Search Results (23,422)

Triple-negative breast cancer (TNBC) urgently requires new therapeutic strategies due to the limited efficacy of conventional treatments. Recently, PANoptosis, an integrated form of apoptosis, necroptosis, and pyroptosis, has emerged as a promising target in cancer therapy, though effective agents remain scarce. Paclitaxel, a Taxus-derived natural product, is often combined with other drugs to enhance efficacy, yet optimal combinations are limited. This study investigates the synergistic antitumor effects of paclitaxel and cephalomannine in TNBC, focusing on oxygen-regulated cell death pathways. Network pharmacology and molecular docking revealed that the combination targets multiple cell death- and inflammation-related proteins, including BCL2L1, MAPK14, SYK, TNF, and ADAM17, suggesting multi-target synergy. In vitro, the combination significantly inhibited MDA-MB-231 cell viability, proliferation, and migration, while inducing apoptosis and necrosis. Mechanistically, co-treatment markedly increased intracellular ROS levels and γ-H2AX expression, indicating oxidative stress and DNA damage, both of which were reversible by ROS inhibition. Further analysis demonstrated that the treatment activated the p38 and p53 pathways, regulated the Bax/Bcl-2 ratio, and initiated mitochondrial apoptosis. It also promoted RIPK1/RIPK3/MLKL phosphorylation and MLKL membrane translocation, triggering necroptosis, as well as upregulated NLRP3, cleaved Caspase-1, and GSDMD, inducing pyroptosis. The use of specific inhibitors partially reversed these effects, confirming the involvement of ROS-mediated PANoptosis. Similar antitumor effects were also observed in BT-549 cells, indicating the broad applicability of this combination in TNBC. MCF-10A cells exhibited mild but acceptable cytotoxicity, reflecting manageable side effects typical of chemotherapeutic agents. In vivo experiments further validated the combination’s antitumor efficacy and safety. In summary, paclitaxel and cephalomannine synergistically induce PANoptosis in TNBC through oxygen-regulated cell death pathways, offering a novel therapeutic strategy based on oxidative stress modulation by natural compounds. Full article

Letrozole, a third-generation aromatase inhibitor initially developed for breast cancer, has become the preferred first-line agent for ovulation induction (OI), particularly in women with polycystic ovary syndrome (PCOS). This narrative review critically evaluates the efficacy, safety, and clinical applications of letrozole across diverse infertility contexts. Compared to clomiphene citrate, letrozole is associated with higher ovulation and live birth rates, a lower risk of multiple gestation, and a more favorable endometrial environment. Its pharmacokinetics—marked by transient estrogen suppression and a short half-life—limit embryonic exposure, supporting its favorable safety profile. Emerging data from large, randomized trials and meta-analyses demonstrate no increase in congenital anomalies, miscarriage, or adverse perinatal outcomes in letrozole-conceived pregnancies. Moreover, maternal side effects are generally mild, and the risk of ovarian hyperstimulation syndrome is low. Letrozole has also shown utility in mild stimulation protocols, fertility preservation for estrogen-sensitive malignancies, and clomiphene-resistant PCOS. Key clinical strategies—such as early-cycle initiation, lowest effective dosing, and individualized monitoring—optimize therapeutic outcomes while minimizing potential risks. While long-term offspring data remain limited and mechanistic concerns persist, current evidence robustly supports letrozole as a safe and effective option for OI, balancing reproductive success with maternal–fetal safety across a range of infertility indications. Full article

This study investigates the effect of polymer film lamination on the tensile performance of wood fiber-reinforced polypropylene (WP) composites. Neat polypropylene (PP) and WP containing 25 wt% wood fiber were injection-molded and laminated with 0.1 mm PP or polyethylene terephthalate (PET) films using a compatible adhesive. Four configurations were examined: unlaminated (0S), single-sided half-length (1S-H), single-sided full-length (1S-F), and double-sided full-length (2S-F). Mechanical properties and fracture morphology were characterized by uniaxial tensile tests and scanning electron microscopy (SEM), alongside measurements of surface roughness. PET lamination produced the greatest strength enhancements, with 2S-F specimens achieving gains of 12% for PP and 21% for WP, whereas PP lamination gave minimal or negative effects, except for a 5% increase in WP. Strength improvements were attributed to surface smoothing and suppression of crack initiation, as confirmed by roughness measurements and SEM observations. PET’s higher stiffness and strength accounted for its superior reinforcement relative to PP. Fractographic analysis revealed flat regions near specimen corners—interpreted as crack initiation sites—indicating that lamination delayed crack propagation. The results demonstrate that PET film lamination is an effective and practical post-processing strategy for enhancing the mechanical performance of wood–plastic composites. Full article

In this study, high-yield biopolymer/ceramic hollow fibers were fabricated via a facile, modified polyol process in a spinneret setup, enabling the controlled adsorption of Cu²⁺ ions. Post sintering transformed these into catalytic copper-decorated carbon/ceramic (alumina) composite hollow fibers, with alginate serving as both a metal ion binder and a copper nanoparticle stabilizer. The resulting hollow fibers featured porous walls with a high surface area and were densely decorated with copper nanoparticles. Their structural and morphological characteristics were analyzed, and their NO reduction performance was assessed in a continuous flow configuration, where the gas stream passed through both the shell and lumen sides of a fiber bundle in a tangential flow mode. This study also examined the stability, longevity and regeneration potential of the catalytic fibers, including the mechanisms of deactivation and reactivation. Carbon content was found to be decisive for catalytic performance. High-carbon fibers exhibited a light-off temperature of 250 °C, maintained about 90% N₂ selectivity and sustained a consistently high NO reduction efficiency for over 300 h, even without reducing gases like CO. In contrast, low-carbon fibers displayed a higher light-off temperature of 350 °C and a reduced catalytic efficiency. The results indicate that carbon enhances both activity and selectivity, counterbalancing deactivation effects. Owing to their scalability, durability and effectiveness, these catalytic fibers and their corresponding bundle-type reactor configuration represent a promising technology for advanced NO abatement. Full article

Self-myofascial release tools like foam rollers and massage guns are being integrated into athlete warm-ups with increasing frequency, but evidence on their acute effects is limited. Sixteen healthy, trained athletes (23.2 ± 1.3 years; four female) completed three warm-up conditions in a randomised, crossover design separated by >48 h: dynamic warm-up plus foam rolling (FOAM), dynamic warm-up plus massage gun (GUN), and dynamic warm-up alone (CON). After each intervention, participants completed a countermovement jump (CMJ; height and reactive strength index [RSImod]), a 10/5 repeated jump test (RJT), a 20 m sprint, and a knee-to-wall ankle mobility test. Perceived soreness and fatigue were recorded. Linear mixed models and Cohen’s d were used to assess between-condition differences. Relative to CON, FOAM and GUN were associated with reduced CMJ height (d = −0.29 to −0.36) and RSImod (d = −0.40 to −0.52; p’s < 0.05). GUN was associated with significantly impaired sprint time (d = 0.34). There were modest improvements in ankle mobility (left side) following FOAM (d = 0.23, p < 0.05) and lower levels of muscle soreness compared to CON (p < 0.05). Despite some improvements in ankle mobility and muscle soreness with foam rolling, both foam rolling and massage gun use may acutely impair aspects of physical performance compared to a dynamic warm-up alone. Full article

Aromatase inhibitors (AIs), with or without gonadotropin-releasing hormone analogs, are the cornerstone of adjuvant endocrine therapy for women with hormone receptor-positive early-stage breast cancer, offering significant reductions in recurrence risk and improving long-term survival. Their use is frequently accompanied by treatment-related toxicities that can adversely affect patients’ quality of life (QoL) and adherence to therapy. Commonly reported side effects include vasomotor symptoms, such as hot flashes; musculoskeletal disorders, such as arthralgia and myalgia; mood disorders; and genitourinary discomfort, such as vaginal dryness and dyspareunia. Additionally, AIs are associated with a heightened risk of bone loss, leading to osteoporosis and fractures, and may have implications for cardiovascular health. Effective management of these adverse events is pivotal in maintaining treatment adherence and preserving QoL. Evidence-based strategies to address these toxicities include pharmacological interventions, such as analgesics for joint pain, bisphosphonates or denosumab for bone health, and hormonal or non-hormonal approaches for vasomotor and genitourinary symptoms. Non-pharmacological measures, including physical activity, dietary adjustments, and complementary therapies, can also help mitigate symptoms. This review examines the broad spectrum of AI-associated toxicities, discusses their clinical implications, and provides an overview of evidence-based management strategies. These insights aim to support clinicians in optimizing patient care while minimizing the toxicities of therapy. Full article

Carboxytherapy is a non-invasive therapeutic method involving the transcutaneous or subcutaneous administration of carbon dioxide (CO₂), which stimulates microcirculation, neoangiogenesis, and collagen production. This narrative review summarizes the latest scientific findings (2020–2025) on the effectiveness of carboxytherapy in treating selected dermatological and aesthetic skin conditions, including periorbital dark circles, stretch marks, scars, and signs of skin aging. The article discusses both monotherapies and combination protocols, particularly with laser therapies and chemical peels. Numerous clinical studies confirm that carboxytherapy significantly improves skin elasticity, tone, hydration, and structure through mechanisms such as improved oxygenation, stimulation of fibroblasts, and controlled inflammation. Moreover, combination therapies frequently offer superior outcomes, especially in scar and stretch mark reduction. Carboxytherapy demonstrates high safety, minimal side effects, and broad applicability, making it a valuable tool in both medical and cosmetic dermatology. Full article

Background: The rise of opioid drug usage in the U.S. correlates with increasing recognition of gastrointestinal side effects, especially in the esophagus. The literature has recently noted that abnormalities in the upper esophageal sphincter (UES) are a poor prognostic factor in Achalasia treatment response. A better understanding of the relationship between opioid therapy and esophageal motility and sphincter function may shape our management guidelines for esophageal dysmotilities. This study aimed to evaluate dysmotility patterns, specifically UES function, among the veteran population, where opioid use is reportedly high. Methods: We performed a retrospective search of all the veterans at a large urban veteran affairs hospital who had undergone esophageal manometry from 2013 to 2022, collecting data on patient demographics, indication for procedure, diagnosis, sphincter pressure values, and presence of chronic opioid use. Results: Of 395 patients, 29% had a history of chronic opioid therapy. Notably, patients that were diagnosed with Achalasia had a greater proportion of chronic opioid use as compared to those who were not. Additionally, there was a statistically significant lower average upper esophageal resting pressure in opioid patients compared to non-opioid patients. Conclusions: Veteran patients with Achalasia have a greater proportion of chronic opioid use as compared to those without. There are significant manometric pressure differences at the upper esophageal sphincter among chronic opioid users when compared to non-opioid users. Full article

Background/Objectives: Laparoscopic appendectomy (LsA) is a standard acute surgical procedure typically performed under general anesthesia (GA). However, GA is associated with side effects such as hemodynamic instability and postoperative nausea/vomiting. Regional anesthesia (RA) has gained attention as an effective alternative in such surgeries, as it reduces surgical stress responses, provides adequate postoperative analgesia, and promotes early mobilization. This study evaluates the effectiveness of the combined use of spinal anesthesia (SA) and transversus abdominis plane block (TAPB) in LsA procedures. Methods: This retrospective observational study included 220 patients who underwent LsA between 2020 and 2023. Patients were divided into two groups: Group 1 (n = 110) received bilateral TAPB, and Group 2 (n = 110) received unilateral TAPB, both under SA. Postoperative pain was assessed using the Visual Analog Scale (VAS), and outcomes such as time to first analgesic requirement, analgesic consumption, and patient satisfaction were recorded. Results: This study evaluated the effects of SA combined with TAPB in LsA. Bilateral TAPB significantly prolonged the time to first analgesic request (13.7 vs. 12.1 h; p = 0.001) and reduced analgesic requirements (p = 0.008) compared to unilateral TAPB. VAS scores were significantly lower in Group 1 at the 9th and 12th hours postoperatively (p = 0.003 and p = 0.039). Although overall satisfaction scores were similar, a higher proportion of patients in Group 1 reported being “very satisfied” or “excellent” (55.5% vs. 42.7%). Conclusions: The combination of spinal anesthesia and bilateral TAPB is a safe and effective anesthetic strategy for LsA. Compared to unilateral TAPB, it offers superior postoperative analgesia and improved patient satisfaction. Full article

The Amur tiger (Panthera tigris altaica) is a flagship and umbrella species of forest ecosystems in northeastern Asia. Climate change is profoundly and irreversibly affecting wildlife habitat suitability, especially for large mammals. To effectively protect the Amur tiger, it is necessary to understand the impact of climate change on the quality and the connectivity of its habitat. We used the species distribution models combined with the latest Shared Socioeconomic Pathway (SSP) climate scenarios to predict current and future changes in habitats and corridors. We found the following: (1) The total area of the Amur tiger’s suitable habitat currently amounts to approximately 4941.94 km², accounting for 27.64% of the study area represented by two adjacent national parks. Among these habitats, the highly suitable areas are mainly located on the both sides of the Sino-Russian border. The landscape connectivity remains relatively stable, and the degree of fragmentation in highly suitable habitats is low. (2) Although the suitable habitat of the Amur tiger shows an expansion trend under most climate scenarios (excluding SSP3-7.0), the area of suitable habitat within the entire study region does not increase significantly. Therefore, we should implement conservation measures to facilitate the continued expansion of suitable habitat for the Amur tiger. The quantity and length of landscape connectivity corridors are expected to vary in response to changes in core habitat patches, while the centroid of highly suitable habitats is also expected to shift to different extents. In such circumstances, new ecological corridors need to be constructed, while existing natural ecological corridors should be preserved. Full article

Context and objective: Post-amputation pain (PAP) is an umbrella term that includes residual limb pain (RLP) and phantom limb pain (PLP), posing a significant challenge to recovery and quality of life after limb loss. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has gained interest for its potential to manage PAP, particularly in refractory cases. This narrative review explores the efficacy of ketamine for PAP and the emerging role of pharmacogenomics in guiding its use. Methods: A literature review of PubMed, Embase, and Cochrane databases was conducted, focusing on clinical trials, systematic reviews, and genetic influences on ketamine metabolism and response. Studies suggest that perioperative ketamine can reduce PAP severity and opioid use. However, outcomes vary, with some patients experiencing transient relief and others achieving prolonged benefit. Results: This variability may be linked to genetic differences in CYP2B6, CYP3A4/5, COMT Val158Met, SLC6A2, and KCNS1, which affect ketamine’s metabolism, efficacy and side effect profile. Understanding these pharmacogenomic factors could enable more personalized and effective ketamine therapy. Conclusion: Despite its promise, inconsistent dosing regimens and limited integration of genetic data hinder standardization. Further research into genotype-guided ketamine protocols may improve treatment outcomes and support precision analgesia in amputee care. Full article

Dry eye disease (DED) is a prevalent and disabling condition. Artificial tears are commonly used but often inadequate for moderate-to-severe cases. Secretagogues such as pilocarpine, cevimeline, and diquafosol offer potential alternatives, though their comparative effectiveness remains unclear. To evaluate the safety and efficacy of these secretagogues versus artificial tears in adults with DED, we searched CENTRAL, PubMed, Scopus, LILACS, ClinicalTrials.gov, and WHO ICTRP without language restrictions. Randomized controlled trials (RCTs) comparing secretagogues to artificial tears were eligible. Data extraction and synthesis were conducted using Covidence and the Cochrane RoB 2 tool, and 19 RCTs (n = 2697) were included. Fifteen were analyzed quantitatively; however, only eight trials evaluating diquafosol were suitable for meta-analysis, as data for pilocarpine and cevimeline were insufficient for quantitative synthesis. GRADE was used to assess evidence certainty. PROSPERO registration: CRD42020218407. Diquafosol significantly improved rose bengal staining at 4 weeks and OSDI scores and TBUT in post-cataract patients at 4 and 12 weeks. However, it increased mild adverse events (RR, 1.81; 95% CI, 1.15–2.84). Evidence for pilocarpine and cevimeline was limited. Diquafosol 3% shows greater efficacy than artificial tears in post-cataract DED but with more side effects. Further research is needed for other secretagogues. Full article

Skin cancer is the most common cancer form worldwide, and it is primarily divided into melanoma and non-melanoma types, with non-melanoma being the most prevalent condition. Cutaneous squamous cell carcinoma (cSCC) accounts for 50% of primary skin cancers and is characterized by uncontrolled keratinocyte proliferation. cSCC’s current standard treatment is surgical resection and chemotherapy. Unfortunately, these methods often lead to disfigurement, functional morbiditly, and compromised function. In contrast to immunotherapy, emerging scenarios have shown promising results, especially in neoadjuvant settings. Cemiplimab (Libtayo^®; Regeneron, Tarrytown, NY, USA), a PD-1 monoclonal antibody, has shown efficacy in treating advanced or metastatic cSCC, and its use as a neoadjuvant therapy has been recently explored. This review aims to evaluate Cemiplimab in the neoadjuvant setting for cSCC treatment. The Methodology followed PRISMA guidelines, this review analyzed studies on Cemiplimab as a neoadjuvant therapy for cSCC that were sourced from PubMed, Web of Science, and Scopus. Only controlled trials, cohort studies, case series, and systematic reviews were included. From 341 records, 21 studies were included, and six clinical trials provided key data about neoadjuvant Cemiplimab’s response rates, efficacy, adverse effects, and safety considerations. The targeted data revealed a neoadjuvant Cemiplimab mean pathologic response rate of 72%, with a 62% objective response rate. Treatment-related adverse events (TRAEs) affect 66% of patients, though most cases are not severe. The most common include fatigue, maculopapular rash, and diarrhea. The studies showed high rates of complete pathological responses (cPRs) and major pathological responses (mPRs), suggesting a strong therapeutic potential. Neoadjuvant Cemiplimab for cSCC therapy shows high response rates, low recurrence, improved survival, and manageable side effects. The current literature indicates that Cemiplimab may also be effective when used in immunosuppressed patients. Despite more research still being needed to confirm its long-term benefits and the effects of the drug’s use outside of clinical trials, there is strong evidence to consider neoadjuvant Cemiplimab as a promising and efficient treatment. Full article

Fractal theory provides a powerful tool for quantifying complex geometric patterns such as concrete cracks. The box-counting method is widely employed for fractal dimension (FD) calculation due to its intuitive principles and compatibility with image data. However, two critical limitations persist in existing studies: (1) the selection of scale parameters (including minimum measurement scale and cutoff scale) lacks systematization and exhibits significant arbitrariness; (2) insufficient attention to the sensitivity of counting origins compromises the stability and comparability of FDs, severely limiting reliable engineering application. To address these limitations, this study first employs classical fractal images and crack samples to systematically analyze the impact of four minimum measurement scales (2, $\sqrt{2}$, 3, $\sqrt{3}$) and three cutoff scale coefficients (cutoff-to-minimum image side ratios: 1, 1/2, 1/3) on computational accuracy. Subsequently, the farthest point sampling (FPS) method is adopted to select counting origins, comparing two optimization strategies—Count-FD-Mean (mean of fits from multiple origins) and Count-Min-FD (fit using minimal box counts across scales). Finally, the optimized approach is validated through static loading tests on concrete beams. Key findings demonstrate that: the optimal scale combination (minimum scale: $\sqrt{2}$; cutoff coefficient: 1) yields a mere 0.5% average error from theoretical FDs; the Count-Min-FD strategy delivers the highest stability and closest alignment with theoretical values; FDs of beam cracks increase continuously with loading, exhibiting an exponential correlation with midspan deflection that effectively captures crack evolution; uncalibrated scale parameters and counting strategies may induce >40% errors in inferred mechanical parameters; results stabilize with 40–45 counting origins across three tested fractal patterns. This work advances standardization in fractal analysis, enhances reliability in concrete crack assessment, and provides critical support for the practical application of fractal theory in structural health monitoring and damage evaluation. Full article

Aim of the Study: To determine whether adding a lateral extra-articular tenodesis (LET) to primary anterior cruciate ligament reconstruction (ACLR) lowers graft-failure risk and improves functional recovery in competitive athletes with high-grade pivot-shift. Methods: Multicentre retrospective cohort with 1:1 propensity-score matching (age, sex, sport, graft, centre). Competitive athletes with pivot-shift grade ≥ 2 who underwent primary ACLR with hamstring or bone–patellar tendon–bone (BPTB) autografts (2018–2024) were eligible. The primary outcome was graft failure within 24 months (composite of revision ACLR, symptomatic rotatory laxity with pivot-shift ≥ 2 plus KT-1000 > 5 mm, or MRI-confirmed rupture). Time-to-event was summarised with Kaplan–Meier (KM) curves and log-rank tests. Secondary outcomes included residual rotatory laxity and functional performance (single-leg hop, side hop, Y-Balance) analysed as the proportion achieving Limb Symmetry Index ≥ 90% at 6 and 24 months and as continuous LSI means. Two-sided α = 0.05; secondary outcomes were prespecified without multiplicity adjustment. Results: Of 1368 ACL reconstructions screened, 97 eligible athletes were identified; 92 were analysed after matching (46 isolated ACLR; 46 ACLR + LET; mean follow-up 30.0 ± 4.2 months). KM survival at 24 months was 95.7% after ACLR + LET versus 82.6% after isolated ACLR (log-rank p = 0.046). The absolute risk reduction was 13.0% (Number Needed to Treat 8; 95% CI 4→∞). In graft-type subgroups, failures were 6/32 vs. 1/30 for hamstring and 2/14 vs. 1/16 for BPTB (ACLR vs. ACLR + LET, respectively); there was no evidence of interaction (Breslow–Day p = 0.56). At 6 months, a higher proportion of ACLR + LET athletes achieved LSI ≥ 90% across tests—single-leg hop 77.8% vs. 40.9% (p = 0.0005), side hop 62.2% vs. 34.9% (p = 0.012), Y-Balance 84.4% vs. 59.1% (p = 0.010), with a larger mean LSI (between-group differences +8.2 to +9.1, all p < 0.001). By 24 months, threshold attainment largely converged (all p ≥ 0.06), while mean LSI differences persisted but were smaller (+3.9 to +4.9, all p ≤ 0.001). Conclusion: In competitive athletes with high-grade pivot-shift undergoing accelerated, criteria-based rehabilitation, adding LET to primary ACLR was associated with lower graft-failure risk and earlier functional symmetry, with consistent effects across hamstring and BPTB autografts. Given the observational design, causal inference is limited; confirmation in randomized and longer-term studies is warranted. Full article