Miracle-dz/UniFAR-FTUs huggingface dataset:
RB1 gene mutations and genetic spectrum in retinoblastoma cases

The aim of the study was to investigate the frequency and types of mutations on the retinoblastoma gene (RB1 gene) in Turkish population. RB1 gene mutation analysis was performed in a total of 219 individuals (122 probands with retinoblastoma, 14 family members with retinoblastoma and 83 clinically healthy family members). All 27 exons and close intronic regions of the RB1 gene were sequenced for small deletions and insertions using both the Sanger sequencing or NGS methods, and the large deletions and duplications were investigated using the MLPA analysis and CNV algorithm. The bilateral/trilateral retinoblastoma rate was 66% in the study population. The general frequency of RB1 gene mutation in the germline of the patients with retinoblastoma was 41.9%. Approximately 51.5% of the patients were diagnosed earlier than 12 months old, and de novo mutation was found in 32.4% of the patients. Germline small genetic rearrangement mutations were detected in 78.9% of patients and LGRs were detected in 21.1% of patients. An association was detected between the eye color of the RB patients and RB1 mutations. 8 of the mutations detected in the RB1 gene were novel in the study.
A transdisciplinary approach for modelling macroinvertebrate habitats in lowland streams.

Manifold anthropogenic influences are the main cause of river habitat degradation and extensive regeneration needs to be conducted to achieve the aims of the Water Framework Directive in Europe. As the outcome of river and stream rehabilitation measures is sometimes difficult to foresee, a GIS-based approach consisting of an eco-hydrologic, a hydraulic and a GIS mapping submodel is suggested for creating an integrated catchment and an in-stream modelling system to dynamically depict the influence of abiotic changes on the habitat quality. The Driver―Pressure―State―Impact―(Response) concept is utilised to depict the complex cause―effect chain of hydromorphological changes on macroinvertebrate habitats in lowland streams. A first application of the three submodels has been conducted in the North German Kielstau catchment and first results of modelling and mapping the impact on selected habitat parameters are displayed. Further work needs to be done in linking the submodels and in assessing the impact of the altered state on the macroinvertebrate fauna by parameter functions derived from a knowledge-based database and sampling schemes.
Bright light treatment counteracts stress-induced sleep alterations in mice, via a visual circuit related to the rostromedial tegmental nucleus

Light in the environment greatly impacts a variety of brain functions, including sleep. Clinical evidence suggests that bright light treatment has a beneficial effect on stress–related diseases. Although stress can alter sleep patterns, the effect of bright light treatment on stress–induced sleep alterations and the underlying mechanism are poorly understood. Here, we show that bright light treatment reduces the increase in nonrapid eye movement (NREM) sleep induced by chronic stress through a di–synaptic visual circuit consisting of the thalamic ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), lateral habenula (LHb), and rostromedial tegmental nucleus (RMTg). Specifically, chronic stress causes a marked increase in NREM sleep duration and a complementary decrease in wakefulness time in mice. Specific activation of RMTg–projecting LHb neurons or activation of RMTg neurons receiving direct LHb inputs mimics the effects of chronic stress on sleep patterns, while inhibition of RMTg–projecting LHb neurons or RMTg neurons receiving direct LHb inputs reduces the NREM sleep–promoting effects of chronic stress. Importantly, we demonstrate that bright light treatment reduces the NREM sleep–promoting effects of chronic stress through the vLGN/IGL–LHb–RMTg pathway. Together, our results provide a circuit mechanism underlying the effects of bright light treatment on sleep alterations induced by chronic stress.
Inhibitory checkpoint molecule mRNA expression in canine soft tissue sarcoma

Canine soft tissue sarcomas (STS) are common neoplasms and considered immune deserts. Tumour infiltrating lymphocytes are sparse in STS and, when present, tend to organize around blood vessels or at the periphery of the neoplasm. This pattern is associated with an immunosuppressive tumour microenvironment linked to overexpression of molecules of the PD-axis. PD-1, PD-L1 and PD-L2 expression correlates with malignancy and poor prognosis in other neoplasms in humans and dogs, but little is known about their role in canine STS, their relationship to tumour grade, and how different therapies affect expression. The objective of this study was to evaluate the expression of checkpoint molecules across STS tumour grades and after tumour ablation treatment. Gene expression analysis was performed by reverse-transcriptase real-time quantitative PCR in soft tissue sarcomas that underwent histotripsy and from histologic specimens of STS from the Virginia Tech Animal Laboratory Services archives. The expression of PD-1, PD-L1 and PD-L2 was detected in untreated STS tissue representing grades 1, 2, and 3. Numerically decreased expression of all markers was observed in tissue sampled from the treatment interface relative to untreated areas of the tumour. The relatively lower expression of these checkpoint molecules at the periphery of the treated area may be related to liquefactive necrosis induced by the histotripsy treatment, and would potentially allow TILs to infiltrate the tumour. Relative increases of these checkpoint molecules in tumours of a higher grade and alongside immune cell infiltration are consistent with previous reports that associate their expression with malignancy.
Real-world impact and effectiveness of MenACWY-TT

ABSTRACT In response to escalating cases of serogroup W (MenW) invasive meningococcal disease (IMD), multiple countries introduced quadrivalent conjugate MenACWY vaccines into their national immunization programs (NIPs). Here, we summarize the real-world impact and vaccine effectiveness (VE) data of MenACWY-TT from Chile, England, the Netherlands, and Australia. Incidence rate reductions (IRRs) and VE from baseline to post-NIP period were extracted from publications or calculated. After the administration of a single dose of MenACWY-TT, substantial IRRs of MenCWY were observed across the countries in vaccine-eligible age groups (83%-85%) and via indirect protection in non-vaccine-eligible age groups (45%-53%). The impact of MenACWY-TT was primarily driven by MenW IRRs, as seen in vaccine-eligible age groups (65%-92%) and non-vaccine-eligible age groups (41%-57%). VE against MenW was reported in vaccine-eligible toddlers (92%) in the Netherlands and in vaccine-eligible adolescents/young adults (94%) in England. These real-world data support the implementation and continued use of MenACWY-TT in NIPs.
Predictors of missed HIV screening opportunities among newly diagnosed individuals at an urban medical center in New York City, 2018–2022

Objective To identify demographic and clinical factors predictive of having a missed opportunity (MO) for HIV screening. Design Retrospective cohort study. Methods Electronic medical records were queried for individuals newly diagnosed with HIV in different sites within a large urban academic medical center in New York City between 2018 and 2022. The primary outcome was having one or more MO for HIV screening within the institution, defined as any encounter at which screening was not performed in the 365 days preceding the HIV diagnosis. Results Over one third of new diagnoses had at least one MO in the preceding year. Older individuals, cisgender women and those assigned female sex at birth, and heterosexual individuals were more likely to have at least one MO. An initial CD4 < 200 cells/ul was more likely among men who have sex with women specifically. Most MOs occurred in the emergency department and outpatient settings, with minimal HIV prevention discussions documented during each MO. Conclusions These findings suggest that populations perceived to be at lower risk for HIV are more likely to have MOs and possibly late diagnoses, and that universal HIV screening must be implemented into the workflows of emergency department and outpatient settings to facilitate early diagnosis and reduce the incidence of HIV.
Increased blood pressure after nonsevere COVID-19

Background: Various sequelae have been described after nonsevere coronavirus disease 2019 (COVID-19), but knowledge on postacute effects on blood pressure is limited. Methods: This is a cross-sectional analysis of blood pressure profiles in individuals after nonsevere COVID-19 compared with matched population-based individuals without prior COVID-19. Data were derived from the ongoing and prospective Hamburg City Health Study, a population-based study in Hamburg, Germany, and its associated COVID-19 program, which included individuals at least 4 months after COVID-19. Matching was performed by age, sex, education, and preexisting hypertension in a 1 : 4 ratio. Results: Four hundred and thirty-two individuals after COVID-19 (mean age 56.1 years) were matched to 1728 controls without prior COVID-19 (56.2 years). About 92.8% of COVID-19 courses were mild or moderate, only 7.2% were hospitalized, and no individual had been treated on an intensive care unit. Even after adjustment for relevant competing risk factors, DBP [+4.7 mmHg, 95% confidence interval (95% CI) 3.97–5.7, P < 0.001] was significantly higher in individuals after COVID-19. For SBP, a trend towards increased values was observed (+1.4 mmHg, 95% CI -0.4 to 3.2, P = 0.120). Hypertensive blood pressures at least 130/80 mmHg (according to the ACC/AHA guideline) and at least 140/90 mmHg (ESC/ESH guideline) occurred significantly more often in individuals after COVID-19 than matched controls (odds ratio 2.0, 95% CI 1.5–2.7, P < 0.001 and odds ratio 1.6, 95% CI 1.3–2.0, P < 0.001, respectively), mainly driven by changes in DBP. Conclusion: Blood pressure is higher in individuals after nonsevere COVID-19 compared with uninfected individuals suggesting a significant hypertensive sequela.
The Impact of Emotions on Habitual Inhibition

Abstract Emotional information prioritizes human behavior. How much emotions influence ongoing behavior critically depends on the extent of executive control functions in a given context. One form of executive control is based on stimulus–stop associations (i.e., habitual inhibition) that rapidly and effortlessly elicits control over the interruption of ongoing behavior. So far, no behavioral accounts have explored the emotional impact on habitual inhibition. We aimed to examine the emotional modulation on habitual inhibition and associated psycho-physiological changes. A go/no-go association task asked participants to learn stimulus–stop and stimulus–response associations during 10-day training to form habitual inhibition (without emotional interference). Probabilistic feedback guided learning with varying probabilities of congruent feedback, generating stronger versus weaker pairings. A reversal test measured habitual inhibition strength counteracted by emotional cues (high-arousal positive and negative stimuli compared with neutral ones). Our training protocol induced stable behavioral and psycho-physiological responses compatible with habitual behavior. At reversal, habitual inhibition was evident as marked by significant speed costs of reversed no-go trials for strongly associated stimuli. Positive and negative emotional cues produced larger impact on habitual inhibition. We report first evidence on a cognitive control mechanism that is vulnerable to emotional stimuli and suggest alternative explanations on how emotions may boost or counteract certain behavioral abnormalities mediated by habitual inhibition.
Acute Subjective Effects of Psychedelics within and Beyond WEIRD Contexts

ABSTRACT Reports of psychedelic experiences may contain similarities and differences across cultural contexts, but most current characterizations and quantifications of psychedelic experiences come from Western medical and naturalistic settings. In this article, we begin with a brief history of the diversity of psychedelic use in non-Western settings. We then compare and contrast accounts of psychedelic experiences within and beyond Western, educated, industrialized, rich, and democratic (WEIRD) contexts. We focus on specific reports of direct testimony of the acute subjective effects of psychedelics experienced across these contexts. We compare themes from each of these various contexts, with special emphasis on psychometric measures such as the mystical experiences questionnaire (MEQ), the five-dimensional altered states of consciousness (5D-ASC) scale, the Survey of God Encounters, and the Survey of Entity Encounters, the Challenging Experiences Questionnaire, and the Inventory of Nonordinary Experiences (INOE). Finally, we offer recommendations for future research to quantify these similarities and differences across cultures to assess them empirically in the future.
Comparison of survival analysis approaches to modelling age at first sex among youth in Kisesa Tanzania

Background Many studies analyze sexual and reproductive event data using descriptive life tables. Survival analysis has better power to estimate factors associated with age at first sex (AFS), but proportional hazards models may not be right model to use. This study used accelerated failure time (AFT) models, restricted Mean Survival time model (RMST) models, with semi and non-parametric methods to assess age at first sex (AFS), factors associated with AFS, and verify underlying assumptions for each analysis. Methods Self-reported sexual debut data was used from respondents 15–24 years in eight cross-sectional surveys between 1994–2016, and from adolescents’ survey in an observational community study (2019–2020) in northwest Tanzania. Median AFS was estimated in each survey using non-parametric and parametric models. Cox regression, AFT parametric models (exponential, gamma, generalized gamma, Gompertz, Weibull, log-normal and log-logistic), and RMST were used to estimate and identify factors associated with AFS. The models were compared using Akaike information criterion (AIC) and Bayesian information criterion (BIC), where lower values represent a better model fit. Results The results showed that in every survey, the Cox regression model had higher AIC and BIC compared to the other models. Overall, AFT had the best fit in every survey round. The estimated median AFS using the parametric and non-parametric methods were close. In the adolescent survey, log-logistic AFT showed that females and those attending secondary and higher education level had a longer time to first sex (Time ratio (TR) = 1.03; 95% CI: 1.01–1.06, TR = 1.05; 95% CI: 1.02–1.08, respectively) compared to males and those who reported not being in school. Cell phone ownership (TR = 0.94, 95% CI: 0.91–0.96), alcohol consumption (TR = 0.88; 95% CI: 0.84–0.93), and employed adolescents (TR = 0.95, 95% CI: 0.92–0.98) shortened time to first sex. Conclusion The AFT model is better than Cox PH model in estimating AFS among the young population.
Serum sclerostin level is positively associated with endothelial dysfunction measured by digital thermal monitoring in patients with type 2 diabetes: A prospective cross-sectional study

Sclerostin and dickkopf-1 (DKK1), extracellular inhibitors of the canonical Wnt/β-catenin signaling pathway, have been associated with vascular aging and atherosclerosis. This study aimed to assess the correlation of sclerostin and DKK1 concentrations with endothelial function measured using vascular reactivity index (VRI) in patients with type 2 diabetes mellitus (T2DM). Fasting blood samples were collected from 100 patients with T2DM. Endothelial function and VRI were measured using digital thermal monitoring and circulating sclerostin and DKK1 levels by enzyme-linked immunosorbent assays. VRI values < 1.0, 1.0–1.9, and > 2.0 indicated poor, intermediate, and good vascular reactivity, respectively. Overall, 30, 38, and 32 patients had poor, intermediate, and good vascular reactivity, respectively. Older age, higher serum glycated hemoglobulin, urinary albumin-to-creatinine ratio, and sclerostin as well as lower hypertension prevalence, systolic blood pressure, and diastolic blood pressure (DBP) were associated with poor VRI. Multivariable forward stepwise linear regression analysis showed that DBP (β = 0.294, adjusted R2 change = 0.098, P < .001), log-glycated hemoglobin (β = −0.235, adjusted R2 change = 0.050, P = .002), log-urine albumin-to-creatinine ratio (β = −0.342, adjusted R2 change = 0.227, P < .001), and log-sclerostin level (β = −0.327, adjusted R2 change = 0.101, P < .001) were independently associated with VRI. Serum sclerostin, along with glycated hemoglobin and albumin-to-creatinine ratio, exhibited a negative correlation with VRI, while DBP showed a positive correlation with VRI. These factors can independently predict endothelial dysfunction in patients with T2DM.
Assessment of drug-susceptible and multidrug-resistant tuberculosis (MDR-TB) in the Central Region of Somalia: A 3-year retrospective study

Background Multidrug-resistant tuberculosis (MDR-TB) remains a public health emergency and a threat globally. Although increasing MDR-TB cases have been recently reported in Somalia, limited information is known. This study aims to determine the prevalence of drug-susceptible and MDR-TB in suspected patients referred to the TB Department in Mudug Hospital, Galkayo, Somalia, and identify potential factors associated with MDR-TB. Methods A 3-year hospital laboratory-based retrospective study was conducted by manually reviewing laboratory records of Mycobacterium tuberculosis specimens and GeneXpert MTB/RIF results from January 2019 to December 2021 at the reference mycobacteria laboratory department in Mudug Hospital. Results A total of 714 positive GeneXpert-MTB results were identified: 619 (86.7%) were drug susceptible (no Rifampin resistance [RR] detected) and 95 (13.3%) with RR detected or defined as MDR-TB. Most of the MDR-TB patients were males (71.6%, 68/95) and between the ages of 15 to 24 (31.6%, 30/95). Most isolates were collected in 2021 (43.2%, 41/95). Multivariate analyses show no significant difference between patients having MDR-TB and/or drug-susceptible TB for all variables. Conclusion This study showed an alarming frequency of MDR-TB cases among M. tuberculosis-positive patients at a regional TB reference laboratory in central Somalia.
Minor Changes Change Memories: Functional Magnetic Resonance Imaging and Behavioral Reflections of Episodic Prediction Errors

Abstract Episodic memories can be modified, a process that is potentially driven by mnemonic prediction errors. In the present study, we used modified cues to induce prediction errors of different episodic relevance. Participants encoded episodes in the form of short toy stories and then returned for an fMRI session on the subsequent day. Here, participants were presented either original episodes or slightly modified versions thereof. Modifications consisted of replacing a single object within the episode and either challenged the gist of an episode (gist modifications) or left it intact (surface modifications). On the next day, participants completed a post-fMRI memory test that probed memories for originally encoded episodes. Both types of modifications triggered brain activation in regions we previously found to be involved in the processing of content-based mnemonic prediction errors (i.e., the exchange of an object). Specifically, these were ventrolateral pFC, intraparietal cortex, and lateral occipitotemporal cortex. In addition, gist modifications triggered pronounced brain responses, whereas those for surface modification were only significant in the right inferior frontal sulcus. Processing of gist modifications also involved the posterior temporal cortex and the precuneus. Interestingly, our findings confirmed the posterior hippocampal role of detail processing in episodic memory, as evidenced by increased posterior hippocampal activity for surface modifications compared with gist modifications. In the post-fMRI memory test, previous experience with surface modified, but not gist-modified episodes, increased erroneous acceptance of the same modified versions as originally encoded. Whereas surface-level prediction errors might increase uncertainty and facilitate confusion of alternative episode representations, gist-level prediction errors seem to trigger the clear distinction of independent episodes.
Endurance Performance Adaptations between SSG and HIIT in Soccer Players: A Meta-analysis

Abstract The objective of this systematic review with meta-analysis was to compare the endurance performance chronic adaptations induced by running-based high-intensity interval training (HIIT), small-sided games (SSGs), and combined HIIT+SSGs in male and female youth and adult soccer players. The studies included in this review followed the PICOS criteria: (i) healthy soccer players; (ii) interventions based on SSGs; (iii) comparators exposed to only HIIT or combined SSGs+HIIT; (iv) endurance performance variables. Studies were searched for in the following databases: (i) PubMed; (ii) Scopus; (iii) SPORTDiscus; (iv) Web of Science. After conducting an initial database search that retrieved a total of 5,389 records, a thorough screening process resulted in the inclusion of 20 articles that met the eligibility criteria. Sixteen studies reported outcomes related to endurance performance measured through field-based tests, while five studies provided results from direct measurements of maximal oxygen uptake (VO2max). Results showed a non-significant small-magnitude favoring effect for the HIIT groups compared to the SSG groups (ES=0.37, p= 0.074) for endurance, while a non-significant small-magnitude favoring SSGs was observed (ES=–0.20, p= 0.303) for VO2max. Despite the very low certainty of evidence, the findings suggest similar effects induced by both SSG and HIIT on improving endurance performance and VO2max.
Update on respiratory lesions in patients with IgG4-related autoimmune pancreatitis

We previously reported respiratory involvement in 25 patients with autoimmune pancreatitis, a pancreatic manifestation of IgG4-related disease that responds well to glucocorticoid treatment. However, whether all respiratory lesions in patients with autoimmune pancreatitis have genuine respiratory involvement is unclear. This study aimed to update respiratory lesions’ clinical and radiological characteristics in patients with autoimmune pancreatitis. We retrospectively reviewed the clinical and radiological data of 74 consecutive patients diagnosed with autoimmune pancreatitis at Shinshu University Hospital and treated with glucocorticoid. Clinical features and chest high-resolution computed tomography findings before and after therapy were reviewed. Fifty-one patients (68.9%) had respiratory lesions. In 65 of the 74 patients, chest high-resolution computed tomography results were evaluated before and after treatment. Patients with IgG4-related disease and respiratory lesions showed significantly higher serum IgG4 levels and hypocomplementemia than those without respiratory lesions; they also had more affected organs. While most abnormal thoracic findings improved, 4 cases of 7 with reticular opacities and all 11 cases with emphysema did not improve. Therefore, these lesions with poor response to glucocorticoid treatment should not be considered due to respiratory involvement of autoimmune pancreatitis based on the current classification criteria for IgG4-related disease. Patients with autoimmune pancreatitis and respiratory lesions exhibited higher disease activity than those without. Most chest high-resolution computed tomography lesions were responsive to glucocorticoid treatment, whereas reticular opacities and emphysema were poorly responsive.