Miracle-dz/UniFAR-FTUs huggingface dataset:
White Matter Differences in Networks in Elders with Mild Cognitive Impairment and Alzheimer's Disease

BACKGROUND Alzheimer's disease is associated with impairment of large -scale brain networks, disruption in structural connections and functional disconnection between distant brain regions. While decreased functional connectivity has been thoroughly investigated and reported by existing functional neuroimaging literature, the present study investigated network-based differences due to the structural changes in white matter pathways in Alzheimer's disease patients. We hypothesize that diffusion metrics of disrupted tracts that go through cognitive networks related with intrinsic awareness, motor movement and executive control can be utilized as biomarkers to distinguish prodromal stage from Alzheimer's disease stage. METHODS Diffusion MRI data of a total 154 subjects including patients with clinical Alzheimer's disease (n=47) and patients with mild cognitive impairment (n=107) was used. To study structural changes associated with white matter fiber pathways voxel-averaged diffusion metrics and fiber density metrics were calculated. RESULTS Study revealed that AD patients exhibit disruptions in intra-hemispheric tracts and projection fiber tracts as suggested by diffusion indices. Our whole brain analysis revealed that network differences within default mode network, sensory motor network and fronto-parietal networks are associated with disruption in Inferior fronto-occipital fasciculus, corticospinal tract and Superior longitudinal fasciculus. CONCLUSION Diffusion metrics appear to be more sensitive than fiber density metrics in differentiating the structural changes in the white matter. Decreased fractional anisotropy along with increased mean diffusivity and radial diffusivity in forceps minor, corticospinal tract and inferior fronto-occipital fasciculus as an imaging biomarker would be ideal to distinguish Alzheimer's disease patients from mild cognitive impairment patients.
Resting frontal EEG asymmetry and schizotypal traits: a test-retest study

ABSTRACT Introduction: Increase in right relative to left frontal electroencephalography (EEG) activity has been observed in patients with schizophrenia, both in cognitive tasks and during rest; and this lateralisation may be related to the severity of schizotypal traits. Methods: We used the Schizotypal Personality Questionnaire (SPQ) to assess schizotypal traits, and examined the correlation between these traits and resting EEG frontal asymmetry (left-right) in 52 college students, as well as the reliability of this correlation over a three-month interval. Results: A higher total score on the SPQ was correlated with reduced asymmetry in different frequency bands: gamma and beta2 frequency bands at baseline, and delta and alpha frequency bands three months later. Additionally, the reduced left relative to right frontal gamma and beta2 asymmetry was correlated with the participants’ verbal fluency ability. However, this correlation was no longer statistically significant after the total SPQ score was controlled. Conclusions: These findings suggest that resting frontal EEG asymmetry is correlated with powers in different frequency bands, and may be an endophenotype for schizophrenia spectrum disorders.
Sampling Variability Is Not Nonreplication: A Bayesian Reanalysis of Forbes, Wright, Markon, and Krueger

Abstract Forbes, Wright, Markon, and Krueger claim that psychopathology network characteristics have “limited” or “poor” replicability, supporting their argument primarily with data from two waves of an observational study on depression and anxiety. They developed “direct metrics” to gauge change across networks (e.g., change in edge sign), and used these results to support their conclusion. Three key flaws undermine their critique. First, nonreplication across empirical datasets does not provide evidence against a method; such evaluations of methods are possible only in controlled simulations when the data-generating model is known. Second, they assert that the removal of shared variance necessarily decreases reliability. This is not true. Depending on the causal model, it can either increase or decrease reliability. Third, their direct metrics do not account for normal sampling variability, leaving open the possibility that the direct differences between samples are due to normal, unproblematic fluctuations. As an alternative to their direct metrics, we provide a Bayesian re-analysis that quantifies uncertainty and compares relative evidence for replication (i.e., equivalence) versus nonreplication (i.e., nonequivalence) for each network edge. This approach provides a principled roadmap for future assessments of network replicability. Our analysis indicated substantial evidence for replication and scant evidence for nonreplication.
Original Contribution EFFECT OF DIET FORMULATION ON BASIS OF DIGESTIBLE AMINO ACIDS AND SUPPLEMENTATION OF PROBIOTIC ON PERFORMANCE OF BROILER CHICKS

The aim of the study was to investigate the effect of diet formulation on digestible amino acids (DAA) basis and supplementation of probiotic Lactina  on performance of broiler chickens. Four treatments were tested: TAA - total amino acids diet formulation, DAA - digestible amino acids diet formulation, TAA+L and DAA+L - diets with Lactina  supplementation. The probiotic preparation Lactina consisted of freeze-dried pure cultures of Streptococcus thermophilus, Enterococcus faecium and 4 strains of Lactobacillus. Each gram of Lactina  contained 0.1x10 9 CFU. Formulation of diets for broilers on DAA basis promoted the existence of increased levels of poor quality protein sources (sunflower meal and meat and bone meal) and resulted in reduced feed cost per 1 kg of yield without negative influence on performance traits. Lactina  fed chickens had decreased feed conversion ration, increased body weight and yield of carcass, meat, liver, gizzard and heart. The tested probiotic preparation did not affect the total cholesterol serum content and the small intestine morphometry but tended to reduce the total counts of bacteria and E. coli and to increase Lactobacilli concentrations in the caecal digesta.
A new aspect of an old friend: the beneficial effect of metformin on anti-tumor immunity

T-cell-based cancer immunotherapies, such as immune checkpoint blockers (ICBs) and chimeric antigen receptor (CAR)-T-cells, have significant anti-tumor effects against certain types of cancer, providing a new paradigm for cancer treatment. However, the activity of tumor infiltrating T-cells (TILs) can be effectively neutralized in the tumor microenvironment (TME) of most solid tumors, rich in various immunosuppressive factors and cells. Therefore, to improve the clinical outcomes of established T-cell-based immunotherapy, adjuvants that can comprehensively relieve multiple immunosuppressive mechanisms of TME are needed. In this regard, recent studies have revealed that metformin has several beneficial effects on anti-tumor immunity. In this mini-review, we understand the immunosuppressive properties of TME and how metformin comprehensively enhances anti-tumor immunity. Finally, we will discuss this old friend’s potential as an adjuvant for cancer immunotherapy.
Cationic Porphyrins as Effective Agents in Photodynamic Inactivation of Opportunistic Plumbing Pathogen Legionella pneumophila

Legionella pneumophila is an environmental bacterium, an opportunistic premise plumbing pathogen that causes the Legionnaires’ disease. L. pneumophila presents a serious health hazard in building water systems, due to its high resistance to standard water disinfection methods. Our aim was to study the use of photodynamic inactivation (PDI) against Legionella. We investigated and compared the photobactericidal potential of five cationic dyes. We tested toluidine blue (TBO) and methylene blue (MB), and three 3-N-methylpyridylporphyrins, one tetra-cationic and two tri-cationic, one with a short (CH3) and the other with a long (C17H35) alkyl chain, against L. pneumophila in tap water and after irradiation with violet light. All tested dyes demonstrated a certain dark toxicity against L. pneumophila; porphyrins with lower minimal effective concentration (MEC) values than TBO and MB. Nanomolar MEC values, significantly lower than with TBO and MB, were obtained with all three porphyrins in PDI experiments, with amphiphilic porphyrin demonstrating the highest PDI activity. All tested dyes showed increasing PDI with longer irradiation (0–108 J/cm2), especially the two hydrophilic porphyrins. All three porphyrins caused significant changes in cell membrane permeability after irradiation and L. pneumophila, co-cultivated with Acanthamoeba castellanii after treatment with all three porphyrins and irradiation, did not recover in amoeba. We believe our results indicate the considerable potential of cationic porphyrins as effective anti-Legionella agents.
EFFECTS OF ECDYSONES, JUVENILE HORMONE ANALOGS, AND 6-OXOOCTANOIC ACID ON THE DEVELOPMENT OF THE MOSQUITO, CULEX TARSALIS (DIPTERA: CULICIDAE)

Abstract Eggs, larvae, and pupae of Culex tarsalis Coquillett were treated with ecdysones, juvenile hormone analogs, and 6-oxooctanoic acid. Effects of these agents on mortality, induction of supernumerary stages, and adult emergence were determined. Topical treatment of eggs with CRD9499 (a juvenile hormone analog), β-ecdysone, and 22-isoecdysone caused a reduction in adult emergence. Treatment of fourth-instar larvae with these chemicals not only induced mortality but also caused the formation of supernumerary intermediate stages. Larvae of C. tarsalis were very susceptible to CRD9499, but pupae were resistant. The ecdysones caused some mortality but only at very high doses and would thus be of little use as larvicides. 6-Oxooctanoic acid caused high rates of mortality at 0.001 M concentrations.
Rational Engineering of a Multi‐Step Biocatalytic Cascade for the Conversion of Cyclohexane to Polycaprolactone Monomers in Pseudomonas taiwanensis

The current industrial production of polymer building blocks such as ε‐caprolactone (ε‐CL) and 6‐hydroxyhexanoic acid (6HA) is a multi‐step process associated with critical environmental issues such as the generation of toxic waste and high energy consumption. Consequently, there is a demand for more eco‐efficient and sustainable production routes. This study deals with the generation of a platform organism that converts cyclohexane to such polymer building blocks without the formation of byproducts and under environmentally benign conditions. Based on kinetic and thermodynamic analyses of the individual enzymatic steps, a 4‐step enzymatic cascade in Pseudomonas taiwanensis VLB120 is rationally engineered via stepwise biocatalyst improvement on the genetic level. It is found that the intermediate product cyclohexanol severely inhibits the cascade which could be optimized by enhancing the expression level of downstream enzymes. The integration of a lactonase enables exclusive 6HA formation without side products. The resulting biocatalyst shows a high activity of 44.8 ± 0.2 U gCDW−1 and fully converts 5 mm cyclohexane to 6HA within 3 h. This platform organism can now serve as a basis for the development of greener production processes for polycaprolactone and related polymers.
Porocarcinoma with areas of mucinous differentiation suggesting multilineage differentiation

Porocarcinoma is an infrequent malignant adnexal carcinoma, with some histopathological variants described, such as the clear cell, the sarcomatoid or the pigmented porocarcinoma. We report an invasive porocarcinoma showing areas of tumor cells floating in prominent dermal mucin, simulating mucinous carcinoma, that we consider a new histopathological variant of porocarcinoma. We report a 74‐year‐old male with previous history of multiple basal cell carcinomas that presented a nodule on his left temple. Histopathologic study showed a large ulcerated multilobular tumor composed of thickened cords of cells emanating from a hyperplastic epidermis and showing a mixed infiltrative and pushing pattern in the dermis. Poroid differentiation was observed in most of the neoplasm, both in intraepidermal and dermal invasive component. Within the neoplasm a prominent area where these small nests with clear formation of ducts were floating in mucinous pools with few septa intermingled was observed, simulating a primary cutaneous mucinous carcinoma. Cytology, immunohistochemistry and the presence of both neoplastic areas as closely related and with multiple points of connectivity favors the consideration of a composite tumor in this peculiar case. Other differentials are discussed.
Classification Model

The Discrete GOM Model at a conceptual level is a model with enormous theoretical appeal as a psychometric model. While it was initially developed as a solution to problems posed in medical classification, social scientists should be quick to realize its many potential applications. This is especially true for sociologists who have been captivated by the intuitive appeal of typological theories, but have been limited by inadequate methodological tools. The GOM models have a number of interesting statistical properties and have proved to be an effective theoretical and data analysis tool in a number of disciplines. The true value of the GOM model will be known by the capacity to make theoretical and practical sense out of data. This paper provides an introduction to GOM Analysis in terms of a heuristic analogy and a concrete sociological example of a two pure type model of parental values. The primary emphasis is on providing a conceptual perspective, rather than a detailed mathematical and statistical specifications.
Local disturbance history and habitat parameters influence the microdistribution of stream invertebrates

SUMMARY 1. We investigated the effects of local disturbance history and habitat parameters (abiotic and biotic) on the microdistribution of benthic invertebrates during several floods in two streams, the Schmiedlaine in Germany (four events) and the Kye Burn in New Zealand (two events). 2. Bed movement patterns were quantified using metal-link scour chains. Before and after each flood, quantitative invertebrate samples were taken from replicate bed patches that had experienced sediment scour, fill or remained stable. 3. Patterns of invertebrate density in the different bed stability types (i.e. scour, fill, stable) varied between floods, sampling dates and streams, but invertebrate density was highest in stable patches in >50% of all the patch type effects detected and lowest in fill patches in 75% of all detected effects. Stable bed patches acted as a refugium for Liponeura spp. and Leuctra spp. in the Schmiedlaine and for Hydracarina and Deleatidium spp. in the Kye Burn. 4. Averaged across both streams, only near-bed current velocity was correlated with invertebrate distribution on the streambed more often than disturbance history. In the Kye Burn, disturbance history and water depth were the most influential habitat parameters. 5. Our results suggest that a thorough understanding of the microdistribution of benthic invertebrates requires knowledge of disturbance history, as well as more readily measured habitat parameters such as current velocity or water depth.
SkQ1 Suppresses the p38 MAPK Signaling Pathway Involved in Alzheimer’s Disease-Like Pathology in OXYS Rats

Alzheimer’s disease (AD) is the most common type of dementia and is currently incurable, and mitogen-activated protein kinase (MAPK) p38 is implicated in the pathogenesis of AD. p38 MAPK inhibition is considered a promising strategy against AD, but there are no safe inhibitors capable of penetrating the blood–brain barrier. Earlier, we have shown that mitochondria-targeted antioxidant plastoquinonyl-decyltriphenylphosphonium (SkQ1) at nanomolar concentrations can prevent, slow down, or partially alleviate AD-like pathology in accelerated-senescence OXYS rats. Here we confirmed that dietary supplementation with SkQ1 during active progression of AD-like pathology in OXYS rats (aged 12–18 months) suppresses AD-like pathology progression, and for the first time, we showed that its effects are associated with suppression of p38 MAPK signaling pathway (MAPKsp) activity. Transcriptome analysis, western blotting, and immunofluorescent staining revealed that SkQ1 suppresses p38 MAPKsp activity in the hippocampus at the level of expression of genes involved in the p38 MAPKsp and reduces the phosphorylation of intermediate kinases (p38 MAPK and MK2) and a downstream protein (αB-crystallin). Thus, the anti-AD effects of SkQ1 are associated with improvement in the functioning of relevant signaling pathways and intracellular processes, thus making it a promising therapeutic agent for human AD.
Molecular Mechanism Contributing to Malnutrition and Sarcopenia in Patients with Liver Cirrhosis

Liver cirrhosis is frequently accompanied by disease-related malnutrition (DRM) and sarcopenia, defined as loss of skeletal muscle mass and function. DRM and sarcopenia often coexist in cirrhotic patients and are associated with increased morbidity and mortality. The clinical manifestation of both comorbidities are triggered by multifactorial mechanisms including reduced nutrient and energy intake caused by dietary restrictions, anorexia, neuroendocrine deregulation, olfactory and gustatory deficits. Maldigestion and malabsorption due to small intestinal bacterial overgrowth, pancreatic insufficiency or cholestasis may also contribute to DRM and sarcopenia. Decreased protein synthesis and increased protein degradation is the cornerstone mechanism to muscle loss, among others mediated by disease- and inflammation-mediated metabolic changes, hyperammonemia, increased myostatin and reduced human growth hormone. The concise pathophysiological mechanisms and interactions of DRM and sarcopenia in liver cirrhosis are not completely understood. Furthermore, most knowledge in this field are based on experimental models, but only few data in humans exist. This review summarizes known and proposed molecular mechanisms contributing to malnutrition and sarcopenia in liver cirrhosis and highlights remaining knowledge gaps. Since, in the prevention and treatment of DRM and sarcopenia in cirrhotic patients, more research is needed to identify potential biomarkers for diagnosis and development of targeted therapeutic strategies.
Regeneration of Genetically Stable Plants from in Vitro Vitrified Leaves of Different Carnation Cultivars

This study was conducted to investigate the efficacy of shoot regeneration from different leaf types (normal leaves and vitrified leaves) from three different carnation cultivars ‘Kumbuyl’, ‘Denev’, and ‘Jinju’ using different combinations of 3-indole butyric acid (IBA) and thidiazuron (TDZ) concentrations. The shoot tips cultured on Murashige and Skoog (MS) basal media (Type 1 media) produced normal leaves, while those cultured-on media supplemented with plant growth regulators and/or vitamin (Type 2 media and Type 3 media) produced vitrified leaves for all cultivars. Culture of normal leaf segments on MS medium containing different combinations of IBA and TDZ concentrations induced callus in all treatments; however, the callus was unable to induce shoots and finally became necrotic. In contrast, no callus induction was observed in the control (hormone-free treatment). When vitrified leaf segments underwent the same treatments, shoots were induced from the vitrified leaves (derived from Type 2 media) but were unhealthy and gradually died, whereas those induced from Type 3 media were vitrified and healthy. The optimal combination for the best shoot regeneration and number of shoots per explants varied depending on the genotypes used. The vitrified shoots induced from the leaves of Type 3 media transformed into normal shoots and survived well under greenhouse conditions. According to the results of random amplified polymorphic DNA (RAPD) analysis, the banding patterns of twelve primers that were detected in vitrified leaf-induced normalized shoots were identical to those of normal in vitro grown plants, indicating that no genetic variation had occurred during the procedure. Taken together, this study indicates that vitrified leaves can be used for shoot regeneration of recalcitrant carnation cultivars, regardless of the genotypes and types of vitrified leaves. However, as the number of shoots per explants was still low, further investigation is warranted to obtain a more efficient shoot regeneration protocol for genetic transformation of the cultivars.
Prevalence and practice of self-medication among undergraduate medical students and non-medical students in south India

Background: Self-medication is commonly practiced worldwide and the irrational use of drugs for self-medication is a major cause of concern. The situation is more complex when a number of prescriptions only medicines are used for self-medication which are easily available over the counter through pharmacies without any prescription. The objective of this study was to assess the prevalence and practice of self-medication among undergraduate medical students and non-medical students.Methods: This cross-sectional questionnaire based study was carried out among 100 undergraduate students of a tertiary care medical college and 100 undergraduate students of an arts and science college in south India. The respondents were selected from the students who were present on the day of study. A pre-tested, self-assessing questionnaire was used to obtain the information on the prevalence and practice of self-medication.Results: Self-medication was practiced by 96% and 92% of medical and nonmedical students respectively. Overall practice of self-medication was 94%. Majority of females were self-medicating than males, 94% and 90% respectively. The most common symptom leading to self-medication among medical students were cough and common cold compared to headache among nonmedical students. The commonly used medicines for self-medication in both the groups were analgesics, antipyretics, cough suppressants and antibiotics. More number of medical students reported the use of antibiotics to treat infections (70%) which was statistically significant.Conclusions: The prevalence and practice of self-medication was alarming in both groups. The use of antimicrobials was also found to be very high among medical students. It is a need of the hour to create better awareness regarding the use of drugs for self-medication, to implement policies to prevent the dispensing of medicines without any prescription which would remain as the cornerstone for reducing the practice of self-medication.