Miracle-dz/UniFAR-FTUs huggingface dataset:
Low Complexity Techniques for SCMA Detection

Sparse code multiple access (SCMA) is a codebook- based non-orthogonal multiplexing technique. In SCMA, the procedure of bit to QAM symbol mapping and spreading of CDMA are combined together and incoming bits are directly mapped to multi-dimensional codewords of SCMA codebook sets. Due to the sparse nature of codewords, SCMA enjoys the low complexity reception, taking advantage of a near optimal message passing algorithm (MPA). This makes SCMA a candidate for supporting massive connectivity in future 5G networks, where the number of users can potentially be higher than the codeword length (spreading factor). To this end, more efficient reception techniques are needed on top of what MPA delivers. In this paper, some complexity reduction techniques are presented to further reduce the SCMA decoding complexity. These techniques are considered from two perspectives: i) transmitter-side technique, by designing SCMA codebooks with a specific structure providing low complexity of detections, and ii) low complexity decoding techniques taking advantage of the SCMA codebook structure. The proposed techniques are evaluated in terms of both complexity and performance. It is shown that significant amount of complexity reduction is possible using the proposed techniques with negligible performance penalty, which paves the way of supporting various applications in future 5G systems using SCMA.
Methicillin-resistant Staphylococcus aureus causes sustained collecting lymphatic vessel dysfunction

Impairment in lymph flow caused by methicillin-resistant Staphylococcus aureus toxins persists after skin and soft tissue infections clear. Lymphatics limp along after MRSA Lymphedema is associated with skin and soft tissue infections, and both can be recurring, causing continual suffering in affected patients. To better understand the relationship between bacterial infections and lymphedema, Jones et al. used intravital imaging to examine the lymphatics of mice infected with MRSA. They observed lymphatic muscle cell death, which led to prolonged dysfunction months after the bacteria had been cleared. In vitro experiments with human cells indicated that bacterial toxins were responsible for damaging the lymphatic muscle cells, suggesting that the toxins could be targeted in patients to interrupt this brutal cycle. Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of morbidity and mortality worldwide and is a frequent cause of skin and soft tissue infections (SSTIs). Lymphedema—fluid accumulation in tissue caused by impaired lymphatic vessel function—is a strong risk factor for SSTIs. SSTIs also frequently recur in patients and sometimes lead to acquired lymphedema. However, the mechanism of how SSTIs can be both the consequence and the cause of lymphatic vessel dysfunction is not known. Intravital imaging in mice revealed an acute reduction in both lymphatic vessel contractility and lymph flow after localized MRSA infection. Moreover, chronic lymphatic impairment is observed long after MRSA is cleared and inflammation is resolved. Associated with decreased collecting lymphatic vessel function was the loss and disorganization of lymphatic muscle cells (LMCs), which are critical for lymphatic contraction. In vitro, incubation with MRSA-conditioned supernatant led to LMC death. Proteomic analysis identified several accessory gene regulator (agr)–controlled MRSA exotoxins that contribute to LMC death. Infection with agr mutant MRSA resulted in sustained lymphatic function compared to animals infected with wild-type MRSA. Our findings suggest that agr is a promising target to preserve lymphatic vessel function and promote immunity during SSTIs.
Reversal of endothelial dysfunction reduces white matter vulnerability in cerebral small vessel disease in rats

Endothelial cell–stabilizing drugs reverse white matter pathology in a rat model of cerebral small vessel disease. Defeating dysfunction Cerebral small vessel disease (SVD) affects arterioles in the brain, increasing risk of stroke and causing symptoms of dementia. To understand the link between vascular changes and white matter pathology, Rajani and colleagues studied a rat model of SVD. Vascular tight junctions were impaired in SVD, and dysfunctional endothelial cells prevented oligodendrocyte precursors from maturing into myelinating cells. SVD rats had a mutation in an ATPase, which was also found in SVD human brain tissue. Drugs that stabilized endothelial cells could reverse the white matter abnormalities in early-stage SVD in the rat model, suggesting a potential therapeutic approach. Dementia is a major social and economic problem for our aging population. One of the most common of dementia in the elderly is cerebral small vessel disease (SVD). Magnetic resonance scans of SVD patients typically show white matter abnormalities, but we do not understand the mechanistic pathological link between blood vessels and white matter myelin damage. Hypertension is suggested as the cause of sporadic SVD, but a recent alternative hypothesis invokes dysfunction of the blood-brain barrier as the primary cause. In a rat model of SVD, we show that endothelial cell (EC) dysfunction is the first change in development of the disease. Dysfunctional ECs secrete heat shock protein 90α, which blocks oligodendroglial differentiation, contributing to impaired myelination. Treatment with EC-stabilizing drugs reversed these EC and oligodendroglial pathologies in the rat model. EC and oligodendroglial dysfunction were also observed in humans with early, asymptomatic SVD pathology. We identified a loss-of-function mutation in ATPase11B, which caused the EC dysfunction in the rat SVD model, and a single-nucleotide polymorphism in ATPase11B that was associated with white matter abnormalities in humans with SVD. We show that EC dysfunction is a cause of SVD white matter vulnerability and provide a therapeutic strategy to treat and reverse SVD in the rat model, which may also be of relevance to human SVD.
Matrix-binding checkpoint immunotherapies enhance antitumor efficacy and reduce adverse events

Matrix-binding peptide conjugation to immune checkpoint blockade antibodies enhances antitumor efficacy and reduces adverse events. Keeping immunotherapy closer to home Immune checkpoint inhibitors are gaining increasing prominence in the field of cancer because of their remarkable success record in many difficult-to-treat tumor types. Unfortunately, activation of the immune system against tumors does not occur in isolation, and these drugs are also associated with a host of immune side effects, which limit their usefulness. To decrease systemic toxicity, Ishihara et al. conjugated immune checkpoint antibodies to a matrix-binding peptide and showed that peritumoral injection of these conjugated antibodies results in their retention in tumor tissue, effective antitumor response, and systemic antitumor immunity with fewer adverse effects. Immune checkpoint blockade exhibits considerable antitumor activity, but previous studies have reported instances of severe treatment-related adverse events. We sought to explore local immune checkpoint blockade, with an antibody (Ab) form that would be retained intra- or peritumorally, limiting systemic exposure. To accomplish this, we conjugated the checkpoint blockade Abs to an extracellular matrix (ECM)–super-affinity peptide derived from placenta growth factor–2 (PlGF-2123–144). We show enhanced tissue retention and lower Ab concentrations in blood plasma after PlGF-2123–144 conjugation, reducing systemic side effects such as the risk of autoimmune diabetes. Peritumoral injections of PlGF-2123–144–anti-CTLA4 (cytotoxic T lymphocyte antigen 4) and PlGF-2123–144–anti–PD-L1 (programmed death ligand 1) Abs delayed tumor growth and prolonged survival compared to the unmodified Abs in genetically engineered murine tumor models of melanoma and breast cancer. The PlGF-2123–144–Abs increased tumor-infiltrating activated CD8+ and CD4+ T cells, resulting in a delay of distant tumor growth as well. This simple and translatable approach of engineered ECM-binding Abs may present a viable and safer approach in checkpoint blockade.
Sarcoplasmic reticulum calcium leak contributes to arrhythmia but not to heart failure progression

Leaky ryanodine receptor does not contribute to heart failure progression, but its normalization reduces arrhythmias and thereby improves survival in mice. Cardiac calcium clarified The subcellular localization of calcium within cardiomyocytes is tightly regulated during the cardiac cycle, and calcium leak from the sarcoplasmic reticulum is linked to alterations in heart rhythm and heart failure. Mohamed et al. investigated whether inhibiting calcium leak by stabilizing the sarcoplasmic calcium channel ryanodine receptor 2 corrected irregular heartbeat and prevented maladaptive myocardial remodeling and heart failure. In a mouse model of pressure overload, reduced calcium leak did not prevent heart failure; increased calcium leak in a volume overload mouse model did not exacerbate heart failure. Rather, inhibiting calcium leak corrected arrhythmias in myocytes derived from patients with heart failure and tachycardia. Although myocardial remodeling was not altered, arrhythmia was mitigated and survival was increased by ryanodine receptor stabilization in mouse models, suggesting a potential therapeutic application for inhibiting sarcoplasmic calcium leak. Increased sarcoplasmic reticulum (SR) Ca2+ leak via the cardiac ryanodine receptor (RyR2) has been suggested to play a mechanistic role in the development of heart failure (HF) and cardiac arrhythmia. Mice treated with a selective RyR2 stabilizer, rycal S36, showed normalization of SR Ca2+ leak and improved survival in pressure overload (PO) and myocardial infarction (MI) models. The development of HF, measured by echocardiography and molecular markers, showed no difference in rycal S36– versus placebo-treated mice. Reduction of SR Ca2+ leak in the PO model by the rycal-unrelated RyR2 stabilizer dantrolene did not mitigate HF progression. Development of HF was not aggravated by increased SR Ca2+ leak due to RyR2 mutation (R2474S) in volume overload, an SR Ca2+ leak–independent HF model. Arrhythmia episodes were reduced by rycal S36 treatment in PO and MI mice in vivo and ex vivo in Langendorff-perfused hearts. Isolated cardiomyocytes from murine failing hearts and human ventricular failing and atrial nonfailing myocardium showed reductions in delayed afterdepolarizations, in spontaneous and induced Ca2+ waves, and in triggered activity in rycal S36 versus placebo cells, whereas the Ca2+ transient, SR Ca2+ load, SR Ca2+ adenosine triphosphatase function, and action potential duration were not affected. Rycal S36 treatment of human induced pluripotent stem cells isolated from a patient with catecholaminergic polymorphic ventricular tachycardia could rescue the leaky RyR2 receptor. These results suggest that SR Ca2+ leak does not primarily influence contractile HF progression, whereas rycal S36 treatment markedly reduces ventricular arrhythmias, thereby improving survival in mice.
Rapid antigen tests for dengue virus serotypes and Zika virus in patient serum

A low-cost, equipment-free rapid antigen test distinguishes dengue virus serotypes and Zika virus in patient sera without detectable cross-reactivity. Distinguishing dengue from Zika More than mere summer pests, mosquitoes can transmit viruses, such as dengue and Zika. Diagnosing infections of these related flaviviruses can be difficult because of cross-reactivity in diagnostic tests. Bosch et al. developed monoclonal antibodies to detect viral nonstructural 1 (NS1) protein antigens specific to dengue and Zika. Incorporating the antibodies into an immunochromatography format yielded a rapid diagnostic assay that produces a visual readout in the presence of NS1. The assay identified the four dengue serotypes and Zika viral infections without cross-reaction when testing human serum samples from endemic areas in Central and South America and India. This approach could be useful for developing rapid diagnostics for other emerging pathogens. The recent Zika virus (ZIKV) outbreak demonstrates that cost-effective clinical diagnostics are urgently needed to detect and distinguish viral infections to improve patient care. Unlike dengue virus (DENV), ZIKV infections during pregnancy correlate with severe birth defects, including microcephaly and neurological disorders. Because ZIKV and DENV are related flaviviruses, their homologous proteins and nucleic acids can cause cross-reactions and false-positive results in molecular, antigenic, and serologic diagnostics. We report the characterization of monoclonal antibody pairs that have been translated into rapid immunochromatography tests to specifically detect the viral nonstructural 1 (NS1) protein antigen and distinguish the four DENV serotypes (DENV1–4) and ZIKV without cross-reaction. To complement visual test analysis and remove user subjectivity in reading test results, we used image processing and data analysis for data capture and test result quantification. Using a 30-μl serum sample, the sensitivity and specificity values of the DENV1–4 tests and the pan-DENV test, which detects all four dengue serotypes, ranged from 0.76 to 1.00. Sensitivity/specificity for the ZIKV rapid test was 0.81/0.86, respectively, using a 150-μl serum input. Serum ZIKV NS1 protein concentrations were about 10-fold lower than corresponding DENV NS1 concentrations in infected patients; moreover, ZIKV NS1 protein was not detected in polymerase chain reaction–positive patient urine samples. Our rapid immunochromatography approach and reagents have immediate application in differential clinical diagnosis of acute ZIKV and DENV cases, and the platform can be applied toward developing rapid antigen diagnostics for emerging viruses.
The Associations Between OPRM 1 and COMT Genotypes and Postoperative Pain, Opioid Use, and Opioid-Induced Sedation

Previous studies have associated mu-opioid receptor (OPRM1) genotype with pain and analgesia responses in postoperative and patient populations. This study investigates the role of catechol-O-methyltransferase (COMT) and OPRM1 genotypes in acute postoperative pain scores, opioid use, and opioid-induced sedation after surgical procedures for orthopedic trauma in an otherwise healthy patient population. Verbal pain/sedation scores, opioid use, and physiologic responses in the immediate postoperative period were examined for association with genetic variants in Caucasians genotyped for OPRM1 single nucleotide polymorphisms (SNPs) A118G and C17T and COMT SNPs. The OPRM1 A118G genotype was associated with patients’ postoperative Numerical Pain scale (NPS) ratings at 15 min in the postanesthesia care unit (PACU) (p = .01) and patients' sedation scores at 15 min in the PACU (p = .02). COMT genotype (rs4818) was associated with opioid consumption in the first 45 min in the PACU (p = .04). NPS ratings at 45 min were also higher in the group of patients with A/A genotype of rs4680 than in patients with the other two genotypes at this SNP (p = .03). Our haplotype trend analysis identified a COMT haplotype “GCGG” significantly associated with NPS at 15 min (p = .0013), amount of opioids consumed in the first 45 min (p = .0024), and heart rate at 45 min in the PACU (p = .017). The results indicate that genetic variations in COMT contribute to the acute postoperative pain and analgesia responses and physiologic responses in this group of otherwise healthy postoperative orthopedic trauma patients.
Combined OX40L and mTOR blockade controls effector T cell activation while preserving Treg reconstitution after transplant

OX40L blockade synergizes with sirolimus to prevent GVHD by controlling effector T cell activation while supporting Treg reconstitution. Tackling T cells in GVHD Graft-versus-host disease (GVHD) after stem cell transplantation is mediated by effector T cells derived from donor stem cells, but GVHD can also be abrogated by donor-derived regulatory T cells. GVHD prophylaxis ideally should then allow regulatory T cell responses while inhibiting effector T cells. Tkachev et al. now provide very promising results in a nonhuman primate model, which suggest that such therapy is possible. They used mTOR inhibition in combination with OX40L blockade, which resulted in reduced damaging T cell reconstitution but preserved regulatory T cell activity. The combination therapy also led to a considerable survival benefit. These findings support testing of this therapy in patients. A critical question facing the field of transplantation is how to control effector T cell (Teff) activation while preserving regulatory T cell (Treg) function. Standard calcineurin inhibitor–based strategies can partially control Teffs, but breakthrough activation still occurs, and these agents are antagonistic to Treg function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. In contrast, blockade of OX40L signaling has the capacity to partially control Teff activation despite maintaining Treg function. We used the nonhuman primate graft-versus-host disease (GVHD) model to probe the efficacy of combinatorial immunomodulation with sirolimus and the OX40L-blocking antibody KY1005. Our results demonstrate significant biologic activity of KY1005 alone (prolonging median GVHD-free survival from 8 to 19.5 days), as well as marked, synergistic control of GVHD with KY1005 + sirolimus (median survival time, >100 days; P < 0.01 compared to all other regimens), which was associated with potent control of both TH/TC1 (T helper cell 1/cytotoxic T cell 1) and TH/TC17 activation. Combined administration also maintained Treg reconstitution [resulting in an enhanced Treg/Teff ratio (40% over baseline) in the KY1005/sirolimus cohort compared to a 2.9-fold decrease in the unprophylaxed GVHD cohort]. This unique immunologic signature resulted in transplant recipients that were able to control GVHD for the length of analysis and to down-regulate donor/recipient alloreactivity despite maintaining anti–third-party responses. These data indicate that combined OX40L blockade and sirolimus represents a promising strategy to induce immune balance after transplant and is an important candidate regimen for clinical translation.
Effects of Napping on Sleepiness and Sleep-Related Performance Deficits in Night-Shift Workers

Night-shift workers are prone to sleep deprivation, misalignment of circadian rhythms, and subsequent sleepiness and sleep-related performance deficits. The purpose of this narrative systematic review is to critically review and synthesize the scientific literature regarding improvements in sleepiness and sleep-related performance deficits following planned naps taken during work-shift hours by night workers and to recommend directions for future research and practice. We conducted a literature search using the Medline, PsychInfo, CINAHL, Cochrane Library, and Health and Safety Science Abstracts databases and included English-language quasi-experimental and experimental studies that evaluated the effects of a nighttime nap taken during a simulated or actual night-work shift. We identified 13 relevant studies, which consisted primarily of small samples and mixed designs. Most investigators found that, despite short periods of sleep inertia immediately following naps, night-shift napping led to decreased sleepiness and improved sleep-related performance. None of the studies examined the effects of naps on safety outcomes in the workplace. Larger-scale randomized clinical trials of night-shift napping and direct safety outcomes are needed prior to wider implementation.
Polymorphisms of Interleukin-1 Beta and Interleukin-17Alpha Genes Are Associated With Restless Legs Syndrome

Objective: Dopamine, iron, and inflammatory pathways are considered important to the development of restless legs syndrome (RLS). Recent genetic studies support involvement of dopamine and iron; however, cytokine gene variation in the inflammatory component remains unexplored. A recent study reported a high prevalence of RLS among HIV-infected adults. We estimate occurrence of RLS in an ethnically diverse sample of HIV-infected adults and examine differences in demographic factors, clinical characteristics, and biomarkers relating to dopamine, iron, and inflammation between adults with and without RLS symptoms. Design: A prospective longitudinal study aimed at identifying biomarkers of RLS symptom experience among HIV-infected adults. Method: 316 HIV-positive adults were evaluated using International RLS Study Group criteria. Genes were chosen for hypothesized relationships to dopamine (NOS1, NOS2), iron (HFE) or inflammation-mediated by cytokine genes (interferon [IFN], interleukin [IL], nuclear factor kappa-B [NFKB], and tumor necrosis factor alpha [TNFA]). Results: Similar to general population estimates, 11% of the sample met all four RLS diagnostic criteria. Controlling for race, gender, and hemoglobin, carrying two copies of the minor allele for IL1B rs1143643, rs1143634, or rs1143633 or carrying the minor allele for IL17A rs8193036 was associated with increased likelihood of meeting RLS diagnostic criteria. Conclusion: This study provides preliminary evidence of a genetic association between IL1B and IL17A genes and RLS.
Eradication of spontaneous malignancy by local immunotherapy

In situ vaccination with low doses of TLR ligands and anti-OX40 antibodies can cure widespread cancers in preclinical models. Deliver locally, act globally Mobilizing endogenous T cells to fight tumors is the goal of many immunotherapies. Sagiv-Barfi et al. investigated a combination therapy in multiple types of mouse cancer models that could provide sustainable antitumor immunity. Specifically, they combined intratumoral delivery of a TLR9 ligand with OX40 activation to ramp up T cell responses. This dual immunotherapy led to shrinkage of distant tumors and long-term survival of the animals, even in a stringent spontaneous tumor model. Both of these stimuli are in clinical trials as single agents and could likely be combined at great benefit for cancer patients. It has recently become apparent that the immune system can cure cancer. In some of these strategies, the antigen targets are preidentified and therapies are custom-made against these targets. In others, antibodies are used to remove the brakes of the immune system, allowing preexisting T cells to attack cancer cells. We have used another noncustomized approach called in situ vaccination. Immunoenhancing agents are injected locally into one site of tumor, thereby triggering a T cell immune response locally that then attacks cancer throughout the body. We have used a screening strategy in which the same syngeneic tumor is implanted at two separate sites in the body. One tumor is then injected with the test agents, and the resulting immune response is detected by the regression of the distant, untreated tumor. Using this assay, the combination of unmethylated CG–enriched oligodeoxynucleotide (CpG)—a Toll-like receptor 9 (TLR9) ligand—and anti-OX40 antibody provided the most impressive results. TLRs are components of the innate immune system that recognize molecular patterns on pathogens. Low doses of CpG injected into a tumor induce the expression of OX40 on CD4+ T cells in the microenvironment in mouse or human tumors. An agonistic anti-OX40 antibody can then trigger a T cell immune response, which is specific to the antigens of the injected tumor. Remarkably, this combination of a TLR ligand and an anti-OX40 antibody can cure multiple types of cancer and prevent spontaneous genetically driven cancers.