Miracle-dz/UniFAR-FTUs huggingface dataset:
Incidence and Management of Cardiovascular Risk Factors in Psoriatic Arthritis and Rheumatoid Arthritis: A Population‐Based Study

To examine the prevalence and incidence of cardiovascular (CV) risk factors, including hypertension, hyperlipidemia, diabetes mellitus (DM), and obesity among patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA) compared to the general population, and to examine the treatment of incident CV risk factors in PsA and RA compared to controls.
Beta‐blockers in patients with advanced liver disease: Has the dust settled?

Nonselective beta‐blockers (NSBBs) have been the backbone for the treatment of portal hypertension in cirrhosis for the last 3 decades. A publication in 2010 of a prospective observational study suggested that NSBBs could increase mortality in patients with refractory ascites. This opened a controversy about the safety and efficacy of NSBBs in patients with advanced liver disease and led to the publication of a large corpus of observational data assessing the safety of NSBBs in patients with advanced cirrhosis. In this article, we briefly review the clinical pharmacology of NSBBs, the pathophysiological basis for the underlying benefits and harms of NSBBs in advanced cirrhosis, and the evidence in favor and against the use of NSBBs in specific scenarios. Finally, we summarize the current recommendations and propose areas of opportunity for future research. Liver Transplantation 23 1058–1069 2017 AASLD.
Pars-plana fluid aspiration for positive vitreous cavity pressure in anterior segment surgeries

Positive vitreous pressure due to misdirection of aqueous or choroidal effusion leads to shallowing of the anterior chamber (AC) before or during anterior segment surgeries. This shallow AC if not addressed makes surgery difficult and increases the risk of surgical complications. Methods to prevent and manage this condition described in literature are not without problems. We describe a minimally invasive technique of passing a 30G needle through the pars-plana to aspirate misdirected fluid from vitreous cavity either as a prophylaxis just before surgery or during it, thereby decreasing positive vitreous pressure. This technique, used in 12 eyes, seems to be effective in patients with angle-closure glaucoma, malignant glaucoma, and per-operative sudden increase in vitreous pressure during surgery. Small-incision surgeries are ideally suited for this procedure. This minimally invasive technique is simple to perform and complications are unlikely to be more than what is seen with intravitreal injections.
Domain adaptation from multiple sources via auxiliary classifiers

We propose a multiple source domain adaptation method, referred to as Domain Adaptation Machine (DAM), to learn a robust decision function (referred to as target classifier) for label prediction of patterns from the target domain by leveraging a set of pre-computed classifiers (referred to as auxiliary/source classifiers) independently learned with the labeled patterns from multiple source domains. We introduce a new data-dependent regularizer based on smoothness assumption into Least-Squares SVM (LS-SVM), which enforces that the target classifier shares similar decision values with the auxiliary classifiers from relevant source domains on the unlabeled patterns of the target domain. In addition, we employ a sparsity regularizer to learn a sparse target classifier. Comprehensive experiments on the challenging TRECVID 2005 corpus demonstrate that DAM outperforms the existing multiple source domain adaptation methods for video concept detection in terms of effectiveness and efficiency.
Conditional knockin of Dnmt3a R878H initiates acute myeloid leukemia with mTOR pathway involvement

Significance DNMT3A is a critical epigenetic modifier and tumor suppressor in the hematopoietic system. This gene is frequently mutated in hematopoietic malignancies, including acute myeloid leukemia (AML), with Dnmt3a R878H being the most common mutant. By using a conditional knockin approach, this study shows that Dnmt3a R878H is sufficient to initiate AML and recapitulate human leukemic features in mice. The leukemia-initiating cells are enriched in hematopoietic stem/progenitor cells. Through gene expression profiling, DNA methylation and histone modification analysis, and functional tests on important regulators for cell proliferation and differentiation in an animal model, this study has not only discovered mTOR pathway activation as a key player in the disease mechanism but also revealed the potential therapeutic effects of mTOR inhibition on DNMT3A mutation-related leukemia. DNMT3A is frequently mutated in acute myeloid leukemia (AML). To explore the features of human AML with the hotspot DNMT3A R882H mutation, we generated Dnmt3a R878H conditional knockin mice, which developed AML with enlarged Lin−Sca1+cKit+ cell compartments. The transcriptome and DNA methylation profiling of bulk leukemic cells and the single-cell RNA sequencing of leukemic stem/progenitor cells revealed significant changes in gene expression and epigenetic regulatory patterns that cause differentiation arrest and growth advantage. Consistent with leukemic cell accumulation in G2/M phase, CDK1 was up-regulated due to mTOR activation associated with DNA hypomethylation. Overexpressed CDK1-mediated EZH2 phosphorylation resulted in an abnormal trimethylation of H3K27 profile. The mTOR inhibitor rapamycin elicited a significant therapeutic response in Dnmt3aR878H/WT mice.
CD16A Activation of NK Cells Promotes NK Cell Proliferation and Memory-Like Cytotoxicity against Cancer Cells

Pre-activation via CD16A, a potent cytotoxicity receptor engaged by therapeutic bispecific antibodies, promoted NK cell proliferation and expansion. These CD16A-experienced NK cells exerted memory-like enhanced cytotoxicity and IFNγ production upon restimulation with tumor cells. CD16A is a potent cytotoxicity receptor on human natural killer (NK) cells, which can be exploited by therapeutic bispecific antibodies. So far, the effects of CD16A-mediated activation on NK cell effector functions beyond classical antibody-dependent cytotoxicity have remained poorly elucidated. Here, we investigated NK cell responses after exposure to therapeutic antibodies such as the tetravalent bispecific antibody AFM13 (CD30/CD16A), designed for the treatment of Hodgkin lymphoma and other CD30+ lymphomas. Our results reveal that CD16A engagement enhanced subsequent IL2- and IL15-driven NK cell proliferation and expansion. This effect involved the upregulation of CD25 (IL2Rα) and CD132 (γc) on NK cells, resulting in increased sensitivity to low-dose IL2 or to IL15. CD16A engagement initially induced NK cell cytotoxicity. The lower NK cell reactivity observed 1 day after CD16A engagement could be recovered by reculture in IL2 or IL15. After reculture in IL2 or IL15, these CD16A-experienced NK cells exerted more vigorous IFNγ production upon restimulation with tumor cells or cytokines. Importantly, after reculture, CD16A-experienced NK cells also exerted increased cytotoxicity toward different tumor targets, mainly through the activating NK cell receptor NKG2D. Our findings uncover a role for CD16A engagement in priming NK cell responses to restimulation by cytokines and tumor cells, indicative of a memory-like functionality. Our study suggests that combination of AFM13 with IL2 or IL15 may boost NK cell antitumor activity in patients by expanding tumor-reactive NK cells and enhancing NK cell reactivity, even upon repeated tumor encounters. Cancer Immunol Res; 6(5); 517–27. ©2018 AACR.
Attentional Avoidance of Emotional Stimuli in Postpartum Women With Childhood History of Maltreatment and Difficulties With Emotion Regulation

Child abuse and neglect can lead to difficulties regulating responses to threatening and emotional situations. Exposure to childhood maltreatment has been linked to conflicting findings of both attention biases toward and away from threat-related information. The aim of the current study was to investigate whether emotion regulation moderated the association between history of childhood maltreatment and attention bias in a sample of postpartum women. One hundred forty women participated in the study at 7 months postpartum. Selective attention to both negative emotional and attachment-related negative emotional words was assessed using the Emotional Stroop task. The latent variable of difficulties with emotion regulation was found to significantly moderate the association between history of childhood maltreatment and attention bias to both negative emotional (&bgr; = −0.15, t = −2.04, p < .05) and attachment-related negative emotional stimuli (&bgr; = −0.16, t = −2.98, p < .05). In women with higher childhood trauma scores, those with greater emotion regulation difficulties displayed decreased attention to negative emotional and attachment-related emotional stimuli. In contrast, women reporting higher exposure to childhood maltreatment with greater emotion regulation capacity, displayed increased attention toward negative emotional and attachment-related emotional stimuli. This study provides evidence for attentional avoidance of emotional material in postpartum women with greater experiences of maltreatment and difficulties with emotion regulation. As the postpartum period has significant implications for maternal well-being and infant development, these findings are discussed in terms of maternal responsiveness, sensitivity to threat, and the intergenerational transmission of risk.
Is Admission to the Intensive Care Unit Associated With Chronic Opioid Use? A 4-Year Follow-Up of Intensive Care Unit Survivors

Purpose: To describe opioid use before and after intensive care unit (ICU) admission and to identify factors associated with chronic opioid use upto 4 years after ICU discharge. Methods: Retrospective review of adult patients admitted to the ICU at a tertiary care center between January 1, 2005, to December 31, 2008. We defined “nonuser,” “intermittent,” and “chronic” opioid status by abstinence, use in <70%, and >70% of days for a given time period, respectively. We assessed opioid use at 3 months prior to ICU admission, at discharge, and annually for upto 4 years following ICU discharge. Results: A total of 2595 ICU patients were included for surgical (48.6%), medical (38.4%), and undetermined (13%) indications. The study population included both elective (26.9%) and emergent (73.1%) admissions. Three months prior to ICU admission, 76.9% were nonusers, 16.9% used opioids intermittently, and 6.2% used opioids chronically. We found an increase in nonuser patients from 87.8% in the early post-ICU period to 95.6% at 48-month follow-up. Consequently, intermittent and chronic opioid use dropped to 8.6% and 3.6% at discharge and 2.6% and 1.8% at 48-month follow-up, respectively. Prolonged hospital length of stay was associated with chronic opioid use. Conclusion: Admission to ICU and duration of ICU stay were not associated with chronic opioid use.
Modeling startle eyeblink electromyogram to assess fear learning

Abstract Pavlovian fear conditioning is widely used as a laboratory model of associative learning in human and nonhuman species. In this model, an organism is trained to predict an aversive unconditioned stimulus from initially neutral events (conditioned stimuli, CS). In humans, fear memory is typically measured via conditioned autonomic responses or fear‐potentiated startle. For the latter, various analysis approaches have been developed, but a systematic comparison of competing methodologies is lacking. Here, we investigate the suitability of a model‐based approach to startle eyeblink analysis for assessment of fear memory, and compare this to extant analysis strategies. First, we build a psychophysiological model (PsPM) on a generic startle response. Then, we optimize and validate this PsPM on three independent fear‐conditioning data sets. We demonstrate that our model can robustly distinguish aversive (CS+) from nonaversive stimuli (CS‐, i.e., has high predictive validity). Importantly, our model‐based approach captures fear‐potentiated startle during fear retention as well as fear acquisition. Our results establish a PsPM‐based approach to assessment of fear‐potentiated startle, and qualify previous peak‐scoring methods. Our proposed model represents a generic startle response and can potentially be used beyond fear conditioning, for example, to quantify affective startle modulation or prepulse inhibition of the acoustic startle response.
Prognostic significance of tumor‐infiltrating lymphocytes in nondisseminated nasopharyngeal carcinoma: A large‐scale cohort study

The American Joint Committee on Cancer (AJCC) staging system is inadequate for an accurate prognosis in nasopharyngeal carcinoma (NPC). Thus, new biomarkers are under intense investigation. Here, we investigated whether the density of TILs could predict prognosis in NPC. First, we used 1490 cases of nasopharyngeal carcinoma samples from two independent cohorts to evaluate the density and distribution of tumor‐infiltrating lymphocytes (TILs). Second, in one cohort, we assessed associations between TILs and clinical outcomes in 593 randomly selected samples (defined as the training set) and validated findings in the remaining 593 samples (defined as the validation set). Furthermore, we confirmed the prognostic value of TILs in a second independent cohort of 304 cases (defined as the independent set). Based on multivariable Cox regression analysis, we also established an effective prognostic nomogram including TILs to improve accuracy in predicting disease‐free survival (DFS) for patients with nondisseminated NPC. We found that high TILs in the training set were significantly associated with favorable DFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28–0.58, p < 0.001], overall survival (OS, HR 0.42, 95% CI 0.27–0.64, p < 0.001), distant metastasis‐free survival (DMFS, HR 0.37, 95% CI 0.23–0.58, p < 0.001) and local‐regional recurrent free survival (LRRFS, HR 0.43, 95% CI 0.25–0.73, p = 0.002). Multivariate analysis showed that TILs are an independent prognostic indicator for DFS in all cohorts. In summary, this study indicated that TILs may reflect the immunological heterogeneity of NPC and could represent a new prognostic biomarker.
Delayed methotrexate elimination: Incidence, interaction with antacid drugs, and clinical consequences?

The aim of this retrospective cohort study was to investigate the incidence of delayed methotrexate elimination in patients treated with high‐dose methotrexate (≥1 g/m2) for haematological malignancy and to identify the impact of interacting drugs, especially proton‐pump inhibitors (PPIs) and ranitidine. All patients treated with high‐dose methotrexate over a 6 year period in the haematology department of the Lyon Sud University Hospital (Hospices Civils de Lyon, France) were included. Potential risk factors for delayed methotrexate elimination were tested in a generalized linear model by univariate analysis: patient age, gender, methotrexate dose, administration of PPI or ranitidine, and concomitant nephrotoxic drugs. A total of 412 cycles of methotrexate were administered to 179 patients. Proton‐pump inhibitors were co‐administered with methotrexate in 127 cycles and ranitidine in 192 cycles. Ninety‐three cycles included no antacid drugs. A total of 918 plasma methotrexate assays were performed. Methotrexate concentrations were checked at 24 hours in 92% of cycles. Delayed methotrexate elimination was observed in 20.9% of cycles. A total of 63 cycles with delayed methotrexate elimination were only identified on plasma methotrexate measures at 72 hours: ie, plasma methotrexate was in the normal range at 24 and 48 hour post injection. Use of PPI/ranitidine or no antacid drugs did not increase risk of delayed elimination, with respectively delayed methotrexate elimination in 20.5%, 21.9%, and 19.4% of cycles (P = .89). Impaired baseline creatinine clearance showed significant association in univariate analysis. Fifteen patients showed grade 1 acute kidney injury, 1 grade 2, 2 grade 3, and none grade 4. For half of these cases, delayed methotrexate elimination was observed and the 2 grade 3 events appeared in patients treated with PPIs. This retrospective study suggests that there is no association between concomitant use of proton‐pump inhibitors (pantoprazole and esomeprazole) or ranitidine and delayed methotrexate elimination.
Ginsenoside Rh2 inhibits proliferation and migration of medulloblastoma Daoy by down‐regulation of microRNA‐31

This study aimed to investigate the effects of ginsenoside Rh2 on proliferation, apoptosis, and migration of the human medulloblastoma cell line Daoy, as well as to explore the potential mechanisms of the effects. The human medulloblastoma cell line Daoy was cultured in vitro and treated with or without ginsenoside Rh2. CCK‐8 assay was performed to investigate the effect of Rh2 on cell survival using a cell counting Kit‐8. Cell proliferation was assessed by BrdU assay. Cell apoptosis was determined using flow cytometry analysis. Cell migration was detected using a modified two‐chamber migration assay. MiR‐31 mimic and the NC control were transfected into Daoy cells and detected by qRT‐PCR. The expression of Wnt3a, Wnt5a, and β‐catein was detected by Western blot analysis. Rh2 efficiently suppressed the proliferation and migration, and promoted the apoptosis of Daoy cells. Additionally, Rh2 could down‐regulate miR‐31. miR‐31 overexpression reversed the effects of Rh2 on proliferation, apoptosis and migration of Daoy cells, and activated the Wnt/β‐catein signaling pathways in Daoy cells. Rh2 could inhibit the proliferation and migration, and induce apoptosis of Daoy medulloblastoma cells through down‐regulation of miR‐31 to inactivate the Wnt/β‐catein signaling pathway. Therefore, Rh2 may have a utility in clinical applications for the treatment of medulloblastoma.
Prognostic enrichment design in clinical trials for autosomal dominant polycystic kidney disease: the HALT-PKD clinical trial

Background Patients with mild autosomal dominant polycystic kidney disease (ADPKD) are less likely to be informative in randomized clinical trials (RCTs). We previously developed an imaging classification of ADPKD (typical diffuse cyst distribution Class 1A-E and atypical cyst distribution Class 2) for prognostic enrichment design in RCTs. We investigated whether using this classification would have increased the power to detect a beneficial treatment effect of rigorous blood pressure (BP) control on HALT-PKD participants with early disease (Study A). Methods Post hoc analysis of the early disease HALT-PKD study, an RCT that studied the effect of rigorous versus standard BP control on rates of total kidney volume (TKV) increase and estimated glomerular filtration rate (eGFR) decline in ADPKD patients with eGFR >60 mL/min/1.73 m2. Results Five hundred and fifty-one patients were classified by two observers (98.2% agreement) into Class 1A (6.2%), 1B (20.3%), 1C (34.1%), 1D (22.1%), 1E (11.8%) and 2 (5.4%). The TKV increase and eGFR decline became steeper from Class 1A through 1E. Rigorous BP control had been shown to be associated with slower TKV increase, without a significant overall effect on the rate of eGFR decline (faster in the first 4 months and marginally slower thereafter). Merging Classes 1A and 2 (lowest severity), 1B and 1C (intermediate severity) and 1D and 1E (highest severity) detected stronger beneficial effects on TKV increase and eGFR decline in Class 1D and E with a smaller number of patients. Conclusions Strategies for prognostic enrichment, such as image classification, should be used in the design of RCTs for ADPKD to increase their power and reduce their cost.
Bilateral Cochlear Implantation Versus Bimodal Hearing in Patients With Functional Residual Hearing: A Within-subjects Comparison of Audiologic Performance and Quality of Life.

OBJECTIVE Evaluate performance and quality of life changes after sequential bilateral cochlear implantation in patients with preoperative residual hearing functioning in a bimodal hearing configuration. STUDY DESIGN Retrospective analysis using within-subjects repeated measures design. SETTING Tertiary otologic center. PATIENTS Twenty-two adult patients with bilateral sensorineural hearing loss who used bimodal hearing before second cochlear implant (CI) meeting the following criteria: 1) preoperative residual hearing (≤80 dB HL at 250 Hz) in the ear to be implanted, 2) implantation with current CI technology (2013-2016), 3) consonant-nucleus-consonant (CNC) speech recognition testing in the bimodal condition preoperatively and bilateral CI condition postoperatively. INTERVENTION Cochlear implantation. MAIN OUTCOME MEASURES CNC and AzBio sentence scores in quiet and noise (+5 SNR). Subjective measures of communication difficulty and sound quality were also administered. RESULTS Twenty-two patients (mean 64 yr, 68% men) were included. At an average follow-up of 11.8 months, CNC scores in the bilateral CI condition (mean 63%, standard deviation [SD] = 22) were significantly better than preoperative bimodal scores with repeated measures analysis (mean 55%, SD = 22) (p = 0.03). AzBio scores in quiet were also higher with bilateral CI (mean 76%, SD = 24) compared with bimodal listening (mean 69%, SD = 29) (p = 0.0007). Global abbreviated profile of hearing aid benefit (APHAB) and overall speech, spatial, and qualities of hearing (SSQ) scores exhibited significant improvement following bilateral implantation (p = 0.006 for both analyses). CONCLUSIONS For patients using a bimodal hearing configuration with substantial residual hearing in the non-CI ear, bilateral cochlear implantation yields improved audiologic performance and better subjective quality of life, irrespective of the ability to preserve acoustic hearing during the second sided implantation.
Why Don&Apos;T the Poor Save More? Evidence from Health Savings Experiments

Using data from a field experiment in Kenya, we document that providing individuals with simple informal savings technologies can substantially increase investment in preventative health and reduce vulnerability to health shocks. Simply providing a safe place to keep money was sufficient to increase health savings by 66 percent. Adding an earmarking feature was only helpful when funds were put toward emergencies, or for individuals that are frequently taxed by friends and relatives. Group-based savings and credit schemes had very large effects.