Miracle-dz/UniFAR-FTUs huggingface dataset:
The trepidations of a PhD researcher – Who are you and why are you here?

This paper contributes to research that has a predominant focus on western researchers in the global South. Firstly, the paper examines how my African identity fits into a western discourse of being a researcher and their intersections with my other personalities as I world‐travel. ‘World‐travelling’ is about the plurality of selves and an opening for self‐construction. Secondly, the paper elaborates on violence and intimidation in the field and how researchers may succeed or fail in negotiating such risks. As a non‐native researcher in a UK‐Based University, I acknowledge my plurality of selves, and the skills needed to navigate these social worlds.
Hypothalamic AMPK and energy balance

AMP‐activated protein kinase (AMPK) is the main cellular energy sensor. Activated following a depletion of cellular energy stores, AMPK will restore the energy homoeostasis by increasing energy production and limiting energy waste. At a central level, the AMPK pathway will integrate peripheral signals (mostly hormones and metabolites) through neuronal networks. Hypothalamic AMPK is directly implicated in feeding behaviour, brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT). It also participates in other metabolic functions: glucose and muscle metabolisms, as well as hepatic function. Numerous anti‐obesity and/or antidiabetic agents, such as nicotine, metformin and liraglutide, are known to induce their effects through a modulation of AMPK pathway, either at central or at peripheral levels. Moreover, the weight‐gaining side effects of antipsychotic drugs, such as olanzapine, are also mediated by hypothalamic AMPK. Therefore, considering hypothalamic AMPK as a therapeutic target in metabolic diseases appears as an interesting strategy due to its implication in feeding and energy expenditure, the two sides of the energy balance equation.
Leptomeningeal Myelomatosis: A Rare but Devastating Manifestation of Multiple Myeloma Diagnosed Using Cytology, Flow Cytometry, and Fluorescent in situ Hybridization

Introduction: Involvement of the central nervous system in patients with multiple myeloma is a rare event. We evaluated the diagnostic workup and prognosis of patients with leptomeningeal myelomatosis (LMM). Methods: Between April 2005 and April 2016, we identified 16 cases with LMM. The involvement was diagnosed by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) cytology as well as flow cytometry. Fluorescence in situ hybridization (FISH) was used in 8/16 cases. In 1 case, genome-wide screening for genetic alterations using single-nucleotide polymorphism (SNP) array analysis was performed. Results: The median time from initial diagnosis until the occurrence of LMM was 434 days. At diagnosis, the median age was 60 years. The median cell count was 21/µL (range 1–1,333/µL). All CSF samples showed malignant pleocytosis, confirmed by flow cytometry in 12/16 patients. FISH revealed high-risk features in the majority of samples. Treatment for LMM consisted of intrathecal chemotherapy and radiation therapy. Genome-wide screening assays revealed different subclones. The outcome was dismal with a median overall survival after the diagnosis of LMM of 82 days. Conclusion: By combining several technical procedures, it is possible to identify most patients with LMM. Management of affected patients is challenging and the survival short after a diagnosis of LMM.
Effect of a Positive Photo Appreciation Program on Depressive Mood in Older Adults: A Pilot Randomized Controlled Trial

Safer and more effective programs are required to cope with an increasing number of older people with depression. Hence, we developed the Positive Photo Appreciation (PPA) program. A three-month pilot randomized controlled trial was conducted with healthy Japanese individuals aged 65–84 years, assigned to a PPA group (n = 28) or Photo Correspondence Education (PCE) (control group) (n = 27). We used the Center for Epidemiologic Studies Depression Scale (CES-D) score as the primary outcome measure. Secondary outcome measures, among others, were cognitive function and positive emotion. Data collected at baseline and post-intervention were analyzed using a linear mixed-effect model. Over 80% of the participants in the PPA group completed and were satisfied with the program. Compared with the PCE group, the CES-D score in the PPA group significantly improved (main effect of group: t = −4.30, p < 0.001; interaction effect of group by time: t = 4.39, p < 0.001), with an effect size of d = 1.23. Additionally, a positive significant interaction effect of group by time was found in the Positive and Negative Affect Schedule (t = −2.33, p = 0.024). The PPA program might be promising for mitigating depressive mood in older adults.
Female Sexual Dysfunction and the Placebo Effect: A Meta-analysis.

OBJECTIVE To quantify the placebo effect of various pharmacologic modalities including neuromodulators, hormonal agents, and onabotulinum toxin A for female sexual dysfunction. DATA SOURCES Using Meta-analyses Of Observational Studies in Epidemiology guidelines, we conducted a systematic review of PubMed, EMBASE, ClinicalTrials.gov, and the Cochrane Review databases. METHODS OF STUDY SELECTION Eleven search terms, "female sexual dysfunction" "treatment" in combination with "hypoactive sexual desire," "arousal disorder," "sexual pain disorder," "genitourinary syndrome of menopause," "orgasmic disorder," "vulvovaginal atrophy," "vaginismus," "vaginal atrophy," "vulvodynia," and "vestibulitis," were used. Studies were included if their design was randomized, included a placebo arm, and used the Female Sexual Function Index as an outcome measure. TABULATION, INTEGRATION, AND RESULTS The placebo effect on the Female Sexual Function Index was compared with each respective study's treatment effect using inverse-variance weighting in a random-effects analysis model. Six hundred five relevant articles were retrieved. Twenty-four randomized controlled trials included a placebo arm. Of these, eight studies used the Female Sexual Function Index. Across these studies, 1,723 women with clinical pretreatment female sexual dysfunction received placebo. Two thousand two hundred thirty-six women were in the treatment arm of the respective studies and received various pharmacologic interventions including flibanserin, bupropion, onabotulinum toxin A, intravaginal prasterone, intranasal oxytocin, ospemifene, and bremelanotide. Women receiving placebo improved 3.62 (95% CI 3.29-3.94) on the Female Sexual Function Index. The treatment arm had a corresponding increase of 5.35 (95% CI 4.13-6.57). CONCLUSION This meta-analysis of Level I evidence demonstrates that 67.7% of the treatment effect for female sexual dysfunction is accounted for by placebo. Our findings suggest that the current treatments for female sexual dysfunction are, overall, minimally superior to placebo, which emphasizes the ongoing need for more efficacious treatment for female sexual dysfunction.
Salt-Mediated Au-Cu Nanofoam and Au-Cu-Pd Porous Macrobeam Synthesis

Multi-metallic and alloy nanomaterials enable a broad range of catalytic applications with high surface area and tuning reaction specificity through the variation of metal composition. The ability to synthesize these materials as three-dimensional nanostructures enables control of surface area, pore size and mass transfer properties, electronic conductivity, and ultimately device integration. Au-Cu nanomaterials offer tunable optical and catalytic properties at reduced material cost. The synthesis methods for Au-Cu nanostructures, especially three-dimensional materials, has been limited. Here, we present Au-Cu nanofoams and Au-Cu-Pd macrobeams synthesized from salt precursors. Salt precursors formed from the precipitation of square planar ions resulted in short- and long-range ordered crystals that, when reduced in solution, form nanofoams or macrobeams that can be dried or pressed into freestanding monoliths or films. Metal composition was determined with X-ray diffraction and energy dispersive X-ray spectroscopy. Nitrogen gas adsorption indicated an Au-Cu nanofoam specific surface area of 19.4 m2/g. Specific capacitance determined with electrochemical impedance spectroscopy was 46.0 F/g and 52.5 F/g for Au-Cu nanofoams and Au-Cu-Pd macrobeams, respectively. The use of salt precursors is envisioned as a synthesis route to numerous metal and multi-metallic nanostructures for catalytic, energy storage, and sensing applications.
3D Analysis of Upper Limbs Motion during Rehabilitation Exercises Using the KinectTM Sensor: Development, Laboratory Validation and Clinical Application

Optoelectronic devices are the gold standard for 3D evaluation in clinics, but due to the complexity of this kind of hardware and the lack of access for patients, affordable, transportable, and easy-to-use systems must be developed to be largely used in daily clinics. The KinectTM sensor has various advantages compared to optoelectronic devices, such as its price and transportability. However, it also has some limitations: (in)accuracy of the skeleton detection and tracking as well as the limited amount of available points, which makes 3D evaluation impossible. To overcome these limitations, a novel method has been developed to perform 3D evaluation of the upper limbs. This system is coupled to rehabilitation exercises, allowing functional evaluation while performing physical rehabilitation. To validate this new approach, a two-step method was used. The first step was a laboratory validation where the results obtained with the KinectTM were compared with the results obtained with an optoelectronic device; 40 healthy young adults participated in this first part. The second step was to determine the clinical relevance of this kind of measurement. Results of the healthy subjects were compared with a group of 22 elderly adults and a group of 10 chronic stroke patients to determine if different patterns could be observed. The new methodology and the different steps of the validations are presented in this paper.
CTL‐associated and NK cell‐associated immune responses induce different HBV DNA reduction patterns in chronic hepatitis B patients

The activation of hepatitis B virus (HBV)‐related hepatitis is associated with both natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). We analyzed the association between the immune response and changes in the proportion of Pre‐S deletion variants. We quantified Pre‐S deleted HBV (HBV‐del) and wild‐type HBV (HBV‐wt) DNA levels in sera obtained from HBV‐infected mice and chronic hepatitis B patients. In chronic hepatitis B patients, the HBV‐del proportion usually increased during or after ALT elevation but did not occur during all ALT elevations. To clarify this difference in the immunological responses, we performed in vivo analyses using HBV‐infected human hepatocyte chimeric mice. Although HBV‐del proportions did not change in mice with NK cell‐associated hepatitis or in mice treated with entecavir, the proportions sharply increased in mice with CTL‐associated hepatitis. Furthermore, the number of patients in which HBV‐del proportions were greater than 5% was significantly higher in chronic hepatitis B patients than in asymptomatic carriers (P = 0.023). We identified associations between virological response in chronic hepatitis B patients and two different immune responses. The proportion of HBV‐del variants could be a useful biomarker for distinguishing between chronic hepatitis and asymptomatic carriers.
Coping trajectories in emerging adulthood: The influence of temperament and gender.

OBJECTIVE The study of coping has far-reaching implications for understanding psychopathology and resilience, as well as for the treatment of psychological disorders. Developmental work has examined how the ability to cope changes across time in children and adolescents; however, work in emerging adulthood is still lacking. Coping is thought to emerge from basic biological and psychological processes, such as temperament and gender, which may influence the trajectory of coping use over time. METHOD Using a sample of college students (N = 1,000), our 4-year longitudinal study with yearly assessments sought to (a) examine the trajectory of coping styles in emerging adulthood and to (b) examine the influence of temperament and gender on these coping trajectories. RESULTS Our findings suggest that young adults' use of avoidance strategies decreased slightly over college, whereas the use of approach strategies and social support seeking remained stable. Temperament (BIS/BAS) and gender were related to certain coping styles at baseline and appeared to have an influence on some of these trajectories over time, though these associations were complex. CONCLUSIONS This work may inform intervention research attempting to promote adaptive coping because it may help identify young adults most in need of such interventions.
A common pattern of DNase I footprinting throughout the human mtDNA unveils clues for a chromatin-like organization

Human mitochondrial DNA (mtDNA) is believed to lack chromatin and histones. Instead, it is coated solely by the transcription factor TFAM, which binds the mtDNA without sequence specificity and packs it into a bacterial-like nucleoid in a dose-dependent fashion. We asked whether mtDNA packaging is more regulated than once thought. As a first step to address this question, we analyzed mtDNA DNase-I-seq experiments in 324 different human cell types and found, for the first time, a pattern of 29 Genomic footprinting (DGF) sites throughout the mtDNA shared by ∼90% of the tested samples. Low SNP density at the DGF sites, and their conservation in mouse DNase-seq experiments, reflect strong selective constraints. Co-localization of the DGFs with known mtDNA regulatory elements and with recently-discovered transcription pausing sites, suggest a role for such DGFs in mtDNA transcription. Altered mtDNA DGF pattern in IL-3 treated CD+34 cells offer first clue to their physiological importance. Taken together, human mtDNA has a conserved and regulated protein-DNA organization, which is likely involved in regulation of mtDNA gene expression.
Prognostic role of snail in lung cancer

Background: Increasing studies were performed to explore the prognostic value of snail in lung cancer (LC), however, with inconsistent results. Hence, this systematic review is aimed to evaluate the prognostic role of snail in patients with LC. Methods: A comprehensive literature search in the PubMed, Embase, the Cochrane Library, and Web of Science databases will be conducted to identify eligible studies. Language is limited as English. We will employ hazard ratios (HRs) and 95% confidence intervals (95% CIs) to estimate the correlations between snail expression and overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), disease-free survival (DFS), and clinicopathological features. Meta-analysis will be performed using STATA 14.0 software. Results: This study will provide a high-quality synthesis of current evidence of the correlations between snail expression and OS, PFS/RFS/DFS, and clinicopathological features. Conclusion: The study will provide updated evidence to assess whether the expression of snail is in association with poor prognosis in patients with LC. Ethics and dissemination: It is not necessary for ethical approval because individuals cannot be identified. The protocol will be disseminated in a peer-reviewed journal or presented at a relevant conference. PROSPERO registration number: This systematic review protocol has been registered in the PROSPERO network (No. CRD42018095191).
Investigating the Role of G Protein &bgr;&ggr; in Kv7-Dependent Relaxations of the Rat Vasculature

Objective— In renal arteries, inhibitors of G protein &bgr;&ggr; subunits (G&bgr;&ggr;) reduce Kv7 activity and inhibit Kv7-dependent receptor-mediated vasorelaxations. However, the mechanisms underlying receptor-mediated relaxation are artery specific. Consequently, the aim of this study was to ascertain the role of G&bgr;&ggr; in Kv7-dependent vasorelaxations of the rat vasculature. Approach and Results— Isometric tension recording was performed in isolated rat renal, mesenteric, and cerebral arteries to study isoproterenol and calcitonin gene-related peptide relaxations. Kv7.4 was knocked down via morpholino transfection while inhibition of G&bgr;&ggr; was investigated with gallein and M119K. Proximity ligation assay was performed on isolated myocytes to study the association between Kv7.4 and G protein &bgr; subunits or signaling intermediaries. Isoproterenol or calcitonin gene-related peptide–induced relaxations were attenuated by Kv7.4 knockdown in all arteries studied. Inhibition of G&bgr;&ggr; with gallein or M119K had no effect on isoproterenol-mediated relaxations in mesenteric artery but had a marked effect on calcitonin gene-related peptide–induced responses in mesenteric artery and cerebral artery and isoproterenol responses in renal artery. Isoproterenol increased association with Kv7.4 and Rap1a in mesenteric artery which were not sensitive to gallein, whereas in renal artery, isoproterenol increased Kv7.4-AKAP (A-kinase anchoring protein) associations in a gallein-sensitive manner. Conclusions— The G&bgr;&ggr;-Kv7 relationship differs between vessels and is an essential requirement for AKAP, but not Rap–mediated regulation of the channel.
Creation and Use of an Electronic Health Record Reporting Database to Improve a Laboratory Test Utilization Program

Abstract Objectives Laboratory-based utilization management programs typically rely primarily on data derived from the laboratory information system to analyze testing volumes for trends and utilization concerns. We wished to examine the ability of an electronic health record (EHR) laboratory orders database to improve a laboratory utilization program. Methods We obtained a daily file from our EHR containing data related to laboratory test ordering. We then used an automated process to import this file into a database to facilitate self-service queries and analysis. Results The EHR laboratory orders database has proven to be an important addition to our utilization management program. We provide three representative examples of how the EHR laboratory orders database has been used to address common utilization issues. We demonstrate that analysis of EHR laboratory orders data has been able to provide unique insights that cannot be obtained by review of laboratory information system data alone. Further, we provide recommendations on key EHR data fields of importance to laboratory utilization efforts. Conclusion We demonstrate that an EHR laboratory orders database may be a useful tool in the monitoring and optimization of laboratory testing. We recommend that health care systems develop and maintain a database of EHR laboratory orders data and integrate this data with their laboratory utilization programs.
Three human aminoacyl-tRNA synthetases have distinct sub-mitochondrial localizations that are unaffected by disease-associated mutations

Human mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are key enzymes in the mitochondrial protein translation system and catalyze the charging of amino acids on their cognate tRNAs. Mutations in their nuclear genes are associated with pathologies having a broad spectrum of clinical phenotypes, but with no clear molecular mechanism(s). For example, mutations in the nuclear genes encoding mt-AspRS and mt-ArgRS are correlated with the moderate neurodegenerative disorder leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) and with the severe neurodevelopmental disorder pontocerebellar hypoplasia type 6 (PCH6), respectively. Previous studies have shown no or only minor impacts of these mutations on the canonical properties of these enzymes, indicating that the role of the mt-aaRSs in protein synthesis is mostly not affected by these mutations, but their effects on the mitochondrial localizations of aaRSs remain unclear. Here, we demonstrate that three human aaRSs, mt-AspRS, mt-ArgRS, and LysRS, each have a specific sub-mitochondrial distribution, with mt-ArgRS being exclusively localized in the membrane, LysRS exclusively in the soluble fraction, and mt-AspRS being present in both. Chemical treatments revealed that mt-AspRs is anchored in the mitochondrial membrane through electrostatic interactions, whereas mt-ArgRS uses hydrophobic interactions. We also report that novel mutations in mt-AspRS and mt-ArgRS genes from individuals with LBSL and PCH6, respectively, had no significant impact on the mitochondrial localizations of mt-AspRS and mt-ArgRS. The variable sub-mitochondrial locations for these three mt-aaRSs strongly suggest the existence of additional enzyme properties, requiring further investigation to unravel the mechanisms underlying the two neurodegenerative disorders.
Cardiovascular and Noncardiovascular Death After Percutaneous Coronary Intervention: Insights From 32 882 Patients Enrolled in 21 Randomized Trials

Background: Despite advances in technology and technique, a substantial proportion of patients still die within several years after percutaneous coronary intervention (PCI). The relative rates of cardiovascular and noncardiovascular death after PCI remain uncertain. Methods and Results: We pooled individual patient-level data from 21 randomized clinical trials of PCI performed in 32 882 patients. All studies had independent adjudication of clinical events. We calculated the relative ratio of cardiovascular to noncardiovascular death in each trial up to 5 years and identified predictors of all-cause, cardiovascular, and noncardiovascular death. At the end of the follow-up period, 1980 patients had died (Kaplan-Meier estimated mortality rate, 9.19%). The rates of cardiovascular and noncardiovascular mortality at 5 years were 4.23% (945) and 5.17% (1035), respectively. The rate of cardiovascular death was higher than noncardiovascular death in the first 30 days after PCI (relative ratio, 6.99; 95% confidence interval, 3.16–15.42; P<0.001), similar between 30 days and 1 year, and lower between 1 and 5 years (relative ratio, 0.70; 95% confidence interval, 0.58–0.84; P=0.0005). Any adverse cardiac event (definite stent thrombosis, spontaneous myocardial infarction, or repeat revascularization) preceded cardiovascular and noncardiovascular mortality in 292 (30.9%) and 151 (14.6%) patients, respectively. In a multivariable model with adverse events entered as time-adjusted covariates, myocardial infarction and definite ST were associated with early and late all-cause and cardiovascular mortality but not noncardiovascular mortality. Conclusions: In this large-scale study of patients undergoing PCI, the 5-year rates of cardiovascular and noncardiovascular mortality were similar, but their relative timing was different.