ABSTRACT The film industry plays a crucial role in driving economic growth, fostering new business ventures, stimulating local economies during production, increasing tourism by shaping audience preferences and advancing globalization through cross-cultural exchange and international content distribution, all of which have been the subject of research. This study examines the location preferences, clustering dynamics and the reasons behind the decline of the film cluster in Beyoğlu, which has historically been the heart of the Istanbul film industry. Based on 110 interviews with representatives from 275 film companies, the results were analysed using the analytic hierarchy process (AHP) and QGIS. The findings highlight that the building's physical quality, proximity to public transport stops and location in the heart of the city are the most important factors in film companies' location choices. The decline of the film cluster in Beyoğlu can be explained by factors such as inadequate building quality, traffic congestion, logistics and parking challenges and high rental costs. Moreover, the results indicate a shift in the film industry towards the Levent-Maslak corridor, which has emerged as the linear extension of Istanbul's central business district since the 1990s.

The global prevalence of obesity has more than doubled between 1990 and 2022, making it a significant public health concern. Obesity is associated with an increased risk of various complications, including cardiovascular diseases, type 2 diabetes, as well as increased risk for all-cause mortality. Existing research also indicates that higher BMI is linked to increased healthcare costs, but most evidence comes from cross-sectional studies and older populations. The present study aims to estimate the direct healthcare cost of obesity from late adolescence through mid-adulthood. The study included a national cohort of 496 404 conscripts for mandatory military service that underwent medical evaluation at age 17. Study participants were retrospectively followed for hospitalization days and total healthcare costs at ages 35, 45 and 55 using data from a large national healthcare provider. Direct medical costs were standardized using gross domestic product (GDP) inflation rates and purchasing power parity. Analyses were adjusted for sex and socioeconomic status. Higher BMI categories in adolescence were associated with increased hospitalization rates and total healthcare costs across all follow-up ages. At age 45, individuals with obesity class I and class II/III had 1.65-fold and 1.62-fold higher costs, respectively, compared to those with normal BMI. This association was stronger among males. The correlation between obesity in adolescence and higher medical costs is evident already in early-and-mid-adulthood. The study underscores the need for comprehensive approaches targeting adolescents to reduce long-term healthcare costs and improve population health outcomes.

The management of patients with generalized myasthenia gravis (gMG) is complex and often involves substantial health care expenses. As the treatment paradigm continues to evolve, understanding the economic burden of gMG must also reflect the availability and increasing use of newly approved and advanced therapies in a diverse patient population. To estimate incremental health care resource utilization (HRU) and costs associated with gMG compared with non-MG controls and identify predictors of high health care costs in gMG in an insured US population cohort. Adults with newly diagnosed gMG were identified from Komodo Research data (January 1, 2017, to September 30, 2023). Characteristics of adults without MG were weighted using entropy balancing to match the gMG cohort. The index date was the first MG diagnosis by a neurologist for the gMG cohort and a random date for the non-MG cohort. Annual per patient HRU and health care costs were compared between the weighted cohorts. Predictors of high health care costs were evaluated among the gMG cohort using a logistic regression model. After weighting, among 6,195 patients in the gMG cohort and 226,008 in the non-MG cohort, the mean age was 61.1years, 49.1% were female, 53.4% were covered by commercial insurance, 41.0% were covered by Medicare Advantage, and 5.6% were covered by Medicaid. The gMG cohort (mean follow-up = 32.7 months) compared with the non-MG cohort (mean follow-up = 31.3 months) had 2.4, 1.6, and 1.9 times more inpatient days, emergency department visits, and outpatient visits annually, respectively (all P < 0.001). Mean annual all-cause total health care costs in the gMG cohort were $43,872 higher than in the non-MG cohort ($58,341 vs $14,469; P < 0.001); 59.3% of the difference was driven by pharmacy costs (mostly immunoglobulin). Prediagnosis weakness and fatigue symptoms, exacerbation or crisis, and use of immunoglobulin were important factors significantly associated with high health care costs in the gMG cohort (all P < 0.001). Despite advances in treatment, the economic burden of gMG remains substantial. Association of high health care costs with early symptoms and disease exacerbations underscores the need for more effective intervention strategies to improve disease control and reduce HRU and costs in patients with gMG.

Negative pressure wound therapy (NPWT) has transformed the management of complex wounds across surgical disciplines. However, widespread adoption in low- and middle-income countries is constrained by the high cost and proprietary nature of commercial systems. This narrative review examines appropriate low-cost NPWT alternatives and discusses strategies to mitigate commonly cited limitations through protocol-driven care. Wider adoption supported by pragmatic evaluation and standardized protocols offers an opportunity to expand equitable access to advanced wound care in resource-constrained settings.

As part of the 2025 diabetes and technology (dt)-report, this study explored indications for use, barriers to adoption, and perceived functionality of smart pens. An online survey conducted between November and December 2024 gathered responses from diabetes specialists and diabetes educators (health care professionals [HCPs]) in Germany (DE), Austria (AT), Switzerland (CH), and Spain (ES). Participants estimated the proportion of individuals with diabetes who would benefit from smart pens, rated the significance of specific functions, and evaluated barriers on 5-point scales. The survey included 1294 HCPs (69.2% DE, 9.7% AT, 7.0% CH; 14.1% ES). Current usage of smart pens is estimated at 4% to 15% for people with type 1 diabetes and 3% to 6% for those with type 2 diabetes. However, the indication rate is markedly higher, ranging from 51% to 73% for people with type 1 and up to 69% for those with type 2 with intensive insulin therapy. Most valued features included reminders for missed insulin doses (4.4 ± 0.7), bolus dose suggestions (4.1 ± 0.8), integration with continuous glucose monitoring (CGM) apps (4.1 ± 0.8), and temperature alerts (3.7 ± 1.0). Basal insulin suggestions were considered less important (3.3 ± 1.1). No significant differences were found between physicians and diabetes educators. Major barriers included preference for disposable pens (57%), limited device options (54%), and high cost (53%). Among DE respondents, concerns over cost reimbursement rose compared to the 2024 dt-report. Smart pens are underutilized compared to expectations. Cost and reimbursement remain the predominant barriers, while reminder functionality stands out as the most valued feature.

Anatomical preservation is essential for teaching and research; however, conventional formaldehyde-based techniques present limitations due to toxicity, volatility and environmental impact. Plastination provides excellent morphological quality, but its high cost, reliance on flammable solvents and requirement for specialized equipment limit its accessibility. This study proposes a low-cost alternative technique for the preservation of hearts and lungs using internal application of poly(vinyl acetate) (PVAc) followed by air drying. Organs from two canines, one ovine and one lagomorph were injected with PVAc, fixed in 3.7% formaldehyde for 72 h, and subsequently dehydrated at room temperature for approximately 30 days. The resulting specimens maintained their three-dimensional conformation, exhibited reduced weight, absence of odour and good resistance to handling, and allowed subsequent painting for didactic purposes. Despite some tissue darkening, overall morphological integrity was preserved, producing specimens suitable for anatomical demonstration. This technique represents a simple, reproducible and cost-effective alternative to traditional plastination, significantly reducing formaldehyde exposure and eliminating the need for flammable solvents or complex laboratory infrastructure.

Research advances in biosynthesis of trans-4-hydroxy-L-proline.

Microsurgery is a specialized field within plastic surgery constrained by the high cost and limited availability of surgical microscopes, particularly in resource-limited settings. This lack of access hinders trainees from developing essential microsurgical skills. Previous efforts have explored smartphone-based alternatives, but there remains a need for high-fidelity, accessible training microscopes. This study presents a novel, low-cost, travel-friendly surgical microscope designed for microsurgery training. Modified binocular objective lenses enable near-field stereoscopic viewing using a dual-mirror array. A 3D-printed chassis provides the correct top-down orientation, and an integrated light source operates on standard or battery power, ensuring usability in low-resource environments. Initial testing demonstrated a fixed 6.5× magnification, allowing trainees to perform end-to-end anastomoses on 2-mm vessels. Prototypes were deployed for microsurgery training in the United States, Rwanda, Ethiopia, and Vietnam through the SHARE (Surgeons in Humanitarian Alliance for Reconstruction, Research and Education) plastic surgery organization, Nuoy Reconstructive International, and the senior author's home institution. The authors' investigation continues to assess the effectiveness of the microscope compared with state-of-the-art surgical microscopes. By offering a low-cost, portable solution without compromising image quality, this innovation has begun to transform microsurgical education and operating room-based microscopy worldwide, increasing accessibility for trainees and patients in diverse settings.

Rhinoplasty can achieve both aesthetic and functional improvements by altering the internal and external structures of the nose. Given the complex anatomy and significant individual variability of the nasal structure, rhinoplasty requires high precision. 3D printing technology, with its advantages of personalization and rapid prototyping, is increasingly being applied in the field of nasal reconstruction. This technology allows for the creation of three-dimensional models from patient imaging data, enhancing preoperative planning and simulation, enabling custom prosthetic design, and providing intraoperative guidance. Additionally, it aids in postoperative evaluation and care, while providing preoperative training models for surgeons. Clinical applications demonstrate that 3D printing can shorten surgical time, reduce complications, and improve patient satisfaction. However, 3D printing still faces several challenges, including insufficient imaging accuracy, high costs, and technical limitations in bioprinting. Future advancements are needed in imaging and modeling technologies, the development of advanced biomaterials, and cost reduction to further enhance and expand the application of 3D printing in rhinoplasty.

Invisible signals, visible dilemmas: The ethical frontiers of liquid biopsy in precision oncology.

The development of appropriate microsurgical and supermicrosurgical skills is essential for reconstructive surgeons. Training courses frequently employ in vivo models, which have various drawbacks: Limited availability, high cost, and/or ethical conflicts. To overcome these limitations, we looked for an inert model that was analogous to the gold standard in vivo, surpassing the classic ex vivo models at the same time. We studied the ex vivo rabbit as an animal training model by means of 10 specimen dissections, microscopically analyzing the mean caliber and length of its main vascular pedicles and comparing them to those of the most common flaps and recipient vessels employed in reconstructive surgery. We designed a routine with increasingly difficult exercises, which we propose as a training plan. The rabbit's main vascular pedicles have a mean caliber of 0.4 mm (internal mammary), 0.8 mm (iliolumbar), 0.9 mm (brachial), 1.2 mm (femoral), 1.5 mm (renal), 1.9 mm (common carotid), and 2.8 mm (aorta). They allow for a progressive increase in the level of complexity, as well as the practice of a wide variety of techniques (end-to-end anastomosis between vessels of different sizes, end-to-side anastomosis, neurorrhaphies, nerve transfers, ortho- and heterotopic replants, and free flaps). The ex vivo rabbit serves as a valid alternative to other recognized high-fidelity microsurgical models, overcoming the limitations of in vivo-it is easily accessible, inexpensive, and inert-as well as ex vivo-it offers a wide range of calibers and the possibility of practicing advanced techniques-models which have been used in the past.

Strictosidinic acid is a key intermediate in the biosynthetic pathway of camptothecin, a plant alkaloid that serves as a precursor for semisynthetic anticancer drugs. At the moment, camptothecin is mainly sourced from trees, causing limited supply and high costs. Improving access to strictosidinic acid would help to elucidate yet unknown biosynthetic steps downstream of this intermediate and in the long term enable sustainable production of camptothecin in heterologous hosts. While structurally similar to the common monoterpene indole alkaloid precursor strictosidine, strictosidinic acid has not been the target of metabolic engineering efforts before. Here, we present a strategy to produce strictosidinic acid from glucose and tryptophan in engineered yeast. First, we create a basic strain that generates 75 mg/L strictosidine. We further optimise this strain by introducing a membrane steroid binding protein and a second copy of the farnesyl pyrophosphate synthase mutant gene ERG20WW, boosting strictosidine levels by 5.5-fold to 398 mg/L. At these higher titres, a previously overlooked shunt product, (2E,6E)-2,6-dimethylocta-2,6-dienedioic acid (DOA), was identified that diverts flux from the pathway. Lastly, we reprogrammed our strictosidine strain to strictosidinic acid production by four genomic modifications. Final fed-batch cultivation in shake flasks resulted in 843 mg/L strictosidine or 548 mg/L strictosidinic acid, respectively, after 168 h. Taken together, our work now grants access to strictosidinic acid by metabolic engineering, while revealing strategies to further enhance the production of strictosidine and related monoterpene indole alkaloids. These findings will help to produce plant alkaloids in microbial cell factories in the future at scale.

Monitoring whale vocalization is of scientific importance and has practical value for marine ecology, hydroacoustics, and geophysics. Conventional monitoring approaches, including hydrophone arrays, ocean-bottom seismometers, and satellite tagging, are limited by sparse spatial coverage, potential biological disturbance, and high cost. Distributed acoustic sensing (DAS) is an emerging method that uses submarine optical cables as dense acoustic arrays, potentially enabling large-scale, high-resolution monitoring of whale vocalization. We investigated the features of the wavefields of fin whale vocalization by integrating DAS observations with numerical modeling. Three distinct features-insensitive response segments (IRSs), high-frequency component loss, and acoustic notches-were identified in the observed wavefields. DAS response modeling based on ray theory indicates that the length of the IRS is correlated positively with the vertical distance between the source and cable, and the gauge length is responsible for the high-frequency loss in whale calls. Furthermore, wavefield modeling using the spectral-element method demonstrates that the notches represent transitions between transmission zones of waterborne multipath waves entering the seafloor and are sensitive to the seafloor P-wave velocity, water depth, and bathymetry. These findings not only improve our understanding of DAS-observed wavefields but also highlight the potential of DAS for ocean environmental parameter estimation and three-dimensional whale localization.

Design and characterization of modified RNA G-quadruplex for Tl+ ion leaching: Insights from computer simulations.

CST-Based Molecular Profiling of Vaginal Microbiota Validated by qRT-PCR and 16S Amplicon Sequencing.

BackgroundStroke remains a leading cause of long-term disability worldwide. Robotic-assisted rehabilitation, particularly with the Hybrid Assistive Limb (HAL), has emerged as an innovative approach to enhance motor recovery and functional outcomes. HAL is a wearable exoskeleton that detects bioelectrical signals and provides real-time support, offering unique opportunities for task-specific and intensive neurorehabilitation.ObjectiveThis narrative review summarizes recent clinical evidence on the application of HAL in stroke rehabilitation, focusing on its effects on gait, upper limb recovery, activities of daily living (ADL), and safety, while discussing its limitations and future directions.MethodsA literature search of PubMed and Scopus was conducted for studies investigating HAL-assisted rehabilitation in stroke patients. Eligible studies included randomized controlled trials, systematic reviews, pilot studies, and relevant narrative reviews.ResultsEvidence from randomized and non-randomized studies suggests that HAL-assisted rehabilitation can improve gait velocity, balance, and, to a lesser extent, upper limb function in both acute and chronic stroke populations. Several systematic reviews and RCTs (2022-2025) have confirmed its potential benefits compared to conventional physiotherapy, though findings remain heterogeneous. HAL is generally safe and well tolerated, but high costs, limited availability, and methodological variations across studies constrain generalizability.ConclusionHAL-assisted rehabilitation represents a promising adjunct to conventional stroke therapy, with growing evidence supporting its efficacy in motor recovery. However, current data are limited by small sample sizes, inconsistent protocols, and lack of long-term follow-up. Large-scale, multicenter randomized controlled trials are warranted to establish its clinical utility, cost-effectiveness, and integration into routine care.

Diabetes mellitus affects over 589million adults globally, with projections exceeding 900million by 2050. Conventional antidiabetic therapies are limited by adverse effects, high cost, and single-target pharmacology. Endophytic microorganisms, fungi and bacteria residing asymptomatically within plant tissues, represent an underexplored yet structurally diverse reservoir of bioactive metabolites developed through co-evolutionary adaptation with their hosts. This scoping review aimed to systematically map the breadth and depth of available evidence on: (1) the antidiabetic biochemical mechanisms of endophyte-derived metabolites; (2) bioprospecting and biotechnological discovery strategies; and (3) key translational barriers to clinical application, to identify research priorities and knowledge gaps. A systematic search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and ScienceDirect covering January 2016 to March 2026, supplemented by hand-searching of reference lists. The Boolean search strategy combined endophyte-specific, antidiabetic, and metabolite-related terms. Studies were screened against explicit inclusion and exclusion criteria following PRISMA for Scoping Reviews (PRISMA-ScR) guidelines. A total of 747 records were identified; following duplicate removal and two-stage screening, 123 studies were included in the final synthesis. Included studies documented seven principal antidiabetic mechanisms of endophyte-derived metabolites: (1) inhibition of α-glucosidase and α-amylase; (2) enhancement of GLUT4 translocation via the IRS1/PI3K/Akt/GSK3β axis; (3) AMPK activation suppressing hepatic gluconeogenesis; (4) PPARγ agonism improving insulin sensitivity; (5) antioxidant protection of pancreatic β-cells from ROS-induced apoptosis; (6) anti-inflammatory modulation of TNF-α, IL-6, and IL-1β via NF-κB/MAPK pathways; and (7) multi-target engagement. Bioprospecting strategies, including OSMAC, genomic mining, co-culture systems, and AI-assisted discovery, are accelerating compound identification. Key translational barriers include inconsistent metabolite yields, strain instability, regulatory complexity, and unresolved intellectual property disputes. Endophytic microorganisms constitute a compelling and sustainable source of multi-target antidiabetic compounds. This review provides the first PRISMA-ScR compliant synthesis of the field, offering clinicians, natural product researchers, pharmaceutical scientists, and policymakers a rigorous evidence base for prioritising endophyte-derived lead compounds for preclinical and clinical development. Substantial knowledge gaps remain in the in vivo validation, clinical translation, and equitable access frameworks for microbial resources from biodiverse regions.

Traditional oral formulations often lead to significant fluctuations in plasma drug concentrations. In contrast, oral osmotic pumps achieve zero-order drug release driven by osmotic pressure, which is largely independent of physiological variables, offering an effective solution to optimize drug delivery outcomes. This review aims to summarize the structural types, functional mechanisms, and key factors influencing drug release of oral osmotic pumps, compare their performance disparities, and provide valuable references for subsequent research and development in this field. Oral osmotic pump systems were classified based on their structural designs, their mechanisms of action and key drug release-influencing factors were elaborated, and the characteristics and application potential of different systems were comparatively evaluated. Oral osmotic pump systems can be categorized into single-chamber, multi-chamber, and specific types, with push-pull osmotic pumps particularly suitable for poorly soluble drugs and targeted systems enabling site-specific therapy. Drug properties, osmotic pressure, semipermeable membrane characteristics, and release orifice parameters are critical factors governing drug release. Despite advantages such as stable release profiles and broad applicability, the system is limited by complex preparation processes and high costs. Oral osmotic pumps represent a highly valuable drug delivery technology. Future integration with intelligent technologies and advanced materials is expected to overcome existing challenges, facilitating more precise and efficient drug delivery.

Chimeric antigen receptor (CAR) T-cell therapy is a new type of highly precise and targeted immunotherapy for urological diseases. It has demonstrated significant therapeutic potential in chronic and autoimmune kidney diseases such as renal fibrosis and membranous nephropathy. However, owing to its high cost, low efficiency, and serious side effects, such as cytokine storm syndrome, a new generation of drugs has emerged to solve these problems. In vivo CAR T-cell therapy is a treatment method that directly modifies specific cells within the patient's body through various delivery systems. Nonviral vectors (nanoparticles and exosomes) and viral vectors (adeno-associated viruses and lentiviruses) can be engineered to achieve better therapeutic effects. By taking advantage of different delivery systems and minimizing their drawbacks, in vivo CAR T-cell therapy can improve the stability and targeting ability, reduce immunogenicity, and minimize side effects. This review summarizes the mechanisms of action and clinical applications of various delivery systems used in in vivo CAR T-cell therapy, highlighting their potential in the treatment of urological diseases. Through a deeper understanding of the construction and optimization of well-designed platforms, the development of optimal delivery systems has valuable implications for the establishment of new pharmaceuticals for in vivo CAR T-cell therapy in urological diseases.

Femoral version deformities are key in the diagnostic evaluation of young patients with hip pain. While computed tomography (CT) and magnetic resonance imaging (MRI) are commonly used for femoral version assessment, their limitations include a lack of standardized reference values, high costs, and accessibility constraints. An accessible and reproducible alternative is needed, particularly in the context of joint-preserving hip surgery. To evaluate the reliability and reproducibility of femoral version measurements on the modified Budin view, to compare these measurements with 4 established cross-sectional imaging methods (CT or MRI), and to determine the diagnostic accuracy of the modified Budin view in identifying abnormal femoral version. Case series; Level of evidence, 4. The authors retrospectively analyzed the records of 93 patients (107 hips; mean age, 31 ± 9 years [range, 16-55 years]; 43 female hips [40%]) evaluated for joint-preserving hip surgery at a specialized tertiary center. Femoral version was measured using the modified Budin view and compared to 4 cross-sectional imaging methods (CT and MRI) using Bland-Altman analysis and diagnostic accuracy metrics. The mean femoral version measured on the modified Budin view was 13°± 7° (95% CI, 12°-14°). The technique demonstrated excellent intra- and interobserver reliability (ICC, 0.99 and 0.98, respectively). Compared to the Reikerås method, the mean difference was 1°± 4° (95% CI, 0°-2°; P = .042; Bonferroni-corrected significance level, P < .01). The mean differences were 3°± 5° (95% CI, 2°-3°) for the Lee method, 11°± 5° (95% CI, 10°-12°) for the Tomczak method, and 12°± 6° (95% CI, 11°-14°) for the Murphy method (all P < .001). Diagnostic accuracy for detecting abnormal femoral version was high, with an area under the curve ranging from 0.88 to 0.98 and a consistently high negative predictive value (91%-100%). The modified Budin view is a highly reliable and accessible radiographic method for femoral version measurement in young patients undergoing joint-preserving hip surgery. It closely reflects the femoral neck version as measured by the Reikerås method, and demonstrates high diagnostic accuracy for detecting abnormal femoral version, making it a valuable screening tool for femoral version deformities in clinical practice.