Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of yoga based lifestyle intervention on psychological stress and quality of life in the parents of children with retinoblastoma

Background Childhood cancers are associated with a psychological burden to the parents and hence, decline their mental and physical health and overall quality of life. Purpose The purpose of the present study is to investigate the impact of 12-weeks yoga based lifestyle intervention on psychological stress and quality of life in the parents of children affected with retinoblastoma. Method Single arm prospective clinical trial conducted from October 2015 to October 2017 at the Laboratory for Molecular Reproduction and Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India. A pre-tested 12-weeks yoga based lifestyle intervention included asanas (physical postures), pranayama (breathing exercises), dhyana (meditation), relaxation techniques, lectures and films on yoga, interactive sessions and individualized advice was administered to the participants. Results 12-weeks of yoga based lifestyle intervention programme leads to a significant improvement in psychological stress and overall quality of life in the parents of retinoblastoma patients. There was a significant improvement in all the domains (physical health, psychological health, social relationships, and environment) of WHOQOL-BREF from baseline (day 0) to 12-weeks of yoga based lifestyle intervention. Yoga based lifestyle intervention also led to a significant increase in the levels of brain derived neurotrophic factor, dehydroepiandrosterone sulphate, sirtuin 1 and decreased the cortisol and IL-6 levels. Conclusion Yoga based lifestyle intervention reduced the severity of psychological stress and resulted in improvement in overall quality of life and upregulation in levels of systemic biomarkers of neuroplasticity. YBLI may serve as a beneficial therapy and may also act as an effective medium for better stress management to develop better coping strategies in the parents of retinoblastoma patients.
Very low protein plus ketoacid analogs of essential aminoacids do not confirm superiority of a low protein diet to retard chronic kidney disease progression

I read with great interest the original work of Satirapoj et al [1], particularly with regard to the number of cases seen in patients affected by chronic kidney disease (CKD III and CKD IV). However, in spite of the use of an amino acid supplement, this study seems to lack clarity and provides no firm evidence by which to evaluate and confirm the aims of the study. In particular, I should like to emphasize the following: 1) There is no explanation as to how glomerular filtration rate (GFR) was calculated. 2) Generally, when assessing the outcome of residual renal function, patient adherence to a very limited diet such as the very low protein diet (VLPD) should be monitored, particularly if the patient is required to take approximately 13 tablets a day of steroids over an extended period of time. Conversely, the compliance assessments cited in this study are based solely on diet records and tables of standard food composition. This type of adherence assessment has never been viewed as a reliable method due to the need to associate it with a strict educational program and to implement monthly or three-monthly checks by an expert nutritionist [2-5]. Furthermore, in routine clinical practice, the deceptive and misleading nature of patient recall is widely acknowledged, and also takes into account poor patient evaluation and failure to introduce specific foods and liquids. 3) A further serious bias of this study is due to omitting to report the amount of energy provided by the kilocalories prescribed and introduced. Evaluation of the latter is a mandatory skill for a renal dietician. Without a strict prescription [6], no comparisons or evaluations of GFR outcome between the two groups can be obtained, as energy intake has a marked effect on anabolism and protein catabolism. 4) No assurance is provided that patients suffering from acute, subacute, or chronic intestinal diseases that exacerbate the microbiota, already severely affected by the uremic milieu and amino acid adsorption, were excluded from the study [7]. 5) Finally, the sole method to have been deemed reliable since 1985, still in use today, is assessment of urea nitrogen appearance, which takes into account the output of urinary and non-urinary nitrogen, in addition to the differences detected in urea distribution volume; indeed, the presence of azoturia did not seem to be assessed in the patients studied, although this simple evaluation yields the protein catabolic rate that provides considerably more reliable information, corresponding to actual protein intake [8,9]. Should the authors not be in a position to provide these data, no firm conclusions may be drawn from this paper.
Release of a disordered domain enhances HspB1 chaperone activity toward tau

Significance Molecular chaperones defend against protein aggregation that can otherwise lead to many diseases, including Alzheimer’s disease and related dementias. The small heat shock protein (sHSP) chaperones are underappreciated in large part because we lack insight into the mechanisms by which they defend against protein aggregation. This study of how the sHSP HspB1 delays aggregation of the Alzheimer’s-linked protein tau leads to a model in which the release of a sequestered disordered region of the chaperone greatly enhances its activity. The model reveals a general mechanism by which sHSPs can be activated and suggests a strategy by which this interaction could be exploited therapeutically. Small heat shock proteins (sHSPs) are a class of ATP-independent molecular chaperones that play vital roles in maintaining protein solubility and preventing aberrant protein aggregation. They form highly dynamic, polydisperse oligomeric ensembles and contain long intrinsically disordered regions. Experimental challenges posed by these properties have greatly impeded our understanding of sHSP structure and mechanism of action. Here we characterize interactions between the human sHSP HspB1 (Hsp27) and microtubule-associated protein tau, which is implicated in multiple dementias, including Alzheimer’s disease. We show that tau binds both to a well-known binding groove within the structured alpha-crystallin domain (ACD) and to sites within the enigmatic, disordered N-terminal region (NTR) of HspB1. However, only interactions involving the NTR lead to productive chaperone activity, whereas ACD binding is uncorrelated with chaperone function. The tau-binding groove in the ACD also binds short hydrophobic regions within HspB1 itself, and HspB1 mutations that disrupt these intrinsic ACD–NTR interactions greatly enhance chaperone activity toward tau. This leads to a mechanism in which the release of the disordered NTR from a binding groove on the ACD enhances chaperone activity toward tau. The study advances understanding of the mechanisms by which sHSPs achieve their chaperone activity against amyloid-forming clients and how cells defend against pathological tau aggregation. Furthermore, the resulting mechanistic model points to ways in which sHSP chaperone activity may be increased, either by native factors within the cell or by therapeutic intervention.
Hierarchical clustering of PI3K and MAPK pathway proteins in breast cancer intrinsic subtypes

The phosphatidylinositol‐3‐kinase (PI3K) and mitogen‐activated protein kinase (MAPK) pathways are frequently activated in breast cancer. We recently demonstrated the importance of analyzing multiple proteins as read‐out for pathway activation in ER+/HER2− breast cancer, since single proteins are known to provide insufficient information. Here, we determined pathway activation in other primary breast cancer intrinsic subtypes derived from postmenopausal patients. Tumor blocks were recollected, and immunohistochemistry was performed using antibodies against PTEN, p‐AKT(Thr308), p‐AKT(Ser473), p‐p70S6K, p‐4EBP1, p‐S6RP(Ser235/236) and p‐ERK1/2, followed by unsupervised hierarchical clustering. In 32 ER+/HER2+, 37 ER−/HER2+ and 74 triple‐negative breast cancer patients, subgroups were identified with preferentially activated (A) and preferentially not activated (N) proteins. These subgroups likely reflect tumors with differences in biological behavior as well as treatment outcome.
Nordic Guidelines for Germline Predisposition to Myeloid Neoplasms in Adults: Recommendations for Genetic Diagnosis, Clinical Management and Follow-up

Abstract Myeloid neoplasms (MNs) with germline predisposition have recently been recognized as novel entities in the latest World Health Organization (WHO) classification for MNs. Individuals with MNs due to germline predisposition exhibit increased risk for the development of MNs, mainly acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Setting the diagnosis of MN with germline predisposition is of crucial clinical significance since it may tailor therapy, dictate the selection of donor for allogeneic hematopoietic stem cell transplantation (allo-HSCT), determine the conditioning regimen, enable relevant prophylactic measures and early intervention or contribute to avoid unnecessary or even harmful medication. Finally, it allows for genetic counseling and follow-up of at-risk family members. Identification of these patients in the clinical setting is challenging, as there is no consensus due to lack of evidence regarding the criteria defining the patients who should be tested for these conditions. In addition, even in cases with a strong suspicion of a MN with germline predisposition, no standard diagnostic algorithm is available. We present the first version of the Nordic recommendations for diagnostics, surveillance and management including considerations for allo-HSCT for patients and carriers of a germline mutation predisposing to the development of MNs.
Endometriosis-Derived Thromboxane A2 Induces Neurite Outgrowth

Hyperinnervation in endometriosis is now well documented, but so far only a few neurotrophins have been identified. Since endometriotic stromal cells secrete thromboxane A2 (TXA2), we sought to determine whether TXA2, derived from endometriotic stromal cells, induces neurite outgrowth. Using primary sensory neurons derived from rat dorsal root ganglia (DRG) and ectopic endometrial stromal cells (EESCs) derived from human ovarian endometrioma tissues, we treated the primary neurons with different concentrations of U-46619, a stable TXA2 mimetic, and performed a neuronal growth assay. The primary neurons were also cocultured with a vehicle, nerve growth factor (NGF, serving as a positive control), the supernatant of EESC culture medium, or the supernatant of EESCs pretreated with ozagrel, a thromboxane synthase inhibitor, and a neuronal growth assay was performed. The total neurite length was evaluated through immunofluorescence microscopy. We found that U-46619 significantly increased the neurite outgrowth in DRG neurons in a concentration-dependent fashion (P < .001). It also increased the number of neurite ends in a concentration-dependent fashion. Ozagrel treatment alone had no effect on the neurite growth (P > .05), and the treatment with the supernatant of EESCs induced neurite outgrowth just as potently as that treated with NGF (positive control; P > .05). Remarkably, treatment with the EESC supernatant increased the neurite outgrowth by nearly 3-fold as compared with the control (P < .01), but the pretreatment with ozagrel abolished the stimulatory effect of the EESC by 31.3% (P < .05). These findings indicate that EESCs potently induce neurite outgrowth, and endometriosis-derived TXA2 is responsible, at least in part, for this neurotrophic effect.
Explaining the Relationship Between Minority Group Status and Health Disparities: A Review of Selected Concepts

Abstract Purpose: There is growing concern that value-based payment for health care may disadvantage health care organizations that serve populations with social risk. In the broader investigation of social risk factors, including income, education, neighborhood deprivation, and other risks, the focus on race and ethnicity as a risk factor for disparities in health and health care has diminished. Understanding the independent contribution of minority group status is critical to this discussion. This narrative review discusses four concepts—minority stress, resilience, epigenetics, and life course—that may help explain the contribution of minority group status and its association with health disparities. Methods: We briefly describe each concept and the supporting evidence. Results: Our results indicate that all four concepts have potential relevance for understanding and addressing health disparities. The life course perspective emphasizes the importance of understanding explanatory mechanisms and factors that contribute to health—including biological, physical, and social factors—over a person's life span. Both minority stress and resilience may influence health in either a negative or positive manner that potentially underlies health changes. Exposure to these factors and others may interact with and modify epigenetic regulation—biological processes that impact how our genes are expressed. This may increase the risk of disease and negative health outcomes, particularly among groups that may be at disproportionate risk because of social circumstances and environmental exposure over the life course. Conclusion: Despite these concepts' relevance, more research is needed to assess how they may explain the relationship between minority status and disparities in health. Such evidence is needed to focus interventions and to inform the design of delivery and payment models that can spur actions to reduce disparities.
Withania somnifera (Indian ginseng) in diabetes mellitus: A systematic review and meta‐analysis of scientific evidence from experimental research to clinical application

Withania somnifera Dunal, also known as Indian ginseng, has been in use since ancient times in the management of diabetes mellitus (DM). This systematic review and meta‐analysis evaluated the efficacy/effectiveness, safety and tolerability of W. somnifera in managing DM. Literature search (published/unpublished) was performed from inception to April 2019 in guidelines recommended databases. A total of 6 in‐vitro, 13 pre‐clinical and 5 clinical studies were included for systematic evaluation. W. somnifera treatment in DM significantly restored the altered levels of blood glucose (experimental data; mean difference, −196.27; 95% confidence interval [−220.96, −171.58]; p < .00001) glycosylated haemoglobin (HbA1c), insulin, lipid profile, serum and oxidative stress markers with no safety concerns. The results suggest the potential role of W. somnifera in managing DM. However, the available clinical data are not considerably enough to provide novel and sufficiently robust evidence for the use of W. somnifera in managing DM. To further strength the anti‐diabetic profile of W. somnifera, well‐designed randomized‐controlled trial(s) with a larger sample size and longer duration is warranted with evaluation of its effect primarily on blood glucose, HbA1c and insulin. Future research also needs to elucidate the molecular mechanism(s) of W. somnifera including its active principles in DM.
Abnormal mTORC1 signaling leads to retinal pigment epithelium degeneration

Retinal pigment epithelial (RPE) degeneration is potentially involved in the pathogenesis of several retinal degenerative diseases. mTORC1 signaling is shown as a crucial regulator of many biological processes and disease progression. In this study, we aimed at investigating the role of mTORC1 signaling in RPE degeneration. Methods: Western blots were conducted to detect mTORC1 expression pattern during RPE degeneration. Cre-loxP system was used to generate RPE-specific mTORC1 activation mice. Fundus, immunofluorescence staining, transmission electron microscopy, and targeted metabolomic analysis were conducted to determine the effects of mTORC1 activation on RPE degeneration in vivo. Electroretinography, spectral-domain optical coherence tomography, and histological experiments were conducted to determine the effects of mTORC1 activation on choroidal and retinal function in vivo. Results: RPE-specific activation of mTORC1 led to RPE degeneration as shown by the loss of RPE-specific marker, compromised cell junction integrity, and intracellular accumulation of lipid droplets. RPE degeneration further led to abnormal choroidal and retinal function. The inhibition of mTORC1 signaling with rapamycin could partially reverse RPE degeneration. Targeted metabolomics analysis further revealed that mTORC1 activation affected the metabolism of purine, carboxylic acid, and niacin in RPE. Conclusion: This study revealed that abnormal activation of mTORC1 signaling leads to RPE degeneration, which could provide a promising target for the treatment of RPE dysfunction-related diseases.
The non-directed living kidney donor: Why donate to strangers?

BACKGROUND Kidney transplantation improves survival and quality of life for patients with end-stage kidney disease (ESKD). However, there is a shortage of donated organs, resulting in long wait times and the potential for death before a donor is found. Non-directed (also called altruistic) living kidney donation is a growing type of donation; however, few studies have examined the values and motivation of individuals evaluated to be a non-directed donor. OBJECTIVES This qualitative study explores the motivations and values of individuals evaluated for non-directed donation. DESIGN Focus groups were conducted with individuals who had been evaluated for non-directed living kidney donation. Grounded theory method guided the data analysis. PARTICIPANTS Participants (N = 11) were individuals who completed the evaluation for a non-directed living kidney donation. FINDINGS Qualitative analyses revealed eight major themes participants considered in making their decision to donate to a non-related person: (i) motivation to donate; (ii) minimise perceived risk; (iii) ideal selected recipient; (iv) change in lifestyle; (v) source of donation knowledge; (vi) history of altruistic acts; (vii) donation chain and (viii) others' response. CONCLUSIONS Results suggest that non-directed living kidney donors think deeply about their decision and have a resolve to help others that is aligned with their values. As organ availability remains at a critical shortage, unwillingness to consider non-directed living donors (NDD) due to beliefs of ill motivations appears unsupported. Future directions call for the need of standard practice of care in kidney donation evaluations across transplant centers.
Comparative Analysis of Gut Microbiota Following Changes in Training Volume Among Swimmers

Abstract Exercise can influence gut microbial community structure and diversity; however, the temporal dynamics of this association have rarely been explored. Here we characterized fecal microbiota in response to short term changes in training volume. Fecal samples, body composition, and training logs were collected from Division I NCAA collegiate swimmers during peak training through their in-season taper in 2016 (n=9) and 2017 (n=7), capturing a systematic reduction in training volume near the conclusion of their athletic season. Fecal microbiota were characterized using 16S rRNA V4 amplicon sequencing and multivariate statistical analysis, Spearman rank correlations, and random forest models. Peak training volume, measured as swimming distance, decreased significantly during the study period from 32.6±4.8 km/wk to 11.3±8.1 km/wk (ANOVA, p<0.05); however, body composition showed no significant changes. Coinciding with the decrease in training volume, the microbial community structure showed a significant decrease in overall microbial diversity, a decrease in microbial community structural similarity, and a decrease in the proportion of the bacterial genera Faecalibacterium and Coprococcus. Together these data demonstrate a significant association between short-term changes in training volume and microbial composition and structure in the gut; future research will establish whether these changes are associated with energy balance or nutrient intake.
Artificial Oxygen Carriers and Red Blood Cell Substitutes: An Historic Overview and Recent Developments Toward Military and Clinical Relevance.

Packed red blood cells are a critical component in the resuscitation of hemorrhagic shock. The availability of donor-derived blood products, however, suffers from issues of supply, immunogenicity, and pathogenic contamination. Deployment in remote or austere environments, such as the battlefield, is further hindered by the inherent perishability of blood products. In order to address the significant limitations of allogenic packed red blood cells and the urgent medical need for better resuscitative therapies for both combat casualties and civilians, there has been significant research invested in developing safe, effective, and field deployable artificial oxygen carriers. This article provides a comprehensive review of the most important technologies in the field of artificial oxygen carriers including cell-free and encapsulated hemoglobin based oxygen carriers, perfluorocarbon emulsions, natural hemoglobin alternatives, as well as other novel technologies. Their development status, clinical, and military relevance are discussed. STUDY TYPE: Review Article LEVEL OF EVIDENCE: Systematic Review.
Implementation of the Identification and Referral to Improve Safety programme for patients with experience of domestic violence and abuse: A theory‐based mixed‐method process evaluation

Abstract Identification and Referral to Improve Safety (IRIS) is a training and support programme to improve the response to domestic violence and abuse (DVA) in general practice. Following a pragmatic cluster‐randomised trial, IRIS has been implemented in over 30 administrative localities in the UK. The trial and local evaluations of the IRIS implementation showed an increase in referrals from general practice to third sector DVA services with a variation in the referral rates within and across practices. Using Normalisation Process Theory (NPT), we aimed to understand the reasons for such variability by identifying factors that influenced the implementation of IRIS in the National Health Service (NHS). We conducted a mixed‐method process evaluation which included: (a) a case study (100 hr of participant observation, 19 interviews); (b) a survey (n = 118); (c) qualitative analysis of free‐text comments from the survey; (d) qualitative interviews (n = 8); (e) document review (n = 44). Data were collected from NHS and third sector staff across five London boroughs from August 2015 to December 2017, analysed descriptively and thematically and triangulated using the NPT constructs coherence, cognitive participation, collection action and reflexive monitoring. The survey showed wide variation in the extent to which practice staff saw IRIS as a normal part of their daily work. Qualitative data and documents illuminated drivers of DVA work, implementation barriers and suggested solutions. The drivers were related to individual professional's characteristics and relationships. The barriers were linked to the differing sense‐making and legitimisation of DVA work and differing contexts between the NHS and third sector. Solutions were adaptations to IRIS relative to these contextual differences. The suggested solutions can be used to update IRIS commissioning guidance, training for trainers and training for general practice. The updates should reflect the importance of ongoing support of IRIS from practice leads and commissioners, extended funding periods for IRIS and continuity of the IRIS team.