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Purpose: Biallelic INPP4A variants have recently been associated with severe neurodevelopmental disease in single case reports. Here, we expand and elucidate the clinical-genetic spectrum and provide a pathomechanistic explanation for genotype-phenotype correlations., Methods: Clinical and genomic investigations of 30 individuals were undertaken alongside molecular and in silico modelling and translation reinitiation studies., Results: We characterize a clinically variable disorder with cardinal features including global developmental delay, severe-profound intellectual disability, microcephaly, limb weakness, cerebellar signs and short stature. A more severe presentation associated with biallelic INPP4A variants downstream of exon 4 has additional features of (ponto)cerebellar hypoplasia, reduced cerebral volume, peripheral spasticity, contractures, intractable seizures and cortical visual impairment. Our studies identify the likely pathomechanism of this genotype-phenotype correlation entailing translational reinitiation in exon 4 resulting in an N-terminal truncated INPP4A protein retaining partial functionality, associated with less severe disease. We also identified identical reinitiation site conservation in Inpp4a -/- mouse models displaying similar genotype-phenotype correlation. Additionally, we show fibroblasts from a single affected individual exhibit disrupted endocytic trafficking pathways, indicating the potential biological basis of the condition., Conclusion: Our studies comprehensively characterise INPP4A-related neurodevelopmental disorder and suggest genotype-specific clinical assessment guidelines. We propose the potential mechanistic basis of observed genotype-phenotype correlations entails exon 4 translation reinitiation., (Copyright © 2024. Published by Elsevier Inc.)

One of the most significant medicinal plants used to treat numerous illnesses is Swertia chirayita. The present study demonstrated the compositional analysis of the Swertia chirayita (S. chirayita) plant using an emerging and non-destructive laser-induced breakdown spectroscopy (LIBS) technique. Mg, Ca, K, Fe, Sr, Cr, and Na were verified as necessary elements by the optical emission investigations, while Al, Ti, Si, Ba, Mn, and Li were non-essential. Using the Boltzmann plot technique with stark broadening parameters, plasma temperature and electron number density were calculated in the range of (10,000-12,000) K ±1000 K and (1.5-1.8) × 1017 cm-3, respectively. Finally, compositional analysis was carried out using calibration-free (CF-LIBS) analysis and results were compared with ICP-MS. It was observed that the concentration of Ca and Fe is higher than other detected elements. All the toxic elements are found to be within the safe limit. So, this medicinal plant can be used to cure a variety of diseases that arise due to the deficiency of these elements., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rehman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Multiple sclerosis (MS) is the most common inflammatory neurodegenerative disease of the central nervous system (CNS) in young adults and results in progressive neurological defects. The relapsing-remitting phenotype (RRMS) is the most common disease course in MS, which ultimately progresses to secondary progressive MS (SPMS), while primary progressive MS (PPMS) is a type of MS that worsens gradually over time without remissions. There is a gap in knowledge regarding whether the relapsing form can be distinguished from the progressive course, or healthy subjects (HS) based on an altered serum metabolite profile. In this study, we performed global untargeted metabolomics with the 2D GC-GC-MS platform to identify altered metabolites between RRMS, PPMS, and HS. We profiled 235 metabolites in the serum of patients with RRMS (n = 41), PPMS (n = 31), and HS (n = 91). A comparison of RRMS and HS patients revealed 22 significantly altered metabolites at p < 0.05 (false-discovery rate [FDR] = 0.3). The PPMS and HS comparisons revealed 28 altered metabolites at p < 0.05 (FDR = 0.2). Pathway analysis using MetaboAnalyst revealed enrichment of four metabolic pathways in both RRMS and PPMS (hypergeometric test p < 0.05): (1) galactose metabolism; (2) amino sugar and nucleotide sugar metabolism; (3) phenylalanine, tyrosine, and tryptophan biosynthesis; and (4) aminoacyl-tRNA biosynthesis. The Qiagen IPA enrichment test identified the sulfatase 2 (SULF2) ( p = 0.0033) and integrin subunit beta 1 binding protein 1 (ITGB1BP1) ( p = 0.0067) genes as upstream regulators of altered metabolites in the RRMS vs. HS groups. However, in the PPMS vs. HS comparison, valine was enriched in the neurodegeneration of brain cells ( p = 0.05), and heptadecanoic acid, alpha-ketoisocaproic acid, and glycerol participated in inflammation in the CNS ( p = 0.03). Overall, our study suggests that RRMS and PPMS may contribute metabolic fingerprints in the form of unique altered metabolites for discriminating MS disease from HS, with the potential for constructing a metabolite panel for progressive autoimmune diseases such as MS.

Background: The healthcare system in India is tiered and has primary, secondary and tertiary levels of facilities depending on the complexity and severity of health challenges at these facilities. Evidence suggests that emergency services in the country is fragmented. This study aims to identify the barriers and facilitators of emergency care delivery for patients with time-sensitive conditions, and develop and implement a contextually relevant model, and measure its impact using implementation research outcomes., Methods: We will study 85 healthcare facilities across five zones of the country and focus on emergency care delivery for 11 time-sensitive conditions. This implementation research will include seven phases: the preparatory phase, formative assessment, co-design of Model "Zero", co-implementation, model optimization, end-line evaluation and consolidation phase. The "preparatory phase" will involve stakeholder meetings, approval from health authorities and the establishment of a research ecosystem. The "formative assessment" will include quantitative and qualitative evaluations of the existing healthcare facilities and personnel to identify gaps, barriers and facilitators of emergency care services for time-sensitive conditions. On the basis of the results of the formative assessment, context-specific implementation strategies will be developed through meetings with stakeholders, providers and experts. The "co-design of Model 'Zero'" phase will help develop the initial Model "Zero", which will be pilot tested on a small scale (co-implementation). In the "model optimization" phase, iterative feedback loops of meetings and testing various strategies will help develop and implement the final context-specific model. End-line evaluation will assess implementation research outcomes such as acceptability, adoption, fidelity and penetration. The consolidation phase will include planning for the sustenance of the interventions., Discussion: In a country such as India, where resources are scarce, this study will identify the barriers and facilitators to delivering emergency care services for time-sensitive conditions across five varied zones of the country. Stakeholder and provider participation in developing consensus-based implementation strategies, along with iterative cycles of meetings and testing, will help adapt these strategies to local needs. This approach will ensure that the developed models are practical, feasible and tailored to the specific challenges and requirements of each region., (© 2024. The Author(s).)

Background: A Society of Abdominal Radiology (SAR) Pancreatic Ductal Adenocarcinoma (PDAC) Disease-Focused Panel (DFP) consensus statement described findings suspicious for local recurrence (LR) on surveillance imaging after PDAC resection. Objective: To evaluate the interreader agreement and predictive utility of potential imaging findings of LR on serial surveillance CT examinations after Whipple procedure for PDAC, using the SAR PDAC DFP consensus statement. Methods: This retrospective study included 126 patients (mean age, 68.5±10.3 years; 72 men, 54 women) who underwent Whipple surgery for PDAC between January 2009 and December 2014. Three radiologists independently reviewed baseline and subsequent postoperative contrast-enhanced abdominopelvic CT examinations performed within 2 years postoperatively, evaluating features in the SAR PDAC DFP consensus statement relating to surgical bed stranding, surgical bed soft tissue, vessel encasement, main pancreatic duct dilatation, and ascites. Interreader agreement was calculated. The reference standard for LR development within 2 years postoperatively incorporated all available information. Imaging features' frequencies were calculated for recurrence examinations (i.e., first surveillance examinations indicating LR). For baseline postoperative examinations, features associations' with eventual LR development were assessed by multivariable logistic regression analysis. Results: LR developed within 2 years postoperatively in 81/126 patients. For both baseline and subsequent examinations, agreement for stranding and soft tissue morphology were poor, for vessel encasement was fair, for soft tissue and ascites were moderate, and for main pancreatic duct dilatation was substantial. On recurrence examinations, across readers, new or increased stranding was present in 27-77%; new or increased soft tissue, 80-86%; soft tissue with vessel encasement and luminal narrowing, 36-59%; new or increased main pancreatic duct dilatation, 25-26%; and new or increased ascites, 20-23%. On baseline postoperative examinations, independent predictors of eventual LR were soft tissue for all three readers (OR=2.78-6.85) and stranding for reader 1 (OR=3.59); main pancreatic duct dilatation and ascites were not independent predictors of LR for any reader. Conclusion: This study highlights the role of soft tissue, particularly when associated with vessel encasement and luminal narrowing, in raising suspicion for LR after PDAC resection. Clinical Impact: This study supports the SAR PDAC DFP consensus statement, while highlighting opportunities for continued optimization.

A wide diversity of mycoviruses has been reported from Botrytis species, some with the potential to suppress the pathogenic abilities of this fungus. Considering their importance, this study was devised to find potential hypovirulence-associated mycoviruses found in Botrytis cinerea strains isolated from Pakistani strawberry fields. Here we report the complete genome characterization of two fusariviruses co-infecting a single isolate of phytopathogenic fungus B. cinerea (Kst14a). The viral genomes were sequenced by deep sequencing using total RNA fractions of the Kst14a isolate. The identified viruses were tentatively named Botrytis cinerea fusarivirus 9 (BcFV9) and Botrytis cinerea fusarivirus 3a (BcFV3a). Both viruses had a single-segmented (ssRNA) genome having a size of 6424 and 8370 nucleotides encoding two discontinuous open reading frames (ORFs). ORF-1 of both mycoviruses encodes for a polyprotein having a conserved domain of RNA-dependent RNA polymerase (RdRP) and a helicase domain (Hel) which function in RNA replication, while ORF2 encodes a hypothetical protein with an unknown function, respectively. Phylogenetic analysis indicated that BcFV9 made a clade with the genus Alphafusarivirus and BcFV3a fall in the genus Betafusarivirus in the family Fusariviridae. To our knowledge, this is the first report of two fusariviruses identified in isolates of B. cinerea from Pakistan. Both mycoviruses successfully transfected to a compatible strain of B. cinerea (Mst11). A comparison of virus-free (VF) and virus-infected (VI) isogenic lines showed the presence of these viruses was causing hypovirulence in infected strains. Virus-infected strains also had a small lesion size while testing the pathogenicity via apple assay., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (<6 months after resection) or late (>6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B + natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B + NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Esophagectomy and lymphadenectomy have been the standard of care for patients at high risk (HR) of lymph node metastasis following a diagnosis of early esophageal adenocarcinoma (OAC) after endoscopic resection (ER). However, recent cohorts suggest lymph node metastasis risk is lower than initially estimated, suggesting organ preservation with close endoscopic follow-up is a viable option. We report on the 3- and 5-year risk of lymph node/distant metastasis among patients diagnosed with early HR-T1 OAC undergoing endoscopic follow-up. Patients diagnosed with HR-T1a or T1b OAC following ER at a tertiary referral center were identified and retrospectively analyzed from clinical records between 2010 and 2021. Patients were included if they underwent endoscopic follow-up after resection and were divided into HR-T1a, low risk (LR)-T1b and HR-T1b cohorts. After ER, 47 patients underwent endoscopic follow-up for early HR OAC. In total, 39 patients had an R0 resection with a combined 3- and 5-year risk of LN/distant metastasis of 6.9% [95% confidence interval (CI): 1.8-25] and 10.9% (95% CI, 3.6-30.2%), respectively. There was no significant difference when stratifying by histopathological subtype (P = 0.64). Among those without persistent luminal disease on follow-up, the 5-year risk was 4.1% (95% CI, 0.6-26.1). Two patients died secondary to OAC with an all-cause 5-year survival of 57.5% (95% CI, 39.5-71.9). The overall risk of LN/distant metastasis for early HR T1 OAC was lower than historically reported. Endoscopic surveillance can be a reasonable approach in highly selected patients with an R0 resection and complete luminal eradication, but clear, evidence-based surveillance guidelines are needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Stem cell (SC) transplantation has shown potential as a therapeutic approach for premature ovarian failure (POF). Despite this, no quantitative analysis has been conducted on the efficacy of SC therapy for POF in humans. To address this gap, the present study conducted a meta-analysis to evaluate the effectiveness of the transplantation of SC in improving ovarian function among POF patients. A systematic review in this regard by searching PubMed, ScienceDirect, clinicalTrial.gov, and Cochrane's library databases was conducted to identify relevant studies, while associated reviews were also considered. The extracted data included parameters such as estradiol (E2), follicle-stimulating hormone (FSH), follicle count (FC), ovarian weight (OW), number of pregnancies, and live birth. As per the combined effect taking the last follow-up time, the level of FSH and AMH for the SC group was lower than these were at the baseline as (SMD: 1.58, 95% CI: 0.76 to 3.92, P-value: 0.185 > 0.05, I 2 : 94.03%) and (SMD: 1.34, 95% CI: 0.77 to 1.92, P-value: 0.001 < 0.05, I 2 : 0%) respectively. While the means of E2 and OW for the SC group was higher than these were at the baseline as (SMD: -0.47, 95% CI: -0.73 to -0.21, P-value: 0.001 < 0.01, I 2 : 38.23%) and (SMD: -1.18, 95% CI: -2.62 to 0.26, P-value: 0.108 > 0.05, I 2 : 76.68%) respectively. The overall effect size measured with proportion of pregnancy and live birth at a 5% level of significance expected SC transplantation results were as (combined proportion: 0.09, 95% CI: 0.03 to 0.15, P-value: 0.002 < 0.05, I 2 : 46.29%) and (SMD: 0.09, 95% CI: 0.03 to 0.15, P-value: 0.003 < 0.05, I 2 : 1.76%) respectively. Based on the fixed-effects model, the estimated average log odds ratio of Follicles count was 1.0234 (95% CI: 0.1252 to 1.9216). Therefore, the average outcome differed significantly from zero (P-value: 0.0255 < 0.05) due to SC transplantation. These results suggest that using SCs to restore ovarian function may be viable for treating POF. However, larger and better-quality investigations would need to be conducted in the future due to the heterogeneity of the examined studies., (© 2024 The Author(s).)

Background: Hemostatic powders are used as second-line treatment in acute gastrointestinal (GI) bleeding (AGIB). Increasing evidence supports the use of TC-325 as monotherapy in specific scenarios. This prospective, multicenter study evaluated the performance of TC-325 as monotherapy for AGIB., Methods: Eighteen centers across Europe and USA contributed to a registry between 2016 and 2022. Adults with AGIB were eligible, unless TC-325 was part of combined hemostasis. The primary endpoint was immediate hemostasis. Secondary outcomes were rebleeding and mortality. Associations with risk factors were investigated (statistical significance at P≤0.05)., Results: One hundred ninety patients were included (age 51-81 years, male: female 2:1), with peptic ulcer (n=48), upper GI malignancy (n=79), post-endoscopic treatment hemorrhage (n=37), and lower GI lesions (n=26). The primary outcome was recorded in 96.3% (95% confidence interval [CI]: 92.6-98.5) with rebleeding in 17.4% (95%CI 11.9-24.1); 9.9% (95%CI 5.8-15.6) died within 7 days, and 21.7% (95%CI 15.6-28.9) within 30 days. Regarding peptic ulcer, immediate hemostasis was achieved in 88% (95%CI 75-95), while 26% (95%CI 13-43) rebled. Higher ASA score was associated with mortality (OR 23.5, 95%CI 1.60-345; P=0.02). Immediate hemostasis was achieved in 100% of cases with malignancy and post-intervention bleeding, with rebleeding in 17% and 3.1%, respectively. Twenty-six patients received TC-325 for lower GI bleeding, and in all but one the primary outcome was achieved., Conclusions: TC-325 monotherapy is safe and effective, especially in malignancy or post-endoscopic intervention bleeding. In patients with peptic ulcer, it could be helpful when the primary treatment is unfeasible, as bridge to definite therapy., Competing Interests: Conflict of Interest: Rehan J. Haidry declares: Pentax Medical, Apollo Endosurgery, Medtronic, Odin Vision, Cook Endoscopy, Fractyl Limited, Endogastric Solutions; Enrique Rodríguez de Santiago declares: Olympus, Norgine and Apollo Endosurgery (Educational activities) Adacyte therapeuthics (Advisory); Seth A. Gross declares: Cook, Medtronic, Olympus, Microtech. The other authors have nothing to declare, (Copyright: © 2024 Hellenic Society of Gastroenterology.)

Postoperative adhesion can cause complications, such as pain and organ blockage, in the abdominal regions. To address this issue, surgical techniques and antiadhesive treatments are applied. Given the significant role of vascularization in adhesion band formation, Avastin (Ava) that targets vascular endothelial growth factor (VEGF) can be applied to prevent peritoneal adhesion bands. Moreover, Alginate (Alg), a natural polysaccharide, is a promising physical barrier to prevent adhesion bands. Incorporating Ava into Alg hydrogel in a form of 3D-printed scaffold (Alg/Ava) has potential to suppress inflammation and angiogenesis, leading to reduce peritoneal adhesion bands. Following physical, morphological, and biocompatibility evaluations, the efficacy of Alg and Ava alone and their combination in Alg/Ava on the formation of postsurgical adhesions is evaluated. Upon confirming physical stability and sustained release of Ava, the Alg/Ava scaffold effectively diminishes both the extent and strength of adhesion bands. Histopathological examination shows that the reduction in fibrosis and inflammation is responsible for preventing adhesion bands by the Alg/Ava scaffold. Additionally, the cytokine assessment reveals that this is due to the inhibition in the secretion of VEGF and Interleukin 6 suppressing vascularization and inflammatory pathways. This study suggests that a 3D-printed Alg/Ava scaffold has great potential to prevent the postsurgical adhesion bands., (© 2024 Wiley‐VCH GmbH.)

Introduction Irrigation of the root canal system is a vital step in endodontic treatment aimed at disinfecting the canal. The efficacy of irrigation can be improved by various irrigation agitation methods. One such novel method of interest is the manual dynamic agitation (MDA) technique. However, the effect of MDA on postoperative pain as compared to needle irrigation (NI) with sodium hypochlorite has been scarcely explored. This study aimed to compare the effects of NI and MDA techniques on postoperative pain in teeth with symptomatic irreversible pulpitis. Materials and methods This quasi-experimental study was conducted at the Department of Operative and Paediatric Dentistry, Fauji Foundation Dental Hospital, over four months after gaining ethical approval. One hundred and sixty-eight participants diagnosed with symptomatic irreversible pulpitis were enrolled in the study through the purposive sampling technique. The participants were divided into two groups based on the irrigation technique used: Group A (NI) and Group B (MDA). Postoperative pain was recorded after six hours, 24 hours, 48 hours, and seven days using the 0-100mm visual analog scale (VAS). The VAS scores were compared using an independent sample t-test. Results Out of 168 participants, 48.2% were in Group A and 51.2% in Group B. The study found that VAS pain scores for Group B (MDA) were significantly lower at six hours, 24 hours, 48 hours, and seven days as compared to Group A (NI), with a p -value less than 0.001. Conclusion This study shows that the MDA technique leads to decreased postoperative pain both immediately after endodontic treatment and a week later as compared to the NI technique. Hence, the use of MDA can aid in controlling postendodontic pain and, therefore, ensure smoother recovery and increased patient satisfaction., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethical Review Board of Foundation University College of Dentistry issued approval FF/FUCD/632/ERC 023. Based on the information submitted by researcher(s), this research project does not raise any ethical issue/is compliant with the Ethical principles of Medical research outlined in WMA declaration of Helsinki made at 64th WMA General assembly, Fortaleza, Brazil, in October 2013. 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, Abbas et al.)

Background: Twenty-two Arab countries share a common language, history, and culture. Nevertheless, governmental policies, healthcare systems, and resources differ from one Arab country to another. We have been following Coronavirus (COVID-19) from the beginning in each Arab country. In the present study, we aimed to assess the prevalence of COVID-19 in the Arab world and to compare these findings with other significantly affected countries., Methods: Websites of the World Health Organization, World COVID-vaccinations tracker, Worldometer, and Ministries of Health were used to extract COVID-19 data in all Arab countries between the period January 2020 to December 2022., Results: All Arab countries had 14,218,042 total confirmed COVID-19 cases, 13,384,924 total recovered cases and 173,544 total related deaths. The trend demonstrated that the third quarter of 2021 recorded the highest death toll and the first quarter of 2022 recorded the highest number of confirmed and recovered cases. Compared to the top 15 affected countries, the Arab world ranked last as it had the lowest overall incidence per million population (PMP) of 31,609. The data on total deaths PMP showed that India had the lowest number of deaths with only 377 cases followed by the Arab world with 386 cases., Conclusions: Although the number of confirmed, death, and recovered cases of COVID-19 have greatly reduced in the last quarter of 2022 in most Arab countries, many Arab countries still need to re-campaign about COVID-19 vaccines and raise awareness programs about boosters. COVID-19 has had a relatively smaller impact on Arab countries than on other countries that have been significantly affected., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Alwahaibi N et al.)

Objective: This meta-analysis includes the systematic literature review and meta-analysis involving clinical trials to assess the efficacy and safety of mesenchymal stem cell (MSC) transplantation for treating T1DM and T2DM., Methods: We searched PubMed, ScienceDirect, Web of Science, clinicaltrials.gov, and Cochrane Library for "published" research from their inception until November 2023. Two researchers independently reviewed the studies' inclusion and exclusion criteria. Our meta-analysis included 13 studies on MSC treatment for diabetes., Results: The MSC-treated group had a significantly lower HbA1c at the last follow-up compared to the baseline (MD: 0.95, 95% CI: 0.33 to 1.57, P -value: 0.003< 0.05), their insulin requirement was significantly lower (MD: 0.19, 95% CI: 0.07 to 0.31, P -value: 0.002< 0.05), the level of FBG with MSC transplantation significantly dropped compared to baseline (MD: 1.78, 95% CI: -1.02 to 4.58, P -value: 0.212), the FPG level of the MSC-treated group was significantly lower (MD: -0.77, 95% CI: -2.36 to 0.81, P -value: 0.339 > 0.05), and the fasting C-peptide level of the MSC-treated group was slightly high (MD: -0.02, 95% CI: -0.07 to 0.02, P- value: 0.231 > 0.05)., Conclusion: The transplantation of MSCs has been found to positively impact both types of diabetes mellitus without signs of apparent adverse effects., Competing Interests: Authors UH, SS, NK, DG, and AU were employed by the companies R3 Medical Research LLC, Pak-American Hospital Pvt. Ltd., and R3 Stem Cell LLC. Authors NK and DG were employed by the company Bello Bio Labs and Therapeutics Pvt. Ltd. The remaining author declares 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 Habiba, Khan, Greene, Ahmad, Shamim and Umer.)

Purpose: Previous studies suggest that besides anatomy (A: resectable, borderline resectable [BR], or locally advanced [LA]) also biologic (B: carbohydrate antigen 19-9 [CA 19-9]) and conditional (C: performance status) factors should be considered when staging patients with localized pancreatic ductal adenocarcinoma (PDAC). The prognostic value of the combined ABC factors has not been quantitatively validated., Methods: In this retrospective cohort study, we evaluated patients with localized PDAC treated with initial (modified) fluorouracil with leucovorin, irinotecan, and oxaliplatin ([m]FOLFIRINOX) at five high-volume pancreatic cancer centers in the United States and the Netherlands (2012-2019). Multivariable Cox proportional hazards analysis was used to investigate the impact of the ABC factors for overall survival (OS)., Results: Overall, 1,835 patients with localized PDAC were included. Tumor stage at diagnosis was potentially resectable in 346 (18.9%), BR in 531 (28.9%), and LA in 958 (52.2%) patients. The baseline CA 19-9 was >500 U/mL in 559 patients (32.5%). Performance status was ≥1 in 1,110 patients (60.7%). Independent poor prognostic factors for OS were BR disease (hazard ratio [HR], 1.26 [95% CI, 1.06 to 1.50]), LA disease (HR, 1.71 [95% CI, 1.45 to 2.02]), CA 19-9 >500 U/mL (HR, 1.36 [95% CI, 1.21 to 1.52]), and WHO performance status ≥1 (HR, 1.31 [95% CI, 1.16 to 1.47]). Patients were assigned 1 point for each poor ABC factor and 2 points for LA disease. The median OS for patients with score 0-4 was 49.7, 29.9, 22.0, 19.1, and 14.9 months with corresponding 5-year OS rates of 47.0%, 28.9%, 19.2%, 9.3%, and 4.8%, respectively., Conclusion: The ABC factors of tumor anatomy, CA 19-9, and performance status at diagnosis were independent prognostic factors for OS in patients with localized PDAC treated with initial (m)FOLFIRINOX. Staging of patients with localized PDAC at diagnosis should be based on anatomy, CA 19-9, and performance status.

Diabetes mellitus (DM) often causes chronic kidney damage despite best medical practices. Diabetic kidney disease (DKD) arises from a complex interaction of factors within the kidney and the whole body. Targeting specific disease-causing agents using drugs has not been effective in treating DKD. However, stem cell therapies offer a promising alternative by addressing multiple disease pathways and promoting kidney regeneration. Mesenchymal stem cells (MSCs) offer great promise due to their superior accessibility ratio from adult tissues and remarkable modes of action, such as the production of paracrine anti-inflammatory and cytoprotective substances. This review critically evaluates the development of MSC treatment for DKD as it moves closer to clinical application. Results from animal models suggest that systemic MSC infusion may positively impact DKD progression. However, few registered and completed clinical trials exist, and whether the treatments are effective in humans is still being determined. Significant knowledge gaps and research opportunities exist, including establishing the ideal source, dose, and timing of MSC delivery, better understanding of in vivo mechanisms, and developing quantitative indicators to obtain a more significant therapeutic response. This paper reviews recent literature on using MSCs in preclinical and clinical trials in DKD. Potent biomarkers related to DKD are also highlighted, which may help better understand MSCs' action in this disease progression. KEY MESSAGES: Mesenchymal stem cells have anti-inflammatory and paracrine effects in diabetic kidney disease. Mesenchymal stem cells alleviate in animal models having diabetic kidney disease. Mesenchymal stem cells possess promise for the treatment of diabetic kidney disease., (© 2024. The Author(s).)

Electrochemical water splitting for sustainable hydrogen and oxygen production have shown enormous potentials. However, this method needs low-cost and highly active catalysts. Traditional nano catalysts, while effective, have limits since their active sites are mostly restricted to the surface and edges, leaving interior surfaces unexposed in redox reactions. Single atom catalysts (SACs), which take advantage of high atom utilization and quantum size effects, have recently become appealing electrocatalysts. Strong interaction between active sites and support in SACs have considerably improved the catalytic efficiency and long-term stability, outperforming their nano-counterparts. This review's first section examines the Hydrogen Evolution Reaction (HER) and the Oxygen Evolution Reaction (OER). In the next section, SACs are categorized as noble metal, non-noble metal, and bimetallic synergistic SACs. In addition, this review emphasizes developing methodologies for effective SAC design, such as mass loading optimization, electrical structure modulation, and the critical role of support materials. Finally, Carbon-based materials and metal oxides are being explored as possible supports for SACs. Importantly, for the first time, this review opens a discussion on waste-derived supports for single atom catalysts used in electrochemical reactions, providing a cost-effective dimension to this vibrant research field. The well-known design techniques discussed here may help in development of electrocatalysts for effective water splitting., (© 2024 The Chemical Society of Japan & Wiley-VCH GmbH.)

An oesophageal stricture refers to a narrowing of the oesophageal lumen, which may be benign or malignant. The cardinal feature is dysphagia, and this may result from intrinsic oesophageal disease or extrinsic compression. Oesophageal strictures can be further classified as simple or complex depending on stricture length, location, diameter, and underlying aetiology. Many endoscopic options are now available for treating oesophageal strictures including dilatation, injectional therapy, stenting, stricturotomy, and ablation. Self-expanding metal stents have revolutionised the palliation of malignant dysphagia, but oesophageal dilatation with balloon or bougienage remains first-line therapy for most benign strictures. The increase in endoscopic and surgical interventions on the oesophagus has seen more benign refractory oesophageal strictures that are difficult to treat, and often require advanced endoscopic techniques. In this review, we provide a practical overview on the evidence-based management of both benign and malignant oesophageal strictures, including a practical algorithm for managing benign refractory strictures., Competing Interests: Declaration of competing interest RH declares educational grants to support research infrastructure from Cook medical, Odin Vision, Pentax medical, Endogastric Solutions, Apollo Endosurgery, Medtronic, and Aqua Medical. The remaining authors (initials) declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: About 25% of patients with localized pancreatic adenocarcinoma have non-elevated serum carbohydrate antigen (CA) 19-9 levels at baseline, hampering evaluation of response to preoperative treatment. Serum carcinoembryonic antigen (CEA) is a potential alternative., Methods: This retrospective cohort study from five referral centers included consecutive patients with localized pancreatic adenocarcinoma (2012-2019), treated with one or more cycles of (m)FOLFIRINOX, and non-elevated CA19-9 levels (i.e., < 37 U/mL) at baseline. Cox regression analyses were performed to assess prognostic factors for overall survival (OS), including CEA level at baseline, restaging, and dynamics., Results: Overall, 277 patients were included in this study. CEA at baseline was elevated (≥5 ng/mL) in 53 patients (33%) and normalized following preoperative therapy in 14 patients (26%). In patients with elevated CEA at baseline, median OS in patients with CEA normalization following preoperative therapy was 33 months versus 19 months in patients without CEA normalization (p = 0.088). At time of baseline, only elevated CEA was independently associated with (worse) OS (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.04-1.98). At time of restaging, elevated CEA at baseline was still the only independent predictor for (worse) OS (HR 1.44, 95% CI 1.04-1.98), whereas elevated CEA at restaging (HR 1.16, 95% CI 0.77-1.77) was not., Conclusions: Serum CEA was elevated in one-third of patients with localized pancreatic adenocarcinoma having non-elevated CA19-9 at baseline. At both time of baseline and time of restaging, elevated serum CEA measured at baseline was the only predictor for (worse) OS. Therefore, serum CEA may be a useful tool for decision making at both initial staging and time of restaging in patients with non-elevated CA19-9., (© 2024. Society of Surgical Oncology.)

Background: Job satisfaction leads to employees being more productive. However, when the job requirements do not meet the capabilities it will cause stress. Therefore, it is important to define the cause of dissatisfaction to reduce work-induced stress as this has a negative impact on the quality of healthcare services. The literature on stress and satisfaction studying medical laboratory professionals (MLPs) is still limited.The aim of this study was to assess the relationships between stress and job satisfaction factors among MLPs in Omani hospitals, and to quantify a possible correlation between job stress and job satisfaction., Methods: A cross sectional study involved all medical laboratory professionals in eight hospitals in Oman from different geographical areas. A survey instrument measuring job satisfaction was developed from the result of earlier qualitative studies done by the authors in the population of 101 participants. In addition, job stress was assessed using a survey based on the Nurse Stress Index (NSI)., Results: The results show a significant statistical association between stress and job satisfaction. Omanis have significantly higher stress scores compared to non-Omani citizens. The youngest MLPs at Omani Hospitals were less satisfied at work and more stressed than their older colleagues. Job satisfaction was lower and job stress higher in the Sultan Qaboos University Hospital than in all the other hospitals. The most important dissatisfaction factors, leading to job stress, are insufficient support for professional development, poor relations with supervisors and co-workers, as well as heavy workload., Conclusion: This study emphasizes the importance of investing in measures to meet the expectations of laboratory staff, to strengthen factors that increase satisfaction and eliminate dissatisfaction factors. It gives concrete advice on what those measures should be and, consequently, guides actions on improving the work environment in medical laboratories. When implemented those would reduce job stress among medical laboratory professionals in Oman, and, possibly, more widely., Competing Interests: 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., (© 2024 The Authors.)

Background: There is increasing evidence that a companionship is an important tool for improving the quality of care provided to pregnant women during the labour and delivery process. The literature review shows very limited studies assessing the role of companions during childbirth from the companion's point of view. Many published papers studied the role and satisfaction of pregnant women but not their companions. Therefore, this study aimed to assess the role and effect of companions during childbirth in Oman., Methods: This cross-sectional observational study was conducted at Sultan Qaboos University Hospital, Oman, between June 2022 and April 2023. Companions were interviewed face-to-face at a time convenient to them. A telephone interview was conducted with those who left the hospital early. The questionnaire comprised sociodemographic data and other sections, including the nature of the help provided by the supportive companion, their effects on the women who gave birth, and the timing of their presence during companionship., Results: A total of 214 companions were included in this study with the mean age of 42.54 years. The most common relationship to the pregnant women was mothers (35.7%), followed by husbands (30.5%). The majority of companions provided support during admission (62.6%), in the immediate post-partum ward (56.5%) and during delivery (54.2%), while a minority helped from admission to discharge (22.4%). The most common type of support provided was encouraging words (89.7%) followed by transferring things (43.9%), massage (37.4%) and touch (33.6%). The majority of companions (96.7%) reported that their support helped very much, and the pregnant women felt better and calmer., Conclusions: Labouring women felt better and calmer because of the presence of companions. Companions preferred to be present in the postpartum and during labour and delivery. The majority of companions support their labouring women by encouraging wards. Companions love and encourage others to support their labouring women during their critical times., (© 2024. The Author(s).)

Background:  Esophageal stenting is an important intervention for managing malignant and benign dysphagia, with stent migration representing a common drawback. This systematic review with meta-analysis aimed to assess the benefit of stent fixation over nonfixation., Methods:  A systematic search was performed in MEDLINE, Cochrane, Scopus, and ClinicalTrials.gov databases until January 2023 for comparative studies evaluating the migration rates of esophageal stents with versus without (control) fixation. The primary outcome was migration rate. Secondary outcomes included adverse event rate. A subgroup analysis stratified the results based on different fixation techniques: suturing, over-the-scope (OTS) clipping, and through-the-scope (TTS) clipping. Meta-analysis was based on a random effects model and the results were reported as odds ratios (ORs) with 95 %CIs., Results:  10 studies (1014 patients) were included. The rate of stent migration was significantly lower after fixation (OR 0.20, 95 %CI 0.11-0.37; I2  = 59 %, P  = 0.01). The adverse event rate was similar between fixation and control groups (OR 0.65, 95 %CI 0.28-1.52; I2  = 55 %, P  = 0.06). In the subgroup analysis, all fixation techniques remained superior to nonfixation of stents (suturing OR 0.23, 95 %CI 0.10-0.53; OTS clips OR 0.31, 95 %CI 0.17-0.58; TTS clips OR 0.10, 95 %CI 0.03-0.38); however, only the OTS and TTS clip groups achieved nonsignificant heterogeneity ( I2  = 0 %, P  = 0.67 and P  = 0.73, respectively). No difference between techniques was recorded for migration rates., Conclusion:  Esophageal stent fixation was associated with significantly lower migration rates compared with nonfixation of stents, regardless of fixation technique and stenting indication., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Pure and Ni-Fe-codoped Zn 1 - 2 x Ni x Fe x O ( x = 0.01, 0.02, 0.03, and 0.04) nanoparticles were effectively synthesized using a sol-gel autocombustion procedure. The structural, optical, morphological, and magnetic properties were determined by using X-ray diffraction (XRD), ultraviolet-visible (UV-vis), scanning electron microscopy, and vibrating sample magnetometer techniques. The XRD confirmed the purity of the hexagonal wurtzite crystal structure. XRD analysis further indicated that Fe and Ni successfully substituted the lattice site of Zn and generated a single-phase Zn 1-2 x Ni x Fe x O magnetic oxide. In addition, a significant morphological change was observed with an increase in the dopant concentration by using high-resolution scanning electron microscopy. The UV-vis spectroscopy analysis indicated the redshift in the optical band gap with increasing dopant concentration signifying a progressive decrease in the optical band gap. The vibrating sample magnetometer analysis revealed that the doped samples exhibited ferromagnetic properties at room temperature with an increase in the dopant concentration. Dopant concentration was confirmed by using energy-dispersive X-ray spectroscopy. The current results provide a vital method to improve the magnetic properties of ZnO nanoparticles, which may get significant attention from researchers in the field of magnetic semiconductors., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Competing Interests: The authors declare that they have no conflict of interest.

Competing Interests: The authors declare that they have no conflict of interest.

Background: In routine histopathology, 10% neutral buffered formalin (NBF) is the choice fixative. However, formalin is a human carcinogen, so there is a necessity for a safer alternative. To the best of our knowledge, neutral honey, not natural or artificial honey, has not been tested to fix histological samples. This study determined the effectiveness of neutral buffered honey and other types of fixatives to fix histological tissues. Methods: The study was conducted between July 2019 and August 2020 at Sultan Qaboos University, Oman. Sections from three rat livers, kidneys, and stomach tissues were fixed with 10% NBF, neutral buffered Sumer honey, neutral buffered date honey, formalin, Sumer honey, date honey, alcoholic formalin, alcoholic Sumer honey, and alcoholic date honey for 24 hours. Samples were stained with hematoxylin and eosin (H&E), special stains, and vimentin methods. Three expert biomedical scientists then evaluated the fixed and stained samples for the quality of all sections. The fixation ability of the different honey solutions was then compared to 10% NBF and the utility was determined using nuclear and cytoplasmic criteria, specificity, and intensity. Results: H&E showed adequate staining in all groups compared to 10% NBF. The specificity and intensity of all groups for the Periodic acid-Schiff method were identical to 10% NBF except for Sumer honey and alcoholic date honey. Vimentin showed comparable findings with 10% NBF as there were no significant differences. Conclusions: The findings of this study encourage the use of honey, including neutral, as a possible safe substitute fixative for formalin, however, further experiments on larger specimens should be conducted., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Alwahaibi N et al.)

Background: For some patients with colorectal liver metastases (CRLMs), surgical resection of all visible disease can lead to long-term survival and even cure. When complete resection is not feasible, microwave ablation (MWA) can help achieve hepatic disease control. As modern 2.45-GHz MWA generators gain popularity, the characteristics of tumors most likely to benefit from this method remain unclear. This study aimed to evaluate local recurrence (LR) rates, patterns of recurrence, and factors contributing to treatment failure after 2.45-GHz MWA of CRLM., Methods: Patients with CRLM who underwent operative 2.45-GHz MWA between 2011 and 2019 were identified in a prospectively maintained single-institution database. Recurrence outcomes were ascertained for each lesion by imaging review. Factors associated with LR were analyzed., Results: The study enrolled 184 patients bearing 416 ablated tumors. Most of the patients (65.8%) had high clinical risk scores (3-5), and 165 (90%) underwent concurrent liver resection. The median tumor size was 10 mm. After a median follow-up period of 28.8 months, LR was observed in 45 tumors, and the cumulative incidence of LR at 24 months was 10.9% (95% confidence interval [CI], 8.0-14.3%]. In 7%, LR was the first recurrence site, often combined with recurrence elsewhere. The cumulative incidence of LR at 24 months was 6.8% (95% CI 3.8-11.0%) for tumors 10 mm in size or smaller, 12.4% (95% CI 7.8-18.1%) for tumors 11 to 20 mm in size, and 30.2% (95% CI 14.2-48.0%) for tumors larger than 20 mm. In the multivariable analysis, tumors larger than 20 mm with a subcapsular location were significantly associated with increased LR risk., Conclusions: Treatment of CRLM with 2.45-GHz MWA offers excellent local control at 2 years and is most successful for small tumors deep within the parenchyma., (© 2023. Society of Surgical Oncology.)

We are currently in a worldwide obesity pandemic, which is one of the most significant health problems of the 21st century. As the prevalence of obesity continues to rise, new and innovate treatments are becoming available. Metabolic and bariatric endoscopic procedures are exciting new areas of gastroenterology that have been developed as a direct response to the obesity crisis. These novel interventions offer a potentially reversible, less invasive, safer, and more cost-effective method of tackling obesity compared to traditional bariatric surgery. Minimally invasive endoscopic treatments are not entirely novel, but as technology has rapidly improved, many of the procedures have been proven to be extremely effective for weight loss and metabolic health, based on high-quality clinical trial data. This mini-review examines the existing evidence for the most prominent metabolic and bariatric procedures, followed by a discussion on the future trajectory of this emerging subspecialty.

Background: The assessment of active aging levels in Pakistani older adults is crucial yet; research tools are scarce in the local language. Therefore, this study aims to translate and validate the English version of an Active Aging Scale into a cross-culturally sensitive Urdu version to assess active aging levels in Pakistani older adults., Methods: To translate and validate the scale, we used the ISPOR (International Society for Pharmacy Economic and Outcome Research) standards. Reliability, concurrent validity, construct validity, convergent validity, and discriminatory validity were checked on a total sample of 160 community-dwelling older adults. After two weeks, the test-retest reliability was examined. AMOS version 23 and SPSS version 23 were used to analyze the data., Results: The average content validity index for clarity was 0.91 and relevancy was 0.80. The total variance in the pilot study of all items secured > 0.3 variances except for two items scored < 0.30 that were omitted before the validity and reliability test. The remaining items explained 65.46% of the overall variation and had factor loadings ranging from 0.46 to 0.90 in the principal factor analysis (PFA). The confirmatory factor analysis of the Active Aging Scale revealed that the model fit was good with a Chi-square value (418.18 (DF = 2.2) which is less than 3.00. This is further evidenced by the root mean square error of approximation (RMSEA) of 0.042, goodness of fit index (GFI) of 0.92, adjusted goodness of fit index (AGFI) of 0.94, and comparative fit index (CFI) values of 0.92 and 0.96 (unstandardized and standardized, respectively). The scale's Cronbach's alpha coefficient was 0.88, indicating dependability and its test-retest reliability with the significance of (P. < 0.05)., Conclusion: The Urdu version of the Active Aging Scale was successfully translated and validated in a culturally sensitive manner, and can be used to evaluate the effectiveness of various active aging interventions for older adults in Pakistan., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Hydroxylated polymethoxyflavones (HPMFs) have been shown to possess various anti-disease effects, including against obesity. This study investigates the anti-obesity effects of HPMFs in further detail, aiming to gain understanding of their mechanism of action in this context. The current study demonstrates that two HPMFs; 3'-hydroxy-5,7,4',5'-tetramethoxyflavone (3'OH-TetMF) and 4'-hydroxy-5,7,3',5'-tetramethoxyflavone (4'OH-TetMF) possess anti-obesity effects. They both significantly reduced pancreatic lipase activity in a competitive manner as demonstrated by molecular docking and kinetic studies. In cell studies, it was revealed that both of the HPMFs suppress differentiation of 3T3-L1 mouse embryonic fibroblast cells during the early stages of adipogenesis. They also reduced expression of key adipogenic and lipogenic marker genes, namely peroxisome proliferator-activated receptor-gamma (PPARγ), CCAAT/enhancer-binding protein α and β (C/EBP α and β), adipocyte binding protein 2 (aP2), fatty acid synthase (FASN), and sterol regulatory element-binding protein 1 (SREBF 1). They also enhanced the expression of cell cycle genes, i.e., cyclin D1 (CCND1) and C-Myc, and reduced cyclin A2 expression. When further investigated, it was also observed that these HPMFs accelerate lipid breakdown (lipolysis) and enhance lipolytic genes expression. Moreover, they also reduced the secretion of proteins (adipokines), including pro-inflammatory cytokines, from mature adipocytes. Taken together, this study concludes that these HPMFs have anti-obesity effects, which are worthy of further investigation., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy., Patients and Methods: In this single-institution retrospective analysis, patients with biopsy-proven IHC treated with either curative-intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver-limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver-limited recurrence was analyzed in the resection cohort., Results: From 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34-0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50-0.65 vs. HR 0.63, 95% CI 0.57-0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver-only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29-0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression-free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46-0.91; p = 0.01), which correlated with improved OS (HR 0.59, 95% CI 0.43-0.80; p < 0.001)., Conclusion: In patients with liver-limited IHC, hepatic disease control is associated with improved OS, emphasizing the potential importance of liver-directed therapy., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Despite the importance of organ donation and transplantation in improving the quality of life, still, there is a shortage of organ donations, worldwide. Lack of knowledge among the public could be the reason. In previous studies, the focus was predominantly on medical students at universities. The aim of this study was to assess university students' knowledge and attitude about organ donation and transplantation among different colleges at the university., Method: A cross-sectional study was conducted among university students between August 2021 and February 2022 using a validated self-designed questionnaire. The questionnaire consisted of five sections. The first section was about the research information. The second section was informed consent. The third section was about sociodemographic information. The fourth section was about the knowledge of organ donation. The last section was about the attitude toward organ donation. The data were analyzed by descriptive statistics and chi-square tests., Results: The study included 2,125 students. 68.1% were females, and 93.1% were in the age group 17-24 years old. Only 34.1% had good knowledge about organ donation, 70.2% had a low attitude, and 7.53% had adequate information about brain death. The most common reason for supporting donating organs among university students was to save a life (76.8%) and the most common reason for refusing organs, was I am still unaware. In addition, only 25.66% of the participants had a high attitude toward people with poor knowledge about organ donation. The majority of the students (84.13%) used online sources and social networks as the primary sources of information about organ donation., Conclusion: The knowledge and attitudes of university students toward organ donation and transplantation were low. Saving a life was the most common reason for supporting organ donation, and knowledge was the biggest obstacle. Online sources and social networks were the primary sources of knowledge. The attitude was greatly influenced by knowledge. Organizing campaigns, and events, and incorporating organ donation and transplantation into university curricula will increase university students' knowledge and attitudes., 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 © 2023 Alwahaibi, Al Wahaibi and Al Abri.)

Botrytis cinerea is one of the top phytopathogenic fungus which ubiquitously cause grey mold on a variety of horticultural plants. The mechanism of respiration in the fungus occurs within the mitochondria. Mitogenomes serve as a key molecular marker for the investigation of fungal evolutionary patterns. This study aimed at the complete assembly, characterization, and comparative relationship of four mitogenomes of Botrytis cinerea strains including Kst5C, Kst14A, Kst32B, Kst33A, respectively. High throughput sequencing of four mitogenomes allowed the full assembly and annotation of these sequences. The total genome length of these 4 isolates Kst5C Kst14A, Kst32B, Kst33A was 69,986 bp, 77,303 bp, 76,204 bp and 55, 226 bp respectively. The distribution of features represented 2 ribosomal RNA genes,14 respiration encoding proteins, 1 mitochondrial ribosomal protein-encoding gene, along with varying numbers of transfer RNA genes, protein-coding genes, mobile intronic regions and homing endonuclease genes including LAGLIDADG and GIY-YIG domains were found in all four mitogenomes. The comparative analyses performed also decipher significant results for four mitogenomes among fungal isolates included in the study. This is the first report on the detailed annotation of mitogenomes as a proof for investigation of variation patterns present with in the B. cinerea causing grey mold on strawberries in Pakistan. This study will also contribute to the rapid evolutionary analysis and population patterns present among Botrytis cinerea., Competing Interests: The authors declare that they have no competing interest., (© 2023 The Authors.)

Autism spectrum disorder (ASD) is a consortium of developmental conditions. As scientists have not yet identified the exact underlying cause for these disorders, it is not easy to narrow down a singular therapy to propose a reliable cure. The preponderance of research suggests that stem-cell therapy improves aspects of outcome measure scales in patients with ASD; therefore, future studies should give us more confidence in the results. This overview considers the data that have emerged from the small set of published trials conducted using different approaches in stem-cell therapy for ASD, evaluates their results and proposes additional steps that could be taken if this field of endeavor is to be pursued further.

Premature ovarian failure (POF) affects 1% of women under 40, leading to infertility. The clinical symptoms of the POF include hypoestrogenism, lack of mature follicles, hypergonadotropinism, and amenorrhea. POF can be caused due to genetic defects, autoimmune illnesses, and environmental factors. The conventional treatment of POF remains a limited success rate. Therefore, an innovative treatment strategy like the regeneration of premature ovaries by using human umbilical cord mesenchymal stem cells (hUC-MSCs) can be a choice. To summarize all the theoretical frameworks for additional research and clinical trials, this review article highlights all the results, pros, and cons of the hUC-MSCs used to treat POF. So far, the data shows promising results regarding the treatment of POF using hUC-MSCs. Several properties like relatively low immunogenicity, multipotency, multiple origins, affordability, convenience in production, high efficacy, and donor/recipient friendliness make hUC-MSCs a good choice for treating basic POF. It has been reported that hUC-MSCs impact and enhance all stages of injured tissue regeneration by concurrently stimulating numerous pathways in a paracrine manner, which are involved in the control of ovarian fibrosis, angiogenesis, immune system modulation, and apoptosis. Furthermore, some studies demonstrated that stem cell treatment could lead to hormone-level restoration, follicular activation, and functional restoration of the ovaries. Therefore, all the results in hand regarding the use of hUC-MSCs for the treatment of POF encourage researchers for further clinical trials, which will overcome the ongoing challenges and make this treatment strategy applicable to the clinic in the near future., (© 2022. The Author(s).)

This study aimed to elucidate differentially expressed proteins in drug resistant Salmonella Typhi. Among 100 samples, S. typhi were identified in 43 samples. In drug susceptibility profile, 95.3% (41/43), 80% (35/43) and 70% (30/43) resistances were observed against Nalidixic acid, Ampicillin, and Chloramphenicol respectively. No resistance was observed against Imipenum and Azithromycin while only 11% (5/43) isolates were found resistant to Ceftriaxone. Mass spectrometric differential analysis resulted in 23 up-regulated proteins in drug resistant isolates. Proteins found up-regulated are involved in virulence (vipB, galU, tufA, and lpp1), translation (rpsF, rpsG, rplJ, and rplR), antibiotic resistance (zwf, phoP, and ompX), cell metabolism (metK, ftsZ, pepD, and secB), stress response (ridA, rbfA, and dps), housekeeping (gapA and eno) and hypothetical proteins including ydfZ, t1802, and yajQ. These proteins are of diverse nature and functions but highly interconnected. Further characterization may be helpful for elucidation of new biomarker proteins and therapeutic drug targets., (Copyright © 2022 Elsevier Inc. All rights reserved.)

There have been numerous concerns about the disease and how it affects the human body since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic began in December 2019. The impact of SARS-CoV-2 on the liver is being carefully investigated due to an increase in individuals with hepatitis and other liver illnesses, such as alcoholic liver disease. Additionally, the liver is involved in the metabolism of numerous drugs used to treat comorbidities and coronavirus disease 2019 (COVID-19). Determining how SARS-CoV-2 affects the liver and what factors place individuals with COVID-19 at a higher risk of developing liver problems are the two main objectives of this study. This evaluation of the literature included research from three major scientific databases. To provide an update on the current impact of COVID-19 on the liver, data was collected and relevant information was incorporated into the review. With more knowledge about the effect of the disease on the liver, better management and therapeutics can be developed, and education can ultimately save lives and reduce the long-term impact of the pandemic on our population., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The prevalence of the gastro-oesophageal reflux disease (GORD) in the western world is increasing. Uncontrolled GORD can lead to harmful long-term sequela such as oesophagitis, stricture formation, Barrett's oesophagus and oesophageal adenocarcinoma. Moreover, GORD has been shown to negatively impact quality of life. The current treatment paradigm for GORD consists of lifestyle modification, pharmacological control of gastric acid secretion or antireflux surgery. In recent years, several minimally invasive antireflux endoscopic therapies (ARET) have been developed which may play a role in bridging the unmet therapeutic gap between the medical and surgical treatment options. To ensure optimal patient outcomes following ARET, considered patient selection is crucial, which requires a mechanistic understanding of individual ARET options. Here, we will discuss the differences between ARETs along with an overview of the current evidence base. We also outline future research priorities that will help refine the future role of ARET., Competing Interests: Competing interests: RH receives educational grants to support research infrastructure from Medtronic. Cook endoscopy (fellowship support), Pentax Europe, C2 therapeutics, Beamline diagnostic and Fractyl. VS receives honorarium for professional services from Pentax Europe, Medtronic, Astra Zeneca and Pharmacosmos. RS receives honoraria for running course and speaking at symposia for Medtronic, Johnson & Johnson, Falk Pharma, Medispar. HE is also on the advisory board for Johnson and Johnson and Falk Pharma., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Laboratory- related musculoskeletal disorders (LMSDs) are injuries resulting from working in the laboratory. Biomedical scientists (BMSs) play an important role in any health care system. However, they are at high risk of exposure to the LMSDs., Objective: This study aimed to estimate the prevalence and the associated risk factors of LMSDs among this group of healthcare professionals., Methods: We conducted a cross-sectional survey using the Nordic Musculoskeletal Questionnaire to estimate the prevalence of the LMSDs among the BMSs. BMSs with occupational or non-occupational accidents that affected their musculoskeletal system were excluded from the study. A Chi-square test was performed to measure the significant association between different risk factors (age, gender, weight, height, nationality, specialty, educational level, nature of the job, and the number of experience years) and the prevalence of the LMSDs among the BMSs., Results: The study included 83 BMSs. Females represented 63.9% and 36.1% were in the age group of 35- 44. The overall prevalence of the LMSDs was 77.1%. The most prevalent LMSDs were neck, shoulders, and lower back with 50.6%, 49.4%, and 43.4%, respectively. A total of 65.57% of BMSs had irregular symptoms of LMSDs., Conclusion: The study found that the prevalence of LMSDs among the BMSs was high. Good practice and training in ergonomics may minimize the prevalence of LMSDs among the BMSs.

Ulcerative colitis (UC) is a chronic relapsing and remitting gastrointestinal disorder of uncertain aetiology. The last two decades have seen an expansion in the therapeutic arsenal used to treat UC. This has resulted in improved clinical remission and response rates. Nonetheless, staples in our current medical management originate from trials conducted in the early 20th century. In this review article, we aim to outline the key milestones in the history of the medical management of UC in addition to highlighting promising therapeutic developments for the future., Competing Interests: The authors declare the following conflict of interests: SL: No conflict of interest to declare NA: No conflict of interest to declare RS: No conflict of interest to declare TB: No conflict of interest to declare JS: Has received speaker fees for Takeda, Abbvie and an unrestricted research grant from Tillots PJS: Has received speaker fees from Takeda, Janssen, Celltrion, Abbvie, Amgen, Dr Falk pharmaceuticals, Tillotts Pharma and has been an advisory board member for Abbvie, Celltrion, Galapagos and Janssen JKL: Has received speaker or consultancy fees from Abbvie, Arena, Galapagos, Janssen, MSD, Takeda, Pfizer and research grants from Takeda and Galapagos, (© The Author(s), 2022.)

A simple process based on the dual roles of both magnesium oxide (MgO) and iron oxide (FeO) with boron (B) as precursors and catalysts has been developed for the synthesis of borate composites of magnesium and iron (Mg 2 B 2 O 5 -Fe 3 BO 6 ) at 1200°C. The as-synthesized composites can be a single material with the improved and collective properties of both iron borates (Fe 3 BO 6 ) and magnesium borates (Mg 2 B 2 O 5 ). At higher temperatures, the synthesized Mg 2 B 2 O 5 -Fe 3 BO 6 composite is found thermally more stable than the single borates of both magnesium and iron. Similarly, the synthesized composites are found to prevent the growth of both gram-positive ( Staphylococcus aureus ) and gram-negative ( Escherichia coli ) pathogenic bacteria on all the tested concentrations. Moreover, the inhibitory effect of the synthesized composite increases with an increase in concentration and is more pronounced against S. aureus as compared to E. coli ., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Pervaiz Ahmad et al.)

Introduction: Neurological manifestations of acute lymphoblastic leukemia (ALL) have been reported as cranial neuropathies or meningeal symptoms most common in children. However, ALL can rarely involve the nerve roots causing symmetrical polyradiculopathy which can present with rapid onset paralysis, mimicking Guillain-Barré Syndrome (GBS). The symmetrical polyradiculopathy can be the earliest manifestation of ALL occurring even before the hematological and systemic manifestations., Case Report: We report a case of a healthy 29-year-old man who presented with subacute bilateral lower extremity weakness and numbness preceded by a respiratory infection. He was initially treated as a suspected (GBS) but cerebrospinal fluid (CSF) findings suggested an alternative diagnosis. His prior TB exposure created a diagnostic confusion. Lumbar spine magnetic resonance imaging revealed nerve root enhancements at L4-L5 and L5-S1 that are seen in GBS and TB arachnoidids. Brain magnetic resonance imaging demonstrated bilateral distention of the optic nerve sheath complexes with CSF suggestive of intracranial hypertension. CSF revealed elevated protein, nucleated cells 2145 leukocytes/mm 3 , numerous atypical lymphoid cells. He was later diagnosed with ALL associated symmetrical polyradiculopathy presenting with GBS-like symptoms., Conclusion: Symmetrical polyradiculopathy is a rare complication of ALL and can be confused with acute inflammatory demyelinating polyneuropathy. ALL associated polyradiculopathy in young individuals can be clinically indistinguishable from GBS. Our case highlights that when CSF findings are atypical for GBS, ALL should be considered on the differential diagnosis in patients presenting with GBS like symptoms., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The primary objectives were to determine the magnitude of COVID-19 infections in the general population and age-specific cumulative incidence, as determined by seropositivity and clinical symptoms of COVID-19, and to determine the magnitude of asymptomatic or subclinical infections., Design, Setting and Participants: We describe a population-based, cross-sectional, age-stratified seroepidemiological study conducted throughout Afghanistan during June/July 2020. Participants were interviewed to complete a questionnaire, and rapid diagnostic tests were used to test for SARS-CoV-2 antibodies. This national study was conducted in eight regions of Afghanistan plus Kabul province, considered a separate region. The total sample size was 9514, and the number of participants required in each region was estimated proportionally to the population size of each region. For each region, 31-44 enumeration areas (EAs) were randomly selected, and a total of 360 clusters and 16 households per EA were selected using random sampling. To adjust the seroprevalence for test sensitivity and specificity, and seroreversion, Bernoulli's model methodology was used to infer the population exposure in Afghanistan., Outcome Measures: The main outcome was to determine the prevalence of current or past COVID-19 infection., Results: The survey revealed that, to July 2020, around 10 million people in Afghanistan (31.5% of the population) had either current or previous COVID-19 infection. By age group, COVID-19 seroprevalence was reported to be 35.1% and 25.3% among participants aged ≥18 and 5-17 years, respectively. This implies that most of the population remained at risk of infection. However, a large proportion of the population had been infected in some localities, for example, Kabul province, where more than half of the population had been infected with COVID-19., Conclusion: As most of the population remained at risk of infection at the time of the study, any lifting of public health and social measures needed to be considered gradually., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)