Miracle-dz/UniFAR-FTUs huggingface dataset:
Activating hotspot L205R mutation in PRKACA and adrenal Cushing’s syndrome

Adrenal Cushing’s syndrome is caused by excess production of glucocorticoid from adrenocortical tumors and hyperplasias, which leads to metabolic disorders. We performed whole-exome sequencing of 49 blood-tumor pairs and RNA sequencing of 44 tumors from cortisol-producing adrenocortical adenomas (ACAs), adrenocorticotropic hormone–independent macronodular adrenocortical hyperplasias (AIMAHs), and adrenocortical oncocytomas (ADOs). We identified a hotspot in the PRKACA gene with a L205R mutation in 69.2% (27 out of 39) of ACAs and validated in 65.5% of a total of 87 ACAs. Our data revealed that the activating L205R mutation, which locates in the P+1 loop of the protein kinase A (PKA) catalytic subunit, promoted PKA substrate phosphorylation and target gene expression. Moreover, we discovered the recurrently mutated gene DOT1L in AIMAHs and CLASP2 in ADOs. Collectively, these data highlight potentially functional mutated genes in adrenal Cushing’s syndrome. Adrenal Cushing’s syndrome involves recurrent mutations in a key signal transduction pathway [Also see Perspective by Kirschner] Candidate Cushing's culprit identified Cushing's syndrome is a rare condition resulting from the excess production of cortisol. About 15% of Cushing's syndrome cases are associated with an adrenocortical tumor. However, the genetic etiology of these adrenocortical tumors is ill defined (see the Perspective by Kirschner). Cao et al. and Sato et al. both performed whole-exome sequencing of tumors from individuals with adrenal Cushing's syndrome and compared it with the patient's own matched non-tumor DNA and identified recurrent mutations in the protein kinase A catalytic subunit alpha (PRKACA) gene, as well as less frequent mutations in other putative pathological genes. The most common recurrent mutation activated the kinase, which may suggest a potential therapeutic target. Science, this issue p. 913, p. 917; see also p. 804
RET proto-oncogene in Sardinia: V804M is the most frequent mutation and may be associated with FMTC/MEN-2A phenotype.

OBJECTIVE Genetic screening of RET proto-oncogene is a powerful tool for the early identification of familial cases of medullary thyroid carcinoma (MTC), comprising isolated familial thyroid medullary carcinoma (FMTC) and multiple endocrine neoplasia syndromes 2A (MEN-2A) and 2B (MEN-2B). We report the results obtained by RET mutation analysis of subjects living in Sardinia, an Italian island whose inhabitants display a peculiar genetic background due to geographic isolation and low immigration rate for several centuries. DESIGN Retrospective study reporting data on 67 patients referred during the last 5 years for RET analysis because affected by MTC or first degree relatives of MTC patients. MAIN OUTCOME Only three mutations were identified affecting codons 620 (exon 10), 634 (exon 11), and 804 (exon 14); surprisingly, the most prevalent mutation found was V804M (overall prevalence: 59%). This finding is quite different from previous studies carried out in other Caucasian and non-Caucasian populations, in which the frequency of the V804M mutation is consistently reported less than 5%. The phenotype associated to V804M mutation was mostly FMTC (16/17 cases = 94.1%), but in one case (5.9%) primary hyperparathyroidism was found, suggesting a MEN-2A. CONCLUSIONS These results underline the importance of the genetic background in the distribution of RET mutations and should be taken into consideration when performing genetic evaluation of MTC patients.
Plasma capric acid concentrations in healthy subjects determined by high-performance liquid chromatography

Background Capric acid (FA10:0, decanoic acid) is a medium-chain fatty acid abundant in tropical oils such as coconut oil, whereas small amounts are present in milk of goat, cow, and human. Orally ingested FA10:0 is transported to the liver and quickly burnt within it. Only few reports are available for FA10:0 concentrations in human plasma. Methods Fasting (n = 5, male/female = 3/2, age 31 ± 9.3 years old) and non-fasting (n = 106, male/female = 44/62, age 21.9 ± 3.2 years old) blood samples were collected from apparently healthy Japanese volunteers. The total FA10:0 in the plasma were measured by high-performance liquid chromatography after derivatization with 2-nitrophenylhydrazine followed by UV detection. Results Inter and intra-assay coefficient of variation of FA10:0 assay at three different concentrations ranged in 1.7–3.9 and 1.3–5.4%, respectively, with an analytical recovery of 95.2–104.0%. FA10:0 concentration was below detection limit (0.1 µmol/L) in each fasting human plasma. FA10:0 was not detected in 50 (47.2%) of 106 non-fasting blood samples, while 29 (27.4%) plasma samples contained FA10:0 less than or equal to 0.5 µmol/L (0.4 ± 0.1), and 27 (25.5%) contained it at more than 0.5 µmol/L (0.9 ± 0.3). Conclusion A half of the non-fasting plasma samples contained detectable FA10:0. This simple, precise, and accurate high-performance liquid chromatography method might be useful for monitoring plasma FA10:0 during medium-chain triglycerides therapy.
A synthesis of approaches to teaching writing : A case study in an Australian primary school

This paper reports on the result of a case study, aiming to investigate the teaching of writing in a grade 5 Australian primary classroom. The paper will report data from three sources: classroom observations over six weeks, in which the researcher acted as a non participant observer, samples of students’ texts and an interview with the teacher at the end of the process of data collection. Data from the classroom observations, samples of students’ texts and the interview indicate that the teaching of writing in this class could be considered eclectic. Despite a strong emphasis on the implementation of the process approach, the teaching practices also drew on the systemic functional linguistic genre pedagogy (the SFL GP).
UFP‐112 a Potent and Long‐Lasting Agonist Selective for the Nociceptin/Orphanin FQ Receptor

Nociceptin/orphanin FQ (N/OFQ) controls several biological functions via selective activation of the N/OFQ peptide receptor (NOP). [(pF)Phe4Aib7Arg14Lys15]N/OFQ‐NH2 (UFP‐112) is an NOP receptor ligand designed using a combination of several chemical modifications in the same peptide sequence that increase NOP receptor affinity/potency and/or reduce susceptibility to enzymatic degradation. In the present review article, we summarize data from the literature and present original findings on the in vitro and in vivo pharmacological features of UFP‐112. Moreover, important biological actions and possible therapeutic indications of NOP receptor agonists are discussed based on the results obtained with UFP‐112 and compared with other peptide and nonpeptide NOP receptor ligands.
An efficient star skeleton extraction for human action recognition using hidden Markov models

This paper aims at finding an efficient approach for automatic human action recognition to classify human actions in both outdoor and indoor environments. A human action recognition system (HARS) collects video frames of human activities, extracts the desired features of each human skeleton. These characteristics are calculated, classified to build a skeleton database that can distinguish almost human gestures. This HARS converts every sequence of human gestures to the sequences of skeletal joint mapping (SJM). Then it assigns corresponding observation symbols to each SJM. Those observation sequences are used to train of hidden Markov models (HMMs) corresponding to seven actions: standing, walking, running, jumping, falling, lying, and sitting. Baum-Welch and forward-backward algorithms are employed to find optimal parameters of each HMM. During a recognition phase, each human gesture sequence is converted to an observation sequence and put into seven optimized HMM models. The current action can be identified by finding a model with the highest probability. The experimental results show that the proposed HARS offers high accuracy of action recognition in real-time.
Biodiesel from microorganisms and other alternative feedstocks: production, composition and properties

La creciente demanda de energia, la dependencia de los combustibles fosiles y las preocupaciones sobre el cambio climatico alientan la busqueda de fuentes de energia sostenibles. Los biocombustibles, respaldados por las politicas actuales de Europa y Estados Unidos, tendran probablemente un papel importante en la presente transicion energetica. El biodiesel puede ser una alternativa al diesel y, actualmente, muchos paises lo utilizan en mezclas con dicho combustible. Sin embargo, estudios recientes han senalado la falta de sostenibilidad del biodiesel cuando se produce a partir de aceites como la soja, la palma, la colza y el girasol. Ademas, algunos fabricantes de automoviles estan preocupados por aumentar el porcentaje de biodiesel de mezcla debido a la posible reduccion de la calidad del combustible, lo que implica que las propiedades del biodiesel y su relacion con su composicion sea un tema de interes relevante. Esta tesis estudia nuevas fuentes de biodiesel y evalua sus propiedades, con el objetivo final de mostrar alternativas sostenibles a los aceites actuales utilizados para la produccion de biodiesel, aumentando la diversidad de fuentes de energia, reduciendo la dependencia de los combustibles fosiles y promoviendo el desarrollo de una economia circular. Las principales propiedades del biodiesel se estiman a partir de su composicion, proponiendo nuevas ecuaciones para estimar la estabilidad a la oxidacion, el comportamiento en frio y la lubricidad de los esteres etilicos de acidos grasos (FAEEs), un tipo de biodiesel que utiliza bioetanol, en lugar de metanol, comunmente utilizado pero que, actualmente, tiene un origen fosil. Los microorganismos son probablemente, entre las materias estudiadas, los que tienen un mayor potencial para convertirse en la principal fuente de biocombustible en un futuro cercano. En esta tesis, se modifica geneticamente la bacteria Escherichia coli para cambiar su composicion de acidos grasos mejorando las propiedades finales del biodiesel obtenido a partir de dichos acidos grasos. Ademas, esta tesis examina un proceso supercritico para la produccion de FAEEs a partir de grasa animal con alto contenido de acidos grasos libres, uno de los mayores problemas de las materias primas residuales. Se evalua la degradacion de los compuestos poliinsaturados, un problema comun de este tipo de procesos. Asimismo, se han evaluado los FAEEs obtenidos a partir de aceite de semilla de uva, opcion de gran potencial en paises productores de vino como Espana. Se ha caracterizado y evaluado el potencial como biocombustible de la macroalga Chaetomorpha cf. gracilis, recogida en humedales de Cuba y posible alternativa a plantas terrestres que ocupan terreno cultivable. Por ultimo, se ha producido biodiesel de plantas del desierto de Tunez y se han analizado sus propiedades, una alternativa interesante debido a su baja necesidad de agua y su capacidad para crecer en tierras aridas.
Maximal exercise capacity and oxygen consumption of lambs with an aortopulmonary left-to-right shunt.

We determined maximal exercise capacity and measured hemodynamics in 10 6-wk-old lambs with an aortopulmonary left-to-right shunt [S, 57 +/- 11%, (SD)] and in 9 control lambs (C) during a graded treadmill test 8 days after surgery. Maximal exercise capacity (3.7 +/- 0.2 km/h and 10 +/- 5% inclination vs. 4.0 +/- 0.9 km/h and 15 +/- 0% inclination, P less than 0.02) and peak oxygen consumption (25 +/- 7 vs. 34 +/- 8 ml O2.min-1.kg-1, P less than 0.02) were both lower in the shunt than in the control lambs. This was due to a lower maximal systemic blood flow in the shunt lambs (271 +/- 38 vs. 359 +/- 71 ml.min-1.kg-1, P less than 0.01). Despite their high maximal left ventricular output, which was higher than in the control lambs (448 +/- 87 vs. 359 +/- 71 ml.min-1.kg-1, P less than 0.05), the left-to-right shunt could not be compensated for during maximal exercise because of a decreased reserve in heart rate (S: 183 +/- 22 to 277 +/- 38 beats/min; C: 136 +/- 25 to 287 +/- 29 beats/min) and in left ventricular stroke volume (S: 1.8 +/- 0.3 to 1.6 +/- 0.4 ml/kg; C: 1.0 +/- 0.3 to 1.3 +/- 0.2 ml/kg). We conclude that exercise capacity of shunt lambs is lower than that of control lambs, despite a good left ventricular performance, because a part of the reserves for increasing the left ventricular output is already utilized at rest.
Pathogenesis of Chlamydia pneumonia Persistent Illnesses in Autoimmune Diseases

Infectious agents have been implicated in the pathogenesis of many autoimmune diseases. In most of these diseases, including those in which specific organisms are known to play a role, the details of pathogenesis remain incompletely defined. Recent studies have aimed to isolate bacterial and viral pathogens from patients with autoimmune diseases, efforts have been made to further define the host immune response to infection, and there have been attempts to develop improved methods of diagnosis and treatment of infectious diseases affecting the Immune system. More recently, C.pneumonia has been linked to many autoimmune diseases [20].
traJ independence in expression of traT on F

Studies of F plasmids in the same cell as a transfer-repressed IncFII R plasmid showed a 100 to 1,000-fold decrease in transfer and a 75-fold decrease in surface exclusion, but no detectable change was shown in the amount of TraTp synthesized. Moreover, a mutation in traJ on F which caused a 10(4)-fold reduction in transfer caused only a 3.6-fold decrease in TraTp. These two findings suggest that a significant amount of traT expression on F is independent of traJ. Furthermore, we showed, using immunoprecipitation of TraTp, that normal amounts of this protein could be present in the cell without producing normal levels of surface exclusion.
Block of HFS‐induced LTP in the dentate gyrus by 1S,3S‐ACPD: further evidence against LTP as a model for learning

WE have previously shown that block of high-frequency stimulation (HFS) induced long-term potentiation (LTP) of synaptic transmission in area CA1 by (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3S-ACPD; 5 μl of a 20 mM solution), an agonist at group II metabotropic glutamate receptors, did not prevent animals from learning a spatial task. Here we show that the same dose of 1S,3S-ACPD also blocked the induction of HFS-induced LTP of the slope of the excitatory post-synaptic potential and of the amplitude of the population spike in the dentate gyrus. We conclude that HFS-induced LTP in the dentate gyrus is not a good model for memory formation.
Tiotropium bromide as add-on therapy to inhaled corticosteroids for treating asthma

Introduction: Bronchial asthma is becoming increasingly prevalent worldwide. Although first-line therapy with inhaled corticosteroids (ICS) with or without long-acting β2 agonists (LABA) has significantly improved the clinical outcomes of asthma, they cannot provide all asthmatics with good control and thus alternatives or add-on drugs are required. Tiotropium is a long-acting muscarinic antagonist that has been used to treat chronic obstructive pulmonary disease and it has been approved for treating asthma in some countries. This agent has similar bronchodilatory effects to those of LABA and might also have anti-inflammatory and anti-remodeling effects. Areas covered: Some pivotal clinical trials have found tiotropium effective as an add-on medication for low-to-medium doses of ICS for treating symptomatic asthma and asthma that remains uncontrolled despite ICS plus LABA therapy. Expert opinion: Whether or not tiotropium has anti-inflammatory and anti-remodeling effects in humans with asthma is an important issue. Predictors that would identify patients who would derive the maximal potential benefit from treatment with tiotropium in addition to their current therapy are also needed. Although the cardiovascular toxicity of tiotropium is less remarkable in asthma than in chronic obstructive pulmonary disease, longer and larger studies are still needed to confirm the safety of tiotropium for treating asthma.
Global Transpiration Fraction Derived From Water Isotopologue Datasets

Transpirasi sebagai salah satu komponen dari evapo-transpirasi memberikan kontribusi aliran masa yang besar dari permukaan tanah. Banyak metode telah di aplikasikan untuk menghitung besarnya komponen-komponen evapotranspirasi ini. Sebagian besar kajian dilakukan pada skala lokal maupun regional dan hanya ada sedikit kajian yang menghitung besarnya transpirasi secara global. Transpirasi global yang dihitung baik dengan model maupun dengan teknik isotop menghasilkan nilai transpirasi yang rendah untuk model dan tinggi untuk teknik isotop dibandingkan dengan pengukuran. Hal ini mengindikasikan bahwa berapa nilai yang akurat dari transpirasi global masih merupakan tantangan. Oleh karena itu, kajian ini bertujuan untuk menghitung besarnya transpirasi global dan penguapan dari tanah dengan menggunakan teknik isotop yang datanya diambil dari hasil model GCM yang dilengkapi dengan modul isotop. Hasil perhitungan dengan teknik isotop nampak menjanjikan dengan nilai fraksi transpirasi sebesar 80% pada daerah yang ditumbuhi tanaman, and lebih rendah dari 50% pada daerah gurun. Fraksi transpirasi global dari hasil perhitungan adalah sebesar 69% dengan 43% air hujan yang jatuh menguap kembali ke atmosfer melalui transpirasi tanaman. Meskipun metode keseimbangan masa isotop dapat diaplikasikan ke TES satelit data, fraksi transpirasi yang dihasilkan masih menunjukkan adanya masalah pada resolusi data yang dihasilkan. Dengan adanya peningkatan resolusi satelit pada masa yang akan datang, perhitungan komponen-komponen evapo-transpirasi dengan menggunakan data isotop akan lebih akurat
Understanding Household Waste Separation Behaviour: Testing the Roles of Moral, Past Experience, and Perceived Policy Effectiveness within the Theory of Planned Behaviour

Due to the increasing waste generation over the years in China, there is an urgent need to addressing this major problem by implementing effective household waste separation programs. Although past studies have tried to explain the waste behaviour from social and psychological motivations, there is little understanding as to the impact of individual moral obligation and past experience on forming waste separating intention. The aim of this study is to investigate key determinants influencing household waste separation intention and behaviour. Based on the theory of planned behaviour (TPB) model, we designed a survey questionnaire by taking account of determinants including residents’ attitude, subjective norm, perceived behavioural control, moral obligation, past behaviour, and demographic factors, with the prediction of household waste separation behaviour in mind. After obtaining 628 valid questionnaires from households in the city of Hangzhou, the partial least squares structural equation modelling (PLS-SEM) was conducted to evaluate the effectiveness of each construct. The results indicate that subjective norms, perceived behavioural control, past behaviour and intention significantly predict household waste separation behaviour, with past behaviour being the most significant construct to predict individuals’ intention and behaviour. Additional analysis on the moderating effect of different kinds of people in terms of their genders, ages, income levels and perceived policy effectiveness, to further evoke household waste separation behaviours is also discussed. The findings suggest insightful future policies that can focus on residents’ habit formation by providing the convenient location of waste separation and collection facilities, encouraging market-driven recycling programs and traders, promoting community campaigns and education which help residents to form favourable habits for protecting the environment.
Regulation of hdc expression and HDC activity by enological factors in lactic acid bacteria

Aims: The aim of this work was to study the influence of enological factors on the histidine decarboxylase gene (hdc) expression and on histidine decarboxylase enzyme (HDC) activity in Lactobacillus hilgardii, Pediococcus parvulus and Oenococcus oeni.
Headache and Psychiatric Comorbidity: Clinical Aspects and Outcome in an 8-Year Follow-Up Study

Migraine with juvenile onset changes over time. The existence of prognostic factors is a point of focus. A strict relationship between migraine or tension-type headache (TTH) and psychiatric factors has been suggested, but the exact role and the influence on evolution of headache is unknown. Objective. To analyze the evolution of migraine and TTH and psychiatric comorbidity (P-Co) from 1988 to 1996. Material and method. 100 subjects (40M, 60F; mean age 17.9 years; SD 2.7 years; range 12–26 years) were examined at our Center. The International Headache Society (IHS) criteria were employed. Psychometric tests and clinical interviews aided psychiatric diagnosis (DSM-III-R). SCID (Structured Clinical Interview for DSM-III-R) was employed in 1996. Chi square and logistic regression are used for statistical analysis. Findings. Migraine and TTH change their clinical characteristics, with a high tendency to remission (mostly in males). The presence of P-Co in 1988 is related to a worsening or unchanging situation in 1996. Headache-free subjects did not present any psychiatric disorders in 1996. Anxiety disorders in 1988 are related to enduring of headache. Migraine shows comorbidity with anxiety disorders and depression. Conclusion. P-Co is a notable problem in clinical practice. Diagnostic, prognostic, and treatment implications require a systematic assessment of P-Co.
Six-month outcomes of customized adherence enhancement (CAE) therapy in bipolar disorder.

BACKGROUND There are few psychosocial interventions specifically focused on improved treatment adherence in people with bipolar disorder (BD). Customized adherence enhancement (CAE) is a needs-based, manualized approach intended to improve medication adherence in individuals with BD. This was a six-month prospective trial of a CAE among 43 medication non-adherent individuals with BD who were receiving treatment in a community mental health clinic (CMHC). METHODS CAE was flexibly administered in modules applied as indicated by an initial adherence vulnerabilities screening. Screening identified reasons for non-adherence and modules were then administered using pre-set criteria. CAE effects were evaluated at six-week, three-month, and six-month follow-up. The six-month follow-up was our primary time point of interest. The primary outcome was change from baseline in adherence using the Tablets Routine Questionnaire (TRQ) and pill counts. Secondary outcomes included change from baseline in BD symptoms [Hamilton Depression Rating Scale (HAM-D), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS)]. RESULTS Subjects completed 86% of scheduled sessions, with only two individuals (5%) not participating in any sessions. The number of dropouts at six months was 12 (28%). Mean baseline non-adherence by TRQ was 48% [standard error (SE) 4.8%] missed tablets within the previous week and 51% (4.1%) missed tablets within the previous month. At six-month follow-up, mean TRQ non-adherence improved to 25% (6.8%) missed tablets for the previous week (p = 0.002) and 21% (5.5%) for the previous month (p < 0.001). Symptoms improved, with a change in the baseline mean (SE) BPRS of 43.6 (1.8) versus an endpoint of 36.1 (2.3) (p = 0.001), and baseline mean (SE) HAM-D of 17.8 (1.1) versus an endpoint of 15.3 (1.6) (p = 0.044). CONCLUSION CAE was associated with improvements in adherence, symptoms, and functional status. Controlled trials are needed to confirm these preliminary findings.