Before and after COVID-19: Changes in symptoms and diagnoses in 13,033 adults.

BACKGROUND: Most patients with COVID-19 report experiencing one or more symptoms after acute infection subsides, known as post-acute sequelae of SARS-CoV-2 infection (PASC). Though research has examined PASC after acute COVID-19, few studies have examined PASC over a longer follow-up duration or accounted for rates of symptoms and diagnoses before COVID-19 infection, and included those not actively seeking treatment for PASC. To determine what symptoms and diagnoses are occurring at higher rates after acute COVID-19 infection from a more inclusive sample, we extracted electronic hospital records (EHR) data from 13,033 adults with previously known diagnoses and symptoms. METHODS: The sample was comprised of patients who had a positive PCR test for SARS-CoV-2 between March 1, 2020, and December 31, 2020, and follow-up was conducted through November 29, 2021. All patients in the sample had medical appointments ≥4 weeks before and ≥4 weeks after their positive PCR test. At these appointments, all ICD-10 codes recorded in the EHR were classified into 21 categories based on the literature and expert review. Conditional logistic regression models were used to quantify the odds of these symptoms and diagnostic categories following COVID-19 infection relative to visits occurring before infection. The sample was comprised of 28.0% adults over 65 and was 57.0% female. After the positive PCR test, the most recorded diagnoses and symptoms were dyspnea and respiratory failure, myositis, musculoskeletal pain/stiffness, anxiety, and depression. RESULTS: Results from regression analyses showed increased odds of diagnosis for 15 of the 21 categories following positive PCR. Relative to pre-COVID, the diagnoses and symptoms with the greatest odds after a positive PCR test were loss of smell or taste [OR (95% CI) = 6.20 (3.18-12.09)], pulmonary fibrosis [3.50 (1.59-7.68)], and dyspnea/respiratory failure [2.14 (1.92-2.40)]. Stratification of these analyses by age, gender, race, and ethnicity showed similar results. CONCLUSION: The increased symptoms and diagnoses detected in the current study match prior analyses of PASC diagnosis and treatment-seeking patients. The current research expands upon the literature by showing that these symptoms are more frequently detected following acute COVID-19 than before COVID-19. Further, our analyses provide a broad snapshot of the population as we were able to describe PASC among all patients who tested positive for COVID-19.

Cobdock: an accurate and practical machine learning-based consensus blind docking method.

Probing the surface of proteins to predict the binding site and binding affinity for a given small molecule is a critical but challenging task in drug discovery. Blind docking addresses this issue by performing docking on binding regions randomly sampled from the entire protein surface. However, compared with local docking, blind docking is less accurate and reliable because the docking space is too largetly sampled. Cavity detection-guided blind docking methods improved the accuracy by using cavity detection (also known as binding site detection) tools to guide the docking procedure. However, it is worth noting that the performance of these methods heavily relies on the quality of the cavity detection tool. This constraint, namely the dependence on a single cavity detection tool, significantly impacts the overall performance of cavity detection-guided methods. To overcome this limitation, we proposed Consensus Blind Dock (CoBDock), a novel blind, parallel docking method that uses machine learning algorithms to integrate docking and cavity detection results to improve not only binding site identification but also pose prediction accuracy. Our experiments on several datasets, including PDBBind 2020, ADS, MTi, DUD-E, and CASF-2016, showed that CoBDock has better binding site and binding mode performance than other state-of-the-art cavity detector tools and blind docking methods.

Sexual beliefs in couple relationships: Exploring the pathways of mindfulness, communication, and sexual functioning on sexual passion and satisfaction.

Two types of sexual beliefs, growth and destiny, have been found in past research to be differentially associated with sexual and relationship outcomes; however, past research has not explored these beliefs with dyadic data nor considered common intervening variables that might be pathways through which beliefs influence outcomes. Consequently, using the sexual wholeness model, we analyzed how couples' specific sexual beliefs (growth and destiny) influenced their sexual mindfulness, communication, and functioning within their couple relationships and how each of these variables influenced sexual satisfaction and harmonious sexual passion. Using a national sample of dyadic data from 964 sexually active individuals (482 heterosexual couples) who had been in a committed relationship for at least 2 years, we evaluated an actor/partner structural equation model with distinguishable dyads. We found that while sexual growth and destiny beliefs had a significant association with sexual mindfulness, communication, and functioning for both partners, sexual beliefs had no direct association with sexual satisfaction and harmonious sexual passion. Because growth beliefs had strong associations with sexual communication, it may be beneficial to help couples identify their implicit beliefs and encourage the development of sexual growth beliefs.

The effects of social support and support types on continuous positive airway pressure use after 1month of therapy among adults with obstructive sleep apnea.

BACKGROUND: The relationship between perceived social support and continuous positive airway pressure remains understudied among individuals with obstructive sleep apnea. The aim of this prospective cohort study was to determine if baseline perceived social support and subtypes predict regular continuous positive airway pressure use after 1month of therapy. METHODS: Adults with obstructive sleep apnea initiating continuous positive airway pressure therapy were recruited from sleep clinics in New York City. Demographics, medical history, and comorbidities were obtained from patient interview and review of medical records. Objective continuous positive airway pressure adherence data was collected at the first clinical follow-up. RESULTS: Seventy-five participants (32% female; non-Hispanic Black 41%; mean age of 56 ± 14years) provided data. In adjusted analyses, poorer levels of overall social support, and subtypes including informational/emotional support, and positive social interactions were associated with lower continuous positive airway pressure use at 1month. Relative to patients reporting higher levels of support, participants endorsing lower levels of overall social support, positive social interaction and emotional/informational support had 1.6 hours (95% CI: 0.5,2.7, hours; p = .007), 1.3 hours (95% CI: 0.2,2.4; p = .026), and 1.2 hours (95% CI: 0.05,2.4; p = .041) lower mean daily continuous positive airway pressure use at 1month, respectively. CONCLUSION: Focusing on social support overall and positive social interaction particularly, could be an effective approach to improve continuous positive airway pressure adherence in patients at risk of suboptimal adherence.

Married women's response to spousal pornography use: A grounded theory.

Empirical research suggests that married women may more commonly experience spousal pornography use as a relational attachment threat and are more likely to experience negative relational outcomes such as distress and loss of trust. The purpose of this study was to develop a grounded theory of married women's response to the discovery or disclosure of spousal pornography use. This study included the experiences of 30 married women who reported spousal pornography use as a threat to relational attachment, who chose to remain with their spouse, and who reported evidence of individual and relational healing thereafter. The research question, "How do married women describe the experience of learning of their spouse's pornography use and the individual and relationship sequelae that follow?" was explored using grounded theory methods to analyze deidentified blogpost accounts emphasizing response to a spouse's pornography use. The results describe a process model highlighting three interrelated informant categories-emotional response, mental response, and physical response-and one resultant category-behavioral response. Implications include (a) the importance of open communication regarding pornography use within relationships, (b) the necessity for individual and relational healing following betrayal trauma, and (c) the role of therapeutic intervention in shaping adaptive healing processes.

Talcarpones A and B: bisnaphthazarin-derived metabolites from the Australian fungus Talaromyces johnpittii sp. nov. MST-FP2594.

Talcarpones A (1) and B (2) are rare bisnaphthazarin derivatives produced by Talaromyces johnpittii (ex-type strain MST-FP2594), a newly discovered Australian fungus, which is formally described and named herein. The talcarpones were isolated along with the previously reported monomeric naphthoquinone, aureoquinone (3), suggesting a biosynthetic link between these metabolites. Talcarpone A is a lower homologue of hybocarpone (4), which was first isolated from a mycobiont of the lichen Lecanora hybocarpa. The structures of 1 and 2 were elucidated by detailed spectroscopic analysis, molecular modelling and comparison with literature data. Talcarpones 1 and 2 exhibited moderate antifungal activity (MIC 0.78-3.1 µg ml-1) and weak activity against Gram-positive bacteria (MIC 13-25 µg ml-1). The talcarpones also demonstrated noteworthy chemical reactivities, with 2 converting rapidly to 1, which in turn converted slowly to the highly coloured 3. These post-biosynthetic reactions point to a potential ecological role for the talcarpones in providing ongoing (slow-release) physicochemical protection for T. johnpittii against solar irradiation.

Protocol for randomized personalized trial for stress management compared to standard of care.

Stress is a significant public health burden in the United States, with most Americans reporting unhealthy levels of stress. Stress management techniques include various evidence-based treatments shown to be effective but with heterogeneous treatment responses, indicating a lack of uniform benefits for all individuals. Designed to assess a participant's response to a specific intervention, personalized (N-of-1) trials provide guidance for which treatment (s) work (s) best for the individual. Prior studies examining the effects of mindfulness meditation, yoga, and walking for stress reduction found all three interventions to be associated with significant reductions in self-reported measures of stress. Delivering these treatments using a personalized trial approach has the potential to assist clinicians in identifying the best stress management techniques for individuals with persistently high stress while fostering treatment decisions that consider their personal condition/barriers. This trial will evaluate a personalized approach compared to standard of care for three interventions (guided mindfulness meditation; guided yoga; and guided brisk walking) to manage perceived stress. Participants will respond to daily surveys and wear a Fitbit device for 18 weeks. After a 2-week baseline period, participants in the personalized trial groups will receive 12 weeks of interventions in randomized order, while participants in the standard-of-care group will have access to all interventions for self-directed stress management. After intervention, all participants will undergo 2 weeks of observation, followed by two additional weeks of the stress management intervention of their choosing while continuing outcome measurement. At study completion, all participants will be sent a satisfaction survey. The primary analysis will compare perceived stress levels between the personalized and standard of care arms. The results of this trial will provide further support for the use of personalized designs for managing stress. Clinical Trial Registration: clinicaltrials.gov, NCT05408832. Protocol version: 9/14/2022, 21-0968-MRB.

A Series of Personalized Virtual Light Therapy Interventions for Fatigue: Feasibility Randomized Crossover Trial for N-of-1 Treatment.

BACKGROUND: Fatigue is one of the most common symptoms treated in primary care and can lead to deficits in mental health and functioning. Light therapy can be an effective treatment for symptoms of fatigue; however, the feasibility, scalability, and individual-level heterogeneity of light therapy for fatigue are unknown. OBJECTIVE: This study aimed to evaluate the feasibility, acceptability, and effectiveness of a series of personalized (N-of-1) interventions for the virtual delivery of bright light (BL) therapy and dim light (DL) therapy versus usual care (UC) treatment for fatigue in 60 participants. METHODS: Participants completed satisfaction surveys comprising the System Usability Scale (SUS) and items assessing satisfaction with the components of the personalized trial. Symptoms of fatigue were measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) daily, PROMIS weekly, and ecological momentary assessment (EMA) questionnaires delivered 3 times daily. Comparisons of fatigue between the BL, DL, and UC treatment periods were conducted using generalized linear mixed model analyses between participants and generalized least squares analyses within individual participants. RESULTS: Participants rated the usability of the personalized trial as acceptable (average SUS score=78.9, SD 15.6), and 92% (49/53) of those who completed satisfaction surveys stated that they would recommend the trial to others. The levels of fatigue symptoms measured using the PROMIS daily fatigue measure were lower or improved in the BL (B=-1.63, 95% CI -2.63 to -0.63) and DL (B=-1.44, 95% CI -2.50 to -0.38) periods relative to UC. The treatment effects of BL and DL on the PROMIS daily measure varied among participants. Similar findings were demonstrated for the PROMIS weekly and EMA measures of fatigue symptoms. CONCLUSIONS: The participant scores on the SUS and satisfaction surveys suggest that personalized N-of-1 trials of light therapy for fatigue symptoms are both feasible and acceptable. Both interventions produced significant (P<.05) reductions in participant-reported PROMIS and EMA fatigue symptoms relative to UC. However, the heterogeneity of these treatment effects across participants indicated that the effect of light therapy was not uniform. This heterogeneity along with high ratings of usability and satisfaction support the use of personalized N-of-1 research designs in evaluating the effect of light therapy on fatigue for each patient. Furthermore, the results of this trial provide additional support for the use of a series of personalized N-of-1 research trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04707846; https://clinicaltrials.gov/ct2/show/NCT04707846.

The effect of a multi-component behavior change technique intervention on medication adherence among individuals on primary prevention statin therapy: a dose-finding protocol.

BACKGROUND: In the USA, the primary cause of death and morbidity continues to be cardiovascular disease (CVD). Numerous trials have shown that statin medication reduces the likelihood of CVD events; it is a cornerstone of CVD prevention. However, studies have also indicated that up to 60% of the estimated 26.8 million Americans prescribed primary prevention statin treatment are nonadherent during the first year. Multi-component behavioral change technique (BCT) therapies have shown moderate promise in improving medication adherence as well as other positive health behaviors (such as physical activity). However, no research has looked at the duration of multi-component BCT intervention needed to result in a clinically significant improvement in statin adherence behaviors. This study aims to determine the necessary dose of a multi-component BCT intervention (defined as duration in weeks) to promote adherence to statin medication among those on primary prevention statin treatment by utilizing the modified time-to-event continuous reassessment method (TiTE-CRM). METHODS AND DESIGN: The study will utilize the modified TiTE-CRM in 42 participants, recruited in 14 cohorts of 3 participants each. The goal of this analysis is to identify the minimum effective dose (MED) of a multi-behavior change technique (BCT) intervention required to increase adherence to statins by 20% between baseline and follow-up periods. Using the TiTE-CRM method, the dose of the behavior intervention in weeks will be assigned to each cohort based on the performance of the prior cohort. At the end of the study, the intervention dose that has been found to be associated with a 20% increase in statin adherence among 80% of participants assigned to that dose will be identified as the MED. DISCUSSION: If successful, the current trial will provide additional guidance to researchers and clinicians seeking to increase statin medication adherence using a BCT intervention by identifying the dose (i.e., the duration) of an intervention required to meaningfully increase adherence. TRIAL REGISTRATION: ClinicalTrials.gov NCT05273736. Registered on March 10, 2022. https://www. CLINICALTRIALS: gov/ct2/show/NCT05273736.

Natural products as anthelmintics: safeguarding animal health.

Covering literature to December 2022This review provides a comprehensive account of all natural products (500 compounds, including 17 semi-synthetic derivatives) described in the primary literature up to December 2022, reported to be capable of inhibiting the egg hatching, motility, larval development and/or the survival of helminths (i.e., nematodes, flukes and tapeworms). These parasitic worms infect and compromise the health and welfare, productivity and lives of commercial livestock (i.e., sheep, cattle, horses, pigs, poultry and fish), companion animals (i.e., dogs and cats) and other high value, endangered and/or exotic animals. Attention is given to chemical structures, as well as source organisms and anthelmintic properties, including the nature of bioassay target species, in vivo animal hosts, and measures of potency.

A Series of Remote Melatonin Supplement Interventions for Poor Sleep: Protocol for a Feasibility Pilot Study for a Series of Personalized (N-of-1) Trials.

BACKGROUND: Poor sleep, defined as short-duration or poor-quality sleep, is a frequently reported condition with many deleterious effects including poorer cognitive functioning, increased accidents, and poorer health. Melatonin has been shown to be an efficacious treatment to manage symptoms of poor sleep. However, the treatment effects of melatonin on sleep can vary greatly between participants. Personalized, or N-of-1, trial designs represent a method for identifying the best treatment for individual participants. Although using N-of-1 trials of melatonin to treat poor sleep is possible, the feasibility, acceptability, and effectiveness of N-of-1 trials using melatonin are unknown. Using the National Institutes of Health Stage Model for Behavioral Intervention Development, a stage IB (intervention refinement, modification, and adaptation and pilot testing) design appeared to be needed to address these feasibility questions. OBJECTIVE: This trial series evaluates the feasibility, acceptability, and effectiveness of a series of personalized interventions for remote delivery of melatonin dose (3 and 0.5 mg) versus placebo supplements for self-reported poor sleep among 60 participants. The goal of this study is to provide valuable information about implementing remote N-of-1 randomized controlled trials to improve poor sleep. METHODS: Participants will complete a 2-week baseline followed by six 2-week alternating intervention periods of 3 mg of melatonin, 0.5 mg of melatonin, and placebo. Participants will be randomly assigned to 2 intervention orders. The feasibility and acceptability of the personalized trial approach will be determined with participants' ratings of usability and satisfaction with the remote, personalized intervention delivery system. The effectiveness of the intervention will be measured using participants' self-reported sleep quality and duration and Fitbit tracker-measured sleep duration and efficiency. Additional measures will include ecological momentary assessment measures of fatigue, stress, pain, mood, concentration, and confidence as well as measures of participant adherence to the intervention, use of the Fitbit tracker, and survey data collection. RESULTS: As of the submission of this protocol, recruitment for this National Institutes of Health stage IB personalized trial series is approximately 78.3% complete (47/60). We expect recruitment and data collection to be finalized by June 2023. CONCLUSIONS: Evaluating the feasibility, acceptability, and effectiveness of a series of personalized interventions of melatonin will address the longer term aim of this program of research-is integrating N-of-1 trials useful patient care? The personalized trial series results will be published in a peer-reviewed journal and will follow the CONSORT (Consolidated Standards of Reporting Trials) extension for N-of-1 trials (CENT 2015) reporting guidelines. This trial series was approved by the Northwell Health institutional review board. TRIAL REGISTRATION: ClinicalTrials.gov NCT05349188; https://www.clinicaltrials.gov/study/NCT05349188. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45313.

Turonicin A, an Antifungal Linear Polyene Polyketide from an Australian Streptomyces sp.

Turonicin A (1) was isolated from Streptomyces sp. MST-123921, which was recovered from soil collected on the banks of the Turon River in New South Wales, Australia. Turonicin A (1) is an amphoteric linear polyene polyketide featuring independent pentaene and tetraenone chromophores and is structurally related to linearmycins A-C (2-4). The structure of 1 was determined by detailed spectroscopic analysis and comparison to literature data. Bioinformatic analysis of the linearmycin biosynthetic gene cluster also allowed the previously unresolved absolute stereostructures of 2-4 to be elucidated. Turonicin A (1) exhibited very potent activity against the fungi Candida albicans (MIC 0.0031 µg/mL, 2.7 nM) and Saccharomyces cerevisiae (MIC 0.0008 µg/mL, 0.7 nM), moderate activity against the bacteria Bacillus subtilis (MIC 0.097 µg/mL, 85 nM) and Staphylococcus aureus (MIC 0.39 µg/mL, 340 nM), and no cytotoxicity against human fibroblasts, making it an attractive candidate for further development as a potential next-generation antibiotic scaffold.

Nanoscaled Discovery of a Shunt Rifamycin from Salinispora arenicola Using a Three-Color GFP-Tagged Staphylococcus aureus Macrophage Infection Assay.

Antimicrobial resistance has emerged as a global public health threat, and development of novel therapeutics for treating infections caused by multi-drug resistant bacteria is urgent. Staphylococcus aureus is a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival of S. aureus in macrophages contributes to immune evasion, dissemination, and resilience to antibiotic treatment. Here, we present a confocal fluorescence imaging assay for monitoring macrophage infection by green fluorescent protein (GFP)-tagged S. aureus as a front-line tool to identify antibiotic leads. The assay was employed in combination with nanoscaled chemical analyses to facilitate the discovery of a new, active rifamycin analogue. Our findings indicate a promising new approach for the identification of antimicrobial compounds with macrophage intracellular activity. The antibiotic identified here may represent a useful addition to our armory in tackling the silent pandemic of antimicrobial resistance.

Accumulation and transport of nutrient and pollutant elements in riparian soils, sediments, and river waters across the Thames River Watershed, Connecticut, USA.

Understanding drivers of nutrient and pollutant elements (NPEs) in soils, sediments, and river water is important for protecting water resources and aquatic ecosystems. The objectives of this study were to quantify accumulation and transport of NPEs (P, As, Cd, Cu, Ni, Pb, and Zn) in riparian soils, sediments, river water, and watershed-scale exports within seven post-industrial subwatersheds of the Thames River, Connecticut, USA. Suspended sediments and river water samples were collected from February 2019 to January 2020. Arsenic concentrations in soil (6 to 18 mg kg-1) and sediments (8 to 85 mg kg-1) generally exceeded state and federal EPA quality targets but not river water. Elevated Pb 'hot spots' occurred in some riparian soils (>2000 mg kg-1) and sediments (>200 mg kg-1), but the other NPEs concentrations were below toxic thresholds. Riparian soil concentrations and watershed land cover were generally weak predictors for NPE concentrations in bottom sediments, suspended sediments, and river water. DOC, Mn, and Fe concentrations were important predictors for area-normalized dissolved and sediment-bound export of NPEs across the seven watersheds. Dissolved export was greater than sediment export for Mn, P, As, Cd, Cu, and Ni but not for Fe, Pb, and Zn. Watersheds with higher farmland had higher P river water concentrations, but the larger, more urbanized watershed had the highest total and area-normalized P export. An estuarine sediment core that captures sediment from the whole watershed and spans pre-industrial conditions through present shows that export of most NPEs has decreased since its peak, but all remain above baseline throughout the Thames River watershed. Future constraints on surface soil-river exchange and erosion inputs are needed to investigate rates of NPE sourcing to the watersheds.

Protocol of a feasibility study of a virtual personalized (N-of-1) trial for increasing low-intensity physical activity in older adults via habit formation.

Background: Personalized interventions that can be delivered remotely are needed to increase physical activity (PA) in older adults to reduce risk of CV disease and mortality. Prior research indicates that Behavioral Change Techniques (BCTs) (e.g., goal setting, self-monitoring, behavioral repetition) can instill a habit for increasing daily walking. However, past interventions relied on between-subject randomized clinical trials, which can only only be informative about response of the hypothetical average person. Personalized trial designs can identify the benefits of an intervention for a specific individual although extended periods are required for collecting frequent measurements within-subject. Advances in remote, virtual technologies (e.g., text messaging, activity trackers), integrated with automatic platforms, can meet these requirements because they capacitate delivery of BCT interventions, and collection of data during daily life without personal contact. This Stage I-b trial is designed test whether a virtual, personalized intervention is feasible and acceptable to older adults, can elicit participant adherence and exhibit preliminary evidence for efficacy. Methods: A series of up to 60 single-arm, personalized trials, involving no personal contact, will recruit adults, 45-75 years of age, to wear an activity tracker during a 2-week baseline and a 10-week intervention. Five BCT prompts to execute a walking plan will be delivered on a daily basis during the intervention phase. Participants will rate satisfaction with personalized trial components and whether automaticity of the walking plan can be achieved. Step-counts, adherence to the walking plan and self-monitoring of step-count will also be recorded.

FLONE: fully Lorentz network embedding for inferring novel drug targets.

Motivation: To predict drug targets, graph-based machine-learning methods have been widely used to capture the relationships between drug, target and disease entities in drug-disease-target (DDT) networks. However, many methods cannot explicitly consider disease types at inference time and so will predict the same target for a given drug under any disease condition. Meanwhile, DDT networks are usually organized hierarchically carrying interactive relationships between involved entities, but these methods, especially those based on Euclidean embedding cannot fully utilize such topological information, which might lead to sub-optimal results. We hypothesized that, by importing hyperbolic embedding specifically for modeling hierarchical DDT networks, graph-based algorithms could better capture relationships between aforementioned entities, which ultimately improves target prediction performance. Results: We formulated the target prediction problem as a knowledge graph completion task explicitly considering disease types. We proposed FLONE, a hyperbolic embedding-based method based on capturing hierarchical topological information in DDT networks. The experimental results on two DDT networks showed that by introducing hyperbolic space, FLONE generates more accurate target predictions than its Euclidean counterparts, which supports our hypothesis. We also devised hyperbolic encoders to fuse external domain knowledge, to make FLONE enable handling samples corresponding to previously unseen drugs and targets for more practical scenarios. Availability and implementation: Source code and dataset information are at: https://github.com/arantir123/DDT_triple_prediction. Supplementary information: Supplementary data are available at Bioinformatics Advances online.