Health care resource use and costs in patients with food allergies: a United States insurance claims database analysis.

Aims: Food allergies impose a large clinical and financial burden on patients and the health care system. However, little is known about the factors associated with health care resource use and costs. The aim of this study was to investigate health care resource use and costs in individuals with food allergies utilizing health care in the United States.Methods: We conducted a retrospective analysis of insurance claims data from the Merative™ MarketScan® Research Databases (indexed from January 1, 2015, to June 30, 2022). All-cause and food allergy-related health care resource use, direct medical, and out-of-pocket costs for medical services were estimated for 12 months post-index using International Classification of Diseases [ICD] codes.Results: Of 355,520 individuals with food allergies continuously enrolled in a health insurance plan for ≥12 months pre- and post-index, 17% had a food allergy-related emergency department visit and 0.9% were hospitalized. The top patient characteristics associated with all-cause and food allergy-related hospitalizations, all-cause costs, and food allergy-related outpatient visit costs was a Charlson Comorbidity Index score of ≥2. Food allergy-related direct medical and out-of-pocket costs were high among patients with a food allergy-related visit. Out-of-pocket cost per patient per year for outpatient visits, emergency department visits, and hospitalizations had an estimated mean of $1,631 for patients with food allergy-related visits, which is approximately 11% of the total costs for these services ($14,395 per patient per year).Limitations: Study limitations are primarily related to the nature of claims databases, including generalizability and reliance on ICD codes. Nevertheless, MarketScan databases provide robust patient-level insights into health care resource use and costs from a large, commercially insured patient population.Conclusion: The health care resource use of patients with food allergies imposes a burden on both the health care system and on patients and their families, especially if patients had comorbidities.

Microalgae-based biofertilizer improves fruit yield and controls greenhouse gas emissions in a hawthorn orchard.

Raising attentions have focused on how to alleviate greenhouse gas (GHG) emissions from orchard system while simultaneously increase fruit production. Microalgae-based biofertilizer represents a promising resource for improving soil fertility and higher productivity. However, the effects of microalgae application more especially live microalgae on GHG emissions are understudied. In this study, fruit yield and quality, GHG emissions, as well as soil organic carbon and nitrogen fractions were examined in a hawthorn orchard, under the effects of live microalgae-based biofertilizer applied at three doses and two modes. Compared with conventional fertilization, microalgae improved hawthorn yield by 15.7%-29.6% with a maximal increment at medium dose by root application, and significantly increased soluble and reducing sugars contents at high dose. While microalgae did not increase GHG emissions except for nitrous oxide at high dose by root application, instead it significantly increased methane uptake by 1.5-2.3 times in root application. In addition, microalgae showed an increasing trend in soil organic carbon content, and significantly increased the contents of soil dissolved organic carbon and microbial biomass carbon, as well as soil ammonium nitrogen and dissolved organic nitrogen at medium dose with root application. Overall, the results indicated that the live microalgae could be used as a green biofertilizer for improving fruit yield without increasing GHG emissions intensity and the comprehensive greenhouse effect, in particular at medium dose with root application. We presume that if lowering chemical fertilizer rates, application of the live microalgae-based biofertilizer may help to reduce nitrous oxide emissions without compromising fruit yield and quality.

Effects of different lactic acid bacteria on phenolic profiles, antioxidant capacities, and volatile compounds in purple sweet potato juice.

The effects of three strains of lactic acid bacteria (Lactobacillus plantarum, Lactobacillus rhamnosus, and Streptococcus thermophilus) on viable counts, physicochemical indicators, phenolic profiles, antioxidant capacities, and volatile compounds in purple sweet potato juice were investigated during fermentation. The results showed the viable count of three bacteria increased and exceeded 11 log CFU/mL after fermentation. At the end of fermentation, the purple sweet potato juice exhibited an increase in total phenolic and flavonoid content. In addition, lactic acid bacteria fermentation changed the phenolic profiles and enhanced antioxidant capacities. Moreover, Pearson's correlation analysis showed that DPPH, ABTS, and hydroxyl radical scavenging capacities were positively correlated with caffeic acid and vanillic acid content (p < 0.05). Furthermore, lactic acid bacteria fermentation improved the aroma complexity and sensory quality of purple sweet potato juice. In conclusion, this study provided useful information for the development of purple sweet potato juice fermented by lactic acid bacteria. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05959-5.

Bimanual Coordination in Individuals Post-stroke: Constraints, Rehabilitation Approaches and Measures: Systematic Review.

To couple or not to couple is a dilemma for the CNS when performing bimanual goal-directed actions. Numerous interacting individual and task-related constraints contribute to the issue of effective movement coordination, and their impact on the emerging actions must be inferred from valid methodologies. This is particularly important when examining coordination in individuals with stroke undergoing rehabilitation. The purpose of this review was to identify the different constraints that may impact inter-limb coupling, and the rehabilitation approaches implemented to enhance those actions. Also, the measures incorporated to examine the effects of rehabilitation methods were reviewed. A literature search was conducted using CINAHL, PubMed and PsycINFO. Following the PRISMA 2020 guidelines, 789 relevant studies were identified, with 20 articles fulfilling the established criteria. Results showed that the impact of sex, time after stroke, type of stroke, and age were not examined in any studies reviewed. In terms of task constraints, most did not examine bimanual coordination explicitly. Bimanual movement training was the most prevalent. Regarding the dependent variables, clinician-reported and performance based scales were frequently used, while only eight studies implemented kinematic analysis, and only three examined inter-limb organization. None made explicit inferences to the existing theories of inter-limb coordination. In conclusion, important individual and task constraints on inter-limb coordination were scarcely examined. Also, majority of the studies did not involve bimanual tasks, or any measures of inter-limb coupling, thus the inferences should be treated with caution. Conceptually, all studies were data driven.

Confinement-Induced Biocatalytic Activity Enhancement of Light- and Thermoresponsive Polymer@Enzyme@MOF Composites.

Metal-organic frameworks (MOFs) are favorable hosting materials for fixing enzymes to construct enzyme@MOF composites and to expand the applications of biocatalysts. However, the rigid structure of MOFs without tunable hollow voids and a confinement effect often limits their catalytic activities. Taking advantage of the smart soft polymers to overcome the limitation, herein, a protection protocol to encapsulate the enzyme in zeolitic imidazolate framework-8 (ZIF-8) was developed using a glutathione-sensitive liposome (L) as a soft template. Glucose oxidase (GOx) and horseradish peroxidase (HRP) were first anchored on a light- and thermoresponsive porous poly(styrene-maleic anhydride-N,N-dimethylaminoethyl methacrylate-spiropyran) membrane (PSMDSP) to produce PSMDSP@GOx-HRP, which could provide a confinement effect by switching the UV irradiation or varying the temperature. Afterward, embedding PSMDSP@GOx-HRP in L and encapsulating PSMDSP@GOx-HRP@L into hollow ZIF-8 (HZIF-8) to form PSMDSP@GOx-HRP@HZIF-8 composites were performed, which proceeded during the crystallization of the framework following the removal of L by adding glutathione. Impressively, the biocatalytic activity of the composites was 4.45-fold higher than that of the free enzyme under UV irradiation at 47 °C, which could benefit from the confinement effect of PSMDSP and the conformational freedom of the enzyme in HZIF-8. The proposed composites contributed to the protection of the enzyme against harsh conditions and exhibited superior stability. Furthermore, a colorimetric assay based on the composites for the detection of serum glucose was established with a linearity range of 0.05-5.0 mM, and the calculated LOD value was 0.001 mM in a cascade reaction system. This work provides a universal design idea and a versatile technique to immobilize enzymes on soft polymer membranes that can be encapsulated in porous rigid MOF-hosts. It also holds potential for the development of smart polymer@enzyme@HMOFs biocatalysts with a tunable confinement effect and high catalytic performance.

Gender-sensitive community weight-loss programmes to address overweight and obesity in men: a scoping review.

OBJECTIVES: To examine how gender-sensitive community weight-loss programmes have been used to address overweight and obesity in men and to identify what can be learnt from this rapidly evolving field. DESIGN: Scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping review checklist for reporting. DATA SOURCES: A database search was conducted using EBSCOhost (Academic Search Complete, CINAHL Complete, Global Health, Health Source: Consumer Edition, Health Source: Nursing/Academic Edition and Medline Complete), Google, Google Scholar, Open Access Theses and Dissertations platform and Scopus. ELIGIBILITY CRITERIA: All weight-loss programmes using a gender-sensitive approach to address men's overweight and obesity in community settings. DATA EXTRACTION AND SYNTHESIS: Narrative synthesis was conducted based on the research questions and objectives. Primary outcomes include operationalisation, context and concept of the gender-sensitive approach. Information was reviewed and extracted to Microsoft Excel by two reviewers. RESULTS: A total of 40 studies (28 quantitative, eight mixed methods and four qualitative) were identified from 4617 records. Gender-sensitive approaches were undertaken in a range of settings and contexts including professional sports clubs (n=21), non-professional sporting clubs (n=16), workplace-based (n=2) and commercial organisation-based (n=1). The most common analysis approaches were evaluating the effect of the programmes (n=31) where positive impact was predominantly shown (eg, up to 3.9 kg weight reduction at 3-month follow-up). Programmes (ie, Football Fans in Training) were short-term cost-effective (eg, the cost was £862-£2228 per 5% weight reduction at 12-month follow-up). Qualitative evidence highlights factors that influenced men's participation (eg, camaraderie) and identifies areas for improvement. CONCLUSION: The findings demonstrate that gender-sensitive programmes for men's weight loss have been effectively applied using a range of different approaches and in a range of different contexts. Further evidence is needed to confirm the effectiveness of the programmes across diverse groups of men.

Gut fungi of black-necked cranes (Grus nigricollis) respond to dietary changes during wintering.

BACKGROUND: Migratory birds exhibit heterogeneity in foraging strategies during wintering to cope with environmental and migratory pressures, and gut bacteria respond to changes in host diet. However, less is known about the dynamics of diet and gut fungi during the wintering period in black-necked cranes (Grus nigricollis). RESULTS: In this work, we performed amplicon sequencing of the trnL-P6 loop and ITS1 regions to characterize the dietary composition and gut fungal composition of black-necked cranes during wintering. Results indicated that during the wintering period, the plant-based diet of black-necked cranes mainly consisted of families Poaceae, Solanaceae, and Polygonaceae. Among them, the abundance of Solanaceae, Polygonaceae, Fabaceae, and Caryophyllaceae was significantly higher in the late wintering period, which also led to a more even consumption of various food types by black-necked cranes during this period. The diversity of gut fungal communities and the abundance of core fungi were more conserved during the wintering period, primarily dominated by Ascomycota and Basidiomycota. LEfSe analysis (P < 0.05, LDA > 2) found that Pyxidiophora, Pseudopeziza, Sporormiella, Geotrichum, and Papiliotrema were significantly enriched in early winter, Ramularia and Dendryphion were significantly enriched in mid-winter, Barnettozyma was significantly abundant in late winter, and Pleuroascus was significantly abundant in late winter. Finally, mantel test revealed a significant correlation between winter diet and gut fungal. CONCLUSIONS: This study revealed the dynamic changes in the food composition and gut fungal community of black-necked cranes during wintering in Dashanbao. In the late wintering period, their response to environmental and migratory pressures was to broaden their diet, increase the intake of non-preferred foods, and promote a more balanced consumption ratio of various foods. Balanced food composition played an important role in stabilizing the structure of the gut fungal community. While gut fungal effectively enhanced the host's food utilization rate, they may also faced potential risks of introducing pathogenic fungi. Additionally, we recongnized the limitations of fecal testing in studying the composition of animal gut fungal, as it cannot effectively distinguished between fungal taxa from food or soil inadvertently ingested and intestines. Future research on functions such as cultivation and metagenomics may further elucidate the role of fungi in the gut ecosystem.

A kinetics-coupled multi-surface complexation model deciphering arsenic adsorption and mobility across soil types.

The diversity of soil adsorbents for arsenic (As) and the often-overlooked influence of manganese (Mn) on As(III) oxidation impose challenges in predicting As adsorption in soils. This study uses Mössbauer spectroscopy, X-ray diffraction of oriented clay, and batch experiments to develop a kinetic coupled multi-surface complexation model that characterizes As adsorbents in natural soils and quantifies their contributions to As adsorption. The model integrates dynamic adsorption behaviors and Mn-oxide interactions with unified thermodynamic and kinetic parameters. The results indicate that As adsorption is governed by five primary adsorbents: poorly crystalline Fe oxides, well crystalline Fe oxides, Fe-rich clay, Fe-depletion clay, and organic carbon (OC). Fe oxides dominate As adsorption at low As concentrations. However, at higher As concentrations, soils from carbonate strata, with higher content of Fe-rich clay, exhibit stronger As adsorption capabilities than soils from Quaternary sediment strata. The enrichment in Fe-rich clay can enhance the resistance of adsorbed As to reduction processes affecting Fe oxides. Additionally, extensive redox cycles in paddy fields increase OC levels, enhancing their As adsorption compared to upland fields. This model framework provides novel insights into the intricate dynamics of As within soils and a versatile tool for predicting As adsorption across diverse soils.

A comprehensive prediction system for silkworm acute toxicity assessment of environmental and in-silico pesticides.

The excessive application and loss of pesticides poses a great risk to the ecosystem, and the environmental safety assessment of pesticides is time-consuming and expensive using traditional animal toxicity tests. In this work, a pesticide acute toxicity dataset was created for silkworm integrating extensive experiments and various common pesticide formulations considering the sensitivity of silkworm to adverse environment, its economic value in China, and a gap in machine learning (ML) research on the toxicity prediction of this species, which addressed the previous limitation of only being able to predict toxicity classification without specific toxicity values. A new comprehensive voting model (CVR) was developed based on ML, combined with three regression algorithms, namely, Bayesian Ridge (BR), K Neighbors Regressor (KNN), Random Forest Regressor (RF) to accurately calculate lethal concentration 50 % (LC50). Three conformal models were successfully constructed, marking the first combination of conformal models with confidence intervals to predict silkworm toxicity. Further, the mechanism by analyzing structural alerts was summarized, and identified 25 warning structures, 24 positive compounds and 14 negative compounds. Importantly, a novel comprehensive prediction system was constructed that can provide LC50 and confidence intervals, structural alerts analysis, lipid-water partition coefficient (LogP) and similarity analysis, which can comprehensively evaluate the ecological toxicity risk of substances to make up for the incomplete toxicity data of new pesticides. The validity and generalization of the CVR model were verified by an external validation set. In addition, five new, low-toxic and green pesticide alternatives were designed through 50,000 cycles. Moreover, our software and ST Profiler can provide low-cost information access to accelerate environmental risk assessment, which can predict not only a single chemical, but also batches of chemicals, simply by inputting the SMILES / CAS / (Chinese / English) name of chemicals.

Synthetic lethal CRISPR screen identifies a cancer cell-intrinsic role of PD-L1 in regulation of vulnerability to ferroptosis.

Despite the success of programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibition in tumor therapy, many patients do not benefit. This failure may be attributed to the intrinsic functions of PD-L1. We perform a genome-wide CRISPR synthetic lethality screen to systematically explore the intrinsic functions of PD-L1 in head and neck squamous cell carcinoma (HNSCC) cells, identifying ferroptosis-related genes as essential for the viability of PD-L1-deficient cells. Genetic and pharmacological induction of ferroptosis accelerates cell death in PD-L1 knockout cells, which are also more susceptible to immunogenic ferroptosis. Mechanistically, nuclear PD-L1 transcriptionally activates SOD2 to maintain redox homeostasis. Lower reactive oxygen species (ROS) and ferroptosis are observed in patients with HNSCC who have higher PD-L1 expression. Our study illustrates that PD-L1 confers ferroptosis resistance in HNSCC cells by activating the SOD2-mediated antioxidant pathway, suggesting that targeting the intrinsic functions of PD-L1 could enhance therapeutic efficacy.

Cellular and circuit architecture of the lateral septum for reward processing.

The lateral septum (LS) is composed of heterogeneous cell types that are important for various motivated behaviors. However, the transcriptional profiles, spatial arrangement, function, and connectivity of these cell types have not been systematically studied. Using single-nucleus RNA sequencing, we delineated diverse genetically defined cell types in the LS that play distinct roles in reward processing. Notably, we found that estrogen receptor 1 (Esr1)-expressing neurons in the ventral LS (LSEsr1) are key drivers of reward seeking via projections to the ventral tegmental area, and these neurons play an essential role in methamphetamine (METH) reward and METH-seeking behavior. Extended exposure to METH increases the excitability of LSEsr1 neurons by upregulating hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, thereby contributing to METH-induced locomotor sensitization. These insights not only elucidate the intricate molecular, circuit, and functional architecture of the septal region in reward processing but also reveal a neural pathway critical for METH reward and behavioral sensitization.

Antibody-drug conjugates in gastric cancer: from molecular landscape to clinical strategies.

Antibody-drug conjugates (ADCs) represent a crucial component of targeted therapies in gastric cancer, potentially altering traditional treatment paradigms. Many ADCs have entered rigorous clinical trials based on biological theories and preclinical experiments. Modality trials have also been conducted in combination with monoclonal antibody therapies, chemotherapies, immunotherapies, and other treatments to enhance the efficacy of drug coordination effects. However, ADCs exhibit limitations in treating gastric cancer, including resistance triggered by their structure or other factors. Ongoing intensive researches and preclinical experiments are yielding improvements, while enhancements in drug development processes and concomitant diagnostics during the therapeutic period actively boost ADC efficacy. The optimal treatment strategy for gastric cancer patients is continually evolving. This review summarizes the clinical progress of ADCs in treating gastric cancer, analyzes the mechanisms of ADC combination therapies, discusses resistance patterns, and offers a promising outlook for future applications in ADC drug development and companion diagnostics.

The intersection of the nervous system and breast cancer.

Breast cancer (BC) represents a paradigm of heterogeneity, manifesting as a spectrum of molecular subtypes with divergent clinical trajectories. It is fundamentally characterized by the aberrant proliferation of malignant cells within breast tissue, a process modulated by a myriad of factors that govern its progression. Recent endeavors outline the interplay between BC and the nervous system, illuminate the complex symbiosis between neural structures and neoplastic cells, and elucidate nerve dependence as a cornerstone of BC progression. This includes the neural modulations on immune response, neurovascular formation, and multisystem interactions. Such insights have unveiled the critical impact of neural elements on tumor dynamics and patient prognosis. This revelation beckons a deeper exploration into the neuro-oncological interface, potentially unlocking novel therapeutic vistas. This review endeavors to delineate the intricate mechanisms between the nervous system and BC, aiming to accentuate the implications and therapeutic strategies of this intersection for tumor evolution and the formulation of innovative therapeutic approaches.

Response to lowering plasma glucose is characterised by decreased oxyntomodulin: Results from a randomised controlled trial.

BACKGROUND: With the prevalence of diabetes reaching an epidemic level, there is a growing interest in the investigation of its remission. Proglucagon-derived peptides (PGDP) have been shown to have a glucose-regulating effect. However, whether they play a role in diabetes remission remains poorly understood. AIM: To investigate changes in plasma levels of PGDP in glycaemic responders versus non-responders. METHODS: The study was a randomised placebo-controlled trial comprising 18 adults with prediabetes (registered at www. CLINICALTRIALS: gov as NCT03889210). Following an overnight fast, participants consumed ketone ß-hydroxybutyrate (KEßHB)-supplemented beverage and placebo beverage in crossover manner. Serial blood samples were collected from baseline to 150 min at 30-min intervals. The endpoints were changes in glucagon-like peptide-1 (GLP-1), glicentin, oxyntomodulin, glucagon, and major proglucagon fragment (MPGF). Participants were stratified into the 'responders' and 'non-responders' subgroups based on their glycaemic changes following the ingestion of KEßHB. The area under the curve (AUC) was calculated to estimate the accumulated changes in the studied PGDP and compared using paired-t test between the KEßHB and placebo beverages. RESULTS: Responders had a significantly greater reduction in plasma glucose compared with non-responders following acute ketosis (p < 0.001). The AUC0-150 for oxyntomodulin was significantly lower following the KEßHB beverage compared with the placebo (p = 0.045) in responders, but not in non-responders (p = 0.512). No significant differences in AUCs0-150 were found for GLP-1, glicentin, glucagon, and MPGF in either responders or non-responders. CONCLUSION: Oxyntomodulin is involved in lowering plasma glucose and may play an important role in diabetes remission.

Subcutaneous biodegradable scaffolds for restimulating the antitumour activity of pre-administered CAR-T cells.

The efficacy of adoptive T-cell therapies based on chimaeric antigen receptors (CARs) is limited by the poor proliferation and persistence of the engineered T cells. Here we show that a subcutaneously injected biodegradable scaffold that facilitates the infiltration and egress of specific T-cell subpopulations, which forms a microenvironment mimicking features of physiological T-cell activation, enhances the antitumour activity of pre-administered CAR-T cells. CAR-T-cell expansion, differentiation and cytotoxicity were driven by the scaffold's incorporation of co-stimulatory bound ligands and soluble molecules, and depended on the types of co-stimulatory molecules and the context in which they were presented. In mice with aggressive lymphoma, a single, local injection of the scaffold following non-curative CAR-T-cell dosing led to more persistent memory-like T cells and extended animal survival. Injectable biomaterials with optimized ligand presentation may boost the therapeutic performance of CAR-T-cell therapies.

ABHD5 regulates midgut-specific lipid homeostasis in Bombyx mori.

Lipids are an important energy source and are utilized as substrates for various physiological processes in insects. Comparative gene identification 58 (CGI-58), also known as α/ß hydrolase domain-containing 5 (ABHD5), is a highly conserved and multifunctional gene involved in regulating lipid metabolism and cellular energy balance in many organisms. However, the biological functions of ABHD5 in insects are poorly understood. In the current study, we describe the identification and characterization of the ABHD5 gene in the lepidopteran model insect, Bombyx mori. The tissue expression profile investigated using quantitative reverse transcription polymerase chain reaction (RT-qPCR) reveals that BmABHD5 is widely expressed in all tissues, with particularly high levels found in the midgut and testis. A binary transgenic CRISPR/Cas9 system was employed to conduct a functional analysis of BmABHD5, with the mutation of BmABHD5 leading to the dysregulation of lipid metabolism and excessive lipid accumulation in the larval midgut. Histological and physiological analysis further reveals a significant accumulation of lipid droplets in the midgut of mutant larvae. RNA-seq and RT-qPCR analysis showed that genes related to metabolic pathways were significantly affected by the absence of BmABHD5. Altogether, our data prove that BmABHD5 plays an important role in regulating tissue-specific lipid metabolism in the silkworm midgut.

Effect of Acute Nutritional Ketosis on Circulating Levels of Growth Differentiation Factor 15: Findings from a Cross-Over Randomised Controlled Trial.

Exogenous supplementation with ketone beverages has been shown to reduce plasma glucose levels during acute nutritional ketosis. It remains to be investigated whether growth differentiation factor 15 (GDF-15)-an anorexigenic hormone-is involved in this process. The aim was to investigate the effect of a ketone ester beverage delivering ß-hydroxybutyrate (KEßHB) on plasma levels of GDF-15, as well as assess the influence of eating behaviour on it. The study was a randomised controlled trial (registered at clinicaltrials.gov as NCT03889210). Individuals were given a KEßHB beverage or placebo in a cross-over fashion. Blood samples were collected at baseline, 30, 60, 90, 120, and 150 min after ingestion. Eating behaviour was assessed using the three-factor eating questionnaire. GDF-15 levels were not significantly different (p = 0.503) after the KEßHB beverage compared with the placebo. This finding remained consistent across the cognitive restraint, emotional eating, and uncontrolled eating domains. Changes in the anorexigenic hormone GDF-15, irrespective of eating behaviour, do not appear to play a major role in the glucose-lowering effect of exogenous ketones.

Direct Melt-Calendaring of Highly Textured (Bi,Sb)2Te3 Thick Films: Superior Thermoelectric and Mechanical Performance via Strain Engineering.

The evolutions of chip thermal management and micro energy harvesting put forward urgent need for micro thermoelectric devices. Nevertheless, low-performance thermoelectric thick films as well as the complicated precision cutting process for hundred-micron thermoelectric legs still remain the bottleneck hindering the advancement of micro thermoelectric devices. In this work, an innovative direct melt-calendaring manufacturing technology is first proposed with specially designed and assembled equipment, that enables direct, rapid, and cost-effective continuous manufacturing of Bi2Te3-based films with thickness of hundred microns. Based on the strain engineering with external glass coating confinement and controlled calendaring deformation degree, enhanced thermoelectric performance has been achieved for (Bi,Sb)2Te3 thick films with highly textured nanocrystals, which can promote carrier mobility over 182.6 cm2 V-1 s-1 and bring out a record-high zT value of 0.96 and 1.16 for n-type and p-type (Bi,Sb)2Te3 thick films, respectively. The nanoscale interfaces also further improve the mechanical strength with excellent elastic modules (over 42.0 GPa) and hardness (over 1.7 GPa), even superior to the commercial zone-melting ingots and comparable to the hot-extrusion (Bi,Sb)2Te3 alloys. This new fabrication strategy is versatile to a wide range of inorganic thermoelectric thick films, which lays a solid foundation for the development of micro thermoelectric devices.

Cumulative incidence and risk factors for medication-related osteonecrosis of the jaw during long-term prostate cancer management.

Bone-modifying agents (BMA) are extensively used in treating patients with prostate cancer with bone metastases. However, this increases the risk of medication-related osteonecrosis of the jaw (MRONJ). The safety of long-term BMA administration in clinical practice remains unclear. We aimed to determine the cumulative incidence and risk factors of MRONJ. One hundred and seventy-nine patients with prostate cancer with bone metastases treated with BMA at our institution since 2008 were included in this study. Twenty-seven patients (15%) had MRONJ during the follow-up period (median, 19 months; interquartile range, 9-43 months). The 2-year, 5-year, and 10-year cumulative MRONJ incidence rates were 18%, 27%, and 61%, respectively. Multivariate analysis identified denosumab use as a risk factor for MRONJ, compared with zoledronic acid use (HR 4.64, 95% CI 1.93-11.1). Additionally, BMA use at longer than one-month intervals was associated with a lower risk of MRONJ (HR 0.08, 95% CI 0.01-0.64). Furthermore, six or more bone metastases (HR 3.65, 95% CI 1.13-11.7) and diabetes mellitus (HR 5.07, 95% CI 1.68-15.2) were risk factors for stage 2 or more severe MRONJ. MRONJ should be considered during long-term BMA administration in prostate cancer patients with bone metastases.