Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of the Tumor Microenvironment by CXCR4 Antagonist-Armed Viral Oncotherapy Enhances the Antitumor Efficacy of Dendritic Cell Vaccines against Neuroblastoma in Syngeneic Mice

The induction of antitumor immune responses in tumor-bearing hosts depends on efficient uptake and processing of native or modified tumors/self-antigens by dendritic cells (DCs) to activate immune effector cells, as well as the extent of the immunosuppressive network in the tumor microenvironment (TME). Because the C-X-C motif chemokine receptor 4 (CXCR4) for the C-X-C motif chemokine 12 (CXCL12) is involved in signaling interactions between tumor cells and their TME, we used oncolytic virotherapy with a CXCR4 antagonist to investigate whether targeting of the CXCL12/CXCR4 signaling axis in murine neuroblastoma cells (NXS2)-bearing syngeneic mice affects the efficacy of bone marrow (BM)-derived DCs loaded with autologous tumor cells treated with doxorubicin for induction of immunogenic cell death. Here, we show that CXCR4 antagonist expression from an oncolytic vaccinia virus delivered intravenously to mice with neuroblastoma tumors augmented efficacy of the DC vaccines compared to treatments mediated by a soluble CXCR4 antagonist or oncolysis alone. This study is the first demonstration that modulating the tumor microenvironment by an armed oncolytic virus could have a significant impact on the efficacy of DC vaccines, leading to the generation of effective protection against neuroblastoma challenge.
Prevalence and correlates of physical and sexual intimate partner violence among women living with HIV in Uganda

Background Intimate partner violence (IPV) is a significant global health problem. Women who experience IPV have increased HIV incidence, reduced antiretroviral adherence, and a lower likelihood of viral load suppression. There is a lack of evidence regarding how to effectively identify and support women living with HIV (WLWH) experiencing IPV, including uncertainty whether universal or targeted screening is most appropriate for lower-resourced settings. We examined physical and sexual IPV prevalence and correlates among WLWH in Uganda to understand the burden of IPV and factors that could help identify women at risk. Methods We utilized data from women receiving ART and enrolled in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort study between 2011 and 2015. Bloodwork and interviewer-administered questionnaires were completed every 4 months. IPV was assessed annually or with any new pregnancy. Multivariate models assessed independent socio-demographic and clinical factors correlated with IPV, at baseline and follow-up visits. Results 455 WLWH were included. Median age was 36 years, 43% were married, and median follow-up was 2.8 years. At baseline 131 women (29%) reported any experience of past or current IPV. In the adjusted models, being married was associated with a higher risk of baseline IPV (ARR 2.33, 95% CI 1.13–4.81) and follow-up IPV (ARR 2.43, 95% CI 1.33–4.45). Older age (ARR 0.96, 95% CI 0.94–0.99) and higher household asset index score (ARR 0.81, 95% CI 0.68–0.96) were associated with lower risk of IPV during follow-up. Conclusion There was a high prevalence of physical and sexual IPV amongst WLWH, and many women experienced both types of violence. These findings suggest the need for clinic-based screening for IPV. If universal screening is not feasible, correlates of having experienced IPV can inform targeted approaches.
The Role of Mammalian Reservoir Hosts in Tick-Borne Flavivirus Biology

Small-to-medium sized mammals and large animals are lucrative sources of blood meals for ixodid ticks that transmit life-threatening tick-borne flaviviruses (TBFVs). TBFVs have been isolated from various organs obtained from wild-caught Myodes and Apodemus species in Europe and Asia. Thus, these rodents are well-established reservoirs of TBFVs. Wild-caught Peromyscus species have demonstrated seropositivity against Powassan virus, the only TBFV known to circulate in North America, suggesting that they may play an important role in the biology of the virus in this geographic region. However, virus isolation from Peromyscus species is yet to be demonstrated. Wild-caught medium-sized mammals, such as woodchucks (Marmota monax) and skunks (Mephitis mephitis) have also demonstrated seropositivity against POWV, and virus was isolated from apparently healthy animals. Despite the well-established knowledge that small-to-medium sized animals are TBFV reservoirs, specific molecular biology addressing host-pathogen interactions remains poorly understood. Elucidating these interactions will be critical for gaining insight into the mechanism(s) of viral pathogenesis and/or resistance.
Determinants of transmission hotspots and filarial infection in households after eight rounds of mass drug administration in India

Lymphatic filariasis (LF) elimination through mass drug administration (MDA) of DEC and albendazole have resulted in very low levels of infection in most endemic districts in India. But small pockets with residual microfilaraemia in the community and antigeneamia in children (‘hotspots’) are a cause of concern. We aimed to identify the determinants of such transmission hotspots and filarial infection in households using data from 33 communities.
Relationship Between Amyloid-β Positivity and Progression to Mild Cognitive Impairment or Dementia over 8 Years in Cognitively Normal Older Adults.

BACKGROUND Preclinical Alzheimer's disease (AD) is defined by cerebral amyloid-β positivity (Aβ+) in cognitively normal (CN) older adults. OBJECTIVE To estimate the risk of progression to the symptomatic stages of AD due to PET Aβ+ and the extent that progression was influenced by other demographic, genetic, and clinical characteristics in a large prospective study. METHODS Fine-Gray subdistribution modeling was used to examine the risk of progression from CN to MCI/dementia due to Aβ+, APOEɛ4 carriage, and their interaction in the Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging CN cohort (n = 599) over 8 years. RESULTS 17.7% Aβ+ and 8.1% Aβ-progressed over 8 years (OR: 2.43). Risk of progression for Aβ+ was 65-104% greater than Aβ-. Aβ+ APOEɛ4 carriers were at 348% greater risk than all other participants. Significant risk factors of progression in Aβ+ were age (HR: 1.05), PET SUVR (HR: 2.49) and APOE ɛ4 carriage (HR: 2.63); only age was a significant risk factor in Aβ-(HR: 1.09). Aβ-progressors were not near the threshold for Aβ+. These relationships were not moderated by hypertension, diabetes, obesity, or stroke/TIA. CONCLUSION Aβ+ is an important prognostic marker for progression from CN to MCI/dementia in older adults and APOEɛ4 carriage provides further predictive value in the presence of Aβ+. These data suggest that Aβ-associated clinical progression is consistent with clinical-pathological models of AD, whereas progression in the absence of elevated Aβ deposition may be the result of neuropathological processes other than AD that accumulate with age.
What is known about consumer nutrition environments in Australia? A scoping review of the literature

Food environments can influence food selection and hold the potential to reduce obesity, non‐communicable diseases and their inequalities. ‘Consumer nutrition environments’ describe what consumers encounter within a food retail outlet, including products, price, promotion and placement. This study aimed to summarize the attributes that have been examined in existing peer‐reviewed studies of Australian consumer nutrition environments, identify knowledge gaps and provide recommendations for future research.
TRAPPopathies: An emerging set of disorders linked to variations in the genes encoding transport protein particle (TRAPP)‐associated proteins

The movement of proteins between cellular compartments requires the orchestrated actions of many factors including Rab family GTPases, Soluble NSF Attachment protein REceptors (SNAREs) and so‐called tethering factors. One such tethering factor is called TRAnsport Protein Particle (TRAPP), and in humans, TRAPP proteins are distributed into two related complexes called TRAPP II and III. Although thought to act as a single unit within the complex, in the past few years it has become evident that some TRAPP proteins function independently of the complex. Consistent with this, variations in the genes encoding these proteins result in a spectrum of human diseases with diverse, but partially overlapping, phenotypes. This contrasts with other tethering factors such as COG, where variations in the genes that encode its subunits all result in an identical phenotype. In this review, we present an up‐to‐date summary of all the known disease‐related variations of genes encoding TRAPP‐associated proteins and the disorders linked to these variations which we now call TRAPPopathies.
Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal Inflammatory Infiltration in Murine Lupus Nephritis

Background: Vascular microthrombotic lesions in lupus nephritis with or without antiphospholipid antibodies may relate to worse renal outcomes. Whether microthrombotic lesions are a consequence of renal inflammation or independently contribute to renal damage is unclear. Our aim was to investigate the relationship between microthrombotic renal vascular lesions and nephritis progression in MRL/lpr mice. Methods: MRL/lpr mice were analyzed for the presence of renal microvascular, glomerular and tubulointerstitial lesions and the effect of anti-aggregation (aspirin or clopidogrel) and dexamethasone on renal clinical and pathological manifestations was evaluated. Intravascular platelet aggregates (CD41), peri- (F4/80), and intraglomerular (Mac-2) macrophage infiltration, and C3 deposition were quantified by immunohistochemistry. Renal function was assessed by measuring proteinuria, and serum levels of creatinine and albumin. Anti-dsDNA and anti-cardiolipin antibodies, and thromboxane B2 levels were quantified by ELISA. Results: Frequency of microthrombotic renal lesions in MRL/lpr mice was high and was associated with immune-mediated renal damage. Proteinuria positively correlated with glomerular macrophage infiltration and was higher in mice with proliferative glomerular lesions. All mice had detectable anti-dsDNA and anti-cardiolipin IgG, regardless the presence of microthrombosis. Proteinuria and glomerular macrophage infiltration were significantly reduced in all treatment groups. Dexamethasone and platelet anti-aggregation similarly reduced glomerular damage and inflammation, but only platelet anti-aggregation significantly reduced anti-cardiolipin antibodies, renal complement deposition and thromboxane B2 levels. Conclusions: Platelet anti-aggregation reduced renal inflammatory damage, renal complement deposition, anti-cardiolipin antibodies, and thromboxane B2 levels and in MRL/lpr mice, suggesting that platelet activation has a pathogenic effect on immune-mediated nephritis. Our results point to MRL/lpr mice with lupus nephritis as an appropriate model to analyze the potential impact of anti-thrombotic intervention on renal inflammation.
Efficacy of bi-monthly hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma.

Background Even though the Barcelona Clinic Liver Cancer (BCLC) staging system is widely accepted, controversies on the management of hepatocellular carcinoma (HCC) still exist. We evaluated the efficacy of an approach with repeated hepatic arterial infusion chemotherapy (HAIC) given at eight-week intervals for the treatment of advanced HCC. Methods Of the 66 compensated cirrhotic patients with advanced HCC refractory to transcatheter arterial chemo-embolization (TACE) enrolled in our study, 21 were treated by bi-monthly hepatic arterial infusion chemotherapy (B-HAIC) and the rest by sorafenib. The overall survival periods, curative responses, and adverse events in each group were retrospectively analyzed. Results The efficacy rate was significantly higher in the B-HAIC group (38%, 11%, P<0.05). The median survival time and the survival rate at 12 months in the B-HAIC group were 567 days and 70.8%, and those in the sorafenib group were 366 days and 47.6%, respectively. Thus, our data suggests that the B-HAIC treatment is not inferior to sorafenib for the treatment of advanced HCC in compensated cirrhotic patients. Furthermore, the occurrence of serious adverse events leading to discontinuation of treatment was less frequent in the B-HAIC group. Conclusions Given the hepatic function reserve preservation afforded by the B-HAIC treatment in our experience, we suggest that B-HAIC should be considered an alternative strategy for advanced HCC patients who do not respond to TACE.
Sexual conflict in its ecological setting

Sexual conflict can lead to rapid and continuous coevolution between females and males, without any inputs from varying ecology. Yet both the degree of conflict and selection on antagonistic traits are known to be sensitive to local ecological conditions. This leads to the longstanding question: to what extent does variation in ecological context drive sexually antagonistic coevolution? In water striders, there is much information about the impacts of ecological factors on conflict, and about patterns of antagonistic coevolution. However, the connection between the two is poorly understood. Here, we first review the multiple ways in which ecological context might affect the coevolutionary trajectory of the sexes. We then review ecological and coevolutionary patterns in water striders, and connections between them, in light of theory and new data. Our analysis suggests that ecological variation does impact observed patterns of antagonistic coevolution, but highlights significant uncertainty due to the multiple pathways by which ecological factors can influence conflict and its evolutionary outcome. To the extent that water striders are a reasonable reflection of other systems, this observation serves as both an opportunity and a warning: there is much to learn, but gaining insight may be a daunting process in many systems. This article is part of the theme issue ‘Linking local adaptation with the evolution of sex differences'.
Drug Seeking and Relapse: New Evidence of a Role for Orexin and Dynorphin Co-transmission in the Paraventricular Nucleus of the Thalamus

The long-lasting vulnerability to relapse remains the main challenge for the successful treatment of drug addiction. Neural systems that are involved in processing natural rewards and drugs of abuse overlap. However, neuroplasticity that is caused by drug exposure may be responsible for maladaptive, compulsive, and addictive behavior. The orexin (Orx) system participates in regulating numerous physiological processes, including energy metabolism, arousal, and feeding, and is recruited by drugs of abuse. The Orx system is differentially recruited by drugs and natural rewards. Specifically, we found that the Orx system is more engaged by drugs than by non-drugs, such as sweetened condensed milk (SCM) or a glucose saccharin solution (GSS), in an operant model of reward seeking. Although stimuli (S+) that are conditioned to cocaine (COC), ethanol, and SCM/GSS equally elicited reinstatement, Orx receptor blockade reversed conditioned reinstatement for drugs vs. non-drugs. Moreover, the hypothalamic recruitment of Orx cells was greater in rats that were tested with the COC S+ vs. SCM S+, indicating of a preferential role for the Orx system in perseverative, compulsive-like COC seeking and not behavior that is motivated by palatable food. Accumulating evidence indicates that the paraventricular nucleus of the thalamus (PVT), which receives major Orx projections, mediates drug-seeking behavior. All Orx neurons contain dynorphin (Dyn), and Orx and Dyn are co-released. In the VTA, they play opposing roles in reward and motivation. To fully understand the physiological and behavioral roles of Orx transmission in the PVT, one important consideration is that Orx neurons that project to the PVT may co-release Orx with another peptide, such as Dyn. The PVT expresses both Orx receptors and κ opioid receptors, suggesting that Orx and Dyn act in tandem when released in the PVT, in addition to the VTA. The present review discusses recent findings that suggest the maladaptive recruitment of Orx/Dyn-PVT neurotransmission by drugs of abuse vs. a highly palatable food reward.
Comparing Attention-Based Convolutional and Recurrent Neural Networks: Success and Limitations in Machine Reading Comprehension

We propose a machine reading comprehension model based on the compare-aggregate framework with two-staged attention that achieves state-of-the-art results on the MovieQA question answering dataset. To investigate the limitations of our model as well as the behavioral difference between convolutional and recurrent neural networks, we generate adversarial examples to confuse the model and compare to human performance. Furthermore, we assess the generalizability of our model by analyzing its differences to human inference, drawing upon insights from cognitive science.
Heterogeneity of colon and rectum cancer incidence across 612 SEER counties, 2000–2014

Recent analyses have suggested decreases over time in colorectal cancer incidence at older ages (≥55 years) but increases at younger ages (20–54 years). Understanding the geographic heterogeneity of incidence facilitates resource allocation for potential interventions and advances our knowledge of differential etiologies for these cancers. We performed age‐period‐cohort analysis using 2000–2014 county‐level incidence from the Surveillance, Epidemiology, and End Results (SEER) database, estimating relative risk (RR) and age‐adjusted annual percent change (Net Drifts) simultaneously for 612 counties via a hierarchical model, separately for colon and rectum cancer, stratified by age group (20–54 vs. 55–84). We also studied correlates of RR and Net Drift with various county‐level characteristics. In all SEER counties, colon and rectum cancer incidence rates increased at ages 20–54, whereas rates decreased at ages 55–84. There was marked heterogeneity in both RR and Net Drift among states and counties for both cancer types. Maps of county RR and Net Drift revealed localized clusters in several states. For both cancer types, counties with high RR and unfavorable Net Drift tended to have higher prevalence of obesity and diabetes and to be of a lower socioeconomic status. Counties with higher overall screening rates tended to have lower Net Drifts for both cancer types. Increasing colorectal cancer incidence in the younger age group is geographically widespread, although there is significant heterogeneity in temporal trends and risk both within and between states. These geographic patterns correlate with different county‐level characteristics depending on cancer type and age group.
Sample Complexity of Sparse System Identification Problem

In this paper, we study the system identification problem for sparse linear time-invariant systems. We propose a sparsity promoting block-regularized estimator to identify the dynamics of the system with only a limited number of input-state data samples. We characterize the properties of this estimator under high-dimensional scaling, where the growth rate of the system dimension is comparable to or even faster than that of the number of available sample trajectories. In particular, using contemporary results on high-dimensional statistics, we show that the proposed estimator results in a small element-wise error, provided that the number of sample trajectories is above a threshold. This threshold depends polynomially on the size of each block and the number of nonzero elements at different rows of input and state matrices, but only logarithmically on the system dimension. A by-product of this result is that the number of sample trajectories required for sparse system identification is significantly smaller than the dimension of the system. Furthermore, we show that, unlike the recently celebrated least-squares estimators for system identification problems, the method developed in this work is capable of \textit{exact recovery} of the underlying sparsity structure of the system with the aforementioned number of data samples. Extensive case studies on synthetically generated systems, physical mass-spring networks, and multi-agent systems are offered to demonstrate the effectiveness of the proposed method.
Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science

Comprehensive literature reviews of historical perspectives and evidence supporting cannabis/cannabinoids in the treatment of pain, including migraine and headache, with associated neurobiological mechanisms of pain modulation have been well described. Most of the existing literature reports on the cannabinoids Δ9‐tetrahydrocannabinol (THC) and cannabidiol (CBD), or cannabis in general. There are many cannabis strains that vary widely in the composition of cannabinoids, terpenes, flavonoids, and other compounds. These components work synergistically to produce wide variations in benefits, side effects, and strain characteristics. Knowledge of the individual medicinal properties of the cannabinoids, terpenes, and flavonoids is necessary to cross‐breed strains to obtain optimal standardized synergistic compositions. This will enable targeting individual symptoms and/or diseases, including migraine, headache, and pain.
Surface Plasmon Resonance Optical Sensor: A Review on Light Source Technology

The notion of surface plasmon resonance (SPR) sensor research emerged more than eight decades ago from the first observed phenomena in 1902 until the first introduced principles for gas sensing and biosensing in 1983. The sensing platform has been hand-in-hand with the plethora of sensing technology advancement including nanostructuring, optical technology, fluidic technology, and light source technology, which contribute to substantial progress in SPR sensor evolution. Nevertheless, the commercial products of SPR sensors in the market still require high-cost investment, component, and operation, leading to unaffordability for their implementation in a low-cost point of care (PoC) or laboratories. In this article, we present a comprehensive review of SPR sensor development including the state of the art from a perspective of light source technology trends. Based on our review, the trend of SPR sensor configurations, as well as its methodology and optical designs are strongly influenced by the development of light source technology as a critical component. These simultaneously offer new underlying principles of SPR sensor towards miniaturization, portability, and disposability features. The low-cost solid-state light source technology, such as laser diode, light-emitting diode (LED), organic light emitting diode (OLED) and smartphone display have been reported as proof of concept for the future of low-cost SPR sensor platforms. Finally, this review provides a comprehensive overview, particularly for SPR sensor designers, including emerging engineers or experts in this field.