Miracle-dz/UniFAR-FTUs huggingface dataset:
siRNA therapeutics: insights, challenges, remedies and future prospects

ABSTRACT Introduction Among conventional and novel therapeutic approaches, the siRNA strategy stands out for treating disease by silencing the gene responsible for the corresponding disorder. Gene silencing is supposedly intended to target any disease-causing gene, and therefore, several attempts and investments were made to exploit siRNA gene therapy and advance it into clinical settings. Despite the remarkable beneficial prospects, the applicability of siRNA therapeutics is very challenging due to various pathophysiological barriers that hamper its target reach, which is the cytosol, and execution of gene silencing action. Areas covered The present review provides insights into the field of siRNA therapeutics, significant in vivo hurdles that mitigate the target accessibility of siRNA, and remedies to overcome these siRNA delivery challenges. Nonetheless, the current review also highlights the on-going clinical trials and the regulatory aspects of siRNA modalities. Expert opinion The siRNAs have the potential to reach previously untreated target sites and silence the concerned gene owing to their modification as polymeric or lipidic nanoparticles, conjugates, and the application of advanced drug delivery strategies. With such mounting research attempts to improve the delivery of siRNA to target tissue, we might shortly witness revolutionary therapeutic outcomes, new approvals, and clinical implications. GRAPHICAL ABSTRACT
Combining random forest and support vector machines for object-based rural-land-cover classification using high spatial resolution imagery

Abstract. Land-cover classification using remote sensing imagery is an important part of environmental research because it provides baseline information for ecological vulnerability and risk assessment, disaster management, landscape conservation, local and regional planning, and so on. Rural-land-cover classification is challenging for both object-based image analysis methods and classifiers. The objective of this study is to improve the object-oriented classification accuracy of rural land cover by combining two models based on high spatial resolution imagery. We apply the C5.0 algorithm in R to combine support vector machines (SVMs) and random forest (RF) to create the model RS_C5.0. The effectiveness of the model combination is assessed by comparing the classification results with the state-of-the-art machine learning algorithm, namely extreme gradient boosting (XGBoost). The comparisons are done based on the classification results of both the study area and the case area. Results show that in the classification of the study area, RF performs slightly better than SVM, and XGBoost performs worse than RF but better than SVM. However, in the classification of the case area, SVM performs slightly better than RF and both SVM and RF perform better than XGBoost. Furthermore, RS_C5.0 obtains the highest overall accuracies and kappa coefficients in the classifications of both the study area and the case area. In terms of training time, XGBoost runs the slowest in the classifications of both the study area and the case area. SVM and RF as well as the combined model (RS_C5.0) run much faster than XGBoost classifier. To summarize, the combination of SVM and RF classifiers using C5.0 algorithm is found to be a fast and effective way to improve rural-land-cover classification.
Relation of Mechanical Ventilation to Acute Kidney Injury in Myocardial Infarction Patients

Introduction: Acute kidney injury (AKI) is a common and serious complication in critically ill patients, particularly those with ST-elevation myocardial infarction (STEMI). Mechanical ventilation (MV) is often needed when respiratory deterioration occurs and is continuously associated with higher risk for AKI. Whether MV is an independent predictor for AKI in STEMI patients has not been evaluated before. We aimed to determine a potential association between MV and the occurrence of AKI in STEMI patients. Methods: A single-center retrospective cohort in a tertiary referral hospital. We evaluated consecutive patients that were admitted to the cardiac intensive care unit with acute STEMI between 2008 and 2019. Patients were divided into groups based on their need for MV upon admission. To minimize baseline differences between the two groups, propensity matching was performed. The primary outcome was the occurrence of AKI after intubation and secondary outcomes included severe AKI (>2 times the baseline creatinine) and renal recovery. Results: 2,929 patients were included and of them, 143 (5%) were intubated. After using the propensity matching, 138 pairs were available for analysis with similar demographic and clinical characteristics. MV was a predictor for AKI (Table 2, odds ratio [OR]: 3.3, 95% confidence interval [CI]: 1.9–5.6) and severe AKI (OR: 6.3, 95% CI: 2.5–16). These results remained significant after adjusting for the occurrence of a new heart failure and bleeding. Early or partial renal recovery was similar between the groups. Conclusion: MV is independently associated with the occurrence of AKI and severe AKI. The possible mechanism might be temporary, reflected by similar rates of renal recovery.
Whole blood transcriptional profiling reveals highly deregulated atherosclerosis genes in Philadelphia‐chromosome negative myeloproliferative neoplasms

The Philadelphia‐negative chronic myeloproliferative neoplasms (MPNs) are associated with a huge comorbidity burden, including an increased risk of cardiovascular diseases. Recently, chronic inflammation has been suggested to be the driving force for clonal evolution and disease progression in MPN but also potentially having an impact upon the development of accelerated (premature) atherosclerosis.
Internalized stigma and self-stigma in people diagnosed with a mental disorder. One concept or two? A scoping review

Background: In the literature on stigma, authors often use self-stigma or internalized stigma interchangeably to refer to this type of stigma. This results in a lack of conceptual clarity with negative repercussions for measurement and intervention. Aims: To identify how internalized stigma and self-stigma are conceptualized in people diagnosed with a mental disorder and establish similarities and differences between both concepts. Method: A scoping review was conducted. Thirty-five studies that conceptualized internalized stigma or self-stigma were selected. Results: It was identified that the concepts are defined from nine components, and there are more conceptualizations that have points in common than those that consider some component of their own. To gain conceptual clarity, the use of the term internalized stigma is recommended, being a process made up of stages: acceptance of stereotypes and prejudices by people with mental disorders and their subsequent internalization. The latter leads to negative consequences for those affected, which can be understood as the personal impact of this process, which has a crucial socio-cultural component. Lines of research are proposed to provide solidity to studies on this type of stigma. Conclusions: The term internalized stigma should be used when referring to the type of stigma that includes acceptance, internalization and personal impact for the subjects of the stigma. In contrast, self-stigma should be reserved to refer to stigma that is directed toward the ‘self’ and includes subtypes of stigma.
Using Machine Learning to Identify Predictors of Sexually Transmitted Infections Over Time Among Young People Living With or at Risk for HIV Who Participated in ATN Protocols 147, 148, and 149

Sexually transmitted infections among youth in high-risk settings in 2 US cities was 19.6% for 24 months and predicted by group sex/parties, moderate dating app usage, and HIV/sexually transmitted infection histories. Background Sexually transmitted infections (STIs) among youth aged 12 to 24 years have doubled in the last 13 years, accounting for 50% of STIs nationally. We need to identify predictors of STI among youth in urban HIV epicenters. Methods Sexual and gender minority (gay, bisexual, transgender, gender-diverse) and other youth with multiple life stressors (homelessness, incarceration, substance use, mental health disorders) were recruited from 13 sites in Los Angeles and New Orleans (N = 1482). Self-reports and rapid diagnostic tests for STI, HIV, and drug use were conducted at 4-month intervals for up to 24 months. Machine learning was used to identify predictors of time until new STI (including a new HIV diagnosis). Results At recruitment, 23.9% of youth had a current or past STI. Over 24 months, 19.3% tested positive for a new STI. Heterosexual males had the lowest STI rate (12%); African American youth were 23% more likely to acquire an STI compared with peers of other ethnicities. Time to STI was best predicted by attending group sex venues or parties, moderate but not high dating app use, and past STI and HIV seropositive status. Conclusions Sexually transmitted infections are concentrated among a subset of young people at highest risk. The best predictors of youth's risk are their sexual environments and networks. Machine learning will allow the next generation of research on predictive patterns of risk to be more robust.
Nutritional properties of giant water bug, Lethocerus indicus a traditional edible insect species of North-East India

ABSTRACT Edible insects play an important role in human health and food security. Among those, the Giant water bug, Lethocerus indicus (Lep.& Ser.) is a widely used edible insect known for its aroma, flavor, and therapeutic purposes. In the present study, we investigated the nutritional profile, natural habitat, and feeding behavior of L. indicus in aquarium conditions. A comparative analysis of male and female insects’ aroma contents and fatty acid (FA) profiles was also conducted. A dry fried male insect yielded volatile oil of 0.96%/2 g body weight, whereas a dry fried female yielded 0.48%/5.36 g of body weight. In terms of lipids, fresh male insects had 0.15%/5.42 g of body weight and fresh female insects had 0.28%/9.48 g of body weight. There are 24 volatile compounds specific to males, 37 specific to females, and 13 commons to both were identified. 2-Hexen-1-ol, acetate, (Z)- which smells like banana, was prevalently found in males while 4-Octene, 2,6-dimethyl-, [S-(Z)] was prevalently found in female insects. Fatty acids profile analysis detected 32 FA with 12 unique FA from males whereas 22 FA and 3 unique FA were identified from female insects. The SFA percentage present in males and females was 77.44% and 85.21%. Males had 6.78% MUFA content while females have 4.75%. Males have 18% PUFA content enriched with DHA, and EPA, while females had 10.04%. This study revealed that with the presence of a banana-like smell of volatile compound and more MUFA and PUFA in males, the native people of North-East India preferred male over female insects for entomophagy. GRAPHICAL ABSTRACT
Sex trafficking survivors’ experiences with the healthcare system during exploitation: A qualitative study

While most individuals who have experienced sex trafficking will seek medical attention during their exploitation, very few will be identified by healthcare professionals (HCP). It constitutes a lost opportunity to provide appropriate support, resources, and services. In this study, we examined the experiences of accessing care of sex trafficking survivors in the Greater Montreal area and their interactions with HCPs to inform trafficking education programs for HCPs and allied health professionals regarding the needs of this patient population. We conducted seven semi-structured in-depth interviews with purposively selected sex trafficking survivors participating in “Les Survivantes,” a program of the SPVM (Service de Police de la Ville de Montréal), designed to support trafficked individuals’ exit journey. We used interpretive description to understand the lived experiences of trafficked individuals with direct applications to clinical education and care. Our results revealed that trafficked individuals accessing care present with a fragile trust in HCPs and how HCPs have many opportunities to conduct comprehensive examinations and query trafficking. Trafficked individuals’ initial trust in HCPs can be strengthened by non-judgemental approaches or damaged by stigmatizing conduct, serving to isolate further and alienate this patient population. Health professionals’ attitudes combined with healthcare settings’ cultures of care (i.e., community vs emergency) and exposure to marginalized groups were key influencers of survivors’ perception of healthcare interactions. The findings also emphasized the importance of routinely querying trafficking through sensitive psychosocial questioning based on observation of trafficking cues. Survivors reported a list of trafficking cues to recognize and emphasized the importance of trust as a condition of disclosure. Finally, survivors identified the need for exit planning to be centered around trafficked individuals’ agency and holistic needs, and for streamlined community-based multidisciplinary collaboration to better serve this population. Our results highlight that most challenges experienced by trafficking survivors in accessing care and resources are modifiable through HCP education and training. Our study also provides new insights and concrete advice to improve care and support throughout the exiting process. We argue that healthcare services for this population be modeled harm reduction approaches that focus on victims’ agency and needs, independent of their desire to exit trafficking. We emphasize the urgent need for proper case management and intersectoral and multidisciplinary care coordination in community-based settings as well as facilitated access to mental health support.
Targeting endothelial coagulation signaling ameliorates liver obstructive cholestasis and dysfunctional angiogenesis

Cholestatic fibrogenesis is a pathobiological process in which cumulative injury to the bile ducts coincides with progressive liver fibrosis. The pathobiologic mechanisms underlying fibrogenesis and disease progression remain poorly understood. Currently, there is no effective treatment for liver fibrosis. In this study, we discovered that components of the coagulation cascade were associated with the advanced progression of obstructive cholestasis, and anticoagulant therapy could improve liver cholestasis-induced fibrosis. In a mouse model of common bile duct ligation (BDL), which mimics cholestatic liver injury, RNA sequencing analysis revealed an increased expression of coagulation factors in endothelial cells. Pharmacological targeting of the coagulation signaling by hirudin, an anticoagulatory antagonist of thrombin, ameliorated obstructive cholestasis, and attenuated liver fibrosis symptoms. Hirudin attenuated fibrosis-associated angiogenesis, endothelial-to-mesenchymal transition (EndMT), and tissue hypoxia and reduced liver inflammation after BDL. Furthermore, hirudin suppressed YAP (Yes-associated protein) signaling and its downstream effectors in vascular endothelial cells, which are considered with profibrotic characteristics. In conclusion, we demonstrated that pharmacological targeting of coagulation signaling by hirudin has the potential to alleviate liver obstructive cholestasis and fibrosis.
Adipose Tissue-Derived Mesenchymal Stromal Cells from Ex-Morbidly Obese Individuals Instruct Macrophages towards a M2-Like Profile In Vitro

Obesity, which continues to increase worldwide, was shown to irreversibly impair the differentiation potential and angiogenic properties of adipose tissue mesenchymal stromal cells (ADSCs). Because these cells are intended for regenerative medicine, especially for the treatment of inflammatory conditions, and the effects of obesity on the immunomodulatory properties of ADSCs are not yet clear, here we investigated how ADSCs isolated from former obese subjects (Ex-Ob) would influence macrophage differentiation and polarization, since these cells are the main instructors of inflammatory responses. Analysis of the subcutaneous adipose tissue (SAT) of overweight (OW) and Ex-Ob subjects showed the maintenance of approximately twice as many macrophages in Ex-Ob SAT, contained within the CD68+/FXIII-A− inflammatory pool. Despite it, in vitro, coculture experiments revealed that Ex-Ob ADSCs instructed monocyte differentiation into a M2-like profile, and under inflammatory conditions induced by LPS treatment, inhibited HLA-DR upregulation by resting M0 macrophages, originated a similar percentage of TNF-α+ cells, and inhibited IL-10 secretion, similar to OW-ADSCs and BMSCs, which were used for comparison, as these are the main alternative cell types available for therapeutic purposes. Our results showed that Ex-Ob ADSCs mirrored OW-ADSCs in macrophage education, favoring the M2 immunophenotype and a mixed (M1/M2) secretory response. These results have translational potential, since they provide evidence that ADSCs from both Ex-Ob and OW subjects can be used in regenerative medicine in eligible therapies. Further in vivo studies will be fundamental to validate these observations.
Cumulative Spike Train Estimation for Muscle Excitation Assessment From Surface EMG Using Spatial Spike Detection

Estimating cumulative spike train (CST) of motor units (MUs) from surface electromyography (sEMG) is essential for the effective control of neural interfaces. However, the limited accuracy of existing estimation methods greatly hinders the further development of neural interface. This paper proposes a simple but effective approach for identifying CST based on spatial spike detection from high-density sEMG. Specifically, we use a spatial sliding window to detect spikes according to the spatial propagation characteristics of the motor unit action potential, focusing on the spikes of activated MUs in a local area rather than those of a specific MU. We validated the effectiveness of our proposed method through an experiment involving wrist flexion/extension and pronation/supination, comparing it with a recognized CST estimation method and an MU decomposition based method. The results demonstrated that the proposed method obtained higher accuracy on multi-DoF wrist torque estimation leveraging the estimated CST compared to the other three methods. On average, the correlation coefficient (R) and the normalized root mean square error (nRMSE) between the estimation results and recorded force were 0.96 $\pm$ 0.03 and 10.1% $\pm$ 3.7%, respectively. Moreover, there was an extremely high interpretive extent between the CSTs of proposed method and the MU decomposition method. The outcomes reveal the superiority of the proposed method in identifying CSTs and can provide promising driven signals for neural interface.
The Apoptotic Potential Activity of Terminalia Brownii Extracts against Various Cancer Cell Lines

The present study aimed to investigate the potential inhibitory activities of various Terminalia brownie extracts against the proliferation of different cancer cell lines. Fractionation was carried out through the process of liquid-liquid extraction produced four fraction types using polarity-enhancing solvents such as, n-hexane, chloroform, ethyl acetate, and water. All extracts have been tested for their cytotoxicity against cancer cell lines using SRB assay and their inhibitory activity on cell cycle phases using flow cytometry. The chloroform extract exhibited a cytotoxic effect against all three types of cancer cell lines and especially the HepG2 cells at 100-µg concentration. Moreover, the most prominent plant extracts of chloroform, acetyl acetate, and hexane showed significant induction of cell death during the S phase cell cycle. The findings of this study suggest that compounds in the Terminalia brownie plant used in traditional Saudi medicine may have the potential to suppress the growth of cancer cell lines.
Phone-Delivered Intervention to Improve HIV Care for Young People Living With HIV: Trial to Inform Implementation and Utility

Supplemental Digital Content is Available in the Text. Background: Phone-delivered counseling has demonstrated improved health outcomes for people living with HIV. However, counseling is hampered by a lack of guidance on the frequency and duration of intervention in relation to clinical benefits. The added benefits of bidirectional (ie, interactive) vs. unidirectional (ie, passive) text messages to augment counseling are also unknown. We conducted a clinical trial of adaptive phone counseling along with either bidirectional or unidirectional text messaging for people living with HIV. Methods: A community sample of 425 young people (aged 16–36 years) living with HIV in Georgia, USA, received weekly phone counseling sessions with the number of sessions determined by the participant and their counselor. Participants were subsequently randomized to either (1) weekly bidirectional text messages with their counselor or (2) weekly automated unidirectional text message reminders. Participants were followed for 16 months to assess 3 primary outcomes: antiretroviral therapy (ART) adherence, HIV care engagement, and HIV suppression. Results: Participants demonstrated improved clinical outcomes over the follow-up period, with 74% of those who were not taking ART initiating treatment, 65% of those on ART improving adherence, and 47% who had detectable viral loads at baseline attaining viral suppression. The number of sessions completed predicted improved ART adherence, greater care engagement, and HIV suppression over follow-ups. Bidirectional text messages impacted care engagement by moderating the effects of counseling sessions on HIV suppression. Conclusions: Phone counseling augmented by bidirectional text messages has the potential to improve HIV care for young adults living with HIV.
External beam radiotherapy of prostate cancer with or without high dose-rate brachytherapy: the Norwegian experience with long-term urinary and bowel adverse effects.

BACKGROUND There are few studies utilizing the Expanded Prostate Index Composite questionnaire-26 (EPIC-26) questionnaire to examine the long-term association between Domain Summary Scores (DSSs) and Quality of Life (QoL) after External Beam Radiation Therapy (EBRT, 3DCRT [3D conventional radiotherapy]/IMRT [intensity modulated radiation therapy]) versus EBRT combined with High-Dose-Rate Brachytherapy (BT+, 3DCRT [3D conventional radiotherapy]/IMRT). In this cross-sectional study we compare long-term adverse effects and QoL after BT+ with EBRT. METHODS Prostate Cancer Survivors who at least 5 years previously, had undergone BT+ at Oslo University Hospital between 2004 and 2010 (n = 259) or EBRT (multicentre cohort) between 2009 and 2010 (n = 99) completed a questionnaire containing EPIC-26, Short Form-12 and questions regarding comorbidity/social status. Results were presented as DSSs and Physical/Mental Composite Scores of QoL (PCS/MCS). Regression analyses explored firstly the associations between treatment modality and DSSs and secondly the impact of DSSs on QoL. We estimated the proportions of patients with big/moderate problems. Clinical relevance was set according to the lowest limit of published Minimal Important Differences. P-values <0.05 were considered statistically significant. RESULTS In multivariate analysis, only the urinary incontinence DSS remained statistically (P < 0.05) and clinically significantly greater after BT+ than EBRT (90 vs. 83). The number of men with moderate/big urinary or bowel problems was halved after BT+ (P < 0.05). The number of patients with impaired PCS (score < 45) were lower in the BT+ group than the EBRT group (P = 0.02). Regression analysis showed that decreasing levels of bowel and urinary irritation/obstructive DSSs predicted worsening of PCS (P < 0.001) and MCS (P = 0.007), respectively. CONCLUSIONS Dose-escalated radiotherapy by BT did not negatively impact long-term adverse effects, substantial problems or QoL compared with EBRT. Future randomised studies using improved EBRT techniques are needed.