Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnosis of susceptibility to malignant hyperthermia with flanking DNA markers.

OBJECTIVE--To define the region on human chromosome 19 carrying the gene for malignant hyperthermia susceptibility and to evaluate the use of flanking DNA markers in diagnosing susceptibility. DESIGN--Prospective molecular genetic linkage studies in a large malignant hyperthermia pedigree. SETTING--Irish malignant hyperthermia testing centre. SUBJECTS--A large Irish malignant hyperthermia pedigree. MAIN OUTCOME MEASURES--Routine diagnosis of susceptibility to malignant hyperthermia with in vitro contracture test on muscle biopsy specimens and genetic linkage between susceptibility and polymorphic DNA markers in a malignant hyperthermia family. RESULTS--Genetic typing of polymorphic DNA markers in a large Irish malignant hyperthermia pedigree generated a lod score of greater than 3 for the marker D19S9 and showed that the gene for susceptibility is flanked by the markers D19S9 and D19S16. These tightly linked flanking markers allowed non-invasive presymptomatic diagnosis of susceptibility in five untested subjects in the large pedigree with an accuracy of greater than 99.7%. CONCLUSIONS--DNA markers flanking the gene for susceptibility to malignant hyperthermia can be used with high accuracy to diagnose susceptibility in subjects in large known malignant hyperthermia pedigrees and may replace the previous in vitro contracture test for diagnosing this inherited disorder in large families with malignant hyperthermia.
Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome.

BACKGROUND The benefits of early continuous neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation remain unclear. METHODS We randomly assigned patients with moderate-to-severe ARDS (defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure [PEEP] of ≥8 cm of water) to a 48-hour continuous infusion of cisatracurium with concomitant deep sedation (intervention group) or to a usual-care approach without routine neuromuscular blockade and with lighter sedation targets (control group). The same mechanical-ventilation strategies were used in both groups, including a strategy involving a high PEEP. The primary end point was in-hospital death from any cause at 90 days. RESULTS The trial was stopped at the second interim analysis for futility. We enrolled 1006 patients early after the onset of moderate-to-severe ARDS (median, 7.6 hours after onset). During the first 48 hours after randomization, 488 of the 501 patients (97.4%) in the intervention group started a continuous infusion of cisatracurium (median duration of infusion, 47.8 hours; median dose, 1807 mg), and 86 of the 505 patients (17.0%) in the control group received a neuromuscular blocking agent (median dose, 38 mg). At 90 days, 213 patients (42.5%) in the intervention group and 216 (42.8%) in the control group had died before hospital discharge (between-group difference, -0.3 percentage points; 95% confidence interval, -6.4 to 5.9; P = 0.93). While in the hospital, patients in the intervention group were less physically active and had more adverse cardiovascular events than patients in the control group. There were no consistent between-group differences in end points assessed at 3, 6, and 12 months. CONCLUSIONS Among patients with moderate-to-severe ARDS who were treated with a strategy involving a high PEEP, there was no significant difference in mortality at 90 days between patients who received an early and continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets. (Funded by the National Heart, Lung, and Blood Institute; ROSE ClinicalTrials.gov number, NCT02509078.).
Activation of f‐channels by cAMP analogues in macropatches from rabbit sino‐atrial node myocytes

1 The action of the two diastereometric phosphorothioate derivatives of cAMP, Rp‐cAMPs and Sp‐cAMPs, was investigated on hyperpolarization‐activated ‘pacemaker’ current (if) recorded in inside‐out macropatches from rabbit sino‐atrial (SA) node myocytes. 2 When superfused on the intracellular side of f‐channels at the concentration of 10 μm, both cAMP derivatives accelerated if activation; their action was moderately less pronounced than that due to the same concentration of cAMP. 3 The measurement of the if conductance‐voltage relation by voltage ramp protocols indicated that both cAMP analogues shift the activation curve of if to more positive voltages with no change in maximal (fully activated) conductance. 4 Dose–response relationships of the shift of the if activation curve showed that both Rp‐cAMPs and Sp‐cAMPs act as agonists in the cAMP‐dependent direct f‐channel activation. Fitting data to the Hill equation resulted in maximal shifts of 9.6 and 9.5 mV, apparent dissociation constants of 0.82 and 5.4 μm, and Hill coefficients of 0.82 and 1.12 for Sp‐cAMPs and Rp‐cAMPs, respectively. 5 The activating action of Rp‐cAMPs, a known antagonist of cAMP in the activation of cAMP‐dependent protein kinase, confirms previously established evidence that f‐channel activation does not involve phosphorylation. These results also suggest that the cAMP binding site of f‐channels may be structurally similar to the cyclic nucleotide binding site of olfactory receptor channels.
Reducing distress in cancer patients—A preliminary evaluation of short‐term coaching by expert volunteers

1 | BACKGROUND Recently, the conceptualization of cancer‐related distress, and consequently of psychosocial interventions adequately dealing with this distress, is shifting. The prevailing idea that distress results from an intense emotional experience of a psychological, social, and/or spiritual nature ignores the fundamental adaptive value of emotions. Instead, cancer‐related emotions may be adaptive—potentially facilitating adjustment to cancer—if they (despite their intensity) alert, motivate, and prepare people to deal with the event of cancer and maladaptive if they perpetuate and linger across time, are extreme or instable, or interfere with one's ability to cope. While people experiencing maladaptive emotions might be in need of specialist mental health care such as psychotherapy or pharmacotherapy, people experiencing (intense) adaptive emotions may instead benefit from nonspecialized emotion support by relatives, friends, or primary caregivers, encouraging awareness, reflection, and self‐management. This pilot study evaluates innovative short‐term coaching sessions, conducted by expert volunteers with a background in the field of psychosocial oncology, that form an intermediary between specialist mental health care and one's private support system of relatives and friends.
Differential regulation of interleukin‐12 p40 and p35 induction via Erk mitogen‐activated protein kinase‐dependent and ‐independent mechanisms and the implications for bioactive IL‐12 and IL‐23 responses

Bioactive interleukin (IL)‐12 is a 70 000‐molecular weight (MW) heterodimeric cytokine comprising p40 and p35 chains. However, p40 can also form homodimers that antagonize bioactive IL‐12 or heterodimerize with p19 to form IL‐23, which exhibits overlapping yet distinct functions to that of IL‐12. We now define distinct signalling mechanisms that regulate lipopolysaccharide (LPS)‐mediated induction of IL‐12 p40 and p35 in macrophages and which may therefore provide therapeutic targets for precise and specific fine‐tuning of cytokine responses. Thus, whilst LPS‐induced p38 mitogen‐activated protein kinase (MAPkinase) activation is required for the induction of both p40 and p35 subunits, Erk MAPkinase signalling mediates negative feedback regulation of p40, but not p35, production. Such Erk MAPkinase activation is downstream of calcium influx and targets LPS‐induced IL‐12 p40 transcription by suppressing the synthesis of the transcription factor, interferon regulatory factor‐1 (IRF‐1). In contrast, negative regulation of the p35 subunit of IL‐12 occurs via a calcium‐dependent, but Erk‐independent, mechanism, which is likely to involve nuclear factor (NF)‐κB signalling. Finally, the importance of both Erk and p38 MAPkinases in differentially regulating IL‐12 p40 and p35 production is underscored by each being targeted by ES‐62, a product secreted by parasitic filarial nematodes to polarize the immune system towards an anti‐inflammatory phenotype conducive to their survival.
Following in the footsteps of tobacco and alcohol? Stakeholder discourse in UK newspaper coverage of the Soft Drinks Industry Levy

Abstract Objective: In politically contested health debates, stakeholders on both sides present arguments and evidence to influence public opinion and the political agenda. The present study aimed to examine whether stakeholders in the Soft Drinks Industry Levy (SDIL) debate sought to establish or undermine the acceptability of this policy through the news media and how this compared with similar policy debates in relation to tobacco and alcohol industries. Design: Quantitative and qualitative content analysis of newspaper articles discussing sugar-sweetened beverage (SSB) taxation published in eleven UK newspapers between 1 April 2015 and 30 November 2016, identified through the Nexis database. Direct stakeholder citations were entered in NVivo to allow inductive thematic analysis and comparison with an established typology of industry stakeholder arguments used by the alcohol and tobacco industries. Setting: UK newspapers. Participants: Proponents and opponents of SSB tax/SDIL cited in UK newspapers. Results: Four hundred and ninety-one newspaper articles cited stakeholders’ (n 287) arguments in relation to SSB taxation (n 1761: 65 % supportive and 35 % opposing). Stakeholders’ positions broadly reflected their vested interests. Inconsistencies arose from: changes in ideological position; insufficient clarity on the nature of the problem to be solved; policy priorities; and consistency with academic rigour. Both opposing and supportive themes were comparable with the alcohol and tobacco industry typology. Conclusions: Public health advocates were particularly prominent in the UK newspaper debate surrounding the SDIL. Advocates in future policy debates might benefit from seeking a similar level of prominence and avoiding inconsistencies by being clearer about the policy objective and mechanisms.
The effect of beta‐amyloid on face processing in young and old adults: A multivariate analysis of the BOLD signal

The recent ability to measure in vivo beta‐amyloid (Aβ), a marker of Alzheimer's disease (AD), has led to an increased focus on the significance of Aβ deposition in clinically normal adults. Evidence suggests that healthy adults with elevated cortical Aβ show differences in neural activity associated with memory encoding—specifically encoding of face stimuli. Here, we examined if Aβ deposition in clinically normal adults was related to differences in neural activity in ventral visual cortex during face viewing. Our sample included 23 high‐Aβ older adults, 23 demographically matched low‐Aβ older adults, and 16 young adults. Participants underwent cognitive testing, Aβ positron emission tomography imaging with 18F‐Florbetapir, and functional magnetic resonance imaging to measure neural activity while participants passively viewed photographs of faces. Using barycentric discriminant analysis—a between‐groups classification technique—we found that patterns of neural activity in the left fusiform gyrus, a region highly responsive to faces, distinguished Aβ status of participants. Older adults with elevated Aβ were characterized by decreased activity in left fusiform compared to Aβ‐negative older adults. Further, we found that the degree to which older adults expressed decreased fusiform activity was related to worse performance on tasks of processing speed. Our results provide unique evidence that, in addition to previously studied memory and default regions, decreased neural activity in a region important for face perception was associated with elevated Aβ and may be an early manifestation of AD. Hum Brain Mapp 36:2514–2526, 2015. © 2015 Wiley Periodicals, Inc.
Self‐control in crows, parrots and nonhuman primates

Abstract Self‐control is critical for both humans and nonhuman animals because it underlies complex cognitive abilities, such as decision‐making and future planning, enabling goal‐directed behavior. For instance, it is positively associated with social competence and life success measures in humans. We present the first review of delay of gratification as a measure of self‐control in nonhuman primates, corvids (crow family) and psittacines (parrot order): disparate groups that show comparable advanced cognitive abilities and similar socio‐ecological factors. We compare delay of gratification performance and identify key issues and outstanding areas for future research, including finding the best measures and drivers of delayed gratification. Our review therefore contributes to our understanding of both delayed gratification as a measure of self‐control and of complex cognition in animals. This article is categorized under: Cognitive Biology > Evolutionary Roots of Cognition Psychology > Comparative Psychology
Polyketides from the Mangrove-Derived Endophytic Fungus Cladosporium cladosporioides

Five new polyketides, namely, 5R-hydroxyrecifeiolide (1), 5S-hydroxyrecifeiolide (2), ent-cladospolide F (3), cladospolide G (4), and cladospolide H (5), along with two known compounds (6 and 7), were isolated from the endophytic fungal strain Cladosporium cladosporioides MA-299 that was obtained from the leaves of the mangrove plant Bruguiera gymnorrhiza. The structures of these compounds were established by extensive analysis of 1D/2D NMR data, mass spectrometric data, ECDs and optical rotations, and modified Mosher’s method. The structures of 3 and 6 were confirmed by single-crystal X-ray diffraction analysis and this is the first time for reporting the crystal structures of these two compounds. All of the isolated compounds were examined for antimicrobial activities against human and aquatic bacteria and plant pathogenic fungi as well as enzymatic inhibitory activities against acetylcholinesterase. Compounds 1–4, 6, and 7 exhibited antimicrobial activity against some of the tested strains with MIC values ranging from 1.0 to 64 μg/mL, while 3 exhibited enzymatic inhibitory activity against acetylcholinesterase with the IC50 value of 40.26 μM.
ACCLIMATION TO LOW TEMPERATURE OF TWO ARTHROSPIRA PLATENSIS (CYANOBACTERIA) STRAINS INVOLVES DOWN‐REGULATION OF PSII AND IMPROVED RESISTANCE TO PHOTOINHIBITION 1

This study aimed to compare the ability of two Arthrospira platensis (Nordst.) Gomont strains, M2 and Kenya, isolated from two different habitats, to acclimate to low temperature (15°C). Both strains had similar growth rates at 30°C, but once acclimated to low temperature, M2 showed a greater decline in growth (59% vs. 41% in the Kenya strain). We suggest that the Kenya strain acclimated better to low temperature by down‐regulating its photosynthetic activity through (i) decreasing antenna size and thus reducing energy flux into the photosystems; (ii) decreasing reaction center density (RC/CSX) and the performance index, thus decreasing the trapping probability and electron transport rate while maintaining electron transport probability for electron transport beyond QA− unchanged; (iii) increasing the energy dissipation flux. In contrast, the M2 strain showed no difference in antenna size and exhibited a much lower decrease in RC/CSX and a lower dissipation rate. Hence, the Kenya strain minimized potential damage on the acceptor side of PSII compared to the M2 cells. Furthermore, acclimation to low temperature was accompanied by an improved mechanism for handling excess energy resulting in an enhanced ability of the Kenya strain to rapidly repair damaged PSII RCs and withstand a high photon flux density (HPFD) stress; this finding might be defined as a cross‐adaptation phenomenon. This study may provide a tool to identify strains suitable for outdoor mass‐production in different regions characterized by different climate conditions.
Urinary and Serum Biomarkers for Prediction of Acute Kidney Injury in Patients Undergoing Liver Transplantation

Acute kidney injury (AKI) is a frequent and serious complication of orthotopic liver transplantation (OLT), with a significant impact on mortality, graft survival, and chronic kidney disease. Currently, the diagnosis of AKI is based on changes in serum creatinine, which is a late marker, usually rising when there is already significant damage to the renal parenchyma. During the last 2 decades, various biomarkers have been studied in many clinical situations, mostly after cardiac surgery, in drug-induced AKI, or in sepsis. The present article summarizes the data on those biomarkers that have been evaluated for the prediction of AKI in patients undergoing OLT.
Spending for Advanced Cancer Diagnoses: Comparing Recurrent Versus De Novo Stage IV Disease.

PURPOSE Spending for patients with advanced cancer is substantial. Past efforts to characterize this spending usually have not included patients with recurrence (who may differ from those with de novo stage IV disease) or described which services drive spending. METHODS Using SEER-Medicare data from 2008 to 2013, we identified patients with breast, colorectal, and lung cancer with either de novo stage IV or recurrent advanced cancer. Mean spending/patient/month (2012 US dollars) was estimated from 12 months before to 11 months after diagnosis for all services and by the type of service. We describe the absolute difference in mean monthly spending for de novo versus recurrent patients, and we estimate differences after controlling for type of advanced cancer, year of diagnosis, age, sex, comorbidity, and other factors. RESULTS We identified 54,982 patients with advanced cancer. Before diagnosis, mean monthly spending was higher for recurrent patients (absolute difference: breast, $1,412; colorectal, $3,002; lung, $2,805; all P < .001), whereas after the diagnosis, it was higher for de novo patients (absolute difference: breast, $2,443; colorectal, $4,844; lung, $2,356; all P < .001). Spending differences were driven by inpatient, physician, and hospice services. Across the 2-year period around the advanced cancer diagnosis, adjusted mean monthly spending was higher for de novo versus recurrent patients (spending ratio: breast, 2.39 [95% CI, 2.05 to 2.77]; colorectal, 2.64 [95% CI, 2.31 to 3.01]; lung, 1.46 [95% CI, 1.30 to 1.65]). CONCLUSION Spending for de novo cancer was greater than spending for recurrent advanced cancer. Understanding the patterns and drivers of spending is necessary to design alternative payment models and to improve value.
Exploration of trauma, dissociation, maladaptive schemas and auditory hallucinations in a French sample

ABSTRACT Objectives: The main goal of the present study was to explore the associations between several key variables that have been shown to partially mediate the link between specific trauma exposure and auditory hallucinations (AH), that is, maladaptive schemas and dissociation in the general population. Methods: In total, 425 voluntary participants were recruited from the general population and completed online the Childhood Trauma Questionnaire, the Young schema questionnaire, the Dissociative Experiences Scale, and the Launay–Slade Hallucination Scale. Data were analysed using Partial Least Squares Structural Equation Modelling. Results: Our model showed that: (1) sexual and emotional abuse impact on AH both through the effect of maladaptive schemas and dissociation; (2) physical abuse impact on AH only through the effect of dissociation. More specifically, we found that four maladaptive schemas impact on AH: Abandonment, Vulnerability, Self-sacrifice and Subjugation. Conclusions: Overall, our findings indicate that specific early maladaptive schemas may play a fundamental role in the association between exposure to trauma and auditory hallucination together with dissociation symptoms in the general population. Consequently, our study suggest considering maladaptive schemas as an important therapeutic target when working with individuals experiencing AH with or without a psychiatry disorder.
Symptom Clusters and Influencing Factors in Children With Acute Leukemia During Chemotherapy

Background: Acute leukemia is the most common malignancy in childhood. Identification of symptom clusters and their influencing factors in children with acute leukemia may improve the management of symptoms. Objective: The aims of this study were to investigate symptom clusters in children with acute leukemia during chemotherapy and analyze the factors influencing their severity. Methods: A cross-sectional survey was administered to 159 Chinese children with acute leukemia during chemotherapy. A demographic questionnaire and the Memorial Symptom Assessment Scale 10-18 were completed by the patients and their parents. Exploratory factor analysis was used to identify symptom clusters. Univariate analyses and multiple linear regression analyses were performed to analyze the factors affecting symptom clusters. Results: Six clusters were identified, including gastrointestinal cluster, emotional cluster, head-related cluster, self-image disorder cluster, skin itching/irritation cluster, and somatic cluster. Factors influencing the severity of symptom clusters included age, gender, stage of chemotherapy, and medical reimbursement. Conclusions: There are multiple symptom clusters in children with acute leukemia during chemotherapy. Medical care staff should manage symptoms from the perspective of symptom cluster and carry out personalized interventions according to factors influencing these clusters. Implications for Practice: The ability to predict symptom clusters in children with acute leukemia undergoing chemotherapy may assist with optimal clinical decision making in order to alleviate the symptom burden and improve children’s quality of life.
Loss of molars in periodontally treated patients: a retrospective analysis five years or more after active periodontal treatment.

OBJECTIVES Evaluation of tooth loss in molars and prognostic factors for molar survival. MATERIAL AND METHODS Five hundred and five molars in 71 patients (mean age 46 years; 40 females) were evaluated. The following inclusion criteria were required: periodontal therapy of at least one molar, at least 5 years of supportive periodontal therapy, and baseline assessment of furcation involvement (FI). RESULTS At baseline 200 of 505 molars exhibited no FI, 116 degree I, 122 degree II, and 67 degree III FI. Twenty-seven molars did not receive periodontal treatment; 127 molars were subjected to non-surgical therapy, and 227 to flap surgery. Tunnel preparation was performed on 14 molars, root resection on 20, regenerative therapy on 57 teeth, and 33 molars were extracted. During the average follow-up period of 107 months 38 molars were lost additionally. Molars with degree III FI had the highest mortality. A multi-level proportional hazard model revealed smoking, baseline bone loss, number of molars left, and degree III FI as risk factors influencing the retention time of molars. CONCLUSION Overall periodontal therapy results in a good prognosis of molars. Degree III FI leads to a significant deterioration of prognosis. Beyond FI smoking, baseline bone loss, and number of molars left influence molar survival.