bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific Associations Between Type of Childhood Abuse and Elevated C-Reactive Protein in Young Adult Psychiatric Rehabilitation Participants
Authors: Jabbi Mbemba M. , Harvey Philip D. , Kotwicki Raymond J. , Nemeroff Charles B.
Published: April 2022

Background

Early life adversity such as childhood emotional, physical, and sexual trauma is associated with a plethora of later-life psychiatric and chronic medical conditions, including elevated inflammatory markers. Although previous research suggests a role for chronic inflammatory dysfunctions in several disease etiologies, specific associations between childhood trauma types and later life inflammation and health status are not well understood.

Methods

We studied patients (n=280) who were admitted to a psychiatric rehabilitation center. Self-reported histories of childhood emotional, physical, and sexual trauma history were collected. At the time of admission, we also assessed individuals’ body mass index (BMI) and collected blood samples that were used to examine levels of inflammatory marker C-reactive protein (CRP).

Results

The prevalence of all three types of abuse were quite high, at 21% or more. 50% of the sample had elevations in CRP, with clinically significant elevations in 26%. We found that compared to a history of emotional or physical abuse, a history of childhood sexual trauma was more specifically associated with elevated CRP. This result held up when controlling for BMI.

Limitation

Our sample is relatively young, with an average age of 27.2 years, with minimal representation of ethnic and racial minority participants.

Conclusion

Relative to childhood emotional and physical trauma, childhood sexual trauma may lead to elevated inflammatory responses, which were common overall in the sample. Future studies need to assess the causal link between childhood sexual trauma and poorer health outcomes later in life.

HIGHLIGHTS

- The prevalence of both childhood abuse experiences and elevations in inflammatory markers were quite high.

- We found that the history and severity of childhood sexual abuse were differentially correlated with later life inflammatory status and body mass index, with childhood emotional and physical abuse not showing the same degree of correlation with inflammatory status later in early adulthood.

- These results demonstrate how specific elements of environmental adversity, which, when suffered at a critical developmental period, can have lingering negative physiological consequences later in life.
Molecular identification of species of family Chaetomiaceae (Sordariomycetes, Ascomycota) from soil, dung and water in Sudan
Authors: Mhmoud Najwa A
Published: April 2022

Species of Chaetomiaceae family are ubiquitous filamentous fungi, that responsible for a wide range of opportunistic human infections. To date, it encompasses more than 300 species have been described in genus Chaetomium. It have been globally reported as being are capable of colonizing various substrates. Due to the lack of genetic studies on the species belonging to this genus in Sudan, This work aimed to investigate the environmental fungal occurrence within the family Chaetomiaceae by using morphological characters and molecular sequencing.

A total of 260 environmental samples from soil, animal dung and water were collected from six different states in Sudan in two ecozones: .desert or semis desert ecozones (Dongola in Northern sudan, El-Obeid in western sudan); a low rainfall woodland savanna ecozone (Gazira, El Geteina and Khartoum from central Sudan and AlQadarif in eastern Sudan).

During a study of environmental fungi in Sudan, 119 isolates were identified as members of Chaetomiaceae after the ITS sequencing combined with an examination of the macro- and micromorphology. Out of 63 Chaetomium strains obtained from soil, animal dung and water samples, 25 were obtained from soil, 22 from animal dung and 16 from water. 56 additional strains isolated from other genus within the Chaetomiaceae family, such as (Amesia, Collariella, Ovatospora, SubramaniulaandThielavia) were recorded for the first time in Sudan.

In conclusion: Sequence-based identification of fungal isolates is often considered to be the most reliable and accurate identification method.
From months to minutes: creating Hyperion, a novel data management system expediting data insights for oncology research and patient care
Authors: Snyder Eric , Rivers Thomas , Smith Lisa , Paoni Scott , Cunliffe Scott , Patel Arpan , Ramsdale Erika
Published: April 2022

Structured Abstract

Objective

Describe the design and implementation of a novel data management platform for an academic cancer center which meets the needs of multiple stakeholders.

Materials and Methods

A small, cross-functional technical team identified key challenges to creating a broad data management and access software solution: lowering the technical skill floor, reducing cost, enhancing user autonomy, optimizing data governance, and reimagining technical team structures in academia. The Hyperion data management platform was designed to meet these challenges in addition to usual considerations of data quality, security, access, stability, and scalability.

Results

Implemented between May 2019 and December 2020 at the Wilmot Cancer Institute, Hyperion includes a sophisticated custom validation and interface engine to process data from multiple sources, storing it in a database. Graphical user interfaces and custom wizards permit users to directly interact with data across operational, clinical, research, and administrative contexts. The use of multi-threaded processing, open-source programming languages, and automated system tasks (normally requiring technical expertise) minimizes costs. An integrated ticketing system and active stakeholder committee support data governance and project management. A co-directed, cross-functional team with flattened hierarchy and integration of industry software management practices enhances problem solving and responsiveness to user needs.

Discussion

Access to validated, organized, and current data is critical to the functioning of multiple domains in medicine. Although there are downsides to developing in-house customized software, we describe a successful implementation of custom data management software in an academic cancer center.
A Voice App Design for Heart Failure Self-Management: A Pilot Study
Authors: Barbaric Antonia , Munteanu Cosmin , Ross Heather J. , Cafazzo Joseph A.
Published: April 2022

There is a growing interest to investigate the feasibility of using voice user interfaces as a platform for digital therapeutics in chronic disease management. While mostly deployed as smartphone applications, some demographics struggle when using touch screens and often cannot complete tasks independently. This research aimed to evaluate how heart failure patients interacted with a voice app version of an already existing digital therapeutic, Medly, using a mixed-methods concurrent triangulation approach. The objective was to determine the acceptability and feasibility of the voice app by better understanding who this platform is be best suited for. Quantitative data included engagement levels and accuracy rates. Participants (n=20) used the voice app over a four week period and completed questionnaires and semi-structured interviews relating to acceptability, ease of use, and workload. The average engagement level was 73%, with a 14% decline between week one and four. The difference in engagement levels between the oldest and youngest demographic was the most significant, 84% and 43% respectively. The Medly voice app had an overall accuracy rate of 97.8% and was successful in sending data to the clinic. Users were accepting of the technology (ranking it in the 80th percentile) and felt it did not require a lot of work (2.1 on a 7-point Likert scale). However, 13% of users were less inclined to use the voice app at the end of the study. The following themes and subthemes emerged: (1) feasibility of clinical integration: user adaptation to voice app’s conversational style, device unreliability, and (2) voice app acceptability: good device integration within household, users blamed themselves for voice app problems, and voice app missing desirable user features. The voice app proved to be most beneficial to those who: are older, have flexible schedules, are confident with using technology, and are experiencing other medical conditions.
Psychosocial predictors of COVID-19 vaccine uptake among pregnant women: a cross-sectional study in Greece
Authors: Galanis Petros , Vraka Irene , Katsiroumpa Aglaia , Konstantakopoulou Olympia , Siskou Olga , Zogaki Eleftheria , Kaitelidou Daphne
Published: April 2022

Background

Unvaccinated pregnant women with symptomatic COVID-19 have been found to have a higher risk of iatrogenic preterm births, intensive care unit admission, and invasive ventilation.

Objective

To estimate the vaccination rate of pregnant women against the COVID-19 and to evaluate psychosocial factors associated with vaccine uptake among them.

Methods

We conducted an anonymous cross-sectional study with a convenience sample in Greece from December 2021 to March 2022. We measured socio-demographic data of pregnant women, COVID-19-related vaccination status, worry about the side effects of COVID-19 vaccines, trust in COVID-19 vaccines, and COVID-19-related stress.

Results

The study population included 812 pregnant women with a mean age of 31.6 years. Among the pregnant women, 58.6% had received a COVID-19 vaccine. The most important reasons that pregnant women were not vaccinated were doubts about the safety and effectiveness of COVID-19 vaccines (31.4%), fear that COVID-19 vaccines could be harmful to fetus (29.4%), and fear of adverse side effects of COVID-19 vaccines (29.4%). Increased danger and contamination fears, increased fears about economic consequences, and higher levels of trust in COVID-19 vaccines were related with COVID-19 vaccine uptake. On the other hand, increased compulsive checking and reassurance seeking and increased worry about the adverse side effects of COVID-19 vaccines reduced the likelihood of pregnant women being vaccinated against the COVID-19.

Conclusions

An understanding of the psychosocial factors associated with COVID-19 vaccine uptake in pregnant women is paramount to persuade women to get vaccinated against the COVID-19. There is a need for targeted educational campaigns to increase knowledge about COVID-19 vaccines and reduce COVID-19 vaccine hesitancy in pregnancy.
Household food insecurity risk indices for English neighbourhoods: measures to support local policy decisions
Authors: Smith Dianna M , Rixson Lauren , Grove Grace , Ziauddeen Nida , Vassilev Ivaylo , Taheem Ravita , Roderick Paul , Alwan Nisreen A
Published: April 2022

Background

In England, the responsibility to address food insecurity lies with local government, yet the prevalence of this social inequality is unknown in small subnational areas. In 2018 an index of small-area household food insecurity risk was developed and utilised by public and third sector organisations to target interventions; this measure needed updating to better support decisions in different contexts.

Methods

We held interviews with stakeholders (n=11) and completed a scoping review to identify appropriate variables to create an updated risk measure. We then sourced a range of open access secondary data to develop an indices of food insecurity risk in English neighbourhoods. Following a process of data transformation and normalisation, we tested combinations of variables and identified the most appropriate data to reflect household food insecurity risk in urban and rural areas.

Results

Eight variables, reflecting both household circumstances and local service availability, were separated into two domains with equal weighting for a new index, the Complex Index, and a subset of these make up the Simple Index. Within the Complex Index the Compositional Domain includes population characteristics while the Structural Domain reflects access to resources. The Compositional Domain is correlated well with free school meal eligibility (rs=0.705) and prevalence of childhood obesity (rs=0.641). This domain was the preferred measure for use in most areas when shared with stakeholders, and when assessed alongside other configurations of the variables. Areas of highest risk were most often located in the North of England.

Conclusion

We recommend the use of the Compositional Domain for all areas, with inclusion of the Structural Domain in rural areas where locational disadvantage makes it more difficult to access services. These measures can aid local policy makers and planners when allocating resources and interventions to support households who may experience food insecurity.
Longitudinal associations between physical activity and other health behaviours during the COVID-19 pandemic: A fixed effects analysis
Authors: Mitchell John J , Bu Feifei , Fancourt Daisy , Steptoe Andrew , Bone Jessica K
Published: April 2022

Background

Government enforced restrictions on movement during the COVID-19 pandemic are likely to have had profound impacts on the daily behaviours of many individuals, including physical activity (PA). Given the pre-pandemic evidence for associations between PA and other health behaviours, changes in PA during the pandemic may have been detrimental for other health behaviours. This study aimed to evaluate whether changes in PA during and after the first national lockdown in the United Kingdom (UK) were associated with concurrent changes in other health behaviours, namely alcohol consumption, sleep, nutrition quality, diet quantity and sedentary time.

Methods

Data were derived from the UCL COVID-19 Social Study. The analytical sample consisted of 52,784 adults followed weekly across 22 weeks of the pandemic from 23rd March to 23rd August 2020. Data were analysed using fixed effects regression.

Results

There was significant within-individual variation in both PA and other health behaviours throughout the study period. Increased PA was positively associated with improved sleep and nutrition quality. However, increases in PA also showed modest associations with increased alcohol consumption and sedentary time.

Conclusion

Our findings indicate that, whilst the first wave of COVID-19 restrictions were in place, increases in PA were associated with improved sleep and better diet. Encouraging people to engage in PA may therefore lead to positive change in other health behaviours in times of adversity. However, increases in PA were also associated with more engagement in the negative health behaviours of alcohol consumption and sedentary time. These associations could be a result of increases in available leisure time for many people during COVID-19 restrictions and require further investigation to inform future public health guidance.
The effect of the COVID-19 lockdown on mental health care use in South Africa: an interrupted time series analysis
Authors: Wettstein Anja , Tlali Mpho , Joska John A , Cornell Morna , Skrivankova Veronika W , Seedat Soraya , Mouton Johannes P , van den Heuvel Leigh L , Maxwell Nicola , Davies Mary-Ann , Maartens Gary , Egger Matthias , Haas Andreas D
Published: April 2022

Aims

In March 2020, South Africa introduced a lockdown in response to the COVID-19 pandemic, entailing the suspension of all non-essential activities and a complete ban of tobacco and alcohol sales. We studied the effect of the lockdown on mental health care utilisation rates in private-sector care in South Africa.

Methods

We did an interrupted time series analysis using insurance claims from January 1, 2017, to June 1, 2020 of beneficiaries 18 years or older from a large private sector medical aid scheme. We calculated weekly outpatient consultation and hospital admission rates for organic mental disorders, substance use disorders, serious mental disorders, depression, anxiety, other mental disorders, any mental disorder, and alcohol withdrawal syndrome. We calculated adjusted odds ratios (OR) for the effect of the lockdown on weekly outpatient consultation and hospital admission rates and the weekly change in rates during the lockdown until June 1, 2020.

Results

710,367 persons were followed up for a median of 153 weeks. Hospital admission rates (OR 0.38; 95% CI 0.33–0.44) and outpatient consultation rates (OR 0.74; 95% CI 0.63–0.87) for any mental disorder decreased substantially after the lockdown and did not recover to pre-lockdown levels until June 1, 2020. Health care utilisation rates for alcohol withdrawal syndrome doubled after the introduction of the lockdown, but the statistical uncertainty around the estimates was large (OR 2.24; 95% CI 0.69-7.24).

Conclusions

Reduced mental health care contact rates during the COVID-19 lockdown likely reflect a substantial unmet need for mental health services with potential long-term consequences for mental health patients and their families. Steps to ensure access and continuity of mental health services during future lockdowns should be considered.
Evaluation and risk communication of effects of alcohol exposure on disposable procedure masks and portable air purifiers
Authors: Ishigaki Yo , Yokogawa Shinji , Kato Tatsuo
Published: April 2022

As electret technology can drastically improve the filtration efficiency of disposable procedure masks and portable air purifiers, it is widely used to prevent the airborne transmission of SARS-CoV-2. Furthermore, alcohol disinfectants are now widely used in offices, hospitals, and homes to prevent contact infection; hence, there is a concern that alcohol exposure may inactivate electret. In this study, 5 types of high-efficiency particulate air filter (HEPA) air purifiers—of which, one was made of fiberglass HEPA filter—14 types of cubical masks, and 11 types of pleated masks available to Japanese citizens were subjected to discharge according to the alcohol exposure protocol based on ISO (International Organization for Standardization) 16890, and changes in filtration efficiency and pressure drop were measured before and after the discharge. The results revealed that 17 (68%) of the 25 masks exhibited a significant decrease in filtration efficiency; this decrease due to discharge depended on the filter material. However, masks of polypropylene, polyethylene, and poly-vinylidene-difluoride composite fiber materials exhibited no significant decrease in filtration efficiency. In addition, 4 (80%) of the 5 HEPA filters showed a 40–64% decrease in filtration efficiency, while no decrease in filtration efficiency was observed for the fiberglass HEPA filter. Our survey (n = 500 Japanese adults, including 30 healthcare professionals) revealed that approximately 90% of the general public was unaware that the performance of masks and air purifiers could be degraded by direct spraying of alcohol—for disinfection purposes—or vapor exposure. Furthermore, 36% of the surveyed healthcare professionals indicated that they had sprayed alcohol directly on their masks. Therefore, based on the results of this experiment, we examined effective consumer warnings that could be utilized on the product labels and in the instructions. The results showed that it would be more effective to detail the extent and duration of the adverse effects of disregarding the precautions.
Limited cross-variant immune response from SARS-CoV-2 Omicron BA.2 in naïve but not previously infected outpatients
Authors: Lee Hye Kyung , Knabl Ludwig , Walter Mary , Furth Priscilla A. , Hennighausen Lothar
Published: April 2022

Omicron is currently the dominant SARS-CoV-2 variant and several sublineages have emerged. Questions remain about the impact of previous SARS-CoV-2 exposure on cross-variant immune responses elicited by BA.2 infection compared to BA.1. Here we show that without previous history of COVID-19, BA.2 infection induces a reduced immune response against all variants of concern (VOC) compared to BA.1 infection. The absence of ACE2 binding in sera of previously naïve BA.1 and BA.2 patients indicates a lack of meaningful neutralization. In contrast, anti-spike antibody levels and neutralizing activity greatly increased in the BA.1 and BA.2 patients with a previous history of COVID-19. Transcriptome analyses of peripheral immune cells showed significant differences in immune response and specific antibody generation between BA.1 and BA.2 patients as well as significant differences in expression of specific immune genes. In summary, prior infection status significantly impacts the innate and adaptive immune response against VOC following BA.2 infection.
Syndemic violence victimization, alcohol and drug use, and HIV transmission risk behavior among transgender women in India: A cross-sectional, population-based study
Authors: Chakrapani Venkatesan , Lakshmi P.V.M. , Newman Peter A. , Kaur Jasvir , Tsai Alexander C. , Vijin P.P. , Singh Bhawani , Kumar Pradeep , Rajan Shobini , Kumar Rajesh
Published: April 2022

Introduction

Transgender women are disproportionately burdened by HIV. Co-occurring epidemics of adverse psychosocial exposures accelerate HIV sexual risk, including among transgender women; however, studies using additive models fail to examine synergies among psychosocial conditions that define a syndemic. We examined the impact of synergistic interactions among 4 psychosocial exposures on condomless anal sex (CAS) among a national probability sample of transgender women in India.

Methods

A probability-based sample of 4,607 HIV-negative transgender women completed the Indian Integrated Bio-behavioral Surveillance survey, 2014−2015. We used linear probability regression and logistic regression to assess 2-, 3-, and 4-way interactions among 4 exposures (physical and sexual violence, drug and alcohol use) on CAS.

Results

Overall, 27.3% reported physical and 22.3% sexual violence victimization (39.2% either physical or sexual violence), one-third (33.9%) reported frequent alcohol use and 11.5% illicit drug use. Physical violence was associated with twofold higher odds of CAS in the main effects model. Significant two- and three-way interactions were identified on both multiplicative and additive scales between physical violence and drug use; physical and sexual violence; physical violence, sexual violence, and alcohol use; and physical violence, alcohol and drug use.

Conclusions

Physical and sexual violence victimization, and alcohol and drug use are highly prevalent and synergistically interact to increase CAS among transgender women in India. Targeted and integrated initiatives to improve assessment of psychosocial comorbidities, to combat transphobic violence, and to provide tailored, trauma-informed alcohol and substance use treatment services may reduce HIV risk among transgender women.
Multiple mating rescues offspring sex ratio but not productivity in a haplodiploid exposed to developmental heat stress
Authors: Costa Sofia G , Magalhães Sara , Rodrigues Leonor R
Published: April 2022

Reproduction is generally more sensitive to high temperatures than survival and arguably a better predictor of the response of populations to climate change than survival estimates. Still, how temperature simultaneously impacts male and female reproductive success, the mating system and the operational sex ratio remains an open question.

Here, we addressed how a sublethal high temperature affects the reproductive system of the haplodiploid spider miteTetranychus urticae. Males and females maintained at 25°C or 36°C during development were paired and the fertility of both sexes, their mating and remating eagerness, and the paternity of the offspring of females with different mating histories were measured.

Female and male fertility decreased at 36°C compared to 25°C, resulting in lower offspring production and a more male-biased sex ratio, respectively, because of haplodiploidy. However, when females remated, the pattern of first male sperm precedence typically seen in this species was disrupted, with more than one male contributing to the offspring. This was accompanied by reduced mating eagerness in pairs with partially sterile males and increased remating eagerness in pairs in which at least one sex was partially sterile in the first mating.

The observed temperature-induced changes in pre- and post-copulatory traits allowed restoring the offspring sex ratio but did not lead to the recovery of offspring number.

Our results show that temperature induces changes in the spider mite mating behaviour and mating system, with potential impact on sexual selection and sexual conflict. However, such changes may not be sufficient to buffer the impact of extreme temperatures on their populations.
Polymer physics-based classification of neurons
Authors: Choi Kiri , Kim Won Kyu , Hyeon Changbong
Published: April 2022

Recognizing that diverse morphologies of neurons are reminiscent of structures of branched polymers, we put forward a principled and systematic way of classifying neurons that employs the ideas of polymer physics. In particular, we use 3D coordinates of individual neurons, which are accessible in recent neuron reconstruction datasets from electron microscope images. We numerically calculate the form factor,F(q), a Fourier transform of the distance distribution of particles comprising an object of interest, which is routinely measured in scattering experiments to quantitatively characterize the structure of materials. For a polymer-like object consisting ofnmonomers spanning over a length scale ofr, F(q) scales with the wavenumberq(= 2π/r) asF(q) ∼q−𝒟at an intermediate range ofq, where 𝒟 is the fractal dimension or the inverse scaling exponent (𝒟 =ν−1) characterizing the geometrical feature (r∼nν) of the object.F(q) can be used to describe a neuron morphology in terms of its size (Rn) and the extent of branching quantified by 𝒟. By defining the distance betweenF(q)s as a measure of similarity between two neuronal morphologies, we tackle the neuron classification problem. In comparison with other existing classification methods for neuronal morphologies, ourF(q)-based classification rests solely on 3D coordinates of neurons with no prior knowledge of morphological features. When applied to publicly available neuron datasets from three different organisms, our method not only complements other methods but also offers a physical picture of how the dendritic and axonal branches of an individual neuron fill the space of dense neural networks inside the brain.
Investigating tri-trophic interactions using bio-energetic demographic models
Authors: Passoni Gioele , Coulson Tim , Cagnacci Francesca , Hudson Peter , Stahler Daniel R. , Smith Douglas W. , Lachish Shelly
Published: April 2022

A central debate in ecology has been the long running discussion on the role of apex predators in affecting the abundance and dynamics of their prey. In terrestrial systems, research has primarily relied on correlational approaches, due to the challenge of implementing robust experiments with replication and appropriate controls. A consequence of this is that we largely suffer from a lack of mechanistic understanding of the population dynamics of interacting species that can be surprisingly complex.

Mechanistic models offer an opportunity to examine the causes and consequences of some of this complexity. We present a bioenergetic mechanistic model of a tri-trophic system where the primary vegetation resource follows a seasonal growth function, and the herbivore and carnivore species are modelled using two integral projection models (IPMs) with body mass as the phenotypic trait. Within each IPM, the demographic functions are structured according to bioenergetic principles, describing how animals acquire and transform resources into body mass, energy reserves and breeding potential. We parameterise this model to reproduce the population dynamics of grass, elk and wolves in northern Yellowstone (USA), and investigate the impact of wolf reintroduction on the system.

Our model generated predictions that closely matched the observed population sizes of elk and wolf in Yellowstone prior to and post wolf reintroduction. The introduction of wolves into our basal grass-elk bioenergetic model resulted in a population of 99 wolves, and a reduction in elk numbers by 61% (from 14,948 to 5,823) at equilibrium. In turn, vegetation biomass increased by approximately 25% in the growing season and more than 3-fold in the non-growing season. The addition of wolves to the model caused the elk population to shift from being food-limited to being predator-limited, and had a stabilising effect on elk numbers across different years. Wolf predation also led to a shift in the phenotypic composition of the elk population, via a small increase in elk average body mass.

Our model represents a novel approach to the study of predator-prey interactions. Explicitly considering and linking bioenergetics, population demography and body mass phenotypes can provide novel insights into the mechanisms behind complex ecosystem processes.
CHD-associated enhancers shape human cardiomyocyte lineage commitment
Authors: Armendariz Daniel A. , Goetsch Sean C. , Sundarrajan Anjana , Sivakumar Sushama , Wang Yihan , Xie Shiqi , Munshi Nikhil , Hon Gary C.
Published: April 2022

Enhancers orchestrate gene expression programs that drive multicellular development and lineage commitment. Thus, genetic variants at enhancers are thought to contribute to developmental diseases by altering cell fate commitment. However, while many variant-containing enhancers have been identified, studies to endogenously test the impact of these enhancers on lineage commitment have been lacking. We perform a single-cell CRISPRi screen to assess the endogenous roles of 25 enhancers and putative cardiac target genes implicated in genetic studies of congenital heart defects (CHD). We identify 16 enhancers whose repression leads to deficient differentiation of human cardiomyocytes (CMs). A focused CRISPRi validation screen shows that repression of TBX5 enhancers delays the transcriptional switch from mid- to late-stage CM states. Endogenous genetic deletions of two TBX5 enhancers phenocopy epigenetic perturbations. Together, these results identify critical enhancers of cardiac development and suggest that misregulation of these enhancers could contribute to cardiac defects in human patients.

HIGHLIGHTS

Single-cell enhancer perturbation screens during human cardiomyocyte differentiation.

Perturbation of CHD-linked enhancers/genes causes deficient CM differentiation.

Repression or knockout of TBX5 enhancers delays transition from mid to late CM states.

Deficient differentiation coincides with reduced expression of known cardiac genes.
Real-World Evidence of the Effectiveness and Safety of Generic Tofacitinib in Rheumatoid Arthritis Patients: A Retrospective, Single-Centre Analysis from Western India
Authors: Phatak Sanat , Khenat Aditya , Malandkar Mansi , Amin Sanjiv
Published: April 2022

Background

Generic tofacitinib has been available in India for more than a year and is widely used in rheumatoid arthritis (RA) therapy. There is scarce real-world data on its effectiveness and safety from India, especially given infection endemicity.

Methods

We retrospectively analysed records (demographic and clinical information, haematology and biochemistry, adverse events) of patients prescribed generic tofacitinib from a single centre in Mumbai, India. Disease activity was calculated using the disease activity score-28 and erythrocyte sedimentation rate (DAS28-ESR) and other tools, and we used paired T-tests for significant response. We defined clinical tofacitinib failure as a composite outcome, including clinician’s decision to change to an alternative disease-modifying anti-rheumatic drug (DMARD) or flare after self-withdrawal. We performed logistic regression and survival analysis for determinants of clinical failure.

Results

We reviewed records of 102 patients (92 female; median age: 53 years) with mean RA duration of 146 months. Thirteen had prior treatment with innovator tofacitinib. There was significant improvement in disease activity parameters at a mean duration of 186 days. No serious adverse events were reported; 4 patients had tuberculosis and 19 patients had mild COVID-19 while on treatment. Clinical failure was seen in 25 patients, and mean time to failure on survival analysis was 357 days. No baseline characteristic predicted clinical failure.

Interpretation

Generic tofacitinib showed good effectiveness and a tolerable adverse effect profile, despite tuberculosis endemicity andCOVID-19.. Setting up registries would be valuable in gaining more data on generic tofacitinib.

Key points

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There is scarce data from India regarding the use of tofacitinib in rheumatoid arthritis, despite widespread use

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In this retrospective analysis of 102 patients at a single centre, we found tofacitinib monotherapy was efficacious and tolerable.

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Tuberculosis was detected in four and nineteen patients had mild covid.
Outpatient and Home Pulmonary Rehabilitation Program Post COVID-19: A study protocol for clinical trial
Authors: Oliveira Luis V. F. , Oliveira Miriã C. , Lino Maria E. M. , Carrijo Marilucia M. , Afonso João Pedro R. , Moura Ricardo S. , Fonseca Adriano L. , Fonseca Daniela R. P. , Oliveira Luis Felipe R. J. , Galvão Letícia S. , Reis Bianca M. , Diniz Raphael H. C. O. , Bernardes Rubens R. , Póvoa Elisângela R. P. , Silva Anderson S. , Santos Dante B. , Maldaner Vinicius Z , Coutinho Jean Carlos , Modesto Guilherme Pacheco , Oliveira-Silva Iransé , Lopes Martins Rodrigo A. B. , Lopes Martins Patrícia S. L. , Oliveira Claudia S. , Júnior Gerson Cipriano , Vieira Rodolfo P , Palma Renata K. , Alves Larissa R. , Insalaco Giuseppe
Published: April 2022

Background

The coronavirus disease 2019 (COVID-19) is a widespread, highly contagious inflammatory process that causes respiratory, physical and psychological dysfunction. COVID-19 mainly affects the respiratory system and evolves in the acute phase from mild cases with common symptoms, such as fever, cough, and fatigue, to the moderate-to-severe form, causing massive alveolar damage resulting in dyspnea and hypoxemia that can rapidly progress to pneumonia, and acute respiratory distress syndrome. The acute form usually causes severe pulmonary sequelae such as pulmonary fibrosis or progression to organ failure, leading to worsening metabolic dysfunction and/or death.

Purpose

To verify the effects of an outpatient and home pulmonary rehabilitation program (PRP) on clinical symptoms, pulmonary function, physical activity level, functional status, autonomic activity, peripheral muscle strength, static and functional balance, functional mobility, anxiety and depression, post-traumatic stress, health-related quality of life, and survival of patients with sequelae from COVID-19.

Methods

This study will be a cohort, parallel, two-arm multicentric study, to be carried out in three clinical centers, with blind evaluation, with 06 weeks of training and follow-up. This study was designed according to the recommendations of the CONSORT statement. To be involved in this clinical study, according to the inclusion criteria, women and men aged between 16 and 75 years affected by COVID-19. The proposed PRP is based on the guidelines recommended by the Global Initiative for Chronic Obstructive Lung Disease and, consists of a combination of aerobic and muscle strengthening exercises, lasting six weeks, with a frequency of three times a week.

Discussion

In patients infected with COVID-19 with persistent symptoms and sequelae, PRP mainly seeks to improve dyspnea, relieve anxiety and depression, prevent, and reduce complications and/or dysfunctions, reduce morbidity and mortality, and improve health-related quality of life.

Trial registration

This study was registered at clinicaltrials.gov (ID: COVID-19 PULMONARY REHAB NCT04982042).
Second round of the interlaboratory comparison (ILC) exercise of SARS-CoV-2 molecular detection assays being used by 45 veterinary diagnostic laboratories in the US
Authors: Deng Kaiping , Uhlig Steffen , Goodman Laura B. , Ip Hon S. , Killian Mary Lea , Nemser Sarah M. , Ulaszek Jodie , Kiener Shannon , Kmet Matthew , Frost Kirstin , Hettwer Karina , Colson Bertrand , Nichani Kapil , Schlierf Anja , Tkachenko Andriy , Mlalazi-Oyinloye Mothomang , Scott Andrew , Reddy Ravinder , Tyson Gregory H.
Published: April 2022

The coronavirus disease 2019 (COVID-19) pandemic presents a continued public health challenge across the world. Veterinary diagnostic laboratories in the U.S. use real-time reverse transcriptase PCR (RT-PCR) for animal testing, and many are certified for testing human samples, so ensuring laboratories have sensitive and specific SARS-CoV-2 testing methods is a critical component of the pandemic response. In 2020, the FDA Veterinary Laboratory Investigation and Response Network (Vet-LIRN) led the first round of an Inter-Laboratory Comparison (ILC) Exercise to help laboratories evaluate their existing real-time RT-PCR methods for detecting SARS-CoV-2. The ILC1 results indicated that all participating laboratories were able to detect the viral RNA spiked in buffer and PrimeStore molecular transport medium (MTM). The current ILC (ILC2) aimed to extend ILC1 by evaluating analytical sensitivity and specificity of the methods used by participating laboratories to detect three SARS-CoV-2 variants (B.1, B.1.1.7 (Alpha) and B.1.351 (Beta)). ILC2 samples were prepared with RNA at levels between 10 to 10,000 copies per 50 μL MTM. Fifty-seven sets of results from 45 laboratories were qualitatively and quantitatively analyzed according to the principles of ISO 16140-2:2016. The results showed that over 95% of analysts detected the SARS-CoV-2 RNA in MTM at 500 copies or higher for all three variants. In addition, 81% and 92% of the analysts achieved a Level of Detection (LOD95eff. vol.) below 20 copies in the assays with nucleocapsid markers N1 and N2, respectively. The analytical specificity of the evaluated methods was over 99%. The study allowed participating laboratories to assess their current method performance, identify possible limitations, and recognize method strengths as part of a continuous learning environment to support the critical need for reliable diagnosis of COVID-19 in potentially infected animals and humans.
Implications of red state/blue state differences in COVID-19 death rates
Authors: Adams Mary L.
Published: April 2022

The study objective was to explore state death rates pre- and post- 4/19/2021 (date vaccines were assumed available) and the relative contributions of 3 factors to state death rates post- 4/19/2021: 1) vaccination rates, 2) prevalence of obesity, hypertension, diabetes, COPD, cardiovascular disease, and asthma and 3) red vs. blue states, to better understand options for reducing deaths. The ratio of red to blue state deaths/million was 1.6 pre-4/19/2021 and 2.3 between 4/19 and 2/28/2022 resulting in >222,000 extra deaths in red states or 305/ day. Adjusted betas from linear regression showed state vaccination rates had the strongest effect on death rates while red vs. blue states explained more of the difference in state death rates (60% vs. 46% for vaccination rates) with mean vaccination rates ~10% higher in blue states. Results suggest that increasing vaccination rates in red states could potentially save thousands of lives as the pandemic continues.
Molecular mechanisms of microbiome modulation by the eukaryotic secondary metabolite azelaic acid
Authors: Shibl Ahmed A. , Ochsenkühn Michael A. , Mohamed Amin R. , Isaac Ashley , Coe Lisa S. Y. , Yun Yejie , Skrzypek Grzegorz , Raina Jean-Baptiste , Seymour Justin R. , Afzal Ahmed J. , Amin Shady A.
Published: April 2022

Photosynthetic eukaryotes, such as microalgae and plants, foster fundamentally important relationships with their microbiome based on the reciprocal exchange of chemical currencies. Among these, the dicarboxylate metabolite azelaic acid (Aze) appears to play an important, but heterogeneous, role in modulating these microbiomes, as it is used as a carbon source for some heterotrophs but is toxic to others. However, the ability of Aze to promote or inhibit growth, as well as its uptake and assimilation mechanisms into bacterial cells are mostly unknown. Here, we use transcriptomics, transcriptional factor coexpression networks, uptake experiments, and metabolomics to unravel the uptake, catabolism and toxicity of Aze on two microalgal-associated bacteria,PhycobacterandAlteromonas, whose growth is promoted or inhibited by Aze, respectively. We identify the first putative Aze transporter in bacteria, a ‘C4-TRAP transporter’, and show that Aze is assimilated through fatty acid degradation, with further catabolism occurring through the glyoxylate and butanoate metabolism pathways when used as a carbon source.Phycobactertook up Aze at an initial uptake rate of 3.8×10-9nmol cell-1hr-1and utilized it as a carbon source in concentrations ranging from 10 μM-1mM, suggesting a broad range of acclimation to Aze availability. For inhibited bacteria, we infer that Aze inhibits the ribosome and/or protein synthesis and that a suite of efflux pumps is utilized to shuttle Aze outside the cytoplasm. We demonstrate that seawater amended with Aze becomes enriched in bacterial families that can catabolise Aze, which appears to be a different mechanism from that in soil, where modulation by the host plant is required. This study enhances our understanding of carbon cycling in the oceans and how microscale chemical interactions can structure marine microbial populations. In addition, our findings unravel the role of a key chemical currency in the modulation of eukaryote-microbiome interactions across diverse ecosystems.
NS1 from Two Zika Virus Strains Differently Interact with a Membrane: A Plausible Explanation for their Differential Virulence
Authors: Poveda-Cuevas Sergio A. , Barroso da Silva Fernando L. , Etchebest Catherine
Published: April 2022

Zika virus (ZIKV) from Uganda (UG) expresses a phenotype related to fetal loss whereas the variant from Brazil (BR) induces microcephaly in neonates. The differential virulence has a direct relation to biomolecular mechanisms that make one strain more aggressive than the other. The non-structural protein 1 (NS1) is a key viral toxin to comprehend these viral discrepancies because of its versatility in many processes of the virus life cycle. Here, we aim to examine through coarse-grained models and molecular dynamics simulations the protein-membrane interactions for both NS1ZIKV-UG and NS1ZIKV-BR dimers. A first evaluation allowed us to establish that the NS1 proteins, in the membrane presence, explore new conformational spaces when compared to systems simulated without a lipid bilayer. These events derive from both differential coupling patterns and discrepant binding affinities to the membrane. The N-terminal domain, intertwined loop, and greasy finger proposed previously as binding membrane regions were also computationally confirmed by us. The anchoring sites have aromatic and ionizable residues that manage the assembly of NS1 toward the membrane, especially for the Ugandan variant. Furthermore, the protein-membrane interaction induces perturbation in the distal part related to putative epitopes. These results open up new strategies for the treatment of flaviviruses.

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DeepTMHMM predicts alpha and beta transmembrane proteins using deep neural networks
Authors: Hallgren Jeppe , Tsirigos Konstantinos D. , Pedersen Mads Damgaard , Almagro Armenteros José Juan , Marcatili Paolo , Nielsen Henrik , Krogh Anders , Winther Ole
Published: April 2022

Transmembrane proteins span the lipid bilayer and are divided into two major structural classes, namely alpha helical and beta barrels. We introduce DeepTMHMM, a deep learning protein language model-based algorithm that can detect and predict the topology of both alpha helical and beta barrels proteins with unprecedented accuracy. DeepTMHMM (https://dtu.biolib.com/DeepTMHMM) scales to proteomes and covers all domains of life, which makes it ideal for metagenomics analyses.
IMPatienT: an Integrated web application to digitize, process and explore Multimodal PATIENt daTa
Authors: Meyer Corentin , Romero Norma Beatriz , Evangelista Teresinha , Cadot Brunot , Laporte Jocelyn , Jeannin-Girardon Anne , Collet Pierre , Chennen Kirsley , Poch Olivier
Published: April 2022

Medical acts, such as imaging, lead to the production of several medical text report that describes the relevant findings. This induces multimodality in patient data by linking image data to free-text and consequently, multimodal data have become central to drive research and improve diagnosis. However, the exploitation of patient data is challenging as the ecosystem of analysis tools is fragmented depending on the type of data (images, text, genetics), the task (processing, exploration) and domains of interest (clinical phenotype, histology). To address the challenges, we present IMPatienT (Integrated digitalMultimodalPATIENt daTa), a simple, flexible and open-source web application to digitize, process and explore multimodal patient data. IMPatienT has a modular architecture to: (i) create a standard vocabulary for a domain, (ii) digitize and process free-text data, (iii) annotate images and perform image segmentation, and (iv) generate a visualization dashboard and perform diagnosis suggestions. We showcased IMPatienT on a corpus of 40 simulated muscle biopsy reports of congenital myopathy patients. As IMPatienT relies on a user-designed vocabulary, it can be adapted to any domain of research and can be used as a patient registry for exploratory data analysis (EDA). A demo instance of the application is available athttps://impatient.lbgi.fr/.
Hypothalamic gene network dysfunction is associated with cognitive decline and body weight loss in Alzheimer’s disease mice
Authors: Dai M , Dunn AR , Hadad N , Zhang J-G , Poirion OB , Korgan AC , White BS , Philip VM , Neuner SM , O’Connell KMS , Kaczorowski CC
Published: April 2022

Recent studies, both clinical and experimental, indicate that many neurodegenerative disorders including Alzheimer’s disease (AD) often display coexisting metabolic dysfunctions, which may exacerbate neurological symptoms. The hypothalamus is a brain region highly involved in maintaining metabolic and other homeostatic processes and is known to be involved in the etiology of AD, although the role of hypothalamic dysfunction in the onset, progression, and severity of AD is poorly understood. In this study, we demonstrate that our new model of genetic diversity in AD, the AD-BXDs, exhibits non-cognitive symptoms consistent with hypothalamic dysfunction and examined hypothalamic bulk RNA sequencing data in the AD-BXD panel to investigate how the AD transgene impacts gene expression profiles in the hypothalamus. Mostly notably, we identified strong neuroinflammatory signatures from the hypothalamus in the AD-BXDs as early as six months of age. A functionally unknown WGCNA module showed correlation to female body weight and contextual fear acquisition. Eigengene expression of microglial/macrophagic modules and their hub gene expressions were correlated to cognitive phenotypes. From these analyses, we nominatedPlekandLaptm5as new targets to attenuate neuroinflammation in AD.