Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancer and super‐enhancer: Positive regulators in gene transcription

Enhancer is a positive regulator for spatiotemporal development in eukaryotes. As a cluster, super‐enhancer is closely related to cell identity‐ and fate‐determined processes. Both of them function tightly depending on their targeted transcription factors, cofactors, and genes through distal genomic interactions. They have been recognized as critical components and played positive roles in transcriptional regulatory network or factory. Recent advances of next‐generation sequencing have dramatically expanded our ability and knowledge to interrogate the molecular mechanism of enhancer and super‐enhancer for transcription. Here, we review the history, importance, advances and challenges on enhancer and super‐enhancer field. This will benefit our understanding of their function mechanism for transcription underlying precise gene expression.
Impaired Calcium Metabolism in Benign Paroxysmal Positional Vertigo: A Topical Review.

BACKGROUND AND PURPOSE Although acute attacks of benign paroxysmal positional vertigo (BPPV) may be treated with canalith repositioning maneuvers, there have been no well-designed prospective trials to prevent this highly prevalent and recurrent disorder. This topical review explores the evidence related to the association between deficient calcium metabolism and BPPV. We also describe the development of therapeutic options to prevent recurrences of BPPV and introduce results from a recent randomized controlled trial on the effect of vitamin D and calcium supplementation in preventing BPPV recurrences. SUMMARY OF KEY POINTS The literature describes 3 lines of evidence on association of impaired calcium metabolism and development of BPPV: (1) decreased bone mineral density was more frequently observed in persons with BPPV than in healthy controls; (2) estrogen plays a vital role in maintenance of otoconia, and estrogen deficiency appears to precipitate degeneration of otoconia and development of BPPV; and (3) lower serum vitamin D level is associated with development of BPPV, and supplementation of vitamin D and calcium carbonate may reduce further attacks of BPPV in persons with BPPV and subnormal serum vitamin D level. RECOMMENDATIONS FOR CLINICAL PRACTICE Restoration of impaired calcium metabolism with supplementation of vitamin D or estrogen should be considered in the treatment of individuals with frequent recurrences of BPPV. Future randomized controlled trials are mandatory to validate these supplementation therapies in individuals with recurrent BPPV.
Colonization, penetration and transformation of manganese oxide nodules by Aspergillus niger

Summary In this study, the ability of the geoactive fungus Aspergillus niger to colonize and transform manganese nodules from the Clarion‐Clipperton Zone in both solid and liquid media was investigated. Aspergillus niger was able to colonize and penetrate manganese nodules embedded in solid medium and effect extensive transformation of the mineral in both fragmented and powder forms, precipitating manganese and calcium oxalates. Transformation of manganese nodule powder also occurred in a liquid medium in which A. niger was able to remove the fine particles from suspension which were accumulated within the central region of the resulting mycelial pellets and transformed into manganese oxalate dihydrate (lindbergite) and calcium oxalate dihydrate (weddellite). These findings contribute to an understanding of environmental processes involving insoluble manganese oxides, with practical relevance to chemoorganotrophic mineral bioprocessing applications, and, to the best of our knowledge, represent the first demonstration of fundamental direct and indirect interactions between geoactive fungi and manganese nodules.
Understanding frames: A qualitative exploration of standing frame use for young people with cerebral palsy in educational settings

BACKGROUND Consensus opinion supports standing frame use as part of postural management for nonambulant young people with cerebral palsy. Most young people with cerebral palsy in the United Kingdom, who use standing frames, use them at nursery or school, rather than at home. In this paper we report professionals' and parents' experiences and views of standing frame use specifically in educational settings. This research was conducted as part of a large mixed methods study to determine the acceptability and inform the design of a future trial of standing frames. METHODS Qualitative methods were used: focus groups with educational professionals, parents and clinicians (paediatricians, physiotherapists and occupational therapists) were convened. Data were analysed thematically using framework analysis. RESULTS Five focus groups were conducted. The overarching theme "flexibility" encompassed four subordinate themes: (i) "balancing education and therapy," which described the way education professionals had to juggle different priorities from health professionals within a multi-disciplinary team; (ii) "young people's autonomy," which highlighted participants' belief that standing frame use should be centred on the individual young person and their needs; (iii) "working within logistical boundaries," which demonstrated that "ideal" standing frame use was not always possible due to logistical issues (e.g., staffing and standing frame availability); and (iv) "competence and confidence," which highlighted that educational professionals felt that they lacked the training to confidently position young people in their standing frame. CONCLUSIONS This paper highlights the complexity of standing frame use in the educational setting. If a standing frame programme is prescribed to be delivered in an educational setting, strong multidisciplinary and interagency communication is essential to balance therapy versus education. Training is required to ensure staff are competent in using the standing frame with the young person understanding their individual requirements. A flexible approach-inclusive of the young person's needs, logistical demands and resource-is necessary.
miRNA‐145‐5p induces apoptosis after ischemia‐reperfusion by targeting dual specificity phosphatase 6

Disorders mainly caused by ischemia‐reperfusion (I/R), including stroke and myocardial infarction, is linked to debilitating health conditions and death. Recent research indicates that microRNAs (miRNAs) mediate the process of ischemic pathology. This study investigated the effects of miR‐145‐5p in regulating myocardial ischemic injury. The I/R models were established in rat cardiomyocytes H9C2 and rats. Western blot analysis and quantitative polymerase chain reaction was performed to analyze protein expression. Annexin V‐FITC/PI staining was conducted to evaluate cell apoptosis. The application of miR‐145‐5p mimics and inhibitor revealed that miR‐145‐5p promoted apoptosis in cardiomyocytes. Furthermore, we found that miR‐145‐5p directly inhibited dual specificity phosphatase 6 (DUSP6) by luciferase reporter assay. The results indicated that DUSP6 was beneficial against I/R injury through inhibiting c‐Jun N‐terminal kinase pathways. In conclusion, the essential roles of miR‐145‐5p and DUSP6 in I/R provide a novel therapeutic target to develop future intervention strategies.
The effect of nursing care delivery models on quality and safety outcomes of care: A cross-sectional survey study of medical-surgical nurses.

AIMS This study examined the effect of two components of a model of nursing care delivery, the mode of nursing care delivery, and skill-mix on: (a) quality of nursing care; and (b) patient adverse events, after controlling for nurse demographics, work environment, and workload factors. DESIGN A cross-sectional exploratory correlational study that drew on secondary data was conducted. METHODS Survey data from 416 direct care registered nurses from medical-surgical settings across British Columbia were analysed using hierarchical multiple regression. Larger study data were collected in 2015. RESULTS Nurses working in a team-based mode reported a greater number of nursing tasks left undone compared with those working in a total patient care. Nurses working in a skill-mix with licensed practical nurses reported a higher frequency of patient adverse events compared with those working in a skill-mix without licensed practical nurses. At higher levels of acuity, nurses in a team-based mode reported a higher frequency of patient adverse events than did nurses in a total patient care. CONCLUSION Models of nursing care delivery components, mode and skill-mix, influenced quality and safety outcomes. Some of the team-based medical-surgical nurses in British Columbia are not functioning as effective teams. Team building strategies should be used to enhance collaboration among them. IMPACT Research into redesigning care delivery has typically focused on only one care delivery component at a time. The study findings could have implications for nurses and patients, nursing leadership and policymakers particularly in medical-surgical settings in British Columbia.
Hemojuvelin is a novel suppressor for Duchenne muscular dystrophy and age‐related muscle wasting

Muscle wasting occurs in response to various physiological and pathological conditions, including ageing and Duchenne muscular dystrophy (DMD). Transforming growth factor‐β1 (TGF‐β1) contributes to muscle pathogenesis in elderly people and DMD patients; inhibition of TGF‐β1 signalling is a promising therapeutic strategy for muscle‐wasting disorders. Hemojuvelin (HJV or Hjv as the murine homologue) is a membrane‐bound protein that is highly expressed in skeletal muscle, heart, and liver. In hepatic cells, Hjv acts as a coreceptor for bone morphogenetic protein, a TGF‐β subfamily member. The aim of this study was to investigate whether Hjv plays an essential role in muscle physiological and pathophysiological processes by acting as a coreceptor for TGF‐β1 signalling.
Drinking Motives and Drinking Behaviors in Romantic Couples: A Longitudinal Actor-Partner Interdependence Model

Excessive alcohol consumption is related to adverse physical and social consequences. Research shows an individual’s own drinking motives (reasons for drinking alcohol) are linked to his or her specific drinking outcomes in a theoretically expected manner. Romantic couples often engage in a “drinking partnership,” where partners reciprocally influence each other’s drinking. Though alcohol consumption partner effects have been studied, partner effects of drinking motives on an individual’s alcohol consumption have not been investigated in romantic couples. We investigated this topic. Romantic couples (N = 203) were assessed once weekly for four weeks using self-report questionnaires. Participants were on average 22.7 years old (SD = 5.5) and were in their relationship an average of 2.3 years (SD = 2.4). Actor-partner interdependence models using multilevel path-analysis with indistinguishable dyads were conducted, with each motive predicting drinking quantity and frequency. There were significant actor effects for social and enhancement motives; moreover, changes in a partner’s enhancement and social motives predicted change in the individual’s drinking quantity during any given week, but only averaged partners’ enhancement motives predicted the individual’s drinking frequency. Coping-with-anxiety motives had significant actor effects when predicting averaged quantity and frequency; moreover, changes in partners’ coping-with-anxiety motives predicted changes in drinking quantity. Enhancement and social motives of the partner influenced the drinking quantity and frequency of the actor by way of influencing the actor’s enhancement and social motives. Intervention efforts targeting both members of a romantic dyad on their reasons for drinking should be tested for preventing escalations in either member’s drinking behavior.
Sensitivity of global soil carbon stocks to combined nutrient enrichment.

Soil stores approximately twice as much carbon as the atmosphere and fluctuations in the size of the soil carbon pool directly influence climate conditions. We used the Nutrient Network global change experiment to examine how anthropogenic nutrient enrichment might influence grassland soil carbon storage at a global scale. In isolation, enrichment of nitrogen and phosphorous had minimal impacts on soil carbon storage. However, when these nutrients were added in combination with potassium and micronutrients, soil carbon stocks changed considerably, with an average increase of 0.04 KgCm-2 year-1 (standard deviation 0.18 KgCm-2 year-1 ). These effects did not correlate with changes in primary productivity, suggesting that soil carbon decomposition may have been restricted. Although nutrient enrichment caused soil carbon gains most dry, sandy regions, considerable absolute losses of soil carbon may occur in high-latitude regions that store the majority of the world's soil carbon. These mechanistic insights into the sensitivity of grassland carbon stocks to nutrient enrichment can facilitate biochemical modelling efforts to project carbon cycling under future climate scenarios.
Advance in genetics of migraine

Purpose of review Migraine is a primary headache disorder and one of the most common and disabling neurological diseases worldwide. Genome-wide association studies have identified ≈40 genetic loci associated with migraine. How these and other genetic findings are used to expand our knowledge on the pathophysiological mechanism of common migraine and rare migraine variants will be discussed. Recent findings The genetic load, based on common polygenic variation, is higher in familial migraine cases than in nonfamilial cases, and higher for migraine with aura and hemiplegic migraine. Migraine shares common genetic variant risks with depression. Specific clinical features of common migraine seem to be determined by genetic factors. A stronger family history of migraine is associated with lower age-at-onset, higher frequency and number of medication days and the migraine with aura subtype. Mild hemiplegic migraine is likely caused by complex polygenic interaction of multiple gene variants and environmental factors, like in common migraine subtypes. Phenotypical features in hemiplegic migraine patients may guide physicians in providing adequate genetic counseling. Summary Integration of genetic, phenotypic and epigenetic data will help to identify the biological mechanisms by which genetic factors contribute to migraine pathogenesis. Recent studies show the impact of genetics on clinical features and comorbidities in migraine and may guide clinicians to an adequate genetic advice for patients.
Three-year results from the Retro-IDEAL study: Real-world data from diabetic macular edema (DME) patients treated with ILUVIEN® (0.19 mg fluocinolone acetonide implant)

Introduction: The Retro-IDEAL (ILUVIEN Implant for chronic DiabEtic MAcuLar edema) study is a retrospective study designed to assess real-world outcomes achieved with the ILUVIEN® (0.19 mg fluocinolone acetonide (FAc)) in patients with chronic diabetic macular edema (DME) in clinical practices in Germany. Methods: This study was conducted across 16 sites in Germany and involved 81 eyes (63 patients) with persistent or recurrent DME and a prior suboptimal response to a first-line intravitreal therapy (primarily anti-VEGF intravitreal therapies). Results: Patients were followed-up for 30.8 ± 11.3 months (mean ± standard deviation) and had a mean age of 68.0 ± 10.4 years. Best-recorded visual acuity (BRVA) improved by +5.5 letters at month 9 (P ⩽ 0.005, n=56; from a baseline of 49 letters) and this was maintained through to month 30 (P ⩽ 0.05, n = 42). There was a concurrent improvement in central macular thickness with a reduction from 502 µm at baseline to 338 µm at year 1 (P ⩽ 0.0001, n = 43). This effect was sustained to year 3 (i.e. 318 µm; P ⩽ 0.0001, n = 29). Mean intraocular pressure (IOP) remained constant between baseline and year 3 with a peak change of 1.9 mm Hg occurring at year 1. Elevated IOP was observed in a similar percentage of patients prior to (22.2% of cases) and following (27.2%) treatment with the FAc implant. In the majority of cases, these elevations were managed effectively with IOP medications. Conclusions: Despite substantial amounts of prior intravitreal treatments – primarily with anti–vascular endothelial growth factor (VEGF) drugs – this real-world study showed that sustained structural and functional improvements can last for up to 3 years with a single FAc implant.
A randomized controlled intervention to promote readiness to genetic counseling for breast cancer survivors

Breast cancer (BC) survivors with a genetic mutation are at higher risk for subsequent cancer; knowing genetic risk status could help survivors make decisions about follow‐up screening. Uptake of genetic counseling and testing (GC/GT) to determine BRCA status is low among high risk BC survivors. This study assessed feasibility, acceptability, and preliminary efficacy of a newly developed psychoeducational intervention (PEI) for GC/GT.
Rapid pleural effusion after discontinuation of lenvatinib in a patient with pleural metastasis from thyroid cancer

Summary We report a case of rapid pleural effusion after discontinuation of lenvatinib. A 73-year-old woman was diagnosed with poorly differentiated thyroid cancer with right pleural metastasis. Weekly paclitaxel treatment was performed for 18 weeks, but it was not effective. Oral administration of lenvatinib, a multi-target tyrosine kinase inhibitor, reduced the size of cervical and thoracic tumors and lowered serum thyroglobulin levels. Lenvatinib was discontinued on day 28 because of Grade 2 thrombocytopenia and Grade 3 petechiae. Seven days after discontinuation of lenvatinib, the patient was hospitalized because of dyspnea and right pleural effusion. Pleural effusion rapidly improved with drainage and re-initiation of lenvatinib and did not recur. Anorexia caused by lenvatinib led to undernutrition, which resulted in death 13 months after initiation of lenvatinib. Autopsy revealed extensive necrosis with primary and metastatic lesions, suggesting that the patient responded to lenvatinib. Physicians should be aware of the possibility of flare-up in patients with thyroid cancer treated with lenvatinib. Learning points: Autopsy findings revealed that lenvatinib was efficacious in treating poorly differentiated thyroid cancer without primary lesion resection. Flare-up phenomenon may occur in thyroid cancer treated with lenvatinib. Attention should be paid to flare-up phenomenon within a few days of discontinuing lenvatinib.
What is multispecies MSY? A worked example from the North Sea

The concept of an optimum yield at intermediate levels of fishing (the so called maximum sustainable yield or MSY) has been with us since the 1930s and is now enshrined in legislation as a key objective of fisheries management. The concept seems intuitively reasonable and is readily applicable to a single stock treated in isolation and assuming a constant environment. However, translating this concept into a mixed and multispecies fishery, where there are complex trade‐offs between fleets and stocks and in general no simple optimum solution, has been problematic. Here I introduce a framework for thinking about multispecies MSY in terms of an integrated risk of stock depletion and expected long‐term yield. Within this framework I consider the performance of a set of simple harvest control rules based upon a single‐limit fishing mortality rate (F) which is common to all stocks and a target biomass which is a set fraction of a stock's virgin biomass. Using a multispecies management strategy evaluation, I compare expected outcomes for a set of these harvest control rules with alternative scenarios, in which each stock has its own F based on the assessment process. I find that the simple framework can produce outcomes that are similar to those from the more sophisticated estimates of F. I therefore conclude that achieving multispecies MSY may depend more upon setting reasonable biomass targets and faithfully applying a harvest control rule approach rather than determining the best possible Fs for each stock.
Activation of Kv7 channels as a novel mechanism for NO/cGMP‐induced pulmonary vasodilation

The NO/cGMP pathway represents a major physiological signalling controlling tone in pulmonary arteries (PA), and drugs activating this pathway are used to treat pulmonary arterial hypertension. Kv channels expressed in PA smooth muscle cells (PASMCs) are key determinants of vascular tone. We aimed to analyse the contribution of Kv1.5 and Kv7 channels in the electrophysiological and vasodilating effects evoked by NO donors and the GC stimulator riociguat in PA.
Telomeres and Telomerase in Cutaneous Squamous Cell Carcinoma

The role of telomere biology and telomerase activation in skin cancers has been investigated in melanoma and basal cell carcinoma but limited evidence is available for cutaneous squamous cell carcinoma (cSCC). We will review the current knowledge on the role of telomere and telomerase pathway in cSCC pathogenesis. At the somatic level, both long and short telomere lengths have been described in cSCC. This telomere dichotomy is probably related to two different mechanisms of tumour initiation which determines two tumour subtypes. Telomere shortening is observed during the invasive progression from in situ forms of cSCC, such as Bowen’s disease (BD) and actinic keratosis (AK), to invasive cSCC. At the germline level, controversial results have been reported on the association between constitutive telomere length and risk of cSCC. Approximately 75–85% of cSCC tumours are characterized by a high level of telomerase activity. Telomerase activation has been also reported in AKs and BD and in sun-damaged skin, thus supporting the hypothesis that UV modulates telomerase activity in the skin. Activating TERT promoter mutations have been identified in 32–70% of cSCCs, with the majority showing the UV-signature. No significant correlation was observed between TERT promoter mutations and cSCC clinico-pathological features. However, TERT promoter mutations have been recently suggested to be independent predictors of an adverse outcome. The attention on telomere biology and telomerase activity in cSCC is increasing for the potential implications in the development of effective tools for prognostic assessment and of therapeutic strategies in patients with cutaneous cSCC.
Predictive values of resonance frequency analysis as a diagnostic tool in palatal implant loss.

OBJECTIVES: To determine the diagnostic value of resonance frequency analysis (RFA) in predicting palatal implant (PI) loss. MATERIALS AND METHODS: RFA values of 32 patients (study center at Mainz and Dresden) were evaluated in a prospective randomized controlled trial addressing clinical performance of two loading concepts on PI (Orthosystem, Straumann, Basel, Switzerland). Group 1: conventional loading after a 12-week healing period vs group 2: immediate loading within one week after insertion. Stability was assessed by RFA after surgical insertion (T1), one week (T2), and 12 weeks (T3) later. RESULTS: All 32 PI were clinically stable after surgical insertion; 14 PI were loaded conventionally and 18 immediately. One implant in group 1 was lost 6 weeks after insertion. One drop-out was registered in group 2. One false positive and three false negative implant stability quotients (ISQ) were observed. ISQ values of clinically stable PI in group 1 were 67.2 (SD ± 9.5) at T1, 62.3 (SD ± 11.7) at T2, and 68.2 (SD ± 5.5) at T3. Group 2 showed 67.1 (SD ± 11.7) at T1, 65.4 (SD ± 10.4) at T2, and 72.3 (SD ± 5.6) at T3. Differences between groups were not statistically significant for starting time ( P = .88) and change from T1 to T2: 0.08 but were significant from T1 to T3: P = . 04; (regression analysis). CONCLUSIONS: RFA had no sensitivity for prediction of stability. General decrease after primary stability and increase with secondary stability gives support for specificity. Within the limits of the study, only the diagnostic value of RFA identifying stable palatal implants could be confirmed.