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Melanoma clinical outcomes emerge from incompletely understood genetic mechanisms operating within the tumor and its microenvironment. Here, we used single-cell RNA-based spatial molecular imaging (RNA-SMI) in patient-derived archival tumors to reveal clinically relevant markers of malignancy progression and prognosis. We examined spatial gene expression of 203,472 cells inside benign and malignant melanocytic neoplasms, including melanocytic nevi and primary invasive and metastatic melanomas. Algorithmic cell clustering paired with intratumoral comparative two-dimensional analyses visualized synergistic, spatial gene signatures linking cellular proliferation, metabolism, and malignancy, validated by protein expression. Metastatic niches included up-regulation of CDK2 and FABP5, which independently predicted poor clinical outcome in 473 patients with melanoma via Cox regression analysis. More generally, our work demonstrates a framework for applying single-cell RNA-SMI technology toward identifying gene regulatory landscapes pertinent to cancer progression and patient survival.

Abstract Background Poor ovarian response (POR) to controlled ovarian stimulation (COS) remains challenging, especially in advanced-age women with diminished ovarian reserve, resulting in low live birth rates. Many patients prefer to conceive with their eggs, underscoring the need for improved treatments. This study explores astaxanthin potential as a COS adjuvant to improve ovarian response and assisted reproductive technology (ART) outcomes, considering its impact on oxidative stress (OS), inflammation, and apoptosis, which are key factors in POR. Methods In this randomized, triple-blind, placebo-controlled trial, 60 infertile POR patients from POSEIDON Group 4 (the poorest prognosis category, age > 35 and poor ovarian reserve (anti-müllerian hormone

Introduction In recent years, the ever-increasing population growth and rampant use of personal transportation and daily trips have caused many problems in the field of transportation, including high fuel consumption, air pollution, noise, high density streets, reduced physical activity, etc. In many metroplolitan areas during the past decades, the sudden increase of motor vehicles has caused heavy street traffic in intra-city trips, and the main reason for this can be considered the weak relationship between urban morphology and transportation, in other words, urban forms that avoid pedestrians and encourage motor trips. Urban morphology is one of the most important and main factors that affect the demand for urban transportation. The quality of land use (density of residential units or their dispersion) forms the important basis of urban morphology. In the formation of urban morphology, natural and human factors play varried roles, among them road network is of paramount importance in construction and morphology of a city. Since urban morphology has a significant effect on urban transportation, how to establish a strong relationship between urban morphology and travel modes has has always been of great interst of researchers. This study is aiming at investigating the impact of morphology characteristics on urban transportation demand. In this research, features of urban morphology, such as overall residential density, connectivity index, and the average width of roads, with the help of demographic characteristics, such as population density, female and female working poulation, total working population etc., on demand for urban transportation have been ivestigated. These include four parameters such as creation of public and personal trips and attraction of public and personal trips on in 186 traffic areas of Isfahan city. Methodology This research has been conducted with a descriptive causal approach based on the data and information required in the study areas. To achieve the research goals, 186 traffic areas of Isfahan City have been studied. For analyzing the characteristics of urban morphology, including average width of roads, overall residential density, and connectivity index (street density), in the form of GIS maps have been investigated, and for demographic characteristics, the population and housing census map of Isfahan City was obtained and researched from the Deputy Planning and Human Capital Development Organization of Isfahan Municipality. Then, using the map of 186 traffic areas of Isfahan City, the amount of these variables was calculated and extracted by GIS software. Moreover, the information related to urban transportation demand based on public transportation demand, including public travel creation, public travel attraction, and personal transportation demand, including personal travel creation and personal travel attraction from the origin-destination matrix of the year 2021 of Isfahan city on a normal working day and at the peak hour of 7:00 to 8:00 a.m., the transportation and traffic department of Isfahan municipality has been obtained and used for evaluation. In the present research, in order to reach a complete and comprehensive answer, after extracting the data from GIS software, the Eviuse software was used. According to the number and nature of the research variables, the specification of the model is done using the multivariate regression method and the weighted least squares method. GIS software was also used for drawing the maps. Findings The research findings show that in the TSS and JSS models, with the increase in the average width of traffic areas, the creation and attraction of personal travel have also increased, and in the TSO and JSO models, the creation and attraction of public travel have decreased with the increase in the average width of traffic areas. In TSS model, the coefficient is negative and in JSO model, the coefficient is positive, which shows that with an increase in the overall residential density, the use of private transportation decreases and the use of public transportation increases. In terms of street density, which also indicates the connection index, the coefficient value is positive in TSS and negative in TSO model. The results also show that women in general use public transportation, but working women use private transportation more. The estimation of TSS model shows that as population is aging in the traffic areas of Isfahan City, the preferrence in using personal transportation has been rising. In JSS model, the parking variable has a direct relationship with the attraction of personal travel. In the personal travel attraction model, health-therapeutic use and commercial use have a direct relationship with the attraction of personal trips, and in the public travel attraction model, commercial, educational, and health-therapeutic uses have a direct relationship with the attraction of public trips. Finally, the increased number and variety of the users will also increase intra-city trips. Discussion and Conclusion In this research, an attempt has been made to investigate the effect of urban morphology variables on urban transportation demand with a general perspective. The results of the estimation of the research models show that the widening of urban roads as a management policy for intra-city travel demand increases people's trips using personal transportation and as a result, increases the number of road users. Street density, which indicates the number of higher streets and therefore greater connectivity, has a direct relationship with citizens' use of private transportation. Residents of areas that have higher overall residential density and population density, which indicates denser urban fabric and more dispersion, are less likely to use personal transportation, and people in those areas prefer to use public transportation and walking options. Also, as the age of the residents of the area increases, they use private cars for their daily trips. Another examination of the results of the research indicates that areas with parking facility, will attract passengers who have used private transportation compared to the areas that do not have such possibility. In general, as the total working population increases in the areas, they use personal transportation to go to their workplace, and it can be said that the female population uses public transportation more for their daily trips. In the public travel attraction model, the positive coefficient of commercial use is higher than the coefficient of health-therapeutic use and educational use, and with the increase in the number of commercial uses, the attraction of public travel increases to a greater extent. In the personal travel absorption model, the effect value of the healthcare usage coefficient is higher than the commercial usage coefficient and it shows that with the increase in the number of healthcare usages, the absorption of personal travel will increase. Moreover, the increased number and variety of the users will also increase intra-city trips.

The translation of song lyrics is challenging for translators primarily due to the intricate poetic and musical elements, which often compel them to employ specific strategies for effective translation. This study was an attempt to investigate the translation strategies in selected translated movie song lyrics and explore the challenges in translating the lyrics. In this qualitative study, the songs were purposefully selected from “Mulan” (1998) and “Aladdin” (2019) movies. Low’s (2013) translation strategies were applied during the process of translation. The “Translation” (transfer of material with a reasonably high degree of semantic fidelity), and “Replacement” (a re-creation of text by only preserving the music element) strategies were found as the common strategies in the translation of song lyrics. The use of a replacement strategy could be due to technical difficulties in translating songs, such as the constraint of rhythm, hence a total replacement of meanings to match the rhythm of the song. A significant challenge in translating song lyrics from English to Chinese was in translating the concept of face-saving, which is an eminent process in social interactions in Chinese culture. It was concluded that the use of a translation strategy depended on the lyrics, translators’ creativity, melody, rhyme, and the differences between the languages and cultures, while the “skopos”, i.e., the correspondence of aim/purpose in the source and target cultures should play the key role.

Reconstruction of peripheral mixed motor/sensory nerves using autografts has remained the gold standard. Inconsistent and nonphysiologic results across nerve allograft studies, including successful and failed motor reinnervation, have limited the current clinical application of nerve allografts to noncritical small-diameter sensory nerve defects less than 3 cm. This scoping review aimed to compare outcomes in both basic science and clinical applications of autograft and allograft nerve reconstruction for mixed motor/sensory nerves.

Introduction: Subthalamic nucleus deep brain stimulation (STN-DBS) is a proven treatment modality for Parkinson’s disease (PD), reducing dyskinesia and time spent in the “OFF” state. This study evaluates the long-term outcomes of STN-DBS in PD patients up to 10 years post-surgery in Singapore. Method: We conducted a retrospective review of Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) scores, activities of daily living (ADLs), disease milestones, dopaminergic drug prescriptions, and adverse events in patients before and after STN-DBS surgery. Results: A total of 94 PD patients who underwent bilateral STN-DBS were included. STN-DBS reduced time in the “OFF” state by 36.9% at 1 year (P=0.034) and 40.9% at 5 years (P=0.006). Time with dyskinesia did not significantly change. Levodopa equivalent daily dose was reduced by 35.1% by 5 years (P less than 0.001). MDS-UPDRS-II and III scores increased from 5 years post-DBS by 40.5% and 35.4%, respectively. Independence in ADLs decreased, though not significantly. The prevalence of frequent falls increased at 5 years. Surgery- and device-related adverse events were uncommon and generally mild. Conclusion: STN-DBS provides sustained relief from motor complications and reduced medication requirements in PD patients in Singapore. This study highlights STN-DBS as an effective treatment option, significantly enhancing the quality of life for those with PD.

Abstract Pain catastrophizing is an exaggerated focus on pain sensations. It may be an independent factor influencing pain and functional outcomes of knee arthroplasty. We aimed to evaluate the association between pre-operative pain catastrophizing with pain and function outcomes up to one year after knee arthroplasty. We used data from a cohort study of patients undergoing primary knee arthroplasty (either total or unicompartmental arthroplasty) for knee osteoarthritis. Pain catastrophizing was assessed pre-operatively using the Pain Catastrophizing scale (PCS). Other baseline variables included demographics, body mass index, radiographic severity, anxiety, depression, and knee pain and function assessed using the Western Ontario and McMaster University Index (WOMAC). Patients completed the WOMAC at 6- and 12-months after arthroplasty. WOMAC pain and function scores were converted to interval scale and the association of PCS and changes of WOMAC pain and function were evaluated in generalized linear regression models with adjustment with confounding variables. Of the 1136 patients who underwent arthroplasty (70% female, 84% Chinese, 92% total knee arthroplasty), 1102 and 1089 provided data at 6- and 12-months post-operatively. Mean (± SD) age of patients was 65.9 (± 7.0) years. PCS was associated with a change in WOMAC pain at both 6-months and 12-months (β = − 0.04, 95% confidence interval: − 0.06, − 0.02; P

Abstract Background Enterobacter cloacae complex (ECC) including different species are isolated from different human clinical samples. ECC is armed by many different virulence genes (VGs) and they were also classified among ESKAPE group by WHO recently. The present study was designed to find probable association between VGs and antibiotic susceptibility in different ECC species. Methods Forty-five Enterobacter isolates that were harvested from different clinical samples were classified in four different species. Seven VGs were screened by PCR technique and antibiotic susceptibility assessment was performed by disk-diffusion assay. Result Four Enterobacter species; Enterobacter cloacae (33.3%), Enterobacter hormaechei (55.6%), Enterobacter kobei (6.7%) and Enterobacter roggenkampii (4.4%) were detected. Minimum antibiotic resistance was against carbapenem agents and amikacin even in MDR isolates. 33.3% and 13.3% of isolates were MDR and XDR respectively. The rpoS (97.8%) and csgD (11.1%) showed maximum and minimum frequency respectively. Blood sample isolated were highly virulent but less resistant in comparison to the other sample isolates. The csgA, csgD and iutA genes were associated with cefepime sensitivity. Conclusion The fepA showed a predictory role for differentiating of E. hormaechei from other species. More evolved iron acquisition system in E. hormaechei was hypothesized. The fepA gene introduced as a suitable target for designing novel anti-virulence/antibiotic agents against E. hormaechei. Complementary studies on other VGs and ARGs and with bigger study population is recommended.

Abstract Studies in Western populations have shown that Black and Hispanic patients have an earlier age of Multiple Sclerosis (MS) onset and a more severe disease course characterised by faster disability accrual compared to Whites. It is yet unclear whether MS disease characteristics and clinical course differ amongst Asian racial groups. Singapore is uniquely poised to investigate this as its multi-racial population comprises three genetically diverse Asian racial groups—Chinese, Malay and South Asian. Herein, we sought to elucidate differences in the clinical phenotypes, disease-modifying therapy (DMT) usage, and disease course amongst these three Asian racial groups by performinga retrospective observational study on MS patients seen at the National Neuroscience Institute, Singapore. Data on demographics, disease characteristics, ancillary investigations, and DMT usage were collected. One hundred and eighty-eight patients were included (90 Chinese, 32 Malay, and 66 South Asian). Our findings showed that MS prevalence was the highest in South Asians followed by Malays and Chinese, while demographics, healthcare access, and longer-term disease course were identical across the racial groups. However, several differences and trends were elucidated: (1) South Asian patients had milder sentinel attacks (p = 0.006), (2) a higher proportion of Malay patients had enhancing lesions on their initial MRI (p = 0.057) and the lesion topography differed across the races (p = 0.034), and (3) more Malay patients switched out of their initial DMT (p = 0.051). In conclusion, MS disease characteristics were largely similar across these three Asian racial groups, and while there were some clinical and radiological differences at presentation, these did not influence longer-term outcomes.

Abstract Gastroenteritis infection is a major public health concern worldwide, especially in developing countries due to the high annual mortality rate. The antimicrobial and antibiofilm activity of human mesenchymal stem cell-derived conditioned medium (hMSCsCM) encapsulated in chitosan nanoparticles (ChNPs) was studied in vitro and in vivo against common gastroenteritis bacteria. The synthesized ChNPs were characterized using Zeta potential, scanning electron microscopy (SEM), and dynamic light scattering (DLS) techniques. HMSC-derived conditioned medium incorporated into chitosan NPs (hMSCsCM-ChNPs) composite was fabricated by chitosan nanoparticles loaded with BM-MSCs (positive for CD73 and CD44 markers). The antimicrobial and antibiofilm activity of composite was investigated against four common gastroenteritis bacteria (Campylobacter jejuni ATCC29428, Salmonella enteritidis ATCC13076, Shigella dysenteriae PTCC1188, and E. coli ATCC25922) in-vitro and in-vivo. Majority of ChNPs (96%) had an average particle size of 329 nm with zeta potential 7.08 mV. The SEM images confirmed the synthesis of spherical shape for ChNPs and a near-spherical shape for hMSCsCM-ChNPs. Entrapment efficiency of hMSCsCM-ChNPs was 75%. Kinetic profiling revealed that the release rate of mesenchymal stem cells was reduced following the pH reduction. The antibacterial activity of hMSCsCM-ChNPs was significantly greater than that of hMSCsCM and ChNPs at dilutions of 1:2 to 1:8 (P 106 CFU/ml to approximately (102 to 10) after 72 h. Both in vitro and in vivo assays demonstrated the antimicrobial and antibiofilm activities of ChNPs at a concentration of 0.1% and hMSCsCM at a concentration of 1000 μg/ml to be inferior to that of hMSCsCM-ChNPs (1000 μg/ml + 0.1%) composite. These results indicated the existence of a synergistic effect between ChNPs and hMSCsCM. The designed composite exhibited notable antibiofilm and antibacterial activities, demonstrating optimal release in simulated intestinal lumen conditions. The utilization of this composite is proposed as a novel treatment approach to combat gastroenteritis bacteria in the context of more challenging infections.

Abstract Children with developmental and epileptic encephalopathies often present with co‐occurring dyskinesias. Pathogenic variants in ARX cause a pleomorphic syndrome that includes infantile epilepsy with a variety of movement disorders ranging from focal hand dystonia to generalized dystonia with frequent status dystonicus. In this report, we present three patients with severe movement disorders as part of ARX‐associated epilepsy‐dyskinesia syndrome, including a patient with a novel pathogenic missense variant (p.R371G). These cases illustrate diagnostic and management challenges of ARX‐related disorder and shed light on broader challenges concerning epilepsy‐dyskinesia syndromes.

Abstract Background During the COVID-19 pandemic, medical workers were concerned about the care of their children or family members and the impact of being separated from them. This increased stress could harm the relationship between nurses and patients. This study assessed how medical workers’ parental role may affect burnout during such a high-stress period. Methods This cross-sectional observational study was carried out in 2021 during the COVID-19 pandemic. The client burnout (CB) scale of the Copenhagen Burnout Inventory, the Nordic Musculoskeletal Questionnaire, and a demographic questionnaire were used. Statistical methods such as the t-test, one-way ANOVA, and univariable/multiple linear regression were applied. Results A total of 612 nurses were included in this study. The likely risk factors of CB were identified and the parenthood effect was found to be associated with reduced CB. The parental role and leisure activity with family and friends on CB were found to have an impact. Engaging in leisure activity with family and playing the role of a parent diligently will help relieve nurses’ burnout from frequent contact with patients and their families, thus lowering the risk of clinical burnout. Conclusion The parental role, family/friends relationships, and a complex work environment associated with nurses’ burnout during the COVID-19 pandemic. This finding allows us to re-examine the importance of family life and parent–child relationships in high-stress work environments.

To the Editor: The hereditary spastic paraplegias (HSPs) are a group of more than 80 neurogenetic disorders that share the feature of progressive lower limb spasticity. Biallelic loss-of-function variants in [...]

This paper reviews the literature on English for Specific Purposes (ESP) research in 15 CSSCI foreign language journals in China's CNKI database over the last two decades. The data have been quantified and visualized with Citespace. This paper analyzes research advances and themes, and then puts forward suggestions based on the current situation of college English teaching in China. The findings reveal that: 1) ESP publications have shown a rising trend during the past 20 years; 2) The study of ESP in academic dissertations is mainly at the MA level; 3) ESP research focuses on such issues as relationships between ESP and college English, academic English, corpus and teaching modes; 4) The dominant method of ESP research in China is non-empirical while more and more empirical studies have emerged since 2011. This study also critically analyzes the research limitations and recommendations of the ESP study.

Education should play an important role in sustainable development. However, we were also faced with the enculturation in the education systems that contribute to the literacy of the environmental issue and challenges in maintaining sustainable development. In this review, we aimed to synthesize the recent research findings on how enculturation was developed among students through social and cultural factors and the role of education for sustainable development. In synthesizing the enculturation in the education system, we found several contributing social and cultural factors such as family cultural background and parental values, school systems, teachers' beliefs, and the attitudes and appraisal of students used in the different school environments. Co-existing differences were also found when examining the environmental issue literacy among students from different cultures in the studies along with energy literacy and ocean literacy from cross-cultural studies perspectives. Drawing on these findings, we further add on how education for sustainable development in different cultures was integrated and emphasized in their existing school curricula to help other cultures to learn more about how education for sustainable development was developed across cultural contexts.

Osteomyelitis caused by drug-resistant pathogens is one of the most important medical challenges due to high rates of mortality and morbidity, and limited therapeutical options. The application of novel nano-scaffolds loaded with antibiotics has widely been studied and extensively evaluated for in vitro and in vivo inhibition of pathogens, regenerating damaged bone tissue, and increasing bone cell proliferation. The treatment of bone infections using the local osteogenic scaffolds loaded with antimicrobial agents may efficiently overcome the problems of the systemic use of antimicrobial agents and provide a controlled release and sufficient local levels of antibiotics in the infected sites. The present study reviewed various nano-scaffolds delivery systems of antimicrobial drugs evaluated to treat osteomyelitis. Nano-scaffolds offer promising approaches because they simulate natural tissue regeneration in terms of their mechanical, structural, and sometimes chemical properties. The potential of several nano-scaffolds prepared by natural polymers such as silk, collagen, gelatin, fibrinogen, chitosan, cellulose, hyaluronic, alginate, and synthetic compounds such as polylactic acid, polyglycolic acid, poly (lactic acid-co-glycolic acid), poly-ɛ-caprolactone have been studied for usage as drug delivery systems of antimicrobial agents to treat osteomyelitis. In addition to incorporated antimicrobial agents and the content of scaffolds, the physical and chemical characteristics of the prepared delivery systems are a determining factor in their effectiveness in treating osteomyelitis.

Background: Problematic use of the internet (PUI) is prevalent, particularly among adolescents and young adults. Given the limited measures to assess specific types of PUI, which encompasses a broad spectrum of activities such as online gaming, social media use, pornography use, shopping, gambling, and web-streaming, Muller et al. (2022) developed the Assessment of Criteria for Specific Internet-use Disorders (ACSID-11) to comprehensively assess different types of PUI (i.e., gaming, shopping, social media use, gambling, and pornography use). The present study aimed to validate the Chinese ACSID-11 among adolescents incorporating cross-cultural adaptations. Methods: Using forward-backward translation method, a culturally adapted version of the ACSID-11 was prepared. Then, a cross-sectional online survey was administered between September 8 and September 26, 2023. Adolescents, using a convenience sample (N = 11,492; mean age = 16.42 years [SD ± 0.91]; 59.1% male), were recruited from six schools to complete the translated ACSID-11, Internet Gaming Disorder Scale-Short Form (IGDS9-SF), Bergen Social Media Addiction Scale (BSMAS), and Smartphone Application Based Addiction Scale (SABAS) via an online platform. Pearson correlation coefficients assessed convergent/discriminant validity. Factor structure and measurement invariance were examined through confirmatory factor analysis (CFA) and multi-group CFA. Cronbach's alpha and McDonald's omega tested internal consistency. Results: Associations between the ACSID-11 components and other scales supported convergent validity (i.e., ACSID-11 gaming scale with IGDS9-SF [0.37 ≤ r ≤ 0.41]; social networks use scale with BSMAS [0.24 ≤ r ≤ 0.31]) and discriminant validity (i.e., online gambling scale with BSMAS [0.16 ≤ r ≤ 0.19] and with SABAS [0.11 ≤ r ≤ 0.13]). A four-factor solution indicated good fit with comparative fit index (CFI) ranging from 0.982 to 0.958. The ACSID-11 was measurement invariant across sexes (∆CFI = -0.001 to 0.000) and different levels of related addictive behaviors (∆CFI = -0.001 to 0.000). Both Cronbach's alpha and McDonald's omega (0.63 to 0.97) were acceptable for both frequency and intensity of responses. Conclusions: The ACSID-11 is an appropriate scale to assess different kinds of PUI among Chinese adolescents and students. Psychometric assessment of the measure in other cultures and among clinical samples is recommended.

Harnessing vibrations in multifunctional nanostructured plates is pivotal to next-gen microsystems but necessitates understanding scale effects under multifield loading. Investigated in this work are the forced and unforced vibrations of multilayered piezoelectric nanoplates supported on a variable viscoelastic medium and loaded hygrothermo-electromechanically with functionally graded porous (FGP) cores. The viscoelastic foundation is supposed to demonstrate non-linear changes in both stiffness and damping characteristics in the x-coordinate direction. The goal is to improve the accuracy of the results by using the nonlocal strain gradient theory (NSGT) and the third-order shear deformation assumption (TSDA), which include the effects of hardening and softening materials. The FGP core layer considers four states of porosity distribution patterns. These porosity distributions are expected to change in both the in-plane and thickness directions. The governing partial differential equations resulting from Hamilton's principle can be reduced to a system of algebraic equations by applying the Galerkin method. The parametric studies evaluate the effects of several factors, such as the initial electric voltage, viscoelastic medium parameters, moisture rise, temperature changes, porosity distributions, FG index, nonlocal and strain gradient features, and boundary conditions, on the vibration response. The novelty lies in the incorporation of advanced theories, such as the NSGT and TSDT, which capture size-dependent effects and material hardening/softening phenomena. Additionally, the consideration of four distinct porosity distribution patterns in the FGP core layer provides insights into the influence of porosity gradients on the dynamic response. The proposed model can guide the design and optimization of multifunctional nanostructured plates for applications in next-generation microsystems, energy harvesting devices, and smart structures.

Abstract Purpose Accurate prognostication may aid in the selection of patients who will benefit from surgery at recurrent WHO grade 4 glioma. This study aimed to evaluate the role of serial tumour volumetric measurements for prognostication at first tumour recurrence. Methods We retrospectively analyzed patients with histologically-diagnosed WHO grade 4 glioma at initial and at first tumour recurrence at a tertiary hospital between May 2000 and September 2018. We performed auto-segmentation using ITK-SNAP software, followed by manual adjustment to measure serial contrast-enhanced T1W (CE-T1W) and T2W lesional volume changes on all MRI images performed between initial resection and repeat surgery. Results Thirty patients met inclusion criteria; the median overall survival using Kaplan-Meier analysis from second surgery was 10.5 months. Seventeen (56.7%) patients received treatment post second surgery. Univariate cox regression analysis showed that greater rate of increase in lesional volume on CE-T1W (HR = 2.57; 95% CI [1.18, 5.57]; p = 0.02) in the last 2 MRI scans leading up to the second surgery was associated with a higher mortality likelihood. Patients with higher Karnofsky Performance Score (KPS) (HR = 0.97; 95% CI [0.95, 0.99]; p = 0.01) and who received further treatment following second surgery (HR = 0.43; 95% CI [0.19, 0.98]; p = 0.04) were shown to have a better survival. Conclusion Higher rate of CE-T1W lesional growth on the last 2 MRI images prior to surgery at recurrence was associated with increase mortality risk. A larger prospective study is required to determine and validate the threshold to distinguish rapidly progressive tumour with poor prognosis.

Background and Aim: Understanding the antibiotic resistance profile of uropathogenic Escherichia coli in urinary tract infections (UTIs) across different populations and regions is crucial for appropriate antibiotic prescribing practices. This study aimed to assess the antibiotic resistance pattern of uropathogenic Escherichia coli isolated from UTIs in outpatients, focusing on gender and age demographics. Methods: This cross-sectional study analyzed 7365 urine culture samples obtained from patients consecutively referred to the Kashan Reference Laboratory between April 2021 and March 2022. Following sterile urine collection, bacterial cultures were grown on McConkey agar, blood agar, and specific media. Escherichia coli isolates were identified, and antibiotic resistance was determined using the disk diffusion method on Mueller Hinton agar, following National Committee for Clinical Laboratory Standards guidelines. Results: Among 401 positive urine cultures, 251 (62.5%) were attributed to E. coli, while 150 (37.4%) were related to other organisms. Of the E. coli cases, 226 isolates (90%) were from women and 25 (10%) from men. The E. coli strains exhibited the highest resistance (54.7%) to cefazolin and the lowest resistance (4.4%) to imipenem and nitrofurantoin. Antibiotic resistance in E. coli from men exceeded that of women across all antibiotics tested, with statistically significant differences observed in ceftriaxone, imipenem, ciprofloxacin, and nitrofurantoin (P

The co-pyrolysis (at 300°C and 600°C) of municipal sewage sludge (SS) with zero-valent iron (Fe0: 1.5% and 3%) was investigated to reduce the toxicity of arsenic (As) and zinc (Zn) in SS. The BCR sequential extraction method, desorption kinetic analysis, and material characterization techniques (Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, X-ray diffraction) were used to evaluate the effects of the treatments on Zn and As behavior. The results showed that co-pyrolysis significantly reduced the acid-soluble fraction (18–43% for Zn; 83–95% for As) and mobility factor (45–85% for Zn; 86–96% for As) of Zn and As compared to untreated SS. Desorption experiments indicated a significant reduction in Zn and As release in treated samples, particularly in the co-pyrolysis sample at 600°C and Fe0 3% (67% for Zn; 88% for As) in comparison with untreated SS. Co-pyrolysis of Fe0 and SS led to the formation of new functional groups (Si–O, aromatic), a more porous surface morphology, and highly stable chemical crystals (ferric arsenate, zinc arsenide), which played a crucial role in Zn and As stabilization. The findings of this study suggest that co-pyrolysis is a promising approach for mitigating As and Zn toxicity in SS. However, additional field testing with plant-based systems is necessary for confirmation.

Summary: Background: Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence-based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH). Methods: This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region. A standardized data set including WHO gross motor milestones, SMA validated motor assessments, need for nutritional and respiratory support, and adverse events was collected using the SMArtCARE registry and the Swiss-Reg-NMD. Outcome data were analyzed using a prespecified statistical analysis plan including potential predictors such as age at GAT, SMN2 copy number, past treatment, and symptom status. Findings: 343 individuals with SMA (46% male, 54% female) with a mean age at OA of 14.0 months (range 0–90, IQR 20.0 months) were included in the analysis. 79 (23%) patients were clinically presymptomatic at the time of treatment. 172 (50%) patients received SMN2 splice-modifying drugs prior to GAT (risdiplam: n = 16, nusinersen: n = 154, both: n = 2). Functional motor improvement correlated with lower age at GAT, with the best motor outcome in those younger than 6 weeks, carrying 3 SMN2 copies, and being clinically presymptomatic at time of treatment. The likelihood of requiring ventilation or nutritional support showed a significantly increase with older age at the time of GAT and remained stable thereafter. Pre-treatment had no effect on disease trajectories. Liver-related adverse events occurred significantly less frequently up to 8 months of age. All other adverse events showed an even distribution across all age and weight groups. Interpretation: Overall, motor, respiratory, and nutritional outcome were dependent on timing of GAT and initial symptom status. It was best in presymptomatic children treated within the first six weeks of life, but functional motor scores also increased significantly after treatment in all age groups up to 24 months. Additionally, OA was best tolerated when administered at a young age. Our study therefore highlights the need for SMA newborn screening and immediate treatment to achieve the best possible benefit-risk ratio. Funding: The SMArtCARE and Swiss-Reg-NMD registries are funded by different sources (see acknowledgements).

Localized myxedema is a rare complication ofautoimmune thyroid diseases including the Hashimoto thyroiditis and Graves’ disease.Localized myxedema results from the accumulation of glycosaminoglycans in the dermis and subcutaneous layer of the skin.Fibroblast-produced hyaluronic acid is the mainglycosaminoglycan in localized myxedema. Localized myxedema presents bilaterally with a “boggy” thickening of the skin. Lesions classically have “waxy” swelling and induration.Myxedematous lesions of the skin most often appear on the anterior aspects of the legs and dorsum of the feet. They are often asymptomatic. Targeted treatment to cutaneous lesions is usually reserved for symptomatic cases.

Myxedema is a rare, cutaneous complication of autoimmune thyroid diseases that most often affects the anterior shins. Herein, we report a patient with a history of Graves disease and Hashimoto thyroiditis who presented with boggy, alopecic patches associated with scalp pruritus. Punch biopsies from these lesions showed increased interstitial mucin in the reticular dermis, consistent with localized myxedema. This report showcases a rare presentation of localized myxedema of the scalp, highlighting the diverse cutaneous manifestations of autoimmune thyroid diseases.

CRISPR-associated (Cas) enzymes have revolutionized biology by enabling RNA-guided genome editing. Homology-directed repair (HDR) in the presence of donor templates is currently the most versatile method to introduce precise edits following CRISPR-Cas-induced double-stranded DNA cuts, but HDR efficiency is generally low relative to end-joining pathways that lead to insertions and deletions (indels). We tested the hypothesis that HDR could be increased using a Cas9 construct fused to PRDM9, a chromatin remodeling factor that deposits histone methylations H3K36me3 and H3K4me3 to mediate homologous recombination in human cells. Our results show that the fusion protein contacts chromatin specifically at the Cas9 cut site in the genome to increase the observed HDR efficiency by threefold and HDR:indel ratio by fivefold compared with that induced by unmodified Cas9. HDR enhancement occurred in multiple cell lines with no increase in off-target genome editing. These findings underscore the importance of chromatin features for the balance between DNA repair mechanisms during CRISPR-Cas genome editing and provide a strategy to increase HDR efficiency.

Due to their improved mechanical properties and adaptability, microplates with tailored variable thickness profiles are becoming essential parts of advanced micro- and nanoelectromechanical systems (MEMS and NEMS). This study conducts a thorough analytical analysis of the vibration properties of thermally loaded, multilayer functionally graded graphene platelet-reinforced composite (FG-GPLRC) microplates of linearly or parabolically varying thickness resting on viscoelastic medium under different boundary conditions. The Halpin–Tsai micromechanical model and the law of mixtures are employed to calculate the effective material characteristics for various reinforcement distributions in the microplate. These distributions encompass uniformly symmetric and asymmetric arrangements. The study utilized the first-order shear deformation theory (FSDT) in conjunction with the modified strain gradient theory (MSGT) and Hamilton's principle to generate the dynamic governing equations for the structure, accounting for size-dependent effects. The resulting equations are afterwards solved using the utilization of the Galerkin technique. This enables the evaluation of the proposed solution's correctness and precision. The impact of various factors on vibration behavior is investigated through numerical analysis. These factors encompass length scale parameters, temperature fluctuations, temperature distribution profiles, boundary conditions, the distribution pattern of the GPL, taper constants in both unidirectional and bidirectional scenarios, the weight fraction of the GPL.