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Background: Intestinal ultrasound (IUS) is used to assess disease activity, complications, and treatment follow-up in Crohn's disease (CD). Less is known about the association of disease activity on IUS with the risk of future disease relapse during biologically sustained clinical remission in CD., Aim: The study aimed to investigate the association between IUS activity parameters and subsequent therapy failure in asymptomatic biologically treated patients with CD., Methods: A retrospective cohort study examined the association between IUS parameters and forthcoming therapy failure (drug discontinuation, dose escalation, corticosteroid use, hospitalization, or surgery) in CD patients on biological therapy in remission., Results: A total of 57 patients with ileal (65%) or ileocolonic (35%) CD on biological therapy were included in the study. Therapy failure occurred in 50.8% [defined as need for dose escalation (31%), drug discontinuation (51.7%), steroid use (10.5%), and hospitalization (6.8%)] during a median follow-up of 5 (SD + 9.5) months after IUS. On univariate analysis, a bowel wall thickness (BWT) of 2.5 vs. 4 mm (P = 0.005), the existence of an enlarged lymph node (P = 0.02), and the loss of bowel wall stratification (P = 0.01) were correlated with therapy failure. On multivariable analysis, only BWT ≥ 4 mm was associated with the risk of future treatment failure (hazard ratio, 3.7; 95% confidence interval, 0.6-15; P = 0.02)., Conclusion: Our findings suggest that BWT ≥4 mm during clinical remission is associated with subsequent treatment failure in patients with CD treated with biologics. Our results support the use of IUS for monitoring CD during remission and may point to a novel threshold for predicting disease reactivation., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Major Depressive Disorder (MDD) is a leading cause of disability and results in excessive utilization of healthcare resources worldwide. The Middle East and North Africa (MENA) region shows a high prevalence of depressive disorders. Generalized Anxiety Disorder (GAD) and MDD have the highest rate of comorbidity of all mood and anxiety disorders, ranging from 40 to 98% in drug studies. Comorbid GAD results in more significant impairment in MDD and increases the severity of symptoms. Although several clinical trials supported the safety and effectiveness of vortioxetine, no data regarding these aspects has been revealed in the MENA region. This study aimed to assess the safety and efficacy of vortioxetine in patients with comorbid GAD in the United Arab Emirates (UAE)., Method: In a multicenter observational study, 118 patients with confirmed anxiety and depressive disorders were evaluated over four visits (baseline visit, two weeks, four weeks, and eight weeks) using MADRS and HAM-A scales to assess depression and anxiety severity, respectively by calculating mean change and the percent using Kendall's W test., Results: A significant mean difference in MADRS score was observed, with a gradual decrease of mean MADRS total scores over the assessment weeks (p < 0.001) as well as in HAM-A scores, from severe to moderate-severe anxiety through the four visits (p < 0.001). Furthermore, only one case was reported as a serious side effect. Nausea and insomnia were the most predominant side effects reported among the studied population., Conclusion: Vortioxetine was found effective and safe among patients with MDD and comorbid GAD., (© 2024. The Author(s).)

Nivolumab, a monoclonal antibody approved in 2014 as an immune checkpoint inhibitor, offers benefits in cancer treatment but can cause serious neurological complications, including multifocal disseminated necrotizing leukoencephalopathy. We report a case of severe central nervous system toxicity in a 13-year-old boy with Hodgkin lymphoma who was treated with nivolumab following an inadequate response to multiple lines of chemotherapy. After six cycles of nivolumab, the patient developed multifocal disseminated necrotizing leukoencephalopathy, presenting with altered mental status, seizures, and neurological deficits with magnetic resonance imaging (MRI) findings of extensive white matter involvement, rendering him completely disabled. This case highlights the potential for disabling neurological complications associated with immune checkpoint inhibitors, emphasizing the importance of early detection through regular neurological assessment and MRI surveillance. The case also underscores the need for careful patient selection and monitoring when using nivolumab to mitigate the risk of severe central nervous system toxicity.

Introduction: ASPS is a rare, soft tissue tumor which represents 0.2-1 % of soft tissue sarcomas. A characteristic nonreciprocal translocation is found in nearly all cases. The resulting ASPSCR1-TFE3 fusion gene is postulated to be involved in the pathogenesis of this tumor., Case Report: 29 years-old female presented with abdominal pain for few months. MRI and CT revealed a large necrotic abdominopelvic mass, which is extra-uterine, extra-ovarian, and peritoneal nodules. Exploratory laparotomy revealed a large mass arising from the distal part of the descending colon involving the mesentery and the surrounding peritoneum. She underwent left colectomy with primary anastomosis, and resection of the involved adjacent peritoneal and mesenteric surface nodules. Histopathology revealed ASPS involving the outer serosal layer of the large bowel wall negative margins. It also involved the resected mesenteric fat, greater omentum, and peritoneum. No further treatment was received as the patient traveled to home country., Discussion: The treatment of early-stage ASPS involves radical surgical excision of the primary tumor. Traditionally, patients with advanced ASPS have limited therapeutic options because of the resistance of the tumor to conventional cytotoxic chemotherapy, however, it is a targetable sarcoma. The response rate of metastatic ASPS to targeted therapy is clinically meaningful, and comparable to that of first-line chemotherapy. Most patients who received targeted therapy achieved disease control. Patients who had refractory or progressive disease to one targeted agent demonstrated a response to other agents. More randomized trials are warranted to expand treatment options and compare them to standard care regimens., Conclusion: In conclusion, while radical surgical excision remains crucial for early-stage ASPS, the landscape for advanced cases is evolving with targeted therapies showing promising results. However, further randomized trials are necessary to broaden the treatment options available and to evaluate these new therapies against existing standard care regimens. This ongoing research is vital to improving outcomes for patients with ASPS and tailoring more effective treatment strategies., Competing Interests: Conflict of interest statement I declare that this manuscript is original and has not been published before. It is not currently being considered for publication elsewhere. I have no conflicts of interest to disclose,, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Kaposi sarcoma (KS) is an angioproliferative neoplasm that affects the skin and lymph nodes. Human herpesvirus-8 (HHV-8) triggers KS by infecting the endothelium and inducing angiogenesis through the production of vascular endothelial growth factors and cytokines. KS is characterized by purplish or hyperpigmented plaques involving the skin and mucous membranes, and visceral involvement is very rare. Pulmonary KS (PKS) is an exceedingly rare visceral manifestation of KS and has a poor prognosis. PKS often presents with cough, hemoptysis, pleuritic chest pain, fever, and weight loss. In this case series, we share our experience in diagnosing and treating two patients with PKS. We also provide a concise review of the epidemiology, signs and symptoms, diagnosis, and management of this rare condition., Competing Interests: None to declare., (Copyright 2024, Pelidis et al.)

Background: Advanced phase Philadelphia chromosome-positive myeloid disease-consisting of chronic myeloid leukaemia in the myeloid blast phase and in the accelerated phase, and Philadelphia chromosome-positive acute myeloid leukaemia-is associated with poor outcomes. Although previous studies have suggested the benefit of chemotherapy and BCR::ABL1 tyrosine kinase inhibitor combinations, the optimal regimen is uncertain and prospective studies for this rare group of diseases are scant. Preclinical and retrospective clinical data suggest possible synergy between the BCL-2 inhibitor venetoclax and BCR::ABL1 tyrosine kinase inhibitors. We therefore aimed to design a study to evaluate the safety and activity of a novel combination of decitabine, venetoclax, and the third-generation BCR::ABL1 tyrosine kinase inhibitor ponatinib in advanced phase Philadelphia chromosome-positive myeloid diseases., Methods: For this phase 2 study, patients aged 18 years or older with previously untreated or relapsed or refractory myeloid chronic myeloid leukaemia-blast phase, chronic myeloid leukaemia-accelerated phase, or advanced phase Philadelphia chromosome-positive acute myeloid leukaemia, and an Eastern Cooperative Oncology Group performance status of 0-3 were eligible. Patients were eligible regardless of the number of previous lines of therapy received or previous receipt of ponatinib. Cycle 1 (induction) consisted of a 7-day lead-in of ponatinib 45 mg orally daily (days 1-7), followed by combination therapy with decitabine 20 mg/m 2 intravenously on days 8-12, venetoclax orally daily with ramp-up to a maximum dose of 400 mg on days 8-28, and ponatinib 45 mg orally daily on days 8-28. Cycles 2-24 consisted of decitabine 20 mg/m 2 intravenously on days 1-5, venetoclax orally 400 mg on days 1-21, and ponatinib orally daily on days 1-28. Response-based dosing of ponatinib was implemented in consolidation cycles, with reduction to 30 mg daily in patients who reached complete remission or complete remission with an incomplete haematological recovery and a reduction to 15 mg daily in patients with undetectable BCR::ABL1 transcripts. The primary endpoint was the composite rate of complete remission or complete remission with incomplete haematological recovery in the intention-to-treat population. Safety was assessed in the intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT04188405) and is still ongoing., Results: Between July 12, 2020, and July 8, 2023, 20 patients were treated (14 with chronic myeloid leukaemia-blast phase, four with chronic myeloid leukaemia-accelerated phase, and two with advanced phase Philadelphia chromosome-positive acute myeloid leukaemia). The median age was 43 years (IQR 32-58); 13 (65%) patients were male and seven (35%) were female; and 12 (60%) were White, three (15%) were Hispanic, four (20%) were Black, and one (5%) was Asian. 12 (60%) patients had received 2 or more previous BCR::ABL1 tyrosine kinase inhibitors, and 14 (70%) patients had at least one high-risk additional chromosomal abnormality or complex karyotype. The median duration of follow-up was 21·2 months (IQR 14·1-24·2). The complete remission or complete remission with an incomplete haematological recovery rate was 50% (10 of 20 patients); complete remission in one [5%] patient and complete remission with incomplete haematological recovery in nine [45%]). An additional six (30%) patients had a morphologic leukaemia-free state. The most common grade 3-4 non-haematological adverse events were febrile neutropenia in eight (40%) patients, infection in six (30%), and alanine or aspartate transaminase elevation in five (25%). Eight (40%) patients had at least one cardiovascular event of any grade. There were three on-study deaths, none of which was considered related to the study treatment and all from infections in the setting of refractory leukaemia., Interpretation: The combination of decitabine, venetoclax, and ponatinib is safe and shows promising activity in patients with advanced phase chronic myeloid leukaemia, including those with multiple previous therapies or high-risk disease features. Further studies evaluating chemotherapy and venetoclax-based combination strategies using newer-generation BCR::ABL1 tyrosine kinase inhibitors are warranted., Funding: Takeda Oncology, the National Institutes of Health, and the National Cancer Institute Cancer Center., Competing Interests: Declaration of interests NJS has received consulting fees from Pfizer, GlaxoSmithKline, NKARTA, Autolus, and Sanofi; research funding from Takeda Oncology, Astellas Pharma, Xencor, Stemline Therapeutics, and NextCure; and honoraria from Adaptive Biotechnologies, Novartis, Amgen, Takeda Oncology, Pfizer, Astellas Pharma, Sanofi, and BeiGene. EJ has received consulting fees and research funding from AbbVie, Adaptive Biotechnologies, Amgen, Ascentage, ASTX Pharmaceuticals, AstraZeneca, Autolus, BMS, Genenenctech, Hikma, Kite, Novartis, Pfizer, Takeda Oncology, and Jazz. HA has received consulting fees from Molecular Partners; research funding from Genentech, GlaxoSmithKline, and EBD-300; and honoraria from Illumina. MK has received consulting fees from AbbVie, AstraZeneca, Auxenion, Bakx, Boehringer, Dark Blue Therapeutics, F Hoffman-La Roche, Genentech, Gilead, Janssen, Legend, MEI Pharma, Redona, Sanofi, Sellas, Stemline, and Vincerx; research funding from AbbVie, Allogene, AstraZeneca, Genentech, Gilead, ImmunoGen, MEI Pharma, Precision, Rafael, Sanofi, and Stemline; honoraria from AbbVie, Baxk Therapeutics, Genentech, and Stemline Therapeutics; stock options in Reata Pharamceuticals; and holds patents with Novartis, Eli Lilly, and Reata Pharmaceutical. HK has received research funding from AbbVie, Amgen, Ascentage, BMS, Daiichi-Sankyo, Immunogen, and Novartis and honoraria from AbbVie, Amgen, Ascentage, Ipsen Biopharmaceuticals, KAHR Medical, Novartis, Pfizer, Shenzhen Target Rx, Stemline, and Takeda Oncology. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Aim: To assess the performance of 18 F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) versus 99m Tc MDP bone scan in assessment of metastatic osseous disease in breast cancer patients in relation to serum markers., Material and Methods: We reviewed PET/CT studies and bone scans for 37 patients (mean age of 55.38 ± 13.08 years) with metastatic breast cancer to bone. To assess metastatic osseous burden, we used semiquantitative scores derived from PET/CT (PMS) and bone scans (BMS). We used McNemar test to compare lesion detection between both modalities and receiver operator characteristic analysis to define the cutoff value of serum CA 15-3 that best predicts additional value for PET/CT over bone scan., Results: In 13 patients (35.1%), more lesions or higher-intensity lesions were detected on PET/CT, while only 4 patients (10.8%) had more prominent lesions on bone scans ( P = 0.049). Additional lesions seen on PET/CT are predominantly osteolytic or medullary (early phase). Most lesions with higher uptake on bone scans appear sclerotic (late phase). CA 15-3 was positively correlated to PMS ( r = 0.386; P = 0.018) but not to BMS ( r = -0.027; P = 0.874). However, serum alkaline phosphatase was positively correlated to both PMS ( r = 0.389; P = 0.017) and BMS ( r = 0.363; P = 0.027). CA 15-3 value of >47 U/ml best predicted additional findings on PET/CT compared to bone scans (area under the curve = 0.708; P = 0.0261)., Conclusion: FDG PET/CT detects metastatic osseous lesions during an earlier phase. A higher CA 15-3 predicts a higher metastatic burden on PET/CT but not on bone scan. Bone scans are less specific, likely by missing early lesions and detecting persistent uptake in healing sclerotic lesions., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Context: Contrast-enhanced ultrasound (CEUS) is a cost-effective radiation-free diagnostic method that can be used for renal tumor postoperative visualization after ablative treatment., Objective: To assess CEUS diagnostic accuracy comparing with CT and MRI as a follow-up method in short-term and long-term postoperative periods after renal tumor ablation., Materials and Methods: A systematic review and meta-analysis were performed in Scopus and Medline databases using the query "(kidney OR rena* OR RCC) AND (ablation OR RFA OR MWA OR cryo*) AND CEUS". The endpoint of the study was the evaluation of the overall accuracy of CEUS., Results: Twelve trials were included in the review. With CT or MRI as a reference, for a short-term group (< 6 weeks after ablation) pooled sensitivity was 90.2%, I 2  = 0%; pooled specificity was 99.3%, I 2  = 0%; pooled NPV was 98.6%, I 2  = 0%; pooled PPV was 94.6%, I 2  = 0%; the AUC on the SROC curve was 0.971. For the long-term group (> 6 weeks after ablation), pooled sensitivity was 95.3%, I 2  = 0%; pooled specificity was 97.6%, I 2  = 0%; PPV was 74.2%, I 2  = 4%; NPV was 99.4%, I 2  = 5%; AUC = 0.93., Conclusion: CEUS has high sensitivity and specificity in ruling out the presence of local recurrence after renal tumor ablation with a higher risk of false-positive results within follow-up > 6 weeks compared with that for CT or MRI. Further studies with a unified protocol and morphological control of local renal tumor recurrence after ablation are needed., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Androgen deprivation therapy (ADT) in prostate cancer (PCa) has been associated with development of insulin resistance. However, the predominant site of insulin resistance remains unclear., Methods: The ADT & Metabolism Study was a single-center, 24-week, prospective observational study that enrolled ADT-naive men without diabetes who were starting ADT for at least 24 weeks (ADT group, n = 42). The control group comprised men without diabetes with prior history of PCa who were in remission after prostatectomy (non-ADT group, n = 23). Prevalent diabetes mellitus was excluded in both groups using all three laboratory criteria defined in the American Diabetes Association guidelines. All participants were eugonadal at enrollment. The primary outcome was to elucidate the predominant site of insulin resistance (liver or skeletal muscle). Secondary outcomes included assessments of body composition, and hepatic and intramyocellular fat. Outcomes were assessed at baseline, 12, and 24 weeks., Results: At 24 weeks, there was no change in hepatic (1.2; 95% confidence interval [CI], -2.10 to 4.43; p = .47) or skeletal muscle (-3.2; 95% CI, -7.07 to 0.66; p = .10) insulin resistance in the ADT group. No increase in hepatic or intramyocellular fat deposition or worsening of glucose was seen. These changes were mirrored by those observed in the non-ADT group. Men undergoing ADT gained 3.7 kg of fat mass., Conclusions: In men with PCa and no diabetes, 24 weeks of ADT did not change insulin resistance despite adverse body composition changes. These findings should be reassuring for treating physicians and for patients who are being considered for short-term ADT., (© 2024 American Cancer Society.)

The production of whey protein concentrates (WPC) from camel milk whey represents an effective approach to valorize this processing byproduct. These concentrates harbor active ingredients with significant bioactive properties. Camel WPC were spray-dried at inlet temperature of 170, 185 and 200°C, or ultrasonicated (US) for 5, 10, and 15 min, then freeze-dried to obtain fine powder. The effect of both treatments on protein degradation was studied by sodium dodecyl sulfate-PAGE and reverse-phase ultraperformance liquid chromatography techniques. Significantly Substantially enhanced protein degradation was observed after US treatment when compared with spray-drying (SPD). Both SPD and US treatments slightly enhanced the WPC samples' antioxidant activities. The US exposure for 15 min exhibited the highest 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) scavenging activity (12.12 mmol Trolox equivalent per gram). Moreover, US treatment for 10 min exhibited the highest in vitro antidiabetic properties (α-amylase and α-glucosidase inhibition), and dipeptidyl peptidase-IV inhibitory activity among all samples. In addition, the US for 10 min and SPD at 170°C showed the lowest median inhibitory concentration (IC 50 ) values for in vitro antihypercholesterolemic activities in terms of pancreatic lipase and cholesteryl esterase inhibition. Conclusively, these green techniques can be adapted in the preservation and processing of camel milk whey into active ingredients with high bioactive properties., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The current study investigated valorization of lignin nanoparticles (LNPs) and phenolic compounds loaded in chitosan (DLECNPs) extracted from date palm leaves into the soy protein isolate (SPI) biocomposite films. The mechanical, structural, barrier, physiochemical, thermal, optical, antioxidant, and antimicrobial properties of the formulated composite films were investigated. The findings showed that the incorporation of DLECNPs into the SPI films significantly improved the film's antioxidant properties by more than 3 times and showed antibacterial inhibition zone in the range of 10-15 mm against six pathogenic bacteria. Further, incorporating LNPs into SPI-DLECNPs films notably improved the mechanical properties from 4.32 MPa and 29.27 % tensile strength and elongation at break, respectively to 10.13 MPa and 54.94 %, the water vapor permeability from 7.38 g/Pa s m to 5.59 g/Pa s m, and the antibacterial inhibition zone from a range of 10.2 mm to 15.0-21.5 mm as well as making the films more heterogeneous and stronger than control SPI film. Moreover, LNPs changed the initial films' color from light yellow to dark red and reduced the films' transparency. The results indicated that LNPs reinforced SPI composite films showed significant improvements in several properties and thus can be used as a potential ingredient for formulation of biodegradable packaging films., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal conflict of interest that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Intrinsically disordered regions (IDRs) are highly enriched in the nucleolar proteome but their physiological role in ribosome assembly remains poorly understood. Our study reveals the functional plasticity of the extremely abundant lysine-rich IDRs of small nucleolar ribonucleoprotein particles (snoRNPs) from protists to mammalian cells. We show in Saccharomyces cerevisiae that the electrostatic properties of this lysine-rich IDR, the KKE/D domain, promote snoRNP accumulation in the vicinity of nascent rRNAs, facilitating their modification. Under stress conditions reducing the rate of ribosome assembly, they are essential for nucleolar compaction and sequestration of key early-acting ribosome biogenesis factors, including RNA polymerase I, owing to their self-interaction capacity in a latent, non-rRNA-associated state. We propose that such functional plasticity of these lysine-rich IDRs may represent an ancestral eukaryotic regulatory mechanism, explaining how nucleolar morphology is continuously adapted to rRNA production levels., (© 2024. The Author(s).)

Objective: Refugees are highly vulnerable to mental health disorders and head injuries. The primary aim of this study is to examine the impact of posttraumatic stress disorder (PTSD) and head injury on reactive and appetitive aggression in adult Syrian refugees in Lebanon., Method: A cross-sectional study was conducted targeting adult Arab United Nations High Commissioner for Refugees-registered Syrian refugees residing in Beirut and southern regions of Lebanon. Eligible refugees completed a battery of questionnaires including the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, fifth edition, the Trauma Events and Head Injury sections of the Harvard Trauma Questionnaire, the Buss-Perry Aggression Questionnaire, and the Appetitive Aggression Scale., Results: A total of 191 Syrian refugees participated in the study: 62.83% were females, and the mean age was 31.01 years ( SD = 10.98). The severity of PTSD (adjusted B = 0.18, 95% CI [0.05, 0.31], p = .006), having experienced at least one head injury trauma event (adjusted B = 10.20, 95% CI [1.61, 18.79], p = .020), and the severity of somatic symptoms (adjusted B = 0.71, 95% CI [0.23, 1.20], p = .004) were significant risk factors of reactive aggression. As for appetitive aggression, males (females adjusted OR [a OR ] = 0.06, 95% CI [0.02, 0.18], p < .001), younger individuals (a OR = 0.95, 95% CI [0.91, 0.99], p = .024), and higher severity of somatic symptoms (a OR = 1.20, 95% CI [1.09, 1.32], p < .001) were significant risk factors., Conclusions: PTSD and head injury are independent risk factors for reactive aggression but not appetitive aggression in Syrian refugees in Lebanon, while the severity of somatic symptoms is an independent risk factor for both reactive and appetitive aggression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Milk, a nutritious global important food commodity, serves as an excellent medium for microbial growth as well. The foodborne pathogen Staphylococcus aureus is a commensal member of human microflora that enters the food chain through poor hygienic practices and cross contamination and causes various clinical manifestations in humans. During this study, raw milk and swab samples (milker's hand, udder, towel, milking bucket, and farm floor) were collected from four middle-scale buffalo dairy farms. The results revealed S. aureus presence in 11.6% ( n = 56/448) bucket raw milk samples and 2.6% ( n = 12/448) udder raw milk samples. Contrarily, S. aureus prevalence was significantly higher in farm floors (100%, n = 84/84), towel (35.7%, n = 10/28), milking bucket (11.6%, n = 56/448), milker's hand (10.7%, n = 3/28), and udder swab samples (4.0%, n = 18/448). The chi-square test yielded p values of 0.000, 0.005, and 0.0011 for udder raw milk, udder swab, and milker's hand swab, respectively. The p values of the milking bucket ( p = 0.048) and farm floors ( p = 0.0183) confirmed their possible role in S. aureus cross contamination. Gene amplifications of nuclease and enterotoxin A indicate potential virulence of S. aureus isolates in collected samples. Antibiotic susceptibility testing revealed multidrug resistance in 44% ( n = 239) of S. aureus isolates with the highest resistance of 61% against penicillin. Resistance against ampicillin, streptomycin, and lincomycin was observed. Fewer S. aureus isolates were resistant to kanamycin and erythromycin, whereas the lowest number of resistant isolates was observed against chloramphenicol. A high prevalence of S. aureus in the farm environment and milking equipment suggested the cross contamination of potentially enterotoxin-producing and multidrug-resistant S. aureus to raw milk. Therefore, good hygiene practices should be enforced to avoid foodborne and zoonotic infections.

Nonketotic hyperglycemia chorea-ballismus (NKH-CB), a rare metabolic syndrome, arises as a secondary condition to hyperglycemia. It is marked by acute or subacute hemichorea-hemiballismus, hyperglycemic state, and unique reversible striatal abnormalities on neuroimaging. This case presents a 70-year-old Hispanic man with a significant medical history of cerebral vascular accidents, hypertension, bipolar disease, and uncontrolled type 2 diabetes mellitus. Notably, the patient was experiencing large-amplitude involuntary movements on his left side for the past 3 weeks. With resolution of hyperglycemia, the amplitude and frequency of the involuntary arm movements were absent. This case highlights the need for careful monitoring and tight control of blood glucose levels in patients with a history of diabetes, to prevent serious neurological complications such as NKH-CB syndrome. Prompt diagnosis through neurological evaluation, blood glucose level assessment, and neuroimaging techniques are critical in managing the symptoms effectively., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: The aim of our study was to assess the impact of sequential embryo transfer on pregnancy outcomes among patients with recurrent implantation failure (RIF)., Methods: We conducted a comprehensive search across various databases for eligible clinical trials from inception to January 2024. Randomized controlled trials (RCTs) were included if they compared sequential embryo transfer, comprising both cleavage-stage and blastocyst-stage embryos, with other transfer protocols in infertile women with repeated implantation failure. Meta-analysis was performed using Revman software. Our primary focus was on the ongoing pregnancy rate. Our secondary measures included rates of chemical pregnancies, clinical pregnancies, miscarriages, and multiple pregnancies., Results: Seven RCTs, encompassing 909 patients, met the inclusion criteria. Sequential embryo transfer demonstrated a significant increase in the ongoing pregnancy rate compared to the control group (OR = 2.28, 95% CI [1.46, 3.56], p = 0.003). Moreover, the sequential embryo transfer group exhibited notable improvements in chemical and clinical pregnancy rates. There were no statistically significant differences between the groups regarding multiple pregnancy and miscarriage rates (p > 0.05)., Conclusions: Sequential embryo transfer shows promise in enhancing pregnancy outcomes among RIF patients. However, additional trials are warranted to validate our findings., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Monkeypox virus (MPXV) is endemic in Western and Central Africa and, in May 2022, a clade IIb lineage (B.1) caused a global outbreak outside Africa, resulting in its detection in 116 countries/territories. To understand the global phylogenetics of MPXV, we analysed all available MPXV sequences, including 10,670 sequences from 65 countries collected between 1958 and 2024. Our analysis reveals high mobility of clade I viruses within Central Africa, sustained human-to-human transmission of clade IIb lineage A viruses within the Eastern Mediterranean region, and distinct mutational signatures that can distinguish sustained human-to-human from animal-to-animal transmission. Moreover, distinct clade I sequences from Sudan suggest local MPXV circulation in areas of Eastern Africa over the past four decades. Our study underscores the importance of genomic surveillance in tracking spatiotemporal dynamics of MXPV clades and the need to strengthen such surveillance, including in some parts of Eastern Africa., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

COVID-19-related critical and acute illness are associated with an increased risk of venous thromboembolism (VTE). These evidence-based recommendations of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other healthcare professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness, acute illness, and those being discharged from the hospital, who do not have suspected or confirmed VTE. ASH formed a multidisciplinary panel, including three patient representatives, and applied a conflicts of interest management policy to minimize potential bias. The Michael G. DeGroote Cochrane Canada and MacGRADE Centres at McMaster University supported the guideline development process, including performing systematic evidence reviews (up to June 2023). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess certainty of the evidence and make recommendations, which were subject to public comment. This is an executive summary of three updated recommendations that have been published which concludes the living phase of the guidelines. For critically ill patients with COVID-19, the panel issued conditional recommendations in favor of (a) prophylactic-intensity over therapeutic-intensity anticoagulation and (b) prophylactic-intensity over intermediate-intensity anticoagulation. For acutely ill patients with COVID-19, conditional recommendations were made in favor of (a) prophylactic-intensity over intermediate-intensity anticoagulation and (b) therapeutic-intensity over prophylactic-intensity anticoagulation. The panel also issued a conditional recommendation against the use of post-discharge extended pharmacologic thromboprophylaxis. These three conditional recommendations were made based on low or very low certainty in the evidence, underscoring the need for additional, high-quality randomized controlled trials in patients with COVID-19-related illness., (Copyright © 2024 American Society of Hematology.)

Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia. The current study aimed to investigate the potential of empagliflozin (EMPA) to protect against acetylcholine (ACh)/calcium chloride (CaCl 2 )-induced AF in rats and elucidate the possible underlying mechanism of action. Rats were randomly assigned to five groups, as follows: CTRL group: received 1 ml/kg isotonic saline; AF group: received 1 ml/kg induction mixture of ACh/CaCl 2 (60 µg ACh and 10 mg CaCl 2 per ml); EMPA group: received 30 mg/kg EMPA; AF + EMPA10 group: received the induction mixture concurrent with 10 mg/kg EMPA; AF + EMPA30 group: received the induction mixture concurrent with 30 mg/kg EMPA. Our results showed that EMPA administration inhibited the AF-related electrocardiographic abnormalities and decreased the serum brain natriuretic peptide levels. EMPA treatment maintained the cardiac redox balance, as indicated by reduced levels of the lipid peroxidation biomarker malonaldehyde while enhancing the antioxidant glutathione levels. Moreover, EMPA markedly repressed ACh/CaCl 2 -induced C-reactive protein, tumor necrosis factor, and interleukin-6 production. Interestingly, EMPA administration strongly suppressed cardiac transforming growth factor beta1, collagen type I, and alpha-smooth muscle actin expression levels in the AF rats. These results were consistent with our histopathological findings, which revealed the ameliorative effect of EMPA on AF-induced inflammatory and fibrotic lesions. Mechanistically, EMPA dose-dependently downregulated nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor (HIF)-1α expressions. Besides, it attenuated the pro-apoptotic active caspase-3 while augmenting the anti-apoptotic B-cell lymphoma 2 expressions. Furthermore, EMPA dose-dependently suppressed cardiac phosphatidylinositol 3-kinase (PI3K)/Akt signaling. In conclusion, this study demonstrates that EMPA intervention, within AF induction, protects against ACh/CaCl 2 -induced AF in rats, exerting powerful antioxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic effects. These effects are mainly mediated through the targeting of the NF-κB/HIF-1α regulatory axis in a dose-dependent manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tumor development necessitates immune escape through different mechanisms. To counteract these effects, the development of therapies targeting Immune Checkpoints (ICP) has generated interest as they have produced lasting objective responses in patients with advanced metastatic tumors. However, many tumors do not respond to inhibitors of ICP, necessitating to further study the underlying mechanisms of exhaustion. Vascular Endothelial Growth Factor a (VEGFa), a pro-angiogenic molecule secreted by tumors, was described to participate to tumor immune exhaustion by increasing ICP, justifying in part the use of an anti-VEGFa monoclonal antibody (mAb), bevacizumab, in patients. However, recent studies from our group have demonstrated that tumors can escape anti-VEGFa therapy through the secretion of soluble CD146 (sCD146). In this study, we show that both VEGFa and sCD146 cooperate to create an immunosuppressive microenvironment by increasing the expression of ICP. In addition, sCD146 favors pro-tumoral M2-type macrophages and induces the secretion of pro-inflammatory cytokines. An anti-sCD146 mAb reverses these effects and displays additive effects with anti-VEGFa antibody to eliminate tumors in a syngeneic murine model grafted with melanoma cells. Combining bevacizumab with mucizumab could thus be of major therapeutic interest to prevent immune escape in malignant melanoma and other CD146-positive tumors.

Among the numerous organochlorines (OCs) applied in the French West Indies (FWI), chlordecone (hydrated form C 10 Cl 10 O 2 H 2 ; CLD) still causes major environmental pollution nowadays. A recent report revealed the unexpected presence in FWI environment of transformation products (TPs) of CLD not routinely monitored due to a lack of commercial standards. Here, we present a method for surface waters and groundwaters to analyze CLD, its main TPs (hydroCLDs, chlordecol (CLDOH), 10-monohydroCLDOH and polychloroindenes) and other OCs. We developed an SPME-GC-SIM/MS method with a PDMS-DVB fiber. Since CLDOH-d commonly used as internal standard (IS) proved unsuitable, we synthesized several IS candidates, and finally identified 10-monohydro-5-methyl-chlordecol as a satisfactory IS for CLDOH and 10-monohydroCLDOH avoiding the use of 13 C-labelled analogue. LODs for CLD and its TPs varied from 0.3 to 10 ng/L, equal to or below LODs of the two laboratories, BRGM (the French geological survey) and LDA26 (one of the French Departmental Analytical Laboratories), requested in FWI pollution monitoring that used liquid-liquid extractions and advanced facilities (LLE-GC-MS/MS and LLE-LC-MS/MS methods, respectively). Then, we extended the multi-residue method to 30 OCs (CLD and its TPs, mirex, β-HCH, lindane, dieldrin, aldrin, HCB, hexachlorobutadiene, TCE, PCE) and applied it to 30 surface and ground waters from FWI. While CLD, 8- and 10-monohydroCLD, CLDOH, 10-monohydroCLDOH, dieldrin, and β-HCH were detected and quantified, pentachloroindene, another CLD TP, was sporadically found in trace levels. A comparison with BRGM and LDA26 confirmed the interest of the SPME method. Results suggested an underestimation of CLDOH and an overestimation of high CLD concentrations with one of the currently used routine protocol. In light of these findings, previous temporal monitoring of environmental waters in FWI were re-examined and revealed some atypical values, which may indeed be due to analytical bias. These discrepancies call for intensified efforts to reliably quantify CLD and its TPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The lysosomal cation channel TRPML1/MCOLN1 facilitates autophagic degradation during amino acid starvation based on studies involving long-term TRMPL1 modulation. Here we show that lysosomal activation (more acidic pH and higher hydrolase activity) depends on incoming vesicle fusions. We identify an immediate, calcium-dependent role of TRPML1 in lysosomal activation through promoting autophagosome-lysosome fusions and lysosome acidification within 10-20 minutes of its pharmacological activation. Lysosomes also become more fusion competent upon TRPML1 activation via increased transport of lysosomal SNARE proteins syntaxin 7 and VAMP7 by SNARE carrier vesicles. We find that incoming vesicle fusion is a prerequisite for lysosomal Ca 2+ efflux that leads to acidification and hydrolytic enzyme activation. Physiologically, the first vesicle fusions likely trigger generation of the phospholipid PI(3,5)P 2 that activates TRPML1, and allosteric TRPML1 activation in the absence of PI(3,5)P 2 restores autophagosome-lysosome fusion and rescues abnormal SNARE sequestration within lysosomes. We thus identify a prompt role of TRPML1-mediated calcium signaling in lysosomal fusions, activation, and SNARE trafficking., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to host intestinal microflora. A hyperactive inflammatory and immunological response in the gut has been shown to be one of the disease's long-term causes despite the complexity of the clinical pathology of IBD. The innate immune system activator known as human gut inflammasome is thought to be a significant underlying cause of pathology and is closely linked to the development of IBD. It is essential to comprehend the function of inflammasome activation in IBD to treat it effectively. Systemic inflammasome regulation may be a proper therapeutic and clinical strategy to manage IBD symptoms since inflammasomes may have a significant function in IBD. Non-coding RNAs (ncRNAs) are a type of RNA transcript that is incapable of encoding proteins or peptides. In IBD, inflammation develops and worsens as a result of its imbalance. Culminating evidence has been shown that ncRNAs, and particularly long non-coding RNAs (lncRNAs), may play a role in the regulation of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in IBD. The relationship between IBD and the gut inflammasome, as well as current developments in IBD research and treatment approaches, have been the main topics of this review. We have covered inflammasomes and their constituents, results from in vivo research, inflammasome inhibitors, and advancements in inflammasome-targeted therapeutics for IBD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The pursuit of efficient and sustainable energy storage solutions has fueled significant interest in the development of advanced materials for supercapacitors. Among these, two-dimensional (2D) materials undoubtingly have emerged as promising candidates due to their unique structural and electrochemical properties. To address the inherent challenges such as restacking, limited ion-accessibility, limited scalability, stability under operational conditions, and the intricate balance between surface area and conductivity that hinder the practical application of 2D materials, this article delves into innovative approaches and emerging strategies and prospects that aim to enhance their performance and durability. A systematic exploration of synthesis methods, structural characteristics, and electrochemical performance as supercapacitor electrodes of key 2D materials, including graphene, MXenes, transition metal dichalcogenides (TMDCs), black phosphorous and phosphorene and their composites has been discussed. The discussion will extend to recent breakthroughs and innovations, shedding light on how researchers are leveraging the unique properties of 2D materials to overcome existing challenges in supercapacitor technology. Beyond mere documentation, this review seeks to inspire future research directions, foster interdisciplinary collaborations, and contribute to the ongoing evolution of energy storage technologies towards a more sustainable and efficient future., Competing Interests: The authors declare no financial conflict of interest., (This journal is © The Royal Society of Chemistry.)

Purpose: The objective of this manuscript is to assess the effect of varicocele repair (VR) in patients with clinical varicoceles on serum total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and inhibin B serum levels., Materials and Methods: The study was performed in compliance with the Meta-Analysis and Systematic Reviews of Observational Studies (MOOSE) guidelines and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). All eligible studies were selected following the PICOS (Population, Intervention, Comparison/Comparator, Outcomes, Study design) model. The values of each outcome measured after VR were compared to the before parameters and, when available, to the values on patients with unrepaired varicocele, and to those of healthy controls with no varicocele. For total testosterone, the values were sub-analyzed based on the mean total testosterone levels before VR (<300 ng/dL or >300 ng/dL), the fertility status, the time of follow-up and the technique used for VR., Results: From a total of 460 abstracts retrieved, 48 articles were included in our meta-analysis. Serum total testosterone levels were significantly higher after VR compared to both pre-treatment levels (mean difference [MD] 82.45 ng/dL, 95% confidence interval [CI]: 64.14-100.76; p<0.00001) and to the levels of patients with unrepaired varicocele (MD 91.64 ng/dL, 95% CI: 62.30-120.99; p<0.00001). They did not differ from the levels of healthy controls with no varicocele (MD -22.01 ng/dL, 95% CI: -68.59-24.58; p=0.35). The increase resulted to be independent from the mean total testosterone levels before VR, fertility status, time of follow-up and type of VR. After VR, a trend toward lower serum LH levels was found compared to before values (MD -0.37 IU/L, 95% CI: -0.74-0.01; p=0.06). When compared to the levels of patients with unrepaired VR, LH levels after VR were significantly lower (MD -0.96 IU/L, 95% CI: -1.56 to -0.35; p=0.002). LH levels were not significantly higher than healthy men without varicocele (MD 0.84 IU/L, 95% CI: -0.68-2.36; p=0.28). Patients with VR had significantly lower FSH levels compared to their pre-treatment values (MD -1.43 IU/L, 95% CI: -1.82 to -1.04; p<0.00001), and also to those of patients with non-repaired varicocele (MD -2.35 IU/L, 95% CI: -4.06 to -0.65; p=0.007). When compared to healthy controls with no varicocele, FSH levels were significantly higher (MD 2.71 IU/L, 95% CI: 1.12-4.31; p=0.0009). Lastly, after VR no significant change in inhibin B serum levels was seen compared to pre-treatment levels (MD 11.76 pg/mL, 95% CI: -3.83-27.35; p=0.14)., Conclusions: The present meta-analysis is the largest to date to assess the impact of VR on Leydig cell and Sertoli cell function using a before-after analysis for uncontrolled studies, and using data from patients with unrepaired varicoceles or healthy patients without varicocele as controls. VR was found to increase and restore to normality serum levels of total testosterone and LH. This evidence could be of value in considering the treatment of varicocele in patients with low testosterone or those who show a progressive decline in testosterone levels., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Irritable bowel syndrome (IBS) is one of the most prevalent gastrointestinal disorders characterized by recurrent abdominal pain and an altered defecation pattern. Chronic abdominal pain represents the hallmark IBS symptom and is reported to have the most bothersome impact on the patient's quality of life. Unfortunately, effective therapeutic strategies reducing abdominal pain are lacking, mainly attributed to a limited understanding of the contributing mechanisms. In the past few years, exciting new insights have pointed out that altered communication between gut immune cells and pain-sensing nerves acts as a hallmark driver of IBS-related abdominal pain. In this review, we aim to summarize our current knowledge on altered neuro-immune crosstalk as the main driver of altered pain signaling, with a specific focus on altered mast cell functioning herein, and highlight the relevance of targeting mast cell-mediated mechanisms as a novel therapeutic strategy for chronic abdominal pain in IBS patients., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This research offers a novel methodology for quantifying water needs by assessing weather variables, applying a combination of data preprocessing approaches, and an artificial neural network (ANN) that integrates using a genetic algorithm enabled particle swarm optimisation (PSOGA) algorithm. The PSOGA performance was compared with different hybrid-based metaheuristic algorithms' behaviour, modified PSO, and PSO as benchmarking techniques. Based on the findings, it is possible to enhance the standard of initial data and select optimal predictions that drive urban water demand through effective data processing. Each model performed adequately in simulating the fundamental dynamics of monthly urban water demand as it relates to meteorological variables, proving that they were all successful. Statistical fitness measures showed that PSOGA-ANN outperformed competing algorithms., (© 2024. The Author(s).)

Objective: Unilateral thin clear rhinorrhea (UTCR) may represent a variety of pathologies including cerebrospinal fluid (CSF) rhinorrhea. Beta-2 transferrin (B2Tf) gel electrophoresis (GE) has become the preferred testing modality due to reportedly high sensitivity (87%-100%) and specificity (71%-100%). However, there have been relatively few studies assessing its diagnostic accuracy. The purpose of this single-institution study was to determine the accuracy of B2Tf GE in detecting CSF rhinorrhea., Methods: A single-center retrospective review was conducted from 2016 and 2024 for all patients who presented with UTCR and underwent B2Tf GE. Institutional review board approval was obtained. The gold standard for diagnostic confirmation of true and false positives (TP, FP) as well as false negatives (FN) was endoscopic exploration. The gold standard for true negative (TN) was response to medical therapy., Results: A total of 105 patients underwent 149 B2Tf GE tests. 40 (38.1%) patients were diagnosed with CSF rhinorrhea. Of the 149 B2-Tf GE tests, there were 51 TPs, 72 TNs, 20 FPs, and 6 FNs yielding 89.5% sensitivity, 78.3% specificity, 71.8% positive predictive value, and 92.3% negative predictive value, respectively. Of the false results the most common causes for error were purulent sinusitis (n = 6, 23.1%), possible mucous contamination from nose-blowing during collection (n = 3, 11.5%), patient collection error (n = 3, 11.5%), and blood contamination (n = 1, 3.8%)., Conclusion: Although these single-institutional data demonstrate test accuracy within ranges previously reported in the literature, they also demonstrate diagnostic limitations. Future studies should explore reasons for erroneous B2Tf GE results and how these may change clinical decision-making., Level of Evidence: IV Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: The maintenance of intestinal homeostasis depends on a complex interaction between the immune system, intestinal epithelial barrier, and microbiota. Alteration in one of these components could lead to the development of inflammatory bowel diseases (IBD). Variants within the autophagy gene ATG16L1 have been implicated in susceptibility and severity of Crohn's disease (CD). Individuals carrying the risk ATG16L1 T300A variant have higher caspase 3-dependent degradation of ATG16L1 resulting in impaired autophagy and increased cellular stress. ATG16L1-deficiency induces enhanced IL-1β secretion in dendritic cells in response to bacterial infection. Infection of ATG16L1-deficient mice with a persistent strain of murine norovirus renders these mice highly susceptible to dextran sulfate sodium colitis. Moreover, persistent norovirus infection leads to intestinal virus specific CD8 + T cells responses. Both Toll-like receptor 7 (TLR7), which recognizes single-stranded RNA viruses, and ATG16L1, which facilitates the delivery of viral nucleic acids to the autolysosome endosome, are required for anti-viral immune responses., Results and Discussion: However, the role of the enteric virome in IBD is still poorly understood. Here, we investigate the role of TLR7 and ATG16L1 in intestinal homeostasis and inflammation. At steady state, Tlr7 -/- mice have a significant increase in large intestinal lamina propria (LP) granzyme B + tissue-resident memory CD8 + T (T RM ) cells compared to WT mice, reminiscent of persistent norovirus infection. Deletion of Atg16l1 in myeloid ( Atg16l1 ΔLyz2 ) or dendritic cells ( Atg16l1 ΔCd11c ) leads to a similar increase of LP T RM . Furthermore, Tlr7 -/- and Atg16l1 ΔCd11c mice were more susceptible to dextran sulfate sodium colitis with an increase in disease activity index, histoscore, and increased secretion of IFN-γ and TNF-α. Treatment of Atg16l1 ΔCd11c mice with the TLR7 agonist Imiquimod attenuated colonic inflammation in these mice. Our data demonstrate that ATG16L1-deficiency in myeloid and dendritic cells leads to an increase in LP T RM and consequently to increased susceptibility to colitis by impairing the recognition of enteric viruses by TLR7., Conclusion: In conclusion, the convergence of ATG16L1 and TLR7 signaling pathways plays an important role in the immune response to intestinal viruses. Our data suggest that activation of the TLR7 signaling pathway could be an attractive therapeutic target for CD patients with ATG16L1 risk variants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hamade, Tsuda, Oshima, Stamps, Wong, Stamps, Thomas, Salumbides, Jin, Nunnelee, Dhall, Targan and Michelsen.)

Objective: Topical nasal decongestants (TNDs) are used to reduce nasal soft tissue edema and obstruction. However, after frequent TND use, patients can develop rhinitis medicamentosa (RM) with rebound nasal edema and obstruction. Management of RM has centered largely on TND cessation ± intranasal corticosteroids. The purpose of this study was to compare nasal obstruction outcomes following nasal obstruction surgery in patients with versus without RM., Methods: A retrospective case-control study was conducted with adult patients who underwent bilateral inferior turbinate reduction (ITR) with or without septoplasty and nasal valve repair. Patients with versus without RM were assessed. RM was defined as at least daily TND use for ≥4 weeks. Preoperative and postoperative Nasal Obstruction Symptom Evaluation (NOSE) scores, and long-term TND cessation rates were collected. NOSE score changes were compared between patients with versus without RM., Results: Of the 36 RM patients, mean age was 52.0 years, and 63.9% were male. Of 116 non-RM patients, mean age was 41.6 years, and 46.6% were male. Postoperative NOSE scores were collected at a mean 972.1 days postoperatively for RM patients, and 565.0 days for non-RM patients. Mean NOSE score reductions were - 9.8 for RM and - 8.6 for non-RM patients, both of which were significant (p < 0.0001). NOSE score reductions were not significantly between the two groups (p = 0.2438). Long-term TND cessation was maintained in 86.1% of RM patients., Conclusion: Patients with and without RM achieved similar long-term significant NOSE score reductions following nasal obstruction surgery, and 86.1% of RM patients maintained long-term TND cessation., Level of Evidence: Level 3 evidence Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Tanzania faces ever-rising concerns due to the recurrence of the Ebola Virus Disease (EVD) in neighbouring Democratic Republic of Congo (DRC) and Uganda. This necessitates a better understanding of the community perspectives in high-risk regions for effective risk communication and preparedness., Methods: This rapid ethnographic assessment study used explorative qualitative methods to collect data. People from diverse backgrounds participated in 59 in-depth interviews, 57 Key Informant interviews, and 35 focus group discussions. Data was analysed using a thematic analysis approach., Finding: The study revealed existence of awareness of EVD and its symptoms, with radio and television being the main sources of information. However, there were varied perceptions of EVD's cause and transmission, some attributed it to bats, monkeys, and wild animal meat, while others associated it with high fever, a dirty environment, changing dietary patterns, and the COVID-19 virus. Physical contact with an infected person's body fluids and eating meat from infected animals were perceived as EVD transmission routes. Women, school children, boda-boda (motorcycle) riders, and fishermen were considered the most susceptible to EVD infections due to their daily activities. Preventive measures included avoiding physical contact, touching fluids, and refraining from eating wild animal meat. Prompt reporting of suspected cases to health facilities was deemed crucial for earlier outbreak identification and containment., Conclusion: The high-risk regions of Tanzania had a high level of awareness and perceived susceptibility to EVD, coupled with varying degrees of misperception about the etiology and its transmission. To improve community perspectives and preparedness in the case of an outbreak, there is a need for ongoing risk communication and participation in EVD prevention and responses., (© 2024. The Author(s).)

Liver cancer represents a substantial global health challenge, contributing significantly to worldwide morbidity and mortality. It has long been understood that tumors are not composed solely of cancerous cells, but also include a variety of normal cells within their structure. These tumor-associated normal cells encompass vascular endothelial cells, fibroblasts, and various inflammatory cells, including neutrophils, monocytes, macrophages, mast cells, eosinophils, and lymphocytes. Additionally, tumor cells engage in complex interactions with stromal cells and elements of the extracellular matrix (ECM). Initially, the components of what is now known as the tumor microenvironment (TME) were thought to be passive bystanders in the processes of tumor proliferation and local invasion. However, recent research has significantly advanced our understanding of the TME's active role in tumor growth and metastasis. Tumor progression is now known to be driven by an intricate imbalance of positive and negative regulatory signals, primarily influenced by specific growth factors produced by both inflammatory and neoplastic cells. This review article explores the latest developments and future directions in understanding how the TME modulates liver cancer, with the aim of informing the design of novel therapies that target critical components of the TME.

Inflammation is a complex process with many contributing factors, and it often causes pain. The pathophysiology of pain involves the release of inflammatory mediators that initiate pain sensation, as well as edema and other inflammation hallmarks. Selenium-containing compounds (OSe) are very promising for developing new medicines because they can treat many different diseases. In this study, we estimated the anti-inflammatory properties of maleanilic and succinanilic acids containing selenium (OSe). These molecules were designed by combining different strategies to enhance their anti-inflammatory properties. Hence, the anti-inflammatory impacts of compounds 8, 9, 10, and 11 were pursued using inflammatory markers COX-2, IL-1β, and IL-6. Notably, it was revealed that compounds 8, 9, 10, and 11 downregulated COX-2, IL-1β, and IL-6 by (2.01, 1.63, 2.26, and 2.05), (1.42, 1.64, 1.93, and 2.59), and (1.67, 2.54, 2.22, and 4.06)-fold changes, respectively. Moreover, molecular docking studies were conducted on compounds 8, 9, 10, and 11 to pursue their binding affinities for the COX-2 enzyme. Notably, very promising binding scores of compounds 8, 9, 10, and 11 towards the binding site of the COX-2 receptor were attained. Additionally, more accurate molecular dynamics simulations were performed for 200 ns for the docked complexes of compounds 8, 9, 10, and 11 to confirm the molecular docking findings, which ignore the protein's flexibility. Therefore, the exact stability of the N -amidic acids OSe compounds 8, 9, 10, and 11 towards the binding pocket of the COX-2 enzyme was examined and explained as well. Also, the MM-GBSA binding energy was calculated for equilibrated MD trajectory, and 200 snapshots were selected with a 50 ps interval for further analysis. Accordingly, the investigated compounds can be treated as prominent lead anti-inflammatory candidates for further optimization., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Leishmaniasis is a common protozoal infection that could be cutaneous (CL), mucocutaneous (MCL), or visceral. CL, which is the most common form, is typically localized. Therefore, it becomes more difficult to diagnose it when presenting with diffuse lesions. In this case, a 54-year-old man presented with skin lesions involving his trunk, extremities, and face, including the nasal mucosa. His past medical history was remarkable for MCL with synovial leishmaniasis, systemic lupus erythematosus (SLE), and non-Hodgkin's lymphoma (NHL). Skin biopsies showed intracytoplasmic leishmania amastigotes; polymerase chain reaction (PCR) was positive for leishmania DNA; and a culture from purulent skin lesions grew Pseudomonas aeruginosa. So, MCL with superimposed cellulitis was diagnosed, and the patient was treated with intravenous liposomal amphotericin B and ceftazidime. Leishmaniasis is an infection that has accurate diagnostic tests and various treatment options. However, the difficulty is in being able to suspect it clinically, as it can mimic a wide range of diseases with cutaneous involvement. Therefore, visual awareness of the spectrum of disease presentations is arguably the most challenging and important skill to acquire in the diagnosis and management of CL. This case represents a rare form of MCL., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Taleb et al.)

Introduction: This study aimed to investigate medical students' perceptions of telehealth in Pakistan and assess the relationship between students' proficiency in computers and technology, gender, and age., Methods: A cross-sectional study was conducted on 330 medical students from various universities in Karachi, Pakistan. Data on demographic characteristics, computer proficiency, and perceptions of telehealth were collected using a self-administered questionnaire. Descriptive statistics, chi-square tests, and Spearman's rank correlation coefficient were utilized for data analysis., Results: The study included 330 participants, predominantly from public universities (83.3%), with a mean age of 21.40 ± 4.24 years. Most participants were pursuing MBBS (67%). In terms of computer proficiency, 41.8% fell into the middle category. Gender correlated significantly with proficiency (p < 0.05), with females more often in the middle category and males in the not-that-amateur category. Age demonstrated a small positive correlation with proficiency (p < 0.05). A majority (77.6%) expressed a general interest in technology. Regarding healthcare apps, 51.8% had 1-3 apps, and 33.6% had none. Most participants believed telehealth would enhance healthcare (72.1%) and make it cheaper (63.3%). Additionally, 56.7% agreed that Pakistan should invest in telehealth, while only 2.7% disagreed., Conclusion: The study revealed that medical students in Pakistan exhibit an interest in technology and perceive telehealth as beneficial. These findings suggest that telehealth holds the potential to enhance healthcare opportunities in Pakistan. Therefore, investing in and expanding telehealth services may represent a viable solution for improving access to healthcare in the country., (© 2024. The Author(s).)

A periodic surface is one that is invariant by a two-dimensional lattice of translations. Deformation modes that stretch the lattice without stretching the surface are effective membrane modes. Deformation modes that bend the lattice without stretching the surface are effective bending modes. For periodic piecewise smooth simply connected surfaces, it is shown that the effective membrane modes are, in a sense, orthogonal to effective bending modes. This means that if a surface gains a membrane mode, it loses a bending mode, and conversely, in such a way that the total number of modes, membrane and bending combined, can never exceed 3. Various examples, inspired from curved-crease origami tessellations, illustrate the results.This article is part of the theme issue 'Origami/Kirigami-inspired structures: from fundamentals to applications'.

Whey protein concentrates (WPCs) are gaining importance as a functional ingredient due to their high technological and functional properties and their diverse application in the food industry. In this study, Camel milk whey (CW) was separated from skimmed camel milk, then either spray-dried (SD) at 170, 185 and 200 °C, or treated by ultrasonication (US) (20 kHz) for 5, 10 and 15 min followed by freeze-drying to obtain camel milk whey powder (CWP). The structural analysis of CWP was carried out by Fourier-Transform Infrared Spectroscopy (FTIR) and X-Ray Diffraction (XRD) which showed no significant difference in the functional groups profile of US samples compared to control and SD samples. US samples showed some degree of crystallinity that was comparable to the control samples, while SD samples exhibited very low degree of crystallinity. The surface morphology, particle size, and surface charge of CWP were evaluated using scanning electron microscopy (SEM) and Zetasizer. The lowest particle size of 215.1 nm with surface charge of -21.6 mv was observed in SD-185 WPC. Moreover, SD samples revealed whiter color compared to the US-treated samples which were having lower L* values (P < 0.05). US-15 sample exhibited high protein solubility (100 %), whereas the SD-200 sample showed reduced solubility (92.7 %). Improvement in the emulsifying activity of CWP samples was observed after SD and US, with highest emulsifying activity index (EAI) values of 143.75 m 2 /g and 143.11 m 2 /g were reported for SD-185 and US-15 CWP samples, respectively. To conclude, SD and US were found to improve the physico-chemical, technological, and functional properties of CWP, and thus can be utilized as a promising strategy to preserve and enhance the technofunctional properties of CWP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

This study focuses on the extraction of bioactive compounds from date seeds using five polyol-based deep eutectic solvents (P-DESs) in combination with hybrid green extraction techniques, specifically microwave-assisted extraction (MAE), homogenization-assisted extraction (HAE), and ultrasound-assisted extraction (UAE). The optimization of these extraction techniques was achieved using P-DESs showing the highest efficiency for extracting date seed bioactive compounds using response surface methodology (RSM) and central composite design (CCD) approach. The optimized conditions from three green techniques were further applied in the form of hybrid green extraction techniques, involving six binary and three ternary methods, to assess the percentage increase in the extraction efficiency of date seed bioactive polyphenolics. Among the five P-DESs tested, choline chloride: ethylene glycol (ChCl:Eg) exhibited the highest extraction efficiency for recovering date seed phenolic compounds. Using ChCl:Eg as the P-DES, the highest extraction efficacy was found with MAE, followed by > HAE and > UAE. In addition, all hybrid extraction techniques showed higher extraction efficiencies than the single extraction methods. Notably, the binary hybrid techniques combining UAE and MAE (UMAE), HAE and MAE (HMAE) resulted in significantly higher recovery of bioactive compounds, with 52 % and 49 % increases in total phenolic content, respectively, compared to single extraction techniques. The lowest MIC and MBC of P-DES (ChCl:Eg) and date seed P-DES based extract recorded against all the tested bacterial strains was 40 % and 20 % respectively. Furthermore, the date seed extract from MAE was used to extend the shelf life of Oreochromis niloticus stored at 4 °C for 10 days. The results indicated that the date seed polyphenolic extract effectively inhibited microbial growth in Oreochromis niloticus during refrigerated storage, with the total bacterial count (TBC) of all the treated samples within the recommended acceptability limit of < 6 log CFU/g compared to the untreated samples, which showed a total bacterial count (TBC) > 6 log CFU/g. This study demonstrated that sequential hybrid techniques enhance and intensify the recovery of bioactive compounds more effectively than any single green technique., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

In addition to high-molecular risk (HMR) mutations (ASXL1, EZH2, SRSF2, IDH, and U2AF1 Q157 ), lower JAK2V617F variant allele frequencies (VAF) have been demonstrated to be associated with poor prognosis of myelofibrosis (MF) patients. Nevertheless, the relationship between JAK2V617F VAF and HMR mutations remains inconclusive. To address this, we analyzed the mutation status of 54 myeloid neoplasm-relevant genes using targeted next-generation sequencing in 124 MF patients. Three cohorts from multiple international centers were analyzed for external validation. Among JAK2-mutated patients, the presence of HMR mutations drove poor prognosis in patients with lower JAK2V617F VAF but not in those with higher JAK2V617F VAF. Survival analyses showed consistent results across validation cohorts. In multivariable analysis, concurrent HMR and a lower JAK2V617F VAF was identified as an independent adverse prognostic factor for survival, irrespective of age, MIPSS70, MIPSS70 + v2, and GIPSS risk groups. Mutation co-occurrence tests revealed no shared mutational pattern over different cohorts, excluding potential confounding effect from other concurrent mutations. Importantly, the integration of HMR/JAK2V617F VAF (≤50%) status significantly enhanced existing prognostic models, as evidenced by higher c-indexes and time-dependent ROC analyses. Single-cell studies with sequential follow-ups are warranted to decipher the clonal evolution of MF and how it relates to JAK2V617F VAF dynamics., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Lung cancer (LC) is the most common form of cancer in the world. Of the proteins involved in cell differentiation and proliferation, the epidermal growth factor receptor (EGFR) is among the most significant. Amino acids play a crucial role in cell physiology as metabolic regulators. The benefits of liquid biopsies are their non-invasive nature, ease of collection, and ability to depict the entire tumor's status. The present study is designed to detect the relation between the EGFR exon 19 747-750 deletion mutation and lung cancer and investigate the patterns of alterations of plasma-free amino acids (PFAA) in lung cancer patients of different histopathological types and stages as biomarkers for early detection of lung cancer., Methods: The study sample comprised 60 lung cancer patients and 60 age- and sex-matched healthy individuals as the control group. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to examine the EGFR exon 19 747-750 deletion mutation, and an AA analyzer was used to quantify the plasma free amino acid (PFAA) profile., Results: Compared with controls, LC patients had significantly higher levels of three AAs and significantly lower levels of fifteen AAs. Thirteen AAs varied significantly between stages I and II. In the lung cancer group, the percentage of cases of mutant EGFR exon-19 deletion increased to 30% from 13.3% in the control group. The histological forms of lung cancer did not significantly differ in this rise. Valine and citrulline plasma levels were substantially greater in the mutant than in the wild-type. Lysine, histidine, and methionine were the independent predictors of the LC group in multivariate analysis., Conclusion: Lung cancer development is influenced by the EGFR exon 19 747-750 deletion mutation, and the prognosis and early prediction of lung cancer are greatly affected by the amino acid profile concentrations., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Tuberculosis (TB) remains a significant cause of mortality globally, yet first-line treatment has hardly changed for fifty years. The dose of rifampicin, the most important drug in this regimen, has been historically based on pragmatic cost- and risk-benefit considerations. Evidence suggests the current recommended dose (8-12 mg/kg) may not maximise the potential benefits of this drug. We sought to evaluate the efficacy and safety of higher doses of rifampicin in adults with presumed drug-susceptible TB., Methods: In this systematic review we searched MEDLINE, EMBASE, CENTRAL and Global Health databases for randomised controlled trials up to 31 July 2024 of adults with presumed drug-susceptible TB receiving first-line treatment with an intervention of rifampicin doses higher than currently recommended. Meta-analyses were performed using random effects models where background regimens were the same. Risk ratio was used as the measure for treatment effect. Outcomes of interest related to efficacy and safety., Findings: Of the 5441 total records identified by our searches, nineteen studies (6332 patients, 31.0% female) were eligible for the systematic review and twelve (3763 patients, 31.0% female) for meta-analysis. Rifampicin doses varied from 8 to 35 mg/kg and implementation of the intervention varied between trials. There was no evidence for increased efficacy with higher doses of rifampicin, however the majority of trials investigated minimally increased doses (up to 20 mg/kg). At higher doses (>20 mg/kg), there may be evidence of increased risk of drug-induced liver injury, albeit with no consistent dose-response relationship., Interpretation: Evidence on the efficacy of higher doses of rifampicin in the first-line regimen for TB remains incomplete. While higher doses appear generally safe, the risk of drug-induced liver injury may be increased above doses of 20 mg/kg. Larger clinical trials reporting definitive outcomes are needed to determine whether dosing up to 40 mg/kg could safely improve treatment outcomes or reduce duration of first-line therapy., Funding: WHO, Wellcome Trust., Competing Interests: GD was supported by a consultancy contract from WHO for the initial published version of this review and chaired the Data Safety Monitoring Board for RIFASHORT and the Trial Steering Committee for TRUNCATE-TB. All other authors declare no competing interests., (© 2024 The Author(s).)

This study aimed to determine the optimal water, temperature, and density conditions, alongside antifungal treatments, for pea ( Pisum sativum L.) germination in a laboratory setting, with implications for research, breeding, and microgreen production. Germination and early seedling growth were assessed across various temperatures (5 °C to 40 °C), water levels (0-14 mL per Petri dish), seed densities (5, 7, 9, and 11 seeds per Petri dish), and antifungal treatments (Hypo and Bordeaux mixture). The results indicated that optimal germination occurred between 15 °C and 25 °C, with peak performance at 25 °C. Water levels between 7 and 11 mL per 9 cm diameter Petri dish supported robust root and shoot development, while minimal water levels initiated germination but did not sustain growth. Five seeds per Petri dish was optimal for healthy development, whereas higher densities led to increased competition and variable outcomes. Antifungal treatments showed slight improvements in germination and growth, though differences were not statistically significant compared to controls. The study's novelty lies in its holistic approach to evaluating multiple factors affecting pea germination, offering practical guidelines for enhancing germination rates and seedling vigor. These findings support efficient and resilient crop production systems adaptable to varying environmental conditions, contributing to sustainable agriculture and food security. Future research should explore these factors in field settings and across different pea cultivars to validate and refine the recommendations.

Across the world and within Europe, a growing number of consumers are choosing to buy gluten-free products. Motivations for a gluten-free diet and the consequences of consuming gluten are varied, from a medical necessity for those diagnosed with celiac disease to a range of health complications and discomfort for those who are gluten-intolerant. In this research, 7296 gluten-free consumers across 13 European countries responded to an online survey on the 33 types of gluten-free products purchased, how frequently they purchased them, their satisfaction with gluten-free quality and availability, the problems they have experienced, and the strategies they have employed to cope with these problems. The investigation examines whether and how these consumer attitudes and behaviors differ between those diagnosed with celiac disease, those who are gluten-intolerant, and those who are caregivers for others with a gluten-free diet. The results show that significant differences existed for all these habits and issues across the three gluten-free consumer groups. Specifically, caregivers purchased most of the gluten-free product types more frequently than the other two groups, experienced more availability problems, and were more likely to shop at multiple stores or make their own gluten-free products. Celiac-diagnosed consumers tended to buy gluten-free products more frequently than those who are gluten-intolerant, and they tended to be the most satisfied with the quality and range of gluten-free offerings. Despite purchasing frequency differences between the groups, the results suggest a similar hierarchy of gluten-free products that could provide the foundation for a European gluten-free food basket.

Papaya leaf curl China virus (PaLCuCNV) is a damaging plant pathogen causing substantial losses to crop. The complete genomes of three PaLCuCNV isolates from Ageratum conyzoides were obtained and combined with the 68 reference isolates in GenBank for comprehensive genetic diversity analyses using specialized computational tools. Sequence alignment revealed nucleotide sequence similarity ranging from 85.3% to 99.9% among 71 PaLCuCNV isolates. Employing phylogenetic analysis, 71 PaLCuCNV sequences were clustered into five groups, with no significant correlation observed between genetic differentiation and either host species or geographical origin. Additionally, 13 recombination events across all PaLCuCNV isolates were identified. Genetic diversity analysis indicated the ongoing expansion and evolution of PaLCuCNV populations, supported by a neutral model. Moreover, significant genetic differentiation was observed among distinct viral populations, primarily attributed to genetic drift. Overall, our findings provide valuable insights into the detection, genetic variation, and evolutionary dynamics of PaLCuCNV.

BackgroundBrown rats ( Rattus norvegicus ) are synanthropic rodents with worldwide distribution, which are known to harbour many zoonotic pathogens and parasites. No systematic zoonotic surveys targeting multiple pathogens and parasites have previously been conducted in urban rats in Finland.AimIn Helsinki, Finland, we explored the presence and prevalence in brown rats of certain pathogens and parasites (including helminths, viruses and bacteria) across potentially zoonotic taxa.MethodsWe opportunistically received rat carcasses from pest management operators and citizens from 2018 to 2023. We searched for heart- or lungworms, performed rat diaphragm digestion to check for Trichinella and morphologically identified intestinal helminths. We assessed virus exposure by immunofluorescence assay or PCR, and detected bacteria by PCR ( Leptospira ) or culture ( Campylobacter ).ResultsAmong the rats investigated for helminths, no heart- or lungworms or Trichinella species were detected and the most common finding was the cestode Hymenolepis nana (in 9.7% of individuals sampled, 28/288). For some of the surveyed virus taxa, several rats were seropositive (orthopoxviruses, 5.2%, 11/211; arenaviruses, 2.8%, 6/211; hantaviruses 5.2%, 11/211) or tested positive by PCR (rat hepatitis E virus, 1.8%, 4/216). Campylobacter jejuni (6.6%, 17/259) and Leptospira interrogans (1.2%, 2/163) bacteria were also present in the rat population examined.ConclusionsPrevalences of potentially zoonotic pathogens and parasites in brown rats in Helsinki appeared low. This may explain low or non-existent diagnosis levels of rat-borne pathogen and parasite infections reported in people there. Nevertheless, further assessment of under-diagnosis, which cannot be excluded, would enhance understanding the risks of zoonoses.