Miracle-dz/UniFAR-FTUs huggingface dataset:
Rab35 regulates insulin secretion via phogrin in pancreatic β cells

Dysfunction of pancreatic β cell insulin secretion is related to the pathogenesis of type 2 diabetes (T2D). Rab proteins have been shown to be key players in insulin secretion by pancreatic β cells, and phogrin is a marker for the processes of exocytosis and insulin secretion. The purposes of this study were to clarify the regulatory role of Rab35 in insulin secretion and analyse the Rab35/phogrin interaction mechanism in β‐TC‐6 cells. We studied the effects of Rab35 gene overexpression and interference on insulin secretion and phogrin expression and levels in β‐TC‐6 cells. The Rab35/phogrin interaction was verified by GST pulldown, co‐IP and co‐localisation experiments. Here, we report that Rab35 is mainly distributed in the β‐TC‐6‐cell plasma membrane and cytoplasm. Rab35 overexpression promotes insulin secretion and decreases phogrin expression in β‐TC‐6 cells, whereas its silencing significantly inhibits insulin secretion, promotes phogrin expression (p < 0.05) and causes phogrin redistribution. Furthermore, Rab35 silencing suppresses exocytosis of insulin. Rab35 interacts with phogrin, and both proteins co‐localise in the plasma membranes and cytoplasm of β‐TC‐6 cells. Our study presents novel evidence that Rab35 regulates insulin secretion by inhibiting phogrin expression and causing intracellular phogrin redistribution in pancreatic β cells.
Prognostic gene expression analysis in a retrospective, multinational cohort of 155 multiple myeloma patients treated outside clinical trials

Typically, prognostic capability of gene expression profiling (GEP) is studied in the context of clinical trials, for which 50%‐80% of patients are not eligible, possibly limiting the generalizability of findings to routine practice. Here, we evaluate GEP analysis outside clinical trials, aiming to improve clinical risk assessment of multiple myeloma (MM) patients.
Unraveling the Underlying Heavy Metal Detoxification Mechanisms of Bacillus Species

The rise of anthropogenic activities has resulted in the increasing release of various contaminants into the environment, jeopardizing fragile ecosystems in the process. Heavy metals are one of the major pollutants that contribute to the escalating problem of environmental pollution, being primarily introduced in sensitive ecological habitats through industrial effluents, wastewater, as well as sewage of various industries. Where heavy metals like zinc, copper, manganese, and nickel serve key roles in regulating different biological processes in living systems, many heavy metals can be toxic even at low concentrations, such as mercury, arsenic, cadmium, chromium, and lead, and can accumulate in intricate food chains resulting in health concerns. Over the years, many physical and chemical methods of heavy metal removal have essentially been investigated, but their disadvantages like the generation of chemical waste, complex downstream processing, and the uneconomical cost of both methods, have rendered them inefficient,. Since then, microbial bioremediation, particularly the use of bacteria, has gained attention due to the feasibility and efficiency of using them in removing heavy metals from contaminated environments. Bacteria have several methods of processing heavy metals through general resistance mechanisms, biosorption, adsorption, and efflux mechanisms. Bacillus spp. are model Gram-positive bacteria that have been studied extensively for their biosorption abilities and molecular mechanisms that enable their survival as well as their ability to remove and detoxify heavy metals. This review aims to highlight the molecular methods of Bacillus spp. in removing various heavy metals ions from contaminated environments.
Bacterial Exposure to Nickel: Influence on Adhesion and Biofilm Formation on Orthodontic Archwires and Sensitivity to Antimicrobial Agents

The presence of nickel could modify bacterial behavior and susceptibility to antimicrobial agents. Adhesion and biofilm formation on orthodontic archwires can be a source of bacterial colonization and possible health hazards. Staphylococcus aureus was subjected to exposure and adaptation to various sub-inhibitory concentrations of nickel. Five strains of bacteria adapted to nickel in concentrations of 62.5–1000 μg/mL were tested for adhesion and biofilm formation on nickel-titanium archwires. Archwires were previously incubated in artificial saliva. Bacteria were incubated with orthodontic wire with stirring for 4 h (adhesion) and 24 h (biofilm formation). The number of adherent bacteria was determined after sonication and cultivation on the Muller-Hinton agar. Disk diffusion method was performed on all bacteria to assess the differences in antimicrobial susceptibility. Bacteria adapted to lower concentrations of nickel adhered better to nickel-titanium than strains adapted to higher concentrations of nickel (p < 0.05). Biofilm formation was highest in strains adapted to 250 and 500 μg/mL of nickel (p < 0.05). The highest biofilm biomass was measured for strains adapted to 250 μg/mL, followed by those adapted to 1000 μg/mL. Bacteria adapted to lower concentrations of nickel demonstrated lower inhibition zone diameters in the disk diffusion method (p < 0.05), indicating increased antimicrobial resistance. In conclusion, bacteria adapted to 250 μg/mL of nickel ions adhered better, demonstrated higher biofilm formation and often had higher antimicrobial resistance than other adapted and non-adapted strains.
Advances with Long Non-Coding RNAs in Alzheimer’s Disease as Peripheral Biomarker

One of the most compelling needs in the study of Alzheimer’s disease (AD) is the characterization of cognitive decline peripheral biomarkers. In this context, the theme of altered RNA processing has emerged as a contributing factor to AD. In particular, the significant role of long non-coding RNAs (lncRNAs) associated to AD is opening new perspectives in AD research. This class of RNAs may offer numerous starting points for new investigations about pathogenic mechanisms and, in particular, about peripheral biomarkers. Indeed, altered lncRNA signatures are emerging as potential diagnostic biomarkers. In this review, we have collected and fully explored all the presented data about lncRNAs and AD in the peripheral system to offer an overview about this class of non-coding RNAs and their possible role in AD.
Neuro-Ophthalmological Findings in Friedreich’s Ataxia

Friedreich ataxia (FRDA) is a progressive neurodegenerative disease caused by a severe autosomal recessive genetic disorder of the central nervous (CNS) and peripheral nervous system (PNS), affecting children and young adults. Its onset is before 25 years of age, with mean ages of onset and death between 11 and 38 years, respectively. The incidence is 1 in 30,000–50,000 persons. It is caused, in 97% of cases, by a homozygous guanine-adenine-adenine (GAA) trinucleotide mutation in the first intron of the frataxin (FXN) gene on chromosome 9 (9q13–q1.1). The mutation of this gene causes a deficiency of frataxin, which induces an altered inflow of iron into the mitochondria, increasing the nervous system’s vulnerability to oxidative stress. The main clinical signs include spinocerebellar ataxia with sensory loss and disappearance of deep tendon reflexes, cerebellar dysarthria, cardiomyopathy, and scoliosis. Diabetes, hearing loss, and pes cavus may also occur, and although most patients with FRDA do not present with symptomatic visual impairment, 73% present with clinical neuro-ophthalmological alterations such as optic atrophy and altered eye movement, among others. This review provides a brief overview of the main aspects of FRDA and then focuses on the ocular involvement of this pathology and the possible use of retinal biomarkers.
Role of Reactive Oxygen Species and Hormones in Plant Responses to Temperature Changes

Temperature stress is one of the major abiotic stresses that adversely affect agricultural productivity worldwide. Temperatures beyond a plant’s physiological optimum can trigger significant physiological and biochemical perturbations, reducing plant growth and tolerance to stress. Improving a plant’s tolerance to these temperature fluctuations requires a deep understanding of its responses to environmental change. To adapt to temperature fluctuations, plants tailor their acclimatory signal transduction events, and specifically, cellular redox state, that are governed by plant hormones, reactive oxygen species (ROS) regulatory systems, and other molecular components. The role of ROS in plants as important signaling molecules during stress acclimation has recently been established. Here, hormone-triggered ROS produced by NADPH oxidases, feedback regulation, and integrated signaling events during temperature stress activate stress-response pathways and induce acclimation or defense mechanisms. At the other extreme, excess ROS accumulation, following temperature-induced oxidative stress, can have negative consequences on plant growth and stress acclimation. The excessive ROS is regulated by the ROS scavenging system, which subsequently promotes plant tolerance. All these signaling events, including crosstalk between hormones and ROS, modify the plant’s transcriptomic, metabolomic, and biochemical states and promote plant acclimation, tolerance, and survival. Here, we provide a comprehensive review of the ROS, hormones, and their joint role in shaping a plant’s responses to high and low temperatures, and we conclude by outlining hormone/ROS-regulated plant responsive strategies for developing stress-tolerant crops to combat temperature changes.
Financial Burdens of Out-of-Pocket Spending Among Medicare Fee-for-Service Beneficiaries: Role of the “Big Four” Chronic Health Conditions

While Medicare is the universal source of health care coverage for Americans aged 65 years or older, the program requires significant cost sharing in terms of out-of-pocket (OOP) spending. We conducted a retrospective study using data from 2016 to 2018 Medicare Current Beneficiary Surveys of elderly community-dwelling beneficiaries (n = 10,431) linked with administrative data to estimate OOP spending associated with the “big four” chronic diseases (cardiovascular disease, cancer, diabetes, and chronic lung disease). We estimated a generalized linear model adjusting for predisposing, enabling, and need factors to estimate annual OOP spending. We found that beneficiaries with any of the “big four” chronic conditions spent 15% (p < .001) higher OOP costs and were 56% more likely to spend ≥20% of annual income on OOP expenditure (adjusted odds ratio = 1.56; p < .001) compared with those without any of those conditions. OOP spending appears to be heterogeneous across disease types and changing by conditions over time.
Adverse childhood experiences and risky behaviors in male college students

Abstract Objective: The current study examined associations between ACEs and health-risk behaviors in male college students. Participants: 795 men who attended a large southern public university. Method: One-way ANOVA was used to explore whether the ACEs of sexual abuse, exposure to interparental violence, household mental illness, and household substance abuse significantly affected male college students’ high risk drinking, number of sexual partners, and/or impulsivity. Results: Sexual abuse was significantly associated with all three measured outcomes and had the strongest associations of all assessed ACEs. Exposure to interparental violence was significantly associated only with number of sexual partners. Household substance abuse was significantly associated with high risk drinking and number of sexual partners. A simple linear regression revealed that for each additional ACE, students in the sample increased their risky behaviors. Conclusions: Results confirm a dose-response between ACEs and negative outcomes. Mindfulness training, policy/funding advocacy, and trauma-informed support are discussed as implications.
Value of 18F-PSMA-PET/MRI for Assessment of Recurring Ranula

We report the case of a 6-year-old patient with suspected recurrence of a plunging ranula in clinical and ultrasonographic examination. Surgical resection of the left submandibular and sublingual glands had already been performed. Since persistent glandular tissue could not be excluded with certainty via MRI, we expanded diagnostics by performing a PET/MRI using a head and neck imaging protocol and the radiotracer 18F-PSMA-1007, which is physiologically expressed by salivary gland tissue. The 18F-PSMA-PET/MRI provided evidence of a cystically transformed, diminishing seroma in the left retro-/submandibular region. No 18F-PSMA expressing glandular tissue could be detected in the area of resection, excluding a relapse of a plunging ranula. As a consequence, we opted for a conservative treatment without further surgical intervention. We conclude that a simultaneous 18F-PSMA-PET/MRI is a comprehensive imaging modality, which can help to rule out persistent salivary tissue and recurring plunging ranula. It is a useful tool to facilitate the decision making of surgical interventions.
The impact of differential lignin S/G ratios on mutagenicity and chicken embryonic toxicity

Lignin and lignin‐based materials have received considerable attention in various fields due to their promise as sustainable feedstocks. Guaiacol (G) and syringol (S) are two primary monolignols that occur in different ratios for different plant species. As methoxyphenols, G and S have been targeted as atmospheric pollutants and their acute toxicity examined. However, there is a rare understanding of the toxicological properties on other endpoints and mixture effects of these monolignols. To fill this knowledge gap, our study investigated the impact of different S/G ratios (0.5, 1, and 2) and three lignin depolymerization samples from poplar, pine, and miscanthus species on mutagenicity and developmental toxicity. A multitiered method consisted of in silico simulation, in vitro Ames test, and in vivo chicken embryonic assay was employed. In the Ames test, syringol showed a sign of mutagenicity, whereas guaiacol did not, which agreed with the T.E. S.T. simulation. For three S and G mixture and lignin monomers, mutagenic activity was related to the proportion of syringol. In addition, both S and G showed developmental toxicity in the chicken embryonic assay and T.E. S.T. simulation, and guaiacol had a severe effect on lipid peroxidation. A similar trend and comparable developmental toxicity levels were detected for S and G mixtures and the three lignin depolymerized monomers. This study provides data and insights on the differential toxicity of varying S/G ratios for some important building blocks for bio‐based materials.
Enhancing Healthcare Access–Smartphone Apps in Arrhythmia Screening: Viewpoint

Atrial fibrillation is the most commonly reported arrhythmia and, if undiagnosed or untreated, may lead to thromboembolic events. It is therefore desirable to provide screening to patients in order to detect atrial arrhythmias. Specific mobile apps and accessory devices, such as smartphones and smartwatches, may play a significant role in monitoring heart rhythm in populations at high risk of arrhythmia. These apps are becoming increasingly common among patients and professionals as a part of mobile health. The rapid development of mobile health solutions may revolutionize approaches to arrhythmia screening. In this viewpoint paper, we assess the availability of smartphone and smartwatch apps and evaluate their efficacy for monitoring heart rhythm and arrhythmia detection. The findings obtained so far suggest they are on the right track to improving the efficacy of early detection of atrial fibrillation, thus lowering the risk of stroke and reducing the economic burden placed on public health.
The Multi-Level Pattern Memory Test (MPMT): Initial Validation of a Novel Performance Validity Test

Performance validity tests (PVTs) are used for the detection of noncredible performance in neuropsychological assessments. The aim of the study was to assess the efficacy (i.e., discrimination capacity) of a novel PVT, the Multi-Level Pattern Memory Test (MPMT). It includes stages that allow profile analysis (i.e., detecting noncredible performance based on an analysis of participants’ performance across stages) and minimizes the likelihood that it would be perceived as a PVT by examinees. In addition, it utilizes nonverbal stimuli and is therefore more likely to be cross-culturally valid. In Experiment 1, participants that were instructed to simulate cognitive impairment performed less accurately than honest controls in the MPMT (n = 67). Importantly, the MPMT has shown an adequate discrimination capacity, though somewhat lower than an established PVT (i.e., Test of Memory Malingering—TOMM). Experiment 2 (n = 77) validated the findings of the first experiment while also indicating a dissociation between the simulators’ objective performance and their perceived cognitive load while performing the MPMT. The MPMT and the profile analysis based on its outcome measures show initial promise in detecting noncredible performance. It may, therefore, increase the range of available PVTs at the disposal of clinicians, though further validation in clinical settings is mandated. The fact that it is an open-source software will hopefully also encourage the development of research programs aimed at clarifying the cognitive processes involved in noncredible performance and the impact of PVT characteristics on clinical utility.
Phytoplankton of the Curonian Lagoon as a New Interesting Source for Bioactive Natural Products. Special Impact on Cyanobacterial Metabolites

The bioprospecting of marine and brackish water systems has increased during the last decades. In this respect, microalgae, including cyanobacteria, and their metabolites are one of the most widely explored resources. Most of the bioactive compounds are isolated from ex situ cultures of microorganisms; however, analysis of field samples could also supply valuable information about the metabolic and biotechnological potential of microalgae communities. In this work, the activity of phytoplankton samples from the Curonian Lagoon was studied. The samples were active against antibiotic resistant clinical and environmental bacterial strains as well as against serine proteases and T47D human breast adenocarcinoma cells. No significant effect was found on Daphnia magna. In addition, using LC-MS/MS, we documented the diversity of metabolites present in field samples. A list of 117 detected cyanopeptides was presented. Cyanopeptolins constituted the largest class of cyanopeptides. As complex bloom samples were analyzed, no link between the observed activity and a specific sample component can be established. However, the results of the study showed a biotechnological potential of natural products from the Curonian Lagoon.
A Plant Endophytic Bacterium, Burkholderia seminalis Strain 869T2, Promotes Plant Growth in Arabidopsis, Pak Choi, Chinese Amaranth, Lettuces, and Other Vegetables

Plant endophytic bacteria live inside host plants, can be isolated from surface-sterilized plant tissues, and are non-pathogenic. These bacteria can assist host plants in obtaining more nutrients and can improve plant growth via multiple mechanisms. Certain Gram-negative Burkholderia species, including rhizobacteria, bioremediators, and biocontrol strains, have been recognized for their plant-growth-promoting abilities, while other isolates have been identified as opportunistic plant or human pathogens. In this study, we observed the auxin production, siderophore synthesis, and phosphate solubilization abilities of B. seminalis strain 869T2. Our results demonstrated that strain 869T2 promoted growth in Arabidopsis, ching chiang pak choi, pak choi, loose-leaf lettuce, romaine lettuce, red leaf lettuce, and Chinese amaranth. Leafy vegetables inoculated with strain 869T2 were larger, heavier, and had more and larger leaves and longer and heavier roots than mock-inoculated plants. Furthermore, inoculations of strain 869T2 into hot pepper caused increased flower and fruit production, and a higher percentage of fruits turned red. Inoculation of strain 869T2 into okra plants resulted in earlier flowering and increased fruit weight. In conclusion, the plant endophytic bacterium Burkholderia seminalis 869T2 exerted positive effects on growth and production in several plant species.
The Psychological Restorative Effects of Campus Environments on College Students in the Context of the COVID-19 Pandemic: A Case Study at Northwest A&F University, Shaanxi, China

During the COVID-19 outbreak, college students experienced different periods of isolation on campus, which has had an impact on students’ mental health. Based on ART theory, this study randomly selected students at Northwest A&F University, Shaanxi, China and distributed questionnaires in order to evaluate the psychological recovery effect of campus environment during the epidemic. The results showed that: (1) There were significant differences in the psychological restoration of four types of campus environments. Blue space had the greatest effect, followed by green space and sports grounds, while grey space had the least. (2) Time of stay had a very significant impact on psychological restoration. Longer time of exposure is not necessarily correlated with a better recovery experience. (3) In the different campus environments, extent is easier to be perceived followed by fascination and compatibility, and the weakest is being away. At the time of stay level, no significant difference was found in the perception of compatibility. Time of stay was negatively correlated with fascination and compatibility. These findings can provide theoretical and practical bases for campus environmental planning and construction following the COVID-19 epidemic.
Progression-Free Survival Prediction in Patients with Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy: Machine Learning vs. Traditional Statistics

Background: The Cox proportional hazards (CPH) model is the most commonly used statistical method for nasopharyngeal carcinoma (NPC) prognostication. Recently, machine learning (ML) models are increasingly adopted for this purpose. However, only a few studies have compared the performances between CPH and ML models. This study aimed at comparing CPH with two state-of-the-art ML algorithms, namely, conditional survival forest (CSF) and DeepSurv for disease progression prediction in NPC. Methods: From January 2010 to March 2013, 412 eligible NPC patients were reviewed. The entire dataset was split into training cohort and testing cohort in a ratio of 90%:10%. Ten features from patient-related, disease-related, and treatment-related data were used to train the models for progression-free survival (PFS) prediction. The model performance was compared using the concordance index (c-index), Brier score, and log-rank test based on the risk stratification results. Results: DeepSurv (c-index = 0.68, Brier score = 0.13, log-rank test p = 0.02) achieved the best performance compared to CSF (c-index = 0.63, Brier score = 0.14, log-rank test p = 0.38) and CPH (c-index = 0.57, Brier score = 0.15, log-rank test p = 0.81). Conclusions: Both CSF and DeepSurv outperformed CPH in our relatively small dataset. ML-based survival prediction may guide physicians in choosing the most suitable treatment strategy for NPC patients.