Miracle-dz/UniFAR-FTUs huggingface dataset:
Longitudinal trajectories of physical functioning among Chinese older adults: the role of depressive symptoms, cognitive functioning and subjective memory.

BACKGROUND AND OBJECTIVE Maintaining physical functioning (i.e. mobility, activities of daily living [ADLs], instrumental activities of daily living [IADLs]) in older adults is essential for independent living. However, little is known about how longitudinal trajectories of physical functioning differ by varying levels of depressive symptoms, subjective memory impairment and cognitive functioning. We aimed to examine whether, and to what degree, the rate of change in physical functioning over time was associated with depressive symptoms, subjective memory and cognitive functioning. DESIGN A correlational longitudinal design. METHODS The sample included 5,519 older adults (mean age = 68.13 years) from the China Health and Retirement Longitudinal Study (three waves: 2011-15) who self-reported their depressive symptoms, subjective memory impairment and physical functioning. Cognitive functioning was assessed through interview-based tests. RESULTS There were significant increases in mobility impairment (β = 0.27, P < 0.001), ADLs impairment (β = 0.05, P < 0.001) and IADLs impairment (β = 0.03, P = 0.006) over time. Compared with the mean score at baseline in 2011, the mobility, ADLs and IADLs impairment increased by 13.32, 10.57 and 4.34% for every 2 years, respectively. Those with high depressive symptoms had accelerated rates of mobility (β = 0.212, P < 0.001), ADLs (β = 0.104, P < 0.001) and IADLs impairment (β = 0.076, P = 0.002). Those with poorer cognitive functioning had more rapid rates of mobility impairment. In contrast, those with differing levels of subjective memory impairment did not experience different physical functioning trajectories. CONCLUSIONS High depressive symptoms and poor cognitive functioning may be precursors to rapid declines in physical functioning. Proactive screening for these precursors may attenuate physical decline among Chinese older adults.
Improving the detection of infectious diseases in at-risk migrants with an innovative integrated multi-infection screening digital decision support tool (IS-MiHealth) in primary care: a pilot cluster-randomized-controlled trial

Abstract Background There are major shortfalls in the identification and screening of at-risk migrant groups. This study aims to evaluate the effectiveness of a new digital tool (IS-MiHealth) integrated into the electronic patient record system of primary care centres in detecting prevalent migrant infections. IS-MiHealth provides targeted recommendations to health professionals for screening multiple infections, including human immunodeficiency virus (HIV), hepatitis B and C, active tuberculosis (TB), Chagas disease, strongyloidiasis and schistosomiasis, based on patient characteristics (including variables of country of origin, age and sex). Methods A pragmatic pilot cluster-randomized-controlled trial was deployed from March to December 2018. Eight primary care centres in Catalonia, Spain, were randomly allocated 1:1 to use of the digital tool for screening, or to routine care. The primary outcome was the monthly diagnostic yield of all aggregated infections. Intervention and control sites were compared before and after implementation with respect to their monthly diagnostic yield using regression models. This study is registered on international standard randomised controlled trial number (ISRCTN) (ISRCTN14795012). Results A total of 15 780 migrants registered across the eight centres had at least one visit during the intervention period (March–December 2018), of which 14 598 (92.51%) fulfilled the criteria to be screened for at least one infection. There were 210 (2.57%) individuals from the intervention group with new diagnoses compared with 113 (1.49%) from the control group [odds ratio: 2.08, 95% confidence interval (CI) 1.63–2.64, P < 0.001]. The intervention centres raised their overall monthly diagnosis rate to 5.80 (95% CI 1.23–10.38, P = 0.013) extra diagnoses compared with the control centres. This monthly increase in diagnosis in intervention centres was also observed if we consider all cases together of HIV, hepatitis B and C, and active TB cases [2.72 (95% CI 0.43–5.00); P = 0.02] and was observed as well for the parasitic infections’ group (Chagas disease, strongyloidiasis and schistosomiasis) 2.58 (95% CI 1.60–3.57; P < 0.001). Conclusions The IS-MiHealth increased screening rate and diagnostic yield for key infections in migrants in a population-based primary care setting. Further testing and development of this new tool is warranted in larger trials and in other countries.
Prevalence of uterine rupture among women with one prior low transverse cesarean and women with unscarred uterus undergoing labor induction with PGE2: A systematic review and meta-analysis

Background As uterine rupture may affect as many as 11/1000 women with 1 prior cesarean birth and 5/10.000 women with unscarred uterus undergoing labor induction, we intended to estimate the prevalence of such rare outcome when PGE2 is used for cervical ripening and labor induction. Methods We searched MEDLINE, ClinicalTrials.gov and the Cochrane library up to September 1st 2020. Retrospective and prospective cohort studies, as well as randomized controlled trials (RCTs) on singleton viable pregnancies receiving PGE2 for cervical ripening and labor induction were reviewed. Prevalence of uterine rupture was meta-analyzed with Freeman-Tukey double arcsine transformation among women with 1 prior low transverse cesarean section and women with unscarred uterus. Results We reviewed 956 full text articles to include 69 studies. The pooled prevalence rate of uterine rupture is estimated to range between 2 and 9 out of 1000 women with 1 prior low transverse cesarean (5/1000; 95%CI 2-9/1000, 122/9000). The prevalence of uterine rupture among women with unscarred uterus is extremely low, reaching at most 0.7/100.000 (<1/100.000.000; 95%CI <1/100.000.000–0.7/100.000, 8/17.684). Conclusions Uterine rupture is a rare event during cervical ripening and labor induction with PGE2.
Competition in aluminium phosphinate-based halogen-free flame retardancy of poly(butylene terephthalate) and its glass-fibre composites

Abstract Aluminium diethylphosphinate (AlPi-Et) and inorganic aluminium phosphinate with resorcinol-bis(di-2,6-xylyl phosphate) (AlPi-H+RXP) were compared with each other as commercially available halogen-free flame retardants in poly(butylene terephthalate) (PBT) as well as in glass-fibre-reinforced PBT (PBT/GF). Pyrolysis behaviour and flame retardancy performance are reported in detail. AlPi-H+RXP released phosphine at very low temperatures, which can become a problem during processing. AlPi-Et provided better limiting oxygen index (LOI) values and UL 94 ratings for bulk and PBT/GF than AlPi-H+RXP. Both flame retardants acted via three different flame-retardancy mechanisms in bulk as well as in PBT/GF, namely, flame inhibition, increased amount of char, and a protection effect of the char. AlPi-Et was more efficient in decreasing the total heat evolved of PBT in the cone calorimeter test. AlPi-H+RXP reduced the peak heat release rate of PBT more efficiently than AlPi-Et. An optimum loading of AlPi-Et in PBT/GF was found, which was below the supplier’s recommendation. This loading provides a maximum increase in LOI and a maximum decrease in total heat evolved.
An Examination of the Factor Structure of the Multidimensional Psychological Flexibility Inventory

The Multidimensional Psychological Flexibility Inventory (MPFI), a 60-item self-report measure, assesses the Acceptance and Commitment Therapy Hexaflex. The factor structure of the MPFI was examined in this study. In a community sample of adults (N = 827), four models (correlated six-factor, one-factor, higher order, and bifactor) were tested for each of the constructs of interest (i.e., psychological flexibility and psychological inflexibility). All models, with the exception of the one-factor, provided adequate fit to the data. Differences between the three adequate fitting models were trivial in magnitude. Additional statistical indices from the bifactor models indicated that the general factors accounted for the large majority of reliable variance. The majority of the domain-specific factors evidenced redundancy with their respective general factors. Results from a series of structural regressions indicated that the domain-specific factors did not provide additional incremental utility above and beyond the general factors in predicting two relevant clinical constructs (i.e., health anxiety and depression). These results provide support for the use of the MPFI Flexibility and Inflexibility total scores, but not subscale scores. The MPFI may require further refinement to either greatly reduce the length of the measure, or to ensure that subscales have incremental utility.
Association Between Prepregnancy Obesity and Health Behaviors, Adverse Conditions, and Birth Outcomes in South Dakota.

INTRODUCTION Prepregnancy obesity has been shown to be associated with increased risk of adverse birth outcomes but little is known about the associations with health-related behaviors and conditions before, during and after pregnancy. METHODS This retrospective cohort study used data from the South Dakota Pregnancy Risk Assessment Monitoring System (SD PRAMS) survey, which is an ongoing state-based surveillance system of maternal behaviors, attitudes, and experiences before, during, and shortly after pregnancy. The 2017 and 2018 SD PRAMS sampled a total of 3,805 mothers who were randomly selected from birth certificate records to be representative of all South Dakota women who delivered a live-born infant. Logistic regression was used to determine whether prepregnancy obesity was associated with adverse health conditions after controlling for demographic factors. RESULTS Women with prepregnancy obesity, compared to those who were non-obese, were more likely to report an unintended pregnancy (45 percent vs. 39 percent), smoking three months before pregnancy (32 percent vs. 22 percent), delayed prenatal care (12 percent vs. 16 percent), hypertension during pregnancy (22 percent vs. 9 percent), gestational diabetes (19 percent vs. 8 percent), depression during pregnancy (21 percent vs. 14 percent), C-section delivery (35 percent vs. 22 percent), high birth weight (15 percent vs. 8 percent), and the infant hospitalized for three or more days (41 percent vs. 30 percent). Of women with prepregnancy obesity, 37 percent had been talked to by health care providers about maintaining a healthy weight the 12 months before pregnancy compared to 13 percent of non-obese women. CONCLUSIONS Health care workers should be more intentional about stressing the potential risks of prepregnancy obesity to properly educate mothers and women of childbearing age.
Aldehyde dehydrogenase 2 protects against acute kidney injury by regulating autophagy via the Beclin-1 pathway

The mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) catalyzes the detoxification of acetaldehyde and endogenous lipid aldehydes. Approximately 40% of East Asians, accounting for 8% of the human population, carry the E504K mutation in ALDH2 that leads to accumulation of toxic reactive aldehydes and increases the risk for cardiovascular disease, cancer, and Alzheimer disease, among others. However, the role of ALDH2 in acute kidney injury (AKI) remains poorly defined and is therefore the subject of the present study using various cellular and organismal sources. In murine models, in which AKI was induced by either the contrast agent iohexol or renal ischemia/reperfusion, KO, activation/overexpression of ALDH2 were associated with increased and decreased renal injury, respectively. In murine renal tubular epithelial cells (RTECs), ALDH2 upregulated Beclin-1 expression, promoted autophagy activation, and eliminated ROS. In vivo and in vitro, both 3-MA and Beclin-1 siRNAs inhibited autophagy and abolished ALDH2-mediated renoprotection. In mice with iohexol-induced AKI, ALDH2 knockdown in RTECs using AAV-shRNA impaired autophagy activation and aggravated renal injury. In human renal proximal tubular epithelial HK-2 cells exposed to iohexol, ALDH2 activation potentiated autophagy and attenuated apoptosis. In mice with AKI induced by renal ischemia/reperfusion, ALDH2 overexpression or pretreatment regulated autophagy mitigating apoptosis of RTECs and renal injury. In summary, our data collectively substantiate a critical role of ALDH2 in AKI via autophagy activation involving the Beclin-1 pathway.
Preparation and Characterization of Co-Processed Mannitol and Sorbitol Using NanoCrySP Technology

Particle engineering of excipients, at sub-particulate level using co-processing, can provide high functionality excipients. NanoCrySP technology has been recently explored as a novel approach for the generation of nanocrystalline solid dispersion of poorly soluble drugs, using spray drying process. The purpose of the present study was to generate co-processed mannitol and sorbitol (SD-CSM) using NanoCrySP technology having similar composition to commercial co-processed excipient (Compressol® SM, CP). The characterization of excipients was performed to evaluate their various physicomechanical properties. The sub-micron crystallite size of sorbitol in the matrix of mannitol was determined using the Williamson-Hall equation and Halder-Wagner equation. The reduction in crystallite size of sorbitol and mannitol, lower melting point, and lower heat of fusion of SD-CSM could be responsible for excellent compactibility, better tabletability, and comparable compressibility with respect to CP. This was confirmed by the compressibility-tabletability-compactibility (CTC) profile and Heckel plot analysis. Overall, SD-CSM generated using NanoCrySP technology improved functionalities of excipients over CP and would be useful for direct compression application.
Clozapine rechallenge following neutropenia using granulocyte colony-stimulating factor: A Quebec case series

Background: Clozapine has a unique efficacy profile among individuals suffering from treatment-resistant schizophrenia, but is associated with hematological side effects. The use of granulocyte colony-stimulating factors (G-CSF) to allow clozapine continuation or rechallenge has emerged as a promising option, but evidence is still scarce. Aim: To describe the largest case series so far published regarding this practice. Method: A national clozapine hematological monitoring database was consulted to identify all patients who had had neutrophil count <1.5 × 109/L since 2004 in Quebec and was cross-referenced with hospital pharmacy software to identify patients who had received at least one dose of G-CSF, such as filgrastim, while being exposed to clozapine. All data were collected retrospectively, using patients’ medical files, from January to July 2019. Results: Using G-CSF, three out of eight patients could maintain clozapine despite neutropenia episodes that otherwise would have required treatment discontinuation. The only side effect reported was mild short-lived back pain, over a mean 3-year follow-up period. In all but one case, filgrastim was used on an “as-needed” basis at doses of 300 mcg administered subcutaneously. Conclusion: These results suggest that the “as-needed” use of G-CSF is well-tolerated and may allow clozapine rechallenge in some well-selected patients, adding to the paucity of data regarding long-term safety and efficacy of this strategy. More research may help to better define potential candidates and optimal regimen of such practice.
Defining Polysaccharide-Specific Antibody Targets against Vibrio cholerae O139 in Humans following O139 Cholera and following Vaccination with a Commercial Bivalent Oral Cholera Vaccine, and Evaluation of Conjugate Vaccines Targeting O139

Cholera is a severe dehydrating illness of humans caused by Vibrio cholerae serogroup O1 or O139. Protection against cholera is serogroup specific, and serogroup specificity is defined by O-specific polysaccharide (OSP). ABSTRACT Cholera caused by Vibrio cholerae O139 could reemerge, and proactive development of an effective O139 vaccine would be prudent. To define immunoreactive and potentially immunogenic carbohydrate targets of Vibrio cholerae O139, we assessed immunoreactivities of various O-specific polysaccharide (OSP)-related saccharides with plasma from humans hospitalized with cholera caused by O139, comparing responses to those induced in recipients of a commercial oral whole-cell killed bivalent (O1 and O139) cholera vaccine (WC-O1/O139). We also assessed conjugate vaccines containing selected subsets of these saccharides for their ability to induce protective immunity using a mouse model of cholera. We found that patients with wild-type O139 cholera develop IgM, IgA, and IgG immune responses against O139 OSP and many of its fragments, but we were able to detect only a moderate IgM response to purified O139 OSP-core, and none to its fragments, in immunologically naive recipients of WC-O1/O139. We found that immunoreactivity of O139-specific polysaccharides with antibodies elicited by wild-type infection markedly increase when saccharides contain colitose and phosphate residues, that a synthetic terminal tetrasaccharide fragment of OSP is more immunoreactive and protectively immunogenic than complete OSP, that native OSP-core is a better protective immunogen than the synthetic OSP lacking core, and that functional vibriocidal activity of antibodies predicts in vivo protection in our model but depends on capsule thickness. Our results suggest that O139 OSP-specific responses are not prominent following vaccination with a currently available oral cholera vaccine in immunologically naive humans and that vaccines targeting V. cholerae O139 should be based on native OSP-core or terminal tetrasaccharide. IMPORTANCE Cholera is a severe dehydrating illness of humans caused by Vibrio cholerae serogroup O1 or O139. Protection against cholera is serogroup specific, and serogroup specificity is defined by O-specific polysaccharide (OSP). Little is known about immunity to O139 OSP. In this study, we used synthetic fragments of the O139 OSP to define immune responses to OSP in humans recovering from cholera caused by V. cholerae O139, compared these responses to those induced by the available O139 vaccine, and evaluated O139 fragments in next-generation conjugate vaccines. We found that the terminal tetrasaccharide of O139 is a primary immune target but that the currently available bivalent cholera vaccine poorly induces an anti-O139 OSP response in immunologically naive individuals.
Outcomes and Prognostic Factors in a Large Cohort of Hospitalized Cancer Patients With COVID-19

PURPOSE Patients with cancer are at increased risk for unfavorable outcomes from COVID-19. Knowledge about the outcome determinants of severe acute respiratory syndrome coronavirus 2 infection in this population is essential for risk stratification and definition of appropriate management. Our objective was to evaluate prognostic factors for all-cause mortality in patients diagnosed with both cancer and COVID-19. METHODS All consecutive patients with cancer hospitalized at our institution with COVID-19 were included. Electronic medical records were reviewed for clinical and laboratory characteristics potentially associated with outcomes. RESULTS Five hundred seventy-six consecutive patients with cancer and COVID-19 were included in the present study. An overall in-hospital mortality rate of 49.3% was demonstrated. Clinical factors associated with increased risk of death because of COVID-19 were age over 65 years, Eastern Cooperative Oncology Group performance status > 0 zero, best supportive care, primary lung cancer, and the presence of lung metastases. Laboratory findings associated with a higher risk of unfavorable outcomes were neutrophilia, lymphopenia, and elevated levels of D-dimer, creatinine, C-reactive protein, or AST. CONCLUSION A high mortality rate in patients with cancer who were diagnosed with COVID-19 was demonstrated in the present study, emphasizing the need for close surveillance in this group of patients, especially in those with unfavorable prognostic characteristics.
Polygenic and major‐locus contributions to sexual maturation timing in Atlantic salmon

Sexual maturation timing is a life‐history trait central to the balance between mortality and reproduction. Maturation may be triggered when an underlying compound trait, called liability, exceeds a threshold. In many different species and especially fishes, this liability is approximated by growth and body condition. However, environmental vs. genetic contributions either directly or via growth and body condition to maturation timing remain unclear. Uncertainty exists also because the maturation process can reverse this causality and itself affect growth and body condition. In addition, disentangling the contributions of polygenic and major loci can be important. In many fishes, males mature before females, enabling the study of associations between male maturation and maturation‐unbiased female liability traits. Using 40 Atlantic salmon families, longitudinal common‐garden experimentation, and quantitative genetic analyses, we disentangled environmental from polygenic and major locus (vgll3) effects on male maturation, and sex‐specific growth and condition. We detected polygenic heritabilities for maturation, growth, and body condition, and vgll3 effects on maturation and body condition but not on growth. Longitudinal patterns for sex‐specific phenotypic liability, and for genetic variances and correlations between sexes suggested that early growth and condition indeed positively affected maturation initiation. However, towards spawning time, causality appeared reversed for males whereby maturation affected growth negatively and condition positively via both the environmental and genetic effects. Altogether, the results indicate that growth and condition are useful traits to study liability for maturation initiation, but only until maturation alters their expression, and that vgll3 contributes to maturation initiation via condition.
Diagnostic yield of advanced genetic testing in patients with hereditary neuropathies: A retrospective single‐site study

Advanced genetic testing including next‐generation sequencing (AGT/NGS) has facilitated DNA testing in the clinical setting and greatly expanded new gene discovery for the Charcot‐Marie‐Tooth neuropathies and other hereditary neuropathies (CMT/HN). Herein, we report AGT/NGS results, clinical findings, and diagnostic yield in a cohort of CMT/HN patients evaluated at our neuropathy care center.