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Parkinson's disease is a prevalent neurological condition that affects around 1% of adults over 60 worldwide. Deep brain stimulation and dopamine replacement therapy are common therapies for Parkinson's disease, yet they are unable to reverse the disease it simply because of the blood brain barrier. The use of bioengineered exosomes to treat Parkinson's disease is being studied because they have the ability to cross the blood-brain barrier. Their natural ability to cross the blood-brain barrier (BBB) and their biocompatibility make them highly suitable for delivering therapeutic agents to manage PD, specifically the role of astrocytes, microglial cells, and alpha-synuclein. It also explores the biogenesis and preparation of these bioengineered exosomes. In comparison to conventional nanocarriers, the modified exosomal-membrane-camouflaged abiotic nanocarriers show improved resilience and compatibility. Improved cellular absorption and targeted delivery of therapeutic payloads, such as medications and enzymes, are being shown in laboratory trials. A viable strategy for treating PD involves combining abiotic nanocarriers with bioengineered exosomal membranes. Despite their promising potential, successful clinical application requires overcoming hurdles related to scalable production, regulatory approval, and long-term safety evaluation. Nevertheless, the innovative use of bioengineered exosomes holds significant promise for advancing PD management and improving patient outcomes through more targeted and effective therapeutic strategies., 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.)

Background: Little is known about quality of life, sleep, and mental health in children with moyamoya arteriopathy (MMA). A better understanding of patient-reported outcomes may lead to improved treatment., Methods: Patients with MMA <26 years old and their caretakers completed validated, age-appropriate questionnaires including the Pediatric Quality of Life (PedsQL) Inventory and Patient-Reported Outcomes Measurement Information System (PROMIS) measuring health-related quality of life, sleep, anxiety, depression, and overall health., Results: All 21 caretaker-proxies and eight of 21 patients with MMA completed questionnaires. Median age of participants with MMA was 7.8 years. The MMA cohort included 10 children with moyamoya disease and 11 with moyamoya syndrome, and 11 participants (52.4%) had a prior clinical stroke. Nine siblings unaffected by moyamoya and 20 participants with perinatal stroke were enrolled as comparator groups. Participants with MMA had greater impairment in school/work quality of life compared with normative values on caretaker and child-reported PedsQL surveys (85.5 vs 62.3 [P < 0.001] and 78.6 vs 51.2 [P = 0.017], respectively). Participants with MMA did not have significantly different physical impairment compared with normative values and siblings on caretaker and child-reported surveys. Caretaker-proxy PROMIS scores revealed high rates of moderate-severe anxiety (57.1% vs 25%, P < 0.001), sleep impairment (47.6% vs 25%, P = 0.017), and fair-poor global health (76.2% vs 25%, P < 0.001) in participants with MMA compared with the general population., Conclusions: Patients with MMA have high rates of school/work impairment, anxiety, sleep impairment, and fair-poor global health. Screening for patient-reported outcomes, even in the absence of stroke or physical impairment, may improve treatment., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Clonal hematopoiesis is highly prevalent in elderly patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), and around 20% of BPDCN patients have an associated myeloid malignancy. We present a patient with localized BPDCN and concomitant myelodysplastic syndrome (MDS), previously followed for several years due to clonal cytopenia of unknown significance. Compared targeted next-generation sequencing (NGS) of the skin tumor and sequential bone marrow samples showed shared variants in ASXL1 and TET2 with a de novo NRAS variant in both BPDCN and MDS compared to preceding bone marrow samples. These findings illustrate a shared clonal origin of BPDCN and MDS resulting from progressive clonal hematopoiesis., (© 2024 The Author(s). APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Background: In total pancreatectomy with islet autotransplantation (TPIAT), a greater number of islets transplanted produces more favorable outcomes. We aimed to determine predictors of islet isolation outcomes., Methods: We investigated factors associated with islet isolation outcomes expressed as islet number (IN), islet equivalents (IEQ; standardized to an islet with 150 μm diameter), IN/kg, or IEQ/kg using data from the multicenter Prospective Observational Study of TPIAT. Single-predictor linear regression was used to estimate the association of individual patient and disease characteristics with islet isolation outcomes, and augmented backward elimination was used to select variables to include in multivariable analyses., Results: In multivariable analyses, only elevated hemoglobin A1c was associated with worse outcomes for all measures ( P  < 0.001 for all). Total IEQ obtained for transplant was higher for participants with Hispanic ethnicity ( P  = 0.002) or overweight status pre-TPIAT ( P  < 0.001) and lower with non-White race ( P  = 0.03), genetic pancreatitis ( P  = 0.02), history of lateral pancreaticojejunostomy ( P  = 0.03), and presence of atrophy ( P  = 0.006) or ductal changes ( P  = 0.014) on imaging. IEQ/kg was higher in females ( P  = 0.01) and Hispanic participants ( P  = 0.046) and generally lower with older age (nonlinear association, P  < 0.001) and pancreatic atrophy ( P  < 0.001) on imaging. Total IN and IN/kg showed trends similar, but not identical, to IEQ and IEQ/kg, respectively., Conclusions: Patient demographics and certain pancreatic disease features were associated with outcomes from islet isolation. Hemoglobin A1c before TPIAT was the metabolic testing measure most strongly associated with islet isolation results., Competing Interests: M.D.B. received research support from Dexcom and Viacyte and had advisory board or consultant roles with Insulet, Vertex, and Emerging Therapy Solutions. G.J.B. was supported by US Army Medical Acquisitions (grant W81XWH1810687). S.J.S. was consultant to UpToDate, Renexxion, Abbvie, and Mirum. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: There have been cases of cardiotoxicity induced by osimertinib in patients with non-small-cell lung cancer (NSCLC). However, limited data exist for a comprehensive cardiotoxicity profile analysis for osimertinib use in NSCLC patients. The aim of this study was to report the entire profile of cardiotoxicities after the initiation of osimertinib in consecutive patients with epidermal growth factor receptor (EGFR) mutation at a single health system., Methods: The data were retrospectively collected from electronic medical records for all patients who were started on osimertinib for NSCLC at West Virginia University Health System. Prevalence of heart failure (HF), atrial fibrillation, and prolonged QT before and after starting osimertinib were calculated., Results: This study had 116 participants and the median age was 72 years. The frequency of each new cardiotoxicity was between 6% and 9%, and the overall percentage of patients who had developed any of the four cardiotoxicities while on osimertinib was 19.9%. The median time of follow-up was 477 days and the median time on osimertinib for all patients was 390 days. The strongest risk factor in predicting a new onset cardiac event was hypertension with a hazard ratio (HR) of 6.35 (confidence interval (CI) 1.48 to 27.23, p=0.013) and HR 5.36 (CI 1.23 to 23.39, p=0.025) in univariate and multivariate analysis respectively., Conclusion: Osimertinib appears to be associated with an increase in cardiac abnormalities. Given the association between this medication exposure and the observed cardiac toxicities, use of osimertinib may entail closer cardiac monitoring of electrocardiogram (ECG) and echocardiogram abnormalities., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

IoT device security has become a major concern as a result of the rapid expansion of the Internet of Things (IoT) and the growing adoption of cloud computing for central monitoring and management. In order to provide centrally managed services each IoT device have to connect to their respective High-Performance Computing (HPC) clouds. The ever increasing deployment of Internet of Things (IoT) devices linked to HPC clouds use various medium such as wired and wireless. The security challenges increases further when these devices communicate over satellite links. This Satellite-Based IoT-HPC Cloud architecture poses new security concerns which exacerbates this problem. An intrusion detection technology integrated in the central cloud is suggested as a potential remedy to monitor and detect aberrant activity within the network in order to allay these worries. However, the enormous amounts of data generated by IoT devices and their constrained computing power dose not allow to implement IDS techniques at source and renders towards typical central Intrusion Detection Systems (IDS) ineffectiveness. Moreover, to protect these systems, powerful intrusion detection techniques are required due to the inherent vulnerabilities of IoT devices and the possible hazards during data transmission.During the course of literature survey it is revealed that the research work has been done to detect few types of attacks by using the old school model of IDS. The computational expensiveness in terms of processing time is also an important parameter to be considered. This work introduces a novel Embedded Hybrid Deep Learning-based intrusion detection technique (EHID) based on embedded hybrid deep learning that is created specifically for IoT devices linked to HPC clouds via satellite connectivity. Two Deep Learning (DL) algorithms are integrated in the proposed method to improve detection abilities with decent accuracy while considering the processing time and number of trainable parameters to detect 14 types of threats. It segregates among the normal and attack traffic. We also modify the conventional IDS approach and propose architectural change to harness the processing power of central server of cloud. This hybrid approach effectively detects threats by harnessing the computing power available at HPC cloud along with leveraging the power of AI. Additionally, the proposed system enables real-time monitoring and detection of intrusions while providing monitoring and management services through HPC using IoT-generated data. Experiments on Edge-IIoTset Cyber Security Dataset of IoT & IIoT indicate improved detection accuracy, reduced false positives, and efficient computational performance., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Intrauterine contraceptive devices (IUCDs) are a measure of temporary sterilization. Misplacement of IUCD is fairly common and most of these women remain asymptomatic. We report a clustered case series of misplaced, mal-positioned, and transmigrated IUCDs with serious complications and their management by minimally invasive surgery in a newly established medical school in North India., Competing Interests: Declarations. Conflict of interest: None., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The emergence of antibiotic resistance in pathogenic bacteria, including Salmonella gallinarum, poses a significant challenge to poultry health and food safety. In response, alternative strategies are urgently needed to mitigate bacterial infections without exacerbating antibiotic resistance. Phytoremediation, a sustainable and environmentally friendly approach, harnesses the natural detoxification capabilities of plants to remediate contaminants. This study explores the potential of combined phytoremediation using Andrographolide, derived from Andrographis paniculata, and Ajwain derived from Trachyspermum ammi as promising alternatives to antibiotics for treating Salmonella gallinarum infection in poultry. Andrographolide, known for its potent antimicrobial properties, exhibits inhibitory effects while Ajwain, rich in bioactive compounds, possesses antimicrobial and immunomodulatory properties. By leveraging their combined phytoremediation potential, Andrographolide and Ajwain offer a multifaceted approach to combat Salmonella gallinarum within the poultry environment. The study employed a rigorous experimental design, including in vitro assessments of antimicrobial susceptibility, cytotoxicity, and optimal concentration determination. Following this, in vivo experiments were conducted using a chicken model infected with Salmonella gallinarum. Results demonstrated that the selected combinations effectively reduced mortality rates, alleviated clinical symptoms, and mitigated gross pathological signs associated with Salmonella infection. Gene expression studies indicated a downregulation of proinflammatory cytokines, underscoring potential implications of a combined phytoremediation strategy as an innovative and sustainable solution to address Salmonella gallinarum infections in poultry production systems., 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.)

The recent resurgence of traditional medicines, driven by a renewed interest in the medicinal use of plant extracts, has garnered significant scientific attention for their therapeutic efficacy in treating a wide range of diseases. Glycyrrhiza species, commonly known as licorice, are widely recognized both as herbal remedies and as natural sweeteners. Among these, Glycyrrhiza uralensis stands out for its exceptional therapeutic potential, particularly in enhancing muscle regeneration, slowing muscle aging, and promoting skeletal muscle myogenesis. This review explores the traditional uses and biological effects of G. uralensis, highlighting the biological significance of its bioactive constituents, such as saponins and flavonoids. The hepatoprotective, antibacterial, antioxidant, anticancer, antidiabetic, antiobesity, anti-inflammatory, skeletal muscle-enhancing and cardiovascular effects of G. uralensis are reviewed, along with its toxicity and safety profile. Additionally, we propose directions for future clinical and scientific investigations, advocating for using G. uralensis as a natural therapeutic agent. The primary aim of this review is to contribute to the incorporation of this ancient medicine into modern clinical practice., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest., (© 2024. The Pharmaceutical Society of Korea.)

Objective: CT hyper-perfusion has been reported in non-convulsive status epilepticus (NCSE), while its occurrence and relevance after single seizures or with rhythmic and periodic patterns (RPPs) that lie along the ictal-interictal continuum (IIC), remain unclear. The goal of the study is to assess the role of CT perfusion (CTP) in diagnosing patients with clinical seizures, subclinical seizures, or RPPs that lie along the IIC, to help in the clinical assessment of these entities., Methods: We retrospectively reviewed inpatients who underwent a CTP and an EEG within 6 h of each other. CTP and EEGs were blindly reviewed independent of electronic medical records., Results: Out of 103 patients, 15 patients (15 %) demonstrated hyper-perfusion, 40 patients (39 %) had hypo-perfusion, while 48 patients (47 %) had normal CTP. Patients with focal CTP hyperperfusion were more likely to have clinical seizures, electrographic seizures, and/or lateralized rhythmic periodic patterns (RPPs) compared to those without CTP hyperperfusion. Focal CTP hyper-perfusion had 34 % sensitivity and 96 % specificity for identifying patients with clinical seizures, and a 40 % sensitivity and 92 % specificity for identifying patients with electrographic seizures or lateralized RPP. Although the numbers were small, none of the patients with generalized periodic discharges or generalized rhythmic delta activity had CTP hyper-perfusion., Conclusions: Focal CTP hyper-perfusion has low sensitivity but high specificity for identifying patients with seizures and lateralized RPPs, and may be considered in the clinical assessment of patients where the clinical information are unclear or insufficient., Significance: The presence of CTP hyper-perfusion should alert the physician to the possibility of an ictal related etiology accounting for the patient's symptoms., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PWK reported receiving Honoraria from Demos and Wiley for textbooks sales, he was expert witness in court on qEEG and issues of coma and EEG, and is on the DSMB for EpiWatch., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objectives: The practice of administration of intravenous (IV) antimicrobial therapy in outpatient settings (OPAT) is a low-cost alternative to in-patient admission and treatment. There is, however, limited evidence supporting OPAT management protocols for children. The primary objective of this study was to describe the use of pediatric emergency-based OPAT, as well as the safety of this practice., Methods: The study was a prospective, observational study conducted in pediatric emergency department of a tertiary care hospital. Children younger than 14 years who required pediatric emergency department-based OPAT were included in the study., Results: Three hundred and ninety-two children were included in the study. The mean duration of OPAT was 3.5 days. Ceftriaxone was the most frequently used antimicrobial. Chest infection was the commonest indication, followed by sickle cell disease with fever and soft tissue infections. There were no major intravenous line-related complications over course of treatment. Most of the patients (89.5%) completed the OPAT course successfully. Only 10.4% patients required subsequent hospital admission, with failure to improve on the OPAT protocol being the main reason patients for admission. None of the admitted patients required intensive care settings or faced unexpected morbidity., Conclusions: Our results affirm that pediatric emergency-based OPAT is a safe yet effective practice in children with good clinical outcome. We believe that a reduction in admissions translates to better hospital resource utilization., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Critical-size bone trauma injuries present a significant clinical challenge because of the limited availability of autografts. In this study, a photocurable composite comprising of polycaprolactone, polypropylene fumarate, and nano-hydroxyapatite (nHAP) (P─P─H) is printed, which shows good osteoconduction in a rat model. A cryogel composed of gelatin-nHAP (GH) is developed to incorporate osteogenic components, specifically bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA), termed as GH+B+Z, which is investigated for osteoinductive property in a rat model. Further, a 3D-printed P─P─H scaffold impregnated with GH+B+Z is designed and implanted in a critical-size defect (25 × 10 × 5 mm) in goat tibia. After 4 months, the scaffold is well-integrated with adjacent native bone, with osteoinduction observed in the cryogel-filled region and osteoconduction over the printed scaffold. X-ray radiography and micro-CT analysis showed bone in-growth in the treatment group with 45 ± 1.4% bone volume/tissue volume (BV/TV), while the defect remained unhealed in the control group with BV/TV of 10.5 ± 0.5%. Histology showed significant cell infiltration and matrix deposition over the printed P─P─H scaffold and within the GH cryogel site in the treatment group. Immunohistochemical staining depicted significantly higher normalized collagen I intensity in the treatment group (34.45 ± 2.61%) compared to the control group (4.22 ± 0.78)., (© 2024 Wiley‐VCH GmbH.)

Skeletal muscle (SM) contains a diverse population of muscle stem (or satellite) cells, which are essential for the maintenance of muscle tissue and positively regulated by prostaglandin E2 (PGE2). However, in aged SM, PGE2 levels are reduced due to increased prostaglandin catabolism by 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a negative regulator of SM tissue repair and regeneration. Screening of a library of 80,617 natural compounds in the ZINC database against 15-PGDH was conducted from PyRx. Further, drug-likeness rules, including those of Lipinski, Ghose, Veber, Egan, and Muegge were performed. The selected complex was forwarded for MD simulations up to 100ns. Based on free energy of binding obtained from docking revealed that ZINC14557836 and ZINC14638400 more potently inhibiting to 15-PGDH than SW033291 (the control and high-affinity inhibitor of 15-PGDH). The free energies of binding obtained from PyRx for 15-PGDH-ZINC14557836, 15-PGDH-ZINC14638400, and 15-PGDH-SW033291 complexes were - 10.30, -9.80, and - 8.0 kcal/mol, respectively. Root mean square deviations (RMSDs), root mean square fluctuations (RMSFs), radii of gyration (Rg), solvent-accessible surface areas (SASAs), and H-bond parameters obtained by 100 ns MD simulations predicted ZINC14557836 and ZINC14638400 more stably complexed with 15-PGDH than SW033291. The several parameters, including physicochemical properties and drug-likenesses, were within acceptable limits, and ZINC14557836 and ZINC14638400 also satisfied other drug-likeness rules, including those of Lipinski, Ghose, Veber, Egan, and Muegge. These findings suggest that ZINC14557836 and ZINC14638400 provide starting points for the development of medications that increase SM regeneration and muscle stem (or satellite) cell numbers by inhibiting 15-PGDH., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflicts of interest. Consent to participate: Not applicable. Consent for publication: All co-authors have read and approved the manuscript. Ethical approval: This is a purely computational study and ethics approvals are not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: The remarkable adaptability to the environment, high growth rate, meat with good taste and aroma, and ornamental appearance of the Pradu Hang Dam (PDH) and Samae Dam (SD) chickens make them valuable for improvement of poultry production to enhance food security. However, despite their close phenotypic similarity, distinct classification of PDH and SD chickens remains controversial. Thus, this study aimed to clarify genetic origins and variation between PDH and SD chickens, genetic diversity and structures of PDH and SD chickens., Methods: This study analyzed 5 populations of PDH and 2 populations of SD chickens using 28 microsatellite markers and compared with those of other indigenous and local chicken breeds using Thailand's "The Siam Chicken Bioresource Project" database., Results: Considerably high genetic variability was observed within PDH (370 total alleles; 4.086±0.312 alleles/locus) and SD chickens (179 total alleles; 3.607±0.349 alleles/locus). A partial overlap of gene pools was observed between SD chickens from the Department of Livestock, Uthai Thani (SD1) and PDH chickens, suggesting a potentially close relationship between the two chicken breeds. A gene pool that partially overlapped with that of the red junglefowl was observed in the SD chicken population from the Sanhawat Farm Uthai Thani population (SD2). Distinct subclusters were observed within SD chickens, indicating the possibility that genetic differentiation occurred early in the process of establishment of SD chickens., Conclusion: These findings could offer valuable insights into genetic verification of Thai local chicken breeds and their sustainable conservation and utilization.

Mastitis is an inflammatory condition that affects dairy cow's mammary glands. Traditional treatment approaches with antibiotics are increasingly leading to challenging scenarios such as antimicrobial resistance. In order to mitigate the unwanted side effects of antibiotics, alternative strategies such as those that harness the host immune system response, also known as immunotherapy, have been implemented. Immunotherapy approaches to treat bovine mastitis aims to enhance the cow's immune response against pathogens by promoting pathogen clearance, and facilitating tissue repair. Various studies have demonstrated the potential of immunotherapy for reducing the incidence, duration and severity of mastitis. Nevertheless, majority of reported therapies are lacking in specificity hampering their broad application to treat mastitis. Meanwhile, advancements in mastitis immunotherapy hold great promise for the dairy industry, with potential to provide effective and sustainable alternatives to traditional antibiotic-based approaches. This review synthesizes immunotherapy strategies, their current understanding and potential future perspectives. The future perspectives should focus on the development of precision immunotherapies tailored to address individual pathogens/group of pathogens, development of combination therapies to address antimicrobial resistance, and the integration of nano- and omics technologies. By addressing research gaps, the field of mastitis immunotherapy can make significant strides in the control, treatment and prevention of mastitis, ultimately benefiting both animal and human health/welfare, and environment health.

Social media has become omnipresent in society, especially given that it enables the rapid and widespread communication of news, events, and information. Social media platforms have become increasingly used by numerous surgical societies to promote meetings and surgical journals to increase the visibility of published content. In September 2020, Annals of Surgical Oncology (ASO) established its Social Media Committee (SMC), which has worked to steadily increase the visibility of published content on social media platforms, namely X (formerly known as Twitter). The purpose of this review is to highlight the 10 ASO original articles with the most engagement on X, based on total number of mentions, since the founding of the SMC. These articles encompass a wide variety of topics from various oncologic disciplines including hepatopancreatobiliary, breast, and gynecologic surgery., (© 2024. Society of Surgical Oncology.)

Treatment of critical-size osteochondral (OC) injuries at load-bearing sites has remained a major clinical challenge in orthopedic surgery. This is due to the anisotropic characteristics of OC tissue and the stratified structure of the cartilage. Here, we developed a multilayered OC scaffold by employing cryogelation technology. Gelatin, chitosan, and chondroitin sulfate were utilized for designing three distinct, 2425 ± 120 μm thick layers of cartilage having different alignments, while nanohydroxyapatite and gelatin were used for the subchondral bone layer. Exosomes derived from articular chondrocytes in the range of 60-110 nm were used to promote chondrogenesis. The biocompatibility and cartilage formation potential of the scaffold and exosomes were initially evaluated in rat OC defects. The application of exosome-loaded scaffolds was then investigated in a critical-size OC injury (8 × 10 mm) created in the goat knee. Artificial synovial fluid was designed and utilized as a carrier for exosomes for a booster dose administered as an intra-articular injection. X-ray imaging and micro-CT analysis revealed that the treatment resulted in improved subchondral bone regeneration. The defect region exhibited healthy hyaline cartilage formation, as detected by MRI imaging. Moreover, histological examination revealed that the treatment group showed augmented cell proliferation, matrix deposition, secretion of proteoglycans, and the formation of stratified hyaline cartilage over a long-term (6 and 12 months), whereas the control group demonstrated the formation of fibrocartilage. Treatment-induced upregulation of collagen II, aggrecan, and SOX 9 genes (∼10 fold) further provided evidence that the cartilage phenotype was well preserved. Hence, the proposed treatment has significant translational potential for treating adverse OC clinical injuries.

Competing Interests: Disclosure: Syed A. Ahmad is a member of the speakers’ bureau of Abbvie Inc. Raja R. Narayan, Andrew M. Fleming, Meredith Gunder, Syed N. Zafar, Zaid Abdelsattar, Esra Bilir, Thuy Tran, Tracey Pu, Lindsay Friedman, and Kelly M. McMasters report no additional conflicts of interest that may be relevant to the contents of this article.

Amentoflavone (AF) is a biflavonoid compound found in many plants. In this study, we first demonstrate that AF has a potent antiviral effect against the influenza virus via the inhibition of viral attachment and virucidal effects. The anti-influenza-viral effect of AF was evaluated using green fluorescent protein-tagged Influenza A virus (IAV) with fluorescent microscopy and flow cytometry analysis. AF decreased the GFP expression by viral infection, dose-dependently. Fifty micromoles of AF suppressed the GFP expression by virus infection of up to 70% of untreated infected control cells. Consistently, immunofluorescence results showed the inhibitory effect of AF on viral protein expression. Time-of-addition and hemagglutination assays revealed that AF inhibits viral binding to cells by interfering with the hemagglutinin (HA) of IAV. Furthermore, AF has a virucidal effect and blocks cytopathic effects caused by the Influenza B virus and H3N2 IAV. Additionally, AF represses the neuraminidase (NA) activity of IAV. In silico analysis confirmed the potential interaction of AF with both HA and NA. Our findings indicate that AF has antiviral effects by modulating HA and NA during the attachment and release stages of influenza viral infection.

Background: The Annals of Surgical Oncology (ASO) launched a Social Media Committee in 2022 to strategically promote surgical science, boost journal impact, and raise awareness of cutting-edge research. This study investigated the impact of the ASO Social Media Committee on journal visibility, publication engagement, and article-level metrics., Methods: Manuscripts accepted by ASO and promoted on Twitter/X between 21 September 2020 and 20 September 2023 were evaluated for differences in article and social media metrics. Pearson correlations evaluated the relationship between normalized article downloads and normalized likes, retweets/reposts, and quote tweets/quotes. Group comparisons of social media engagement by article type were performed., Results: In the 18 months before the formation of the ASO Social Media Committee, 1023 manuscripts were published, and 1023 were published in the 18 months afterward. The median Altmetric scores for articles published before (3.0; IQR, 0-7.0) and afterward (2.0; IQR, 0-7.0) were similar (p = 0.480). In contrast, the normalized median number of downloads per article was significantly greater after the Social Media Committee was formed (0.85 downloads per article [IQR, 0.55-1.48] vs 1.37 [IQR, 0.93-2.51]; p < 0.001). Positive correlations were noted for normalized downloads with likes (r = 0.14; p < 0.001), retweets/reposts (r = 0.08; p < 0.001), and quote tweets/quotes (r = 0.16; p < 0.001). No difference in social media engagement by article type was observed., Conclusion: More downloads were noted for ASO articles posted by the Social Media Committee after normalization. An organized effort to promote surgical science likely improves article exposure. Future efforts should seek to expand article promotion to additional social media and networking platforms with a more international, multi-lingual approach., Competing Interests: Disclosure Syed A. Ahmad is involved with Speaker Bureau of Abbvie Inc. The remaining authors have no conflicts of interest., (© 2024. Society of Surgical Oncology.)

Competing Interests: Disclosures The authors declare no conflicts of interest.

This study aimed to evaluate the effects of deteriorated physicochemical conditions in the river Jhelum on parasitic infestations and to investigate the potential of fish parasites as bioindicators of water quality. All the physicochemical parameters exhibited statistically significant differences based on both site and season (p < 0.01). The interaction term (Site × Season) was also kept in the model since it was statistically significant (p < 0.01). A parasitological survey of 360 schizothoracine fish revealed a 30.3% prevalence (109/360) of endohelminth infection. The study identified four predominant parasitic taxa across two distinct classes: Cestoda, including Adenoscolex oreini and Schyzocotyle acheilognathi, and Acanthocephala, comprising Pomphorhynchus kashmirensis and Neoechinorhynchus manasbalensis. For the assessment of parasitic load, we calculated the prevalence, mean intensity, mean abundance, and index of infection for each sampling period. Correspondence analysis identified associations between parasite occurrence and specific water quality parameters. Regression analysis, including R 2 and p values, demonstrated a positive correlation between the number of parasites and both the proportion of infected fish and the ratio of infected to examined fish. Given that parasitic load is significantly influenced by a range of water quality parameters, fish parasites can serve as a robust indicator of declining water quality. Fish parasites are highly sensitive to water quality changes such as pollutants, toxins, and fluctuations in pH, temperature, and oxygen levels. Deteriorating water quality can stress fish, compromising their immune systems and increasing their susceptibility to parasitic infections. Additionally, complex life cycles of parasites can be disrupted by poor water conditions, making them indicators of water quality issues., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Sex differences in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) susceptibility, illness severity, and hospital course are widely acknowledged. The effects of sex on outcomes experienced by patients with severe Coronavirus Disease 2019 (COVID-19) admitted to the intensive care unit (ICU) remains unknown., Objectives: To determine the effects of sex on ICU mortality in patients with COVID-19 METHODS: This retrospective analysis of an international multi-center prospective observational database included adults admitted to ICU for treatment of acute COVID-19 between 1st January 2020 and 30th June 2022. The primary outcome was ICU mortality. Multivariable Cox regression was used to ascertain the hazard of death (Hazard Ratio=HR) adjusted for pre-selected covariates. The secondary outcome was sex differences in complications of COVID-19 during hospital stay., Results: Overall, 10,259 patients (3,314 females, 6,945 males) were included with a median age of 60 (interquartile range [IQR]=49-68) and 59 (IQR=49-67) years, respectively. Baseline characteristics were similar between sexes. More females were non-smokers (65% vs. 44 %, p < 0.01) and obese (39% vs. 30 %, p < 0.01), compared to males. Also, males received greater ICU intervention (mechanical ventilation, prone ventilation, vasopressors, and tracheostomy) than females. Males had a greater hazard of death (compared to females, HR=1.14; 95 % CI=1.02-1.26). Adjustment for complications during hospital stay did not alter the hazard of death (HR=1.16; 95 % CI=1.05-1.28). Males had a significantly elevated hazard of death among patients who received ECMO (HR=1.24; 95 % CI=1.01-1.53). Male sex was associated with cardiac arrest (adjusted OR [aOR]=1.37; 95 % CI=1.16-1.62) and PE (aOR=1.28; 95 % CI=1.06-1.55)., Conclusion: Among patients admitted to ICU for severe COVID-19, males experienced higher severity of illness and more frequent intervention than females. Ultimately, the hazard of death was moderately elevated in males compared to females despite greater PE and cardiac arrest., Competing Interests: Declaration of competing interest We, the authors of the manuscript “Sex Differences in The Outcome of Critically Ill COVID-19 Patients - An International Multicentre COVID-19 Critical Care Consortium Study” declare that we have no competing interests in any of the categories listed: employment, consultancies, stock ownership, honoraria, paid expert testimony, patient applications/registrations (as listed on the journal website). Our funding statement as presented in the manuscript is accurate as of the submission date and presents no conflict of interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This review explores recent progress in sequencing batch reactors (SBRs) and hybrid systems for wastewater treatment, emphasizing their adaptability and effectiveness in managing diverse wastewater compositions. Through extensive literature analysis from 1985 to 2024, the integration of advanced technologies like photocatalysis within hybrid systems is highlighted, showing promise for improved pollutant removal efficiencies. Insights into operational parameters, reactor design, and microbial communities influencing SBR performance are discussed. Sequencing batch biofilm reactors (SBBRs) demonstrate exceptional efficiency in Chemical Oxygen Demand, nitrogen, and phosphorus removal, while innovative anaerobic-aerobic-anoxic sequencing batch reactors (AOA-SBRs) offer effective nutrient removal strategies. Hybrid systems, particularly photocatalytic sequencing batch reactors (PSBRs), show potential for removing persistent pollutants like antibiotics and phenols, underscoring the significance of advanced oxidation processes. However, research gaps persist, including the need for comparative studies between different SBR types and comprehensive evaluations of long-term performance, environmental variability, and economic viability. Addressing these gaps will be vital for the practical deployment of SBRs and hybrid systems. Further exploration of synergies, economic considerations, and reactor stability will enhance the sustainability and scalability of these technologies for efficient and eco-friendly wastewater treatment., 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 Inc. All rights reserved.)

Background: In this COVID-19 Critical Care Consortium (CCCC) sub-study, we qualified neurological complications associated with SARS-CoV2 infection., Methods: The CCCC is an international, multicenter study. Eligible patients were COVID-19 patients admitted to intensive care units (ICU) across 23 centers between 1/7/2020 to 6/23/2022. Incidence of neurological complications was estimated as number of events per hospital days and per admission using Poisson regression. Associations between neurological complications and risk factors were assessed using multivariable Poisson regression., Results: 713 patients were included. Median age = 56 years (interquartile range (IQR) = 45-65). Neurological complications reported in 61/480 patients (12.7%) with the majority being ischemic stroke (2.9%), intracranial hemorrhage (ICH) (2.8%), and seizures (2.6%). Multivariable analysis for neurological complications per admitted days showed comorbid neurological conditions (incidence rate ratio (IRR) = 6.35, 2.57-15.7) were an independent risk factor for ischemic stroke. Extracorporeal membrane oxygenation (IRR = 5.32, 1.52-18.6), low-middle income countries (LMIC) vs high income countries (HIC) (IRR = 4.70, 1.62-13.7), and age >55 (IRR = 3.66, 1.23-10.9) were independent risk factors for ICH. Co-morbid neurological conditions (IRR = 3.43, 1.11-10.6), LMIC vs HIC (IRR = 8.69, 2.15-35.2), July-December 2020 vs January-June 2020 (IRR = 0.17, 0.04-0.69) and age >55 (IRR = 4.05, 1.15-14.3) were independent risk factors for seizure., Conclusions: Decision-making should incorporate salient risk factors to inform management of SARS-CoV2 infection and avoid neurological complications., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Burn injuries are serious injuries that have a big impact on a person's health and can even cause death. Incurring severe burns can incite an immune response and inflammation within the body, alongside metabolic changes. It is of utmost importance to grasp the fact that the effects of the burn injury extend beyond the body, affecting the mind and overall well-being. Burn injuries cause long-lasting changes that need to be taken care of in order to improve their quality of life. The intricate process of skin regeneration at the site of a burn wound involves a complex and dynamic interplay among diverse cells, growth factors, nerves, and blood vessels. Exciting opportunities have arisen in the field of stem cells and regenerative medicine, allowing us to explore the development of cell-free-based alternatives that can aid in the treatment of burn injuries. These cell-free-based therapies have emerged as a promising facet within regenerative medicine. Exosomes, also referred to as naturally occurring nanoparticles, are small endosome-derived vesicles that facilitate the delivery of molecular cargo between the cells, thus allowing intercellular communication. The knowledge gained in this field has continued to support their therapeutic potential, particularly in the domains of wound healing and tissue regeneration. Notably, exosomes derived from mesenchymal stem cells (MSCs) can be safely administered in the system, which is then adeptly uptaken and internalized by fibroblasts/epithelial cells, subsequently accelerating essential processes such as migration, proliferation, and collagen synthesis. Furthermore, exosomes released by immune cells, specifically macrophages, possess the capability to modulate inflammation and effectively diminish it in adjacent cells. Exosomes also act as carriers when integrated with a scaffold, leading to scarless healing of cutaneous wounds. This comprehensive review examines the role of exosomes in burn wound healing and their potential utility in regeneration and repair., (© 2024. The Author(s).)

Objective: To investigate the effects of Alogliptin in chemical-induced post-menopausal osteoporosis., Methodology: The binding affinity of alogliptin with osteogenic proteins was analysed in silico. The effect of alogliptin on osteogenic proteins and mineralization of osteoblastic cells was evaluated in UMR-106 cells. Further, in vivo anti-osteoporotic activity of alogliptin was evaluated in postmenopausal osteoporosis. Various bone turnover markers were assayed in serum. This followed the analysis of microarchitecture of bone, histology, and immunohistochemistry (IHC) of bone tissue., Results: Docking scores showed that alogliptin has binding affinity for bone alkaline phosphatase (BALP), osteocalcin, and bone morphogenic protein (BMP-2). Alogliptin also enhanced mineralization of osteoblast cells, evidenced with increased ALP, osteocalcin, and BMP-2. Animal studies revealed significant elevation of bone formation markers, bone ALP, osteocalcin and BMP-2, and decreased bone resorption markers, receptor activator of NF-κβ (RANKL), cathepsin K (CTSK), tartrate resistant acid phosphatase (TRAcP5b) in VCD-induced post-menopausal osteoporosis. Micro computed tomography (μCT) analysis and histology of femur bone and lumbar vertebrae demonstrated decrease in trabecular separation and improved bone density. IHC of femur showed reduced DPP4 enzyme., Conclusions: Alogliptin increased mineralization in osteoblast cells. It had beneficial effects also altered bone turnover markers, repaired the trabecular microstructure, improved bone mineral density, and exhibited bone forming capacity targeting DPP-4 enzyme in postmenopausal osteoporosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

While pancreatic adenocarcinoma requires surgical resection definitive cure, treatment paradigms are shifting toward a neoadjuvant approach to systemic therapy. Rationale is twofold: micro-metastatic disease is likely present in a majority of patients, reinforcing the importance of systemic therapy regardless of resectability; moreover, systemic therapy is well-tolerated and improves surgical outcomes when delivered preoperatively. Second, a neoadjuvant approach allows for selection of biology and patients most likely to benefit from potentially morbid surgery. This review examines the increasing body of evidence in support of empiric neoadjuvant therapy in pancreatic adenocarcinoma., Competing Interests: Disclosure The listed authors have no disclosures to submit., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In patients with localized pancreatic ductal adenocarcinoma (PDAC) undergoing neoadjuvant therapy (NAT) and resection, selection of adjuvant chemotherapy (AC) is typically guided by high-risk features on histopathologic examination. We evaluated the interaction between post-NAT lymph node metrics and AC receipt on survival., Methods: Patients who received NAT followed by pancreatectomy (2010-2020) at seven centers were reviewed. Overall survival (OS) in patients receiving AC or not was stratified by lymph node positivity (LNP) or lymph node ratio (LNR) dichotomized at 0.1. Cox models evaluated the independent association between these nodal metrics, AC receipt, and OS., Results: Of 464 patients undergoing NAT and resection, 264 (57%) received AC. Patients selected for AC were younger (median 63 vs. 67 years; p < 0.001), received shorter duration of NAT (2.8 vs. 3.2 months; p = 0.01), had fewer postoperative complications (Clavien-Dindo grade > 3: 1.2% vs. 11.7%; p < 0.001), and lower rates of pathologic complete response (4% vs. 11%; p = 0.01). The median number of nodes evaluated was similar between cohorts (n = 20 in both; p = 0.9). Post-NAT LNP rates were not different, and median LNR was 0.1, in AC and non-AC cohorts. Both LNP (hazard ratio [HR]: 2.1, p < 0.001) and LNR (0 < LNR ≤ 0.1: HR: 1.98, p = 0.002; LNR > 0.1: HR 2.46, p < 0.001) were independently associated with OS on Cox modeling, although receipt of AC was not associated with improved OS (median 30.6 vs. 29.4 months; p = 0.2). In patients with LNR > 0.1, receipt of AC was associated with significantly longer OS compared to non-AC (24 vs. 20 months, respectively; p = 0.04)., Conclusions: LNR following NAT, not simply nodal positivity, may be useful to refine selection of AC in resected PDAC., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Introduction: Surgery followed by pathology-guided adjuvant therapy is standard treatment for colon cancer. Data from the FOxTROT clinical trial showed potential benefit of a 6-wk neoadjuvant chemotherapy (NACT) in T3/T4 patients. The present study evaluated real-world outcomes of neoadjuvant therapy in a national cohort of patients with resectable colon cancer., Methods: 169,120 patients with clinical stage I, II, or III colon cancer from the National Cancer Database registry were included. Patients were categorized as having received neoadjuvant therapy followed by surgery (NACT), surgery then adjuvant chemotherapy (AC), or surgery alone. Factors associated with treatment sequencing and outcomes were assessed., Results: Of identified patients, 1.4% received NACT including 0.5% of stage I, 1.8% of stage II, and 3.0% of stage III. For stage I, 5-y overall survival (OS) was 74.7% after AC, 62.2% after NACT, and 76.4% after SA. For stage II, 5-y OS was 73.2% after AC, 66.8% after NACT, and 64.3% after SA. For stage III, 5-y OS was 67.3% after AC, 67.7% after NACT, and 42.4% after SA. Cox proportional-hazards model suggested NACT had worse outcomes versus AC in clinical stages I (hazard ratio [HR] = 1.59, 95% confidence interval [CI] 1.39-1.85, P < 0.01) and II (HR = 1.37, 95% CI 1.23-1.52, P < 0.01). In stage III, there was no difference in OS between NACT and AC (HR = 1.1, 95% CI 0.99-1.22, P = 0.05)., Conclusions: In a real-world national cohort of patients with resectable colon cancer, NACT had no OS benefit over AC. Future studies should examine which subset of patients might benefit from neoadjuvant approaches., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Postoperative adverse events (AEs) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PC) treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. We conducted a preplanned secondary analysis of patients enrolled on the Alliance A021501 clinical trial to quantify perioperative AE rates., Methods: The A021501 phase 2 trial randomized patients with BR-PC to receive 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX and hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (December 31, 2016 to May 31, 2019). Adverse events were assessed 90 days after pancreatectomy., Results: Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n = 32, Arm 1; n = 19, Arm 2) at 28 institutions. Five (10%) patients required reoperation within 90 days; 56% of patients (n = 27/48) experienced at least one grade 3 or higher AE (50% vs. 67%, p = 0.37). Ninety-day mortality was 2.0%. Readmission was less frequent in Arm 1 (16% vs. 42%, p = 0.05), but there were no differences between study arms in rates of reoperation (13% vs. 5%), pancreatic fistula or intra-abdominal abscess requiring drainage (9% vs. 16%), or wound infection (6% vs. 16%). Pancreatic fistula or intra-abdominal abscess requiring drainage was associated with receipt of adjuvant therapy (p = 0.012). No difference in overall survival was observed based on occurrence of postoperative AEs (hazard ratio = 1.1; 95% confidence interval 0.5-2.6)., Conclusions: In this multicenter study, rates of postoperative AEs were consistent with those previously reported. Multimodality trials of preoperative therapy for BR-PC may be performed in the cooperative group setting with careful quality assurance and safety monitoring., Trial Registration: Clinicaltrials.gov identifier: NCT02839343., (© 2024. Society of Surgical Oncology.)

High levels of purine and uric acid, which are associated with health issues such as gout and cardiovascular disease, are found in the meat of fast-growing broiler chickens, which raises concerns about the quality of chicken meat and the health of the consumers who consume it. High genetic homogeneity and uniformity, particularly in genes involved in the synthesis of inosine monophosphate (IMP) and subsequent process of purine synthesis, which are associated with the meat quality, are exhibited in commercial broiler chickens owing to intensive inbreeding programs. Adenosine succinate lyase (ADSL) is a key enzyme involved in de novo purine biosynthetic pathway and its genetic polymorphisms affect IMP metabolism and purine content. In this study, we investigated the polymorphism of the ADSL gene in indigenous and local chicken breeds and red junglefowl in Thailand, using metabarcoding and genetic diversity analyses. Five alleles with 73 single nucleotide polymorphisms in exon 2, including missense and silent mutations, which may act on the synthesis efficiency of IMP and purine. Their protein structures revealed changes in amino acid composition that may affect ADSL enzyme activity. Weak purifying selection in these ADSL alleles was observed in the chicken population studied, implying that the variants have minor fitness impacts and a greater probability of fixation of beneficial mutations than strong purifying selection. A potential selective sweep was observed in Mae Hong Son chickens, whose purine content was lower than that in other breeds. This suggests a potential correlation between variations of the ADSL gene and reduced purine content and an impact of ADSL expression on the quality of chicken meat. However, further studies are required to validate its potential availability as a genetic marker for selecting useful traits that are beneficial to human health and well-being., 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.)

Invasive fungal infections in patients with leukemia carry a high mortality rate, but early diagnosis has the potential to modify this natural history. A novel screening method using Aspergillus droplet-digital polymerase chain reaction in exhaled breath condensate may have a similar performance to serum galactomannan screening. Larger studies, including other molds, are necessary., Competing Interests: Potential conflicts of interest. R.B. and S.H. report receiving the 2021 Princess Margaret Cancer Centre Catalyst Grant in support of this study. V.G. reports receiving grant support from AbbVie and Novartis, consulting fees from Novartis, BMS Celgene, Daichii Sankyo, AbbVie, GSK, and Pfizer, honoraria from Novartis, BMS Celgene, AbbVie, and GSK, and participation in DSMB/advisory board for BMS Celgene, Incyte, and GSK, all not directly related to this study. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Considerable advancements have been made in breast cancer therapeutics in the past few decades. However, the advent of chemo-resistance and adverse drug reactions coupled with tumor metastasis and recurrence posed a serious threat to combat this lethal disease. Novel anti-cancer agents, as well as new therapeutic strategies, are needed to complement conventional breast cancer therapies. The quest for developing novel anti-cancer drugs caused an upsurge in exploring and harnessing natural compounds, especially phytochemicals. Various research groups have explored and documented the anti-cancer potential of wide variety of phytochemical groups including flavonoids (curcumin, kaempferol, myricetin, quercetin, naringenin, apigenin, genistein epigallocatechin gallate), stilbenes (resveratrol), carotenoids (crocin, lycopene, lutein), and anthraquinone (Emodin). However, low chemical stability, poor water solubility, and short systemic half-life impede their clinical utility. The implication of nano-technological approaches to decode the pharmacokinetic challenges associated with phytochemical usage, as well as selective drug targeting, have markedly enhanced the pre-clinical anti-cancer activity, thus aiding in their clinical translation. This review documented the recent advances in utilizing phytochemicals for breast cancer prevention and lipidbased nanotechnological approaches for circumventing their pharmacokinetic concerns to enhance their systemic availability, cytotoxicity, and targeted delivery against breast cancer alone as well as in combination with conventional therapeutic agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Patients presenting with large ventral abdominal wall hernias require pretreatment with injection botulinum toxin A before surgery. Currently, multipoint and multilayered botulinum injection techniques are practiced. We are describing a new ultrasound-guided, 1-point, single interfascial plane botulinum toxin A injection technique for the closure of big hernial defects., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Background: Treatment cost and high prevalence of Poly Cystic Ovarian Syndrome (PCOS) is a very challenging issue globally. Due to this reason; current study was conducted to determine pharmaco-economy of conventional and non-conventional treatments for the management of PCOS., Methods: Prospective Cross-Sectional study was conducted in the metropolitan city of Karachi from January - December 2019. Primary data of 200 PCOS patients were collected from different hospitals and clinics. An instrument was used to collect data pertaining to the direct and indirect cost associated with the disease management. Collected data was analyzed by the tools for cost analysis and software called Statistical Package of Social Sciences (SPSS) - 22., Results: In Cost Minimization Analysis (CMA); Allopathic treatment [Mean cost/month: PKR:4479.32 ± 350.95 (USD:27.46 ± 2.15)], Herbal treatment [Mean cost/month: PKR:1527.78 ± 78.15 (USD:9.37 ± 0.48)], Combination treatment [Mean cost/month: PKR:2803.09 ± 654.22 (USD:17.18 ± 4.01)], and Homoeopathic treatment [Mean cost/month: PKR:976.95 ± 46.19 (USD:5.99 ± 0.28)]. Incremental cost/month for Allopathic treatment is 358%, Herbal treatment is 56%, Combination treatment is 187%. In Cost Effectiveness Analysis (CEA); Allopathic treatment (Incremental cost-effectiveness ratio/month: 1334.24), Herbal treatment (Incremental cost-effectiveness ratio/month: 936.41), Combination treatment (Incremental cost-effectiveness ratio/month: 1017.09). Due to lowest cost of Homeopathic treatment, cost of Homeopathic treatment was considered as a threshold value. In-direct cost/month of Allopathic treatment is PKR:593.33 ± 24.00 (USD:3.64 ± 0.15), Herbal treatment is PKR:307.84 ± 26.69 (USD:1.89 ± 0.16), Combination treatment is PKR:409.09 ± 45.63 (USD:2.51 ± 0.28) and Homoeopathic treatment is PKR:300.00 ± 26.39 (USD:1.84 ± 0.16)., Conclusion: The most cost-effective is treatment is Homeopathic; Herbal treatment is second most cost-effective option for the treatment of PCOS. Lowest direct and indirect costs and short treatment duration collaboratively lessen the %incremental cost per year and incremental cost effectiveness ratio per year., (© 2024. The Author(s).)

Objectives: This study aimed to investigate the role of dipeptidyl peptidase-8 and 9 (DPP-8/9) enzymes in inflammatory bone loss using a 4-vinylcyclohexene diepoxide (VCD)-induced model in Wistar rats. Additionally, we evaluated the therapeutic potential of inhibiting these enzymes with the flavonoid chrysin., Methods: Inflammatory osteoporosis was induced by administering VCD that elevated interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) levels. DPP-8/9 enzyme expression and various bone markers were assayed using serum. Further analysis included bone microarchitecture, histology, and immunohistochemistry. Additionally, chrysin's potential to inhibit DPP-8/9 and mitigate VCD-induced inflammatory bone loss was also evaluated., Key Findings: VCD administration in rats caused ovotoxicity that increased IL-6 and TNF-α levels, resulting in significant bone loss. Serum analysis revealed elevated bone resorption markers and DPP-8/9 enzyme levels. Inhibiting DPP-8/9 with 1G244 reversed these effects, confirmed by histology, immunohistochemistry, and micro-CT scans. Moreover, chrysin significantly reduced DPP-8/9 levels compared with the untreated group, improved bone markers, and lower inflammatory cytokines, indicating reduced osteoclastogenesis., Conclusion: This study highlights the role of DPP-8/9 in inflammation-induced osteoporosis. Following inhibition of DPP-8/9, we observed improved bone markers with preservation of trabecular bone mineral density in rats. Additionally, chrysin demonstrated potential as an anti-DPP-8/9 agent, suggesting its viability for future therapeutic interventions in DPP-8/9-related inflammatory diseases., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction and Importance: Laryngeal Spindle Cell Carcinoma (SpCC), a rare subtype constituting only 0.5% of cases, poses diagnostic challenges due to its biphasic nature and histological resemblance to other neoplasms. Our study explores unique observations, including monoclonal epithelial origin and an unusually large tumor triggering respiratory distress., Case Report: In this comprehensive case report, a 62-year-old male with a history of tuberculosis and extensive smoking presented with respiratory distress and a white vocal cord mass, diagnosed as spindle cell carcinoma (SpCC). Laryngoscopic and imaging evaluations revealed an ill-defined mass originating from the right supraglottic larynx. Histopathological examination and immunohistochemistry confirmed confirming the diagnosis. The management included immediate tracheostomy, surgical resection, adjuvant radiation therapy, and chemotherapy. Regular follow-ups and a multidisciplinary approach contributed to a successful three-year outcome without recurrence., Clinical Discussion: Spindle Cell Carcinomas (SpCCs) of the larynx, historically termed carcinosarcoma and sarcomatoid carcinoma, are rare and predominantly affect middle-aged to elderly males. These biphasic tumors arise from both epithelial and spindle cell elements and present with symptoms like hoarseness and dysphagia. Risk factors include tobacco use, alcohol, and viral infections. Accurate diagnosis relies on histological and immunohistochemical analysis. Early detection facilitates favorable outcomes, with five-year survival rates ranging from 65 to 95%., Conclusion: Spindle Cell Carcinoma (SpCC) of the larynx, originating from epithelial and spindle cell elements, requires early detection through histological and immunohistochemical analysis. Early diagnosis leads to a notably optimistic five-year survival prognosis., Competing Interests: Conflict of interest statement None declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Wound healing represents a complex biological process crucial for tissue repair and regeneration. In recent years, biomaterial-based scaffolds loaded with bioactive compounds have emerged as promising therapeutic strategies to accelerate wound healing. In this study, we investigated the properties and wound healing effects of cryogels loaded with calcium peroxide (CP) and berberine (BB). The cryogels were synthesized through a cryogenic freezing technique and displayed pore diameters of 83 ± 39 μm, with porosity exceeding 90%. Following 20 days of degradation, the percentage of remaining weight for GPC and GPC-CP-BB cryogels was determined to be 12.42 ± 2.45% and 10.78 ± 2.08%, respectively. Moreover, the swelling ratios after 3 minutes for GPC and GPC-CP-BB were found to be 22.10 ± 0.05 and 21.00 ± 0.07, respectively. In vitro investigations demonstrated the cytocompatibility of the cryogels, with sufficient adhesion and proliferation of fibroblast (NIH-3T3) cells observed on the scaffolds, along with their hemocompatibility. Furthermore, the cryogels exhibited sustained release kinetics of both calcium peroxide and berberine, ensuring prolonged therapeutic effects at the wound site. In vivo assessment using a rat model of full-thickness skin wounds demonstrated accelerated wound closure rates in animals treated with the GPC-CP-BB scaffold compared to controls. Histological analysis revealed enhanced granulation tissue formation, re-epithelialization, and collagen deposition in the GPC-CP-BB group. Overall, our findings suggest that the scaffold loaded with CP and BB holds great promise as a therapeutic approach for promoting wound healing. Its multifaceted properties offer a multifunctional platform for localized delivery of therapeutic agents while providing mechanical support and maintaining a favorable microenvironment for tissue regeneration.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with diverse clinical manifestations. Among these, ocular complications are notably prevalent, affecting up to one-third of patients. One rare but serious ocular complication of SLE is central retinal artery occlusion (CRAO), which can result in significant vision loss. We report a case of a young woman with sudden, painless vision loss in her right eye over two days. Fundoscopy confirmed CRAO, with no light perception in the affected eye and normal vision in the left eye. Physical examination revealed symptoms suggestive of a connective tissue disorder, including malar rash and Raynaud's phenomenon. Laboratory tests confirmed SLE. Despite treatment with methylprednisolone, hydroxychloroquine, aspirin, and nifedipine, the patient's vision did not improve. CRAO in SLE indicates severe retinal vasculopathy and has a poor prognosis. This case highlights the importance of considering SLE in patients with sudden vision loss and systemic symptoms, emphasizing early diagnosis and comprehensive management to prevent severe complications., 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, Khan et al.)

Hybrid sterility, a hallmark of postzygotic isolation, arises from parental genome divergence disrupting meiosis. While chromosomal incompatibility is often implicated, the underlying mechanisms remain unclear. This study investigated meiotic behavior and genome-wide divergence in bighead catfish (C. macrocephalus), North African catfish (C. gariepinus), and their sterile male hybrids (important in aquaculture). Repetitive DNA analysis using bioinformatics and cytogenetics revealed significant divergence in satellite DNA (satDNA) families between parental species. Notably, one hybrid exhibited successful meiosis and spermatozoa production, suggesting potential variation in sterility expression. Our findings suggest that genome-wide satDNA divergence, rather than chromosome number differences, likely contributes to meiotic failure and male sterility in these catfish hybrids., 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 © 2023. Published by Elsevier Inc.)

Pancreas ductal adenocarcinoma belongs to the most common cancers, but also to the tumors with the poorest prognosis. Here, we pharmacologically targeted a mitochondrial potassium channel, namely mitochondrial Kv1.3, and investigated the role of sphingolipids and mutated Kirsten Rat Sarcoma Virus (KRAS) in Kv1.3-mediated cell death. We demonstrate that inhibition of Kv1.3 using the Kv1.3-inhibitor PAPTP results in an increase of sphingosine and superoxide in membranes and/or membranes associated with mitochondria, which is enhanced by KRAS mutation. The effect of PAPTP on sphingosine and mitochondrial superoxide formation as well as cell death is prevented by sh-RNA-mediated downregulation of Kv1.3. Induction of sphingosine in human pancreas cancer cells by PAPTP is mediated by activation of sphingosine-1-phosphate phosphatase and prevented by an inhibitor of sphingosine-1-phosphate phosphatase. A rapid depolarization of isolated mitochondria is triggered by binding of sphingosine to cardiolipin, which is neutralized by addition of exogenous cardiolipin. The significance of these findings is indicated by treatment of mutated KRAS-harboring metastasized pancreas cancer with PAPTP in combination with ABC294640, a blocker of sphingosine kinases. This treatment results in increased formation of sphingosine and death of pancreas cancer cells in vitro and, most importantly, prolongs in vivo survival of mice challenged with metastatic pancreas cancer. KEY MESSAGES: Pancreatic ductal adenocarcinoma (PDAC) is a common tumor with poor prognosis. The mitochondrial Kv1.3 ion channel blocker induced mitochondrial sphingosine. Sphingosine binds to cardiolipin thereby mediating mitochondrial depolarization. Sphingosine is formed by a PAPTP-mediated activation of S1P-Phosphatase. Inhibition of sphingosine-consumption amplifies PAPTP effects on PDAC in vivo., (© 2024. The Author(s).)

Originating in Thailand, the Thai Ridgeback dog is known for its unique fur ridge that grows in the opposite direction along its back. Selective breeding and a limited populations in Thailand have led to significant close inbreeding among related individuals. The current Thai Ridgeback population is assumed to have experienced a loss of genetic diversity and bottleneck events. Furthermore, studies on the genetic diversity and structure of Thai Ridgeback dogs are limited. Therefore, the aim of this study was to assess the genetic diversity in Thai Ridgeback dogs. Microsatellite genotyping and mitochondrial DNA D-loop sequences were used to assess genetic diversity in 105 Thai Ridgeback dogs from various farms throughout Thailand. Significant genetic diversity and minimal inbreeding were observed in the current Thai Ridgeback population. Signs of bottlenecks were not observed because the exchange of genetic material among Thai Ridgeback owners effectively preserved the genetic diversity. Moreover, the genetic parameters in this study supported owner-to-owner exchanges animals for mating programs. To sustain the genetic diversity of Thai Ridgeback dogs, the use of genetic parameters to manage genetic closeness while preserving breed characteristics is essential. These data are crucial for ensuring demographic stability, which is pivotal for long-term conservation and effective population management., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The Bangkaew dog is an indigenous dog breed in the Phitsanulok province of Thailand. This breed is recognized by the Fédération Cynologique Internationale (FCI), a global canine organization. The unique traits of the Bangkaew breed lead to purebred selection for breeding, while only their traits and pedigree from parental history are recorded. Determination of the risk of inbreeding depression and the origin of unknown DNA profiles is essential due to the challenges in predicting puppy characteristics, which are crucial for breed management and conservation., Objective: This study aimed to emphasize that current allelic frequency data for the Bangkaew dog breed must be considered for precise individual identification., Methods: Approximately 82 Bangkaew dogs from various Thai localities were studied using 15 microsatellite markers for genotypic monitoring and individual identification. Maternal genetic inheritance was assessed via mtDNA D-loop analysis., Results: The results revealed high genetic diversity in the Bangkaew breed, indicating low potential for inbreeding. We also found that using a 15 loci microsatellite panel was effective for the identification of Bangkaew dogs. The optimized 10 loci microsatellite genotyping panel developed in this study presents improved identification testing efficiency, promoting both time- and cost-effectiveness., Conclusion: Analysis of microsatellite DNA markers in Bangkaew dogs using an optimized panel of 10 loci selected from 15 loci effectively facilitated individual identification. This approach not only enhances time and cost efficiency, but also provides accurate allelic frequency estimates, which are crucial for the realistic evaluation of DNA evidence., (© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Background & Aims: Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease characterized by a spatially heterogeneous tumor microenvironment. Within the PDA microenvironment, cells organize into communities where cell fate is influenced by neighboring cells of diverse ontogeny and function. However, it remains unclear how cell neighborhoods in the tumor microenvironment evolve with treatment and impact clinical outcomes., Methods: Here, using automated chromogenic multiplex immunohistochemistry and unsupervised computational image analysis of human PDA tumors, we investigated cell neighborhoods in surgically resected tumors from patients with chemotherapy-naïve PDA (n = 59) and neoadjuvant chemotherapy-treated PDA (n = 57). Single cells were defined by lineage markers (CD3, CD8, Foxp3, CD68, CK19), proliferation (Ki67), and neighboring cells., Results: Distinct intratumoral immune and tumor cell subsets were defined by neighboring cells. Higher content of stromal-associated macrophages was seen in chemotherapy-naïve tumors from long-term survivors (overall survival >3 years) compared with short-term survivors (overall survival <1 year), whereas immune-excluded tumor cells were higher in short-term survivors. Chemotherapy-treated vs -naïve tumors showed lower content of tumor-associated T cells and macrophages but similar densities of stromal-associated immune cells. However, proliferating tumor cell subsets with immune-rich neighborhoods were higher in chemotherapy-treated tumors. In a blinded analysis of tumors from patients treated with neoadjuvant chemotherapy, a composite index comprising lower quantities of immune-excluded tumor cells and higher spatially distinct immune cell subsets was associated with prolonged survival., Conclusions: Together, these data provide new insights into discrete cell communities in PDA and show their clinical relevance., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The increasing frequency of zoonotic spillover events and viral mutations in low and middle-income countries presents a critical global health challenge. Contributing factors encompass cultural practices like bushmeat consumption, wildlife trade for traditional medicine, habitat disruption, and the encroachment of impoverished settlements onto natural habitats. The existing "vaccine gap" in many developing countries exacerbates the situation by allowing unchecked viral replication and the emergence of novel mutant viruses. Despite global health policies addressing the root causes of zoonotic disease emergence, there is a significant absence of concrete prevention-oriented initiatives, posing a potential risk to vulnerable populations. This article is targeted at policymakers, public health professionals, researchers, and global health stakeholders, particularly those engaged in zoonotic disease prevention and control in low and middle-income countries. The article underscores the importance of assessing potential zoonotic diseases at the animal-human interface and comprehending historical factors contributing to spillover events. To bridge policy gaps, comprehensive strategies are proposed that include education, collaborations, specialized task forces, environmental sampling, and the establishment of integrated diagnostic laboratories. These strategies advocate simplicity and unity, breaking down barriers, and placing humanity at the forefront of addressing global health challenges. Such a strategic and mental shift is crucial for constructing a more resilient and equitable world in the face of emerging zoonotic threats., Competing Interests: Mudasir Ahmad Syed is an Academic Editor for PeerJ., (© 2024 Haq et al.)

Background: Helicobacter pylori ( H. pylori ) infection is widely recognized for its association with gastric diseases. Prior studies on the relationship between H. pylori infection and biliary diseases have faced constraints, including inadequate control of confounding factors and small sample sizes. This study aims to explore the association between H. pylori infection and biliary diseases using a large, population-based sample with adequate control for various covariates., Methods:  The National Inpatient Sample (NIS) from 2016 to 2020 was used to investigate the association between H. pylori infection and biliary diseases. We identified patients with H. pylori infection using the International Classification of Diseases, Tenth Revision (ICD-10) code (B96.81). Descriptive analysis and inferential statistics, including univariate and multivariate regression, were performed to explore the relationship between H. pylori and selected biliary diseases.  Results: Overall, 32,966,720 patients were analyzed. Among them, 736,585 patients had biliary diseases (n=1,637 with H. pylori and n=734,948 without H. pylori ). The baseline characteristics revealed notable differences in demographics and healthcare variables between both groups. Univariate regression analysis demonstrated significant associations between H. pylori infection and various biliary diseases such as gallbladder stones, gallbladder cancer, cholangitis, acute cholecystitis, and biliary pancreatitis, with the highest risk for chronic cholecystitis (odds ratio: 5.21; 95% confidence interval: 4.1-6.62; p<0.0001). Multivariate regression analysis, after adjusting for various covariates, confirmed these associations, providing insights into the potential causal relationship between H. pylori and biliary diseases., Conclusion:  This study strengthens the evidence suggesting a potential association between H. pylori infection and biliary diseases. The findings need to be validated in prospective clinical studies., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. 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, Ahmad et al.)

Read-through chimeric RNAs are being recognized as a means to expand the functional transcriptome and contribute to cancer tumorigenesis when mis-regulated. However, current software tools often fail to predict them. We have developed RTCpredictor, utilizing a fast ripgrep tool to search for all possible exon-exon combinations of parental gene pairs. We also added exonic variants allowing searches containing common SNPs. To our knowledge, it is the first read-through chimeric RNA specific prediction method that also provides breakpoint coordinates. Compared with 10 other popular tools, RTCpredictor achieved high sensitivity on a simulated and three real datasets. In addition, RTCpredictor has less memory requirements and faster execution time, making it ideal for applying on large datasets., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: Early diagnosis of acute brain injury (ABI) is critical for patients on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) to guide anticoagulation strategy; however, neurological assessment in ECMO is often limited by patient sedation., Methods: In this pilot study of adults from June 2018 to May 2019, plasma samples of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), and tubulin associated unit (Tau) were collected daily after V-A ECMO cannulation and measured using a multiplex platform. Primary outcomes were occurrence of ABI, assessed clinically, and neurologic outcome, assessed by modified Rankin Scale (mRS)., Results: Of 20 consented patients (median age = 48.5°years; 55% female), 8 (40%) had ABI and 15 (75%) had unfavorable neurologic outcome at discharge. 10 (50%) patients were centrally cannulated. Median duration on ECMO was 4.5°days (IQR: 2.5-9.5). Peak GFAP, NFL, and Tau levels were higher in patients with ABI vs. without (AUC = 0.77; 0.85; 0.57, respectively) and in patients with unfavorable vs. favorable neurologic outcomes (AUC = 0.64; 0.59; 0.73, respectively). GFAP elevated first, NFL elevated to the highest degree, and Tau showed limited change regardless of ABI., Conclusion: Further studies are warranted to determine how plasma biomarkers may facilitate early detection of ABIs in V-A ECMO to assist timely clinical decision-making., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.