Miracle-dz/UniFAR-FTUs huggingface dataset:
Clarifying the information and support needs of family caregivers of nursing home residents with advancing dementia

Background Research has identified inadequacies in the quality and quantity of dementia-related information, particularly end-of-life information provided to those living with dementia and their family caregivers. The purpose of this study was to identify what types of information family caregivers of persons living with dementia in nursing homes would deem useful in preparing them for their relative’s end-of-life and assist them to make decisions about care along the dementia trajectory. Methods The qualitative methodology of interpretive description was used to guide the study in which semi-structured interviews were conducted with nursing home staff in clinical roles (e.g., nurses, health care aides, social workers, speech language pathologists; N = 26), palliative care clinicians (N = 7), and bereaved family caregivers of persons with dementia (N = 17). Data were analyzed using thematic analysis. Findings Eight substantive categories essential to meeting family members’ needs for information and preparing them for the future were identified including: (i) dementia in general, (ii) dementia toward the end-of-life, (iii) care of persons dying with dementia, (iv) the role of family caregiver as decision maker, (v) sustaining connection, (vi) emotional impact of dementia on caregivers, (vii) relationships with staff, and (viii) general questions about life in a NH. Conclusion Our findings suggest that family caregivers of nursing home residents with dementia have unique information and support needs, some disease specific, others more related to life in a nursing home in general. Health care providers need to support and encourage dementia literacy for family caregivers. A key strategy is to proactively broach these topic areas, as too often family caregivers may not recognize or value their need for information.
Understanding chord mu through a large population‐based study

osmotic regulation. It was reported that more than 20 mutations in the MIP gene had been associated with congenital cataract until now (Cat-Map). Phenotypic and genotypic heterogeneity has been well documented in congenital cataract related to MIP these years. Inheritance of the same mutation in different families or in different individuals within the same family can result in radically different cataract phenotypes (phenotypic heterogeneity). Conversely, mutations in different genes active in apparently unrelated biological processes can cause cataracts having similar or identical morphologies (genotypic heterogeneity). In our study, the variant c. 430 T > C induced changes in the H4 of the MIP structure with almost all patients had similar lens features, except one individual (III.11) with an aphakic eye and a total cataract eye. In summary, the current study identified a novel missense mutation c. 430 T > C of the MIP gene in a non-consanguineous marriage of Chinese family. The value and novelty of this finding are not only to enrich the MIP gene mutation database but also to highlight the significance of MIP for the lens microcirculation system and the maintenance of lens transparency. Further investigations are necessary to elucidate the role of this novel MIP point mutation in cataract pathogenesis.
Expanding the phenotype of biallelic RNPC3 variants associated with growth hormone deficiency

Pathogenic variants in components of the minor spliceosome have been associated with several human diseases. Recently, it was reported that biallelic RNPC3 variants lead to severe isolated growth hormone deficiency and pituitary hypoplasia. The RNPC3 gene codes for the U11/U12‐65K protein, a component of the minor spliceosome. The minor spliceosome plays a role in the splicing of minor (U12‐type) introns, which are present in ~700–800 genes in humans and represent about 0.35% of all introns. Here, we report a second family with biallelic RNPC3 variants in three siblings with a growth hormone deficiency, central congenital hypothyroidism, congenital cataract, developmental delay/intellectual deficiency and delayed puberty. These cases further confirm the association between biallelic RNPC3 variants and severe postnatal growth retardation due to growth hormone deficiency. Furthermore, these cases show that the phenotype of this minor spliceosome‐related disease might be broader than previously described.
INTERACTION OF SUBSTRATE C:N RATIO AND OSMOTIC POTENTIAL ON GROWTH AND OSMOREGULATION OF FOUR FILAMENTOUS FUNGI.

Variation in the carbon to nitrogen ratio in the range 10:1 to 1000:1 had only a small effect on the radial growth rate of four species of fungus on a basic nutrient agar medium. There was no obvious pattern to the differences observed, whether the nitrogen source was organic or inorganic or the medium osmotic potential high or low. The final fresh weight of the colonies was more sensitive to C: N ratio and was depressed by high C: N ratios by as much as 90 % in some treatments. Polyporus versicolor L. ex Fr. was the most efficient accumulator of biomass at C: N of 1000:1, but Penicillium chrysogenum Thorn had the highest mycelial N content. Colony yield did not show the same relationship to external osmotic potential as did the radial growth rate, and the ratio at which the maximum yield at each osmotic potential occurred varied with the different treatments. Turgor potential was reduced by high C:N in the majority of treatments in Polyporus versicolor, Poria vincta (Berk.) Cke. and Phytophthora cinnamomi Rands but not at all in Penicillium chrysogenum. Water content increased with the C: N ratio and decreased with external osmotic potential in all the species except Phytophthora cinnamomi. There was no clear effect of C:N ratio on any of the hyphal solutes measured, that is Na+ , K+ , Cl- , proline or glycerol. Lower concentrations of the organic solutes were present in Phytophthora cinnamomi and Penicillium chrysogenum in these conditions than when KCl and Czapek-Dox with yeast extract medium was used; turgor potential of Penicillium chrysogenum also was 50% lower. Sodium chloride was used to adjust the external osmotic potential and Na+ and Cl- were taken up in increasing amounts as the osmotic potential decreased in all species. Potassium concentrations were similar between species and treatments. The hyphal osmotic potentials, calculated from these solutes alone, were lower (more negative) than the values measured in Poria vincta grown at -1 MPa and Penicillium chrysogenum grown at - 10MPa, but very close to those for Phytophthora cinnamomi grown at - 2.5 MPa.
Psychological impact of COVID-19 on ophthalmologists-in-training and practising ophthalmologists in India

Purpose: To evaluate the psychological impact of the COVID 19 crisis on ophthalmologists-in-training and practising ophthalmologists during lockdown in India. Methods: An online survey was completed by ophthalmologists and ophthalmology trainees during the lockdown. The information collected included demographics (age, gender), domicile (state, union territory), current professional status (in training or practising), type of practice (solo, group, institutional, governmental, non-governmental), marital status (married, single), impact of COVID-19 on their training or practice, and impact on income and ability to meet living expenses. Psychological distress was assessed using the Patient Health Questionnaire-9 (PHQ-9). Results: In all, 2,355 ophthalmologists responded. Mean age was 42.5 (range, 25-82 years; SD, 12.05) years. Of these, 1,332 (56.7%) were males; 475 (20.2%) were still not in practice; 366 (15.5%) were single; 1,244 (52.8%) felt that COVID-19 would impact on their training or professional work; and 869 (37%) had difficulty in meeting their living expenses. The mean PHQ-9 score was 3.98 (range, 0-27; SD, 4.65). In terms of psychological impact, 768 (32.6%) had some degree of depression; mild in 504 (21.4%), moderate in 163 (6.9%), and severe in 101 (4.3%). Multivariable analysis showed that depression was significantly higher at younger age. The odds of depression decreased by 3% with 1 year increase in age. It was higher in non-practicing ophthalmologists, especially those who were considerably worried about their training or professional growth, and those with difficulty in meeting living expenses. Conclusion: A strikingly high proportion of ophthalmologists are psychologically affected and may require personalized mental health care.
A parallelized, automated platform enabling individual or sequential ChIP of histone marks and transcription factors

Significance Chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) has become the most widely used method to infer the genomic binding locations of chromatin-associated proteins such as histones and transcription factors. Since its emergence in 2007, ChIP-seq has been performed through a long sequence of manual steps, with consequent limitations in throughput and sensitivity of the technique. Here, we present a microfluidic implementation of the ChIP procedure, named FloChIP, which greatly streamlines the experimental workflow. We show that FloChIP can perform standard ChIP and sequential ChIP assays in parallel and reproducibly in an automated fashion for histone marks and transcription factors. Despite its popularity, chromatin immunoprecipitation followed by sequencing (ChIP-seq) remains a tedious (>2 d), manually intensive, low-sensitivity and low-throughput approach. Here, we combine principles of microengineering, surface chemistry, and molecular biology to address the major limitations of standard ChIP-seq. The resulting technology, FloChIP, automates and miniaturizes ChIP in a beadless fashion while facilitating the downstream library preparation process through on-chip chromatin tagmentation. FloChIP is fast (<2 h), has a wide dynamic range (from 106 to 500 cells), is scalable and parallelized, and supports antibody- or sample-multiplexed ChIP on both histone marks and transcription factors. In addition, FloChIP’s interconnected design allows for straightforward chromatin reimmunoprecipitation, which allows this technology to also act as a microfluidic sequential ChIP-seq system. Finally, we ran FloChIP for the transcription factor MEF2A in 32 distinct human lymphoblastoid cell lines, providing insights into the main factors driving collaborative DNA binding of MEF2A and into its role in B cell-specific gene regulation. Together, our results validate FloChIP as a flexible and reproducible automated solution for individual or sequential ChIP-seq.
Distinct mitochondrial defects trigger the integrated stress response depending on the metabolic state of the cell

Mitochondrial dysfunction is associated with activation of the integrated stress response (ISR) but the underlying triggers remain unclear. We systematically combined acute mitochondrial inhibitors with genetic tools for compartment-specific NADH oxidation to trace mechanisms linking different forms of mitochondrial dysfunction to the ISR in proliferating mouse myoblasts and in differentiated myotubes. In myoblasts, we find that impaired NADH oxidation upon electron transport chain (ETC) inhibition depletes asparagine, activating the ISR via the eIF2α kinase GCN2. In myotubes, however, impaired NADH oxidation following ETC inhibition neither depletes asparagine nor activates the ISR, reflecting an altered metabolic state. ATP synthase inhibition in myotubes triggers the ISR via a distinct mechanism related to mitochondrial inner-membrane hyperpolarization. Our work dispels the notion of a universal path linking mitochondrial dysfunction to the ISR, instead revealing multiple paths that depend both on the nature of the mitochondrial defect and on the metabolic state of the cell.
Differences in growth and wood property traits in cloned Norway spruce (Picea abies)

Volume growth has typically been used as a selection trait of prime importance in forest tree breeding. Less attention has been given to the genetic or phenotypic relationships between the growth or yield and wood density traits. In the above context, we aimed to investigate the phenotypic relationships among different growth, yield, and wood density traits of 20 Norway spruce (Picea abies (L.) Karst. ) clones grown in southeastern Finland, in order to identify whether a high growth rate was associated with low wood density in any of the clones. Compared with growth or yield traits, the wood density traits showed lower phenotypic variations. The phenotypic correlations between growth, yield, and wood density traits were, on average, from moderate to high, suggesting that selection for one trait would simultaneously affect the other traits. Compared with volume production, selection based on stem mass could be more profitable if a clonal stand is managed for pulpwood rather than mechanical wood processing a.
Willingness of Patients Prescribed Medications for Lifestyle-Related Diseases to Use Personal Health Records: Questionnaire Study

Background Personal health record (PHR) systems let individuals utilize their own health information to maintain and improve quality of life. Using PHRs is expected to support self-management in patients with lifestyle-related diseases. Objective The aim of this study was to identify predictors of the willingness to use PHRs among patients who are prescribed medications for lifestyle-related diseases. Methods We recruited pharmacy patrons, aged 20 years or older, who had received at least one medication indicated for hypertension, dyslipidemia, or diabetes. Participants completed self-administered questionnaires regarding their previous diseases, awareness of health care, experience in using PHRs, willingness to use PHRs, and barriers to using PHRs. Data were analyzed using multivariate logistic regression models. Results Of the 3708 subjects meeting eligibility criteria, 2307 replies (62.22%) were collected. While only 174 (7.54%) participants had previous PHR experience, 853 (36.97%) expressed willingness to use PHRs. In the multivariate analysis, considering exercise to be important for health management (odds ratio [OR] 1.57, 95% CI 1.12-2.21; P=.009), obtaining medical information from books or magazines (OR 1.23, 95% CI 0.96-1.59; P=.10), and obtaining medical information from the internet (OR 1.45, 95% CI 1.13-1.87; P=.004) were newly identified predictors. These were in addition to known predictors, such as being employed, owning information terminals, and previous PHR experience. Conclusions Patients who have an active and positive attitude toward health seem to be more willing to use PHRs. Investigating willingness should contribute to the development of more useful PHRs for self-management among patients prescribed medications for lifestyle-related diseases.
Comparison of Transverse Craniofacial Dimensions Between Growing Individuals With Unilateral Cleft Lip and Palate and Age-and Sex-Matched Noncleft Controls

Objective: The study aimed to assess the transverse craniofacial dimensions of patients (age, 7-14 years) with unilateral cleft lip and palate (UCLP), compare these dimensions with those of noncleft individuals, and identify the correlations between the nasal and maxillary transverse widths of patients with UCLP. Design: A cross-sectional study. Participants: Eighty patients operated on for complete UCLP (UCLP group; 35 girls, 45 boys; median age: 10.7 [7.9-14] years) and 80 age- and sex-matched noncleft individuals (control group; 35 girls, 45 boys; median age: 10.7 [7.3-14] years). Interventions: Interorbital, bizygomatic, nasal, maxillary skeletal, maxillary molar, mandibular molar, and antegonial width measurements were performed using posteroanterior cephalometric radiographs. Intergroup comparisons were conducted by using the independent samples t-test and Mann-Whitney U test. Correlation between the variables was examined using Pearson correlation analysis. Results: The bizygomatic, maxillary skeletal and molar, mandibular molar, and antegonial widths in the UCLP group were significantly less than those in the control group (P < .05). A positive correlation was found between the maxillary skeletal and nasal widths (r = 0.550, P < .001) and between the maxillary molar and nasal widths (r = 0.560, P < .001). Conclusions: In individuals with UCLP, the bizygomatic, maxillary skeletal and molar, mandibular molar, and antegonial widths were significantly less than those in noncleft individuals. As the maxillary skeletal and dental widths presented a positive correlation with the nasal width, a decrease in nasal width must be considered when maxillary constriction is noted.
‘Being a good girl’: mother-daughter sexual communication in contemporary Vietnam

Abstract This paper examines the ways in which certain fractions of urban educated women residing in Hanoi, Vietnam communicate with their daughters about sex and pleasure, and the various meanings attributed to these verbal interchanges. Drawing on a limited number of qualitative in-depth interviews, the findings suggests that these intimate conversations were framed by discourses concerning the purity of ‘modern’ women. A distinct lack of sexual knowledge and experience, along with a more generalised shyness in communicating about sexual matters, continue to be highly indicative of those deemed to be ‘women of purity’, especially before marriage. Such beliefs and allied practices were adhered to not only by mothers, but also by women themselves, exerting significant influence on the determination and expression of sexual perceptions and behaviours.
Granzyme B is correlated with clinical outcome after PD-1 blockade in patients with stage IV non-small-cell lung cancer

Background A minority of patients with advanced non-small-cell lung cancer (NSCLC) benefit from treatment with immune checkpoint inhibitors (ICIs). Ineffective effector function of activated T and NK cells may lead to reduced tumor cell death, even when these activated effector cells are released from their immune checkpoint brake. Hence, in this study we aimed to assess the association of baseline serum granzyme B, as well as germline variation of the GZMB gene, with clinical outcome to programmed cell death protein 1 (PD-1) blockade. Methods A total of 347 patients with stage IV NSCLC who started nivolumab treatment between June 2013 and June 2017 were prospectively included. Baseline serum and whole blood was available, allowing for protein quantification and targeted DNA sequencing. Clinical outcome was based on best overall response (BOR) according to Response Evaluation Criteria in Solid Tumors, V.1. 1, progression-free survival (PFS), and overall survival (OS). Results Patients with low serum levels of granzyme B had worse PFS (HR: 1.96; 95% CI: 1.12 to 3.43; p=0.018) and worse OS (HR: 2.08; 95% CI: 1.12 to 3.87; p=0.021) than patients with high baseline serum levels. To validate the findings, germline variation of GZMB rs8192917 was assessed. Patients with homozygous and heterozygous variants of GZMB rs8192917 had worse BOR (OR: 1.60; 95% CI: 1.01 to 2.52; p=0.044) and worse PFS (HR: 1.38; 95% CI:1.02 to 1.87; p=0.036) than wild types. Conclusions A low baseline serum level of granzyme B and germline variation of GZMB was associated with worse clinical outcome in NSCLC, emphasizing the relevance and additional value of monitoring germline genetic variations which mirror cytotoxic functions of T cells in ICI therapy. Trail registration number Dutch Trial Registry (NL6828).
Seroepidemiology of tetanus in Hangzhou from 2009 to 2018

ABSTRACT Objective: The seroepidemiologic study aimed to delineate the immune status against tetanus in Hangzhou and its influential factors to provide evidence on strategies for tetanus prevention. Methods: We used a multi-stage stratified random sampling method to recruit participants from several Community Health Centers in Hangzhou during 2009–2018. Demographic data and vaccination histories of all subjects born during the period from 2004 to 2018 were collected from Hangzhou Immunization Information System (HZIIS), while the data of all subjects born before 2003 were acquired through case investigation. We used Enzyme Linked Immunosorbent Assay (ELISA) to detect Immunoglobulin G (IgG) antibodies against tetanus in serum samples and univariate and multivariate analysis to detect association between level of tetanus IgG and related factors. Results: A total of 3695 subjects were included, of which were 1904 males and 1791 females. About 59.84% of people had a clear immunization history of tetanus-toxoid-containing vaccines (TTCVs). The percentage of people whose tetanus IgG antibody titers were above the minimum protective level (0.1 IU/ml) was 76.02% (95% CI: 74.6–77.4%) and the geometric mean concentration (GMC) for tetanus IgG was 1.70 IU/ml. Antibody levels of people were higher in rural areas than in urban areas, in males than in females, in subjects who had inoculation vaccine history than those without inoculation of vaccine or with unknown history, and lower in groups aged >15 y compared to <15 y. Conclusions: The positive rate and GMC of tetanus IgG were significantly influenced by gender, age and immunization history of TTCVs. We should seek to achieve early and timely infant vaccination and maintain high coverage of the complete 3-dose primary series plus 3-dose booster series prior to adolescence. Besides basic immunization, we should stress the importance of using booster doses of tetanus vaccine in adolescents and adults; it is necessary to adopt corresponding immunization measures for women at childbearing age.
Age‐related changes to the satellite cell niche are associated with reduced activation following exercise

Skeletal muscle satellite cell (SC) function and responsiveness is regulated, in part, through interactions within the niche, in which they reside. Evidence suggests that structural changes occur in the SC niche as a function of aging. In the present study, we investigated the impact of aging on SC niche properties. Muscle biopsies were obtained from the vastus lateralis of healthy young (YM; 21 ± 1 yr; n = 10) and older men (OM; 68 ± 1 yr; n = 16) at rest. A separate group of OM performed a single bout of resistance exercise and additional muscle biopsies were taken 24 and 48 hours post‐exercise; this was performed before and following 12 wks of combined exercise training (OM‐Ex; 73 ± 1; n = 24). Muscle SC niche measurements were assessed using high resolution immunofluorescent confocal microscopy. Type II SC niche laminin thickness was greater in OM (1.86 ± 0.06 µm) as compared to YM (1.55 ± 0.09 µm, P < .05). The percentage of type II‐associated SC that were completely surrounded by laminin was greater in OM (13.6%±4.2%) as compared to YM (3.5%±1.5%; P < .05). In non‐surrounded SC, the proportion of active MyoD+/Pax7+ SC were higher compared to surrounded SC (P < .05) following a single bout of exercise. This “incarceration” of the SC niche by laminin appears with aging and may inhibit SC activation in response to exercise.