Miracle-dz/UniFAR-FTUs huggingface dataset:
Inventory and Analysis of Controlled Trials of Mobile Phone Applications Targeting Substance Use Disorders: A Systematic Review

Background: Less than 20% of people with addictions have access to adequate treatment. Mobile health could improve access to care. No systematic review evaluates effectiveness of mobile health applications for addiction. Objectives: First aim was to describe controlled trials evaluating the effectiveness of smartphone applications targeting substance use disorders and addictive behaviors. Secondly, we aimed to understand how the application produced changes in behavior and craving management. Method: A systematic review based on PRISMA recommendations was conducted on MEDLINE, CENTRAL, and PsycINFO. Studies had to be controlled trials concerning addictive disorders (substance/behavior), mobile application-based interventions, assessing effectiveness or impact of those applications upon use, published after 2008. Relevant information was systematically screened for synthesis. Quality and risk of bias were evaluated with JADAD score. Results: Search strategy retrieved 22 articles (2014-2019) corresponding to 22 applications targeting tobacco, alcohol, other substances and binge eating disorder. Control groups had access to usual treatments or a placebo-application or no treatment. Eight applications showed reduced use. Most of the applications informed about risks of use and suggestions for monitoring use. Twelve applications managed craving. Discussion: Heterogeneity limited study comparisons. Duration of studies was too short to predict sustainable results. A reduction of craving seemed related to a reduction in use. Conclusion: There is a lack of robust and comparable studies on mHealth applications for addiction treatment. Such applications could become significant contributors in clinical practice in the future so longer-termed double-blind studies are needed. Targeting craving to prevent relapse should be systematic.
Modeling Cell Selectivity of Antimicrobial Peptides: How Is the Selectivity Influenced by Intracellular Peptide Uptake and Cell Density

Antimicrobial peptides (AMPs) are known to attack bacteria selectively over their host cells. Many attempts have been made to use them as a template for designing peptide antibiotics for fighting drug-resistant bacteria. A central concept in this endeavor is “peptide selectivity,” which measures the “quality” of peptides. However, the relevance of selectivity measurements has often been obscured by the cell-density dependence of the selectivity. For instance, the selectivity can be overestimated if the cell density is larger for the host cell. Furthermore, recent experimental studies suggest that peptide trapping in target bacteria magnifies the cell-density dependence of peptide activity. Here, we propose a biophysical model for peptide activity and selectivity, which assists with the correct interpretation of selectivity measurements. The resulting model shows how cell density and peptide trapping in cells influence peptide activity and selectivity: while these effects can alter the selectivity by more than an order of magnitude, peptide trapping works in favor of host cells at high host-cell densities. It can be used to correct selectivity overestimates.
Case Report: First Evidence of a Benign Bone Cyst in an Adult Teckel Dog Treated With Shark Teeth-Derived Bioapatites

Bone cysts are a very rare orthopedic pathology in veterinary medicine, the general prevalence of which is unknown. A unicameral bone cyst was diagnosed in an adult female Teckel dog with a limp that was treated surgically by filling the defect with marine bioapatites. The treatment was effective and at 8 weeks the defect had remodeled 50.24%. Eighteen months after surgery, the defect had remodeled 94.23%. The limp disappeared after surgery, and functional recovery was good in all stages after surgery. No adverse reactions were observed at the local or systemic level. This is the first report of a benign bone cyst in an lame adult female Teckel successfully treated with a novel marine bioapatite.
Inside the Thrombus: Association of Hemostatic Parameters With Outcomes in Large Vessel Stroke Patients

Background: Actual clinical management of ischemic stroke (IS) is based on restoring cerebral blood flow using tissue plasminogen activator (tPA) and/or endovascular treatment (EVT). Mechanical thrombectomy has permitted the analysis of thrombus structural and cellular classic components. Nevertheless, histological assessment of hemostatic parameters such as thrombin-activatable fibrinolysis inhibitor (TAFI) and matrix metalloproteinase 10 (MMP-10) remains unknown, although their presence could determine thrombus stability and its response to thrombolytic treatment, improving patient's outcome. Methods: We collected thrombi (n = 45) from large vessel occlusion (LVO) stroke patients (n = 53) and performed a histological analysis of different hemostatic parameters [TAFI, MMP-10, von Willebrand factor (VWF), and fibrin] and cellular components (erythrocytes, leukocytes, macrophages, lymphocytes, and platelets). Additionally, we evaluated the association of these parameters with plasma levels of MMP-10, TAFI and VWF activity and recorded clinical variables. Results: In this study, we report for the first time the presence of MMP-10 and TAFI in all thrombi collected from LVO patients. Both proteins were localized in regions of inflammatory cells, surrounded by erythrocyte and platelet-rich areas, and their content was significantly associated (r = 0.41, p < 0.01). Thrombus TAFI was lower in patients who died during the first 3 months after stroke onset [odds ratio (OR) (95%CI); 0.59 (0.36–0.98), p = 0.043]. Likewise, we observed that thrombus MMP-10 was inversely correlated with the amount of VWF (r = −0.30, p < 0.05). Besides, VWF was associated with the presence of leukocytes (r = 0.37, p < 0.05), platelets (r = 0.32, p < 0.05), and 3 months mortality [OR (95%CI); 4.5 (1.2–17.1), p = 0.029]. Finally, plasma levels of TAFI correlated with circulating and thrombus platelets, while plasma MMP-10 was associated with cardiovascular risk factors and functional dependence at 3 months. Conclusions: The present study suggests that the composition and distribution of thrombus hemostatic components might have clinical impact by influencing the response to pharmacological and mechanical therapies as well as guiding the development of new therapeutic strategies.
Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients

Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed ~140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with ~30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-γ production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease.
Different Disease Endotypes in Phenotypically Similar Vasculitides Affecting Small-to-Medium Sized Blood Vessels

Objectives: Chronic primary vasculitis describes a group of complex and rare diseases that are characterized by blood vessel inflammation. Classification of vasculitis subtypes is based predominantly on the size of the involved vessels and clinical phenotype. There is a recognized need to improve classification, especially for small-to-medium sized vessel vasculitides, that, ideally, is based on the underlying biology with a view to informing treatment. Methods: We performed RNA-Seq on blood samples from children (n = 41) and from adults (n = 11) with small-to-medium sized vessel vasculitis, and used unsupervised hierarchical clustering of gene expression patterns in combination with clinical metadata to define disease subtypes. Results: Differential gene expression at the time of diagnosis separated patients into two primary endotypes that differed in the expression of ~3,800 genes in children, and ~1,600 genes in adults. These endotypes were also present during disease flares, and both adult and pediatric endotypes could be discriminated based on the expression of just 20 differentially expressed genes. Endotypes were associated with distinct biological processes, namely neutrophil degranulation and T cell receptor signaling. Conclusions: Phenotypically similar subsets of small-to-medium sized vessel vasculitis may have different mechanistic drivers involving innate vs. adaptive immune processes. Discovery of these differentiating immune features provides a mechanistic-based alternative for subclassification of vasculitis.
Comparison of Flowmetric Plethysmography and Forced Oscillatory Mechanics to Measure Airway Hyperresponsiveness in Horses

Airway hyperresponsiveness (AHR) is linked to airway inflammation and is considered a key manifestation of mild/moderate equine asthma (EA). The study purpose was to determine whether two modalities of non-invasive lung function testing (FOM—forced oscillatory mechanics vs. FP—flowmetric plethysmography) establish the same clinical diagnosis of AHR in horses, using histamine bronchoprovocation. Nineteen horses (3–25 years, 335–650 kg) with clinical signs suggestive of mild/moderate equine asthma were enrolled. FOM and FP testing was performed in each horse on two consecutive days, using a randomized cross-over design. AHR was defined by the histamine dose needed to double FOM baseline resistance, or to achieve a 35% increase in FP delta flow. Bronchoalveolar lavage fluid (BALF) was subsequently collected and stained with modified Wright's and toluidine blue stains. Binary statistical tests (related samples T-test, Mann-Whitney U, Chi-square analyses) were performed to compare study groups, with P < 0.05 considered significant. Abnormal BALF cytology confirmed EA in 14/19 (73.7%) horses. Both FOM and FP revealed AHR in 7/14 (50%) of these EA horses. An additional 4/19 (21.1%) horses showed AHR based on FP but not FOM, including two horses with normal BALF cytology. A diagnosis of AHR was more often associated with FP than FOM (P = 0.013), although the prevalence of AHR was significantly higher in EA vs. non-EA horses, regardless of testing methodology. The phase angle between thoracic and abdominal components of breathing did not differ between test groups. In conclusion, FP diagnosed AHR more frequently than did FOM, including horses with no other diagnostic evidence of EA. Without further evaluation, these two testing modalities of AHR cannot be used interchangeably.
Cultural Sources of Strength and Resilience: A Case Study of Holistic Wellness Boxes for COVID-19 Response in Indigenous Communities

The COVID-19 pandemic has had disproportionately severe impacts on Indigenous peoples in the United States compared to non-Indigenous populations. In addition to the threat of viral infection, COVID-19 poses increased risk for psychosocial stress that may widen already existing physical, mental, and behavioral health inequities experienced by Indigenous communities. In recognition of the impact of COVID-19 related psychosocial stressors on our tribal community partners, the Johns Hopkins Center for American Indian Health Great Lakes Hub began sending holistic wellness boxes to our community partners in 11 tribal communities in the Midwestern United States and Canada in summer of 2020. Designed specifically to draw on culturally relevant sources of strength and resilience, these boxes contained a variety of items to support mental, emotional, cultural, and physical wellbeing. Feedback from recipients suggest that these wellness boxes provided a unique form of COVID-19 relief. Additional Johns Hopkins Center for American Indian Health offices have begun to adapt wellness boxes for the cultural context of their regions. This case study describes the conceptualization, creation, and contents of these wellness boxes and orients this intervention within a reflection on foundations of community-based participatory research, holistic relief, and drawing on cultural strengths in responding to COVID-19.
Dissimilatory Fe(III) Reduction Controls on Arsenic Mobilization: A Combined Biogeochemical and NanoSIMS Imaging Approach

Microbial metabolism plays a key role in controlling the fate of toxic groundwater contaminants, such as arsenic. Dissimilatory metal reduction catalyzed by subsurface bacteria can facilitate the mobilization of arsenic via the reductive dissolution of As(V)-bearing Fe(III) mineral assemblages. The mobility of liberated As(V) can then be amplified via reduction to the more soluble As(III) by As(V)-respiring bacteria. This investigation focused on the reductive dissolution of As(V) sorbed onto Fe(III)-(oxyhydr)oxide by model Fe(III)- and As(V)-reducing bacteria, to elucidate the mechanisms underpinning these processes at the single-cell scale. Axenic cultures of Shewanella sp. ANA-3 wild-type (WT) cells [able to respire both Fe(III) and As(V)] were grown using 13C-labeled lactate on an arsenical Fe(III)-(oxyhydr)oxide thin film, and after colonization, the distribution of Fe and As in the solid phase was assessed using nanoscale secondary ion mass spectrometry (NanoSIMS), complemented with aqueous geochemistry analyses. Parallel experiments were conducted using an arrA mutant, able to respire Fe(III) but not As(V). NanoSIMS imaging showed that most metabolically active cells were not in direct contact with the Fe(III) mineral. Flavins were released by both strains, suggesting that these cell-secreted electron shuttles mediated extracellular Fe(III)-(oxyhydr)oxide reduction, but did not facilitate extracellular As(V) reduction, demonstrated by the presence of flavins yet lack of As(III) in the supernatants of the arrA deletion mutant strain. 3D reconstructions of NanoSIMS depth-profiled single cells revealed that As and Fe were associated with the cell surface in the WT cells, whereas for the arrA mutant, only Fe was associated with the biomass. These data were consistent with Shewanella sp. ANA-3 respiring As(V) in a multistep process; first, the reductive dissolution of the Fe(III) mineral released As(V), and once in solution, As(V) was respired by the cells to As(III). As well as highlighting Fe(III) reduction as the primary release mechanism for arsenic, our data also identified unexpected cellular As(III) retention mechanisms that require further investigation.
Establishment and Characterization of an Irinotecan-Resistant Human Colon Cancer Cell Line

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Irinotecan is widely used as a chemotherapeutic drug to treat CRC. However, the mechanisms of acquired resistance to irinotecan in CRC remain inconclusive. In the present study, we established a novel irinotecan-resistant human colon cell line to investigate the underlying mechanism(s) of irinotecan resistance, particularly the overexpression of ABC transporters. The irinotecan-resistant S1-IR20 cell line was established by exposing irinotecan to human S1 colon cancer cells. MTT cytotoxicity assay was carried out to determine the drug resistance profile of S1-IR20 cells. The drug-resistant cells showed about 47-fold resistance to irinotecan and cross-resistance to ABCG2 substrates in comparison with S1 cells. By Western blot analysis, S1-IR20 cells showed significant increase of ABCG2, but not ABCB1 or ABCC1 in protein expression level as compared to that of parental S1 cells. The immunofluorescence assay showed that the overexpressed ABCG2 transporter is localized on the cell membrane of S1-IR20 cells, suggesting an active efflux function of the ABCG2 transporter. This finding was further confirmed by reversal studies that inhibiting efflux function of ABCG2 was able to completely abolish drug resistance to irinotecan as well as other ABCG2 substrates in S1-IR20 cells. In conclusion, our work established an in vitro model of irinotecan resistance in CRC and suggested ABCG2 overexpression as one of the underlying mechanisms of acquired resistance to irinotecan. This novel resistant cell line may enable future studies to overcome drug resistance in vitro and improve CRC treatment in vivo.
Rotavirus as an Expression Platform of the SARS-CoV-2 Spike Protein

Rotavirus, a segmented double-stranded RNA virus, is a major cause of acute gastroenteritis in young children. The introduction of live oral rotavirus vaccines has reduced the incidence of rotavirus disease in many countries. To explore the possibility of establishing a combined rotavirus-SARS-CoV-2 vaccine, we generated recombinant (r)SA11 rotaviruses with modified segment 7 RNAs that contained coding sequences for NSP3 and FLAG-tagged portions of the SARS-CoV-2 spike (S) protein. A 2A translational element was used to drive separate expression of NSP3 and the S product. rSA11 viruses were recovered that encoded the S-protein S1 fragment, N-terminal domain (NTD), receptor-binding domain (RBD), extended receptor-binding domain (ExRBD), and S2 core (CR) domain (rSA11/NSP3-fS1, -fNTD, -fRBD, -fExRBD, and -fCR, respectively). Generation of rSA11/fS1 required a foreign-sequence insertion of 2.2-kbp, the largest such insertion yet made into the rotavirus genome. Based on isopycnic centrifugation, rSA11 containing S sequences were denser than wildtype virus, confirming the capacity of the rotavirus to accommodate larger genomes. Immunoblotting showed that rSA11/-fNTD, -fRBD, -fExRBD, and -fCR viruses expressed S products of expected size, with fExRBD expressed at highest levels. These rSA11 viruses were genetically stable during serial passage. In contrast, rSA11/NSP3-fS1 failed to express its expected 80-kDa fS1 product, for unexplained reasons. Moreover, rSA11/NSP3-fS1 was genetically unstable, with variants lacking the S1 insertion appearing during serial passage. Nonetheless, these results emphasize the potential usefulness of rotavirus vaccines as expression vectors of portions of the SARS-CoV-2 S protein (e.g., NTD, RBD, ExRBD, and CR) with sizes smaller than the S1 fragment. Importance Among the vaccines administered to children in the US and many other countries are those targeting rotavirus, a segmented double-stranded RNA virus that is a major cause of severe gastroenteritis. In this study, we have examined the feasibility of modifying the rotavirus genome by reverse genetics, such that the virus could serve as an expression vector of the SARS-CoV-2 spike protein. Results were obtained showing that recombinant rotaviruses can be generated that express domains of the SARS CoV-2 spike protein, including the receptor-binding domain (RBD), a common target of neutralizing antibodies produced in individuals infected by the virus. Our findings raise the possibility of creating a combined rotavirus-COVID-19 vaccine that could be used in place of current rotavirus vaccines.
Implicit Theories of Intelligence and Achievement Goals: A Look at Students’ Intrinsic Motivation and Achievement in Mathematics

The present research seeks to utilize Implicit Theories of Intelligence (mindsets) and Achievement Goal Theory to understand students’ intrinsic motivation and academic performance in mathematics in Singapore. 1,201 lower-progress stream students (596 males, 580 females, 25 missing data), ages ranged from 13 to 17 years (M = 14.68 years old, SD = 0.57), from 17 secondary schools in Singapore took part in the study. Using structural equation modeling, results confirmed hypotheses that incremental mindset predicted mastery-approach goals and, in turn, predicted intrinsic motivation and mathematics performance. Entity mindset predicted performance-approach and performance-avoidance goals. Performance-approach goal was positively linked to intrinsic motivation and mathematics performance; performance-avoidance goal, however, negatively predicted intrinsic motivation and mathematics performance. The model accounted for 35.9% of variance in intrinsic motivation and 13.8% in mathematics performance. These findings suggest that intrinsic motivation toward mathematics and achievement scores might be enhanced through interventions that focus on incremental mindset and mastery-approach goal. In addition, performance-approach goal may enhance intrinsic motivation and achievement as well, but to a lesser extent. Finally, the study adds to the literature done in the Asian context and lends support to the contention that culture may affect students’ mindsets and adoption of achievement goals, and their associated impact on motivation and achievement outcomes.
A candidate neuroimaging biomarker for detection of neurotransmission-related functional alterations and prediction of pharmacological analgesic response in chronic pain

Background Chronic pain is a world-wide clinical challenge. Response to analgesic treatment is limited and difficult to predict. Functional MRI (fMRI) has been suggested as a potential solution. However, while most analgesics target specific neurotransmission pathways, fMRI-based biomarkers are not specific for any neurotransmitter system, limiting our understanding of how they might contribute to predict treatment response. Methods Here, we sought to bridge this gap by applying Receptor-Enriched Analysis of Functional Connectivity by Targets (REACT) to investigate whether neurotransmission-enriched functional connectivity (FC) mapping can provide insights into the brain mechanisms underlying chronic pain and inter-individual differences in analgesic response after a placebo or duloxetine. Chronic knee osteoarthritis (OA) pain patients (n=56) underwent pre-treatment brain scans in two clinical trials. Study 1 (n=17) was a 2-week single-blinded placebo pill trial. Study 2 (n=39) was a 3-month double-blinded randomized trial comparing placebo to duloxetine, a dual serotonin-noradrenaline reuptake inhibitor. Results Across two independent studies, we found that chronic pain OA patients present FC alterations in the FC related to the serotonin (SERT) and noradrenaline (NET) transporters, when compared to age-matched healthy controls. Placebo responders presented with higher pre-treatment dopamine transporter (DAT)-enriched FC than non-responders. Duloxetine responders presented with higher pre-treatment SERT and NET-enriched FC than non-responders. Pre-treatment SERT and NET-enriched FC achieved predictive positive values of duloxetine response up to 85.71%. Conclusion Neurotransmission-enriched FC mapping might hold promise as a new mechanistic-informed biomarker for functional brain alterations and prediction of response to pharmacological analgesia in chronic pain.