Miracle-dz/UniFAR-FTUs huggingface dataset:
BPAP is an effective second‐line therapy for obese patients with OSA failing regular CPAP: A prospective observational cohort study

Continuous positive airway pressure (CPAP) is the most common treatment for obstructive sleep apnoea (OSA), but many patients fail long‐term therapy. Bilevel positive airway pressure (BPAP) is a potential alternative. We hypothesized that BPAP could improve treatment adherence and outcomes in patients who cannot tolerate CPAP.
Higher Emotional Awareness Is Associated With Reduced Pain in Irritable Bowel Syndrome Patients: Preliminary Results

Objective Recent evidence indicates that interventions designed to improve emotional awareness reduce pain in irritable bowel syndrome. This preliminary study sought to determine whether trait emotional awareness is associated with typical pain in patients with irritable bowel syndrome. Methods Healthy volunteers (n = 66) and irritable bowel syndrome patients (n = 50) were asked to self-report their typical levels of pain intensity and complete both the Levels of Emotional Awareness Scale and the Somatization Scale of the Brief Symptom Inventory. Results Levels of Emotional Awareness Scale scores in irritable bowel syndrome patients did not differ from scores in healthy participants; however, higher Levels of Emotional Awareness Scale scores in irritable bowel syndrome patients predicted lower levels of typical pain intensity (r(45) = −. 36, p = . 01, 95% CI [−. 59, −. 08]) and lower levels of somatization (r(45)= −. 31, p = . 03, 95% CI [−. 55, −. 02]). Conclusions This inverse relationship between emotional awareness and both pain and somatization symptoms is consistent with evidence that irritable bowel syndrome patients experience reduced pain from therapies designed to improve emotional awareness. The Levels of Emotional Awareness Scale could potentially be used to identify patients who could benefit from such therapy and could potentially be a moderator of response to efficacious psychological therapies.
Association of ghrelin dynamics with beta cell function in Japanese subjects with normal glucose tolerance

Ghrelin is involved in feeding regulation and energy metabolism and is also known to inhibit insulin secretion (β). However, few clinical studies have demonstrated the relationship between β and ghrelin dynamics. This study tested the hypothesis that, in oral glucose tolerance tests (OGTT), ghrelin dynamics are associated with β.
Daily and bidirectional linkages between pain catastrophizing and spouse responses.

Pain catastrophizing has been shown to predict greater pain and less physical function in daily life for chronic pain sufferers, but its effects on close social partners have received much less attention. The overall purpose of the present study was to examine the extent to which pain catastrophizing is an interpersonal coping strategy that is maladaptive for patients and their spouses. A total of 144 older knee osteoarthritis patients and their spouses completed baseline interviews and a 22-day diary assessment. Multilevel lagged models indicated that, on days when patients reported greater catastrophizing in the morning, their spouses experienced more negative affect throughout the day. In addition, a higher level of punishing responses from the spouse predicted greater pain catastrophizing the next morning, independent of patient pain and negative affect. Multilevel mediation models showed that patients' morning pain catastrophizing was indirectly associated with spouses' negative affect and punishing responses via patients' own greater negative affect throughout the day. There was no evidence that spouses' empathic or solicitous responses either followed or preceded patients' catastrophizing. These findings suggest that cognitive-behavioral interventions that reduce pain catastrophizing should be modified for partnered patients to address dyadic interactions and the spouse's role in pain catastrophizing.
Pancratistatin Inhibits the Growth of Colorectal Cancer Cells by Inducing Apoptosis, Autophagy, and G2/M Cell Cycle Arrest

Background Worldwide, colorectal cancer is ranked as the third most prevalent cancer. The natural compound, pancratistatin, extracted from the spider lily, has previously been shown to target apoptosis in cancer cells lines. This study aimed to investigate the effects of pancratistatin in human colorectal cancer cells in vitro. Material/Methods Human colorectal cancer cell lines, including HTC-15 cells, were compared with a normal human colonic fibroblast cell line, CDD-18Co. Cells were treated with increasing doses of pancratistatin. The MTT assay was used to assess cell viability. Fluorescence microscopy using DAPI and Annexin-V/propidium iodide (PI) was used to detect cell apoptosis. Cell autophagy was detected by electron microscopy. Cell migration was evaluated using a wound healing assay, and Western blot determined the expression levels of cell cycle proteins. Results Pancratistatin inhibited the growth of the colorectal cancer cells with an IC50 ranging from 15–25 μM, but had a limited effect in normal CCD-18Co cells, with an IC50 of >100 μM. Pancratistatin reduced HCT-15 cell migration. Growth inhibition due to pancratistatin was associated with morphological changes of HCT-15 cells and included autophagy and apoptosis, and increased expression the autophagic proteins, LC3II, beclin-1, and Bax. Pancratistatin induced arrest of HCT-15 cells at G2/M of the cell cycle and inhibited phosphorylation of cdc2/cyclin-dependent kinase 1 (CDK1) and Cdc25c and the expression of cyclin B1. Conclusions Pancratistatin inhibited the growth of colorectal cancer cells in vitro by inducing apoptosis, autophagy, and G2/M cell cycle arrest.
Childhood Facial Palsy: Etiologic Factors and Clinical Findings, an Observational Retrospective Study

The purpose of this study was to determine the etiologic factors, clinical characteristics, seasonal distributions, family history, response to corticosteroid therapy, recurrence and residual paralysis rates, and factors affecting these in pediatric facial palsy. Patients aged <18 years diagnosed with acute peripheral facial palsy were included in the study. Demographic data and clinical findings were retrieved from patients’ records. The study was completed with 113 patients. Causes were idiopathic in 74 (65.4%) cases. Complete healing was not achieved in 6 (5.3%) patients, and recurrence was observed in 11 (9.7%). None of the patients with residual paralysis used corticosteroid, but all the patients with recurrence had employed them. We determined that young age may have an adverse impact on complication development and that corticosteroid therapy may be useful in the healing process in idiopathic facial nerve palsy. In conclusion, age may have an adverse impact in idiopathic facial nerve palsy, whereas corticosteroid therapy has a positive effect.
Randomized trial of a dissonance-based transdiagnostic group treatment for eating disorders: An evaluation of target engagement.

OBJECTIVE Test whether a dissonance-based transdiagnostic eating disorder treatment reduces valuation of the thin beauty ideal and high-calorie binge foods, the intervention targets, and eating pathology relative to waitlist controls. METHOD Women with Diagnostic and Statistical Manual of Mental Disorders-5 eating disorders (N = 100) were randomized to an 8-week group-implemented Body Project Treatment (BPT) redesigned to encourage rapid symptom reduction or a waitlist control condition, completing functional MRI paradigms assessing neural response to thin models and binge foods, questionnaires, and diagnostic interviews at pretest and posttest. RESULTS Compared to controls, BPT participants showed greater reductions in responsivity of regions involved in reward valuation (ventromedial prefrontal cortex, dorsolateral prefrontal cortex, caudate) to thin models but not binge foods, pursuit of the thin ideal (d = .72), palatability ratings of binge foods (d = .78), and greater increases in attractiveness ratings of average-weight models (d = .44), the intervention targets. BPT participants also showed significantly greater reductions in body dissatisfaction (d = .83), negative affect (d = .76), and eating disorder symptoms (d = .59), and marginally greater abstinence from binge eating and compensatory behaviors (39% vs. 21%) than controls. CONCLUSIONS Results provide novel evidence that BPT affected the hypothesized intervention targets and reduced variables that are putatively secondary to pursuit of the thin ideal, including body dissatisfaction, negative affect, and eating disorder symptoms. Symptom reductions were smaller than in past trials, suggesting that it may be optimal to reduce valuation of the thin ideal before asking participants to reduce disordered eating behaviors that are used to pursue this ideal. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Rainfall variations in central Indo-Pacific over the past 2,700 y

Significance We present a high-resolution, replicated speleothem δ18O record from Klang Cave in southern Thailand that characterizes rainfall variation in NCIP over the past 2,700 y. This record reveals notable dry climate conditions during the current and past warm periods, similar to the observations in SCIP, which resemble enhanced El Niño-like conditions. Using a newly developed ITCZ shift index, we find a southward shifted ITCZ during the early MWP and the CWP. Our results suggest that detecting changes in rainfall due to anthropogenic forcing still remains indistinguishable from natural variability in the northern tropics. Tropical rainfall variability is closely linked to meridional shifts of the Intertropical Convergence Zone (ITCZ) and zonal movements of the Walker circulation. The characteristics and mechanisms of tropical rainfall variations on centennial to decadal scales are, however, still unclear. Here, we reconstruct a replicated stalagmite-based 2,700-y-long, continuous record of rainfall for the deeply convective northern central Indo-Pacific (NCIP) region. Our record reveals decreasing rainfall in the NCIP over the past 2,700 y, similar to other records from the northern tropics. Notable centennial- to decadal-scale dry climate episodes occurred in both the NCIP and the southern central Indo-Pacific (SCIP) during the 20th century [Current Warm Period (CWP)] and the Medieval Warm Period (MWP), resembling enhanced El Niño-like conditions. Further, we developed a 2,000-y-long ITCZ shift index record that supports an overall southward ITCZ shift in the central Indo-Pacific and indicates southward mean ITCZ positions during the early MWP and the CWP. As a result, the drying trend since the 20th century in the northern tropics is similar to that observed during the past warm period, suggesting that a possible anthropogenic forcing of rainfall remains indistinguishable from natural variability.
Mitochondrial DNA somatic mutation burden and heteroplasmy are associated with chronological age, smoking, and HIV infection

The gradual accumulation of mitochondrial DNA (mtDNA) mutations is implicated in aging and may contribute to the accelerated aging phenotype seen with tobacco smoking and HIV infection. mtDNA mutations are thought to arise from oxidative damage; however, recent reports implicate polymerase γ errors during mtDNA replication. Investigations of somatic mtDNA mutations have been hampered by technical challenges in measuring low‐frequency mutations. We use primer ID‐based next‐generation sequencing to quantify both somatic and heteroplasmic blood mtDNA point mutations within the D‐loop, in 164 women and girls aged 2–72 years, of whom 35% were smokers and 56% were HIV‐positive. Somatic mutations and the occurrence of heteroplasmic mutations increased with age. While transitions are theorized to result from polymerase γ errors, transversions are believed to arise from DNA oxidative damage. In our study, both transition and transversion mutations were associated with age. However, transition somatic mutations were more prevalent than transversions, and no heteroplasmic transversions were observed. We also measured elevated somatic mutations, but not heteroplasmy, in association with high peak HIV viremia. Conversely, heteroplasmy was higher among smokers, but somatic mutations were not, suggesting that smoking promotes the expansion of preexisting mutations rather than de novo mutations. Taken together, our results are consistent with blood mtDNA mutations increasing with age, inferring a greater contribution of polymerase γ errors in mtDNA mutagenesis. We further suggest that smoking and HIV infection both contribute to the accumulation of mtDNA mutations, though in different ways.
Silymarin antiproliferative and apoptotic effects: Insights into its clinical impact in various types of cancer

Silymarin is a complex extract isolated from the plant Silybum marianum, widely known for its prominent antioxidant and hepatoprotective effects, although increasing evidences have reported extraordinary antiproliferative and apoptotic abilities. As a result, several signaling pathways involved in cell cycle control, cell proliferation, and cell death have been deconvoluted as critical mechanisms. In this regard, cyclin and cyclin‐dependent pathways have been the most studied ones. Following that, apoptotic pathways, such as p53, Akt, STAT‐3, Ras, and caspases pathways, have been extensively studied, although other mechanisms involved in inflammation and angiogenesis have also been highlighted as silymarin‐likely targets in cancer therapy. Therefore, the main challenge of this review is to discuss the diverse molecular mechanisms for silymarin antiproliferative and apoptotic effects; most of them largely studied in various types of cancers so far. Clinical trials and combination therapies related to silymarin application in cancer prevention and treatment are presented as well.
A pilot study of pembrolizumab in smoldering myeloma: report of the clinical, immune, and genomic analysis.

Multiple myeloma is, in most patients, an incurable cancer. Its precursors can be identified with routine tests setting the stage for early intervention to prevent active myeloma. We investigated the efficacy and safety of pembrolizumab, an antiprogrammed cell death 1 antibody, in smoldering myeloma patients with intermediate/high risk of progression to symptomatic myeloma. Thirteen patients were treated with a median number of 8 cycles. One patient achieved a stringent complete response with bone marrow next-generation sequencing negativity at 10-4 that is ongoing at 27 months (8%); 11 had stable disease (85%), and 1 progressed (8%). Three patients discontinued therapy due to immune-related adverse events: 2 with transaminitis and 1 due to tubulointerstitial nephritis. Immune profiling of bone marrow samples at baseline showed markers associated with a preexisting immune response in the responder compared with nonresponders and features of increased T-cell exhaustion in nonresponders. Consistent with this, transcriptome sequencing of bone marrow samples at baseline revealed an increased interferon-γ signature in the responder compared with the nonresponders. In summary, our results suggest that smoldering myeloma may be immunogenic in a subset of patients, and therapies that enhance antitumor T-cell responses may be effective in preventing its progression. This trial was registered at www.clinicaltrials. gov as #NCT02603887.
A Randomized Open-Label Evaluation of the Antimalarial Prophylactic Efficacy of Azithromycin-Piperaquine versus Sulfadoxine-Pyrimethamine in Pregnant Papua New Guinean Women

Emerging malaria parasite sulfadoxine-pyrimethamine (SP) resistance has prompted assessment of alternatives for intermittent preventive treatment in pregnancy (IPTp). The objective was to evaluate the tolerability and prophylactic efficacy of azithromycin (AZ) plus piperaquine (PQ) in pregnant women in Papua New Guinea. The study was an open-label, randomized, parallel-group trial. ABSTRACT Emerging malaria parasite sulfadoxine-pyrimethamine (SP) resistance has prompted assessment of alternatives for intermittent preventive treatment in pregnancy (IPTp). The objective was to evaluate the tolerability and prophylactic efficacy of azithromycin (AZ) plus piperaquine (PQ) in pregnant women in Papua New Guinea. The study was an open-label, randomized, parallel-group trial. A total of 122 women (median gestation, 26 weeks [range, 14 to 32 weeks]) were randomized 1:1 to three daily doses of 1 g AZ plus 960 mg PQ tetraphosphate or single-dose SP (4,500 mg sulfadoxine plus 225 mg pyrimethamine), based on computer-generated block randomization. Tolerability was assessed to day 7, and efficacy was assessed to day 42 (when participants were returned to usual care) and at delivery. Data for 119 participants (AZ-PQ, n = 61; SP, n = 58) were analyzed. Both regimens were well tolerated, but AZ-PQ was associated with more gastrointestinal side effects (31%) and dizziness (21%). Eight women (6.7%) were parasitemic at recruitment but all were aparasitemic by 72 h. There were no differences in blood smear positivity rates between AZ-PQ and SP up to day 42 (0% versus 5.2%; relative risk [RR], 0.14 [95% confidence interval [CI], 0.01 to 2.58] [P = 0.18]; absolute risk reduction [ARR], 5.2% [95% CI, −1.3 to 11.6%]) and at the time of delivery (0% versus 8.7%; RR, 0.11 [95% CI, 0.01 to 2.01] [P = 0.14]; ARR, 8.7% [95% CI, −0.2 to 17.6%]). Of 92 women who were monitored to parturition, 89 (97%) delivered healthy babies; there were 3 stillbirths (SP, n = 1; AZ-PQ, n = 2 [twins]). There was a higher live birth weight (mean ± standard deviation) in the AZ-PQ group (3.13 ± 0.42 versus 2.88 ± 0.55 kg [P = 0.016]; mean difference, 0.25 kg [95% CI, 0.02 to 0.48 kg]). AZ-PQ is a promising candidate for IPTp.
Regulation of KIR3DL3 Expression via miRNA

Killer-cell immunoglobulin-like receptor (KIR) 3DL3 is a framework gene present in all human KIR haplotypes. Although the structure of KIR3DL3 is suggestive of an inhibitory receptor, the function of KIR3DL3 has not been demonstrated and cognate ligands have not been identified. KIR3DL3 has been shown to be constitutively expressed at a low RNA level in peripheral blood mononuclear cell (PBMC) and decidual natural kill (NK) cells, but cell surface expression of KIR3DL3 cannot be detected. Accordingly, post-transcriptional regulation of KIR3DL3 should exist. Using bioinformatics analysis, we identified three candidate micro ribonucleic acids (miRNAs; miR-26a-5p, -26b-5p and -185-5p) that potentially regulate KIR3DL3 expression. Luciferase reporter assays utilizing constructs with mutated miRNA-binding sites of miR-26a-5p, -26b-5p and -185-5p in the 3’-untranslated region (3’ UTR) of KIR3DL3 resulted in up-regulation of luciferase activity demonstrating a potential mechanism of gene regulation. Furthermore, knockdown of the same endogenous miRNAs using silencing ribonucleic acid (siRNA) led to induced surface expression of KIR3DL3. In conclusion, we provide a novel mechanism of functional regulation of KIR3DL3 via miRNAs. These findings are relevant in understanding the generation of KIR repertoire and NK cell clonality.
Characterizing the morphology of somatostatin‐expressing interneurons and their synaptic innervation pattern in the barrel cortex of the GFP‐expressing inhibitory neurons mouse

Somatostatin‐expressing (SST+) cells form the second largest subpopulation of neocortical GABAergic neurons that contain diverse subtypes, which participate in layer‐specific cortical circuits. Martinotti cells, as the most abundant subtype of SST+ interneurons, are mainly located in layers II/III and V/VI, and are characterized by dense axonal arborizations in layer I. GFP‐expressing inhibitory neurons (GIN), representing a fraction of mainly upper layer SST+ interneurons in various cortical areas, were recently claimed to include both Martinotti cells and non‐Martinotti cells. This makes it necessary to examine in detail the morphology and synaptic innervation pattern of the GIN cells, in order to better predict their functional implications. In our study, we characterized the neurochemical specificity, somatodendritic morphology, synaptic ultrastructure as well as synaptic innervation pattern of GIN cells in the barrel cortex in a layer‐specific manner. We showed that GIN cells account for 44% of the SST+ interneurons in layer II/III and around 35% in layers IV and Va. There are 29% of GIN cells coexpressing calretinin with 54% in layer II/III, 8% in layer IV, and 13% in layer V. They have diverse somatodendritic configurations and form relatively small synapses across all examined layers. They almost exclusively innervate dendrites of excitatory cells, preferentially targeting distal apical dendrites and apical dendritic tufts of pyramidal neurons in layer I, and rarely target other inhibitory neurons. In summary, our study reveals unique features in terms of the morphology and output of GIN cells, which can help to better understand their diversity and structure–function relationships.
Exploiting Social Media Sensor Networks through Novel Data Fusion Techniques

Unprecedented amounts of data are continuously being generated by sensors (“hard” data) and by humans (“soft” data), and this data needs to be exploited to its full potential. The first step in exploiting this data is determine how the hard and soft data are related to each other. In this project we fuse hard and soft data, using the attributes of each (e.g., time and space), to gain more information about interesting events. Next, we attempt to use social networking textual data to predict the present (i.e., predict that an interesting event is occurring and details about the event) using data mining, machine learning, natural language processing, and text analysis techniques.