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Abstract Introduction Rectal prolapse is prevalent in children and the elderly, impacting quality of life significantly. Traditional surgical interventions carry risks, especially in pediatric patients. Ethanol sclerotherapy offers a less invasive alternative, inducing fibrosis and thickening of the rectal wall. Despite its potential benefits, procedural complications are possible, emphasizing the need for careful patient selection and procedural expertise. This study aims to evaluate the safety and efficacy of sclerotherapy in treating rectal prolapse in a tertiary referral center in southern Iran. Methods Patient records from Nemazee Hospital covering January 2014 to December 2023 were retrospectively analyzed. Pediatric patients undergoing ethanol sclerotherapy for rectal prolapse were included. Data on demographics, presentation, procedures, and outcomes were collected. Ethical approval was obtained, and specific inclusion/exclusion criteria were applied. Statistical analyses were conducted using SPSS version 26. Results One hundred thirty patients were evaluated, with a mean age of 10.74 ± 5.320 years. Most patients experienced constipation (56.9%). 74.2% responded well to sclerotherapy, with 12.9% needing a second injection. Complications were minimal, with bleeding being the most common (4.6%). Recurrence occurred in 18.6% of cases. Male patients showed a higher total complication rate (P = 0.010). Diarrhea-dominant patients had no recurrences post-sclerotherapy. Age significantly influenced treatment response and recurrence (P = 0.017, P = 0.035). Conclusion Male predominance contradicted global pediatric rectal prolapse ratios, possibly influenced by cultural factors. Sclerotherapy remains effective, though response rates vary. Older age correlated with lower response rates and higher recurrence. Constipation-dominant prolapse was associated with increased recurrence risk. Male patients had a higher complication rate, highlighting the need for tailored management strategies.

Abstract Background Alcohol septal ablation (ASA) is recommended for moderate to severe symptomatic patients with hypertrophic obstructive cardiomyopathy. The current guidelines don not recommend particular alcohol doses and the amount of alcohol injected into the septal artery is based more on the interventionalist’s decision rather than on systematic evidence. Our objective is to execute a comprehensive assessment of the efficacy and safety of low alcohol doses (1–2 ml)) in comparison to large ones (2–4 ml). Methods Multiple databases, encompassing PubMed, WOS, Scopus, Embase, and Cochrane library were systemically assessed from inception to October 2023. Randomized controlled trials (RCTs) and observational studies comparing low-alcohol and high-alcohol dose in patients with HOCM was included. The main outcome was creatine kinase-MB (CK-MB). The secondary ones are septal thickness, left ventricular outflow pressure gradient, and atrioventricular (AV) block. Results Eight studies, with a total of 1446 individuals, were finally involved in our investigation. low alcohol doses showed lower CK-MB levels relative to high ones (MD=-0.93, 95% CI [-1.15 to -0.72], P = 0.00001). Furthermore, in terms of septal thickness, left ventricular outflow pressure gradient, and AV block, neither of the two doses was preferred. Conclusion We propose that the low alcohol dose is equally effective as the high dose. moreover, the low alcohol dose was associated with a lower CK-MB levels in comparison to the high one. PROSPERO registration CRD42024511537

Abstract Background Drug-coated balloons (DCB) have promising results in the management of in-stent restenosis (ISR), still their role remains a major challenge, and not well established in contemporary clinical practice. Aims To provide a comprehensive appraisal of the efficacy and safety of DCBs in patients with in-stent restenosis (ISR). Methods We searched PubMed, Scopus, web of Science, Ovid, and Cochrane Central from inception until 30 March, 2023. We included randomized controlled trials (RCTs) that compared DCB versus DES in ISR patients. Our primary endpoints were major adverse cardiac events (MACE) and late lumen loss (LLL). Secondary clinical endpoints were all-cause death, cardiac death, MI, TLR, TVR, and stent thrombosis, and angiographic outcomes were MLD, and in-stent binary restenosis. Results Ten RCTs comprising 1977 patients were included in this meta-analysis. The incidence of MACE was 15.57% in the DCB group compared to 14.13% in the DES group, with no significant difference in the risk of MACE following DCB (odds ratio [OR] 1.04, 95% confidence interval [CI]: 0.87 to 1.44). Compared with the DES intervention, the risk of LLL was comparable to the DCB intervention (mean difference [MD] -0.08, 95% CI: -0.18 to 0.02), while the incidence of TLR was increased in the DCB intervention (OR: 1.54, 95% CI: 1.2 to 1.99). Conclusion DCB was comparable to DES implantation is ISR patients regarding clinical outcomes, however it showed an increase in TLR events. Moreover, a RCT with large sample size and longer follow-up duration is warrened to validate these results.

Abstract Purpose Juvenile systemic lupus erythematosus (J-SLE) is a complex, heterogeneous disease affecting multiple organs. However, the classification of its subgroups is still debated. Therefore, we investigated the aggregated clinical features in patients with J-SLE using cluster analysis. Methods: Patients (≤ 16 years) diagnosed using the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria were identified from the clinical database of the Egyptian College of Rheumatology (ECR) SLE study group. Demographic data, clinical characteristics, laboratory features, and current therapies were selected. A cluster analysis was performed to identify different clinical phenotypes. Results: Overall, 404 patients, of whom 355 (87.9%) were female, had a mean age at diagnosis of 11.2 years and a mean disease duration of 2.3 years. We identified four distinct subsets of patients. Patients in cluster 1 (n = 103, 25.5%) were characterized predominantly by mucocutaneous and neurologic manifestations. Patients in cluster 2 (n = 101, 25%) were more likely to have arthritis and pulmonary manifestations. Cluster 3 (n = 71, 17.6%) had the lowest prevalence of arthritis and lupus nephritis (LN), indicative of mild disease intensity. Patients in cluster 4 (n = 129, 31.9%) have the highest frequency of arthritis, vasculitis, and LN. Cluster 1 and 4 patients had the highest disease activity index score and were less likely to use low-dose aspirin (LDA). The SLE damage index was comparable across clusters. Conclusions: Four identified J-SLE clusters express distinct clinical phenotypes. Attention should be paid to including LDA in the therapeutic regimen for J-SLE. Further work is needed to replicate and clarify the phenotype patterns in J-SLE.

Abstract Background This meta-analysis aims to establish a more precise association between gestational diabetes mellitus (GDM) incidence and H. pylori infection by amalgamating findings from prior case–control and cohort studies. Methods To identify relevant studies, we conducted a comprehensive search using the Excerpta Medica Database (Embase), PubMed (Medline), Web of Science (ISI), and Scopus from January 1990 to November 2022. The screening process involved reviewing the entire text, abstracts, and titles of retrieved articles. Subsequently, data extraction was performed from the selected articles, and their quality was assessed using the Newcastle–Ottawa Scale checklist. Version 17 of STATA software was utilized for the analysis, with relative risks (RR) calculated along with their 95% confidence intervals (CI) to quantify the impact of the included studies. Results This meta-analysis included eight observational and analytical studies. The combined risk of gestational diabetes mellitus (GDM) in pregnant women with H. pylori infection was found to be 1.97 times higher compared to pregnant women without infection (RR: 1.97; 95% CI 1.57–2.47; I2 = 0.00%; P = 0.84). Conclusion Pregnant women with H. pylori infection are at an increased risk of developing gestational diabetes.

Abstract Background Appreciating the various dimensions of the coronavirus disease 2019 (COVID-19) pandemic can improve health systems and prepare them to deal better with future pandemics and public health events. This study was conducted to investigate the association between the survival of hospitalized patients with COVID-19 and the epidemic risk stratification of the disease in Golestan province, Iran. Methods In this study, all patients with COVID-19 who were hospitalized in the hospitals of Golestan province of Iran from February 20, 2020, to December 19, 2022, and were registered in the Medical Care Monitoring Center (MCMC) system (85,885 individuals) were examined.The community's epidemic risk status (ERS) was determined based on the daily incidence statistics of COVID-19. The survival distribution and compare Survival in different subgroups was investigated using Kaplan–Meier and log-rank test and association between the survival and ERS by multiple Cox regression modeling. Results Out of 68,983 individuals whose data were correctly recorded, the mean age was 49 (SD = 23.98) years, and 52.8% were women. In total, 11.1% eventually died. The length of hospital stay was varying significantly with age, gender, ERS, underlying diseases, and COVID-19 severity (P

Abstract Background Among gynaecological malignancies, endometrial cancer (EC) is the most prevalent type of uterine cancer affecting women. This study explored the proteomic profiles of plasma samples obtained from EC patients, those with hyperplasia (Hy), and a control group (CO). A combination of techniques, such as 2D-DIGE, mass spectrometry, and bioinformatics, including pathway analysis, was used to identify proteins with modified expression levels, biomarkers and their associated metabolic pathways in these groups. Methods Thirty-four patients, categorized into three groups—10 with EC, 12 with Hy, and 12 CO—between the ages of 46 and 75 years old were included in the study. Untargeted proteomic analysis was carried out using two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Results In all three groups, 114 proteins that were significantly (p ≤ 0.05 and fold change ≥ 1.5) altered were successfully identified using peptide mass fingerprints (PMFs). Compared with those in the control group (CO), the EC samples had 85 differentially expressed proteins (39 upregulated and 46 downregulated), and in the Hy group, 81 proteins were dysregulated (40 upregulated and 41 downregulated) compared to those in the CO group, while 33 proteins exhibited differential regulation (12 upregulated and 21 downregulated) in the EC plasma samples compared to those in the Hy group. Vitamin D binding protein and complement C3 distinguished Hy and EC from CO with the greatest changes in expression. Among the differentially expressed proteins identified, enzymes with catalytic activity represented the largest group (42.9%). In terms of biological processes, most of the proteins were involved in cellular processes (28.8%), followed by metabolic processes (16.7%). STRING analysis for protein interactions revealed that the significantly differentially abundant proteins in the three groups are involved in three main biological processes: signalling of complement and coagulation cascades, regulation of insulin-like growth factor (IGF) transport and uptake by insulin-like growth factor binding proteins (IGFBPs), and plasma lipoprotein assembly, remodelling, and clearance. Conclusion The identified plasma protein markers have the potential to serve as biomarkers for differentiating between EC and Hy, as well as for early diagnosis and monitoring of cancer progression.

Abstract Volumetric loss is one of the challenging issues in muscle tissue structure that causes functio laesa. Tissue engineering of muscle tissue using suitable hydrogels is an alternative to restoring the physiological properties of the injured area. Here, myogenic properties of type I collagen (0.5%) and keratin (0.5%) were investigated in a mouse model of biceps femoris injury. Using FTIR, gelation time, and rheological analysis, the physicochemical properties of the collagen (Col)/Keratin scaffold were analyzed. Mouse C2C12 myoblast-laden Col/Keratin hydrogels were injected into the injury site and histological examination plus western blotting were performed to measure myogenic potential after 15 days. FTIR indicated an appropriate interaction between keratin and collagen. The blend of Col/Keratin delayed gelation time when compared to the collagen alone group. Rheological analysis revealed decreased stiffening in blended Col/Keratin hydrogel which is favorable for the extrudability of the hydrogel. Transplantation of C2C12 myoblast-laden Col/Keratin hydrogel to injured muscle tissues led to the formation of newly generated myofibers compared to cell-free hydrogel and collagen groups (p 0.05). The blend of Col/Keratin loaded with myoblasts provides a suitable myogenic platform for the alleviation of injured muscle tissue.

Abstract Background Inflammatory bowel disease (IBD) imposes a huge burden on the healthcare systems and greatly declines the patient’s quality of life. However, there is a paucity of detailed data regarding information and supportive needs as well as sources and methods of obtaining information to control different aspects of the disease from the perspectives of the patients themselves. This study aimed to establish the IBD patients’ preferences of informational and supportive needs through Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). Methods IBD patients were recruited from different centers. Considering inclusion and exclusion criteria, 521 participants were filled a predefined questionnaire. This questionnaire was prepared through literature review of the recent well-known guidelines on the needs of IBD patients, which was further approved by the experts of IBD area in three rounds of Delphi consensus. It includes 56 items in four sections of informational needs (25), supportive needs (15), sources of information (7), and methods of obtaining information (9). Results In particular, EFA was used to apply data reduction and structure detection. Given that this study tries to identify patterns, structures as well as inter-relationships and classification of the variables, EFA was utilized to simplify presentation of the variables in a way that large amounts of observations transform into fewer ones. Accordingly, the EFA identified five factors out of 25 items in the information needs section, three factors out of 15 items in the supportive needs section, two factors out of 7 items in the information sources section, and two factors out of 9 items in the information presentation methods. Through the CFA, all 4 models were supported by Root Mean Squared Error of Approximation (RMSEA); Incremental Fit Index (IFI); Comparative Fit Index (CFI); Tucker-Lewis Index (TLI); and SRMR. These values were within acceptable ranges, indicating that the twelve factors achieved from EFA were validated. Conclusions This study introduced a reliable 12-factor model as an efficient tool to comprehensively identify preferences of IBD patients in informational and supportive needs along with sources and methods of obtaining information. An in-depth understanding of the needs of IBD patients facilitates informing and supporting health service provision. It also assists patients in a fundamental way to improve adaptation and increase the quality of life. We suggest that health care providers consider the use of this tool in clinical settings in order to precisely assess its efficacy.

Abstract Background Disasters have affected the physical and mental health of people around the world. Since nurses are frontlines in disasters, it seems necessary to prepare for this responsibility. This study investigates the effect of psychological first-aid virtual education on the communication skills of nurses in disasters such as COVID pandemic. Methods In a randomized controlled trial, 55 nurses were selected by purposive sampling method from two hospitals in Isfahan and Tehran, Iran in December—November 2022 and randomly replaced in the intervention group who participated in psychological first aid virtual training and control group. The data were collected through the personal information form and Communication Skills –Test-Revised (CSTR). Results Two groups were homogeneous in terms of communication skills (p = 0.177), the total score of communication skills was significant between the two groups after the intervention (p 0.05). However, it was significant between the two groups after the intervention (p 0.05). Conclusion Pre-disaster training and virtual education can increase nurses’ communication skills in their ability to handle a disaster such as COVID pandemic. Virtual education of post-disaster psychological interventions is suggested. Trial registration IRCT20220923056023N1; date: 2023–01-31.

Abstract Background The aim of the present study was to investigate the possible connection between occupational status and chronic respiratory diseases (CRDs) among the Iranian population. Methods The present cross-sectional study was conducted on 9934 individuals aged 35–70 years enrolled in the Rafsanjan Cohort Study (RCS), a component of the Prospective Epidemiological Research Studies in Iran (PERSIAN). Detailed questionnaires were used to collect information on various factors, such as occupation, sociodemographic characteristics, medical history, anthropometric measurements, physical activity, cigarette and hookah smoking, opium use, and alcohol consumption. The association between occupational class and CRD was evaluated using logistic regression models for rare events. Results In the present study, 4624 (46.55%) participants were male, and 5310 (53.45%) were female. The prevalence of CRD among all participants was 2.61%. Occupational activities were classified into two categories: In class I, the largest group was the homemaker and unemployment category (41.73%), followed by self-employment (34.39%), employment (13.03%), and retired individuals (10.84%). In class II, there were pistachio farmers (12.61%), copper miners (3.62%), and others in various occupations (83.76%). Subjects with CRD were significantly more likely to be homemakers, unemployed, elderly, female, less educated, and obese. There was no significant relationship between CRD and job type/occupational status after adjusting for some potential confounding variables. Conclusions There was no significant relationship between CRD and job type/occupational status. However, longitudinal studies are needed to assess the impact of job type/occupational status on the risk of CRD.

Abstract Background Tele-rehabilitation, also known as tele-rehab, uses communication technologies to provide rehabilitation services from a distance. The COVID-19 pandemic has highlighted the importance of tele-rehab, where the in-person visits declined and the demand for remote healthcare rises. Tele-rehab offers enhanced accessibility, convenience, cost-effectiveness, flexibility, care quality, continuity, and communication. However, the current systems are often not able to perform a comprehensive movement analysis. To address this, we propose and validate a novel approach using depth technology and skeleton tracking algorithms. Methods Our data involved 14 participants (8 females, 6 males) performing shoulder abduction exercises. We collected depth videos from an LiDAR camera and motion data from a Motion Capture (Mocap) system as our ground truth. The data were collected at distances of 2 m, 2.5 m, and 3.5 m from the LiDAR sensor for both arms. Our innovative approach integrates LiDAR with the Cubemos and Mediapipe skeleton tracking frameworks, enabling the assessment of 3D joint angles. We validated the system by comparing the estimated joint angles versus Mocap outputs. Personalized calibration was applied using various regression models to enhance the accuracy of the joint angle calculations. Results The Cubemos skeleton tracking system outperformed Mediapipe in joint angle estimation with higher accuracy and fewer errors. The proposed system showed a strong correlation with Mocap results, although some deviations were present due to noise. Precision decreased as the distance from the camera increased. Calibration significantly improved performance. Linear regression models consistently outperformed nonlinear models, especially at shorter distances. Conclusion This study showcases the potential of a marker-less system, to proficiently track body joints and upper-limb angles. Signals from the proposed system and the Mocap system exhibited robust correlation, with Mean Absolute Errors (MAEs) consistently below $$10^\circ$$ 10 ∘ . LiDAR’s depth feature enabled accurate computation of in-depth angles beyond the reach of traditional RGB cameras. Altogether, this emphasizes the depth-based system’s potential for precise joint tracking and angle calculation in tele-rehab applications.

Abstract Background An enhanced aerobic glycolysis (“Warburg effect”) associated with an increase in lactic acid in the tumor microenvironment contributes to tumor aggressiveness and resistance to radiation and chemotherapy. We investigated the radiation- and chemo-sensitizing effects of the nonsteroidal anti-inflammatory drug (NSAID) diclofenac in different cancer cell types. Methods The effects of a non-lethal concentration of diclofenac was investigated on c-MYC and Lactate Dehydrogenase (LDH) protein expression/activity and the Heat shock Protein (HSP)/stress response in human colorectal (LS174T, LoVo), lung (A549), breast (MDA-MB-231) and pancreatic (COLO357) carcinoma cells. Radiation- and chemo-sensitization of diclofenac was determined using clonogenic cell survival assays and a murine xenograft tumor model. Results A non-lethal concentration of diclofenac decreases c-MYC protein expression and LDH activity, reduces cytosolic Heat Shock Factor 1 (HSF1), Hsp70 and Hsp27 levels and membrane Hsp70 positivity in LS174T and LoVo colorectal cancer cells, but not in A549 lung carcinoma cells, MDA-MB-231 breast cancer cells and COLO357 pancreatic adenocarcinoma cells. The impaired lactate metabolism and stress response in diclofenac-sensitive colorectal cancer cells was associated with a significantly increased sensitivity to radiation and 5Fluorouracil in vitro, and in a human colorectal cancer xenograft mouse model diclofenac causes radiosensitization. Conclusion These findings suggest that a decrease in the LDH activity and/or stress response upon diclofenac treatment predicts its radiation/chemo-sensitizing capacity.

Abstract Background Iatrogenic portal vein (PV) injuries following pleural drainage catheter (PDC) insertion are rare but life-threatening. This case report emphasizes the importance of prompt recognition and effective interventional radiology (IR) management. Case presentation A 38-year-old Asian male, admitted for a non-ST-segment elevation myocardial infarction, suffered a critical PV injury during PDC insertion, leading to rapid clinical deterioration. The IR team conducted a portogram, retrieved the catheter, and successfully executed an embolization procedure. The patient's recovery, confirmed through imaging and improving liver function tests, enabled discharge with follow-up instructions. Conclusions This case highlights the clinical significance of promptly recognizing and effectively managing iatrogenic PV injuries during PDC insertion, with the pivotal role of IR. Collaboration between IR and surgical teams is crucial for optimizing patient outcomes.

Abstract Objectives This is the first national study to investigate the incidence of non-syndromic oro-facial clefts (NSOFC) and Pierre-Robin-Sequence in Saudi Arabia over the Covid-19 pandemic period. Methods All maternity hospitals (30-hospitals) in the major regions and cities of Saudi from November 2020-to-2021 were included in the study. Patients were evaluated for cleft phenotype using the LASHAL-classification system. The incidence of NSOFC in Saudi Arabia was calculated by comparing the number of NSOFCs cases born out of all live births during the study period at the included hospitals. Clinical examination was performed and information was gathered using a validated data collection form. Results In one year, 140,380 live-infants were born at the selected hospitals. Of these, 177 were diagnosed with NSOFC giving an incidence of 1.26/1,000 live-births in Saudi Arabia and the highest incidence in Medina city (2.46/1000 live-births). The incidence of cleft lip-and-palate (0.67/1000 live-births) was higher than that of cleft-palate (0.37/1000 live-births) and cleft-lip (0.22/1000 live-births). Pierre-Robin Sequence incidence was (0.04/1000 live-births). There were 21(12.1) or 23(13.2%) of NSOFC’s mothers exposed or vaccinated with Covid-19, respectively. Conclusion The national incidence of NSOFC in Saudi Arabia was 1.26/1000 live births with variation between phenotypes and regions in the country. In addition, to reporting Covid-19 infection prevalence and vaccine exposure among NSOFC's mothers, this study represents the first of its type to evaluate NSOFC prevalence in Saudi Arabia on a national level.

Abstract Background Drug-coated balloons (DCBs) are an established strategy for coronary artery disease. However, the new generation drug-eluting stent (DES) is recommended for patients with Acute myocardial infarction (AMI) for coronary artery revascularization. Our aim is to provide a comprehensive appraisal of the efficacy of DCBs in patients with AMI undergoing PCI. Methods We searched the WOS, PubMed, Scopus, and Cochrane CENTRAL till March 2023, for studies that compared DCBs versus DES in patients with AMI undergoing PCI. We used a random-effects model to compare major adverse cardiac events (MACE), cardiac death, all-cause death, myocardial infarction, target lesion revascularization (TLR), stent thrombosis, Late lumen Loss (LLL), and minimum lumen diameter (MLD) between the two groups. Results Thirteen studies comprising 2644 patients were included. The pooled OR showed non-inferiority of DCB over DES in terms of MACE (OR = 0.89, 95% CI [0.57 to 1.40], p = 0.63). When we defined MACE as a composite of cardiac death, MI, and TLR; the pooled OR favored DCB over DES (OR = 0.50, 95% CI [0.28 to 0.9], p = 0.02). Moreover, DCB was not inferior to DES in terms of all-cause mortality (OR = 0.88, 95% CI: 0.43 to 1.8, p = 0.73), cardiac mortality, (OR = 0.59, 95% CI: 0.22 to 1.56, p = 0.29), MI (OR = 0.88, 95% CI: 0.34 to 2.29, p = 0.79), stent thrombosis (OR = 1.21, 95% CI: 0.35 to 4.23, p = 0.76), TLR (OR = 0.9, 95% CI: 0.43 to 1.93, p = 0.8), LLL (MD = -0.6, 95% CI: -0.3 to 0.19, p = 0.64), or MLD (MD = -0.4, 95% CI: -0.33 to 0.25, p = 0.76). Conclusion Our meta-analysis indicated that DCB intervention was not inferior to DES in the PCI setting in patients with AMI, and can be recommended as a feasible strategy in AMI. PROSPERO registration CRD42023412757.

Abstract Background Aflatoxins are regarded as the most potent genotoxic and carcinogenic type of mycotoxins. This meta-analysis was performed to investigate a the relation of aflatoxin B1 (AFB1) to growth measurements of infants/children, including wasting, underweight, stunting, as well as weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ) z-scores. Methods Electronic databases of PubMed, Web of Science, and Scopus were searched to identify related publications. Effect sizes for associations were pooled using the random effects analysis. Subgroup analysis by study design, method used to assess AFB1, and adjustment for covariateswas performed to detect possible sources of heterogeneity. Results Pooled analysis of available data showed that AFB1 exposure was negatively associated growth z-scores, including WHZ (β = -0.02, 95%CI = -0.07 to 0.03), with WAZ (β = -0.18, 95%CI = -0.33 to -0.02), and HAZ (β = -0.17, 95%CI = -0.30 to -0.03) in infants/children. There was a remarkable heterogeneity among studies on WAZ and HAZ (P ≤ 0.001). In prospective cohort studies, AFB1 exposure was found to be significantly associated with the elevated risk of underweight (OR = 1.20, 95%CI = 1.03 to 1.40) and stunting (OR = 1.21, 95%CI = 1.11 to 1.33). Conclusions This meta-analysis highlighted the importance of AFB1 exposure as a potential risk factor for growth impairment in infants/children.

Abstract Background The sturgeon group has been economically significant worldwide due to caviar production. Sturgeons consist of 27 species in the world. Mitogenome data could be used to infer genetic diversity and investigate the evolutionary history of sturgeons. A limited number of complete mitogenomes in this family were sequenced. Here, we annotated the mitochondrial Huso huso genome, which revealed new aspects of this species. Results In this species, the mitochondrial genome consisted of 13 genes encoding proteins, 22tRNA and 2rRNA, and two non-coding regions that followed other vertebrates. In addition, H. huso had a pseudo-tRNA-Glu between ND6 and Cytb and a 52-nucleotide tandem repeat with two replications in 12S rRNA. This duplication event is probably related to the slipped strand during replication, which could remain in the strand due to mispairing during replication. Furthermore, an 82 bp repeat sequence with three replications was observed in the D-loop control region, which is usually visible in different species. Regulatory elements were also seen in the control region of the mitochondrial genome, which included termination sequences and conserved regulatory blocks. Genomic compounds showed the highest conservation in rRNA and tRNA, while protein-encoded genes and nonencoded regions had the highest divergence. The mitochondrial genome was phylogenetically assayed using 12 protein-encoding genes. Conclusions In H. huso sequencing, we identified a distinct genome organization relative to other species that have never been reported. In recent years, along with the advancement in sequencing identified more genome rearrangements. However, it is an essential aspect of researching the evolution of the mitochondrial genome that needs to be recognized.

Abstract Background The prevalence of breast cancer and its mortality rate are increasing rapidly among women worldwide. On other hand, the courses of chemotherapy as the main treatment for these patients are too much exhaustive and annoying. This study was designed to evaluate the use of synbiotics (probiotics + prebiotics) supplementation as a safe and inexpensive adjuvant treatment in reducing common chemotherapy side effects in women with breast cancer. Methods The current study was conducted on 67 women with definitive diagnosis of breast cancer who were hospitalized to receive one-day chemotherapy sessions, and met the inclusion criteria. The patients were randomly allocated to the intervention or control group to receive synbiotics or placebo, respectively. They received oral consumption of synbiotics supplements twice a day for 8 weeks. The primary outcome was the changes in severity or experience of chemotherapy complication, analyzed by intention to treat (ITT). The instruments included 7 validated questionnaires which were used to assess chemotherapy complications in the initiation, 4 weeks and 8 weeks after intervention. Dietary intake was measured by 24-h dietary recall at the beginning, week 4 and week 8. Data were analyzed by SPSS software version 24. P-value

Abstract Background Sclerosing angiomatoid nodular transformation of the spleen is a relatively rare benign vascular lesion in both adult and pediatric age groups with unclear etiopathogenesis and variable clinical presentations. Many benign and also malignant splenic masses could mimic sclerosing angiomatoid nodular transformation, both clinically and radiologically. Herein, we report our experience with a case of sclerosing angiomatoid nodular transformation in a 3-year-old girl. Case report A 3-year-old Iranian girl presented with abdominal pain, back pain, and constipation for 2 weeks. She was being followed up by a pediatrician due to her short stature and persistent anemia. Physical examination showed stable vital signs, short stature, pallor, and a puffy face. Laboratory evaluation showed normochromic normocytic anemia with a normal reticulocyte count, ferritin, and hemoglobin electrophoresis. Radiologic assessments revealed a hypoechoic lesion in the spleen with high vascularity, clinically suspected to be lymphoma. She was operated on, and after partial splenectomy, pathologic evaluation of the spleen showed a solitary, well-demarcated, and unencapsulated dark mass. Microscopic examination revealed micronodular appearance composed of irregular-shaped vascular spaces lined by plump endothelial cells and surrounded by concentric collagen fibers, features in keeping with sclerosing angiomatoid nodular transformation. The patient’s anemia was resolved after surgery, and no clinical or radiologic deficits were noted during the 10-month follow-up visits. Conclusion Although sclerosing angiomatoid nodular transformation is exceedingly rare in children, it should be considered a differential diagnosis in pediatric splenic neoplasms with concurrent hematologic manifestations, such as anemia.

Abstract Introduction Acute myeloid leukemia is a rare event in post-liver-transplantation recipients. In the present report, we described a case of extramedullary acute myeloid leukemia, M4/M5 subtype, following orthotopic liver transplant. Case presentation The patient was a 50-year-old Iranian woman who underwent orthotopic liver transplant due to hepatitis B-related cirrhosis (Child C, MELD (model for end-stage liver disease score) = 22). Orthotopic liver transplant was performed using the piggy back technique in January 2022. Induction immunosuppressive therapy was 1 gm methylprednisolone for 3 days followed by a triple maintenance immunosuppressive regimen including mycophenolate mofetil, prednisolone, and tacrolimus. About 5 months after orthotopic liver transplant in June 2022, the patient presented with leukocytosis, with white blood cell count of 99.4 × 103/µl, and physical examination revealed only cervical lymphadenopathy. Biopsy of cervical lymph nodes showed a myeloid tumor. She was immediately hospitalized. Eight hours after hospitalization, the patient gradually developed lethargy and decreased O2 saturation to approximately 89%. Flow cytometry demonstrated the markers of a myelomonocytic acute myeloid leukemia (M4/M5). Cytoreduction was immediately started by intensive leukopheresis followed by induction therapy. Because of a septic complication during the induction therapy, further chemotherapy was discontinued and broad-spectrum antibiotics and antifungal treatments started. Unfortunately, our patient died of severe septic shock 42 days after hospitalization. Conclusion Acute myeloid leukemia is a rare phenomenon after liver transplantation, and it can follow a rapidly fatal clinical course.

Abstract Background The benefits and harms of vitamin D supplementation in the treatment of COVID-19 have not yet been fully documented. In this study, we aimed to evaluate the effects of high-dose vitamin D supplementation on liver function tests in COVID-19. Method This double-blinded randomized clinical trial was conducted on 140 hospitalized patients aged > 30 years. Patients were randomly allocated to receive either intervention group (n = 70 receiving 50,000 IU of vitamin D capsules orally as a single dose and then 10,000 IU syrup daily from the second day of admission for 30 days) and the control group (n = 70 receiving 1000 IU vitamin D syrup orally per day). Liver function tests (LFT), including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and Lactate Dehydrogenase (LDH) were evaluated at baseline and at the end of the intervention. Decision tree analysis was performed to identify the predictors for change in liver enzymes. Results Among COVID-19 patients, a significant decrease was observed in serum level of ALP between intervention and placebo groups (p = 0.04). In addition, decision tree analysis revealed that GGT, temperature, serum magnesium level at baseline and gender were the most important predictors of ALT changes in COVID-19 patients. Conclusion High-dose vitamin D supplementation improved ALP markers among COVID-19 patients. More randomized controlled trials with longer follow-up times will be required.

Abstract To evaluate shear stress influence on ex vivo expansion of hematopoietic cell lineages for clinical application, in this study, human pro-monocytic cell (namely U937 cell line) was selected as a hematopoietic stem cell (HSC) model and cultured in suspension mode at two different agitation rates (50, 100 rpm) in the stirred bioreactor. At the agitation rate of 50 rpm, the cells achieved higher expansion folds (27.4 fold) with minimal morphological changes as well as apoptotic cell death, while at 100 rpm the expansion fold decreased after 5-day of culture in suspension culture in comparison with static culture and reached 24.5 fold at the end of the culture. The results of glucose consumption and lactate production were also in agreement with the data of fold expansion and indicated the preference of culture in the stirred bioreactor when agitated at 50 rpm. This study indicated the stirred bioreactor system with an agitation rate of 50 rpm and surface aeration may be used as a potential dynamic culture system for clinical applications of hematopoietic cell lineage. The current experiments shed data related to the effect of shear stress on human U937 cells, as a hematopoietic cell model, to set a protocol for expansion of HSCs for biomedical applications.

Abstract We compared outcomes of adult patients with secondary acute myeloid leukemia (sAML) versus de novo AML after non-T-depleted haploidentical stem cell transplant (HaploSCT) with post-transplant cyclophosphamide (PTCy). Seventeen hundred and eleven AML patients (sAML-231, de novo-1480) in first complete remission transplanted from 2010 to 2021, were included. Patients with de novo AML were younger, median age 55.8 versus 60.8 years, p

Abstract Background Colorectal cancer is one of the prominent leading causes of fatality worldwide. Despite recent advancements within the field of cancer therapy, the cure rates and long-term survivals of patients suffering from colorectal cancer have changed little. The application of conventional chemotherapeutic agents like doxorubicin is limited by some drawbacks such as cardiotoxicity and hematotoxicity. Therefore, nanotechnology has been exploited as a promising solution to address these problems. In this study, we synthesized and compared the anticancer efficacy of doxorubicin-loaded liposomes that were surface engineered with the 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-matrix metalloproteinase-2 (MMP-2) cleavable peptide-polyethylene glycol (PEG) conjugate. The peptide linker was used to cleave in response to the upregulated MMP-2 in the tumor microenvironment, thus exposing a positive charge via PEG-deshielding and enhancing liposomal uptake by tumor cells/vasculature. Liposomal formulations were characterized in terms of size, surface charge and morphology, drug loading, release properties, cell binding and uptake, and cytotoxicity. Results The formulations had particle sizes of ~ 100–170 nm, narrow distribution (PDI ˂ 0.2), and various surface charges (− 10.2 mV to + 17.6 mV). MMP-2 overexpression was shown in several cancer cell lines (C26, 4T1, and B16F10) as compared to the normal NIH-3T3 fibroblast cells by gelatin zymography and qRT-PCR. In vitro results demonstrated enhanced antitumor efficacy of the PEG-cleavable cationic liposomes (CLs) as compared to the commercial Caelyx® (up to fivefold) and the chick chorioallantoic membrane assay showed their great antiangiogenesis potential to target and suppress tumor neovascularization. The pharmacokinetics and efficacy studies also indicated higher tumor accumulation and extended survival rates in C26 tumor-bearing mice treated with the MMP-2 cleavable CLs as compared to the non-cleavable CLs with no remarkable sign of toxicity in healthy tissues. Conclusion Altogether, the MMP-2-cleavable CLs have great potency to improve tumor-targeted drug delivery and cellular/tumor-vasculature uptake which merits further investigation.

Abstract Background We aimed to prospectively compare the diagnostic performance of gadoxetic acid-enhanced MRI (EOB-MRI) and contrast-enhanced Computed Tomography (CECT) for hepatocellular carcinoma (HCC) detection and liver transplant (LT) eligibility assessment in cirrhotic patients with explant histopathology correlation. Methods In this prospective, single-institution ethics-approved study, 101 cirrhotic patients were enrolled consecutively from the pre-LT clinic with written informed consent. Patients underwent CECT and EOB-MRI alternately every 3 months until LT or study exclusion. Two blinded radiologists independently scored hepatic lesions on CECT and EOB-MRI utilizing the liver imaging reporting and data system (LI-RADS) version 2018. Liver explant histopathology was the reference standard. Pre-LT eligibility accuracies with EOB-MRI and CECT as per Milan criteria (MC) were assessed in reference to post-LT explant histopathology. Lesion-level and patient-level statistical analyses were performed. Results Sixty patients (49 men; age 33–72 years) underwent LT successfully. One hundred four non-treated HCC and 42 viable HCC in previously treated HCC were identified at explant histopathology. For LR-4/5 category lesions, EOB-MRI had a higher pooled sensitivity (86.7% versus 75.3%, p

Abstract Background Eye lesions, occur in nearly half of patients with Behçet’s Disease (BD), can lead to irreversible damage and vision loss; however, limited studies are available on identifying risk factors for the development of vision-threatening BD (VTBD). Using an Egyptian college of rheumatology (ECR)-BD, a national cohort of BD patients, we examined the performance of machine-learning (ML) models in predicting VTBD compared to logistic regression (LR) analysis. We identified the risk factors for the development of VTBD. Methods Patients with complete ocular data were included. VTBD was determined by the presence of any retinal disease, optic nerve involvement, or occurrence of blindness. Various ML-models were developed and examined for VTBD prediction. The Shapley additive explanation value was used for the interpretability of the predictors. Results A total of 1094 BD patients [71.5% were men, mean ± SD age 36.1 ± 10 years] were included. 549 (50.2%) individuals had VTBD. Extreme Gradient Boosting was the best-performing ML model (AUROC 0.85, 95% CI 0.81, 0.90) compared with logistic regression (AUROC 0.64, 95%CI 0.58, 0.71). Higher disease activity, thrombocytosis, ever smoking, and daily steroid dose were the top factors associated with VTBD. Conclusions Using information obtained in the clinical settings, the Extreme Gradient Boosting identified patients at higher risk of VTBD better than the conventional statistical method. Further longitudinal studies to evaluate the clinical utility of the proposed prediction model are needed.

Abstract Background Total knee arthroplasty (TKA) is an effective procedure for patients with a variety of knee conditions. The main cause of aseptic TKA failure is implant loosening, which has been linked to poor cement mantle quality. Cementless components were introduced to offer better longer-term biological fixation through osseointegration; however, early designs led to increased rate of revision due to a lack of initial press-fit and bony ingrowth. Newer highly porous metal designs may alleviate this issue but randomised data of fully uncemented TKA (tibial, femoral, patella) is lacking. The aim of the Knee-Fix study is to investigate the long-term implant survival and patient outcomes of fully uncemented compared with cemented fixation in TKA. Our study hypothesis was that uncemented TKA would be as clinically reliable and durable as the gold-standard cemented TKA. Methods The Knee-Fix study is a two-arm, single-blinded, non-inferiority randomised controlled trial with 160 patients in each arm and follow-up at 6 weeks, 6 months, 12 months, 24 months, 5 years and 10 years. The primary outcome of interest is implant fixation, which will be measured by assessment of postoperative progressive radiolucencies with the Knee Society Total Knee Arthroplasty Roentgenographic Evaluation and Scoring System. Secondary outcome measures are patient-reported outcomes, measured using Oxford Knee Score (OKS), International Knee Society System (IKSS), Forgotten Joint Score-12 (FJS-12), EuroQol (EQ-5D-5L), VAS Pain, Patient Satisfaction Score and Net Promoter Score. Discussion While cemented fixation remains the gold standard, a growing proportion of TKA are now implanted cementless. Highly porous metal cementless components for TKA can offer several benefits including potentially improved biological fixation; however, long-term outcomes need further investigation. This prospective study will help discern long-term differences between the two techniques. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12616001624471 . Registered trial name: Knee-Fix study (Cemented vs Uncemented Total Knee Replacement). Registered on 24 November 2016.

Abstract Background The bacterial mechanisms responsible for hydrogen peroxide (H2O2) scavenging have been well-reported, yet little is known about how bacteria isolated from cold-environments respond to H2O2 stress. Therefore, we investigated the transcriptional profiling of the Planomicrobium strain AX6 strain isolated from the cold-desert ecosystem in the Qaidam Basin, Qinghai-Tibet Plateau, China, in response to H2O2 stress aiming to uncover the molecular mechanisms associated with H2O2 scavenging potential. Methods We investigated the H2O2-scavenging potential of the bacterial Planomicrobium strain AX6 isolated from the cold-desert ecosystem in the Qaidam Basin, Qinghai-Tibet Plateau, China. Furthermore, we used high-throughput RNA-sequencing to unravel the molecular aspects associated with the H2O2 scavenging potential of the Planomicrobium strain AX6 isolate. Results In total, 3,427 differentially expressed genes (DEGs) were identified in Planomicrobium strain AX6 isolate in response to 4 h of H2O2 (1.5 mM) exposure. Besides, Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analyses revealed the down- and/or up-regulated pathways following H2O2 treatment. Our study not only identified the H2O2 scavenging capability of the strain nevertheless also a range of mechanisms to cope with the toxic effect of H2O2 through genes involved in oxidative stress response. Compared to control, several genes coding for antioxidant proteins, including glutathione peroxidase (GSH-Px), Coproporphyrinogen III oxidase, and superoxide dismutase (SOD), were relatively up-regulated in Planomicrobium strain AX6, when exposed to H2O2. Conclusions Overall, the results suggest that the up-regulated genes responsible for antioxidant defense pathways serve as essential regulatory mechanisms for removing H2O2 in Planomicrobium strain AX6. The DEGs identified here could provide a competitive advantage for the existence of Planomicrobium strain AX6 in H2O2-polluted environments.

Abstract Objectives To compare the diagnostic performance of international hepatocellular carcinoma (HCC) guidelines with gadoxetic acid-enhanced MRI (EOB-MRI) and contrast-enhanced Computed tomography (CECT) and their impact on liver transplant (LT) allocation in cirrhotic patients with explant histopathology correlation. Methods In this prospective single-centre ethics-approved study, 101 cirrhotic patients were consecutively enrolled with informed consent from the pre-LT clinic. They underwent CECT and EOB-MRI alternately at three monthly intervals until LT or removal from LT list. Two abdominal radiologists, blinded to explant histopathology, independently recorded liver lesions visible on CECT and EOB-MRI. Imaging-based HCC scores were assigned to non-treated liver lesions utilizing Liver Imaging Reporting and Data System (LI-RADS), European Association for the Study of the Liver (EASL), Asian-Pacific Association for the Study of the Liver (APASL) and Korean Liver Cancer Association-National Cancer Center (KLCA) guidelines. Liver explant histopathology was the reference standard. Simulated LT eligibility was assessed as per Milan criteria (MC) in reference to explant histopathology. Results One hundred and three non-treated HCC and 12 non-HCC malignancy were identified at explant histopathology in 34 patients (29 men, 5 women, age 55–73 years). Higher HCC sensitivities of statistical significance were observed with EOB-MRI for LI-RADS 4 + 5, APASL and KLCA compared to LI-RADS 5 and EASL with greatest sensitivity obtained for LIRADS 4 + 5 lesions. HCC sensitivities by all guidelines with both EOB-MRI and CECT were significantly lower if all histopathology-detected HCCs were included in the analysis, compared to imaging-visible lesions only. A significantly greater variation in HCC sensitivity was noted across the guidelines with EOB-MRI compared to CECT. No significant differences in simulated LT eligibility based on MC were observed across the HCC scoring guidelines with EOB-MRI or CECT. Conclusion HCC sensitivities are variable depending on scoring guideline, lesion size and imaging modality utilised. Prior studies that included only lesions visible on pre-operative imaging overestimate the diagnostic performance of HCC scoring guidelines. Per-lesion differences in HCC diagnosis across these guidelines did not impact patient-level LT eligibility based on MC.

Abstract Background Acceptance is considered a key variable in chronic diseases such as chronic renal failure. To achieve adaptation and acceptance, people face obstacles, and identifying these obstacles primarily requires self-awareness. logo-therapy can help a person achieve this goal. To this end, this study aimed to investigate the effect of logo-therapy on disease acceptance and self-awareness of patients undergoing hemodialysis referred to a medical centers supervised by Kerman medical science university in 2021. Methods This quasi-experimental study was conducted with a pre-test-post-test research design on 80 patients with chronic renal failure undergoing hemodialysis in Kerman. The patients who met the inclusion criteria were selected using convenience sampling and were then randomly assigned to intervention and control groups (40 patients in each group). The logo-therapy training program was performed for the participants in the intervention group during 4 sessions of 45–60 min, individually and three times a week. The instruments used for data collection were a demographic information questionnaire, the Acceptance of Illness Scale (AIS), and the Self-Awareness Outcomes Questionnaire (SAOQ). The collected data were analyzed using SPSS software (version 22). Results The analysis didn’t show a significant difference in the acceptance of illness scores in the intervention group before and after the intervention (P > 0.05). Besides, a statistically significant difference was observed between the intervention and control groups in terms of self-awareness, indicating that the intervention improved the dialysis patients’ self-awareness (P

Abstract Background Portomesenteric Vein Thrombosis (PMVT) following Laparoscopic Sleeve Gastrectomy (LSG) is an uncommon but potentially debilitating complication. Catheter-Directed Thrombolysis (CDT) has an evolving role in recanalizing the venous flow and preventing thrombus propagation. Therefore, it can be used as an alternative or in combination with systemic anticoagulants in selected patients. We report two trans-hepatic and trans-splenic CDT. The patient’s clinical details, radiological findings, safety, and efficacy are reported. Cases presentation Two patients presented to the Emergency Department (ED) within 14 days of surgery. The presenting complaints were generally nonspecific. The diagnosis of PMVT was established in both patients based on abdominal Contrast-Enhanced Computed Tomography (CECT). The two patients received a combined therapy of subcutaneous (SC) heparinization and CDT using a trans-hepatic approach in case 1 and a trans-splenic approach in case 2. Subsequent post-procedure venograms and CECT were performed and showed significant thrombus resolution. Both patients received oral anticoagulant therapy upon discharge with a successful overall recovery. Conclusion PMVT is an infrequent and severe post LSG complication. Various approaches for re-establishing the portal venous flow have been described according to the severity of venous thrombosis. This article describes CDT therapy as a safe and effective option for treating PMVT in symptomatic patients.

Abstract Myelodysplastic syndromes (MDS) are a heterogeneous clonal disease of myeloid neoplasms characterized by ineffective hematopoiesis, variable degree of cytopenias, and an increased risk of progression to acute myeloid leukemia (AML). Molecular and genetic characterization of MDS has led to a better understanding of the disease pathophysiology and is leading to the development of novel therapies. Targeted and immune therapies have shown promising results in different hematologic malignancies. However, their potential use in MDS is yet to be fully defined. Here, we review the most recent advances in therapeutic approaches in MDS, focusing on higher-risk disease. Allogeneic hematopoietic cell transplantation is beyond the scope of this article.

Abstract Background Improving the functional outcome following total knee arthroplasty (TKA) by using different alignment techniques remains controversial. The surgical techniques and technologies used so far to obtain these alignments have all suffered from inaccuracies. The use of robotic technology to plan and execute the bony resection provides increased accuracy for these various alignment techniques and may determine which will deliver superior function. Functional alignment (FA) is a newer surgical technique that aims to position the prosthesis with respect to each patients’ specific bony anatomy whilst minimising disruption to the soft tissue envelope. This trial aims to compare the patient and surgical outcomes of FA to the current gold standard surgical technique, mechanical alignment (MA), under randomised and blinded conditions. Methods Patients with symptomatic knee osteoarthritis will be prospectively recruited. Following informed consent, 240 patients will be randomised to either a MA surgical technique (the control group) or a FA surgical technique (the intervention group) at a ratio of 4:1 using a random number generator. All patients will undergo computer tomography (CT) based robotic arm-assisted surgery to execute planned implant positioning and alignment with high levels of accuracy. The primary outcome is the forgotten joint score (FJS) at 2 years post-operation. Secondary outcome measures include patient reported outcome measures of post-operative rehabilitation, pain, function and satisfaction, as well as limb alignment, implant revisions and adverse events. Intention-to-treat and per-protocol population analysis will also be conducted. Standardisation of the surgical system and care pathways will minimise variation and assist in both patient and physiotherapist blinding. Ethical approval was obtained from the Northern B Health and Disability Ethics Committee (20/NTB/10). Discussion Currently, MA remains the gold standard in knee replacement due to proven outcomes and excellent long-term survivorship. There are many alternative alignment techniques in the literature, all with the goal of improving patient outcomes. This study is unique in that it leverages an advanced analytics tool to assist the surgeon in achieving balance. Both alignment techniques will be executed with high precision using the CT-based robotic arm-assisted surgery system which will minimise surgical variation. This trial design will help determine if FA delivers superior outcomes for patients. Trial registration Australia and New Zealand Clinical Trials Registry (ANZCTR), ACTRN12620000009910 . Registered on 9 January 2020. ClinicalTrials.gov, NCT04600583 . Registered on 29 September 2020.

Abstract Background Beta thalassemia major (β-TM) is a common cause of skeletal morbidity and is associated with increased bone fracture risk, particularly in inadequately transfused children. The aim of this study was to investigate some potential biochemical markers as possible early predictors of BMD variations in children with β-TM. Methods The study included 38 children with β-TM and 40 sex-age matched controls. All patients were subjected to BMD assessment by dual-energy X-ray absorptiometry (DEXA). Serum beta-crosslaps (beta-CTx), osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B ligand (RANKL), urinary deoxypyridinoline (DPD) and ferritin levels were compared between the groups. Results Serum OPG levels were significantly lower in thalassemic children than in controls. The mean ratio of RANKL/OPG was significantly higher in the thalassemic patients than in the control group. Osteoporosis was detected in 10 (3 female and 7 male) of 38 patients (26.3%) according to the femur Z score and in 6 of them (4 male and 2 female) (15.8%) according to the spine Z score. Conclusions Serum OPG concentrations can be used as a biochemical marker in screening patients with beta-thalassemia major for the development of osteoporosis.

Abstract Background Mantle cell lymphoma is the rarest subtype of non-Hodgkin’s lymphoma. It can exhibit diverse extranodal manifestations. However, renal involvement is uncommon, and if it occurs, it usually only gets detected postmortem. There are several mechanisms by which mantle cell lymphoma can damage the kidneys. Renal failure is a potential complication, and prompt evaluation and diagnosis are critical steps to prevent long-term complications. Case presentation We present the case of a 75-year-old non-Hispanic White male with past medical history significant for hypertension and dyslipidemia, presenting with fever, weight loss, and night sweats. Work-up showed markedly elevated white blood cells, multiple enlarged lymph nodes, and a kidney mass. The patient was diagnosed with mantle cell lymphoma with kidney involvement confirmed with a kidney biopsy. His disease was positive for cyclin D1 overexpression despite t(11; 14) absence. The patient received six cycles of alternating vincristine, rituximab, cyclophosphamide, doxorubicin, and prednisone then dexamethasone, high-dose cytarabine, and oxaliplatin, after which he was maintained on ibrutinib and rituximab, with resolution of symptoms and disease regression. Conclusion We present a case of a rare presentation of Mantle cell lymphoma while describing the clinical presentation and diagnostic and treatment approaches. This case report can assist physicians in the clinical work-up and treatment of patients with similar diagnosis or presentation.

Abstract Background Apart from infecting a large number of people around the world and causing the death of many people, the COVID-19 pandemic seems to have changed the healthcare processes of other diseases by changing the allocation of health resources and changing people’s access or intention to healthcare systems. Objective To compare the incidence of endpoints marking delayed healthcare seeking in medical emergencies, before and during the pandemic. Methods Based on a PICO model, medical emergency conditions that need timely intervention was selected to be evaluated as separate panels. In a systematic literature review, PubMed was quarried for each panel for studies comparing the incidence of various medical emergencies before and during the COVID-19 pandemic. Markers of failure/disruption of treatment due to delayed referral were included in the meta-analysis for each panel. Result There was a statistically significant increased pooled median time of symptom onset to admission of the acute coronary syndrome (ACS) patients; an increased rate of vasospasm of aneurismal subarachnoid hemorrhage; and perforation rate in acute appendicitis; diabetic ketoacidosis presentation rate among Type 1 Diabetes Mellitus patients; and rate of orchiectomy among testicular torsion patients in comparison of pre-COVID-19 with COVID-19 cohorts; while there were no significant changes in the event rate of ruptured ectopic pregnancy and median time of symptom onset to admission in the cerebrovascular accident (CVA) patients. Conclusions COVID-19 has largely disrupted the referral of patients for emergency medical care and patient-related delayed care should be addressed as a major health threat.

Abstract Background Hydrogels based on organic/inorganic composites have been at the center of attention for the fabrication of engineered bone constructs. The establishment of a straightforward 3D microenvironment is critical to maintaining cell-to-cell interaction and cellular function, leading to appropriate regeneration. Ionic cross-linkers, Ca2+, Ba2+, and Sr2+, were used for the fabrication of Alginate-Nanohydroxyapatite-Collagen (Alg-nHA-Col) microspheres, and osteogenic properties of human osteoblasts were examined in in vitro and in vivo conditions after 21 days. Results Physicochemical properties of hydrogels illustrated that microspheres cross-linked with Sr2+ had reduced swelling, enhanced stability, and mechanical strength, as compared to the other groups. Human MG-63 osteoblasts inside Sr2+ cross-linked microspheres exhibited enhanced viability and osteogenic capacity indicated by mineralization and the increase of relevant proteins related to bone formation. PCR (Polymerase Chain Reaction) array analysis of the Wnt (Wingless-related integration site) signaling pathway revealed that Sr2+ cross-linked microspheres appropriately induced various signaling transduction pathways in human osteoblasts leading to osteogenic activity and dynamic growth. Transplantation of Sr2+ cross-linked microspheres with rat osteoblasts into cranium with critical size defect in the rat model accelerated bone formation analyzed with micro-CT and histological examination. Conclusion Sr2+ cross-linked Alg-nHA-Col hydrogel can promote functionality and dynamic growth of osteoblasts. Graphical Abstract

Abstract Background Penile duplication or diphallia is a rare congenital anomaly with unclear pathophysiological cause. Most cases of diphallia are reported postnatally; however, today with the use of a high-resolution ultrasound device, in-uterine diagnosis of many congenital anomalies is possible. Case presentation Herein we report a multiparous mother at 25 weeks of gestation who referred due to an abnormal cystic structure protruding from a large abdominal wall defect located below the umbilicus that was noted during a routine exam. Target scan revealed two penile-like protrusions with an empty scrotal sac and double bladder in an otherwise normal fetus, which was confirmed postnatally. Neonatal microarray study and karyotype were normal. Conclusion Diphallia could be detected prenatally as an isolated anomaly, associated with caudal duplication syndrome, or as an exstrophy-epispadias complex. As this is a rare congenital anomaly, all sonographers should be familiar with prenatal ultrasound features and associated anomalies, an important issue in prenatal counseling with parents, delivery planning, psychological support of the family, and postnatal management.

Abstract Background The bone tissue engineering (BTE) approach has been introduced as an alternative to conventional treatments for large non-healing bone defects. Magnetism promotes stem cells' adherence to biocompatible scaffolds toward osteoblast differentiation. Furthermore, osteogenic differentiation media are expensive and any changes in its composition affect stem cells differentiation. Moreover, media growth factors possess a short half-life resulting in the rapid loss of their functions in vivo. With the above in mind, we fabricated a multilayered nanocomposite scaffold containing the wild type of Type I collagen (Col I) with endogenous magnetic property to promote osteogenesis in rat ADSCs with the minimum requirement of osteogenic differentiation medium. Methods Fe3O4 NPs were synthesized by co-precipitation method and characterized using SEM, VSM, and FTIR. Then, a PCL/Col I nanocomposite scaffold entrapping Fe3O4 NPs was fabricated by electrospinning and characterized using SEM, TEM, AFM, VSM, Contact Angle, tensile stretching, and FTIR. ADSCs were isolated from rat adipose tissue and identified by flow cytometry. ADSCs were loaded onto PCL/Col I and PCL/Col I/Fe3O4-scaffolds for 1–3 weeks with/without osteogenic media conditions. The cell viability, cell adhesion, and osteogenic differentiation were evaluated using MTT assay, SEM, DAPI staining, ALP/ARS staining, RT-PCR, and western blotting, respectively. Results SEM, VSM, and FTIR results indicated that Fe3O4 was synthesized in nano-sized (15–30 nm) particles with spherical-shaped morphology and superparamagnetic properties with approved chemical structure as FTIR revealed. According to SEM images, the fabricated magnetic scaffolds consisted of nanofiber (500–700 nm). TEM images have shown the Fe3O4 NPs entrapped in the scaffold's fiber without bead formation. FTIR spectra analysis confirmed the maintenance of the natural structure of Col I, PCL, and Fe3O4 upon electrospinning. AFM data have shown that MNPs incorporation introduced stripe-like topography to nanofibers, while the depth of the grooves has decreased from 800 to 500 nm. Flow cytometry confirmed the phenotype of ADSCs according to their surface markers (i.e., CD29 and CD105). Additionally, Fe3O4 NP improved nanocomposite scaffold strength, wettability, porosity, biocompatibility and also facilitates the ALP activity, calcium-mineralization. Finally, magnetic nanocomposite scaffolds upregulated osteogenic-related genes or proteins’ expression (e.g., Col I, Runx2, OCN, ON, BMP2) in seeded ADSCs with/without osteo-differentiation media conditions. Conclusions Together, these results indicate that Fe3O4 NPs within the natural structure of Col I increase osteogenic differentiation in osteogenic cues-free media conditions. This effect could be translated in vivo toward bone defects healing. These findings support the use of natural ECM materials alongside magnetic particles as composite scaffolds to achieve their full therapeutic potential in BTE treatments. Graphical Abstract

Abstract Background Glycogen storage diseases (GSDs) are inherited glycogen metabolic disorders which have various subtypes. GSDs of type I, III, IV, VI, and IX show liver involvement and are considered as hepatic types of GSDs. Thus, liver transplantation (LT) has been proposed as a final therapy for these types of GSD. LT corrects the primary hepatic enzyme defect; however, the long-term outcomes of LT in these patients have not been extensively evaluated so far. There are few reports in the English literature about the outcome of GSD patients after LT. There has been no report from Iran. The present retrospective study aimed to evaluate the long-term outcomes of eight patients with GSD types I, III, and IV who underwent LT in the affiliated hospitals of Shiraz University of Medical Sciences, from March 2013 to June 2021. During this period, there were no patients with GSD VI and IX identified in this center. Results The median time of diagnosis of the GSDs and at transplant was 1 year and 11 years, respectively. All eight transplanted patients were alive at the time of follow-up in this study. None of them required a re-transplant. All of the patients showed normalized liver enzymes after LT with no sign of hypoglycemia. Conclusions LT is an achievable treatment for end-stage hepatic involvement of GSDs with a cure for metabolic deficiency. Our experience in these eight patients shows a favorable outcome with no mortality and no major complication.

Abstract Background Data on childhood disability is essential for planning health, education and other services. However, information is lacking in many low- and middle-income countries, including Niger. This study uses the Key Informant Method, an innovative and cost-effective strategy for generating population-based estimates of childhood disability, to estimate the prevalence and causes of moderate/severe impairments and disabling health conditions in children of school-going age (7–16 years) in the Kollo department of western Niger. Methods Community-based key informants were trained to identify children who were suspected of having the impairment types/health conditions included in this study. Children identified by key informants were visited by paediatricians and underwent an assessment for moderate/severe vision, hearing, physical and intellectual impairments, as well as epilepsy, albinism and emotional distress. Results Two thousand, five hundred sixty-one children were identified by key informants, of whom 2191 were visited by paediatricians (response rate = 85.6%). Overall, 597 children were determined to have an impairment/health condition, giving a prevalence of disability of 11.4 per 1000 children (10.6- 12.2). Intellectual impairment was most common (6.5 per 1000), followed by physical (4.9 per 1000) and hearing impairments (4.7 per 1000). Many children had never sought medical attention for their impairment/health condition, with health seeking ranging from 40.0% of children with visual impairment to 67.2% for children with physical impairments. Conclusion The Key Informant Method enabled the identification of a large number of children with disabling impairments and health conditions in rural Niger, many of whom have unmet needs for health and other services.

Abstract Background Undifferentiated embryonal sarcoma of the liver (UESL) is a rare liver tumor accounting for 6–13% of primary liver tumors. Accurate preoperative diagnosis is difficult, with a rather high misdiagnosis rate. Herein, we reported a very large UESL treated with anatomical resection. Our case is amongst the largest pediatric UESLs in the literature. Case presentation Herein, we report a 13-year-old girl presenting with right upper quadrant abdominal pain, postprandial vomiting, and abdominal distention, in which radiographic imaging demonstrated a huge UESL (28 × 20 × 12 cm). The patient was treated with partial hepatectomy and the 5 kg tumor was removed. The patient was discharged in good condition, with no significant complaints in her follow-up. Conclusions Although different treatment strategies have been reported for UESL cases, anatomical resection is still the main treatment approach, especially for large tumors.

Abstract Background Early detection and appropriate treatment of precancerous, mucosal changes could significantly decrease the prevalence of life-threatening gastric cancer. Biopsy of the normal-appearing mucosa to detect Helicobacter pylori and these conditions is not routinely obtained. This study assesses the prevalence and characteristics of H. pylori infection and precancerous conditions in a group of patients suffering from chronic dyspepsia who were subjected to gastric endoscopy and biopsy mapping. Methods This cross-sectional study included dyspeptic patients, not previously treated for H. pylori, undergoing esophagogastroduodenoscopy (EGD) with their gastric endoscopic biopsies obtained for examination for evidence of H. pylori infection and precancerous conditions. Demographic and clinical data on the gender, smoking, opium addiction, alcohol consumption, medication with aspirin, corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) and family history of cancer were collected by interviewing the patients and evaluating their health records. The cohort examined consisted of 585 patients with a mean (SD) age of 48.0 (14.46) years, 397 (67.9%) of whom were women. Results H. pylori infection was identified in 469 patients (80.2%) with the highest prevalence (84.2%) in those aged 40–60 years. Opium addiction correlated with a higher a H. pylori infection rate, while alcohol consumption was associated with a lower rate by Odds Ratio 1.98 (95% CI 1.11–3.52) and 0.49 (95% CI 0.26–0.92), respectively. The prevalence of intestinal metaplasia, gastric atrophy and gastric dysplasia was 15.2, 12.6 and 7.9%, respectively. Increased age, positive H. pylori infection, endoscopic abnormal findings and opium addiction showed a statistically significant association with all precancerous conditions, while NSAID consumption was negatively associated with precancerous conditions. For 121 patients (20.7% of all), the EGD examination revealed normal gastric mucosa, however, for more than half (68/121, 56.2%) of these patients, the histological evaluation showed H. pylori infection, and also signs of atrophic mucosa, intestinal metaplasia and dysplasia in 1.7, 4.1 and 1.7%, respectively. Conclusion EGD with gastric biopsy mapping should be performed even in the presence of normal-appearing mucosa, especially in dyspeptic patients older than 40 years with opium addiction in north-eastern Iran. Owing to the high prevalence of precancerous conditions and H. pylori infection among patients with dyspepsia in parts of Iran, large-scale national screening in this country should be beneficial.

Abstract Objective We aimed to detect the effect of a couple of parameters including Alg, H2O2, and HRP concentrations on the gelation time of Alg-based hydrogels using an enzymatic cross-linked procedure. Results NMR, UV–Vis, and ATR-FTIR analyses confirmed the conjugation of Ph to the Alg backbone. Data showed gelation time was delayed with the increase and reduction of H2O2 and HRP, respectively. We noted that hydrogel consisted of 1.2% (w/v) Alg, 5 U HRP, and 100 mM H2O2 yielded an appropriate gelation time with appropriate mechanical properties. The addition of 0.5% (v/v) Col developed hydrogel increased the gelation time. The data showed that Alg, HRP, and H2O2 with the ratio of 1:0.54:0.54 had proper physicochemical features for cartilage engineering.

Abstract Introduction The relationship between H. pylori infection and obesity development has remained controversial among various studies. The aim of this study was to clarify the pooled effect of H. pylori infection on the development of obesity and vice versa. Methods We searched international databases including Medline (PubMed), Web of sciences, Scopus, EMBASE, Cochrane, Ovid, and CINHAL to retrieve all case–control studies reporting the effect of H. pylori on obesity and vice versa, which had been published in English between January 1990 and June 2019. The quality of included studies was assessed by the Modified Newcastle–Ottawa Scale for Case–Control studies. The logarithm of the odds ratio (OR) and its standard error was used for the meta-analysis. Results Eight case–control studies with 25,519 participants were included for qualitative and quantitative analyses. The pooled analysis showed that obese participants had a higher risk of H. pylori infection than lean participants with an odds ratio of 1.46 (95%CI: 1.26, 1.68). Also, the pooled analysis revealed that participants infected by H. pylori had a higher risk of obesity than non-infected participants with an odds ratio of 1.01 (95%CI: 1.01, 1.02). Conclusion The results of this meta-analysis showed that there was a positive correlation between the risk of H. pylori infection and the prevalence of obesity development. Thus, H. pylori positive patients were more likely to be obese, and obese individuals had higher risks of H. pylori infection.

Abstract Background Undifferentiated embryonal sarcoma of liver (UESL) and hepatic mesenchymal hamartoma (HMH) are two rare entities which mainly affect the pediatric population. The aim of this investigation was to provide a comprehensive overview of the clinicopathologic characteristics of the patients diagnosed with these two conditions in a tertiary referral center in Iran. Methods In this retrospective study patients diagnosed with UESL or HMH between 2012 and 2020 were studied. A comprehensive histopathologic evaluation of the cases along with immunohistochemistry evaluation using a panel of antibodies was conducted. Furthermore, clinical, paraclinical, and treatment data and follow up information was collected. Results A total of 16 patients (8 UESL, 8 HMH) were studied in this investigation. Patients with UESL had a significantly (p = 0.002) higher age at diagnosis compared with those with HMH. Histologically, UESL cases were characterized by anaplastic cells with eosinophilic cytoplasm and bizarre nuclei and frequent atypical mitosis and spindling in a myxoid stroma while disordered arrangement of hepatic parenchyma, bile ducts, and primitive mesenchyme was seen in HMH. Furthermore, small round cells and extramedullary hematopoiesis were seen in 2 UESL and 3 HMH cases, respectively. Concurrent HMH was also seen in two UESL cases. Immunohistochemistry panel showed positive staining for Vimentin, Glypican-3, Desmin, CD56, CD10, and BCL2 in UESL cases and immunoreactivity for Vimentin, HepPar 1, Glypican-3, SMA, CD56, BCL2, and CD34 in various components of HMH. Conclusions In this study, the clinicopathologic features of UESL and HMH cases are presented. We also evaluated the utility of an immunohistochemistry panel in the diagnosis of these two rare entities and suggested novel markers. Our study corroborated the findings of previous investigations and expanded the clinicopathologic features of these two rare entities with diagnostic and potential therapeutic implications.

Abstract Objectives To evaluate gadoxetic acid-enhanced liver MRI (EOB-MRI) versus contrast-enhanced computed tomography (CECT) for preoperative detection of liver metastasis (LM) and reduction of open-close laparotomies for pancreatic ductal adenocarcinoma (PDAC). Methods Sixty-six patients with PDAC had undergone preoperative EOB-MRI and CECT. LM detection by EOB-MRI and CECT and their impact on surgical planning, open-close laparotomies were compared by clinical and radiology reports and retrospective analysis of imaging by two blinded independent readers. Histopathology or imaging follow-up was the reference standard. Statistical analysis was performed at patient and lesion levels with two-sided McNemar tests. Results EOB-MRI showed higher sensitivity versus CECT (71.7% [62.1-80.0] vs. 34% [25.0-43.8]; p = 0.009), comparable specificity (98.6%, [96.9-99.5] vs. 100%, [99.1-100], and higher AUROC (85.1%, [80.4-89.9] vs. 66.9%, [60.9-73.1]) for LM detection. An incremental 7.6% of patients were excluded from surgery with a potential reduction of up to 13.6% in futile open-close laparotomies due to LM detected on EOB-MRI only. Conclusions Preoperative EOB-MRI has superior diagnostic performance in detecting LM from PDAC. This better informs surgical eligibility with potential reduction of futile open-close laparotomies from attempted curative intent pancreatic cancer surgery.