Miracle-dz/UniFAR-FTUs huggingface dataset:
The Impact of Text Message Reminders on Adherence to Antimalarial Treatment in Northern Ghana: A Randomized Trial

Background Low rates of adherence to artemisinin-based combination therapy (ACT) regimens increase the risk of treatment failure and may lead to drug resistance, threatening the sustainability of current anti-malarial efforts. We assessed the impact of text message reminders on adherence to ACT regimens. Methods Health workers at hospitals, clinics, pharmacies, and other stationary ACT distributors in Tamale, Ghana provided flyers advertising free mobile health information to individuals receiving malaria treatment. The messaging system automatically randomized self-enrolled individuals to the control group or the treatment group with equal probability; those in the treatment group were further randomly assigned to receive a simple text message reminder or the simple reminder plus an additional statement about adherence in 12-hour intervals. The main outcome was self-reported adherence based on follow-up interviews occurring three days after treatment initiation. We estimated the impact of the messages on treatment completion using logistic regression. Results 1140 individuals enrolled in both the study and the text reminder system. Among individuals in the control group, 61.5% took the full course of treatment. The simple text message reminders increased the odds of adherence (adjusted OR 1.45, 95% CI [1.03 to 2.04], p-value 0.028). Receiving an additional message did not result in a significant change in adherence (adjusted OR 0.77, 95% CI [0.50 to 1.20], p-value 0.252). Conclusion The results of this study suggest that a simple text message reminder can increase adherence to antimalarial treatment and that additional information included in messages does not have a significant impact on completion of ACT treatment. Further research is needed to develop the most effective text message content and frequency. Trial Registration ClinicalTrials.gov NCT01722734
Dual-specific Chimeric Antigen Receptor T Cells and an Indirect Vaccine Eradicate a Variety of Large Solid Tumors in an Immunocompetent, Self-antigen Setting

Purpose: While adoptive transfer of T cells bearing a chimeric antigen receptor (CAR) can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors for most cancers. We aimed to develop an immunotherapy approach effective against large tumors in an immunocompetent, self-antigen preclinical mouse model. Experimental Design: In this study, we generated dual-specific T cells expressing both a CAR specific for Her2 and a TCR specific for the melanocyte protein (gp100). We used a regimen of adoptive cell transfer incorporating vaccination (ACTIV), with recombinant vaccinia virus expressing gp100, to treat a range of tumors including orthotopic breast tumors and large liver tumors. Results: ACTIV therapy induced durable complete remission of a variety of Her2+ tumors, some in excess of 150 mm2, in immunocompetent mice expressing Her2 in normal tissues, including the breast and brain. Vaccinia virus induced extensive proliferation of T cells, leading to massive infiltration of T cells into tumors. Durable tumor responses required the chemokine receptor CXCR3 and exogenous IL2, but were independent of IFNγ. Mice were resistant to tumor rechallenge, indicating immune memory involving epitope spreading. Evidence of limited neurologic toxicity was observed, associated with infiltration of cerebellum by T cells, but was only transient. Conclusions: This study supports a view that it is possible to design a highly effective combination immunotherapy for solid cancers, with acceptable transient toxicity, even when the target antigen is also expressed in vital tissues. Clin Cancer Res; 23(10); 2478–90. ©2016 AACR.
In-situ measurement of lens aberrations

Linewidth control across an exposure field is becoming increasingly challenging as design rules shrink. Contributions to linewidth variation can arise from the reticle, the exposure tool and the resist process. For the exposure system, errors may originate from the illuminator ste-up, the projection lens aberrations using a new reticle and measurement technique. The technique uses a special reticle, which converts wavefront phase errors to displacements on the wafer. These offsets can be measured using conventional overlay tools with greater speed and accuracy than SEM measurements of small linewidths. Reconstruction of the wavefront using this data provides a more reliable in-situ characterization of aberrations.
IL-12+IL-18 Cosignaling in Human Macrophages and Lung Epithelial Cells Activates Cathelicidin and Autophagy, Inhibiting Intracellular Mycobacterial Growth

The ability of Mycobacterium tuberculosis to block host antimicrobial responses in infected cells provides a key mechanism for disease pathogenesis. The immune system has evolved to overcome this blockade to restrict the infection, but it is not clear whether two key innate cytokines (IL-12/IL-18) involved in host defense can enhance antimycobacterial mechanisms. In this study, we demonstrated that the combination of IL-12 and IL-18 triggered an antimicrobial response against mycobacteria in infected macrophages (THP-1 and human primary monocyte-derived macrophages) and pulmonary epithelial A549 cells. The inhibition of intracellular bacterial growth required p38–MAPK and STAT4 pathways, the vitamin D receptor, the vitamin D receptor–derived antimicrobial peptide cathelicidin, and autophagy, but not caspase-mediated apoptosis. Finally, the ability of IL-12+IL-18 to activate an innate antimicrobial response in human primary macrophages was dependent on the autonomous production of IFN-γ and the CAMP/autophagy pathway. Together, these data suggest that IL-12+IL-18 cosignaling can trigger the antimicrobial protein cathelicidin and autophagy, resulting in inhibition of intracellular mycobacteria in macrophages and lung epithelial cells.
Identification and location tasks rely on different mental processes: a diffusion model account of validity effects in spatial cueing paradigms with emotional stimuli

ABSTRACT Spatial cueing paradigms are popular tools to assess human attention to emotional stimuli, but different variants of these paradigms differ in what participants’ primary task is. In one variant, participants indicate the location of the target (location task), whereas in the other they indicate the shape of the target (identification task). In the present paper we test the idea that although these two variants produce seemingly comparable cue validity effects on response times, they rest on different underlying processes. Across four studies (total N = 397; two in the supplement) using both variants and manipulating the motivational relevance of cue content, diffusion model analyses revealed that cue validity effects in location tasks are primarily driven by response biases, whereas the same effect rests on delay due to attention to the cue in identification tasks. Based on this, we predict and empirically support that a symmetrical distribution of valid and invalid cues would reduce cue validity effects in location tasks to a greater extent than in identification tasks. Across all variants of the task, we fail to replicate the effect of greater cue validity effects for arousing (vs. neutral) stimuli. We discuss the implications of these findings for best practice in spatial cueing research.
Differential Expression of CD8+ T Cell Cytotoxic Effector Molecules in Blood and Gastrointestinal Mucosa in HIV-1 Infection

We previously reported that CD8+ T cells in human gastrointestinal mucosa exhibit reduced perforin expression and weak or impaired cytotoxic capacity compared with their counterparts in blood. Nevertheless, these cells degranulate and express cytokines and chemokines in response to cognate Ag. In addition to weak expression of perforin, earlier studies suggested differential regulation of perforin and granzymes (Gzms), with GzmA and B expressed by significantly higher percentages of mucosal CD8+ T cells than perforin. However, this topic has not been fully explored. The goal of this study was to elucidate the expression and coexpression patterns of GzmA, B, and K in conjunction with perforin in rectosigmoid CD8+ T cells during HIV-1 infection. We found that expression of both perforin and GzmB, but not GzmA or GzmK, was reduced in mucosa compared with blood. A large fraction of rectosigmoid CD8+ T cells either did not express Gzms or were single-positive for GzmA. Rectosigmoid CD8+ T cells appeared skewed toward cytokine production rather than cytotoxic responses, with cells expressing multiple cytokines and chemokines generally lacking in perforin and Gzm expression. These data support the interpretation that perforin and Gzms are differentially regulated, and display distinct expression patterns in blood and rectosigmoid T cells. These studies may help inform the development of strategies to combat HIV-1 and other mucosal pathogens.
ON 01910.Na (rigosertib) inhibits PI3K/Akt pathway and activates oxidative stress signals in head and neck cancer cell lines

Squamous cell carcinoma of the head and neck (HNSCC) is characterized by high morbidity and mortality. Treatment failure, drug resistance and chemoradiation toxicity have necessitated the development of alternative treatment strategies. Styryl benzyl sulfones, a family of novel small molecule inhibitors, are being evaluated as anti-neoplastic agents in multiple clinical trials. The activity of these compounds has been well characterized in several preclinical tumor studies, but their activity has yet to be fully examined in HNSCC. We tested ON 01910.Na (rigosertib), a styryl benzyl sulfone in late-stage development, in HNSCC preclinical models. Rigosertib induced cytotoxicity in both HPV(+) and HPV(−) HNSCC cells in a dose-dependent manner. Characterization of the underlying molecular mechanism indicated that rigosertib induced inhibition of the PI3K/Akt/mTOR pathway, induced oxidative stress resulting in increased generation of reactive oxygen species (ROS), and activated extracellular signal-regulated kinases (ERK1/2) and c-Jun NH2-terminal kinase (JNK). Increased phosphorylation and cytoplasmic translocation of ATF-2 were also observed following rigosertib treatment. These changes in cell signaling led us to consider combining rigosertib with HNSCC standard-of-care therapies, such as cisplatin and radiation. Our study highlights the promising preclinical activity of rigosertib in HNSCC irrespective of HPV status and provides a molecular basis for rigosertib in combination with standard of care agents for HNSCC.
The novel late Na+ current inhibitor, GS‐6615 (eleclazine) and its anti‐arrhythmic effects in rabbit isolated heart preparations

Enhanced late Na+ current (late INa) in the myocardium is pro‐arrhythmic. Inhibition of this current is a promising strategy to stabilize ventricular repolarization and suppress arrhythmias. Here, we describe GS‐6615, a selective inhibitor of late INa, already in clinical development for the treatment of long QT syndrome 3 (LQT3).
Inducing the Alternative Oxidase Forms Part of the Molecular Strategy of Anoxic Survival in Freshwater Bivalves

Hypoxia in freshwater ecosystems is spreading as a consequence of global change, including pollution and eutrophication. In the Patagonian Andes, a decline in precipitation causes reduced lake water volumes and stagnant conditions that limit oxygen transport and exacerbate hypoxia below the upper mixed layer. We analyzed the molecular and biochemical response of the North Patagonian bivalve Diplodon chilensis after 10 days of experimental anoxia (<0.2 mg O2/L), hypoxia (2 mg O2/L), and normoxia (9 mg O2/L). Specifically, we investigated the expression of an alternative oxidase (AOX) pathway assumed to shortcut the regular mitochondrial electron transport system (ETS) during metabolic rate depression (MRD) in hypoxia-tolerant invertebrates. Whereas, the AOX system was strongly upregulated during anoxia in gills, ETS activities and energy mobilization decreased [less transcription of glycogen phosphorylase (GlyP) and succinate dehydrogenase (SDH) in gills and mantle]. Accumulation of succinate and induction of malate dehydrogenase (MDH) activity could indicate activation of anaerobic mitochondrial pathways to support anoxic survival in D. chilensis. Oxidative stress [protein carbonylation, glutathione peroxidase (GPx) expression] and apoptotic intensity (caspase 3/7 activity) decreased, whereas an unfolded protein response (HSP90) was induced under anoxia. This is the first clear evidence of the concerted regulation of the AOX and ETS genes in a hypoxia-tolerant freshwater bivalve and yet another example that exposure to hypoxia and anoxia is not necessarily accompanied by oxidative stress in hypoxia-tolerant mollusks.
Staphylococcus lugdunensis:: An Emerging Pathogen

Objective: To evaluate the clinical relevance and impact of an emerging bacterial pathogen, Staphylococcus lugdunensis, in a large teaching hospital. Methods: Three-year retrospective microbiological and clinical review of all S. lugdunensis isolates from a single medical center. Results: Seventy-seven isolates were identified; 70 had complete data. Soft tissue, bone, joint, central nervous system, urine and bloodstream infections occurred. Soft tissue infections were primarily abscesses. There were four infections of prosthetic joints and nine cases of osteomyelitis. There were 21 bacteremias, 5 of which were associated with endocarditis; 2 died. Most isolates were penicillin resistant. Conclusion: S. lugdunensis has emerged as a major human pathogen, capable of causing significant infections at many sites. It should never be dismissed as a contaminant without careful review.
All-in-One Theranostic Nanoplatform Based on Hollow MoSx for Photothermally-maneuvered Oxygen Self-enriched Photodynamic Therapy

Photodynamic therapy (PDT) kills cancer cells by converting tumor-dissolved oxygen into reactive singlet oxygen (1O2) using a photosensitizer under laser irradiation. However, pre-existing hypoxia in tumors and oxygen consumption during PDT can result in an inadequate oxygen supply, which in turn hampers PDT efficacy. Herein, an O2 self-sufficient nanotheranostic platform based on hollow MoSx nanoparticles (HMoSx) with oxygen-saturated perfluorohexane (O2@PFH) and surface-modified human serum albumin (HSA)/chloride aluminium phthalocyanine (AlPc) (O2@PFH@HMoSx-HSA/AlPc), has been designed for the imaging and oxygen self-enriched photodynamic therapy (Oxy-PDT) of cancer. Methods: The in vitro anti-cancer activity and intracellular 1O2 generation performance of the nanoparticles were examined using 4T1 cells. We also evaluated the multimodal imaging capabilities and anti-tumor efficiency of the prepared nanoparticles in vivo using a 4T1 tumor-bearing nude mouse model. Results: This nanoplatform could achieve the distinct in vivo fluorescence (FL)/photoacoustic (PA)/X-ray computed tomography (CT) triple-model imaging-guided photothermally-maneuvered Oxy-PDT. Interestingly, the fluorescence and Oxy-PDT properties of O2@PFH@HMoSx-HSA/AlPc were considerably quenched; however, photothermal activation by 670 nm laser irradiation induced a significant increase in temperature, which empowered the Oxy-PDT effect of the nanoparticles. In this study, O2@PFH@HMoSx-HSA/AlPc demonstrated a great potential to image and treat tumors both in vitro and in vivo, showing complete tumor-inhibition over 16 days after treatment in the 4T1 tumor model. Conclusion: O2@PFH@HMoSx-HSA/AlPc is promising to be used as novel multifunctional theranostic nanoagent for triple-modal imaging as well as single wavelength NIR laser triggered PTT/Oxy-PDT synergistic therapy.
No News Is News: Do Markets Underreact to Nothing?

As illustrated in the tale of "the dog that did not bark," the absence of news and the passage of time often contain information. We test whether markets fully incorporate this information using the empirical context of mergers. During the year after merger announcement, the passage of time is informative about the probability that the merger will ultimately complete. We show that the variation in hazard rates of completion after announcement strongly predicts returns. This pattern is consistent with a behavioral model of underreaction to the passage of time and cannot be explained by changes in risk or frictions.
The Effects of Bougie Diameters on Tissue Oxygen Levels After Sleeve Gastrectomy: A Randomized Experimental Trial

Background: Staple-line leak is the most frightening complication of laparoscopic sleeve gastrectomy and several predisposing factors such as using improper staple sizes regardless of gastric wall thickness, narrower bougie diameter and ischemia of the staple line are asserted. Aims: To evaluate the effects of different bougie diameters on tissue oxygen partial pressure at the esophagogastric junction after sleeve gastrectomy. Study Design: A randomized and controlled animal experiment with 1:1:1:1 allocation ratio. Methods: Thirty-two male Wistar Albino rats were randomly divided into 4 groups of 8 each. While 12-Fr bougies were used in groups 1 and 3, 8-Fr bougies were used in groups 2 and 4. Fibrin sealant application was also carried out around the gastrectomy line after sleeve gastrectomy in groups 3 and 4. Burst pressure of gastrectomy line, tissue oxygen partial pressure and hydroxyproline levels at the esophagogastric junction were measured and compared among groups. Results: Mortality was detected in 2 out of 32 rats (6.25%) and one of them was in group 2 and the cause of this mortality was gastric leak. Gastric leak was detected in 2 out of 32 rats (6.25%). There was no significant difference in terms of burst pressures, tissue oxygen partial pressure and tissue hydroxyproline levels among the 4 groups. Conclusion: The use of narrower bougie along with fibrin sealant has not had a negative effect on tissue perfusion and wound healing.
Comparison of MicroRNA Expression in Aqueous Humor of Normal and Primary Open-Angle Glaucoma Patients Using PCR Arrays: A Pilot Study.

We read with great interest the article published by Jayaram et al. The investigators used a cost-effective approach to assay the microRNA (miRNA) expression in aqueous humor (AH) of normal patients and those with primary open-angle glaucoma (POAG). They found that miRNA expression within the AH of patients with POAG differed from that of age-matched controls. Only a few studies investigated the expression of miRNA within human AH samples. In the past, we also tried to identify the miRNA expression profile from patients with glaucoma using next-generation small RNA sequencing. Unfortunately, the high throughput screening technique is restricted by the pooled AH samples. We congratulate the investigators for their excellent work on this field. They firstly used preamplification to increase RNA yield before further analysis. This technique has an important apocalypse meaning for our future research and we would like to make some contributions and criticisms related to this study. The first one is about patient selection. Six patients with stable POAG and eight age-matched controls were recruited for this study. However, 57.1% (8/14) of volunteers were suffering from additional ocular comorbidities. In particular, three patients diagnosed with dry age-related macular degeneration (AMD) were enrolled. Numerous studies have analyzed miRNA dysregulation in patients with AMD and some miRNAs have been shown to be involved in AMD pathology. Although no one has studied the change in miRNA expression in AH of patients with AMD, that possibility cannot be ruled out. Therefore, we feared that the selected patients may confound the results. Secondly, we think that miRNA expression within the plasma is of equal importance to that of AH. The investigators found that six of the most abundant miRNAs in AH of both groups also were detected in human plasma. However, Williams et al. tested the miRNAs profile in cell-free serum and plasma from pregnant women and their husbands using deep sequencing of barcoded small RNA cDNA libraries. The differences among the volunteers and the methods of separating and detecting miRNAs as well as analyses of biological information may account for the different results. Conjoint analysis of the altered expression of specific miRNAs in AH and plasma may provide more useful information about the relationship between the pathogenesis of glaucoma and miRNA. So, what do you think?
Pretransplant angiotensin II type 1-receptor antibodies are a risk factor for earlier detection of de novo HLA donor-specific antibodies.

BACKGROUND Angiotensin II type 1 receptor antibodies (AT1Rabs) have been associated with significantly reduced graft survival. Earlier graft loss has been observed in patients who had pretransplant AT1Rabs and posttransplant donor-specific antibodies (DSA). METHODS The main goal of this retrospective cohort study was to examine the association between AT1Rabs and the time period to detection of de novo human leukocyte antigen (HLA-DSA) posttransplantation in living donor kidney transplant recipients (KTR). The analysis included 141 KTRs. Pretransplant frozen serum samples were tested for AT1Rabs by ELISA and HLA-DSA by SAB (Luminex) at both the pre- and post-KT time points. RESULTS The median AT1Rab level was 9.13 U (interquartile range 5.22-14.33). After a mean follow-up period of 3.55 years, 48 patients were found to harbour de novo HLA-DSAs. The presence of AT1Rabs [hazard ratio (HR) 1.009, 95% confidence interval (CI) 1.002-1.01, P = 0.010], male-to-male transplantation (HR 2.57, 95% CI 1.42-4.67, P = 0.002) and antecedent borderline changes or acute cellular rejection (ACR) (HR 2.47, 95% CI 1.29-4.75, P = 0.006) were significantly associated with de novo DSA detection. A dose-dependent association between AT1Rab levels (<10 U, 10.1-16.9 U, 17-29.9 U and >30 U) and de novo DSA detection was observed (log-rank P = 0.0031). After multivariate analysis of AT1Rab levels (continuous variable), AT1Rabs >30 U, male-to-male transplantation, donor age, higher class I percentage of Panel Reactive Antibody and antecedent borderline changes or ACR remained as independent significant risk factors for the detection of de novo DSAs. CONCLUSIONS The findings suggest that higher levels of pretransplant circulating antibodies against AT1R (>30 U) in kidney graft recipients constitute an independent risk factor for earlier de novo HLA-DSA detection during the posttransplant period.
Plectin 1f scaffolding at the sarcolemma of dystrophic (mdx) muscle fibers through multiple interactions with β-dystroglycan

In skeletal muscle, the cytolinker plectin is prominently expressed at Z-disks and the sarcolemma. Alternative splicing of plectin transcripts gives rise to more than eight protein isoforms differing only in small N-terminal sequences (5–180 residues), four of which (plectins 1, 1b, 1d, and 1f) are found at substantial levels in muscle tissue. Using plectin isoform–specific antibodies and isoform expression constructs, we show the differential regulation of plectin isoforms during myotube differentiation and their localization to different compartments of muscle fibers, identifying plectins 1 and 1f as sarcolemma-associated isoforms, whereas plectin 1d localizes exclusively to Z-disks. Coimmunoprecipitation and in vitro binding assays using recombinant protein fragments revealed the direct binding of plectin to dystrophin (utrophin) and β-dystroglycan, the key components of the dystrophin–glycoprotein complex. We propose a model in which plectin acts as a universal mediator of desmin intermediate filament anchorage at the sarcolemma and Z-disks. It also explains the plectin phenotype observed in dystrophic skeletal muscle of mdx mice and Duchenne muscular dystrophy patients.