Miracle-dz/UniFAR-FTUs huggingface dataset:
Systolic and Diastolic Blood Pressure Changes in Relation With Myocardial Infarction and Stroke in Patients With Coronary Artery Disease

Abstract—Excessively high and low achieved blood pressure (BP) may be associated with a bad outcome in patients with coronary artery disease, the J curve phenomenon. The effect of BP changes from baseline in relation with the subsequent risk of stroke and myocardial infarction (MI) is unknown. Of the 25 620 patients randomized in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) study, we selected 19 102 patients with coronary artery disease at baseline. BP at entry was 141/82 mm Hg, and its average decrease during follow-up was 7/6 mm Hg. BP entered the analysis as time-varying variable modeled with restricted cubic splines. After adjustment for several potential determinants of reverse causality, a change in BP from baseline by –34/–21 mm Hg (10th percentile) was associated with a lesser risk of stroke without any significant increase in the risk of MI. A rise in systolic/diastolic BP from baseline by 20/10 mm Hg (90th percentile) was associated with an increased risk of stroke, whereas the risk of MI increased with systolic BP and not with diastolic BP. In conclusion, in patients with coronary artery disease and initially free from congestive heart failure, a BP reduction from baseline over the examined BP range had little effect on the risk of MI and predicted a lower risk of stroke. An increase in systolic BP from baseline increased the risk of stroke and MI. The relationships of BP with risk were much steeper for stroke than for MI. A treatment-induced BP reduction over the explored range seems to be safe in patients with coronary artery disease. Clinical Trial Registration—URL: http://www.clinicaltrials. gov. Unique identifier: NCT00153101.
A Novel Tissue-Engineered Corneal Stromal Equivalent Based on Amniotic Membrane and Keratocytes.

Purpose To investigate a novel strategy in constructing tissue-engineered corneal stromal equivalent based on amniotic membrane and keratocytes. Methods The ultrathin amniotic membrane (UAM) was laminated, with corneal stromal cells (CSCs) distributed between the space of the layered UAMs. Calcein AM staining was used to evaluate cellular viability, morphology, and arrangement. Immunostaining, qRT-PCR, and Western blot were performed to detect gene and protein expression in keratocytes. Optical coherence tomography visualized the cross sections and thickness of the UAM construction. The microstructure of the CSC-secreted extracellular matrix (ECM) was investigated by scanning electron microscopy and transmission electron microscopy (TEM). To evaluate the feasibility of the multilayer UAM-CSC lamination for surgery, the corneal substitute was used to perform lamellar keratoplasty. Slit lamp microscopy and corneal fluorescein staining were performed in postsurgery observation. Results The CSCs maintained their keratocyte phenotype and secreted well-organized ECM on the aligned UAM surface. The four-layer UAM-CSC lamination attained half thickness of the human cornea (250 ± 18 μm) after 8 weeks' culture, which also showed promising optimal transparency. In TEM images, the CSC-generated ECM displayed stratified, multilayered lamellae with orthogonal fibril arrangement, which was similar to the human cornea microstructure. Furthermore, the stromal equivalent was successfully preformed in lamellar keratoplasty. Four weeks post surgery, the substitute was well integrated into the recipient cornea and completely epithelialized without myofibroblast differentiation. Conclusions Our study established a novel 3D biomimetic corneal model to replicate the corneal stromal organization with multilayer UAM, which was capable of promoting the development of corneal stroma-like tissues in vitro, establishing a new avenue for basic research and therapeutic potential.
Short-Term Ultramicronized Palmitoylethanolamide Therapy in Patients with Myasthenia Gravis: a Pilot Study to Possible Future Implications of Treatment.

BACKGROUND The cannabinoid system may be involved in the humoral mechanisms at the neuromuscular junction. Ultramicronized-palmitoylethanolamide (μm-PEA) has recently been shown to reduce the desensitization of Acetylcholine (ACh)-evoked currents in denervated patients modifying the stability of ACh receptor (AChR) function. OBJECTIVE To analyze the possible beneficial effects of μm-PEA in patients with myasthenia gravis (MG) on muscular fatigue and neurophysiological changes. METHOD The duration of this open pilot study, which included an intra-individual control, was three weeks. Each patient was assigned to a 1-week treatment period with μm-PEA 600 mg twice a day. A neurophysiological examination based on repetitive nerve stimulation (RNS) of the masseteric and the axillary nerves was performed, and the quantitative MG (QMG) score was calculated in 22 MG patients every week in a three-week follow-up period. AChR antibody titer was investigated to analyze a possible immunomodulatory effect of PEA in MG patients. RESULTS PEA had a significant effect on the QMG score (p=0.03418) and on RNS of the masseteric nerve (p=0.01763), thus indicating that PEA reduces the level of disability and decremental muscle response. Antibody titers did not change significantly after treatment. CONCLUSION According to our observations, μm-PEA as an add-on therapy could improve muscular response to fatigue in MG. The possible modulation of AChR currents as a means of eliciting a direct effect from PEA on the conformation of ACh receptors should be investigated. The co-role of cytokines also warrants an analysis. Given the rapidity and reversibility of the response, we suppose that PEA acts directly on AChR, though further studies are needed to confirm this hypothesis.
Validity of hemoglobin A1c for diagnosing diabetes among people with and without HIV in Uganda

Sub-Saharan Africa (SSA) is facing a growing co-epidemic of chronic HIV infection and diabetes. Hemoglobin A1c (A1c) may underestimate glycemia among people living with HIV (PLWH). We estimated the validity of A1c to diagnose diabetes among PLWH and HIV-uninfected persons in rural Uganda. Data were derived from a cohort of PLWH and age- and gender-matched HIV-uninfected comparators. We compared A1c to fasting blood glucose (FBG) using Pearson correlations, regression models, and estimated the sensitivity and specificity of A1c for detecting diabetes with FBG ≥126 mg/dL as reference standard. Approximately half (48%) of the 212 participants were female, mean age of 51.7 years (SD = 7.0) at enrollment. All PLWH (n = 118) were on antiretroviral therapy for a median of 7.5 years with mean CD4 cell count of 442 cells/µL. Mean FBG (89.7 mg/dL) and A1c (5.6%) were not different between PLWH and HIV-uninfected (P > 0.50) groups, but the HIV-uninfected group had a higher prevalence of A1c >5.7% (33% vs. 20%, P = 0.024). We found a relatively strong correlation between A1c and FBG (r = 0.67). An A1c ≥6.5% had a poor sensitivity (46%, 95% CI 26–67%) but high specificity (98%, 95% CI 96–99%) for detecting diabetes. More work is needed to define an optimal A1c for screening diabetes in SSA.
Social and structural factors and engagement in HIV care of sub-Saharan African migrants diagnosed with HIV in the Paris region

ABSTRACT Migrants from sub-Saharan Africa (SSA) are often diagnosed at an advanced stage of HIV, and many of them have harsh living conditions. We aimed to evaluate the entry into care after HIV diagnosis and examine the related social determinants. The ANRS PARCOURS study is a life-event survey conducted in 2012–2013 in the Paris region among. Time between HIV diagnosis of SSA migrants living diagnosed HIV positive in France and HIV care and the determinants was assessed yearly by using mixed-effects logistic regression models. Among a total of 792 participants, 94.2% engaged in HIV care within the year of HIV diagnosis, 4.3% in the following year and 2.5% beyond the second year after diagnosis. The participants were more likely to engage in HIV care during years when they were effectively covered by health insurance and if the HIV test was carried out at the initiative of the doctor. Immigration for economic reasons or owing to threats in his/her country of origin was associated with delayed engagement in HIV care. Additionally, 4.3% of treated participants discontinued HIV care at least once at the time of the survey and more often if diagnosed at an advanced HIV disease stage and financially dependent.
A review of screening tools for the identification of autism spectrum disorders and developmental delay in infants and young children: recommendations for use in low‐ and middle‐income countries

Without intervention, developmental delay (DD) and autism spectrum disorders (ASDs) severely restrict children from reaching their developmental potential. Monitoring child development through the use of screening tools can help identify children who need further assessment or intervention. Screening has been widely encouraged to identify children with ASD or DD, and a large variety of screening instruments are suggested in the literature. There is a lack of consensus around which screening tools are most effective, especially where tools are used in cultures other than those in which they were created. We conducted a review of the literature for screening tools for DD and autism to make recommendations for tool selection and use in low‐ and middle‐income countries (LMIC). We included 99 screening tools in the review and created profiles for each tool to evaluate their properties and determine which tools could be effectively used in various LMIC. Our review identified a substantial number (35 for DD and 6 for ASD) of screening tools from LMIC. We identified 10 tools which show promise for use across settings; these tools are brief, low‐cost and can be implemented by paraprofessionals or lay community health workers. Routine screening is an important first step toward addressing the need for services in LMIC, but high‐quality tools take time to be conceptualized, developed, piloted, and validated, before implementation can happen. A focus on improving the scientific rigor of early detection approaches and on enhancing the reach to underserved populations should be prioritized. Autism Res 2019, 12: 176–199 © 2019 International Society for Autism Research, Wiley Periodicals, Inc.
Surface functionalization of electrospun PAN nanofibers with ZnO–Ag heterostructure nanoparticles: synthesis and antibacterial study

In this work, we have prepared polyacrylonitrile (PAN) polymer nanofibers by electrospinning method. The surface of the electrospun PAN nanofibers membrane has been functionalized with ZnO–Ag heterostructure nanoparticles by using three different chemical pathways such as reflux, blending, hydrothermal methods and accordingly the prepared composite nanofibers membranes were named as PAN/ZnO–Ag (R), PAN/ZnO–Ag (B) and PAN/ZnO–Ag (H) respectively. The obtained heterostructure nanoparticles functionalized PAN nanofibers membranes were characterized using ATR-FTIR, XRD, FESEM and TEM analytical techniques. From the FESEM and TEM images it was clearly observed that 20–30 nm size spherical nanoparticles have been decorated uniformly on the surface of PAN nanofibers. XRD study confirmed the formation of ZnO–Ag mixed/hybrid nanoparticles on PAN nanofibers surface. The ZnO–Ag heterostructure nanoparticles functionalized PAN nanofibers membranes were used for antibacterial application. It was observed from inhibition zone study that the ZnO–Ag heterostructure nanoparticles functionalized PAN nanofibers membrane shows excellent antibacterial properties towards both gram-negative Escherichia coli and gram-positive Micrococcus luteus bacteria than their single component counterparts. Thus this study demonstrated the simple and cost-effective approach to develop antibacterial functional membrane that has many potential applications in water and air filtration, protective mask, textile and packaging industries.
External mechanical work done during the acceleration stage of maximal sprint running and its association with running performance

ABSTRACT This study aimed to elucidate how external mechanical work done during maximal acceleration sprint running changes with increasing running velocity and is associated with running performance. In twelve young males, work done at each step over 50 m from the start was calculated from mechanical energy changes in horizontal anterior–posterior and vertical directions and was divided into braking (−Wkap and −Wv, respectively) and propulsive (+Wkap and +Wv, respectively) phases. The maximal running velocity (Vmax) appeared at 35.87±7.76 m and the time required to run 50 m (T50 m) was 7.11±0.54 s. At 80% Vmax or higher, +Wkap largely decreased and −Wkap abruptly increased. The change in the difference between +Wkap and |−Wkap| (ΔWkap) at every step was relatively small at 70% Vmax or lower. Total work done over 50 m was 82.4±7.5 J kg−1 for +Wkap, 36.2±4.4 J kg−1 for |−Wkap|, 14.3±1.9 J kg−1 for +Wv, and 10.4±1.2 J kg−1 for |−Wv|. The total ΔWkap over 50 m was more strongly correlated with T50 m (r=−0.946, P<0.0001) than the corresponding associations for the other work variables. These results indicate that in maximal sprint running over 50 m, work done during the propulsive phase in the horizontal anterior–posterior direction accounts for the majority of the total external work done during the acceleration stage, and maximizing it while suppressing work done during the braking phase is essential to achieve a high running performance. Summary: In accelerated sprint running over 50 m, work done at every step mainly consists of that during the propulsive phase in the horizontal anterior–posterior direction.
Histone Methylation Directs Myeloid TLR4 Expression and Regulates Wound Healing following Cutaneous Tissue Injury

Myeloid cells are critical for orchestrating regulated inflammation during wound healing. TLRs, particularly TLR4, and its downstream-signaling MyD88 pathway play an important role in regulating myeloid-mediated inflammation. Because an initial inflammatory phase is vital for tissue repair, we investigated the role of TLR4-regulated, myeloid-mediated inflammation in wound healing. In a cutaneous tissue injury murine model, we found that TLR4 expression is dynamic in wound myeloid cells during the course of normal wound healing. We identified that changes in myeloid TLR4 during tissue repair correlated with increased expression of the histone methyltransferase, mixed-lineage leukemia 1 (MLL1), which specifically trimethylates the histone 3 lysine 4 (H3K4me3) position of the TLR4 promoter. Furthermore, we used a myeloid-specific Mll1 knockout (Mll1f/fLyz2Cre+) to determine MLL1 drives Tlr4 expression during wound healing. To understand the critical role of myeloid-specific TLR4 signaling, we used mice deficient in Tlr4 (Tlr4−/−), Myd88 (Myd88−/−), and myeloid-specific Tlr4 (Tlr4f/fLyz2Cre+) to demonstrate delayed wound healing at early time points postinjury. Furthermore, in vivo wound myeloid cells isolated from Tlr4−/− and Myd88−/− wounds demonstrated decreased inflammatory cytokine production. Importantly, adoptive transfer of monocyte/macrophages from wild-type mice trafficked to wounds with restoration of normal healing and myeloid cell function in Tlr4-deficient mice. These results define a role for myeloid-specific, MyD88-dependent TLR4 signaling in the inflammatory response following cutaneous tissue injury and suggest that MLL1 regulates TLR4 expression in wound myeloid cells.
Centipede KCNQ Inhibitor SsTx Also Targets KV1.3

It was recently discovered that Ssm Spooky Toxin (SsTx) with 53 residues serves as a key killer factor in red-headed centipede’s venom arsenal, due to its potent blockage of the widely expressed KCNQ channels to simultaneously and efficiently disrupt cardiovascular, respiratory, muscular, and nervous systems, suggesting that SsTx is a basic compound for centipedes’ defense and predation. Here, we show that SsTx also inhibits KV1.3 channel, which would amplify the broad-spectrum disruptive effect of blocking KV7 channels. Interestingly, residue R12 in SsTx extends into the selectivity filter to block KV7.4, however, residue K11 in SsTx replaces this ploy when toxin binds on KV1.3. Both SsTx and its mutant SsTx_R12A inhibit cytokines production in T cells without affecting the level of KV1.3 expression. The results further suggest that SsTx is a key molecule for defense and predation in the centipedes’ venoms and it evolves efficient strategy to disturb multiple physiological targets.
Mix it to fix it: Emotion regulation variability in daily life.

Emotion regulation (ER) strategies are often categorized as universally adaptive or maladaptive. However, it has recently been proposed that this view is overly simplistic: instead, adaptive ER involves applying strategies variably to meet contextual demands. Using data from four experience-sampling studies (Ns = 70, 95, 200, and 179), we tested the relationship between ER variability and negative affect (NA) in everyday life. The constantly changing demands of daily life provide a more ecologically valid context in which to test the role of variability. We calculated 2 global indicators of variability: within-strategy variability (of particular strategies across time) and between-strategy variability (across strategies at one time-point). Associations between within-strategy variability and NA were inconsistent. In contrast, when controlling for mean strategy endorsement, between-strategy variability was associated with reduced NA across both individuals and measurement occasions. This is the first evidence that variably choosing between different strategies within a situation may be adaptive in daily life. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
A Biocompatible Therapeutic Catheter‐Deliverable Hydrogel for In Situ Tissue Engineering

Hydrogels have emerged as a diverse class of biomaterials offering a broad range of biomedical applications. Specifically, injectable hydrogels are advantageous for minimally invasive delivery of various therapeutics and have great potential to treat a number of diseases. However, most current injectable hydrogels are limited by difficult and time‐consuming fabrication techniques and are unable to be delivered through long, narrow catheters, preventing extensive clinical translation. Here, the development of an easily‐scaled, catheter‐injectable hydrogel utilizing a polymer–nanoparticle crosslinking mechanism is reported, which exhibits notable shear‐thinning and self‐healing behavior. Gelation of the hydrogel occurs immediately upon mixing the biochemically modified hyaluronic acid polymer with biodegradable nanoparticles and can be easily injected through a high‐gauge syringe due to the dynamic nature of the strong, yet reversible crosslinks. Furthermore, the ability to deliver this novel hydrogel through a long, narrow, physiologically‐relevant catheter affixed with a 28‐G needle is highlighted, with hydrogel mechanics unchanged after delivery. Due to the composition of the gel, it is demonstrated that therapeutics can be differentially released with distinct elution profiles, allowing precise control over drug delivery. Finally, the cell‐signaling and biocompatibility properties of this innovative hydrogel are demonstrated, revealing its wide range of therapeutic applications.
ST-segment-elevation myocardial infarction treatment and the seductive lure of observational analyses.

Randomized trials have demonstrated the clinical superiority of timely transfer for primary percutaneous coronary intervention (PCI) compared with onsite fibrinolytic therapy for reperfusion in the setting of ST-segment–elevation myocardial infarction (STEMI). 1,2 On this point, there is relative clarity. What remains nebulous, however, is the degree to which these findings apply broadly across care systems that often have substantial transfer delays. Article see p 2512 Providers continue to face the challenging question posed by transfer delays: How long is too long to justify transfer of STEMI patients for primary PCI? The American College of Cardiology/American Heart Association guidelines have, until recently, called for transfer for primary PCI when reperfusion can be accomplished within 90 minutes of initial presentation to the non-PCI center or with a PCI-related delay (time interval from when fibrinolytic therapy can be given until when PCI can be performed) of <60 minutes.3 The latest ACCF/AHA/SCAI guidelines for PCI extend the acceptable first door-to-device time to 120 minutes for patients presenting to non-PCI-capable hospitals, an adjustment in line with current European guidelines.4,4a The Figure depicts the temporal anatomy of a transfer, the key time-based elements of the reperfusion delivery process. The guidelines acknowledge that the selection of reperfusion method also hinges on additional variables, such as time since symptom onset, risk of death, and relative or absolute contraindications to fibrinolysis.3 Moreover, the guidelines emphasize that the selected method of reperfusion may be less important than the use of some type of reperfusion for all eligible patients in a timely fashion. Regional systems of care (as supported by Mission: Lifeline5) have been identified as essential elements of optimal care provision. Figure. ST-segment–elevation myocardial infarction reperfusion pathways for non–percutaneous coronary intervention (PCI) centers. For the primary PCI pathway, both the latest American College …
Prevalence of Germline Mutations Associated With Cancer Risk in Patients With Intraductal Papillary Mucinous Neoplasms.

BACKGROUND & AIMS Many patients with pancreatic adenocarcinoma carry germline mutations associated with increased risk of cancer. It is not clear whether patients with intraductal papillary mucinous neoplasms (IPMNs), which are precursors to some pancreatic cancers, also carry these mutations. We assessed the prevalence of germline mutations associated with cancer risk in patients with histologically confirmed IPMN. METHODS We obtained nontumor tissue samples from 315 patients with surgically resected IPMNs from 1997 through 2017, and we sequenced 94 genes with variants associated with cancer risk. Mutations associated with increased risk of cancer were identified and compared with individuals from the Exome Aggregation Consortium. RESULTS We identified 23 patients with a germline mutation associated with cancer risk (7.3%; 95% confidence interval, 4.9-10.8). Nine patients had a germline mutation associated with pancreatic cancer susceptibility (2.9%; 95% confidence interval, 1.4-5.4). More patients with IPMNs carried germline mutations in ATM (P < .0001), PTCH1 (P < .0001), and SUFU (P < .0001) compared with controls. Patients with IPMNs and germline mutations associated with pancreatic cancer were more like to have concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations (P < .0320). CONCLUSIONS In sequence analyses of 315 patients with surgically resected IPMNs, we found that almost 3% to carry mutations associated with pancreatic cancer risk. More patients with IPMNs and germline mutations associated with pancreatic cancer had concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations. Genetic analysis of patients with IPMNs might identify those at greatest risk for cancer.
Importance of incorporating intraoperative neuromonitoring of the external branch of the superior laryngeal nerve in thyroidectomy: A review and meta‐analysis study

Voice changes are frequently reported after thyroidectomy due to injury to the external branch of the superior laryngeal nerve (EBSLN) and paralysis of the cricothyroid muscle, The objective is to evaluate the advantage of intraoperative neuromonitoring (IONM) in identifying EBSLN during thyroid surgery.