From islet transplantation to beta-cell regeneration: an update on beta-cell-based therapeutic approaches in type 1 diabetes.

INTRODUCTION: Type 1 diabetes (T1D) mellitus is an autoimmune disease in which immune cells, predominantly effector T cells, destroy insulin-secreting beta-cells. Beta-cell destruction led to various consequences ranging from retinopathy and nephropathy to neuropathy. Different strategies have been developed to achieve normoglycemia, including exogenous glucose compensation, whole pancreas transplantation, islet transplantation, and beta-cell replacement. AREAS COVERED: The last two decades of experience have shown that indigenous glucose compensation through beta-cell regeneration and protection is a peerless method for T1D therapy. Tremendous studies have tried to find an unlimited source for beta-cell regeneration, on the one hand, and beta-cell protection against immune attack, on the other hand. Recent advances in stem cell technology, gene editing methods, and immune modulation approaches provide a unique opportunity for both beta-cell regeneration and protection. EXPERT OPINION: Pluripotent stem cell differentiation into the beta-cell is considered an unlimited source for beta-cell regeneration. Devising engineered pancreas-specific regulatory T cells using Chimeric Antigen Receptor (CAR) technology potentiates an effective immune tolerance induction for beta-cell protection. Beta-cell regeneration using pluripotent stem cells and beta-cell protection using pancreas-specific engineered regulatory T cells promises to develop a curative protocol in T1D.

Prevalence of hepatitis B and C viruses among migrant workers in Qatar.

Limited data exist on viral hepatitis among migrant populations. This study investigated the prevalence of current hepatitis B virus (HBV) infection and lifetime hepatitis C virus (HCV) infection among Qatar's migrant craft and manual workers (CMWs), constituting 60% of the country's population. Sera collected during a nationwide COVID-19 population-based cross-sectional survey on CMWs between July 26 and September 9, 2020, underwent testing for HBsAg and HCV antibodies. Reactive samples underwent confirmatory testing, and logistic regression analyses were employed to explore associations with HBV and HCV infections. Among 2528 specimens tested for HBV infection, 15 were reactive, with 8 subsequently confirmed positive. Three samples lacked sufficient sera for confirmatory testing but were included in the analysis through multiple imputations. Prevalence of current HBV infection was 0.4% (95% CI 0.2-0.7%). Educational attainment and occupation were significantly associated with current HBV infection. For HCV infection, out of 2607 specimens tested, 46 were reactive, and 23 were subsequently confirmed positive. Prevalence of lifetime HCV infection was 0.8% (95% CI 0.5-1.2%). Egyptians exhibited the highest prevalence at 6.5% (95% CI 3.1-13.1%), followed by Pakistanis at 3.1% (95% CI 1.1-8.0%). Nationality, geographic location, and occupation were significantly associated with lifetime HCV infection. HBV infection is relatively low among CMWs, while HCV infection falls within the intermediate range, both compared to global and regional levels.

Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19.

The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) also frequently experience hyposmia. We previously postulated that microglial activation as well as α-synuclein and tau misprocessing can occur during host responses following microbial encounters. Using semiquantitative measurements of immunohistochemical signals, we examined OB and olfactory tract specimens collected serially at autopsies between 2020 and 2023. Deceased subjects comprised 50 adults, which included COVID19 + patients (n = 22), individuals with Lewy body disease (e.g., PD; dementia with Lewy bodies (n = 6)), Alzheimer disease (AD; n = 3), and other neurodegenerative disorders (e.g., progressive supranuclear palsy (n = 2); multisystem atrophy (n = 1)). Further, we included neurologically healthy controls (n = 9), and added subjects with an inflammation-rich brain disorder as neurological controls (NCO; n = 7). When probing for microglial and histiocytic reactivity in the anterior olfactory nuclei (AON) by anti-CD68 immunostaining, scores were consistently elevated in NCO and AD cases. In contrast, microglial signals on average were not significantly altered in COVID19 + patients relative to healthy controls, although anti-CD68 reactivity in their OB and tracts declined with progression in age. Mild-to-moderate increases in phospho-α-synuclein and phospho-tau signals were detected in the AON of tauopathy- and synucleinopathy-afflicted brains, respectively, consistent with mixed pathology, as described by others. Lastly, when both sides were available for comparison in our case series, we saw no asymmetry in the degree of pathology of the left versus right OB and tracts. We concluded from our autopsy series that after a fatal course of COVID-19, microscopic changes in the rostral, intracranial portion of the olfactory circuitry -when present- reflected neurodegenerative processes seen elsewhere in the brain. In general, microglial reactivity correlated best with the degree of Alzheimer's-linked tauopathy and declined with progression of age in COVID19 + patients.

Evaluation of left ventricular function in patients with mitral annular disjunction using speckle tracking echocardiography.

BACKGROUND: Mitral annular disjunction (MAD) is a structural abnormality characterized by the systolic detachment of the posterior mitral annulus and the ventricular myocardium. It is usually observed coexistent with mitral valve prolapse (MVP) and associated with a mechanical dysfunction despite preserved electrical isolation function of the mitral annulus. This study aimed to evaluate left ventricular (LV) function using speckle tracking echocardiography in MVP patients with MAD. METHODS: This study was designed as a prospective, single-center study including 103 patients with MVP and 40 age- and sex-matched control subjects. Transthoracic echocardiography and cardiac magnetic resonance imaging were performed to assess LV function and MAD presence. RESULTS: MAD (+) MVP (n = 34), MAD (-) MVP (n = 69), and control (n = 40) groups were enrolled in the study. Among the MVP patients, 34 (33%) had MAD. T-negativity in the inferior leads on electrocardiography was more frequent in the MAD (+) group than in the MAD (-) patients (4.3% vs. 20.6%, p = .014). Mitral regurgitation degree, Pickelhaube sign (17.6% vs. 1.4%, p = .005), and late gadolinium enhancement frequency (35.3% vs. 10.6%, p = .002) were significantly higher in MAD (+) patients. MAD (+) patients had significantly impaired global longitudinal strain (-23.1 ±  2.1 vs. -23.5 ± 2.3, p < .001), basal longitudinal strain (BLS) (-19.6 ±  1.5 vs. -20.5 ± 1.9, p < .001), Mid-Ventricular Longitudinal Strain (-22.2 ± 1.7 vs. -23.2 ± 2.2, p < .001) and LA strain (-24.5 ± 3.9 vs. -27.2 ± 3.6, p < .001) when compared to MAD (-) MVP patients, despite similar LV ejection fraction. All these values of MVP patients were also significantly lower than the control group. The mean MAD distance was 7.8 ± 3.2 mm in MAD (+) patients. Patients with two or more symptoms were higher in the MAD (+) group than in the MAD (-) group (4.3% vs. 44.1%, p < .001). CONCLUSION: This study demonstrated a significant decrease in longitudinal strain in MVP patients with MAD, indicating myocardial dysfunction. These findings suggest that MAD may contribute to LV dysfunction and highlight the importance of early detection in younger patients. Further research is needed to explore the functional implications and long-term outcomes of MAD.

The impact of preoperative anxiety on pain and analgesia consumption in women undergoing vaginal hysterectomy with general anesthesia and spinal anesthesia.

OBJECTIVES: To assess the impact of preoperative anxiety on pain and analgesic consumption in patients undergoing vaginal hysterectomy (VH) with general and spinal anesthesia. MATERIAL AND METHODS: A total of 200 participants, including 100 undergoing vaginal hysterectomy with general anesthesia (group 1) and 100 with spinal anesthesia (group 2), were enrolled. A visual analog scale (VAS) was used for the postoperative pain intensity. RESULTS: The 1st hour, 6th hour, 12th hour, and 18th hour VAS scores were higher in vaginal hysterectomy with general anesthesia than in vaginal hysterectomy with spinal anesthesia. CONCLUSIONS: Although participants undergoing VH with spinal anesthesia (preoperative state anxiety inventory score > 45) had lower pain intensity scores in the first 18 hours compared to those undergoing VH with general anesthesia, their postoperative analgesic requirements were similar.

Physiological and chaos effect on dynamics of neurological disorder with memory effect of fractional operator: A mathematical study.

BACKGROUND AND OBJECTIVE: To study the dynamical system, it is necessary to formulate the mathematical model to understand the dynamics of various diseases that are spread worldwide. The main objective of our work is to examine neurological disorders by early detection and treatment by taking asymptomatic. The central nervous system (CNS) is impacted by the prevalent neurological condition known as multiple sclerosis (MS), which can result in lesions that spread across time and place. It is widely acknowledged that multiple sclerosis (MS) is an unpredictable disease that can cause lifelong damage to the brain, spinal cord, and optic nerves. The use of integral operators and fractional order (FO) derivatives in mathematical models has become popular in the field of epidemiology. METHOD: The model consists of segments of healthy or barian brain cells, infected brain cells, and damaged brain cells as a result of immunological or viral effectors with novel fractal fractional operator in sight Mittag Leffler function. The stability analysis, positivity, boundedness, existence, and uniqueness are treated for a proposed model with novel fractional operators. RESULTS: Model is verified the local and global with the Lyapunov function. Chaos Control will use the regulate for linear responses approach to bring the system to stabilize according to its points of equilibrium so that solutions are bounded in the feasible domain. To ensure the existence and uniqueness of the solutions to the suggested model, it makes use of Banach's fixed point and the Leray Schauder nonlinear alternative theorem. For numerical simulation and results the steps Lagrange interpolation method at different fractional order values and the outcomes are compared with those obtained using the well-known FFM method. CONCLUSION: Overall, by offering a mathematical model that can be used to replicate and examine the behavior of disease models, this research advances our understanding of the course and recurrence of disease. Such type of investigation will be useful to investigate the spread of disease as well as helpful in developing control strategies from our justified outcomes.

Autoimmunity Against Surfactant Protein B Is Associated with Pneumonitis During Checkpoint Blockade.

RATIONALE: Immune checkpoint inhibitor-related pneumonitis is a serious autoimmune event affecting up to 20% of patients with non-small cell lung cancer, yet the factors underpinning its development in some patients and not others are poorly understood. OBJECTIVES: To investigate the role of autoantibodies and autoreactive T cells against surfactant-related proteins in the development of pneumonitis. METHODS: The study cohort consisted of non-small cell lung cancer patients who gave blood samples before and during immune checkpoint inhibitor treatment. Serum was used for proteomics analyses and to detect autoantibodies present during pneumonitis. T cell stimulation assays and single-cell RNA sequencing were performed to investigate the specificity and functionality of peripheral autoreactive T cells. The findings were confirmed in a validation cohort comprising patients with non-small cell lung cancer and patients with melanoma. MEASUREMENTS AND MAIN RESULTS: Across both cohorts, patients who developed pneumonitis had higher pre-treatment levels of immunoglobulin G autoantibodies targeting surfactant protein-B. At the onset of pneumonitis, these patients also exhibited higher frequencies of CD4+ interferon-gamma-positive surfactant protein B-specific T cells, and expanding T cell clonotypes recognizing this protein, accompanied by a pro-inflammatory serum proteomic profile. CONCLUSIONS: Our data suggest that the co-occurrence of surfactant protein-B-specific immunoglobulin G autoantibodies and CD4+ T cells is associated with the development of pneumonitis during ICI therapy. Pre-treatment levels of these antibodies may represent a potential biomarker for elevated risk of developing pneumonitis and on-treatment levels may provide a diagnostic aid. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Comparison of Two Presbyopia-Correcting Trifocal Intraocular Lenses: A Prospective Study.

Objectives: To evaluate the clinical results of a new trifocal intraocular lens (IOL) with sinusoidal design by comparing with a traditional trifocal IOL. Materials and Methods: A total of 79 patients undergoing uneventful microincisional cataract surgery with bilateral implantation of one of two types of trifocal IOLs, the Acriva Trinova IOL (VSY) or Acrysof IQ PanOptix IOL (Alcon), were enrolled in this prospective study. Visual and refractive outcomes, contrast sensitivity (CS), and defocus curve were assessed at 3 months after surgery. Patient satisfaction and incidence of photic phenomena were also evaluated. Results: The number of patients/eyes were 48/96 in the Trinova group and 31/62 in the PanOptix group. There were no significant differences between the groups for monocular and binocular corrected/uncorrected distance or intermediate (at 60 cm) and near visual acuities (VA) postoperatively. The Trinova group had statistically significantly better intermediate VA at 80 cm than the PanOptix group (p<0.05). The CS results of both groups were within the normal limits. In the binocular defocus curve of both IOLs, we observed a peak of good VA at 0.0 diopters defocus and a useful wide range for intermediate distances. The incidence of photic phenomena in the Trinova group was lower at postoperative 1 month (p<0.05) but this difference disappeared at 3 months. A total of 47 patients (97.9%) in the Trinova group and 30 patients (96.7%) in the PanOptix group stated that they would recommend the same IOL. Conclusion: Both trifocal IOLs provide good visual quality outcomes and patient satisfaction.

Hysteroscopic management of complete septate uterus with septate cervix, and longitudinal vaginal septum: a case report.

Mullerian anomalies occur as a result of errors during embryogenesis. The estimated incidence of these anomalies is around 1% in the general population and 3% in women complaining of suboptimal reproductive outcomes and infertility. A 21-year-old female patient was referred to our hospital due to primary infertility for 18 months. After a proper history, physical examination and further diagnostic steps, including ultrasound and magnetic resonance imaging, a diagnosis of complete septate uterus with septate cervix and longitudinal vaginal septum was made. Following hysteroscopic resection of all the septa and two cycles of ovulation induction, the patient was able to conceive. However, she needed cervical cerclage later due to cervical insufficiency. The baby was delivered at term and was healthy. A uterine, cervical and longitudinal vaginal septum is a unique entity of Mullerian anomalies. Resection of all septa through a hysteroscopic approach resulted in a good outcome for our patient.

Long-term outcomes following double kissing crush or mini-culotte stenting for complex coronary bifurcation lesions: the EVOLUTE-CRUSH IV study.

BACKGROUND: This study aimed to evaluate the long-term outcomes of double kissing crush stenting (DKC) and mini-culotte technique (MCT) in patients with complex bifurcation lesions. METHODS: This retrospective study enrolled 236 patients who underwent percutaneous coronary intervention (PCI) for complex coronary bifurcation disease between January 2014 and November 2022. The primary endpoint was target lesion failure (TLF), defined as the combination of cardiac death, myocardial infarction (MI), or clinically driven target lesion revascularization (TLR). The secondary endpoint was major cardiovascular and cerebral events (MACCE) including all-cause death, MI, TLR, stroke, or stent thrombosis. The regression models were adjusted by applying the inverse probability weighted (IPW) approach to reduce treatment selection bias. RESULTS: The initial management strategy was DKC in 154 (65.3%) patients and MCT in 82 (34.7%) patients (male: 194 [82.2%], mean age: 60.85 ± 10.86 years). The SYNTAX scores were similar in both groups. The rates of long-term TLF and MACCE rates were 17.4% and 20%, respectively. The rate of TLF (26.8% vs. 12.3%, p = 0.005) was higher in patients treated with MCT than those treated with the DKC technique, mainly driven by more frequent TLR (15.9% vs. 7.1%, p = 0.035). The long-term TLF and MACCE rates were notably lower in the DKC group compared to the others: adjusted hazard ratio (HR; IPW): 0.407, p = 0.009 for TLF, and adjusted HR(IPW): 0.391 [95% CI: 0.209-0.730], p = 0.003 for MACCE. CONCLUSION: At long-term follow-up, the rates of TLF and MACCE were 17.4% and 20%, respectively. However, long-term TLF was significantly higher in patients treated with MCT than those treated with the DKC technique, primarily due to a more frequent occurrence of clinically driven TLR.

Intra- and post-operative outcomes of the Enhanced Recovery after Surgery (ERAS) Program in laparoscopic hysterectomy.

PURPOSE: To investigate the effect of the Enhanced Recovery After Surgery (ERAS) protocol on perioperative and post-operative outcomes in laparoscopic hysterectomies (LHs) performed for benign gynecological diseases. METHODS: This prospective study was conducted with randomized 100 participants who underwent LH between 1 January and 31 December, 2022. A standard care protocol was applied to 50 participants (Group 1, control) and the ERAS protocol to the other 50 (Group 2, study). Length of hospitalization was compared between the groups as the primary outcome, and the duration of the operation, the amount of bleeding, post-operative nausea-vomiting, gas discharge time, visual analog scale (VAS) pain scores, and complications as the secondary outcomes. RESULTS: No statistically significant difference was seen between the groups in terms of sociodemographic characteristics, medical history, operation indications, surgical procedures applied in addition to hysterectomy, operative time, pre-operative and post-operative hemoglobin levels, amount of bleeding, or drain use (p > 0.05). However, a statistically significant difference was observed in terms of nausea (60% vs. 26%, p = 0.001), vomiting (28% vs. 10%, p = 0.040), duration of gassing (17.74 ± 6.77 vs. 14.20 ± 7.05 h, p = 0.012), length of hospitalization (41.78 ± 12.17 vs. 34.12 ± 10.90 h, p = 0.001), analgesic requirements (4.62 ± 1.36 vs. 3.34 ± 1.27 h, p < 0.001), or VAS scores at the 1st (5.86 ± 1.21 vs. 4.58 ± 1.31, p < 0.001), 6th (5.16 ± 1.12 vs. 4.04 ± 1.08, p < 0.001), 12th (4.72 ± 1.12 vs. 3.48 ± 1.12, p < 0.001), 18th (4.48 ± 1.21 vs. 3.24 ± 1.34, p < 0.001), and 24th (4.08 ± 1.29 vs. 3.01 ± 1.30, p < 0.001) hours. CONCLUSION: The findings of this study show that the ERAS protocol has a positive effect on peri- and post-operative outcomes in LH. Further prospective studies are now needed to confirm the validity of the results.

Breakthrough electroneutron multi-response miniature dosimetry/spectrometry in medical accelerator.

Breakthrough multi-response miniature dosimetry/spectrometry of electroneutrons (EN) was made on surface and in-depths of whole-body polyethylene phantom under 10 cm × 10 cm electron beam of 20 MV Varian Clinac 2100C electron medical accelerator commonly applied for prostate treatment. While dosimetry/spectrometry of photoneutrons (PN) has been well characterized for decades, those of ENs lagged behind due to very low EN reaction cross section and lack of sensitive neutron dosimeters/spectrometers meeting neutron dosimetry requirements. Recently, Sohrabi "miniature neutron dosimeter/spectrometer" and "Stripe polycarbonate dosimeter" have broken this barrier and determined seven EN ambient dose equivalent (ENDE) (µSv.Gy-1) responses from electron beam and from albedo ENs including beam thermal (21 ± 2.63), albedo thermal (43 ± 3.70), total thermal (64 ± 6.33), total epithermal (32 ± 3.90), total fast (112.00), total thermal + epithermal (l96 ± 10), and total thermal + epithermal + fast (208 ± 10.23) ENs. Having seven ENDE responses of this study and seven PNDE responses of previous study with the same accelerator obtained at identical conditions by the same principle author provided the opportunity to compare the two sets of responses. The PNDE (µSv.Gy-1) responses have comparatively higher values and 22.60 times at isocenter which provide for the first time breakthrough ENDE responses not yet reported in any studies before worldwide.

Early Diagnosis of Cardiovascular Diseases in the Era of Artificial Intelligence: An In-Depth Review.

Cardiovascular diseases (CVDs) are significant health issues that result in high death rates globally. Early detection of cardiovascular events may lower the occurrence of acute myocardial infarction and reduce death rates in people with CVDs. Traditional data analysis is inadequate for managing multidimensional data related to the risk prediction of CVDs, heart attacks, medical image interpretations, therapeutic decision-making, and disease prognosis due to the complex pathological mechanisms and multiple factors involved. Artificial intelligence (AI) is a technology that utilizes advanced computer algorithms to extract information from large databases, and it has been integrated into the medical industry. AI methods have shown the ability to speed up the advancement of diagnosing and treating CVDs such as heart failure, atrial fibrillation, valvular heart disease, hypertrophic cardiomyopathy, congenital heart disease, and more. In clinical settings, AI has shown usefulness in diagnosing cardiovascular illness, improving the efficiency of supporting tools, stratifying and categorizing diseases, and predicting outcomes. Advanced AI algorithms have been intricately designed to analyze intricate relationships within extensive healthcare data, enabling them to tackle more intricate jobs compared to conventional approaches.

Effect of different salinity on seed germination, growth parameters and biochemical contents of pumpkin (Cucurbita pepo L.) seeds cultivars.

Soil and water salinity is an important limiting factor affecting yield and production levels in arid and semi-arid areas. Salt tolerance during germination is an important parameter that also affects the other plant development stages. In this respect, this study was designed to determine the responses of pumpkin seed varieties (Develi, Ürgüp, Hybrid) to different NaCl salinities. The study was carried out in 2022 in the laboratory of Biosystems Engineering Department of Erciyes University in randomized plots design with 3 replications. Experiments were conducted with 5 different water salinity. Germination percentage (GP), germination index (GI), mean germination time (MGT), seedling vigor index (SVI), ion leakage (Il), radicula length (RL) and plumule length (PL), root and shoot fresh and dry weights and some mineral composition (Na, K, Ca) were examined. Proline, antioxidant capacity, total phenolic and DPPH content were significantly affected by salinity. In scatter plot correlation analysis SVI a positive correlation was observed between GP (r2 = 0.774), GI (r2 = 0.745), RL (r2 = 0.929), FRW (r2 = 0.837), FSW (r2 = 0.836), DRW (r2 = 0.894), AC (r2 = 0.747), TP (r2 = 0.640) and DPPH (r2 = 0.635). It was determined that there were negative correlations between SVI and MGT (r2 = - 0.902), II (r2 = - 0.588), DSW (r2 = - 0.682) and PR (r2 = - 0.344). Present findings revealed that investigated parameters were significantly affected by increasing salinity levels. While Hybrid cultivar was the most affected by salinity, Develi cultivar was found to be resistant to saline conditions.

The relationship between sleep quality and chronotype differences and urticaria severity in patients with chronic spontaneous urticaria.

INTRODUCTION: Chronic spontaneous urticaria (CSU) is characterized by persistent or recurrent pruritic lesions that last more than 6 weeks. Patients with CSU may experience sleep disturbances, particularly due to itching. Biological rhythms (chronotypes) are categorized as morningness, intermediate, and eveningness types. This study evaluates the relationship between sleep quality, chronotype, and disease severity in CSU patients. METHODS: The study included 53 CSU patients and 50 healthy controls. A sociodemographic data form was completed, and the disease severity was determined utilizing the Urticaria Activity Score over 7 days (UAS7). The Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), and Pittsburgh Sleep Quality Index (PSQI) scales as well as the Morningness-Eveningness Scale (MEQ) were applied to the participants. RESULTS: The CSU group had a significantly higher body mass index (BMI) than that of the healthy control group. In terms of sleep and chronotype scales, compared to the control group, the CSU group had higher ISI scores as well as subscale scores on the PSQI subscales, with the exception of habitual sleep efficiency and total PSQI scores. There was no difference between MEQ scores. In the correlation analysis, the UAS7 and PSQI total scores were found to be correlated, whereas in the logistic regression analysis the estimated relative risk of BMI and PSQI total score for CSU was found to be 1.13 and 1.45, respectively. CONCLUSIONS: When dealing with CSU patients, it is necessary to conduct a sleep quality assessment as part of a holistic evaluation.

Real-World Data on Clinical Outcomes and Treatment Management of Advanced Melanoma Patients: Single-Center Study of a Tertiary Cancer Center in Switzerland.

BACKGROUND: Immune checkpoint inhibitors (ICIs) and BRAF/MEK inhibitors (BRAF/MEKi) have drastically changed the outcomes of advanced melanoma patients in both the resectable/adjuvant and unresectable/metastatic setting. In this follow-up analysis of real-world data, we aimed to investigate the clinical management and outcomes of advanced melanoma patients in a tertiary referral center in Switzerland approximately a decade after the introduction of ICIs and BRAF/MEKi into clinical use. Moreover, we aimed to compare the results with seminal phase 3 trials and to identify areas of high unmet clinical need. METHODS: This single-center retrospective cohort study analyzed the melanoma registry of the University Hospital Zurich, a tertiary cancer center in Switzerland, and included patients treated in the resectable/adjuvant (n = 331) or unresectable/metastatic setting (n = 375). RESULTS: In the resectable setting, adjuvant anti-PD1 or BRAF/MEKi showed a 3-year relapse-free survival (RFS) of 53% and 67.6%, respectively, and the overall median RFS was 50 months. Patients with lymph node plus in-transit metastases or with distant metastases prior to commencing adjuvant treatment had a significantly reduced overall survival (OS). In 10.9% of patients, the treatment was stopped due to toxicity, which did not affect RFS/OS, unless the duration of the treatment was <3 months. Following a relapse of the disease during the first adjuvant treatment, the median progression-free survival (PFS2) was only 6.6 months; outcomes were particularly poor for relapses that were unresectable (median PFS2 3.9 months) or occurred within the first 2 months (median PFS2 2.7 months). A second adjuvant treatment for patients with resectable relapses still showed efficacy (median RFS2 43.7 months). Elevated LDH levels in patients with an unresectable relapse was correlated with a strong reduction in OS2 (HR 9.84, p = 0.018). In the unresectable setting, first-line anti-PD1, anti-CTLA4/PD1 combination, or BRAF/MEKi showed a 5-year OS of 46.5%, 52.4%, and 49.2%, respectively. In a multivariate analysis, elevated LDH levels or the presence of brain metastases substantially shortened OS (HR > 1.78, p < 0.035). There was a non-significant trend for the improved survival of patients treated with anti-CTLA4/PD1 compared to anti-PD1 (HR 0.64, p = 0.15). After a progression on first-line therapy, the median OS2 was reduced to below two years. Elevated LDH (HR 4.65, p < 0.001) levels and widespread disease with at least three metastatic sites, particularly bone metastases (HR 2.62, p = 0.026), affected OS2. CONCLUSION: Our study offers real-world insights into the clinical management, treatment patterns, and outcomes of advanced melanoma patients in both the adjuvant and unresectable setting. Early relapses in patients undergoing adjuvant treatment pose a particular challenge but these patients are generally excluded from first-line trials. The approved first-line metastatic treatments are highly effective in the real-world setting with 5-year OS rates around 50%. However, outcomes remain poor for patients with brain metastases or who fail first-line treatment.

Do Smartphone Addiction and Self-Regulation Failures Affect Students' Academic Life Satisfaction? The Role of Students' Mind Wandering and Cognitive Failures.

Purpose: The purpose of this study is to investigate how smartphone addiction and self-regulation failure influence students' academic life satisfaction considering the impacts of students' mind wandering and cognitive failures. It also sought to look at how students' minds wander, and cognitive failures are affected by smartphone addiction and self-regulation failure among university students. Methods: The WarpPLS-SEM software was used to analyze the research data retrieved from a sample of 950 undergraduate students from universities in Egypt and the Kingdom of Saudi Arabia (KSA). Results: In both countries, the findings revealed that students' smartphone addiction and self-regulation failures negatively affect students' academic life satisfaction and positively affect students' mind wandering and cognitive failures. Additionally, smartphone addiction is positively related to failures of students' self-regulation. Besides the negative influences of students' cognitive failures on their academic life satisfaction, cognitive failures mediated negatively the relationship between mind wandering and students' academic life satisfaction. Finally, students' mind wandering mediated the relationship between smartphone addiction, self-regulation failure, and academic life satisfaction. Discussion: The study introduces fresh insights into the study variables that can be used to expand the literature on academic life satisfaction. The study provides theoretical and practical contributions to students, educators, and policymakers of education.

Medieval DNA from Soqotra points to Eurasian origins of an isolated population at the crossroads of Africa and Arabia.

Soqotra, an island situated at the mouth of the Gulf of Aden in the northwest Indian Ocean between Africa and Arabia, is home to ~60,000 people subsisting through fishing and semi-nomadic pastoralism who speak a Modern South Arabian language. Most of what is known about Soqotri history derives from writings of foreign travellers who provided little detail about local people, and the geographic origins and genetic affinities of early Soqotri people has not yet been investigated directly. Here we report genome-wide data from 39 individuals who lived between ~650 and 1750 CE at six locations across the island and document strong genetic connections between Soqotra and the similarly isolated Hadramawt region of coastal South Arabia that likely reflects a source for the peopling of Soqotra. Medieval Soqotri can be modelled as deriving ~86% of their ancestry from a population such as that found in the Hadramawt today, with the remaining ~14% best proxied by an Iranian-related source with up to 2% ancestry from the Indian sub-continent, possibly reflecting genetic exchanges that occurred along with archaeologically documented trade from these regions. In contrast to all other genotyped populations of the Arabian Peninsula, genome-level analysis of the medieval Soqotri is consistent with no sub-Saharan African admixture dating to the Holocene. The deep ancestry of people from medieval Soqotra and the Hadramawt is also unique in deriving less from early Holocene Levantine farmers and more from groups such as Late Pleistocene hunter-gatherers from the Levant (Natufians) than other mainland Arabians. This attests to migrations by early farmers having less impact in southernmost Arabia and Soqotra and provides compelling evidence that there has not been complete population replacement between the Pleistocene and Holocene throughout the Arabian Peninsula. Medieval Soqotra harboured a small population that showed qualitatively different marriage practices from modern Soqotri, with first-cousin unions occurring significantly less frequently than today.

Relationship between Traumatic Experiences, Circadian Preference and ADHD Symptoms in Adolescents with ADHD Residing in Institutional Care: A Controlled Study.

Circadian preference, describes biological and behavioural characteristics that influence the ability to plan daily activities according to optimal waking times. It is divided into three main categories: morning, evening and intermediate. In particular, the evening chronotype is associated with conditions such as Attention Deficit Hyperactivity Disorder (ADHD) and Post Traumatic Stress Disorder (PTSD). This study was conducted in three groups aged 14-18 years: The first group consisted of 34 adolescents diagnosed with ADHD who had been in institutional care for at least two years and had not used medication in the last six months. The second group included 29 adolescents with ADHD living with their families who had not used medication in the last six months. The third control group consisted of 32 healthy adolescents. The study utilized sociodemographic data forms, the Turgay DSM-IV Disruptive Behavior Disorders Rating Scale (T-DSM-IV-S) to measure ADHD symptoms, the Childhood Chronotype Questionnaire (CCQ), and the Childhood Trauma Questionnaire (CTQ). In institutionalized adolescents with diagnosed ADHD, ADHD and disruptive behavior symptoms were more severe. Increased trauma scores were associated with higher ADHD and disruptive behaviour symptom severity and evening chronotype. In the conducted mediation analysis, evening chronotype was identified as a full mediator in the relationship between trauma symptoms and ADHD symptoms, while it was determined as a partial mediator in the relationship between trauma symptoms and PTSD symptoms. In conclusion, traumatic experiences in institutionalized adolescents with diagnosed ADHD may exacerbate ADHD and disruptive behavior symptoms. Evening chronotype is associated with ADHD and disruptive behavior symptoms, and therefore, the chronotypes of these adolescents should be assessed. Chronotherapeutic interventions may assist in reducing inattention, hyperactivity, and behavioral problems.

Clinical correlations and impact of conjunctivochalasis in soft contact lens wearers.

PURPOSE: To evaluate the correlation between clinical tests, patient symptoms, and conjunctivochalasis in contact lens wearers and non-wearers. METHODS: This study comprised 40 eyes of 40 current soft contact lens users and 40 eyes of 40 control subjects. Cross-sectional areas of conjunctivochalasis at three locations (nasal, central, temporal) during straight and downward gazes were determined using anterior segment optical coherence tomography in all participants. Tear film break up time test and Schirmer test with anesthesia were performed and for evaluation of symptoms, the participants completed ocular surface disease index questionnaire. RESULTS: During straight gaze, the mean cross-sectional areas of conjunctivochalasis were 0.0112 ± 0.009 and 0.006 ± 0.005 mm2 at nasal, 0.0096 ± 0.007 and 0.002 ± 0.004 mm2 at central, 0.0176 ± 0.014 and 0.008 ± 0.009 mm2 at temporal in contact lens and control groups, respectively. Regardless of location and gaze direction, the mean cross-sectional conjunctivachalasis areas of the contact lens group were significantly higher than those of the controls (all, p < 0.05). Significant positive correlations between ocular surface disease index score and measured conjunctivachalasis areas (in all sites) during straight gaze and downward gaze were observed in the contact lens group (all, p < 0.05 and r > 0.450). CONCLUSION: Wearing soft contact lenses is associated with increased conjunctivochalasis areas. Anterior segment optical coherence tomography determined conjunctivochalasis area is an objective clinical measurement value that is positively correlated with patients' symptoms in soft contact lens wearers.