bluuebunny/crossref_metadata_2025 huggingface dataset:
Overcoming key challenges in cancer immunotherapy with engineered T cells
Authors: Arcangeli Silvia , Mestermann Katrin , Weber Justus , Bonini Chiara , Casucci Monica , Hudecek Michael
Published: August 2020

Purpose of review

A number of clinical trials are currently testing chimeric antigen receptor (CAR) and T cell receptor (TCR) engineered T cells for the treatment of haematologic malignancies and selected solid tumours, and CD19-CAR-T cells have produced impressive clinical responses in B-cell malignancies. Here, we summarize the current state of the field, highlighting the key aspects required for the optimal application of CAR and TCR-engineered T cells for cancer immunotherapy.

Recent findings

Toxicities, treatment failure and disease recurrence have been observed at different rates and kinetics. Several strategies have been designed to overcome these hurdles: the identification and combination of known and new antigens, together with the combination of immunotherapeutic and classical approaches may overcome cancer immune evasion. New protocols for genetic modification and T cell culture may improve the overall fitness of cellular products and their resistance to hostile tumour immunomodulatory signals. Finally, the schedules of T cell administration and toxicity management have been adapted to improve the safety of this transformative therapeutic approach.

In order to develop effective adoptive T cell treatments for cancer, therapeutic optimization of engineered CAR and TCR T cells is crucial, by simultaneously focusing on intrinsic and extrinsic factors. This review focuses on the innovative approaches designed and tested to overcome the hurdles encountered so far in the clinical practice, with new excitement on novel laboratory insights and ongoing clinical investigations.
Understanding the Health Literacy in Patients With Thrombotic Thrombocytopenic Purpura
Authors: Pereira Leydi C. Velasquez , Ercig Bogac , Kangro Kadri , Jamme Matthieu , Malot Sandrine , Galicier Lionel , Poullin Pascale , Provôt François , Presne Claire , Kanouni Tarik , Servais Aude , Benhamou Ygal , Daguindau Nicolas , Vanhoorelbeke Karen , Azoulay Elie , Veyradier Agnès , Coppo Paul
Published: August 2020

Supplemental Digital Content is available in the text
Epithelial basement membrane dystrophy after femtosecond laser–assisted LASIK successfully treated with in vivo confocal microscopy–assisted photorefractive keratectomy
Authors: Wu Po-Ying , Tsui Mei-Chi , Chang Chao-Kai , Chang Huai-Wen , Chen Wei-Li
Published: August 2020

Photorefractive keratectomy (PRK) was performed to treat corneal epithelial basement membrane dystrophy (EBMD) found after femtosecond laser–assisted laser in situ keratomileusis (FS-LASIK) in a 29-year-old man with previous silent cornea. The patient was diagnosed with post–FS-LASIK EBMD by slitlamp examination and in vivo confocal microscopy (IVCM). Initial treatment with topical lubricants and alcohol soaking was unsuccessful, and the patient continued to have blurred vision and discomfort. The patient underwent a PRK procedure, and the symptoms resolved dramatically; residual refractive errors were also corrected. IVCM revealed a characteristic presentation of EBMD before PRK and normal corneal epithelium after treatment. Patients with asymptomatic EBMD might suffer from recurrent corneal erosions after FS-LASIK. Surface ablation including PRK might lead to successful treatment outcomes, and IVCM might provide helpful information before and after treatment.
Remote corneal suturing wet lab: microsurgical education during the COVID-19 pandemic
Authors: Pasricha Neel D. , Haq Zeeshan , Ahmad Tessnim R. , Chan Lawrence , Redd Travis K. , Seitzman Gerami D. , Parikh Neeti , Kim Tyson N. , Schallhorn Julie M. , Ramanathan Saras
Published: August 2020

Purpose:

To study the feasibility and efficacy of a new remote wet lab for microsurgical education using a corneal suturing task.

Setting:

Department of Ophthalmology, University of California San Francisco, San Francisco, California, USA.

Design:

Prospective randomized controlled study.

Methods:

Ten ophthalmology residents were stratified by postgraduate year and randomized to perform a corneal suturing task consisting of placing the 4 cardinal sutures for a penetrating keratoplasty in porcine eyes with or without remote ophthalmology attending feedback. Subsequently, both groups repeated the same task without remote feedback to test whether initial remote feedback affected subsequent performance. Finally, the group without feedback was crossed over to repeat the same corneal suturing task with remote feedback. The effectiveness of the remote wet lab was assessed subjectively by survey and objectively by grading each suture pass.

Results:

Resident-reported comfort with corneal suturing improved significantly after the remote wet lab for all residents. Residents and attendings rated the remote wet lab as equally or more effective compared with previous in-person wet labs and overall effective in corneal suturing. Attendings rated the remote wet lab as effective in multiple domains of microsurgical education using a modified microsurgical global rating scale. Objective corneal suturing performance was similar for both groups.

Conclusions:

The remote wet lab was feasible and effective for training ophthalmology residents in corneal suturing. This represents a new social distancing compliant platform for microsurgical education during the COVID-19 pandemic.
Improving Utilization of Vaccine Two-Dimensional (2D) Barcode Scanning Technology Maximizes Accuracy Benefits
Authors: Reed Jenica H. , Evanson Heather V. , Cox Regina , Williams Warren W. , Vallero Judi , Caughron Seth , Rodgers Loren , Greene Michael , Koeppl Patrick , Gerlach Ken
Published: August 2020

Background:

Recording vaccine data accurately can be problematic in medical documentation, including blank and inaccurate records. Vaccine two-dimensional (2D) barcode scanning has shown promise, yet scanner use to record vaccine data is limited. We sought to identify strategies to improve scanning rates and assess changes in accuracy.

Methods:

Between January and June 2017, 27 pilot sites within a large health system were assigned to one of four groups to test strategies to maximize scanner use: training only, commitment card, scanning report, or combination. Seventy-two thousand vaccine records were assessed for completeness, accuracy, and scanning.

Results:

Significant increases in vaccinator scanning rates found with commitment card and scanning report inclusion (alone and paired) compared with the training-only group. Record completeness and accuracy significantly improved with use of scanning. When manually entered, about 1 in 9 records had a missing or inaccurate expiration date; when scanned, this dropped to 1 in 5,000.

Conclusions:

Pilot findings indicate 2D scanning has the potential to eliminate most omissions and inaccuracies in vaccine records. Such data are critical during a recall or need to trace specific vaccines or patients.

Implications:

Consistent use and expanded adoption of 2D scanning can meaningfully improve the quality of vaccine records and clinical practices.
A Multicenter Focus Group Analysis of Medicare Beneficiaries Perception of Annual Wellness Visits
Authors: Solinsky Paul , Rochester-Eyeguokan Charmaine , Brandt Nicole , Pincus Kathleen J.
Published: August 2020

National utilization of Medicare's Annual Wellness Visits (AWVs) benefit is low. Few studies have evaluated how beneficiaries perceive this service. This study aimed to characterize beneficiaries' opinion on the value of AWVs, preventive care services offered by Medicare, and barriers and facilitators to receiving those services. This qualitative study used semistructured focus group interviews of Medicare beneficiaries aged 65 years or older with a standardized facilitator guide. Four focus groups were conducted with 30 Medicare beneficiaries in an assisted-living facility, senior housing apartments, and a primary care office. Qualitative thematic analysis of focus group responses revealed that preventive healthcare was valued, but access to quality preventive care remains an issue for patients. Most participants did not know about AWVs and reported confusion over the terminology “wellness visit” compared with checkup or physical. Medicare beneficiaries are not commonly aware of AWVs. Increased promotion of AWV services by healthcare professionals may increase the number of beneficiaries participating in these preventive visits.
Psychosocial support interventions for cancer caregivers: reducing caregiver burden
Authors: Treanor Charlene J.
Published: August 2020

Purpose of review

Informal caregivers of individuals affected by cancer undertake a range of activities and responsibilities throughout the course of the cancer care trajectory. This role is often undertaken alongside employment and other caring roles and can contribute to caregiver burden, which may be ameliorated through psychosocial intervention.

Recent findings

Fifteen new studies investigating the potential of psychosocial interventions for reducing caregiver burden were identified from the period January 2019 to February 2020. Studies were mostly quasi-experimental or randomised controlled trials (RCTs). Psychoeducation was the main intervention identified, though content varied, psychoeducation was associated with improvements in burden, quality of life (QoL) domains and psychological symptoms for caregivers. A small number of counselling/therapeutic interventions suggest that caregivers supporting patients with advanced cancer or cancers with high symptom burden may experience reduced psychological symptoms and QoL benefits. There was a paucity of evidence for other psychosocial interventions (e.g. mindfulness, acceptance and commitment therapy) and methodological quality was variable across all intervention types.

Psychosocial interventions may help to reduce burden for informal caregivers of individuals affected by cancer, though there remains a need for rigorously designed, multicentred RCTs and to examine the long-term impact of psychosocial interventions for caregivers.
Second-line tyrosine kinase inhibitor-therapy after immunotherapy-failure
Authors: Deuker Marina , Chun Felix K.H. , Karakiewicz Pierre I.
Published: August 2020

Purpose of review

Most contemporary metastatic renal-cell carcinoma patients receive first-line immunotherapy and tyrosine kinase inhibitor (TKI) combination or immunotherapy–immunotherapy combination, as first-line standards of care. However, second-line therapy choices are less well established. To address this void, we examined existing evidence supporting second and subsequent-line treatment options after immunotherapy-based combination therapy.

Recent findings

Evidence regarding efficacy of second-line therapy after immunotherapy-based combination is mainly retrospective, except for axitinib, which is the only TKI with prospective efficacy data in this setting. Cabozantinib demonstrated excellent second-line progression-free survival (PFS) that remained in third or later line use, albeit based on small numbers of observations. Moreover, pazopanib demonstrated excellent PFS, but showed wider variability in PFS rates. Sunitinib's PFS rates appeared lower than for axitinib, cabozantinib or pazopanib. Finally, inhibitors of the mammalian target of rapamycin pathway appeared to offer even lower efficacy than any TKI after immunotherapy-based therapy combinations.

All available contemporary evidence about TKI efficacy after immunotherapy-based therapy combinations is based on institutional studies. No major differences in efficacy for the examined TKIs after immunotherapy-based combination therapies were recorded. In general, these showed similar efficacy to their efficacy data recorded in first-line.
A Classification Approach for Predicting COVID-19 Patient’s Survival Outcome with Machine Learning Techniques
Authors: Osi Abdulhameed Ado , Abdu Mannir , Muhammad Usman , Ibrahim Auwalu , Isma’il Lawan Adamu , Suleiman Ahmad Abubakar , Abdulkadir Hasssan Sarki , Sada Safiya Sani , Dikko Hussaini Garba , Ringim Muftahu Zubairu
Published: August 2020

COVID-19 is an infectious disease discovered after the outbreak began in Wuhan, China, in December 2019. COVID-19 is still becoming an increasing global threat to public health. The virus has been escalated to many countries across the globe. This paper analyzed and compared the performance of three different supervised machine learning techniques; Linear Discriminant Analysis (LDA), Random Forest (RF), and Support Vector Machine (SVM) on COVID-19 dataset. The best level of accuracy between these three algorithms was determined by comparison of some metrics for assessing predictive performance such as accuracy, sensitivity, specificity, F-score, Kappa index, and ROC. From the analysis results, RF was found to be the best algorithm with 100% prediction accuracy in comparison with LDA and SVM with 95.2% and 90.9% respectively. Our analysis shows that out of these three classification models RF predicts COVID-19 patient’s survival outcome with the highest accuracy. Chi-square test reveals that all the seven features except sex were significantly correlated with the COVID-19 patient’s outcome (P-value < 0.005). Therefore, RF was recommended for COVID-19 patient’s outcome prediction that will help in early identification of possible sensitive cases for quick provision of quality health care, support and supervision.
COVID-19 and Mental Health: A Study of its Impact on Students in Maharashtra, India
Authors: Moghe Kshipra , Kotecha Disha , Patil Manjusha
Published: August 2020

This study identifies and analyzes the personal, social and psychological impact of COVID - 19 on the mental health of students of age group 16 to 25. A response from N= 351 students provided a comparative analysis based on the gender, and background via t-test with significance factor of p ≤ 0.5, to understand the pandemic’s impact. The results show that female students are more concerned about health, and future, and are more prone to psychological issues like feelings of uncertainty, helplessness and outbursts than male students. Urban student’s population is more mentally affected than their rural counterparts. An increase is seen in need for solitude, being withdrawn and self-harm in male students. A shift in perception from seeing family as a source of support to that of a restriction is indicated, although the benefits of a collectivistic society are undisputed.

Impact Statement

This study performs an analysis of the student’s response to questions based on social and self-perception as a result of COVID-19. It also discusses the nature of adaptive strategies espoused by them and their effectiveness in dealing with the pandemic, isolation, and the new normal.
Digoxin is Associated with Increased Mortality in Patients with Atrial Fibrillation without Concomitant Heart Failure
Authors: Tysarowski Maciej , Nigri Rafael , Patel Brijesh , Suero-Abreu Giselle A. , Pratap Balaji , Bastawrose Joseph , Aziz Joshua , Kim Hyoeun , Herzog Eyal , Aziz Emad F.
Published: August 2020

Introduction

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and is a significant risk factor for ischemic stroke and death. Digitalis has been used for more than 200 years to treat heart conditions, including AF, and its use remains controversial due to uncertain long-term morbidity and mortality.

Methods

We conducted a cohort study of hospitalized patients with AF assessing the effects of digoxin on longterm all-cause mortality. Patients were divided into two groups: with and without heart failure (HF). We performed multivariable Cox regression analysis to assess hazard ratios (HR) for all-cause mortality depending on digoxin treatment and used propensity score matching to adjust for differences in background characteristics between treatment groups.

Results

Among 2179 consecutive patients hospitalized with AF, the median age was 73 ± 14, and 52.5% of patients were male, 49% had HF, and 18.8% were discharged on digoxin. Median left ventricular ejection fraction in the whole cohort was 60 (IQR 40-65). Among patients with HF, 34.5% had preserved, 17.3% had mid-range and 48.1% had reduced left ventricular ejection fraction. The mean follow-up time was 3 ± 2.05 years. In patients without HF there was a statistically significant increased mortality in the digoxin subgroup after propensity score matching (HR = 2.23, 95% CI 1.42-3.51, p < 0.001). In contrast, in patients with HF, there was no difference in mortality between the treatment groups (p = 0.92).

Conclusions

Digoxin use in our study was associated with increased mortality in patients with AF and without concomitant HF.
Model to Describe Fast Shutoff of CoVID-19 Pandemic Spread
Authors: Eng Genghmun
Published: August 2020

Early CoVID-19 growth obeys: N{t*}=N/I\ exp[+K/o\ t*], with K/o\ = [(ln 2) / (t/dbl\)], where t/dbl\ is the pandemic growth doubling time. Given N{t*}, the daily number of new CoVID-19 cases is ρ{t*}=dN{t*}/dt*. Implementing society-wide Social Distancing increases the t/dbl\ doubling time, and a linear function of time for t/dbl\ was used in our Initial Model:
N/o\[t] = 1 exp[+K/A\ t / (1 + γ/o\ t) ] = exp(+G/o\) exp( - Z/o\[t] ) ,
to describe these changes, with G/o\ = [K/A\ / γ/o\]. However, this equation could not easily model some quickly decreasing ρ[t] cases, indicating that a second Social Distancing process was involved. This second process is most evident in the initial CoVID-19 data from China, South Korea, and Italy. The Italy data is analyzed here in detail as representative of this second process. Modifying Z/o\[t] to allow exponential cutoffs:
Z/E\[t] = +[G/o\ / (1 + γ/o\ t) ] [exp( - δ/o\ t - q/o\ t^2 ] = Z/o\[t] [exp( - δ/o\ t - q/o\ t^2 ] ,
provides a new Enhanced Initial Model (EIM), which significantly improves datafits, where N/E\[t] = exp(+G/o\) exp( - Z/E\[t] ). Since large variations are present in ρ/data\[t], these models were generalized into an orthogonal function series, to provide additional data fitting parameters:
N(Z) = Sum{m = (0, M/F\)} g/m\ L/m\(Z) exp[-Z].
Its first term can give N/o\[t] or N/E\[t], for Z=Z/o\[t] or Z=Z/E\[t]. The L/m\(Z) are Laguerre Polynomials, with L/0\(Z)=1, and {g/m\; m= (0, M/F\)} are constants derived from each dataset. When ρ[t]=dN[t]/dt gradually decreases, using Z/o\[t] provided good datafits at small M/F\ values, but was inadequate if ρ[t] decreased faster. For those cases, Z/E\[t] was used in the above N(Z) series to give the most general Enhanced Orthogonal Function [EOF] model developed here. Even with M/F\=0 and q/o\=0, this EOF model fit the Italy CoVID-19 data for ρ[t] = dN[t]/dt fairly well. When the ρ[t] post-peak behavior is not Gaussian, then Z/E\[t] with δ/o\≠0, q/o\=0; which we call Z/A\[t], is also likely to be a sufficient extension of the Z/o\[t] model. The EOF model also can model a gradually decreasing ρ[t] tail using small {δ/o\, q/o\} values [with 6 Figures].
Switching from algorithm-based to universal admission screening for COVID-19 in hospital settings
Authors: Donker Tjibbe , Grundmann Hajo , Bürkin Fabian , Hengel Hartmut , Bürkle Hartmut , Hammer Thorsten , Wenz Frederik , Kern Winfried
Published: August 2020

Detection of COVID-19 positive cases on admission to hospitals is crucial to protect patients and staff at the same time. While universal admission screening can prevent more undetected introductions than the algorithm-based screening, which preselects patient based on their symptoms and exposure, it is a more costly strategy as it involves testing a large number of patients.

We construct a simple tool to help determine when the benefit of additionally found cases outweighs the cost of the additionally tested patients, based on the numbers of patients to be screened in an acceptable time span to find an additional case when screening all admitted patients.
Amputee, clinician, and regulator perspectives on current and prospective upper extremity prosthetic technologies
Authors: Rekant Julie S. , Fisher Lee E. , Boninger Michael L. , Gaunt Robert A. , Collinger Jennifer L.
Published: August 2020

Existing prosthetic technologies for people with upper limb amputation are being adopted at moderate rates and unfortunately these devices are often abandoned. The aims of this study were to: 1) understand the current state of satisfaction with upper extremity prostheses, 2) solicit feedback about prosthetic technology and important device design criteria from amputees, clinicians, and device regulators, and 3) compare and contrast these perspectives to identify common or divergent priorities. Twenty-one adults with upper limb loss, 35 clinicians, and 3 regulators completed a survey on existing prosthetic technologies and a conceptual sensorimotor prosthesis driven by implanted myoelectric electrodes with sensory feedback provided via stimulation of dorsal root ganglion. User and clinician ratings of satisfaction with existing prosthetic devices were similar. While amputees, clinicians, and regulators were similarly accepting of technology in general, amputees were most accepting of the proposed implantable sensorimotor prosthesis. Overall, stakeholders valued user-centred outcomes such as individualized task goals, improved quality of life, device reliability, and user safety; a large emphasis was put on these last two outcomes by regulators. The results of this study provide insight into the priorities of amputees, clinicians, and regulators that will inform future upper-limb prosthetic design and clinical trial protocol development.
Naturally acquired Rift Valley fever virus neutralizing antibodies predominantly target the Gn glycoprotein
Authors: Wright Daniel , Allen Elizabeth R. , Clark Madeleine H.A. , Gitonga John N. , Karanja Henry K. , Hulswit Ruben , Taylor Iona , Biswas Sumi , Marshall Jennifer , Mwololo Damaris , Muriuki John , Bett Bernard , Bowden Thomas A. , Warimwe George M.
Published: August 2020

Rift Valley fever (RVF) is a viral haemorrhagic disease first discovered in Kenya in 1930. Numerous animal studies have demonstrated that protective immunity is acquired following RVF virus (RVFV) infection, and that this correlates with acquisition of virus neutralizing antibodies (nAb) that target the viral envelope glycoproteins. However, naturally acquired immunity to RVF in humans is poorly described. Here, we characterized the immune response to the viral envelope glycoproteins, Gn and Gc, in RVFV-exposed Kenyan adults. Long-lived IgG (dominated by IgG1 subclass) and T cell responses were detected against both Gn and Gc. However, antigen-specific antibody depletion experiments showed that Gn-specific antibodies dominate the RVFV nAb response. IgG avidity against Gn, but not Gc, correlated with nAb titers. These data are consistent with the greater level of immune accessibility of Gn on the viral envelope surface and confirm the importance of Gn as an integral component for RVF vaccine development.
Retrieving Lab Test Related Questions from Social Q&A Sites by Combining Shallow Features and Deep Representations
Authors: Lu Yu , Luo Xiao , Zhang Zhan , Ding Haoran , He Zhe
Published: August 2020

Patients face challenges in accurately interpreting their lab test results. To fulfill their knowledge gap, patients often turn to online resources, such as Community Question-Answering (CQA) sites, to seek meaningful information and support from their peers. Retrieving the most relevant information to patients’ queries is important to help patients understand lab test results. However, few studies investigated the retrieval of lab test-related questions on CQA platforms. To address this research gap, we build and evaluate a system that automatically ranks questions about lab tests based on their similarity to a given question. The system is tested using diabetes-related questions collected from Yahoo! Answers’ health section. Experimental results show that the regression-weighted combination of deep representations and shallow features was most effective in the Yahoo! Answers dataset. The proposed system can be extended to medical question retrieval, where questions contain a variety of lab tests.
Association between Abnormal Fetal Head Growth and Autism Spectrum Disorder
Authors: Regev Ohad , Cohen Gal , Hadar Amnon , Schuster Jenny , Flusser Hagit , Michaelovski Analya , Meiri Gal , Dinstein Ilan , Hershkovitch Reli , Menashe Idan
Published: August 2020

Despite evidence for prenatal onset of abnormal head growth in children with autism spectrum disorder (ASD), fetal ultrasound studies in ASD are limited and controversial. We conducted a longitudinal matched case-sibling-control study on fetal ultrasound biometric measures from 174 ASD children, their own typically developed siblings (TDS; n=178) and other population-based typically developed children (TDP; n=176). During second trimester, ASD and TDS fetuses had significantly smaller biparietal diameter (BPD) than TDP fetuses (aORzBPD=0.685, 95%CI=0.527-0.890 and aORzBPD=0.587, 95%CI=0.459-0.751, respectively). Interestingly, sex had a significant effect on head growth with males having larger heads than females within and across groups. Also, males and females with ASD showed different head shapes which were inversely correlated with ASD severity across different gestation periods. Our findings suggest that abnormal fetal head growth is a familial trait of ASD, which is modulated by sex and is associated with the severity of the disorder.
Customize Deep Learning-based De-Identification Systems Using Local Clinical Notes - A Study of Sample Size
Authors: Yang Xi , Bian Jiang , Wu Yonghui
Published: August 2020

Electronic Health Records (EHRs) are a valuable resource for both clinical and translational research. However, much detailed patient information is embedded in clinical narratives, including a large number of patients’ identifiable information. De-identification of clinical notes is a critical technology to protect the privacy and confidentiality of patients. Previous studies presented many automated de-identification systems to capture and remove protected health information from clinical text. However, most of them were tested only in one institute setting where training and test data were from the same institution. Directly adapting these systems without customization could lead to a dramatic performance drop. Recent studies have shown that fine-tuning is a promising method to customize deep learning-based NLP systems across different institutes. However, it’s still not clear how much local data is required. In this study, we examined the customizing of a deep learning-based de-identification system using different sizes of local notes from UF Health. Our results showed that the fine-tuning could significantly improve the model performance even on a small local dataset. Yet, when the local data exceeded a threshold (e.g., 700 notes in this study), the performance improvement became marginal.
Mutual anticipation can contribute to self-organization in human crowds
Authors: Murakami Hisashi , Feliciani Claudio , Nishiyama Yuta , Nishinari Katsuhiro
Published: August 2020

Human crowds provide paradigmatic examples of collective behavior emerging through self-organization. Although the underlying interaction has been considered to obey the distance-dependent law, resembling physical particle systems, recent findings emphasized that pedestrian motions are fundamentally influenced by the anticipated future positions of their neighbors rather than their current positions. Therefore, anticipatory interaction may play a crucial role in collective patterning. However, whether and how individual anticipation functionally benefits the group is not well-understood. We suggest that collective patterning in human crowds is promoted by anticipatory path-seeking behavior resulting in a scale-free movement pattern, called the Lévy walk. In our experiments of lane formation, a striking example of self-organized patterning in human crowds where people moving in opposite directions spontaneously segregate into several unidirectional lanes, we manipulated some pedestrians’ ability to anticipate by having them type on a mobile phone while walking. The manipulation slowed overall walking speeds and delayed the onset of global patterning, and the distracted pedestrians sometimes failed to achieve their usual walking strategy. Moreover, we observed that the delay of global patterning depends on decisions made by pedestrians who were moving toward the distracted ones and had no choice but to take sudden large steps, presumably because of difficulty in anticipating the motions of their counterparts. These results imply that mutual anticipation between pedestrians facilitates efficient transition to emergent patterning in situations where nobody within a crowd is distracted. Our findings may contribute to efficient crowd management and inform future models of self-organizing systems.
A novel, dichloromethane-fermenting bacterium in thePeptococcaceaefamily, ‘CandidatusFormamonas warabiya’, gen. nov. sp. nov.
Authors: Holland Sophie I , Ertan Haluk , Manefield Michael J , Lee Matthew
Published: August 2020

Dichloromethane (DCM; CH2Cl2) is a toxic groundwater pollutant that also has a detrimental effect on atmospheric ozone levels. As a dense non-aqueous phase liquid, DCM migrates vertically through groundwater to low redox zones, yet information on anaerobic microbial DCM transformation remains scarce due to a lack of cultured organisms. We report here the characterisation of strain DCMF, the dominant organism in an anaerobic enrichment culture (DFE) that is capable of fermenting DCM to the environmentally benign product acetate. Stable carbon isotope experiments demonstrated that the organism assimilated carbon from DCM and bicarbonate via the Wood-Ljungdahl pathway. Strain DCMF is the first anaerobic DCM-degrading bacterium also shown to metabolise non-chlorinated substrates. It appears to be a methylotroph utilising the Wood-Ljungdahl pathway for metabolism of methyl groups from methanol, choline, and glycine betaine, which has implications for the flux of climate-active compounds from subsurface environments. Community profiling and enrichment of the cohabiting taxa in culture DFE to the exclusion of strain DCMF suggest that it is the sole organism in this culture responsible for substrate metabolism, while the cohabitants persist via necromass recycling. Genomic and physiological evidence support placement of strain DCMF in a novel genus, ‘CandidatusFormamonas warabiya’.
Post-exertion oxygen saturation as a prognostic factor for adverse outcome in patients attending the emergency department with suspected COVID-19: Observational cohort study
Authors: Goodacre Steve
Published: August 2020

Background

Measurement of post-exertion oxygen saturation has been proposed to assess illness severity in suspected COVID-19 infection. We aimed to determine the accuracy of post-exertional oxygen saturation for predicting adverse outcome in suspected COVID-19.

Methods

We undertook an observational cohort study across 70 emergency departments during first wave of the COVID-19 pandemic in the United Kingdom. We collected data prospectively, using a standardised assessment form, and retrospectively, using hospital records, from patients with suspected COVID-19, and reviewed hospital records at 30 days for adverse outcome (death or receiving organ support). Patients with post-exertion oxygen saturation recorded were selected for this analysis.

Results

We analysed data from 817 patients with post-exertion oxygen saturation recorded after excluding 54 in whom measurement appeared unfeasible. The c-statistic for post-exertion change in oxygen saturation was 0.589 (95% confidence interval 0.465 to 0.713), and the positive and negative likelihood ratios of a 3% or more desaturation were respectively 1.78 (1.25 to 2.53) and 0.67 (0.46 to 0.98). Multivariable analysis showed that post-exertion oxygen saturation was not a significant predictor of adverse outcome when baseline clinical assessment was taken into account (p=0.368). Secondary analysis excluding patients in whom post-exertion measurement appeared inappropriate resulted in a c-statistic of 0.699 (0.581 to 0.817), likelihood ratios of 1.98 (1.26 to 3.10) and 0.61 (0.35 to 1.07), and some evidence of additional prognostic value on multivariable analysis (p=0.019).

Conclusions

Post-exertion oxygen saturation provides modest prognostic information in the assessment of patients attending the emergency department with suspected COVID-19.

Registration

ISRCTN registry, ISRCTN56149622, http://www.isrctn.com/ISRCTN28342533

Key messages

What is already known on this subject?

Post exertional decrease in oxygen saturation can be used to predict prognosis in chronic lung diseases

Post exertional desaturation has been proposed as a way of predicting adverse outcome in people with suspected COVID-19

What this study adds:

Post-exertion oxygen saturation provides modest prognostic information in the assessment of patients attending the emergency department with suspected COVID-19
Application of Optimal Control to the Dynamics of COVID-19 Disease in South Africa
Authors: Gatyeni S. P. , Chukwu C.W. , Chirove F. , Fatmawati  , Nyabadza F.
Published: August 2020

SARS-CoV-2 (COVID-19) belongs to the beta-coronavirus family, which include: the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). Since its outbreak in South Africa in March 2020, it has lead to high mortality and thousands of people contracting the virus. Mathematical analysis of a model without controls was done and the basic reproduction number (ℛ0) of the COVID-19 for the South African pandemic determined. We introduced permissible controls and formulate an optimal control problem using the Pontraygain Maximum Principle. Our numerical findings suggest that joint implementation of effective mask usage, physical distancing and active screening and testing, are effective measures to curtail the spread of the disease in the human population. The results obtained in this paper are of public health importance in the control and management of the spread for the novel coronavirus, SARS-CoV-2, in South Africa.
Janus Kinase-Inhibitor and Type I Interferon Ability to Produce Favorable Clinical Outcomes in COVID-19 Patients: A Systematic Review and Meta-Analysis
Authors: Walz Lucas , Cohen Avi J. , Rebaza Andre P. , Vanchieri James , Slade Martin D. , Dela Cruz Charles S. , Sharma Lokesh
Published: August 2020

Background

Novel coronavirus (SARS-CoV-2) has infected over 17 million. Novel therapies are urgently needed. Janus-kinase (JAK) inhibitors and Type I interferons have emerged as potential antiviral candidates for COVID-19 patients for their proven efficacy against diseases with excessive cytokine release and by their ability to promote viral clearance in past coronaviruses, respectively. We conducted a systemic review and meta-analysis to evaluate role of these therapies in COVID-19 patients.

Methods

MEDLINE and MedRxiv were searched until July 30th, 2020, including studies that compared treatment outcomes of humans treated with JAK-inhibitor or Type I interferon against controls. Inclusion necessitated data with clear risk estimates or those that permitted back-calculation.

Results

We searched 733 studies, ultimately including four randomized and eleven non-randomized clinical trials. JAK-inhibitor recipients had significantly reduced odds of mortality (OR, 0.12; 95%CI, 0.03–0.39, p=0.0005) and ICU admission (OR, 0.05; 95%CI, 0.01–0.26, p=0.0005), and had significantly increased odds of hospital discharge (OR, 22.76; 95%CI, 10.68–48.54, p<0.00001), when compared to standard treatment group. Type I interferon recipients had significantly reduced odds of mortality (OR, 0.19; 95%CI, 0.04–0.85, p=0.03), and increased odds of discharge bordering significance (OR, 1.89; 95%CI, 1.00–3.59, p=0.05).

Conclusions

JAK-inhibitor treatment is significantly associated with positive clinical outcomes regarding mortality, ICU admission, and discharge. Type I interferon treatment is associated with positive clinical outcomes regarding mortality and discharge. While these data show promise, additional randomized clinical trials are needed to further elucidate the efficacy of JAK-inhibitors and Type I interferons and clinical outcomes in COVID-19.

KEY MESSAGES

Key Question

Can treatment of hospitalized COVID-19 patients with JAK-inhibitor or Type I interferon confer favorable clinical outcomes?

Bottom Line

Meta-analysis demonstrates that JAK-inhibitor treatment was significantly associated with favorable clinical outcomes in terms of mortality, requiring mechanical ventilation, and hospital discharge, while treatment with Type I interferon was significantly associated with decreased mortality.

Why Read On?

This study conducted a systematic review of human trials that treated patients with JAK-inhibitors or Type I interferon, and it elaborates on the potential benefits of administering these therapies at different moments of the disease course despite apparently opposite mechanism of action of these two interventions.
Lying in wait: the resurgence of dengue virus after the Zika epidemic in Brazil
Authors: Brito Anderson Fernandes , Machado Lais Ceschini , Siconelli Márcio Junio Lima , Oidtman Rachel J. , Fauver Joseph R. , de Oliveira Carvalho Rodrigo Dias , Dezordi Filipe Zimmer , Pereira Mylena Ribeiro , de Castro-Jorge Luiza Antunes , Minto Elaine Cristina Manini , Passos Luzia Márcia Romanholi , Kalinich Chaney C. , Petrone Mary E. , Allen Emma , España Guido Camargo , Huang Angkana T. , Cummings Derek A. T. , Baele Guy , Franca Rafael Freitas Oliveira , Perkins T. Alex , da Fonseca Benedito Antônio Lopes , Wallau Gabriel Luz , Grubaugh Nathan D.
Published: August 2020

After Zika virus (ZIKV) emerged and caused an epidemic in the Americas in 2016, both Zika and dengue incidence declined in the following years (2017-2018) to a record low in many countries. Following this period of low incidence, dengue resurged in 2019 in Brazil, causing ~2.1 million cases. The reasons for the recent fluctuations in dengue incidence and the maintenance of dengue virus (DENV) through periods of low transmission are unknown. To investigate this, we used a combination of epidemiological and climatological data to estimate dengue force of infection (FOI) and model mosquito-borne transmission suitability since the early 2000s in Brazil. Our estimates of FOI revealed that the rate of DENV transmission in 2018-2019 was exceptionally low, due to a low proportion of susceptible population rather than changes to ecological conditions. This supports the hypothesis that the synchronous decline of dengue in Brazil may be explained by protective immunity from pre-exposure to ZIKV and/or DENV in prior years. Furthermore, we sequenced 69 genomes of dengue virus serotype 1 (DENV-1) and DENV-2 circulating in Northeast and Southeast Brazil, and performed phylogeographic analyses to uncover patterns of viral spread. We found that the outbreaks in Brazil in 2019 were caused by DENV lineages that were circulating locally prior to the Zika epidemic and spread cryptically during the period of low transmission. Despite the period of low transmission, endemic DENV lineages persisted for 5-10 years in Brazil before causing major outbreaks. Our study challenges the paradigm that dengue outbreaks are caused by recently introduced new lineages, but rather they may be driven by established lineages circulating at low levels until the conditions are conducive for outbreaks.
Is there reporting and citation bias for completed phase III interventional brain tumor trials?
Authors: Rayi Appaji , Alnahhas Iyad , Giglio Pierre , Puduvalli Vinay
Published: August 2020

Aims

Reporting and citation bias based on positive versus negative outcome among completed phase III interventional brain tumor trials (IBTTs) have not been previously reported. Thus, we aimed to assess the evidence.

Methods

Clinicaltrials.gov was used to obtain all phase III IBTTs completed prior to December 31st 2016. Trials closed due to poor accrual or non-phase III were excluded. Data about the funding source, type of intervention, conducted at U.S or Non-U.S locations, patients enrolled, primary completion date, time to dissemination of results in months (either reported on Clinicaltrials.gov or published in a journal), citations per year (from web of science) and outcome (positive or neutral/negative) were abstracted. Median time to dissemination was estimated using Kaplan-Meier estimates and a log rank test for statistical significance. The number of citations per year for positive and negative/neutral studies was compared using a t-test.

Results

67 studies were analyzed. The median time from primary completion to dissemination of results for trials with a positive outcome was 20 months (n = 20; 95% CI: 12-31) compared to 30 months for trials with a negative outcome (n=35; 95 % CI: 22 – 37) (p = 0.095). The average number of citations per year for trials with a positive outcome is 62.4 (n = 21; range 1.1 – 614.8) compared to 25.0 for trials with a negative outcome (n=35; range 0.14 - 158.8) (p = 0.213). There was no significant difference in time to dissemination based on the funding source, type of intervention or the location where the trial was conducted.

Conclusion

There was no evidence of reporting or citation bias among completed phase III IBTTs. Nevertheless, positive phase III IBTTs were reported more promptly and cited more often compared to negative or neutral trials. These findings might need consideration for risk of bias assessment while conducting systematic reviews.
Probability of elimination for COVID-19 in Aotearoa New Zealand
Authors: Binny Rachelle N. , Hendy Shaun C. , James Alex , Lustig Audrey , Plank Michael J. , Steyn Nicholas
Published: August 2020

On 25th March 2020, New Zealand implemented stringent lockdown measures (Alert Level 4, in a four-level alert system) with the goal of eliminating community transmission of COVID-19. Once new cases are no longer detected over consecutive days, the probability of elimination is an important measure for informing decisions on when certain COVID-19 restrictions should be relaxed. Our model of COVID-19 spread in New Zealand estimates that after 2-3 weeks of no new reported cases, there is a 95% probability that COVID-19 has been eliminated. We assessed the sensitivity of this estimate to varying model parameters, in particular to different likelihoods of detection of clinical cases and different levels of control effectiveness. Under an optimistic scenario with high detection of clinical cases, a 95% probability of elimination is achieved after 10 consecutive days with no new reported cases, while under a more pessimistic scenario with low case detection it is achieved after 22 days.
Antigen-Specific T Cell Recall Assay To Screen Drugs For Off-Target Effects
Authors: Kleiman Eden , Sierra Gloria , Magcase Dennie , George Marybeth V , Daftarian Pirouz M
Published: August 2020

Extracellular adenosine suppresses T cell immunity in the tumor microenvironment. We have developed an in vitro recall assay utilizing a sequential adenosine dosing regimen guide for testing drug off-target effects on memory T cell expansion/function. As a proof of principle, we show low dose adenosine analog GS-5734, a monophosphoramidate prodrug of an adenosine analog, does not alter memory T cell recall whereas toxicity observed at high dose favors antigen-specific memory T cell survival/proliferation over non-specific CD8+T cells. Parent drug GS-445124 at high dosage interferes with antigen-specific T cell recall without cellular toxicity. Despite similar chemical structure, these drugs displayed opposing effects on memory T cell expansion. This assay platform has broad utility in screening memory T cell off-target effects.
Resolving the data asynchronicity in high-speed atomic force microscopy measurement via the Kalman Smoother
Authors: Kubo Shintaroh , Kato Suguru , Nakamura Kazuyuki , Kodera Noriyuki , Takada Shoji
Published: August 2020

High-speed atomic force microscopy (HS-AFM) is a scanning probe microscopy that can capture structural dynamics of biomolecules in real time at single molecule level near physiological condition. Albeit much improvement of the instruments, while scanning one frame of HS-AFM movies, biomolecules often change their conformations largely. Thus, the obtained frame images can be hampered by the time-difference, the asynchronicity, in the data acquisition. Here, to resolve this data asynchronicity in the HS-AFM movie, we developed Kalman filter and smoother methods, some of the sequential Bayesian filtering approaches. The Kalman filter/smoother methods use alternative steps of a short time-propagation by a linear dynamical system and a correction by the likelihood of AFM data acquired pixel by pixel. We first tested the method using a toy model of a diffusing cone, showing that the Kalman smoother method outperforms to reproduce the ground-truth movie, compared to that mimics the raw AFM movie, and the Kalman filter result. We then applied the Kalman smoother to a synthetic movie for conformational change dynamics of a motor protein, i.e., dynein, confirming the superiority of the Kalman smoother. Finally, we applied the Kalman smoother to two real HS-AFM movies, FlhAc and centralspindlin, reducing distortion and noise in the AFM movies. The method is general and can be applied to any HS-AFM movies.
The PNUTS-PP1 axis regulates endothelial aging and barrier function via SEMA3B suppression
Authors: Lozano-Vidal Noelia , Stanicek Laura , Bink Diewertje I. , Kremer Veerle , MacInnes Alyson W. , Dimmeler Stefanie , Boon Reinier A.
Published: August 2020

Age-related diseases pose great challenges to health care systems worldwide. During aging, endothelial senescence increases the risk for cardiovascular disease. Recently, it was described that Phosphatase 1 Nuclear Targeting Subunit (PNUTS) has a central role in cardiomyocyte aging and homeostasis. Here, we determined the role of PNUTS in endothelial cell aging. We confirmed that PNUTS is repressed in senescent endothelial cells (ECs). Moreover, PNUTS silencing elicits several of the hallmarks of endothelial aging: senescence, reduced angiogenesis and loss of barrier function. To validate our findings in vivo, we generated an endothelial-specific inducible PNUTS-deficient mouse line (Cdh5-CreERT2;PNUTSfl/fl), termed PNUTSEC-KO. Two weeks after PNUTS deletion, PNUTSEC-KOmice presented severe multiorgan failure and vascular leakage. We showed that the PNUTS binding motif for protein phosphatase 1 (PP1) is essential to maintain endothelial barrier function. Transcriptomic analysis of PNUTS-silenced HUVECs and lungs of PNUTSEC-KOmice revealed that the PNUTS-PP1 axis tightly regulates the expression of semaphorin 3B (SEMA3B). Indeed, silencing of SEMA3B completely restored barrier function after PNUTS loss-of-function. These results reveal a pivotal role for PNUTS in endothelial homeostasis through a PP1-SEMA3B downstream pathway that provides a potential target against the effects of aging in ECs.