Miracle-dz/UniFAR-FTUs huggingface dataset:
Leptomeningeal Contrast Enhancement Is Related to Focal Cortical Thinning in Relapsing-Remitting Multiple Sclerosis: A Cross-Sectional MRI Study

BACKGROUND AND PURPOSE: Leptomeningeal inflammation is associated with the development of global cortical gray matter atrophy in multiple sclerosis. However, its association with localized loss of tissue remains unclear. The purpose of this study was to evaluate the relationship between leptomeningeal contrast enhancement, a putative marker of leptomeningeal inflammation, and focal cortical thinning in MS. MATERIALS AND METHODS: Forty-three patients with relapsing-remitting MS and 15 with secondary-progressive MS were imaged on a 3T scanner. Cortical reconstruction was performed with FreeSurfer. Leptomeningeal contrast-enhancement foci were visually identified on 3D-FLAIR postcontrast images and confirmed using subtraction imaging. Leptomeningeal contrast-enhancement foci were mapped onto the cortex, and ROIs were obtained by dilating along the surface multiple times (n = 5, 10, 15, 20, 25, 30, 35, 40). Resulting ROIs were then mapped onto the homologous region of the contralateral hemisphere. Paired t tests compared the thickness of the cortex surrounding individual leptomeningeal contrast-enhancement foci and the corresponding contralateral region. Results were corrected for the false discovery rate. RESULTS: Differences between ipsilateral and contralateral ROIs progressively decreased with larger ROIs, but no significant effects were detected when considering the entire MS sample. In patients with relapsing-remitting MS only, significantly reduced cortical thickness was found for 5 dilations (−8.53%, corrected P = .04) and 10 dilations (−5.20%, corrected P = .044). CONCLUSIONS: Focal leptomeningeal contrast enhancement is associated with reduced thickness of the surrounding cortex in patients with relapsing-remitting MS, but not in those with secondary-progressive MS. Our results suggest that pathology associated with the presence of leptomeningeal contrast-enhancement foci has a stronger, localized effect on cortical tissue loss earlier in the disease.
Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial

Importance Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain. Objective To determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in AF. Design, Setting, and Participants The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017. Interventions The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines. Main Outcomes and Measures The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence. Results Of the 2204 patients randomized (median age, 68 years; 37.2% female; 42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0% (n = 89) of patients in the ablation group vs 9.2% (n = 101) of patients in the drug therapy group (hazard ratio [HR], 0.86 [95% CI, 0.65-1.15]; P = .30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2% vs 6.1% for all-cause mortality (HR, 0.85 [95% CI, 0.60-1.21]; P = .38), 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 [95% CI, 0.74-0.93]; P = .001), and 49.9% vs 69.5% for AF recurrence (HR, 0.52 [95% CI, 0.45-0.60]; P < .001). Conclusions and Relevance Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial. Trial Registration ClinicalTrials.gov Identifier: NCT00911508
Dihydroartemisinin, an antimalarial drug, induces absent in melanoma 2 inflammasome activation and autophagy in human hepatocellular carcinoma HepG2215 cells

As an effective antimalarial drug, Dihydroartemisinin (DHA) is readily isolated from the traditional Chinese medicine of Artemisia annua. DHA is not only an autophagy promoter but also a substance with strong antitumor efficiency. The relationship between autophagy and inflammasomes has been suggested in hepatocellular carcinoma (HCC). However, there are few reports describing relationships between inflammasomes and autophagy in HCC therapy. The present study demonstrated that DHA suppressed cell proliferation in HepG2215 cells in a dose‐ and time‐dependent manner. The inhibitory activity is mediated by autophagy, in which reactive oxygen species (ROS) production induced nuclear and mitochondrial DNA damage. Then, DHA were first shown to promote AIM2/caspase‐1 inflammasome. Compared with the DHA group, the autophagy inhibitor 3‐MA significantly inhibited the expressions of activated Caspase‐1, a pyroptotic marker proteins. Meanwhile, repression of mTOR by rapamycin promoted autophagy and AIM2/caspase‐1 activation. The caspase‐1 inhibitor Z‐YVAD‐FMK also notably blocked autophagy cell death characterized by the downexpression of Beclin‐1 and LC3‐II. Additionally, the study demonstrated that DHA suppressed pseudopodium formation and cell mobility. Therefore, we first reveal a novel mechanism that DHA promotes AIM2/caspase‐1 inflammasome, which contributes to autophagy in HepG2215 cells. Moreover, nuclear and mitochondrial DNA damage was also involved in this process via ROS production.
New York City Panel on Climate Change 2019 Report Chapter 3: Sea Level Rise

Vivien Gornitz,1 Michael Oppenheimer,2 Robert Kopp,3 Philip Orton,4 Maya Buchanan,2 Ning Lin,2 Radley Horton,5 and Daniel Bader1 1Center for Climate Systems Research, Columbia University, New York, New York. 2Princeton University, Princeton, New Jersey. 3Rutgers University, New Brunswick, New Jersey. 4Stevens Institute of Technology, Hoboken, New Jersey. 5Lamont-Doherty Earth Observatory, Columbia University, New York, New York
The Use and Perceived Barriers of the Partograph at Public Health Institutions in East Gojjam Zone, Northwest Ethiopia

Introduction: The partograph is a vital tool used to reduce maternal and fetal mortality and morbidity and to prevent prolonged and obstructed labor, as well as postpartum hemorrhage and fistula formation. This study explored the use and barriers of the partograph among obstetric caregivers in East Gojam Zone, Northwest Ethiopia. Methods and materials: A cross-sectional study design consisting of both quantitative and qualitative methods was utilized. Data was collected through a structured clinical observation checklist and semistructured questions. The content of the checklists was developed according to modified WHO partograph. Thematic analysis was employed using open code software version 3.6. Coding was done immediately after the data was collected. The coded data was defined and categorized into groups. Once the categories were identified and the names given, the data was related to the objectives of the study. Data was crosschecked to ensure consistency between the themes and the categories. Then we summarized the themes and drew conclusions that gave answers to the research questions. Results and conclusion: This study showed that participants believed partograph is an essential tool used to reduce maternal and fetal mortality and morbidity and to prevent prolonged and obstructed labor, as well as postpartum hemorrhage. They explained that work overload, lack of skill and competency, negligence, lack of motivation and a shortage of infrastructure and resources hindered utilization of the partograph.
Why do bilinguals code-switch when emotional? Insights from immigrant parent-child interactions.

Previous research has found that bilingual speakers' first (L1) and second languages (L2) are differentially associated with their emotional experiences. Moreover, bilinguals appear to code-switch (alternate between two or more languages in a single conversation) during emotional episodes. However, prior evidence has been limited to clinical case studies and self-report studies, leaving open the specificity of the link between code-switching (CS) and emotion and its underlying mechanisms. The present study examined the dynamic associations between CS and facial emotion behavior in a sample of 68 Chinese American parents and children during a dyadic emotion-inducing puzzle box task. Specifically, bilingual parents' language use (L1 Chinese or L2 English), CS behavior (L1→L2 or L2→L1 switches), and facial emotion behavior (positive and negative valence) were coded at each 5-s interval. Multilevel modeling was used to analyze whether facial emotion behavior predicted later CS and vice versa. We found that negative facial emotion predicted higher subsequent CS in both L1→L2 and L2→L1 directions, with stronger associations for the L2→L1 direction. On the other hand, positive facial emotion was associated with lower contemporaneous L2→L1 CS. CS did not predict later facial emotion behavior, suggesting language switching may not have an immediate effect on emotion. The present findings are consistent with the idea that emotional arousal, especially negative arousal, reduces cognitive control and may trigger spontaneous CS. Together, these findings provide insight into why bilingual speakers switch languages during emotional episodes and hold implications for clinical interventions serving bilingual individuals and families. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Identifying Women at High Risk for Breast Cancer Using Data From the Electronic Health Record Compared With Self-Report.

PURPOSE A barrier to chemoprevention uptake among high-risk women is the lack of routine breast cancer risk assessment in the primary care setting. We calculated breast cancer risk using the Breast Cancer Surveillance Consortium (BCSC) model, accounting for age, race/ethnicity, first-degree family history of breast cancer, benign breast disease, and mammographic density, using data collected from the electronic health records (EHRs) and self-reports. PATIENTS AND METHODS Among women undergoing screening mammography, we enrolled those age 35 to 74 years without a prior history of breast cancer. Data on demographics, first-degree family history, breast radiology, and pathology reports were extracted from the EHR. We assessed agreement between the EHR and self-report on information about breast cancer risk. RESULTS Among 9,514 women with known race/ethnicity, 1,443 women (15.2%) met high-risk criteria based upon a 5-year invasive breast cancer risk of 1.67% or greater according to the BCSC model. Among 1,495 women with both self-report and EHR data, more women with a first-degree family history of breast cancer (14.6% v 4.4%) and previous breast biopsies (21.3% v 11.3%) were identified by self-report versus EHR, respectively. However, more women with atypia and lobular carcinoma in situ were identified from the EHR. There was moderate agreement in identification of high-risk women between EHR and self-report data (κ, 0.48; 95% CI, 0.42-0.54). CONCLUSION By using EHR data, we determined that 15% of women undergoing screening mammography had a high risk for breast cancer according to the BCSC model. There was moderate agreement between information on breast cancer risk derived from the EHR and self-report. Examining EHR data may serve as an initial screen for identifying women eligible for breast cancer chemoprevention.
Outcome of surgical repair of adult digital nerve injury: a systematic review

Objectives A systematic review to assess the evidence supporting surgical repair of digital nerve injury versus no repair in adults in terms of clinical outcomes. Design A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review with methodology based on the Cochrane Handbook of Systematic Reviews of Interventions. Data sources Databases included OvidMEDLINE, EMBASE, AMED, clinicaltrials.gov and the Cochrane Database of Systematic Reviews, searched from inception until 10 November 2018. Eligibility criteria Adult digital nerve injury in which either direct repair or no repair was undertaken and an outcome measure was recorded. Data extraction and synthesis Study data extracted included demographics, injury type and extent, timing, treatment details, outcome data and time points, adverse outcomes, hand therapy and return to work. The National Institute of Health quality assessment tool for case series was used to assess risk of bias. Results Thirty studies were included. One compared surgical repair with non-repair. All studies were case series of between 15 and 110 nerve injuries, with heterogeneous patient, injury and treatment characteristics. Two studies detailed nerve repair without magnification. Static 2-point discrimination (s2PD) was the most commonly reported outcome measure. Return of protective sensation was achieved in most cases in the nerve repair and no nerve repair groups. Repair resulted in better s2PD than no repair, but <25% repaired nerves achieved normal levels. Adverse outcomes were similar between repair and no repair groups. Conclusions Only level IV evidence is available to support surgical repair of digital nerves in adults. Return of normal sensibility is uncommon and almost all unrepaired nerves regained protective sensation by 6 months and all patients declined further surgery. There was no difference in adverse outcomes. There is currently a lack of high-quality evidence to support surgical repair of digital nerve injuries in adults and further research is needed. PROSPERO registration number CRD42017065092.
The Impact of HIV-1 Genetic Diversity on CRISPR-Cas9 Antiviral Activity and Viral Escape

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system is widely explored for sequence-specific attack on HIV-1 proviral DNA. We recently identified dual-guide RNA (dual-gRNA) combinations that can block HIV-1 replication permanently in infected cell cultures and prevent viral escape. Although the gRNAs were designed to target highly conserved viral sequences, their efficacy may be challenged by high genetic variation in the HIV-1 genome. We therefore evaluated the breadth of these dual-gRNA combinations against distinct HIV-1 isolates, including several subtypes. Replication of nearly all virus isolates could be prevented by at least one gRNA combination, which caused inactivation of the proviral genomes and the gradual loss of replication-competent virus over time. The dual-gRNA efficacy was not affected by most single nucleotide (nt) mismatches between gRNA and the viral target. However, 1-nt mismatches at the Cas9 cleavage site and two mismatches anywhere in the viral target sequence significantly reduced the inhibitory effect. Accordingly, sequence analysis of viruses upon breakthrough replication revealed the acquisition of escape mutations in perfectly matching and most 1-nt mismatching targets, but not in targets with a mismatch at the Cas9 cleavage site or with two mismatches. These results demonstrate that combinatorial CRISPR-Cas9 treatment can cure T cells infected by distinct HIV-1 isolates, but even minor sequence variation in conserved viral target sites can affect the efficacy of this strategy. Successful cure attempts against isolates with divergent target sequences may therefore require adaptation of the gRNAs.
Sustained Release from Injectable Composite Gels Loaded with Silver Nanowires Designed to Combat Bacterial Resistance in Bone Regeneration Applications

One-dimensional nanostructures, such as silver nanowires (AgNWs), have attracted considerable attention owing to their outstanding electrical, thermal and antimicrobial properties. However, their application in the prevention of infections linked to bone tissue regeneration intervention has not yet been explored. Here we report on the development of an innovative scaffold prepared from chitosan, composite hydroxyapatite and AgNWs (CS-HACS-AgNWs) having both bioactive and antibacterial properties. In vitro results highlighted the antibacterial potential of AgNWs against both gram-positive and gram-negative bacteria. The CS-HACS-AgNWs composite scaffold demonstrated suitable Ca/P deposition, improved gel strength, reduced gelation time, and sustained Ag+ release within therapeutic concentrations. Antibacterial studies showed that the composite formulation was capable of inhibiting bacterial growth in suspension, and able to completely prevent biofilm formation on the scaffold in the presence of resistant strains. The hydrogels were also shown to be biocompatible, allowing cell proliferation. In summary, the developed CS-HACS-AgNWs composite hydrogels demonstrated significant potential as a scaffold material to be employed in bone regenerative medicine, as they present enhanced mechanical strength combined with the ability to allow calcium salts deposition, while efficiently decreasing the risk of infections. The results presented justify further investigations into the potential clinical applications of these materials.
Systematic analysis of Type I‐E Escherichia coli CRISPR‐Cas PAM sequences ability to promote interference and primed adaptation

CRISPR interference occurs when a protospacer recognized by the CRISPR RNA is destroyed by Cas effectors. In Type I CRISPR‐Cas systems, protospacer recognition can lead to «primed adaptation» – acquisition of new spacers from in cis located sequences. Type I CRISPR‐Cas systems require the presence of a trinucleotide protospacer adjacent motif (PAM) for efficient interference. Here, we investigated the ability of each of 64 possible trinucleotides located at the PAM position to induce CRISPR interference and primed adaptation by the Escherichia coli Type I‐E CRISPR‐Cas system. We observed clear separation of PAM variants into three groups: those unable to cause interference, those that support rapid interference and those that lead to reduced interference that occurs over extended periods of time. PAM variants unable to support interference also did not support primed adaptation; those that supported rapid interference led to no or low levels of adaptation, while those that caused attenuated levels of interference consistently led to highest levels of adaptation. The results suggest that primed adaptation is fueled by the products of CRISPR interference. Extended over time interference with targets containing «attenuated» PAM variants provides a continuous source of new spacers leading to high overall level of spacer acquisition.
Adaptive Neural Command Filtering Control for Nonlinear MIMO Systems With Saturation Input and Unknown Control Direction

In this paper, the tracking control problem is considered for a class of multiple-input multiple-output (MIMO) nonlinear systems with input saturation and unknown direction control gains. A command filtered adaptive neural networks (NNs) control method is presented with regard to the MIMO systems by designing the virtual controllers and error compensation signals. First, the command filtering is used to solve the “explosion of complexity” problem in the conventional backstepping design and the nonlinearities are approximated by NNs. Then, the error compensation signals are developed to conquer the shortcoming of the dynamic surface method. In addition, the Nussbaum-type functions are utilized to cope with the unknown direction control gains. The effectiveness of the proposed new design scheme is illustrated by simulation examples.
Age, Period, and Cohort Trends in Mood Disorder Indicators and Suicide-Related Outcomes in a Nationally Representative Dataset, 2005–2017

Drawing from the National Survey on Drug Use and Health (NSDUH; N = 611,880), a nationally representative survey of U.S. adolescents and adults, we assess age, period, and cohort trends in mood disorders and suicide-related outcomes since the mid-2000s. Rates of major depressive episode in the last year increased 52% 2005–2017 (from 8.7% to 13.2%) among adolescents aged 12 to 17 and 63% 2009–2017 (from 8.1% to 13.2%) among young adults 18–25. Serious psychological distress in the last month and suicide-related outcomes (suicidal ideation, plans, attempts, and deaths by suicide) in the last year also increased among young adults 18–25 from 2008–2017 (with a 71% increase in serious psychological distress), with less consistent and weaker increases among adults ages 26 and over. Hierarchical linear modeling analyses separating the effects of age, period, and birth cohort suggest the trends among adults are primarily due to cohort, with a steady rise in mood disorder and suicide-related outcomes between cohorts born from the early 1980s (Millennials) to the late 1990s (iGen). Cultural trends contributing to an increase in mood disorders and suicidal thoughts and behaviors since the mid-2000s, including the rise of electronic communication and digital media and declines in sleep duration, may have had a larger impact on younger people, creating a cohort effect.
In vitro model to compare the oxygen offloading behaviour of dodecafluoropentane emulsion (DDFPe)

Abstract The aim of this paper was to create an in vitro setup to quantify the oxygen offloading capabilities of dodecafluoropentane emulsion (DDFPe) in a hypoxic environment. Oxygen offloading from DDFPe was characterized under different gaseous environments and under pre-oxygenated conditions. Results of this study showed that (1) oxygen offloading is inversely related to the solubility of the selected sparging gas in saline and (2) both pre-oxygenated and simultaneously oxygenated DDFPe display similar magnitudes of oxygen transport. These results could be applicable to on-going and future studies involving a variety of hypoxic conditions where oxygen delivery might be therapeutically beneficial.