Miracle-dz/UniFAR-FTUs huggingface dataset:
Factors influencing adherence among youth with Type-1-Diabetes Mellitus - the Hungarian case.

Background & Introduction: Due to the increasing prevalence of type-1-diabetes an increasing number of studies draws investigation draws attention to its psychological effects and long-term consequences. As Type 1 Diabetes Mellitus is a chronic, non-curable, yet maintanable condition, with the affected children and their families facing a lifelong challenge. Our research focuses on the factors influencing adherence. Methods & Results: The adherence of youth was examined in a sample involving 114 patients treated in the Medical and Health Science Centre at the University of Debrecen by employing a new adherence questionnaire (DAQ abbreviated version, Munkácsi et al, 2019) (DAF 2017; N=114). The influence of socio-demographic variables and those related to the disease (age at the diagnosis, time elapsed since diagnosis, method of treatment, the time elapsed since the use of the pump) were measured by linear regression. Furthermore, the between-group comparisons were made by independent sample t-tests and variance analysis. The investigation was carried out between September 2017 and May 2018. The effect of using insulin pump as therapy is significant and positive (0.36. p=0.045). The adherence of the patients using insulin pump is higher while the effect of the age at the diagnosis has a significantly negative effect (-.247, p=0.035). Thus, earlier detection of the disease may lead to a higher level of adherence. The effects of the socio-demographic variables (gender, family structure, educational level, type of the settlement, owning sibling and birth order) were not significant (p>0.05). Regarding the between-group comparisons, a significant difference could be pointed out concerning the siblings and birth-order as the adherence of the those with siblings was higher (p=0.044). Moreover, concerning insulin pump therapy, the adherence of patients using pump was significantly better (p=0.048). Also, regarding the age of the diagnosis, the adherence of those diagnosed before 12 was seemingly higher (p=0.039). Concerning the other socio-demographical and disease-related variables, no significant differences could be detected. Conclusions: The results suggest that the treatment has an outstanding role in the adherence of the disease. Moreover, the role of the appropriate treatment, living conditions as well as the early diagnosis is relevant.
Bedside Postpyloric Tube Placement and Enteral Nutrition Delivery in the Pediatric Intensive Care Unit.

BACKGROUND Enteral nutrition (EN) delivery may be more effective via a postpyloric (PP) feeding tube in critically ill children, but tube placement can be challenging. We aimed to describe PP tube placement and EN practices in a multidisciplinary pediatric intensive care unit (PICU) after the implementation of a nurse-led bedside PP tube-placement program. METHODS In a single-center retrospective study, we identified 100 consecutive patients admitted to the PICU for >48 hours and for whom PP tube placement was attempted. Demographics, clinical characteristics, and details of PP tube placement and EN delivery were examined. RESULTS The study cohort had a median age (25th, 75th percentiles) of 3.89 years (0.55, 14.86); 66% were male. Respiratory illness was the primary diagnosis of admission (55%); 92% were on respiratory support. Risk of aspiration was the primary indication for PP tube placement (48%). Bedside placement was the initial technique for PP tube placement in 93% of patients (successful for 84.9%) and was not associated with serious complications. Eighty-seven patients with a PP tube started EN and received a median 73.9% (12.3%, 100%) of prescribed energy goal on day 3 after EN initiation. PP EN allowed 14 of 39 patients receiving parenteral nutrition (PN) to transition off PN 7 days after EN initiation. Thirty-five percent of EN interruptions were due to feeding-tube dysfunction. CONCLUSION Bedside PP tube placement is safe and feasible and allows for effective EN delivery and decreased PN use when applicable. Interruptions in PP EN due to tube malfunction are prevalent.
Melatonin‐stimulated exosomes enhance the regenerative potential of chronic kidney disease‐derived mesenchymal stem/stromal cells via cellular prion proteins

Chronic kidney disease (CKD) is caused by dysfunctional kidneys, which result in complications like cardiovascular diseases. Chronic kidney disease‐induced pathophysiological conditions decrease efficacy of autologous mesenchymal stem/stromal cell (MSC)‐based therapy by reducing MSC functionality. To enhance therapeutic potential in patients with CKD, we isolated exosomes derived from melatonin‐treated healthy MSCs (MT exosomes) and assessed the biological functions of MT exosome–treated MSCs isolated from patients with CKD (CKD‐MSCs). Treatment with melatonin increased the expression of cellular prion protein (PrPC) in exosomes isolated from MSCs through the upregulation of miR‐4516. Treatment with MT exosomes protected mitochondrial function, cellular senescence, and proliferative potential of CKD‐MSCs. MT exosomes significantly increased the level of angiogenesis‐associated proteins in CKD‐MSCs. In a murine hindlimb ischemia model with CKD, MT exosome–treated CKD‐MSCs improved functional recovery and vessel repair. These findings elucidate the regenerative potential of MT exosome–treated CKD‐MSCs via the miR‐4516‐PrPC signaling axis. This study suggests that the treatment of CKD‐MSCs with MT exosomes might be a powerful strategy for developing autologous MSC‐based therapeutics for patients with CKD. Furthermore, miR‐4516 and PrPC could be key molecules for enhancing the regenerative potential of MSCs in ischemic diseases.
The shape effect of flagella is more important than bottom-heaviness on passive gravitactic orientation in Chlamydomonas reinhardtii

ABSTRACT The way the unicellular, biflagellated, green alga Chlamydomonas orients upward has long been discussed in terms of both mechanics and physiology. In this study, we focus on the mechanics, i.e. the ‘passive’ mechanisms, of gravitaxis. To rotate the body upwards, cellular asymmetry is critical. Chlamydomonas can be depicted as a nearly spherical cell body with two anterior, symmetric flagella. The present study looks at the question of whether the existence of the flagella significantly affects torque generation in upward reorientation. The ‘density asymmetry model’ assumes that the cell is spherical and bottom-heavy and that the shape and weight of the flagella are negligible, while the ‘shape asymmetry model’ considers the shape of the flagella. Both our experimental and simulation results revealed a considerable contribution from shape asymmetry to the upward orientation of Chlamydomonas reinhardtii, which was several times larger than that of density asymmetry. From the experimental results, we also quantified the extent of bottom-heaviness, i.e. the distance between the centers of gravity and the figure when the cell body is assumed to be spherical. Our estimation was approximately 30 nm, only one-third of previous assumptions. These findings indicate the importance of the viscous drag of the flagella to the upward orientation, and thus negative gravitaxis, in Chlamydomonas. Summary: Viscous drag of flagella rather than density asymmetry orients the Chlamydomonas cells upwards in gravitaxis.
Let it be: mindful acceptance down-regulates pain and negative emotion

Abstract Mindfulness training ameliorates clinical and self-report measures of depression and chronic pain, but its use as an emotion regulation strategy—in individuals who do not meditate—remains understudied. As such, whether it (i) down-regulates early affective brain processes or (ii) depends on cognitive control systems remains unclear. We exposed meditation-naïve participants to two kinds of stimuli: negative vs. neutral images and painful vs. warm temperatures. On alternating blocks, we asked participants to either react naturally or exercise mindful acceptance. Emotion regulation using mindful acceptance was associated with reductions in reported pain and negative affect, reduced amygdala responses to negative images and reduced heat-evoked responses in medial and lateral pain systems. Critically, mindful acceptance significantly reduced activity in a distributed, a priori neurologic signature that is sensitive and specific to experimentally induced pain. In addition, these changes occurred in the absence of detectable increases in prefrontal control systems. The findings support the idea that momentary mindful acceptance regulates emotional intensity by changing initial appraisals of the affective significance of stimuli, which has consequences for clinical treatment of pain and emotion.
The Big Six Personality Traits and Mental Distress: Dynamic Modeling in a Population Panel Study Reveals Bidirectional Relationships Involving Neuroticism, Extraversion, and Conscientiousness

In a single comprehensive model, using a large nationally representative sample, we investigate longitudinal relationships between mental distress and “Big Six” personality using an analysis approach sensitive to dynamic effects (i.e., to effects of deviations from individual trajectories). We find that, consistent with a mechanism involving scarring by distress, upward deviations (flare-ups) in distress predict flare-ups in Neuroticism 12 months later. Among younger adults (n = 4,775), distress flare-ups predict dips in Conscientiousness. Consistent with a dynamic precursor model, (a) flare-ups in Neuroticism and Extraversion predict subsequent flare-ups in distress among older adults (n = 11,167), and (b) slopes of distress correlate with slopes of a number of traits (e.g., positively for Neuroticism, and, among older adults, negatively for Extraversion). While demonstrating these scarring and dynamic precursor effects, we draw attention to a nuanced direction of dynamic effect for Extraversion, a newly discovered dynamic effect of Conscientiousness, and previously undocumented dynamic effects of traits on each other.
Function, Innervation, and Neurotransmitter Signaling in Mice Lacking Type-II Taste Cells

Abstract The Skn-1a transcription factor (Pou2f3) is required for Type II taste cell differentiation in taste buds. Taste buds in Skn-1a-/- mice lack Type II taste cells but have a concomitant expansion of Type III cells, providing an ideal model to determine the relative role of taste cell types in response specificity. We confirmed that chorda tympani responses to sweet, bitter, and umami stimuli were greatly reduced in the knock-outs (KOs) compared with wild-type (WT) littermates. Skn-1a-/- mice also had reductions to NaCl that were partially amiloride-insensitive, suggesting that both Type II and Type III cells contribute to amiloride-insensitive salt detection in anterior tongue. We also confirmed that responses to sour stimuli are equivalent in the KOs, despite the large increase in the number of Type III taste cells. To examine their innervation, we crossed the Htr3a-GFP (5-HT3A-GFP) reporter mouse with the Skn-1a-/- mice and examined geniculate ganglion neurons for GFP expression and responses to 5-HT. We found no change in the number of 5-HT3A-expressing neurons with KO of Skn-1a. Calcium imaging showed that only 5-HT3A-expressing neurons respond to exogenous 5-HT, while most neurons respond to ATP, similar to WT mice. Interestingly, despite loss of all Type II cells, the P2X3 antagonist AF353 blocked all chorda tympani responses. These data collectively raise questions pertaining the source of ATP signaling in the absence of Type II taste cells and whether the additional Type III cells are innervated by fibers that would have normally innervated Type II cells.
The effect of a six-week plyometric training on dynamic balance and knee proprioception in female badminton players.

Objective Non-contact anterior cruciate ligament (ACL) injury is one of the most common severe injuries among female badminton players. Dynamic balance (DB) and knee proprioception (KP) are critical in preventing this injury. The purpose of this study was to investigate the effect of a six-week plyometric training (PT) program on DB and KP in female badminton players. Methods Twenty-two healthy beginner female badminton players were randomly assigned to either control (CG) or experimental group (ExG). The ExG went through PT for six weeks. Pre- and post-intervention Y balance and photography tests were used to assess DB and KP, respectively. Results There was no difference between groups prior to PT in DB (p=0.804) and KP (at 45°, p=0.085 and at 60°, p=0.472 angles; p>0.05). However, after the PT only ExG improved significantly in DB (p=0.003) and KP (at 45°, p=0.004 and at 60°, p=0.010 angles; p<0.05). Conclusion Female badminton players' dynamic balance and knee proprioception improved significantly after plyometric training (PT). These results may be important in preventing non-contact anterior cruciate ligament (ACL) injury, which requires further investigation.
NHG standaard COPD (derde herziening)

Belangrijkste wijzigingen • Luchtwegobstructie is aanwezig bij een FEV1/FVC-ratio (na bronchusverwijding) kleiner dan het 5e percentiel (van de referentiewaarden); het gefixeerde afkappunt voor obstructie (FEV1/FVC-ratio < 0,7) is vervallen. • De ernst van COPD wordt bepaald door de ziektelast, dat wil zeggen: de combinatie van klachten en beperkingen, frequentie van exacerbaties, FEV1 en voedingstoestand (en dus niet alleen door de mate van luchtwegobstructie). • In de monitoring fase wordt gestandaardiseerde bronchusverwijding bij spirometrie niet aanbevolen en wordt spirometrie verricht met behoud van de eigen luchtwegmedicatie van de patiënt. • Er is meer aandacht voor de wensen en behoeften van de patiënt en voor zelfmanagement bij de behandeling en het omgaan met COPD. • De Landelijke Transmurale Afspraak COPD uit 2009 is herzien en opgenomen in deze standaard.
Streptomyces sp. BV410 isolate from chamomile rhizosphere soil efficiently produces staurosporine with antifungal and antiangiogenic properties

Applying a bioactivity‐guided isolation approach, staurosporine was separated and identified as the active principle in the culture extract of the new isolate Streptomyces sp. BV410 collected from the chamomile rhizosphere. The biotechnological production of staurosporine by strain BV410 was optimized to yield 56 mg/L after 14 days of incubation in soy flour–glucose–starch–mannitol‐based fermentation medium (JS). The addition of FeSO4 significantly improved the staurosporine yield by 30%, while the addition of ZnSO4 significantly reduced staurosporine yield by 62% in comparison with the starting conditions. Although staurosporine was first isolated in 1977 from Lentzea albida (now Streptomyces staurosporeus) and its potent kinase inhibitory effect has been established, here, the biological activity of this natural product was assessed in depth in vivo using a selection of transgenic zebrafish (Danio rerio) models, including Tg(fli1:EGFP) with green fluorescent protein‐labeled endothelial cells allowing visualization and monitoring of blood vessels. This confirmed a remarkable antiangiogenic activity of the compound at doses of 1 ng/ml (2.14 nmol/L) which is below doses inducing toxic effects (45 ng/ml; 75 nmol/L). A new, efficient producing strain of commercially significant staurosporine has been described along with optimized fermentation conditions, which may lead to optimization of the staurosporine scaffold and its wider applicability.
Impairment of motor but not anxiety‐like behavior caused by the increase of dopamine during development is sustained in zebrafish larvae at later stages

Many neuropsychiatric disorders are associated with both dopaminergic (DAergic) and developmental hypotheses. Since DAergic receptors are expressed in the developing brain, it is possible that alterations in dopamine (DA) signaling may impair brain development and consequent behavior. In our previous study, using a zebrafish model, we showed that an increase of DA during the 3 to 5 days postfertilization (dpf) developmental window (an important window for GABAergic neuronal differentiation) affects the motor behavior of 5 dpf larvae. In this study, we set out to determine whether these behavioral alterations were sustained in larvae at older stages (7 and 14 dpf). To test this hypothesis, we chronically treated zebrafish larvae from 3 to 5 dpf with DA. After washing the drug, we recorded and analyzed the first 5 and 30 min of the motor behavior of 5, 7, and 14 dpf subjects. We analyzed mobile episodes, distance traveled, time mobile, distance traveled per mobile episode, time in movement per mobile episode, and distance traveled per time mobile. We showed, once again, that an increase of DA during the 3 to 5 dpf developmental window reduces the number of movement episodes initiated by 5 dpf larvae. We also detected a decrease of other motor behavior parameters in 5 dpf DA‐treated larvae. We observed that these alterations are sustained in the 7 dpf larvae. However, we did not see these general locomotor alterations in the 14 dpf larvae. Moreover, we detected a decrease of distance traveled and an increase of time of locomotion per episode in the first 5 min of behavioral analyses in 14 dpf DA‐treated larvae. To test if the alterations in the first 5 min were due to anxiety‐like behavior, we used a light/dark preference paradigm. We recorded 5dpf, 7dpf, and 14dpf larvae for 5 min and analyzed time of freezing, preference for light or dark, number of entries to the dark, percentage of time in the light. We observed that 5dpf larvae treated with DA showed more freezing, less passages to the dark, and more time spent in the light as compared to their control counterparts. But 7dpf and 14dpf larvae did not show these alterations. Taken overall, therefore, our results suggest that DA does play a role in the development of zebrafish motor behavior, and, furthermore, that some behaviors are more sensitive than others to the effects of DAergic imbalances during development.
Involvement of Myeloid Cells and Noncoding RNA in Abdominal Aortic Aneurysm Disease

Significance: Abdominal aortic aneurysm (AAA) is a potentially fatal condition, featuring the possibility of high-mortality rupture. To date, prophylactic surgery by means of open surgical repair or endovascular aortic repair at specific thresholds is considered standard therapy. Both surgical options hold different risk profiles of short- and long-term morbidity and mortality. Targeting early stages of AAA development to decelerate disease progression is desirable. Recent Advances: Understanding the pathomechanisms that initiate formation, maintain growth, and promote rupture of AAA is crucial to developing new medical therapeutic options. Inflammatory cells, in particular macrophages, have been investigated for their contribution to AAA disease for decades, whereas evidence on lymphocytes, mast cells, and neutrophils is sparse. Recently, there has been increasing interest in noncoding RNAs (ncRNAs) and their involvement in disease development, including AAA. Critical Issues: The current evidence on myeloid cells and ncRNAs in AAA largely originates from small animal models, making clinical extrapolation difficult. Although it is feasible to collect surgical human AAA samples, these tissues reflect end-stage disease, preventing examination of critical mechanisms behind early AAA formation. Future Directions: Gaining more insight into how myeloid cells and ncRNAs contribute to AAA disease, particularly in early stages, might suggest nonsurgical AAA treatment options. The utilization of large animal models might be helpful in this context to help bridge translational results to humans.
Interspecific variation in hypoxia tolerance and hypoxia acclimation responses in killifish from the family Fundulidae

ABSTRACT Hypoxia is a pervasive stressor in aquatic environments, and both phenotypic plasticity and evolutionary adaptation could shape the ability to cope with hypoxia. We investigated evolved variation in hypoxia tolerance and the hypoxia acclimation response across fundulid killifishes that naturally experience different patterns of hypoxia exposure. We compared resting O2 consumption rate (ṀO2), and various indices of hypoxia tolerance [critical O2 tension (Pcrit), regulation index (RI), O2 tension (PO2) at loss of equilibrium (PLOE) and time to LOE (tLOE) at 0.6 kPa O2] in Fundulus confluentus, Fundulus diaphanus, Fundulus heteroclitus, Fundulus rathbuni, Lucania goodei and Lucania parva. We examined the effects of chronic (28 days) exposure to constant hypoxia (2 kPa) or nocturnal intermittent hypoxia (12 h normoxia:12 h hypoxia) in a subset of species. Some species exhibited a two-breakpoint model in ṀO2 caused by early, modest declines in ṀO2 in moderate hypoxia. We found that hypoxia tolerance varied appreciably across species: F. confluentus was the most tolerant (lowest PLOE and Pcrit, longest tLOE), whereas F. rathbuni and F. diaphanus were the least tolerant. However, there was not a consistent pattern of interspecific variation for different indices of hypoxia tolerance, with or without taking phylogenetic relatedness into account, probably because these different indices are underlain by partially distinct mechanisms. Hypoxia acclimation generally improved hypoxia tolerance, but the magnitude of plasticity and responsiveness to different hypoxia patterns varied interspecifically. Our results therefore suggest that hypoxia tolerance is a complex trait that is best appreciated by considering multiple indices of tolerance. Summary: Substantial interspecific variation and plasticity of hypoxia tolerance exist across fundulid killifish and are only fully appreciated by considering multiple indices of tolerance.
Mucosal dysbiosis in patients with gastrointestinal follicular lymphoma

Because the pathogenesis of gastrointestinal follicular lymphoma (GI‐FL) remains unclear, no standardized treatment strategy has been established. Of the gastrointestinal lymphomas, gastric mucosa‐associated lymphoid tissue lymphomas are strongly associated with Helicobacter pylori; hence, the microbiota may be involved in GI‐FL pathogenesis. However, the association between GI‐FL and the microbiota remains uninvestigated. Therefore, we compared the mucosal microbiotas of GI‐FL patients with those of controls to identify microbiota changes in GI‐FL patients. Mucosal biopsy samples were obtained from the second portion of the duodenum from 20 GI‐FL patients with duodenal lesions and 20 controls. Subsequent 16S rRNA gene sequencing was performed on these samples. QIIME pipeline and LEfSe software were used to analyze the microbiota. The GI‐FL patients had significantly lower alpha diversity (P = .049) than did the controls, with significant differences in the microbial composition (P = .023) evaluated by the beta diversity metrics between the two groups. Comparing the taxonomic compositions indicated that the genera Sporomusa, Rothia, and Prevotella and the family Gemellaceae were significantly less abundant in the GI‐FL patients than in the controls. GI‐FL patients presented altered duodenal mucosal microbial compositions, suggesting that the microbiota might be involved in the GI‐FL pathogenesis.