed that the oxidative stress level correlated significantly with cytokine level (tumor necrosis factor-α) and gene expression levels (CYCS, TP53, SLC24A24 and TSPO).

Conclusions

These findings suggest that impaired immune cell metabolism is present in infection patients without presenting sepsis, thereby opening potential window for early diagnosis and intervention (e.g. antioxidant therapy) in such patients.
Comprehensive analysis of SARS-CoV-2 antibody dynamics in New Zealand
Authors: Whitcombe Alana L. , McGregor Reuben , Craigie Alyson , James Alex , Charlewood Richard , Lorenz Natalie , Dickson James M.J. , Sheen Campbell R. , Koch Barbara , Fox-Lewis Shivani , McAuliffe Gary , Roberts Sally A. , Morpeth Susan C. , Taylor Susan , Webb Rachel H. , Jack Susan , Upton Arlo , Ussher James , Moreland Nicole J.
Published: December 2020

Objectives

Circulating antibodies are important markers of previous infection and immunity. Questions remain with respect to the durability and functionality of SARS-CoV-2 antibodies. This study explored antibody responses in recovered COVID-19 patients in a setting where the probability of re-exposure is effectively nil, owing to New Zealand’s successful elimination strategy.

Methods

A triplex bead-based assay that detects antibody isotype (IgG, IgM and IgA) and subclass (IgG1, IgG2, IgG3, IgG4) responses against Nucleocapsid (N) protein, Receptor Binding Domain (RBD) and Spike (S) protein of SARS-CoV-2 was developed. After establishing baseline levels with pre-pandemic control sera (n=113), samples from PCR-confirmed COVID-19 patients with mild-moderate disease (n=189) collected up to eight months post-infection were examined. The relationship between antigen-specific antibodies and neutralising antibodies (NAbs) was explored with a surrogate neutralisation assay that quantifies inhibition of the RBD/hACE-2 interaction.

Results

While most individuals had broad isotype and subclass responses to each antigen shortly after infection, only RBD and S protein IgG, as well as NAbs, were stable over the study period, with 99%, 96% and 90% of samples, respectively, having responses over baseline 4-8 months post-infection. Anti-RBD antibodies were strongly correlated with NAbs at all time points (Pearson’s r ≥ 0.87) and feasibility of using finger prick sampling to accurately measure anti-RBD IgG was demonstrated.

Conclusion

Antibodies to SARS-CoV-2 persist for up to eight months following mild to moderate infection. This robust response can be attributed to the initial exposure without immune boosting given the lack of community transmission in our setting.
Low case numbers enable long-term stable pandemic control without lockdowns
Authors: Contreras Sebastian , Dehning Jonas , Mohr Sebastian B. , Bauer Simon , Spitzner F. Paul , Priesemann Viola
Published: December 2020

The traditional long-term solutions for epidemic control involve eradication or population immunity. Here, we analytically derive the existence of a third viable solution: a stable equilibrium at low case numbers, where test-trace-and-isolate policies partially compensate for local spreading events, and only moderate restrictions remain necessary. In this equilibrium, daily cases stabilize around ten new infections per million people or less. However, stability is endangered if restrictions are relaxed or case numbers grow too high. The latter destabilization marks a tipping point beyond which the spread self-accelerates. We show that a lockdown can reestablish control and that recurring lockdowns are not necessary given sustained, moderate contact reduction. We illustrate how this strategy profits from vaccination and helps mitigate variants of concern. This strategy reduces cumulative cases (and fatalities) 4x more than strategies that only avoid hospital collapse. In the long term, immunization, large-scale testing, and international coordination will further facilitate control.
Mechanically assisted walking training during inpatient rehabilitation after stroke: perceptions of physiotherapists
Authors: Brauer Sandra G , Waters Lauren , Kuys Suzanne S , Ada Louise
Published: December 2020

Background and Purpose

Despite evidence supporting the use of mechanically assisted walking training in stroke rehabilitation, it is not extensively used. The purpose of this study was to explore the perceptions of physiotherapists regarding their use of mechanically assisted walking training, specifically treadmill training, during inpatient rehabilitation after stroke. Better understanding of physiotherapists’ perceptions can inform the development of translation strategies.

Methods

A qualitative study using focus groups comprising 14 physiotherapists (including students) working in stroke inpatient rehabilitation at two sites was conducted. Transcripts were analysed using an inductive approach to thematic analysis.

Results

Physiotherapists perceived two main themes related to using mechanically assisted walking training during inpatient rehabilitation: therapeutic consequences (eg, patients able to walk earlier, further, longer; less fatiguing for therapist, ability to manipulate walking parameters) and practical considerations (eg, safety, efficiency, staff skill, access to equipment, weight and level of disability of patient, fear of treadmill).

Discussion

Therapists’ perceptions of using mechanically assisted walking training during inpatient rehabilitation after stroke were mixed. There is a need to educate physiotherapy staff about the evidence of therapeutic value as well as how to perform mechanically assisted walking training.