Miracle-dz/UniFAR-FTUs huggingface dataset:
Connectedness structure of the solution sets of vector variational inequalities

By a scalarization method and properties of semi-algebraic sets, it is proved that both the Pareto solution set and the weak Pareto solution set of a vector variational inequality, where the constraint set is polyhedral convex and the basic operators are given by polynomial functions, have finitely many connected components. Consequences of the results for vector optimization problems are discussed in details. The results of this paper solve in the affirmative some open questions for the case of general problems without requiring monotonicity of the operators involved.
Morphology does not allow differentiating the species of the Phlebotomus perniciosus complex: Molecular characterization and investigation of their natural infection by Leishmania infantum in Morocco

Morphological and DNA‐based complemented approaches were applied for characterization of sympatric populations of Phlebotomus longicuspis and Phlebotomus perniciosus in Morocco. Both sand fly species are generally recorded in sympatry in North Africa but on few occasions have been molecularly characterized. The diagnostic confusion of these species has led to errors in their geographical distribution and probably, in the assignment of their role in the transmission of L. infantum. Sand flies were caught inside households in El Borouj, central Morocco, in 2014–2015. For female sand flies, detection of L. infantum natural infection and blood meal identification were carried out. According to morphological identification, Phlebotomus longicuspis s.l. (34.7%) was the second most abundant Phlebotomus species after P. sergenti, followed by atypical Phlebotomus perniciosus (7.1%); 11.6% of the male specimens of P. longicuspis s.l. were identified as P. longicuspis LCx according to the number of coxite setae. The density of Larroussius species was very high (31 Larroussius/light trap/night) in the peripheral neighbourhood of Oulad Bouchair (p = 0.001) where the first case of cutaneous leishmaniasis due to Leishmania infantum was detected in 2017. Phylogenetic trees based on three independent genes highlighted three well‐supported clusters within P. perniciosus complex that could be interpreted as corresponding to P. perniciosus, P. longicuspis s.s. and an undescribed species, all coexisting in sympatry. Some females with typical morphology of P. longicuspis were genetically homologous to P. perniciosus. The taxa cannot be differentiated by morphological methods but characterized by a distinctive genetic lineage for which the synapomorphic characters are described. Leishmania infantum was detected in females of all clusters with a low parasite load. Population genetics will help to assess the threat of the geographical spread of L. infantum in Morocco by determining the density, abundance and vector role of the species of the P. perniciosus complex identified correctly.
A Portable Chip-Based NMR Relaxometry System With Arbitrary Phase Control for Point-of-Care Blood Analysis

In this article, we present a portable NMR relaxometry system optimized for the point-of-care analysis of body liquids such as blood. The presented system is centered on an NMR-on-a-chip transceiver ASIC, a reference frequency generator with arbitrary phase control, and a custom-designed miniaturized NMR magnet with a field strength of 0.29 T and a total weight of 330 g. The NMR-ASIC co-integrates a low-IF receiver, a power amplifier, and a PLL-based frequency synthesizer on a total chip area of 1100 <inline-formula><tex-math notation="LaTeX">$\boldsymbol{\times }$</tex-math></inline-formula> 900 <inline-formula><tex-math notation="LaTeX">$\mu$</tex-math></inline-formula>m<inline-formula><tex-math notation="LaTeX">$\boldsymbol{^{2}}$</tex-math></inline-formula>. The arbitrary reference frequency generator enables the use of conventional CPMG and inversion sequences, as well as modified water-suppression sequences. Moreover, it is used to implement an automatic frequency lock to correct temperature-induced magnetic field drifts. Proof-of-concept measurements on NMR phantoms and human blood samples show an excellent concentration sensitivity of <italic>v</italic><inline-formula><tex-math notation="LaTeX">$\boldsymbol{_\text{c,min}}$</tex-math></inline-formula> = 2.2 mM/<inline-formula><tex-math notation="LaTeX">$\boldsymbol{\sqrt{\text{Hz}}}$</tex-math></inline-formula>. This very good performance renders the presented system an ideal candidate for the future NMR-based point-of-care detection of biomarkers such as the blood glucose concentration.
The effects of 3-year growth hormone treatment and body composition in Polish patients with Silver-Russell syndrome.

INTRODUCTION Silver-Russell syndrome (SRS) is characterized by clinical and genetic heterogeneity. SRS is the only disease entity associated with (epi)genetic abnormalities of 2 different chromosomes: 7 and 11. In SRS, the 2 most frequent molecular abnormalities are hypomethylation (loss of methylation) of region H19/IGF2:IG-DMR on chromosome 11p15.5 (11p15 LOM) and maternal uniparental disomy of chromosome 7 (upd(7)mat). Therapy with recombinant human growth hormone (rhGH) is implemented to increase body height in children with SRS. The effect of the administered rhGH on height, weight, body mass index (BMI), body composition, and height velocity in patients with SRS during 3 years of rhGH therapy was analysed. MATERIAL AND METHODS 31 SRS patients (23 with 11p15 LOM, 8 with upd(7)mat) and 16 patients small for gestational age (SGA) as a control group were diagnosed and followed up in The Children's Memorial Health Institute. Patients were eligible for the 2 Polish rhGH treatment programmes [for patients with SGA or with growth hormone deficiency (GHD)]. Anthropometric parameters were collected in all patients. Body composition using bioelectrical impedance was measured in 13 SRS and 14 SGA patients. RESULTS Height, weight, and weight for height (SDS) at baseline of rhGH therapy were lower in SRS patients than in the SGA control group: -3.3 ± 1.2 vs. -2.6 ± 06 (p = 0.012), -2.5 vs. -1.9 (p = 0.037), -1.7 vs. -1.1 (p = 0.038), respectively. Height SDS was increased from -3.3 ± 1.2 to -1.8 ± 1.0 and from -2.6 ± 0.6 to -1.3 ± 0.7 in the SRS and SGA groups, respectively. Patients with 11p15 LOM and upd(7) mat achieved similar height, 127.0 ± 15.7 vs. 128.9 ± 21.6 cm, and -2.0 ± 1.3 vs. -1.7 ± 1.0 SDS, respectively. Fat mass percentage decreased in SRS patients from 4.2% to 3.0% (p < 0.05) and in SGA patients from 7.6% to 6.6% (p < 0.05). CONCLUSIONS Growth hormone therapy has a positive influence on the growth of SRS patients. Regardless of molecular abnormality type (11p15 LOM vs. upd(7)mat), height velocity was similar in SRS patients during 3 years of rhGH therapy.
Pharyngeal Communities and Antimicrobial Resistance in Pangolins in Gabon

There is an ongoing debate if pangolins are a relevant reservoir for viruses such as SARS-CoV-2. Here, we wanted to know if African pangolins are colonized with bacteria that are relevant for human health. ABSTRACT Wildlife can be a reservoir and source of zoonotic pathogens for humans. For instance, pangolins were considered one of the potential animal reservoirs of SARS-CoV-2. The aim of this study was to assess the prevalence of antimicrobial-resistant species (e.g., extended-spectrum β-lactamase [ESBL]-producing Enterobacterales) and Staphylococcus aureus-related complex and to describe the bacterial community in wild Gabonese pangolins. The pharyngeal colonization of pangolins sold in Gabon (n = 89, 2021 to 2022) was analyzed using culture media selective for ESBL-producing Enterobacterales, S. aureus-related complex, Gram-positive bacteria and nonfermenters. Phylogenetic analyses of ESBL-producing Enterobacterales was done using core-genome multilocus sequence typing (cgMLST) and compared with publicly available genomes. Patterns of cooccurring species were detected by network analysis. Of the 439 bacterial isolates, the majority of species belonged to the genus Pseudomonas (n = 170), followed by Stenotrophomonas (n = 113) and Achromobacter (n = 37). Three Klebsiella pneumoniae isolates and one Escherichia coli isolate were ESBL-producers, which clustered with human isolates from Nigeria (MLST sequence type 1788 [ST1788]) and Gabon (ST38), respectively. Network analysis revealed a frequent cooccurrence of Stenotrophomonas maltophilia with Pseudomonas putida and Pseudomonas aeruginosa. In conclusion, pangolins can be colonized with human-related ESBL-producing K. pneumoniae and E. coli. Unlike in other African wildlife, S. aureus-related complex was not detected in pangolins. IMPORTANCE There is an ongoing debate if pangolins are a relevant reservoir for viruses such as SARS-CoV-2. Here, we wanted to know if African pangolins are colonized with bacteria that are relevant for human health. A wildlife reservoir of antimicrobial resistance would be of medical relevance in regions were consumption of so-called bushmeat is common. In 89 pangolins, we found three ESBL-producing Klebsiella pneumoniae strains and one ESBL-producing Escherichia coli strains, which were closely related to isolates from humans in Africa. This points toward either a transmission between pangolins and humans or a common source from which both humans and pangolins became colonized.
Patient-controlled analgesia for the management of adults with acute trauma in the emergency department: A systematic review and meta-analysis

In this systematic review, PCA use for trauma in the ED was not found to result in significant improvement in pain relief or patient satisfaction, but available evidence is of low quality. #Patientcontrolledanalgesia #analgesia #acutetraumaticpain BACKGROUND Patient-controlled analgesia (PCA) has potential as a form of analgesia for trauma patients in the emergency department (ED). The objective of this review was to evaluate the effectiveness and safety of PCA for the management of adults with acute traumatic pain in the ED. The hypothesis was that PCA can effectively treat acute trauma pain in adults in the ED, with minimal adverse outcomes and better patient satisfaction compared with non-PCA modalities. METHODS MEDLINE (PubMed), Embase, SCOPUS, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception date to December 13, 2022. Randomized controlled trials involving adults presenting to the ED with acute traumatic pain who received intravenous (IV) analgesia via PCA compared with other modalities were included. The Cochrane Risk of Bias tool and the Grading of Recommendation, Assessment, Development, and Evaluation approach were used to assess the quality of included studies. RESULTS A total of 1,368 publications were screened, with 3 studies involving 382 patients meeting the eligibility criteria. All three studies compared PCA IV morphine with clinician-titrated IV morphine boluses. For the primary outcome of pain relief, the pooled estimate was in favor of PCA with a standard mean difference of −0.36 (95% confidence interval, −0.87 to 0.16). There were mixed results concerning patient satisfaction. Adverse event rates were low overall. The evidence from all three studies was graded as low-quality because of a high risk of bias from lack of blinding. CONCLUSION This study did not demonstrate a significant improvement in pain relief or patient satisfaction using PCA for trauma in the ED. Clinicians wishing to use PCA to treat acute trauma pain in adult patients in the ED are advised to consider the available resources in their own practice settings and to implement protocols for monitoring and responding to potential adverse events. LEVEL OF EVIDENCE Systematic Review/Meta-Analyses; Level III.
An assessment of the safety, hemostatic efficacy, and clinical impact of low-titer group O whole blood in children and adolescents

A retrospective observational study that demonstrated that non-leukoreduced Type O whole blood (LTOWB) could be safely used in a pediatric patient population. We also found increased survival in those receiving LTOWB when compared to those receiving component therapy alone. BACKGROUND Low-titer group O whole blood (LTOWB) use has been associated with improved survival and less blood transfusions in adult trauma patients. Its use in pediatric trauma has been shown to be safe when using leukoreduced, LTOWB with anti-A, anti-B antibody titers of <1:50. We set out to evaluate the safety, hemostatic potential, and impact on pediatric outcomes at a center using non-leukoreduced, LTOWB with anti-A, anti-B antibody titers of <1:200. METHODS Patients younger than 18 years, who received emergency-release, uncrossed matched blood, and presented to our trauma center from November 2017 to April 2021 were included. Patients were divided into those receiving any LTOWB and those receiving only RBC and or plasma (COMP). Primary outcome was 30-day survival. RESULTS One hundred sixty-four patients received emergency release blood products. Of these, 73 received at least one unit of LTOWB. The LTOWB group were younger (14 years vs. 13 years), more likely to be male (87% vs. 49%), and to have sustained penetrating trauma (44% vs. 23%); all p < 0.05. Low-titer group O whole blood patients received more blood than their COMP counterparts prior to arrival. Serial hemolysis panels (K+, bilirubin, LDH, haptoglobin) obtained at 24 hours, 48 hours, and 72 hours were similar between groups; all p > 0.05. There was no difference in survival by univariate analysis but after adjusting for inverse probability of treatment weights there was an observed association between WB administration and improved survival, with an odds ratio of 2.48 (1.15–5.47). CONCLUSION Non-leukoreduced, LTOWB in anti-A/anti-B antibody titers of <1:200 appear safe in children and adolescents. While patients receiving LTOWB had more evidence of shock, higher torso injury severity, and received more prehospital blood products, there may be a mortality benefit with whole blood. Larger, multicenter studies are needed. LEVEL OF EVIDENCE Therapeutic/Care Management; Level IV.
A glimpse into Long COVID characteristics and the mental health impact within a highly vaccinated population: a Malta observational study.

BACKGROUND Post-acute COVID-19 consequences are gaining global recognition. This study explores Long COVID characteristics and associated mental health impact/s among the highly vaccinated adult population of Malta. METHODS A social media survey gathered demographics, vaccination, and COVID-19 data. Generalised Anxiety Disorder and Patient Health Questionnaire-9 assessment tools were used for anxiety and depression. Quantitative analyses were performed. RESULTS 41% reported Long COVID, mostly female, 30-39 years, absence of chronic disease/s and vaccinated. Shortness of breath commonest persistent symptom among males, and fatigue for females. Significantly higher depression scores were present in Long COVID cohort compared to no persistent symptoms (p=0.001) and never acquiring COVID-19 (p=<0.01). A significant higher anxiety scores was present for Long COVID cohort than never acquiring COVID-19 (p=<0.01). CONCLUSIONS Long COVID occurs even in healthy individuals and vaccinated, while exacerbating mental health burdens. Urgent action is required to manage Long COVID and preventing the sequela.
Correction to: Comparative analysis of 3 pollen sterilization methods for feeding bumble bees

Pollen is an essential component of bee diets, and rearing bumble bees (Bombus spp.) for commercial use necessitates feeding pollen in mass quantities. This pollen is collected from honey bee (Apis mellifera L.) colonies because neither an artificial diet nor an economical, large-scale pollen collection process from flowers is available. The provenance of honey bee-collected pollen is often unknown, and in some cases has crossed international borders. Both deformed wing virus (DWV) and the fungal pathogen Ascosphaera apis (Claussen) Olive & Spiltoir (cause of chalkbrood disease); occur in honey bee-collected pollen, and infections have been observed in bumble bees. We used these pathogens as general surrogates for viruses and spore-forming fungal diseases to test the efficacy of 3 sterilization methods, and assessed whether treatment altered pollen quality for the bumble bee. Using honey bee-collected pollen spiked with known doses of DWV and A. apis, we compared gamma irradiation (GI), ozone fumigation (OZ), and ethylene oxide fumigation (EO) against an untreated positive control and a negative control. Following sterilization treatments, we tested A. apis spore viability, detected viral presence with PCR, and tested palatability to the bumble bee Bombus impatiens Cresson. We also measured bacterial growth from pollens treated with EO and GI. GI and EO outperformed OZ treatment in pathogen suppression. EO had the highest sterilizing properties under commercial conditions and retained palatability and supported bee development better than other treatments. These results suggest that EO sterilization reduces pathogen risks while retaining pollen quality as a food source for rearing bumble bees. Graphical Abstract
Optimization of Extracellular Vesicle Release for Targeted Drug Delivery

Targeted drug delivery is a promising approach for many serious diseases, such as glioblastoma multiforme, one of the most common and devastating brain tumor. In this context, this work addresses the optimization of the controlled release of drugs which are carried by extracellular vesicles. Towards this goal, we derive and numerically verify an analytical solution for the end-to-end system model. We then apply the analytical solution either to reduce the disease treatment time or to reduce the amount of required drugs. The latter is formulated as a bilevel optimization problem, whose quasiconvex/quasiconcave property is proved here. For solving the optimization problem, we propose and utilize a combination of bisection method and golden-section search. The numerical results demonstrate that the optimization can significantly reduce the treatment time and/or the required drugs carried by extracellular vesicles for a therapy compared to the steady state solution.
Cardiac Magnetic Resonance in Systemic Sclerosis

Poster: "ECR 2012 / C-2507 / Cardiac Magnetic Resonance in Systemic Sclerosis" by: "C. Napolitano1, V. Semeraro1, R. Marano2, A. Meduri2, B. Merlino2, L. Bonomo2; 1Roma/IT, 2Rome/IT"
Alteration in resting‐state effective connectivity within the Papez circuit in Presbycusis

Previous studies have suggested that the Papez circuit may be involved in the cognitive impairment observed after hearing loss in presbycusis patients, yet relatively little is known about the pattern of changes in effective connectivity within the circuit. The aim of this study was to investigate abnormal alterations in resting‐state effective connectivity within the Papez circuit and their association with cognitive decline in presbycusis patients. The spectral dynamic causal modelling (spDCM) approach was used for resting‐state effective connectivity analysis in 61 presbycusis patients and 52 healthy controls (HCs) within the Papez circuit. The hippocampus (HPC), mamillary body (MB), anterior thalamic nuclei (ATN), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), entorhinal cortex (ERC), subiculum (Sub) and parahippocampal gyrus (PHG) were selected as the regions of interest (ROIs). The fully connected model difference in effective connectivity between the two groups was assessed, and the correlation between effective connectivity alteration and cognitive scale was analysed. We found that presbycusis patients demonstrated decreased effective connectivity from MB, PCC, and Sub to ACC relative to HCs, whereas higher effective connectivity strength was shown from HPC to MB, from ATN to PHG and from PHG to Sub. The effective connectivity from PHG to Sub was significantly negatively correlated with the complex figure test (CFT)‐delay score (rho = −0.259, p = 0.044). The results support and reinforce the role of abnormal effective connectivity within the Papez circuit in the pathophysiology of presbycusis‐related cognitive impairment and reveal its potential as a novel imaging marker.
SIRT3 Activator Honokiol Inhibits Th17 Cell Differentiation and Alleviates Colitis

Abstract Background Honokiol (HKL), a natural extract of the bark of the magnolia tree and an activator of the mitochondrial protein sirtuin-3 (SIRT3), has been proposed to possess anti-inflammatory effects. This study investigated the inhibitory effects of HKL on T helper (Th) 17 cell differentiation in colitis. Methods Serum and biopsies from 20 participants with ulcerative colitis (UC) and 18 healthy volunteers were collected for the test of serum cytokines, flow cytometry analysis (FACS), and relative messenger RNA (mRNA) levels of T cell subsets, as well as the expression of SIRT3 and phosphorylated signal transducer and activator of transcription/retinoic acid-related orphan nuclear receptor γt (p-STAT3/RORγt) signal pathway in colon tissues. In vitro, naïve clusters of differentiation (CD) 4 + T cells isolated from the mouse spleen differentiated to subsets including Th1, Th2, Th17, and regulatory T (Treg) cells. Peripheral blood monocytes (PBMCs) from healthy volunteers were induced to the polarization of Th17 cells. After HKL treatment, changes in T cell subsets, related cytokines, and transcription factors were measured. The dextran sulfate sodium (DSS)-induced colitis and interleukin (IL)-10-deficient mice were intraperitoneally injected with HKL. These experiments were conducted to study the effect of HKL on the development, cytokines, and expression of signaling pathway proteins in colitis. Results Patients with UC had higher serum IL-17 and a higher proportion of Th17 differentiation in blood compared with healthy participants; while IL-10 level and the proportion of Treg cells were lower. Higher relative mRNA levels of RORγt and a lower SIRT3 expression in colon tissues were observed. In vitro, HKL had little effect on the differentiation of naïve CD4+ T cells to Th1, Th2, or Treg cells, but it downregulated IL-17 levels and the Th17 cell ratio in CD4+ T cells from the mouse spleen and human PBMCs under Th17 polarization. Even with a STAT3 activator, HKL still significantly inhibited IL-17 levels. In DSS–induced colitis mice and IL-10 deficient mice treated with HKL, the length of the colon, weight loss, disease activity index, and histopathological scores were improved, IL-17 and IL-21 levels, and the proportion of Th17 cells were decreased. Sirtuin-3 expression was increased, whereas STAT3 phosphorylation and RORγt expression were inhibited in the colon tissue of mice after HKL treatment. Conclusions Our study demonstrated that HKL could partially protect against colitis by regulating Th17 differentiation through activating SIRT3, leading to inhibition of the STAT3/RORγt signaling pathway. These results provide new insights into the protective effects of HKL against colitis and may facilitate the research of new drugs for inflammatory bowel disease.
The peripheral endocannabinoid system and its association with biomarkers of inflammation in untreated patients with multiple sclerosis

The endocannabinoid system (ECS) has been found altered in patients with multiple sclerosis (MS). However, whether the ECS alteration is present in the early stage of MS remains unknown. First, we aimed to compare the ECS profile between newly diagnosed MS patients and healthy controls (HCs). Next, we explored the association of the ECS, biomarkers of inflammation, and clinical parameters in newly diagnosed MS patients.