Miracle-dz/UniFAR-FTUs huggingface dataset:
Pou3f1 orchestrates a gene regulatory network controlling contralateral retinogeniculate projections

The balance of contralateral and ipsilateral retinogeniculate projections is critical for the establishment of binocular vision, but the transcriptional programs regulating this process remain ill-defined. In this study, we show that the Pou class homeobox protein POU3F1 is selectively expressed in developing mouse contralateral retinal ganglion cells (cRGCs). Inactivation of Pou3f1 increases the number of ipsilateral RGCs produced, leading to abnormal ipsilateral to contralateral projection ratio at the optic chiasm, whereas expression of Pou3f1 in retinal progenitors increases the production of cRGCs. Using Cut&Run and RNA sequencing in wildtype and Pou3f1 mouse knockout retinas, we demonstrate that Pou3f1 is necessary for the establishment of a cRGC gene regulatory network through activation and repression of several known contralateral and ipsilateral determinants, respectively. Finally, we report that POU3F1 is sufficient to induce production of RGC-like cells sending projections to the optic nerve, even in late-stage retinal progenitors not normally competent to generate RGCs. This work uncovers POU3F1 as a master regulator of the cRGC transcriptional program and opens new possibilities for optic nerve regenerative therapies.
Hope in Every Breath: Navigating the Therapeutic Landscape of Cystic Fibrosis

Cystic fibrosis (CF) has long posed a complex challenge to medical science. Still, the tides are turning with remarkable progress in prognosis and demographics, thanks to cutting-edge medical management and treatment breakthroughs. It affects multiple systems, necessitating a comprehensive approach to its management. This article thoroughly reviews the latest advancements in CF treatment across three key areas: respiratory care, infection prevention, and pharmacological management. In respiratory care, emphasis is placed on airway clearance therapies and nebulized saline, while infection prevention strategies encompass hand hygiene, respiratory etiquette, and environmental cleaning and disinfection. Pharmacological management explores pancreatic enzyme replacement therapy (PERT), antimicrobial treatments, cystic fibrosis transmembrane regulator (CFTR) modulators, and promising gene therapies. Patient education and support are highlighted as crucial components of effective CF management, while mental health assessments are emphasized due to CF patients' susceptibility to anxiety and depression. This review highlights the tremendous progress made in the management of CF. Integrating early detection, infection prevention, pharmacological interventions, gene therapy, and patient support is revolutionizing the care and quality of life for individuals with CF.
Fiscal Decentralization and Corruption: The Facts of Regional Autonomy Policies in Indonesia

Decentralization has posed new problems in Indonesian local governments, including disparities between regions, poor public services, fiscal indiscipline, and corruption cases. Before the implementation of regional autonomy, corruption cases were reported only in a few regions. A year after decentralization started, in 2002, more corruption cases were reported in more regions nationwide. The irony is that such decentralization, initiated to reduce corruption in the government, ended up with more corruption in the regions. This study investigates the relationship between fiscal decentralization—as proxied by capital expenditure and fiscal independence index—and the corruption index. This study also analyzes the macro factors and regional characteristics: inflation, civil servants’ salaries, education levels, and the differences in the corruption index at the regional level. The method used in this study is regression analysis by using panel data from longitudinal studies involving 15 cities in Indonesia in 2008, 2010, 2015, and 2017. The finding shows that the relationship of fiscal decentralization—expenditure, inflation rates, civil servants’ salaries, and local corruption—are not statistically significant to the corruption index. By contrast, the relationship between the fiscal independence index and educational level are statistically significant. The implementation of fiscal decentralization on expenditure increases corruption risks due to ineffective budget management, individual corrupt tendencies, and weak supervision system. Meanwhile, fair allocation of local income can increase public trust and prosperity and lower corruption risks.
Calmodulin mutations affecting Gly114 impair binding to the NaV1.5 IQ-domain

Missense variants in CALM genes encoding the Ca2+-binding protein calmodulin (CaM) cause severe cardiac arrhythmias. The disease mechanisms have been attributed to dysregulation of RyR2, for Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) and/or CaV1.2, for Long-QT Syndrome (LQTS). Recently, a novel CALM2 variant, G114R, was identified in a mother and two of her four children, all of whom died suddenly while asleep at a young age. The G114R variant impairs closure of CaV1.2 and RyR2, consistent with a CPVT and/or mild LQTS phenotype. However, the children carrying the CALM2 G114R variant displayed a phenotype commonly observed with variants in NaV1.5, i.e., Brugada Syndrome (BrS) or LQT3, where death while asleep is a common feature. We therefore hypothesized that the G114R variant specifically would interfere with NaV1.5 binding. Here, we demonstrate that CaM binding to the NaV1.5 IQ-domain is severely impaired for two CaM variants G114R and G114W. The impact was most severe at low and intermediate Ca2+ concentrations (up to 4 µM) resulting in more than a 50-fold reduction in NaV1.5 binding affinity, and a smaller 1.5 to 11-fold reduction at high Ca2+ concentrations (25–400 µM). In contrast, the arrhythmogenic CaM-N98S variant only induced a 1.5-fold reduction in NaV1.5 binding and only at 4 µM Ca2+. A non-arrhythmogenic I10T variant in CaM did not impair NaV1.5 IQ binding. These data suggest that the interaction between NaV1.5 and CaM is decreased with certain CaM variants, which may alter the cardiac sodium current, INa. Overall, these results suggest that the phenotypic spectrum of calmodulinopathies may likely expand to include BrS- and/or LQT3-like traits.
Update on Biomarkers Associated with Large-Artery Atherosclerosis Stroke

Intracranial and extracranial large-artery atherosclerosis (LAA) are a main cause of ischemic stroke. Biomarkers may aid in the diagnosis of LAA and help to stratify patients’ risk of stroke. We performed a narrative review of the literature, mainly published in the last five years, with the aim of identifying biomarkers associated either with intracranial or extracranial LAA in humans. Several potential biomarkers of LAA, mainly related to lipidic pathways and inflammation, have been studied. Diagnostic biomarkers of LAA were evaluated by measuring biomarkers levels in patients with LAA stroke and other stroke etiologies. Some biomarkers were associated with the functional prognosis of LAA stroke patients. Increased levels of IL-6 and sLOX-1 were associated with a risk of progression of carotid atherosclerotic disease. Findings support the notion that the immune system plays a central role in the pathogenesis of LAA. Overall, in most studies, results were not externally validated. In the future, biomarkers could be useful for the selection of patients for clinical trials. To adopt these biomarkers in clinical practice, we will need robust multicentric studies proving their reproducibility and a clear practical applicability for their use.
Suicidal attempt among patients with schizophrenia: A cross-sectional study from Morocco

Suicide constitutes the greatest risk factor for mortality in individuals with schizophrenia. Although numerous risk factors have been suggested as important predictors of suicidality in schizophrenia, most studies have focused on Caucasian and Chinese patients. This study aimed to examine the prevalence of suicide attempts in schizophrenia patients in Rabat-Sale-Kenitra, Morocco, and to identify associated clinical and sociodemographic characteristics. A cross-sectional study was conducted at the Ar-RAZI Psychiatric Center of Ibn Sina Hospital in Rabat. We examined 175 Moroccan schizophrenic patients. The sociodemographic and clinical variables were analyzed based on the presence or absence of suicide attempts. The prevalence of suicide attempts among patients was 32%. 43% of them had reported multiple suicide attempts. The majority of those who attempted suicide were single, younger, and with a lower economic status. Visual hallucinations were significantly prevalent among attempter patients compared to non-attempters (p =0.032). Consequently, visual hallucinations could be a risk factor for suicide attempts in the Moroccan population. Understanding sociodemographic and clinical characteristics associated with suicide attempts can help identify patients at higher risk and provide appropriate support and interventions to prevent suicide among the Moroccan population.
Length-weight relationships for 47 fish species from Izmir Bay (eastern Aegean Sea, Turkey)

Length-weight relationships were calculated for 4 7 fish species from the Izmir Bay in the Aegean Sea, Turkey. A total of 13243 fish specimens were sampled with several fishing gears in 1998-2001. The sample size ranged from 11 individuals for Nerophis ophidion to 1197 for Boops boops. The r2 values ranged from 0.82 for Nerophis ophidion to 0.99 for Scorpaena scrofa, and all regressions were highly significant (p<0.001). Values of the exponent b in the length-weight regression (W = aL b ) ranged 1.970-3.727. The median was 3.042 and over 50% of the values were within 2.937-3.186. Information from the present survey may be used for fisheries management or other practical purposes.
Strategic digital city: Concept, model, and research cases

Cities, in addition to being physical, are also digital, requiring the use of information technology resources and strategies, information, and services to make appropriate decisions. The objective is to present the strategic digital city (SDC) concept and project model and its research considering the subprojects: city strategies; city information; public services to citizens; and information technology resources applied in cities. The research methodology comprises approaches mixing techniques in respective phases, including bibliometrics assignment, and model theory applied in SDC cases with more than 11 doctoral, 100 master’s, undergraduate, scientific initiation, and postdoctoral program orientations obtained from more than 300 cities since 2003. The results showed that the SDC can be understood as a social project of public policy and is on the city managers’ agenda, as demonstrated in the 8 cases researched and in the more than 86 publications in different scientific international journals in the recent decade. The conclusion reiterates the importance of the participatory and democratic SDC original project accepted to contribute to the proper city management and the citizens’ quality of life expansion, including infrastructure, policy, and city development. Then, the SDC contemporary concept and model have been maintained regularly over the 10 years.
A Quality-of-Service-Aware Service Composition Method in the Internet of Things Using a Multi-Objective Fuzzy-Based Hybrid Algorithm

The Internet of Things (IoT) represents a cutting-edge technical domain, encompassing billions of intelligent objects capable of bridging the physical and virtual worlds across various locations. IoT services are responsible for delivering essential functionalities. In this dynamic and interconnected IoT landscape, providing high-quality services is paramount to enhancing user experiences and optimizing system efficiency. Service composition techniques come into play to address user requests in IoT applications, allowing various IoT services to collaborate seamlessly. Considering the resource limitations of IoT devices, they often leverage cloud infrastructures to overcome technological constraints, benefiting from unlimited resources and capabilities. Moreover, the emergence of fog computing has gained prominence, facilitating IoT application processing in edge networks closer to IoT sensors and effectively reducing delays inherent in cloud data centers. In this context, our study proposes a cloud-/fog-based service composition for IoT, introducing a novel fuzzy-based hybrid algorithm. This algorithm ingeniously combines Ant Colony Optimization (ACO) and Artificial Bee Colony (ABC) optimization algorithms, taking into account energy consumption and Quality of Service (QoS) factors during the service selection process. By leveraging this fuzzy-based hybrid algorithm, our approach aims to revolutionize service composition in IoT environments by empowering intelligent decision-making capabilities and ensuring optimal user satisfaction. Our experimental results demonstrate the effectiveness of the proposed strategy in successfully fulfilling service composition requests by identifying suitable services. When compared to recently introduced methods, our hybrid approach yields significant benefits. On average, it reduces energy consumption by 17.11%, enhances availability and reliability by 8.27% and 4.52%, respectively, and improves the average cost by 21.56%.
Effects of Supplementation with the Standardized Extract of Saffron (affron®) on the Kynurenine Pathway and Melatonin Synthesis in Rats

Melatonin is a hormone that regulates sleep–wake cycles and is mainly synthesized in the pineal gland from tryptophan after its conversion into serotonin. Under normal conditions, less than 5% of tryptophan is reserved for the synthesis of serotonin and melatonin. The remaining 95% is metabolized in the liver through the kynurenine pathway. Increased levels of proinflammatory cytokines and cortisol increase the metabolism of tryptophan through the kynurenine pathway and reduce its availability for the synthesis of melatonin and serotonin, which may cause alterations in mood and sleep. The standardized saffron extract (affron®) has shown beneficial effects on mood and sleep disorders in humans, but the underlying mechanisms are not well understood. Thus, the aim of this work was to study the effects of affron® supplementation on the kynurenine pathway and the synthesis of melatonin in rats. For this purpose, adult male Wistar rats were supplemented for 7 days with 150 mg/kg of affron® or vehicle (2 mL/kg water) administered by gavage one hour before sleep. Affron® supplementation reduced body weight gain and increased the circulating levels of melatonin, testosterone, and c-HDL. Moreover, animals supplemented with affron® showed decreased serum levels of kynurenine, ET-1, and c-LDL. In the pineal gland, affron® reduced Il-6 expression and increased the expression of Aanat, the key enzyme for melatonin synthesis. In the liver, affron® administration decreased the mRNA levels of the enzymes of the kynurenine pathway Ido-2, Tod-2, and Aadat, as well as the gene expression of Il-1β and Tnf-α. Finally, rats treated with affron® showed increased mRNA levels of the antioxidant enzymes Ho-1, Sod-1, Gsr, and Gpx-3, both in the liver and in the pineal gland. In conclusion, affron® supplementation reduces kynurenine levels and promotes melatonin synthesis in rats, possibly through its antioxidant and anti-inflammatory effects, making this extract a possible alternative for the treatment and/or prevention of mood and sleep disorders.
The Effectiveness of Home-Based Inspiratory Muscle Training on Small Airway Function and Disease-Associated Symptoms in Patients with Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitations, occurring mainly in the small airways. Weakness in the respiratory muscles contributes to dyspnea and a decreased exercise capacity in COPD patients. This study aimed to investigate the effectiveness of home-based inspiratory muscle training (IMT) on small airway function and symptoms in COPD patients. This research adopted a non-randomized controlled-study quasi-experimental design. The IMT program consisted of two 15 min sessions·d−1, 5 d·wk−1, with 40% of the maximal inspiratory pressure (PImax) on each participant’s assessment results and lasted for 12 weeks. Small airway function was assessed using plethysmography at baseline and after 12 weeks. The modified British Medical Research Council (mMRC), COPD assessment test (CAT), PImax, and 6 min walking distance (6MWD) were recorded at baseline as well as four, eight, and twelve weeks. Twenty-three participants with at least moderate COPD were enrolled in IMT (n = 16) or in the control group (n = 7) in this study. The study participants were mostly male (82.6%), and the average age was 68.29 ± 10.87 years, with a mean body mass index (BMI) of 23.54 ± 4.79. After 12 weeks, the ratios of the first second of forced expiration to the forced vital capacity (FEV1/FVC%) (B coefficient [95% Wald confidence interval] of 5.21 [0.46 to 9.96], p = 0.032), forced expiratory flow (FEF25–75%) (0.20 [0.04 to 0.35] L/s, p = 0.012), and FEF50% (0.26 [0.08 to 0.43] L/s, p = 0.004) in the IMT group were significantly better than in the control group. The IMT group showed significantly lower CAT scores at week 8 (−5.50 [−10.31 to −0.695] scores, p = 0.025) than the control group. The mMRC grade, CAT score, PImax, and 6MWD were significantly improved compared to their values at baseline in the IMT group. Home-based IMT effectively improved post-bronchodilator small airway function and disease-associated symptoms in COPD patients.
Cultural Marginality: Exploration of Self-Esteem and Cross Cultural Adaptation of the Marginalized Individual: An investigation of the second generation Hare Krishnas .

The purpose of this study was to explore the cross-cultural adaptation of a sample of adults raised in the Hare Krishna culture. Fifteen second generation ISKCON (International Society for Krishna Consciousness) adults were asked to describe their family, peer, and social interactions and the perceived impact on their cross-cultural adaptation. An analysis of participant responses generated the following fifteen themes: (1) age and context of first contact with mainstream culture, (2) process of cultural adaptation, (3) parents’ marital status, (4) family relationships, (5) layers of marginality, (6) community norms and values, (7) identity crises, (8) self-esteem and self-esteem scores, (9) views of ISKCON culture, (10) views of mainstream culture, (11) cultural vernacular, (12) cultural emblems, (13) role models, (14) current cultural membership, and (15) future family vision. The outcome of the study was discussed with possible clinical issues which included the complexities of cultural belongingness, healthy and self-destructive aspects of adaptation, and feelings of terminal uniqueness.
Magnetic resonance imaging features of bile duct adenoma

Objectives To evaluate the magnetic resonance imaging (MRI) features of bile duct adenoma. Methods The data of 28 patients [with 32 pathologically confirmed bile duct adenomas, including 15 with malignant change (malignant group) and 17 without malignant change (benign adenoma group)] were retrospectively reviewed. Abdominal MRI was performed for all patients; in addition, dynamic enhanced MRI was performed for 18 lesions. The MRI features, including lesion location, maximum size, morphology, signal characteristics, enhancement type, and appearance of the bile duct, were assessed by two abdominal radiologists. Apparent diffusion coefficient (ADC) values were measured and compared. Results Of the 32 bile duct adenomas, 22 (68.75%) involved the common bile duct (CBD). While 14/32 (43.75%) lesions presented as focal eccentric-type masses, 9/32 (28.13%) presented as plaque-like masses, 4/32 (12.50%) as bile duct casting masses, and 5/32 (15.62%) as infiltrative masses. A frond-like superficial appearance was seen in 8/32 (25%) lesions. Infiltrative masses were significantly more common in the malignant group than in the benign adenoma group (P = 0.015). While 23/32 (71.88%) lesions were isointense on T1-weighted imaging (T1WI), 24/32 (75%) were hyperintense on T2-weighted imaging (T2WI). Bile duct dilatation was present upstream of the lesion in all cases. Bile duct dilatation at the lesion was seen in 24/32 (75%) cases and downstream of the lesion in 6/32 (18.75%) cases. Of the 18 lesions that underwent dynamic enhanced MRI, 14 (77.78%) showed moderate enhancement and 13 (72.22%) showed persistent enhancement. On diffusion-weighted imaging (DWI), 27/32 (84.37%) lesions showed hyperintensity. Mean ADC value was comparable between the malignant group and the benign adenoma group (P = 0.156). Conclusions Bile duct adenoma primarily presents as intraductal growth in the CBD, usually with bile duct dilatation at the lesion site or upstream to it. Most lesions are isointense on T1WI, are hyperintense on T2WI and DWI, and show moderate enhancement. A superficial frond-like appearance of the lesion and bile duct dilatation at the lesion or downstream to it might be characteristics of bile duct adenoma. An infiltrative appearance might indicate malignant transformation.
A Comparative Study of Immunogenicity, Antibody Persistence, and Safety of Three Different COVID-19 Boosters between Individuals with Comorbidities and the Normal Population

Data on immunogenicity, immune response persistency, and safety of COVID-19 boosters in patients with comorbidities are limited. Therefore, we aimed to evaluate three different boosters’ immunogenicity and safety in individuals with at least one underlying disease (UD) (obesity, hypertension, and diabetes mellitus) with healthy ones (HC) who were primed with two doses of the BBIBP-CorV vaccine and received a booster shot of the same priming vaccine or protein subunit vaccines, PastoCovac Plus or PastoCovac. One hundred and forty subjects including sixty-three ones with a comorbidity and seventy-seven healthy ones were enrolled. The presence of SARS-CoV-2 antibodies was assessed before the booster injection and 28, 60, 90, and 180 days after it. Moreover, the adverse events (AEs) were recorded on days 7 and 21 postbooster shot for evaluating safety outcomes. Significantly increased titers of antispike, antiRBD, and neutralizing antibodies were observed in both UD and HC groups 28 days after the booster dose. Nevertheless, the titer of antispike IgG and anti-RBD IgG was lower in the UD group compared to the HC group. The long-term assessment regarding persistence of humoral immune responses showed that the induced antibodies were detectable up to 180 days postbooster shots though with a declined titer in both groups with no significant differences (p > 0.05). Furthermore, no significant difference in antibody levels was observed between each UD subgroup and the HC group, except for neutralizing antibodies in the hypertension subgroup. PastoCovac Plus and PastoCovac boosters induced a higher fold rise in antibodies in UD individuals than BBIBP-CorV booster recipients. No serious AEs after the booster injection were recorded. The overall incidence of AEs after the booster injection was higher in the UD group than the HC group among whom the highest systemic rate of AEs was seen in the BBIBP-CorV booster recipients. In conclusion, administration of COVID-19 boosters could similarly induce robust and persistent humoral immune responses in individuals with or without UD primarily vaccinated with two doses of the BBIBP-CorV. Protein-based boosters with higher a higher fold rise in antibodies and lower AEs in individuals with comorbidities might be considered a better choice for these individuals.