Miracle-dz/UniFAR-FTUs huggingface dataset:
Household Smoke-Exposure Risks Associated with Cooking Fuels and Cooking Places in Tanzania: A Cross-Sectional Analysis of Demographic and Health Survey Data

Household smoke-exposure risk (SER) can be defined through the assessment of cooking fuels (smoke and no smoke-producing) and cooking places (indoor and outdoor) related information, which represent different levels of household air pollution. This study aimed to explore the prevalence and geographical variations in smoke-exposure risks (SERs) associated with indoor and outdoor cooking practices and use of smoke-producing and non-smoke-producing cooking fuels in Tanzania. We further investigated the social and spatial features associated with household SERs. We defined an indicator variable, the household SER, using country-level, cross-sectional data on cooking fuels and cooking places obtained from the 2015–2016 Tanzania Demographic and Health Survey and then estimated zone-level average SERs. We used an ordered logistic regression model to assess the social and spatial characteristics associated with household SER. We identified 76.4% of the 12,425 households that practiced indoor cooking using smoke-producing fuels as having a high SER. High-level SER was more prevalent in the Central, Southern highland, and Southwest highland zones. Overall, wealthier households, female-headed households, and households with higher education attainments were more likely to be categorized as households with very low SER. Meanwhile, households headed by older individuals and with larger family sizes were less likely to be in the very low SER category. The prevalence of high SER is a major public health concern in Tanzania. Improved cooking stoves and cleaner fuels should be adopted simultaneously to minimize the adverse effects associated with household SER.
The Economic Burden of Dementia: Evidence from a Survey of Households of People with Dementia and Their Caregivers

Although a cognitive impairment such as dementia causes serious economic problems among older people, its impact on economic activities is unclear. This study investigated the actual conditions of economic activities and the current status of the financial support systems among people with dementia and caregivers. One hundred and five dyads participated in the survey. Each dyad consisted of an older person with Alzheimer’s disease and their caregiver. The Mini-Mental State Examination (MMSE) and Functional Assessment Staging (FAST) were used to evaluate the cognitive functions of people with dementia. The caregivers were asked questions concerning the financial status of the household and their utilization of the financial support systems available to people with dementia. Average monthly care costs significantly increased according to the severity of dementia, while household income and spending incurred no significant changes. People with dementia experienced financial problems (including a large amount of erroneously purchased, unnecessary shopping), even though their assets were informally managed by their caregivers. Financial support systems such as adult guardianship and civil trust systems were rarely known and used. We proposed the propagation of the adult guardianship and civil trust systems and the development of contract guidelines for elderly customers including people with dementia.
Is COVID-19 impacting prostate cancer screening? A survey of prostate-specific antigen test requests during a local outbreak

Background Although the ongoing pandemic of coronavirus disease 2019 (COVID-19) is directly contributing to negatively affect global health and fitness, the restrictive measures applied for containing the outbreaks are also impacting detection and management of many diseases, including cancers. This study aimed to establish if and how the COVID-19 outbreak may have impacted the practice of routine prostate cancer screening in Verona, Italy. Methods We searched the laboratory information system of the Service of Laboratory Medicine of the University Hospitals of Verona to identify all test requests for total prostate-specific antigen (PSA) and vitamin D (Vit D; i.e., the locally most requested immunochemical test) for outpatients during the last five years (December 10, 2016, to December 10, 2020). The weekly requests for these tests placed between February 25 and December 9, 2020, were compared to those placed during the same period of previous four years (i.e., 2016-2019). Results The volume of test requests for both Vit D and PSA did not differ in 2020 compared to previous four years. However, a dramatic decline was observed during the local lockdown period (between March 10 and May 17, 2020), with median decrease of 76% for Vit D and 62% for total PSA, respectively. This reduction was compensated by 13% increase for Vit D and 43% increase for total PSA in post-lockdown period. Conclusion These results show that the lockdown period established during the first peak of the COVID-19 outbreak in Italy’s Verona province was associated with a dramatic decrease in routine prostate cancer screenings.
Structure of an ancestral ADP-dependent kinase with fructose-6P reveals key residues for binding, catalysis, and ligand-induced conformational changes

ADP-dependent kinases were first described in archaea, although their presence has also been reported in bacteria and eukaryotes (human and mouse). This enzyme family comprises three substrate specificities; specific phosphofructokinases (ADP-PFKs), specific glucokinases (ADP-GKs), and bifunctional enzymes (ADP-PFK/GK). Although many structures are available for members of this family, none exhibits fructose-6-phosphate (F6P) at the active site. Using an ancestral enzyme, we obtain the first structure of an ADP-dependent kinase (AncMsPFK) with F6P at its active site. Key residues for sugar binding and catalysis were identified by alanine scanning, D36 being a critical residue for F6P binding and catalysis. However, this residue hinders glucose binding because its mutation to alanine converts the AncMsPFK enzyme into a specific ADP-GK. Residue K179 is critical for F6P binding, while residues N181 and R212 are also important for this sugar binding, but to a lesser extent. This structure also provides evidence for the requirement of both substrates (sugar and nucleotide) to accomplish the conformational change leading to a closed conformation. This suggests that AncMsPFK mainly populates two states (open and closed) during the catalytic cycle, as reported for specific ADP-PFK. This situation differs from that described for specific ADP-GK enzymes, where each substrate independently causes a sequential domain closure, resulting in three conformational states (open, semiclosed, and closed).
Escherichia coli vacuolating factor, involved in avian cellulitis, induces actin contraction and binds to cytoskeleton proteins in fibroblasts

Abstract Background Avian pathogenic Escherichia coli (APEC) isolated from avian cellulitis lesions produces a toxin, named Escherichia coli vacuolating factor (ECVF), that causes cell vacuolization and induces inflammatory response in broiler chicken. Methods We investigated the intracellular activities of ECVF in avian fibroblasts using fluorescence staining, electron microscopy, MTT and LDH measurements. As ECVF act specifically in avian cells, we performed blotting assay followed by mass spectrometry to better understand its initial intracellular protein recognition. Results ECVF induced actin contraction, mitochondrial damage and membrane permeability alterations. Ultrastructural analysis showed intracellular alterations, as nuclear lobulation and the presence of degraded structures inside the vacuoles. Moreover, ECVF induced cell death in fibroblasts. ECVF-biotin associates to at least two proteins only in avian cell lysates: alpha-actinin 4 and vinculin, both involved in cytoskeleton structure. Conclusion These findings demonstrated that ECVF plays an important role in avian cellulitis, markedly in initial steps of infection. Taken together, the results place this toxin as a target for drug and/or vaccine development, instead of the use of large amounts antibiotics.
Antibiotic use in children and youths with asthma: a population-based case-control study

Rationale Antibiotics are among the most common medications dispensed to children and youths. The objective of this study was to characterise and compare antibiotic use patterns between children and youths with and without asthma. Methods We conducted a population-based nested case–control study using health administrative data from Ontario, Canada, in 2018. All Ontario residents aged 5–24 years with asthma were included as cases. Cases were matched to controls with a 1:1 ratio based on age (within 0.5 year), sex and location of residence. Multivariable conditional logistic regression was used to obtain an odds ratio and 95% confidence interval for having filled at least one antibiotic prescription, adjusted for socioeconomic status, rurality, and presence of common infections, allergic conditions and complex chronic conditions. Results The study population included 1 174 424 Ontario children and youths aged 5–24 years. 31% of individuals with asthma and 23% of individuals without asthma filled at least one antibiotic prescription. The odds of having filled at least one antibiotic prescription were 34% higher among individuals with asthma compared to those without asthma (OR 1.34, 95% CI 1.32–1.35). In the stratified analysis, the odds ratios were highest in the youngest group of children studied, aged 5–9 years (OR 1.45, 95% CI 1.41–1.48), and in females (OR 1.36, 95% CI 1.34–1.38). Conclusion Asthma is significantly associated with increased antibiotic use in children and youths. This association is the strongest in younger children and in females. Asthma is significantly associated with increased antibiotic use in children and youths. The odds of antibiotic use are 34% higher in individuals with asthma. This association is the strongest in younger children and in females. https://bit.ly/3dusuz9
Single-cell transcriptome analysis of the heterogeneous effects of differential expression of tumor PD-L1 on responding TCR-T cells

Rationale: TCR-T cell therapy plays a critical role in the treatment of malignant cancers. However, it is unclear how TCR-T cells are affected by PD-L1 molecule in the tumor environment. We performed an in-depth evaluation on how differential expressions of tumor PD-L1 can affect the functionality of T cells. Methods: We used MART-1-specific TCR-T cells (TCR-TMART-1), stimulated with MART-127-35 peptide-loaded MEL-526 tumor cells, expressing different proportions of PD-L1, to perform cellular assays and high-throughput single-cell RNA sequencing. Results: Different clusters of activated or cytotoxic TCR-TMART-1 responded divergently when stimulated with tumor cells expressing different percentages of PD-L1 expression. Compared to control T cells, TCR-TMART-1 were more sensitive to exhaustion, and secreted not only pro-inflammatory cytokines but also anti-inflammatory cytokines with increasing proportions of PD-L1+ tumor cells. The gene profiles of chemokines were modified by increased expression of tumor PD-L1, which concurrently downregulated pro-inflammatory and anti-inflammatory transcription factors. Furthermore, increased expression of tumor PD-L1 showed distinct effects on different inhibitory checkpoint molecules (ICMs). In addition, there was a limited correlation between the enrichment of cell death signaling in tumor cells and T cells and increased tumor PD-L1 expression. Conclusion: Overall, though the effector functionality of TCR-T cells was suppressed by increased expression percentages of tumor PD-L1 in vitro, scRNA-seq profiles revealed that both the anti-inflammatory and pro-inflammatory responses were triggered by a higher expression of tumor PD-L1. This suggests that the sole blockade of tumor PD-L1 might inhibit not only the anti-inflammatory response but also the pro-inflammatory response in the complicated tumor microenvironment. Thus, the outcome of PD-L1 intervention may depend on the final balance among the highly dynamic and heterogeneous immune regulatory circuits.
Monovalent antibody-conjugated lipid-polymer nanohybrids for active targeting to desmoglein 3 of keratinocytes to attenuate psoriasiform inflammation

To improve the treatment of psoriasiform inflammation, we developed actively targeted nanocarriers loaded with the phosphodiesterase 4 inhibitor AN2728. Methods: Phospholipid-poly(lactic-co-glycolic acid) nanohybrids were prepared and conjugated with monovalent anti-desmoglein 3 antibody to bind keratinocytes. Results: The actively targeted nanohybrids were 229 nm in mean size with a nearly neutral surface charge. Flow cytometry and confocal microscopy showed a 9-fold increase in keratinocyte uptake of targeted nanohybrids relative to non-targeted nanoparticles. The nanoparticles localized mainly in lysosomes after internalization. AN2728-loaded antibody-conjugated nanocarriers inhibited cytokine/chemokine overexpression in activated keratinocytes without affecting cell viability. The targeted nanohybrids also suppressed neutrophil migration by reducing CXCL1 and CXCL2 release from keratinocytes. Following subcutaneous administration in mice, the nanohybrids distributed to the epidermis and hair follicles. In a psoriasis-like skin mouse model, the actively targeted nanoparticles were superior to free drug and non-targeted nanoparticles in mitigating skin inflammation. Intervention with the targeted nanosystem reduced the epidermal thickness of the psoriasiform lesion from 191 to 42 µm, decreased the Psoriasis Area Severity Index by 74%, restored barrier function, and returned chemokine levels to baseline. Conclusions: Our developed nanosystem was safe and demonstrated efficient targeting properties for the treatment of cutaneous inflammation.
Dabigatran activates inflammation resolution by promoting fibrinogen-like protein 2 shedding and RvD5n-3 DPA production

Rationale: The interaction between coagulation and inflammation resolution remains elusive. We recently highlighted a link between fibrinogen-like protein 2 (Fgl2) and a specialized pro-resolving mediator (SPM)-n-3 docosapentaenoic acid-derived resolvin D5 (RvD5n-3 DPA) in sepsis. This study aimed to investigate the functions of commonly used anticoagulants warfarin, dabigatran and heparin in regulating inflammation resolution. Methods: Peripheral blood was collected from clinical sepsis patients and healthy control for the determination of indicated indexes. Mouse sepsis models of zymosan-induced peritonitis and cecal ligation and puncture (CLP) were employed for the measurement of inflammation- and coagulation-related indexes. Western-blotting, ELISA and flow cytometry were applied to assess proteins. UPLC-MS/MS was used to evaluate lipid metabolites. Results: Here we report that the transmembrane Fgl2 (mFgl2) was positively associated with coagulation, while soluble Fgl2 (sFgl2) level correlated with the enhanced number of peripheral blood mononuclear cells in the sepsis patients. The anticoagulants dabigatran and warfarin attenuated zymosan-induced peritonitis, which was not shared by heparin, while only dabigatran significantly improved sepsis survival in the CLP sepsis mouse model. Although these anticoagulants consistently inhibited pro-inflammatory mediators including prostaglandin E2 and leukotriene B4, only dabigatran increased sFgl2 at both the initiation and resolution phases of inflammation. Mechanistically, dabigatran elicited the shedding of sFgl2 via prothrombin-related metalloproteases, thereby enhanced the subsequent biosynthesis of RvD5n-3 DPA via STAT6-ALOX15 axis. Blocking metalloproteases or ALOX15 significantly impaired dabigatran-enhanced macrophage efferocytosis in vitro, as well as delayed the dabigatran-accelerated inflammation resolution in vivo. Conclusions: Our findings identify the dual anti-inflammatory and pro-resolving actions of dabigatran, through promoting sFgl2-triggered RvD5n-3 DPA production, which has important implications for promoting tissue homeostasis of sepsis.
BAFF receptor antibody for mantle cell lymphoma therapy

ABSTRACT Mantle cell lymphoma (MCL) is an aggressive form of B cell non-Hodgkin’s lymphoma and remains incurable under current treatment modalities. One of the main reasons for treatment failure is the development of drug resistance. Accumulating evidence suggests that B cell activating factor (BAFF) and BAFF receptor (BAFF-R) play an important role in the proliferation and survival of malignant B cells. High serum BAFF levels are often correlated with poor drug response and relapse in MCL patients. Our study shows that BAFF-R is expressed on both MCL patient cells and cell lines. BAFF-R knockdown leads to MCL cell death showing the importance of BAFF-R signaling in MCL survival. Moderate knockdown of BAFF-R in MCL cells did not affect its viability, but sensitized them to cytarabine treatment in vitro and in vivo, with prolonged mice survival. Anti-BAFF-R antibody treatment promoted drug-induced MCL cell death. Conversely, the addition of recombinant BAFF (rhBAFF) to MCL cells protected them from cytarabine-induced apoptosis. We tested the efficacy of a humanized defucosylated ADCC optimized anti-BAFF-R antibody in killing MCL. Our data show both in vitro and in vivo efficacy of this antibody for MCL therapy. To conclude, our data indicate that BAFF/BAFF-R signaling is crucial for survival and involved in drug resistance of MCL. Targeting BAFF-R using BAFF-R antibody might be a promising therapeutical strategy to treat MCL patients resistant to chemotherapy.
Associations between Sociodemographic, Dietary, and Substance Use Factors with Self-Reported 24-Hour Movement Behaviors in a Sample of Brazilian Adolescents

We aimed to identify sociodemographic, dietary, and substance use factors associated with self-reported sleep duration, physical activity (PA), and sedentary behavior (SB) indicators in a sample of Brazilian adolescents. Adolescents (n = 731, 51% female, mean age: 16.4 years) answered a questionnaire. The volume of total PA, sports, non-sports, total SB, leisure-time SB, involuntary SB, sleep duration, dietary behaviors, sociodemographic, and substance use indicators were self-reported. Multilevel linear models were fitted. Females engaged in less total PA, sports, total SB, and leisure-time SB, but in more involuntary SB than males. Age was positively associated with non-sports and involuntary SB. Socioeconomic status was positively associated with total PA. Adolescents who lived with the mother only practiced more sports compared to those living with two parents. Unprocessed food was positively associated with total PA and sports. Processed food was inversely associated with total PA and non-sports, and positively associated with total SB and leisure-time SB. Alcohol use was positively associated with total PA, and tobacco smoking was negatively associated with total PA. No associations were observed for sleep duration. In conclusion, sociodemographic, dietary, and substance use factors are associated with the 24 h movement behaviors among Brazilian adolescents, and some associations are type specific.
Cybervictimization and Adolescent Internet Addiction: A Moderated Mediation Model

Previous research indicates that cybervictimization can lead to adolescent Internet addiction; however, there is a gap in the knowledge about the mediating and moderating variables facilitating this relationship. This study examines the role of rejection sensitivity as a mediator in this relationship and the role of parent–adolescent communication as a moderator for this mediation effect among Chinese adolescents. Participants were 1006 adolescents (M = 13.16 years, SD = 0.67), who completed the questionnaires anonymously. The questionnaires assessed the four variables of interest. Descriptive statistics and structural equation modeling were used for data analysis. The results show that the positive association between cybervictimization and adolescent Internet addiction is mediated by rejection sensitivity. Moreover, this indirect effect is stronger for adolescents with low parent–adolescent communication than for those with high parent–adolescent communication.
Study on the Relationship between Drivers’ Personal Characters and Non-Standard Traffic Signs Comprehensibility

Drivers’ incorrect perception and interpretation of the road space are among reasons for human errors. Proper road markings are elements improving perception of road space. Their effectiveness relies on traffic participants receiving the provided information correctly. The range of signs used is constantly expanding and unusual situations in traffic require use of non-standard signs or an unusual combination of existing standard signs. The aim of this study was to explore the level of comprehensibility of four different types of non-standard signs. The relationship between the level of comprehensibility of these signs and personality traits of the drivers was also studied. A total of 369 drivers were tested using a questionnaire to analyze the traffic signs comprehensibility and Five Factor Inventory (NEO-FFI). The obtained results indicate that symbolic signs, unlike symbolic and text ones, are much better comprehended by drivers. Men comprehend the significance of non-standard symbolic regulatory signs better than women. Higher level of comprehensibility of symbolic and text regulatory signs is shown by older, better educated drivers and professional drivers. The study found there is a link between personality traits of the driver and the comprehensibility of symbolic regulatory signs.