Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased zinc levels facilitate phenotypic detection of ceftazidime-avibactam resistance in metallo-β-lactamase-producing Gram-negative bacteria

Ceftazidime-avibactam is one of the last resort antimicrobial agents for the treatment of carbapenem-resistant, Gram-negative bacteria. Metallo-β-lactamase-producing bacteria are considered to be ceftazidime-avibactam resistant. Here, we evaluated a semi-automated antimicrobial susceptibility testing system regarding its capability to detect phenotypic ceftazidime-avibactam resistance in 176 carbapenem-resistant, metallo-β-lactamase-producing Enterobacterales and Pseudomonas aeruginosa isolates. Nine clinical isolates displayed ceftazidime-avibactam susceptibility in the semi-automated system and six of these isolates were susceptible by broth microdilution, too. In all nine isolates, metallo-β-lactamase-mediated hydrolytic activity was demonstrated with the EDTA-modified carbapenemase inactivation method. As zinc is known to be an important co-factor for metallo-β-lactamase activity, test media of the semi-automated antimicrobial susceptibility testing system and broth microdilution were supplemented with zinc. Thereby, the detection of phenotypic resistance was improved in the semi-automated system and in broth microdilution. Currently, ceftazidime-avibactam is not approved as treatment option for infections by metallo-β-lactamase-producing, Gram-negative bacteria. In infections caused by carbapenem-resistant Gram-negatives, we therefore recommend to rule out the presence of metallo-β-lactamases with additional methods before initiating ceftazidime-avibactam treatment.
Inequalities for eigenfunctions of the $p$-Laplacian

Motivated by the work of P. Lindqvist, we study eigenfunctions of the one-dimensional $p$-Laplace operator, the $\sin_p$ functions, and prove several inequalities for these and $p$-analogues of other trigonometric functions and their inverse functions. Similar inequalities are given also for the $p$-analogues of the hyperbolic functions and their inverses.
Recovery of the physiological status in professional basketball players using NESA neuromodulation treatment during different types of microcycles in season: A preliminary randomized clinical trial

The purpose of the study was to describe and compare recovery status after official basketball competition in players who underwent NESA neuromodulation treatment (NNT) in weeks with one or two matches. The recovery parameters of 12 professional male basketball players (mean ± SD, age: 20.6 ± 2.7 yr; height: 197.8 ± 11.7 cm; and body mass: 89.0 ± 21.2 kg) that competed in the LEB Plata (Spanish third division) were monitored 2 days after match-play over 6 weeks, and included: 1) the Hooper Test, which combines four subjective variables (sleep, stress, fatigue and soreness); 2) common biochemical markers (e.g., testosterone, cortisol and ratio T:C); and 3) lowest heart rate [HR], average HR, HR variability, sleep duration, awake time during night and onset latency before asleep). Players that completed NNT presented differences compared to the control group in sleep data. For instance, the lowest HR (p < 0.001), average HR (p < 0.001) and total awake time (p = 0.04) were significantly reduced in the NNT group. On the contrary, the control group presented greater values than the NNT group in the subjective Hooper Test, although only stress presented significant differences (Control 2.5 ± 1.2 vs. NNT cost or 3.2 ± 0.9; p = 0.01). Additionally, there were no significant differences in recovery parameters between weeks with one or two matches. In conclusion, the results suggest that players that underwent NNT tended to improve their sleep quality. Nevertheless, player’s values in the biochemical markers and wellness status remained similar in both groups. The fact that no significant differences were found between weeks with one or two matches could help basketball professionals to determine that a congested schedule does not seem to negatively alter recovery status. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04939181? term=NCT04939181, NCT04939181
Fetal mesenchymal hamartoma of the liver: A case report and literature review

This paper reports the diagnosis and treatment process of a case of fetal mesenchymal hamartoma of the liver (MHL), and reviews the previous literature reports. At 38+2 weeks of gestation, prenatal ultrasound found a well bound mixed solid and cystic mass, which was located at the lower edge of the right lobe of the liver and in front of the right kidney of the fetus, but the source and nature of the mass were not clear by ultrasound. Due to the approaching due date, the fetus showed no other abnormal symptoms, and no special treatment was given with the consent of the family members. A female fetus was delivered weighing 3,520 g at 39 weeks. An exploratory laparotomy was performed on the eighth day after delivery. During the operation, it was found that the tumor originated from the fifth, sixth and seventh hepatic segment and the corresponding hepatic segments were removed. Recovery was uneventful and the infant was discharged on the 6th day after surgery. Follow-up at 2 years showed a thriving young girl, and there was no tumor recurrence.
Metabolic and hormonal changes after laparoscopic sleeve gastrectomy in pediatric population: An observational study

Introduction Despite the growing popularity of laparoscopic sleeve gastrectomy (SG) for managing severe obesity in children, adolescents, and adults, there is a paucity of studies reporting the effects of SG on metabolic and hormonal outcomes in pediatric populations. Methodology In this single-centre, retrospective study, we assessed nutritional biomarkers (hemoglobin, ferritin, iron profile, Vitamin B12, Vitamin D, and calcium), glucose homeostasis indicators (C-peptide, HbA1C, and random blood glucose), blood lipids (triglycerides and cholesterol components), hormones involved in the hypothalamic-pituitary-adrenal axis (cortisol and adrenocorticotropic hormone), and thyroid hormones (T3, T4, thyroid-stimulating hormone, and parathyroid hormone) preoperatively and 12-month after SG in children aged 5–15 years. Results This study included 64 adolescents (mean age = 11.2 ± 2.3 years) who underwent laparoscopic SG. Significant reduction in circulatory C-peptide (−62.1%; p = 0.005), HbA1C (−10.9%; p = 0.001), random blood glucose (−15.4%; p = 0.036), and triglycerides (−39.4%; p = 0.003) were observed postoperatively at 12 months compared to baseline. Although we did not observe any changes in cortisol levels, adrenocorticotropic hormone levels declined significantly by −40.9% postoperatively (p = 0.033). However, cholesterol components, thyroid hormones, and nutritional biomarkers remained unchanged from baseline. Conclusions Consistent with prior literature, our study demonstrates improvement or resolution of diabetes and hypertriglyceridemia in the year following SG. However, given that blood cholesterol components, nutritional biomarkers, and thyroid profiles remained unchanged warrants long-term monitoring of nutritional, metabolic, and endocrine factors in adolescents undergoing laparoscopic SG. To the best of our knowledge, this is the first study reporting the effects of SG on thyroid and hypothalamic-pituitary-adrenal axis hormones in pediatric populations.
Online taxi users' optimistic bias: China youths' digital travel and information privacy protection

Digital travel platforms not only provided people with convenient travel but also raised a series of problems regarding information privacy protection. In order to analyze privacy protection behavior, this study surveyed 441 subjects aged 18–35 who utilized digital travel platforms based on a structural model of protective motivation theory. The results indicated that a perceived threat, self-efficacy, and response efficacy positively and significantly impacted youths' privacy concerns. Furthermore, privacy concerns were positively related to privacy protection behavior and were an intermediate variable between the relationships among perceived threat, self-efficacy, response efficacy, and privacy protection behavior. This study identified the moderating effect of youths' knowledge of platform privacy settings on the relationship between privacy concerns and protection behavior. In addition, the results confirmed that an optimistic bias did exist among talented youth with high privacy knowledge in terms of a practical level of privacy management. These unique findings represent the exceptional contributions and innovation points of this study.
An EGFR L858R mutation identified in 1862 Chinese NSCLC patients can be a promising neoantigen vaccine therapeutic strategy

Background This study aimed to develop a vaccine that targets mutation-derived neoantigen in Chinese non-small-cell lung cancer (NSCLC). Methods A cohort of 1862 Chinese NSCLC patients who underwent targeted sequencing with a 1021-gene panel was investigated. HLA typing was done using OptiType v1.0 and neoantigens were predicted by netMHCpan v4.0. HLA LOH was inferred using the lohhla algorithm and TMB were quantified by counting the total number of non-synonymous ones based on our panel data. CIBERSORT was utilized to estimate the TME in different EGFR mutant subtype by using TCGA data. Results HLA-A*11:01(42.59%) was the top one allele and HLA-A*33:03(12.94%) ranked 12th. EGFR L858R (22.61%) was the most prevalent gene variant. The binding affinity (IC50 MT = 22.9 nM) and shared frequency (2.93%) of EGFR L858R in combination with HLA-A*33:03 were optimal. In a subsequent further analysis on immunological features of EGFR mutant subtypes, 63.1% HLA loss of heterozygosity LOH (HLA LOH) and 0.37% (7 of 1862) B2M aberrations were found in our population, both had no significant association with EGFR mutant subtypes suggesting that the process of antigen presentation involved HLA LOH and B2M mechanisms in EGFR L858R is working. Tumor mutation burden (TMB) was investigated by utilizing our panel and showed that EGFR L858R had the lowest TMB compared with other EGFR mutant subtypes. In addition, analysis of 22 immune cell types from The Cancer Genome Atlas (TCGA) data showed EGFR L858R was correlated with low level of CD8 T cells, activated CD4 memory T cells and elevated level of macrophage M2 suggesting an inhibited tumor microenvironment (TME). Conclusion Our study identified that EGFR L858R neoantigen had the potential to generate cancer vaccines in NSCLC patients with HLA A*33:03. The neoantigen-based vaccines may become an effective salvage regimen for EGFR L858R subgroup after targeted therapy or immune checkpoint inhibitors (ICIs) failure.
Inflamed adipose tissue: A culprit underlying obesity and heart failure with preserved ejection fraction

The incidence of heart failure with preserved ejection fraction is increasing in patients with obesity, diabetes, hypertension, and in the aging population. However, there is a lack of adequate clinical treatment. Patients with obesity-related heart failure with preserved ejection fraction display unique pathophysiological and phenotypic characteristics, suggesting that obesity could be one of its specific phenotypes. There has been an increasing recognition that overnutrition in obesity causes adipose tissue expansion and local and systemic inflammation, which consequently exacerbates cardiac remodeling and leads to the development of obese heart failure with preserved ejection fraction. Furthermore, overnutrition leads to cellular metabolic reprogramming and activates inflammatory signaling cascades in various cardiac cells, thereby promoting maladaptive cardiac remodeling. Growing evidence indicates that the innate immune response pathway from the NLRP3 inflammasome, to interleukin-1 to interleukin-6, is involved in the generation of obesity-related systemic inflammation and heart failure with preserved ejection fraction. This review established the existence of obese heart failure with preserved ejection fraction based on structural and functional changes, elaborated the inflammation mechanisms of obese heart failure with preserved ejection fraction, proposed that NLRP3 inflammasome activation may play an important role in adiposity-induced inflammation, and summarized the potential therapeutic approaches.
Organizational democracy and meaningful work: The mediating role of employees corporate social responsibility perceptions

Meaningful work is an important field of research, relating to both organizational outcomes and employee welfare. Organizational democracy has been theoretically proposed as an important antecedent to meaningful work. Nevertheless, this relationship is yet to be empirically explored. Thus, the objective of the current research is to explore the relationship between organizational democracy and meaningful work. We used structural equation modeling with self-reported, cross-sectional data from different nations and industries to test a mediation model in which corporate social responsibility (CSR) perceptions mediate the positive relationship between organizational democracy and meaningful work. Our findings confirmed that CSR perceptions partially mediate in the relationship between organizational democracy and meaningful work. Thus, based on our findings we can conclude that organizational democracy can play a direct role in increasing the experience of meaningful work, but also an indirect role trough the employees experience of CSR. Our findings have theoretical implications by adding to the classical theoretical literature that connect organizational democracy and meaningful work, and by disentangling the role of CSR perceptions in this relationship. Moreover, our findings have practical implications as our results give important knowledge to managers and organizational stakeholders that wish to increase the experience of meaningful work in organizations.
Shifting sensitivity of septoria tritici blotch compromises field performance and yield of main fungicides in Europe

Septoria tritici blotch (STB; Zymoseptoria tritici) is a severe leaf disease on wheat in Northern Europe. Fungicide resistance in the populations of Z. tritici is increasingly challenging future control options. Twenty-five field trials were carried out in nine countries across Europe from 2019 to 2021 to investigate the efficacy of specific DMI and SDHI fungicides against STB. During the test period, two single DMIs (prothioconazole and mefentrifluconazole) and four different SDHIs (fluxapyroxad, bixafen, benzovindiflupyr and fluopyram) along with different co-formulations of DMIs and SDHIs applied at flag leaf emergence were tested. Across all countries, significant differences in azole performances against STB were seen; prothioconazole was outperformed in all countries by mefentrifluconazole. The effects also varied substantially between the SDHIs, with fluxapyroxad providing the best efficacy overall, while the performance of fluopyram was inferior to other SDHIs. In Ireland and the UK, the efficacy of SDHIs was significantly lower compared with results from continental Europe. This reduction in performances from both DMIs and SDHIs was reflected in yield responses and also linked to decreased sensitivity of Z. tritici isolates measured as EC50 values. A clear and significant gradient in EC50 values was seen across Europe. The lower sensitivity to SDHIs in Ireland and the UK was coincident with the prevalence of SDH-C-alterations T79N, N86S, and sporadically of H152R. The isolates’ sensitivity to SDHIs showed a clear cross-resistance between fluxapyroxad, bixafen, benzovindiflupyr and fluopyram, although the links with the latter were less apparent. Co-formulations of DMIs + SDHIs performed well in all trials conducted in 2021. Only minor differences were seen between fluxapyroxad + mefentrifluconazole and bixafen + fluopyram + prothioconazole; the combination of benzovindiflupyr + prothioconazole gave an inferior performance at some sites. Fenpicoxamid performed in line with the most effective co-formulations. This investigation shows a clear link between reduced field efficacy by solo SDHIs as a result of increasing problems with sensitivity shifting and the selection of several SDH-C mutations. The presented data stress the need to practice anti-resistance strategies to delay further erosion of fungicide efficacy.
In vitro antimicrobial activity and resistance mechanisms of the new generation tetracycline agents, eravacycline, omadacycline, and tigecycline against clinical Staphylococcus aureus isolates

In this study, we investigated the in vitro activity and resistance mechanisms of the new generation tetracycline agents, namely eravacycline, omadacycline, and tigecycline, against Staphylococcus aureus isolates. A total of 1,017 non-duplicate S. aureus isolates were collected and subjected to susceptibility testing against eravacycline, omadacycline, and tigecycline using the broth microdilution method. Tetracyclines-resistant (eravacycline/omadacycline/tigecycline-resistant) isolates were selected to elucidate the resistance mechanisms using polymerase chain reaction (PCR), cloning experiment, efflux pump inhibition, and quantitative real-time PCR. The results of the antibacterial susceptibility testing showed that compared with omadacycline, eravacycline and tigecycline had superior antibacterial activity against S. aureus isolates. Among 1,017 S. aureus, 41 tetracyclines-resistant isolates were identified. These resistant isolates possessed at least one tetracycline resistance gene and genetic mutation in the MepRAB efflux pump and 30S ribosome units. A frameshift mutation in mepB was detected in most tetracyclines-resistant strains (except for JP3349) compared with tetracyclines-susceptible (eravacycline/omadacycline/tigecycline-susceptible) strains. This was first shown to decrease susceptibility to omadacycline, but not to eravacycline and tigecycline. After treatment with eravacycline, omadacycline or tigecycline, overexpression of mepA, tet38, tet(K) and tet(L) was detected. Moreover, multi-locus sequence typing showed a major clonal dissemination type, ST5, and its variant ST764 were seen in most tetracyclines-resistant strains. To conclude, eravacycline and tigecycline exhibited better activity against S. aureus including tetracycline-resistant isolates than omadacycline. The resistance to these new generation tetracyclines due to an accumulation of many resistance mechanisms.
Binge drinking indirectly predicts a negative emotional memory bias through coping motivations and depressive symptoms: The role of sex/gender

Background In this three-part study, we investigate whether the associations between binge and problematic drinking patterns with a negative emotional memory bias (NMB) are indirectly related through coping motivations and depressive symptoms. We also address potential sex differences in these relations. Methods Participants (N = 293) completed the Timeline Followback to assess binge drinking, the Alcohol Use Disorder Identification Test (AUDIT) to assess problematic alcohol use, the Drinking Motives Questionnaire-Revised to assess coping motivations, and the Depression, Anxiety, and Stress Scales-21 to assess depression. Participants were asked to identify whether 30 emotional sentences were self-referent or not in an incidental encoding task; 24 h later they were asked to recall as many sentences as possible and a negative memory bias score was calculated. Results Across all three studies, we found significant bivariate relations between AUDIT scores, coping, depression, and an NMB, particularly for sentences participants deemed self-referent. In two undergraduate samples, there were significant indirect effects through coping motivations and depressive symptoms between binge drinking and an NMB in females as well as between AUDIT scores and an NMB in females only. In the community sample, there was only an indirect effect through coping motives, but this was observed in both females and males. Conclusion These findings support a relation between binge drinking as well as problematic alcohol use and a self-referent NMB in the context of coping motivations for alcohol use and depressive symptoms. Moreover, the pattern of findings suggests this model primarily holds for females, yet may also apply to males at higher levels of problematic alcohol use.
Conserved longitudinal alterations of anti-S-protein IgG subclasses in disease progression in initial ancestral Wuhan and vaccine breakthrough Delta infections

Introduction COVID-19 has a wide disease spectrum ranging from asymptomatic to severe. While humoral immune responses are critical in preventing infection, the immune mechanisms leading to severe disease, and the identification of biomarkers of disease progression and/or resolution of the infection remains to be determined. Methods Plasma samples were obtained from infections during the initial wave of ancestral wildtype SARS-CoV-2 and from vaccine breakthrough infections during the wave of Delta variant, up to six months post infection. The spike-specific antibody profiles were compared across different severity groups and timepoints. Results We found an association between spike-specific IgM, IgA and IgG and disease severity in unvaccinated infected individuals. In addition to strong IgG1 and IgG3 response, patients with severe disease develop a robust IgG2 and IgG4 response. A comparison of the ratio of IgG1 and IgG3 to IgG2 and IgG4 showed that disease progression is associated with a smaller ratio in both the initial wave of WT and the vaccine breakthrough Delta infections. Time-course analysis revealed that smaller (IgG1 and IgG3)/(IgG2 and IgG4) ratio is associated with disease progression, while the reverse associates with clinical recovery. Discussion While each IgG subclass is associated with disease severity, the balance within the four IgG subclasses may affect disease outcome. Acute disease progression or infection resolution is associated with a specific immunological phenotype that is conserved in both the initial wave of WT and the vaccine breakthrough Delta infections.
Smart triage: Development of a rapid pediatric triage algorithm for use in low-and-middle income countries

Introduction Early and accurate recognition of children at risk of progressing to critical illness could contribute to improved patient outcomes and resource allocation. In resource limited settings digital triage tools can support decision making and improve healthcare delivery. We developed a model for rapid identification of critically ill children at triage. Methods This was a prospective cohort study of acutely ill children presenting at Jinja Regional Referral Hospital in Eastern Uganda. Variables collected in the emergency department informed the development of a logistic model based on hospital admission using bootstrap stepwise regression. Low and high-risk thresholds for 90% minimum sensitivity and specificity, respectively generated three risk level categories. Performance was assessed using receiver operating characteristic curve analysis on a held-out test set generated by an 80:20 split with 10-fold cross validation. A risk stratification table informed clinical interpretation. Results The model derivation cohort included 1,612 participants, with an admission rate of approximately 23%. The majority of admitted patients were under five years old and presenting with sepsis, malaria, or pneumonia. A 9-predictor triage model was derived: logit (p) = −32.888 + (0.252, square root of age) + (0.016, heart rate) + (0.819, temperature) + (−0.022, mid-upper arm circumference) + (0.048 transformed oxygen saturation) + (1.793, parent concern) + (1.012, difficulty breathing) + (1.814, oedema) + (1.506, pallor). The model afforded good discrimination, calibration, and risk stratification at the selected thresholds of 8% and 40%. Conclusion In a low income, pediatric population, we developed a nine variable triage model with high sensitivity and specificity to predict who should be admitted. The triage model can be integrated into any digital platform and used with minimal training to guide rapid identification of critically ill children at first contact. External validation and clinical implementation are in progress.