Miracle-dz/UniFAR-FTUs huggingface dataset:
Circadian Rhythm Disruption and Alzheimer’s Disease: The Dynamics of a Vicious Cycle

All mammalian cells exhibit circadian rhythm in cellular metabolism and energetics. Autonomous cellular clocks are modulated by various pathways that are essential for robust time keeping. In addition to the canonical transcriptional translational feedback loop, several new pathways of circadian timekeeping - non-transcriptional oscillations, post-translational modifications, epigenetics and cellular signaling in the circadian clock - have been identified. The physiology of circadian rhythm is expansive, and its link to the neurodegeneration is multifactorial. Circadian rhythm disruption is prevelant in contamporary society where light-noise, shift-work, and transmeridian travel are commonplace, and is also reported from the early stages of Alzheimer's disease (AD). Circadian alignment by bright light therapy in conjunction with chronobiotics is beneficial for treating sundowning syndrome and other cognitive symptoms in advanced AD patients. We performed a comprehensive analysis of the clinical and translational reports to review the physiology of the circadian clock, delineate its dysfunction in AD, and unravel the dynamics of the vicious cycle between two pathologies. The review delineates the role of putative targets like clock proteins PER, CLOCK, BMAL1, ROR, and clock-controlled proteins like AVP, SIRT1, FOXO, and PK2 towards future approaches for management of AD. Furthermore, the role of circadian rhythm disruption in aging is delineated.
Comparison of Cardiovascular Risk Factors in European Population Cohorts for Predicting Atrial Fibrillation and Heart Failure, Their Subsequent Onset, and Death

Background Differences in risk factors for atrial fibrillation (AF) and heart failure (HF) are incompletely understood. Aim of this study was to understand whether risk factors and biomarkers show different associations with incident AF and HF and to investigate predictors of subsequent onset and mortality. Methods and Results In N=58 693 individuals free of AF/HF from 5 population‐based European cohorts, Cox regressions were used to find predictors for AF, HF, subsequent onset, and mortality. Differences between associations were estimated using bootstrapping. Median follow‐up time was 13.8 years, with a mortality of 15.7%. AF and HF occurred in 5.0% and 5.4% of the participants, respectively, with 1.8% showing subsequent onset. Age, male sex, myocardial infarction, body mass index, and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) showed similar associations with both diseases. Antihypertensive medication and smoking were stronger predictors of HF than AF. Cholesterol, diabetes mellitus, and hsCRP (high‐sensitivity C‐reactive protein) were associated with HF, but not with AF. No variable was exclusively associated with AF. Population‐attributable risks were higher for HF (75.6%) than for AF (30.9%). Age, male sex, body mass index, diabetes mellitus, and NT‐proBNP were associated with subsequent onset, which was associated with the highest all‐cause mortality risk. Conclusions Common risk factors and biomarkers showed different associations with AF and HF, and explained a higher proportion of HF than AF risk. As the subsequent onset of both diseases was strongly associated with mortality, prevention needs to be rigorously addressed and remains challenging, as conventional risk factors explained only 31% of AF risk.
Does root respiration in Australian rainforest tree seedlings acclimate to experimental warming?

Plant respiration can acclimate to changing environmental conditions and vary between species as well as biome-types, though belowground respiration responses to on-going climate warming is not well-understood. Understanding the thermal acclimation capacity of root respiration (Rroot) in relation to increasing temperatures is therefore critical in elucidating a key uncertainty in plant function in response to warming. However, the degree of temperature acclimation of Rroot in rainforest trees and how root chemical and morphological traits are related to acclimation is unknown. Here we investigated the extent to which respiration of fine roots (≤ 2 mm) of four tropical and four warm-temperate rainforest tree seedlings differed in response to warmer growth temperatures (control and + 6°C), including temperature sensitivity (Q10) and the degree of acclimation of Rroot. Regardless of biome-type, we found no consistent pattern in the short-term temperature responses of Rroot to elevated growth temperature: a significant reduction in the temperature response of Rroot to +6°C treatment was only observed for a tropical species, Cryptocarya mackinnoniana, whereas the other seven species had either some stimulation or no alteration. Across species, Rroot was positively correlated with root tissue nitrogen concentration (mg g-1), while Q10 was positively correlated with root tissue density (g cm-3). Warming increased root tissue density by 20.8%, but did not alter root nitrogen across species. We conclude that thermal acclimation capacity of Rroot to warming is species-specific, and suggest that root tissue density is a useful predictor of Rroot and its thermal responses of rainforest tree seedlings.
MULTI-TROPHIC LEVEL INTERACTIONS BETWEEN THE INVASIVE PLANT CENTAUREA STOEBE, INSECTS AND NATIVE PLANTS

Centaurea stoebe is one of the most common and problematic invasive plants in the western United States and Canada. To fully comprehend C. stoebe’s impact on native organisms and enhance methods for its control, we must come to a better understanding of how it integrates into the ecological networks of its introduced range. My research objectives addressed this need by assessing (1) how pollinator communities vary with C. stoebe density, (2) the impact of C. stoebe invasion on pollinator visitation to and reproduction of the native plant Heterotheca villosa, and (3) the extent to which C. stoebe biological control agents are attacked by native parasitoids. Objective 1 was completed during summer 2012 at nine C. stoebe infested sites in western Montana. Each site was visited once per week from June to August to document plant-pollinator interactions. Differences in pollinator abundance, richness, and community composition were found across varying C. stoebe densities, but differences depended on the time of season. Prior to C. stoebe blooming, plots without C. stoebe were visited by a higher abundance and richness of pollinators than plots with high C. stoebe density. The opposite pattern was observed during peak C. stoebe bloom. Objective 2 was completed during summer 2013 at a site near Bozeman, Montana. Potted C. stoebe plants were placed at densities of 1, 2, or 4 plants next to naturally occurring H. villosa plants to assess effects on pollinator visitation to and reproductive output of H. villosa. Centaurea stoebe, at the densities used, had no effect on the visitation to or reproduction of H. villosa. For objective 3, throughout 2012 and 2013, 19 and 45 sites were visited to make C. stoebe root and seedhead collections, respectively. Collections were then monitored for biological control agent and parasitoid emergence in the laboratory. Nine parasitoid species (four of which were not previously known to be associated with C. stoebe) emerged along with ten biological control agent species. Host-parasitoid associations were verified for three of the nine parasitoid species: Urophora affinis – Pronotalia carlinarum, Larinus spp. – Scambus brevicornis, and Agapeta zoegana – Bracon sp.
Effect of Lupin-Enriched Biscuits as Substitute Mid-Meal Snacks on Post-Prandial Interstitial Glucose Excursions in Post-Surgical Hospital Patients with Type 2 Diabetes

Hospital biscuit snacks offered to Type 2 Diabetes Mellitus (T2DM) patients may adversely affect glycaemic control. This study investigated the effect of lupin mid-meal biscuit snacks, compared to spelt or standard hospital biscuits, on interstitial glucose levels in post-operative T2DM inpatients. In a pilot cross-over pragmatic study, 20 patients (74 ± 12 years) consumed, in order, lupin biscuits (20% lupin), wholemeal spelt and standard plain sweet biscuits as mid-meal snacks (2 biscuits each for morning and afternoon tea) on three consecutive days. Continuous glucose monitoring, appetite perceptions and bowel motions were recorded. Glucose levels were not significantly different in the first 90 min after mid-meal biscuit consumption at morning and afternoon tea, irrespective of type. However, after consuming the lupin biscuits only, glucose levels were significantly (p < 0.001) reduced 90 min postprandially after dinner, indicating a potential second-meal effect. Patients also reported improved satiety after lupin biscuit consumption on day 1, compared to days 2 and 3 (p = 0.018). These findings suggest that lupin-enriched biscuits may improve both glycaemic control and satiety in hospitalised T2DM patients, potentially contributing to reduced length of stay. Larger controlled studies are warranted to confirm these findings and inform potential revision of hospital menu standards for T2DM patients.
Multi-dimensional machine learning approaches for fruit shape phenotyping in strawberry

Abstract Background Shape is a critical element of the visual appeal of strawberry fruit and is influenced by both genetic and non-genetic determinants. Current fruit phenotyping approaches for external characteristics in strawberry often rely on the human eye to make categorical assessments. However, fruit shape is an inherently multi-dimensional, continuously variable trait and not adequately described by a single categorical or quantitative feature. Morphometric approaches enable the study of complex, multi-dimensional forms but are often abstract and difficult to interpret. In this study, we developed a mathematical approach for transforming fruit shape classifications from digital images onto an ordinal scale called the Principal Progression of k Clusters (PPKC). We use these human-recognizable shape categories to select quantitative features extracted from multiple morphometric analyses that are best fit for genetic dissection and analysis. Results We transformed images of strawberry fruit into human-recognizable categories using unsupervised machine learning, discovered 4 principal shape categories, and inferred progression using PPKC. We extracted 68 quantitative features from digital images of strawberries using a suite of morphometric analyses and multivariate statistical approaches. These analyses defined informative feature sets that effectively captured quantitative differences between shape classes. Classification accuracy ranged from 68% to 99% for the newly created phenotypic variables for describing a shape. Conclusions Our results demonstrated that strawberry fruit shapes could be robustly quantified, accurately classified, and empirically ordered using image analyses, machine learning, and PPKC. We generated a dictionary of quantitative traits for studying and predicting shape classes and identifying genetic factors underlying phenotypic variability for fruit shape in strawberry. The methods and approaches that we applied in strawberry should apply to other fruits, vegetables, and specialty crops.
Fermentation Characteristics of Kochujang Containing Horseradish or Mustard

Traditional Kochujang was prepared adding horseradish or mustard powder to repress the gas formation which used to cause swelling problem during distribution. The koji for Kochujang was prepared by the strains which had high amylase and protease activities with superior flavor. The gas production from Kochujang during fermentation at was ceased after stopping yeast growth completely by bactericidal components from of horseradish or mustard addition. Total viable bacterial count was not affected by adding horseradish or mustard. The amino type nitrogen content in Kochujang, which was one of the most important parameters in quality of Kochujang, increased continually during fermentation. The Kochujang fermented by P-2 isolate and added with mustard was significantly higher in amino type nitrogen content than other treatments after 120 days' fermentation. activity was very low while activity was high in Kochujang fermented by adding horseradish and mustard powder. The protease(acid and neutral) activities gradually increased by fermentation with no difference between treatments. The color and flavor were not different, but overall palatability of the Kochujang evaluated by sensory test showed significantly high rank in Kochujang fermented by P-2 isolate and with horseradish.
The fitness versus body fat hypothesis in relation to hippocampal structure.

The Fitness Versus Body Fat Hypothesis argues that cardiorespiratory fitness (CRF) plays a more important role in cardiovascular health than adiposity. It remains poorly understood whether CRF or adiposity accounts for a greater amount of variation in measures of brain health. We examined the contribution of CRF, adiposity, and their interaction with hippocampal structure. This study included 124 sedentary adults (M = 44.34) with overweight/obesity (Body Mass Index mean = 32.43). FMRIB's Integrated Registration and Segmentation Tool was used to segment the hippocampus. Using hierarchical regression, we examined whether CRF, assessed via a submaximal graded exercise test, or adiposity, assessed as percent body fat using dual-energy x-ray absorptiometry (DXA) was associated with left and right hippocampal volume. Vertex-wise shape analysis was performed to examine regional shape differences associated with CRF and adiposity. Higher CRF was significantly associated with greater left hippocampal volume (p = .031), with outward shape differences along the surface of the subiculum and CA1 regions. Adiposity was not associated with left or right hippocampal volume or shape. The interaction between adiposity and CRF was not significant. Neither CRF nor adiposity were associated with thalamus or caudate nucleus volumes or shapes, two control regions. Higher CRF, but not adiposity, was related to greater left hippocampal volume, with outward shape differences along the surface of the subiculum and CA1 regions in a midlife sample with overweight/obesity. These findings indicate that, within the context of obesity, CRF is an important contributor to hippocampal structure, highlighting the importance of interventions targeting CRF.
Integrated weed management in zero-till direct-seeded rice (Oryza sativa) - wheat (Triticum aestivum) cropping system

A field experiment was conducted during 2004-05 and 2005-06 on clay-loam soil at Jabalpur in Madhya Pradesh to find out the effect of integrated weed-management practices on weeds and yield of zero-till direct- seeded rice (Oryza sativa L.). Different methods of crop establishment were evaluated for getting higher produc- tivity and profitability of irrigated rice-wheat cropping system. For rice there were four methods, viz. direct seeding by zero-till drill, direct drilling in friable soil by seed drill, direct seeding of sprouted seeds in puddled soil, and transplanting; and for the succeeding wheat (Triticum aestivum L. emend. Fiori & Paol.) there were two methods, viz. sowing with zero-till drill and conventional sowing. Echinochloa colona and Commelina spp. were the major weeds in zero-till, direct-seeded rice, which reduced the grain yield by 27.4%. Pre-emergence application of pretilachlor at 750 glha or pendimethalin at 1.0 kglha each, followed by one hand-weeding at 30 days after sow- ing was on a par with hand-weeding twice, giving significantly higher grain yield (5.20 and 3.50 tlha) compared with the weedy check (3.98 and 2.25 tlha). Zero-till, direct-seeded rice with proper weed management resulted in significantly higher yield than transplanted rice. In the succeeding wheat crop, population of dominant weeds, viz. Chenopodium album and Medicago hispida, was found to be reduced when wheat was grown after zero-till, direct-seeded rice compared with other methods of rice establishment. The wheat sown after zero-till, direct- seeded rice yielded significantly higher (3.76 and 3.61 tlha) than when sown after other methods of rice estab- lishment. Zero tillage in direct-seeded rice-wheat system reduced the weed problem and increased the system productivity as well as profitability.
Initial experiences from patients with COVID-19 on ventilatory support in Denmark.

INTRODUCTION The coronavirus disease 2019 (COVID-19)pandemic reached Denmark in early 2020. This paper presents initial intensive-care unit (ICU) experiences with COVID-19 patients at Roskilde Hospital, which was the primary recipient of COVID-19 patients in need of intensive care in the Zealand Region, Denmark. METHODS An evaluation was conducted of the COVID-19 patients admitted to the ICU due to respiratory failure from 11 March 2020 to 01 April 2020. The number of ICU beds was increased from eight to 22 beds during this period. RESULTS Sixteen patients (four women) were evaluated. The median age was 69.5 years (range: 56-84 years). All the patients were admitted to the ICU for hypoxemic respiratory failure and all needed mechanical ventilation by orotracheal intubation. By 16 April, six patients were still admitted to the ICU, four patients had been discharged from the ICU and seven had died. At present, the average length of ICU stay is 14 ± 9 days (mean ± standard deviation). One patient has remained on ventilatory support for 31 days. The evaluation revealed four key themes. COVID-19 patients 1) had greatly increased C-reactive protein levels, 2) needed a significant inspiratory O2fraction, 3) were highly positive end-expiratory pressure (PEEP) dependent on ventilatory support and 4) suffered highly fluctuating respiratory failure requiring ventilatory support for a significantly longer period of time than non-COVID-19 patients. CONCLUSIONS COVID-19 patients have characteristic reproducible laboratory findings and present a major challenge due to their illness severity and required treatment length. FUNDING none. TRIAL REGISTRATION not relevant.
A high‐affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain

Maladaptive plasticity involving increased expression of AMPA‐type glutamate receptors is involved in several pathologies, including neuropathic pain, but direct inhibition of AMPARs is associated with side effects. As an alternative, we developed a cell‐permeable, high‐affinity (~2 nM) peptide inhibitor, Tat‐P4‐(C5)2, of the PDZ domain protein PICK1 to interfere with increased AMPAR expression. The affinity is obtained partly from the Tat peptide and partly from the bivalency of the PDZ motif, engaging PDZ domains from two separate PICK1 dimers to form a tetrameric complex. Bivalent Tat‐P4‐(C5)2 disrupts PICK1 interaction with membrane proteins on supported cell membrane sheets and reduce the interaction of AMPARs with PICK1 and AMPA‐receptor surface expression in vivo. Moreover, Tat‐P4‐(C5)2 administration reduces spinal cord transmission and alleviates mechanical hyperalgesia in the spared nerve injury model of neuropathic pain. Taken together, our data reveal Tat‐P4‐(C5)2 as a novel promising lead for neuropathic pain treatment and expand the therapeutic potential of bivalent inhibitors to non‐tandem protein–protein interaction domains.
Yöneticilerin etik liderlik davranışlarının örgütsel özdeşleşme, sapkın davranışlar ve sinizme etkisi

The purpose of this study is to investigate the effects of ethical leadership behavior on organizational identification, cynicism, and deviant behavior. For this purpose, data was collected via questionnaires applied on Nevsehir Municipality Personnel. The questionnaire consists of four parts and the part where demographic information is included. In the first part, ethical leadership questions from ‘Ethical Leadership Scale’ of Brown, Trevino and Harrison (2005); in the second part, organizational identification items from ‘Organizational Identity Scale’ of Mael and Ashforth (1992); in the third part, deviant behaviors items from ‘Deviant Behavior Scale’ of Bennet and Robinson (1995); and in the fourth part, organizational cynicism items from ‘Organizational Cynicism Scale’ which are of 5 dimensions and were developed by Pugh and others (2003) are included in this study. Data analysis was done through hierarchical multiple regression analysis. According to the results of the analysis, ethical leadership behaviors have a positive effect on organizational identification; but there is a negative relationship between ethical leadership and organizational cynicism. On the other hand, it was found that there was a positive but low relationship between ethical leadership and deviant behavior.
miR-22 and cerebral microbleeds in brainstem and deep area are associated with depression one month after ischemic stroke

In this study, we aimed to explore the relationship among miR-22, deep cerebral microbleeds (CMBs), and post-stroke depression (PSD) 1 month after ischemic stroke. We consecutively recruited 257 patients with first-ever and recurrent acute cerebral infarction and performed PSD diagnosis in accordance with the Diagnostic and Statistical Manual IV criteria for depression. Clinical information, assessments of stroke severity, and imaging data were recorded on admission. We further detected plasma miR-22 using quantitative PCR and analyzed the relationship among miR-22, clinical data, and PSD using SPSS 23.0 software. Logistic regression showed that deep (OR=1.845, 95%CI: 1.006-3.386, P=0.047) and brain stem CMBs (OR=2.652, 95%CI: 1.110–6.921, P=0.040), as well as plasma miR-22 levels (OR=2.094, 95%CI: 1.066–4.115, P=0.032) were independent risk factors for PSD. In addition, there were significant differences in baseline National Institutes of Health Stroke Scale scores (OR=1.881, 95%CI: 1.180–3.011, P=0.007) and Widowhood scores (OR=1.903, 95%CI: 1.182–3.063, P=0.012). Analysis of the receiver operating curve (AUC=0.723, 95%CI: 0.562–0.883, P=0.016) revealed that miR-22 could predict PSD one month after ischemic stroke. Furthermore, plasma miR-22 levels in brainstem and deep CMBs patients showed an upward trend (P=0.028) relative to the others. Patients with acute ischemic stroke, having brainstem and deep cerebral microbleeds, or a higher plasma miR-22 were more likely to develop PSD. These findings indicate that miR-22 might be involved in cerebral microvascular impairment and post-stroke depression.
Role of imaging in multiple myeloma

With rapid advancements in the diagnosis and treatment of multiple myeloma (MM), imaging has become instrumental in detection of intramedullary and extramedullary disease, providing prognostic information, and assessing therapeutic efficacy. Whole‐body low dose computed tomography (WBLDCT) has emerged as the study of choice to detect osteolytic bone disease. Positron emission tomography/computed tomography (PET/CT) combines functional and morphologic information to identify MM disease activity and assess treatment response. Magnetic resonance imaging (MRI) has excellent soft‐tissue contrast and is the modality of choice for bone marrow evaluation. This review focuses on the imaging modalities available for MM patient management, highlighting advantages, disadvantages, and applications of each.