Miracle-dz/UniFAR-FTUs huggingface dataset:
A molecular barcode to inform the geographical origin and transmission dynamics of Plasmodium vivax malaria

Although Plasmodium vivax parasites are the predominant cause of malaria outside of sub-Saharan Africa, they not always prioritised by elimination programmes. P. vivax is resilient and poses challenges through its ability to re-emerge from dormancy in the human liver. With observed growing drug-resistance and the increasing reports of life-threatening infections, new tools to inform elimination efforts are needed. In order to halt transmission, we need to better understand the dynamics of transmission, the movement of parasites, and the reservoirs of infection in order to design targeted interventions. The use of molecular genetics and epidemiology for tracking and studying malaria parasite populations has been applied successfully in P. falciparum species and here we sought to develop a molecular genetic tool for P. vivax. By assembling the largest set of P. vivax whole genome sequences (n = 433) spanning 17 countries, and applying a machine learning approach, we created a 71 SNP barcode with high predictive ability to identify geographic origin (91.4%). Further, due to the inclusion of markers for within population variability, the barcode may also distinguish local transmission networks. By using P. vivax data from a low-transmission setting in Malaysia, we demonstrate the potential ability to infer outbreak events. By characterising the barcoding SNP genotypes in P. vivax DNA sourced from UK travellers (n = 132) to ten malaria endemic countries predominantly not used in the barcode construction, we correctly predicted the geographic region of infection origin. Overall, the 71 SNP barcode outperforms previously published genotyping methods and when rolled-out within new portable platforms, is likely to be an invaluable tool for informing targeted interventions towards elimination of this resilient human malaria.
High Prevalence of Strongyloidiasis in Spain: A Hospital-Based Study

Introduction: Strongyloidiasis is a prevailing helminth infection ubiquitous in tropical and subtropical areas, however, seroprevalence data are scarce in migrant populations, particularly for those coming for Asia. Methods: This study aims at evaluating the prevalence of S. stercoralis at the hospital level in migrant populations or long term travellers being attended in out-patient and in-patient units as part of a systematic screening implemented in six Spanish hospitals. A cross-sectional study was conducted and systematic screening for S. stercoralis infection using serological tests was offered to all eligible participants. Results: The overall seroprevalence of S. stercoralis was 9.04% (95%CI 7.76–10.31). The seroprevalence of people with a risk of infection acquired in Africa and Latin America was 9.35% (95%CI 7.01–11.69), 9.22% (7.5–10.93), respectively. The number of individuals coming from Asian countries was significantly smaller and the overall prevalence in these countries was 2.9% (95%CI −0.3–6.2). The seroprevalence in units attending potentially immunosuppressed patients was significantly lower (5.64%) compared with other units of the hospital (10.20%) or Tropical diseases units (13.33%) (p < 0.001). Conclusions: We report a hospital-based strongyloidiasis seroprevalence of almost 10% in a mobile population coming from endemic areas suggesting the need of implementing strongyloidiasis screening in hospitalized patients coming from endemic areas, particularly if they are at risk of immunosuppression.
The Potential of Ultraviolet Radiation Meters in Secondary Schools as a Sun Protection Intervention Mechanism for Adolescents

The aim of this pilot study was to assess whether the installation of ultraviolet radiation (UVR) meters in secondary schools has the potential to improve adolescents’ sun protection-related knowledge, attitudes, and behaviours and reduce their exposure to UVR during school hours. Data were collected from students at two schools via online pre- and post-intervention surveys, measurement of sunscreen usage, polysulfone UVR exposure badges, and photographs of the schoolyards to assess hat and shade use. Several operational issues limited the quantity and quality of data that could be collected, and findings were mixed. While there were no significant changes in either self-reported or observed sun protection behaviours, there were significant improvements in UVR knowledge among students at the intervention school, and reactions to the meter were highly favourable. Students reported consulting the meter regularly and using it to make decisions about their sun protection behaviours. Overall, the study results offer some support for the use of UVR meters in areas frequented by adolescents and provide insights into the process issues that are likely to need to be addressed when attempting to trial sun protection interventions in schools.
Age-Related Changes in Physical Fitness Among Community-Living Middle-Aged and Older Japanese: A 12-Year Longitudinal Study

ABSTRACT Physical fitness is one of the key factors in healthy aging. Although physical fitness is widely recognized to decline with age, age-related decreases in the individual dimensions of physical fitness in later life are less clear. Purpose: The purpose of the present study was to describe the age-related changes in six fitness components covering a variety of motor dimensions in men and women through a 12-year longitudinal epidemiological study. Method: Participants were randomly selected community-living men (n = 1,139) and women (n = 1,128) aged 40 to 79 years at baseline who were repeatedly tested over a mean (standard deviation) follow-up period of 9.8 (3.4) years with a mean of 4.9 (2.3) examinations. The six physical fitness tests were sit-and-reach, grip strength, sit-ups, one-leg standing, reaction time and leg extension power. The effect of age on each physical fitness task was analyzed using a mixed-effects model controlling for habitual physical activity level. Results: The fixed effect of the interaction of age and time in all fitness tests was significant in men. Higher age at baseline was significantly associated with a greater decrease over time except in one-leg standing. In women, no significant interaction effect of age and time was found in grip strength or reaction time. Age-related changes in grip strength and reaction time were constant with increasing age. Conclusion: Twelve-year longitudinal data showed that the age-related decrease in physical fitness over time, especially musculoskeletal fitness in men, was pronounced, whereas in women, the decrease was less pronounced.
Internal mammary harvesting: Techniques and evidence from the literature

Coronary artery bypass graft (CABG) is one of the most commonly performed cardiac surgeries in the world. CABG using the internal mammary artery (IMA) remains the gold standard intervention for myocardial intervention in multivessel coronary artery disease. IMA harvesting can be performed with various techniques and approaches: pedicled vs skeletonized harvesting technique as well as approaches such as conventional sternotomy, robotic and endoscopic approaches. While each technique and approach have their respective advantages and disadvantages, evidence remains varied between cohorts. Traditionally, IMA has been used as an in situ conduit; however, IMA free grafts also provide satisfactory outcomes in certain situations. This literature review aims to explore the efficacy of different techniques and approaches of IMA harvesting and grafting. With evidence compiled, this will provide an overview of the complexity of CABG and locate gaps in current literature to direct future research.
Prognostic value of arterial stiffness measurements in cardiovascular disease, diabetes, and its complications: The potential role of sodium‐glucose co‐transporter‐2 inhibitors

Type 2 diabetes mellitus (T2DM) constitutes a global pandemic, representing the 7th cause of death worldwide. Morbidity and mortality of patients with T2DM are gradually increasing, while prevalence of cardiovascular disease (CVD) among these patients is almost 14% greater compared to the general population. Arterial stiffness is nowadays a valuable biomarker of CVD and a promising treatment target in specific patient groups, including those suffering from T2DM. Despite that fact, design of the available studies cannot prove causal relationship. Recently, a new antidiabetic drug class, namely sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitors, has attracted scientific interest, due to their multiple, beneficial, pleiotropic effects, especially those focused on CVD. There is limited relevant literature concerning the effects of SGLT‐2 inhibitors on arterial stiffness, while retrieved results might be considered as conflicting. The aim of the present review article is to summarize acquired knowledge regarding the prognostic role of arterial stiffness in T2DM, along with the presentation of retrieved data on the potential role of SGLT‐2 inhibitors.
Oxidative Stress in Canine Histiocytic Sarcoma Cells Induced by an Infection with Canine Distemper Virus Led to a Dysregulation of HIF-1α Downstream Pathway Resulting in a Reduced Expression of VEGF-B In Vitro

Histiocytic sarcomas represent malignant tumors which require new treatment strategies. Canine distemper virus (CDV) is a promising candidate due to its oncolytic features reported in a canine histiocytic sarcoma cell line (DH82 cells). Interestingly, the underlying mechanism might include a dysregulation of angiogenesis. Based on these findings, the aim of the present study was to investigate the impact of a persistent CDV-infection on oxidative stress mediated changes in the expression of hypoxia-inducible factor (HIF)-1α and its angiogenic downstream pathway in DH82 cells in vitro. Microarray data analysis, immunofluorescence for 8-hydroxyguanosine, superoxide dismutase 2 and catalase, and flow cytometry for oxidative burst displayed an increased oxidative stress in persistently CDV-infected DH82 cells (DH82Ond pi) compared to controls. The HIF-1α expression in DH82Ond pi increased, as demonstrated by Western blot, and showed an unexpected, often sub-membranous distribution, as shown by immunofluorescence and immunoelectron microscopy. Furthermore, microarray data analysis and immunofluorescence confirmed a reduced expression of VEGF-B in DH82Ond pi compared to controls. In summary, these results suggest a reduced activation of the HIF-1α angiogenic downstream pathway in DH82Ond pi cells in vitro, most likely due to an excessive, unusually localized, and non-functional expression of HIF-1α triggered by a CDV-induced increased oxidative stress.
The Role of the Cutaneous Microbiome in Hidradenitis Suppurativa—Light at the End of the Microbiological Tunnel

The development of next generation sequencing, coupled with advances in bio-informatics, has provided new insights into the role of the cutaneous microbiome in the pathophysiology of a range of inflammatory skin diseases. In fact, it has even been suggested that the identification of specific skin microbial signatures may not only be useful in terms of diagnosis of skin diseases but they may also ultimately help inform personalised treatment strategies. To date, research investigating the role of microbiota in the development of inflammatory skin diseases has largely focused on atopic eczema and psoriasis vulgaris. The role of the microbiome in Hidradenits suppurativa (HS)—also known as acne inversa—a chronic auto-inflammatory skin disease associated with significant morbidity, has received comparatively little attention. This is despite the fact that antimicrobial therapy plays a central role in the treatment of HS. After briefly outlining the clinical features of HS and current treatment strategies, we move on to review the evidence of microbial dysbiosis in HS pathophysiology. We conclude by outlining the potential for metagenomic studies to deepen our understanding of HS biology but more importantly to identify novel and much needed treatment strategies.
Camel-Related Head Injury in a High-Income Developing Country

Introduction: Injury caused by large animals varies according to the regional distribution of the animals and their relationship to humans. Camels are usually friendly to humans; however, occasionally they become very hostile, especially in rutting season. Most in-hospital trauma deaths are related to head injury. Very few studies in the literature have discussed camel-related head injuries. We aimed to study the incidence, mechanism of injury, types, and outcome of camel-related head injury in a high-income developing country to give recommendations on preventive measures. Methods: We retrospectively collected data from all patients who were admitted to Al Ain Hospital with a camel-related head injury from January 1, 2015, to January 1, 2021. Data collected included demography, mechanism of injury, anatomical location, severity of the injury, associated injuries, and management. The patients were followed up during their hospital stay to record the length of hospital stay, complications, and outcome. Results: During the study period, 98 patients were admitted to Al Ain Hospital with camel-related injury. Thirty-nine (39.8%) of the admitted patients with a camel-related injury sustained a head injury; a camel-related head injury was more common during August (23.1%). Thirty-four (87.2%) patients were camel caregivers. Thirty-three patients (84.6%) were injured on farms. Seven patients suffered an intracranial hemorrhage, and six (85.7%) of them had a history of fall from a camel. Glasgow Coma Score was significantly correlated to the severity of head injury measured by Abbreviated Injury Severity of the head (P = 0.006, Spearman's correlation). One patient died during the study period after having decompressive craniectomy for subdural hemorrhage (overall mortality 2.6%). Conclusions: The majority of camel-related head injury occurred in camel caregivers at camel farms and can be considered a work-related injury. Careful handling of camels, especially during the summertime can reduce the toll of camel-related head injury and its serious consequences. None of the injured patients was wearing a helmet at the time of injury. Legislation for compulsory helmet usage by camel caregivers at farms may decrease the incidence of head injuries in those patients.
Patient Preferences in Adjuvant and Palliative Treatment of Advanced Melanoma: A Discrete Choice Experiment

Treatment paradigms for advanced melanoma have changed fundamentally over recent years. A discrete choice experiment was performed to explore patient preferences regarding outcome (overall response rate, 2-year survival rate, progression-free survival, time to response, type of adverse events, probability of adverse event-related treatment discontinuation) and process attributes (frequency and route of administration, frequency of consultations) of modern treatments for melanoma. Mean preferences of 150 patients with melanoma stage IIC-IV were highest for overall response rate (relative importance score (RIS) 26.8) and 2-year survival (RIS 21.6), followed by type of adverse events (RIS 11.7) and probability of adverse event-related treatment discontinuation (RIS 9.2). Interest in overall response rate and 2-year survival declined with increasing age, whereas process attributes gained importance. Participants who had experienced treatment with immune checkpoint inhibitors valued overall response rate more highly and worried less about the type of adverse events. In conclusion, patients with advanced melanoma consider efficacy of treatment options most important, followed by safety, but preferences vary with individual and disease-related characteristics.
RECENT HIV INFECTION SURVEILLANCE IN ROUTINE HIV TESTING IN NAIROBI, KENYA: A FEASIBILITY STUDY.

BACKGROUND Serological tests can distinguish recent (in the prior 12 months) from long-term HIV infection. Integrating recency testing into routine HIV testing services (HTS) can provide important information on transmission clusters and prioritize clients for partner testing. This study assessed the feasibility and utility of integrating HIV recency into routine testing. METHODS We conducted a multi-method study at fourteen facilities in Kenya, and key informant interviews with healthcare providers. We abstracted clinical record data, collected specimens, tested specimens for recent infection, returned results to participants, and conducted a follow-up survey for those recently infected. RESULTS From March to October 2018, we enrolled 532 clients who were diagnosed HIV positive for the first time. Of these, 46 (8.6%) were recently infected. Women aged 15- 24 years had 2.9 (95% CI, 1.46-5.78) times higher adjusted odds of recent infection compared to 15-24-year-old men and those tested within the past 12 months having 2.55 (95% CI .38-4.70) times higher adjusted odds compared to those tested ≥12 months previously. Fourteen of seventeen providers interviewed found the integration of receny testing into routine HTS services acceptable and feasible. Among clients who completed the follow up interview, majority (92%) felt that the recency results were useful. CONCLUSIONS Integrating recent infection testing into routine HTS services in Kenya is feasible and largely acceptable to clients and providers. More studies should be done on possible physical and social harms related to returning results, and the best uses of the recent infection data at an individual and population level.
CD4/CD8 ratio is a prognostic factor in IgG nonresponders among peptide vaccine‐treated ovarian cancer patients

The identification of useful biomarkers is an urgent issue in cancer treatment, particularly for immunotherapy, as only some patients experience benefits from this treatment. The early induction of the IgG response has been reported as a useful biomarker of favorable prognosis for cancer patients treated with a personalized peptide vaccination, but a portion of these patients (IgG nonresponders) fail to achieve an early induction of IgG response yet experience long‐term survival. It is thus necessary to identify other biomarkers of favorable prognosis among these patients. Here we report the usefulness of classical T‐cell markers (ie, the CD8 content and the CD4/CD8 ratio in peripheral blood) in IgG nonresponders among advanced or recurrent ovarian cancer patients treated with a personalized peptide vaccination. Among IgG nonresponders (n = 25), the overall survival (OS) of the increased‐CD8 group (n = 7) was significantly longer than that of the decreased‐CD8 group (n = 18; P = .018), and the OS of the patients with a decreased CD4/CD8 ratio (n = 10) was significantly longer than that of the patients with an increased ratio (n = 15; P = .0055). Thus, an increased content of CD8 and a decreased CD4/CD8 ratio are each favorable prognosis markers in IgG nonresponders treated with a personalized peptide vaccination.
A Multifunctional β-cyclodextrin Polymer for Simultaneous Removal of Natural Organic Matter and Organic Micropollutants and Detrimental Microorganisms from Water.

Natural organic matter (NOM), organic micropollutants (OMPs) and detrimental microorganisms are three major pollutants that affect water quality. To remove these pollutants, a quaternary ammonium-functionalized β-cyclodextrin polymer (β-CDP) is successfully synthesized in the aqueous phase. The N2 and CO2 adsorption/desorption analysis showed that the polymer mainly contains ultra-micro pores (＜1 nm), with Langmuir surface area of 89 m2 g-1. Two kinds of NOM: humic acid and fulvic acid, and five OMPs: 2-naphthol (2-NO), 3-phenylphenol (3-PH), 2,4,6-trichlorophenol (2,4,6-TCP), bisphenol A (BPA), and bisphenol S (BPS), were selected as model pollutants to study the performance of β-CDP and three kinds of commercial adsorbents, including granular activated carbon, DARCO-AC, and two resigns, XAD-4 and D-201, were used for comparison. The polymer shows ultra-rapid adsorption kinetics for the removal of these pollutants, with pseudo-second-order rate constants two to three orders of magnitude higher than that of the commercial activated carbon and resins. Due to the different adsorption sites of NOM and OMPs, β-CDP can simultaneously remove these pollutants without competitive adsorption. The maximum adsorption capacity of β-CDP for HA, FA, 2-NO, 3-PH, 2,4,6-TCP, BPA and BPS based on the Langmuir model are 40, 166, 74, 101, 108, 103, and 117 mg g-1, respectively. After use, the polymer can be easily regenerated at room temperature. In addition, β-CDP also showed excellent bactericidal properties due to the quaternary ammonium groups. At a concentration of 15 g L-1, β-CDP can remove 98% of the tested Escherichia coli. Moreover, the synthesis of β-CDP is simple, green and easy to industrialize. All these findings indicate that β-CDP, as an ideal multifunctional material, presents potential for practical applications for water treatment and disinfection.
Effectiveness and safety of adalimumab biosimilar ABP 501 in Crohn's disease: an observational study.

BACKGROUND AND OBJECTIVE there are no studies in the literature about the effectiveness of adalimumab biosimilar ABP 501 in Crohn's disease. The aim of this study was to evaluate its effectiveness and safety. METHODS an observational study was performed in Crohn's disease patients treated with ABP 501, with the classic induction and maintenance regimen and in Crohn's disease patients who were switched from the adalimumab originator to ABP 501. RESULTS eighty-seven patients were included in the study, of which 25 were naïve to the adalimumab originator and 62 were switched to ABP 501. In adalimumab-naïve patients, clinical response at three months was 60% (15/25) and clinical remission at three months was 56% (14/25). At six months, 95.2% (59/62) of the patients switched to ABP 501 were still in therapy, without a significant increase of clinical activity (Harvey-Bradshaw index from 3.4, 95% CI = 2.4-4.4, to 3.8, 95% CI = 2.7-4.9, p = 0.23) and inflammatory biomarkers (C-reactive protein from 4.2 mg/l, 95% CI = 2.5-5.9 mg/l, to 3.6 mg/l, 95% CI = 2.2-5 mg/l, p = 0.32). There were no unexpected adverse events during the study period. CONCLUSIONS our results support ABP 501 as an effective and well-tolerated drug, with a good interchangeability with its originator for the treatment of Crohn's disease.
Innovative preclinical models for pulmonary drug delivery research

ABSTRACT Introduction: Pulmonary drug delivery is a complex field of research combining physics which drive aerosol transport and deposition and biology which underpins efficacy and toxicity of inhaled drugs. A myriad of preclinical methods, ranging from in-silico to in-vitro, ex–vivo and in-vivo, can be implemented. Areas covered: The present review covers in-silico mathematical and computational fluid dynamics modelization of aerosol deposition, cascade impactor technology to estimated drug delivery and deposition, advanced in-vitro cell culture methods and associated aerosol exposure, lung-on-chip technology, ex–vivo modeling, in-vivo inhaled drug delivery, lung imaging, and longitudinal pharmacokinetic analysis. Expert opinion: No single preclinical model can be advocated; all methods are fundamentally complementary and should be implemented based on benefits and drawbacks to answer specific scientific questions. The overall best scientific strategy depends, among others, on the product under investigations, inhalation device design, disease of interest, clinical patient population, previous knowledge. Preclinical testing is not to be separated from clinical evaluation, as small proof-of-concept clinical studies or conversely large-scale clinical big data may inform preclinical testing. The extend of expertise required for such translational research is unlikely to be found in one single laboratory calling for the setup of multinational large-scale research consortiums.