Miracle-dz/UniFAR-FTUs huggingface dataset:
Arabidopsis thaliana RNase H2 Deficiency Counteracts the Needs for the WEE1 Checkpoint Kinase but Triggers Genome Instability[C][W]

Absence of the RNAse H2 complex, mediating the excision of ribonucleotides from DNA, was found to overcome the growth inhibitory phenotype of plants lacking a functional replication checkpoint because of tolerating the substitution of deoxynucleotides with ribonucleotides. This substitution, however, results in replication errors, demonstrating the need of RNase H2 activity for genome stability. The WEE1 kinase is an essential cell cycle checkpoint regulator in Arabidopsis thaliana plants experiencing replication defects. Whereas under non-stress conditions WEE1-deficient plants develop normally, they fail to adapt to replication inhibitory conditions, resulting in the accumulation of DNA damage and loss of cell division competence. We identified mutant alleles of the genes encoding subunits of the ribonuclease H2 (RNase H2) complex, known for its role in removing ribonucleotides from DNA-RNA duplexes, as suppressor mutants of WEE1 knockout plants. RNase H2 deficiency triggered an increase in homologous recombination (HR), correlated with the accumulation of γ-H2AX foci. However, as HR negatively impacts the growth of WEE1-deficient plants under replication stress, it cannot account for the rescue of the replication defects of the WEE1 knockout plants. Rather, the observed increase in ribonucleotide incorporation in DNA indicates that the substitution of deoxynucleotide with ribonucleotide abolishes the need for WEE1 under replication stress. Strikingly, increased ribonucleotide incorporation in DNA correlated with the occurrence of small base pair deletions, identifying the RNase H2 complex as an important suppressor of genome instability.
Serum phosphate but not pulse wave velocity predicts decline in renal function in patients with early chronic kidney disease.

BACKGROUND The rate of decline in kidney function is a powerful predictor of cardiovascular risk in patients with chronic kidney disease (CKD). Serum phosphate and increased arterial stiffness are associated with elevated cardiovascular risk in CKD and the general population. We sought to determine whether serum phosphate and markers of arterial stiffness predict progression of renal dysfunction in patients with early CKD. METHODS Two hundred and twenty-five patients with Stage II-IV CKD were prospectively followed up at University Hospital Birmingham. Serum phosphate was measured at baseline and arterial stiffness was determined through measurement of aortic pulse wave velocity (PWV) and augmentation index (AIx). Progression of renal dysfunction was defined as the slope of estimated glomerular filtration rate (eGFR) against time. We determined the associations between possible predictors and rate of progression and also examined a combined end point of start of dialysis or ≥ 25% decline in eGFR. RESULTS Mean baseline eGFR was 43 ± 19 mL/min/1.73 m(2) and serum phosphate 1.22 ± 0.27 mmol/L. Median follow-up was 924 days. Serum phosphate independently predicted a greater decline in eGFR; a 1 mmol/L increment in serum phosphate was associated with a 0.34 mL/min/month steeper decline (P = 0.02). Brachial and aortic systolic pressure independently predicted the rate of renal function decline but aortic PWV and AIx had no significant influence. Forty-one patients (18%) reached the combined end point; serum phosphate was significantly higher in this group (1.32 ± 0.36 versus 1.19 ± 0.24 mmol/L, P = 0.04) and was an independent predictor for the combined end point. CONCLUSIONS Serum phosphate independently predicts decline in renal function in early CKD. Further studies are required to determine the mechanisms involved and to investigate the potential benefits of phosphate lowering on preserving kidney function.
Teacher Preparation Programs in the United States

According to Baker and Rytina’s (2014), the total number of legal immigrants coming to the United States during the ten years from 1980 to 1989 is 990,000, whereas in two more recent years from 2010 to 2012, the number rose to 2,810,000. As a country with an increasing influx of immigrants from all over the world, the United States has expressed a paramount need for the proportionately rising number of well-trained English as a Second Language (ESL) teachers. This paper presents the origin of American teacher education dated back from the nineteenth century, noticing common features and variations amongst teacher preparation programs. The significance as well as desirable goals of American teacher training programs are also discussed. Additionally, realities at teacher preparation institutions and workplace, and enormous challenges facing programs of pre-service preparation in the U.S. are demonstrated. Perceptions of qualified teacher preparation programs held by teacher educators’, teacher candidates’, school administrators’ perspectives, and the correlation amongst these three perceptions are explored. Finally, exemplars of qualified teacher education programs in the United States are demonstrated for replication.
Better Life Expectancy in Women with BRCA2 Compared with BRCA1 Mutations Is Attributable to Lower Frequency and Later Onset of Ovarian Cancer

Purpose: No formal assessment of life expectancy in women with BRCA1 and BRCA2 mutations in these genes has been reported previously. We have evaluated life expectancy using actuarial analysis and assessed the effect of breast and ovarian cancers on premature death in >1,000 BRCA1/2 carriers. Methods: Families with pathogenic mutations in BRCA1 and BRCA2 have been ascertained in a 10-million population region of United Kingdom since 1996. Mutation carriers and their first-degree relatives were used in an analysis of breast and ovarian cancer incidence and mortality as well as to derive and compare an actuarial assessment of life expectancy. Results: Six hundred twelve BRCA1 and 482 BRCA2 female mutation carriers were identified from 482 families. Life expectancy was significantly reduced for BRCA1 carriers compared with BRCA2 (P = 0.0002). This effect was attributable to an increased death rate from ovarian cancer (P = 0.04). Kaplan-Meier analysis revealed a better long-term survival from early-stage ovarian cancer in BRCA2 carriers but no significant differences in deaths from breast cancer or from women presenting with late-stage ovarian cancer. There was no other major contributing cause to death other than breast/ovarian cancer in BRCA1/2 female carriers. Conclusion: Interventions to reduce ovarian cancer incidence are likely to have a greater effect on life expectancy in BRCA1 compared with BRCA2 carriers. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1535–42)
A review of oesophageal manometry testing in a district general hospital

Although several modalities are available to investigate oesophageal motility disorders, manometry is the gold standard. The procedure is increasingly available in district general hospitals but the clinical utility of this investigation in this setting remains unclear. The aim in this study was to evaluate the use and outcome of oesophageal manometry in a district general hospital. Data on 100 consecutive oesophageal manometry procedures were analysed, taking into account the referral pattern, indications, and results. The indications were gastro-oesophageal reflux disease (preoperative assessment before fundoplication) (58), dysphagia (28), chest pain (12), and epigastric pain (2). Diagnoses were made using predefined standard criteria and were as follows: normal (41), non-specific motility disorder (NSMD) (38), achalasia (15), diffuse oesophageal spasm (4), and scleroderma (2). Of the 58 patients who had undergone manometry as a preoperative assessment of oesophageal motility, 27 (47%) were abnormal. Twenty five (43%) had NSMD and two (3%) had achalasia. Forty eight of these preoperative cases were combined with 24 hour pH recording, which confirmed acid reflux in 35 (73%). The experience reported here reflects the published evidence that the use of manometry is changing. It is now more commonly used for assessment before antireflux surgery and for dysphagia, and the use in the assessment of chest pain is declining. The findings confirm the importance of eliminating achalasia before inappropriate antireflux surgery.
Melatonin Entrains PER2::LUC Bioluminescence Circadian Rhythm in the Mouse Cornea.

PURPOSE Previous studies have reported the presence of a circadian rhythm in PERIOD2::LUCIFERASE (PER2::LUC) bioluminescence in mouse photoreceptors, retina, RPE, and cornea. Melatonin (MLT) modulates many physiological functions in the eye and it is believed to be one of the key circadian signals within the eye. The aim of the present study was to investigate the regulation of the PER2::LUC circadian rhythm in mouse cornea and to determine the role played by MLT. METHODS Corneas were obtained from PER2::LUC mice and cultured to measure bioluminescence rhythmicity in isolated tissue using a Lumicycle or CCD camera. To determine the time-dependent resetting of the corneal circadian clocks in response to MLT or IIK7 (a melatonin type 2 receptor, MT2, agonist) was added to the cultured corneas at different times of the day. We also defined the location of the MT2 receptor within different corneal layers using immunohistochemistry. RESULTS A long-lasting bioluminescence rhythm was recorded from cultured PER2::LUC cornea and PER2::LUC signal was localized to the corneal epithelium and endothelium. MLT administration in the early night delayed the cornea rhythm, whereas administration of MLT at late night to early morning advanced the cornea rhythm. Treatment with IIK7 mimicked the MLT phase-shifting effect. Consistent with these results, MT2 immunoreactivity was localized to the corneal epithelium and endothelium. CONCLUSIONS Our work demonstrates that MLT entrains the PER2::LUC bioluminescence rhythm in the cornea. Our data indicate that the cornea may represent a model to study the molecular mechanisms by which MLT affects the circadian clock.
Transfer Prices and Innovation in Public Healthcare: Costing and Clinical Choices in the NHS

Successive reforms of the NHS in the UK have been characterized by a greater transparency over the financial cost of various medical procedures; a commitment to a client/supplier split governed by administered market processes; and the development of market type incentives for staff based around financial performance targets. Although in this organizational context, issues around the “optimal” cost of specific treatments would seem to be a potentially fruitful domain for the application of the well-known prescriptions of the transfer pricing, prescriptions derived from a simple and reductionist view of Economic Man are likely to be a particularly inappropriate way of modeling the values and logics of actors in a public health care system. Using data from a case study of a specialist health care centre in English NHS, we found that clinical actors in the study were willing to spread a technological innovation but were not being supported by the financial and managerial goals and performance management systems. A pragmatic constructivist approach was used to analyse cost and qualitative data which revealed that the perceptions of clinicians was different to that of managers. Each group’s perceptions were conditionally constructed by different values, beliefs, logics and facts. The challenge was then to develop a management approach recognizing these differences and promoting a process of engagement between these groups. Avoiding a top-down ‘command and control’ model of governance, institutional mechanisms need to be designed which routinely promote the spread of new innovative procedures which are not only clinically superior but, as this case illustrates, are often cheaper than the current procedures.
Activities of N-Myc in the developing limb link control of skeletal size with digit separation

The developing limb serves as a paradigm for studying pattern formation and morphogenetic cell death. Here, we show that conditional deletion of N-Myc (Mycn) in the developing mouse limb leads to uniformly small skeletal elements and profound soft-tissue syndactyly. The small skeletal elements are associated with decreased proliferation of limb bud mesenchyme and small cartilaginous condensations, and syndactyly is associated with a complete absence of interdigital cell death. Although Myc family proteins have pro-apoptotic activity, N-Myc is not expressed in interdigital cells undergoing programmed cell death. We provide evidence indicating that the lack of interdigital cell death and associated syndactyly is related to an absence of interdigital cells marked by expression of Fgfr2 and Msx2. Thus, instead of directly regulating interdigital cell death, we propose that N-Myc is required for the proper generation of undifferentiated mesenchymal cells that become localized to interdigital regions and trigger digit separation when eliminated by programmed cell death. Our results provide new insight into mechanisms that control limb development and suggest that defects in the formation of N-Myc-dependent interdigital tissue may be a root cause of common syndromic forms of syndactyly.
The gap in transition between child and adolescent psychiatry and general adult psychiatry.

BACKGROUND During transition from child and adolescent psychiatry (CAP) to general adult psychiatry (GenP) young adults with mental illness face multilevel transitions along with a risk for disruption in continuity of care. The aim of this study was to describe professionals' experiences and views of the transition process from CAP to GenP. METHOD Data were collected through six focus group discussions with professionals from both CAP and GenP and analyzed by content analysis. RESULTS The results showed a gap in transition between CAP and GenP when different perspectives and care cultures meet in a complex process. CONCLUSIONS Cooperation, transition planning, and a mutual understanding of care can support young adults in transition from CAP to GenP.
Determinants and Effects of Fiscal Counter-Cyclicality

This paper provides a novel dataset of time-varying measures of fiscal counter-cyclicality for an unbalanced panel of advanced and emerging market economies from 1980 to 2014. The use of time-varying measures of fiscal counter-cyclicality overcomes the major limitation of existing studies assessing the determinants and the effects of fiscal countercyclicality that rely on cross-country regressions and, therefore, are not able to account for country-specific as well as global factors. The key findings of the paper are as follows: (i) fiscal counter-cyclicality has increased over time for many economies over the last two decades; (ii) fiscal counter-cyclicality is positively associated with financial deepening, the level of economic development, trade openness, government size as well as with political factors; (iii) fiscal counter-cyclicality significantly reduces output volatility. Our results are robust to various specifications and endogeneity checks. ****** Este documento ofrece un novedoso conjunto de datos con medidas de la contraciclicidad de la politica fiscal que son variantes en el tiempo, para un panel desbalanceado de economias avanzadas y emergentes desde 1980 hasta 2014. El uso de medidas fiscales contraciclicas que cambian en el tiempo, supera la principal limitacion de los estudios existentes sobre la materia, que usualmente evaluan los determinantes y los efectos de la contraciclicidad fiscal basados en regresiones a traves de paises y, por lo tanto, no dan cuenta de los efectos especificos por pais ni de los efectos globales. Los hallazgos mas importantes del trabajo son los siguientes: (i) la contraciclicidad fiscal ha aumentado durante las ultimas dos decadas en muchas economias; (ii) la contraciclicidad fiscal esta asociada positivamente con la profundizacion financiera, el nivel de desarrollo economico, la apertura comercial, el tamano del gobierno, asi como con factores politicos; y (iii) la contraciclicidad fiscal reduce significativamente la volatilidad del producto. Nuestros resultados son robustos a varias especificaciones y verificaciones de endogeneidad.
Cognitive Dysfunction After Fast-Track Hip and Knee Replacement

BACKGROUND:Postoperative cognitive dysfunction (POCD) is reported to occur after major surgery in as many as 20% of patients, elderly patients may especially experience problems in the weeks and months after surgery. Recent studies vary greatly in methods of evaluation and diagnosis of POCD, and the pathogenic mechanisms are still unclear. We evaluated a large uniform cohort of elderly patients in a standardized approach, after major joint replacement surgery (total hip and knee replacement). Patients were in an optimized perioperative approach (fast track) with multimodal opioid-sparing analgesia, early mobilization, and short length of stay (LOS ⩽3 days) and discharged to home. METHODS:In a prospective multicenter study, we included 225 patients aged ≥60 years undergoing well-defined fast-track total hip or total knee replacement. Patients had neuropsychological testing preoperatively and 1 to 2 weeks and 3 months postoperatively. LOS, pain, opioid use, inflammatory response, and sleep quality were recorded. The practice effect of repeated cognitive testing was gauged using data from a healthy community-dwelling control group (n = 161). RESULTS:Median LOS was 2 days (interquartile range 2–3). The incidence of POCD at 1 to 2 weeks was 9.1% (95% confidence interval [CI], 5.4%–13.1%) and 8.0% (95% CI, 4.5%–12.0%) at 3 months. There was no statistically significant difference between patients with and without early POCD, regarding pain, opioid use, sleep quality, or C-reactive protein response, although the CIs were wide. Patients with early POCD had a higher Mini Mental State Examination score preoperatively (difference in medians 0.5 [95% CI, −1.0% to 0.0%]; P = 0.034). If there was an association between early POCD and late POCD, the sample size was unfortunately too small to verify this (23.6% of patients with early POCD had late onset vs 6.7% in non-POCD group; risk difference 16.9 (95% CI, −2.1% to 41.1%; P = 0.089). CONCLUSIONS:The incidence of POCD early after total hip and knee replacement seems to be lower after a fast-track approach than rates previously reported for these procedures, but late POCD occurred with an incidence similar to that in previous studies of major noncardiac elective surgery. No association between early and late POCD could be verified.
Rapid increase of Nurr1 mRNA expression in limbic and cortical brain structures related to coping with depression‐like behavior in mice

The immediate‐early gene Nurr1 is a member of the inducible orphan nuclear receptor family. Nurr1 is essential to the differentiation, maturation, and maintenance of midbrain dopaminergic neurons and is expressed in different brain regions. We have reported that adult mice with reduced Nurr1 expression displayed an increase in immobility response to acute stress. These mice were also deficient in the retention of emotional memory. Thus, Nurr1 expression seems to be relevant to normal cognitive processes. To investigate the response of Nurr1 to a stress stimulus, Nurr1 mRNA expression was examined by in situ hybridization in adult mice using a depression‐like behavior paradigm, the forced swim test. The Nurr1 gene was rapidly and widely up‐regulated throughout the brain, including cortical areas (i.e., prefrontal cortex, primary and secondary visual cortex, primary auditory cortex, and secondary somatosensory cortex), hippocampus (dentate gyrus, CA1, CA2, and CA3), and midbrain (substantia nigra pars compacta and ventral tegmental area) at 30 min and 3 hr after the forced swim test. Dopamine content was reduced in prefrontal cortex and midbrain following swim stress. These results suggest that the increase in Nurr1 expression might be a compensatory mechanism to counteract the changes in forebrain dopamine transmission in coping with acute stress. © 2010 Wiley‐Liss, Inc.
Predicting Financial Distress and Closure in Rural Hospitals

PURPOSE Annual rates of rural hospital closure have been increasing since 2010, and hospitals that close have poor financial performance relative to those that remain open. This study develops and validates a latent index of financial distress to forecast the probability of financial distress and closure within 2 years for rural hospitals. METHODS Hospital and community characteristics are used to predict the risk of financial distress 2 years in the future. Financial and community data were drawn for 2,466 rural hospitals from 2000 through 2013. We tested and validated a model predicting a latent index of financial distress (FDI), measured by unprofitability, equity decline, insolvency, and closure. Using the predicted FDI score, hospitals are assigned to high, medium-high, medium-low, and low risk of financial distress for use by practitioners. FINDINGS The FDI forecasts 8.01% of rural hospitals to be at high risk of financial distress in 2015, 16.3% as mid-high, 46.8% as mid-low, and 28.9% as low risk. The rate of closure for hospitals in the high-risk category is 4 times the rate in the mid-high category and 28 times that in the mid-low category. The ability of the FDI to discriminate hospitals experiencing financial distress is supported by a c-statistic of . 74 in a validation sample. CONCLUSION This methodology offers improved specificity and predictive power relative to existing measures of financial distress applied to rural hospitals. This risk assessment tool may inform programs at the federal, state, and local levels that provide funding or support to rural hospitals.
Primary Site Predicts Grade for Gastroenteropancreatic Neuroendocrine Tumors

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and abstruse neoplasms with increasing incidence and clinical relevance. The National Cancer Data Base was examined to identify GEP-NETcases from 2004 to 2013. In total, 39,454 patients diagnosed with GEP-NET were identified. Median age was 61 years. Majority was female (50.13%), white (79.49%), and had low-grade neoplasms (84.39%). On univariate analysis, age, sex, race, primary site, tumor size, and regional lymph node involvement were associated with tumor grade (P < 0.0001). On multivariate analysis, older age [odds ratio (OR) = 9.57], gender (male, OR = 1.29), and race continued to be associated with high-grade neoplasms. The primary site also remained a significant predictor of tumor grade. High-grade neoplasms were more likely to arise from the esophagus (OR = 317.75), hepatobiliary system (OR = 23.15), colorectum (OR = 14.37), ampulla of Vater (OR = 11.61), and stomach (OR = 7.84) compared with the appendix (OR = 5.41), pancreas (OR = 5.31), and small bowel (referent). The tumor grade for GEP-NETs is highly dependent on the primary site, suggesting different sites may be biologically distinct diseases. A personalized approach to GEP-NET treatment, tailored to the site of origin, is imperative.