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This study aimed to examine factors, healthcare utilization, and medical costs associated with potentially inappropriate use of benzodiazepines in persons living with HIV (PLWH). We used big data from Medicare claims in 2017. Potentially inappropriate use of benzodiazepines was defined as having any benzodiazepine claims in individuals 65+ years or having benzodiazepine claims for more than four weeks in individuals 18–64 years. Logistic regressions, zero-inflated negative binomial regressions, and generalized linear models were used. This study included 1,211 PLWH and 235 (19.41%) had potentially inappropriate use of benzodiazepines. PLWH who were 65+ years (OR: 0.56; 95% CI: 0.33, 0.96), non-Hispanic blacks (OR: 0.29; 95% CI: 0.20, 0.41), or Hispanics (OR: 0.55; 95% CI: 0.35, 0.88) were less likely to use benzodiazepines inappropriately. PLWH who had potentially inappropriate use of benzodiazepines had more inpatient (IRR: 1.46; 95% CI: 1.10, 1.94), outpatient (IRR: 1.14; 95% CI 1.02, 1.28), and emergency room (IRR: 1.32; 95% CI: 1.03, 1.68) visits. Potentially inappropriate use of benzodiazepines was associated with higher total (β: 0.16; 95% CI: 0.07, 0.25), Medicare (β: 0.18; 95% CI: 0.07, 0.28), and out-of-pocket (β: 0.21; 95% CI: 0.05, 0.36) costs. This study provides real-world evidence to support deprescribing benzodiazepines in PLWH. [ABSTRACT FROM AUTHOR]

Human chromosomes carry genetic information about our life. Chromosome classification is crucial for karyotype analysis. Existing chromosome classification methods do not take into account reasoning, such as: analyzing the relationship between variables, modeling uncertainty, and performing causal reasoning. In this paper, we introduce a knowledge engine for reasoning-based human chromosome classification that stores knowledge of chromosomes via a novel representation structure, the Chromosome Part Description (CPD), and reasons over CPDs by utilizing the probability tree model (PTM) for classification. Each CPD keeps information on a particular feature of chromosomes, while the PTM provides causal reasoning capability taking CPDs as nodes and dependencies between CPDs and types as edges. Experimental results show that the proposed knowledge engine's performance increases when providing more CPDs and achieves 100% classification accuracy with more than three CPDs. [ABSTRACT FROM AUTHOR]

AbstractTo evaluate the co-transplantation efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) and peripheral blood stem cells (PBSCs) as a novel approach for refractory or relapsed severe aplastic anemia (R/R SAA) in children and adolescents, thirty-two children and adolescents diagnosed with R/R SAA underwent a retrospective chart review. The patients were categorized into two groups based on the source of PBSCs: the matched sibling donor (MSD) group and the unrelated donor (UD) group. No adverse events related to UC-MSC infusion occurred in any of the patients. The median time for neutrophil engraftment was 13 days (range: 10–23 days), and for platelets, it was 15 days (range: 11–28 days). Acute GVHD of Grade I–II and moderate chronic GVHD were observed in 21.8 and 12.5% of cases, respectively. No statistically significant differences were found between the MSD and UD groups in terms of engraftment, GVHD, and complications, including infection and hemorrhagic cystitis. The median follow-up time was 38.6 months (range: 1.4–140.8 months). As of October 31, 2021, five patients had succumbed, while 27 (84.4%) survived. The 5-year OS rate showed no statistically significant difference between the MSD and UD groups (84.8 ± 10.0 vs. 82.4 ± 9.2%, p = 0.674). In conclusion, the application of UC-MSCs in the treatment of R/R SAA in PBSC transplantation is reliable and safe, they had no graft rejection, low incidence of severe GVHD which may have been contributed by the co-infusion of MSC. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a commonly studied chemotherapeutic agent for the treatment of solid tumors, but the severe side effects limit its clinical application. It is shown that DOX-metal chelate has lower in vitro cytotoxicity compared with DOX, as the anthracyclines of DOX can form coordinative interaction with transition metal ions. In addition, the transition metal ions could catalyze the production of hydroxyl radicals (·OH) via Fenton/Fenton-like reactions to achieve antitumor chemodynamic therapy (CDT). In this study, copper ions (Cu2+) were applied to obtain DOX/Cu(II) prodrug, and a liposomal formulation was used to avoid the rapid blood clearance and optimize the biodistribution of this prodrug. In vitro and in vivo antitumor results demonstrated that this pH sensitive Cu-chelating prodrug can reduce adverse effects of DOX but improve the antitumor efficiency due to the combination of chemotherapy and chemodynamic therapy. Our study provided a facile and effective approach of metal-chelating prodrug strategy for combination cancer therapy strategy. [ABSTRACT FROM AUTHOR]

In transdermal drug delivery systems, the physicochemical properties of the drug affect its percutaneous permeability. However, whether the physicochemical properties of drugs change their transdermal permeability in the presence of pores in the presence of solid microneedles (MNs) has been less studied in this area. In this project, cinnamaldehyde, curcumin, ferulic acid and geniposide were selected as model drugs for the study of their transdermal permeability under the action of MNs, and a combination of classical experiments and visualization means such as scanning electron microscopy and laser confocal was used to investigate the permeation-promoting mechanism of MNs. The results showed that the MNs had significant permeation-promoting effects on different properties of drugs, with the permeation-promoting effects on cinnamaldehyde, curcumin, ferulic acid and geniposide being 6.36, 17.43, 29.54 and 8.91 times, respectively, and the permeation-promoting effects were more pronounced for lipid-soluble and amphiphilic drugs. Using scanning electron microscopy, transmission electron microscopy and other means to confirm that MNs can promote the penetration by acting on the skin to produce pores, and their effect on skin structure is greater than that of drugs. In addition, the existence of pores increases the amount of drug transdermal, which may enhance the diffusion of drug on the skin, and has no effect on lipid exchange and transdermal route. Through the research, it has been found that MNs is equivalent to direct peeling of the stratum corneum (SC), but it is simpler and safer for the patient. [ABSTRACT FROM AUTHOR]

Low meat performance is the defect of Small Tail Han sheep. Intramuscular fat affects meat quality and largely determined by adipogenesis. In previous study, miR136 was showed one of differentially expressed microRNAs between preadipocytes and mature adipocytes of Small Tail Han sheep but its role in adipogenesis is still not elucidated. Here, we investigated the effect of miR136 on adipogenesis and the underlying mechanism. qPCR data showed that miR136 level increased with preadipocytes proliferation while declined with preadipocytes differentiation. Moreover, miR136 mimics blocked lipid droplet formation, reduced lipid content and triglyceride accumulation while miR136 inhibitor showed the opposite effects, revealing that miR136 promoted preadipocytes proliferation but inhibited preadipocytes differentiation. Bioinformatics and biochemical validation manifested that PPARGC1B was a target of miR136. Furthermore, miR136 mimics decreased PPARγ and C/EBPα expression accompanied by PPARGC1B expression descending. Reverse effects were observed with miR136 inhibitor. Besides, overexpression of miR136 elevated IGF1 expression. Collectively, our data first exhibited a regulatory role of miR136 in adipogenesis, which is promoting preadipocytes proliferation through elevating IGF1 expression while inhibiting preadipocytes differentiation through targeting PPARGC1B and further declined PPARγ and C/EBPα expression. The modulation of PPARGC1B by miR136 may provide a new potential target for increasing intramuscular fat. [ABSTRACT FROM AUTHOR]

Let G and A be finite groups of relative coprime orders and A acts on G via automorphisms. When certain A-invariant subgroups of G are TI-subgroups or subnormal subgroups, we study the solubility and other structure properties of G. [ABSTRACT FROM AUTHOR]

Clinical management of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is progressing to include chronic/metabolic complications, which may impose a significant economic burden on beneficiaries and Medicare. We assessed the national economic impact of comorbid Type-II Diabetes Mellitus (T2DM) on HIV/AIDS patients and potential raical disparities. This study was a cross-sectional study of Medicare database 2013–2017. Analytical sample included HIV/AIDS positive beneficiaries continuously enrolled in Part A/B. Total medical costs, prescription costs, inpatient costs, outpatient costs, out-of-pocket (OOP) costs, and Medicare costs were assessed from Medicare claims. Generalized linear models with log-link and gamma distribution were used to examine the impact of T2DM on different costs. A total of 2,509 eligible HIV/AIDS positive beneficiaries were identified of which 19.9% (n=498) had T2DM. After adjusting for covariates, T2DM beneficiaries had higher inpatient costs: 63.34% (95% CI: 42.73%−86.94%), outpatient costs: 50.26% (95% CI: 30.70%−72.75%), Medicare costs: 27.95% (95% CI: 13.81%−43.84%), OOP costs: 59.15% (95% CI: 40.02%−80.92%), and total medical costs: 27.83% (95% CI: 14.27%−43.00%) than non-T2DM beneficiaries. Incremental costs were higher among African Americans than Caucasians. Comorbid T2DM mposes a significant economic burden on HIV/AIDS patients and Medicare, which is higheramong African Americans. [ABSTRACT FROM AUTHOR]

Association between protease inhibitors (PI) and Type II diabetes mellitus (T2DM) in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients is largely debated. This study examined the odds of developing T2DM among HIV/AIDS Medicare beneficiaries treated with PI and possible racial disparities in the odds. We performed a nested casecontrol study of Medicare database 2013–2017. We included HIV/AIDS positive beneficiaries who were enrolled continuously in Medicare Part A/B with no previous history of T2DM. PI-users were matched to non-PI users and non-anti-retroviral therapies (ART) users using a1:1 greedy propensity score (PS) matching. Multivariablee logistic regressions were performed to assess the odds of developing T2DM. The analysis included 2,353 HIV/AIDS beneficiaries. Matched samples were generated for PI vs. non-PI groups (n = 484) and PI vs. non-ART groups (n = 490). Compared to the non-PI group, the odds of developing T2DM were higher in PI-users (AOR: 1.76; 95% CI: 1.17–2.64), in Caucasian PI-users (AOR: 1.81; 95% CI: 1.02–3.22) and in African-American PI-users (AOR: 1.86; 95% CI: 1.03–3.36). Compared to the non-ART group, the odds of developing T2DM were higher in PI-users (AOR: 1.87; 95% CI: 1.25–2.81), in Caucasian PI-users (AOR: 1.96; 95% CI: 1.14–3.39) and in African-American PI-users (AOR: 2.05; 95% CI: 1.03–4.09). The use of PI is associated with higher odds of T2DM; odds were higher among African-Americans than Caucasians. [ABSTRACT FROM AUTHOR]

Outbursts comprise the predominant natural hazards in Chinese underground coal mines. Extracting high content gas within coal seams is one of the most effective ways to reduce the risk of triggering outbursts. However, with the depth increase of coal mining production, conventional gas drainage might be failed due to the low permeability of coal seams. Additional permeability enhancement methods should be adopted to improve the gas drainage efficiency. In this study, we proposed the application of liquid carbon dioxide fracturing for enhancing gas drainage in a underground coal mine in China with low permeability coal seams. By drilling cross-seam boreholes, liquid carbon dioxide fracturing was simultaneously performed in the two drilled fracturing boreholes. The effective damage radius of liquid carbon dioxide fracturing was further identified by continuously monitoring pure gas flow rates in different observation boreholes. After liquid carbon dioxide fracturing, there was no significant decrease in pure gas flow rate of observation boreholes for a period of 2 weeks. A conceptual model of liquid carbon dioxide fracturing was proposed for illustrating the mechanisms of improving gas drainage efficiency. Some methods for further optimizing gas drainage with the operation of liquid carbon dioxide fracturing under various thickness of coal seams and geological conditions were discussed. These results suggest that the application of liquid carbon dioxide fracturing are effective for gas control and hazards prevention in underground coal mines. [ABSTRACT FROM AUTHOR]

Real-world evidence is a valuable source of information in healthcare. This study describes the challenges and successes during algorithm development to identify cancer cohorts and multi-agent chemotherapy regimens from claims data to perform a comparative effectiveness analysis of granulocyte colony stimulating factor (G-CSF) use. Using the Biologics and Biosimilars Collective Intelligence Consortium's Distributed Research Network, we iteratively developed and tested a de novo algorithm to accurately identify patients by cancer diagnosis, then extract chemotherapy and G-CSF administrations for a retrospective study of prophylactic G-CSF. After identifying patients with cancer and subsequent chemotherapy exposures, we observed only 12% of patients with cancer received chemotherapy, which is fewer than expected based on prior analyses. Therefore, we reversed the initial inclusion criteria to identify chemotherapy receipt, then prior cancer diagnosis, which increased the number of patients from 2,814 to 3,645, or 68% of patients receiving chemotherapy had diagnoses of interest. Additionally, we excluded patients with cancer diagnoses that differed from those of interest in the 183 days before the index date of G-CSF receipt, including early-stage cancers without G-CSF or chemotherapy exposure. By removing this criterion, we retained 77 patients who were previously excluded. Finally, we incorporated a 5-day window to identify all chemotherapy drugs administered (excluding oral prednisone and methotrexate, as these medications may be used for other non-malignant conditions) as patients may fill oral prescriptions days to weeks prior to infusion. This increased the number of patients with chemotherapy exposures of interest to 6,010. The final cohort of included patients, based on G-CSF exposure, increased from 420 from the initial algorithm to 886 using the final algorithm. Medications used for multiple indications, sensitivity and specificity of administrative codes, and relative timing of medication exposure must all be evaluated to identify patient cohorts receiving chemotherapy from claims data. [ABSTRACT FROM AUTHOR]

Serving as a medium between source water and cellulose, leaf water contributes to the isotope ratios (δ18O, δ2H) of plant organic matter, which can be used for paleoclimate reconstruction. This study is the first to examine the diurnal variations in the δ18O and δ2H of leaf water on the southern Tibetan Plateau. The δ18O and δ2H of leaf water were relatively low when precipitation events occurred. In particular, 18O and 2H of leaf water became extremely depleted 5 h after the precipitation event. Our findings demonstrate that precipitation can modify the isotope ratios of leaf water from external and internal causes. First, precipitation events affect meteorological elements, lead to decreases in leaf transpiration, and immediately weaken the isotope enrichment of leaf water ('rapid effect' of precipitation). Second, precipitation events affect the internal plant–soil water cycle process, causing the plant to preferentially use deeper soil water, and the corresponding isotope ratios of leaf water exhibit extremely low values 5 h after precipitation events ('delay effect' of precipitation). This study suggests that researchers need to be cautious in separating the signals of precipitation and hydrological processes when interpreting isotope records preserved in tree-ring cellulose archives from the Tibetan Plateau. [ABSTRACT FROM AUTHOR]

Little is known about the effect of CFO (chief financial officer) tenure and earnings management using classification shifting. Based on upper echelons theory, this paper empirically investigates the impact of CFO tenure on classification shifting using data on Chinese A-share listed companies from 2009 to 2015. The results show that CFO tenure is negatively related to classification shifting, indicating that CFOs with longer tenures can mitigate the classification shifting behavior. Further tests show that firms have higher levels of classification shifting when CFOs are in the early or final years of their tenure. This research helps to understand the relationship between CFO tenure and earnings management. [ABSTRACT FROM AUTHOR]

Against the backdrop of Sino-US trade friction, we use Chinese President Xi Jinping's visit to rare earth companies as an exogenous event to investigate market investors' pursuit effect, on 11 rare earth companies. We find that (1) Xi's visit had an important signal effect, causing abnormal fluctuations in the stock prices and a significantly positive cumulative average abnormal return (CAAR) of the 11 companies. (2) After government political visits (GPV), firms located in developing regions, younger firms, firms with poor historical performance, and firms with high ownership concentration can generate higher cumulative excess returns than those in developed regions, more established firms, firms with better financial performance, and firms with lower ownership concentration. (3) Our findings can be interpreted from two perspectives: the information asymmetry between market investors and enterprises and the signal effects of GPV. Finally, we discuss policy recommendations from the perspective of information transfer and securities analysts. [ABSTRACT FROM AUTHOR]

We prospectively investigated the neurological development in infants born from mothers treated with telbivudine (LdT) in the third trimester for prevention of hepatitis B virus (HBV) mother-to-infant transmission. Mothers with high HBV load were assigned to either the LdT group (n = 81, 600 mg of LdT each day from gestational week 28 to delivery) or the Control group (n = 39, untreated). Their infants were followed for 36 months to assess physical and neurological developments with Gesell Developmental Schedule tools. At 12 months after birth, the mean scores in the LdT group for gross motor, fine motor, adaptive, linguistic, and personal social domains were similar to those in the Control group. At 36 months, infants in the LdT group had higher mean scores for gross motor than the Control group (98.42 ± 9.69 vs. 94.54 ± 7.48, P = 0.03). In the LdT group, the rates of normal development were higher for gross motor (96.30% vs. 82.05% P = 0.01) and lower for adaptive (74.07% vs. 92.31% P = 0.02). Multivariate regression analyses showed that exposure to LdT during pregnancy was independently associated with infant's development in gross motor (OR 6.49, 95% CI 1.37–30.20, P = 0.02) and adaptive (OR 0.18, 95% CI 0.05–0.71, P = 0.01) at 36 months. These results suggest that prenatal LdT exposure might affect neurological development in long-term observation. Abbreviations: LdT: telbivudine; HBV: hepatitis B virus; HBsAg: hepatitis B surface antigen; HBeAg: hepatitis Be antigen; HbsAb: hepatitis B surface antibody; ALT: alanine aminotransferase; NA: nucleoside/nucleotide analog; LAM: lamivudine; MTCT: mother-to-child transmission; GDS: Gesell Developmental Schedule; OR: odds ratio; CI: confidence interval; DQ: developmental quotient; RMB: renminbi; BMI: body mass Index; HBIG: hepatitis B immunoglobulin. [ABSTRACT FROM AUTHOR]

This article offers a comparative analysis of the transformation of midwifery practices in Beijing city and its rural neighborhood in China between 1926 and 1937. From the 1920s onwards, impelled by supports of governments, academic groups and foreign foundations, a reform of midwifery practices was triggered across China. Beijing was one of the forerunners in this reform. Through examining the midwifery regulations, the new style midwifery service, the midwife education/training programs, as well as the consequential influences on birth attendants and birth outcomes (neonatal, infant and maternal mortality rates) in Beijing's first health district and the nearby Qinghe district, this article shows that in the urban district the trained birth attendants performed better than the untrained personnel in preventing neonatal deaths. Also, the growing use of trained midwifery contributed to the reduction of infant and maternal mortality rates in the urban community. However, because of the paucity of sources of rural areas, such positive outcomes cannot be ascertained in the rural district. Yet an obvious urban-rural divergence in midwifery services and maternal care is still observed. [ABSTRACT FROM AUTHOR]

In the present study, a simple and fast method for simultaneous detection of zearalenone, citrinin, and ochratoxin A utilising capillary zone electrophoresis with an ultraviolet detector was developed. The optimised approach was validated and applied using pepper samples. The proposed method yielded satisfactory linearity between the signal and the mycotoxin concentration in the range of 1.5–150 μg/kg for zearalenone, 4.5–150 μg/kg for citrinin, and 0.8–150 μg/kg for ochratoxin A. The limits of detection for these mycotoxins ranged from 0.3 to 1.5 μg/kg. The corresponding intra- and inter-day precisions were less than 3.5 % and 4.1 %, respectively. Moreover, the matrix effect was also assessed and the result was compared using the capillary zone electrophoresis and high-performance liquid chromatography methods. The developed approach could be used for simultaneous detection of zearalenone, citrinin, and ochratoxin A in pepper. [ABSTRACT FROM AUTHOR]

Ligands are an important part of targeted drug delivery systems. Optimised lignads not only improve the target efficiency, but also enhance therapeutical effect of drugs. In our research, five sugar molecules (Mannose, Galactose, Glucose, Malt disaccharide, and Maltotriose) conjugated PEG600-DSPE were synthesised, of which polysaccharides were first discovered by us as sugar ligands to modify liposomes, which interacts with over expressive GLUT on cancer cells. DiO was encapsulated as fluorescent probe to evaluate their cellular uptake abilities of targeting C6 glioma cells, and the distribution in different visceral organs of rats. The results demonstrated that Malt disaccharide and Glucose-PEG600-DSPE had the strong efficiency of cellular uptake by C6 glioma cells. The distribution and accumulation of liposomes showed that different sugars modified liposomes could target different visceral organs in rats. It has provided a novel idea for ligand selectivity and optimisation of nanocarriers for tumour targeted therapy. [ABSTRACT FROM AUTHOR]

Aim: Cardiac extracellular matrix (cECM) scaffolds are promising biomaterials for clinical applications. Our aim is to determine the immunogenicity of decellularized scaffolds from different sources for use as artificial organs during organ transplantation. Materials & methods: We transplanted Lewis rats with syngeneic (Lewis rat cECM), allogeneic (BN rat cECM) or xenogeneic (hamster cECM) decellularized cardiac scaffolds. Acute vascular and cellular rejection was quantified by immunohistochemistry and immune cell infiltration. Results: BN rat and hamster hearts were rejected following transplantation. BN and hamster cECMs had similarly low immunogenicity compared with Lewis rat cECMs and did not lead to increased rejection. Conclusion: We found that scaffolds from all sources did not induce vascular or cellular rejection and exhibited low immunogenicity. [ABSTRACT FROM AUTHOR]

In most large field of view (FOV) observations, the distortion problem is inevitably and significantly more serious than in small FOV ones. In the circumstances, many traditional star identification approaches are not able to efficiently identify stars any more. In order to deal with this problem, we put forward a star identification method that is less sensitive to distortion. The method first processes stars in the central area of the image, using traditional identification logic, and then applies the region growing strategy to enlarge the identified regions iteratively until the entire image is covered. The performance of the new scheme is analysed in the presence of both simulated data and real data. The results show that the proposed algorithm has the advantage of speed, and the strategy of regional extension can efficiently identify stars in large FOV images compared with other existing algorithms. [ABSTRACT FROM PUBLISHER]

Several chemotherapy regimens have been used as second-line therapies for relapsed and refractory diffuse large B-cell lymphoma (DLBCL). None have emerged as a preferred regimen. This retrospective study aimed to identify a regimen with high efficacy and low toxicity for patients with relapsed and refractory DLBCL. Fifty-eight patients diagnosed with relapsed or refractory DLBCL were included in the study. Patients were treated with cyclophosphamide, vindesine, cytarabine, dexamethasone and bleomycin (COAD-B). The overall response rate (ORR) was 70.7%, and the median remission duration was 13 months (3-48 months). The 1-, 2- and 4-year overall survival rates were 62.4%, 45.7% and 34.6%, respectively. The 1-, 2- and 4-year progression-free survival rates were 50.0%, 36.7% and 20.7%, respectively. The responses of patients with relapsed DLBCL to COAD-B were significantly better than those of patients with refractory DLBCL ( p = 0.005). The main adverse reaction of patients was myelosuppression. Our data indicate that COAD-B should be used in treatment of patients with relapsed DLBCL. [ABSTRACT FROM AUTHOR]