Miracle-dz/UniFAR-FTUs huggingface dataset:
Drug‐induced hepatic injury: an analysis of 1100 cases reported to The Danish Committee on Adverse Drug Reactions between 1978 and 1987

The Danish Committee on Adverse Drug Reactions received 1100 reports of suspected drug‐induced hepatic injury during the decade 1978–1987. The causal relationship between drug and hepatic injury was classified as definite in 57 (5.2%) reports, probable in 989 (89.9%) reports, possible in 50 (4.5%) reports and unclassifiable in four (0.4%) reports. Hepatic injuries accounted for 5.9% of all adverse drug reactions reported, and 14.7% of the lethal adverse drug reactions. A total of 47.2% were classified as acute cytotoxic, 16.2% as acute cholestatic and 26.9% as abnormal hepatic function. In 52 (4.7%) cases the hepatic injury was lethal; only 14 (1.3%) cases were chronic. Halothane accounted for 25% of the cases. The incidence of halothane‐induced hepatic injury is decreasing, and only one lethal case has been reported since 1981. Next to halothane, sulfasalazine was the drug most often suspected during the last 2 years of the decade. Based on consumption data, the incidence of hepatic injury due to sulindac was estimated to be 18‐fold higher than that due to ibuprofen. Paracetamol was reported to induce acute cytotoxic as well as cholestatic reactions in non‐alcoholic subjects taking therapeutic doses.
NF-kappaB in cultivated middle ear epithelium.

OBJECTIVE Otitis media with effusion (OME) may develop into a chronic course in some patients. In the majority of cases lipopolysaccharide (LPS) is detected in the middle ear fluid being capable of initiating and maintaining the inflammatory process associated with the disease. In addition, various extracellular signs of the inflammatory cascade are present, such as cytokines and ICAM-1 receptors. However, the underlying regulatory mechanisms situated intracellularily are sparsely recognized. NF-kappaB is a ubiquitously transcription factor complexed to its inhibitor within the cytoplasm. In response to stimuli, e.g. LPS or cytokines, NF-kappaB becomes activated and is translocated to the nucleus. At this level it induces transcription of various genes and subsequent expression of mRNA encoding for many immunoglobulins and cytokines, e.g. interleukin 8 (IL-8) which may be responsible for prolonging and maintaining the inflammatory process. METHODS To evaluate if NF-kappaB is present in middle ear epithelium including to identify possible stimulating factors in vitro studies using rabbit middle ear epithelial cells (meec) were undertaken. Both normal cells and LPS exposed cells were studied. ELISA techniques were applied to detect NF-kappaB, ICAM-1 receptors and IL-8. All measurements were adjusted to the concentration of total cell protein (TP). RESULTS NF-kappaB was detected in the normal middle ear epithelium in concentrations between 16.8 and 28.6 ng/microg TP. In response to LPS the NF-kappaB content increased with 25-33%. This enhancement became more pronounced with longer duration of the LPS exposition. A relatively distinct expression of ICAM-1 preceded the NF-kappaB increase, after which the ICAM-1 measurements declined. IL-8 was hardly measurable in normal cells. The IL-8 concentrations were higher in LPS exposed cultures. The time related curve demonstrated a diphasic shape with an early and a late maximum. CONCLUSION The chronic inflammation seen in some OME patients may be due to LPS activating ICAM-1 receptors and NF-kappaB followed by release of IL-8. An autocrine pathway may be established through activation of TNF alpha and IL-1beta. Thus, elucidation of alternative pathways in the inflammatory cascade and elimination of LPS, alternatively inhibition of NF-kappaB and/or IL-8, should be an issue for future investigation.
Superconducting properties of the s±-wave state: Fe-based superconductors

Although the pairing mechanism of Fe-based superconductors (FeSCs) has not yet been settled with consensus with regard to the pairing symmetry and the superconducting (SC) gap function, the vast majority of experiments support the existence of spin-singlet sign-changing s-wave SC gaps on multi-bands (s±-wave state). This multi-band s±-wave state is a very unique gap state per se and displays numerous unexpected novel SC properties, such as a strong reduction of the coherence peak, non-trivial impurity effects, nodal-gap-like nuclear magnetic resonance signals, various Volovik effects in the specific heat (SH) and thermal conductivity, and anomalous scaling behaviors with a SH jump and condensation energy versus Tc, etc. In particular, many of these non-trivial SC properties can easily be mistaken as evidence for a nodal-gap state such as a d-wave gap. In this review, we provide detailed explanations of the theoretical principles for the various non-trivial SC properties of the s±-wave pairing state, and then critically compare the theoretical predictions with experiments on FeSCs. This will provide a pedagogical overview of to what extent we can coherently understand the wide range of different experiments on FeSCs within the s±-wave gap model.
Risk factors for lower respiratory complications of rhinovirus infections in elderly people living in the community: prospective cohort study

Abstract Objective: To assess the role of rhinoviruses in elderly people living in the community. Design: Prospective community based surveillance of elderly people, without intervention. Subjects were telephoned weekly to identify symptomatic upper respiratory tract infections. Symptoms and impact of illnesses were monitored, and specimens were collected for diagnostic serology and human rhinovirus polymerase chain reaction. Setting: Leicestershire, England. Subjects: 533 subjects aged 60 to 90. Main outcome measures: Symptoms, restriction of activity, medical consultations, and antibiotic use during 96 rhinovirus infections. Adjusted odds ratios for lower respiratory syndromes with respect to smoking and health status. Results: A viral cause was established in 211 (43%) of 497 respiratory illnesses; rhinoviruses were identified in 121 (24%) and as single pathogens in 107. The median duration of the first or only rhinovirus infection in the 96 people with 107 rhinovirus infections was 16 days; 18 of the 96 patients were confined to bed and 25 were unable to cope with routine household activities. Overall, 60 patients with rhinovirus infections had lower respiratory tract syndromes; 41 patients consulted their doctor, 31 of them (76%) receiving antibiotics. One patient died. Logistic regression analysis showed that chronic medical conditions increased the estimated probability of lower respiratory rhinovirus illness by 40% (95% confidence interval 17% to 68%) and smoking by 47% (14% to 90%). There were almost six times as many symptomatic rhinovirus infections as influenza A and B infections. Conclusions: Rhinoviruses are an important cause of debility and lower respiratory illness among elderly people in the community. Chronic ill health and smoking increase the likelihood of lower respiratory complications from such infections. The overall burden of rhinovirus infections in elderly people may approach that of influenza. Key messages Rhinoviruses are responsible for more colds in elderly people living in the community than are other respiratory pathogens combined Almost two thirds of elderly people with rhino- virus infections can be expected to develop lower respiratory illness More than 40% of rhinovirus infections in elderly people are seen by medical practitioners, and three quarters of those consulting are prescribed antibiotics Risk factors for lower respiratory rhinovirus illness include chronic medical conditions and cur- rent smoking; past smoking is not an independent risk factor and stopping smoking is the only factor identified thus far that could reduce the severity of rhinovirus illness in elderly people
Comparison of primary dentition caries experience in pre-term low birth-weight and full-term normal birth-weight children aged one to six years.

AIM The aims of the study were to determine and compare the primary dentition caries experience and the variables that may influence the occurrence of caries, in preterm low birth weight and full term normal birth weight children aged one to six years. SETTINGS AND DESIGN A cross-sectional comparative study was conducted among 250 full term normal birth weight (FTNBW) and 250 preterm low birth weight (PTLBW) children one to six years, born in the two hospitals in Davangere: Bapuji Hospital and Chigatere Hospital. A purposive sampling was used to select the study group. MATERIALS AND METHODS Required and relevant information regarding demographic characteristics, feeding practices and oral hygiene practices were obtained. Dentition status and treatment need index (World Health Organization 1997) was used to record dental caries. STATISTICAL ANALYSIS USED Chi-square test, Student's t-test and ANalysis Of VAriance (ANOVA) test were used for statistical analysis. RESULTS Statistically significant difference was observed in caries prevalence between PTLBW and FTNBW groups (P<0.05), however, the difference in mean Decayed, missing and filled teeth index (dmft) was not statistically significant (P=0.30). Statistically significant differences were observed in caries experience between the two groups in relation to exclusive breast feeding for longer duration, i.e 7-12 months (P<0.05), bottle feeding habits (P<0.05) and sticky food consumption (P<0.01). CONCLUSIONS A significant relationship was found between caries and PTLBW status though the difference in caries experience between the groups was not statistically significant, thus illustrating the higher caries risk in PTLBW children compared to FTNBW children.
Effects of Strength Training on Postpubertal Adolescent Distance Runners

PurposeStrength training activities have consistently been shown to improve running economy (RE) and neuromuscular characteristics, such as force-producing ability and maximal speed, in adult distance runners. However, the effects on adolescent (<18 yr) runners remains elusive. This randomized control trial aimed to examine the effect of strength training on several important physiological and neuromuscular qualities associated with distance running performance. MethodsParticipants (n = 25, 13 female, 17.2 ± 1.2 yr) were paired according to their sex and RE and randomly assigned to a 10-wk strength training group (STG) or a control group who continued their regular training. The STG performed twice weekly sessions of plyometric, sprint, and resistance training in addition to their normal running. Outcome measures included body mass, maximal oxygen uptake (V˙O2max), speed at V˙O2max, RE (quantified as energy cost), speed at fixed blood lactate concentrations, 20-m sprint, and maximal voluntary contraction during an isometric quarter-squat. ResultsEighteen participants (STG: n = 9, 16.1 ± 1.1 yr; control group: n = 9, 17.6 ± 1.2 yr) completed the study. The STG displayed small improvements (3.2%–3.7%; effect size (ES), 0.31–0.51) in RE that were inferred as “possibly beneficial” for an average of three submaximal speeds. Trivial or small changes were observed for body composition variables, V˙O2max and speed at V˙O2max; however, the training period provided likely benefits to speed at fixed blood lactate concentrations in both groups. Strength training elicited a very likely benefit and a possible benefit to sprint time (ES, 0.32) and maximal voluntary contraction (ES, 0.86), respectively. ConclusionsTen weeks of strength training added to the program of a postpubertal distance runner was highly likely to improve maximal speed and enhances RE by a small extent, without deleterious effects on body composition or other aerobic parameters.
Energy use scenarios in an informal urban settlement in Johannesburg, South Africa

This paper presents a survey from a sample of 52 households from three informal urban settlements in Tembisa, Johannesburg, namely Vusimuzi, Madela Kufa Section 1 and Madela Kufa Section 2. The survey covered energy needs for cooking, space heating, water heating and lighting. No information was requested on the age, gender, status in the household, income level of the respondents, or the number of persons in the household. Coal was the primary source of energy for cooking, water heating and space heating, while kerosene was frequently used for cooking and lighting, and less for water heating. The majority of informal dwellings were not connected to the electricity grid at the time of the survey, save for a few which were connected through petrol-powered electric generators or through electricity obtained from a network of illegal connections. None of the households purchased LP gas for domestic use; the fuel is generally perceived to be unsafe for use in these settlements. Factors such as seasonality, the availability and price of fuels, and socio-cultural aspects affect fuel choices and the quantity consumed.
Microdroplet Digital PCR: Detection and Quantitation of Biomarkers in Archived Tissue and Serial Plasma Samples in Patients with Lung Cancer

Introduction: There is much interest in the use of noninvasive biomarkers in the management of lung cancer, particularly with respect to early diagnosis and monitoring the response to intervention. Cell-free tumor DNA in patients with cancer has been shown to hold potential as a noninvasive biomarker, in which the response to treatment may be evaluated using a blood test only. Multiple technologies have been suggested as being appropriate to measure cell-free tumor DNA. Microdroplet digital polymerase chain reaction (mdPCR) has a number of attributes that suggest it may be a useful tool for detecting clinically relevant genetic events. It offers precise and accurate quantitation of mutant alleles, including rare variants. Methods: We evaluate the performance of mdPCR in the analysis of DNA extracted from reference standards, tumor biopsies, and patient plasma. Results: The potential of mdPCR to detect clinically relevant mutations is demonstrated, in both formalin-fixed paraffin-embedded material and plasma. Furthermore, we show that mdPCR can be used to track changes in peripheral blood biomarkers in response to treatment and to detect the emergence of drug-resistant clones. Conclusions: MdPCR has potential as a tool to detect and quantify tumor-derived mutational events in cell-free DNA from patients with lung cancer.
Effect of liver transplant on pulmonary functions in adult patients with alpha 1 antitrypsin deficiency: 7 cases.

OBJECTIVES Alpha 1 antitrypsin (A1A) is a 52 kD glycoprotein that is mainly synthesized in the liver. As a major protease inhibitor, it binds to and neutralizes neutrophil elastase, thereby limiting the damage to the normal tissues after an inflammatory response. A deficiency in A1A leads to end-stage liver disease, both in children and in adults. In addition, the deficiency also has a detrimental effect in the lungs of the adult population. Alpha 1 antitrypsin deficiency is corrected with hepatic replacement; however, the changes in pulmonary functions have not been studied before and after liver transplant. The purpose of this study was to observe the changes in the pulmonary functions of patients who underwent liver transplant for the treatment of A1A deficiency. MATERIALS AND METHODS Nine patients underwent liver transplant for A1A deficiency. Seven patients (5 men, 2 women; mean age, 49.95 -/+ 7.09 years) had their pulmonary function tests available before the liver transplant (mean, 5.6 -/+ 3.4; range, 0.9-10.1 months) and after the liver transplant (mean, 30.3 -/+ 18.4, range 7.8-48.1 months) for analysis. RESULTS The mean, preliver, transplant, FEV1 was 2.69 -/+ 0.9 L, which was nearly unchanged after the liver transplant to a mean of 2.7 -/+ 1.2 L. During the mean total interval of nearly 3 years, an estimated decline of 250 mL in FEV1 was expected. CONCLUSIONS It appears from the results of our study that liver transplant probably prevented the progression of pulmonary disease in A1A-deficient patients. Further study and close, postliver, transplant follow-up is warranted to support our initial findings.
Ellobius lutescens: Sex Determination and Sex Chromosome

The mole vole Ellobius lutescens is an interesting animal, not only concerning its sex determination mechanism without the Y-chromosomal Sry gene, that triggers sex determination in nearly all other mammalian species, but also regarding the karyotype with an odd number of chromosomes, being identical in male and female animals. The odd chromosome represents the X chromosome, and therefore, even males do not have a Y chromosome. We present an overview of a search for candidate genes of male sex determination in the mole vole Ellobius lutescens. A singular X raises questions about the need for X chromosome inactivation in female cells. We present preliminary data that support a hypothesis that the E. lutescensXist gene may be degenerated and thus non-functional.
Identification of Open Stomata1-Interacting Proteins Reveals Interactions with Sucrose Non-fermenting1-Related Protein Kinases2 and with Type 2A Protein Phosphatases That Function in Abscisic Acid Responses1[OPEN]

Abscisic acid-activated protein kinases interact with each other and with protein phosphatases that modulate abscisic acid responses. The plant hormone abscisic acid (ABA) controls growth and development and regulates plant water status through an established signaling pathway. In the presence of ABA, pyrabactin resistance/regulatory component of ABA receptor proteins inhibit type 2C protein phosphatases (PP2Cs). This, in turn, enables the activation of Sucrose Nonfermenting1-Related Protein Kinases2 (SnRK2). Open Stomata1 (OST1)/SnRK2.6/SRK2E is a major SnRK2-type protein kinase responsible for mediating ABA responses. Arabidopsis (Arabidopsis thaliana) expressing an epitope-tagged OST1 in the recessive ost1-3 mutant background was used for the copurification and identification of OST1-interacting proteins after osmotic stress and ABA treatments. These analyses, which were confirmed using bimolecular fluorescence complementation and coimmunoprecipitation, unexpectedly revealed homo- and heteromerization of OST1 with SnRK2.2, SnRK2.3, OST1, and SnRK2.8. Furthermore, several OST1-complexed proteins were identified as type 2A protein phosphatase (PP2A) subunits and as proteins involved in lipid and galactolipid metabolism. More detailed analyses suggested an interaction network between ABA-activated SnRK2-type protein kinases and several PP2A-type protein phosphatase regulatory subunits. pp2a double mutants exhibited a reduced sensitivity to ABA during seed germination and stomatal closure and an enhanced ABA sensitivity in root growth regulation. These analyses add PP2A-type protein phosphatases as another class of protein phosphatases to the interaction network of SnRK2-type protein kinases.
Pleiotropic Role of PPARγ in Intracerebral Hemorrhage: An Intricate System Involving Nrf2, RXR, and NF‐κB

Intracerebral hemorrhage (ICH) is a subtype of stroke involving formation of hematoma within brain parenchyma, which accounts for 8–15% of all strokes in Western societies and 20–30% among Asian populations, and has a 1‐year mortality rate >50%. The high mortality and severe morbidity make ICH a major public health problem. Only a few evidence‐based targeted treatments are used for ICH management, and interventions focus primarily on supportive care and comorbidity prevention. Even in patients who survive the ictus, extravasated blood (including plasma components) and subsequent intrahematoma hemolytic products trigger a series of adverse events within the brain parenchyma, leading to secondary brain injury, edema and severe neurological deficits or death. Although the hematoma in humans gradually resolves within months, full restoration of neurological function can be slow and often incomplete, leaving survivors with devastating neurological deficits. During past years, peroxisome proliferator‐activated receptor gamma (PPARγ) transcription factor and its agonists received recognition as important players in regulating not only glucose and lipid metabolism (which underlies its therapeutic effect in type 2 diabetes mellitus), and more recently, as an instrumental pleiotropic regulator of antiinflammation, antioxidative regulation, and phagocyte‐mediated cleanup processes. PPARγ agonists have emerged as potential therapeutic target for stroke. The use of PPARγ as a therapeutic target appears to have particularly strong compatibility toward pathogenic components of ICH. In addition to its direct genomic effect, PPARγ may interact with transcription factor, NF‐κB, which may underlie many aspects of the antiinflammatory effect of PPARγ. Furthermore, PPARγ appears to regulate expression of Nrf2, another transcription factor and master regulator of detoxification and antioxidative regulation. Finally, the synergistic costimulation of PPARγ and retinoid X receptor, RXR, may play an additional role in the therapeutic modulation of PPARγ function. In this article, we outline the main components of the role of PPARγ in ICH pathogenesis.
The impact of a simulated grand tour on sleep, mood, and well-being of competitive cyclists.

AIM Professional cycling is considered one of the most demanding of all endurance sports. The three major professional cycling stages races (i.e. Tour de France, Giro d'Italia and Vuelta a España) require cyclists to compete daily covering between ~150-200 km for three consecutive weeks. Anecdotal evidence indicates that such an event has a significant effect on the sleep, mood, and general well-being of cyclists, particularly during the latter stages of the event. The primary aim of this study was to simulate a grand tour and determine the impact a grand tour has on the sleep, mood, and general well-being of competitive cyclists. METHODS Twenty-one male cyclists (M±SD, age 22.2±2.7 years) were examined for 39 days across three phases (i.e. baseline, simulated grand tour, and recovery). Sleep was assessed using sleep diaries and wrist activity monitors. Mood and general well-being were assessed using the Brunel Mood Scale (BRUMS) and Visual Analogue Scales (VAS). RESULTS The amount and quality of sleep as assessed by the wrist activity monitors declined during the simulated grand tour. In contrast, self-reported sleep quality improved throughout the study. Cyclists' mood and general well-being as indicated by vigour, motivation, physical and mental state declined during the simulated tour. CONCLUSION Future investigations should examine sleep, mood and well-being during an actual grand tour. Such data could prove instrumental toward understanding the sleep and psychological changes that occur during a grand tour.