Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA‐mediated metabolic reprogramming of chimeric antigen receptor T cells

Advances made in chimeric antigen receptor (CAR) T cell therapy have revolutionized the treatment and management of certain cancers. Currently, B cell malignancies have been among the few cancers to which CAR T cells have shown persistent and resilient anti‐tumor responses. A growing body of evidence suggests that the persistence of CAR T cells within patients following infusion is linked to the mitochondrial fitness of the CAR T cell, which could affect clinical outcomes. Analysis of CAR T cells from patients undergoing successful treatment has shown an increase in mitochondrial mass and fusion events, and a reduction in aerobic metabolism, highlighting the importance of mitochondria in CAR T cell function. Consequently, there has been recent interest and investment in approaches that focus on mitochondrial programming. In this regard, miRNAs are promising agents in mitochondrial reprogramming for several reasons: (1) natural and artificial miRNAs are non‐immunogenic, (2) one miRNA can simultaneously modulate the expression of multiple genes within a pathway, (3) the small size of a sequence required for producing mature miRNA is ideal for use in viral vectors and (4) different precursor miRNAs (pre‐miRNAs) hairpins can be incorporated into a polycistronic miRNA cluster to create a miRNA cocktail. In this perspective, we describe the latest genetic engineering strategies that can be used to achieve the optimal expression of candidate miRNAs alongside a CAR construct. In addition, we include an in silico analysis of rational candidate miRNAs that could promote the mitochondrial fitness of CAR T cells.
Coherent modeling of longitudinal causal effects on binary outcomes

Analyses of biomedical studies often necessitate modeling longitudinal causal effects. The current focus on personalized medicine and effect heterogeneity makes this task even more challenging. Toward this end, structural nested mean models (SNMMs) are fundamental tools for studying heterogeneous treatment effects in longitudinal studies. However, when outcomes are binary, current methods for estimating multiplicative and additive SNMM parameters suffer from variation dependence between the causal parameters and the noncausal nuisance parameters. This leads to a series of difficulties in interpretation, estimation, and computation. These difficulties have hindered the uptake of SNMMs in biomedical practice, where binary outcomes are very common. We solve the variation dependence problem for the binary multiplicative SNMM via a reparameterization of the noncausal nuisance parameters. Our novel nuisance parameters are variation independent of the causal parameters, and hence allow for coherent modeling of heterogeneous effects from longitudinal studies with binary outcomes. Our parameterization also provides a key building block for flexible doubly robust estimation of the causal parameters. Along the way, we prove that an additive SNMM with binary outcomes does not admit a variation independent parameterization, thereby justifying the restriction to multiplicative SNMMs.
Which test is the best? An updated literature review of imaging modalities for acute ankle diastasis injuries

Ankle diastasis injuries, or ankle syndesmotic injuries, are common among athletes who usually experience a traumatic injury to the ankle. Long‐term complications are avoidable when these injuries are diagnosed promptly and accurately treated. Whilst ankle arthroscopy remains the gold standard diagnostic modality for ankle diastasis injuries, imaging modalities are still widely utilised due to the treatment having greater accessibility, being less invasive and the most cost effective. There are various imaging modalities used to diagnose diastasis injuries, varying in levels of specificity and sensitivity. These observation methods include; X‐ray, computed tomography (CT), magnetic resonance imaging (MRI) and ankle arthroscopy. This article uncovers common criteria and parameters to diagnose diastasis injuries through the implementation of different imaging modalities. The conclusions addressed within this article are deduced from a total of 338 articles being screened with only 43 articles being selected for the purposes of this examination. Across most articles, it was concluded that that plain X‐ray should be used in the first instance due to its wide availability, quick processing time, and low cost. CT is the next recommended investigation due to its increased sensitivity and specificity, ability to show the positional relationship of the distal tibiofibular syndesmosis, and reliability in detecting minor diastasis injuries. MRI is recommended when ankle diastasis injuries are suspected, but not diagnosed on previous imaging modalities. It has the highest sensitivity and specificity compared to X‐ray and CT.
lncRNA H19 promotes glioblastoma multiforme development by activating autophagy by sponging miR-491-5p

ABSTRACT Glioblastoma multiforme (GBM) is a malignant cancer with severely poor survival, and the cells continue to thrive during hypoxia and toxic stress through autophagy. To validate the oncogenic role of long noncoding RNA H19 in GBM progression and examine whether autophagy and/or miR-491-5p participate in the process. The expression of H19 and autophagy-related genes in GBM and healthy control tissues was assessed via quantitative polymerase chain reaction. In addition, cell viability, proliferation, apoptosis and autophagy were respectively determined via cell counting kit-8 assay, clone formation assay, flow cytometry, western blotting and green fluorescent protein–microtubule-associated protein 1 light chain 3 alpha fluorescence analysis in vitro. Furthermore, a rescue assay was performed using rapamycin or miR-491-5p antagomir to examine the role of autophagy or miR-491-5p in H19-mediated regulation of proliferation and apoptosis. RNA pull-down and dual-luciferase reporter assays were employed to analyze the interaction between H19 and miR-491-5p. Additionally, tumor growth in a xenograft-bearing mouse model and autophagy in tumor mass were analyzed in vivo. The expression H19 was increased in GBM and was positively correlated with LC3 or Beclin-1. Silencing H19 inhibited growth and promoted apoptosis in GBM cells both in vitro and in vivo, and miR-491-5p was identified as one of the important mediators. H19 regulated the autophagy signaling pathway at least partly via miR-491-5p. Increased H19 expression in GBM exerts oncogenic effects by sponging miR-491-5p and enhancing autophagy. Therefore, H19 may be explored as a target for GBM therapy. GRAPHICAL ABSTRACT
General Drinking Motives and Alcohol Consumption across Three Contexts: Drinking Games, Tailgating, and in Stadium

Abstract Background Alcohol consumption across specific events and contexts has been identified as an important area of research related to college student drinking. Contexts associated with increased risk for negative outcomes include drinking games and football games at large universities. Additionally, drinking motives have been linked to increased consumption and consequences. The current study aimed to assess the role of general drinking motives across a variety of specific contexts. Methods Self-report measures related to general alcohol consumption, general drinking motives, and context-specific consumption were completed by a final sample of 553 predominantly female and white students. Three sets of hierarchical regression analyses were conducted to measure relations between drinking motives and the number of drinks consumed in the contexts of drinking games, tailgating outside of the stadium prior to home football games, and while inside the football stadium during home games, after accounting for the number of times participating in each respective context. Results Concerning tailgates, conformity and enhancement motives were positively related to the number of drinks consumed. Conformity motives were associated with greater consumption in the contexts of drinking games and in-stadium drinking. Social motives were inversely related to the number of drinks consumed in-stadium. Conclusion Different general drinking motives may contribute to individuals’ alcohol consumption across specific contexts. While conformity motives are not traditionally viewed as a unique risk factor for problematic use, the relation between conformity motives and consumption while playing drinking games and within the stadium provides novel results about their potential role in alcohol-related outcomes.
Task allocation in multi-robot system using resource sharing with dynamic threshold approach

Task allocation is a fundamental requirement for multi-robot systems working in dynamic environments. An efficient task allocation algorithm allows the robots to adjust their behavior in response to environmental changes such as fault occurrences, or other robots’ actions to increase overall system performance. To address these challenges, this paper presents a Task Allocation technique based on a threshold level which is an accumulative value aggregated by a centralized unit using the Task-Robot ratio and the number of the available resource in the system. The threshold level serves as a reference for task acceptance and the task acceptance occurs despite resource shortage. The deficient resources for the accepted task are acquired through an auction process using objective minimization. Despite resource shortage, task acceptance occurs. The threshold approach and the objective minimization in the auction process reduce the overall completion time and increase the system’s resource utilization up to 96%, which is demonstrated theoretically and validated through simulations and real experimentation.
Arthrospira (Spirulina) platensis feeding reduces the early stage of chemically induced rat colon carcinogenesis

Abstract Colorectal cancer is the third most diagnosed cancer worldwide and linked to dietary/lifestyle factors. Arthrospira (Spirulina) platensis (AP) contains bioactive compounds with beneficial effects in vivo/in vitro. We evaluated the effects of AP feeding against 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Male Sprague Dawley rats were given subcutaneous injections of DMH (4 × 40 mg/kg body weight) (G1–G3) or vehicle (G4–G5) twice a week (weeks 3–4). During weeks 1–4, animals were fed a diet containing 1 % (G2) or 2 % (G3–G4) AP powder (w/w). After this period, all groups received a balanced diet until week 12. Some animals were euthanised after the last DMH injection (week 4) for histological, immunohistochemical (Ki-67, γ-H2AX and caspase-3) and molecular analyses (real time-PCR for 91 genes), while other animals were euthanised at week 12 for preneoplastic aberrant crypt foci (ACF) analysis. Both AP treatments (G2–G3) significantly decreased the DMH-induced increase in γ-H2AX (DNA damage) and caspase 3 (DNA damage-induced cell death) in colonic crypts at week 4. In addition, Cyp2e1 (Drug metabolism), Notch1, Notch2 and Jag1 genes (Notch pathway) and Atm, Wee1, Chek2, Mgmt, Ogg1 and Xrcc6 genes (DNA repair) were also down-regulated by 2 % AP feeding (G3) at week 4. A significant reduction in ACF development was observed in both AP-treated groups (G2–G3) at week 12. In conclusion, findings indicate that AP feeding reduced acute colonic damage after DMH, resulting in fewer preneoplastic lesions. Our study provided mechanistic insights on dietary AP-preventive effects against early colon carcinogenesis.
Joint effects of voluntary participation and group selection on the evolution of altruistic punishment

It is puzzling how altruistic punishment of defectors can evolve in large groups of nonrelatives, since punishers should voluntarily bear individual costs of punishing to benefit those who do not pay the costs. Although two distinct mechanisms have been proposed to explain the puzzle, namely voluntary participation and group-level competition and selection, insights into their joint effects have been less clear. Here we investigated what could be combined effects of these two mechanisms on the evolution of altruistic punishment and how these effects can vary with nonparticipants’ individual payoff and group size. We modelled altruistic punishers as those who contribute to a public good and impose a fine on each defector, i.e., they are neither pure punishers nor excluders. Our simulation results show that voluntary participation has negative effects on the evolution of cooperation in small groups regardless of nonparticipants’ payoffs, while in large groups it has positive effects within only a limited range of nonparticipants’ payoff. We discuss that such asymmetric effects could be explained by evolutionary forces emerging from voluntary participation. Lastly, we suggest that insights from social science disciplines studying the exit option could enrich voluntary participation models.
SLAMF8 promotes the proliferation and migration of synovial fibroblasts by regulating the ERK/MMPs signalling pathway

Abstract Rheumatoid arthritis is troublesome to treat effectively and often requires concomitant long-term treatment. Meanwhile, synovial fibroblasts could induce inflammation response and lead to joint erosion, finally causing progressive joint destruction, disability, and increased mortality. This study focussed on the role of SLAM family member 8 (SLAMF8) in mediating cell function from rheumatoid arthritis synovial fibroblasts stimulated with TNF-α. Cell Counting Kit-8 (CCK-8) and colony-forming unit assay were used to evaluate cell proliferation. SLAMF8 expression was analysed by reverse transcription-quantitative PCR (RT-qPCR) and western blot. Annexin V‐FITC/PI double staining was used to measure the apoptosis rate. The cell migration and invasion in TNF-α-stimulated MH7A (human rheumatoid arthritis synovial cell line) and HFLS-RA cells (human fibroblast-like synoviocytes: rheumatoid arthritis) were tested via wound healing assay and transwell migration assay. In the present study, after TNF-α treatments, the SLAMF8 mRNA and protein expression in both MH7A and HFLS-RA cell lines have a time-dependent increase. The attenuation of SLAMF8 ameliorated TNF-α-induced proliferation, invasion and migration in MH7A and HFLS-RA cells. Simultaneously, when SLAMF8 was silenced, the expression of p-ERK, MMP-1, and MMP-13 was suppressed significantly. In summary, these results indicated that the knockdown of the SLAMF8 significantly attenuated TNF-α-induced proinflammatory responses in MH7A and HFLS-RA cells. Therefore, SLAMF8 exhibits therapeutic potential for the management of inflammation in rheumatoid arthritis.
High striped hyena density suggests coexistence with humans in an agricultural landscape, Rajasthan

Understanding the mechanism of coexistence, where carnivores adapt to humans and vice versa in the shared landscape, is a key determinant of long-term carnivore conservation but is yet to be comprehensively examined. We explored the coexistence mechanism of striped hyena (Hyaena hyaena) and humans in the shared landscape of Sawai Mansingh Wildlife Sanctuary (SMS WLS), Rajasthan, from November 2019 to March 2021. We used data derived from motion sensors-based surveys, satellite remote sensing images, and household questionnaires to understand socio-ecological, environmental and anthropogenic factors facilitating hyena persistence in the shared landscape. The high density (12 individuals/100 km2) striped hyena in the landscape revealed the coexistence with humans. Being scavengers, they get subsidised food sources and are perceived as low-risk species by humans. Striped hyena minimised temporal activity during the daytime when human activity peaked. However, the highest activity overlap was observed in the agricultural area (Δ1 = 0.39), and likely depicts the high activity due to agricultural practices. While the human settlement was positively associated with the detection of hyenas, the probability of striped hyena captures increased with decreasing distance from human settlement, possibly influenced by high carcass availability, providing the easiest food resources to striped hyena, and allowing them to coexist with humans. This study demonstrates the coexistence of hyenas and humans in the shared landscape supported by mutual benefits, where hyenas benefit from anthropogenic food from scavenging, while humans benefit from waste removal and the non-lethal nature hyenas.
Ensuring Learning in Slow Learners

Education is relevant only if we take care of our learners. Teachers must therefore be sensitive not to the covering of the curriculum but to the learning that has taken place in the transaction. Teachers cannot ignore the students who do not keep pace with the teaching-learning process. Some students do feel neglected and unwanted in the whole transaction of the school system. This category of students need to be taken utmost care and tackled in a manner that will produce better output from them. In the process, they will tend to realize themselves in a better way and develop positive attitudes towards themselves. The study thus has focused its attention on teachers in particular, their attitude towards slow learners and the efforts taken for them for their overall development.
Catalyzing new product adoption at the base of the pyramid

One of the more perplexing of the entrepreneurial issues at the Base of the Pyramid (BoP) is how to catalyze new product adoption by BoP consumers. Because S-shaped adoption dynamics are the result of cultural transmission bias, the question can be rephrased as, how can an entrepreneur overcome conformity bias. We modified the Technology Acceptance Model (TAM) to include conformity bias. We then qualitatively applied the model to three examples from the literature, namely fuel stoves in Darfur refugee camps, M-Pesa in Kenya and Tata Nano in India. We found that selling in road shows and tent shows catalyzed technology adoption; and all other things being equal, the less radical innovation diffused more easily than the more radical innovation. Operationalization of the results is discussed.
Mechanistic basis for multidrug resistance and collateral drug sensitivity conferred to the malaria parasite by polymorphisms in PfMDR1 and PfCRT

Polymorphisms in the Plasmodium falciparum multidrug resistance protein 1 (pfmdr1) gene and the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene alter the malaria parasite’s susceptibility to most of the current antimalarial drugs. However, the precise mechanisms by which PfMDR1 contributes to multidrug resistance have not yet been fully elucidated, nor is it understood why polymorphisms in pfmdr1 and pfcrt that cause chloroquine resistance simultaneously increase the parasite’s susceptibility to lumefantrine and mefloquine—a phenomenon known as collateral drug sensitivity. Here, we present a robust expression system for PfMDR1 in Xenopus oocytes that enables direct and high-resolution biochemical characterizations of the protein. We show that wild-type PfMDR1 transports diverse pharmacons, including lumefantrine, mefloquine, dihydroartemisinin, piperaquine, amodiaquine, methylene blue, and chloroquine (but not the antiviral drug amantadine). Field-derived mutant isoforms of PfMDR1 differ from the wild-type protein, and each other, in their capacities to transport these drugs, indicating that PfMDR1-induced changes in the distribution of drugs between the parasite’s digestive vacuole (DV) and the cytosol are a key driver of both antimalarial resistance and the variability between multidrug resistance phenotypes. Of note, the PfMDR1 isoforms prevalent in chloroquine-resistant isolates exhibit reduced capacities for chloroquine, lumefantrine, and mefloquine transport. We observe the opposite relationship between chloroquine resistance-conferring mutations in PfCRT and drug transport activity. Using our established assays for characterizing PfCRT in the Xenopus oocyte system and in live parasite assays, we demonstrate that these PfCRT isoforms transport all 3 drugs, whereas wild-type PfCRT does not. We present a mechanistic model for collateral drug sensitivity in which mutant isoforms of PfMDR1 and PfCRT cause chloroquine, lumefantrine, and mefloquine to remain in the cytosol instead of sequestering within the DV. This change in drug distribution increases the access of lumefantrine and mefloquine to their primary targets (thought to be located outside of the DV), while simultaneously decreasing chloroquine’s access to its target within the DV. The mechanistic insights presented here provide a basis for developing approaches that extend the useful life span of antimalarials by exploiting the opposing selection forces they exert upon PfCRT and PfMDR1.
Parent/guardian intentions to vaccinate children against COVID-19 in the United States

ABSTRACT Vaccination is critical for protecting adults and children from COVID-19 infection, hospitalization, and death. Analyzing subsamples of parent/guardians of children age 0–11 (n = 343) and 12–17 (n = 322) from a larger national survey of US adults (n = 2,022), we aimed to assess intentions to vaccinate children and how intentions might vary across parent/guardian sociodemographic characteristics, healthcare coverage, vaccination status, political affiliation, prior COVID-19 infection, exposure to COVID-19 death(s) of family or friends, perceived norms of vaccination, and COVID-19 vaccine hesitancy. We also report the prevalence of vaccinated children for parents whose oldest child was eligible for vaccination at the time of the survey. More than one third of parents whose oldest child was not yet eligible for vaccination (11 or younger) planned to get them vaccinated right away when a vaccine became available to them. Among parents whose child was eligible to be vaccinated (age 12–17 years), approximately a third reported their child had already been vaccinated and approximately a third planned to do so right away. Intentions to vaccinate children age 0 to 11 were significantly associated with age, gender, race/ethnicity, education, COVID-19 vaccination, political affiliation, social norms, and COVID-19 vaccine hesitancy. Intentions to vaccinate children age 12 to 17 were significantly associated with age, education, healthcare coverage, COVID-19 vaccination, political affiliation, social norms, and COVID-19 vaccine hesitancy. We discuss implications for public health officials and for future research.
Increasing nodal vulnerability and nodal efficiency implied recovery time prolonging in patients with supplementary motor area syndrome

Supplementary motor area (SMA) syndrome is a surgery‐related complication that commonly occurs after removing SMA glioma, and needs weeks to recover. However, susceptible factors of patients suffering from SMA syndrome remain unknown. Graphic theory was applied to reveal topological properties of sensorimotor network (SMN) by processing resting‐state functional magnetic resonance images in 66 patients with SMA gliomas. Patients were classified into SMA and non‐SMA groups based on whether they suffered from SMA syndrome. We collected recovery time and used causal mediation analysis to find association between topological properties and recovery time. Compared with the non‐SMA group, higher vulnerability (left: p = .0018; right: p = .0033) and lower fault tolerance (left: p = .0022; right: p = .0248) of the whole SMN were found in the SMA group. Moreover, higher nodal properties of lesional‐hemispheric cingulate cortex (nodal efficiency: left, p = .0389; right, p = .0169; nodal vulnerability: left, p = .0185; right, p = .0085) and upper limb region of primary motor cortex (PMC; nodal efficiency: left, p = .0132; right, p = .0001; nodal vulnerability: left, p = .0091; right, p = .0209) were found in the SMA group. Nodal efficiency and nodal vulnerability of cingulate cortex and upper limb region of PMC were important predictors for SMA syndrome occurring and recovery time prolonging. Neurosurgeons should carefully deal with upper limb region of PMC and cingulate cortex, and protect them if these two region were unnecessary to damage during SMA glioma resection.