bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracranial Stenting: Angioplasty Basic Technique, Indications, and Sizing: 2-Dimensional Operative Video
Authors: Dossani Rimal H , Waqas Muhammad , Cappuzzo Justin M , Sonig Ashish , Siddiqui Adnan H , Levy Elad I , Davies Jason M ,   Endovascular Neurosurgery Research Group (ENRG), Arthur Adam , Bain Mark , Bendock Bernard , Jo Binning Mandy , Boulos Alan S , Crowley Webster , Fessler Richard , Grande Andrew , Guterman Lee , Hanel Ricardo , Hoit Daniel , Hopkins L Nelson , Howington Jay , James Robert , Jankowitz Brian , Kan Peter , Khalessi Alex A , Kim Louis , Langer David , Lanzino Giuseppe , Levitt Michael , Levy Elad I , Lopes Demetrius , Mack William , Mericle Robert , Mocco J , Ogilvy Chris , Pandey Aditya , Replogle Robert , Riina Howard , Ringer Andrew , Rodriguez Rafael , Saugaveau Eric , Schirmer Clemens , Siddiqui Adnan H , Spiotta Alex , Sultan Ali , Tawk Rabih , Thomas Ajith , Turner Raymond , Veznedaroglu Erol , Welch Babu , White Jonathan
Published: May 2021

Intracranial atherosclerotic disease (ICAD) is a common cause of stroke. Antiplatelet therapy is the mainstay for symptomatic ICAD treatment. Endovascular management with submaximal angioplasty and/or intracranial stenting is reserved for patients with repeated ischemic events despite optimal medical therapy. We demonstrate intracranial angioplasty and stenting technique, technique indications, and sizing of stent and target vessel diameter. Stenting and angioplasty have been described in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis and Wingspan Stent System Post Market Surveillance trials.
1,2
Submaximal angioplasty has also been described.
3
This patient, who had been on dual antiplatelet therapy for several months, initially presented with occlusion of the left middle cerebral artery M2 inferior division and underwent mechanical thrombectomy with successful reperfusion. Postoperatively, the patient's symptoms did not improve. Medical management was optimized with heparin infusion. However, repeat stroke study demonstrated M2 inferior division reocclusion. A decision was made to proceed with intracranial angioplasty and stenting. P2Y12 levels were therapeutic. Under moderate conscious sedation, submaximal angioplasty of up to 80% of the normal M2 caliber was attempted. However, we observed persistent high-grade stenosis of the M2 inferior division. The major risk of crossing the lesion for angioplasty is vessel perforation. To safely perform this maneuver, we used a J-configured Synchro-2 microwire (Stryker). Because of the patient's recent thrombectomy, we also had prior tactile feedback about how much resistance was encountered while crossing the occlusion. We then deployed a balloon-mounted intracranial stent for optimal radial force across the stenotic area to restore perfusion. Postoperative computed tomography perfusion showed resolution of the previously noticed perfusion deficit.

The patient gave informed consent for the procedures and video recording. Institutional review board approval was deemed unnecessary.

Video. ©University at Buffalo Neurosurgery, September 2020. With permission.
Wildfire smoke affects detection of birds in Washington State
Authors: Sanderfoot Olivia V , Gardner Beth
Published: May 2021

Wildfire smoke is likely to have direct health effects on birds as well as influence movement, vocalization, and other avian behaviors. These behavioral changes may affect if and how birds are observed in the wild, although research on the effects of wildfire smoke on bird behavior is limited. To evaluate how wildfire smoke affects detection of birds, we combined data from eBird, an online community science program, with data from an extensive network of air quality monitors in the state of Washington over a 4-year period. We assessed how PM2.5, a marker of smoke pollution, affected the probability of observing 71 bird species during the wildfire seasons of 2015–2018 using bird observations from 62,908 eBird checklists. After accounting for habitat, weather conditions, seasonality, and survey effort, we found that PM2.5 affected the probability of observing 37% of study species. The ambient concentration of PM2.5 was negatively associated with the probability of observing 16 species and positively associated with the probability of observing 10 species, indicating that birds exhibit species-specific behavioral changes during wildfire smoke events that influence how they are observed. Our results suggest that wildfire smoke impacts the presence, availability, and/or perceptibility of birds. Impacts of smoke pollution on human observers, such as impaired visibility, may also influence detection of birds. These results provide a foundation for developing mechanistic hypotheses to explain how birds, and our studies of them, are impacted by wildfire smoke. Given the projected increase in large-scale wildfire smoke events under future climate change scenarios, understanding how birds are affected by wildfire smoke—and how air pollution may influence our ability to detect them—are important next steps to inform wildlife research and avian conservation.
Temperature and vegetation complexity structure mixed-species flocks along a gradient of elevation in the tropical Andes
Authors: Montaño-Centellas Flavia A , Jones Harrison H
Published: May 2021

Mixed-species flocks constitute community modules that can help test mechanisms driving changes to community composition across environmental gradients. Here, we examined elevational patterns of flock diversity (species richness, taxonomic diversity, species, and guild composition) and asked if these patterns were reflections of the full bird community at a given elevation (open-membership hypothesis), or if they were instead structured by environmental variables. We surveyed both the overall avian community and mixed-species flocks across an undisturbed elevational gradient (~1,350–3,550 m) in the Bolivian Andes. We then tested for the role of temperature (a surrogate for abiotic stress), resource diversity (arthropods, fruits), and foraging niche diversity (vegetation vertical complexity) in structuring these patterns. Patterns for the overall and flocking communities were similar, supporting our open-membership hypothesis that Andean flocks represent dynamic, unstructured aggregations. Membership openness and the resulting flock composition, however, also varied with elevation in response to temperature and vegetation complexity. We found a mid-elevation peak in flock species richness, size, and Shannon’s diversity at ~2,300 m. The transition of flocking behavior toward a more open-membership system at this elevation may explain a similar peak in the proportion of insectivores joining flocks. At high elevations, increasing abiotic stress and decreasing fruit diversity led more generalist, gregarious tanagers (Thraupidae) to join flocks, resulting in larger yet more even flocks alongside a loss of vegetation structure. At lower elevations, flock species richness increased with greater vegetation complexity, but a greater diversity of foraging niches resulted in flocks that were more segregated into separate canopy and understory sub-types. This segregation likely results from increased costs of interspecific competition and activity matching (i.e., constraints on movement and foraging rate) for insectivores. Mid-elevation flocks (~2,300 m) seemed, therefore, to benefit from both the open-membership composition of high-elevation flocks and the high vegetation complexity of mid- and low-elevation forests.
The Spread of COVID-19 Among 15,000 Physical Therapists in Italy: A Cross-Sectional Study
Authors: Gianola Silvia , Bargeri Silvia , Campanini Isabella , Corbetta Davide , Gambazza Simone , Innocenti Tiziano , Meroni Roberto , Castellini Greta , Turolla Andrea ,   Scientific Committee of AIFI
Published: May 2021

Objectives

The purpose of this study was to explore the prevalence, personal- and work-related exposures, and signs and symptoms among physical therapists during the first wave of coronavirus disease 2019 (COVID-19) in Italy.

Methods

This cross-sectional, survey-based study collected demographic and exposure data from physical therapists from April to May 2020. All physical therapists working in inpatient and outpatient care in Italy were eligible. A self-administered questionnaire was distributed among all eligible physical therapists to collect (1) demographic characteristics, (2–3) personal- and work-related exposures, and (4) signs and symptoms of COVID-19. Factors associated with a COVID-19–positive nasopharyngeal swab (NPS) were explored through logistic regression models and multivariate methods.

Results

A total of 15,566 respondents completed the survey, with a response rate of 43.3%, achieving high statistical precision (99% CI, 1% type I error). Among physical therapists who received NPS testing, 13.1% (95% CI = 12.1–14.1%) had a positive result, with a peak reached in March 2020 (36%). The top 5 symptoms were fatigue and tiredness (69.1%), loss of smell (64.5%), aches and pains (60.8%), loss of taste (58.3%), and headache (51.1%). No symptoms were reported by 8.9%. Working in a health care institution (odds ratio [OR] = 12.0; 95% CI = 7.8–18.4), being reallocated to a different unit (OR = 1.9; 95% CI = 1.3–2.7), and changing job tasks (OR = 1.6; 95% CI = 1.2–2.3) increased the risk of being COVID-19 positive. In therapists with a confirmed diagnosis of COVID-19, comorbidities were associated with male sex and age older than 51 years.

Conclusion

During the first wave in Italy, almost 1 out of 7 physical therapists tested positive on the COVID-19 NPS test. Considering personal- and work-related exposures, health care organizations should adopt prevention measures and adequate preparedness to prevent high rate of infections during future pandemics.

Impact

This is the largest investigation about the spread of and main risk factors for COVID-19 in the physical therapy field.
Early maternal care and amygdala habituation to emotional stimuli in adulthood
Authors: Holz Nathalie E , Häge Alexander , Plichta Michael M , Boecker-Schlier Regina , Jennen-Steinmetz Christine , Baumeister Sarah , Meyer-Lindenberg Andreas , Laucht Manfred , Banaschewski Tobias , Brandeis Daniel
Published: May 2021

Evidence suggests that maternal care constitutes a protective factor for psychopathology which may be conditional on the level of family adversity. Given that psychopathology is frequently linked with social deficits and the amygdala with social functioning, we investigated the impact of early maternal care on amygdala function under high vs low familial risk for psychopathology. Amygdala activity and habituation during an emotional face-matching paradigm was analyzed in participants of an epidemiological cohort study followed since birth (n = 172, 25 years). Early mother–infant interaction was assessed during a standardized nursing and play setting at the age of 3 months. Information on familial risk during the offspring’s childhood and on the participants’ lifetime psychopathology was obtained with diagnostic interviews. An interaction between maternal stimulation and familial risk was found on amygdala habituation but not on activation, with higher maternal stimulation predicting stronger amygdala habituation in the familial risk group only. Furthermore, amygdala habituation correlated inversely with Attention Deficit Hyperactivity Disorder (ADHD) diagnoses. The findings underline the long-term importance of early maternal care on the offspring’s socioemotional neurodevelopment and of interventions targeting maternal sensitivity early in life, particularly by increasing maternal interactive behavior in those with familial risk.
Prejudicial beliefs and COVID-19 disruptions among sexual minority men living with and not living with HIV in a high SARS-CoV-2 prevalence area
Authors: Kalichman Seth C , El-Krab Renee , Shkembi Bruno , Kalichman Moira O , Eaton Lisa A
Published: May 2021

The COVID-19 pandemic has had profound health and social impacts. COVID-19 also affords opportunities to study the emergence of prejudice as a factor in taking protective actions. This study investigated the association of COVID-19 concerns, prejudicial beliefs, and personal actions that involve life disruptions among people not living with and people living with HIV. 338 Black/African American men not living with HIV who reported male sex partners and 148 Black/African American men living with HIV who reported male sex partners completed a confidential survey that measured COVID-19 concern, COVID-19 prejudice, and personal action and institutionally imposed COVID-19 disruptions. Participants reported having experienced multiple social and healthcare disruptions stemming from COVID-19, including reductions in social contacts, canceling medical appointments, and inability to access medications. Mediation analyses demonstrated that COVID-19 concerns and COVID-19 prejudice were associated with personal action disruptions, indicating that these social processes are important for understanding how individuals modified their lives in response to COVID-19. It is imperative that public health efforts combat COVID-19 prejudice as these beliefs undermine investments in developing healthcare infrastructure to address COVID-19 prevention.
Rare and Atypical Presentations of Acute Disseminated Encephalomyelitis in Children: A Case Series
Authors: Hemram Sunil Kumar , Ghosh Arindam , Annigeri Saba
Published: May 2021

Acute disseminated encephalomyelitis (ADEM) is a monophasic demyelinating disorder of central nervous system occurring in children with a wide range of clinical manifestations after infection or vaccination. There are few case reports in literature, describing atypical presentations of ADEM with fever of unknown origin, autonomic dysfunction, complex movement disorders such as myoclonus, dystonia and chorea, acute psychosis and myocarditis. Here, we report four cases of ADEM with atypical features like uniocular blindness, myelin oligodendrocyte glycoprotein antibodies negative multiphasic disseminated encephalomyelitis, ADEM mimicking Guillain-Barre syndrome at presentation and isolated spinal ADEM. Treatment with high-dose steroids elicited an excellent neurological outcome in all patients. A high index of clinical suspicion along-with awareness of atypical features, magnetic resonance imaging and cerebrospinal fluid studies are of paramount importance in establishing ADEM diagnosis and initiation of early treatment for better outcome.
Sharing Reflections on Multisource Feedback in a Peer Group Setting: Stimulating Physicians’ Professional Performance and Development
Authors: Bindels Elisa , van den Goor Myra , Scherpbier Albert , Lombarts Kiki , Heeneman Sylvia
Published: May 2021

Purpose

Reflecting on and using feedback are important for physicians’ continuous professional development (CPD). A common format is the discussion of multisource feedback (MSF) in a one-on-one session with a trusted peer or coach. A new approach is to discuss MSF during a peer group session moderated by a professional facilitator. This qualitative study explored how physicians experience participation in these peer group sessions in the context of their CPD.

Method

Between March and July 2018, 26 physicians were interviewed about their experiences in a peer group session. These physicians represented 13 monospecialty physician groups from 5 general hospitals in the Netherlands. Interviews were transcribed verbatim and analyzed iteratively, following the interpretative phenomenological approach.

Results

Participation was experienced as a process of disclosing and sharing personal reflections with peers while striking a balance between interpersonal proximity to and distance from peers. Sharing reflections with peers rendered the feedback more meaningful, deepened collegial relationships, and created a sense of urgency for improvement. Improvement goals were mostly related to relational fine-tuning in collaboration; goals related to individual career management remained in the background. Influential factors for the perceived effectiveness of the group sessions were related to the facilitator’s expertise, group size, continuity and quality of collegial relationships, personal vulnerabilities, and the context of CPD policy.

Conclusions

Peer group sessions offered interactivity and established a clear link between individual physicians and their work environments. Sharing reflections on MSF in a peer group setting provided physicians with nuanced insight into their professional performance and fostered a community spirit that supported the implementation of intended changes. Future research should focus on the role of group dynamics and communication strategies and the application of coaching principles, such as drawing up a detailed plan of action and monitoring the follow-up process.
Peristomal Skin Health
Authors: Ratliff Catherine R. , Goldberg Margaret , Jaszarowski Kelly , McNichol Laurie , Pittman Joyce , Gray Mikel
Published: May 2021

The Wound, Ostomy, and Continence Nurses (WOCN) Society identified the need to define and promote peristomal skin health. A task force was appointed to complete a scoping literature review, to develop evidence-based statements to guide peristomal skin health best practices. Based on the findings of the scoping review, the Society convened a panel of experts to develop evidence- and consensus-based statements to guide care in promoting peristomal skin health. These consensus statements also underwent content validation using a different panel of clinicians having expertise in peristomal skin health. This article reports on the scoping review and subsequent 6 evidenced-based statements, along with the generation and validation of 19 consensus-based statements, to assist clinical decision-making related to promoting peristomal skin health in adults.
Negative Pressure Wound Therapy Devices With Instillation/Irrigation
Authors: Crumley Carolyn
Published: May 2021

PURPOSE:

The purpose of this technologic analysis was to critique technologic features of devices designed to deliver negative pressure wound therapy with instillation or irrigation (iNPWT).

APPROACH:

Published literature regarding negative pressure wound therapy (NPWT) devices with the added feature of instillation or irrigation was reviewed to provide an overview of iNPWT. Varied features of devices currently available in the United States were described based on instructions published by individual manufacturers. Safety information regarding iNPWT was derived from the Manufacturer and User Facility Device Experience (MAUDE) Database.

CONCLUSIONS:

The additional option of instillation or irrigation available with some NPWT devices may provide clinical benefits in carefully selected patients. Advantages may be related to facilitated removal of thick exudate and necrotic tissue. Devices with instillation options are indicated for inpatient settings, with ongoing monitoring of health care professionals. A simpler device with an intermittent irrigation option may be used in the home setting, with proper supervision. More research is needed to demonstrate the clinical effectiveness and cost of the therapy.
The Use of Prophylactic Foam Dressings for Prevention of Hospital-Acquired Pressure Injuries
Authors: Sillmon Katherine , Moran Carter , Shook Lauren , Lawson Claire , Burfield Allison H.
Published: May 2021

PURPOSE:

The purpose of this systematic review was to identify and evaluate the use of prophylactic foam dressings for prevention of hospital-acquired pressure injuries (HAPIs).

METHODS:

A systematic review was conducted in accordance with the Preferred Reporting Items of Systematic Reviews and Meta-analysis Statement (PRISMA).

SEARCH STRATEGY:

Four researchers independently conducted searches in Health Source, Cochrane of Systematic Reviews, CINAHL, and PubMed. Search terms included: “pressure* OR skin breakdown AND sacrum*”; “ICU patient* OR critical care patient*”; and “foam dressing OR prophylactic* or prevent*.”

FINDINGS:

The search identified 380 articles; 14 met eligibility criteria. The methodological quality of the included studies was variable. Findings from all studies included in our review support a decrease in HAPI incidence with use of sacral foam dressings.

IMPLICATIONS:

Findings from this review suggest that prophylactic foam dressings decrease sacral HAPI occurrences in critical care patients. While additional research is needed, current best evidence supports use of prophylactic foam sacral dressings for patients at risk for HAPI.
Association of Systemic or Intravitreal Antivascular Endothelial Growth Factor (Anti-VEGF) and Impaired Wound Healing in Pediatric Patients
Authors: Boyar Vita
Published: May 2021

BACKGROUND:

Bevacizumab is a humanized monoclonal antibody to vascular endothelial growth factor (VEGF) that has been used as a systemic chemotherapy treatment of various malignancies in adults since 2000. It has been used for pediatric patients over the last decade. In addition, bevacizumab is used for neonatal intravitreal administration for retinopathy of prematurity, a major complication of preterm birth, characterized by incomplete and abnormal vascularization of the retina that can lead to retinal detachment and blindness without treatment.

CASES:

The objective of this multiple case series is to report impaired wound healing seen in 3 adolescents and 1 premature neonate receiving bevacizumab and to propose collagen-based dermal template as a choice for the management of such wounds. The 3 adolescents were undergoing treatment of malignancies and developed wound healing complication within weeks of receiving anti-VEGF. The premature neonate experienced an extravasation and had a slow wound healing trajectory after receiving intravitreal administration of bevacizumab for retinopathy of prematurity. All wounds achieved closure following topical treatment with a collagen dermal template.

CONCLUSION:

Use of bevacizumab is increasing in the pediatric population. Clinicians should be aware of compromised wound healing and higher likelihood of wound dehiscence after bevacizumab administration. We recommend waiting for at least 4 to 6 weeks between anti-VEGF administration (either systemic or vitreous) and elective surgical procedures, consistent with adult literature recommendations. If patient has an existing wound, we assert that bevacizumab should not be administered until that wound is healed. If wound healing is stalled, we recommend dermal template as a safe and effective accelerator of wound healing.
A Novel Method to Offload Neuropathic Ulcers of the Distal Phalanges in the Presence of First Ray Metatarsal Hypermobility
Authors: Christensen Deborah , Coviello Jane , Munn Sally , Petersen Birgit , Whitaker Elizabeth
Published: May 2021

BACKGROUND:

The standard practice to heal neuropathic ulcers on the toes is to offload the affected areas with special types of therapeutic footwear including shoes and boots to reduce the amount of pressure on the wound. Once healed, the individual wears custom insoles to prevent the development of new wounds. In our practice, we found that some newly healed wounds will reulcerate despite wearing therapeutic footwear. We devised a method to prevent and offload neuropathic foot ulcers on the distal phalanges in the presence of first ray metatarsal hypermobility, a common problem associated with the development of wounds.

CASES:

Three individuals with first ray metatarsal hypermobility and recurrent neuropathic ulcers demonstrated healing using a buttress constructed from a tampon placed under the plantar surface of the proximal interphalangeal joint. The buttress was successful in supporting the first ray metatarsal to keep it in proper alignment.

CONCLUSION:

We found using a buttress was an effective nonsurgical intervention for these 3 individuals with first ray metatarsal hypermobility to prevent and offload neuropathic hallux ulcers.
ICTV Virus Taxonomy Profile: Plectroviridae
Authors: Knezevic Petar , Adriaenssens Evelien M. ,   ICTV Report Consortium
Published: May 2021

Members of the family Plectroviridae produce particles that are non-enveloped rigid rods (70–280×10–16 nm). The supercoiled, circular, single-stranded DNA genome of about 4.5–8.3 kb, encodes 4–13 proteins. Viruses of this family infect cell wall-less bacteria, adsorbing to the bacterial surface, replicating their DNA by a rolling-circle mechanism or transposition, and releasing progeny from cells by extrusion, without killing the host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Plectroviridae which is available at ictv.global/report/plectroviridae.
Evaluation of metal-based antimicrobial compounds for the treatment of bacterial pathogens
Authors: Evans Andris , Kavanagh Kevin A.
Published: May 2021

Antimicrobial resistance (AMR) is one of the greatest global health challenges of modern times and its prevalence is rising worldwide. AMR within bacteria reduces the efficacy of antibiotics and increases both the morbidity and the mortality associated with bacterial infections. Despite this growing risk, few antibiotics with a novel mode of action are being produced, leading to a lack of antibiotics that can effectively treat bacterial infections with AMR. Metals have a history of antibacterial use but upon the discovery of antibiotics, often became overlooked as antibacterial agents. Meanwhile, metal-based complexes have been used as treatments for other diseases, such as the gold-containing drug auranofin, used to treat rheumatoid arthritis. Metal-based antibacterial compounds have novel modes of action that provide an advantage for the treatment of bacterial infections with resistance to conventional antibiotics. In this review, the antibacterial activity, mode of action, and potential for systemic use of a number of metal-based antibacterial complexes are discussed. The current limitations of these compounds are highlighted to determine if metal-based agents are a potential solution for the treatment of bacterial infections, especially those resistant to conventional antibiotics.
Deep Learning for Caries Detection using Optical Coherence Tomography
Authors: Huang Yu-Ping , Lee Shyh-Yuan
Published: May 2021

Early detection of dental caries has been one of the most predominant topics studied over the last few decades. Conventional examination through visual-tactile inspection and radiography can be inaccurate and destructive to the tooth structure. The development of optical coherence tomography (OCT) has given dentistry an alternative diagnostic technique, which has been proven by numerous studies, that it has better sensitivity, specificity, and non-invasive characteristics. The growing popularity of artificial intelligence (AI) also contributes to a more efficient and effective way of image-based detection and decision-making. However, previous studies, which have attempted to employ AI for caries assessment, did not incorporate high-quality ground truth data. Therefore, this study aims to bypass this issue and highlights the importance of high-quality data. A two-phase study was carried out to explore different methods for caries detection. Initially, the comparison of caries detection based on OCT and apical radiography by 5 experienced clinicians was conducted. Then, five convolutional neural networks (CNNs), including AlexNet, VGG-16, ResNet-152, Xception, and ResNext-101, in the scope of AI were employed to detect caries and compared with the findings of the 5 clinicians. The data was preprocessed and labeled with the ground truth corresponding to microcomputed tomography (micro-CT) with rigorous definition. The weighted Kappa statistics suggested that OCT (ϰ= .699, SD = .090) showed a higher accuracy rate than radiography (ϰ= .407, SD = .049), and CNNs (ϰ= .860, SD = .049) were rated higher than clinicians (ϰ= .679, SD = .113), both at a .05 significance level. The best result was carried out by ResNet-152, which demonstrated a high accuracy rate of 95.21% and a sensitivity of 98.85%. These findings illustrate the importance of ground truth data for AI training and the potential of deep CNN algorithms combined with OCT for diagnosing dental caries.
Computing the Prevalence and Severity of an Epidemic Using only the Distribution of Simple Tests for Infection Confirmation
Authors: Shahar Yuval , Mokryn Osnat
Published: May 2021

Epidemics and Pandemics such as COVID-19 require estimating total infection prevalence. Accurate estimates support better monitoring, evaluation of proximity to herd immunity, estimation of infection fatality rates (IFRs), and assessment of risks due to infection by asymptomatic individuals, especially in developing countries, which lack population-wide serological testing.

We suggest a method for estimating the infection prevalence by finding thePivot group, the population sub-group with the highest susceptibility for being confirmed as positively infected. We differentiatesusceptibility to infection, assumed to be uniform across all population sub-groups (a key assumption), fromsusceptibility to developing symptoms and complications, which differs between sub-groups (e.g., by age). We compute the minimal infection-prevalence factor by which the number of positively confirmed patients should be multiplied that allows for a sufficient number of Pivot-group infections that explains the number of Pivot group confirmations.

We applied the method to the COVID-19 pandemic, using UK and Spain serological surveys. Our key assumption held, and actual infection-prevalence factors were consistent with our predictions. We computed minimal infection-prevalence factors, and when possible, assessed IFRs and serology-based IFRs, for the COVID-19 pandemic in eight countries.

Estimating a lower bound for an epidemic’s infection prevalence using our methodology is feasible, and the assumptions underlying it are valid. The use of our methodology is often necessary for developing countries, especially in the early phases of an epidemic when serological data are not yet available or when new mutations of a known virus appear.
The first GAEN-based COVID-19 contact tracing app in Norway identifies 80% of close contacts in “real life” scenarios
Authors: Meijerink Hinta , Madslien Elisabeth H. , Mauroy Camilla , Johansen Mia Karoline , Møgster Braaten Sindre , Steen Lunde Christine Ursin , Arnesen Trude Margrete , Feruglio Siri Laura , Nygård Karin
Published: May 2021

The COVID-19 response in most countries depends on testing, isolation, contact tracing, and quarantine, which is labor- and time consuming. Therefore, several countries worldwide launched Bluetooth based apps as supplemental tools. We evaluated the new Norwegian GAEN (Google Apple Exposure Notification) based contact tracing app “Smittestopp” under two relevant simulated scenarios, namely standing in a queue and riding public transport.

We compared two configurations (C1: 58/63 dBm; C2: 58/68 dBm) with multiple weights (1.0-2.5) and time thresholds (10-15 min), by calculating notification rates among close contacts (≤2 meters, ≥15 min) and other non-close contacts. In addition, we estimated the effect of using different operating systems and locations of phone (hand/pocket) using χ2.

C2 resulted in significantly higher notification rates than C1 (p-value 0.05 - 0.005). The optimal setting resulted in notifications among 80% of close contacts and 34% of other contacts, using C2 with weights of 2.0 for the low and 1.5 for the middle bucket with a 13-minutes time threshold. Among other contacts, the notification rate was 67% among those ≤2 meters for <15 minutes compared to 19% among those >2 meters (p=0.004). Significantly (p-values 0.046 - 0.001) lower notification rates were observed when using the iOS operating systems or carrying the phone in the pocket instead of in the hand.

This study highlights the importance of testing and optimizing the performance of contact tracing apps under “real life” conditions to optimized configuration for identifying close contacts.
Vps501, a novel vacuolar SNX-BAR protein cooperates with the SEA complex to
induce autophagy
Authors: Goyal Shreya , Segarra Verónica A. , Nitika  , Stetcher Aaron M. , Truman Andrew W. , Reitzel Adam M. , Chi Richard J.
Published: May 2021

The sorting nexins (SNX), constitute a diverse family of molecules that play
varied roles in membrane trafficking, cell signaling, membrane remodeling,
organelle motility and autophagy. In particular, the SNX-BAR proteins, a SNX
subfamily characterized by a C-terminal dimeric Bin/Amphiphysin/Rvs (BAR) lipid
curvature domain and a conserved Phox-homology domain, are of great interest. In
budding yeast, many SNX-BARs proteins have well-characterized endo-vacuolar
trafficking roles. Phylogenetic analyses allowed us to identify an additional
SNX-BAR protein, Vps501, with a novel endo-vacuolar role. We report that Vps501
uniquely localizes to the vacuolar membrane and works with the SEA complex to
regulate autophagy. Furthermore, we found cells displayed a severe deficiency in
starvation-induced/nonselective autophagy only when SEA complex subunits are
ablated in combination with Vps501, indicating a cooperative role with the SEA
complex during autophagy. Additionally, we found the SEA complex becomes
destabilized in
vps501Δsea1Δ cells,
which resulted in aberrant TORC1 hyperactivity and misregulation of autophagy
induction.
Irx3Promotes Gap Junction Communication Between Uterine Stromal Cells to Regulate Vascularization during Embryo Implantation
Authors: Brown Ryan M. , Wang Linda , Fu Anqi , Kannan Athilakshmi , Mussar Michael , Bagchi Indrani C. , Jorgensen Joan S.
Published: May 2021

Spontaneous abortions have been reported to affect up to 43% of parous women, with over 20% occurring before pregnancy is clinically diagnosed. Establishment of pregnancy is critically dependent on proper embryo-uterine interactions at the time of implantation. Besides oocyte abnormalities, implantation failure is a major contributor to early pregnancy loss. Previously, we demonstrated that two members of the Iroquois homeobox transcription factor family, IRX3 and IRX5, exhibited distinct and dynamic expression profiles in the developing ovary to promote oocyte and follicle survival. Elimination of each gene independently caused subfertility, but with different breeding pattern outcomes.Irx3KO (Irx3LacZ/LacZ) females produced fewer pups throughout their reproductive lifespan which could only be partially explained by poor oocyte quality. Thus, we hypothesized that IRX3 is also expressed in the uterus where it acts to establish functional embryo-uterine interactions to support pregnancy. To test this hypothesis, we harvested pregnant uteri from control andIrx3KO females to evaluate IRX3 expression profiles and the integrity of embryo implantation sites. Our results indicate that IRX3 is expressed in the endometrial stromal cells of the pregnant uterus. Notably, of the days evaluated, IRX3 expression expanded into the endometrial stroma starting at day 4 of pregnancy (D4) with peak expression at D5-6, and then greatly diminished by D7. This pattern corresponds to the critical window for implantation and remodeling of the vasculature network in mice. Further, histology and immunohistochemistry at D7 showed that while embryos were able to attach to the uterus, implantation sites inIrx3KO pregnant mice exhibited impaired vascularization. In addition, our results showed significantly diminished expression of decidualization markers and disruptions in GJA1 organization in the decidual bed. These data, taken together with previous reports focused on the ovary, suggest that IRX3 promotes fertility via at least two different mechanisms: 1) promoting competent oocytes and 2) facilitating functional embryo-uterine interactions during implantation. Future research aims to tease apart the roles for IRX3 in the oocyte versus the uterus and the mechanisms by which it promotes early embryo survival and a successful pregnancy outcome.
Pharmacologically induced weight loss is associated with distinct gut microbiome changes in obese rats
Authors: Raineri Silvia , Sherriff Julia A. , Thompson Kevin S.J. , Jones Huw , Pfluger Paul T. , Ilott Nicholas E. , Mellor Jane
Published: May 2021

Background

Obesity, metabolic disease and some psychiatric conditions are associated with changes to relative abundance of bacterial species and specific genes in the fecal microbiome. Little is known about the impact of pharmacologically induced weight loss on distinct gut microbiome species and their respective gene programs in obese individuals.

Results

Using shotgun metagenomics, the composition of the microbiome was obtained for two cohorts of obese female Wistar rats (n=10-12, total of 82) maintained on a high fat diet before and after a 42-day treatment with a panel of four investigatory or approved anti-obesity drugs (tacrolimus/FK506, bupropion, naltrexone and sibutramine), alone or in combination. We found that sibutramine treatment induced consistent weight loss through reducing food intake. Decreased weight loss in sibutramine-treated rats was associated with changes to the gut microbiome that included increased beta-diversity, increased Bacteroides/Firmicutes ratio and increased relative abundance of multipleBacteroidesspecies. In addition, the relative abundance of multiple genes was found to be differentially abundant, including significant reductions in components of flagellum and genes involved in flagellum assembly.

Conclusions

This study provides a large resource comprising complete shotgun metagenomics datasets of the fecal microbiome coupled with weight change and food intake at day 3, day 15 and day 42 from 82 obese rats treated with a range of compounds used for weight loss, which are available to the community for detailed analysis. Furthermore, by conducting a detailed analysis of the microbiome associated with sibutramine-induced weight loss, we have identified multiple weight-loss associated microbial taxa and pathways. These include a reduction in components of flagellum and the flagellum assembly pathway that points to a potential role of sibutramine-induced weight-loss on regulating bacterially driven anti-inflammatory responses.
Restoring vascular endothelial autophagic flux reduces atherosclerotic lesions
Authors: Chatterjee Shruti , Kheloufi Marouane , Mazlan Stephane , Loyer Xavier , McKinsey Timothy A. , Boulanger Chantal M. , Coly Pierre-Michaël
Published: May 2021

Atherosclerotic lesions preferentially develop in arterial areas exposed to low shear stress, where endothelial cells express a pro-inflammatory, apoptotic, and senescent phenotype. Endothelial cells exposed to atheroprone low shear stress present a defective autophagic flux, which favors a pro-inflammatory phenotype and the formation of atherosclerotic lesions. We tested the hypothesis that HDAC6 inhibition could restore adequate levels of autophagy in endothelial cells exposed to low shear stress. We found that blocking HDAC6 activity, either by pharmacological inhibition (Tubastatin-A) or genetic approaches (shHDAC6), raised levels of acetylated α-tubulin, as well as LC3-II/I ratio, LC3 puncta area, nuclear TFEB translocation and autophagic flux in cultured endothelial cells exposed to low shear stress. This effect was associated with a reduced expression of inflammatory markers (ICAM-1, VCAM-1 and MCP-1) in TNF-α-stimulated cells. Impaired endothelial autophagic flux was restored in the aortic arch (atheroprone conditions) ofHDAC6-/-mice, when compared to control littermates. Atherosclerotic plaque size was significantly decreased in the aortic arch of chimericHDAC6-/-/ApoE-/-mice, transplanted withHDAC6+/+/ApoE-/-bone marrow, when compared toHDAC6+/+/ApoE-/-littermate controls. Taken together, these results indicate that HDAC6-inhibition may be an interesting strategy to restore endothelial autophagic flux, to help promote an atheroprotective endothelial phenotype despite unfavorable shear stress conditions.
Cardioluminescence in transgenic zebrafish embryos: a Ca2+imaging tool to study drug effects and pathological modeling
Authors: Vicente Manuel , Salgado-Almario Jussep , Collins Michelle M. , Martínez-Sielva Antonio , Minoshima Masafumi , Kikuchi Kazuya , Domingo Beatriz , Llopis Juan
Published: May 2021

The zebrafish embryo has emerged as an excellent model in cardiovascular research. The existing techniques to monitor Ca2+in the heart based on fluorescent Ca2+biosensors are limited due to phototoxicity and photobleaching. To overcome these issues, we have used bioluminescence. We generated a transgenic line expressing GFP-Aequorin in the heart,Tg(cmlc2:GA), and optimized anin vivoaequorin reconstitution protocol to improve the luminescence capacity. This allowed imaging Ca2+in long duration recordings in embryos of 3 to 5 days post-fertilization. The analogsdiacetyl h-coelenterazine andf-coelenterazine enhanced the light output and signal-to-noise ratio from the embryos. With this cardioluminescence model, we monitored the time-averaged Ca2+levels and beat-to-beat Ca2+oscillations. Changes in Ca2+levels were observed by incubation with BayK8644, an L-type Ca2+channel agonist, the channel blocker nifedipine, and β-adrenergic blocker propranolol. Treatment of zebrafish embryos with terfenadine for 24 hours has been proposed as a model of heart failure.Tg(cmlc2:GA) embryos treated with terfenadine showed a 2:1 atrioventricular block and a decrease in the ventricular Ca2+levels.
Scaling of cellular proteome with ploidy
Authors: Yahya Galal , Menges Paul , Ngandiri Devi Anggraini , Schulz Daniel , Wallek Andreas , Kulak Nils , Mann Matthias , Cramer Patrick , Savage Van , Raeschle Markus , Storchova Zuzana
Published: May 2021

Ploidy changes are frequent in nature and contribute to evolution, functional specialization and tumorigenesis (1,2). Analysis of model organisms of different ploidies revealed that increased ploidy leads to an increase in cell and nuclear volume, reduced proliferation (2-4), metabolic changes (5), lower fitness (6,7), and increased genomic instability (8,9), but the underlying mechanisms remain poorly understood. To investigate how the gene expression changes with cellular ploidy, we analyzed isogenic series of budding yeasts from 1N to 4N. We show that mRNA and protein abundance scales allometrically with ploidy, with tetraploid cells showing only threefold increase in proteins compared to haploids. This ploidy-specific scaling occurs via decreased rRNA and ribosomal protein abundance and reduced translation. We demonstrate that the Tor1 activity is reduced with increasing ploidy, which leads to rRNA gene repression via a novel Tor1-Sch9-Tup1 signaling pathway. mTORC1 and S6K activity are also reduced in human tetraploid cells and the concomitant increase of the Tup1 homolog Tle1 downregulates the rDNA transcription. Our results revealed a novel conserved mTORC1-S6K-Tup1/Tle1 pathway that ensures proteome remodeling in response to increased ploidy.
Intrinsic circadian timekeeping properties of the thalamic lateral geniculate nucleus
Authors: Chrobok L. , Pradel K. , Janik M.E. , Sanetra A.M. , Bubka M. , Myung J. , Rahim A.R. , Klich J.D. , Jeczmien-Lazur J.S. , Palus-Chramiec K. , Lewandowski M.H.
Published: May 2021

Circadian rhythmicity in mammals is sustained by the central brain clock – the suprachiasmatic nucleus of the hypothalamus (SCN), entrained to the ambient light-dark conditions through a dense retinal input. However, recent discoveries of autonomous clock gene expression cast doubt on the supremacy of the SCN and suggest circadian timekeeping mechanisms devolve to local brain clocks. Here we use a combination of molecular, electrophysiological and optogenetic tools to evaluate intrinsic clock properties of the main retinorecipient thalamic centre – the lateral geniculate nucleus (LGN). We identify the dorsolateral geniculate nucleus (DLG) as a slave oscillator, which exhibits core clock gene expression exclusivelyin vivo. Additionally, we provide compelling evidence for intrinsic clock gene expression accompanied by circadian variation in neuronal activity in the intergeniculate leaflet (IGL) and ventrolateral geniculate nucleus (VLG). Finally, our optogenetic experiments propose the VLG as a light-entrainable oscillator, whose phase may be advanced by retinal input at the beginning of the projected night. Altogether, this study for the first time demonstrates autonomous timekeeping mechanisms shaping circadian physiology of the LGN.
The miR-424/503 cluster modulates Wnt/β-catenin signaling in the mammary epithelium by regulating the expression of the LRP6 co-receptor
Authors: Nekritz Erin A. , Rodriguez-Barrueco Ruth , Yan Koon-Kiu , Davis Meredith L. , Werner Rachel L. , Devis-Jauregui Laura , Mukhopadhyay Partha , Yu Jiyang , Llobet-Navas David , Silva Jose
Published: May 2021

During the female lifetime, the enlargement of the epithelial compartment dictated by the ovarian cycles is supported by a transient increase in the MaSC population. Notably, activation of Wnt/β-catenin signaling is an important trigger for MaSC expansion. Here, we report that the miR-424/503 cluster is a novel modulator of canonical Wnt-signaling in the mammary epithelium that exerts its function by targeting the LRP6 co-receptor. Additionally, we show that the loss of this microRNA cluster is associated with breast cancers possessing high levels of Wnt/β-catenin signaling.
Multi-site enzymes as a mechanism for bistability in reaction networks
Authors: Hayes Clarmyra , Feliu Elisenda , Soyer Orkun S
Published: May 2021

Here, we focus on a common class of enzymes that have multiple substrate-binding sites (multi-site enzymes), and analyse their capacity to generate bistable dynamics in the reaction systems that they are embedded in. Using mathematical techniques, we show that the inherent binding and catalysis reactions arising from multiple substrate-enzyme complexes creates a potential for bistable dynamics in a reaction system. We construct a generic model of an enzyme withnsubstrate binding sites and derive an analytical solution for the steady state concentration of all enzyme-substrate complexes. By studying these expressions, we obtain a mechanistic understanding for bistability and derive parameter combinations that guarantee bistability and show how changing specific enzyme kinetic parameters and enzyme levels can lead to bistability in reaction systems involving mjulti-site enzymes. Thus, the presented findings provide a biochemical and mathematical basis for predicting and engineering bistability in multi-site enzymes.