Miracle-dz/UniFAR-FTUs huggingface dataset:
Inositol pyrophosphates impact phosphate homeostasis via modulation of RNA 3′ processing and transcription termination

Fission yeast phosphate acquisition genes pho1, pho84, and tgp1 are repressed in phosphate-rich medium by transcription of upstream lncRNAs. Here we show that phosphate homeostasis is subject to metabolite control by inositol pyrophosphates (IPPs), exerted through the 3’-processing/termination machinery and the Pol2 CTD code. Increasing IP8 (via Asp1 IPP pyrophosphatase mutation) de-represses the PHO regulon and leads to precocious termination of prt lncRNA synthesis. pho1 de-repression by IP8 depends on cleavage-polyadenylation factor (CPF) subunits, termination factor Rhn1, and the Thr4 letter of the CTD code. pho1 de-repression by mutation of the Ser7 CTD letter depends on IP8. Simultaneous inactivation of the Asp1 and Aps1 IPP pyrophosphatases is lethal, but this lethality is suppressed by mutations of CPF subunits Ppn1, Swd22, Ssu72, and Ctf1 and CTD mutation T4A. Failure to synthesize IP8 (via Asp1 IPP kinase mutation) results in pho1 hyper-repression. Synthetic lethality of asp1Δ with Ppn1, Swd22, and Ssu72 mutations argues that IP8 plays an important role in essential 3’-processing/termination events, albeit in a manner genetically redundant to CPF. Transcriptional profiling delineates an IPP-responsive regulon composed of genes overexpressed when IP8 levels are increased. Our results establish a novel role for IPPs in cell physiology.
When “a headache is not just a headache”: A qualitative examination of parent and child experiences of pain after childhood cancer

Today, more than 80% of children diagnosed with cancer are expected to survive. Despite the high prevalence of pain associated with the diagnosis and treatment of childhood cancer, there is a limited understanding of how having cancer shapes children's experience and meaning of pain after treatment has ended. This study addresses this gap by exploring childhood cancer survivors' (CCS') experiences of pain from their perspective and the perspective of their parents.
Linking Transformational Leadership with Nurse-Assessed Adverse Patient Outcomes and the Quality of Care: Assessing the Role of Job Satisfaction and Structural Empowerment

The purpose of this study was to examine the relationships between transformational leadership (TL), structural empowerment (SE), job satisfaction (JS), nurse-assessed adverse patient outcomes (APO), and the quality of care (QOC). The study further investigates the mediating effects of SE and JS on TL-APO and TL-QOC relationships. A total of 600 nurses working at 17 government hospitals in Pakistan completed the survey. The hypothesized model was tested using a confirmatory factor analysis and structural equation modeling. We found a positive relationship between TL, SE, JS, and QOC but negative relationships between TL and APO, SE and APO, and JS and APO. Our study further suggests that SE and JS strongly mediate both TL-APO and TL-QOC relationships.
Self-enhancement in moral hypocrisy: Moral superiority and moral identity are about better appearances

People often consider themselves as more moral than average others (i.e., moral superiority) and present themselves as more moral than they actually are (i.e., moral hypocrisy). We examined whether feelings of moral superiority—as a manifestation of self-enhancement motives—motivates people’s hypocritical behavior, that is, their discrepant moral performances in public versus private settings. In three studies (total N = 1,151), participants distributed two tasks (one favorable and one unfavorable) between themselves and an anonymous partner, with the option of using an ostensibly fair randomizer (e.g., a self-prepared coin). We found that when experiencing feelings of moral superiority (vs. non-superiority), people, especially those who highly identified with moral values (Studies 1 and 2), were less likely to directly give themselves the favorable task, but they were not less likely to cheat in private after using the randomizer (Studies 1 to 3). Both self-enhancement motives and moral identity have implications for hypocritical behavior, by motivating public moral appearances but not private moral integrity.
Muscle strength is longitudinally associated with mobility among older adults after acute hospitalization: The Hospital-ADL study

Background 30 to 60% of the acute hospitalized older adults experience functional decline after hospitalization. The first signs of functional decline after discharge can often be observed in the inability to perform mobility tasks, such as raising from a chair or walking. Information how mobility develops over time is scarce. Insight in the course of mobility is needed to prevent and decrease mobility limitations. Objectives The objectives of this study were to determine (i) the course of mobility of acute hospitalized older adults and (ii) the association between muscle strength and the course of mobility over time controlled for influencing factors. Methods In a multicenter, prospective, observational cohort study, measurements were taken at admission, discharge, one- and three months post-discharge. Mobility was assessed by the De Morton Mobility Index (DEMMI) and muscle strength by the JAMAR. The longitudinal association between muscle strength and mobility was analysed with a Linear Mixed Model and controlled for potential confounders. Results 391 older adults were included in the analytic sample with a mean (SD) age of 79.6 (6.7) years. Mobility improved significantly from admission up to three months post-discharge but did not reach normative levels. Muscle strength was associated with the course of mobility (beta = 0.64; p<0.01), even after controlling for factors as age, cognitive impairment, fear of falling and depressive symptoms (beta = 0.35; p<0.01). Conclusion Muscle strength is longitudinally associated with mobility. Interventions to improve mobility including muscle strength are warranted, in acute hospitalized older adults.
Diagnosis and management of postpartum hemorrhage and intrapartum asphyxia in a quality improvement initiative using nurse-mentoring and simulation in Bihar, India

Background In the state of Bihar, India a multi-faceted quality improvement nurse-mentoring program was implemented to improve provider skills in normal and complicated deliveries. The objective of this analysis was to examine changes in diagnosis and management of postpartum hemorrhage (PPH) of the mother and intrapartum asphyxia of the infant in primary care facilities in Bihar, during the program. Methods During the program, mentor pairs visited each facility for one week, covering four facilities over a four-week period and returned for subsequent week-long visits once every month for seven to nine consecutive months. Between- and within-facility comparisons were made using a quasi-experimental and a longitudinal design over time, respectively, to measure change due to the intervention. The proportions of PPH and intrapartum asphyxia among all births as well as the proportions of PPH and intrapartum asphyxia cases that were effectively managed were examined. Zero-inflated negative binomial models and marginal structural methodology were used to assess change in diagnosis and management of complications after accounting for clustering of deliveries within facilities as well as time varying confounding. Results This analysis included 55,938 deliveries from 320 facilities. About 2% of all deliveries, were complicated with PPH and 3% with intrapartum asphyxia. Between-facility comparisons across phases demonstrated diagnosis was always higher in the final week of intervention (PPH: 2.5–5.4%, intrapartum asphyxia: 4.2–5.6%) relative to the first week (PPH: 1.2–2.1%, intrapartum asphyxia: 0.7–3.3%). Within-facility comparisons showed PPH diagnosis increased from week 1 through 5 (from 1.6% to 4.4%), after which it decreased through week 7 (3.1%). A similar trend was observed for intrapartum asphyxia. For both outcomes, the proportion of diagnosed cases where selected evidence-based practices were used for management either remained stable or increased over time. Conclusions The nurse-mentoring program appears to have built providers’ capacity to identify PPH and intrapartum asphyxia cases but diagnosis levels are still not on par with levels observed in Southeast Asia and globally.
Long-Lasting Anti-Inflammatory and Antinociceptive Effects of Acute Ammonium Glycyrrhizinate Administration: Pharmacological, Biochemical, and Docking Studies

The object of the study was to estimate the long-lasting effects induced by ammonium glycyrrhizinate (AG) after a single administration in mice using animal models of pain and inflammation together with biochemical and docking studies. A single intraperitoneal injection of AG was able to produce anti-inflammatory effects in zymosan-induced paw edema and peritonitis. Moreover, in several animal models of pain, such as the writhing test, the formalin test, and hyperalgesia induced by zymosan, AG administered 24 h before the tests was able to induce a strong antinociceptive effect. Molecular docking studies revealed that AG possesses higher affinity for microsomal prostaglandin E synthase type-2 compared to type-1, whereas it seems to locate better in the binding pocket of cyclooxygenase (COX)-2 compared to COX-1. These results demonstrated that AG induced anti-inflammatory and antinociceptive effects until 24–48 h after a single administration thanks to its ability to bind the COX/mPGEs pathway. Taken together, all these findings highlight the potential use of AG for clinical treatment of pain and/or inflammatory-related diseases.
Acetabular reconstruction for primary and revision total hip arthroplasty using Kerboull-type acetabular reinforcement devices—case–control study with factors related to poor outcomes of surgery

Abstract Kerboull-type acetabular support rings (KT) and allogenic bone graft were used for severe periacetabular bone loss with primary and revision total hip arthroplasty (THA). The purpose of this case–control study is to evaluate the risk factors related to poor outcomes of surgery. Sixty patients underwent primary THA and revision THA using allogenic bone graft with KT for large acetabular deficiency. These patients were retrospectively evaluated postoperatively and followed-up by radiograph. The minimum follow-up period was 4 years and averaged 7 years. A radiological failure was defined by the following criteria: 1) substantial migration defined as change in the angle of inclination of more than 5 degrees or migration of more than 5 mm,2) breakage of the screw or device,3) acetabular revision due to aseptic loosening. Expected risk factors were defined as female, age >75 years, body mass index (BMI) >25%, medical history of hypertension, renal failure, liver steatosis, diabetes, hyperlipidemia, cardiac infarction, smoking, American Academy of Orthopedic Surgery (AAOS) classification III or IV, bleeding>500 mL, time of surgery >3hours, high hip center-type KT, inclination of KT >45 degrees, screw angle >25 degrees, morselized bone graft, Kawanabe's classification stage 3 or 4 and revision surgery. Nineteen hips (31.6%) revealed radiological failure according to our criteria, and revision THA was performed in 2 hips (3.3%). In the statistical analysis, morselized bone graft and high hip center-type KT were identified as factors of poor outcomes of surgery.
Long Non-Coding RNAs in Kidney Disease

Non-coding RNA species contribute more than 90% of all transcripts and have gained increasing attention in the last decade. One of the most recent members of this group are long non-coding RNAs (lncRNAs) which are characterized by a length of more than 200 nucleotides and a lack of coding potential. However, in contrast to this simple definition, lncRNAs are heterogenous regarding their molecular function—including the modulation of small RNA and protein function, guidance of epigenetic modifications and a role as enhancer RNAs. Furthermore, they show a highly tissue-specific expression pattern. These aspects already point towards an important role in cellular biology and imply lncRNAs as players in development, health and disease. This view has been confirmed by numerous publications from different fields in the last years and has raised the question as to whether lncRNAs may be future therapeutic targets in human disease. Here, we provide a concise overview of the current knowledge on lncRNAs in both glomerular and tubulointerstitial kidney disease.
Socioeconomic Inequalities in the Retail Food Environment around Schools in a Southern European Context

Across Europe, excess body weight rates are particularly high among children and adolescents living in Southern European contexts. In Spain, current food policies appeal to voluntary self-regulation of the food industry and parents’ responsibility. However, there is no research (within Spain) assessing the food environment surrounding schools. We examined the association between neighborhood-level socioeconomic status (NSES) and the spatial access to an unhealthy food environment around schools using both counts and distance measures, across the city of Madrid. We conducted a cross-sectional study citywide (n = 2443 census tracts). In 2017, we identified all schools (n = 1321) and all food retailers offering unhealthy food and beverages surrounding them (n = 6530) using publicly available data. We examined both the counts of retailers (within 400 m) and the distance (in meters) from the schools to the closest retailer. We used multilevel regressions to model the association of neighborhood-level socioeconomic status (NSES) with both measures, adjusting both models for population density. Almost all schools (95%) were surrounded by unhealthy retailers within 400 m (median = 17 retailers; interquartile range = 8–34). After adjusting for population density, NSES remained inversely associated with unhealthy food availability. Schools located in low-NSES areas (two lowest quintiles) showed, on average, 29% (IRR (Incidence Rate Ratio) = 1.29; 95% CI (Confidence Interval) = 1.12, 1.50) and 62% (IRR = 1.62; 95% CI = 1.35, 1.95) more counts of unhealthy retailers compared with schools in middle-NSES areas (ref.). Schools in high-NSES areas were farther from unhealthy food sources than those schools located in middle-NSES areas (β = 0.35; 95% CI = 0.14, 0.47). Regulating the school food environment (within and beyond school boundaries) may be a promising direction to prevent and reduce childhood obesity.
Dual Crosslinked Gelatin Methacryloyl Hydrogels for Photolithography and 3D Printing

Gelatin methacryloyl (GelMA) hydrogels have been used in tissue engineering and regenerative medicine because of their biocompatibility, photopatternability, printability, and tunable mechanical and rheological properties. However, low mechanical strength limits their applications in controlled drug release, non-viral gene therapy, and tissue and disease modeling. In this work, a dual crosslinking method for GelMA is introduced. First, photolithography was used to pattern the gels through the crosslinking of methacrylate incorporated amine groups of GelMA. Second, a microbial transglutaminase (mTGase) solution was introduced in order to enzymatically crosslink the photopatterned gels by initiating a chemical reaction between the glutamine and lysine groups of the GelMA hydrogel. The results showed that dual crosslinking improved the stiffness and rheological properties of the hydrogels without affecting cell viability, when compared to single crosslinking with either ultraviolet (UV) exposure or mTGase treatment. Our results also demonstrate that when treated with mTGase, hydrogels show decreased swelling properties and better preservation of photolithographically patterned shapes. Similar effects were observed when three dimensional (3D) printed and photocrosslinked substrates were treated with mTGase. Such dual crosslinking methods can be used to improve the mechanical properties and pattern fidelity of GelMA gels, as well as dynamic control of the stiffness of tissue engineered constructs.
Delays in Patient Presentation and Diagnosis for Buruli Ulcer (Mycobacterium ulcerans Infection) in Victoria, Australia, 2011–2017

Uncertainty regarding transmission pathways and control measures makes prompt presentation and diagnosis for Buruli ulcer critical. To examine presentation and diagnosis delays in Victoria, Australia, we conducted a retrospective study of 703 cases notified between 2011 and 2017, classified as residing in an endemic (Mornington Peninsula; Bellarine Peninsula; South-east Bayside and Frankston) or non-endemic area. Overall median presentation delay was 30 days (IQR 14–60 days), with no significant change over the study period (p = 0.11). There were significant differences in median presentation delay between areas of residence (p = 0.02), but no significant change over the study period within any area. Overall median diagnosis delay was 10 days (IQR 0–40 days), with no significant change over the study period (p = 0.13). There were significant differences in median diagnosis delay between areas (p < 0.001), but a significant decrease over time only on the Mornington Peninsula (p < 0.001). On multivariable analysis, being aged <15 or >65 years; having non-ulcerative disease; and residing in the Bellarine Peninsula or South-East Bayside (compared to non-endemic areas) were significantly associated with shorter presentation delay. Residing in the Bellarine or Mornington Peninsula and being notified later in the study period were significantly associated with shorter diagnosis delay. To reduce presentation and diagnosis delays, awareness of Buruli ulcer must be raised with the public and medical professionals, particularly those based outside established endemic areas.
Apical hypertrophic cardiomyopathy with apical endomyocardial fibrosis and calcification

Abstract Rationale: Apical hypertrophic cardiomyopathy (AHCM) is a rare form of hypertrophic cardiomyopathy which affects predominantly the apex of the left ventricle. Generally, left ventricular enlargement is not present in AHCM; additionally, endomyocardial fibrosis, and calcification are also rare. Patient concerns: A 61-year-old female (Case 1) and a 60-year-old female (Case 2) both presented with the symptoms of atypical chest pain, dyspnoea, exercise intolerance, palpitations. Diagnosis: Magnetic resonance and single-photon emission computed tomography (SPECT) revealed apical hypertrophic cardiomyopathy. Furthermore, 2D-transthoracic echocardiogram showed left atrium and ventricular enlargement, as well as endomyocardial fibrosis and calcification. Based on these findings, the patients were diagnosed with AHCM. Interventions: Both the patients were treated with ACEI, metoprolol, and aspirin. Additionally, both these patient underwent genetic test. Outcomes: The results of the genetic test of the 2 cases for hypertrophic cardiomyopathy (HCM) were negative. However, the gene mutation for dilated cardiomyopathy (TMPO) was detected in one of the cases. No change in condition during follow-up. Lessons: In past reports, Apical hypertrophic cardiomyopathy has been shown to have a benign prognosis. But in this case report, the imaging studies of the 2 patients suggest a poor prognosis. Furthermore, diagnosing cardiomyopathy should require multimodality imaging examinations to rule out differential diagnoses.
Next‐generation sequencing of endoscopic ultrasound guided microbiopsies from pancreatic cystic neoplasms

Interpretation of cytology samples from pancreatic cysts is challenging. A novel microbiopsy forceps used during endoscopic ultrasound examinations offers new opportunities for histological examination of tissue from pancreatic cysts as well as next‐generation sequencing. The aim of this study was to analyse the results of next‐generation sequencing of microbiopsies from pancreatic cysts.
The Role of Overseas Field Courses in Student Learning in the Biosciences

AbstractField courses provide excellent opportunities to engage students with their subject. Previous research has confirmed the considerable academic and pastoral benefits gained from taking students out of the classroom, especially in Biosciences and related disciplines. Here, we compare student attendance/attainment on a Level 5 Biosciences field course to South Africa to: (1) attainment on other Level 5 modules; (2) attainment at Level 6; (3) dissertation performance; and (4) grade trajectory between Level 5 and Level 6 for two successive cohorts. Students who attended the overseas field course tended to attain higher dissertation marks than non-attending peers and had a better grade trajectory, being more likely to improve their degree classification between Levels 5 and 6. We discuss possible (non-mutually-exclusive) reasons for this, including academic experience, undertaking challenging assessment at the end of Level 5 based on independent research (essentially a mini-dissertation), piquing studen.
The effect of sex hormones on normal breast tissue metabolism

Abstract This study investigated the effect of sex hormones on 18F-fluorodeoxyglucose (FDG) uptake in normal breast tissue. The retrospective study included 249 premenopausal women (median age, 45 years) who were diagnosed with unilateral breast cancer and underwent FDG positron emission tomography/computed tomography and hormone tests. The volume of interest was within the contralateral normal breast and the standardized uptake values (SUVs) were measured. The correlations of sex hormones (including estrogen, progesterone, testosterone, follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) with the SUVs of the normal breast were analyzed. There was a weak negative correlation between age and breast FDG uptake (P = .012, Spearman coefficient = −.16 for the maximum standardized uptake values [SUVmax]), especially in the luteal phase group (P = .005, Spearman coefficient = −.27 for SUVmax). The SUVs of normal breast tissue were increased when progesterone levels were higher (P = .043, Spearman coefficient = .13 for SUVmax). In the irregular menstrual cycle group, FDG uptake in the breast decreased as FSH (P = .027, Spearman coefficient = −.42 for SUVmax) and LH (P = .048, Spearman coefficient = −.44 for SUVmax) increased. Glucose metabolism of normal breast tissue decreases with age, and progesterone weakly affects breast FDG uptake. Gonadotropins may affect breast FDG uptake in premenopausal women with irregular menstrual cycles.
Chemical Structures and Pharmacological Profiles of Ginseng Saponins

Ginseng is a group of cosmopolitan plants with more than a dozen species belonging to the genus Panax in the family Araliaceae that has a long history of use in traditional Chinese medicine (TCM). Among the bioactive constituents extracted from ginseng, ginseng saponins are a group of natural steroid glycosides and triterpene saponins found exclusively throughout the plant. Studies have shown that these ginseng saponins play a significant role in exerting multiple therapeutic effects. This review covers their chemical structure and classification, as well as their pharmacological activities, including their regulatory effects on immunomodulation, their anticancer effects, and their functions in the central nervous and cardiovascular systems. The general benefits of ginseng saponins for boosting physical vitality and improving quality of life are also discussed. The review concludes with fruitful directions for future research in the use of ginseng saponins as effective therapeutic agents.