Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of faecal microbiota transplantation in Crohn’s disease: a new target treatment?

The efficacy of faecal microbiota transplantation (FMT) in Crohn’s disease (CD) remains unclear due to lack of data. This study aimed to assess the value of FMT in treating CD‐related clinical targets. The use of FMT for CD as a registered trial (NCT01793831) was performed between October 2012 and December 2017. Seven therapeutic targets included abdominal pain, diarrhoea, hematochezia, fever, steroid‐dependence, enterocutaneous fistula and active perianal fistula. Each target was recorded as 1 (yes) or 0 (no) during the long‐term follow‐up for each patient. The primary outcome was the rate of improvement in each therapeutic target. Overall, 174 patients completed the follow‐up. The median follow‐up duration was 43 (interquartile range, 28–59) months. The median score of the total targets was 2 (range, 1–4) before FMT, and it decreased significantly at 1, 3, 6, 12, 24 and 36 months after FMT (P < 0.001 respectively). At 1 month after FMT, 72.7% (101/139), 61.6% (90/146), 76% (19/25) and 70.6% (12/17) of patients achieved improvement in abdominal pain, diarrhoea, hematochezia and fever respectively. Furthermore, 50% (10/20) of steroid‐dependent patients achieved steroid‐free remission after FMT. The present findings indicate that it is important to understand the efficacy of FMT in CD as a targeted therapy, especially for abdominal pain, hematochezia, fever and diarrhoea.
Chronic vagal nerve stimulation has no effect on tachycardia‐induced heart failure progression or excitation–contraction coupling

Autonomic dysregulation plays a key role in the development and progression of heart failure (HF). Vagal nerve stimulation (VNS) may be a promising therapeutic approach. However, the outcomes from clinical trials evaluating VNS in HF have been mixed, and the mechanisms underlying this treatment remain poorly understood. Intermittent high‐frequency VNS (pulse width 300 µs, 30 Hz stimulation, 30 s on, and 300 s off) was used in healthy sheep and sheep in which established HF had been induced by 4 weeks rapid ventricular pacing to assess (a) the effects of VNS on intrinsic cardiac vagal tone, (b) whether VNS delays the progression of established HF, and (c) whether high‐frequency VNS affects the regulation of cardiomyocyte calcium handling in health and disease. VNS had no effect on resting heart rate or intrinsic vagal tone in the healthy heart. Although fewer VNS‐treated animals showed subjective signs of heart failure at 6 weeks, overall VNS did not slow the progression of clinical or echocardiographic signs of HF. Chronic VNS did not affect left ventricular cardiomyocyte calcium handling in healthy sheep. Rapid ventricular pacing decreased the L‐type calcium current and calcium transient amplitude, but chronic VNS did not rescue dysfunctional calcium handling. Overall, high‐frequency VNS did not prevent progression of established HF or influence cellular excitation–contraction coupling. However, a different model of HF or selection of different stimulation parameters may have yielded different results. These results highlight the need for greater insight into VNS dosing and parameter selection and a deeper understanding of its physiological effects.
The efficacy of metformin in combination with life style intervention on body weight,blood lipid and blood glucose in schizophrenia during clozapine treatment

Objective To test the efficacy of metformin in combination with life style intervention on body weight,blood lipid and blood glucose in during clozapine treatment.Methods 60 schizophrenic patients who were treated with clozapine 250~400mg/day were divided into 2 groups:study group received 12-week individual treatments (metformine 750mg/day in combination with life style intervention),control group received no intervention.Before and after four-week,eight-week and twelve-week treatment,the height,body weight,waist circumference,and the fasting blood glucose and blood lipid were measured.In addition,the body mass index(BMI)and the proportion of patients gained more than 7% at the end of the 12-week treatment were caleulated.The Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms(PANSS)were used to assess the treatment.Results There was a significant increase in body weight and BMI within 2 groups from baseline to week 12:study group(2.03±1.26)kg and (0.54±0.62)kg/m2;control group(4.98±3.09)kg and(2.03±1.02)kg/m2.The increase in weight,BMI of control group was more than that of study group(P0.05). Significantly fewer patients in study[6(20%)]than patients in control group[16(53%)]increased their baseline weight by more than 7%(P0.05). The increase in fasting bloog glucose and blood lipid of control group was more than that of study group (P0.05). Conclusion Metformin in combination with life style intervention was effective in attenuating clozapine-induced weight gain and increase of blood glucose and blood lipid in schizophrenic patients.
Characterizing intrinsic functional connectivity in relation to impaired self-regulation in intellectually able male youth with autism spectrum disorder

While a considerable number of youth with autism spectrum disorder exhibit impaired self-regulation (dysregulation), little is known about the neural correlates of dysregulation in autism spectrum disorder. In a sample of intellectually able boys with autism spectrum disorder (further categorized as those with and without dysregulation) and typically developing boys (aged 7–17 years), we conducted a multivariate connectome-wide association study to examine the intrinsic functional connectivity with resting-state functional magnetic resonance imaging. Dysregulation was defined by the sum of Attention, Aggression, and Anxiety/Depression subscales on the Child Behavior Checklist. We identified that both categorical and dimensional neural correlates of dysregulation in youth with autism spectrum disorder involved atypical connectivity among the components of multiple brain networks, especially between those subserving sensorimotor processing and salience encoding, beyond higher-level cognitive control circuitries. Interaction within the attention network might serve as autism spectrum disorder–specific neural correlates underpinning dysregulation. Our results highlight that the inter-individual variability in dysregulation might contribute to the inconsistency in the neuroimaging literature of autism spectrum disorder. Collectively, the present findings provide evidence to suggest that dysregulation might be considered as both categorical and dimensional moderators to parse heterogeneity of autism spectrum disorder. Lay Abstract Impaired self-regulation (i.e., dysregulation in affective, behavioral, and cognitive control), is commonly present in young people with autism spectrum disorder (ASD). However, little is known about what is happening in people’s brains when self-regulation is impaired in young people with ASD. We used a technique called functional MRI (which measures brain activity by detecting changes associated with blood flow) at a resting state (when participants are not asked to do anything) to research this in intellectually able young people with ASD. We found that brains with more connections, especially between regions involved in sensorimotor processing and regions involved in the processes that enable peoples to focus their attention on the most pertinent features from the sensory environment (salience processing), were related to more impaired self-regulation in young people with and without ASD. We also found that impaired self-regulation was related to increased communication within the brain system involved in voluntary orienting attention to a sensory cue (the dorsal attention network) in young people with ASD. These results highlight how different people have different degrees of dysregulation, which has been largely overlooked in the earlier brain imaging reports on ASD. This might contribute to understanding some of the inconsistencies in the existing published literature on this topic.
Calcium and phosphorus metabolism in peripartal dogs.

Recommended allowances for calcium and phosphorus are mostly based on factorial calculations partly set at the level determined adequate for giant breeds (Nutrient requirements of dogs and cats. Washington, DC, USA: The National Academies Press. 2006). Information about appropriateness of supply with both minerals during the peripartal phase is limited. From other species is known that bone mineral stores are used in addition to oral intake of calcium and phosphorus in periods of higher needs such as gestation and lactation. The aim of this study was to determine parameters of calcium and phosphorus homeostasis in female dogs receiving the recommended amount of these minerals according to NRC (Nutrient requirements of dogs and cats. Washington, DC, USA: The National Academies Press. 2006) during the peripartal phase. In five Beagles and four Foxhound crossbreds, all primiparous with a litter size of 1-8 puppies, apparent digestibility of calcium and phosphorus as well as serum parameters of mineral metabolism (total and ionised calcium, phosphorus, parathyroid hormone, bone specific alkaline phosphatase, crosslaps) was determined in the period of 12-9 days before and 4-9 days after parturition. The apparent digestibility of calcium was relatively low and did not differ significantly between both peripartal phases, whereas the apparent digestibility of phosphorus increased during lactation. Serum concentrations of calcium (total as well as ionised), phosphorus and parathyroid hormone did not differ between gestation and lactation. The bone resorption marker serum crosslaps increased in lactating dogs but most individual values were within the reference range for adult female dogs at maintenance. On the other hand, the bone formation marker bone specific alkaline phosphatase decreased from prepartal to postpartal phase with values clearly above reference range in both phases. Based on the results especially of the bone markers, which stayed within the reference range during the peripartal phase without indicating predominant bone resorption, we hypothesise that the applied recommended daily allowances defined for peripartal dogs are appropriate.
The Influence of Current Mood States on Screening Accuracy of the Mood Disorder Questionnaire

Objective In this study we investigated whether current mood states of patients with bipolar disorder have an influence on the screening accuracy of the Mood Disorder Questionnaire (MDQ). Methods A total of 452 patients with mood disorder (including 192 with major depressive disorder and 260 with bipolar disorder completed the Korean version of the MDQ. Patients with bipolar disorder were subdivided into three groups (bipolar depressed only, bipolar euthymic only, bipolar manic/hypomanic only) according to current mood states. The screening accuracy of the MDQ including sensitivity, specificity and area under the curve (AUC) of receiver operating characteristic (ROC) curves were evaluated according to current mood states. Results The optimal cutoff of MDQ was 5 in this study sample. Sensitivity and specificity were not significantly different according to current mood states. Significant differences in AUCs of four independent ROC curves were not found (ROC 1st curve included all bipolar patients; ROC 2nd curve included only bipolar depressed patients; ROC 3rd curve included only bipolar manic/hypomanic patients; ROC 4th curve included only bipolar euthymic patients). Conclusion The study results showed that current mood states (either euthymic state, depressed or manic/hypomanic) did not significantly influence the screening accuracy of the MDQ suggesting that the MDQ could be a useful screening instrument for detecting bipolar disorder in clinical practice regardless of the current mood symptoms of subjects.
Endoplasmic reticulum distribution during bovine oocyte activation is regulated by protein kinase C via actin filaments

Fertilization‐induced [Ca2+]i oscillations generally depend on the release of calcium ions from the endoplasmic reticulum (ER). Since ER is the main store of calcium ions, it plays an important role in oocyte fertilization. However, the mechanism of ER organization at oocyte activation is unknown. Here, we show that protein kinase C (PKC) is involved in ER distribution during bovine oocyte activation, but not involved in cell cycle resumption and spindle organization. Actin filaments were affected by PKC pharmacological inhibition. In addition, similar to PKC results, the actin‐depolymerizing drug cytochalasin B affected the ER distribution during oocyte activation. Specifically, we have demonstrated that ER organization during bovine oocyte activation is regulated by PKC possibly through its action on actin filaments regulation. Taken together, the results presented here provide further information on the pathway involved in the regulation of ER organization during oocyte activation and new insight into the functional role of PKC and actin filaments during this process.
The microtubule targeting agents eribulin and paclitaxel activate similar signaling pathways and induce cell death predominantly in a caspase-independent manner

ABSTRACT Microtubule-targeting agents (MTAs) are the most effective chemotherapeutics used in cancer therapy to date, but their clinical use is often hampered by the acquisition of resistance. Thereby, elucidation of the molecular signaling pathways activated by novel FDA-approved MTAs such as eribulin is important for future therapeutic applications. In contrast to several reports, we show here that regardless of the presence of caspase-3, clinically relevant concentrations of eribulin and the classical MTA paclitaxel predominantly induce caspase-independent cell death in MCF-7 breast carcinoma cells. On the molecular level, several key proteins involved in apoptosis such as p53, Plk1, caspase-2, and Bim as well as the two MAPKs ERK and JNK were activated by both compounds to a similar extent. However, none of them proved to be important for eribulin- and paclitaxel-induced cytotoxicity, as their siRNA-mediated knockdown or inactivation by small molecule inhibitors did not alter cell death rates. In contrast, knockdown of the anti-apoptotic Bcl-2 protein, which becomes heavily phosphorylated at Ser70 during MTA treatment, resulted surprisingly in a reduction of MTA-mediated cell death. This phenomenon can be most likely explained by our observation that the absence of Bcl-2 slowed down cell cycle progression resulting in fewer cells entering mitosis, thereby delaying the mitotic capability of these MTAs to induce cell death. Taken together, although eribulin and paclitaxel disturb the mitotic spindle differently, they exhibit no functional differences in downstream molecular cell death signaling in MCF-7 breast cancer cells.
Low‐dose caffeine administration increases fatty acid utilization and mitochondrial turnover in C2C12 skeletal myotubes

Caffeine has been shown to directly increase fatty acid oxidation, in part, by promoting mitochondrial biogenesis. Mitochondrial biogenesis is often coupled with mitophagy, the autophagy‐lysosomal degradation of mitochondria. Increased mitochondrial biogenesis and mitophagy promote mitochondrial turnover, which can enhance aerobic metabolism. In addition, recent studies have revealed that cellular lipid droplets can be directly utilized in an autophagy‐dependent manner, a process known as lipophagy. Although caffeine has been shown to promote autophagy and mitochondrial biogenesis in skeletal muscles, it remains unclear whether caffeine can increase lipophagy and mitochondrial turnover in skeletal muscle as well. The purpose of this study was to determine the possible contribution of lipophagy to caffeine‐dependent lipid utilization. Furthermore, we sought to determine whether caffeine could increase mitochondrial turnover, which may also contribute to elevated fatty acid oxidation. Treating fully differentiated C2C12 skeletal myotubes with 0.5 mM oleic acid (OA) for 24 hr promoted an approximate 2.5‐fold increase in cellular lipid storage. Treating skeletal myotubes with 0.5 mM OA plus 0.5 mM caffeine for an additional 24 hr effectively returned cellular lipid stores to control levels, and this was associated with an increase in markers of autophagosomes and autophagic flux, as well as elevated autophagosome density in TEM images. The addition of autophagy inhibitors 3‐methyladenine (10 mM) or bafilomycin A1 (10 μM) reduced caffeine‐dependent lipid utilization by approximately 30%. However, fluorescence and transmission electron microscopy analysis revealed no direct evidence of lipophagy in skeletal myotubes, and there was also no lipophagy‐dependent increase in fatty acid oxidation. Finally, caffeine treatment promoted an 80% increase in mitochondrial turnover, which coincided with a 35% increase in mitochondrial fragmentation. Our results suggest that caffeine administration causes an autophagy‐dependent decrease in lipid content by increasing mitochondrial turnover in mammalian skeletal myotubes.
Global research priorities for youth mental health

Over the past two decades, the youth mental health field has expanded and advanced considerably. Yet, mental disorders continue to disproportionately affect adolescents and young adults. Their prevalence and associated morbidity and mortality in young people have not substantially reduced, with high levels of unmet need and poor access to evidence‐based treatments even in high‐income countries. Despite the potential return on investment, youth mental disorders receive insufficient funding. Motivated by these continual disparities, we propose a strategic agenda for youth mental health research.
Assessing utility of a lifestyle-based tool in the clinical setting as a primordial prevention strategy: The Healthy Heart Score

Objective To evaluate the opinions of primary health-care providers and patients regarding the use of the Healthy Heart Score 20-year cardiovascular disease risk assessment tool in the clinical setting. Methods Semi-structured in person or phone interviews among 20 patients with no self-reported cardiovascular disease diagnoses and 20 health-care providers in Central (Columbus) and Southeastern (Athens) regions of Ohio. The researchers independently coded transcribed interviews, discussed codes to resolve discrepancies, and agreed on common themes. Results Participants suggested ways to best utilize and improve the tool, including adding graphics for visual reference of serving size. Patients showed interest in cardiovascular disease primordial prevention and expressed willingness to take the assessment prior to seeing a health-care provider. Health-care providers said that they would recommend the assessment to their patients and would be willing to use the tool in their practice. Health-care providers stated few barriers to using the tool, yet discussed numerous challenges to successful primordial prevention. Conclusions Our findings support the utilization of the Healthy Heart Score as a cardiovascular disease primordial prevention tool in the clinical setting. Additional research implementing the tool into the clinical setting will provide deeper insight into how the tool can impact behavior change and cardiovascular disease prevention.
Lianas reduce biomass accumulation in early successional tropical forests.

Early successional tropical forests could mitigate climate change via rapid accumulation of atmospheric carbon. However, liana (woody vine) abundance and biomass has been increasing in many tropical forests over the past decades, which may slow the speed at which secondary forests accumulate biomass. Lianas decrease biomass accumulation in tropical forests, and may have a particularly strong effect on young forests by stalling tree growth. As forests mature, trees may outgrow or shed lianas, thus escaping some of the negative effects of lianas. Alternatively, lianas may have the strongest effect in older successional forests if the effect of lianas is commensurate with their density, which increases dramatically in the first decades of forest succession. We tested these two hypotheses using a landscape liana removal experiment in 30 forest stands that ranged from 10 to 35 years old in Central Panama. We measured tree growth and biomass accumulation in the stands every year from 2014 to 2017. We found that the effect of liana removal on large trees (>= 20 cm diameter) decreased with forest age, supporting the hypothesis that lianas have the strongest negative effects on trees, and thus biomass uptake and carbon storage, in very young successional forests. Large trees accumulated more biomass in the absence of lianas in younger forests than in older forests (compared to controls) even after accounting for the effect of canopy completeness and crown illumination, implying that the detrimental effects of lianas go well beyond resource availability and crown health. There was no significant effect of lianas on small trees (1-20 cm diameter), likely because lianas seek light and thus do not deploy their leaves on small trees that are trapped in the forest understory. Our results show that high liana density early in forest succession reduces forest biomass accumulation by negatively impacting large trees, thus decreasing the capacity of young secondary forests to mitigate climate change. While the negative effects of lianas on forest biomass diminish as forests age, they do not disappear, and thus lianas are an important component of tropical forest carbon budgets throughout succession.
Chronic Human Pegivirus 2 without Hepatitis C Virus Co-infection

Most human pegivirus 2 (HPgV-2) infections are associated with past or current hepatitis C virus (HCV) infection. HPgV-2 is thought to be a bloodborne virus: higher prevalence of active infection has been found in populations with a history of parenteral exposure to viruses. We evaluated longitudinally collected blood samples obtained from injection drug users (IDUs) for active and resolved HPgV-2 infections using a combination of HPgV-2–specific molecular and serologic tests. We found evidence of HPgV-2 infection in 11.2% (22/197) of past or current HCV-infected IDUs, compared with 1.9% (4/205) of an HCV-negative IDU population. Testing of available longitudinal blood samples from HPgV-2–positive participants identified 5 with chronic infection (>6 months viremia in >3 timepoints); 2 were identified among the HCV-positive IDUs and 3 among the HCV-negative IDUs. Our findings indicate that HPgV-2 can establish chronic infection and replicate in the absence of HCV.
The novel GLP‐1/GIP analogue DA5‐CH reduces tau phosphorylation and normalizes theta rhythm in the icv. STZ rat model of AD

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease for which there is no cure. Recent studies have shown a close link between type 2 diabetes and AD, which suggested that drugs for type 2 diabetes may be effective for AD. GLP‐1 and GIP are incretin hormones that can ameliorate diabetes.