bluuebunny/crossref_metadata_2025 huggingface dataset:
Abiotrophia defectiva endophthalmitis following routine cataract surgery: the first reported case in the United Kingdom
Authors: Chihaia Madalina , Richardson-May James , Al-Saffar Layth , Kettledas Hiron , Rashid Mohammed
Published: March 2020

Introduction.

Abiotrophia defectiva

is a fastidious organism that has been implicated in severe infections such as endocarditis in immunocompetent patients. Modern tools are available to aid identification, but the main challenge remains clinical suspicion of

A. defectiva

.

Case presentation. An otherwise fit and well 65-year-old female presented with reduced vision, red eye and discomfort 2 days following routine left cataract surgery. She had visual acuity of light perception only, significant anterior chamber inflammation (including hypopyon) and limited fundal view. She was diagnosed with post-operative endophthalmitis and 0.1 ml of ceftazidime (2 mg/0.1 ml) and 0.1 ml vancomycin (2 mg/0.1 ml) were injected intravitreally after vitreous aspiration. Subconjunctival cefuroxime was also injected. A repeat injection was performed on day three of admission. Gram staining revealed Gram-positive long-chain cocci, which were identified as

A. defectiva

. The patient was discharged on oral ciprofloxacin 500 mg twice a day with oral prednisolone 60 mg once a day; this was tapered and stopped at 8 weeks post-discharge. The left eye received dexamethasone 0.1 % 6 times a day (again, tapered over 8 weeks), moxifloxacin 5 % 6 times a day and atropine 1 % twice a day. Vision improved to 6/12 unaided (6/9.5 with pinhole) at 9 weeks post-operatively, with a clear fundal view.

Conclusion. We present a case of

A. defectiva

endophthalmitis following routine cataract surgery. To our knowledge, this is the first reported case in the UK and the fourth globally, which with prompt treatment ended with a good visual outcome.
Reaching health facilities in situations of emergency: Experiences of pregnant women in Africa’s largest megacity
Authors: Banke-Thomas Aduragbemi , Balogun Mobolanle , Wright Ololade , Ajayi Babatunde , Abejirinde Ibukun-Oluwa , Olaniran Abimbola , Giwa-Ayedun Rokibat Olabisi , Odusanya Bilikisu , Afolabi Bosede Bukola
Published: March 2020

Travel of pregnant women requiring emergency obstetric care (EmOC) to health facilities remains a ‘black box’ of many unknowns to the health system, more so in megacities which are fraught with wide inequalities. This in-depth study on travel of pregnant women in Africa’s largest megacity is based on interviews conducted between September 2019 and January 2020 with 47 women and 11 of their relatives who presented at comprehensive EmOC facilities in situations of emergency, requiring some EmOC services. Despite recognising danger signs, pregnant women are often faced with conundrums on “when”, “where” and “how” to reach EmOC facilities. While the decision-making process is a shared activity amongst all women, the available choice-options vary depending on socio-economic status. Women preferred to travel to facilities deemed to have “nicer” health workers, even if these were farther from home. Reported travel time ranged from 5-240 minutes in daytime and 5-40 minutes at night. Many women reported facing remarkably similar travel experiences, with varied challenges faced in the daytime (traffic congestion) compared to night-time (security concerns and scarcity of public transportation). This was irrespective of their age, socio-economic background, or obstetric history. However, the extent to which this experience impacted on their ability to reach facilities depended on their agency and support systems. Travel experience was better if they had their personal vehicle for travel at night, support of relatives or direct/indirect connections with senior health workers at comprehensive EmOC facilities. Referral barriers between facilities further prolonged delays and increased cost of travel for many women. If the goal to leave no one behind remains a priority, in addition to other health systems strengthening interventions, referral systems need to be improved, advocacy on policies to encourage women to utilise nearby functional facilities when in situations of emergency and private sector partnerships should be explored.
Operationalization of the learned non-use phenomenon - A Delphi study
Authors: Hirsch Theresa , Barthel Maria , Aarts Pauline , Chen Yi-An , Freivogel Susanna , Johnson Michelle J. , Jones Theresa A. , Jongsma Marijtje L.A. , Maier Martina , Punt David , Sterr Annette , Wolf Steven L. , Heise Kirstin-Friederike
Published: March 2020

The discrepancy between residual functional capacity and reduced use of the contralesional hand, frequently observed after a brain lesion, has been termed Learned Non-Use (LNU) and is thought to depend on the interaction of neuronal mechanisms during recovery and learning-dependent mechanisms such as negative reinforcement. Despite the generally accepted existence of the LNU phenomenon among clinicians and researchers, no unequivocal and transdisciplinary definition exists to date. Furthermore, although therapeutic approaches are implemented in clinical practice to explicitly target LNU, no standardized diagnostic routine is described in the current literature.

Based on a structured group communication following the Delphi method among clinical and scientific experts in the field of LNU, knowledge from both, the work with patient populations and with animal models, was synthesized and integrated to reach consensus regarding a transdisciplinary definition of the LNU phenomenon. Furthermore, the mode and strategy of the diagnostic process, as well as the sources of information and outcome parameters relevant for the clinical decision making, were described with a wide range showing the current lack of a consistent universal diagnostic approach. Building on these results, the need for the development of a structured diagnostic procedure and its implementation into clinical practice is emphasized. Moreover, it exists a striking gap between the prevailing hypotheses regarding the mechanisms underlying the LNU phenomenon and the actual evidence. Therefore, basic research is needed to bridge between bedside and bench and eventually improve clinical decision making and further development of interventional strategies beyond the field of stroke rehabilitation.
The contribution of X-linked coding variation to severe developmental disorders
Authors: Martin Hilary C. , Gardner Eugene J. , Samocha Kaitlin E. , Kaplanis Joanna , Akawi Nadia , Sifrim Alejandro , Eberhardt Ruth Y. , Tavares Ana Lisa Taylor , Neville Matthew D. C. , Niemi Mari E. K. , Gallone Giuseppe , McRae Jeremy , Wright Caroline F. , FitzPatrick David R. , Firth Helen V. , Hurles Matthew E.
Published: March 2020

Over 130 X-linked genes have been robustly associated with developmental disorders (DDs), and X-linked causes have been hypothesised to underlie the higher DD rates in males. We evaluated the burden of X-linked coding variation in 11,046 DD patients, and found a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We developed an improved strategy to detect novel X-linked DDs and identified 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known DD-associated genes. Importantly, we estimated that, in male probands, only 13% of inherited rare missense variants in known DD-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders.
Differentiating the Effect of Medication and Illness on Brain Volume Reductions in First-Episode Psychosis: A Longitudinal, Randomized, Triple-blind, Placebo-controlled MRI Study
Authors: Chopra Sidhant , Fornito Alex , Francey Shona M. , O’Donoghue Brian , Cropley Vanessa , Nelson Barnaby , Graham Jessica , Baldwin Lara , Tahtalian Steven , Yuen Hok Pan , Allott Kelly , Alvarez-Jimenez Mario , Harrigan Susy , Sabaroedin Kristina , Pantelis Christos , Wood Stephen J , McGorry Patrick
Published: March 2020

Changes in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the underlying illness or represent iatrogenic effects of antipsychotic medication. Here, we report MRI findings from a triple-blind randomised placebo-controlled study where 62 antipsychotic-naïve patients with first episode psychosis (FEP) received either an atypical antipsychotic or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n=27) was also recruited. Structural MRI scans were obtained at baseline, 3-months and 12- months. Our primary aim was to differentiate illness-related brain volume changes from medication-related changes within the first 3 months of treatment. We secondarily investigated long-term effects at the 12-month timepoint. From baseline to 3 months, we observed a significant group x time interaction in the pallidum (p < 0.05 FWE-corrected), such that patients receiving antipsychotic medication showed increased volume, patients on placebo showed decreased volume, and healthy controls showed no change. In patients, a greater increase in pallidal grey matter volume over 3 months was associated with a greater reduction in symptom severity. We additionally found preliminary evidence for illness- related volume reductions in prefrontal cortices at 12 months and medication-related volume reductions in cerebellum at both 3-months and 12-months. Our findings indicate that psychotic illness and antipsychotic exposure exert distinct and spatially distributed effects on brain volume. Our results align with prior work in suggesting that the therapeutic efficacy of antipsychotic medications may be primarily mediated through their effects on the basal ganglia.
Nucleotide Analogues as Inhibitors of SARS-CoV-2 Polymerase
Authors: Chien Minchen , Anderson Thomas K. , Jockusch Steffen , Tao Chuanjuan , Kumar Shiv , Li Xiaoxu , Russo James J. , Kirchdoerfer Robert N. , Ju Jingyue
Published: March 2020

SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously demonstrated that three nucleotide analogues inhibit the SARS-CoV RNA-dependent RNA polymerase (RdRp). Here, using polymerase extension experiments, we have demonstrated that the active triphosphate form of Sofosbuvir (a key component of the FDA approved hepatitis C drug EPCLUSA), is incorporated by SARS-CoV-2 RdRp, and blocks further incorporation. Using the same molecular insight, we selected the active triphosphate forms of three other anti-viral agents, Alovudine, AZT (an FDA approved HIV/AIDS drug) and Tenofovir alafenamide (TAF, an FDA approved drug for HIV and hepatitis B) for evaluation as inhibitors of SARS-CoV-2 RdRp. We demonstrated the ability of these three viral polymerase inhibitors, 3’-fluoro-3’-deoxythymidine triphosphate, 3’-azido-3’-deoxythymidine triphosphate and Tenofovir diphosphate (the active triphosphate forms of Alovudine, AZT and TAF, respectively) to be incorporated by SARS-CoV-2 RdRp, where they also terminate further polymerase extension. These results offer a strong molecular basis for these nucleotide analogues to be evaluated as potential therapeutics for COVID-19.
Assessment of a combined manual therapy and taping method for the treatment of chronic lower back pain A randomized controlled trial
Authors: Schmidt Stefan , Keim Nicolas , Schultz Claudia , Sielmann Dieter , Huber Roman , Walach Harald
Published: March 2020

Background

Chronic lower back pain is the most frequent medical problem and the condition with the most years lived with disability. A pragmatic RCT was performed to assess a new treatment, Medi-Taping, which aims at reducing complaints by treating pelvic obliquity with a combination of manual treatment of trigger points and kinesio taping.

Methods

110 patients were randomized at two study centers either to Medi-Taping or to a standard treatment consisting of psychoeducation and physiotherapy as control. Treatment duration was three weeks. Measures were taken at baseline, end of treatment and at follow-up after two months. Main outcome criteria were lower back pain measured with VAS, the Chronic Pain Grade Scale and the Oswestry Low Back Pain Disability Questionnaire.

Results

Patients of both groups benefited from the treatment by medium to large effect sizes. All effects were pointing towards the intended direction with patients receiving Medi-Taping doing better. But at end of treatment and follow-up there were no significant differences for the primary endpoints between groups. Health related quality of life was significantly higher (p=.004) in patients receiving Medi-Taping compared to controls.

Conclusions

Medi-Taping, a purported way of correcting pelvic obliquity and chronic tension resulting from it, is a treatment modality similar in effectiveness as a complex physiotherapy and patient education program.

Significance

This RCT evaluated the effect of a combined therapy consisting of manual treatment and kinesio tape in patients with lower back pain. Patients receiving this treatment benefitted substantially but so did patients in the active control condition receiving physiotherapy and patient education. However, patients receiving the combined treatment had a significant higher quality of life.
Trend analysis of the COVID-19 pandemic in China and the rest of the world
Authors: Weber Albertine , Iannelli Flavio , Gonçalves Sebastián
Published: March 2020

The recent epidemic of Coronavirus (COVID-19) that started in China has already been “exported” to more than 140 countries in all the continents, evolving in most of them by local spreading. In this contribution we analyze the trends of the cases reported in all the Chinese provinces, as well as in some countries that, until March 15th, 2020, have more than 500 cases reported. Notably and differently from other epidemics, the provinces did not show an exponential phase. The data available at the Johns Hopkins University site [1] seem to fit well an algebraic sub-exponential growing behavior as was pointed out recently [2]. All the provinces show a clear and consistent pattern of slowing down with growing exponent going nearly zero, so it can be said that the epidemic was contained in China. On the other side, the more recent spread in countries like, Italy, Iran, and Spain show a clear exponential growth, as well as other European countries. Even more recently, US —which was one of the first countries to have an individual infected outside China (Jan 21st, 2020)— seems to follow the same path. We calculate the exponential growth of the most affected countries, showing the evolution along time after the first local case. We identify clearly different patterns in the analyzed data and we give interpretations and possible explanations for them. The analysis and conclusions of our study can help countries that, after importing some cases, are not yet in the local spreading phase, or have just started.

HIGHLIGHTS

All the provinces of China show very similar epidemic behaviour.

Early stages of spreading can be explained in terms of SIR standard model, considering that reported cases accounts for the removed individuals, with algebraic growing (sub-exponential) in most locations.

Worldwide, we observe two classes of epidemic growth: sub-exponential during almost all stages (China and Japan) and exponential on the rest of the countries, following the early stage.

The exponential growth rates ranges from 0.016day−1 (South Korea) to 0.725day−1 (Brunei) which means 1.6% to 107% of new cases per day, for the different countries but China.
Association between Clinical, Laboratory and CT Characteristics and RT-PCR Results in the Follow-up of COVID-19 patients
Authors: Fu Hang , Xu Huayan , Zhang Na , Xu Hong , Li Zhenlin , Chen Huizhu , Xu Rong , Sun Ran , Wen Lingyi , Xie Linjun , Liu Hui , Zhang Kun , Fu Chuan , Hou Keke , Yang Zhigang , Yang Ming , Guo Yingkun
Published: March 2020

Background

Since December 2019, more than 100,000 coronavirus disease 2019 (COVID-19) patients have been confirmed globally based on positive viral nucleic acids with real-time reverse transcriptase-polymerase chain reaction (RT-PCR). However, the association between clinical, laboratory and CT characteristics and RT-PCR results is still unclear. We sought to examine this association in detail, especially in recovered patients.

Methods

We analysed data from 52 confirmed patients who had been discharged with COVID-19. The clinical, laboratory, and radiological data were dynamically recorded and compared with the admission and follow-up RT-PCR results.

Results

In this cohort, 52 admitted COVID-19 patients who had confirmed positive RT-PCR results were discharged after 2 rounds of consecutively negative RT-PCR results. Compared with admission levels, CRP levels (median 4.93 mg/L [IQR: 1.78-10.20]) decreased significantly (p<0.001). and lymphocyte counts (median 1.50×109/L [IQR: 1.11-1.88]) increased obviously after obtaining negative RT-PCR results (p<0.001). Additionally, substantially improved inflammatory exudation was observed on chest CT except for 2 progressed patients. At the two-week follow-up after discharge, 7 patients had re-positive RT-PCR results, including the abovementioned 2 progressed patients. Among the 7 patients, new GGO was demonstrated in 2 patients. There were no significant differences in CPR levels or lymphocyte counts when comparing the negative and re-positive PCT results (all p >0.05).

Conclusion

Heterogeneity between CT features and RT-PCR results was found in COVID-19, especially in some recovered patients with negative RT-PCR results. Our study highlights that both RT-PCR and chest CT should be considered as the key determinants for the diagnosis and management of COVID-19 patients.
State Laws and Regulations Addressing Nurse-Initiated Protocols and Use of Nurse-Initiated Protocols in Emergency Departments: A Mixed-methods Cross-sectional Survey Study
Authors: Castner Jessica , Boris Lenore
Published: March 2020

Introduction

State regulations may impede the use of nurse-initiated protocols to begin life-saving treatments when patients arrive to the emergency department. In crowding and small-scale disaster events, this could translate to life and death practice differences. Nevertheless, research demonstrates nurses do utilize nurse-initiated protocols despite legal prohibitions. The purpose of this study was to explore the relationship of the state regulatory environment as expressed in nurse practice acts and interpretive statements prohibiting the use of nurse-initiated protocols with hospital use of nurse-initiated protocols in emergency departments.

Methods

A mixed-methods approach was used with a cross-sectional nationwide survey. The independent variable categorized the location of the hospital in states that have a protocol prohibition. Outcomes included protocols for blood laboratory tests, x-rays, over the counter medication, and electrocardiograms. A second analysis was completed with New York State alone because this state has the strongest language prohibiting nurse-initiated protocols.

Results

350 surveys from 48 states and the District of Columbia were received. A hospital was more likely to have policies supporting nurse-initiated protocols if they were not in a state with scope of practice prohibitions. Four qualitative categories emerged: advantages, approval, prohibition, and conditions under which protocols can be used. Prohibitive language was associated with less protocol use for emergency care.

Conclusion

State scope of practice inconsistencies create misalignment with emergency nurse education and training, which may impede timely care and contribute to inequalities and inefficiencies in emergency care. In addition, prohibitive language places practicing nurses responding to emergencies in crowded work environments at risk.
A model for COVID-19 prediction in Iran based on China parameters
Authors: Zareie Bushra , Roshani Amin , Mansournia Mohammad Ali , Rasouli Mohammad Aziz , Moradi Ghobad
Published: March 2020

Background

The rapid spread of COVID-19 virus from China to other countries and outbreaks of disease require an epidemiological analysis of the disease in the shortest time and an increased awareness of effective interventions. The purpose of this study was to estimate the COVID-19 epidemic in Iran based on the SIR model. The results of the analysis of the epidemiological data of Iran from January 22 to March 8, 2020 were investigated and the prediction was made until March 29, 2020.

Methods

By estimating the three parameters of time-dependent transmission rate, time-dependent recovery rate, and time-dependent mortality rate from Covid-19 outbreak in China, and using the number of Covid-19 infections in Iran, we predicted the number of patients for the next month in Iran. Each of these parameters was estimated using GAM models. All analyses were conducted in R software using the mgcv package.

Findings

On average, 925 people with COVID-19 are expected to be infected daily in Iran. The epidemic peaks within one week (15.03.2020 to 03.21.2020) and reaches its highest point on 03.18.2020 with 1126 infected cases.

Conclusion

The most important point is to emphasize the timing of the epidemic peak, hospital readiness, government measures and public readiness to reduce social contact.
Integrating Wikipedia editing into health professions education: A curricular inventory and review of the literature
Authors: Maggio Lauren A. , Willinsky John M. , Costello Joseph A. , Skinner Nadine A. , Martin Paolo C. , Dawson Jennifer E.
Published: March 2020

Introduction

Wikipedia is an online encyclopedia read by millions seeking medical information. To provide health professions students with skills to critically assess, edit, and improve Wikipedia’s medical content, a skillset aligned with evidence-based medicine (EBM), Wikipedia courses have been integrated into health professions schools’ curriculum. This study describes a literature review and curricular inventory of Wikipedia educational initiatives to provide an overview of current approaches and identify directions for future initiatives and research.

Methods

Five databases were searched for articles describing educational interventions to train health professional students to edit Wikipedia. Course dashboards, maintained by Wiki Education (WikiEdu), were searched for curricular materials. From these sources, key details were extracted and synthesized, including student and instructor type, course content, educational methods, and student outcomes.

Results

Six articles and 27 dashboards reported on courses offered between 2015-2019. Courses were predominantly offered to medical and nursing students. Instructors delivered content via videos, live lectures, and online interactive modules. Course content included logistics of Wikipedia editing, EBM skills, and health literacy. All courses included assignments requiring students to edit Wikipedia independently or in groups. Limited details of student evaluation were available.

Discussion

A small but growing number of schools are training HPE students to improve Wikipedia’s medical content. Course details are available on WikiEdu dashboards and, to a lesser extent, in peer-reviewed publications. There is limited evidence of the initiatives’ impacts on student learning, however, integrating Wikipedia into health professions education has potential to facilitate learning of EBM and communication skills, improve Wikipedia’s online content, and engage students with an autonomous environment while learning. Future considerations should include a thorough assessment of student learning and practices, a final review of student edits to ensure they follow Wikipedia’s Guidelines and are written in clear language, and improved sharing of teaching resources by instructors.
AI-assisted CT imaging analysis for COVID-19 screening: Building and deploying a medical AI system in four weeks
Authors: Jin Shuo , Wang Bo , Xu Haibo , Luo Chuan , Wei Lai , Zhao Wei , Hou Xuexue , Ma Wenshuo , Xu Zhengqing , Zheng Zhuozhao , Sun Wenbo , Lan Lan , Zhang Wei , Mu Xiangdong , Shi Chenxin , Wang Zhongxiao , Lee Jihae , Jin Zijian , Lin Minggui , Jin Hongbo , Zhang Liang , Guo Jun , Zhao Benqi , Ren Zhizhong , Wang Shuhao , You Zheng , Dong Jiahong , Wang Xinghuan , Wang Jianming , Xu Wei
Published: March 2020

The sudden outbreak of novel coronavirus 2019 (COVID-19) increased the diagnostic burden of radiologists. In the time of an epidemic crisis, we hoped artificial intelligence (AI) to help reduce physician workload in regions with the outbreak, and improve the diagnosis accuracy for physicians before they could acquire enough experience with the new disease. Here, we present our experience in building and deploying an AI system that automatically analyzes CT images to detect COVID-19 pneumonia features. Different from conventional medical AI, we were dealing with an epidemic crisis. Working in an interdisciplinary team of over 30 people with medical and / or AI background, geographically distributed in Beijing and Wuhan, we were able to overcome a series of challenges in this particular situation and deploy the system in four weeks. Using 1,136 training cases (723 positives for COVID-19) from five hospitals, we were able to achieve a sensitivity of 0.974 and specificity of 0.922 on the test dataset, which included a variety of pulmonary diseases. Besides, the system automatically highlighted all lesion regions for faster examination. As of today, we have deployed the system in 16 hospitals, and it is performing over 1,300 screenings per day.
Chinese and Italian COVID-19 outbreaks can be correctly described by a modified SIRD model
Authors: Caccavo Diego
Published: March 2020

The COVID-19 disease is rapidly spreading in whole globe, affecting millions of people and pushing governments to take drastic measures to contain the outbreaks. The understanding of the dynamics of the epidemic is of great interest for the governments and health authorities that are facing COVID-19 outbreaks. The scarce presence of epidemiologic data, due to the still ongoing outbreaks, makes prediction difficult and mainly based on heuristic (fitting) models. However, these models with non-physical based parameters, can only give limited insight in the evolution of the outbreaks. In this work a SIRD compartmental model was developed to describe and predict the evolution of the Chinese and Italian outbreaks. Exploiting the similarities of the measures taken by the governments to contain the virus and of the total population number of Hubei province and Italy, the model was tuned on the Chinese outbreak (almost extinguished) and by perturbation the Italian outbreak was describe and predicted.
Projected geographic disparities in healthcare worker absenteeism from COVID-19 school closures and the economic feasibility of child care subsidies: a simulation study
Authors: Chin Elizabeth T , Huynh Benjamin Q , Lo Nathan C , Hastie Trevor , Basu Sanjay
Published: March 2020

Background

School closures have been enacted as a measure of mitigation during the ongoing COVID-19 pandemic. It has been shown that school closures could cause absenteeism amongst healthcare workers with dependent children, but there remains a need for spatially granular analyses of the relationship between school closures and healthcare worker absenteeism to inform local community preparedness.

Methods

We provide national- and county-level simulations of school closures and unmet child care needs across the United States. We develop individual simulations using county-level demographic and occupational data, and model school closure effectiveness with age-structured compartmental models. We perform multivariate quasi-Poisson ecological regressions to find associations between unmet child care needs and COVID-19 vulnerability factors.

Results

At the national level, we estimate the projected rate of unmet child care needs for healthcare worker households to range from 7.5% to 8.6%, and the effectiveness of school closures to range from 3.2% (R0 = 4) to 7.2% (R0 = 2) reduction in fewer ICU beds at peak demand. At the county-level, we find substantial variations of projected unmet child care needs and school closure effects, ranging from 1.9% to 18.3% of healthcare worker households and 5.7% to 8.8% reduction in fewer ICU beds at peak demand (R0 = 2). We find significant positive associations between estimated levels of unmet child care needs and diabetes prevalence, county rurality, and race (p < 0.05). We estimate costs of absenteeism and child care and observe from our models that an estimated 71.1% to 98.8% of counties would find it less expensive to provide child care to all healthcare workers with children than to bear the costs of healthcare worker absenteeism during school closures.

Conclusions

School closures are projected to reduce peak ICU bed demand, but could disrupt healthcare systems through absenteeism, especially in counties that are already particularly vulnerable to COVID-19. Child care subsidies could help circumvent the ostensible tradeoff between school closures and healthcare worker absenteeism.
State Dependent Beta Oscillations in the Cortico-Basal Ganglia Circuit and their Neuromodulation under Phase-Locked Inputs
Authors: West Timothy O. , Farmer Simon F. , Magill Peter J. , Sharott Andrew , Litvak Vladimir , Cagnan Hayriye
Published: March 2020

State-of-the-art therapeutic brain stimulation strategies are delivered open loop, using fixed parameters. However, brain states exhibit spontaneous fluctuations dependent upon different behavioural or disease states. Here, we use a model of the cortico-basal ganglia-thalamic circuit to demonstrate how connectivity underpins changes in subcortical beta oscillations – a commonly used control parameter for deep brain stimulation in Parkinson’s disease. We show that recurrent cortical-subcortical loops involving either the cortico-subthalamic or pallido-subthalamic pathways can act in antagonism to modulate the expression of beta band activity (14-30 Hz). These pathways alter the relative timing of intermittent activity across the network, with increased pallido-subthalamic connectivity increasing the propensity of the circuit to enter a state of autonomous oscillation. We demonstrate that phase-locked stimulation can modulate these oscillations, with an efficacy that ultimately depends upon the connectivity across the circuit. This work outlines critical factors required to implement state-adaptive closed-loop brain stimulation.

Highlights

Converging inputs to the subthalamic nucleus arriving via the external segment of globus pallidus and cortex act in antagonism and promote different beta rhythms.

Phase locked stimulation has the capacity to selectively enhance or suppress a brain rhythm depending on the stimulation timing.

The efficacy of stimulation and the parameters required to deliver it, e.g. stimulation timing, effective sensing and stimulation locations, are functions of network state.
Glucose extends lifespan through enhanced intestinal barrier integrity inDrosophila
Authors: Galenza Anthony , Foley Edan
Published: March 2020

Dietary intervention has received considerable attention as an approach to extend lifespan and improve aging. However, questions remain regarding optimal dietary regime and underlying mechanism of lifespan extension. Here, we asked how glucose-enriched food extends the lifespan ofDrosophila. We showed that glucose-dependent lifespan extension is independent of caloric restriction, or insulin activity, two established mechanisms of lifespan extension. Instead, we found that flies raised on glucose-enriched food increased the expression of cell junction proteins, and extended intestinal barrier integrity with age. Furthermore, chemical disruption of the intestinal barrier removed the lifespan extension associated with glucose-treatment, suggesting that glucose-enriched food prolongs adult viability by enhancing the intestinal barrier. We believe our data contribute to our understanding of intestinal health and may help efforts to develop preventative measures to limit the effects of aging and disease.
The Effectiveness of Social Distancing in Mitigating COVID-19 Spread: a modelling analysis
Authors: Milne George J , Xie Simon
Published: March 2020

Background

The novel coronavirus COVID-19 has been classified by the World Health Organisation as a pandemic due to its worldwide spread. The ability of countries to contain and control transmission is critical in the absence of a vaccine. We evaluated a range of social distancing measures to determine which strategies are most effective in reducing the peak daily infection rate, and consequential pressure on the health care system.

Methods

Using COVID-19 transmission data from the outbreak source in Hubei Province, China, collected prior to activation of containment measures, we adapted an established individual based simulation model of the city of Newcastle, Australia, population 272,409. Simulation of virus transmission in this community model without interventions provided a baseline from which to compare alternative social distancing strategies. The infection history of each individual was determined, as was the time infected. From this model-generated data, the rate of growth in cases, the magnitude of the epidemic peak, and the outbreak duration were obtained.

Findings

The application of all four social distancing interventions: school closure, workplace non-attendance, increased case isolation, and community contact reduction is highly effective in flattening the epidemic curve, reducing the maximum daily case numbers, and lengthening outbreak duration. These were also found to be effective even after 10 weeks delay from index case arrivals. The most effective single intervention was found to be increasing case isolation, to 100% of children and 90% of adults.

Interpretation

As strong social distancing intervention strategies had the most effect in reducing the epidemic peak, this strategy may be considered when weaker strategies are first tried and found to be less effective. Questions arise as to the duration of strong social distancing measures, given they are highly disruptive to society. Tradeoffs may need to be made between the effectiveness of social distancing strategies and population willingness to adhere to them.
Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs
Authors: Jeon Sangeun , Ko Meehyun , Lee Jihye , Choi Inhee , Byun Soo Young , Park Soonju , Shum David , Kim Seungtaek
Published: March 2020

COVID-19 is an emerging infectious disease and was recently declared as a pandemic by WHO. Currently, there is no vaccine or therapeutic available for this disease. Drug repositioning represents the only feasible option to address this global challenge and a panel of 48 FDA-approved drugs that have been pre-selected by an assay of SARS-CoV was screened to identify potential antiviral drug candidates against SARS-CoV-2 infection. We found a total of 24 drugs which exhibited antiviral efficacy (0.1 μM < IC50< 10 μM) against SARS-CoV-2. In particular, two FDA-approved drugs - niclosamide and ciclesonide – were notable in some respects. These drugs will be tested in an appropriate animal model for their antiviral activities. In near future, these already FDA-approved drugs could be further developed following clinical trials in order to provide additional therapeutic options for patients with COVID-19.
Prostatic Peripheral Zone Thickness: What is Normal on Magnetic Resonance Imaging?
Authors: Wasserman Neil F. , Spilseth Benjamin , Sanghvi Tina
Published: March 2020

Purpose

To report the precision of a technique of measuring the PZ thickness on T2-weighted MRI and report normal parameters in patients with normal-sized prostates. We also wanted to establish the mean and second standard deviations (2SD) above and below the mean as criteria for abnormally narrow or expanded PZ thickness.

Methods

Of the initial 1566 consecutive cohort referred for evaluation for carcinoma based on elevated PSA (prostate specific antibody) or DRE (digital rectal examination), 132 separate subjects with normal-sized prostates were selected for this study. Mean age was 58.2 years (15-82). Median serum PSA was 6.2ng/ML (range, 0.3-145). Most were asymptomatic for lower urinary tract symptoms (LUTS). Inclusion criteria in this study required technically adequate T2-weighted MRI and total prostatic volume (TPV) ≤ 25 cc. Exclusion criteria included post prostatic surgical and radiation patients, patients having had medical management or minimally invasive therapy for BPH, those being treated for prostatitis. Patients with suspected tumor expanding or obscuring measurement boundaries were also not considered. Transition zone (TZ) and peripheral zone (PZ) volumes were determined using the prolate ellipsoid model. Postero-lateral measurement of the PZ was obtained at the axial level of maximal transverse diameter of the prostate on a line drawn from the outer boundary of the TZ to the inner boundary of the external prostatic capsule. The data was normally distributed. Therefore, it was analyzed using the 2-sided student t-test and Pearson produce correlation statistic.

Results

Mean pooled (composite) measurement for the postero-lateral PZ (PLPZ) was 10 mm (CI= 9.5-10.5 mm) with SD of 2.87 mm. Means were statistically the same for the 2 observers (p=0.75). Pearson correlation between the two observers was 0.63.

Conclusions

In a prostate ≤ 25 cc volume the postero-lateral PZ should be no thicker than 15.8 mm and averages 10.0 mm. when measured in the maximal axial plane on MRI. These norms were independent of age or use of endorectal coil. The technique measurement demonstrated clinically useful precision.
Genetic analyses identify widespread sex-differential participation bias
Authors: Pirastu Nicola , Cordioli Mattia , Nandakumar Priyanka , Mignogna Gianmarco , Abdellaoui Abdel , Hollis Benjamin , Kanai Masahiro , Rajagopal Veera M. , Parolo Pietro Della Briotta , Baya Nikolas , Carey Caitlin , Karjalainen Juha , Als Thomas D. , Van der Zee Matthijs D. , Day Felix R. , Ong Ken K. ,   Finngen Study,   23andMe Research Team,   iPSYCH Consortium, Morisaki Takayuki , de Geus Eco , Bellocco Rino , Okada Yukinori , Børglum Anders D. , Joshi Peter , Auton Adam , Hinds David , Neale Benjamin M. , Walters Raymond K. , Nivard Michel G. , Perry John R.B. , Ganna Andrea
Published: March 2020

Genetic association results are often interpreted with the assumption that study participation does not affect downstream analyses. Understanding the genetic basis of this participation bias is challenging as it requires the genotypes of unseen individuals. However, we demonstrate that it is possible to estimate comparative biases by performing GWAS contrasting one subgroup versus another. For example, we show that sex exhibits autosomal heritability in the presence of sex-differential participation bias. By performing a GWAS of sex in ~3.3 million males and females, we identify over 158 autosomal loci significantly associated with sex and highlight complex traits underpinning differences in study participation between sexes. For example, the body mass index (BMI) increasing allele at the FTO locus was observed at higher frequency in males compared to females (OR 1.02 [1.02-1.03], P=4.4×10−36). Finally, we demonstrate how these biases can potentially lead to incorrect inferences in downstream analyses and propose a conceptual framework for addressing such biases. Our findings highlight a new challenge that genetic studies may face as sample sizes continue to grow.
EAT-UpTF: Enrichment Analysis Tool for Upstream Transcription Fctors of a gene group
Authors: Shim Sangrea , Seo Pil Joon
Published: March 2020

EAT-UpTF (EnrichmentAnalysisTool forUpstreamTranscriptionFactors of a gene group) is an open-source Python script that analyzes the enrichment of upstream transcription factors (TFs) in a group of genes-of-interest (GOIs). EAT-UpTF utilizes genome-wide lists of TF-target genes generated by DNA affinity purification followed by sequencing (DAP-seq) or chromatin immunoprecipitation followed by sequencing (ChIP-seq). Unlike previous methods based on the two-step prediction ofcis-motifs and DNA-element-binding TFs, our EAT-UpTF analysis enabled a one-step identification of enriched upstream TFs in a set of GOIs using lists of empirically determined TF-target genes.

Contact

sangreashim@gmail.comorpjseo1@snu.ac.kr

Availability

https://github.com/sangreashim/EAT-UpTF
Structural determinants of persulfide-sensing specificity in a dithiol-based transcriptional regulator
Authors: Capdevila Daiana A. , Walsh Brenna J. C. , Zhang Yifan , Dietrich Christopher , Gonzalez-Gutierrez Giovanni , Giedroc David P.
Published: March 2020

Cysteine thiol-based transcriptional regulators orchestrate coordinated regulation of redox homeostasis and other cellular processes by “sensing” or detecting a specific redox-active molecule, which in turn activates the transcription of a specific detoxification pathway. The extent to which these sensors are truly specific in cells for a singular class of reactive small molecule stressors, e.g., reactive oxygen or sulfur species, is largely unknown. Here we report novel structural and mechanistic insights into a thiol-based transcriptional repressor SqrR, that reacts exclusively with organic and inorganic oxidized sulfur species, e.g., persulfides, to yield a unique tetrasulfide bridge that allosterically inhibits DNA operator-promoter binding. Evaluation of five crystallographic structures of SqrR in various derivatized states, coupled with the results of a mass spectrometry-based kinetic profiling strategy, suggest that persulfide selectivity is determined by structural frustration of the disulfide form. This energetic roadblock effectively decreases the reactivity toward major oxidants to kinetically favor formation of the tetrasulfide product. These findings lead to the identification of an uncharacterized repressor from the increasingly antibiotic-resistant bacterial pathogen, Acinetobacter baumannii, as a persulfide sensor, illustrating the predictive power of this work and potential applications to bacterial infectious disease.
celldeath: a tool for detection of cell death in transmitted light microscopy images by deep learning-based visual recognition
Authors: La Greca Alejandro , Pérez Nelba , Castañeda Sheila , Milone Paula Melania , Scarafía María Agustina , Möbbs Alan Miqueas , Waisman Ariel , Moro Lucía , Sevlever Gustavo , Luzzani Carlos , Miriuka Santiago Gabriel
Published: March 2020

Cell death experiments are routinely done in many labs around the world, these experiments are the backbone of many assays for drug development. Cell death detection is usually performed in many ways, and requires time and reagents. However, cell death is preceded by slight morphological changes in cell shape and texture. In this paper, we trained a neural network to classify cells undergoing cell death. We found that the network was able to highly predict cell death after one hour of exposure to camptothecin. Moreover, this prediction largely outperforms human ability. Finally, we provide a simple python tool that can broadly be used to detect cell death.
Epidemiological and Clinical Characteristics of Coronavirus Disease 2019 in Shenzhen, the Largest Migrant City of China
Authors: Wen Ying , Wei Lan , Li Yuan , Tang Xiujuan , Feng Shuo , Leung Kathy , Wu Xiaoliang , Pan Xiong-Fei , Chen Cong , Xia Junjie , Zou Xuan , Feng Tiejian , Mei Shujiang
Published: March 2020

We conducted a retrospective study among 417 confirmed COVID-19 cases from Jan 1 to Feb 28, 2020 in Shenzhen, the largest migrant city of China, to identify the epidemiological and clinical features in settings of high population mobility. We estimated the median incubation time to be 5.0 days. 342 (82.0%) cases were imported, 161 (38.6%) cases were identified by surveillance, and 247 (59.2%) cases were reported from cluster events. The main symptoms on admission were fever and dry cough. Most patients (91.4%) had mild or moderate illnesses. Age of 50 years or older, breathing problems, diarrhea, and longer time between the first medical visit and admission were associated with higher level of clinical severity. Surveillance-identified cases were much less likely to progress to severe illness. Although the COVID-19 epidemic has been contained in Shenzhen, close monitoring and risk assessments are imperative for prevention and control of COVID-19 in future.

Article Summary Line

We characterized epidemiological and clinical features of a large population-based sample of COVID-19 cases in the largest migrant city of China, and our findings could provide knowledge of SARS-CoV-2 transmission in the context of comprehensive containment and mitigation efforts in similar settings.
Transcriptome reconstruction and functional analysis of eukaryotic marine plankton communities via high-throughput metagenomics and metatranscriptomics
Authors: Vorobev Alexey , Dupouy Marion , Carradec Quentin , Delmont Tom O. , Annamalé Anita , Wincker Patrick , Pelletier Eric
Published: March 2020

Large-scale metagenomic and metatranscriptomic data analyses are often restricted by their gene-centric approach, limiting the ability to understand organismal and community biology. De novo assembly of large and mosaic eukaryotic genomes from complex meta-omics data remains a challenging task, especially in comparison with more straightforward bacterial and archaeal systems. Here, we use a transcriptome reconstruction method based on clustering co-abundant genes across a series of metagenomic samples. We investigated the co-abundance patterns of ∼37 million eukaryotic unigenes across 365 metagenomic samples collected during the Tara Oceans expeditions to assess the diversity and functional profiles of marine plankton. We identified ∼12,000 co-abundant gene groups (CAGs), encompassing ∼7 million unigenes, including 924 metagenomics-based transcriptomes (MGTs, CAGs larger than 500 unigenes). We demonstrated the biological validity of the MGT collection by comparing individual MGTs with available references. We identified several key eukaryotic organisms involved in dimethylsulfoniopropionate (DMSP) biosynthesis and catabolism in different oceanic provinces, thus demonstrating the potential of the MGT collection to provide functional insights on eukaryotic plankton. We established the ability of the MGT approach to capture interspecies associations through the analysis of a nitrogen-fixing haptophyte-cyanobacterial symbiotic association. This MGT collection provides a valuable resource for analyses of eukaryotic plankton in the open ocean by giving access to the genomic content and functional potential of many ecologically relevant eukaryotic species.