Miracle-dz/UniFAR-FTUs huggingface dataset:
Receptor–ligand pair typing and prognostic risk model for papillary thyroid carcinoma based on single-cell sequencing

The papillary thyroid carcinoma (PTC) microenvironment consists of various cancer and surrounding cells, and the communication between them is mainly performed through ligand–receptor (LR) interactions. Single-cell RNA sequencing (scRNA-seq) has been performed to investigate the role of intercellular communication networks in tumor progression. In addition, scRNA-seq can accurately identify the characteristics of immune cell subsets, which is of great significance for predicting the efficacy of immunotherapy. In this study, the cell–cell communication network was analyzed through LR pairs, and a new PTC molecular phenotype was developed based on LR pairs. Furthermore, a risk model was established to predict patient response to PD-1 blockade immunotherapy. The scRNA-seq dataset was obtained from GSE184362, and the bulk tumor RNA-seq dataset was obtained from The Cancer Genome Atlas. CellPhoneDB was used for cellular communication analysis. LR pair correlations were calculated and used to identify molecular subtypes, and the least absolute shrinkage and selection operator (Lasso) Cox regression was used to develop a risk model based on LR pairs. The IMvigor210 and GSE78220 cohorts were used as external validations for the LR.score to predict responses to PD-L1 blockade therapy. A total of 149 LR pairs with significant expression and prognostic correlation were included, and three PTC molecular subtypes were obtained from those with significant prognostic differences. Then, five LR pairs were selected to construct the risk scoring model, a reliable and independent prognostic factor in the training set, test set, and whole dataset. Furthermore, two external validation sets confirmed the predictive efficacy of the LR.score for response to PD-1 blockade therapy.
Transcriptome Dynamics in the Developing Larynx, Trachea, and Esophagus

The larynx, trachea, and esophagus share origin and proximity during embryonic development. Clinical and experimental evidence support the existence of neurophysiological, structural, and functional interdependencies before birth. This investigation provides the first comprehensive transcriptional profile of all three organs during embryonic organogenesis, where differential gene expression gradually assembles the identity and complexity of these proximal organs from a shared origin in the anterior foregut. By applying bulk RNA sequencing and gene network analysis of differentially expressed genes (DEGs) within and across developing embryonic mouse larynx, esophagus, and trachea, we identified co-expressed modules of genes enriched for key biological processes. Organ-specific temporal patterns of gene activity corresponding to gene modules within and across shared tissues during embryonic development (E10.5-E18.5) are described, and the laryngeal transcriptome during vocal fold development and maturation from birth to adulthood is characterized in the context of laryngeal organogenesis. The findings of this study provide new insights into interrelated gene sets governing the organogenesis of this tripartite organ system within the aerodigestive tract. They are relevant to multiple families of disorders defined by cardiocraniofacial syndromes.
Efficient cellular and humoral immune response and production of virus-neutralizing antibodies by the Hepatitis B Virus S/preS116-42 antigen

Despite the availability of improved antiviral therapies, infection with Hepatitis B virus (HBV) remains a3 significant health issue, as a curable treatment is yet to be discovered. Current HBV vaccines relaying on the efficient expression of the small (S) envelope protein in yeast and the implementation of mass vaccination programs have clearly contributed to containment of the disease. However, the lack of an efficient immune response in up to 10% of vaccinated adults, the controversies regarding the seroprotection persistence in vaccine responders and the emergence of vaccine escape virus mutations urge for the development of better HBV immunogens. Due to the critical role played by the preS1 domain of the large (L) envelope protein in HBV infection and its ability to trigger virus neutralizing antibodies, including this protein in novel vaccine formulations has been considered a promising strategy to overcome the limitations of S only-based vaccines. In this work we aimed to combine relevant L and S epitopes in chimeric antigens, by inserting preS1 sequences within the external antigenic loop of S, followed by production in mammalian cells and detailed analysis of their antigenic and immunogenic properties. Of the newly designed antigens, the S/preS116–42 protein assembled in subviral particles (SVP) showed the highest expression and secretion levels, therefore, it was selected for further studies in vivo. Analysis of the immune response induced in mice vaccinated with S/preS116–42- and S-SVPs, respectively, demonstrated enhanced immunogenicity of the former and its ability to activate both humoral and cellular immune responses. This combined activation resulted in production of neutralizing antibodies against both wild-type and vaccine-escape HBV variants. Our results validate the design of chimeric HBV antigens and promote the novel S/preS1 protein as a potential vaccine candidate for administration in poor-responders to current HBV vaccines.
Combined Effect of Healthy Lifestyle Factors and Risks of Colorectal Adenoma, Colorectal Cancer, and Colorectal Cancer Mortality: Systematic Review and Meta-Analysis

Background In addition to adiposity, lifestyle factors such as poor diet, low physical activity, alcohol intake and smoking are noted to be associated with the development of colorectal cancer (CRC). This study aims to investigate the association and dose-response relationship between adherence to a healthy lifestyle and CRC risk. Methods A systematic literature search was conducted in MEDLINE and EMBASE for studies examining multiple lifestyle factors with risk of CRC, incident colorectal adenoma (CRA), and CRC-specific mortality through June 2021 without restrictions on language or study design. Meta-analysis was performed to pool hazard ratios using random-effects model. Subgroup analyses were performed based upon study and sample characteristics. Random-effects dose-response analysis was also conducted for CRC risk to assess the effect of each additional healthy lifestyle factor. Results A total of 28 studies (18 cohort studies, eight case-control studies, and two cross-sectional study) were included. When comparing subjects with the healthiest lifestyle to those with the least healthy lifestyle, the pooled HR was statistically significant for CRC (0.52, 95% CI 0.44-0.63), colon cancer (0.54, 95% CI 0.44-0.67), rectal cancer (0.51, 95% CI 0.37-0.70), CRA (0.39, 95% CI 0.29-0.53), and CRC-specific mortality (0.65, 95% CI 0.52-0.81). The pooled HR for CRC was 0.91 (95% CI: 0.88-0.94) for each increase in the number of healthy lifestyles. The inverse association between healthy lifestyle and CRC risk was consistently observed in all subgroups (HR ranging from 0.26 to 0.86). Conclusions Adoption of a higher number of healthy lifestyles is associated with lower risk of CRC, CRA, and CRC-specific mortality. Promoting healthy lifestyle could reduce the burden of CRC. Systematic Review Registration https://www.crd. york.ac. uk/PROSPERO/display_record. php? RecordID=231398, identifier CRD42021231398.
IL-10 Overexpression After BCG Vaccination Does Not Impair Control of Mycobacterium tuberculosis Infection

Control of tuberculosis depends on the rapid expression of protective CD4+ T-cell responses in the Mycobacterium tuberculosis (Mtb)-infected lungs. We have recently shown that the immunomodulatory cytokine IL-10 acts intrinsically in CD4+ T cells and impairs their parenchymal migratory capacity, thereby preventing control of Mtb infection. Herein, we show that IL-10 overexpression does not impact the protection conferred by the established memory CD4+ T-cell response, as BCG-vaccinated mice overexpressing IL-10 only during Mtb infection display an accelerated, BCG-induced, Ag85b-specific CD4+ T-cell response and control Mtb infection. However, IL-10 inhibits the migration of recently activated ESAT-6-specific CD4+ T cells into the lung parenchyma and impairs the development of ectopic lymphoid structures associated with reduced expression of the chemokine receptors CXCR5 and CCR7. Together, our data support a role for BCG vaccination in preventing the immunosuppressive effects of IL-10 in the fast progression of Mtb infection and may provide valuable insights on the mechanisms contributing to the variable efficacy of BCG vaccination.
Epidemic characteristics and transmission risk prediction of brucellosis in Xi'an city, Northwest China

Human brucellosis (HB) has re-emerged in China since the mid-1990s, and exhibited an apparent geographic expansion shifted from the traditional livestock regions to the inland areas of China. It is often neglected in non-traditional epidemic areas, posing a serious threat to public health in big cities. We carried out a retrospective epidemiological study in Xi'an, the largest city in northwestern China. It utilizes long-term surveillance data on HB during 2008–2021 and investigation data during 2014–2021. A total of 1989 HB cases were reported in Xi'an, consisting of 505 local cases, i.e., those located in Xi'an and 1,484 non-local cases, i.e., those located in other cities. Significantly epidemiological heterogeneity was observed between them, mainly owing to differences in the gender, occupation, diagnostic delays, and reporting institutions. Serological investigations suggested that 59 people and 1,822 animals (sheep, cattle, and cows) tested positive for brucellosis from 2014 to 2021, with the annual average seroprevalence rates were 1.38 and 1.54%, respectively. The annual animal seroprevalence rate was positively correlated with the annual incidence of non-local HB cases. Multivariate boosted regression tree models revealed that gross domestic product, population density, length of township roads, number of farms, and nighttime lights substantially contributed to the spatial distribution of local HB. Approximately 7.84 million people inhabited the potential infection risk zones in Xi'an. Our study highlights the reemergence of HB in non-epidemic areas and provides a baseline for large and medium-sized cities to identify regions, where prevention and control efforts should be prioritized in the future.
Building trust and responsibility into autonomous human-machine teams

Harm can be caused to people and property by any highly-automated system, even with a human user, due to misuse or design; but which human has the legal liability for the consequences of the harm is not clear, or even which laws apply. The position is less clear for an interdependent Autonomous Human Machine Team System (A-HMT-S) which achieves its aim by reallocating tasks and resources between the human Team Leader and the Cyber Physical System (CPS). A-HMT-S are now feasible and may be the only solution for complex problems. However, legal authorities presume that humans are ultimately responsible for the actions of any automated system, including ones using Artificial Intelligence (AI) to replace human judgement. The concept of trust for an A-HMT-S using AI is examined in this paper with three critical questions being posed which must be addressed before an A-HMT-S can be trusted. A hierarchical system architecture is used to answer these questions, combined with a method to limit a node’s behaviour, ensuring actions requiring human judgement are referred to the user. The underpinning issues requiring Research and Development (R&D) for A-HMT-S applications are identified and where legal input is required to minimize financial and legal risk for all stakeholders. This work takes a step towards addressing the problems of developing autonomy for interdependent human-machine teams and systems.
Lactate Thresholds and the Simulation of Human Energy Metabolism: Contributions by the Cologne Sports Medicine Group in the 1970s and 1980s

Today, researchers, practitioners, and physicians measure the concentration of lactate during a graded exercise test to determine thresholds related to the maximal lactate steady state (maxLass) as a sensitive measure of endurance capacity. In the 1970s and 1980s, a group of Cologne-based researchers around Wildor Hollmann, Alois Mader, and Hermann Heck developed the methodology for systematic lactate testing and introduced a 4 mmol.L−1 lactate threshold. Later, they also developed the concept of the maxLass, and Mader designed a sophisticated mathematical model of human energy metabolism during exercise. Mader`s model simulates metabolic responses to exercise based on individual variables such as maximum oxygen uptake ( V ˙ O2max) and the maximal rate of lactate formation (νLa.max). Mader’s model predicts that the νLa. max reduces the power at the anaerobic threshold and endurance performance but that a high νLa. max is required for events with high power outputs in elite athletes. Mader’s model also assumed before the millennium that the rate of fat oxidation is explained by the difference between glycolytic pyruvate synthesis and the actual rate of pyruvate oxidation which is consistent with current opinion. Mader’s model also simulated the V ˙ O2max slow component in the mid-1980s. Unfortunately, several landmark studies by the Cologne group were only published in German, and as a result, contributions by the Cologne group are under-appreciated in the English-speaking world. This narrative review aims to introduce key contributions of the Cologne group to human metabolism research especially for readers who do not speak German.
Role of chitosan in titanium coatings. trends and new generations of coatings

Survival studies of dental implants currently reach high figures. However, considering that the recipients are middle-aged individuals with associated pathologies, research is focused on achieving bioactive surfaces that ensure osseointegration. Chitosan is a biocompatible, degradable polysaccharide with antimicrobial and anti-inflammatory properties, capable of inducing increased growth and fixation of osteoblasts around chitosan-coated titanium. Certain chemical modifications to its structure have been shown to enhance its antibacterial activity and osteoinductive properties and it is generally believed that chitosan-coated dental implants may have enhanced osseointegration capabilities and are likely to become a commercial option in the future. Our review provided an overview of the current concepts and theories of osseointegration and current titanium dental implant surfaces and coatings, with a special focus on the in vivo investigation of chitosan-coated implants and a current perspective on the future of titanium dental implant coatings.
Thankful employees: The manifestation of gratitude at work during a pandemic in South Africa

Gratitude or the appreciation of being given something of value, is an important element in positive emotions within positive psychology. Gratitude has been linked to wellbeing and gratitude in the workplace is positively associated with constructs such as performance and organizational citizenship behavior. The pandemic brought on many negative experiences but employees could still find things to be grateful for during this time. The purpose of the study was to understand what aspects of work and the organization employees were grateful for during the pandemic. A generic qualitative approach was used. Participants were sourced from various industries in South Africa using purposive sampling. Data were gathered through 21 semi-structured interviews of working people in South Africa. Braun and Clarke’s thematic analysis revealed five themes, namely, (1) gratitude for no negative work-life changes; (2) gratitude for a caring workplace; (3) gratitude for a new way of working; (4) gratitude for the ability to put oneself first; and (5) gratitude for having resilience, optimism and spirituality as a psychological buffer. Managers should deliberately engage in behaviors that will bring about gratitude from their employees. Employees should reflect on the positive things at work that they are thankful for as a way of enhancing gratitude and thereby, wellness, performance, and commitment. The study combines existing knowledge on gratitude during the pandemic with gratitude in the workplace.
An Introduction to Qualitative Methods for the Nurse Researcher

Editor's note: This is the 11th article in a series on clinical research by nurses. The series is designed to give nurses the knowledge and skills they need to participate in research, step by step. Each column will present the concepts that underpin evidence-based practice—from research design to data interpretation. The articles will be accompanied by a podcast offering more insight and context from the authors. To see all the articles in the series, go to https://links.lww. com/AJN/A204.
Association of sorting and assembly machinery component 50 homolog gene polymorphisms with nonalcoholic fatty liver disease susceptibility

Background: Sorting and assembly machinery component 50 homolog (SAMM50) gene single-nucleotide polymorphisms (SNPs) have been connected with the susceptibility of nonalcoholic fatty liver disease (NAFLD), but with inconsistent results across the current evidence. The present work was schemed to explore the association between SAMM50 gene SNPs and NAFLD vulnerability via meta-analysis. Methods: PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang were retrieved for eligible literature previous to June 10, 2021. The odds ratios (ORs) of the dichotomic variables and the standardized mean difference of quantitative variables with corresponding 95% confidence intervals (95% CIs) were computed to evaluate the strength of the associations. The quality of included studies was assessed using Newcastle-Ottawa Scale (NOS). Results: In total, 8 case-control studies encompassing 6297 NAFLD patients and 7306 disease-free controls in this meta-analysis. Ultimately, this analysis included 8, 6, and 5 studies for rs2143571, rs3761472, and rs738491 polymorphisms respectively. The pooled data revealed that the 3 polymorphisms had conspicuous associations with NAFLD susceptibility: rs2143571, A vs. G, OR=1.51, 95% CI, 1.37–1.66, P < . 01; rs3761472, A vs. G, OR=1.50, 95% CI, 1.35–1.67, P < . 01; rs738491, A vs. G, OR=1.51, 95% CI, 1.40–1.63, P < . 01. Conclusion: This meta-analysis suggests that rs2143571, rs3761472, and rs738491 polymorphisms of the SAMM50 gene are appreciably associated with augmented risk of NAFLD vulnerability. It will provide the latest evidence to support the susceptibility of SAMM50 gene polymorphisms and NAFLD, and provide strategies for the prevention and treatment of NAFLD.
Farmers’ Willingness to Participate in the Management of Small‐Scale Irrigation in China from a Social Capital Perspective

Because of the different patterns of rural clan society and the 'peer' mode of farmers' interactions, rural households make decisions based on learning, imitation, interaction, and trial and error, the realization of which depends on farmers' social capital. The concept of social capital is introduced to analyse farmers' willingness to participate in the management of small‐scale irrigation. The study deconstructs social capital pathways of reducing costs and improving productivity in agriculture. Based on field survey data of 285 farmers in Hubei Province, China, an ordered Logit model is used to analyse farmers' willingness to participate in irrigation management. It is shown that social capital and its four dimensions, i.e. social trust, institutional trust, social networks and social norms, all significantly improve farmers' willingness to participate in such management. Other factors also influence willingness to participate. The larger the cultivated area, agricultural income, or proportion of paddy field, the greater the willingness to participate in this management. The educational level of the head of a household significantly reduces farmers' willingness. Hence, it is recommended to improve farmers' willingness to participate in irrigation management by attaching importance to traditional social cohesiveness, promoting moderate scale management, and orienting rural education toward agriculture. © 2017 John Wiley & Sons, Ltd.
Solar light‐assisted rod‐shaped CPTF@FACC photocatalyst: An efficient platform for oxygenation reactions and coenzymes regeneration

Solar light active oxygenation reactions and coenzyme regenerations are play crucial role in the area of pharmaceutical industry. The highly selective and efficient synthesis of oxygen‐containing molecules in an environmental friendly manner is challenging at both industrial and laboratory level. Here, we proposed a new synthetic approach for oxygenation reactions along with coenzyme regenerations using flexible‐activated carbon cloth (FACC) oriented covalent (C) tetrakis(4‐carboxyphenyl) porphyrin (P) and thiourea (T)‐based framework (F), namely, CPTF@FACC photocatalyst. CPTF@FACC exhibits excellent solar light‐harvesting ability, well‐distinct photocatalytic centers, high molar extinction coefficient, excellent charge transport ability, and suitable optical band gap, which make the photocatalyst more efficient for oxygenation (sulfoxidation and epoxidation) reactions along with coenzyme regenerations. The oxygenation reactions were carried out in isopropyl alcohol via in situ production of hydrogen peroxide (H2O2) under solar light using CPTF@FACC photocatalyst with high yields (~97%‐98%). Finally, the CPTF@FACC photocatalyst also show a benchmark example in the coenzymes regeneration with high yields 81.1% and 73.1% for NADH and NADPH in 2 h, respectively.
Improving the Therapeutic Index of Smp24, a Venom-Derived Antimicrobial Peptide: Increased Activity against Gram-Negative Bacteria

Antimicrobial peptides (AMPs) are naturally occurring compounds which possess a rapid killing mechanism and low resistance potential. Consequently, they are being viewed as potential alternatives to traditional antibiotics. One of the major factors limiting further development of AMPs is off-target toxicity. Enhancements to antimicrobial peptides which can maximise antimicrobial activity whilst reducing mammalian cytotoxicity would make these peptides more attractive as future pharmaceuticals. We have previously characterised Smp24, an AMP derived from the venom of the scorpion Scorpio maurus palmatus. This study sought to better understand the relationship between the structure, function and bacterial selectivity of this peptide by performing single amino acid substitutions. The antimicrobial, haemolytic and cytotoxic activity of modified Smp24 peptides was determined. The results of these investigations were compared with the activity of native Smp24 to determine which modifications produced enhanced therapeutic indices. The structure–function relationship of Smp24 was investigated by performing N-terminal, mid-chain and C-terminal amino acid substitutions and determining the effect that they had on the antimicrobial and cytotoxic activity of the peptide. Increased charge at the N-, mid- and C-termini of the peptide resulted in increased antimicrobial activity. Increased hydrophobicity at the N-terminus resulted in reduced haemolysis and cytotoxicity. Reduced antimicrobial, haemolytic and cytotoxic activity was observed by increased hydrophobicity at the mid-chain. Functional improvements have been made to modified peptides when compared with native Smp24, which has produced peptides with enhanced therapeutic indices.