Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization and prognostic significance of mortalin, Bcl-2 and Bax in intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is an aggressive type of cancer, and its incidence and mortality rates are increasing worldwide. Mortalin is a highly conserved chaperone protein involved in multiple pathological and physiological processes, including anti-apoptosis, carcinogenesis and metastasis. The Bcl-2 family of proteins can be divided into pro-survival and pro-apoptotic members, including B-cell lymphoma 2 (Bcl-2) and Bcl-2-like protein 4 (Bax). The aim of the present study was to investigate the association between mortalin, Bcl-2 and Bax, as well as the prognostic significance of the combined expression of mortalin, Bcl-2 and Bax in ICC. Immunohistochemistry was used to determine the expression of mortalin, Bcl-2 and Bax in 116 ICC samples and to assess the association between expression of 3 markers and clinicopathological features of ICC patients. This revealed that ICC tumor tissues overexpressed mortalin and Bcl-2 and exhibited low expression of Bax in ICC tumor tissues compared with that in corresponding peritumoral samples. According to Pearson's correlation coefficient analysis, high expression of mortalin in ICC was positively correlated with Bcl-2 expression and negatively correlated with Bax expression. Furthermore, multiple linear regression analysis demonstrated that mortalin was positively associated with Bcl-2, but not with Bax, in patients with ICC. Patients with ICC exhibiting high expression of mortalin/Bcl-2 or low expression of Bax were closely associated with a malignant ICC phenotype, a relatively low overall survival rate and a high recurrence rate. Multivariate analysis indicated that mortalin and Bcl-2 were independent prognostic indicators for ICC patients. Meanwhile, the concomitant overexpression of mortalin and Bcl-2 and the low expression of Bax were independent markers for predicting a relatively poor prognosis of ICC. The overexpression of mortalin and Bcl-2 and/or the low expression of Bax are implicated in the anti-apoptotic effect and tumor progression of ICC. Mortalin or Bcl-2, or a combination of mortalin, Bcl-2 and Bax may be used to predict the prognosis of ICC, as well as potential therapeutic targets.
Characterization of silver particles in the stratum corneum of healthy subjects and atopic dermatitis patients dermally exposed to a silver-containing garment

Abstract Silver is increasingly being used in garments to exploit its antibacterial properties. Information on the presence of silver nanoparticles (AgNPs) in garments and their in vivo penetration across healthy and impaired skin from use is limited. We investigated the presence of AgNPs in a silver containing garment and in the stratum corneum (SC) of healthy subjects (CTRLs) and individuals with atopic dermatitis (AD). Seven CTRLs and seven AD patients wore a silver sleeve (13% Ag w/w) 8 h/day for five days on a forearm and a placebo sleeve on the other forearm. After five days, the layers of the SC were collected by adhesive tapes. The silver particles in the garment and SC were characterized by scanning electron microscopy with energy dispersive X-ray analysis (SEM-EDX) and atomic force microscopy (AFM). AFM and SEM revealed the presence of sub-micrometre particles having a broad range of sizes (30–500 nm) on the surface of the garment that were identified as silver. On the SC tapes collected from different depths, aggregates with a wide range of sizes (150 nm–2 μm) and morphologies were found. Most aggregates contained primarily silver, although some also contained chlorine and sulfur. There was no clear difference in the number or size of the aggregates observed in SC between healthy and AD subjects. After use, AgNPs and their aggregates were present in the SC at different depths of both healthy subjects and AD patients. Their micrometre size suggests that aggregation likely occurred in the SC.
Eradication of minimal residual disease improves overall and progression‐free survival in patients with chronic lymphocytic leukaemia, evidence from NCRN CLL207: a phase II trial assessing alemtuzumab consolidation

With immunochemotherapy, remission duration and survival in patients with chronic lymphocytic leukaemia is dependent on the level of minimal residual disease (MRD) after treatment. This phase II trial assessed alemtuzumab consolidation post‐chemotherapy in patients who responded with persistent low levels of detectable disease. Blood was screened for MRD using multi‐parameter flow cytometry, 6–24 months post‐chemotherapy. MRD‐positive participants received alemtuzumab 30 mg subcutaneously 3 times weekly for 6 weeks. Following a marrow assessment, MRD‐negative participants or non‐responders stopped therapy and MRD‐positive participants with 1 + log reduction had 6 more weeks of alemtuzumab. Alemtuzumab consolidation was received by 47 participants. One death and 19 of 22 serious adverse events reported from 17 (36%) participants were alemtuzumab‐related. MRD eradication from blood and bone marrow was achieved in 39 (83%) participants at the end of consolidation, with 18 (38%) remaining MRD‐negative in the blood 6 months later. Of the 18 participants who were MRD‐negative at 6 months, the median time to MRD relapse was 46 months, which was similar to patients who were MRD‐negative at baseline and were followed up. The 5‐year progression‐free survival (PFS) and overall survival (OS) of participants who were MRD‐negative at 6 months was significantly better than MRD‐positive participants [PFS: 78% vs. 39% (P = 0·010), OS: 89% vs. 64% (P = 0·029)].
Childhood psychosocial adversity and female reproductive timing: a cohort study of the ALSPAC mothers

Background Previous studies of childhood psychosocial adversity and age at menarche mostly evaluated single or a few measures of adversity, and therefore could not quantify total psychosocial adversity. Limited knowledge is currently available regarding childhood psychosocial adversity in relation to age at menopause and reproductive lifespan. Methods We examined the associations of total and specific components of childhood psychosocial adversity with age at menarche (n=8984), age at menopause (n=945), and length of reproductive lifespan (n=841), in mothers participating in the Avon Longitudinal Study of Parents and Children. We used confirmatory factor analysis to characterise lack of care, maladaptive family functioning, non-sexual abuse, overprotective parenting, parental mental illness and sexual abuse. These specific components of childhood psychosocial adversity were combined into a total psychosocial adversity score using a second-order factor analysis. We used structural equation models to simultaneously conduct the factor analysis and estimate the association with the continuous outcomes of interest. Results Total childhood psychosocial adversity was not associated with age at menarche, age at menopause or length of reproductive lifespan. When we examined the separate psychosocial adversity constructs, sexual abuse was inversely associated with age at menarche, with a mean difference of −0.17 (95% CI −0.23 to −0.12) years per SD higher factor score, and with age at menopause, with a mean difference of −0.17 (95% CI −0.52 to 0.18) per SD higher factor score. Conclusion Childhood sexual abuse was associated with lower age at menarche and menopause, but the latter needs to be confirmed in larger samples.
Issues promoting and hindering girls' well-being in Northern Finland

Well-being is a complex concept that includes elements of inequality due to socio-economics, living environment or gender. Every person also encounters unique situations and has different experiences of well-being. This qualitative study aims to describe what issues promote and hinder the well-being of girls aged 13-16 in Northern Finland. A total of 117 girls aged 13-16 living in Northern Finland were asked to write about the issues that hinder and promote their well-being. The girls' responses were analysed using content analysis. After analysis, two combining categories were discovered: issues hindering well-being were a debilitating sphere of life and negative experiences in life, and issues promoting well-being were positive subjective sensations and favourably perceived conditions. The results of this study indicate that girls' well-being is connected to their social and physical environment. As the girls' view of the issues that promote or hinder health are connected and interact with their living environment, there is also a need for health promotion measures to take into account both the individuals and the environment in which they function and live. This view challenges us to see health promotion in a broader way-a way which takes into account structural and political factors, individual consultation and empowerment.
White matter abnormalities and dystonic motor disorder associated with mutations in the SLC16A2 gene

Aim Mutations in the SLC16A2 gene have been implicated in Allan–Herndon–Dudley syndrome (AHDS), an X‐linked learning disability * syndrome associated with thyroid function test (TFT) abnormalities. Delayed myelination is a non‐specific finding in individuals with learning disability whose genetic basis is often uncertain. The aim of this study was to describe neuroimaging findings and neurological features in males with SLC16A2 gene mutations.
Resting-State Functional Connectivity Within Medial Prefrontal Cortex Mediates Age Differences in Risk Taking

ABSTRACT To investigate the association between age-related changes in risk taking and resting-state functional activity, we recorded resting-state scans from both young (n = 26) and older adults (n = 27). In addition, all participants completed two decision-making tasks: the Cambridge Gambling Task and the Balloon Analogue Risk Task. We found that older adults showed decreased functional connectivity within the medial prefrontal cortex, particularly between the ventromedial prefrontal cortex and the dorsal medial prefrontal cortex. Moreover, these changes in resting-state functional connectivity were associated with the individuals’ risk-taking behavior, and mediated the influence of age on risk taking.
Caring for patients with brain tumors compared to patients with non-brain tumors: Experiences and needs of informal caregivers in home care settings

ABSTRACT Background/Objective: Informal caregivers of patients with advanced cancer experience a challenging time, especially while caring for the patient at home. The aim of this study is to compare experiences, perceived burdens, and needs during home care of informal caregivers of brain tumor patients and informal caregivers of non-brain tumor patients. Methods: 28 informal caregivers (17 brain tumor group, 11 non-brain tumor group) participated in this study. Semi-structured interviews were conducted to gather information retrospectively. Data was analyzed using principles of thematic analysis method. Results: The results support existing evidence that the themes assessment of the situation, dealing with the situation, effects of the situation, and support by others are of importance to all informal caregivers. Caregivers in the brain tumor group put more emphasis on information and perception of the situation by others than caregivers in the non-brain tumor group. Conclusion: The emerging need for information of caregivers and the effects for caregivers of changes in the perception of the situation by others should be addressed to better support informal caregivers of brain tumor patients.
Highly Activated Cytotoxic CD8 T Cells Express Protective IL-10 at the Peak of Coronavirus-Induced Encephalitis

Acute viral encephalitis requires rapid pathogen elimination without significant bystander tissue damage. In this article, we show that IL-10, a potent anti-inflammatory cytokine, is produced transiently at the peak of infection by CD8 T cells in the brains of coronavirus-infected mice. IL-10+CD8 and IL-10−CD8 T cells interconvert during acute disease, possibly based on recent Ag exposure. Strikingly, IL-10+CD8 T cells were more highly activated and cytolytic than IL-10−CD8 T cells, expressing greater levels of proinflammatory cytokines and chemokines, as well as cytotoxic proteins. Even though these cells are highly proinflammatory, IL-10 expressed by these cells was functional. Furthermore, IL-10 produced by CD8 T cells diminished disease severity in mice with coronavirus-induced acute encephalitis, suggesting a self-regulatory mechanism that minimizes immunopathological changes.
Skipping on uneven ground: trailing leg adjustments simplify control and enhance robustness

It is known that humans intentionally choose skipping in special situations, e.g. when descending stairs or when moving in environments with lower gravity than on Earth. Although those situations involve uneven locomotion, the dynamics of human skipping on uneven ground have not yet been addressed. To find the reasons that may motivate this gait, we combined experimental data on humans with numerical simulations on a bipedal spring-loaded inverted pendulum model (BSLIP). To drive the model, the following parameters were estimated from nine subjects skipping across a single drop in ground level: leg lengths at touchdown, leg stiffness of both legs, aperture angle between legs, trailing leg angle at touchdown (leg landing first after flight phase), and trailing leg retraction speed. We found that leg adjustments in humans occur mostly in the trailing leg (low to moderate leg retraction during swing phase, reduced trailing leg stiffness, and flatter trailing leg angle at lowered touchdown). When transferring these leg adjustments to the BSLIP model, the capacity of the model to cope with sudden-drop perturbations increased.
Waist circumference and risk of breast cancer in Korean women: A nationwide cohort study

Although postmenopausal breast cancer (BC) risk has been linked to adiposity, associations between adiposity and premenopausal BC remain unclear. To address this question, we investigated the association of BC risk with measures of adiposity, including body mass index (BMI) and waist circumference (WC), in a large cohort of Asian women. We used a nationwide cohort of adult Korean women selected from the National Health Insurance Corporation database merged with national health examination data from 2009 to 2015. A total of 11,227,948 women were tracked to retrospectively identify incident cases of BC. Our analysis used Cox proportional hazards models to calculate hazard ratios and assess the association of BC risk with BMI and/or WC in both pre‐ and postmenopausal women. BMI and WC were robustly associated with increased risk for postmenopausal BC (ptrend<0.001 for both BMI and WC) but not with premenopausal BC. Association between WC and premenopausal BC was only statistically significant when considering BMI (ptrend=0.044). In contrast, postmenopausal BC was negatively associated with WC when considering BMI (ptrend=0.011). In premenopausal women, WC may predict increased BC risk when considering BMI. However, in postmenopausal women, WC is not superior to BMI as an indicator of BC risk.
Drp1 polymerization stabilizes curved tubular membranes similar to those of constricted mitochondria

ABSTRACT Dynamin-related protein 1 (Drp1), an 80 kDa mechanochemical GTPase of the dynamin superfamily, is required for mitochondrial division in mammals. Despite the role of Drp1 dysfunction in human disease, its molecular mechanism remains poorly understood. Here, we examined the effect of Drp1 on membrane curvature using tubes pulled from giant unilamellar vesicles (GUVs). We found that GTP promoted rapid rearrangement of Drp1 from a uniform distribution to discrete foci, in line with the assembly of Drp1 scaffolds at multiple nucleation sites around the lipid tube. Polymerized Drp1 preserved the membrane tube below the protein coat, also in the absence of pulling forces, but did not induce spontaneous membrane fission. Strikingly, Drp1 polymers stabilized membrane curvatures similar to those of constricted mitochondria against pressure changes. Our findings support a new model for mitochondrial division whereby Drp1 mainly acts as a scaffold for membrane curvature stabilization, which sets it apart from other dynamin homologs. Summary: Drp1 follows an unprecedented molecular mechanism when assembling on lipid tubes, which sets it apart from other dynamins. Drp1 stabilizes mitochondrial curvature rather than being a membrane scissor.
Lubrication Mechanism of the Larynx during Phonation: An Experiment in Excised Canine Larynges

To evaluate how the viscosity of the laryngeal mucus influences vocal fold vibration, two fluids of differing viscosity were applied separately to excised canine larynges and experimental phonation was induced. Vibration of the vocal folds was measured by use of a laryngostroboscope and an X-ray stroboscope. With the high viscosity fluid, the amplitude of vibration of the free edge and the peak glottal area was decreased while the open quotient was increased. Because the viscosity of this fluid affected the wave motion of the vocal fold mucosa, changes in viscosity of the mucus may be involved in causing such disorders as hoarseness, in the absence of apparent changes in the vocal folds themselves.
Silymarin nanoemulsion against human hepatocellular carcinoma: development and optimization

Abstract Objective: Nanoemulsion of silymarin was developed and optimized. Materials and methods: Nanoemulsion was made by aqueous titration method. Sefsol 218 (5.8% v/v), Kolliphor RH40 and polyethylene glycol 400 (Smix; 2:1; 28.99% v/v) were used as oil phase, surfactant and co-surfactant while distilled water (65.22% v/v) acted as an aqueous phase. Nanoemulsion was characterized on the basis of particle size, viscosity, electrical conductivity and refractive index. Further, in vitro release, in vivo pharmacokinetic study, stability study and cancer cell line studies were also performed. Results and discussion: The optimized formulation (NE9) with mean particle size of 21.24 nm showed a minimum viscosity of 9.59 cps, maximum drug release (97.75%) in 24 h. The NE9 formulation also showed higher AUC (p < .01) and Cmax (p < .01) and shorter Tmax (p < .05) compared with conventional and standard suspensions of silymarin. The stability study also showed considerably stable formulations at refrigerator temperature as compared with room temperature (p > .05). The cancer cell line studies also confirmed that silymarin nanoemulsion reduced the cell viability and increased ROS intensity and chromatin condensation (p < .05). Conclusion: Our results concluded that nanoemulsion may be an efficient carrier for oral delivery of silymarin against human hepatocellular carcinoma without damaging normal cells.
Which children and young people are excluded from school? Findings from a large British birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC)

BACKGROUND Exclusion from school is increasingly recognized as pertinent to child health. National educational data reveal that boys, children who are looked-after, living in poverty, have special educational needs, or from certain ethnic minorities, are disproportionately excluded from school. As population-based data on the wider characteristics of excluded children are scarce, we aimed to describe predictors of school exclusion in the Avon Longitudinal Study of Parents and Children. METHOD Avon Longitudinal Study of Parents and Children, a prospective U.K. population-based birth cohort study, collected parent reports of permanent school exclusions by 8 years and parent and self-reports of permanent and fixed-term exclusions in the preceding 12 months at 16 years. Potential risk factors were examined for associations with exclusion using logistic regression, with a focus on child mental health and neurodevelopment. RESULTS Analyses were based on all available data on 53/8,245 (0.6%) pupils excluded from school by 8 years and 390/4,482 (8.7%) at 16 years. Key factors associated with exclusion at both time points included male gender, lower socio-economic status, maternal psychopathology, mental health and behavioural difficulties, psychiatric disorder, social communication difficulties, language difficulties, antisocial activities, bullying/being bulled, lower parental engagement with education, low school engagement, poor relationship with teacher, low educational attainment, and special educational needs (all p < .05). CONCLUSION Exclusion from school was associated with child, family and school-related factors identifiable at, or prior to, primary school age. Child health professionals have an important role in the holistic, multidisciplinary assessment of children who are at risk of exclusion from school. Mental health and neurodevelopmental difficulties should be recognized and supported, to improve the health and educational outcomes among this vulnerable group.
Transrectal ultrasound-guided prostate rebiopsy: How many core sampling should be applied to which patient?

Background: We investigated the correlation between the sampled number of cores in rebiopsy and the cancer detection rate (CDR). Materials and Methods: Two hundred and twelve patients with normal rectal examination who had undergone rebiopsy in the past 5 years were examined retrospectively. Moreover, 68% of them had undergone 12 cores (Group 1) while 32% had undergone 20 cores (Group 2). Both groups were compared with respect to the CDR. Results: There was no difference between groups in terms of age, total prostate-specific antigen, and prostate volume (P > 0.05). Forty-one (19%) of 212 patients were diagnosed with cancer, and the CDR was significantly higher in Group 2 (30.9% vs. 13.9%, P = 0.004). This rate increased from 6.5% to 20% (P = 0.025) and from 0% to 33.3% (P = 0.023), respectively, with 12-core and 20-core rebiopsies in patients whose initial pathology indicated benign and high-grade prostatic intraepithelial neoplasia (HGPIN). Furthermore, cancer was detected in 24 (40%) of 60 patients who were diagnosed with atypical small acinar proliferation (ASAP) in the initial biopsy. However, despite being higher in 20-core biopsy group (47.6% vs. 35.9%), this was not statistically significant (P = 0.377). Conclusions: At least 20 cores should be sampled in rebiopsy, especially in the patients diagnosed with benign and HGPIN. However, we believe that standard systematic sampling will be sufficient for the patients diagnosed with ASAP.