Miracle-dz/UniFAR-FTUs huggingface dataset:
Impaired Sensitivity to Thyroid Hormones is Associated with the Risk of Diabetic Nephropathy in Euthyroid Patients with Type 1 Diabetes Mellitus

Purpose This study aims to investigate the relationship between thyroid and type 1 diabetic nephropathy (T1DN) in euthyroid populations, focusing on thyroid hormone sensitivity. Methods A cross-sectional study was conducted between January 2016 and December 2021, including 357 euthyroid patients with type 1 diabetes mellitus (T1DM). Parameters representing thyroid hormone sensitivity were assessed, including the thyroid feedback quantile-based index (TFQI), parameter thyroid feedback quantile index (PTFQI), thyroid stimulating hormone index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free triiodothyronine/free thyroxine (FT3/FT4). Logistic regression and restricted cubic spline regression were performed to detect the association between thyroid hormone sensitivity and the risk of T1DN. Results The study found a negative correlation between the risk of T1DN and FT3/FT4 in euthyroid T1DM patients (OR 0.71, 95% CI 0.51–0.97, P <0.01). PTFQI (P<0.05), TSHI (P<0.05), and TT4RI (P<0.01) showed an M-shaped nonlinear relationship with the risk of T1DN. Elevated risk of T1DN was associated with PTFQI, TSHI, and TT4RI values outside the range of zero, 2.3–3.88, and 27.56–32.19, respectively. Conclusion This study confirms the relationship between impaired thyroid hormone sensitivity and the risk of T1DN in euthyroid patients. It emphasizes the importance of evaluating thyroid hormone sensitivity in T1DM patients, even when their thyroid function appears normal, to promptly prevent the occurrence of T1DN.
Are all lobes made equal? Comparing the sedimentological processes and depositional architecture of submarine lobes in different palaeogeographic and sequence stratigraphic positions

Submarine lobes are high aspect ratio sand-rich deposits fed by sediment gravity flows via channels. They are a major component of submarine fans, the largest depositional bodies on the planet, and therefore represent an important archive of palaeo-environmental change. Basin-floor, or terminal, lobes, are well-studied. Here, lobes in other geographical positions and the influence of confinement (especially when subtle and dynamic) and stratigraphic position on submarine lobe geometry, stacking patterns, and sedimentary facies are investigated. Extensive outcrop exposures and near-outcrop research boreholes from Permian fine-grained basin-floor and intraslope lobes in the Karoo Basin (South Africa) allow spatial and stratigraphic variability in sedimentary facies and architecture to be constrained. One hundred and seventy outcrop logs (~6.9 km total length) and 11 core logs (~1 km) from Units A and E, Laingsburg depocentre and Fan 4, Tanqua depocentre, were integrated to enable the analysis of different lobe types within a physical hierarchy and enabled detailed facies distribution trends, stacking patterns and depositional models to be established. The main outcomes of the study are: 1) recognition criteria for three distinctive lobe fringe settings: frontal, lateral and aggradational lobe fringes; observed differences between frontal and lateral lobe fringe deposits are controlled by flow processes, while aggradational lobe fringes form in response to subtle confinement by intrabasinal slopes; 2) the documentation of lobe stacking patterns within lobe complexes and complex sets. Karoo lobes show a range of stacking patterns that are controlled by seabed topography and sediment supply; 3) the evaluation of hybrid bed distribution that indicates strong geographic but weak stratigraphic trends at different hierarchical scales. Lobe stacking patterns are shown to be a major control in these trends; and 4) the comparison of depositional models established from basin-floor and rare examples of exhumed intraslope lobe complexes that show distinct differences.
Bilad al-Qadim revisited: recent archaeological research at the Al-Khamis Mosque, Ain Abu Zaydan and Abu Anbra, Bahrain

In comparison to our understanding of pre-Islamic occupation and land use on Bahrain, that of the Islamic period has remained less well known. In connection with the building of a visitor centre at the Al-Khamis Mosque and the planning of an associated heritage trail, renewed archaeological research has taken place in Bilad al-Qadim, an archaeologically important area of Islamic settlement in the north-east of the main island of Awal. This has involved excavations in the Abu Anbra cemetery, at Ain Abu Zaydan and at the Al-Khamis Mosque. The results of these excavations are reported here and these contribute to our understanding of Islamic settlement on Bahrain by supporting the interpretation that Bilad al-Qadim was the main centre of Islamic settlement in the eleventh–thirteen century AD.
Real-Life Use of [68Ga]Ga-DOTANOC PET/CT in Confirmed and Suspected NETs from a Prospective 5-Year Electronic Archive at an ENETS Center of Excellence: More Than 2000 Scans in More Than 1500 Patients

Simple Summary Neuroendocrine neoplasms’ (NENs) rarity and heterogeneity represent a clinical challenge. Somatostatin receptor (SST) positron emission tomography/computed tomography (PET/CT) availability and different reimbursement policies across countries account for its heterogenous employment on a single-case basis. The aim of this study was to prospectively collect data of the real-life use of and indications for [68Ga-DOTA0-1NaI3]octreotide ([68Ga]Ga-DOTANOC) PET/CT in a prospective 5-year electronic archive at a single center. Overall, more than 2000 scans were included. This systematic data collection in a high-volume diagnostic center represents a reliable cohort reflecting the trends of [68Ga]Ga-DOTANOC PET/CT use across different clinical indications and primary tumor sites. Abstract The recent introduction of novel treatments for advanced neuroendocrine tumors (NETs) and the well-established impact of clinical case discussion within dedicated multidisciplinary teams indicates the need to promote the centralization of rare diseases, such as NENs (neuroendocrine neoplasms). Data on the real-life use of and indications for [68Ga]Ga-DOTANOC PET/CT were collected from a prospective monocentric 5-year electronic archive including consecutive patients with confirmed and suspected NETs (September 2017 to May 2022). Overall, 2082 [68Ga]Ga-DOTANOC PET/CT scans (1685 confirmed NETs, 397 suspected NETs) were performed in 1537 patients. A high positivity rate was observed across different clinical settings (approximately 70%). Approximately 910/2082 scans were requested by the local oncology ward (851 confirmed NETs, 59 suspected NETs). The following observations were found: (i) the detection rate across all indications was 73.2% (higher for staging, peptide receptor radioligand therapy (PRRT) selection, and treatment response assessment); (ii) in suspected NETs, PET was more often positive when based on radiological findings. This systematic data collection in a high-volume diagnostic center represents a reliable cohort reflecting the global trends in the use of [68Ga]Ga-DOTANOC PET/CT for different clinical indications and primary tumor sites, but prompts the need for further multicenter data sharing in such a rare and slowly progressive disease setting.
A Preliminary Evaluation on the Antifungal Efficacy of VT-1161 against Persister Candida albicans Cells in Vulvovaginal Candidiasis

Persister cells are a small fraction of the microbial population that survive lethal concentrations of antimicrobial agents. Candida albicans causes vaginal candidiasis, including recurrent vulvovaginal candidiasis, and may survive common antifungal treatments. The triazole VT-1161 is an antifungal agent that specifically targets fungal CYP51, as opposed to the human CYP enzyme. This work illustrates a new role of VT-1161 in eradicating the biofilm created from the persister cells of a primary biofilm of a clinical vaginal isolate of C. albicans. Antifungal activity was determined by the minimum inhibitory concentration (MIC), and the primary biofilm was treated with amphotericin B to obtain persister cells that were able to form a new biofilm. Results obtained using the new azole VT-1161 showed that VT-1161 not only eradicated a secondary biofilm formed from the persister-derived biofilm and counteracted the adhesion of C. albicans in vitro to human cells but also ameliorated C. albicans-induced infection in vivo in Galleria mellonella larvae, suggesting that it could be proposed as an alternative therapeutic strategy for the treatment of recurrent candidiasis.
Study on the gasification of pine sawdust with dolomite catalyst in a pilot-scale fluidized bed gasifier

ABSTRACT An experimental study on air-blown gasification of pine sawdust was conducted in a pilot-scale bubbling fluidized bed gasifier. Pine sawdust was fed into lower-center of the gasifier continuously with 60 kg/h and air as the gasifying agent was introduced from the bottom into a distributor. A mixture of inert silica sand and calcined dolomite with different ratios was used as the bed material in order to maintain stable fluidization and to realize the catalytic cracking of in-situ tar. The whole test run was performed as a continuous operation without any interruptions or operational problems.
Assessing Cognitive Workload in Motor Decision-Making through Functional Connectivity Analysis: Towards Early Detection and Monitoring of Neurodegenerative Diseases

Neurodegenerative diseases (NDs), such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, and frontotemporal dementia, among others, are increasingly prevalent in the global population. The clinical diagnosis of these NDs is based on the detection and characterization of motor and non-motor symptoms. However, when these diagnoses are made, the subjects are often in advanced stages where neuromuscular alterations are frequently irreversible. In this context, we propose a methodology to evaluate the cognitive workload (CWL) of motor tasks involving decision-making processes. CWL is a concept widely used to address the balance between task demand and the subject’s available resources to complete that task. In this study, multiple models for motor planning during a motor decision-making task were developed by recording EEG and EMG signals in n=17 healthy volunteers (9 males, 8 females, age 28.66±8.8 years). In the proposed test, volunteers have to make decisions about which hand should be moved based on the onset of a visual stimulus. We computed functional connectivity between the cortex and muscles, as well as among muscles using both corticomuscular and intermuscular coherence. Despite three models being generated, just one of them had strong performance. The results showed two types of motor decision-making processes depending on the hand to move. Moreover, the central processing of decision-making for the left hand movement can be accurately estimated using behavioral measures such as planning time combined with peripheral recordings like EMG signals. The models provided in this study could be considered as a methodological foundation to detect neuromuscular alterations in asymptomatic patients, as well as to monitor the process of a degenerative disease.
Evaluation of oxygen isotope and Mg/Ca ratios in high‐magnesium calcite from benthic foraminifera as a proxy for water temperature

Oxygen isotope ratios (δ18O) and Mg/Ca ratios in organically produced calcium carbonate (calcite and aragonite) by marine species have been used as proxies for paleotemperature. The relationship between the components of large benthic foraminiferal tests (high‐magnesium calcite) and seawater temperature has been little investigated yet. We conducted culture experiments using two species of reef‐dwelling large benthic foraminifera under six temperature conditions (21–30°C). We selected the perforate species Calcarina gaudichaudii, and the imperforate species Amphisorus kudakajimensis, both of which are host to algal symbionts, for the experiments. The results indicated the significant correlation of Mg/Ca ratios (C. gaudichaudii and A. kudakajimensis) and δ18O (C. gaudichaudii) with temperature. The test weight of both species showed temperature dependency, with maxima at 27°C or 29°C and subsequent decline at 30°C. After correction for the contribution of the initial tests, which can be calculated from the weight ratios of the initial and cultured tests, the relationships of the Mg/Ca ratios and δ18O to temperature were obtained with the least squares best fit method as follows: C. gaudichaudii: T = 18.5–4.52 (δ18Oc–δ18Osw), A. kudakajimensis: T = 25.0–4.96 (δ18Oc–δ18Osw), and C. gaudichaudii and A. kudakajimensis: Mg/Ca = 2.85 T + 81.20. We concluded that species‐specific calibration is unnecessary for Mg/Ca‐temperature relationship, although it is necessary for δ18O related to the different calcification mechanisms of imperforate (A. kudakajimensis) and perforate (C. gaudichaudii) species.
Health-Related Quality of Life Assessment for Liver Cirrhosis Patients at a Tertiary Care Hospital in Karachi, Pakistan

Background The global health challenge of cirrhosis affects millions of individuals. Still, there is a notable lack of research on the health-related quality of life (HRQOL) of cirrhosis patients, especially in specific regions. This study aims to assess the impact of cirrhosis on HRQOL, including factors influencing it in a tertiary care setting in Pakistan. Methodology A cross-sectional study was conducted on a cohort of 115 patients diagnosed with cirrhosis, confirmed on imaging. HRQOL was measured using the short-form 36 (SF-36) survey. Furthermore, socioeconomic factors and self-rated health perceptions regarding HRQOL were recorded. Factors Influencing HRQOL domains in liver cirrhosis patients were also analyzed. Results Among 115 liver cirrhosis patients, 63.5% (N=73) were aged 40-60 years, and 73.9% (N=85) lived primarily in urban areas. HRQOL assessments highlighted moderate disability in physical functioning (62.6 ± 26.5) and notable impacts on mental health, emotional well-being, and bodily pain. Statistical analysis demonstrated the complexity of factors influencing HRQOL. Physical functioning was significantly associated with a higher Child-Turcotte-Pugh class, diabetes mellitus, hypertension, smoking status, and family monthly income (p-value < 0.05). While the duration of liver cirrhosis showed a significant association with bodily pain (p < 0.05). Additionally, residence status with social well-being (p-value = 0.01), and family monthly income with vitality (p-value < 0.05). Conclusion Our study in Pakistan highlights significant impacts on the HRQOL of liver cirrhosis patients, affecting physical function, mental health, emotional well-being, and bodily pain. Factors influencing HRQOL include liver disease severity, comorbidities, and socio-economic status. Recommendations include educational programs and specialized nursing care to address diverse challenges. The findings stress the importance of a personalized approach to patient care, urging urgent, targeted efforts to improve the health-related standard of life for cirrhotic patients.
Assessing Population-level Target Product Profiles of Broadly-protective Human Influenza A Vaccines

Influenza A has two main clades, with stronger cross-immunity to reinfection within than between clades. Here, we explore the implications of this heterogeneity for proposed cross-protective influenza vaccines that may offer broad, but not universal, protection. While the development goal for the breadth of human influenza A vaccine is to provide cross-clade protection, vaccines in current development stages may provide better protection against target clades than non-target clades. To evaluate vaccine formulation and strategies, we propose a novel perspective: a vaccine population-level target product profile (PTPP). Under this perspective, we use dynamical models to quantify the epidemiological impacts of future influenza A vaccines as a function of their properties. Our results show that the interplay of natural and vaccine-induced immunity could strongly affect seasonal clade dynamics. A broadly protective bivalent vaccine could lower the incidence of both clades and achieve elimination with sufficient vaccination coverage. However, a univalent vaccine at low vaccination rates could permit a resurgence of the non-target clade when the vaccine provides weaker immunity than natural infection. Moreover, as a proxy for pandemic simulation, we analyze the invasion of a variant that evades natural immunity. We find that a future vaccine providing sufficiently broad and long-lived cross-clade protection at a sufficiently high vaccination rate, could prevent pandemic emergence and lower the pandemic burden. This study highlights that as well as effectiveness, breadth and duration should be considered in epidemiologically informed TPPs for future human influenza A vaccines.
Sub-second and multi-second dopamine dynamics underlie variability in human time perception

Timing behaviour and the perception of time are fundamental to cognitive and emotional processes in humans. In non-human model organisms, the neuromodulator dopamine has been associated with variations in timing behaviour, but the connection between variations in dopamine levels and the human experience of time has not been directly assessed. Here, we report how dopamine levels in human striatum, measured with sub-second temporal resolution during awake deep brain stimulation surgery, relate to participants perceptual judgements of time intervals. Fast, phasic, dopaminergic signals were associated with underestimation of temporal intervals, whereas slower, tonic, decreases in dopamine were associated with poorer temporal precision. Our findings suggest a delicate and complex role for the dynamics and tone of dopaminergic signals in the conscious experience of time in humans.
ENHANCING VENTRICULAR TACHYCARDIA ABLATION OUTCOMES: THE IMPACT OF FUNCTIONAL MAPPING IN CHAGAS CARDIOMYOPATHY

Background: Chagas cardiomyopathy presents a significant public health challenge in Latin America, marked by high rates of ventricular tachycardia (VT) and implantable cardioverter-defibrillator (ICD) interventions. This study explores the efficacy of functional mapping strategies in VT ablation for Chagas cardiomyopathy compared to conventional voltage map-based approaches. Methods: This observational study, involving 66 patients, employed electroanatomic mapping for both epicardial and endocardial regions. In voltage-based mapping (group 1), all patients underwent bipolar substrate mapping with standard scar settings for epicardial and endocardial regions, while functional mapping (group 2) was obtained using a single ventricular extra-stimulus with Late Potential and Isochronal Late Activation Maps associated with annotation of decremental and blocked electrograms. The primary endpoint was post-ablation VT recurrence over a 30-month follow-up. Results: Voltage-based and functional mapping groups presented 42 and 24 patients, respectively. When compared to the voltage-based mapping strategy, functional mapping-assisted procedures were associated with lower post-ablation VT recurrence on Kaplan-Meier's log-rank test (P=0.045). After multivariate analysis, functional mapping independently associated with a 90.3% reduction in the risk of 30-month VT recurrence (HR: 0.097, 95% CI: 0.012-0.760, P=0.026) compared to voltage-based mapping. Conclusion: Functional mapping in Chagas cardiomyopathy VT ablation is associated with significantly reduced recurrence rates, emphasizing its potential as an effective strategy in this challenging condition. This study provides valuable insights for improving VT ablation outcomes. However, there is a dire need for a large-scale randomized controlled trial to generate high-quality evidence in this field.
Interactions in abnormal synergies between the upper and lower extremities in various phases of stroke: A cohort study

Objective: The flexion synergy and extension synergy are a representative consequence of a stroke and appear in the upper extremity and lower extremity. Since the ipsilesional corticospinal tract (CST) is the most influential neural pathway for both extremities in motor execution, damage by a stroke to this tract could lead to similar motor pathological features (e.g., abnormal synergies) in both extremities. However less attention has been paid to the inter-limb correlations in the flexion synergy and extension synergy across different recovery phases of a stroke. Methods: In this study, we used results of the Fugl-Meyer assessment (FMA) to characterize those correlations in a total of 512 participants with hemiparesis post stroke from the acute phase to 1 year. The FMA provides indirect indicators of the degrees of the flexion synergy and extension synergy post stroke. Results: We found that generally, strong inter-limb correlations (r>0.65 with all p-values<0.0001) between the flexion synergy and extension synergy appeared in the acute-to-subacute phase (<90 days). But correlations of lower-extremity extension synergy with upper-extremity flexion synergy and extension synergy decreased (down to r=0.38) around 360 days after stroke (p<0.05). Interpretation: These results suggest that the preferential use of alternative neural pathways after damage by a stroke to the CST enhances inter-limb correlations between the flexion synergy and extension, however a recovery of the CST or/and the functional fragmentation (remodeling) of the alternative neural substrates in the chronic phase contribute to diversity in neural pathways in motor execution, eventually leading to reduced inter-limb correlations.
Sex-specific genetic determinants of right ventricular structure and function

Background: While sex differences in right heart phenotypes have been observed, the molecular drivers remain unknown. We used common genetic variation to provide biological insights into sex differences in the structure and function of the right ventricle (RV). Methods: RV phenotypes were obtained from cardiac magnetic resonance imaging in 18,156 women and 16,171 men from the UK Biobank, based on a deep-learning approach, including end-diastolic, end-systolic, and stroke volumes, as well as ejection fraction. Observational analyses and sex-stratified genome-wide association studies were performed. Candidate female-specific loci were evaluated against invasively measured hemodynamics in 479 female patients with idiopathic or heritable pulmonary arterial hypertension (PAH), recruited to the UK National Institute for Health Research BioResource Rare Diseases study. Results: Sex was associated with differences in RV volumes and ejection fraction in models adjusting for left heart counterparts and lung function. Six genome-wide significant loci (13%) revealed heterogeneity of allelic effects between women and men. These included two sex-specific candidate loci present in women only; namely, a locus for RV ejection fraction in BMPR1A and a locus for RV end-systolic volume near DMRT2. Epigenetic data indicate that variation at the BMPR1A locus likely alters transcriptional regulation in RV tissue. In female patients with PAH, a variant located in the promoter of BMPR1A was significantly associated with cardiac index (effect size 0.16 l/min/m2), despite similar RV afterload among genotypic groups. Conclusions: We report sex-specific genetic loci for RV structure and function. BMPR1A has emerged as a biologically plausible candidate gene for female-specific genetic determination of RV function, showing associations with cardiac performance under chronically increased afterload in female patients with PAH. Further studies are needed to explore the underlying biological pathways.