Deficiency States Research Articles

Is patient participation in hypertension care based on patients' preferences? - A cross-sectional study in primary healthcare.

The purpose of this study was to address the need to improve opportunities for patient participation in their health and health services. This paper reports if and how patients' preferences matched their experiences of participation in treatment for hypertension in primary healthcare, and what factors were linked with having had opportunities for participation that matched one's preferences. A total of 949 adult patients treated for hypertension completed the 4Ps (Patient Preferences for Patient Participation) tool, with which they ranked their preferences for and experiences of patient participation. Descriptive and comparative analyses of 4Ps data were performed to identify patient characteristics associated with preference-based participation.Approximately half of the participants experienced patient participation to the extent that they preferred. Women were more likely to have had less patient participation than their preference compared to men. Women were also more likely to prefer being more engaged in hypertension care than men. There were also marked associations between age and educational level with the extent of participation preferred and experienced, leaving patients younger than or with lower education than the mean in this study with more insufficient conditions for patient participation. There is a lack of concurrence between patients' preferences for, and experiences of, patient participation, especially for women. Further efforts to facilitate person-centred engagement are required, along with research on what strategies can overcome human and organisational barriers. The PERHIT- trial was registered with ClinicalTrials.gov: NCT03554382.

Zinc transporters expression profile in professional handball players supplemented with zinc

IntroductionZinc (Zn) deficiency has been described not only on general human health but also within the sports context –as negatively affecting performance–. Thus, Zn status assessment is of great interest for athletes, especially in order to correct deficiency states of this mineral. ObjectiveThe overall objective of this work was to assess Zn status in professional handball players during the competitive period (through plasma levels, dietary intake and gene expression of the Zn transporters), as well as to determine the effect of Zn supplementation. MethodsA total of twenty-two participants were recruited, –twelve belonged to the Control Group (CG) and ten male handball players comprised the experimental group (ATH-G)–, being monitored over a 2-month period with 2 evaluation moments: baseline (i.e., initial conditions) and follow-up (i.e., after 8 weeks of training and competition). Zn intake, plasma Zn levels, and gene expression of Zn transporters were obtained. ResultsPlasma Zn levels were higher in ATH-G than in CG at the end of Zn intervention (p ≤ 0.010). Moreover, differences in the gene expression profile of Zn transporters were observed in ATH-G –with the down-regulation of several Zn transporters–, compared to the CG at baseline (p ≤ 0.05). Likewise, differences in the Zn transporters expression were observed in ATH-G at 8 weeks (all, p ≤ 0.001) –with ZnT2, ZnT5, ZIP3, ZIP5, ZIP11, ZIP13 and ZIP14 transporters being up-regulated–. ConclusionHandball players seemed to have different nutritional needs for Zn, with differences in the gene expression of Zn transporters compared to controls. Zn intervention in our athletes may have influenced the expression of Zn transporters, indicating a potential increase in Zn transporters expression to mobilize Zn at the cellular level at 8 weeks of Zn intervention.

In Vitro Assessment of Knee Joint Biomechanics Using a Virtual Anterior Cruciate Ligament Reconstruction.

Understanding the biomechanical impact of injuries and reconstruction of the anterior cruciate ligament (ACL) is vital for improving surgical treatments that restore normal knee function. The purpose of this study was to develop a technique that enables parametric analysis of the effect of the ACL reconstruction (ACLR) in cadaver knees, by replacing its contributions with that of a specimen-specific virtual ACLR that can be enabled, disabled, or modified. Twelve ACLR reconstructed knees were mounted onto a motion simulator. In situ ACLR graft forces were measured using superposition, and these data were used to design specimen-specific virtual ACLRs that would yield the same ligament force-elongation behaviors. Tests were then repeated using the virtual ACLR in place of the real ACLR and following that in ACL deficient knee by disabling the virtual ACLR. In comparison to the ACL deficient state, the virtual ACLRs were able to restore knee stability to the same extent as real ACLRs. The average differences between the anterior tibial translation (ATT) of the virtual ACLR versus the real ACLR were +1.6 ± 0.9 mm (p = 0.4), +2.1 ± 0.4 mm (p = 0.4), and +1.0 ± 0.9 mm (p = 0.4) during Anterior drawer, Lachman and Pivot-shift tests, respectively, which is small in comparison to the full ATT range of motion (ROM) of these knees. Therefore, we conclude that a virtual ACLR can be used in place of real ACLR during biomechanical testing of cadaveric knees. This capability opens the door for future studies that can leverage parameterization of the ACLR for surgical design optimization.

Iron homeostasis, recycling and vulnerability in the stressed kidney: A neglected dimension of iron-deficient heart failure.

The available evidence suggests that the kidney may contribute importantly to the development of an iron deficiency state in patients with heart failure and may be injured by therapeutic efforts to achieve iron repletion. The exceptional workload of the proximal renal tubule requires substantial quantities of iron for ATP synthesis, which it derives from Fe3+ bound to transferrin in the bloodstream. Following ferrireduction, Fe2+ is conveyed by divalent transporters (e.g. DMT1) out of the endosome of the proximal renal tubule, and highly reactive Fe2+ can be directed to the mitochondria, sequestered safely in a ferritin nanocage or exported through the actions of hepcidin-inhibitable ferroportin. The actions of ferroportin, together with transferrin endocytosis and DMT1-mediated transport, play a key role in the recycling of iron from the tubular fluid into the bloodstream and preventing the loss of filtered iron in the urine. Activation of endogenous neurohormonal systems and proinflammatory signalling in heart failure decrease megalin-mediated uptake and DMT1 expression, and increase hepcidin-mediated suppression of ferroportin, promoting the loss of iron in the urine and contributing to the development of an iron deficiency state. Furthermore, the failure of ferroportin-mediated efflux at the basolateral membrane heightens the susceptibility of the renal tubules to cytosolic excesses of Fe2+, causing lipid peroxidation and synchronized cell death (ferroptosis) through the iron-dependent free radical theft of electrons from lipids in the cell membrane. Ferroptosis is a central mechanism to most disorders that can cause acute and chronic kidney disease. Short-term bolus administration of intravenous iron can cause oxidative stress and is accompanied by markers of renal injury. Experimentally, long-term maintenance of an iron-replete state is accompanied by accelerated loss of nephrons, oxidative stress, inflammation and fibrosis. Intravenous iron therapy increases glomerular filtration rate rapidly in patients with heart failure (perhaps because of a haemodynamic effect) but not in patients with chronic kidney disease, and the effects of intravenous iron on the progression of renal dysfunction in the long-term trials - AFFIRM-AHF, IRONMAN and HEART-FID - have not yet been reported. Given the potential role of dysregulated renal iron homeostasis in the pathogenesis of iron deficiency and the known vulnerability of the kidney to intravenous iron, the appropriate level of iron repletion with respect to the risk of acute and chronic kidney injury in patients with heart failure requires further study.

Critical re-evaluation of the identification of iron deficiency states and effective iron repletion strategies in patients with chronic heart failure.

According to current guidelines, iron deficiency is defined by a serum ferritin level <100 ng/ml or a transferrin saturation (TSAT) <20% if the serum ferritin level is 100-299 μg/L. These criteria were developed to encourage the use of intravenous iron as an adjunct to erythropoiesis-stimulating agents in the treatment of renal anaemia. However, in patients with heart failure, these criteria are not supported by any pathophysiological or clinical evidence that they identify an absolute or functional iron deficiency state. A low baseline TSAT-but not serum ferritin level-appears to be a reliable indicator of the effect of intravenous iron to reduce major heart failure events. In randomized controlled trials, intravenous iron decreased the risk of cardiovascular death or total heart failure hospitalization in patients with a TSAT <20% (risk ratio 0.67 [0.49-0.92]) but not in patients with a TSAT ≥20% (risk ratio 0.99 [0.74-1.30]), with the magnitude of the risk reduction being proportional to the severity of hypoferraemia. Patients who were enrolled in clinical trials solely because they had a serum ferritin level <100 μg/L showed no significant benefit on heart failure outcomes, and it is noteworthy that serum ferritin levels of 20-300 μg/L lie entirely within the range of normal values for healthy adults. Current guidelines reflect the eligibility criteria of clinical trials, which inadvertently adopted unvalidated criteria to define iron deficiency. Reliance on these guidelines would lead to the treatment of many patients who are not iron deficient (serum ferritin level <100 μg/L but normal TSAT) and ignores the possibility of iron deficiency in patients with a low TSAT but with serum ferritin level of >300 μg/L. Importantly, analyses of benefit based on trial eligibility-driven guidelines substantially underestimate the magnitude of heart-failure-event risk reduction with intravenous iron in patients who are truly iron deficient. Based on all available data, we recommend a new mechanism-based and trial-tested approach that reflects the totality of evidence more faithfully than the historical process adopted by clinical investigators and by the guidelines. Until additional evidence is forthcoming, an iron deficiency state in patients with heart failure should be defined by a TSAT <20% (as long as the serum ferritin level is <400 μg/L), and furthermore, the use of a serum ferritin level <100 μg/L alone as a diagnostic criterion should be discarded.

The impact of working memory testing on long-term associative memory.

The long-term fate of to-be-remembered information depends in part on the conditions of initial learning, including mental operations engaged via working memory. However, the mechanistic role of working memory (WM) processes in subsequent episodic memory (EM) remains unclear. Does re-exposure to word-pairs during WM recognition testing improve EM for those associations? Are benefits from WM re-exposure greater after an opportunity for retrieval practice compared to mere re-exposure to the memoranda? These questions are addressed in three experiments (N = 460) designed to assess whether WM-based recognition testing benefits long-term associative memory relative to WM-based restudying. Our results show null or negative benefits of WM recognition testing minutes later when initial WM accuracy was not considered. An EM benefit of WM recognition testing only emerges when the analyses are limited to pairs responded to correctly during WM. However, even when compared with accurate WM recognition, restudying can lead to similar associative EM benefits in specific experimental conditions. Taken together, the present results suggest that while WM re-exposure to studied pairs is beneficial to long-term associative memory, successful retrieval on initial tests may be a necessary but insufficient condition for the emergence of a "WM-based testing effect." We consider these results in relation to several hypotheses proposed to explain the testing effect in long-term memory (LTM). In view of empirical parallels with the LTM testing effect, we propose that similar processes influence the benefits of practice tests administered within the canonical boundaries of WM, suggesting continuities in memory over the short and long term.

Calabi-Yau four-, five-, sixfolds as Pwn hypersurfaces: Machine learning, approximation, and generation

Calabi-Yau fourfolds may be constructed as hypersurfaces in weighted projective spaces of complex dimension five defined via weight systems of six weights. In this work, neural networks were implemented to learn the Calabi-Yau Hodge numbers from the weight systems, where gradient saliency and symbolic regression then inspired a truncation of the Landau-Ginzburg model formula for the Hodge numbers of any dimensional Calabi-Yau constructed in this way. The approximation always provides a tight lower bound, is shown to be dramatically quicker to compute (with computation times reduced by up to 4 orders of magnitude), and gives remarkably accurate results for systems with large weights. Additionally, complementary datasets of weight systems satisfying the necessary but insufficient conditions for transversality were constructed, including considerations of the interior point, reflexivity, and intradivisibility properties, overall producing a classification of this weight system landscape, further confirmed with machine learning methods. Using the knowledge of this classification and the properties of the presented approximation, a novel dataset of transverse weight systems consisting of seven weights was generated for a sum of weights ≤200, producing a new database of Calabi-Yau fivefolds, with their respective topological properties computed. Furthermore, an equivalent database of candidate Calabi-Yau sixfolds was generated with approximated Hodge numbers. Published by the American Physical Society 2024

Research on Export Flow and Potential of Agricultural Products in China Based on Machine Learning Algorithm

The MLR (multiple linear regression) method in machine learning algorithm is a comprehensive method to study the correlation of variables, and it is also an important measure to study the relationship between variables by using linear fitting method. By combining qualitative analysis with quantitative analysis, this paper will use MLR model to make an empirical analysis of the determinants of agricultural trade flow, and use the estimated parameters to calculate the agricultural trade potential of China. The results show that the economic scale and distance have an important influence on the export flow of agricultural products in China, indicating that the economic scale is an important factor affecting the export flow of agricultural products. Regional trade arrangements have dual effects of trade transfer and trade creation, and free trade arrangements have created favorable conditions for trade expansion between countries with different demand and income levels. China's exports to Russia, Thailand, Singapore, the Philippines, Malaysia and Indonesia are in a state of deficiency, and there is still potential for developing agricultural products exports to these countries.

Turning alkalinity deficiency-induced metabolic disorder into an opportunity for promoting granulation and enhancing heat generation

Shortage of alkalinity is a common problem in treating low carbon/nitrogen (C/N) wastewater and industrial influents. It negatively affects system stability and efficiency, but its positive effects remain unclear. To address this issue, insufficient (R1: 400 mg CaCO3/L) and sufficient alkalinity (R2: 750 mg CaCO3/L) levels were established in our study, where R1 served as the experimental group and R2 as the control group. In the experimental group, alkalinity deficiency deteriorated the nitrification and phosphorus removal process by reducing the abundance of functional microbes (Nitrosomonas, genus ammonia-oxidizing bacteria, AOB, and Dechloromonas, genus polyphosphate-accumulating organisms, PAOs) and genes (hao). At the same time, the alkalinity deficiency enriched slow-growing functional microbes (Candidatus_Competibacter, genus glycogen-accumulating organisms, GAOs) and key genes (nirK, norB, nosZ, acnB, fumA, fumB) increased the content of extracellular polymeric substances (EPS) and the ratio of protein to polysaccharide (PN/PS). By day 113, over 87 % of the particles were larger than 200 μm, and complete granulation was achieved. Microbial energy metabolism further indicated that alkalinity deficiency diverted some energy to non-growth metabolism, thereby enhancing microbial heat generation. Our results highlight an innovative approach, using the setting of insufficient alkalinity conditions to improve heat recovery and address the challenges of WWTPs. These research findings are in favor of wastewater treatment plants seeking to meet multiple sustainable objectives, including improving water quality, saving footprint, and maximizing energy recovery.

Knowledge, Attitudes, and Practices About the Use of Silver Diamine Fluoride Among Dentists in Riyadh, Saudi Arabia: A Cross-Sectional Study.

Introduction Dental caries is a worldwide disease affecting children and older populations.There aremultiple interventionsto treatdentalcariesthat could be sometimeshard todeliver,due to the general statusof patientssuch as insufficient cooperationormedicallycompromising conditions. Therefore, another alternative to control dental caries is being used andhasbeenrecentlyintroduced and approved by the Saudi FDA which is silver diamine fluoride (SDF). Objectives This study aimed toinvestigate the level of knowledge, attitudes, and practices about the use of SDF among dentists in Riyadh, Saudi Arabia. Materials and methods Thiscross-sectionalstudywas conductedusingpretested,anonlinedigitally designedquestionnairesentto500 Saudi Commission for Health Specialties (SCFHS) registereddentists working in the following specialties: general practitioners, interns,restorative,family, pediatric, and public health dentistswho are working in public and private hospitals and clinics. One-way ANOVAwas usedto determine the comparison of participants'knowledge and Practice with three variables (participants' specialty, place of work, and years of experience), while Chi-square was used for the comparison of respondent's attitudes about the use of SDF and the above same variables. Result A totalof265responseswerereceived(response rate is53%). Themajority of therespondents were general practitioners and interns 144 (54.3%).Over50% of dentists believedthat theywereveryinformedaboutSDF. The mean score of knowledgeand practices of SDF of participants was found below average 49.13 (19.81) and 43 (26.12), respectively. Correlation ofthemeanscoreknowledgeand practicing SDFwith the type of specialty showed that pediatric dentists had statically significant (P<0.05)higher mean of knowledge 66.94 (SD=17.64)and practicing of SDF 61.93 (22.12) as compared to other specialties,whileno statistically significant differences were found among the groups in the overall knowledge andpractices based on years of experience andworkplace.Attitudeswere correlated with the three above variables (specialty, years of experience, and place of work)and showed thatpediatric dentists had the highest satisfaction with the results of SDF (85.3%)andweremorewilling to recommend using it to others(91.2%) as compared totheother groups(P<0.05).Nostatistically significant differenceswerefound with respect to the latervariables. Conclusion The findings of this studyshowed that irrespective of the positive attitude of participants towards SDF,pediatric dentistswere found to have higher knowledge and use SDF more than other dentists in different specialties. Furthermore, they showed higher satisfaction with its use. Years of experienceand workplace had no effect on the level of knowledge or practice among participants.

АЛГОРИТМ ЭФФЕКТИВНОГО ПРИМЕНЕНИЯ ВИТАМИННО-МИНЕРАЛЬНЫХ КОМПЛЕКСОВ

At present time, there is a huge range of vitamin and mineral supplements (VMS), that differ in composition and doses of micronutrients, which complicates the choice and their effective use. The purpose of the review is to substantiate the algorithm for effective use of VMS for the correction of micronutrient deficiency. The general pattern in the VMS administration is that there is an inverse relationship between the dose of micronutrients and the increase in their concentration in a fasting blood test after an overnight break. Improving vitamin status requires time, that is longer when taking VMS with low doses, and for each vitamin the time to achieve optimal concentrations is different. To optimize the vitamin status by means of VMS administration containing vitamins in doses corresponding to 100% of the recommended daily intake (RDI) takes from 1.5 months for B vitamins to 3-5 months for vitamin D. A course of VMS administration for 1 months may not be enough to correct the deficiency of all vitamins. After stopping additional use of VMS, a “wash-out” of vitamins occurs for one to several weeks, i.e. decrease of blood concentration and return to the original state of deficiency. A universal, scientifically based scheme for the effective use of VMS consists of a course of VMS administration with high (200-300% of the RDI) micronutrients, especially after an illness or taking antibiotics, and then switching to constant use of VMS containing deficient micronutrients in a dose of 50-100 % of RDI. Women during the periconceptional period and throughout pregnancy are recommended to take daily multicomponent VMS, specifically designed for pregnant women, containing doses of micronutrients that correspond to the physiological needs of the body.

Mycobacterium avium paratuberculosis Infection Suppresses Vitamin D Activation and Cathelicidin Production in Macrophages through Modulation of the TLR2-Dependent p38/MAPK-CYP27B1-VDR-CAMP Axis.

Vitamin D plays a vital role in modulating both innate and adaptive immune systems. Therefore, vitamin D deficiency has been associated with higher levels of autoimmune response and increased susceptibility to infections. CYP27B1 encodes a member of the cytochrome P450 superfamily of enzymes. It is instrumental in the conversion of circulating vitamin D (calcifediol) to active vitamin D (calcitriol). This is a crucial step for macrophages to express Cathelicidin Anti-microbial Peptide (CAMP), an anti-bacterial factor released during the immune response. Our recent study indicated that a Crohn's disease (CD)-associated pathogen known as Mycobacterium avium paratuberculosis (MAP) decreases vitamin D activation in macrophages, thereby impeding cathelicidin production and MAP infection clearance. The mechanism by which MAP infection exerts these effects on the vitamin D metabolic axis remains elusive. We used two cell culture models of THP-1 macrophages and Caco-2 monolayers to establish the effects of MAP infection on the vitamin D metabolic axis. We also tested the effects of Calcifediol, Calcitriol, and SB203580 treatments on the relative expression of the vitamin D metabolic genes, oxidative stress biomarkers, and inflammatory cytokines profile. In this study, we found that MAP infection interferes with vitamin D activation inside THP-1 macrophages by reducing levels of CYP27B1 and vitamin D receptor (VDR) gene expression via interaction with the TLR2-dependent p38/MAPK pathway. MAP infection exerts its effects in a time-dependent manner, with the maximal inhibition observed at 24 h post-infection. We also demonstrated the necessity to have toll-like receptor 2 (TLR2) for MAP infection to influence CYP27B1 and CAMP expression, as TLR2 gene knockdown resulted in an average increase of 7.78 ± 0.88 and 13.90 ± 3.5 folds in their expression, respectively. MAP infection also clearly decreased the levels of p38 phosphorylation and showed dependency on the p38/MAPK pathway to influence the expression of CYP27B1, VDR, and CAMP which was evident by the average fold increase of 1.93 ± 0.28, 1.86 ± 0.27, and 6.34 ± 0.51 in their expression, respectively, following p38 antagonism. Finally, we showed that calcitriol treatment and p38/MAPK blockade reduce cellular oxidative stress and inflammatory markers in Caco-2 monolayers following macrophage-mediated MAP infection. This study characterized the primary mechanism by which MAP infection leads to diminished levels of active vitamin D and cathelicidin in CD patients, which may explain the exacerbated vitamin D deficiency state in these cases.

Change in parameters of the microcirculatory tissue system of the peri implant zone in patients with peri implantitis during complex use of mesodiencephalic modulation and ozone therapy

Abstract. Purpose of the study: The article examines the role of microcirculation disorders in the pathogenesis of peri-implantitis in patients after dental implantation. Materials and methods. It is shown that the development of peri-implantitis is characterized by significant changes in the parameters of microhemodynamics and oxygen exchange in the tissue involved in the inflammatory process. The state of oxygen and energy deficiency prompts the progression of inflammatory changes with the formation of signs of tissue destruction around dental implants. The application of a standard scheme of peri-implantitis therapy is accompanied by a correction of the microcirculatory tissue system indicators. The supplementation of standard treatment with course use of medical physical factors promotes the strengthening of the positive dynamics of microcirculation parameters of the peri-implant zone. The corrective influence of MDM-therapy is connected with the activation of the mechanisms of neuroendocrine regulation of vegetative functions, while the basis of ozone therapy is the polymodality of the factor, including the relaxation of the precapillary blood flow, improvement of the rheological properties of the blood, and the stimulating effect on angiogenesis processes. Results. The complex application of medical physical factors, combining systemotropic and local impacts, different modalities and points of application of their corrective activity, contributes to the manifestation of functional potentiation with a maximal corrective effect.

151 A Primary Neurological Presentation of CASP-8 Deficiency State

151 A Primary Neurological Presentation of CASP-8 Deficiency State

How Ratings Shape the Supply on Sharing Economy Platforms: A Longitudinal Cohort Study on Listing Survival on Airbnb

ABSTRACT Customer reviews on sharing economy platforms like Airbnb have been studied extensively. However, their effectiveness has recently been questioned. We investigate their role regarding listing churn on Airbnb using panel data. We find that listings with few or poor ratings will likely leave the platform. Correcting for the listings’ characteristics, we find that the best possible rating strongly predicts the listings’ success. We conclude that the best rating is a necessary but insufficient condition for success.

Switch of ELF3 and ATF4 transcriptional axis programs the amino acid insufficiency-linked epithelial-to-mesenchymal transition

Epithelial-to-mesenchymal transition (EMT) that endows cancer cells with increased invasive and migratory capacity enables cancer dissemination and metastasis. This process is tightly associated with metabolic reprogramming acquired for rewiring cell status and signaling pathways for survival in dietary insufficiency conditions. However, it remains largely unclear how transcription factor (TF)-mediated transcriptional programs are modulated during the EMT process. Here we reveal that depletion of a key epithelial TF, ELF3, triggers a TGFβ signaling activation-like mesenchymal transcriptomic profile and metastatic features linked to the aminoacyl-tRNA biogenesis pathway. Moreover, the transcriptome alterations elicited by ELF3 depletion perfectly resemble an ATF4-dependent weak response to amino acid starvation. Intriguingly, we observe an exclusive enrichment of ELF3 and ATF4 in epithelial and TGFβ-induced or ELF3 depletion-elicited mesenchymal enhancers, respectively, with rare co-binding on altered enhancers. We also find that the upregulation of aminoacyl-tRNA synthetases and some mesenchymal genes upon amino acid deprivation is diminished in ATF4-depleted cells. In sum, the loss of ELF3 binding on epithelial enhancers and the gain of ATF4 binding on the enhancers of mesenchymal factors and amino acid-deprivation responsive genes facilitate the loss of epithelial cell features and the gain of TGFβ signaling-associated mesenchymal signatures, which further promote lung cancer cell metastasis.

Chemotherapy activates inflammasomes to cause inflammation-associated bone loss.

Chemotherapy is a widely used treatment for a variety of solid and hematological malignancies. Despite its success in improving the survival rate of cancer patients, chemotherapy causes significant toxicity to multiple organs, including the skeleton, but the underlying mechanisms have yet to be elucidated. Using tumor-free mouse models, which are commonly used to assess direct off-target effects of anti-neoplastic therapies, we found that doxorubicin caused massive bone loss in wild-type mice, a phenotype associated with increased number of osteoclasts, leukopenia, elevated serum levels of danger-associated molecular patterns (DAMPs; e.g. cell-free DNA and ATP) and cytokines (e.g. IL-1β and IL-18). Accordingly, doxorubicin activated the absent in melanoma (AIM2) and NLR family pyrin domain containing 3 (NLRP3) inflammasomes in macrophages and neutrophils, causing inflammatory cell death pyroptosis and NETosis, which correlated with its leukopenic effects. Moreover, the effects of this chemotherapeutic agent on cytokine secretion, cell demise, and bone loss were attenuated to various extent in conditions of AIM2 and/or NLRP3 insufficiency. Thus, we found that inflammasomes are key players in bone loss caused by doxorubicin, a finding that may inspire the development of a tailored adjuvant therapy that preserves the quality of this tissue in patients treated with this class of drugs.

Chemotherapy activates inflammasomes to cause inflammation-associated bone loss

Chemotherapy is a widely used treatment for a variety of solid and hematological malignancies. Despite its success in improving the survival rate of cancer patients, chemotherapy causes significant toxicity to multiple organs, including the skeleton, but the underlying mechanisms have yet to be elucidated. Using tumor-free mouse models, which are commonly used to assess direct off-target effects of anti-neoplastic therapies, we found that doxorubicin caused massive bone loss in wild-type mice, a phenotype associated with increased number of osteoclasts, leukopenia, elevated serum levels of danger-associated molecular patterns (DAMPs; e.g. cell-free DNA and ATP) and cytokines (e.g. IL-1β and IL-18). Accordingly, doxorubicin activated the absent in melanoma (AIM2) and NLR family pyrin domain containing 3 (NLRP3) inflammasomes in macrophages and neutrophils, causing inflammatory cell death pyroptosis and NETosis, which correlated with its leukopenic effects. Moreover, the effects of this chemotherapeutic agent on cytokine secretion, cell demise, and bone loss were attenuated to various extent in conditions of AIM2 and/or NLRP3 insufficiency. Thus, we found that inflammasomes are key players in bone loss caused by doxorubicin, a finding that may inspire the development of a tailored adjuvant therapy that preserves the quality of this tissue in patients treated with this class of drugs.

Trade-in strategies in closed-loop supply chain when considering manufacturer entrustment behavior and wholesale price contract

Many enterprises are implementing trade-in programs through multiple methods, but some lack experience or insufficient conditions to carry out the trade-in program. The previous literature did not consider the impacts of the manufacturer authorizing the third-party information platform (3IP) to implement the trade-in strategy for each member of the closed-loop supply chain. To address this gap, we established three models based on consumer choice behavior: (1) the benchmark model without trade-in strategy; (2) the trade-in model with manufacturer entrustment behavior; (3) the extension model with wholesale price contract. We obtained and compared the equilibrium solutions of the three models. Our results indicate that, compared to the case where there is no entrustment, the manufacturer’s profit is higher if they entrust the 3IP to implement the trade-in program under certain conditions (which is related to the proportion of primary and replacement consumers in the market). Under reasonable circumstances, we find that introducing a wholesale price contract can benefit the manufacturer and increase the profit of the 3IP, stimulate the 3IP to carry out trade-in better, and achieve a win-win situation. Some numerical examples are provided to explain these findings further.

Multimodal fall detection for solitary individuals based on audio-video decision fusion processing

Falls often pose significant safety risks to solitary individuals, especially the elderly. Implementing a fast and efficient fall detection system is an effective strategy to address this hidden danger. We propose a multimodal method based on audio and video. On the basis of using non-intrusive equipment, it reduces to a certain extent the false negative situation that the most commonly used video-based methods may face due to insufficient lighting conditions, exceeding the monitoring range, etc. Therefore, in the foreseeable future, methods based on audio and video fusion are expected to become the best solution for fall detection. Specifically, this article outlines the following methodology: the video-based model utilizes YOLOv7-Pose to extract key skeleton joints, which are then fed into a two stream Spatial Temporal Graph Convolutional Network (ST-GCN) for classification. Meanwhile, the audio-based model employs log-scaled mel spectrograms to capture different features, which are processed through the MobileNetV2 architecture for detection. The final decision fusion of the two results is achieved through linear weighting and Dempster-Shafer (D-S) theory. After evaluation, our multimodal fall detection method significantly outperforms the single modality method, especially the evaluation metric sensitivity increased from 81.67% in single video modality to 96.67% (linear weighting) and 97.50% (D-S theory), which emphasizing the effectiveness of integrating video and audio data to achieve more powerful and reliable fall detection in complex and diverse daily life environments.