Unraveling the genetic variations underlying virulence disparities among SARS-CoV-2 strains across global regions: insights from Pakistan.

Over the course of the COVID-19 pandemic, several SARS-CoV-2 variants have emerged that may exhibit different etiological effects such as enhanced transmissibility and infectivity. However, genetic variations that reduce virulence and deteriorate viral fitness have not yet been thoroughly investigated. The present study sought to evaluate the effects of viral genetic makeup on COVID-19 epidemiology in Pakistan, where the infectivity and mortality rate was comparatively lower than other countries during the first pandemic wave. For this purpose, we focused on the comparative analyses of 7096 amino-acid long polyprotein pp1ab. Comparative sequence analysis of 203 SARS-CoV-2 genomes, sampled from Pakistan during the first wave of the pandemic revealed 179 amino acid substitutions in pp1ab. Within this set, 38 substitutions were identified within the Nsp3 region of the pp1ab polyprotein. Structural and biophysical analysis of proteins revealed that amino acid variations within Nsp3's macrodomains induced conformational changes and modified protein-ligand interactions, consequently diminishing the virulence and fitness of SARS-CoV-2. Additionally, the epistatic effects resulting from evolutionary substitutions in SARS-CoV-2 proteins may have unnoticed implications for reducing disease burden. In light of these findings, further characterization of such deleterious SARS-CoV-2 mutations will not only aid in identifying potential therapeutic targets but will also provide a roadmap for maintaining vigilance against the genetic variability of diverse SARS-CoV-2 strains circulating globally. Furthermore, these insights empower us to more effectively manage and respond to potential viral-based pandemic outbreaks of a similar nature in the future.

Database Commons: A Catalog of Worldwide Biological Databases.

Biological databases serve as a global fundamental infrastructure for the worldwide scientific community, which dramatically aid the transformation of big data into knowledge discovery and drive significant innovations in a wide range of research fields. Given the rapid data production, biological databases continue to increase in size and importance. To build a catalog of worldwide biological databases, therefore, we curate a total of 5825 biological databases from 8931 publications, which are geographically distributed in 72 countries/regions and developed by 1975 institutions (as of September 20, 2022). We further devise a z-index, a novel index to characterize the scientific impact of a database, and rank all these biological databases as well as their hosting institutions and countries in terms of citation and z-index. Consequently, we present a series of statistics and trends of worldwide biological databases, yielding a global perspective to better understand their status and impact for life and health sciences. An up-to-date catalog of worldwide biological databases as well as their curated meta-information and derived statistics is publicly available at Database Commons (https://ngdc.cncb.ac.cn/databasecommons/).

Phenomenological support for escape theory: a qualitative study using explicitation interviews with emotional eaters.

The current study explored the phenomenology of emotional eating, that is, the descriptive knowledge of what one perceives, senses, and knows in one's immediate awareness and experience during emotional eating. Eight individuals with emotional eating were interviewed twice using explicitation interviewing. Data were analyzed using thematic analysis, which resulted in nine themes describing the diachronic (or temporal) unfolding of emotional eating and several sub-themes that described various synchronic (or experiential) dimensions of this unfolding. The core findings of this study support the escape theory of emotional eating and recommend future directions to investigate the self-related shifts proposed by this theory. Namely, the findings show that individuals tend to use food to regulate their emotions by reducing the unpleasant experience of negative emotions and the associated unpleasant narrative processing or ruminations about stressors that caused the negative emotions. This then leads to an urge to eat associated with a desire for the sensory experience of eating. Eating then enables individuals to reduce thoughts about their stressors and bring themselves into the present moment through embodiment. Future quantitative research could investigate this mechanism of shifting from narrative to embodied processing to regulate emotions in emotional eating to develop treatment programs, such as mindfulness-based programs, that could encourage such a shift and emotion regulation without the use of food.

Emotional eating, or overeating when feeling negative emotions, is problematic because it is linked with being overweight or having obesity, diabetes, and heart disease. So far, several theories have been proposed to explain the psychological experiences of a person that leads them to emotionally eat. In this study, we explored the subjective experience, or phenomenology, of emotional eating. We interviewed eight individuals with emotional eating using a method called explicitation interviewing, which was developed to allow an interviewer to help an individual describe their subjective experience or phenomenology of a particular event or experience. Upon analyzing the data, we found support for the escape theory of emotional eating, which states that individuals eat to regulate their emotions by escaping the unpleasant feelings and thoughts that they experience while feeling negative emotions. We found that emotional eaters escape unpleasant thoughts and feelings about their past, future, or identity by shifting their attention away from these thoughts and emotions and towards the bodily sensations that they feel in the present moment while eating. Our findings encourage future studies that further investigate these shifts in attention to develop treatment methods that can help individuals regulate their emotions without using food.

Genomic Epidemiology of SARS-CoV-2 in Pakistan.

COVID-19 has swept globally and Pakistan is no exception. To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan, we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1, 2020. We identified a total of 347 mutated positions, 31 of which were over-represented in Pakistan. Meanwhile, we found over 1000 intra-host single-nucleotide variants (iSNVs). Several of them occurred concurrently, indicating possible interactions among them or coevolution. Some of the high-frequency iSNVs in Pakistan were not observed in the global population, suggesting strong purifying selections. The genomic epidemiology revealed five distinctive spreading clusters. The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure, indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation (G8371T in ORF1ab) of this cluster. Furthermore, 28 putative international introductions were identified, several of which are consistent with the epidemiological investigations. In all, this study has inferred the possible pathways of introductions and transmissions of SARS-CoV-2 in Pakistan, which could aid ongoing and future viral surveillance and COVID-19 control.

Evolutionary and structural analysis of SARS-CoV-2 specific evasion of host immunity.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading fast worldwide. There is a pressing need to understand how the virus counteracts host innate immune responses. Deleterious clinical manifestations of coronaviruses have been associated with virus-induced direct dysregulation of innate immune responses occurring via viral macrodomains located within nonstructural protein-3 (Nsp3). However, no substantial information is available concerning the relationship of macrodomains to the unusually high pathogenicity of SARS-CoV-2. Here, we show that structural evolution of macrodomains may impart a critical role to the unique pathogenicity of SARS-CoV-2. Using sequence, structural, and phylogenetic analysis, we identify a specific set of historical substitutions that recapitulate the evolution of the macrodomains that counteract host immune response. These evolutionary substitutions may alter and reposition the secondary structural elements to create new intra-protein contacts and, thereby, may enhance the ability of SARS-CoV-2 to inhibit host immunity. Further, we find that the unusual virulence of this virus is potentially the consequence of Darwinian selection-driven epistasis in protein evolution. Our findings warrant further characterization of macrodomain-specific evolutionary substitutions in in vitro and in vivo models to determine their inhibitory effects on the host immune system.

The effects of if-then plans on weight loss: results of the 24-month follow-up of the McGill CHIP Healthy Weight Program randomized controlled trial.

BACKGROUND: Current evidence suggests that some of the most effective weight loss approaches are changes in dietary and physical activity behaviors through lifestyle modification programs. The Group Lifestyle Balance (GLB) program is a group-based behavior modification program aimed at changing diet and physical activity for weight loss. It was developed to be more cost-effective and easier to disseminate than its individually administered parent program, the Diabetes Prevention Program (DPP). However, the average weight loss following participation in the GLB is only approximately 3.5%, with low long-term weight loss maintenance. PURPOSE: We aimed to optimize the weight loss outcomes of the GLB to increase the efficacy already afforded by its cost-effectiveness and ease of dissemination. We did this by integrating the habit formation tool of if-then plans into the program. This program is called the enriched GLB or the McGill Comprehensive Health Improvement (CHIP) Healthy Weight Program. Results at 3 and 12 months of participation have already been published elsewhere. They showed no between-group differences between the standard and enriched GLB but higher weight loss in both groups compared to the DPP. This paper reports the long-term weight loss maintenance data following participation in the program. METHODS: Of the 172 participants enrolled at the beginning of the study, data from 110 participants were available and analyzed at 24 months, i.e., 12 months after the end of the 12-month intervention. RESULTS: No between-group difference in weight loss maintenance was observed. Pooled results showed a significant weight regain from 12 to 24 months, i.e., an average of 7.85 lbs. of the 20.36 lbs. lost. However, participants from both groups were still 12.51lbs or 6.13% lighter at 24 months than at baseline. CONCLUSION: If-then plans did not result in a higher percentage of weight loss at 24-month follow-up compared to the standard GLB. However, at 24 months, both groups did show a maintenance of a significant portion of the weight lost at the end of intervention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02008435, registered 6 December 2013.

Community Curation and Expert Curation of Human Long Noncoding RNAs with LncRNAWiki and LncBook.

In recent years, the number of human long noncoding RNAs (lncRNAs) that have been identified has increased exponentially. However, these lncRNAs are poorly annotated compared to protein-coding genes, posing great challenges for a better understanding of their functional significance and elucidating their complex functioning molecular mechanisms. Here we employ both community and expert curation to yield a comprehensive collection of human lncRNAs and their annotations. Specifically, LncRNAWiki (http://lncrna.big.ac.cn/index.php/Main_Page) uses a wiki-based community curation model, thus showing great promise in dealing with the flood of biological knowledge, while LncBook (http://bigd.big.ac.cn/lncbook) is an expert curation-based database that provides a complement to LncRNAWiki. LncBook features a comprehensive collection of human lncRNAs and a systematic curation of lncRNAs by multi-omics data integration, functional annotation, and disease association. These protocols provide step-by-step instructions on how to browse and search a specific lncRNA and how to obtain a range of related information including expression, methylation, variation, function, and disease association. © 2019 by John Wiley & Sons, Inc.

Cognitive-behavioural social skills training for first-episode psychosis: a feasibility study.

AIM: To conduct a preliminary feasibility examination of cognitive-behavioural social skills training (CBSST) in a first-episode psychosis population. METHODS: Twenty two first-episode psychosis clients participated in an 18-week CBSST group adapted for a younger population. RESULTS: Adaptive functioning significantly improved following group participation and was maintained at 3-month follow-up. CONCLUSION: The CBSST group was feasible and well accepted in the first episode programme. These preliminary findings warrant further testing in a larger trial to determine efficacy.