bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombus in transit through a patent foramen ovale: catch it if you can—a case report
Authors: Pires Maria Inês Fiuza Branco , Almeida Inês , Santos João Miguel , Correia Miguel
Published: October 2021

Background

Patent foramen ovale (PFO) is one of the most common congenital heart defects, but the finding of a thrombus in transit (TIT) through a PFO is extremely rare. It is a therapeutic challenge, and systemic anticoagulation, cardiac surgery, or fibrinolysis should be considered.

Case summary

A 43-year-old woman was admitted with intermediate-high-risk pulmonary embolism. Transthoracic echocardiogram revealed a large right atrial mobile mass that crossed the interatrial septum through a PFO, compatible with TIT, and the patient was started on unfractionated heparin. The diagnosis was confirmed by transoesophageal echocardiogram (TOE). However, during TOE probe removal, the patient developed dyspnoea, sudoresis, and peripheral desaturation, and new image acquisition revealed sudden mass disappearance. Due to the possibility of paradoxical embolization associated with Valsalva manoeuvre, fibrinolysis with alteplase was promptly started. The patient had no signs of embolic or haemorrhagic complications and remained clinically stable. She was discharged on warfarin and then underwent percutaneous transcatheter closure of PFO.

Discussion

The treatment strategy of a TIT through a PFO is controversial, but surgery might be the most appropriate treatment for haemodynamically stable patients, while thrombolysis should be used in cases of haemodynamic instability. Transoesophageal echocardiogram is generally a safe procedure but pressure changes associated with Valsalva manoeuvre may induce embolization of a TIT and attention should be given to patient sedation and tolerance. After complete embolization of a TIT, emergent thrombolysis may be the only treatment option, in order to prevent disastrous consequences related to paradoxical embolism.
Same-day discharge after transcatheter mitral valve repair using MitraClip in a tertiary community hospital: a case series
Authors: Chowdhury Medhat , Buttar Rupinder , Rai Devesh , Tahir Muhammad Waqas , Tan Bryan E-Xin , Thakkar Samarthkumar , Ali Hammad , Patel Harsh P , Bhatt Deepak L , Depta Jeremiah P
Published: October 2021

Background

Due to the current Coronavirus Disease 2019 (COVID-19) pandemic, there is a realization for innovation in procedures and protocols to minimize hospital stay and at the same time ensure continued evidence-based treatment delivered to the patients. We present a same-day discharge protocol for transcatheter mitral valve repair (TMVR) using MitraClip under general anaesthesia in a six-patient case series. This protocol aims to reduce the length of hospital stay, thereby minimizing potential for nosocomial COVID-19 infections and to promote safe discharge with cautious follow-up.

Case summary

Six patients with severe symptomatic mitral valve (MV) regurgitation underwent successful transfemoral MV repair using standard procedures. Following repair, patients were monitored on telemetry in the recovery area for 3 h, ambulated to assess vascular access stability and underwent post-procedural transthoracic echocardiogram to assess for any pericardial effusion or post-procedural prosthetic mitral stenosis.

Conclusion

Same-day discharge after TMVR is possible when done cautiously with close follow-up, can minimize hospital stay, improve resource utilization, and reduce risk of nosocomial COVID-19 infection.
Multiple categories of non-cardiac QT-prolonging drugs are associated with increased risk of out-of-hospital cardiac arrest: real-world data from a population-based study
Authors: Eroglu Talip E , Blom Marieke T , Souverein Patrick C , de Boer Anthonius , Tan Hanno L
Published: October 2021

Aim

Drugs causing QT-prolongation as off-target effect [non-cardiac QT-prolonging drugs (QT-drugs)] increase the risk of out-of-hospital cardiac arrest (OHCA). Such drugs are categorized in multiple clinically widely used CredibleMeds.org lists. Category 1 (‘known risk of Torsade de Pointes’) and category 2 (‘possible risk of Torsade de Pointes’) are of particular clinical relevance. However, a category-stratified analysis of OHCA-risk is presently unavailable.

Methods and results

We conducted a case–control study with OHCA-cases from presumed cardiac causes included from the ARREST registry in the Netherlands (2009–2018) that was specifically designed to study OHCA, and age/sex/OHCA-date matched non-OHCA-controls. Adjusted odds ratios for OHCA (ORadj) of QT-drugs from categories 1 or 2 were calculated, using conditional logistic regression. Stratified analysis was performed according to sex, age, and presence of cardiovascular drugs (proxy for cardiovascular disease). We included 5473 OHCA-cases (68.8 years, 69.9% men) and matched them to 20 866 non-OHCA-controls. Compared with no use of non-cardiac QT-drugs, drugs of both categories were associated with increased OHCA-risk, but seemingly weaker for category 2 {category 1: case 3.2%, control 1.4%, ORadj 1.7 [95% confidence interval (CI): 1.3–2.1]}; [category 2: case 7.3%, control 4.0%, ORadj 1.4 (95% CI: 1.2–1.6)]. The increased risk occurred in men and women, at all ages (highest in patients aged ≤50 years), and both in the presence or absence of cardiovascular drug use.

Conclusion

Both category 1 and category 2 QT-drugs are associated with increased OHCA-risk in both sexes, at all ages, and in patients taking or not taking cardiovascular drugs.
Bend or break: how biochemically versatile molecules enable metabolic division of labor in clonal microbial communities
Authors: Varahan Sriram , Laxman Sunil
Published: October 2021

In fluctuating nutrient environments, isogenic microbial cells transition into “multicellular” communities composed of phenotypically heterogeneous cells, showing functional specialization. In fungi (such as budding yeast), phenotypic heterogeneity is often described in the context of cells switching between different morphotypes (e.g., yeast to hyphae/pseudohyphae or white/opaque transitions in Candida albicans). However, more fundamental forms of metabolic heterogeneity are seen in clonal Saccharomyces cerevisiae communities growing in nutrient-limited conditions. Cells within such communities exhibit contrasting, specialized metabolic states, and are arranged in distinct, spatially organized groups. In this study, we explain how such an organization can stem from self-organizing biochemical reactions that depend on special metabolites. These metabolites exhibit plasticity in function, wherein the same metabolites are metabolized and utilized for distinct purposes by different cells. This in turn allows cell groups to function as specialized, interdependent cross-feeding systems which support distinct metabolic processes. Exemplifying a system where cells exhibit either gluconeogenic or glycolytic states, we highlight how available metabolites can drive favored biochemical pathways to produce new, limiting resources. These new resources can themselves be consumed or utilized distinctly by cells in different metabolic states. This thereby enables cell groups to sustain contrasting, even apparently impossible metabolic states with stable transcriptional and metabolic signatures for a given environment, and divide labor in order to increase community fitness or survival. We speculate on possible evolutionary implications of such metabolic specialization and division of labor in isogenic microbial communities.
Multiple Reasons for Perceived Everyday Discrimination and All-Cause Mortality Risk Among Older Black Adults
Authors: Cobb Ryon J , Sheehan Connor M , Louie Patricia , Erving Christy L
Published: October 2021

Background

This study assessed whether reporting multiple reasons for perceived everyday discrimination was associated with an increased risk for all-cause mortality risk among older Black adults.

Methods

This study utilized data from a subsample of older Black adults from the Health and Retirement Study (HRS), a nationally representative panel study of older adults in the United States. Our measure of multiple reasons for perceived everyday discrimination was based on self-reports from the 2006/2008 HRS waves. Respondents’ vital status was obtained from the National Death Index and reports from key household informants (spanning 2006–2019). Cox proportional hazard models, which accounted for covariates linked to mortality, were used to estimate the risk of all-cause mortality.

Results

During the observation period, 563 deaths occurred. Twenty percent of Black adults attributed perceived everyday discrimination to 3 or more sources. In demographic adjusted models, attributing perceived everyday discrimination to 3 or more sources was a statistically significant predictor of all-cause mortality risk (hazard ratio = 1.45; 95% confidence interval = 1.12–1.87). The association remained significant (hazard ratio = 1.49; 95% confidence interval = 1.15–1.93) after further adjustments for health, behavioral, and economic characteristics.

Conclusions

Examining how multiple reasons for perceived everyday discrimination relate to all-cause mortality risk has considerable utility in clarifying the unique contributions of perceived discrimination to mortality risk among older Black adults. Our findings suggest that multiple reasons for perceived everyday discrimination are a particularly salient risk factor for mortality among older Black adults.
Dietary zinc concentration and lipopolysaccharide injection affect circulating trace minerals, acute phase protein response, and behavior as evaluated by an ear-tag–based accelerometer in beef steers
Authors: VanValin Katherine R , Carmichael-Wyatt Remy N , Deters Erin L , Messersmith Elizabeth M , Heiderscheit Katie J , Hochmuth Katherine G , Jackson Trey D , Peschel Joshua M , Johnson Anna K , Hansen Stephanie L
Published: October 2021

To assess plasma trace mineral (TM) concentrations, the acute phase protein response, and behavior in response to a lipopolysaccharide (LPS) challenge, 96 Angus cross steers (average initial body weight [BW]: 285 ± 14.4 kg) were sorted into two groups by BW (heavy and light; n = 48/group), fitted with an ear-tag–based accelerometer (CowManager SensOor; Agis, Harmelen, Netherlands), and stagger started 14 d apart. Consecutive day BW was recorded to start the 24-d trial (days −1 and 0). Dietary treatments began on day 0: common diet with either 30 (Zn30) or 100 (Zn100) mg supplemental Zn/kg DM (ZnSO4). On day 17, steers received one of the following injection treatments intravenously to complete the 2 × 3 factorial: 1) SALINE (~2–3 mL of physiological saline), 2) LOWLPS: 0.25 µg LPS/kg BW, or 3) HIGHLPS: 0.375 µg LPS/kg BW. Blood, rectal temperature (RT), and BW were recorded on day 16 (−24 h relative to injection), and BW was used to assign injection treatment. Approximately 6, 24 (day 18), and 48 (day 19) h after treatment, BW, RT, and blood were collected, and final BW recorded on day 24. Data were analyzed in Proc Mixed of SAS with fixed effects of diet, injection, diet × injection; for BW, RT, dry matter intake (DMI), plasma TM, and haptoglobin-repeated measures analysis were used to evaluate effects over time. Area under the curve analysis determined by GraphPad Prism was used for analysis of accelerometer data. Body weight was unaffected by diet or injection (P ≥ 0.16), but there was an injection × time effect for DMI and RT (P < 0.05), where DMI decreased in both LPS treatments on day 16, but recovered by day 17, and RT was increased in LPS treatments 6 h post-injection. Steers receiving LPS spent less time highly active and eating than SALINE (P < 0.01). Steers in HIGHLPS spent lesser time ruminating, followed by LOWLPS and then SALINE (P < 0.001). An injection × time effect (P < 0.001) for plasma Zn showed decreased concentrations within 6 h of injection and remained decreased through 24 h before recovering by 48 h. A tendency for a diet × time effect (P = 0.06) on plasma Zn suggests plasma Zn repletion occurred at a greater rate in Zn100 compared to Zn30. These results suggest that increased supplemental Zn may alter the rate of recovery of Zn status from an acute inflammatory event. Additionally, ear-tag–based accelerometers used in this study were effective at detecting sickness behavior in feedlot steers, and rumination may be more sensitive than other variables.
Leaping and differential habitat use in sympatric tamarins in Amazonian Peru
Authors: Berles Patricia , Heymann Eckhard W , Golcher Felix , Nyakatura John A
Published: October 2021

Differential habitat use in sympatric species can provide insight into how behavior relates to morphological differences and as a general model for the study of biological adaptations to different functional demands. In Amazonia, closely related sympatric tamarins of the genera Saguinus and Leontocebus regularly form stable mixed-species groups, but exhibit differences in foraging height and locomotor activity. To test the hypothesis that two closely related species in a mixed-species group prefer different modes of leaping regardless of the substrates available, we quantified leaping behavior in a mixed-species group of Saguinus mystax and Leontocebus nigrifrons. We studied leaping behavior in relation to support substrate type and foraging height in the field for 5 months in the Amazonian forest of north-eastern Peru. Saguinus mystax spent significantly more time above 15 m (79%) and used predominantly horizontal and narrow supports for leaping. Leontocebus nigrifrons was predominantly active below 10 m (87%) and exhibited relatively more trunk-to-trunk leaping. Both species preferred their predominant leaping modes regardless of support type availability in the different forest layers. This indicates that the supports most commonly available in each forest layer do not determine the tamarins’ leaping behavior. This apparent behavioral adaptation provides a baseline for further investigation into how behavioral differences are reflected in the morphology and species-specific biomechanics of leaping behavior and establishes callitrichid primates as a model well-suited to the general study of biological adaptation.
Neutrino absorption and other physics dependencies in neutrino-cooled black hole accretion discs
Authors: Just O , Goriely S , Janka H-Th , Nagataki S , Bauswein A
Published: October 2021

Black hole (BH) accretion discs formed in compact-object mergers or collapsars may be major sites of the rapid-neutron-capture (r-)process, but the conditions determining the electron fraction (Ye) remain uncertain given the complexity of neutrino transfer and angular-momentum transport. After discussing relevant weak-interaction regimes, we study the role of neutrino absorption for shaping Ye using an extensive set of simulations performed with two-moment neutrino transport and again without neutrino absorption. We vary the torus mass, BH mass and spin, and examine the impact of rest-mass and weak-magnetism corrections in the neutrino rates. We also test the dependence on the angular-momentum transport treatment by comparing axisymmetric models using the standard α-viscosity with viscous models assuming constant viscous length-scales (lt) and 3D magnetohydrodynamic (MHD) simulations. Finally, we discuss the nucleosynthesis yields and basic kilonova properties. We find that absorption pushes Ye towards ∼0.5 outside the torus, while inside increasing the equilibrium value $Y_\mathrm{ e}^{\mathrm{eq}}$ by ∼0.05–0.2. Correspondingly, a substantial ejecta fraction is pushed above Ye = 0.25, leading to a reduced lanthanide fraction and a brighter, earlier, and bluer kilonova than without absorption. More compact tori with higher neutrino optical depth, τ, tend to have lower $Y_\mathrm{ e}^{\mathrm{eq}}$ up to τ ∼ 1–10, above which absorption becomes strong enough to reverse this trend. Disc ejecta are less (more) neutron rich when employing an lt = const. viscosity (MHD treatment). The solar-like abundance pattern found for our MHD model marginally supports collapsar discs as major r-process sites, although a strong r-process may be limited to phases of high mass-infall rates, $\dot{M}\, \, \raise0.14em\rm{\gt }\lower0.28em\rm{\sim }\, \, 2\times 10^{-2}$ M⊙ s−1.
Results of a phase I trial to assess the safety of macitentan in combination with temozolomide for the treatment of recurrent glioblastoma
Authors: Weathers Shiao-Pei , Rood-Breithaupt Julie , de Groot John , Thomas Gail , Manfrini Marianna , Penas-Prado Marta , Puduvalli Vinay K , Zwingelstein Christian , Yung W K Alfred
Published: October 2021

Background

There is an urgent need for additional therapies to treat recurrent glioblastoma (GBM). Preclinical studies suggest that high dose macitentan, an oral dual endothelin receptor antagonist, enhances the cytotoxic effects of temozolomide (TMZ) in GBM, improving survival. This phase I trial investigated the maximum tolerated dose of macitentan combined with TMZ in patients with recurrent GBM and assessed the safety and tolerability of high dose macitentan in these patients (NCT01499251).

Methods

Adults with recurrent GBM received ascending doses of macitentan from 30 mg once daily concomitantly with TMZ. Safety and tolerability were assessed in addition to exploratory efficacy and pharmacokinetic endpoints. An ancillary study examined biomarker expression following macitentan treatment prior to surgical resection of recurrent GBM.

Results

Thirty-eight patients with recurrent GBM were administered macitentan doses up to 300 mg once daily; no dose-limiting toxicities were observed, and a maximum tolerated dose was not determined. All patients experienced at least one treatment-emergent adverse event (TEAE), the majority associated with GBM or TMZ treatment. TEAEs related to macitentan and TMZ were reported for 16 (42.1%) and 26 (68.4%) patients, respectively, with no serious macitentan-related TEAEs. Macitentan concentrations increased with dose, with no plateau in exposure. Substantial heterogeneity was observed in the expression of efficacy biomarkers within tumors. The Kaplan-Meier estimate of median overall survival across all dose groups was 9.4 (95% CI 8.5, 13.4) months.

Conclusion

High-dose macitentan was well tolerated in recurrent GBM patients concomitantly receiving TMZ. TEAEs were consistent with those seen in patients receiving either drug individually.
Generous Hosts: ‘Candidatus Liberibacter asiaticus’ Growth in Madagascar Periwinkle (Catharanthus roseus) Highlights Its Nutritional Needs
Authors: Killiny Nabil
Published: October 2021

‘Candidatus Liberibacter asiaticus’, the putative causal agent of citrus greening, is not available in pure culture yet. In addition to trees of citrus and citrus relatives, ‘Ca. L. asiaticus’ can grow in Madagascar periwinkle (Catharanthus roseus). Using gas chromatography-mass spectrometry, we compared the phloem sap composition in sweet orange ‘Valencia’ (Citrus sinensis) and periwinkle plants after the infection with ‘Ca. L. asiaticus’. Interestingly, in contrast to our previous studies of total leaf metabolites, we found that, compared with uninfected phloem sap, the organic acids implicated in the tricarboxylic acid cycle (TCA) cycle including citrate, isocitrate, succinate, fumarate, and malate were reduced significantly in the infected phloem saps of both species. As a result of the reduction of organic acids content, the pH of infected phloem saps was increased. We hypothesize that the bacterial growth induces the mitochondrial TCA cycle in parenchyma cells to produce more of these compounds to be used as a bacterial carbon source. Once these compounds reach a low level in the phloem sap, the bacterium may send a signal, yet to be identified, to initiate a feedback loop to further induce the TCA cycle. Phloem blockage might be another reason behind the reduced translocation of TCA cycle intermediates within the phloem. The net result, localized availability of organic acids, likely benefits bacterial growth and may explain the unequal distribution of ‘Ca. L. asiaticus’ within infected trees. These findings may help in designing media for the pure culturing of ‘Ca. L. asiaticus’.
Consensus-Based Guidelines for the Recognition, Diagnosis, and Management of Hemophagocytic Lymphohistiocytosis in Critically Ill Children and Adults
Authors: Hines Melissa R. , von Bahr Greenwood Tatiana , Beutel Gernot , Beutel Karin , Hays J. Allyson , Horne AnnaCarin , Janka Gritta , Jordan Michael B. , van Laar Jan A. M. , Lachmann Gunnar , Lehmberg Kai , Machowicz Rafal , Miettunen Päivi , La Rosée Paul , Shakoory Bita , Zinter Matt S. , Henter Jan-Inge
Published: October 2021

OBJECTIVE:

Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome that often requires critical care support and remains difficult to diagnose. These guidelines are meant to aid in the early recognition, diagnosis, supportive care, and treatment of patients with hemophagocytic lymphohistiocytosis in ICUs.

DATA SOURCES:

The literature searches were performed with PubMed (MEDLINE).

STUDY SELECTION:

Keywords and medical subject headings terms for literature search included “macrophage activation syndrome,” hemophagocytic lymphohistiocytosis,” and “hemophagocytic syndrome.”

DATA EXTRACTION:

The Histiocyte Society developed these consensus recommendations on the basis of published reports and expert opinions with level of evidence provided for each recommendation. They were endorsed by the Society of Critical Care Medicine.

DATA SYNTHESIS:

Testing for hemophagocytic lymphohistiocytosis should be initiated promptly in all patients admitted to ICUs with an unexplained or disproportionate inflammatory response, especially those with rapid clinical deterioration. Meeting five or more of eight hemophagocytic lymphohistiocytosis 2004 diagnostic criteria serves as a valuable diagnostic tool for hemophagocytic lymphohistiocytosis. Early aggressive critical care interventions are often required to manage the multisystem organ failure associated with hemophagocytic lymphohistiocytosis. Thorough investigation of the underlying triggers of hemophagocytic lymphohistiocytosis, including infections, malignancies, and autoimmune/autoinflammatory diseases, is essential. Early steroid treatment is indicated for patients with familial hemophagocytic lymphohistiocytosis and is often valuable in patients with acquired hemophagocytic lymphohistiocytosis (i.e., secondary hemophagocytic lymphohistiocytosis) without previous therapy, including macrophage activation syndrome (hemophagocytic lymphohistiocytosis secondary to autoimmune/autoinflammatory disease) without persistent or relapsing disease. Steroid treatment should not be delayed, particularly if organ dysfunction is present. In patients with macrophage activation syndrome, whose disease does not sufficiently respond, interleukin-1 inhibition and/or cyclosporine A is recommended. In familial hemophagocytic lymphohistiocytosis and severe, persistent, or relapsing secondary macrophage activation syndrome, the addition of prompt individualized, age-adjusted etoposide treatment is recommended.

CONCLUSIONS:

Further studies are needed to determine optimal treatment for patients with hemophagocytic lymphohistiocytosis in ICUs, including the use of novel and adjunct therapies.
Epilepsy in children with perinatal arterial ischemic stroke
Authors: Kühne Fabienne , Jungbluth Alexander , Schneider Joanna , Bührer Christoph , Prager Christine , Kaindl Angela M.
Published: October 2021

Purpose

Perinatal ischemic stroke (PIS) is a frequent cause for perinatal brain structure defects resulting in epilepsy, cerebral palsy and disability. Since the severity of symptoms is variable, the aim of this study was to evaluate the outcome of children with PIS and seizures/epilepsy to aid parental counseling and therapy decisions.

Material

We studied retrospectively patients with arterial PIS and structural epilepsy or seizures in the newborn treated at a single center in 2000-2019. Specifically, signs and symptoms of cerebral palsy (CP), developmental and motor delay, epilepsy and thrombophilia were assessed.

Results

From the identified 69 individuals with arterial PIS, we only included the 50 patients (64% male) who had structural epilepsy at the time of investigation or previously in their medical history.The mean age of the included patients was 7.1 years (range 0.08-22) at last consultation. Infarct localisation was predominantly unilateral (86%), left sided (58%) and affecting the middle cerebral artery (94%). Genetic thrombophilia was identified in 52% of the patients examined with genetic testing. More than half of the individuals had CP (52%), and 38.5% had a cognitive outcome below average. First seizures occurred in the neonatal period in 58% of patients and developed into drug-refractory epilepsy in 24.1%. Children with late-onset of epilepsy were twice as likely to develop drug-refractory epilepsy (52.4%).

Discussion

Our study shows that patients with PIS and seizures as common sequela often also develop CP. Children with later onset of epilepsy have a worse outcome. Patients with seizure onset in the neonatal period and reccuring seizures have a good response to treatment. Therefore, early diagnosis, follow-up examination and adequate therapy are important. Most children need intensive physiotherapy and speech therapy; however, participation in life is usually age-appropriate.
Evaluation of liver function tests and C-reactive protein in COVID-19 (SARS Cov-2) positive patients diagnosed by Real-time PCR
Authors: Khurshid Fatima , Iqbal Sajjad , Mumtaz Madiha
Published: October 2021

BACKGROUND AND AIMS

The SARS-CoV-2 pandemic, has caused an unconventional social and economic impact globally. To date, there was limited data regarding the effect of COVID-19 infection on the trend of RT-PCR Ct value, risk factors for disease, effect on liver enzymes, etc. This study aimed to assess the frequency of COVID-19 infection in different age groups and genders. Association of cycle threshold (Ct) values with disease severity and to describe the effect of COVID-19 infection on LFT, Deritis ratio, and CRP. That can be used as indicators for COVID-19 infection diagnosis, the guidance for treatment decisions, and prognosis in infected individuals.

METHODS

This was a cross-sectional study conducted in the Molecular Biology and Chemical Pathology sections of the Pathology Department, Shalamar Teaching Hospital Lahore from November 2020 to March 2021.

Results

Males 51% were more likely to be infected by SARS-CoV-2. Most of the infected individuals 36.5% were in the age group 20-40. Age and underlying comorbidities are important factors that play a significant role in COVID-19 severity. The uppermost number of the patients had symptoms of fever 78.3%, cough 50.4% and myalgias 50.1% RT-PCR low Ct value could be an important indicator related with the disease severity and mortality risk p value < 0.001 and 0.003 respectively. Bilirubin indirect, ALT, AST, and CRP were significantly associated with disease severity. Deritis ratio and CRP was found to be significantly associated with the risk of mortality.

CONCLUSIONS

Real-Time PCR results along with Ct values for SARS-CoV-2 may have benefit for clinicians in patient management decisions. Several risk factors e.g., age and comorbidities for developing severe disease and mortality risk have been identified. These biochemical laboratory parameters ALT, AST, Deritis ratio and CRP can be used as predictive biomarkers for progression towards severe disease and risk of mortality.
Telemedicine and molecular Sars-CoV-2 early detection to face the COVID-19 pandemic
Authors: Cherem José , Pylro Victor Satler , Poles Katia , Carvalho Richardson Costa , Carvalho Ewerton , dos Santos Juliana Anacleto , Alvarenga Ingrid Marciano , Rocha Denise Alvarenga , Teixeira Karla Silva , de Castro Joseane Camilla , Torquete Mariana Almeida , de Almeida Ferreira Sidney , de Paiva Barçante Joziana Muniz
Published: October 2021

The COVID-19 pandemic brought a series of challenges to the academic community. Social distancing measures imposed the interruption of face-to-face activities besides the implementation of remote work and online classes. For safe and gradual return, the monitoring of individuals, quick detection of infection, contact tracing, and isolation of those infected became essential. In this sense, we developed strategies to face the pandemic at the Federal University of Lavras (UFLA) - Brazil. A Telemedicine Program (TeleCovid) and the assemblage of a laboratory for SARS-CoV-2 molecular diagnosis (LabCovid) were essential measures for monitoring, preventing, and controlling outbreaks at the university. TeleCovid works with a team of students who guide and answer questions regarding COVID-19 and, when necessary, make the referral for online consultation with medical professionals. In the suspicion of SARS-CoV-2 infection, the doctor refers the patient for testing at LabCovid. LabCovid performs the sample collection using nasal swabs, followed by processing samples by the RT-qPCR method. We have placed all positive patients in isolation and tested their contacts. This approach meant that positive cases were identified early, thus avoiding outbreaks in different environments in face-to-face activities.
Characteristics associated with COVID-19 vaccination status among staff and faculty of a large, diverse University in Los Angeles
Authors: Nicolo Michele , Kawaguchi Eric , Ghanem-Uzqueda Angie , Kim Andre E. , Soto Daniel , Deva Sohini , Shanker Kush , Rogers Christopher , Lee Ryan , Casagrande Yolee , Gilliland Frank , Orman Sarah Van , Klausner Jeffery , Kovacs Andrea , Conti David , Hu Howard , Unger Jennifer B.
Published: October 2021

Objective

This study examined characteristics associated with being unvaccinated among a sample of university staff and faculty prior to university campus reopening for in-person learning in spring-summer 2021.

Methods

Staff and faculty responded to an email invitation to complete an online survey. Survey questions included demographic data (race/ethnicity, age, sex), COVID-19 knowledge and behaviors, employment specific data including division and subdivision (healthcare vs. non-healthcare related division); and self-reported vaccination status. A multivariable logistic regression analysis was performed to determine significant characteristics associated with the likelihood of being unvaccinated for COVID-19.

Results

Participants identifying as Asian and Asian American, Hispanic/Latinx or Multicultural/Other had greater odds of being unvaccinated compared to Non-Hispanic White participants. Other characteristics associated with greater likelihood of being unvaccinated included working as university staff member (vs. faculty), older age, decrease in income, inability to work remotely and not traveling outside of Los Angeles area. Political affiliation as an Independent or as something else were more likely to be unvaccinated compared to participants identifying as Democrat.

Conclusions

Findings suggest several factors associated with racial and social disparities may delay the uptake of COVID-19 vaccination. This study highlights the need for targeted educational interventions to promote vaccination among university staff and faculty.
Electrocardiogram Analysis of Post-Stroke Elderly People Using One-dimensional Convolutional Neural Network Model with Gradient-weighted Class Activation Mapping
Authors: Ho Eric S. , Ding Zhaoyi
Published: October 2021

Background and purposes

Stroke is the second leading cause of death globally after ischemic heart disease, also a risk factor of cardioembolic stroke. Thus, we postulate that heartbeats encapsulate vital signals related to stroke. With the rapid advancement of deep neural networks (DNNs), it emerges as a powerful tool to decipher intriguing heartbeat patterns associated with post-stroke patients. In this study, we propose the use of a one-dimensional convolutional network (1D-CNN) architecture to build a binary classifier that distinguishes electrocardiogram s (ECGs) between the post-stroke and the stroke-free.

Methods

We have built two 1D-CNNs that were used to identify distinct patterns from an openly accessible ECG dataset collected from elderly post-stroke patients. In addition to prediction accuracy, which is the primary focus of existing ECG deep neural network methods, we have utilized Gradient-weighted Class Activation Mapping (GRAD-CAM) to ease model interpretation by uncovering ECG patterns captured by our model.

Results

Our stroke model has achieved ∼90% accuracy and 0.95 area under the Receiver Operating Characteristic curve. Findings suggest that the core PQRST complex alone is important but not sufficient to differentiate the post-stroke and the stroke-free.

Conclusions

We have developed an accurate stroke model using the latest DNN method. Importantly, our work has illustrated an approach to enhance model interpretation, overcoming the black-box issue facing DNN, fostering higher user confidence and adoption of DNN in medicine.
Equivalence of saliva RT-qPCR testing to nasal-throat/nasopharyngeal swab testing in the general practitioner’s setting to detect SARS-CoV-2
Authors: Jonckheere Ilse , Faes Liesbeth , Overmeire Yarah , De Vleeschauwer An , Vanden Daele Laura , Van Bruaene Nathalie , Vandecandelaere Ilse , Merlaen Britt , van Cann Joannes , Vandesompele Jo
Published: October 2021

Study design

Saliva has been proposed as valid alternative for nasopharyngeal swab for RT-qPCR detection of SARS-CoV-2. The sensitivity is generally equivalent, and it comes with much less discomfort for the patient. While there is an overall good performance in the literature for adults, there is much less information on the use of saliva in children or in the general practitioner’s setting.

Methods

We tested a novel commercially available saliva collection kit with a virus inactivating and RNA stabilizing buffer (InActiv Blue®) in matched saliva and swab samples from 245 individuals, including 216 children, collected by general practitioners.

Results

Blind RT-qPCR testing of the saliva samples confirmed all 23 positives identified by swab testing (100% concordance), irrespective of age, presence of symptoms, or high-risk status. One child’s saliva sample was found low positive while negative on the nasopharyngeal swab, resulting in an overall relative sensitivity of RT-qPCR saliva testing of 104.3%.

Conclusion

Saliva collected in InActiv Blue® can be a valid alternative for SARS-CoV-2 RT-qPCR testing in the general practitioner’s setting, including children.
Humoral and cellular immune responses upon SARS-CoV-2 vaccines in patients with anti-CD20 therapies: A systematic review and meta-analysis of 1342 patients
Authors: Schietzel Simeon , Anderegg Manuel A. , Limacher Andreas , Born Alexander , Horn Michael P. , Maurer Britta , Hirzel Cédric , Sidler Daniel , Moor Matthias B.
Published: October 2021

Background

Immune responses upon SARS-CoV-2 vaccination in patients receiving anti-CD20 therapies are impaired but vary considerably. We conducted a systematic review and meta-analysis of the literature on SARS-CoV-2 vaccine induced humoral and cell-mediated immune response in patients previously treated with anti-CD20 antibodies.

Methods

We searched PubMed, EMBASE, Medrxiv and SSRN using variations of search terms “anti-CD20”, “vaccine” and “COVID” and included original studies up to August 21st,2021. We excluded studies with missing data on humoral or cell-mediated immune response, unspecified methodology of response testing, unspecified timeframes between vaccination and blood sampling or low number of participants (≤ 3). We excluded individual patients with prior SARS-CoV-2 infection or incomplete vaccine courses. Primary endpoints were humoral and cell-mediated immune response rates. Pre-specified subgroups were time of vaccination after anti-CD20 therapy (< vs > 6 months), time point of response testing after vaccination (< vs > 4 weeks) and disease entity (autoimmune vs cancer vs renal transplant). We used random-effects models of proportions.

Findings

Ninety studies were assessed. Inclusion criteria were met by 23 studies comprising 1342 patients. Overall rate of humoral response was 0.41 (95% CI 0.35 – 0.47). Overall rate of cell-mediated immune responses was 0.71 (95% CI 0.47 – 0.90). Longer time interval since last anti-CD20 therapy was associated with higher humoral response rates > 6 months 0.63 (95% CI 0.53 – 0.72) vs < 6 months 0.2 (95% CI 0.03 – 0.43); p = 0.001. Compared to patients with haematological malignancies or autoimmune diseases, anti-CD20 treated kidney transplant recipients showed the lowest vaccination response rates.

Interpretation

Patients on anti-CD20 therapies can develop humoral and cell-mediated immune responses after SARS-CoV-2 vaccination, but subgroups such as kidney transplant recipients or those with very recent B-cell depleting therapy are at high risk for non-seroconversion and should be individually assessed for personalized SARS-CoV-2 vaccination strategies. Potential limitations are small patient numbers, heterogeneous diseases and assays used.

Funding

This study was funded by Bern University Hospital.
Physician-confirmed and administrative definitions of stroke in UK Biobank reflect the same underlying genetic trait
Authors: Rannikmäe Kristiina , Rawlik Konrad , Ferguson Amy C , Avramidis Nikos , Jiang Muchen , Pirastu Nicola , Shen Xia , Davidson Emma , Woodfield Rebecca , Malik Rainer , Dichgans Martin , Tenesa Albert , Sudlow Cathie
Published: October 2021

Background

Stroke in UK Biobank (UKB) is ascertained via linkages to coded administrative datasets and self-report. We studied the accuracy of these codes using genetic validation.

Methods

We compiled stroke-specific and broad cerebrovascular disease (CVD) code lists (Read V2/V3, ICD-9/-10) for medical settings (hospital, death record, primary care) and self-report. Among 408,210 UKB participants we identified all with a relevant code, creating 12 stroke definitions based on the code type and source. We performed genome-wide association studies (GWASs) for each definition, comparing summary results against the largest published stroke GWAS (MEGASTROKE), assessing genetic correlations, and replicating 32 stroke-associated loci.

Results

Stroke case numbers identified varied widely from 3,976 (primary care stroke-specific codes) to 19,449 (all codes, all sources). All 12 UKB stroke definitions were significantly correlated with the MEGASTROKE summary GWAS results (rg 0.81-1) and each other (rg 0.4-1). However, Bonferroni-corrected confidence intervals were wide, suggesting limited precision of some results. Six previously reported stroke-associated loci were replicated using ≥1 UKB stroke definitions.

Conclusions

Stroke case numbers in UKB depend on the code source and type used, with a 5-fold difference in the maximum case-sample size. All stroke definitions are significantly genetically correlated with the largest stroke GWAS to date.
Keeping students connected and engaged in a wet-lab research experience during a time of social distancing via mobile devices and video conferencing software
Authors: Shamoon-Pour Michel , Light Caitlin J. , Fegley Megan
Published: October 2021

Two major COVID-19 pandemic challenges presented for in-person instruction included adhering to social distancing guidelines and accommodating remote learners who were temporarily isolated or permanently participating from afar. At Binghamton University, our First-year Research Immersion (FRI) program was challenged with providing students with a wet lab course-based undergraduate research experience (CURE), an intense hands-on experience that emphasized student teamwork, lab protocol development, iteration, troubleshooting and other elements of the process of science that could not be replicated in a fully remote environment. We developed an innovative technology approach to maximize all students’ connection to the lab research experience utilizing dedicated mobile devices (iPod Touch) and video conferencing software (Zoom) to synchronously connect remote learners to in-person learners, peer mentors and instructors in our FRI research labs. In this way, despite limited lab capacities and fluctuating remote learning populations, we were able to connect remote learners to their peers and mentors in real-time and give them responsibilities that allowed them to be engaged and feel like meaningful participants in the research process. Although our students reported a preference for in-person labs, they noted this hybrid model was better than other traditionally employed remote-learning lab options. We believe lessons learned here can be applied to improve access to research in all situations and allow us to be prepared for other catastrophic disruptions to the educational system.
Classifying Literature Extracted Events for Automated Model Extension
Authors: Hansen Casey , Kisslinger Julia , Krishna Neal , Holtzapple Emilee , Ahmed Yasmine , Miskov-Zivanov Natasa
Published: October 2021

1

In this study, we investigate the integration of three previously developed tools: FLUTE, VIOLIN, and CLARINET. We show how using these tools together adds additional capabilities in extending models from relevant research literature. We illustrate how we plan to address current modeling pitfalls with these tools (such as machine reading errors and literature volume), and how we plan to use these tools as the foundation for an automated model extension framework. Documentation and links to our tools can be found at:

violin-tool.readthedocs.io

clarinet-docs.readthedocs.io

flute.readthedocs.io
Organoid co-culture model of the cycling human endometrium in a fully-defined synthetic extracellular matrix reveals epithelial-stromal crosstalk
Authors: Gnecco Juan S. , Brown Alexander , Buttrey Kira , Ives Clara , Goods Brittany A. , Baugh Lauren , Hernandez-Gordillo Victor , Loring Megan , Isaacson Keith , Griffith Linda G.
Published: October 2021

The human endometrium undergoes recurring cycles of growth, differentiation, and breakdown in response to sex hormones. Dysregulation of epithelial-stromal communication during hormone cycles is linked to myriad gynecological disorders for which treatments remain inadequate. Here, we describe a completely defined, synthetic extracellular matrix that enables co-culture of human endometrial epithelial and stromal cells in a manner that captures healthy and disease states across a simulated menstrual cycle. We parsed cycle-dependent endometrial integrin expression and matrix composition to define candidate cell-matrix interaction cues for inclusion in a polyethylene glycol (PEG)-based hydrogel crosslinked with matrix metalloproteinase-labile peptides. We semi-empirically screened a parameter space of biophysical and molecular features representative of the endometrium to define compositions suitable for hormone-driven expansion and differentiation of epithelial organoids, stromal cells, and co-cultures of the two cell types. Each cell type exhibited characteristic morphological and molecular responses to hormone changes when co-encapsulated in hydrogels tuned to a stiffness regime similar to the native tissue and functionalized with a collagen-derived adhesion peptide (GFOGER) and a fibronectin-derived peptide (PHSRN-K-RGD). Analysis of cell-cell crosstalk during IL-1β-induced inflammation revealed dysregulation of epithelial proliferation mediated by stromal cells. Altogether, we demonstrate the development of a fully synthetic matrix to sustain the dynamic changes of the endometrial microenvironment and support its applications to understand menstrual health and endometriotic diseases.

Abstract Figure
CellDepot: A unified repository for scRNA-seq data and visual exploration
Authors: Lin Dongdong , Chen Yirui , Negi Soumya , Cheng Derrick , Ouyang Zhengyu , Sexton David , Li Kejie , Zhang Baohong
Published: October 2021

CellDepot serves as an integrated web application to assist users in exploring single-cell RNA-seq (scRNA-seq) datasets and comparing the datasets among various studies through a user-friendly interface with advanced visualization and analytical tools. To begin with, it provides an efficient data management system that users can upload single cell datasets and query the database by multiple attributes such as species and cell types. In addition, the advanced query function incorporated in MySQL database system and its conditional filtering, allows users to quickly query and compare the expression of gene(s) across the datasets of interest. Moreover, by embedding the cellxgene VIP tool, CellDepot enables fast exploration of individual dataset in the manner of interactivity and scalability to gain more refined insights such as cell composition, gene expression profiles, and differentially expressed genes among cell types. In summary, the web portal allows large scale single cell data sharing, analysis and visualization for supporting decision-making, and encouraging scientists to contribute to the single-cell community in a tractable and collaborative way. Finally, CellDepot is released as open-source software to motivate crowd contribution, broad adoption, and local deployment for private data.
Plausible Mechanistic Insights in Biofilm Eradication Potential of against Candida spp. using In Situ Synthesized Tyrosol Functionalized Chitosan Gold Nanoparticles as a versatile Antifouling Coating on Implant Surfaces
Authors: Yadav Tara Chand , Gupta Payal , Saini Saakshi , Pruthi Vikas , Prasad Ramasare
Published: October 2021

In the present study, tyrosol functionalized chitosan gold nanoparticles (Chi-TY-AuNP’s) were prepared as an alternative treatment strategy to combat fungal infections. Various biophysical techniques were used to characterize the synthesized Chi-TY-AuNP’s. The antifungal and antibiofilm activities of Chi-TY-AuNP’s were evaluated against C. albicans and C. glabrata and efforts have been made to elucidate the possible mechanism of action. Chi-TY-AuNP’s showed a high fungicidal effect against both sessile and planktonic cells of Candida spp. Additionally, Chi-TY-AuNP’s completely eradicated (100%) the mature biofilms of both the Candida spp. FESEM analysis highlighted the morphological alterations in Chi-TY-AuNP’s treated Candida biofilm cells. Effect of Chi-TY-AuNP’s on the ECM components showed significant reduction in protein content in C. glabrata biofilm and substantial decrease in extracellular DNA (eDNA) content of both the Candida spp. ROS generation analysis using DCFDA-PI staining showed high ROS levels in both the Candida spp., whereas pronounced ROS production was observed in Chi-TY-AuNP’s treated C. glabrata biofilm. Biochemical analysis revealed decreased ergosterol content in Chi-TY-AuNP’s treated C. glabrata cells, while inconsequential changes were observed in C. albicans. Furthermore, the transcriptional expression of selected genes (ergosterol biosynthesis, efflux, sterol importer, and glucan biogenesis) was reduced in C. glabrata in response to Chi-TY-AuNP’s except ERG11 and CDR1. Conclusively the result showed the biofilm inhibition and biofilm eradication efficacy of Chi-TY-AuNP’s in both the Candida spp. Findings of the present study manifest Chi-TY-AuNP’s as a potential therapeutic solution to Candida biofilm-related chronic infections and overcome biofilm antifungal resistance.