Miracle-dz/UniFAR-FTUs huggingface dataset:
The Complex Role of Autophagy in Melanoma Evolution: New Perspectives From Mouse Models

Despite tremendous efforts in the last decade to improve treatments, melanoma still represents a major therapeutic challenge and overall survival of patients remains poor. Therefore, identifying new targets to counteract melanoma is needed. In this scenario, autophagy, the “self-eating” process of the cell, has recently arisen as new potential candidate in melanoma. Alongside its role as a recycling mechanism for dysfunctional and damaged cell components, autophagy also clearly sits at a crossroad with metabolism, thereby orchestrating cell proliferation, bioenergetics and metabolic rewiring, all hallmarks of cancer cells. In this regard, autophagy, both in tumor and host, has been flagged as an essential player in melanomagenesis and progression. To pave the way to a better understanding of such a complex interplay, the use of genetically engineered mouse models (GEMMs), as well as syngeneic mouse models, has been undoubtedly crucial. Herein, we will explore the latest discoveries in the field, with particular focus on the potential of these models in unraveling the contribution of autophagy in melanoma, along with the therapeutic advantages that may arise.
CARDIORESPIRATORY POWER AND FORCE-VELOCITY CHARACTERISTICS IN ROAD CYCLING: THE EFFECT OF AGING AND UNDERLYING PHYSIOLOGICAL MECHANISMS

Introduction: Although a considerable amount of research is available describing the physiological characteristics of competitive adolescent and senior level cyclists, research describing the same characteristics in master level cyclists is rare. Aim of this study was to compare cardiorespiratory power and force-velocity characteristics between two groups, one of master and one of senior level cyclists in an attempt to examine the effect of aging on these parameters. Methods: Eighteen master (43.25±5.37 y) and 13 senior level male road cyclists (28.78±4.95 y) were examined for anthropometric characteristics, body composition, and they performed the anaerobic force-velocity test and a graded exercise test to determine maximal oxygen consumption and anaerobic threshold. Results: Maximal heart rate (accordingly 176.9±13.8 bpm vs. 189.1±8.3 bpm) and heart rate at anaerobic threshold (157±13.9 bpm vs. 170.5±8.3 bpm) were the only parameters that differed significantly (P<0.001). Conclusions: Based on these results, it was concluded that optimal training could attenuate the decline of physiological parameters in cyclists until the beginning of the 5 th decade of human life. In addition, considering the variability of heart rate values (either maximal or at anaerobic threshold), i.e. wider range of scores in master than in senior level participants, it was suggested the need for individualized data, especially in master level road cyclists.
National Working Group on the RE-AIM Planning and Evaluation Framework: Goals, Resources, and Future Directions

The National Working Group on RE-AIM Planning and Evaluation Framework (herein Workgroup) was established in 2004 to support the application of the framework and advance dissemination and implementation science (D&I). Workgroup members developed and disseminated products and resources (and continue to do so) to advocate for consistent application of RE-AIM and allow for cross study comparisons. The purpose of this paper is to summarize key Workgroup activities, products, and services (e.g., webinars, consultations, planning tools) and enhance bidirectional communication between the Workgroup and RE-AIM users. The ultimate goal of this work is to serve as a forum for dissemination to improve the balance between RE-AIM user demand (needs) and the currently limited RE-AIM Workgroup supply (consultation and resources) to demonstrate and expand the utility of RE-AIM as a D&I planning and evaluation framework. A summary of resources is provided as well as specific examples of how the Workgroup has been responsive to user needs.
Lipid-Based Antimicrobial Delivery-Systems for the Treatment of Bacterial Infections

Many nanotechnology-based antimicrobials and antimicrobial-delivery-systems have been developed over the past decades with the aim to provide alternatives to antibiotic treatment of infectious-biofilms across the human body. Antimicrobials can be loaded into nanocarriers to protect them against de-activation, and to reduce their toxicity and potential, harmful side-effects. Moreover, antimicrobial nanocarriers such as micelles, can be equipped with stealth and pH-responsive features that allow self-targeting and accumulation in infectious-biofilms at high concentrations. Micellar and liposomal nanocarriers differ in hydrophilicity of their outer-surface and inner-core. Micelles are self-assembled, spherical core-shell structures composed of single layers of surfactants, with hydrophilic head-groups and hydrophobic tail-groups pointing to the micellar core. Liposomes are composed of lipids, self-assembled into bilayers. The hydrophilic head of the lipids determines the surface properties of liposomes, while the hydrophobic tail, internal to the bilayer, determines the fluidity of liposomal-membranes. Therefore, whereas micelles can only be loaded with hydrophobic antimicrobials, hydrophilic antimicrobials can be encapsulated in the hydrophilic, aqueous core of liposomes and hydrophobic or amphiphilic antimicrobials can be inserted in the phospholipid bilayer. Nanotechnology-derived liposomes can be prepared with diameters <100–200 nm, required to prevent reticulo-endothelial rejection and allow penetration into infectious-biofilms. However, surface-functionalization of liposomes is considerably more difficult than of micelles, which explains while self-targeting, pH-responsive liposomes that find their way through the blood circulation toward infectious-biofilms are still challenging to prepare. Equally, development of liposomes that penetrate over the entire thickness of biofilms to provide deep killing of biofilm inhabitants still provides a challenge. The liposomal phospholipid bilayer easily fuses with bacterial cell membranes to release high antimicrobial-doses directly inside bacteria. Arguably, protection against de-activation of antibiotics in liposomal nanocarriers and their fusogenicity constitute the biggest advantage of liposomal antimicrobial carriers over antimicrobials free in solution. Many Gram-negative and Gram-positive bacterial strains, resistant to specific antibiotics, have been demonstrated to be susceptible to these antibiotics when encapsulated in liposomal nanocarriers. Recently, also progress has been made concerning large-scale production and long-term storage of liposomes. Therewith, the remaining challenges to develop self-targeting liposomes that penetrate, accumulate and kill deeply in infectious-biofilms remain worthwhile to pursue.
Intersectional Stigma and Multi-Level Barriers to HIV Testing Among Foreign-Born Black Men From the Caribbean

Testing is the entry point into the HIV care continuum that includes linkage to and retention in prevention services, and adherence to prevention strategies, including repeat HIV testing. Despite US policy approaches to expand HIV testing to diverse clinical care and community settings, disparities in HIV testing among Black populations persist. Foreign-born (FB) Black persons from the Caribbean have higher annual rates of HIV diagnosis and a higher percentage of late-stage HIV diagnosis, compared with US-born Black persons; and most HIV infections among FB Blacks are among men. In this article, we provide an overview of HIV testing barriers among FB Black men who engage in HIV risk-taking behaviors (e.g., condomless sex with male and/or female partners of unknown HIV serostatus). Barriers to HIV testing for both FB and US-born Black men, include HIV stigma (anticipated, perceived, internalized), low perceived HIV risk, medical or government mistrust, and perceived low access to testing resources. We examine beliefs about masculinity and gender roles that may perpetuate heteronormative stereotypes associated with perceptions of low HIV risk and barriers to HIV testing. We also discuss the impact of recent immigration policies on accessing HIV testing and treatment services and how intersectional stigmas and structural forms of oppression, such as racism, prejudice against select immigrant groups, and homophobia that may further amplify barriers to HIV testing among FB Black men. Finally, we review comprehensive prevention approaches, and suggest innovative approaches, that may improve the uptake of HIV testing among FB Black men.
CRISPR-Cas System in Antibiotic Resistance Plasmids in Klebsiella pneumoniae

CRISPR-Cas (clustered regularly interspersed short palindromic repeats-CRISPR-associated protein) is a microbial adaptive immune system involved in defense against different types of mobile genetic elements. CRISPR-Cas systems are usually found in bacterial and archaeal chromosomes but have also been reported in bacteriophage genomes and in a few mega-plasmids. Klebsiella pneumoniae is an important member of the Enterobacteriaceae with which they share a huge pool of antibiotic resistance genes, mostly via plasmids. CRISPR-Cas systems have been identified in K. pneumoniae chromosomes, but relatively little is known of CRISPR-Cas in the plasmids resident in this species. In this study, we searched for CRISPR-Cas system in 699 complete plasmid sequences (>50-kb) and 217 complete chromosomal sequences of K. pneumoniae from GenBank and analyzed the CRISPR-Cas systems and CRISPR spacers found in plasmids and chromosomes. We found a putative CRISPR-Cas system in the 44 plasmids from Klebsiella species and GenBank search also identified the identical system in three plasmids from other Enterobacteriaceae, with CRISPR spacers targeting different plasmid and chromosome sequences. 45 of 47 plasmids with putative type IV CRISPR had IncFIB replicon and 36 of them had an additional IncHI1B replicon. All plasmids except two are very large (>200 kb) and half of them carried multiple antibiotic resistance genes including blaCTX–M, blaNDM, blaOXA. To our knowledge, this is the first report of multi drug resistance plasmids from Enterobacteriaceae with their own CRISPR-Cas system and it is possible that the plasmid type IV CRISPR may depend on the chromosomal type I-E CRISPRs for their competence. Both chromosomal and plasmid CRISPRs target a large variety of plasmids from this species, further suggesting key roles in the epidemiology of large plasmids.
Of Apples and Oranges? The Evolution of “Monogamy” in Non-human Primates

Behavioral ecologists, evolutionary biologists, and anthropologists have been long fascinated by the existence of “monogamy” in the animal kingdom. Multiple studies have explored the factors underlying its evolution and maintenance, sometimes with contradicting and contentious conclusions. These studies have been plagued by a persistent use of fuzzy terminology that often leads to researchers comparing “apples with oranges” (e.g., comparing a grouping pattern or social organization with a sexual or genetic mating system). In this review, we provide an overview of research on “monogamy” in mammals generally and primates in particular, and we discuss a number of problems that complicate comparative attempts to understand this issue. We first highlight why the muddled terminology has hindered our understanding of both a rare social organization and a rare mating system. Then, following a short overview of the main hypotheses explaining the evolution of pair-living and sexual monogamy, we critically discuss various claims about the principal drivers of “monogamy” that have been made in several recent comparative studies. We stress the importance of using only high quality and comparable data. We then propose that a productive way to frame and dissect the different components of pair-living and sexual or genetic monogamy is by considering the behavioral and evolutionary implications of those components from the perspectives of all participants in a species' social system. In particular, we highlight the importance of integrating the perspective of “floater” individuals and considering their impacts on local operational sex ratios, competition, and variance in reproductive success across a population. We stress that pair-living need not imply a reduced importance of intra-sexual mate competition, a situation that may have implications for the sexual selection potential that have not yet been fully explored. Finally, we note that there is no reason to assume that different taxa and lineages, even within the same radiation, should follow the same pathway to or share a unifying evolutionary explanation for “monogamy”. The study of the evolution of pair-living, sexual monogamy, and genetic monogamy remains a challenging and exciting area of research.
The Application of EEG Mu Rhythm Measures to Neurophysiological Research in Stuttering

Deficits in basal ganglia-based inhibitory and timing circuits along with sensorimotor internal modeling mechanisms are thought to underlie stuttering. However, much remains to be learned regarding the precise manner how these deficits contribute to disrupting both speech and cognitive functions in those who stutter. Herein, we examine the suitability of electroencephalographic (EEG) mu rhythms for addressing these deficits. We review some previous findings of mu rhythm activity differentiating stuttering from non-stuttering individuals and present some new preliminary findings capturing stuttering-related deficits in working memory. Mu rhythms are characterized by spectral peaks in alpha (8–13 Hz) and beta (14–25 Hz) frequency bands (mu-alpha and mu-beta). They emanate from premotor/motor regions and are influenced by basal ganglia and sensorimotor function. More specifically, alpha peaks (mu-alpha) are sensitive to basal ganglia-based inhibitory signals and sensory-to-motor feedback. Beta peaks (mu-beta) are sensitive to changes in timing and capture motor-to-sensory (i.e., forward model) projections. Observing simultaneous changes in mu-alpha and mu-beta across the time-course of specific events provides a rich window for observing neurophysiological deficits associated with stuttering in both speech and cognitive tasks and can provide a better understanding of the functional relationship between these stuttering symptoms. We review how independent component analysis (ICA) can extract mu rhythms from raw EEG signals in speech production tasks, such that changes in alpha and beta power are mapped to myogenic activity from articulators. We review findings from speech production and auditory discrimination tasks demonstrating that mu-alpha and mu-beta are highly sensitive to capturing sensorimotor and basal ganglia deficits associated with stuttering with high temporal precision. Novel findings from a non-word repetition (working memory) task are also included. They show reduced mu-alpha suppression in a stuttering group compared to a typically fluent group. Finally, we review current limitations and directions for future research.
Murine SIGNR1 (CD209b) Contributes to the Clearance of Uropathogenic Escherichia coli During Urinary Tract Infections

Uropathogenic Escherichia coli (UPEC), a Gram-negative bacterial pathogen, is a major causative agent of urinary tract infections (UTIs). However, the molecular mechanisms of how UPEC causes infections have not been determined. Recent studies indicated that certain enteric Gram-negative bacteria interact with and hijack innate immune receptors DC-SIGN (CD209a) and SIGNR1 (CD209b), often expressed by antigen-presenting cells (APCs), such as macrophages, leading to dissemination and infection. It was not known whether UPEC could utilize DC-SIGN receptors to promote its infection and dissemination similarly to the enteric pathogens. The results of this study reveal that UPEC interacts with CD209-expressing macrophages and transfectants. This interaction is inhibited by anti-CD209 antibody, indicating that CD209s are receptors for UPEC. Additionally, in contrast to the results of previous studies, mice lacking SIGNR1 are more susceptible to infection of this uropathogen, leading to prolonged bacterial persistence. Overall, the results of our study indicate that the innate immune receptor CD209s participate in the clearance of UPEC during UTIs.
Development of a Psychological Intervention to Address Anxiety During Pregnancy in a Low-Income Country

Background: One in five women suffer from anxiety during pregnancy. Untreated anxiety is a risk factor for postnatal depression and is associated with adverse birth outcomes. Despite the high prevalence of prenatal anxiety in low- and middle-income countries (LMICs), efforts to develop and evaluate context-specific interventions in these settings are lacking. We aimed to develop a culturally appropriate, feasible, and acceptable psychological intervention for perinatal anxiety in the context of a low-income population in Pakistan. Methods: We conducted this research in Rawalpindi District at the Obstetrics Department of the Holy Family Hospital, Rawalpindi Medical University a government facility catering to a mixture of low-income urban, peri-urban, and rural populations. We used a mixture of research methods to: a) investigate the clinical, cultural, and health-service delivery context of perinatal anxiety; b) select an evidence-based approach that suited the population and health-delivery system; c) develop an intervention with extensive reference documentation/manuals; and d) examine issues involved in its implementation. Qualitative data were collected through in-depth interviews and focus group discussions, and analyzed using framework analysis. Results: Informed by the qualitative findings and review of existing evidence-based practices, we developed the “Happy Mother, Healthy Baby” intervention, which was based on principles of cognitive behavior therapy. Its evidence-based elements included: developing an empathetic relationship, challenging thoughts, behavior activation, problem solving, and involving family. These elements were applied using a three-step approach: 1) learning to identify unhealthy or unhelpful thinking and behavior; 2) learning to replace unhealthy or unhelpful thinking and behavior with helpful thinking and behavior; and 3) practicing thinking and acting healthy. Delivered by non-specialist providers, the intervention used culturally appropriate illustrations and examples of healthy activities to set tasks in collaboration with the women to encourage engagement in helpful behaviors. Feedback from the non-specialist providers indicated that the intervention was acceptable, feasible, and perceived to be helpful by the women receiving it. Conclusion: This new psychosocial intervention for perinatal anxiety, based on principles of cognitive behavior therapy and delivered by non-specialists, has the potential to address this important but neglected condition in LMICs.
The Fungal Pathogen Candida albicans Promotes Bladder Colonization of Group B Streptococcus

Group B Streptococcus (GBS) is a common cause of bacterial urinary tract infections (UTI) in susceptible populations, including pregnant women and the elderly. However, the factors that govern GBS persistence and disease severity in this niche are not fully understood. Here, we report that the presence of the fungus Candida albicans, a common urogenital colonizer, can promote GBS UTI. Co-inoculation of GBS with C. albicans increased bacterial adherence to bladder epithelium and promoted GBS colonization in vivo in a C. albicans adhesin-dependent manner. This study demonstrates that fungal colonization of the urogenital tract may be an important determinant of bacterial pathogenesis during UTI.
Optimal 10-Aminoartemisinins With Potent Transmission-Blocking Capabilities for New Artemisinin Combination Therapies–Activities Against Blood Stage P. falciparum Including PfKI3 C580Y Mutants and Liver Stage P. berghei Parasites

We have demonstrated previously that amino-artemisinins including artemiside and artemisone in which an amino group replaces the oxygen-bearing substituents attached to C-10 of the current clinical artemisinin derivatives dihydroartemisinin (DHA), artemether and artesunate, display potent activities in vitro against the asexual blood stages of Plasmodium falciparum (Pf). In particular, the compounds are active against late blood stage Pf gametocytes, and are strongly synergistic in combination with the redox active drug methylene blue. In order to fortify the eventual selection of optimum amino-artemisinins for development into new triple combination therapies also active against artemisinin-resistant Pf mutants, we have prepared new amino-artemisinins based on the easily accessible and inexpensive DHA-piperazine. The latter was converted into alkyl- and aryl sulfonamides, ureas and amides. These derivatives were screened together with the comparator drugs DHA and the hitherto most active amino-artemisinins artemiside and artemisone against asexual and sexual blood stages of Pf and liver stage P. berghei (Pb) sporozoites. Several of the new amino-artemisinins bearing aryl-urea and -amide groups are potently active against both asexual, and late blood stage gametocytes (IC50 0.4-1.0 nM). Although the activities are superior to those of artemiside (IC50 1.5 nM) and artemisone (IC50 42.4 nM), the latter are more active against the liver stage Pb sporozoites (IC50 artemisone 28 nM). In addition, early results indicate these compounds tend not to display reduced susceptibility against parasites bearing the Pf Kelch 13 propeller domain C580Y mutation characteristic of artemisinin-resistant Pf. Thus, the advent of the amino-artemisinins including artemiside and artemisone will enable the development of new combination therapies that by virtue of the amino-artemisinin component itself will possess intrinsic transmission-blocking capabilities and may be effective against artemisinin resistant falciparum malaria.
Exercise Promotion and Distress Reduction Using a Mobile App-Based Community in Breast Cancer Survivors

Physical activity (PA) enhancement and mental distress reduction are important issues in cancer survivorship care. Mobile technology, as an emerging method for changing health behaviors, is gaining attention from many researchers. This study aimed to investigate the effect of a mobile app-based community on enhancing PA and decreasing distress in breast cancer survivors. We conducted a non-randomized, prospective, interventional study that had a mobile community-later arm and mobile community-first arm. With an Android smartphone app (WalkON®), daily walk steps and weekly distress scores using app-based Distress Thermometer (DT) questionnaires were collected from participants for about 12 weeks. To examine the difference in weekly step counts before and during the community activity, we used a paired t-test method. For a comparative analysis, we referred to a previous prospective observational study without a mobile community intervention that had the same setting as the present study. After propensity score matching (PSM), multivariable regression modeling with difference-in-difference (DID) was performed to estimate the effect of the mobile app-based community on PA and mental distress. From January to August 2018, a total of 64 participants were enrolled in this study. In the univariate analysis, after participation in the mobile community, the participants showed a significant increase in total weekly steps (t = −3.5341; P = 0.00208). The mean of the differences was 10,408.72 steps. In the multivariate analysis after PSM, the mobile community significantly increased steps by 8,683.4 per week (p value <0.0001) and decreased DT scores by 0.77 per week (p value = 0.009) in the mixed effect model. In the two-way fixed effect model, the mobile community showed a significant increase in weekly steps by 8,723.4 (p value <0.0001) and decrease in weekly DT by 0.73 (p value = 0.013). The mobile app-based community is an effective and less resource-intensive tool to increase PA and decrease distress in breast cancer survivors. Trial Registration: NCT03190720, NCT03072966