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Abstract Background Despite routine echocardiographic surveillance for childhood cancer survivors, the ability to predict cardiomyopathy risk in individual patients is limited. We explored the feasibility and optimal processes for machine learning-enhanced cardiomyopathy prediction in survivors using serial echocardiograms from five centers. Methods We designed a series of deep convolutional neural networks (DCNNs) for prediction of cardiomyopathy (shortening fraction ≤ 28% or ejection fraction ≤ 50% on two occasions) for at-risk survivors ≥ 1-year post initial cancer therapy. We built DCNNs with four subsets of echocardiographic data differing in timing relative to case (survivor who developed cardiomyopathy) index diagnosis and two input formats (montages) with differing image selections. We used holdout subsets in a 10-fold cross-validation framework and standard metrics to assess model performance (e.g., F1-score, area under the precision-recall curve [AUPRC]). Performance of the input formats was compared using a combined 5 × 2 cross-validation F-test. Results The dataset included 542 pairs of montages: 171 montage pairs from 45 cases at time of cardiomyopathy diagnosis or pre-diagnosis and 371 pairs from 70 at-risk survivors who didn’t develop cardiomyopathy during follow-up (non-case). The DCNN trained to distinguish between non-case and time of cardiomyopathy diagnosis or pre-diagnosis case montages achieved an AUROC of 0.89 ± 0.02, AUPRC 0.83 ± 0.03, and F1-score: 0.76 ± 0.04. When limited to smaller subsets of case data (e.g., ≥ 1 or 2 years pre-diagnosis), performance worsened. Model input format did not impact performance accuracy across models. Conclusions This methodology is a promising first step toward development of a DCNN capable of accurately differentiating pre-diagnosis versus non-case echocardiograms to predict survivors more likely to develop cardiomyopathy. Graphical Abstract

Abstract Prostate-Specific Antigen (PSA) based screening of prostate cancer (PCa) needs refinement. The aim of this study was the identification of urinary biomarkers to predict the Prostate Imaging—Reporting and Data System (PI-RADS) score and the presence of PCa prior to prostate biopsy. Urine samples from patients with elevated PSA were collected prior to prostate biopsy (cohort = 99). The re-analysis of mass spectrometry data from 45 samples was performed to identify urinary biomarkers to predict the PI-RADS score and the presence of PCa. The most promising candidates, i.e. SPARC-like protein 1 (SPARCL1), Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), Alpha-1-microglobulin/bikunin precursor (AMBP), keratin 13 (KRT13), cluster of differentiation 99 (CD99) and hornerin (HRNR), were quantified by ELISA and validated in an independent cohort of 54 samples. Various biomarker combinations showed the ability to predict the PI-RADS score (AUC = 0.79). In combination with the PI-RADS score, the biomarkers improve the detection of prostate carcinoma-free men (AUC = 0.89) and of those with clinically significant PCa (AUC = 0.93). We have uncovered the potential of urinary biomarkers for a test that allows a more stringent prioritization of mpMRI use and improves the decision criteria for prostate biopsy, minimizing patient burden by decreasing the number of unnecessary prostate biopsies.

This study examined the effects of three task conditions on young EFL learners’ oral performance of a picture prompted task and their grammatical knowledge gain. To this end, 34 EFL learners were randomly assigned into three experimental groups, namely online planning, pre-planning, and explicit instruction, and one control group. Pictures were employed as prompts to implement the tasks in all groups. A Grammatical Judgment Test was used to compare students’ knowledge of simple present passive structure before and after the treatment. Learners’ oral task performance was measured in terms of Complexity, Accuracy, and Fluency (CAF). The findings demonstrated significant differences among groups as for CAF measures. However, no significant differences were spotted in GJT posttest scores. The paper calls for the incorporation of diverse prompt-based planning conditions in task-oriented teaching practices in order to target learners' higher levels of oral competence.

Dilated cardiomyopathy (DCM) is a disorder of cardiac ventricular dilation and contractile dysfunction that often progresses to heart failure. Multiple genes have been associated with DCM, including SCN5A which has been linked to 2 % of all DCM cases. Peripheral mononuclear blood cells from DCM patients with SCN5A variants (c.2440C>T and c.665G>A) were utilized to generate two human induced pluripotent stem cell (iPSC) lines. Both lines exhibited typical iPSC morphology, expressed pluripotency markers, normal karyotypes, and trilineage differentiation capabilities. These lines offer valuable resources for investigating the mechanism of SCN5A-associated DCM, facilitating studies of ion channel protein involvement in the disease.

Vascular Ehlers-Danlos Syndrome (vEDS) is an inherited connective tissue disorder caused by COL3A1 gene, mutations that encodes type III collagen, a crucial component of blood vessels. vEDS can be life-threatening as these patients can have severe internal bleeding due to arterial rupture. Here, we generated induced pluripotent stem cell (iPSC) lines from two vEDS patients carrying a missense mutation in the COL3A1 (c.226A > G, p.Asn76Asp) gene. These lines exhibited typical iPSC characteristics including morphology, expression of pluripotency markers, and could differentiate to all three germ layer. These iPSC lines can serve as valuable tools for elucidating the pathophysiology underlying vEDS.

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by anti-nuclear autoantibodies whose production is promoted by autoreactive T follicular helper (TFH) cells. During SLE pathogenesis, basophils accumulate in secondary lymphoid organs (SLO), amplify autoantibody production and disease progression through mechanisms that remain to be defined. Here, we provide evidence for a direct functional relationship between TFH cells and basophils during lupus pathogenesis, both in humans and mice. PD-L1 upregulation on basophils and IL-4 production are associated with TFH and TFH2 cell expansions and with disease activity. Pathogenic TFH cell accumulation, maintenance, and function in SLO were dependent on PD-L1 and IL-4 in basophils, which induced a transcriptional program allowing TFH2 cell differentiation and function. Our study establishes a direct mechanistic link between basophils and TFH cells in SLE that promotes autoantibody production and lupus nephritis.

Abstract Background Transversus abdominis plane block (TAPB) guided by laparoscopy and ultrasound showed promise in enhancing the multimodal analgesic approach following several abdominal procedures. This study aimed to compare the efficacy and safety between Laparoscopic (LAP) TAP block (LTAP) and ultrasound-guided TAP block (UTAP) block in patients undergoing LAP bariatric surgery. Patients and methods This non-inferiority randomized controlled single-blind study was conducted on 120 patients with obesity scheduled for LAP bariatric surgeries. Patients were allocated into two equal groups: LTAP and UTAP, administered with 20 mL of 0.25% bupivacaine on each side. Results There was no statistically significant difference in the total morphine consumption, Visual Analogue Scale (VAS) score at all times of measurements, and time to the first rescue analgesia (p > .05) between both groups. The duration of anesthesia and duration of block performance were significantly shorter in the LTAP group than in the UTAP group (p

The aim of the study was to assess the role of diffusion-weighted imaging (DWI) to evaluate treatment response in patients with liver metastases of colorectal cancer.

Background: Infection is one of the most common complications of cancer and cancer treatment. Most patients admitted for fever or infection come through the Emergency Department (ED), which is a primary site for blood culture collection. Contamination of blood cultures complicates the diagnoses, compromises quality of care, leads to unnecessary antibiotic exposure and increases financial burdens. It may also lead to unnecessary removal of central venous access devices or delay of critical therapy or procedures. At our institution, the contamination rate of blood cultures drawn in the ED was over twice that of the remainder of the hospital (2.8 versus 0.8), prompting this quality improvement project. Unlike on hospital floors, nurses, instead of phlebotomists, draw most blood cultures due to the urgency of managing suspected sepsis. Our aim was to decrease the ED contamination rate by 20 percent after the first PDSA cycle, and ultimately bring it on par with the remainder of the hospital. Methods: First, we compared ED contamination rates versus other hospital inpatient floors and outpatient centers over a three-month period. We then evaluated the contamination rates of ED nurses versus ED phlebotomists and peripheral versus central line blood draws. Process mapping and fishbone analysis helped identify practices contributing to higher contamination rates. Key drivers of these practices were diagrammed, and potential interventions were ranked on a prioritization matrix. Results: We identified use of alcohol rather than chlorhexidine swabs for peripheral disinfection and inconsistent techniques of blood draw by nurses as critical contributors to increased contamination rates in the ED. Our intervention was creating premade blood culture kits promoting the use of chlorhexidine swabs through availability and easy access in the fast-paced ED environment. Ten cubic centimeter (cc) syringes in the kits encouraged withdrawal of adequate blood samples in compliance with the 7-10 cc guideline. Designated nursing team leaders checked off ED nurses at the bedside, implementing education and adherence in using the blood culture collection kits. The average number of blood cultures in the emergency department was 1,400. A reduction in blood culture contamination from 2.46 percent to 1.89 percent was seen after two months. Conclusions: A guideline-driven, standardized blood culture collection process followed by ED nurses is vital to reducing blood culture contamination. Chlorhexidine is necessary to maintain the lowest contamination rates. Readily available premade blood culture kits improve compliance with materials and techniques associated with best practices.

Abstract Measuring the temperature changes of the deep ocean will be critical to understanding how the earth system will respond to climate change. In this work, we present a method for measuring the depth‐averaged, deep ocean temperature at local (∼3 km) spatial scales using passive estimates of acoustic propagation. These passive acoustic estimates of deep ocean temperature can be used with existing and future passive acoustic monitoring infrastructure to provide complimentary observations of the ocean to in situ measurements, and could be particularly useful in areas of poor ocean observation coverage. Using 8 years of ambient sound data, we demonstrate that the passive estimates agree with global ocean models and measurements by ARGO floats. The rms difference between the HYCOM ocean model is shown to be 0.13°C, and the rms difference between ARGO measurements is shown to be 0.086°C.

Let K = Q(α) be a number field, where α satisfies the monic irreducible polynomial F (x) = x5 + ax + b belonging to Z[x]. The purpose of this paper is to caracterise when a prime p is a common index divisor of K. More precisely, we give explicitly a necessary and sufficient conditions, on a and b for which K is not monogenic. Some useful examples are also given.

Abstract Introduction Extended pelvic lymph node dissection (ePLND) in men undergoing robot-assisted laparoscopic radical prostatectomy (RARP) is a widely used procedure. However, little is known about anatomical site-specific yields and subsequent metastatic patterns in these patients. Patients and methods Data on a consecutive series of 1107 patients undergoing RARP at our centre between 2004 and 2018 were analysed. In men undergoing LN dissection, the internal, external and obturator nodes were removed and sent in separately. We performed an analysis of LN yields in total and for each anatomical zone, patterns of LN metastases and complications. Oncological outcome in pN+ disease was assessed including postoperative PSA persistence and survival. Results A total of 823 ePLNDs were performed in the investigated cohort resulting in 98 men being diagnosed as pN+ (8.9%). The median (IQR) LN yield was 19 (14–25), 10 (7–13) on the right and 9 (6–12) on the left side (P

Abstract Rheumatoid arthritis (RA) is an autoimmune disease involving T and B lymphocytes. Autoantibodies contribute to joint deterioration and worsening symptoms. Adenosine deaminase (ADA), an enzyme in purine metabolism, influences adenosine levels and joint inflammation. Inhibiting ADA could impact RA progression. Intracellular ATP breakdown generates adenosine, which increases in hypoxic and inflammatory conditions. Lymphocytes with ADA play a role in RA. Inhibiting lymphocytic ADA activity has an immune-regulatory effect. Synovial fluid levels of ADA are closely associated with the disease’s systemic activity, making it a useful parameter for evaluating joint inflammation. Flavonoids, such as quercetin (QUE), are natural substances that can inhibit ADA activity. QUE demonstrates immune-regulatory effects and restores T-cell homeostasis, making it a promising candidate for RA therapy. In this review, we will explore the impact of QUE in suppressing ADA and reducing produced the inflammation in RA, including preclinical investigations and clinical trials. Graphical Abstract

Machine learning techniques are extensively used to understand and predict complex non-linear phenomena across various applications. Moreover, these techniques minimize the time and costs associated with experimental and numerical analysis. In this work, a deep learning technique, specifically artificial neural networks (ANN), was employed to predict the density/porosity of laser powder-bed fusion (LPBF) additively manufactured (AM) parts by training the ANN model with X-ray computed tomography (CT) images. In addition to the experimental data, synthetic CT data was generated and used to improve the performance of the ANN model. The ANN model was then optimized for the number of hidden layers and neurons. Different errors like mean absolute error (MAE), root mean square error (RMSE), and square of co-relation coefficient (R2) were used as performance metrics to determine the accuracy and effectiveness of the network. The proposed ANN model was validated and showed excellent predictions (R2 = 0.9981, MAE = 1.6944 x 10−5). The framework proposed in this work can be used to speed-up the quality assurance of AM parts by reducing the time required for the analysis of CT data.

Abstract Relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) outcomes remain poor. A targeted cluster of differentiation (CD)33 × CD3 bispecific antibody, JNJ‐67571244, was assessed to identify the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety and tolerability, and preliminary clinical activity in patients with r/rAML or r/rMDS. This first‐in‐human, open‐label, phase I, dose‐escalation/dose‐expansion study included patients with r/rAML or r/rMDS who were ineligible for or had exhausted standard therapeutic options. JNJ‐67571244 was administered intravenously or subcutaneously using step‐up dosing until ≥1 discontinuation condition was met. Outcomes included safety/tolerability, preliminary clinical activity, and systemic pharmacokinetics and pharmacodynamics. The study was terminated after evaluating 10 dose‐escalation cohorts (n = 68) and before starting dose‐expansion. Overall, 11 (16.2%) patients experienced ≥1 dose‐limiting toxicity; all experienced ≥1 treatment‐emergent adverse event (TEAE; treatment related: 60 [88.2%]); and 64 (94.1%) experienced ≥1 TEAE of Grade ≥3 toxicity (treatment related: 28 [41.2%]). Although some patients had temporary disease burden reductions, no responses were seen. JNJ‐67571244 administration increased multiple cytokines, which coincided with incidence of cytokine release syndrome, infusion‐related reactions, and elevated liver function tests. A prolonged step‐up strategy was tested to improve tolerability, though this approach did not prevent hepatotoxicity. T‐cell activation following treatment suggested target engagement but did not correlate with clinical activity. Safely reaching the projected exposure level for JNJ‐67571244 efficacy was not achieved, thus MTD and RP2D were not determined.

Arterial calcification due to deficiency of CD73 (ACDC) is an adult onset, rare genetic vascular disorder signified by calcium deposition in lower extremity arteries and joints of hands and feet. Mutations in NT5E gene has been shown to be responsible for the inactivation of enzyme CD73 causing calcium buildup. Here, we report a iPSC line generated from a patient showing signs of ACDC and carrying a missense mutation in NT5E (c.1126A→G,p.T376A) gene. This iPSC line shows normal morphology, pluripotency, karyotype, and capability to differentiate into three germ layers, making it useful for disease modeling and investigating pathological mechanisms of ACDC.

Introduction: Cadmium (Cd) is a harmful heavy metal that results in many toxic issues. Urtica pilulifera showed potential pharmaceutical applications. This study investigated the possible ameliorative mechanism of Urtica pilulifera leaves extract (UPLE) against hepatotoxicity induced by cadmium chloride (CdCl2) in mice.Methods:In vitro phytochemical screening and the metal-chelating activity of UPLE were ascertained. Four groups of forty male mice were used (n = 10) as follows; Group 1 (G1) was a negative control. G2 was injected i.p., with UPLE (100 mg/kg b. wt) daily. G3 was injected i.p., with Cd (5 mg/kg b. wt) daily. G4 was injected with Cd as in G3 and with UPLE as in G2. On day 11, the body weight changes were evaluated, blood, and serum samples were collected for hematological and biochemical assessments. Liver tissues were used for biochemical, molecular, and histopathological investigations.Results: The results showed that UPLE contains promising secondary metabolites that considerably lessen the negative effects of Cd on liver. Furthermore, UPLE inhibited oxidative stress and inflammation; restored antioxidant molecules; and promoted nuclear-related factor-2 (Nrf-2) expression. Also, UPLE improved the histopathological alterations induced by Cd.Discussion: This study explored the beneficial role of UPLE treatment in Cd-induced liver injury through enhancing Nrf-2 signaling and antioxidant enzyme gene expression in the liver of mice. Therefore, UPLE could have valuable implications against hepatotoxicity induced by environmental cadmium exposure. Which can be used as a chelating agent against Cd.

ObjectivesTo develop a novel biopsy prostate cancer (PCa) prevention calculator (BioPrev-C) using data from a prospective cohort all undergoing mpMRI targeted and transperineal template saturation biopsy.Materials and methodsData of all men who underwent prostate biopsy in our academic tertiary care center between 11/2016 and 10/2019 was prospectively collected. We developed a clinical prediction model for the detection of high-grade PCa (Gleason score ≥7) based on a multivariable logistic regression model incorporating age, PSA, prostate volume, digital rectal examination, family history, previous negative biopsy, 5-alpha-reductase inhibitor use and MRI PI-RADS score. BioPrev-C performance was externally validated in another prospective Swiss cohort and compared with two other PCa risk-calculators (SWOP-RC and PBCG-RC).ResultsOf 391 men in the development cohort, 157 (40.2%) were diagnosed with high-grade PCa. Validation of the BioPrev C revealed good discrimination with an area under the curve for high-grade PCa of 0.88 (95% Confidence Interval 0.82-0.93), which was higher compared to the other two risk calculators (0.71 for PBCG and 0.84 for SWOP). The BioPrev-C revealed good calibration in the low-risk range (0 - 0.25) and moderate overestimation in the intermediate risk range (0.25 - 0.75). The PBCG-RC showed good calibration and the SWOP-RC constant underestimation of high-grade PCa over the whole prediction range. Decision curve analyses revealed a clinical net benefit for the BioPrev-C at a clinical meaningful threshold probability range (≥4%), whereas PBCG and SWOP calculators only showed clinical net benefit above a 30% threshold probability.ConclusionBiopPrev-C is a novel contemporary risk calculator for the prediction of high-grade PCa. External validation of the BioPrev-C revealed relevant clinical benefit, which was superior compared to other well-known risk calculators. The BioPrev-C has the potential to significantly and safely reduce the number of men who should undergo a prostate biopsy.

Hereditary transthyretin amyloidosis with polyneuropathy (ATTR-PN) results from specific TTR gene mutations. In this study, we generated two induced pluripotent stem cell (iPSC) lines derived from ATTR-PN patients with heterozygous TTR gene mutations (Ala97Ser and Phe64Leu). These iPSC lines exhibited normal morphology, karyotype, high pluripotency marker expression, and differentiation into cells representing all germ layers. The generation of these iPSC lines serve as a valuable tool for investigating the mechanisms of ATTR-PN across various cell types and facilitating patient-specific in vitro amyloidosis modeling.

Lead (Pb) is a common pollutant that is not biodegradable and gravely endangers the environment and human health. Annona squamosa fruit has a wide range of medicinal uses owing to its phytochemical constituents. This study evaluated the effect of treatment with A. squamosa fruit extract (ASFE) on testicular toxicity induced in male rats by lead acetate. The metal-chelating capacity and phytochemical composition of ASFE were determined. The LD50 of ASFE was evaluated by probit analysis. Molecular docking simulations were performed using Auto Dock Vina. Forty male Sprague Dawley rats were equally divided into the following groups: Gp1, a negative control group; Gp2, given ASFE (350 mg/kg body weight (b. wt.)) (1/10 of LD50); Gp3, given lead acetate (PbAc) solution (100 mg/kg b. wt.); and Gp4, given PbAc as in Gp3 and ASFE as in Gp2. All treatments were given by oro-gastric intubation daily for 30 days. Body weight changes, spermatological parameters, reproductive hormone levels, oxidative stress parameters, and inflammatory biomarkers were evaluated, and molecular and histopathological investigations were performed. The results showed that ASFE had promising metal-chelating activity and phytochemical composition. The LD50 of ASFE was 3500 mg/kg b. wt. The docking analysis showed that quercetin demonstrated a high binding affinity for JAK-1 and STAT-3 proteins, and this could make it a more promising candidate for targeting the JAK-1/STAT-3 pathway than others. The rats given lead acetate had defective testicular tissues, with altered molecular, biochemical, and histological features, as well as impaired spermatological characteristics. Treatment with ASFE led to a significant mitigation of these dysfunctions and modulated the JAK-1/STAT-3/SOCS-1 axis in the rats.

Abstract Background Maxillary sinus septa increase perforation risk of Schneiderian membrane during the sinus floor elevation (SFE). Cone Beam Computed Tomography (CBCT) allows for a more precise assessment of the septal position; thus, preoperative CBCT analysis is substantial to avoid possible complications. This study aims to investigate the 3D characteristics of the maxillary sinus septa based on CBCT images. To our knowledge, no study reported the CBCT-based investigation for the sinus septa among Yemeni population. Materials and methods This is a retrospective cross-sectional analysis of 880 sinus CBCT images 440 patients. The septa prevalence, locations, orientations, morphology, and associated factors were analyzed. The effect of age, gender, and dental status on the sinus septa and the relationship between sinus membrane pathology and sinus septa were also analyzed. Anatomage (Invivo version 6) was used for CBCT images analysis. Descriptive and analytical statistics were performed, and a P-value

Introduction: Twins conjoined at the sacrum present a complex anatomy that requires the highest levels of medical and surgical care. We present the successful management and separation of pygopagus babies in a tertiary care center. Case presentation: The conjoined female twins were diagnosed by routine prenatal ultrasonography (US) and magnetic resonance (MR) imaging and were delivered uneventfully at 37 weeks of gestation. Postnatal imaging included US of the brain and urinary system, contrast enema, intravenous (IV) contrast-enhanced computed tomography (CT), and MR of the pelvis, which confirmed the sacral and pelvic-perineal organ fusion as well as brain abnormalities in twin B. For the separation, appropriate allocation of the intrapelvic muscles was guided by preoperative and intraoperative sphincter muscle mapping. Baby A received a repaired sphincter with a natural anus, while a functional neo-anus was created for the other baby. Mild superficial wound dehiscence occurred in both twins, which resolved conservatively in twin B and by temporary colostomy diversion in twin A A. Twin B underwent placement of a gastrostomy and a tracheostomy and remains hospitalized. Conclusion: Careful preoperative planning can lead to the successful separation of pygopagus conjoined twins, even in places with limited resources.

Abstract Environmental contamination by phenol has been reported in both aquatic and atmospheric environments. This study aimed to separate and purify the peroxidase enzyme from bacteria that degrade phenol from wastewater sources. An enrichment culture of MSM was used to screen 25 bacterial isolates from different water samples for peroxidase production, six of the isolates exhibited high levels of peroxidase enzyme activity. Qualitative analysis of peroxidase revealed that isolate No. 4 had the highest halo zones (Poly-R478: 14.79 ± 0.78 mm, Azure B: 8.81 ± 0.61 mm). The promising isolate was identified as Bacillus aryabhattai B8W22 by 16S rRNA gene sequencing with accession number OP458197. As carbon and nitrogen sources, mannitol and sodium nitrate were utilized to achieve maximum peroxidase production. A 30-h incubation period was used with pH 6.0, 30 °C, mannitol, and sodium nitrate, respectively, for maximal production of peroxidase. Purified peroxidase enzyme showed 0.012 U/mg specific activity, and SDS-PAGE analysis indicated a molecular weight of 66 kDa. The purified enzyme exhibits maximum activity and thermal stability at pH values of 4.0 and 8.0, respectively, with maximum activity at 30 °C and complete thermal stability at 40 °C. In the purified enzyme, the Km value was 6.942 mg/ml and the Vmax value was 4.132 mol/ml/hr, respectively. The results demonstrated that Bacillus aryabhattai B8W22 has promising potential for degrading phenols from various phenol-polluted wastewater sources.

With the change in the social role of horses and the development of veterinary medicine, their average life expectancy has increased, so the problem of the quality of life of geriatric horses has become relevant nowadays. The purpose of the study is to determine the main approaches to the assessment of the quality of life of horses in old age. The study employed the following methods: analysis, synthesis, comparison, graphical presentation of data. Five main ways to improve life expectancy and QoL indicators and reduce mortality of old horses were determined: full and sufficient feeding; ensuring optimal ADL performance; creation of comfortable housing conditions; conducting cryotherapy maintenance vibrotherapy, manual therapy, horseshoe therapy, therapeutic and preventive exercises, magnetotherapy, phototherapy, shock wave and ultrasound therapy; use of modern methods of early detection and treatment of oncological diseases. It was found that the most common causes of death were diseases of the gastrointestinal tract, followed by diseases of the musculoskeletal system and reproductive system, and oncological diseases. Among the latter, tumours of the pituitary and thyroid glands, melanoma, sarcoidosis, lymphoma, squamous cell carcinoma (SCC) prevailed – up to 60% of oncological sick horses. It was summarised that quality of life assessments, including evaluation of factors related to health, activities of daily living and mental well-being, are useful in informing decisions regarding management, health care and euthanasia. The results of this study can be used by equestrian professionals, farmers or veterinarians to help them choose the safest and most beneficial care for horses

Specific mutations in the TTR gene are responsible for the development of variant (hereditary) ATTR amyloidosis. Here, we generated two human induced pluripotent stem cell (iPSC) lines from patients diagnosed with Transthyretin Cardiac Amyloidosis (ATTR-CM) carrying heterozygous mutation in the TTR gene (i.e., p.Val30Met). The patient-derived iPSC lines showed expression of high levels of pluripotency markers, trilineage differentiation capacity, and normal karyotype. The generation of these iPSC lines represents a great tool for modeling patient-specific amyloidosis in vitro, allowing the investigation of the pathological mechanisms related to the disease in different cell types and tissues.

PURPOSE: Prostate-specific antigen (PSA) screening for men at risk of prostate cancer is controversial. The current recommendation is to raise awareness of prostate cancer and offer PSA screening in accordance with shared decision- making. Whether the possibility of a PSA screen is discussed with the patient depends on the treating physician, but data on physicians’ attitudes towards PSA screening are scarce. This study aimed to examine internists’ and urologists’ personal PSA screening activity as an indicator of their attitude towards PSA screening. MATERIALS AND METHODS: Members of the Swiss Society of Urology and the Swiss Society of General Internal Medicine were asked in 08/2020 to anonymously complete an online survey about personal PSA screening behaviour for themselves, their fathers, brothers and partners. Categorical and continuous variables were compared by chi-squared tests and t-tests, respectively. RESULTS: In total, 190/295 (response rate: 64%) urologists and 893/7400 (response rate: 12%) internists participated in the survey. Of the participants, 297/1083 (27.4%) were female. Male urologists >50 years of age screened themselves more often than male internists >50 years of age (89% vs 70%, p 50 years of age have screened themselves for prostate cancer. Furthermore, PSA screening of relatives was significantly associated with the urology specialty. The reasons physicians screen themselves substantially more often than the public and why male and female urologists as well as male internists perform PSA screening more frequently in their private environment than female internists should be further examined.

One of the most important common issues between criminal jurisprudence and Iranian penal law is the issue of blood money. Determining the amount of blood money and Arsh through forensic expertise in the field of the type and amount of crimes and their effects is one of the basic issues related to blood money law.Therefore, relying on advances in medical sciences and technology as a bridge, forensic medicine connects experts and judges in the field of criminology and truth discovery in order to achieve the rights and administrate the justice, and thus be effective in the work of the judiciary and How-ness of judgment and sentencing. However, in this way, we dealt with the challenging issues between law and forensic medicine based on jurisprudential documents and with emphasis on the expertise of forensic physicians, which is influenced by the advances of medical sciences and technology and cultural and social developments in society.The present study, using a descriptive-analytical method to investigate and analyze these challenging cases in three fields of fractures and bone injuries, beauty, injuries and limb injuries, at first, examined the relationship among forensic medicine, law and jurisprudence and then, introduced and analyzed some examples of challenges of determining of the amount of blood money and Arsh. Finally, reviewing the laws of blood money as well as updating the jurisprudential rules based on the requirements of time in order to solve the existing challenges revealed themselves of great necessity

Abstract Background Morocco is considered one of the main biodiversity hotspots in the Mediterranean region and contains various plant species including wild and domestic Rosa. This genus is the most important among cultivated ornamental plants in the world, with a high economic value in cosmetics, pharmaceutical industries, and floriculture. In the present study, genetic diversity among the collected accessions of wild Rosa species in Morocco was assessed using Inter-Simple Sequence Repeat (ISSR) and Directed Amplification of Minisatellites DNA (DAMD) markers. Results Results confirmed that both markers used have a good efficiency to assess genetic diversity in wild roses. Ten ISSR and eight DAMD primers amplified 276 and 203 loci, with an average of 27.4 and 25 polymorphic alleles per primer, respectively. The polymorphic information content (PIC) values were 0.34 with ISSR and 0.31 with DAMD. Analysis of molecular variance (AMOVA) showed that genetic variation in wild rose occurs mainly within populations (86%) rather than between populations (14%). The region of Azrou (Middle Atlas of Morocco) is the area that registered the highest genetic diversity in the present study with He = 0.21. The 39 rose accessions were divided into three main groups with among-group similarity of 30%. Principal component analysis and the hierarchical classification were consistent with genetic relationships derived by structure analysis. Conclusion The findings revealed that the patterns of grouping are weakly correlated with geographical origin. ISSR and DAMD markers showed that the accessions have a good genetic diversity.

Teachers serving at the front lines of education during difficult times of the pandemic seem to have been forgotten in these bustling days around the world. While delivery of high-quality education is on the shoulders of these people, their life and wellbeing have been affected as a result of the COVID-19 pandemic; however, there is little documented evidence on how the pandemic has impacted language teachers’ wellbeing. To fill this gap, this qualitative study examines the wellbeing of English as a Foreign Language teachers in Iranian public schools during the COVID-19 pandemic. Ten participants who attended in-depth interviews were found to have their wellbeing levels severely affected by the pandemic. Indeed, the newly emerged challenges have been added to the existing obstacles and augmented the already stressful teaching profession. Based on the findings, recommendations are provided for authorities and parents to be employed during the pandemic and afterward to help teachers flourish and subsequently improve quality education.

Background: Electrospinning is an effective method for producing high-quality biopolymer nanofibers, such as cellulose and chitosan. Cellulose nanofibers have excellent mechanical properties and biocompatibility, making them a promising material for tissue engineering. Chitosan nanofibers are biodegradable, biocompatible, and antimicrobial, making them ideal for biomedical applications. The electrospinning parameters, including solution concentration, power supply voltage, orifice diameter, temperature, humidity, and flow rate, play a crucial role in determining the nanofiber diameter, morphology, and mechanical properties, as well as their suitability for various applications. Objective: This systematic review aims to synthesize and evaluate the current evidence on the influence of electrospinning parameters on the production and properties of cellulose and chitosan nanofibers. Methods: A comprehensive search of electronic databases was conducted to identify relevant studies. The inclusion criteria were studies that investigated the effect of electrospinning parameters on cellulose and chitosan nanofibers. Results: It was found that for cellulose, the average fiber diameter increased with increasing each of solution concentration, power supply voltage, orifice diameter, temperature, and humidity. Contrary to tip - collector distance and some optimal points in temperature, where average fiber diameter decreased. For chitosan, the change in voltage and tip to collector distance did not alter the average fiber diameter except for some readings of voltage, which behaved differently. On the other hand, the average fiber diameter increased with increasing flow rate. Conclusion: The review highlights the importance of considering electrospinning parameters in the production of high-quality biopolymer nanofibers and provides insights into the optimization of these parameters for specific applications. This review also highlights the need for further research to better understand the underlying mechanisms of electrospinning and to optimize the process to produce biopolymer nanofibers with improved properties.

IntroductionThe extent of the hemodynamic benefit from AV-synchronous pacing in patients with sinus rhythm and AV block is not completely understood. Thus, we systematically investigated the association of an array of echocardiographic and epidemiological parameters with the change in cardiac output depending on the stimulation mode (AV-synchronous or AV-asynchronous pacing).MethodsPatients in sinus rhythm after previous dual chamber pacemaker implantation underwent a thorough basic echocardiographic assessment of diastolic and systolic left ventricular function, and atrial function (26 echo parameters, including novel speckle tracking strain measurements). Then, stroke volume was measured with AV-synchronous (DDD) and AV-asynchronous (VVI) pacing. Each patient represented their own control, and the sequence of stroke volume measurements was randomized.ResultsIn this prospective single-center study (NCT04068233, registration August 22nd 2019), we recruited 40 individuals. The stroke volume was higher in all patients when applying AV-synchronous DDD pacing [median increase 12.8 ml (16.9%), P

Background: mAbs (biologics) are indicated in patients with poorly controlled moderate-to-severe asthma. The process of prior authorization and administration of a biologic requires exceptional commitment from clinical teams. Objective: Our aim was to evaluate the process of approval and administration of biologics for asthma and determine the most common reasons associated with denials of biologics and delays in administration. Methods: We examined the records of patients with asthma who were prescribed biologics from January 2018 to January 2020 at 2 centers, Montefiore Medical Center (Bronx, NY) and Scripps Clinics (San Diego, Calif). Demographics, insurance information, and details on the approval process were collected. Results: After querying of electronic health records, the records of 352 and 70 patients with moderate-to-severe asthma were included from Montefiore and Scripps, respectively. Most patients at Montefiore (58.2%) were insured under Managed Care Medicaid (MC Medicaid), whereas most patients at Scripps (61.4%) had commercial insurance. The median times from prescription to administration of a biologic were similar: 34 days (interquartile range [IQR] = 18-63 days) and 34 days (IQR = 22.5-56.0 days) (P = .97) for Montefiore and Scripps, respectively. However, the median approval time for Montefiore was 6 days (IQR = 1-20 days) and that for Scripps was 22 days (IQR = 10-36 days) (P < .001). Approval times for prescriptions requiring appeals were significantly longer than for prescriptions approved after the initial submission: 23 days versus 2.5 days and 40.5 days versus 15.5 days (for Montefiore and Scripps, respectively [P < .001 for both]). Conclusions: Lengthy appeals contribute to delays between prescribing and administering a biologic. Site-specific practices and insurance coverage influence approval timing of the biologics for asthma.

Herein, ordered mesoporous materials like SBA-15 and Al/SBA-15 were prepared using the pH adjustment method. Thus, these materials were developed in different pH of synthesis, from the pH adjustment method using a KCl/HCl solution and varying the Si/Al molar ratio (5, 25, and 75). All the ordered mesoporous materials were characterized by FRX, 27Al NMR, SEM, XRD, N2 adsorption/desorption, and CO2 adsorption. From the applied method, it was possible to obtain SBA-15 and Al/SBA-15 with high mesoscopic ordering based on the XRD patterns, independent of the pH employed. From the chemical composition, the insertion of higher amounts of Al into the synthesis caused a progressive improvement in the structural and textural properties of the ordered mesoporous materials. Thus, the chosen synthesis conditions can lead to different aluminum coordination (tetrahedral and octahedral), which gives these materials a greater potential to be applied. The presence of Al in high amounts provides material with the ability to form micropores. Finally, the proposed method proved to be innovative; low-cost; less aggressive to the environment, with efficient insertion of aluminum in the framework of SBA-15 mesoporous material; and practical, based on only one step.

Abstract Background We compared six commonly used logistic regression methods for accommodating missing risk factor data from multiple heterogeneous cohorts, in which some cohorts do not collect some risk factors at all, and developed an online risk prediction tool that accommodates missing risk factors from the end-user. Methods Ten North American and European cohorts from the Prostate Biopsy Collaborative Group (PBCG) were used for fitting a risk prediction tool for clinically significant prostate cancer, defined as Gleason grade group ≥ 2 on standard TRUS prostate biopsy. One large European PBCG cohort was withheld for external validation, where calibration-in-the-large (CIL), calibration curves, and area-underneath-the-receiver-operating characteristic curve (AUC) were evaluated. Ten-fold leave-one-cohort-internal validation further validated the optimal missing data approach. Results Among 12,703 biopsies from 10 training cohorts, 3,597 (28%) had clinically significant prostate cancer, compared to 1,757 of 5,540 (32%) in the external validation cohort. In external validation, the available cases method that pooled individual patient data containing all risk factors input by an end-user had best CIL, under-predicting risks as percentages by 2.9% on average, and obtained an AUC of 75.7%. Imputation had the worst CIL (-13.3%). The available cases method was further validated as optimal in internal cross-validation and thus used for development of an online risk tool. For end-users of the risk tool, two risk factors were mandatory: serum prostate-specific antigen (PSA) and age, and ten were optional: digital rectal exam, prostate volume, prior negative biopsy, 5-alpha-reductase-inhibitor use, prior PSA screen, African ancestry, Hispanic ethnicity, first-degree prostate-, breast-, and second-degree prostate-cancer family history. Conclusion Developers of clinical risk prediction tools should optimize use of available data and sources even in the presence of high amounts of missing data and offer options for users with missing risk factors.

The scaffold pore size influences many critical physical aspects of tissue engineering, including tissue infiltration, biodegradation rate, and mechanical properties. Manual measurements of pore sizes from scanning electron micrographs using ImageJ/FIJI are commonly used to characterize scaffolds, but these methods are both time-consuming and subject to user bias. Current semi-automated analysis tools are limited by a lack of accessibility or limited sample size in their verification process. The work here describes the development of a new MATLAB algorithm, PoreScript, to address these limitations. The algorithm was verified using three common scaffold fabrication methods (e.g., salt leaching, gas foaming, emulsion templating) with varying pore sizes and shapes to demonstrate the versatility of this new tool. Our results demonstrate that the pore size characterization using PoreScript is comparable to manual pore size measurements. The PoreScript algorithm was further evaluated to determine the effect of user-input and image parameters (relative image magnification, pixel intensity threshold, and pore structure). Overall, this work validates the accuracy of the PoreScript algorithm across several fabrication methods and provides user-guidance for semi-automated image analysis and increased throughput of scaffold characterization.

Abstract IFNα and anti-IFNα autoantibodies have been implicated in susceptibility both for systemic lupus erythematosus (SLE) and viral infection. We aimed to analyze the SLE disease phenotype and risk for infection associated with anti-IFN-α IgG autoantibodies in SLE patients In this multidisciplinary retrospective single referral center study, all consecutive patients with SLE admitted between January 1st and November 30th 2020 were considered. All subjects fulfilled the ACR/EULAR 2019 criteria for SLE. Anti-IFNα IgG autoantibodies were quantified at admission by ELISA. Demographic, medical history, laboratory, treatment, and outcome data were extracted from electronic medical records using a standardized data collection form. 180 patients [female 87.2%, median age of 44.4 (34–54.2) years] were included. The median disease duration was 10 years [4–20] with a median SLEDAI score of 2 [0–4] at study time. Fifty-four (30%) patients had a past-history of lupus nephritis. One hundred and forty-four (80%) had received long-term glucocorticoids and 99 (55%) immunosuppressive drugs. Overall, 127 infections—mostly bacterial and viral—were reported in 95 (52.8%) patients. Twenty SLE patients (11.1%) had positive anti-IFNα IgG autoantibodies with a titer ranging from 10 to 103 UA/mL. Age, sex, SLE phenotype and treatment did not significantly differ between SLE patients with or without anti-IFNα. Infection rate was similar in both groups except for tuberculosis which was more frequent in patients with anti-IFNα (20% vs. 3.1%, p = 0.01). The prevalence of autoantibodies against IFNα is high in SLE and associated with a higher frequency of tuberculosis.