Miracle-dz/UniFAR-FTUs huggingface dataset:
A Gain-of-Function Mutation in Tnni2 Impeded Bone Development through Increasing Hif3a Expression in DA2B Mice

Distal arthrogryposis type 2B (DA2B) is an important genetic disorder in humans. However, the mechanisms governing this disease are not clearly understood. In this study, we generated knock-in mice carrying a DA2B mutation (K175del) in troponin I type 2 (skeletal, fast) (TNNI2), which encodes a fast-twitch skeletal muscle protein. Tnni2K175del mice (referred to as DA2B mice) showed typical DA2B phenotypes, including limb abnormality and small body size. However, the current knowledge concerning TNNI2 could not explain the small body phenotype of DA2B mice. We found that Tnni2 was expressed in the osteoblasts and chondrocytes of long bone growth plates. Expression profile analysis using radii and ulnae demonstrated that Hif3a expression was significantly increased in the Tnni2K175del mice. Chromatin immunoprecipitation assays indicated that both wild-type and mutant tnni2 protein can bind to the Hif3a promoter using mouse primary osteoblasts. Moreover, we showed that the mutant tnni2 protein had a higher capacity to transactivate Hif3a than the wild-type protein. The increased amount of hif3a resulted in impairment of angiogenesis, delay in endochondral ossification, and decrease in chondrocyte differentiation and osteoblast proliferation, suggesting that hif3a counteracted hif1a-induced Vegf expression in DA2B mice. Together, our data indicated that Tnni2K175del mutation led to abnormally increased hif3a and decreased vegf in bone, which explain, at least in part, the small body size of Tnni2K175del mice. Furthermore, our findings revealed a new function of tnni2 in the regulation of bone development, and the study of gain-of-function mutation in Tnni2 in transgenic mice opens a new avenue to understand the pathological mechanism of human DA2B disorder.
A common base answer to "Which country is most redistributive?"

Which country is most redistributive? This question is often discussed in terms of comparisons of measures of redistribution when each country's tax schedule is applied to its pre-tax income distribution. However, we believe that what most authors have in mind when referring to the "most redistributive country" is one in which the tax schedule is unanimously most redistributive across all pre-tax income distributions. A stronger identification of the most redistributive tax schedule therefore implies applying each tax schedule to all pre-tax income distributions and compare redistribution for all possible combinations. Given that this is practically complicated, we suggest applying the transplant-and-compare method of Dardanoni and Lambert (2002), which provides a tax progressivity ordering of schedules according to a common base. This paper shows how the transplant-and-compare approach can be utilized to approach an identification of the most redistributive country. The method and its implications are discussed by employing micro data from Luxembourg Income Studies, also contrasting results to those obtained using standard measures of redistribution.
Achalasia of the Cardia in Allgrove's (Triple A) Syndrome: Histopathologic Study of 10 Cases

&NA; Allgrove's syndrome, i.e., achalasia, addisonianism, alacrima (OMIM 231550) is an autosomal recessive disorder recently associated with the AAAS gene coding for the Aladin protein. However, the pathophysiology of achalasia in Allgrove's syndrome remains obscure. Here we investigated the histopathology of the cardia in Allgrove's syndrome. Myectomy specimens from 10 children with Allgrove's syndrome and four normal cardia were studied by routine staining and by immunohistochemistry for the pan‐neuronal marker PGP9.5, neuronal NO synthase, interstitial cells of Cajal, and CD3+ lymphocytes. In the normal cardia, myenteric ganglia, intramuscular nerve fibers, and interstitial cells of Cajal were numerous, whereas myenteric fibrosis and lymphocyte infiltrates were absent. In Allgrove's syndrome, fibrosis of the intermuscular plane was prevalent in all patients. Myenteric ganglia were absent, decreased, or apparently normal in 1 of 10, 8 of 10, and 1 of 10, respectively. Neuronal NO synthase was absent in 7 of 10 and decreased in 3 of 10, whereas interstitial cells of Cajal appeared normal in 7 of 10 and decreased in 3 of 10. Lymphocytes infiltrating the myenteric plexus were present in 6 of 10. Pyloromyectomy specimens available for six patients showed normal histopathologic features. In conclusion, the lack of neuronal NO synthase and fibrosis of the intermuscular plane can be linked to the defective cardia relaxation. Other features were less constant and may reflect the variability of disease expression and progression among patients with Allgrove's syndrome.
Effects of tetrabromobisphenol A on the green alga Chlorella pyrenoidosa

Flow cytometry (FC) was used to determine effects of tetrabromobisphenol A (TBBPA) on the green alga Chlorella pyrenoidosa (C. pyrenoidosa) by evaluating esterase activity, membrane integrity, concentrations of intracellular reactive oxygen species (ROS) and chlorophyll a (Chl-a) auto-fluorescence. TBBPA can inhibit esterase activity. Esterase activity was inversely proportional with TBBPA with a 24 h EC50 value of 3.13 mg TBBPA/L. After 48 h of exposure to TBBPA intracellular ROS was significantly greater than in the unexposed cells. TBBPA inhibited Chl-a fluorescence after 168 h. Concentrations of ROS were directly proportional to both magnitude and duration of exposure and was inversely proportional to cellular Chl-a. FC was useful as an integrated, ecologically relevant, measure of a functional response of the algae. The possible action pathway of TBBPA in C. pyrenoidosa is that TBBPA can cause toxic effects on esterase activity. As concentrations and exposure time increased, TBBPA change the ROS level in the internal. The role of anti-oxidative action is marked and significant at the duration of 48 h exposure, compared to the control. This suggested there was a redox cycle. TBBPA changes physiological status of cells, further decreased Chl-a fluorescence indicating inhibition.
Mitigating Photosensitivity of Erythropoietic Protoporphyria Patients by an Agonistic Analog of α‐Melanocyte Stimulating Hormone †

Erythropoietic protoporphyria (EPP) is a rare hereditary disorder characterized by dermal accumulation of the photosensitizer protoporphyrin IX. Following sunlight exposure, the resulting photosensitivity is manifested first as pain, later as erythema, edema and dermal lesions. Afamelanotide (Nle4‐d‐Phe7‐α‐MSH), a synthetic analog of α‐melanocyte stimulating hormone and agonist of the melanocortin‐1‐receptor, promotes melanin synthesis, increasing skin pigmentation. This study examines the efficacy of afamelanotide in preventing symptoms in patients with EPP. A sustained‐release subcutaneous implant of 20 mg afamelanotide was administered twice, with a 60‐day interval to five EPP patients. Therapeutic efficacy was assessed by a photoprovocation test using standardized white light irradiation, melanin density (MD) determination and daily recording of sunlight exposure and symptoms. From Day 30 to Day 120 tolerance to photoprovocation significantly increased compared with baseline (P = 0.007) and skin MD was significantly higher than that recorded at baseline (P = 0.004). Except for two low‐grade pain episodes, patients recorded no phototoxic events past Day 4 of treatment. Tolerance to natural sunlight was up to 24 times longer than prior to therapy. The findings demonstrate beneficial effects of afamelanotide in patients with EPP. Due to the limited number of patients enrolled and the design being an open‐label study, confirmation by a large‐scale trial is required.
Reconstruction of Late Craniofacial Deformities after Irradiation of the Head and Face During Childhood

Little is known about the results of surgical management of late craniofacial abnormalities arising after irradiation of the head and face for treatment of childhood cancers. The clinical records of 10 children (4 males and 6 females) who received 4500 to 6500 rads (mean 5160 rads) of craniofacial radiation between birth and 8 years of age (mean 5 years) and who subsequently had reconstructive surgery were reviewed. Six of the 10 patients received orbital radiation, 3 received maxillary-midfacial radiation, and 1 patient underwent radiation to the frontal bone. Histologic tumor types included retinoblastoma (4), rhabdomyosarcoma (3), Ewing's sarcoma (2), and neurofibrosarcoma (1). In addition to radiation, 7 of the 10 patients underwent surgical resection or debulking of their tumors and 6 received adjuvant chemotherapy. All patients presented from 4 to 20 years after treatment (mean 10 years) with varying, but severe degrees of soft-tissue and bony hypoplasia of the irradiated territories. Onlay bone grafting with soft-tissue reconstruction by a combination of local pedicle flaps and dermal-fat grafts was initially performed in 9 patients, and an occipitoparietal bone-flap switch procedure was done in 1 patient. Late follow-up ranged from 11 months to 7.5 years (mean 34 months). A total of 8 secondary procedures were necessary in 4 of the 10 patients (40 percent). Of these 4 patients, major revisions were performed in 3 and minor adjustments in 1. In addition, 2 patients in whom secondary procedures had not been done would benefit from further reconstruction. Therapy for cancer of the head and face during childhood has profound and ongoing effects on the growth of soft tissue and bone. The resultant deformities represent formidable problems that may be difficult to reconstruct with conventional surgical techniques. Increased utilization of free-tissue transfer is anticipated.
Reliability of individual diagnostic criterion items for psychoactive substance dependence and the impact on diagnosis.

OBJECTIVE Reliability of diagnostic criterion items for psychoactive substance dependence and the impact of each on the reliability of the diagnosis were analyzed. METHOD As part of a reliability study for a new interview developed for the multisite Collaborative Study on the Genetics of Alcoholism (COGA), data were collected from both within-center and across centers. The impact of each diagnostic item on the reliability of the substance dependence diagnosis was studied by forcing each item to be reliable one at a time and recomputing the kappa statistic for the diagnosis. RESULTS Findings indicated that the majority of individual diagnostic criterion items were reliable; 87% and 81% were in the fair or better range of reliability for the within- and cross-center studies, respectively. Individual kappa estimates were statistically similar for the two studies. Reliability findings for two classes of substance, alcohol and cocaine, were good, while those for stimulants were less satisfactory. CONCLUSIONS Forcing items one at a time to be reliable did not affect reliability of the overall substance dependence diagnosis, because more than one criterion item changed from Time 1 to Time 2. Because no single item was influential, weighting criteria equally, as is done in the DSM and ICD classification systems, appears to be a reasonable approach.
Predicting the Outcome in Schizophrenia *

Current concepts of schizophrenia and recent changes in diagnostic practice, multidimensional outcome assessment, and predictive methodology are reviewed. The highly successful results of earlier studies are not borne out in recent work which indicates that only about 8–40% of the outcome variance can be predicted using multivariate analysis of symptoms or groups of symptoms. Other influences during the illness which may significantly modify the outcome include the economic situation, life events, social class, the family, extrinsic handicaps, migration and culture. These factors have been inadequately considered in prognosis research, and are probably not considered sufficiently in therapy.
Platelet Rich Plasma in Musculoskeletal Pathology: A Necessary Rescue or a Lost Cause?

BACKGROUND Platelet rich plasma (PRP) has been used for decades to facilitate surgical tissue repair; therefore, the current trend of percutaneously injecting PRP to theoretically enhance tissue regeneration and repair is a logical progression. Applications include treatment of osteoarthritis, tendinopathy, chondropathy, acute and chronic soft tissue injuries, muscle or ligament tear, as well as enhancement of healing after bone or tissue reconstruction. However, there is limited evidence to support the use of PRP in the abovementioned conditions. Variations in the preparation of PRP and its application in various conditions influence its effect on various orthopedic conditions. OBJECTIVE To provide a basic overview of the current use of PRP in treating musculoskeletal conditions. METHODS Studies relevant to PRP were extracted from the PubMed and Medline database within the dates ranging from 1990 through 2015. These studies included in vitro as well as in-vivo animal experiments and careful analysis of the study population, type of intervention, and outcomes was made. RESULTS PRP has been noted to be a beneficial solution for tissue healing based on limited current literature. However a variety of factors such as method of preparation, composition, medical condition of the patient, anatomic location of the lesion, and tissue type can alter outcome. CONCLUSION The effectiveness and potential adverse effects of this treatment require high quality studies prior to widespread clinical application.Key words: Growth factors, platelet rich plasma, regeneration, regenerative healing, tissue repair, stem cells, mesenchymal stem cells, tissue engineering.
The liver sieve and atherosclerosis

Summary The ‘liver sieve’ is a term developed to describe the appearance and the role of fenestrations in the liver sinusoidal endothelial cell (LSEC). LSECs are gossamer-thin cells that line the hepatic sinusoid and they are perforated with pores called fenestrations clustered in sieve plates. There is growing evidence that fenestrations act like a permselective ultrafiltration system which is important for the hepatic uptake of many substrates, particularly chylomicron remnant lipoproteins. The liver sieve is a very efficient exchange system, however in conditions such as hepatic cirrhosis and fibrosis, diabetes mellitus and old age, there is defenestration of the liver sieve. Such defenestration has been shown to influence the hepatic uptake of various substrates including lipoproteins. In the future, pharmacological manipulation of the liver sieve may play a number of therapeutic roles including the management of dyslipidaemia; increasing the efficiency of liver-targeted gene therapy; and improving regeneration of old livers.
Sociality, selection, and survival: Simulated evolution of mortality with intergenerational transfers and food sharing

Why do humans survive so long past reproductive age, and why does juvenile mortality decline after birth, both contrary to the classic theory of aging? Previous work has shown formally that intergenerational transfers can explain both these patterns. Here, simulations confirm those results under weaker assumptions and explore how different social arrangements shape life-history evolution. Simulated single-sex hunter–gatherers survive, forage, reproduce, and share food with kin and nonkin in ways guided by the ethnographic literature. Natural selection acts on probabilistically occurring deleterious mutations. Neither stable population age distributions nor homogeneous genetic lineages are assumed. When food is shared only within kin groups, an infant death permits reallocation of its unneeded food to the infant's kin, offsetting the fitness cost of the death and weakening the force of selection against infant mortality. Thus, evolved infant mortality is relatively high, more so in larger kin groups. Food sharing with nonkin reduces the costs to kin of child rearing, but also reduces the resources recaptured by kin after an infant death, so evolved infant mortality is lower. Postreproductive adults transfer food to descendants, enhancing their growth and survival, so postreproductive survival is selected. The force of selection for old-age survival depends in complicated ways on the food-sharing arrangements. Population-level food sharing with nonkin leads to the classic pattern of constant low mortality up to sexual maturity and no postreproductive survival.
Layoff Taxes, Unemployment Insurance, and Business Cycle Fluctuations

This paper studies the role of labor market institutions in business cycle fluctuations. We develop a DSGE model with search and matching frictions and incorporate a US unemployment insurance experience rating system. Layoff taxes based on experience rating finance the cost of unemployment benefits and create considerable employment adjustment costs. Our framework helps realign the search and matching model with the empirical properties of its most salient variables. The model reproduces the negative correlation between vacancies and unemployment, i.e., the Beveridge curve. Simulations show that the model generates more cyclical volatility in its key variable - the ratio of job vacancies to unemployment (labor market tightness). Moreover, layoff taxes reduce the excess sensitivity of job destruction found in Krause and Lubik (2007) and strengthen the negative correlation of job creation and job destruction. Thus, the model matches key labor market data while incorporating an important feature of the US labor market.
ICT IN INITIAL TEACHER TRAINING: FIRST FINDINGS AND CONCLUSIONS OF AN OECD STUDY

This paper presents the preliminary findings of a recent study on the use of Information and Communication Technologies (ICT) in initial teacher training in nine OECD countries. The study aimed to address questions related to the national and institutional frameworks and requirements in place, the extent and types of use of ICT in initial teacher training by student teachers and their trainers, as well as the latter’s views on their preparation and confidence in using ICT in the classroom. The findings suggest that although student teachers and teacher trainers have generally good access to equipment and an adequate level of technical skills, they lack competencies in the pedagogical use of ICT. A number of barriers to and drivers for the development of these competencies are discussed at personal, institutional and policy levels.
Beneficial Effect of Leptin on Spatial Learning and Memory in Streptozotocin-Induced Diabetic Rats.

BACKGROUND Diabetes mellitus is a chronic disease which may be accompanied by cognitive impairments. The expression of the obesity gene (ob) is decreased in insulin-deficient diabetic animals and increased after the administration of insulin or leptin. Plasma leptin levels are reduced in the streptozotocin (STZ)-induced diabetic rats. Therefore, the deleterious effects of diabetes on memory may be due to the reduction of leptin. AIMS Investigate the effect of subcutaneous injection of leptin on spatial learning and memory in STZ-induced diabetic rats. STUDY DESIGN Animal experimentation. METHODS The rats were divided into three groups: 1-control, 2- diabetic, and 3- diabetic-leptin. Diabetes was induced in groups 2 and 3 by STZ injection (55 mg/kg) intraperitoneally (i.p). The animals received leptin (0.1 mg/kg) or saline subcutaneously (s.c) for 10 days before behavioral studies. Then, they were examined in the Morris water maze over 3 blocks after 3 days of the last injection of leptin. RESULTS The travelled path length and time spent to reach the platform significantly increased in the diabetic group (p<0.001) and decreased with leptin treatment (p<0.01 & p<0.001 respectively); also, a significant increase in path length and time was observed between the diabetic-leptin group and the diabetic group (p<0.01, p<0.001, respectively) in the probe test. CONCLUSION Leptin can exert positive effects on memory impairments in diabetic rats.
Retrospective cohort study of changes in hip joint phenotype of dogs in the United States.

OBJECTIVE To determine whether there had been a significant improvement in hip joint phenotype of dogs in the United States by comparing results of evaluations done by the Orthopedic Foundation for Animals of dogs born between 1972 and 1980 with those of dogs born between 1989 and 1992 and determining whether there had been an increase in the percentage of dogs classified as having excellent hip joint phenotype. DESIGN Retrospective cohort study. SAMPLE POPULATION 270,978 evaluations. PROCEDURE Numbers and percentages of dogs classified as having excellent hip joint phenotype during each period and change between periods in percentages of dogs classified as having excellent hip joint phenotype were calculated. RESULTS Percentage of dogs born between 1989 and 1992 that were classified as having excellent hip joint phenotype (15,289/143,668; 10.64%) was significantly higher than percentage of dogs born between 1972 and 1980 that were classified as having excellent hip joint phenotype (9,960/127,310; 7.82%). The increase in percentage of dogs classified as having excellent hip joint phenotype was significantly higher for male (51%) than for female (27%) dogs. CLINICAL IMPLICATIONS Results suggest that there has been an improvement in the hip joint phenotype of dogs in the United States between the 1970s and early 1990s and that the improvement has been greater among male than among female dogs.
Outcome of Laparoscopic Surgery in Patients with Cystic Lesions in the Distal Pancreas

Context Recent guidelines for the management of cystic lesions of the pancreas recommend observation for selected neoplasms using imaging criteria. However, current imaging modalities lack diagnostic accuracy, and the indication for surgery is debated. Objective In this study we have explored the outcome of laparoscopic distal pancreatic resections in all patients referred with potential pancreatic cystic neoplasms, with histological diagnosis as endpoint. Methods Between 1997 and 2009 all patients referred to our tertiary referral centre having a cystic neoplasm of the distal pancreas accepted for surgery were included in the present observational study. Results A total of 69 patients were included. Sixty-two patients underwent distal pancreatectomies, in whom 19 were spleen-preserving, and 7 enucleations were performed. Two procedures were converted to open technique. The lesions removed in 27 patients (39%) were either malignant or premalignant. The final diagnoses were serous cystic neoplasm (n=29), mucinous cystic neoplasm (n=12), pseudocyst (n=11), solid pseudopapillary neoplasm (n=10), intraductal papillary mucinous neoplasm (n=5) and other (n=2). Overall morbidity was 33%; 56% of the complications were classified as mild. Fistula rate was 10%. One patient died postoperatively from a cerebral haemorrhage. Conclusion Most complications after laparoscopic distal resection of cystic pancreatic lesions are mild, but the proportion of patients with benign lesions (61%) has to be reduced by focused preoperative investigations. Endoscopic ultrasound examination (EUS), enabling aspiration of cyst fluid and fine needle aspiration is an additional option for the preoperative workup. Image: Histological diagnosis of the resected specimens.