Miracle-dz/UniFAR-FTUs huggingface dataset:
Historical Perspective of Pediatric Health Disparities in Infectious Diseases: Centuries in the Making

Abstract Coronavirus (COVID-19) laid bare the disproportionate effects of infectious agents on vulnerable communities. However, historically, infectious diseases have long been known to affect certain communities to a greater extent than others. The mechanisms behind these differences are multifactorial, and lie less in biological susceptibility and instead more on socioeconomic factors and other social determinants of health. This article highlights health disparities in common infections such as respiratory syncytial virus, tuberculosis, HIV, syphilis, and influenza and will use lessons learned from previous pathogens and infectious disease disparities in vulnerable populations to provide context to the COVID-19 pandemic.
Dark matter at the pseudoscalar Higgs resonance in the phenomenological MSSM and SUSY GUTs

We study dark matter at the MSSM pseudoscalar Higgs resonance (A-funnel), which is one of the few remaining MSSM thermal dark matter candidates in the $100-1000$ GeV range safe from direct detection constraints. To illustrate the various factors at play, this study is performed in two contrasting set-ups: a bottom-up phenomenological MSSM (pMSSM) approach that allows significant freedom, and the top-down, highly constrained Yukawa unified $SO(10)$ GUT model. In the pMSSM, for $\mu > 0$, the entire parameter space lies above the coherent neutrino background and mostly within reach of XENON1T and LZ, while blind spots exist at $m_A\,> \, 800\,$GeV for $\mu < 0$; the strongest constraints come from $A/H \rightarrow \tau \tau$ searches at the LHC. For Yukawa unified models, the confluence of $B_s \rightarrow \mu^+ \mu^-$ constraints, fits to the bottom quark and Higgs masses, and gluino mass bounds from the LHC result in a prediction: realizing the pseudoscalar resonance $requires$ gaugino mass non-universality, with a mass ratio that is determined to within a small range.
Outreach dental care program for older adults using residential care or day care services in Hong Kong: A cohort study.

AIM To evaluate the effects of an outreach dental care program (ODCP) on the oral health status and oral health-related quality of life (OHRQoL) of older adults who used residential or day care services in Hong Kong. METHODS Older adults who had received dental treatments provided in the ODCP were recruited. Clinical examinations were performed by one calibrated examiner (SXY) at baseline and 1-year follow-up in the residential homes or day care centres. Face-to-face interviews were conducted using the transition scale of the Oral Health Impacts on Daily Living (OHIDL) questionnaire to investigate the perceived change in OHRQoL at baseline, 2-month and 1-year follow-ups. The Wilcoxon matched-pair signed-rank test or McNemar/McNemar-Bowker test was used to explore the change in oral health status after dental treatments. Factors associated with the perceived change in OHRQoL were explored with binary logistic regression. RESULTS Four hundred and thirteen older adults (mean age = 83.8 years) participated in the study at baseline, and 377 (91.3%) and 359 (86.9%) were successfully followed 2 months and 1 year after receiving the outreach dental service, respectively. At the 1-year follow-up, the number of decayed teeth and functional tooth units, and the prevalence of poor denture hygiene decreased while there was more dental plaque deposition and a higher proportion of participants with gingival bleeding upon probing. More than 50% of the participants perceived no change or an improvement in OHRQoL in all domains at both follow-ups. Older adults who perceived their oral health status as 'healthy or fair' and those who suffered from toothache at baseline had a higher chance to perceive having a better or at least the same OHRQoL at the 2-month and 1-year follow-ups, respectively. CONCLUSIONS The ODCP in Hong Kong can solve some of the dental problems of older adults using long-term care services and keep most of them from deterioration in OHRQoL, especially those suffering from toothache.
Treatment of periprosthetic joint infections guided by minimum biofilm eradication concentration (MBEC) in addition to minimum inhibitory concentration (MIC): protocol for a prospective randomised clinical trial

Introduction Prosthetic joint infections (PJIs) are disastrous complications for patients and costly for healthcare organisations. They may promote bacterial resistance due to the extensive antibiotic use necessary in the PJI treatment. The PJI incidence is estimated to be 1%–3%, but the absolute numbers worldwide are high and increasing as large joint arthroplasties are performed by the millions each year. Current treatment algorithms, based on implant preserving surgery or full revision followed by a semitailored antibiotic regimen for no less than 2–3 months, lead to infection resolution in approximately 60% and 90%, respectively. Antibiotic choice is currently guided by minimum inhibitory concentrations (MICs) of free-living bacteria and not of bacteria in biofilm growth mode. Biofilm assays with relatively rapid output for the determination of minimum biofilm eradication concentrations (MBECs) have previously been developed but their clinical usefulness have not been established. Methods and analysis This single-blinded, two-arm randomised study of hip or knee staphylococcal PJI will evaluate 6-week standard of care (MIC guided), or an alternative antibiotic regimen according to an MBEC-guided-based decision algorithm. Sixty-four patients with a first-time PJI treated according to the debridement, antibiotics, and implant retention principle will be enrolled at a single tertiary orthopaedic centre (Sahlgrenska University Hospital). Patients will receive 14 days of standard parenteral antibiotics before entering the comparative study arms. The primary outcome measurement is the proportion of changes in antimicrobial regimen from first-line treatment dependent on randomisation arm. Secondary endpoints are unresolved infection, how microbial properties including biofilm abilities and emerging antimicrobial resistance correlate to infection outcomes, patient reported outcomes and costs with a 12-month follow-up. Ethics and dissemination Approval is received from the Swedish Ethical Review Authority, no 2020-01471 and the Swedish Medical Products Agency, EudraCT, no 2020-003444-80. Trial registration number ClinicalTrials.gov ID: NCT04488458.
The relationship of masked hypertension with autonomic dysfunction and cardiometabolic parameters: a case-control study.

OBJECTIVE Masked hypertension (MH) is associated with cardiovascular events and mortality. Data on the association between exaggerated blood pressure response (EBPR) to exercise, heart rate recovery (HRR), which are indicators of autonomic dysfunction, and MH are lacking. This study aimed at evaluating the association between EBPR, HRR, and MH. PATIENTS AND METHODS Between January 2020 and January 2021, 130 MH (57 male, median age = 52.8 years) and 60 healthy (28 male, median age = 40.8 years) subjects were included in this single-center, case-control, and cross-sectional study. Office blood pressure measurement, 24-hour ambulatory blood pressure monitoring, treadmill test, echocardiography, and specific biochemical parameters were evaluated. RESULTS The frequency of blunted HRR (73 subjects, 56.2%) and EBPR (40 subjects, 30.8%) were significantly higher in patients with MH (p < 0.001). Patients with MH had higher serum uric acid levels and frequency of hyperlipidemia (p < 0.05). Diameters of the left atrium (LA), aortic root, and ascending aorta were significantly higher in MH patients (p < 0.05). Thirty-two (24.6%) patients with MH had left ventricular hypertrophy and 33 (25.4%) had diastolic dysfunction (p < 0.001). Multivariate analysis identified the presence of blunted HRR as an independent predictor factor of MH as well as smoking, hyperlipidemia, GFR, LA diameter, and aortic root diameter were other independent factors. CONCLUSIONS The frequency of blunted HRR and EBPR were significantly higher in the MH group compared to the control group, suggesting a close relationship between MH and autonomic dysfunction.
Pharmacogenomic Testing and Depressive Symptom Remission: A Systematic Review and Meta‐Analysis of Prospective, Controlled Clinical Trials

Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical efficacy of this strategy has been questioned. We systematically reviewed and meta‐analyzed clinical trials for an association between the use of PGx‐guided antidepressant therapy and depressive symptom remission in patients with major depressive disorder (MDD). We included prospective, controlled clinical trials published in English up to July 12, 2022. Data extraction and synthesis adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Each trial was assessed for risk of bias and a random‐effects model was used to estimate pooled risk ratios. Thirteen trials comprising 4,767 patients were analyzed, including 10 randomized controlled trials, and three open label trials. Across all included trials, those that received PGx‐guided antidepressant therapy (n = 2,395) were 1.41 (95% confidence interval (CI) = 1.15–1.74, P = 0.001) more likely to achieve remission compared with those that received unguided antidepressant therapy (n = 2,372). Pooled risk ratios for randomized controlled trials and open label trials were 1.46 (95% CI: 1.13–1.88) and 1.26 (95% CI = 0.84–1.88), respectively. These results suggest that PGx‐guided antidepressant therapy is associated with a modest but significant increase in depressive symptom remission in adults with MDD. Efforts to address the heterogeneity in PGx test composition (i.e., genes and alleles tested) and accompanying prescribing recommendations across trials will likely reduce the uncertainty about the efficacy of PGx‐guided antidepressant therapy in the literature.
The very long-chain fatty acid elongase FgElo2 governs tebuconazole sensitivity and virulence in Fusarium graminearum.

Very long-chain fatty acids (VLCFAs), the precursors for the synthesis of sphingolipids (SLs), play pivotal roles in the development and stress response in eukaryotes. In Saccharomyces cerevisiae, VLCFAs are synthesized in the endoplasmic reticulum (ER) through a four-step elongation cycle. However, the functions of VLCFA elongases in phytopathogenic fungi remain largely unexplored. Here, we identified a single copy of the VLCFA elongase gene FgELO2 in Fusarium graminearum that causes Fusarium head blight worldwide. FgElo2 localized to ER membrane, and deletion mutant of FgELO2 exhibited serious defects in vegetative growth and conidiation. Importantly, ΔFgElo2 led to ergosterol content reduction and disrupted the ER-localization of 14-α-demethylase FgCYP51s, indicating that the scarce of sphingolipids reduced ergosterol, which ultimately elevated the sensitivity of ΔFgElo2 to tebuconazole. Fluorescent microscopic examination suggested that FgElo2 was degraded upon cell membrane stress. ΔFgElo2 showed decreased phosphorylation of high osmolarity glycerol (HOG) pathway, and subsequently exhibited remarkable sensitivity to osmotic stress. In addition, fungal virulence was dramatically reduced in FgElo2 via inhibiting deoxynivalenol production and formation of infection structures. Together, this study demonstrates that the VLCFA elongase FgElo2 modulates fungal development, tebuconazole sensitivity, stress responses and virulence, which may advance our understanding of pathogen-host interactions mediated by VLCFAs.
Elevated neutrophil‐to‐lymphocyte ratio (NLR) is associated with poorer progression‐free survival in unresectable stage III NSCLC treated with consolidation durvalumab

Sustained elevation in neutrophil‐to‐lymphocyte ratio (NLR) after initial chemoradiotherapy (CRT) has been shown to correlate with worse prognosis in a number of solid organ malignancies. Here, we conducted a retrospective observational cohort study involving six sites across Sydney, Australia, including all patients with unresectable stage III NSCLC treated with CRT and consolidation durvalumab between January 2018 and September 2021. Patients had NLR collected prior to CRT and prior to cycle one of durvalumab. We used an NLR value of 3 to stratify patients into high and low groups. Patients with sustained NLR were defined as those with values ≥3 at both timepoints. A total of 145 patients were included in the study. The median age of patients was 66 years with median follow‐up of 15.1 months. The median PFS was 17.6 months in the pre‐CRT NLR high cohort and not reached (NR) in the pre‐CRT NLR low cohort (HR 1.99; p = 0.01). The median OS was 35.5 months in the high pre‐CRT NLR cohort compared with 42.0 months in the low pre‐CRT NLR cohort (HR 2.62; 95% CI: 1.23–5.56, p < 0.01). Median PFS for sustained NLR elevation was 17.1 months versus NR (HR 1.5; p < 0.01). Pre‐CRT NLR and sustained NLR remained independently prognostic for PFS on multivariate analysis (p = 0.04, p = 0.01) respectively. Pre‐CRT NLR and sustained NLR is associated with worse PFS outcomes in unresectable stage III NSCLC treated with CRT and durvalumab. Pre‐CRT NLR is also associated with worse OS.
Content CN-21-5

Dopamine (DA) agonists, as an excellent dopamine replacement therapy for patients with early and advanced Parkinson's disease (PD), play a vital role in controlling motor and several nonmotor symptoms. Besides, the application of DA agonists may delay levodopa therapy and the associated risk of motor complications. Indeed, each DA agonist has unique pharmacokinetic and pharmacodynamic characteristics and therefore has different therapeutic efficacy and safety profile. The comorbidities, significant non-motor manifestations, concomitant medications, and clinical features of PD individuals should guide the selection of a specific DA agonist to provide a more patient-tailored treatment option. Thorough knowledge of DA agonists helps clinicians better balance clinical efficacy and side effects. Therefore, this review refers to recent English-written articles on DA agonist therapy for PD patients and summarizes the latest findings on non-ergot DA agonists as well as the advantages and disadvantages of each compound to help clinicians in the selection of a specific DA agonist. In addition, novel D1/D5 partial agonists and new formulations of DA agonists are also discussed. A R T I C L E H I S T O R Y Received: April 10, 2022 Revised: May 25, 2022 Accepted: July 18, 2022
Characteristics of BAY 2599023 in the Current Treatment Landscape of Hemophilia A Gene Therapy

Hemophilia A, a single gene disorder leading to deficient Factor VIII (FVIII), is a suitable candidate for gene therapy. The aspiration is for single administration of a genetic therapy that would allow the production of endogenous FVIII sufficient to restore hemostasis and other biological processes. This would potentially result in reliable protection from bleeding and its associated physical and emotional impacts. Gene therapy offers the possibility of a clinically relevant improvement in disease phenotype and transformational improvement in quality of life, including an opportunity to engage in physical activities more confidently. Gene therapy products for hemophilia A in advanced clinical development use adeno-associated viral (AAV) vectors and a codon-optimized B-domain deleted FVIII transgene. However, the different AAV-based gene therapies have distinct design features, such as choice of vector capsid, enhancer and promoter regions, FVIII transgene sequence and manufacturing processes. These, in turn, impact patient eligibility, safety and efficacy. Ideally, gene therapy technology for hemophilia A should offer bleed protection, durable FVIII expression, broad eligibility and limited response variability between patients, and long-term safety. However, several limitations and challenges must be overcome. Here, we introduce the characteristics of the BAY 2599023 (AAVhu37.hFVIIIco, DTX 201) gene therapy product, including the low prevalence in the general population of anti-AAV-hu37 antibodies, as well as other gene therapy AAV products and approaches. We will examine how these can potentially meet the challenges of gene therapy, with the ultimate aim of improving the lives of patients with hemophilia A.
Public Deliberation Process on Patient Perspectives on Health Information Sharing: Evaluative Descriptive Study

Background Precision oncology is one of the fastest-developing domains of personalized medicine and is one of many data-intensive fields. Policy for health information sharing that is informed by patient perspectives can help organizations align practice with patient preferences and expectations, but many patients are largely unaware of the complexities of how and why clinical health information is shared. Objective This paper evaluates the process of public deliberation as an approach to understanding the values and preferences of current and former patients with cancer regarding the use and sharing of health information collected in the context of precision oncology. Methods We conducted public deliberations with patients who had a current or former cancer diagnosis. A total of 61 participants attended 1 of 2 deliberative sessions (session 1, n=28; session 2, n=33). Study team experts led two educational plenary sessions, and trained study team members then facilitated discussions with small groups of participants. Participants completed pre- and postdeliberation surveys measuring knowledge, attitudes, and beliefs about precision oncology and data sharing. Following informational sessions, participants discussed, ranked, and deliberated two policy-related scenarios in small groups and in a plenary session. In the analysis, we evaluate our process of developing the deliberative sessions, the knowledge gained by participants during the process, and the extent to which participants reasoned with complex information to identify policy preferences. Results The deliberation process was rated highly by participants. Participants felt they were listened to by their group facilitator, that their opinions were respected by their group, and that the process that led to the group’s decision was fair. Participants demonstrated improved knowledge of health data sharing policies between pre- and postdeliberation surveys, especially regarding the roles of physicians and health departments in health information sharing. Qualitative analysis of reasoning revealed that participants recognized complexity, made compromises, and engaged with trade-offs, considering both individual and societal perspectives related to health data sharing. Conclusions The deliberative approach can be valuable for soliciting the input of informed patients on complex issues such as health information sharing policy. Participants in our two public deliberations demonstrated that giving patients information about a complex topic like health data sharing and the opportunity to reason with others and discuss the information can help garner important insights into policy preferences and concerns. Data on public preferences, along with the rationale for information sharing, can help inform policy-making processes. Increasing transparency and patient engagement is critical to ensuring that data-driven health care respects patient autonomy and honors patient values and expectations.
Cannabidiol Impairs Brain Mitochondrial Metabolism and Neuronal Integrity

Background: The mechanisms underlying the clinical effects of CBD remain poorly understood. Given the increasing evidence for CBD's effects on mitochondria, we sought to examine in more detail whether CBD impacts mitochondrial function and neuronal integrity. Methods: We utilized BE(2)-M17 neuroblastoma cells or acutely isolated brain mitochondria from rodents using a Seahorse extracellular flux analyzer and a fluorescent spectrofluorophotometer assay. Mitochondrial ion channel activity and hippocampal long-term potentiation were measured using standard cellular electrophysiological methods. Spatial learning/memory function was evaluated using the Morris water maze task. Plasma concentrations of CBD were assessed with liquid chromatography–mass spectrometry, and cellular viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction neuronal injury assay. Results: At low micromolar concentrations, CBD reduced mitochondrial respiration, the threshold for mitochondrial permeability transition, and calcium uptake, blocked a novel mitochondrial chloride channel, and reduced the viability of hippocampal cells. These effects were paralleled by in vitro and in vivo learning/memory deficits. We further found that these effects were independent of cannabinoid receptor 1 and mitochondrial G-protein-coupled receptor 55. Conclusion: Our results provide evidence for concentration- and dose-dependent toxicological effects of CBD, findings that may bear potential relevance to clinical populations.
Another failure of the latent disease model? The case of compulsive sexual behavior disorder •

Abstract Recent debates have evolved regarding the classification/conceptualization of compulsive sexual behavior disorder (CSBD). Conclusions regarding an agreed upon CSBD model are hindered by reliance on the latent disease model. Competing biological-based frameworks are moving forward to replace latent disease classification more broadly but have been met with limited success. We suggest that CSBD researchers move towards developing dimensional, transtheoretical, process-based models. We further suggest additional research, particularly mixed methods and longitudinal studies. Finally, we request that federal funding bodies take a more active role in supporting CSBD research.
An alien in Marseille: investigations on a single Aedes aegypti mosquito likely introduced by a merchant ship from tropical Africa to Europe

Control of invasive species relies partly on permanent surveillance at international points of entry. We report the exceptional trapping of one adult mosquito (Diptera: Culicidae) in the port of Marseille, France, in July 2018, during a routine survey conducted according to International Health Regulations. Morphological and molecular identification classified the specimen as a female Aedes (Stegomyia) aegypti (L.), vector of many arboviruses, absent from Europe and the Mediterranean rim since the 1950s. A world reference panel of approximately 23,000 genome-wide single nucleotide polymorphisms determined that the mosquito originated from Cameroon, west Africa. Cross-reference of this geographic location with boats traveling from Central Africa to Marseille during the trapping period suggests that the mosquito travelled within an identified merchant ship, a vehicles carrier connecting Douala, Cameroon to Marseille, France. This ship left Douala on June 25, 2018 and arrived 20 days later in Marseille on July 15. The mosquito was captured 350 m away from the dock. The interception of a propagule of an invasive species is a rare event that must be considered a priority to prevent its successful establishment.