Search Results (832)

Localised cutaneous leishmaniasis (LCL) is a common neglected tropical disease in Ethiopia, which is mainly treated with intralesional (IL) pentavalent antimonial such as sodium stibogluconate (SSG) and/or cryotherapy. Both treatments are painful, and studies are lacking on the pain associated with these or affected individuals’ experiences of them. A cross-sectional, observational study was conducted at ALERT Comprehensive Specialized Hospital, Addis Ababa/Ethiopia. The socio-demographic and clinical data of individuals affected by LCL receiving IL SSG and/or cryotherapy was gathered, and their treatment was observed. Participants quantified their treatment-associated pain using the Wong–Baker Pain Scale. Health-related quality of life was measured using the (Children’s) Dermatology Life Quality Index. Adverse effects, participant experiences with local therapies, and dermatologists’ experiences and opinions of local LCL treatment were assessed using structured questionnaires. Of the thirty-six individuals with LCL included (64% male, 14% children), 52% reported a treatment-associated pain score ≥ 8. Cryotherapy administered with a cotton bud was associated with lower pain scores ≤ 6 (odds ratio: 0.15, 95% confidence interval: 0.03–0.89) compared to a cryotherapy spray device. There was wide variation in treatment administration. Local LCL treatment is painful, and most individuals experience significant pain. This study highlights the need for less painful but effective treatments, structured training, and clear standard operating procedures. Full article

Introduction: Near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) is now widely regarded as a valuable aid in decision-making for complex hepatobiliary procedures, with increasing support from recent studies. Methods: We performed a systematic review following PRISMA guidelines, utilizing PubMed, CINAHL, and EMBASE databases to locate studies on the perioperative use ICG in pediatric hepatobiliary surgeries. Two independent reviewers assessed all articles for eligibility based on predefined inclusion criteria. We collected data on study design, patient demographics, surgical indications, ICG dosing, timing of ICG injection, and perioperative outcomes. Results: Forty-three articles, including 930 pediatric patients, from 1989 to 2025 met the inclusion criteria for narrative synthesis in our systematic review, of which 22/43 (51.2%) were retrospective studies, 15/43 were case reports (34.9%), 3/43 (7.0%) were experimental studies, and the other three were prospective comparative studies (7.0%). The current clinical applications of ICG in hepatobiliary pediatric surgery include bile duct surgery (cholecystectomy, choledochal cyst, biliary atresia), reported in 17 articles (39.5%), liver tumor resection, reported in 15 articles (34.9%), liver transplantation, reported in 6 articles (14.6%), and liver function determination, reported in 5 articles (12.2%). Conclusions: ICG fluorescence navigation in pediatric hepatobiliary surgery is a highly promising and safe technology that allows for the intraoperative localization of anatomic biliary structures, aids in the identification and resection of liver tumors, and can accurately determine hepatic function. The lack of comparative and prospective studies, and the variability of the dose and timing of administration are the main limitations. Full article

Data scarcity hampers the implementation of circular economy (CE) in rural historical small towns (HSTs) where traditional agricultural practices persist outside formal monitoring systems. In this regard, this study proposes and tests an estimation framework to quantify agricultural waste flows and energy recovery potential. The methodology combines waste generation coefficients from peer-reviewed literature with administrative data to generate actionable CE assessments. Application to four Sicilian HSTs within the Local Action Group (LAG) “Terre dell’Etna e dell’Alcantara” exhibits substantial waste generation potential despite their small size. The agricultural enterprises generate an estimated 6930–7130 tons of annual agricultural waste under moderate production scenarios, comprising grape pomace (3250 tons), pruning residues (3030 tons), and mixed processing wastes (650–850 tons). The energy recovery potential ranges from 20–30 TJ through direct combustion to 4.9–8.1 TJ via anaerobic digestion. Sensitivity analysis indicates balanced contributions from all three key parameters (enterprise density, yields, and waste coefficients), each accounting for 31–35% of output variance. The framework provides resource-constrained municipalities with a cost-effective tool for preliminary CE assessment, enabling identification of priority interventions without expensive primary data collection. From a managerial perspective, local administrators can leverage this tool to transform routine administrative data into actionable CE strategies. Full article

Background/Objectives: After many years of research and the successful development of therapeutic products by a few industrial actors, the COVID-19 vaccines brought messenger RNAs, as well as other nucleic acid modalities, such as antisense oligonucleotides, small interfering RNA, and aptamers, into the spotlight, eliciting renewed interest from both academia and industry. However, owing to their structure, relative “fragility”, and the (usually) intracellular site of action, the delivery of these therapeutics has frequently proven to be a key limitation, especially when considering endosomal escape, which still needs to be overcome. Methods: By compiling delivery-related data on approved and late clinical-phase ribonucleic acid therapeutics, this review aims to assess the delivery strategies that have proven to be successful or are emerging, as well as areas where more research is needed. Results: In very specific cases, some strategies appeared to be quite effective, such as the N-acetylgalactosamine moiety in the case of liver delivery. Surprisingly, it also appears that for some modalities, efforts in molecular design have led to more “drug-like” properties, enablingthe administration of naked nucleic acids, without any form of encapsulation. This appears to be especially true when local administration, i.e., by injection, is possible, as this provides de facto targeting and a high local concentration, which can compensate for the small proportion of nucleic acids that reach the cytoplasm. Conclusions: Nucleic acid-based therapeutics have come a long way in terms of their physicochemical properties. However, due to their inherent limitations, targeting appears to be crucial for their efficacy, even more so than for traditional pharmaceutical modalities. Full article

Preterm birth and the neonatal pathological sequelae that follow spontaneous preterm labor are closely associated with maternal and fetal inflammatory activation. Previous studies have indicated a role for the complement system in this inflammatory response. Utilizing an LPS inflammation-induced model of preterm birth, we investigated various delivery outcomes and their correlation with complement activation products within cervical, uterine, and fetal brain tissue after administration of LPS. We provide further evidence that complement-mediated inflammation within cervical and uterine tissue contributes to aberrant cellular changes and an increase in preterm delivery. We additionally show that a targeted complement inhibitor that specifically targets to sites of complement activation (CR2-Crry) mitigates the effects of LPS-induced pathology and preterm birth. Complement inhibition increased latency to delivery, mean gestational age at delivery, and average number of viable pups. Furthermore, the improved delivery outcomes seen with CR2-Crry treatment correlated with a reduced inflammatory response in maternal tissue and in fetal brain tissue in terms of reduced complement activation, reduced pro-inflammatory cytokines, and reduced macrophage recruitment. These data indicate that complement inhibition represents a potential therapeutic strategy for preventing preterm birth. The localization of complement inhibition by a site-targeting approach reduces the possibility of unwanted off-target effects. Full article

Amidst the dual challenges of escalating ecological environmental pressures and economic transformation globally, green innovation emerges as a pivotal pathway toward achieving high-quality sustainable development. To elucidate how digitalization and novel productive forces synergistically drive the green transition, the research utilizes panel data from 30 provincial-level administrative regions in China spanning 2009 to 2022, constructing a green innovation efficiency measurement frame-work grounded in the Super Slack-Based Measure (Super-SBM)model, alongside a novel productive forces evaluation system based on the triad of laborers, labor objects, and means of production. Employing spatial difference-in-differences and double machine learning methodologies within a quasi-natural experimental design, the research investigates the causal mechanisms through which digital empowerment and novel productive forces influence regional green innovation efficiency. The findings reveal that both digital empowerment and novel productive forces significantly enhance regional green innovation efficiency, exhibiting pronounced positive spatial spillover effects on neighboring regions. Heterogeneity analyses demonstrate that the promotive impacts are more pronounced in eastern provinces compared to central and western counterparts, in provinces participating in carbon trading relative to those that do not, and in innovation-driven provinces versus non-innovative ones. Mediation analysis indicates that digital empowerment operates by fostering the aggregation of innovative talent and elevating governmental ecological attentiveness, whereas new-type productivity exerts its influence primarily through intellectual property protection and the clustering of high-technology industries. The results offer empirical foundations for policymakers to devise coordinated regional green development strategies, refine digital transformation policies, and promote industrial structural optimization. Furthermore, this research provides valuable data-driven insights and theoretical guidance for local governments and enterprises in cultivating green innovation and new-type productivity. Full article

Community-Based Forest Management (CBFM) efforts are critical for sustainable natural resource governance in Northwest Ethiopia. This study investigated the various aspects of CBFM, emphasizing practical implementation in the context of the Awi Administrative Zone, Northwest Ethiopia. A structured questionnaire was handed out to 412 farmers across three districts—Dangila, Fagita Lokoma, and Banja. The quantitative data was analyzed using the Likert scale with SPSS version 23 software. Findings indicate that insufficient financial support (44%), limited community participation (30%), and weak institutional arrangements (19%) are the major factors impeding effective CBFM, with statistically significant regional variation (χ² = 242.8, df = 3, p = 0.000). On the other side, increased awareness and international support (34%) and enhanced local participation (36%) were the leading facilitators (χ² = 512.05, df = 11, p = 0.000). We look at the practical aspects of CBFM, from community-led conservation efforts to sustainable harvesting techniques, emphasizing the importance of indigenous knowledge alongside modern methodologies. The CBFM project in the northwest part of Ethiopia have facilitated biodiversity protection and environmental resilience by integrating local perspectives with broader developmental goals. However, obstacles such as land tenure, resource conflicts, and capacity restrictions continue, requiring adaptive methods and legislative reforms. This paper contributes to the ongoing discussion on sustainable natural resource management by offering empirical insights into the dynamics of CBFM in the Awi administrative zone of northwest Ethiopia. Full article

This study explores the fundamental components and specificities of agroforestry policies in France and Quebec, with a particular focus on the regions of Brittany and Montérégie. It uses a mixed-methods approach, combining an in-depth literature review and 14 semi-structured interviews with various stakeholders, including research institutions, agricultural advisory organizations, independent experts, and regional public agencies engaged in agroforestry and environmental initiatives. The collected data were qualitatively analyzed using word frequency and co-occurrence techniques, based on Elinor Ostrom’s Institutional Analysis and Development (IAD) framework. The results reveal that in France, agroforestry benefits from a well-structured policy environment, centered on the Common Agricultural Policy (CAP) and the Agroforestry Development Plan (PDA). The Breizh Bocage initiative is making a positive contribution to this, with more than 5000 km of hedges planted thanks to its localized governance model and direct community funding. In Quebec, agroforestry is also supported by various policies and programs such as Prime-Vert, with more than 2370 hedge planting projects completed. Despite its strengths, the French case, particularly the Breizh Bocage program, is limited by cumbersome administrative procedures. In both contexts, stakeholders emphasize the need to improve the transparency and efficiency of the program by simplifying administrative processes and harmonizing financial support mechanisms. Full article

Questionnaire data plays a key role in social research, especially when evaluating public attitudes using Likert-type scales. Yet, traditional analyses often merge some ordinal categories and exclude responses such as Don’t Know, No Answer, or Refused—risking the loss of valuable information. This study introduces BS-TOSIE (Belief Structure-Based TOPSIS for Survey Item Evaluation), a novel method that preserves and integrates all response types, including ambiguous ones. By combining the Belief Structure framework with the TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) method, BS-TOSIE offers a structured approach to ranking and evaluating individual survey items measured on an ordinal scale, even in the presence of missing or incomplete data. Response distributions are transformed into a belief structure vector, enabling comparison against ideal and anti-ideal benchmarks. We demonstrate this approach using data from the Quality of Life in European Cities survey to assess perceptions of local governance in European cities. This study analyzes changes in citizen satisfaction with local public administration across five key dimensions—timeliness, procedural clarity, fairness of fees, digital accessibility, and perceived corruption—in 83 European cities between 2019 and 2023. The findings reveal persistent regional disparities, with Northern and Western European cities consistently outperforming those in Southern and Eastern Europe, although some cities in Central Europe show signs of improvement. Zurich consistently received high satisfaction scores, while other cities, such as Rome and Palermo, showed lower scores. Unlike traditional methods, our approach preserves the full spectrum of responses, yielding more nuanced and interpretable insights. The results show that BS-TOSIE enhances both the clarity and depth of survey analysis, making a methodological contribution to the evaluation of ordinal data and offering empirical insights into public perceptions of local city administration. Full article

Background: Locally acting gastrointestinal (GI) drugs present challenges for generic drug development because traditional bioequivalence measures, which rely on systemic drug levels, do not reflect local efficacy. This review examines regulatory guidelines for establishing therapeutic equivalence for such drugs, using rifaximin—a minimally absorbed, gut-localized antibiotic—as a case study. Methods: We reviewed bioequivalence guidelines from the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA), along with the literature on rifaximin’s biopharmaceutical and clinical properties, to identify strategies and challenges for establishing equivalence for locally acting GI drugs. Results: Rifaximin exemplifies the limitations of standard bioequivalence methods: as a Biopharmaceutics Classification System (BCS) class IV drug with minimal absorption and low solubility, in vitro dissolution may not predict local drug availability. Clinical endpoint trials (e.g., traveler’s diarrhea, hepatic encephalopathy, IBS-D) are resource-intensive and insensitive to formulation differences. Pharmacokinetic (PK) studies in healthy volunteers show low, variable plasma levels, which may inaccurately discriminate between formulations. The EMA requires evidence of non-saturable absorption to accept PK data, a difficult-to-establish but potentially irrelevant criterion. Differences between FDA and EMA approaches highlight a lack of harmonization, complicating global generic development. Conclusions: A tailored, multifaceted approach is needed to demonstrate bioequivalence for GI-localized drugs like rifaximin. This case underscores the need for more sensitive surrogate methods (e.g. advanced in vitro or pharmacodynamic models) and flexible regulatory criteria. Harmonization across international guidelines and innovative bioequivalence study designs are key to facilitating the approval of safe and effective generic alternatives in this drug class. Full article

Background/Objectives: Sepsis is one of the most common causes of death worldwide, and its diagnosis remains a challenge for clinicians. The main purpose of this study was to appraise the diagnosis and antibiotic prescription pattern for sepsis admitted to the Emergency Department (ED), comparing Sepsis-2 to Sepsis-3 criteria. Methods: The study was conducted in an ED of a tertiary care medical center in Hungary. We included all adult patients who were diagnosed with sepsis in 2023. Data collection was made manually from UD MED System. Diagnosis was assessed based on Sepsis-2 and Sepsis-3 criteria, then compared. Further analyses were made only in cases with confirmed sepsis diagnosis. Antibiotic guideline adherence was determined according to the local guideline in force. Fisher’s exact test, t-test, and ANOVA were applied to compare categorical and continuous variables between groups. The Kaplan–Meier test was applied for probability of survival. Significant p-values were defined as below 0.05. Results: The substantial majority of patients recorded with sepsis in the ED met both the Sepsis-2 and Sepsis-3 criteria (80%), while the rate of misdiagnosis was similar (Sepsis-2: 16/91, 17.6% and Sepsis-3: 14/91, 15.4%). The most important identified risk factors in sepsis were old age (60+ years) and comorbidities (CCI ≥ 4). Elevated LDH (median 325 mg/dL) and decreased albumin levels (median 26 g/L) can be used as early indicators of sepsis. Although the time to first antibiotic administration was not associated with significantly better clinical outcomes, the guideline-adherent agent selection (Sepsis-2: 18/43, 41.9% and Sepsis-3: 19/46: 41.3%) led to a significantly longer survival (median 37 vs. 4 days). Conclusions: No significant differences were found in diagnostic accuracy or prediction of mortality between Sepsis-2 and Sepsis-3. Guideline-adherent antibiotics may lead to significantly higher survival rate in sepsis. Full article

The new energy vehicle (NEV) industry has become one of the most important industries in China’s economic development. Based on the panel data of 27 provincial administrative regions in China from 2011 to 2022, combined with the random effect panel of the Tobit model and the Bootstrap method to test the multiple intermediary paths, this paper studies the impact of new energy vehicle promotion (NEVP) in China on regional green development, taking into account the intermediary effect and regional heterogeneity of NEVP on the green development level (GDL). The results show that NEVP significantly promotes the GDL. The mediating effect of NEVP to improve local-level green development through the digital economy level is significant in the eastern region, while in the central and western regions, it is not significant. NEVP can significantly promote the upgrading of regional industrial structure and the construction of transportation infrastructure in the eastern, central, and western regions so as to improve the local GDL. Full article

Allocation models are essential tools for optimally distributing client requests across multiple services under defined restrictions and objective functions. This study evaluates several heuristics to address an allocation problem involving young individuals reaching voting age. A five-step methodology was implemented: defining variables, executing heuristics, compiling results, evaluating outcomes, and selecting the most effective heuristic. Using experimental data from the Mexican National Electoral Institute (INE), the study focuses on 88,107 individuals aged 17–18 in the 16 municipalities of the Toluca Valley, who can access any of the 10 INE service modules. Six heuristics were analyzed in sequence: genetic algorithm, ant colony optimization, local search, tabu search, simulated annealing, and greedy algorithm. The results indicate that genetic algorithm significantly reduces the processing time when used as the initial heuristic. Furthermore, given the current capacity of the 10 INE modules, serving the entire target population would require nine working days. These findings align with principles of spatial justice and highlight the practical efficiency of heuristic-based solutions in administrative resource allocation. The main contribution of this study is the development and evaluation of a hybrid heuristic framework for allocating INE modules, demonstrating that combining multiple heuristics—with a genetic algorithm as the initial phase—significantly improves solution quality and computational efficiency. Full article

(1) Background: Geospatial associations for COVID-19 mortality were estimated using a cohort of 28,128 hospitalized Medicaid patients identified from the 2020–2021 Kentucky Health Facility and Services administrative claims data. (2) Methods: County-level patient information (age, sex, chronic obstructive pulmonary disease [COPD], and mechanical ventilation use [96 hrs. plus]); social deprivation index (SDI) scores; physician and nurse rates per 100,000; and annual average particulate matter 2.5 (PM_2.5) were used as the predictors. Ordinary least-squares (OLS) regression and multiscale geographically weighted regression (MGWR) with the dependent variable, COVID-19 mortality per 100,000, were performed to compute global and local effects, respectively. (3) Results: MGWR (adjusted R²: 0.52; corrected Akaike information criterion [AICc]: 292.51) performed better at explaining the association between the dependent variable and predictors than the OLS regression (adjusted R²: 0.36; AICc: 301.20). The percentages of patients with COPD and who were mechanically ventilated (96 hrs. plus) were significantly associated with COVID-19 mortality, respectively (OLS standardized βCOPD: 0.22; βventilation: 0.53; MGWR mean βCOPD: 0.38; βventilation: 0.57). Other predictors were not statistically significant in both models. (4) Conclusions: A risk of COVID-19 mortality was observed among patients with COPD and prolonged mechanical ventilation use, after controlling for social determinants, the healthcare workforce, and PM_2.5 in rural and Appalachian counties of Kentucky. These counties are characterized by persistent poverty, healthcare workforce shortages, economic distress, and poor population health outcomes. Improving population health protection through multisector collaborations in rural and Appalachian counties may help reduce future health burdens. Full article

Public welfare land allocation in China’s land expropriation process plays a crucial role in balancing economic development with social equity, but limited research has examined the driving factors influencing public welfare land ratio determination from a central–local relationship perspective. This study investigates how central–local government interactions shape public welfare land ratios in China’s land development process. Based on a comprehensive analysis of land expropriation data across different regions and administrative levels, we examine the spatial heterogeneity and underlying mechanisms of public welfare land allocation. The results reveal the following: (1) Significant regional variations exist for regional public welfare land ratios, with the national average public welfare land ratio reaching 41.21% in 2019 (for plots ≥4 hectares), varying from 39.60% in eastern regions to 44.93% in western regions. (2) Administrative hierarchy influences allocation patterns, with county-level cities (43.73%) showing higher proportions than provincial capitals (36.42%). (3) Local governments strategically use public welfare land development as an instrument to expand land-based fiscal resources by attracting investments and population. (4) Provincial governments serve as crucial intermediaries in central–local policy implementation, balancing central mandates with local conditions. This study contributes to the land governance literature by providing empirical evidence on how institutional arrangements affect land resource allocation. The findings suggest that establishing unified national standards while allowing provincial-level adaptations would improve the effectiveness of public welfare land policy in the post-land finance era, enhancing both governance efficiency and public welfare outcomes. Full article