Miracle-dz/UniFAR-FTUs huggingface dataset:
A Virtual Reality Game to Change Sun Protection Behavior and Prevent Cancer: User-Centered Design Approach

Background Public health sun safety campaigns introduced during the 1980s have successfully reduced skin cancer rates in Australia. Despite this success, high rates of sunburn continue to be reported by youth and young adults. As such, new strategies to reinforce sun protection approaches in this demographic are needed. Objective This study aims to develop a virtual reality (VR) game containing preventive skin cancer messaging and to assess the safety and satisfaction of the design based on end user feedback. Methods Using a two-phase design approach, we created a prototype VR game that immersed the player inside the human body while being confronted with growing cancer cells. The first design phase involved defining the problem, identifying stakeholders, choosing the technology platform, brainstorming, and designing esthetic elements. In the second design phase, we tested the prototype VR experience with stakeholders and end users in focus groups and interviews, with feedback incorporated into refining and improving the design. Results The focus groups and interviews were conducted with 18 participants. Qualitative feedback indicated high levels of satisfaction, with all participants reporting the VR game as engaging. A total of 11% (2/8) of participants reported a side effect of feeling nauseous during the experience. The end user feedback identified game improvements, suggesting an extended multistage experience with visual transitions to other environments and interactions involving cancer causation. The implementation of the VR game identified challenges in sharing VR equipment and hygiene issues. Conclusions This study presents key findings highlighting the design and implementation approaches for a VR health intervention primarily aimed at improving sun protection behaviors. This design approach can be applied to other health prevention programs in the future.
Barriers and facilitators of meaningful engagement among older migrants living with dementia in residential aged care facilities: A mixed studies systematic review

Abstract Background Migrants with dementia living in residential care may be at risk of disengagement. Objective To synthesize research relating to the meaningful engagement of migrants with dementia who are living in residential care. Method Mixed studies systematic review following PRISMA guidelines. Nine electronic databases were searched for relevant studies. Studies were eligible for inclusion if they reported original research relating to meaningful engagement of migrants with dementia living in residential aged care and were published in English. Two independent reviewers screened the title and abstracts, full texts of eligible studies and conducted a quality appraisal of included texts. A convergent qualitative synthesis approach was used. Results From 1460 articles, 14 papers representing 12 studies were included. Facilitators of meaningful engagement included: the presence of cultural artefacts in the care environment, the use of multimodal communication and a shared but flexible understanding of residents’ culture. Barriers were the absence of a common language and a task-orientated approach to care. Conclusions Migrants with dementia who are living in residential care are at increased risk of disengagement. Our review highlights the need for culturally congruent residential care to go beyond issues of language and to consider how occupations can be tailored to support ongoing participation and engagement.
LU-Optimality Conditions in Optimization Problems With Mechanical Work Objective Functionals

In this article, we introduce interval-valued Kuhn–Tucker (KT)-pseudoinvex optimization problems governed by interval-valued path-independent curvilinear integral objective functionals. Concretely, it is proven that an interval-valued KT-pseudoinvex variational control problem is described such that every KT point is an LU-optimal solution. In addition, the main results are highlighted by two illustrative applications describing the controlled behavior of an artificial neural system.
Triggering an unexpected earthquake in an uncoupled subduction zone

Two large earthquakes in the Aleutian subduction zone provide unexpected evidence for low plate interface coupling. In the 1970s, the Shumagin Islands region of the Alaska subduction zone was identified as a seismic gap expected to host a future great [moment magnitude (Mw) ≥8.0] earthquake. More recent geodetic data indicate that this region is weakly coupled, and the geologic record shows little evidence of past large events. From July to October 2020, a series of earthquakes occurred in this region, raising the possibility of greater coupling. The initial Mw 7.8 thrust faulting earthquake straddled the eastern edge of the Shumagin Gap and was followed by an Mw 7.6 strike-slip earthquake within the Shumagin Gap. Stress modeling indicates that this strike-slip earthquake is in fact favored if the Shumagin Gap has low coupling, whereas a highly coupled Shumagin Gap inhibits that type and location of earthquake. The initial thrust earthquake and its afterslip enhanced the strike-slip loading within the subducting slab, helping to trigger the October event.
Enhanced wound healing using a 3D printed VEGF-mimicking peptide incorporated hydrogel patch in a pig model

There is a need for effective wound healing through rapid wound closure, reduction of scar formation, and acceleration of angiogenesis. Hydrogel is widely used in tissue engineering, but it is not an ideal solution because of its low vascularization capability and poor mechanical properties. In this study, gelatin methacrylate (GelMA) was tested as a viable option with tunable physical properties. GelMA hydrogel incorporating a vascular endothelial growth factor (VEGF) mimicking peptide was successfully printed using a three-dimensional (3D) bio-printer owing to the shear-thinning properties of hydrogel inks. The 3D structure of the hydrogel patch had high porosity and water absorption properties. Furthermore, the bioactive characterization was confirmed by cell culture with mouse fibroblasts cell lines (NIH 3T3) and human umbilical vein endothelial cells. VEGF peptide, which is slowly released from hydrogel patches, can promote cell viability, proliferation, and tubular structure formation. In addition, a pig skin wound model was used to evaluate the wound-healing efficacy of GelMA-VEGF hydrogel patches; the results suggest that the GelMA-VEGF hydrogel patch can be used for wound dressing.
Association of Genetic Structure and Diversity in Iranian Wild Germplasms of Mentha longifolia L. Based on Phenotypical, Biochemical, and Molecular Markers

Mentha longifolia L. is well‐known to be one of the most pervasive wild‐growing species of the Lamiaceae family, which has extensive beneficial properties in the fields of pharmacology and biological products. In the present study, the correlation between Inter‐simple sequence repeat (ISSR) markers and morpho‐chemical parameters of twenty different M. longifolia accessions (MLACs) were assessed. The geographic information system (GIS) has been employed to interpret the original habitat of the accessions in Iran. ISSR analysis indicated a remarkable difference in the studied accessions, segregated them into three main groups, constructed by an unweighted pair‐group method with arithmetic (UPGMA) and principal coordinate analysis (PCoA). A total of 89 bands were generated by 12 ISSR primers, among which 82 (91.97 %) of them were polymorphic. The cluster analysis based on agro‐morphological data scattered MLACs into two main groups. The essential oils (EOs) were analyzed through GC/FID/MS, and four chemotypes were characterized according to the major constituents. Pulegone ranged from 0.17 to 69.50 % was the main oil constituent with the highest content. Also, HPLC‐PDA was employed to identify and to quantify the phenolic compounds in the MeOH extracts of MLACs. Heatmap cluster based on phenolic compounds produced three main categories of accessions. The components identified in the extracts were rosmarinic acid, rutin, vanillic acid, ferulic acid, chlorogenic acid, caffeic acid, 3,4‐dihydroxybenzoic acid, 2,5‐dihydroxybenzoic acid, and p‐coumaric acid, which among them rosmarinic acid (RA) varied from 39.16 to 261.55 mg/100 g (DW) as a predominant constituent. Subsequently, multiple regression analyses between ISSR fragments and morpho‐chemical data illustrated considerable relationships in the plant materials. The high variation and correlation observed in metabolic and phenotypic traits of MLACs establish an adequate source to conduct reserves conservation programs.
Mitochondrial functional resilience after TFAM ablation in the adult heart.

The nuclear genome-encoded mitochondrial DNA (mtDNA) transcription factor A (TFAM) is indispensable for mitochondrial energy production in the developing and postnatal heart; a similar role for TFAM is inferred in adult heart. Here, we provide evidence that challenges this long-standing paradigm. Unexpectedly, conditionalTfam ablation in vivo in adult mouse cardiomyocytes resulted in a prolonged period of functional resilience characterized by preserved mtDNA content, mitochondrial function, and cardiac function, despite mitochondrial structural alterations and decreased transcript abundance. Remarkably, TFAM protein levels did not directly dictate mtDNA content in the adult heart, and mitochondrial translation was preserved with acute TFAM inactivation, suggesting maintenance of respiratory chain assembly/function. Long-term Tfam inactivation, however, downregulated the core mtDNA transcription and replication machinery, leading to mitochondrial dysfunction and cardiomyopathy. Collectively, in contrast to the developing heart, these data reveal a striking resilience of the differentiated adult heart to acute insults to mtDNA regulation.
Effects of Soy Isoflavones on Glycemic Parameters and Blood Pressure in Peritoneal Dialysis Patients: A Randomized, Double Blind, Placebo-Controlled Trial.

INTRODUCTION High serum concentrations of glucose, advanced glycation end products (AGEs), and hypertension are some of the major risk factors for cardiovascular disease and peritoneal membrane fibrosis in peritoneal dialysis (PD) patients. Some investigations in nonuremic individuals have indicated that isoflavones can reduce serum glucose, blood pressure, and increase insulin sensitivity. However, such study in this field in PD patients is still lacking. Therefore, we aimed to determine the effects of isoflavones on serum glucose, fructosamine, AGEs, and blood pressure in PD patients. METHODS This study was a randomized, double blind, placebocontrolled trial. Thirty-eight PD patients were randomly assigned to either the isoflavone group or the placebo. The patients in the isoflavone group received 100 mg/d soy isoflavone for 8 weeks, while the control group received corresponding placebo. At baseline and the end of the 8th week, 7 mL of blood was collected from each patient and serum glucose, fructosamine, carboxymethyl lysine, pentosidine, accompanied by systolic and diastolic blood pressures were measured. RESULTS Serum glucose and pentosidine reduced significantly in the isoflavone group at the end of 8th week compared with baseline (P < .05), whereas no statistically significant changes were observed in the placebo group. Serum carboxymethyl lysine, fructosamine, and systolic and diastolic blood pressures did not significantly change within each group during the study. CONCLUSION This study indicates that soy isoflavones could decrease serum glucose and pentosidine in PD patients.
DNA Damage Response Protein CHK2 Regulates Metabolism in Liver Cancer

This study uncovers a link between a central effector of DNA damage response, CHK2, and cellular metabolism, revealing potential therapeutic strategies for targeting hepatocellular carcinoma. Defective mitosis with chromosome missegregation can have a dramatic effect on genome integrity by causing DNA damage, activation of the DNA damage response (DDR), and chromosomal instability. Although this is an energy-dependent process, mechanisms linking DDR to cellular metabolism are unknown. Here we show that checkpoint kinase 2 (CHK2), a central effector of DDR, regulates cellular energy production by affecting glycolysis and mitochondrial functions. Patients with hepatocellular carcinoma (HCC) had increased CHK2 mRNA in blood, which was associated with elevated tricarboxylic acid cycle (TCA) metabolites. CHK2 controlled expression of succinate dehydrogenase (SDH) and intervened with mitochondrial functions. DNA damage and CHK2 promoted SDH activity marked by increased succinate oxidation through the TCA cycle; this was confirmed in a transgenic model of HCC with elevated DNA damage. Mitochondrial analysis identified CHK2-controlled expression of SDH as key in sustaining reactive oxygen species production. Cells with DNA damage and elevated CHK2 relied significantly on glycolysis for ATP production due to dysfunctional mitochondria, which was abolished by CHK2 knockdown. This represents a vulnerability created by the DNA damage response that could be exploited for development of new therapies. Significance: This study uncovers a link between a central effector of DNA damage response, CHK2, and cellular metabolism, revealing potential therapeutic strategies for targeting hepatocellular carcinoma.
Culture bovine prospermatogonia with 2i medium

Germplasm cryopreservation and expansion of gonocytes/prospermatogonia or spermatogonial stem cells (SSCs) are important; however, it's difficult in cattle. Since inhibitors of Mek1/2 and Gsk3β (2i) can enhance pluripotency maintenance, effects of 2i‐based medium on the cultivation of bovine prospermatogonia from the cryopreserved tissues were examined. The testicular tissues of newborn bulls were well cryopreserved. High mRNA levels of prospermatogonium/SSC markers (PLZF, GFRα‐1) and pluripotency markers (Oct4/Pouf5, Sox2, Nanog) were detected and the PLZF+/GFRα‐1+ prospermatogonia were consistently identified immunohistochemically in the seminiferous cords. Using differential plating and Percoll‐based centrifugation, 41.59% prospermatogonia were enriched and they proliferated robustly in 2i medium. The 2i medium boosted mRNA abundances of Pouf5, Sox2, Nanog, GFRα‐1, PLZF, anti‐apoptosis gene Bcl2, LIF receptor gene LIFR and enhanced PLZF protein expression, but suppressed mRNA expressions of spermatogonial differentiation marker c‐kit and pro‐apoptotic gene Bax, in the cultured prospermatogonia. It also alleviated H2O2‐induced apoptosis of the enriched cells and decreased histone H3 lysine (K9) trimethylation (H3K9me3) and its methylase Suv39h1/2 mRNA level in the cultured seminiferous cords. Overall, 2i medium improves the cultivation of bovine prospermatogonia isolated from the cryopreserved testes, by inhibiting Suv39h1/2‐mediated H3K9me3 through Mek1/2 and Gsk3β signalling, evidencing successful cryopreservation and expansion of bovine germplasm.
Xiaochaihu decoction for nonalcoholic fatty liver disease

Abstract Background: Nonalcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome characterized by excessive deposition of fat in hepatocytes except for alcohol and other specific hepatic factors. Xiaochaihu decoction (XD) has been widely used to treat NAFLD in China. However, there is no systematic review found. In order to evaluate the efficacy and safety of XD in the treatment of NAFLS, we need to conduct a meta-analysis and systematic evaluation. Methods: There are enrolled randomized controlled trials (RCTs) evaluating the effectiveness and safety of XD in the treatment of NAFLD. Data come mainly from 4 Chinese databases (CNKI, CBM, Wanfang, and VIP Database) and 4 English databases (Pubmed, Embase, Cochrane Library, and Web of science). The enrollment of RCTs is from the starting date of database establishment till September 30, 2021. The work such as selection of literature, data collection, quality evaluation of included literature, and assessment of publication bias will be conducted by 2 independent researchers. Meta-analysis will be performed by RevMan 5.0 software. Results: This study will provide high-quality evidence for the effectiveness and safety of XD in the treatment of NAFLD. Conclusion: The results of the study will help us determine whether XD can effectively treat NAFLD. Ethics and dissemination: This study does not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal. OSF registration number: DOI 10.17605/OSF.IO/A5XEM
Impact, Trapping, and Accommodation of Hydroxyl Radical and Ozone at Aqueous Salt Aerosol Surfaces. A Molecular Dynamics Study

Collisions of the gaseous hydroxyl (OH) radical and ozone (O3) with the surfaces of sodium chloride or iodide solutions, as well as with the surface of neat water, were investigated by molecular dynamics simulations. The principal intent was to answer atmospherically relevant questions concerning the trapping and accommodation of the OH and O3 species at the surface and their uptake into the bulk solution. Although trapping is substantial for both species, OH adsorbs and absorbs significantly better than O3. Most of the trapped O3 molecules desorb from the surface within 50 ps, whereas a significant fraction of OH radicals remains at the interface for time intervals exceeding 100 ps. The aqueous surface has also an orientational effect on the OH species, favoring geometries with the H atom pointing toward the aqueous bulk. The effect of the dissolved salt on the trapping efficiency is minor; therefore, most likely, atomic ions solvated in aqueous aerosols do not act as strong scavengers of reactive gases .
A retrospective study

Overweight and obesity may be associated with poor clinical outcome, including chronic kidney disease (CKD). However, whether body mass index (BMI), waist-to-hip ratio (WHR), and waist circumference (WC) are related to CKD is yet to be elucidated. A total of 7593 adults were divided into 4 groups based on the estimated glomerular filtration rate (eGFR) quartile. The eGFR was calculated with the CKD Epidemiology Collaboration. Multiple linear regression analyzed the association between eGFR and WHR, BMI, and WC. Logistic regression analysis determined whether the CKD patients were associated with WHR, BMI, and WC after adjusting for other variables. The mean age of the cohort was 72.34±7.30years. Multiple linear regression analysis showed that WC (P= .006) was associated with eGFR, although adjusted by lifestyle factor and biochemical indicators. The individuals in the underweight, overweight, and obese groups had significantly lower eGFR value than those in the healthy weight group in moderate CKD. The eGFR in the overweight group with WHR 0.894 was higher than in the healthy weight group with WHR >0.894 group (P= .036). Overweight with WHR 0.894 group had a longer WCwith a pronounced increase in the hip circumference. Logistic regression analysis showed that the WC (OR=1.362, P< .001) and BMI (OR=1.227, P= .031) were independent risk factors for moderate CKD patients. Each standard deviation (SD) of high BMI andWC level was associated with 23.0% and 17.3% higher odds of moderate CKD (OR=1.230, P= .017 and OR=1.173, P= .021, respectively). WC is an independent risk factor for eGFR.CombinedBMI andWCare important factors that would predict moderateCKDpatients. Abbreviations: Alb = albumin, BMI = body mass index, CKD = chronic kidney disease, DBP = diastolic blood pressure, eGFR = estimated glomerular filtration rate, Hb = hemoglobin, HDL = high density lipoprotein, LDL = low density lipoprotein cholesterol, SBP = systolic blood pressure, SD = standard deviation, TC = total cholesterol, TG = triglyceride, WC = waist circumference, WHR = waist-to-hip ratio.
Protein farnesylation negatively regulates brassinosteroid signaling via reducing BES1 stability in Arabidopsis thaliana

Abstract Brassinosteroids (BRs) are a group of steroidal phytohormones, playing critical roles in almost all physiological aspects during the life span of a plant. In Arabidopsis, BRs are perceived at the cell surface, triggering a reversible phosphorylation‐based signaling cascade that leads to the activation and nuclear accumulation of a family of transcription factors, represented by BES1 and BZR1. Protein farnesylation is a type of post‐translational modification, functioning in many important cellular processes. Previous studies demonstrated a role of farnesylation in BR biosynthesis via regulating the endoplasmic reticulum localization of a key bassinolide (BL) biosynthetic enzyme BR6ox2. Whether such a process is also involved in BR signaling is not understood. Here, we demonstrate that protein farnesylation is involved in mediating BR signaling in Arabidopsis. A loss‐of‐function mutant of ENHANCED RESPONSE TO ABA 1 (ERA1), encoding a β subunit of the protein farnesyl transferase holoenzyme, can alter the BL sensitivity of bak1‐4 from a reduced to a hypersensitive level. era1 can partially rescue the BR defective phenotype of a heterozygous mutant of bin2‐1, a gain‐of‐function mutant of BIN2 which encodes a negative regulator in the BR signaling. Our genetic and biochemical analyses revealed that ERA1 plays a significant role in regulating the protein stability of BES1.
Deciphering Tumor Heterogeneity in Hepatocellular Carcinoma (HCC)—Multi-Omic and Singulomic Approaches

Abstract Tumor heterogeneity, a key hallmark of hepatocellular carcinomas (HCCs), poses a significant challenge to developing effective therapies or predicting clinical outcomes in HCC. Recent advances in next-generation sequencing-based multi-omic and single cell analysis technologies have enabled us to develop high-resolution atlases of tumors and pull back the curtain on tumor heterogeneity. By combining multiregion targeting sampling strategies with deep sequencing of the genome, transcriptome, epigenome, and proteome, several studies have revealed novel mechanistic insights into tumor initiation and progression in HCC. Advances in multiparametric immune cell profiling have facilitated a deeper dive into the biological complexity of HCC, which is crucial in this era of immunotherapy. Moreover, studies using liquid biopsy have demonstrated their potential to circumvent the need for tissue sampling to investigate heterogeneity. In this review, we discuss how multi-omic and single-cell sequencing technologies have advanced our understanding of tumor heterogeneity in HCC.
Thalamic state influences timing precision in the thalamocortical circuit.

Sensory signals from the outside world are transduced at the periphery, passing through thalamus before reaching cortex, ultimately giving rise to the sensory representations that enable us to perceive the world. The thalamocortical circuit is particularly sensitive to the temporal precision of thalamic spiking due to highly convergent synaptic connectivity. Thalamic neurons can exhibit burst and tonic modes of firing that strongly influence timing within the thalamus. The impact of these changes in thalamic state on sensory encoding in the cortex, however, remains unclear. Here, we investigated the role of thalamic state on timing in the thalamocortical circuit of the vibrissa pathwayin the anesthetized rat. We optogenetically hyperpolarized thalamus while recording single unit activity in both thalamus and cortex. Tonic spike triggered analysis revealed temporally precise thalamic spiking that was locked to weak white-noise sensory stimuli, while thalamic burst spiking was associated with a loss in stimulus-locked temporal precision. These thalamic state dependent changes propagated to cortex such that the cortical timing precision was diminished during the hyperpolarized (burst biased) thalamic state. While still sensory driven, the cortical neurons became significantly less precisely locked to the weak white-noise stimulus. The results here suggests a state dependent differential regulation of spike timing precision in the thalamus that could gate what signals are ultimately propagated to cortex.