Miracle-dz/UniFAR-FTUs huggingface dataset:
Antidiabetic Drugs and Prostate Cancer Prognosis in a Finnish Population-Based Cohort

Background: Hyperinsulemia and glycemic control may play a role as prostate cancer prognostic factors, whereas use of certain antidiabetic drugs, that is metformin, could improve the prognosis. We examined the link between antidiabetic medication use and prostate cancer survival taking into account simultaneous use of multiple drugs. Methods: The study cohort composed of 6,537 men in The Finnish Randomized Study of Screening for Prostate Cancer with prostate cancer diagnosed 1996 to 2009. Use of medication was attained from the nationwide prescription database of the Social Insurance Institution of Finland. Median follow-up was 9.2 years postdiagnosis. A total of 1,603 (24,5%) men had used antidiabetic medication. A total of 771 men died of prostate cancer during the follow-up. We used multivariable-adjusted Cox regression to evaluate the risk of prostate cancer death and onset of androgen deprivation therapy (ADT) with adjustment for prostate cancer clinical characteristics, comorbidities and use of other drugs. Separate analyses were further adjusted for blood glucose. Results: Risk of prostate cancer death was higher among antidiabetic drug users overall (HR = 1.42; 95% CI, 1.18–1.70) compared with nonusers, separately among insulin and metformin users. Adjustment for blood glucose level abolished the risk increase. Risk of ADT initiation was increased among the medication users (HR = 1.26; 95% CI, 1.05–1.49). Conclusions: Men with prostate cancer using antidiabetic medication are generally at increased risk of dying from prostate cancer compared with nonusers. The risk association is driven by underlying diabetes, as adjustment for blood glucose level ameliorates the risk increase. Impact: Type 2 diabetes should be considered as a risk factor when considering prostate cancer prognosis.
Neuroacanthocytosis Syndromes in an Italian Cohort: Clinical Spectrum, High Genetic Variability and Muscle Involvement

Neuroacanthocytosis (NA) syndromes are a group of genetically defined diseases characterized by the association of red blood cell acanthocytosis, progressive degeneration of the basal ganglia and neuromuscular features with characteristic persistent hyperCKemia. The main NA syndromes include autosomal recessive chorea-acanthocytosis (ChAc) and X-linked McLeod syndrome (MLS). A series of Italian patients selected through a multicenter study for these specific neurological phenotypes underwent DNA sequencing of the VPS13A and XK genes to search for causative mutations. Where it has been possible, muscle biopsies were obtained and thoroughly investigated with histochemical assays. A total of nine patients from five different families were diagnosed with ChAC and had mostly biallelic changes in the VPS13A gene (three nonsense, two frameshift, three splicing), while three patients from a single X-linked family were diagnosed with McLeod syndrome and had a deletion in the XK gene. Despite a very low incidence (only one thousand cases of ChAc and a few hundred MLS cases reported worldwide), none of the 8 VPS13A variants identified in our patients is shared by two families, suggesting the high genetic variability of ChAc in the Italian population. In our series, in line with epidemiological data, McLeod syndrome occurs less frequently than ChAc, although it can be easily suspected because of its X-linked mode of inheritance. Finally, histochemical studies strongly suggest that muscle pathology is not simply secondary to the axonal neuropathy, frequently seen in these patients, but primary myopathic alterations can be detected in both NA syndromes.
Training executive functions using an adaptive procedure over 21 days (10 training sessions) and an active control group

The degree to which executive function (EF) abilities (including working memory [WM], inhibitory control [IC], and cognitive flexibility [CF]) can be enhanced through training is an important question; however, research in this area is inconsistent. Previous cognitive training studies largely agree that training leads to improvements in the trained task, but the generalisability of this improvement to other related tasks remains controversial. In this article, we present a pre-registered experiment that used an adaptive training procedure to examine whether EFs can be enhanced through cognitive training, and directly compared the efficacy and generalisability across sub-components of EF using training programmes that target WM, IC, or CF versus an active control group. Participants (n = 160) first completed a battery of tasks that assessed EFs, then were randomly assigned to one of the four training groups, and completed an adaptive procedure over 21 days (10 training sessions) that targeted a specific sub-component of EF (or was comparatively engaging and challenging, but did not train a specific EF). At post-test, participants returned to the lab to repeat the battery of EF tasks. Results revealed robust direct training effects (i.e., on trained task), but limited evidence to support near (i.e., same EF, different task) and far (i.e., different EF and task) transfer effects. Where indirect training benefits emerged, the effects were more readily attributable to the overlapping training/assessment task routines, rather than more general enhancements to the underlying cognitive processes or neural circuits.
Relation-Induced Multi-Modal Shared Representation Learning for Alzheimer’s Disease Diagnosis

The fusion of multi-modal data (e.g., magnetic resonance imaging (MRI) and positron emission tomography (PET)) has been prevalent for accurate identification of Alzheimer’s disease (AD) by providing complementary structural and functional information. However, most of the existing methods simply concatenate multi-modal features in the original space and ignore their underlying associations which may provide more discriminative characteristics for AD identification. Meanwhile, how to overcome the overfitting issue caused by high-dimensional multi-modal data remains appealing. To this end, we propose a relation-induced multi-modal shared representation learning method for AD diagnosis. The proposed method integrates representation learning, dimension reduction, and classifier modeling into a unified framework. Specifically, the framework first obtains multi-modal shared representations by learning a bi-directional mapping between original space and shared space. Within this shared space, we utilize several relational regularizers (including feature-feature, feature-label, and sample-sample regularizers) and auxiliary regularizers to encourage learning underlying associations inherent in multi-modal data and alleviate overfitting, respectively. Next, we project the shared representations into the target space for AD diagnosis. To validate the effectiveness of our proposed approach, we conduct extensive experiments on two independent datasets (i.e., ADNI-1 and ADNI-2), and the experimental results demonstrate that our proposed method outperforms several state-of-the-art methods.
A Fast and Implantation-Free Sample Production Method for Large Scale Electron-Transparent Metallic Samples Destined for MEMS-Based In Situ S/TEM Experiments

Microelectromechanical systems (MEMS) are currently supporting ground-breaking basic research in materials science and metallurgy as they allow in situ experiments on materials at the nanoscale within electron microscopes in a wide variety of different conditions such as extreme materials dynamics under ultrafast heating and quenching rates as well as in complex electro-chemical environments. Electron-transparent sample preparation for MEMS e-chips remains a challenge for this technology as the existing methodologies can introduce contaminants, thus disrupting the experiments and the analysis of results. Herein we introduce a methodology for simple and fast electron-transparent sample preparation for MEMS e-chips without significant contamination. The quality of the samples as well as their performance during a MEMS e-chip experiment in situ within an electron microscope are evaluated during a heat treatment of a crossover AlMgZn(Cu) alloy.
Social Contact with Family and Non-Family Members Differentially Affects Physical Activity: A Parallel Latent Growth Curve Modeling Approach

Background: Social contact leads to an increased likelihood of engaging in physical activity (PA). However, the influence of social contact on PA would be different depending on the social contact source. This study aimed to identify the association of changes in social contact with family and non-family members with the change in PA using a parallel latent growth curve modeling. Methods: Participants were randomly selected from among residents in the study area age ≥ 20 years (n = 7000). We conducted mail surveys in 2014, 2016, and 2019. The 1365 participants completed all surveys. PA was assessed with validated single-item physical activity measure. Social contact was assessed by summing frequencies of face-to-face and non-face-to-face contacts with family/relatives not living with the participant and friends/neighbors. Parallel latent growth curve modeling was used to assess the cross-sectional, prospective, and parallel associations of social contact with PA change. Results: There was a positive cross-sectional association between contact with friends/neighbors and PA, whereas prospective and parallel associations between contact with family/relatives and PA. Conclusion: Contacting friends/neighbors did not predict the change in PA, and a high frequency of contact with family/relatives at baseline and increasing contact with family/relatives was associated with increased PA over 5-year.
Effect of water temperature on the morbidity of Tetracapsuloides bryosalmonae (Myxozoa) to brown trout (Salmo trutta) under laboratory conditions

Abstract Proliferative kidney disease (PKD) is a disease found in salmonid fish that is widespread in Europe and North America. The dependency of the clinical signs on the water temperature is extensively reported in rainbow trout, but detailed information on brown trout is lacking. In this study, juvenile brown trout were exposed to the spores of Tetracapsuloides bryosalmonae and then kept at different ambient water temperatures (16°C, 19°C and 22°C) for 10 weeks along with recording of morbidity throughout the experiment. At 6, 8 and 10 weeks post‐exposure, fish from each temperature group were sampled and underwent pathoanatomical examination to survey disease progression. At 16°C, brown trout showed a significantly higher survival probability compared to those kept in 19°C and 22°C water. Additionally, the parasitic burden (MSQ) was higher and the clinical signs were more pronounced in the brown trout kept at 19°C and 22°C compared with the ones kept at 16°C. This study highlights the correlation of PKD outbreaks and water temperature increases related to global climate change, which will impact the future distribution of brown trout in natural waters.
Prolonged Maternal and Child Health, Food and Nutrition Problems after the Kumamoto Earthquake: Semantic Network Analysis of Interviews with Dietitians

Infants need sufficient nutrients even during disasters. Only qualitative descriptive analysis has been reported regarding nutritional problems of mothers and children after the Kumamoto earthquake, and non-subjective analysis is required. This study examined issues concerning maternal and child health, food and nutrition after the Kumamoto earthquake using automatic computer quantitative analysis from focus group interviews (FGIs). Study participants (n = 13) consisted of dietitians in charge of nutrition assistance of infants in affected areas. The content of the interviews was converted into text, nouns were extracted, and co-occurrence network diagram analysis was performed. In the severely damaged area, there were hygienic problems not only in the acute phase but also in the mid-to-long-term phase. “Allergy” was extracted in the surrounding area in the acute and the mid-to-long-term phase, but not in the severely damaged area as the acute phase issue. In the surrounding area, problems have shifted to health and the quality of diet in the mid-to-long-term phase. This objective analysis suggested that dietary problems for mothers and children after disaster occurred also in the mid-to-long-term phase. It will be necessary to combine the overall trends obtained in this study with the results of qualitative descriptive analysis.
Statistical Evidence for a Helical Nascent Chain

We investigate the hypothesis that protein folding is a kinetic, non-equilibrium process, in which the structure of the nascent chain is crucial. We compare actual amino acid frequencies in loops, α-helices and β-sheets with the frequencies that would arise in the absence of any amino acid bias for those secondary structures. The novel analysis suggests that while specific amino acids exist to drive the formation of loops and sheets, none stand out as drivers for α-helices. This favours the idea that the α-helix is the initial structure of most proteins before the folding process begins.
Fatigue in Cancer Patients in Palliative Care—A Review on Pharmacological Interventions

Simple Summary Cancer related fatigue is a common and distressing symptom for patients with cancer during and after primary treatment, and also in the palliative phase of the disease trajectory. This review focuses on the pharmacological treatment of cancer related fatigue in patients with advanced or metastatic cancer. There are few high-quality studies performed in this setting, but both methylphenidate and corticosteroids might be used to relieve fatigue. Abstract Fatigue is one of the most distressing symptoms experienced by cancer patients. The suggested biological mechanism for cancer related fatigue (CRF) includes immune activation triggered by tumor tissue or by anticancer treatment but other mechanisms have also been proposed. Previous large meta-analysis of interventions on fatigue focuses mostly on patients early in the disease trajectory, with only one tenth of included studies performed in palliative cohorts. The aim of this narrative review is therefore to present a background on CRF with focus on the palliative setting. A summary of recent randomized, controlled trials on pharmacological interventions on CRF in palliative care is presented, including studies on psychostimulants, corticosteroids, testosterone and melatonin. Interestingly, in several of these studies there was a positive and similar effect on fatigue in both the intervention and the placebo arm—indicating an important placebo effect for any pharmacological treatment. In addition, studies on dietary supplements and on pharmacological complementary medicines are discussed. To conclude, the evidence is still weak for using pharmacological treatments on CRF in palliative care patients—although methylphenidate and corticosteroids might be considered.
Identification and characterization of a novel 5-hydroxytryptamine receptor in the sea cucumber Apostichopus japonicus (Selenka).

Serotonin (5-hydroxytryptamine [5-HT]) receptors (5-HTRs) mediate neuroendocrine signaling via interactions with the ligand serotonin (5-HT). The 5-HT signaling system has been well studied in vertebrates, but rarely known in invertebrate animals, especially in the marine invertebrates. In this study, we identified and characterized a novel 5-HTR from the sea cucumber Apostichopus japonicus (Aj5-HT4/6 ). The cloned Aj5-HT4/6 open reading frame comprised 1290 bp and encoded 429 amino acids. Bioinformatic analysis of the receptor indicated that it was a member of the class A of the G protein-coupled receptor family. Further experiments using Aj5-HT4/6 -transfected HEK293 cells demonstrated that treatment with 5-HT could induce rapid internalization of Aj5-HT4/6 fused with enhanced green fluorescent protein from the cell surface into the cytoplasm and triggered a significant increase in levels of the second messenger cAMP as well as mitogen-activated protein kinase phosphorylation in a 5-HT dose-dependent manner. Quantitative real time-polymerase chain reaction demonstrated that Aj5-HT4/6 was predominantly expressed in the muscle and respiratory tree, and its expression was significantly decreased during estivation. Taken together, these results imply that Aj5-HT4/6 is potentially involved in the movement and metabolism of the sea cucumber.
Gender, acculturation, and alcohol-related consequences among college students of color

Abstract Objective The present study examined if identification with mainstream American culture (acculturation) and heritage culture (enculturation) are differentially associated with blackouts and other drinking consequences among male and female college students of color. Participants Participants were college students (N = 150) who self-identified as a racial/ethnic minority and endorsed blackouts in the past year. Methods Regression models were used to examine gender-by-acculturation/enculturation interaction effects on alcohol-induced blackout and other alcohol-related consequences. Results While acculturation was not significantly associated with either drinking outcome, enculturation showed a significant relationship with blackout frequency. Gender moderated this relationship; greater enculturation was associated with increased blackout frequency among male but not female students. Conclusions The present findings suggest the importance of considering the interplay between enculturation and gender in understanding alcohol use among college students of color. Men who endorse high levels of enculturation may be at an increased risk of experiencing negative drinking-related consequences.
Local induction of bladder Th1 responses to combat urinary tract infections

Significance Urinary tract infections (UTIs) are the second most common bacterial infections. Caring for UTI patients is very difficult and often perplexing. We typically view our immune system as an adaptive line of defense that becomes more responsive to specific pathogens after episodes of infection. However, the opposite is seen in these patients, in whom each infection actually increases the risk of a subsequent infection. Our group recently identified the underlying basis as a highly Th2-biased response in bladder that inhibits Th1-mediated bacterial clearance. To resolve this situation, we investigated whether immunizing mice intravesically with bacterial antigens combined with a Th1-skewing adjuvant (CpG) would evoke a more balanced and protective immune response. Given the high frequency of urinary tract infections (UTIs) and their recurrence, there is keen interest in developing effective UTI vaccines. Currently, most vaccine studies, including those in humans, involve parenteral vaccination aimed at evoking and sustaining elevated levels of systemic antibody directed at the uropathogens. In view of recent reports of aberrant Th2-biased bladder immune responses to infection, we hypothesized that immunizing mice intravesically with antigens from uropathogenic Escherichia coli (UPEC) combined with a Th1-skewing adjuvant could correct this defect and promote protection against UTIs. Here we report that compared with mice immunized subcutaneously with this vaccine combination, intravesically immunized mice were markedly more protected from UTIs because of their distinctive ability to recruit Th1 cells into the bladder. This mode of vaccination was effective even in mice that experienced multiple UTIs and displayed pronounced aberrant bladder immune responses. Thus, intravesical vaccination with one or more UPEC antigens to induce bladder Th1 responses represents a superior strategy to combat UTIs, especially in UTI-prone subjects.
Endoscopic Suturing for the Prevention and Treatment of Complications Associated with Endoscopic Mucosal Resection of Large Duodenal Adenomas

Background/Aims Endoscopic mucosal resection (EMR) is the primary treatment for duodenal adenomas; however, it is associated with a high risk of perforation and bleeding, especially with larger lesions. The goal of this study was to demonstrate the feasibility and safety of endoscopic suturing (ES) for the closure of mucosal defects after duodenal EMR. Methods Consecutive adult patients who underwent ES of large mucosal defects after EMR of large (>2 cm) duodenal adenomas were retrospectively enrolled. The OverStitch ES system was employed for closing mucosal defects after EMR. Clinical outcomes and complications, including delayed bleeding and perforation, were documented. Results During the study period, ES of mucosal defects was performed in seven patients in eight sessions (six for prophylaxis and two for the treatment of perforation). All ES sessions were technically successful. No early or delayed post-EMR bleeding was recorded. In addition, no clinically obvious duodenal stricture or recurrence was encountered on endoscopic follow-up evaluation, and no patients required subsequent surgical intervention. Conclusions ES for the prevention and treatment of duodenal perforation after EMR is technically feasible, safe, and effective. ES should be considered an option for preventing or treating perforations associated with EMR of large duodenal adenomas.
Passive Prophylactic Administration with a Single Dose of Anti–Fel d 1 Monoclonal Antibodies REGN1908–1909 in Cat Allergen–induced Allergic Rhinitis: A Randomized, Double-Blind, Placebo-controlled Clinical Trial

Rationale: Sensitization to Fel d 1 (Felis domesticus allergen 1) contributes to persistent allergic rhinitis and asthma. Existing treatment options for cat allergy, including allergen immunotherapy, are only moderately effective, and allergen immunotherapy has limited use because of safety concerns. Objectives: To explore the relationship among the pharmacokinetic, clinical, and immunological effects of anti–Fel d 1 monoclonal antibodies (REGN1908–1909) in patients after treatment. Methods: Patients received REGN1908–1909 (n = 36) or a placebo (n = 37) in a phase 1b study. Fel d 1–induced basophil and IgE-facilitated allergen binding responses were evaluated at baseline and Days 8, 29, and 85. Cytokine and chemokine concentrations in nasal fluids were measured, and REGN1908–1909 inhibition of allergen–IgE binding in patient serum was evaluated. Measurements and Main Results: Peak serum drug concentrations were concordant with maximal observed clinical response. The anti–Fel d 1 IgE/cat dander IgE ratio in pretreatment serum correlated with Total Nasal Symptom Score improvement. The allergen-neutralizing capacity of REGN1908–1909 was observed in serum and nasal fluid and was detected in an inhibition assay. Type 2 cytokines (IL-4, IL-5, and IL-13) and chemokines (CCL17/TARC, CCL5/RANTES [regulated upon activation, normal T-cell expressed and secreted]) in nasal fluid were inhibited in REGN1908–1909–treated patients compared with placebo (P < 0.05 for all); IL-13 and IL-5 concentrations correlated with Total Nasal Symptom Score improvement. Ex vivo assays demonstrated that REGN1908 and REGN1909 combined were more potent than each alone for inhibiting FcεRI- and FcεRII (CD23)–mediated allergic responses and subsequent T-cell activation. Conclusions: A single, passive-dose administration of Fel d 1–neutralizing IgG antibodies improved nasal symptoms in cat-allergic patients and was underscored by suppression of FcεRI-, FcεRII-, and T-helper cell type 2–mediated allergic responses. Clinical trial registered with www.clinicaltrials. gov (NCT02127801)