Miracle-dz/UniFAR-FTUs huggingface dataset:
The values and meanings of social activities for older urban men after retirement

Previous studies have indicated that older men often experience disconnection from the community after retirement. Social activities have been shown to be effective in preventing social isolation among older urban men. Nevertheless, it has been reported that they often do not participate in community social activities and tend to be reluctant to do so. We explored the values and meanings of social activities for retired older men living in an urban area of Japan to understand support using social activities that are more suitable for them. Semi-structured interviews were conducted with 15 older men (aged 68–80 years; M = 74.6 ± 3.79 years) about their interactions with family and non-family members, and their participation in various community social activities. The grounded theory approach was used for the analysis. As a result, the following five categories were derived as the values that participants place on the social activities that they engage in: “health as a resource and reward for social activities,” “feeling I am still useful,” “feeling that something is my responsibility,” “feeling of time well spent,” and “finding interest through interactions. ” In addition, the following three categories were extracted as meanings of social activities: “fulfilling social life,” “maintaining stable family relationships,” and “maintaining safety and peace in the community. ” When considering the social activities that older urban retired men are interested in and likely to participate in, these five values can be considered indicators. In contrast, to maintain stable family relationships and safety and peace in the community, participants sometimes used strategies to stop or abandon social activities. Therefore, in situations where a peaceful life within a family or neighborhood is threatened, it may be useful to help set aside sufficient time and allow for psychological leeway in advance to incorporate social activities into their lives.
Targeting the nucleotide metabolism proteins of the NUDIX family and SAMHD1 in cancer.

The nucleotide metabolism has been targeted for many years and in various clinical settings, including cancer. The increased knowledge of certain enzymes involved in this metabolism and in associated cellular processes accumulated over the last few years, gives important information to the druggability of certain proteins and to the use of inhibitors for others. Here, we review recent data on such enzymes with major interest in drug development, i.e. SAMHD1 and the proteins of the NUDIX family. These include information on their roles in cancer progression, correlations with clinical outcome in cancer patients, and development and study of enzymatic inhibitors.
The Sense of Dignity at the End of Life: Reflections on Lifetime Values through the Family Photo Album

This study focuses on the dimensions of dignity, linking Chochinov’s Dignity Therapy to Schwartz’s Theory of Values. The use of family photo albums has enriched the application of dignity therapy. Seven terminal patients in home-based palliative care participated in the therapeutic intervention. To measure the effects of the intervention, we administered the Edmonton Symptom Assessment Scale and the Patient Dignity Inventory, then, at the end of the meetings, collected the opinions of participants, available nurses, and relatives who attended the sessions. The resulting generativity documents were then analyzed through thematic analysis, which revealed three main themes linked to both fundamental values and the dimensions of dignity: The relationship between continuity of self and myriad values in the context of family relationships; personal dignity as characterized by the values of personal success, hope, and wisdom; and hope and generativity. The fourth theme reflected the participants’ final judgements on the intervention, which were highly positive and greatly encouraged further use of photographs in similar therapeutic interventions. The assessment protocol highlighted a significant decrease in tiredness amongst the participants and a trend towards a significant decrease in drowsiness after the intervention.
Epidemiology, Pathophysiology, Diagnosis, and Management of Cerebral Toxoplasmosis

Toxoplasma gondii is known to infect a considerable number of mammalian and avian species and a substantial proportion of the world’s human population. The parasite has an impressive ability to disseminate within the host’s body and employs various tactics to overcome the highly regulatory blood-brain barrier and reside in the brain. In healthy individuals, T. gondii infection is largely tolerated without any obvious ill effects. However, primary infection in immunosuppressed patients can result in acute cerebral or systemic disease, and reactivation of latent tissue cysts can lead to a deadly outcome. SUMMARY Toxoplasma gondii is known to infect a considerable number of mammalian and avian species and a substantial proportion of the world’s human population. The parasite has an impressive ability to disseminate within the host’s body and employs various tactics to overcome the highly regulatory blood-brain barrier and reside in the brain. In healthy individuals, T. gondii infection is largely tolerated without any obvious ill effects. However, primary infection in immunosuppressed patients can result in acute cerebral or systemic disease, and reactivation of latent tissue cysts can lead to a deadly outcome. It is imperative that treatment of life-threatening toxoplasmic encephalitis is timely and effective. Several therapeutic and prophylactic regimens have been used in clinical practice. Current approaches can control infection caused by the invasive and highly proliferative tachyzoites but cannot eliminate the dormant tissue cysts. Adverse events and other limitations are associated with the standard pyrimethamine-based therapy, and effective vaccines are unavailable. In this review, the epidemiology, economic impact, pathophysiology, diagnosis, and management of cerebral toxoplasmosis are discussed, and critical areas for future research are highlighted.
COSIFER: a Python package for the consensus inference of molecular interaction networks

Abstract Summary The advent of high-throughput technologies has provided researchers with measurements of thousands of molecular entities and enable the investigation of the internal regulatory apparatus of the cell. However, network inference from high-throughput data is far from being a solved problem. While a plethora of different inference methods have been proposed, they often lead to non-overlapping predictions, and many of them lack user-friendly implementations to enable their broad utilization. Here, we present Consensus Interaction Network Inference Service (COSIFER), a package and a companion web-based platform to infer molecular networks from expression data using state-of-the-art consensus approaches. COSIFER includes a selection of state-of-the-art methodologies for network inference and different consensus strategies to integrate the predictions of individual methods and generate robust networks. Availability and implementation COSIFER Python source code is available at https://github.com/PhosphorylatedRabbits/cosifer. The web service is accessible at https://ibm.biz/cosifer-aas. Supplementary information Supplementary data are available at Bioinformatics online.
Pain in the neurodegenerating brain: insights into pharmacotherapy for Alzheimer disease and Parkinson disease

The effects of neurodegeneration on the experience of pain remain poorly understood, despite the risk of suffering from both pain and neurodegenerative diseases rising concurrently with age. Given the anticipated increase in magnitude and median age of the global population, the interaction of these 2 clinically unmet needs will become an increasingly pressing challenge. In particular, a significant proportion of patients with Alzheimer disease (AD) and Parkinson disease (PD), the 2 most prevalent neurodegenerative diseases, suffer chronic pain of variable origin (Box 1). As such, they have been the most extensively studied and, for brevity, will be the focus of this review. Persistent pain in AD and PD is partially attributable to various concomitant disease manifestations and comorbidities (Fig. 1). In addition, disease-specific neurodegenerative changes may affect a multitude of regions implicated in the perceptual and cognitive processes underlying pain. Despite this, the precise perceptual sequelae of neurodegenerative pathophysiology in these 2 diseases remain equivocal, and whether this may result in differential responses to analgesic treatment remains largely unexplored. Three key principles lay conceptual foundations for the investigation of the effects of neurodegenerative pathophysiology on treatment mechanisms: (1) a given intensity of stimulus produces heterogeneous levels of reported pain and unpleasantness, (2) genetic and environmental factors predispose some to chronic pain, and (3) diversity of pain physiology and pathophysiology results in heterogeneous responses to pharmacotherapy. Collectively, these support the notion that heterogeneous physiology and pathophysiology can give rise to divergent treatment responses. Within this framework, neurodegeneration and its effects on the central nervous system can be considered as one such external factor contributing to heterogeneity, resulting in putative perturbation of pain processing (1 and 2) and responses to analgesic treatments (3) (Fig. 1). Chronic pain in AD and PD not only impacts patients’ quality of life but also presents a formidable healthcare and socioeconomic challenge. Drugs available for treatment of chronic pain are associated with high numbers needed to treat and may have serious side effects. Moreover, poorly managed pain is associated with depression, anxiety, and functional loss. Given the high prevalence of pain and frailty in these patient groups, clear scientific rationale is imperative to ensure safe and effective clinical management (Fig. 2). In this article, we discuss pain processing and perception in AD and PD as well as its emerging relevance to pharmacological treatment.
Epidermal Growth Factor and Tocotrienol-Rich Fraction Cream Formulation Accelerates Burn Healing Process Based on Its Gene Expression Pattern in Deep Partial-Thickness Burn Wound Model

Our previous study has demonstrated that epidermal growth factor (EGF) with tocotrienol-rich fraction (TRF) cream formulation accelerating postburn wound healing with deep partial-thickness burn in rats. Current study was conducted to determine the gene expression levels related to burn wound healing process. A total of 180 Sprague-Dawley rats were randomly divided into 6 groups: untreated control, treated with Silverdin cream, base cream, base cream with 0.00075% EGF, base cream with 3% TRF or base cream with 0.00075% EGF, and 3% TRF, respectively. Burn wounds were created and the above-mentioned creams were applied once daily. Six animals from each group were sacrificed on days 3, 7, 11, 14, and 21 postburn. RNA was extracted from wound tissues and quantitative real-time polymerase chain reaction was performed to analyze the 9 wound healing-related genes against time postburn. Results demonstrated that topically applied EGF + TRF formulation downregulated the expression levels of IL-6 (interluekin-6), TNF-α (tumor necrosis factor-α) and iNOS (inducible nitric oxide synthase) throughout the whole healing process. TGF-β1 (transforming growth factor-β) and VEGF-A (vascular endothelial growth factor-A) were reduced on day 14 postburn. On the contrary, increased expression of Collagen-1 in the early stage of wound healing was observed with no effects on epidemal growth factor receptor (EGFR). The results showed beneficial application of EGF + TRF cream in the treatment of burn wound since it accelerated wound healing by relieving oxidative stress, decreasing inflammation, and promoting proper tissue modelling in the burn wound.
Implications of Oligomeric Amyloid-Beta (oAβ42) Signaling through α7β2-Nicotinic Acetylcholine Receptors (nAChRs) on Basal Forebrain Cholinergic Neuronal Intrinsic Excitability and Cognitive Decline

Neuronal and network-level hyperexcitability is commonly associated with increased levels of amyloid-β (Aβ) and contribute to cognitive deficits associated with Alzheimer's disease (AD). However, the mechanistic complexity underlying the selective loss of basal forebrain cholinergic neurons (BFCNs), a well-recognized characteristic of AD, remains poorly understood. In this study, we tested the hypothesis that the oligomeric form of amyloid-β (oAβ42), interacting with α7-containing nicotinic acetylcholine receptor (nAChR) subtypes, leads to subnucleus-specific alterations in BFCN excitability and impaired cognition. We used single-channel electrophysiology to show that oAβ42 activates both homomeric α7- and heteromeric α7β2-nAChR subtypes while preferentially enhancing α7β2-nAChR open-dwell times. Organotypic slice cultures were prepared from male and female ChAT-EGFP mice, and current-clamp recordings obtained from BFCNs chronically exposed to pathophysiologically relevant level of oAβ42 showed enhanced neuronal intrinsic excitability and action potential firing rates. These resulted from a reduction in action potential afterhyperpolarization and alterations in the maximal rates of voltage change during spike depolarization and repolarization. These effects were observed in BFCNs from the medial septum diagonal band and horizontal diagonal band, but not the nucleus basalis. Last, aged male and female APP/PS1 transgenic mice, genetically null for the β2 nAChR subunit gene, showed improved spatial reference memory compared with APP/PS1 aged-matched littermates. Combined, these data provide a molecular mechanism supporting a role for α7β2-nAChR in mediating the effects of oAβ42 on excitability of specific populations of cholinergic neurons and provide a framework for understanding the role of α7β2-nAChR in oAβ42-induced cognitive decline.
Machine Learning–Based Risk Assessment for Cancer Therapy–Related Cardiac Dysfunction in 4300 Longitudinal Oncology Patients

Background The growing awareness of cardiovascular toxicity from cancer therapies has led to the emerging field of cardio‐oncology, which centers on preventing, detecting, and treating patients with cardiac dysfunction before, during, or after cancer treatment. Early detection and prevention of cancer therapy–related cardiac dysfunction (CTRCD) play important roles in precision cardio‐oncology. Methods and Results This retrospective study included 4309 cancer patients between 1997 and 2018 whose laboratory tests and cardiovascular echocardiographic variables were collected from the Cleveland Clinic institutional electronic medical record database (Epic Systems). Among these patients, 1560 (36%) were diagnosed with at least 1 type of CTRCD, and 838 (19%) developed CTRCD after cancer therapy (de novo). We posited that machine learning algorithms can be implemented to predict CTRCDs in cancer patients according to clinically relevant variables. Classification models were trained and evaluated for 6 types of cardiovascular outcomes, including coronary artery disease (area under the receiver operating characteristic curve [AUROC], 0.821; 95% CI, 0.815–0.826), atrial fibrillation (AUROC, 0.787; 95% CI, 0.782–0.792), heart failure (AUROC, 0.882; 95% CI, 0.878–0.887), stroke (AUROC, 0.660; 95% CI, 0.650–0.670), myocardial infarction (AUROC, 0.807; 95% CI, 0.799–0.816), and de novo CTRCD (AUROC, 0.802; 95% CI, 0.797–0.807). Model generalizability was further confirmed using time‐split data. Model inspection revealed several clinically relevant variables significantly associated with CTRCDs, including age, hypertension, glucose levels, left ventricular ejection fraction, creatinine, and aspartate aminotransferase levels. Conclusions This study suggests that machine learning approaches offer powerful tools for cardiac risk stratification in oncology patients by utilizing large‐scale, longitudinal patient data from healthcare systems.
Influence of Parental Fatty Acid Desaturase 2 (fads2) Expression and Diet on Gilthead Seabream (Sparus aurata) Offspring fads2 Expression during Ontogenesis

Simple Summary The present study was on the gene expression of a rate-limiting enzyme in long chain polyunsaturated fatty acids (LC-PUFAs), fatty acyl desaturase 2 (fads2), throughout the embryonic development of a gilthead sea bream. The results showed a maternal transfer of fads2 mRNA to the developing oocyte. The embryonic fads2 expression might start after the neurula stage. No effect was found in fads2 expression in developing eggs from broodstock fed with a diet rich in rapeseed oil or fish oil. The present study provides information on the change of LC-PUFA biosynthesis during embryogenesis. Abstract Previous studies have shown that it is possible to increase the ability of marine fish to produce long-chain polyunsaturated fatty acid from their 18C precursors by nutritional programming or using broodstock with a higher fatty acyl desaturase 2 (fads2) expression. However, those studies failed to show the effect of these interventions on the expression of the fads2 gene in the developing egg. Moreover, there were no studies on the temporal expression of the fads2 during ontogeny in the gilthead sea bream (Sparus aurata). In order to determine the changes in expression of fads2 during ontogeny, gilthead sea bream broodstock with a high (HRO) or low (LRO) fads2 expression fed a diet previously used for nutritional programming, or a fish oil-based diet (LFO) were allowed to spawn. The samples were taken at the stages of spawning, morula, high blastula, gastrula, neurula, heart beating, hatch and 3 day-old first exogenous feeding larvae to determine fads2 expression throughout embryonic development. The results showed the presence of fads2 mRNA in the just spawned egg, denoting the maternal mRNA transfer to the developing oocyte. Later, fads2 expression increased after the neurula, from heart beating until 3-day-old larvae, denoting the transition from maternal to embryonic gene expression. In addition, the eggs obtained from broodstock with high fads2 expression showed a high docosahexaenoic acid content, which correlated with the downregulation of the fads2 expression found in the developing embryo and larvae. Finally, feeding with the nutritional programming diet with the partial replacement of fish oil by rapeseed oil did not affect the long chain polyunsaturated fatty acid (LC-PUFA) contents nor fads2 expression in the gilthead sea bream developing eggs.
Heart rate variability in dairy cows with postpartum fever during night phase

Autonomic nervous function evaluated by heart rate variability (HRV) and blood characteristics were compared between Holstein Friesian cows that developed postpartum fever (PF; n = 5) and clinically healthy (CH; n = 6) puerperal cows in this case-control study. A cow was defined as having PF when its rectal temperature rose to ≥39.5°C between 1 and 3 days postpartum. We recorded electrocardiograms during this period using a Holter-type electrocardiograph and applied power spectral analysis of HRV. Comparisons between the groups were analyzed by t test or Mann-Whitney U test, and the relationship between rectal temperature and each parameter was analyzed using multiple regression analysis. Heart rate was higher in PF cows than in CH cows (Mean ± SE, 103.3 ± 2.7 vs. 91.5 ± 1.7 bpm). This result suggested that PF cows had a relatively dominant sympathetic nervous function. Total (44,472 ± 2,301 vs. 55,373 ± 1,997 ms) and low frequency power (24.5 ± 3.8 vs. 39.9 ± 5.3 ms) were lower in PF cows than in CH cows. These findings were possibly caused by a reduction in autonomic nervous function. The total white blood cell count (54.3 ± 5.1 vs. 84.5 ± 6.4 ×102/μL) and the serum magnesium (2.1 ± 0.1 vs. 2.4 ± 0.1 mg/dL) and iron (81.5 ± 8.0 vs. 134.4 ± 9.1 μg/dL) concentrations were lower and the serum amyloid A concentration (277 ± 33 vs. 149 ± 21 μg/mL) was higher in PF cows than in CH cows. These results imply that more inflammation was present in PF cows than in CH cows. Multiple regression analysis showed that both of low frequency power and concentration of serum iron were associated with rectal temperature. We found differences in changes in hematologic results, biochemical findings, and HRV patterns between PF cows and CH cows.
Controlling colloidal crystals via morphing energy landscapes and reinforcement learning

A feedback control scheme is developed for rapid assembly of perfect target structures on morphing energy landscapes. We report a feedback control method to remove grain boundaries and produce circular shaped colloidal crystals using morphing energy landscapes and reinforcement learning–based policies. We demonstrate this approach in optical microscopy and computer simulation experiments for colloidal particles in ac electric fields. First, we discover how tunable energy landscape shapes and orientations enhance grain boundary motion and crystal morphology relaxation. Next, reinforcement learning is used to develop an optimized control policy to actuate morphing energy landscapes to produce defect-free crystals orders of magnitude faster than natural relaxation times. Morphing energy landscapes mechanistically enable rapid crystal repair via anisotropic stresses to control defect and shape relaxation without melting. This method is scalable for up to at least N = 103 particles with mean process times scaling as N0.5. Further scalability is possible by controlling parallel local energy landscapes (e.g., periodic landscapes) to generate large-scale global defect-free hierarchical structures.
Clinicopathological and Molecular Profiles of Sporadic Microsatellite Unstable Colorectal Cancer with or without the CpG Island Methylator Phenotype (CIMP)

Simple Summary The 5’-C-phosphate-G-3’ island methylator phenotype (CIMP) is a phenotype of colorectal cancer associated with microsatellite instability (MSI). The aim of the present study was to analyze the CIMP phenotype and genetic mutations in MSI-high colorectal cancer. Our results demonstrated that among MSI-high colorectal cancer patients, CIMP-high tumors were associated with specific mutation profiles and clinicopahtological features compared with CIMP-low or CIMP-0 tumors, however, the CIMP status was not an independent prognostic factor. Abstract Background: The 5’-C-phosphate-G-3’ island methylator phenotype (CIMP) is a specific phenotype of colorectal cancer (CRC) associated with microsatellite instability-high (MSI-high) tumors. Methods: In this study, we determined the CIMP status using eight methylation markers in 92 MSI-high CRC patients after excluding five germline mismatch repair (MMR) gene mutations analyzed by next-generation sequencing (NGS) and confirmed by Sanger sequencing. The mutation spectra of 22 common CRC-associated genes were analyzed by NGS. Results: Of the 92 sporadic MSI-high tumors, 23 (25%) were considered CIMP-high (expressed more than 5 of 8 markers). CIMP-high tumors showed proximal colon preponderance and female predominance. The mutation profiles of CIMP-high tumors were significantly different from those of CIMP-low or CIMP-0 tumors (i.e., higher frequencies of BRAF, POLD1, MSH3, and SMAD4 mutations but lower frequencies of APC, TP53, and KRAS mutations). Multivariate analysis demonstrated that tumor, node, metastasis (TNM) stage was the independent prognostic factor affecting overall survival (OS). Among the MSI-high cases, the CIMP status did not impact the outcome of patients with MSI-high tumors. Conclusions: Only TNM stage was a statistically significant predictor of outcomes independent of CIMP profiles in MSI-high CRC patients. Sporadic MSI-high CRCs with different mechanisms of carcinogenesis have specific mutation profiles and clinicopathological features.