Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer of the oral cavity, pharynx, larynx and upper airway. HNSCC is subdivided into distinct clinical entities based on the presence or absence of high-risk human papillomavirus (HPV) infection. While HPV-positive HNSCC patients respond better to conventional and targeted therapies than HPV-negative cases, recurrence is more frequent in HPV-negative cases with limited treatment options. Ferroptosis is a form of iron-based programmed cell death caused by excessive lipid peroxide accumulation. Biomarkers of ferroptosis have proven useful for identifying and triggering ferroptosis in models of treatment-resistant cancers. Identifying and understanding ferroptosis biomarker function in HPV-negative HNSCC allows the possibility for more effective treatment strategies. Methods: Literature searches combined with the public online ferroptosis database FerrDB V3 were utilized for the objective identification and classification of established and non-established ferroptosis biomarkers in HPV-negative HNSCC. Additional novel biomarkers were identified based on known roles in HNSCC oncogenesis. Results: A total of 30 ferroptosis biomarkers were identified associated with HPV-negative disease. Biomarkers were grouped according to shared biological functions, with each marker summarized for prognostic and mechanistic roles in HNSCC ferroptosis. Conclusions: The described biomarkers present a means for stratifying tumors for ferroptotic induction, with several offering potential novel methods for overcoming refractory HPV-negative disease. These biomarkers may warrant further investigation into devising future patient-tolerant strategies that selectively activate ferroptosis in HPV-negative HNSCC.

To address the difficulty in controlling the filtration performance of water-based drilling fluids under high-temperature and high-salinity conditions during the drilling of deep and ultra-deep wells, a salt-responsive micro-crosslinked polymer gel filtration loss reducer, designated LZX, was developed. The synthesis employed 2-acrylamido-2-methylpropane sulfonic acid (AMPS), N,N-dimethylacrylamide (DMAA), dimethyldiallylammonium chloride (DMDAAC), and a betaine monomer containing an unsaturated double bond as monomers, with polyethylene glycol diacrylate (PEGDA) introduced as a crosslinker. Experimental results showed that the product structure matched the design expectations, and the thermal decomposition temperature of the main molecular chain exceeded 290 °C, indicating good thermal stability. At 220 °C under saturated salt conditions, a dosage of 2.5 wt% LZX maintained the API filtration loss at 5.8 mL and the HPHT filtration loss at 28.6 mL. Comparative experiments at different temperatures demonstrated that LZX exhibited superior filtration control performance compared to the commercial high-temperature filtration reducer Driscal Temp and Driscal D. The micro-crosslinked structure of LZX enhanced the rigidity of the molecular chains, raising the upper limit of its thermal resistance. Rheological and viscosity-average molecular weight measurements revealed that LZX exhibited typical antipolyelectrolyte behavior in high-salinity environments-the molecular chains tended to extend and the filtration reduction capability was accordingly maintained-preliminarily achieving a functional transition from passive salt tolerance to active salt responsiveness. LZX is expected to support the construction of high-performance water-based drilling fluids with high temperature and high salt resistance for future deep-earth drilling.

Objective To evaluate the validity, safety, and feasibility of automated algorithm-based arterial occlusion pressure (AOP) measurement compared to pulsed wave Doppler ultrasound across supine, seated, and standing positions.Approach This two-phase sequential study enrolled healthy adults. In Phase One (n=46), AOP was measured using both automated and Doppler ultrasound methods at three body positions in randomized order. Validity was assessed using intraclass correlation coefficients (ICC), Bland-Altman analysis, and proportional bias testing. Safety was evaluated through measurement duration and pain perception. Feasibility was assessed by the first-attempt success rate. In Phase Two (n=15), a post hoc study examined whether averaging two automated measurements improved accuracy in supine position.Main results Automated algorithm-based AOP measurement demonstrated good agreement withDoppler ultrasound in supine (ICC=0.76), seated (ICC=0.87), and standing (ICC=0.83) positions. However, 95% limits of agreement ranged from -38 to +48 mmHg across positions. A significant negative proportional bias was observed in supine (p=0.031), indicating underestimation at higher AOP values. Automated measurements required significantly longer duration than Doppler across all positions (p<0.001). Pain perception was comparable between methods. First-attempt success rate was significantly lower for automated measurement in standing compared to Doppler method (87% vs. 100%, p=0.041). In Phase Two, 73% of participants demonstrated improved accuracy when averaging two automated measurements.Significance Automated algorithm-based arterial occlusion pressure (AOP) assessment demonstrates acceptable validity and safety when performed in seated and standing positions, supporting its use for individualized pressure prescription in these postures. However, clinicians and practitioners should exercise caution when determining AOP in the supine position, as proportional bias and reduced agreement with Doppler ultrasound may result in underestimation at higher AOP values. When measuring AOP in standing positions, providing external support (e.g., upper limb support on a stable surface) to reduce lower limb muscle activation may improve first-attempt success rates.

Intensive vegetable production can increase the transfer of persistent toxic trace elements from agricultural soils into the food chain, particularly where agrochemical use, irrigation inputs, and local geochemical conditions are insufficiently characterized. This study was undertaken to assess toxic trace-metal contamination levels in soils and vegetables from two renowned vegetable-producing subdistricts-Shibganj and Kahaloo-in the Bogra district, Bangladesh. The study also estimated potential human health risks by evaluating the dietary intake of these elements. It measured Pb, Ni, Cd, and Cr content in six vegetables and their respective farm soils using an atomic absorption spectrophotometer (AAS). The average concentrations of Pb, Ni, Cd, and Cr in farm soils of Shibganj and Kahaloo subdistricts were 158.3 ± 8.83, 31.5 ± 5.25, 0.43 ± 0.08, and 14.1 ± 2.16 µg g[-1] and 164.1 ± 4.60, 35.7 ± 6.91, 0.53 ± 0.14, and 9.37 ± 2.87 µg g[-1], respectively. Soils collected from all locations in both subdistricts of Bogra fall under 'moderate' ecological risk. Regarding the pollution load index (PLI), 66.7% of Shibganj and 75.0% of Kahaloo sampling sites had a PLI > 1.0, confirming that 'metal pollution exists.' Based on the calculated bioconcentration factors (BCFs), Cr and Cd show a high tendency to migrate from soil to various vegetables in the study area, though the mean Cd BCF for brinjal in Shibganj exceeded 1.0 due to a single high observation. The results demonstrated that the edible parts of potatoes, onions, and chilies accumulate significant amounts of toxic trace elements. The calculated mean daily intake of Pb and Cr in all vegetables ranged from 0.33 to 1.21 mg person[-1] day[-1] and from 0.10 to 0.64 mg person[-1] day[-1], respectively, exceeding the upper tolerable intake limits. Similarly, dietary intake of potatoes showed both non-carcinogenic and carcinogenic risks, while brinjal showed only carcinogenic risks for adults. Redundancy analysis (RDA) indicates that the measured soil parameters are strong predictors of the response variables (trace element content in various vegetables). Overall, the results identified Pb-dominated soil contamination and human exposure to Pb and Cr associated with vegetables as the principal concerns. To address these issues, priority actions should be given to source apportionment and testing of various agricultural inputs. Additionally, before implementing site-specific remediation or issuing consumption advisories, these risks should be validated through metal speciation and bioaccessibility analyses.

Bees are key global pollinators but face long-term exposure to pesticide residues. Although the western honey bee (Apis mellifera) shows tolerance to the persistent organic pollutant DDT, the underlying molecular basis remains unclear. Glutathione S-transferases (GSTs) are important detoxification enzymes in bees, yet direct evidence for their involvement in pesticide metabolism remains limited. In insects, Delta- and Epsilon-class GSTs are typically associated with xenobiotic detoxification. However, the A. mellifera genome encodes only a single Delta-class GST, AmGSTD1, and lacks the Epsilon class, suggesting that AmGSTD1 may play an important role in xenobiotic detoxification in honey bees. Here, we combined genetic, biochemical, and computational analyses to investigate the role of AmGSTD1 in DDT detoxification. Silencing of AmGSTD1 in A. mellifera increased susceptibility to DDT stress, whereas transgenic expression of AmGSTD1 in Drosophila melanogaster conferred increased DDT tolerance. Enzyme kinetics and HPLC analyses demonstrated that recombinant AmGSTD1 protein catalyzed the biotransformation of DDT to DDE, while molecular docking further supported the interaction between AmGSTD1 protein and DDT. AmGSTD1 protein was also associated with alleviation of oxidative stress under DDT exposure. Furthermore, the A170V mutation was identified as an important factor affecting the detoxification activity of the AmGSTD1 protein. Overall, these findings provide functional evidence that AmGSTD1 protein contributes to DDT detoxification through both xenobiotic biotransformation and oxidative stress regulation. This study improves our understanding of the molecular mechanisms underlying pesticide tolerance in honey bees.

Upper limb spasticity is a common and disabling complication of stroke. Botulinum toxin type A (BoNT-A) is widely used for focal spasticity treatment, but naturally derived products may present limitations related to immunogenicity and manufacturing variability. Recombinant botulinum toxin type A, produced by genetic engineering without complexing proteins, may provide improved product consistency. This Ib/II study evaluated the safety, tolerability, and preliminary efficacy of recombinant botulinum toxin type A in adults with post-stroke upper limb spasticity. This multicenter, seamless Ib/II clinical study included an open-label dose-escalation Ib phase and a randomized, double-blind, placebo-controlled II phase. Adult patients with post-stroke upper limb spasticity received a single intramuscular injection of recombinant botulinum toxin type A or placebo. The primary endpoint in Phase II was the change from baseline in the Modified Ashworth Scale (MAS) score of the primary target muscle group at Week 4. Secondary endpoints included MAS and Tardieu scale changes in individual muscle groups, Disability Assessment Scale (DAS), Physician's Global Assessment (PGA), and immunogenicity. The Ib phase showed improvements in MAS, DAS, and PGA, indicating an early efficacy signal. In Phase II, recombinant botulinum toxin type A produced a significant reduction in MAS score of the primary target muscle group at Week 4 compared with placebo, with effects sustained through Week 12. At Week 4, the PGA score in the Eveotox® group showed a statistically significant improvement compared with the placebo group. While MAS and PGA scores showed significant improvement, DAS functional scores did not differ statistically from the placebo group at week 4. The treatment was generally well tolerated, and low incidence of antibodies were observed. Recombinant botulinum toxin type A was safe and effective in reducing post-stroke upper limb spasticity after a single administration. These results support further Phase III clinical evaluation.

Stroke-related shoulder subluxation is a common musculoskeletal complication that may interfere with upper limb rehabilitation and negatively affect recovery. Although previous studies have reported beneficial effects of sling suspension-based exercise programs for post-stroke shoulder subluxation, limited information is available regarding their detailed clinical application, treatment progression, and individual patient response. This case report describes the outcome of a physiotherapy intervention in a 45-year-old male with left hemiparesis following a right-sided intraparenchymal hemorrhage with intraventricular extension. The patient was evaluated four months after the neurological event and presented with shoulder pain, increased muscle tone, restricted shoulder mobility, and inferior shoulder subluxation. Shoulder subluxation was assessed using a standardized tape measurement of the distance between the acromion process and the humeral head, which was 18 mm at baseline. A four-week rehabilitation program was implemented, comprising sling suspension-based active shoulder exercises, scapular stabilization exercises, and weight-bearing activities. The intervention was progressively advanced according to the patient's tolerance and clinical response. Therapy sessions were conducted for 30 minutes per day, five days per week. Following the intervention, the distance between the acromion process and the humeral head decreased from 18 mm to 11 mm, indicating improved shoulder alignment and reduced shoulder subluxation. Improvements were also observed in shoulder pain, muscle tone, active shoulder range of motion, and functional use of the affected upper extremity. These findings suggest that a multimodal rehabilitation program incorporating sling suspension-based active shoulder exercises may be associated with improved shoulder alignment and favorable clinical outcomes in individuals with post-stroke shoulder subluxation. However, the specific contribution of each intervention component cannot be determined from a single case report. Further studies involving larger samples and controlled study designs are required to establish the effectiveness and generalizability of these findings.

Environmental complexity can reduce overlap in resource use by generating fine-scale spatial variation, allowing species to occupy distinct microhabitats. Mixed intertidal shores, where rocky substrates alternate with sandy patches, are highly heterogeneous systems that provide benthic organisms with wide physical, chemical, and structural heterogeneity. In such environments, substrate use may reflect species-specific microhabitat preferences that facilitate species coexistence. However, species distributions can also be influenced by their tolerance of proximity to conspecific and heterospecific competitors. Here, we examined how social conditions affect microhabitat use in two competing intertidal hermit crab species. We first determined each species' preference among four intertidal microhabitats defined by substrate type and exposure conditions (sand, upper submerged rock surfaces, under-rock microhabitats, and air-exposed rock surfaces) under solitary conditions. We then evaluated how their microhabitat use changed as a function of competition with conspecifics versus heterospecifics, and as a function of competitor density. The two species differed significantly in their microhabitat preferences: Clibanarius albidigitus, which is typically associated with the upper intertidal, primarily occupied the upper side of submerged rocks, whereas the mid-intertidal species Calcinus californiensis preferred under-rock microhabitats. Both species largely avoided sandy and fully air-exposed microhabitats. The microhabitat use of C. californiensis was largely unaffected by competition, while C. albidigitus occupied its preferred habitat significantly less often under intra-specific competition but was not affected by inter-specific competition. The contrasting microhabitat preferences exhibited by the two species likely limit direct interspecific competition. Therefore, habitat segregation is largely structured by environmental conditions and intrinsic microhabitat preferences rather than direct interference, while population density exerts little influence on spatial organization.

Pulmonary carcinoid (PC) tumors are rare, well-differentiated neuroendocrine neoplasms of the lung with indolent progression and limited therapeutic consensus in advanced stages. While surgery remains the mainstay for localized disease, optimal management strategies for progressive or unresectable cases remain debated. A case of a 56-year-old man diagnosed with a left upper lobe PC was presented. Initial treatment consisted of platinum-based chemotherapy followed by traditional Chinese medicine. Upon disease progression, he received thoracic radiotherapy, achieving transient stabilization. However, subsequent radiologic surveillance revealed enlargement of mediastinal lymph nodes, prompting the initiation of a triple-modality systemic regimen comprising lobaplatin, the PD-1 inhibitor sintilimab, and the antiangiogenic agent anlotinib. After two treatment cycles, follow-up imaging demonstrated marked lymph node regression with satisfactory tolerability. This case highlights the potential therapeutic value of integrating chemotherapy, immunotherapy and antiangiogenic therapy in advanced PCs, particularly when standard surgical approaches are unfeasible. Although randomized data remain scarce, experience suggests that multimodal systemic therapy may offer disease control in selected patients. Further prospective studies are warranted to refine treatment paradigms for this uncommon malignancy.

Background/Objectives: Severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) frequently coexist and are associated with type 2 inflammation, leading to poor symptom control and high healthcare burden. Biologic therapies targeting IL-4Rα and IL-5/IL-5R have shown efficacy in type 2 inflammatory asthma and CRSwNP, but comprehensive evidence on their efficacy, safety, and research trends is limited. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating dupilumab, mepolizumab, benralizumab, or reslizumab in patients with type 2 inflammatory asthma and/or CRSwNP. Primary outcomes included lung function (FEV1), symptom control (ACQ, SNOT-22, nasal polyp score), and serious adverse events (SAEs). Risk of bias was assessed using the Cochrane RoB 2.0 tool. Publication bias was evaluated with funnel plots and Trim-and-Fill analysis. Bibliometric analysis was performed to identify publication trends and emerging research directions. Results: A total of 23 RCTs involving 8758 participants were included. Biologic therapy was not associated with a significant increase in serious adverse events (RR = 1.15, 95% CI: 0.89-1.50). Compared with control treatment, biologics significantly improved FEV1 (MD = 100.67 mL, 95% CI: 65.94-135.40) and ACQ scores (MD = -0.40, 95% CI: -0.54 to -0.25). In patients with CRSwNP and comorbid asthma, biologics also improved SNOT-22 scores (MD = -13.16, 95% CI: -24.85 to -1.47) and nasal polyp scores (MD = -1.31, 95% CI: -1.95 to -0.68). Dupilumab trials showed larger reductions in nasal polyp score than IL-5/IL-5R-targeted trials, although this indirect comparison should be interpreted cautiously. Bibliometric analysis indicated increasing research attention to upstream epithelial targets such as TSLP. Conclusions: Both IL-4Rα and IL-5/IL-5R-targeted biologics are effective and well-tolerated in type 2 inflammatory airway diseases. IL-4Rα inhibition shows favorable upper-airway outcomes in CRSwNP with asthma, but head-to-head trials are needed to clarify its comparative efficacy relative to IL-5/IL-5R-targeted therapies. Emerging research directions are shifting toward upstream epithelial alarmin antibodies.

Background/Objectives: Malnutrition affects 20-71% of patients with head and neck cancer (HNC), owing to tumor location, treatment-induced toxicities, and systemic inflammation. Enteral nutrition is preferred when oral intake is inadequate, yet standard powdered formulas require labor-intensive reconstitution and carry a contamination risk. PSU Blen, a ready-to-drink chicken-protein-based polymeric formula, was developed to address these limitations. Methods: In this single-center study, thirty clinically stable patients with HNC on tube feeding were randomized 1:1 to PSU Blen or a commercial powdered polymeric formula (Blendera) for 4 weeks. The primary outcome was change in Patient-Generated Subjective Global Assessment (PG-SGA) score from baseline to week 4, analyzed under a prespecified non-inferiority framework (margin δ = 2 points, selected as a clinically acceptable upper bound based on published PG-SGA data). Secondary outcomes were handgrip strength, body weight, body mass index, serum albumin, hemoglobin, and platelet count. Results: The mean change in PG-SGA score was -1.13 (SD 0.92) and -0.87 (SD 1.36) in the PSU Blen and Blendera groups; the between-group difference was -0.27 points (two-sided 90% CI: -0.99 to +0.45), with the upper bound below the non-inferiority margin. Sensitivity analyses yielded consistent results. No significant between-group differences were observed for secondary outcomes, and both formulas were well tolerated, with no gastrointestinal intolerance or serious adverse events. Conclusions: PSU Blen demonstrated non-inferior nutritional outcomes based on the PG-SGA endpoint over 4 weeks, with comparable tolerability. Longer-term and multicenter studies are warranted to further evaluate its clinical utility and practical advantages in routine enteral nutrition practice.