Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of inflammatory cytokine and adipokine gene variations in the development of HIV‐associated lipodystrophy

Cytokines affect lipid and glucose metabolism and also alter the body's habitus. They play a role in the development of lipodystrophy syndrome. Adipocytes secrete the pro‐inflammatory cytokines IL‐1, TNF‐α and IL‐6. The plasma cytokine concentration is associated with the percentage and distribution of fat tissue in the body. The metabolic disturbances are strongly associated with increased levels of pro‐inflammatory cytokines (IL‐1, IL‐6 and TNF‐α). Plasma levels of cytokines such as TNF‐α, IL‐6 and leptin were found to be increased while plasma resistin levels were found to be variable in patients suffering from obesity and type II diabetes mellitus. Until now, limited information has been available on the polymorphism of cytokine and adipokine genes in patients of HIV‐associated lipodystrophy (HIVLD), which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. Hence, we studied the association of cytokine and adipokine gene polymorphisms in various diseases and their impact on HIVLD. We carry out an extensive search using several databases, including PubMed, EMBASE and Google Scholar. The distribution of cytokine and adipokine gene polymorphisms and their expression levels varied among various populations. We examined the variants of cytokine and adipokine genes, which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. In the current review, we present a brief account of the risk factors of HIVLD, the pathogenesis of HIVLD and the polymorphism of cytokine and adipokine genes in various diseases with special reference to their impact on HIVLD.
The relative contributions of multiarticular snake muscles to movement in different planes

Muscles spanning multiple joints play important functional roles in a wide range of systems across tetrapods; however, their fundamental mechanics are poorly understood, particularly the consequences of anatomical position on mechanical advantage. Snakes provide an excellent study system for advancing this topic. They rely on the axial muscles for many activities, including striking, constriction, defensive displays, and locomotion. Moreover, those muscles span from one or a few vertebrae to over 30, and anatomy varies among muscles and among species. We characterized the anatomy of major epaxial muscles in a size series of corn snakes (Pantherophis guttatus) using diceCT scans, and then took several approaches to calculating contributions of each muscle to force and motion generated during body bending, starting from a highly simplistic model and moving to increasingly complex and realistic models. Only the most realistic model yielded equations that included the consequence of muscle span on torque‐displacement trade‐offs, as well as resolving ambiguities that arose from simpler models. We also tested whether muscle cross‐sectional areas or lever arms (total magnitude or pitch/yaw/roll components) were related to snake mass, longitudinal body region (anterior, middle, posterior), and/or muscle group (semispinalis‐spinalis, multifidus, longissimus dorsi, iliocostalis, and levator costae). Muscle cross‐sectional areas generally scaled with positive allometry, and most lever arms did not depart significantly from geometric similarity (isometry). The levator costae had lower cross‐sectional area than the four epaxial muscles, which did not differ significantly from each other in cross‐sectional area. Lever arm total magnitudes and components differed among muscles. We found some evidence for regional variation, indicating that functional regionalization merits further investigation. Our results contribute to knowledge of snake muscles specifically and multiarticular muscle systems generally, providing a foundation for future comparisons across species and bioinspired multiarticular systems.
Computational Limits of Divide-and-Conquer Method

This theoretical note explores statistical versus computational trade-off to address a basic question in the application of divide-and-conquer method: what is the minimal computational cost in obtaining statistical optimality? In smoothing spline setup, we observe a phase transition phenomenon for the number of deployed machines that ends up being a simple proxy for computing cost. Specifically, a sharp upper bound for the number of machines is established: when the number is below this bound, statistical optimality (in terms of nonparametric estimation or testing) is achievable; otherwise, statistical optimality becomes impossible. These sharp bounds capture intrinsic computational limits of divide-and-conquer method, which turn out to be fully determined by the smoothness of the regression function. As a side remark, we argue that sample spitting may be viewed as a new form of regularization, playing a similar role as smoothing parameter.
Beyond the kidney biopsy: genomic approach to undetermined kidney diseases

ABSTRACT Background According to data from large national registries, almost 20%–25% of patients with end-stage kidney disease have an undetermined kidney disease (UKD). Recent data have shown that monogenic disease-causing variants are under-diagnosed. We performed exome sequencing (ES) on UKD patients in our center to improve the diagnosis rate. Methods ES was proposed in routine practice for patients with UKD including kidney biopsy from January 2019 to December 2021. Mutations were detected using a targeted bioinformatic customized kidney gene panel (675 genes). The pathogenicity was assessed using American College of Medical Genetics guidelines. Results We included 230 adult patients, median age 47.5 years. Consanguinity was reported by 25 patients. A family history of kidney disease was documented in 115 patients (50%). Kidney biopsies were either inconclusive in 69 patients (30.1%) or impossible in 71 (30.9%). We detected 28 monogenic renal disorders in 75 (32.6%) patients. Collagenopathies was the most common genetic kidney diagnosis (46.7%), with COL4A3 and COL4A4 accounting for 80% of these diagnoses. Tubulopathies (16%) and ciliopathies (14.7%) yielded, respectively, the second and third genetic kidney diagnosis category and UMOD-associated nephropathy as the main genetic findings for tubulopathies (7/11). Ten of the 22 patients having ES “first” eventually received a positive diagnosis, thereby avoiding 11 biopsies. Among the 44 patients with glomerular, tubulo-interstitial or vascular nephropathy, 13 (29.5%) were phenocopies. The diagnostic yield of ES was higher in female patients (P = .02) and in patients with a family history of kidney disease (P < .0001), reaching 56.8% when the patient had both first- and second-degree family history of renal disease. Conclusion Genetic diagnosis has provided new clinical insights by clarifying or reclassifying kidney disease etiology in over a third of UKD patients. Exome “first” may have a significant positive diagnostic yield, thus avoiding invasive kidney biopsy; moreover, the diagnostic yield remains elevated even when biopsy is impossible or inconclusive. ES provides a clinical benefit for routine nephrological healthcare in patients with UKD.
Essential Involvement of Neutrophil Elastase in Acute Acetaminophen Hepatotoxicity Using BALB/c Mice

Intense neutrophil infiltration into the liver is a characteristic of acetaminophen-induced acute liver injury. Neutrophil elastase is released by neutrophils during inflammation. To elucidate the involvement of neutrophil elastase in acetaminophen-induced liver injury, we investigated the efficacy of a potent and specific neutrophil elastase inhibitor, sivelestat, in mice with acetaminophen-induced acute liver injury. Intraperitoneal administration of 750 mg/kg of acetaminophen caused severe liver damage, such as elevated serum transaminase levels, centrilobular hepatic necrosis, and neutrophil infiltration, with approximately 50% mortality in BALB/c mice within 48 h of administration. However, in mice treated with sivelestat 30 min after the acetaminophen challenge, all mice survived, with reduced serum transaminase elevation and diminished hepatic necrosis. In addition, mice treated with sivelestat had reduced NOS-II expression and hepatic neutrophil infiltration after the acetaminophen challenge. Furthermore, treatment with sivelestat at 3 h after the acetaminophen challenge significantly improved survival. These findings indicate a new clinical application for sivelestat in the treatment of acetaminophen-induced liver failure through mechanisms involving the regulation of neutrophil migration and NO production.
Maternal and Neonatal Factors Modulating Breast Milk Cytokines in the First Month of Lactation

Breast milk (BM) cytokines support and modulate infant immunity, being particularly relevant in premature neonates with adverse outcomes (NAO). This study aimed to examine, in a cohort of Spanish breastfeeding women, changes in BM cytokines in the first month of lactation, their modulation by neonatal factors (sex, gestational age, and NAO), maternal factors (obstetric complications, C-section, and diet), and their relationship with oxidative status. Sixty-three mother-neonate dyads were studied at days 7 and 28 of lactation. Dietary habits were assessed by a 72-h dietary recall, and the maternal dietary inflammatory index (mDII) was calculated. BM cytokines (IL-10, IL-13, IL-8, MCP-1, and TNFα) were assessed by ultra-sensitive chemiluminescence. Total antioxidant capacity was assessed by the ABTS method and lipid peroxidation by the MDA+HNE kit. From days 7 to 28 of lactation, the levels of IL-10 and TNFα remained stable, while IL-13 increased (β = 0.85 ± 0.12, p < 0.001) and IL-8 and MCP-1 levels decreased (β = −0.64 ± 0.27, p = 0.019; β = −0.98 ± 0.22, p < 0.001; respectively). Antioxidant capacity and lipid peroxidation also decrease during lactation. Neonatal sex did not influence any of the cytokines, but BM from mothers with male infants had a higher antioxidant capacity. Gestational age was associated with male sex and NAO, being inversely correlated with the BM proinflammatory cytokines IL-8, MCP-1, and TNFα. From days 7 to 28 of lactation, BM from women with NAO infants increased MCP-1 levels and had a larger drop in antioxidant capacity, with the opposite trend in lipid peroxidation. MCP-1 was also significantly higher in women undergoing C-section; this cytokine declined in women who decreased mDII during lactation, while IL-10 increased. Linear mixed regression models evidenced that the most important factors modulating BM cytokines were lactation period and gestational age. In conclusion, during the first month of lactation, BM cytokines shift towards an anti-inflammatory profile, influenced mainly by prematurity. BM MCP-1 is associated with maternal and neonatal inflammatory processes.
Study on acute respiratory infection in children aged 1 year to 5 years-A hospital-based cross-sectional study

Background: Acute respiratory infections (ARIs) are the single greatest cause of death among children throughout the world. They are responsible every year for the deaths of 4.3 million children under 5 years of age worldwide. Community- or hospital-based surveys for finding out the prevalence and various factors associated with ARI are very few, especially in urban areas. Also, surveys to study the use of vaccines in preventing ARIs are scarce. Hence, we studied ARI in children aged 1 year to 5 years in a tertiary care hospital in Kerala. The aim was to determine the frequency of ARIs in the last 1 year in children aged 1 year to 5 years, attending the immunization clinic at Lourdes Hospital, Kochi, and assess the selected epidemiological, socio-demographic, nutritional and immunization factors associated with ARIs in the study group. Methods: Children attending the immunization clinic at a tertiary care hospital, Kochi, in the age group of 1 year to 5 years were selected. A brief introduction was given to the mother/caregiver of the child regarding the purpose of the study and was asked to fill out the questionnaire. Informed consent was taken. For the study, ARI is defined as the presence of one or more of the following: cough, running nose, blocked nose, sore throat, difficulty breathing, or ear problems; with or without fever. Results were analyzed. Results: Mother was the caregiver in 67% of the cases. When the caregiver was the mother, ARI is found to be less. Among those mothers who had no formal education, 100% of their children got ARI. Children whose caregivers were 30 years and older had lesser ARI. The proportion of children with ARIs was more with a history of respiratory infection among family members (parents/siblings) compared to those with no such history. The occurrence of ARI was more frequent in rural compared to urban areas. There is a significant proportion of ARI in non-exclusively breastfed infants, bottle feeding, and early initiation of complementary feeding. Children with a history of exposure to cigarette smoke had an increased occurrence of ARI. Similar results followed for exposure to biomass fuel and exposure to cold and rain. Children who were not immunized to vaccines-pneumococcal, Hib, measles, vitamin A, showed a higher occurrence of ARI compared to immunization. Conclusion: The studies regarding factors influencing ARI are relatively rare in an urban setting, thus this calls for more studies in urban areas. Health education can change the healthcare-seeking behavior and attitude of parents for preventing ARI-related deaths. Family physicians can play a significant role by educating caregivers of children and giving timely services. Promoting and ensuring exclusive breastfeeding practices, timely weaning after 6 months, and avoidance of bottle feeds can dramatically decrease the episodes of ARI.
High Content of Thermoplastic Starch, Poly(butylenes adipate-co-terephthalate) and Poly(butylene succinate) Ternary Blends with a Good Balance in Strength and Toughness

The ternary blends of a high content of thermoplastic starch (TPS), poly(butylenes adipate-co-terephthalate) (PBAT), and poly(butylene succinate) (PBS) were first melt-compounded in a twin screw extruder. The TPS contents in ternary blends were fixed at 60 wt%. The miscibility, morphology, thermal behavior, mechanical properties, and thermal resistance of the blends were investigated. The results showed that dispersions of PBS and PBAT minor phases improved the tensile strength and elongation at break. TPS/PBS/PBAT60/10/30 formed a good balance in strength and toughness. Dynamic mechanical analysis of the blends exhibits an intermediate and peak suggesting the ternary blend is compatible. Minor phase-separated structure SEM results showed that TPS/PBS/PBAT60/10/30 blend formed a typical mixture with core−shell morphology. As the PBAT composition was increased, phase morphology changes occurred in the blends, leading to decreased values of complex viscosity, storage modulus, and loss modulus. Moreover, the thermal resistances and melt flow properties of the materials were also studied by analysis of the heat deflection temperature (HDT) and melt flow index (MFI) value in the work.
Can Oncologists Prompt Patient Prognostic Awareness to Enhance Decision-Making? Data From the NEOetic Study

Abstract Introduction Anti-neoplastic therapy improves the prognosis for advanced cancer, albeit it is not curative. An ethical dilemma that often arises during patients’ first appointment with the oncologist is to give them only the prognostic information they can tolerate, even at the cost of compromising preference-based decision-making, versus giving them full information to force prompt prognostic awareness, at the risk of causing psychological harm. Methods We recruited 550 participants with advanced cancer. After the appointment, patients and clinicians completed several questionnaires about preferences, expectations, prognostic awareness, hope, psychological symptoms, and other treatment-related aspects. The aim was to characterize the prevalence, explanatory factors, and consequences of inaccurate prognostic awareness and interest in therapy. Results Inaccurate prognostic awareness affected 74%, conditioned by the administration of vague information without alluding to death (odds ratio [OR] 2.54; 95% CI, 1.47-4.37, adjusted P = .006). A full 68% agreed to low-efficacy therapies. Ethical and psychological factors oriented first-line decision-making, in a trade-off in which some lose quality of life and mood, for others to gain autonomy. Imprecise prognostic awareness was associated with greater interest in low-efficacy treatments (OR 2.27; 95% CI, 1.31-3.84; adjusted P = .017), whereas realistic understanding increased anxiety (OR 1.63; 95% CI, 1.01-2.65; adjusted P = 0.038), depression (OR 1.96; 95% CI, 1.23-3.11; adjusted P = .020), and diminished quality of life (OR 0.47; 95% CI, 0.29-0.75; adjusted P = .011). Conclusion In the age of immunotherapy and targeted therapies, many appear not to understand that antineoplastic therapy is not curative. Within the mix of inputs that comprise inaccurate prognostic awareness, many psychosocial factors are as relevant as the physicians’ disclosure of information. Thus, the desire for better decision-making can actually harm the patient.
Multiserver Queue with Guard Channel for Priority and Retrial Customers

This paper considers a retrial queueing model where a group of guard channels is reserved for priority and retrial customers. Priority and normal customers arrive at the system according to two distinct Poisson processes. Priority customers are accepted if there is an idle channel upon arrival while normal customers are accepted if and only if the number of idle channels is larger than the number of guard channels. Blocked customers (priority or normal) join a virtual orbit and repeat their attempts in a later time. Customers from the orbit (retrial customers) are accepted if there is an idle channel available upon arrival. We formulate the queueing system using a level dependent quasi-birth-and-death (QBD) process. We obtain a Taylor series expansion for the nonzero elements of the rate matrices of the level dependent QBD process. Using the expansion results, we obtain an asymptotic upper bound for the joint stationary distribution of the number of busy channels and that of customers in the orbit. Furthermore, we develop an efficient numerical algorithm to calculate the joint stationary distribution.
The Relative Importance of Personality, Financial Satisfaction, and Autonomy for Different Subjective Well-Being Facets

Abstract Using a nationally representative sample (N = 507) from Singapore, this study examined whether personality, financial satisfaction, and autonomy were important to subjective well-being (SWB), and how the importance of these predictors varied across different SWB facets—life satisfaction, happiness, positive feelings, and negative feelings. The findings indicated that neuroticism, financial satisfaction, and autonomy, were important predictors of happiness. Personality was most important for affective well-being (i.e., positive and negative feelings), whereas financial satisfaction was most important for life satisfaction. Specifically, neuroticism accounted for substantial variance in positive and negative feelings, and was the strongest correlate among the Big Five traits. In contrast, financial satisfaction explained most of the variance in life satisfaction. This highlights that the importance of well-being predictors depended on the facet of well-being examined. The findings suggest that residents in an affluent nation like Singapore do not emphasize only postmaterialist values (e.g., autonomy) and disregard materialist concerns (e.g., financial satisfaction). Though certain SWB facets (positive and negative affect) are largely influenced by dispositional factors, other facets (life satisfaction and happiness) are closely related to factors (e.g., financial satisfaction, autonomy) that may be affected by social policies. Policymakers can thus target those aspects to enhance people’s SWB.
Subjective well-being and its impact on online game addiction

ABSTRACT This study examined how an individual's subjective well-being (SWB) affects their online game addiction levels, which, in turn, affect their happiness and overall health. Partial least squares structural equation modelling (PLS-SEM) was used to analyze the data. The results showed that SWB had a negative relationship with online game addiction but a positive relationship with happiness and life health. Additionally, online game addiction had a negative impact on both happiness and life health. Furthermore, there was a significant positive relationship between happiness and life health. Overall, the proposed model explained 1.60%, 51.60%, and 31.80% of the variance in online game addiction, happiness, and life health, respectively. PLS-SEM analysis provided evidence that the indirect effect of SWB on life health and happiness was fully mediated by online game addiction. These findings indicate that SWB has a significant indirect effect on life health and happiness through online game addiction.
Genetic landscape and macro-evolution of co-circulating Coxsackieviruses A and Vaccine-derived Polioviruses in the Democratic Republic of Congo, 2008-2013

Enteroviruses (EVs) are among the most common viruses infecting humans worldwide but only a few Non-Polio Enterovirus (NPEV) isolates have been characterized in the Democratic Republic of Congo (DR Congo). Moreover, circulating vaccine-derived polioviruses (PVs) [cVDPVs] isolated during multiple outbreaks in DR Congo from 2004 to 2018 have been characterized so far only by the sequences of their VP1 capsid coding gene. This study was carried to i) investigate the circulation and genetic diversity of NPEV and polio vaccine isolates recovered from healthy children and Acute Flaccid Paralysis (AFP) patients, ii) evaluate the occurrence of genetic recombination among EVs belonging to the Enterovirus C species (including PVs) and iii) identify the virological factors favoring multiple emergences of cVDPVs in DR Congo. The biological material considered in this study included i) a collection of 91 Sabin-like PVs, 54 cVDPVs and 150 NPEVs isolated from AFP patients between 2008 and 2012 in DR Congo and iii) a collection of 330 stool specimens collected from healthy children in 2013 in the Kasai Oriental and Maniema provinces of DR Congo. Studied virus isolates were sequenced in four distinct sub-genomic regions 5’-UTR, VP1, 2CATPase and 3Dpol. Resulting sequences were compared through comparative phylogenetic analyses. Virus isolation showed that 19.1% (63/330) healthy children were infected by EVs including 17.9% (59/330) of NPEVs and 1.2% (4/330) of type 3 Sabin-like PVs. Only one EV-C type, EV-C99 was identified among the NPEV collection from AFP patients whereas 27.5% of the 69 NPEV isolates typed in healthy children belonged to the EV-C species: CV-A13 (13/69), A20 (5/69) and A17 (1/69). Interestingly, 50 of the 54 cVDPVs featured recombinant genomes containing exogenous sequences in at least one of the targeted non-structural regions of their genomes: 5’UTR, 2CATPase and 3Dpol. Some of these non-vaccine sequences of the recombinant cVDPVs were strikingly related to homologous sequences from co-circulating CV-A17 and A20 in the 2CATPase region as well as to those from co-circulating CV-A13, A17 and A20 in the 3Dpol region. This study provided the first evidence uncovering CV-A20 strains as major recombination partners of PVs. High quality AFP surveillance, sensitive environmental surveillance and efficient vaccination activities remain essential to ensure timely detection and efficient response to recombinant cVDPVs outbreaks in DR Congo. Such needs are valid for any epidemiological setting where high frequency and genetic diversity of Coxsackieviruses A13, A17 and A20 provide a conducive viral ecosystem for the emergence of virulent recombinant cVDPVs.