bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise training for low-risk patients
Authors: Wilhelm Matthias
Published: September 2020

Low-risk cardiac patients should start exercise training (ET) as early as possible after the index event to maintain or improve their cardiorespiratory fitness, muscular strength, and prognosis. Ideally, ET is provided within a multidisciplinary cardiac rehabilitation (CR) programme. It can be delivered as an early outpatient or home-based (HB) programme or as a combination of the two approaches, based on patient preference and local facilities. ET should be prescribed on an individual basis after careful clinical and functional assessment, including risk stratification, evaluation of fitness level, behavioural characteristics, personal goals, and exercise preferences. Importantly, the programme should empower the patient for individual long-term physical activity and ET. Aerobic endurance training three to five times weekly should be prescribed, with a goal of at least 150 min of moderate to vigorous exercise per week. Resistance training (RT) twice to three times weekly should also be prescribed. The initial duration and intensity of ET should be adapted to the patient’s condition and gradually increased.
Exercise training programmes for high-risk and specific groups of patients
Authors: Schmid Jean-Paul , Corrà Ugo
Published: September 2020

Exercise training (ET) in cardiac patients is considered safe, even early after an acute event or in the case of advanced heart disease. However, clinical incidents during rehabilitation may occur, in particular in patients considered to be ‘high risk’. Therefore these patients have to be identified at the beginning of an exercise-based cardiac rehabilitation (CR) programme and deserve particular attention. This includes a thorough clinical assessment, a tailored exercise prescription, and appropriate monitoring.
Cardiac rehabilitation for geriatric and frail patients
Authors: Vigorito Carlo , Abreu Ana
Published: September 2020

The progressive ageing of populations leads to a high burden of elderly patients with cardiac disease and is associated with comorbidities, cognitive/psychological deterioration, disability, social deprivation, and frailty. All these conditions complicate the clinical course of cardiac disease and worsen the outcome. Cardiac rehabilitation (CR), as a multidisciplinary intervention, improves mortality, morbidity, re-hospitalization, physical function, and quality of life in adult patients after acute cardiac events. Older patients without clinical complexity can follow a CR programme slightly different from that for middle-aged patients, mainly based on aerobic training, with similar functional improvement. CR for elderly cardiac patients with comorbidities, sarcopenia, or frailty should be based mainly on strength exercise integrated with aerobic and balance training, but the most appropriate exercise programme has yet to be defined. Future studies should test whether interventions tailored to the presence and severity of frailty are effective in improving specific outcomes, with particular reference to functional capacity, physical function, health-related quality of life (HQoL), disability, frailty, hospitalization, and institutionalization.
Specific issues with physical activity after cardiac rehabilitation
Authors: Ambrosetti Marco , Garcia-Porrero Esteban
Published: September 2020

The transition between phase II (structured, supervised) and phase III (long-term, unsupervised) cardiac rehabilitation (CR) provides an opportunity to promote regular physical activity (PA) in cardiac patients, with the aim of maintaining functional capacity and improving cardiovascular (CV) prognosis. Unfortunately, barriers at the individual and organizational/environmental level may lead to poor adherence to PA, with a consequent need for a call to action by the whole multidisciplinary CR staff. In particular, improvement of patients’ self-efficacy—defined as beliefs about one’s ability to perform a specific action—is clearly associated with better adherence to the programme. The gold standard is individualized prescription of a PA plan—type, intensity, duration, and frequency—which should be monitored and revised periodically on the basis of serial direct evaluations of cardiorespiratory fitness. If this is not available, good PA practice focusing on training intensity and volume should be recommended. In selected cases, the delivery of a long-term PA programme could be supported by digital health tools.
Cardiopulmonary exercise test
Authors: Moderato Luca , Piepoli Massimo Francesco
Published: September 2020

Cardiopulmonary exercise testing (CPET) is a safe and reproducible diagnostic tool for the global assessment of cardiovascular (CV), ventilatory, and metabolic responses to exercise. It can be extremely useful for understanding the reasons for dyspnoea, fatigue, and exercise limitation, and for differentiating between cardiac and pulmonary disorders. CPET can also help the clinician to optimize the decision-making process and outcome prediction, especially in heart failure (HF) patients.
Merger-inspired rotation laws and the low-T/W instability in neutron stars
Authors: Passamonti A , Andersson N
Published: September 2020

Implementing a family of differential rotation laws inspired by binary neutron-star merger remnants, we consider the impact of the rotation profile on the low-T/W instability. We use time evolutions of the linearized dynamical equations, in Newtonian gravity, to study non-axisymmetric oscillations and identify the unstable modes. The presence and evolution of the low-T/W instability is monitored with the canonical energy and angular momentum, while the growth time is extracted from the evolved kinetic energy. The results for the new rotation laws highlight similarities with the commonly considered j-constant law. The instability sets in when an oscillation mode corotates with the star (i.e. whenever there is a point at which the mode’s pattern speed matches the bulk angular velocity) and grows faster deep inside the co-rotation region. However, the new profiles add features, like an additional co-rotation point, to the problem, and these affect the onset of instability. The rotation laws have the most drastic influence on the oscillation frequencies of the l = m = 2 f mode in fast-rotating models, but affect the instability growth time at some level for any rotation rate. We also identify models where the low-T/W instability appears to be triggered by inertial modes. We discuss to what extent the inferred qualitative behaviour is likely to be of observational relevance.
Rosette-forming glioneuronal tumor: an illustrative case and a systematic review
Authors: Wilson Caleb P , Chakraborty Arpan R , Pelargos Panayiotis E , Shi Helen H , Milton Camille K , Sung Sarah , McCoy Tressie , Peterson Jo Elle , Glenn Chad A
Published: September 2020

Background

Rosette-forming glioneuronal tumors (RGNTs) are rare, low-grade, primary CNS tumors first described in 2002 by Komori et al. RGNTs were initially characterized as a World Health Organization (WHO) grade I tumors typically localized to the fourth ventricle. Although commonly associated with an indolent course, RGNTs have the potential for aggressive behavior.

Methods

A comprehensive search of PubMed and Web of Science was performed through November 2019 using the search term “rosette-forming glioneuronal tumor.” Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. English, full-text case reports and series with histopathological confirmation were included. Patient demographics, presentations, MRI features, tumor location, treatment, and follow-up of all 130 cases were extracted.

Results

A 19-year-old man with a history of epilepsy and autism presented with acute hydrocephalus. MRI scans from 2013 to 2016 demonstrated unchanged abnormal areas of cortex in the left temporal lobe with extension into the deep gray-white matter. On presentation to our clinic in 2019, the lesion demonstrated significant progression. The patient’s tumor was identified as RGNT, WHO grade I. One hundred thirty patients were identified across 80 studies.

Conclusion

RGNT has potential to transform from an indolent tumor to a tumor with more aggressive behavior. The results of our systematic review provide insight into the natural history and treatment outcomes of these rare tumors.
Unjust Enrichment: What We Owe to Each Other
Authors: Cutts Tatiana
Published: September 2020

In some quarters, the focus of unjust enrichment scholarship has shifted from loss and gain towards the defendant’s ‘involvement in the story’—what she has done to warrant liability. The goal of this shift is to fit unjust enrichment within the ‘doer-sufferer’ template of ‘corrective justice’ theories of private law. I argue that this shift fails to reconcile unjust enrichment with the commitment to equal freedom upon which these theories depend. But we can justify restitution without forsaking the Kantian concern with rational agency. In this article, I endorse a contractualist approach to mistaken payments: a particular use of the state’s coercive power is just if it is one that everyone could rationally choose; everyone could rationally choose a rule placing the burden of risk for mistake with payees, if that rule does not make any such payee worse off than she was prior to the impugned transaction.
Technology Can Augment, but Not Replace, Critical Human Skills Needed for Patient Care
Authors: Alrassi James , Katsufrakis Peter J. , Chandran Latha
Published: September 2020

The practice of medicine is changing rapidly as a consequence of electronic health record adoption, new technologies for patient care, disruptive innovations that breakdown professional hierarchies, and evolving societal norms. Collectively, these have resulted in the modification of the physician’s role as the gatekeeper for health care, increased shift-based care, and amplified interprofessional team-based care. Technological innovations present opportunities as well as challenges. Artificial intelligence, which has great potential, has already transformed some tasks, particularly those involving image interpretation. Ubiquitous access to information via the Internet by physicians and patients alike presents benefits as well as drawbacks: patients and providers have ready access to virtually all of human knowledge, but some websites are contaminated with misinformation and many people have difficulty differentiating between solid, evidence-based data and untruths. The role of the future physician will shift as complexity in health care increases and as artificial intelligence and other technologies advance. These technological advances demand new skills of physicians; memory and knowledge accumulation will diminish in importance while information management skills will become more important. In parallel, medical educators must enhance their teaching and assessment of critical human skills (e.g., clear communication, empathy) in the delivery of patient care. The authors emphasize the enduring role of critical human skills in safe and effective patient care even as medical practice is increasingly guided by artificial intelligence and related technology, and they suggest new and longitudinal ways of assessing essential noncognitive skills to meet the demands of the future. The authors envision practical and achievable benefits accruing to patients and providers if practitioners leverage technological advancements to facilitate the development of their critical human skills.
A Novel Ticket System for Capping Residency Interview Numbers: Reimagining Interviews in the COVID-19 Era
Authors: Burk-Rafel Jesse , Standiford Taylor C.
Published: September 2020

The 2019 novel coronavirus (COVID-19) pandemic has led to dramatic changes in the 2020 residency application cycle, including halting away rotations and delaying the application timeline. These stressors are laid on top of a resident selection process already under duress with exploding application and interview numbers—the latter likely to be exacerbated with the widespread shift to virtual interviewing. Leveraging their trainee perspective, the authors propose enforcing a cap on the number of interviews that applicants may attend through a novel interview ticket system (ITS). Specialties electing to participate in the ITS would select an evidence-based, specialty-specific interview cap. Applicants would then receive unique electronic tickets—equal in number to the cap—that would be given to participating programs at the time of an interview, when the tickets would be marked as used. The system would be self-enforcing and would ensure each interview represents genuine interest between applicant and program, while potentially increasing the number of interviews—and thus match rate—for less competitive applicants. Limitations of the ITS and alternative approaches for interview capping, including an honor code system, are also discussed. Finally, in the context of capped interview numbers, the authors emphasize the need for transparent preinterview data from programs to inform applicants and their advisors on which interviews to attend, learning from prior experiences and studies on virtual interviewing, adherence to best practices for interviewing, and careful consideration of how virtual interviews may shift inequities in the resident selection process.
Prognostic Significance of Tumor-infiltrating Lymphocytes on Survival Outcomes of Patients With Resected Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis
Authors: Tan Harold N.C. , Catedral Lance I.G. , San Juan Michael D.
Published: September 2020

Tumor-infiltrating lymphocytes (TILs) play an important role in mediating treatment response in pancreatic cancer. This meta-analysis investigated the prognostic significance of TIL subsets on overall survival (OS) and disease-free survival (DFS) of patients with pancreatic cancer. Studies were gathered via search of PubMed, Google Scholar, and Cochrane Library databases up to August 1, 2019. Using Review Manager version 5.3.5, pooled hazard ratios and 95% confidence intervals (CIs) were calculated using random or fixed-effects models, depending on the heterogeneity of studies. A total of 11 studies comprising 1760 patients were included in the meta-analysis. Pooled analysis revealed that high CD8+ TILs were associated with improved OS [hazard ratio (HR)=0.59, 95% CI=0.51–0.69, P<0.00001] and DFS (HR=0.60, 95% CI=0.50–0.73, P<0.00001). Similarly, high CD3+ TILs correlated with better OS (HR=0.64, 95% CI=0.54–0.75, P<0.00001) and DFS (HR=0.53, 95% CI=0.31–0.92, P<0.0001). In contrast, high FoxP3+ TILs were associated with worse OS (HR=1.39, 95% CI=1.03–1.88, P=0.03). Finally, high CD4+ TILs showed significant improvement in OS (HR=0.74, 95% CI=0.63–0.86, P=0.0001). TILs are a promising prognostic biomarker in pancreatic cancer. Prospective studies evaluating TILs are recommended as well as the establishment of standards in the assessment of TILs.
A Smart Chest Pain Center to Improve Quality Control and Reduce Doctor’s Workload of Acute Myocardial Infarction
Authors: Zhao Yifan , Ding Sixiao , Peng Wenhui , Zhang Yi , Xu Yawei
Published: September 2020

The establishment of a chest pain center (CPC) is an important strategy to improve the treatment of urgent cardiovascular disease, especially acute myocardial infarction. In order to monitor and continuously improve the quality of diagnosis and treatment of CPCs, accurate records of key time points must be made in the diagnosis and treatment of fatal chest pain, which consumes tremendous manpower and resources. Our research combined the application of the Internet of Things, big data, artificial intelligence, and other techniques, to establish a smart CPC that can automatically record key time points, which significantly reduced the workload of doctors with more reliable, unified, and traceable data. Our solution to the CPC should be a promising plan for future CPC construction.
A Case of Primary Open-angle Glaucoma With Conjunctival Laceration After Micropulse Transscleral Cyclophotocoagulation
Authors: Kiyama Yu , Nakashima Kei-Ichi , Inoue Toshihiro
Published: September 2020

Purpose:

We report a case of primary open-angle glaucoma with conjunctival laceration after micropulse transscleral cyclophotocoagulation (MP-CPC).

Patients and Methods:

A 74-year-old man with primary open-angle glaucoma underwent MP-CPC using a Cyclo G6 device (IRIDEX) due to an increase in intraocular pressure (IOP) to 25 mm Hg in his left eye. At 1 week after surgery, IOP had decreased to 12 mm Hg. However, at 2 months after surgery, IOP had increased again to 25 mm Hg. MP-CPC was performed again at 3 months after the first surgery using a Cyclo G6 device, in accordance with treatment guidelines outlined by the manufacturer. Before the MP-CPC treatment, the patient received anesthesia with 2% lidocaine in the sub-Tenon space. A large amount of subconjunctival hemorrhage was observed in the sub-Tenon space.

Results:

At 1 day after the second MP-CPC treatment, an arc-shaped conjunctival erosion and a brown lesion were observed in the MP-CPC-irradiated area in the lower hemisphere. The possibility of scleral laceration was considered. The IOP was 25 mm Hg and no aqueous humor leakage was observed. The wound had become enlarged. At 20 days after the second MP-CPC, the patient was hospitalized to close the wound. During the repair surgery, the brown lesion was easily detached from the sclera. There was conjunctival laceration, but no scleral laceration. Pathologic examination revealed that the exfoliated tissue contained abundant clots, connective tissue, and elastic fibers.

Conclusion:

Special care and consideration are required when performing MP-CPC in cases of severe subconjunctival hemorrhage.
The Natural Course of Gastroesophageal Reflux Disease
Authors: Shah Aun , Shibli Fahmi , Kitayama Yoshitaka , Fass Ronnie
Published: September 2020

Interpreting natural course studies have been very difficult due to their retrospective design, lack of standardization, reliability of reported mucosal findings, liberal use of antireflux medications and accuracy of chart documentation. Studies provided a wide range of progression rates of patients from nonerosive reflux disease (NERD) to erosive esophagitis (EE). However, direct progression from NERD to Barrett’s esophagus appears to be an uncommon phenomenon. Importantly, progression of NERD patients was commonly reported to low grades of EE, which are currently considered inconclusive of gastroesophageal reflux disease. Reports of progression rates from low grades to high grades EE also vary considerably. Progression of patients with EE, without metaplastic epithelium underneath the inflammation, to Barrett’s esophagus is relatively uncommon. Recently, it was also recognized that regression from high grades to low grades EE and from EE to NERD is a common phenomenon affecting up to 25% of the patients from each group.
Modeling an integrated HIV prevention and care continuum to achieve the Ending the HIV Epidemic goals
Authors: Jenness Samuel M. , Johnson Jordan A. , Hoover Karen W. , Smith Dawn K. , Delaney Kevin P.
Published: September 2020

Objective:

We sought to evaluate, which combinations of HIV prevention and care activities would have the greatest impact towards reaching the US Ending the HIV Epidemic (EHE) plan goals of HIV incidence reduction.

Design:

A stochastic network-based HIV transmission model for men who have sex with men (MSM), calibrated to surveillance estimates in the Atlanta area, a focal EHE jurisdiction.

Methods:

Model scenarios varied HIV screening rates under different assumptions of how HIV-negative MSM would be linked to PrEP initiation, and rates of HIV care linkage and retention for those screening positive.

Results:

A ten-fold relative increase in HIV screening rates (to approximately biannual screening for black and Hispanic MSM and quarterly for white MSM) would lead to 43% of infections averted if integrated with PrEP initiation. Improvements focused only on black MSM would achieve nearly the same outcome (37% of infections averted). Improvements to HIV care retention would avert 41% of infections if retention rates were improved ten-fold. If both screening and retention were jointly improved ten-fold, up to 74% of cumulative infections would be averted. Under this scenario, it would take 4 years to meet the 75% EHE goal and 12 years to meet the 90% goal for Atlanta MSM.

Conclusion:

Reaching the EHE 75% incidence reduction goals by their target dates will require immediate and substantial improvements in HIV screening, PrEP, and ART care retention. Meeting these EHE goals in target jurisdictions like Atlanta will be possible only by addressing the HIV service needs of black MSM.
Characteristics and outcomes of adolescents living with perinatally acquired HIV within Southern Africa
Authors: Tsondai Priscilla R. , Braithwaite Kate , Fatti Geoffrey , Bolton Moore Carolyn , Chimbetete Cleophas , Rabie Helena , Phiri Sam , Sawry Shobna , Eley Brian , Hobbins Michael A. , Boulle Andrew , Taghavi Katayoun , Sohn Annette H. , Davies Mary-Ann
Published: September 2020

Background:

Using data from 15 International epidemiology Databases to Evaluate AIDS in Southern Africa sites, we compared the characteristics and outcomes of adolescents living with perinatally acquired HIV (ALPH).

Methods:

We included ALPH entering care aged less than 13 years with at least one HIV care visit during adolescence (10–19 years). We compared the characteristics and cross-sectional outcomes: transfer out, loss to follow-up (no visit in the 12 months prior to database closure), mortality, and retention between those who entered care aged less than 10 vs. aged 10–13 years; and explored predictors of mortality after age 13 years using Cox Proportional Hazards models.

Results:

Overall, 16 229 (50% female) ALPH who entered HIV care aged less than 10 years and 8897 (54% female) aged 10–13 years were included and followed for 152 574 person-years. During follow-up, 94.1% initiated antiretroviral therapy, with those who entered care aged less than 10 more likely to have initiated antiretroviral therapy [97.9%, 95% confidence interval (CI) 97.6; 98.1%] than those who presented aged 10–13 years (87.3%, 95% CI 86.6; 88.0%). At the end of follow-up, 3% had died (entered care aged <10 vs. 10–13 years; 1.4 vs. 5.1%), 22% were loss to follow-up (16.2 vs. 33.4%), and 59% (66.4 vs. 45.4%) were retained. There was no difference in the risk of dying after the age of 13 years between adolescents entering care aged less than 10 vs. 10–13 years (adjusted hazard ratio 0.72; 95% CI 0.36; 1.42).

Conclusion:

Retention outcomes for ALPH progressively worsened with increasing age, with these outcomes substantially worse among adolescents entering HIV care aged 10–13 vs. less than 10 years.
In Situ Simulation
Authors: Sharara-Chami Rana , Sabouneh Rami , Zeineddine Rida , Banat Rim , Fayad Joe , Lakissian Zavi
Published: September 2020

Introduction

Working under extreme stress can cause medical professionals to deviate from clinical guidelines even if they know of their existence, let alone in situations such as COVID-19 where guidelines are unclear, fluid, and resources limited. In situ simulation has been proven an effective tool for training medical professionals during previous healthcare crises, eg, Ebola, influenza, as well as for assessing the preparedness of centers by identifying potential latent safety threats. In this article, we describe our ongoing simulation activities to ensure that our staff is best prepared to adapt to the challenges of COVID-19.

Methods

This is a prospective preparedness assessment and training intervention at a tertiary care academic center in Lebanon during the COVID-19 pandemic. In situ simulations followed by debriefing with good judgment occur daily involving native teams of 3 to 5 professionals in the newly established COVID intensive care unit and wards, the adult and pediatric intensive care unit and wards, and the emergency department. The simulations are assessed by the instructor using the Simulation Team Assessment Tool and by the participants using the Simulation Effectiveness Tool. Transcripts of recorded simulation debriefings are analyzed for content for latent safety threats using the SHELL Framework (Software-Hardware-Equipment-Liveware).

Results

In 2 weeks, we conducted 15 simulations with 106 participants and 47 observers. Simulation Team Assessment Tool scores show an overall improvement across the hospital over time [101.5 ± 13 (80–134)]. Participants' feedback on the Simulation Effectiveness Tool has been predominantly positive on the educational and practical benefits of the simulation activity. Data from debriefings and observations demonstrated the following categories of latent safety threats: inadequate preparedness on infection control, uncertainty of guidelines on oxygen supplementation and intubation protocols, lack of leadership and communication, overall panic, and others.

Conclusions

Our single-center preparedness intervention demonstrated multiple latent safety threats in relation to COVID-19, which can be recognized through simulation before translating into actual patient care.
Image-guided Endoscopic Parathyroidectomy Using the Axillo-breast Approach in the Treatment of Primary Hyperparathyroidism
Authors: Elzahaby Islam A. , Abouzid Amr , Saleh Saleh , Shetiwy Mosab
Published: September 2020

Background:

Focused parathyroidectomy is currently performed using minimal access techniques. Here, we aim to evaluate the outcomes of the axillo-breast totally endoscopic approach (ABTEA) in patients with primary hyperparathyroidism caused by a single parathyroid adenoma.

Patients and Methods:

Ten patients with primary hyperparathyroidism were retrospectively evaluated. In all patients, the presence of a single parathyroid adenoma was confirmed using cervical ultrasonography by an expert radiologist with or without the use of parathyroid scintigraphy. All patients underwent focused parathyroidectomy using ABTEA. Clinicopathologic characteristics, surgical outcomes, biochemical cure rates, and cosmetic outcomes were evaluated.

Results:

The parathyroid adenoma was successfully excised in all patients without significant complications and without conversion to open approach. All patients were cured, with ≥6 months of follow-up. Temporary hoarseness of the voice was observed in 1 case. The mean surgical time was 91±17.61 minutes. The mean blood loss was 20 mL. The postoperative pain scores were satisfactory and 90% of patients were extremely satisfied with the procedure.

Conclusion:

With accurate preoperative sonographic localization of a single parathyroid adenoma, focused parathyroidectomy using ABTEA is a safe and feasible technique even for posteriorly located parathyroid adenomas.
Relationship Between Maternal Age at First Delivery and Subsequent Pelvic Organ Prolapse
Authors: Wang Rui , Tulikangas Paul K. , Tunitsky-Bitton Elena
Published: September 2020

Objective

To determine the relationship between age at first delivery and subsequent risk of pelvic organ prolapse.

Study Design

We performed a retrospective cross-sectional study using the National Health and Nutrition Examination Survey data from 2005 to 2012. Our primary outcome was self-reported prolapse. Survival analyses and Cox proportional hazard models were used to estimate parous women’s risks of reporting prolapse in terms of time since first delivery, adjusting for parity, body mass index, prior hysterectomy, ethnicity, and education. We performed subgroup analyses on women with at least 1 vaginal delivery and those with only cesarean deliveries.

Results

The survey-weighted prevalence of prolapse was 2.82%. A total of 6203 women, 79% of all parous women surveyed, reported age at first delivery. Kaplan-Meier curves were different for women based on age at first delivery (P = 0.034). For each year increase in age at first delivery, there was a 6% increase in the rate of developing prolapse (adjusted hazard ratio, 1.06; 95% confidence interval, 1.01–1.11; P = 0.011). Compared with a woman who was 20 years at her first delivery, someone who was 30 years had 1.79 times the risk, while at 40 years the risk was 3.21 times. Among women with at least 1 vaginal delivery, the same relationship was found (adjusted hazard ratio, 1.06; 95% confidence interval, 1.01–1.12; P = 0.019). However, this was not significant for women with only cesarean deliveries (P = 0.367).

Conclusions

Older age at the time of first delivery was associated with a higher risk of subsequent prolapse. These results should be interpreted with caution given the limitations of cross-sectional survey data.
Idebenone protects mitochondrial function against amyloid beta toxicity in primary cultured cortical neurons
Authors: Wang Huiting , Li Lei , Jia Kun , Wang Qi , Sui Shaomei , Lin Yicheng , He Yan
Published: September 2020

Mitochondrial dysfunction has been repeatedly identified to be hallmark brain pathology underlying neuronal stress in Alzheimer’s disease. As a result, mitochondrial medicine for the treatment of Alzheimer’s disease has received increasing recognition. Idebenone (IDB) is a synthetic analog of Coenzyme Q10 (CoQ10) carrying antioxidizing property. Previous clinical trials reported a conflicting disease-modifying effect of IDB on Alzheimer’s disease patients. However, whether IDB is preventive against amyloid beta (Aβ)-induced mitochondrial and neuronal stress has not been comprehensively investigated. In this study, we adopted an in-vitro setting by using primary cultured cortical neurons for the test. Neurons were pretreated with IDB prior to Aβ exposure. IDB pretreatment significant prevented neurons from Aβ-induced collapse of mitochondrial bioenergetics and perturbations of the protein kinase A (PKA)/cAMP response element-binding protein (CREB) signaling. Importantly, the treatment of IDB alone demonstrated an indiscernible side effect on the measured mitochondrial function, PKA/CREB signaling and neuronal viability. Therefore, our findings in together show a preventive effect of IDB against Aβ-mediated mitochondrial and neuronal injury. The use of IDB may hold potential to reduce the risk of Alzheimer’s disease as a preventive strategy.
Bioluminescence dynamics in single germinating bacterial spores reveal metabolic heterogeneity
Authors: Frentz Zak , Dworkin Jonathan
Published: September 2020

Spore-forming bacteria modulate their metabolic rate by over five orders of magnitude as they transition between dormant spores and vegetative cells and thus represent an extreme case of phenotypic variation. During environmental changes in nutrient availability, clonal populations of spore-forming bacteria exhibit individual differences in cell fate, the timing of phenotypic transitions and gene expression. One potential source of this variability is metabolic heterogeneity, but this has not yet been measured, as existing single-cell methods are not easily applicable to spores due to their small size and strong autofluorescence. Here, we use the bacterial bioluminescence system and a highly sensitive microscope to measure metabolic dynamics in thousands of
B. subtilis
spores as they germinate. We observe and quantitate large variations in the bioluminescence dynamics across individual spores that can be decomposed into contributions from variability in germination timing, the amount of endogenously produced luminescence substrate and the intracellular reducing power. This work shows that quantitative measurement of spore metabolism is possible and thus it opens avenues for future study of the thermodynamic nature of dormant states.
The impact of incorrect social information on collective wisdom in human groups
Authors: Jayles Bertrand , Escobedo Ramón , Cezera Stéphane , Blanchet Adrien , Kameda Tatsuya , Sire Clément , Theraulaz Guy
Published: September 2020

A major problem resulting from the massive use of social media is the potential spread of incorrect information. Yet, very few studies have investigated the impact of incorrect information on individual and collective decisions. We performed experiments in which participants had to estimate a series of quantities, before and after receiving social information. Unbeknownst to them, we controlled the degree of inaccuracy of the social information through ‘virtual influencers’, who provided some incorrect information. We find that a large proportion of individuals only partially follow the social information, thus resisting incorrect information. Moreover, incorrect information can help improve group performance more than correct information, when going against a human underestimation bias. We then design a computational model whose predictions are in good agreement with the empirical data, and sheds light on the mechanisms underlying our results. Besides these main findings, we demonstrate that the dispersion of estimates varies a lot between quantities, and must thus be considered when normalizing and aggregating estimates of quantities that are very different in nature. Overall, our results suggest that incorrect information does not necessarily impair the collective wisdom of groups, and can even be used to dampen the negative effects of known cognitive biases.
On the Role of Artificial Intelligence in Medical Imaging of COVID-19
Authors: Born Jannis , Beymer David , Rajan Deepta , Coy Adam , Mukherjee Vandana V. , Manica Matteo , Prasanna Prasanth , Ballah Deddeh , Guindy Michal , Shaham Dorith , Shah Pallav L. , Karteris Emmanouil , Robertus Jan L. , Gabrani Maria , Rosen-Zvi Michal
Published: September 2020

The global COVID-19 pandemic has accelerated the development of numerous digital technologies in medicine from telemedicine to remote monitoring. Concurrently, the pandemic has resulted in huge pressures on healthcare systems. Medical imaging (MI) from chest radiographs to computed tomography and ultrasound of the thorax have played an important role in the diagnosis and management of the coronavirus infection.

We conducted the, to date, largest systematic review of the literature addressing the utility of Artificial Intelligence (AI) in MI for COVID-19 management. Through keyword matching on PubMed and preprint servers, including arXiv, bioRxiv and medRxiv, 463 papers were selected for a meta-analysis, with manual reviews to assess the clinical relevance of AI solutions. Further, we evaluated the maturity of the papers based on five criteria assessing the state of the field: peer-review, patient dataset size and origin, algorithmic complexity, experimental rigor and clinical deployment.

In 2020, we identified 4977 papers on MI in COVID-19, of which 872 mentioned the term AI. 2039 papers of the 4977 were specific to imaging modalities with a majority of 83.8% focusing on CT, while 10% involved CXR and 6.2% used LUS. Meanwhile, the AI literature predominantly analyzed CXR data (49.7%), with 38.7% using CT and 1.5% LUS. Only a small portion of the papers were judged as mature (2.7 %). 71.9% of AI papers centered on disease detection.

This review evidences a disparity between clinicians and the AI community, both in the focus on imaging modalities and performed tasks. Therefore, in order to develop clinically relevant AI solutions, rigorously validated on large-scale patient data, we foresee a need for improved collaboration between the two communities ensuring optimal outcomes and allocation of resources. AI may aid clinicians and radiologists by providing better tools for localization and quantification of disease features and changes thereof, and, with integration of clinical data, may provide better diagnostic performance and prognostic value.
Caffeine Increases the Reinforcing Efficacy of Alcohol, an Effect that is Independent of Dopamine D2Receptor Function
Authors: Holstein Sarah E. , Barkell Gillian A. , Young Megan R.
Published: September 2020

The rising popularity of alcohol mixed with energy drinks (AmEDs) has become a significant public health concern, with AmED users reporting higher levels of alcohol intake than non-AmED users. One mechanism proposed to explain heightened levels of alcohol intake in AmED users is that the high levels of caffeine found in energy drinks may increase the reinforcing properties of alcohol, an effect which may be dependent on interactions between adenosine signaling pathways and the dopamine D2receptor. Therefore, the purpose of the current study was to confirm whether caffeine increases the reinforcing efficacy of alcohol using both fixed ratio (FR) and progressive ratio (PR) designs, and to investigate a potential role of the dopamine D2receptor in caffeine’s reinforcement-enhancing effects. Male Long Evans rats were trained to self-administer a sweetened alcohol or sucrose solution on an FR2 schedule of reinforcement. Pretreatment with caffeine (5-10 mg/kg) significantly increased operant responding for the sweetened alcohol reinforcer, but not sucrose. PR tests of motivation for alcohol or sucrose likewise confirmed a caffeine-dependent increase in motivation for a sweetened alcohol solution, but not sucrose. However, the D2receptor antagonist eticlopride did not block the reinforcementenhancing effects of caffeine using either an FR or PR schedule of reinforcement. Taken together, these results support the hypothesis that caffeine increases the reinforcing efficacy of alcohol, which may explain caffeine-induced increases in alcohol intake. However, the reinforcement-enhancing effects of caffeine appear to be independent of D2receptor function.
Cuticular Hydrocarbons on Old Museum Specimens of the Spiny Mason Wasp,Odynerus spinipes, (Hymenoptera: Vespidae: Eumeninae) Shed Light on the Distribution and on Regional Frequencies of Distinct Chemotypes
Authors: Moris Victoria C. , Christmann Katharina , Wirtgen Aline , Belokobylskij Sergey A. , Berg Alexander , Liebig Wolf-Harald , Soon Villu , Baur Hannes , Schmitt Thomas , Niehuis Oliver
Published: September 2020

The mason waspOdynerus spinipesshows an exceptional case of intrasexual CHC dimorphism. Females of this species express one of two cuticular hydrocarbon (CHC) profiles (chemotypes) that differ qualitatively and quantitatively from each other. The ratio of the two chemotypes was previously shown to be close to 1:1 at three sites in Southern Germany, which might not be representative given the Palearctic distribution of the species. To infer the frequency of the two chemotypes across the entire distributional range of the species, we analyzed with GC-MS the CHC profiles of 1,042 dry-mounted specimens stored in private and museum collections. We complemented our sampling by including 324 samples collected and preserved specifically for studying their CHCs. We were capable of reliably identifying the chemotypes in 91% of dry-mounted samples, some of which collected almost 200 years ago. We found both chemotypes to occur in the Far East, the presumed glacial refuge of the species, and their frequency to differ considerably between sites and geographic regions. The geographic structure in the chemotype frequencies could be the result of differential selection regimes and/or different dispersal routes during the colonization of the Western Palearctic. The presented data pave the route for disentangling these factors by providing information where to geographically sampleO. spinipesfor population genetic analyses. They also form the much-needed basis for future studies aiming to understand the evolutionary and geographic origin as well as the genetics of the astounding CHC dimorphism thatO. spinipesfemales exhibit.
Healthcare workers in elderly care: a source of silent SARS-CoV-2 transmission?
Authors: Dautzenberg Mirjam , Eikelenboom-Boskamp Andrea , Drabbe Miranda , Janssen Jacqueline , de Jong Ewoud , Weesendorp Eefke , Koopmans Marion , Voss Andreas
Published: September 2020

Importance

Healthcare workers (HCWs), including those with mild symptoms, may be an important source of COVID-19 within elderly care.

Objective

To gain insight into the spread of SARS-CoV-2 among HCWs working in elderly care settings.

Design

Cross-sectional study among HCWs working in elderly care in the South-East of the Netherlands, testing for SARS-CoV-2, between March 31 and April 17, 2020.

Setting

HCWs working in geriatric rehabilitation, somatic and psychogeriatric wards or small-scale living groups and district nursing, with a total of 5245 HCWs within 4 organisations.

Participants

621 HCWs with mild respiratory symptoms.

Main Outcomes

Number of HCWs testing positive for SARS-CoV-2 in pharyngeal swabs, using realtime reverse-transcriptase PCR targeting the SARS-CoV-2 E-gene, N-gene, and RdRP. HCWs filled out a survey to collect information on symptoms and possible sources of infection.

Results

133/615 (21.6%) HCWs tested positive for SARS-CoV-2, ranging from 15.6 to 44.4% per elderly care organisation, and from 0 to 64.3% per separate location of the organizations, respectively. 74.6% of tested HCWs were nursing staff, 1.7% elderly care physicians, 20.3% other HCWs with patient contact and 3.4% HCWs without patient contact. In the univariate analysis, fever, runny or stuffy nose, anosmia, general malaise, myalgia, headache and ocular pain were associated with SARS-CoV-2 positivity, while gastro-intestinal symptoms and respiratory symptoms, other than runny or stuffy nose were not. Risk factors for SARS-CoV-2 positivity were contact with patients or colleagues with suspected or proven COVID-19. Whole genome sequencing of 22 samples in 2 facilities strongly suggests spread within facilities.

Conclusions and Relevance

We found a high SARS-CoV-2 prevalence among HCWs in nursing homes and district nursing, supporting the hypothesis of undetected spread within elderly care facilities. Structural testing of elderly care HCWs, including track and trace of contacts, should be performed to control this spread, even when only mild symptoms are present.
The Geography of Excess Deaths in England during the Covid-19 pandemic: Longer term impacts and monthly dynamics
Authors: Breen Richard , Ermisch John
Published: September 2020

Physical social interaction relevant to the spread of infectious diseases occurs, by its nature, at a local level. If infection and related mortality are associated with social background, it is therefore natural to study variation in them in relation to the social composition of local areas. The first part of the paper studies the geographical impact of Covid-19 infection on age-standardised sex-specific excess death rates during the peak months of the pandemic so far, March through May 2020. The second part examines monthly mortality dynamics in relation to predictions from a spatial SIR (Susceptible, Infected, Recovered) model of infection introduced by Bisin and Moro (2020). The analysis indicates that during the peak months of the Covid-19 pandemic, a larger non-white population and higher social deprivation in an area were associated with higher excess mortality, particularly among men. Regarding dynamics, higher population density accelerated the growth in mortality during the upsurge in infection and increased its rate of decline after the peak of the epidemic, thereby producing a more peaked mortality profile. There is also evidence of a slower post-peak decline in mortality in more socially deprived areas but a more rapid decline in areas with a larger non-white population.
Influenza may facilitate the spread of SARS-CoV-2
Authors: Domenech de Cellès Matthieu , Casalegno Jean-Sébastien , Lina Bruno , Opatowski Lulla
Published: September 2020

As in past pandemics, co-circulating pathogens may play a role in the epidemiology of coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). Here we hypothesized that influenza interacted with SARS-CoV-2 during the early 2020 epidemic of COVID-19 in Europe. We developed a population-based model of SARS-CoV-2 transmission, combined with mortality incidence data in four European countries, to test a range of assumptions about the impact of influenza. We found consistent evidence for a 2–2.5-fold population-level increase in SARSCoV-2 transmission associated with influenza during the period of co-circulation. These results suggest the need to increase vaccination against influenza, not only to reduce the burden due to influenza viruses, but also to counteract their facilitatory impact on SARS-CoV-2.
Ongoing natural selection drives the evolution of SARS-CoV-2 genomes
Authors: Liu Qi , Zhao Shilei , Hou Yali , Ye Sicheng , Sha Tong , Su Yankai , Zhao Wenming , Bao Yiming , Xue Yongbiao , Chen Hua
Published: September 2020

SARS-CoV-2 is a new RNA virus affecting humans and spreads extensively through world populations since its first outbreak in late December, 2019. Whether the transmissibility and pathogenicity of SARS-CoV-2 is actively evolving, and driven by adaptation to the new host and environments is still unknown. Understanding the evolutionary mechanism underlying epidemiological and pathological characteristics of COVID-19 is essential for predicting the epidemic trend, and providing guidance for disease control and treatments. Interrogating 22,078 SARS-CoV-2 genome sequences of 84 countries, we demonstrate with convincing evidence that (i) SARS-CoV-2 genomes are overall conserved under purifying selection. (ii) Ongoing positive selection is actively driving the evolution of specific genes. Notably, genes related to coronavirus infection and host immune system defense are under adaptive evolution while genes related to viral RNA replication, transcription and translation are under purifying selection. A spatial and temporal landscape of 54 critical mutants is constructed based on their divergence among viral haplotype clusters, of which multiple mutants potentially conferring viral transmissibility, infectivity and virulence of SARS-CoV-2 are highlighted.
COVID-19 Belgium: Extended SEIR-QD model with nursing homes and long-term scenarios-based forecasts
Authors: Franco Nicolas
Published: September 2020

Following the spread of the COVID-19 pandemic and pending the establishment of vaccination campaigns, several non pharmaceutical interventions such as partial and full lockdown, quarantine and measures of physical distancing have been imposed in order to reduce the spread of the disease and to lift the pressure on healthcare system. Mathematical models are important tools for estimating the impact of these interventions, for monitoring the current evolution of the epidemic at a national level and for estimating the potential long-term consequences of relaxation of measures. In this paper, we model the evolution of the COVID-19 epidemic in Belgium with a deterministic age-structured extended compartmental model. Our model takes special consideration for nursing homes which are modelled as separate entities from the general population in order to capture the specific delay and dynamics within these entities. The model integrates social contact data and is fitted on hospitalisations data (admission and discharge), on the daily number of COVID-19 deaths (with a distinction between general population and nursing home related deaths) and results from serological studies, with a sensitivity analysis based on a Bayesian approach. We present the situation as in November 2020 with the estimation of some characteristics of the COVID-19 deduced from the model. We also present several mid-term and long-term projections based on scenarios of reinforcement or relaxation of social contacts for different general sectors, with a lot of uncertainties remaining.