Search

Yujuan Fan,* Yu Zhang,* Xuesong Li,* Hui Zheng, Yuping Song, Ning Zhang, Chunfang Shen, Xiaofang Fan, Fengdong Ren, Jiayi Shen, Guoguang Ren, Jialin Yang Department of Endocrinology, Central Hospital of Minhang District, Minhang Hospital affiliated to Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The objective of this study was to assess the effects of metformin monotherapy or combined treatment with a dipeptidyl peptidase-4 inhibitor (vildagliptin) on apelin levels in patients with type 2 diabetes mellitus. Methods: Twenty-five patients with poor glycemic control (glycosylated hemoglobin >6.5% [48 mmol/mol]) taking 1,000 mg of metformin daily and 25 healthy controls matched for age and body mass index were enrolled in this study. Anthropometric parameters, glycemic and lipid profile, insulin resistance (homeostasis model assessment of insulin resistance index), and apelin levels were measured at baseline and at 12-week and 24-week visits. Results: At baseline, apelin levels were higher in the T2DM patients than in the controls (1.93±1.81 ng/mL versus 6.09±4.90 ng/mL; P

Jin-Yang Shen,1,* Xiao-Lin Yang,2,* Zhong-Lin Yang,1 Jun-Ping Kou,1 Fei Li11State Key Laboratory of Natural Medicines, China Pharmaceutical University, 2Key Laboratory of Pharmaceutical and Biological Marine Resources Research and Development of Jiangsu Province, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China*These authors contributed equally to this workPurpose: This present study investigated the absorption kinetics of echinacoside (ECH) in situ and in vitro and its oral bioavailability in rats. Additional aim was to find an agent(s) to promote ECH absorption and oral bioavailability among two efflux proteins and three absorption promoters.Methods: ECH absorption behaviors were investigated by everted gut sac model in vitro and single-pass intestinal perfusion model in situ. Pharmacokinetics study was performed to investigate the influences of verapamil and clove oil on ECH bioavailability in vivo. All samples were measured at different time intervals by high performance liquid chromatography.Results: The results showed that the effective permeability coefficient (Peff) and apparent permeability coefficient of ECH were 0.83×10-6–3.23×10-6 cm/s and 2.99×10-6–9.86×10-6 cm/s, respectively. The Peff among duodenum, jejunum, and ileum were not statistically different, but they were higher than colon (P

There are amounts of patients with locomotor dysfunction caused by stroke until now. Body weight supported treadmill training (BWSTT) has proved to be an efficient method of rehabilitation training for those people. The lower exoskeleton consists of two legs which is used to guide and assist motions of patients with the help of weight support devices and a treadmill. A prototype of the body weight support exoskeleton rehabilitation device (BWSERD) has been designed in this paper, which contains two pairs of direct drives at hip and knee joints. It has also four torque transducers and four encoders. In order to conduct the patients-passive rehabilitation training after stroke, a control strategy based on neuro network and sliding mode controller is developed. The effectiveness of the proposed method is confirmed by the simulation results.

RATIONALE: Although the phosphodiesterase type 5 inhibitors sildenafil and tadalafil have demonstrated efficacy in patients with pulmonary arterial hypertension (PAH), monotherapy with these agents has not been conclusively shown to reduce clinical worsening events. OBJECTIVES: To evaluate the safety and efficacy of the phosphodiesterase type 5 inhibitor vardenafil in Chinese patients with PAH. METHODS: In a randomized, double-blind, placebo-controlled study, 66 patients with PAH were randomized 2:1 to vardenafil (5 mg once daily for 4 wk then 5 mg twice daily; n = 44) or placebo (n = 22) for 12 weeks. Patients completing this phase were then treated with open-label vardenafil (5 mg twice daily) for a further 12 weeks. MEASUREMENTS AND MAIN RESULTS: At Week 12, the mean placebo-corrected 6-minute walking distance was increased with vardenafil (69 m; P < 0.001), and this improvement was maintained for at least 24 weeks. Vardenafil also increased the mean placebo-corrected cardiac index (0.39 L·min(-1)·m(-2); P = 0.005) and decreased mean pulmonary arterial pressure and pulmonary vascular resistance (-5.3 mm Hg, P = 0.047; -4.7 Wood U, P = 0.003; respectively) at Week 12. Four patients in the placebo group (20%) and one in the vardenafil group (2.3%) had clinical worsening events (hazard ratio 0.105; 95% confidence interval, 0.012-0.938; P = 0.044). Vardenafil was associated with only mild and transient adverse events. CONCLUSIONS: Vardenafil is effective and well tolerated in patients with PAH at a dose of 5 mg twice daily. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the early cognitive development characteristics of children with Williams syndrome (WS) at different age stages., Methods: From September 2018 to June 2023, 106 children diagnosed with WS at the Department of Pediatric Health Care, Children's Hospital, Zhejiang University School of Medicine, aged 1 to <5 years, were prospectively enrolled. All children underwent Gesell developmental diagnostic assessments to analyze the cognitive development characteristics of WS children across different age groups., Results: The average age of the 106 WS children was (3.1±1.2) years; 58 were male, and 48 were female. There were no significant differences in developmental levels between males and females in the five domains of gross motor skills, fine motor skills, language, personal-social skills, and adaptive behavior ( P >0.05). The incidence rates of mild, moderate, severe, and profound developmental disabilities among children of different age groups showed no significant differences ( P >0.05). Comparisons of developmental levels in gross motor skills, language, personal-social skills, and adaptive behavior among different age groups were also not statistically significant ( P >0.05). With the increase of age, the developmental level of fine motor skills showed a decreasing trend ( P <0.05). There were no significant differences in verbal IQ and non-verbal IQ within each age group of WS children ( P >0.05)., Conclusions: The overall developmental level of WS children stabilizes with age, and their early language abilities do not significantly exceed their non-verbal abilities.

We explore the construction of gluing together an arbitrary number of spacetimes along a common interface. This provides a general tool to construct new gravitational backgrounds with multiple boundaries. We derive junction conditions across the interface, in both Einstein gravity and dilaton gravity, using two methods (1) by developing a geometrical technique of introducing an auxiliary reverse extension manifold and (2) by the variational principle. Our junction condition works for both spacelike and timelike interfaces. We illustrate applications of the junction conditions in Jackiw-Teitelboim gravity and analyze their constraints on the allowed dilaton profile. We further comment on the geometry of a web of spacetime in the presence of multiple interfaces and its resemblance to Feynman diagrams.

Background: Evaluating the potential of using both synthetic and biological products as targeting agents for the diagnosis, imaging, and treatment of infections due to particularly antibiotic-resistant pathogens is important for controlling infections. This study examined the interaction between Gp45, a receptor-binding protein of the ϕ11 lysogenic phage, and its host Staphylococcus aureus (S. aureus), a common cause of nosocomial infections., Methods: Using molecular dynamics and docking simulations, this study identified the peptides that bind to S. aureus wall teichoic acids via Gp45. It compared the binding affinity of Gp45 and the two highest-scoring peptide sequences (P1 and P3) and their scrambled forms using microscopy, spectroscopy, and ELISA., Results: It was found that rGp45 (recombinant Gp45) and chemically synthesised P1 had a higher binding affinity for S. aureus compared with all other peptides, except for Escherichia coli. Furthermore, rGp45 had a capture efficiency of > 86%; P1 had a capture efficiency of > 64%., Conclusion: These findings suggest that receptor-binding proteins such as rGp45, which provide a critical initiation of the phage life cycle for host adsorption, might play an important role in the diagnosis, imaging, and targeting of bacterial infections. Studying such proteins could accordingly enable the development of effective strategies for controlling infections., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Copper, an indispensable micronutrient, is implicated in numerous vital biological processes and is essential for all physiological activities. Recently, the discovery of a novel type of copper-dependent cell death, known as cuproptosis, has shed light on its role in cancer development. Extensive research is currently underway to unravel the mechanisms underlying cuproptosis and its correlation with various cancer types. In this review, we summarize the findings regarding the roles and mechanisms of cuproptosis in various cancer types, including colorectal cancer, lung cancer, gastric cancer, breast cancer, liver cancer and cutaneous melanoma. Furthermore, the effects of copper-related agents such as copper chelators and copper ionophores on cell proliferation, apoptosis, angiogenesis, tumor immunity, and chemotherapy resistance have been explored in cancer preclinical and clinical trials. These insights provide promising avenues for the development of prospective anticancer drugs aimed at inducing cuproptosis., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

With the increasing adoption of carbon-based strategies to enhance methanogenic processes, there is a growing concern regarding the correlation between biochar properties and its stimulating effects on anaerobic digestion (AD) under ammonia inhibition. This study delves into the relevant characteristics and potential mechanisms of biochar in the context of AD system under ammonia inhibition. The introduction of optimized biochar, distinguished by rich CO bond, abundant defect density, and high electronic capacity, resulted in a significant reduction in the lag period of anaerobic digestion system under 5.0 g/L ammonia stress, approximately by around 63 % compared to the control one. Biochar helps regulate the community structure, promotes the accumulation of acetate-consuming bacteria, in the AD system under ammonia inhibition. More examinations show that biochar promotes direct interspecies electron transfer in AD system under ammonia inhibition, as evidenced by diminished levels of bound electroactive extracellular polymeric substances, increased abundance of electroactive bacteria, and notably, the up-regulation of direct interspecies electron transfer associated genes, including the conductive pili and Cytochrome C genes, as revealed by meta-transcriptomic analysis. Additionally, gene expression related to proteins associated with ammonium detoxification were found to be up-regulated in systems supplemented with biochar. These findings provide essential evidence and insights for the selection and potential engineering of effective biochar to enhance AD performance under ammonia inhibition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Status epilepticus (SE) in the neurology intensive care unit (ICU) is associated with significant morbidity. We aimed to evaluate the utility of existing prognostic scores, namely the Status Epilepticus Severity Score (STESS), Epidemiology Based Mortality Score in Status Epilepticus (EMSE)-EACE and Encephalitis-Nonconvulsive Status Epilepticus-Diazepam Resistance-Image Abnormalities-Tracheal Intubation (END-IT), among SE patients in the neurology ICU., Methods: Neurology ICU patients with SE requiring continuous electroencephalography (cEEG) monitoring over a 10 year period were included. The STESS, EMSE-EACE and END-IT scores were applied retrospectively. Receiver operating characteristic (ROC) analysis was performed to assess the discriminatory value of the scores for inpatient mortality and functional decline, as measured by increase in the modified Rankin Scale (mRS) on discharge., Results: Eighty-five patients were included in the study, of which 71 (83.5%) had refractory SE. Inpatient mortality was 36.5%. Sixty - seven (78.8%) of patients suffered functional decline, with a median mRS of 5 upon hospital discharge. The AUCs of the STESS, EMSE-EACE and END-IT scores associated with inpatient mortality were 0.723 (95% CI 0.613-0.833), 0.722 (95% CI 0.609-0.834) and 0.560 (95% CI 0.436-0.684) respectively. The AUCs of the STESS, EMSE-EACE and END-IT scores associated with functional decline were 0.604 (95% CI 0.468-0.741), 0.596 (95% CI 0.439-0.754) and 0.477 (95% CI 0.331-0.623)., Significance: SE was associated with high mortality and morbidity in this cohort of neurology ICU patients requiring cEEG monitoring. The STESS and EMSE-EACE scores had acceptable AUCs for prediction of inpatient mortality. However, the STESS, EMSE-EACE and END-IT were poorly-correlated with discharge functional outcomes. Further refinements of the scores may be necessary among neurology ICU patients for predicting discharge functional outcomes., Competing Interests: Declaration of competing interest Dr. Nigel Choon Kiat TAN owns shares in Pfizer, Johnson & Johnson and Novartis. The remaining authors have no conflicts of interest. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Ultrasonic flow ratio (UFR) is a novel intravascular ultrasound (IVUS)-derived modality for fast computation of fractional flow reserve (FFR) without pressure wires and adenosine., Aims: This study was sought to compare the diagnostic performance of UFR and quantitative flow ratio (QFR), using FFR as the reference standard., Methods: This is a retrospective study enrolling consecutive patients with intermediate coronary artery lesions (diameter stenosis of 30%-90% by visual estimation) for IVUS and FFR measurement. UFR and QFR were performed offline in a core-lab by independent analysts blinded to FFR., Results: From December 2022 to May 2023, a total of 78 eligible patients were enrolled. IVUS and FFR measurements were successfully conducted in 104 vessels, finally 98 vessels with both FFR, UFR and QFR evaluation were analyzed. Mean FFR was 0.79 ± 0.12. UFR showed a strong correlation with FFR similar to QFR (r = 0.83 vs. 0.82, p = 0.795). Diagnostic accuracy of UFR was non-inferior to QFR (94% [89%-97%] versus 90% [84%-94%], p = 0.113). Sensitivity and specificity in identifying hemodynamically significant stenosis were comparable between UFR and QFR (sensitivity: 89% [79%-96%] versus 85% [74%-92%], p = 0.453; specificity: 97% [91%-99%] versus 95% [88%-99%], p = 0.625). The area under curve for UFR was 0.95 [0.90-0.98], non-inferior to QFR (difference = 0.021, p = 0.293), and significantly higher than minimum lumen area (MLA; difference = 0.13, p < 0.001). Diagnostic accuracy of UFR and QFR was not statically different in bifurcation nor non-bifurcation lesions., Conclusions: UFR showed excellent concordance with FFR, non-inferior to QFR, superior to MLA. UFR provides a potentiality for the integration of physiological assessment and intravascular imaging in clinical practice., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Over half of older adults experience polypharmacy, including medications that may be inappropriate or unnecessary. Deprescribing, which is the process of discontinuing or reducing inappropriate and/or unnecessary medications, is an effective way to reduce polypharmacy. This review summarizes (1) the process of deprescribing and conceptual models and tools that have been developed to facilitate deprescribing, (2) barriers, enablers, and factors associated with deprescribing, and (3) characteristics of deprescribing interventions in completed trials, as well as (4) implementation considerations for deprescribing in routine practice. In conceptual models of deprescribing, multilevel factors of the patient, clinician, and health-care system are all related to the efficacy of deprescribing. Numerous tools have been developed for clinicians to facilitate deprescribing, yet most require substantial time and, thus, may be difficult to implement during routine health-care encounters. Multiple deprescribing interventions have been evaluated, which mostly include one or more of the following components: patient education, medication review, identification of deprescribing targets, and patient and/or provider communication about high-risk medications. Yet, there has been limited consideration of implementation factors in prior deprescribing interventions, especially with regard to the personnel and resources in existing health-care systems and the feasibility of incorporating components of deprescribing interventions into the routine care processes of clinicians. Future trials require a more balanced consideration of both effectiveness and implementation when designing deprescribing interventions., (© 2022 The Association for the Publication of the Journal of Internal Medicine.)

Ribozymes are catalytic RNAs with diverse functions including self-splicing and polymerization. This work aims to discover natural ribozymes that behave as hydrolytic and sequence-specific DNA endonucleases, which could be repurposed as DNA manipulation tools. Focused on bacterial group II-C introns, we found that many systems without intron-encoded protein propagate multiple copies in their resident genomes. These introns, named HYdrolytic Endonucleolytic Ribozymes (HYERs), cleaved RNA, single-stranded DNA, bubbled double-stranded DNA (dsDNA), and plasmids in vitro. HYER1 generated dsDNA breaks in the mammalian genome. Cryo-electron microscopy analysis revealed a homodimer structure for HYER1, where each monomer contains a Mg 2+ -dependent hydrolysis pocket and captures DNA complementary to the target recognition site (TRS). Rational designs including TRS extension, recruiting sequence insertion, and heterodimerization yielded engineered HYERs showing improved specificity and flexibility for DNA manipulation.

This study aims to investigate the effect of Erchen Decoction(ECD) on liver mitochondrial function in mice with a high-fat diet and its possible mechanism. A total of sixty C57BL/6J mice were randomly divided into a normal group, high-fat group, ECD group, mTORC1 activator(MHY) group, ECD+MHY group, and polyene phosphatidyl choline(PPC) group, with 10 rats in each group. The normal group was given a normal diet, and the other groups were fed a high-fat diet for 20 weeks. At the 17th week, the ECD group and ECD+MHY group were given ECD(8.7 g·kg~(-1)) daily, and the PPC group was given PPC(0.18 g·kg~(-1)) daily, while the remaining groups were given normal saline(0.01 mL·g~(-1)) daily for four weeks. In the 19th week, the MHY group and ECD+MHY group were injected intraperitoneally with MHY(5 mg·kg~(-1)) every other day for two weeks. During the experiment, the general conditions of the mice were observed. The contents of triglyceride(TG) and total cholesterol(TC) in serum were measured. Morphological changes in liver tissue were examined through HE and oil red O staining. The content of adenosine triphosphate(ATP) was determined using chemiluminescence, and mitochondrial membrane potential was assessed using a fluorescence probe(JC-1). Western blot was performed to detect the expression of rapamycin target protein complex 1(mTOR1), ribosomal protein S6 kinase B1(S6K), sterol regulatory element binding protein 1(SREBP1), and caveolin 1(CAV1). RESULTS:: revealed that compared with the normal group, the mice in the high-fat group exhibited significant increases in body weight and abdominal circumference(P&lt;0.01). Additionally, there were significant increases in TG and TC levels(P&lt;0.01). HE and oil red O staining showed that the boundaries of hepatic lobules were unclear; hepatocytes were enlarged, round, and irregularly arranged, with obvious lipid droplet deposition and inflammatory cell infiltration. The liver ATP content and mitochondrial membrane potential decreased significantly(P&lt;0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 increased significantly(P&lt;0.01), while the expression of CAV1 decreased significantly(P&lt;0.01). Compared with the high-fat group, the body weight and TG content of mice in the ECD group and PPC group decreased significantly(P&lt;0.05). Improvements were observed in hepatocyte morphology, lipid deposition, and inflammatory cell infiltration. Furthermore, there were significant increases in ATP content and mitochondrial membrane potential(P&lt;0.05 or P&lt;0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly in the ECD group(P&lt;0.01), while CAV1 expression increased significantly(P&lt;0.01). However, the indices mentioned above did not show improvement in the MHY group. When the ECD+MHY group was compared with the MHY group, there were significant reductions in body weight and TG contents(P&lt;0.05). The morphological changes of hepatocytes, lipid deposition, and inflammatory cell infiltration were recovered. Moreover, there were significant increases in liver ATP content and mitochondrial membrane potential(P&lt;0.05 or P&lt;0.05). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly(P&lt;0.01), while CAV1 expression increased significantly(P&lt;0.01). In conclusion, ECD can improve mitochondrial function by regulating the mTORC1/SREBP1/CAV1 pathway. This mechanism may be involved in the resolution of phlegm syndrome and the regulation of lipid metabolism.

Objectives: Medications with a higher risk of harm or that are unlikely to be beneficial are used by nearly all older patients in home health care (HHC). The objective of this study was to understand stakeholders' perspectives on challenges in deprescribing these medications for post-acute HHC patients., Design: Qualitative individual interviews were conducted with stakeholders involved with post-acute deprescribing., Setting and Participant: Older HHC patients, HHC nurses, pharmacists, and primary/acute care/post-acute prescribers from 9 US states participated in individual qualitative interviews., Measures: Interview questions were focused on the experience, processes, roles, training, workflow, and challenges of deprescribing in hospital-to-home transitions. We used the constant comparison approach to identify and compare findings among patient, prescriber, and pharmacist and HHC nurse stakeholders., Results: We interviewed 9 older patients, 11 HHC nurses, 5 primary care physicians (PCP), 3 pharmacists, 1 hospitalist, and 1 post-acute nurse practitioner. Four challenges were described in post-acute deprescribing for HHC patients. First, PCPs' time constraints, the timing of patient encounters after hospital discharge, and the lack of prioritization of deprescribing make it difficult for PCPs to initiate post-acute deprescribing. Second, patients are often confused about their medications, despite the care team's efforts in educating the patients. Third, communication is challenging between HHC nurses, PCPs, specialists, and hospitalists. Fourth, the roles of HHC nurses and pharmacists are limited in care team collaboration and discussion about post-acute deprescribing., Conclusions and Implications: Post-acute deprescribing relies on multiple parties in the care team yet it has challenges. Interventions to align the timing of deprescribing and that of post-acute care visits, prioritize deprescribing and allow clinicians more time to complete related tasks, improve medication education for patients, and ensure effective communication in the care team with synchronized electronic health record systems are needed to advance deprescribing during the transition from hospital to home., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Antipsychotic use is a safety concern among older patients in home health care (HHC), particularly for those with Alzheimer's disease and related dementias (ADRD). The objective of this study was to examine the prevalence and predictors of antipsychotic use among older adults with and without ADRD who received HHC, and the association of antipsychotic use with outcomes among patients living with ADRD., Methods: In this secondary analysis of adults ≥65 years receiving care from an HHC agency in New York in 2019 (N = 6684), we used data from the Outcome and Assessment Information Set, Medicare HHC claims, and home medication review results in the electronic HHC records during a 60-day HHC episode. ADRD was identified by diagnostic codes. Functional outcome was the change in the composite activities of daily living (ADL) score from HHC admission to HHC discharge (measured in 5833 patients), where a positive score means improvement and a negative score means decline. Data were analyzed using logistic (predictors) and linear regression (association with outcome) analyses., Results: The point prevalence of antipsychotic use was 17.2% and 6.6% among patients with and without ADRD, respectively. Among patients living with ADRD, predictors of antipsychotic use included having greater ADL limitations (odds ratio [OR] = 1.30, p = 0.01), taking more medications (OR = 1.04, p = 0.02), having behavioral and psychological symptoms (OR = 5.26, p = 0.002), and living alone (OR = 0.52, p = 0.06). Among patients living with ADRD, antipsychotic use was associated with having less ADL improvement at HHC discharge (β = -0.70, p < 0.001)., Conclusions: HHC patients living with ADRD were more likely to use antipsychotics and to experience worse functional outcomes when using antipsychotics. Antipsychotics should be systematically reviewed and, if contraindicated or unnecessary, deprescribed. Efforts are needed to improve HHC patients' access to nonpharmacological interventions and to provide education for caregivers regarding behavioral approaches to manage symptoms in ADRD., (© 2023 The American Geriatrics Society.)

Increasing the carrier density in a Mott insulator by chemical doping gives rise to a generic superconducting dome in high temperature superconductors. An intriguing question is whether a second superconducting dome may exist at higher dopings. Here we heavily overdope La 2-x Sr x CuO 4 (0.45 ≤ x ≤ 1.0) and discover an unprecedented reentrance of interface superconductivity in La 2-x Sr x CuO 4 /La 2 CuO 4 heterostructures. As x increases, the superconductivity is weakened and completely fades away at x = 0.8; but it revives at higher doping and fully recovers at x = 1.0. This is shown to be correlated with the suppression of the interfacial charge transfer around x = 0.8 and the weak-to-strong localization crossover in the La 2-x Sr x CuO 4 layer. We further construct a theoretical model to account for the sophisticated relation between charge localization and interfacial charge transfer. Our work advances both the search for and control of new superconducting heterostructures., (© 2023. The Author(s).)

Objectives: Automated seizure detection modalities can increase safety among people with epilepsy (PWE) and reduce seizure-related anxiety. We evaluated the potential cost-effectiveness of a seizure detection mobile application for PWE in Singapore., Methods: We used a Markov cohort model to estimate the expected changes to total costs and health outcomes from a decision to adopt the seizure detection application versus the current standard of care from the health provider perspective. The time horizon is ten years and cycle duration is one month. Parameter values were updated from national databases and published literature. As we do not know the application efficacy in reducing seizure-related injuries, a conservative estimate of 1% reduction was used. Probabilistic sensitivity analysis, scenario analyses, and value of information analysis were performed., Results: At a willingness-to-pay of $45,000/ quality-adjusted life-years (QALY), the incremental cost-effectiveness ratio was $1,096/QALY, and the incremental net monetary benefit was $13,656. Probabilistic sensitivity analyses reported that the application had a 99.5% chance of being cost-effective. In a scenario analysis in which the reduction in risk of seizure-related injury was 20%, there was a 99.8% chance that the application was cost-effective. Value of information analysis revealed that health utilities was the most important parameter group contributing to model uncertainty., Conclusions: This early-stage modeling study reveals that the seizure detection application is likely to be cost-effective compared to current standard of care. Future prospective trials will be needed to demonstrate the real-world impact of the application. Changes in health-related quality of life should also be measured in future trials., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests or personal relationships that may be considered potential competing interests: Yee-Leng Tan reports that financial support was provided by SingHealth Duke-NUS Academic Medical Centre., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Bacteriophages, which selectively infect bacteria, and phage-derived structures are considered promising agents for the diagnosis and treatment of bacterial infections due to the increasing antibiotic resistance. The binding of phages to their specific receptors on host bacteria is highly specific and irreversible, and therefore, the characterization of receptor-binding proteins(RBPs), which are key determinants of phage specificity, is crucial for the development of new diagnostic and therapeutic products. This study highlights the biotechnological potential of Gp144, an RBP located in the tail baseplate of bacteriophage K and responsible for adsorption of phageK to S. aureus. Once it was established that recombinant Gp144 (rGp144)is biocompatible and does not exhibit lytic effects on bacteria, its interaction with the host, the binding efficiency and performance were assessed in vitro using microscopic and serological methods. Results showed that rGp144 has a capture efficiency (CE) of over 87% and the best CE score is %96 which captured 9 CFU mL -1 out of 10 CFU mL -1 bacteria, indicating that very low number of bacteria could be detected. Additionally, it was shown for the first time in the literature that rGp144 binds to both S. aureus and methicillin-resistant S. aureus (MRSA) cells in vitro, while its affinity to different Gram-positive bacteria (E. faecalis and B. cereus) was not observed. The findings suggest that rGp144 can be effectively used for the diagnosis of S. aureus and MRSA, and that the use of RBPs in host-phage interaction can be a novel and effective strategy for imaging and diagnosing the site of infection., (© 2023 Wiley-VCH GmbH.)

Purpose: Nearly all older patients receiving postacute home health care (HHC) use potentially inappropriate medications (PIMs) that carry a risk of harm. Deprescribing can reduce and optimize the use of PIMs, yet it is often not conducted among HHC patients. The objective of this study was to gather perspectives from patient, practitioner, and HHC clinician stakeholders on tasks that are essential to postacute deprescribing in HHC., Methods: A total of 44 stakeholders, including 14 HHC patients, 15 practitioners (including 9 primary care physicians, 4 pharmacists, 1 hospitalist, and 1 nurse practitioner), and 15 HHC nurses, participated. The stakeholders were from 12 US states, including New York (n = 29), Colorado (n = 2), Connecticut (n = 1), Illinois (n = 2), Kansas (n = 2), Massachusetts (n = 1), Minnesota (n = 1), Mississippi (n = 1), Nebraska (n = 1), Ohio (n = 1), Tennessee (n = 1), and Texas (n = 2). First, individual interviews were conducted by experienced research staff via video conference or telephone. Second, the study team reviewed all interview transcripts and selected interview statements regarding stakeholders' suggestions for important tasks needed for postacute deprescribing in HHC. Third, concept mapping was conducted in which stakeholders sorted and rated selected interview statements regarding importance and feasibility. A content analysis was conducted of data collected in the individual interviews, and a mixed-method analysis was conducted of data collected in the concept mapping., Findings: Four essential tasks were identified for postacute deprescribing in HHC: (1) ongoing review and assessment of medication use, (2) patent-centered and individualized plan of deprescribing, (3) timely and efficient communication among members of the care team, and (4) continuous and tailored medication education to meet patient needs. Among these tasks, developing patient-centered deprescribing considerations was considered the most important and feasible, followed by medication education, review and assessment of medication use, and communication., Implications: Deprescribing during the transition of care from hospital to home requires the following: continuous medication education for patients, families, and caregivers; ongoing review and assessment of medication use; patient-centered deprescribing considerations; and effective communication and collaboration among the primary care physician, HHC nurse, and pharmacist., Competing Interests: Declaration of Competing Interest Jinjiao Wang received grants from the NIA funded U.S. Deprescribing Research Network and the Alliance for Home Health Quality and Innovation. Sandra Simmons received consulting fee from Abt Associates and participated on the data safety monitoring or advisory board of the CAPABLE study, Prepare for your Diabetes Care, and the Porchlight Project. Amanda Mixon received grants from VA HSR&D and NIA, and consulting fees from American Society of Health-System Pharmacists. Other authors reported no conflicts of interest pertinent to this manuscript. The views expressed in this article are those of the authors and do not necessarily represent the view of the funders. The funders had no role in study design, data collection, analyses, or interpretation of results., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Portal hypertension combined with esophagogastric variceal bleeding (EGVB) is a serious complication in patients with hepatitis B virus (HBV)-related cirrhosis in China. Splenectomy plus pericardial devascularization (SPD) and transjugular intrahepatic portosystemic shunt (TIPS) are effective treatments for EGVB. However, a comparison of the effectiveness and safety of those methods is lacking., Aim: To compare the prognosis after SPD vs TIPS for acute EGVB after failure of endoscopic therapy or secondary prophylaxis of variceal rebleeding (VRB) in patients with HBV-related cirrhosis combined with portal hypertension., Methods: This retrospective cohort study included 318 patients with HBV-related cirrhosis and EGVB who underwent SPD or TIPS at West China Hospital of Sichuan University during 2009-2013. Propensity score-matched analysis (PSM), the Kaplan-Meier method, and multivariate Cox regression analysis were used to compare overall survival, VRB rate, liver function abnormality rate, and hepatocellular carcinoma (HCC) incidence between the two patient groups., Results: The median age was 45.0 years ( n = 318; 226 (71.1%) males). During a median follow-up duration of 43.0 mo, 18 (11.1%) and 33 (21.2%) patients died in the SPD and TIPS groups, respectively. After PSM, SPD was significantly associated with better overall survival (OS) ( P = 0.01), lower rates of abnormal liver function ( P < 0.001), and a lower incidence of HCC ( P = 0.02) than TIPS. The VRB rate did not differ significantly between the two groups ( P = 0.09)., Conclusion: Compared with TIPS, SPD is associated with higher postoperative OS rates, lower rates of abnormal liver function and HCC, and better quality of survival as acute EGVB treatment after failed endoscopic therapy or as secondary prophylaxis of VRB in patients with HBV-related cirrhosis combined with portal hypertension. There is no significant between-group difference in VRB rates., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Many epidemiologic investigations have explored the relationship between viatmins and polycystic ovary syndrome (PCOS). However, the effectiveness of vitamin, vitamin-like nutrient, or mineral supplementation in reducing the risk of PCOS remains a subject of debate., Aim: To investigate the impact of plasma levels of vitamins A, B12, D, E, and K on PCOS and key pathways implicated in its development, namely, insulin resistance, hyperlipidemia, and obesity, through Mendelian randomization (MR) analysis., Methods: Single nucleotide polymorphisms associated with vitamin levels were selected from genome-wide association studies. The primary analysis was performed using the random-effects inverse-variance-weighted approach. Complementary analyses were conducted using the weighted median, MR-Egger, MR-robust adjusted profile score, and MR-PRESSO approaches., Results: The results provided suggestive evidence of a decreased risk of PCOS with genetically predicted higher levels of vitamin E (odds ratio [OR] = 0.118; 95% confidence interval [CI]: 0.071-0.226; P < 0.001) and vitamin B12 (OR = 0.753, 95%CI: 0.568-0.998, P = 0.048). An association was observed between vitamin E levels and insulin resistance (OR = 0.977, 95%CI: 0.976-0.978, P < 0.001). Additionally, genetically predicted higher concentrations of vitamins E, D, and A were suggested to be associated with a decreased risk of hyperlipidemia. Increased vitamins K and B12 levels were linked to a lower obesity risk (OR = 0.917, 95%CI: 0.848-0.992, P = 0.031)., Conclusion: The findings of this MR study suggest a causal relationship between increased vitamins A, D, E, K, and B12 levels and a reduced risk of PCOS or primary pathways implicated in its development., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflicts of interest to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Fungi, particularly filamentous fungi and macrofungi, have a very powerful ability to produce secondary metabolites and can serve as excellent chassis cells for the production of enzymes or natural products of great value in synthetic biology. Thus, it is imperative to establish simple, reliable, and efficient techniques for their genetic modification. However, the heterokaryosis of some fungi and the dominance of nonhomologous end-joining (NHEJ) repair mechanisms in vivo have been greatly affecting the efficiency of fungal gene editing. In recent years, the CRISPR/Cas9 system has been applied as a widely used gene editing technology in life science research and has also played an important role in the genetic modification of filamentous and macrofungi. The various functional components (cas9, sgRNA, promoter, and screening marker) of the CRISPR/Cas9 system and its development, as well as the difficulties and potential of the CRISPR/Cas9 system in filamentous fungus and macrofungi, are the main topics of this paper.

Competing Interests: The authors have no conflicts of interest to declare.

Litchi ( Litchi chinensis ) is an economically important fruit tree in southern China and is widely cultivated in subtropical regions. However, irregular flowering attributed to inadequate floral induction leads to a seriously fluctuating bearing. Litchi floral initiation is largely determined by cold temperatures, whereas the underlying molecular mechanisms have yet to be identified. In this study, we identified four CRT/DRE BINDING FACTORS ( CBF ) homologs in litchi, of which LcCBF1 , LcCBF2 and LcCBF3 showed a decrease in response to the floral inductive cold. A similar expression pattern was observed for the MOTHER OF FT AND TFL1 homolog ( LcMFT ) in litchi. Furthermore, both LcCBF2 and LcCBF3 were found to bind to the promoter of LcMFT to activate its expression, as indicated by the analysis of yeast-one-hybrid (Y1H), electrophoretic mobility shift assays (EMSA), and dual luciferase complementation assays. Ectopic overexpression of LcCBF2 and LcCBF3 in Arabidopsis caused delayed flowering and increased freezing and drought tolerance, whereas overexpression of LcMFT in Arabidopsis had no significant effect on flowering time. Taken together, we identified LcCBF2 and LcCBF3 as upstream activators of LcMFT and proposed the contribution of the cold-responsive CBF to the fine-tuning of flowering time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shan, Yang, Wei, Wang, Shen, Chen and Shen.)

Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: To assess how age-friendly deprescribing trials are regarding intervention design and outcome assessment. Reduced use of potentially inappropriate medications (PIMs) can be addressed by deprescribing-a systematic process of discontinuing and/or reducing the use of PIMs. The 4Ms-"Medication", "Mentation", "Mobility", and "What Matters Most" to the person-can be used to guide assessment of age-friendliness of deprescribing trials., Data Source: Published literature., Study Design: Scoping review., Data Extraction Methods: The literature was identified using keywords related to deprescribing and polypharmacy in PubMed, EMBASE, Web of Science, ProQuest, CINAHL, and Cochrane and snowballing. Study characteristics were extracted and evaluated for consideration of 4Ms., Principal Findings: Thirty-seven of the 564 trials identified met the review eligibility criteria. Intervention design: "Medication" was considered in the intervention design of all trials; "Mentation" was considered in eight trials; "Mobility" (n = 2) and "What Matters Most" (n = 6) were less often considered in the design of intervention. Most trials targeted providers without specifying how matters important to older adults and their families were aligned with deprescribing decisions., Outcome Assessment: "Medication" was the most commonly assessed outcome (n = 33), followed by "Mobility" (n = 13) and "Mentation" (n = 10) outcomes, with no study examining "What Matters Most" outcomes., Conclusions: "Mentation" and "Mobility", and "What Matters Most" have been considered to varying degrees in deprescribing trials, limiting the potential of deprescribing evidence to contribute to improved clinical practice in building an age-friendly health care system., (© 2022 Health Research and Educational Trust.)

Aim: To investigate the treatment pattern and safety of tafluprost for glaucoma and ocular hypertension (OH) in clinical practice in China., Methods: This post-marketing observational study included patients who received tafluprost to lower intraocular pressure (IOP) within 30d between September 2017 and March 2020 in 20 hospitals in China. Adverse drug reactions (ADRs) during tafluprost treatment and within 30d after the treatment were collected., Results: A total of 2544 patients were included in this study, of them 58.5% (1488/2544) had primary open angle glaucoma (POAG), 21.9% (556/2544) had OH and 19.7% (500/2544) used tafluprost for other reasons. Of 359 ADRs occurred in 10.1% (258/2544) patients, and no serious adverse event occurred. The most common ADR was conjunctival hyperemia (128 ADRs in 124 patients, 4.9%). Totally 1670 participants (65.6%) combined tafluprost with carbonic anhydrase inhibitors (CAIs; 37.1%, 620/1670), sympathomimetics (33.5%, 559/1670), β-blockers (33.2%, 555/1670), other prostaglandin analogs (PGAs; 15.6%, 260/1670) and other eye drops (15.1%, 253/1670). The highest incidence of conjunctival hyperemia was noted in patients who received tafluprost in combination with other PGAs (23 ADRs in 23 patients, 8.8%, 23/260) and the lowest was in combination with CAIs (16 ADRs in 16 patients, 2.6%, 16/620). Tafluprost was applied in primary angle-closure glaucoma (41.6%, 208/500), after glaucoma surgery (17.8%, 89/500) and after non-glaucoma surgery (15.8%, 79/500)., Conclusion: Tafluprost is safe for POAG and OH, and tolerable when combined with other eye drops and under various clinical circumstances., (International Journal of Ophthalmology Press.)

The molecular basis underlying nasopharyngeal carcinoma (NPC) remains unclear. Recent progress in transcriptional regulatory network analysis helps identify the master regulator (MR) proteins that transcriptionally define malignant tumor phenotypes. Here, we investigated transcription factor-target interactions and identified TEA domain transcription factor 4 (TEAD4) as an MR of high-risk NPC. Precisely, TEAD4 promoted NPC migration, invasion and cisplatin resistance, depending on its autopalmitoylation. Mechanistically, YTHDF2 (YTH domain family 2) recognized WTAP (Wilms tumor 1-associating protein)-mediated TEAD4 m 6 A methylation to facilitate its stability and led to aberrant up-regulation of TEAD4. Up-regulated TEAD4 further drove NPC progression by transcriptionally activating BZW2 (basic leucine zipper and W2 domains 2) to induce the oncogenic AKT pathway. Moreover, the transcriptional activity of TEAD4 was independent of its canonical coactivators YAP/TAZ. Clinically, TEAD4 serves as an independent predictor of unfavorable prognosis and cisplatin response in NPC. Our data revealed the crucial role of TEAD4 in driving tumor malignancy, thus, may provide therapeutic vulnerability in NPC.

The AT(N) framework enables the classification of an individual within the biological Alzheimer's disease (AD) continuum by pairing the cognitive stage with the biomarker status of amyloid-beta (Aβ, A), tau (T) and neurodegeneration (N). AD is a multifactorial disease that may involve different pathogenic mechanisms such as cerebrovascular disease (CVD). Therefore, biomarkers of these mechanisms can be added to the AT(N) framework to enhance the biomarker characterization of individuals within the AD continuum. In AD, white matter hyperintensities (WMH) which are postulated to develop as a result of chronic ischemia from small vessel CVD are shown to play a role in the aetiology. However, the interplay of WMH with Aβ and tau pathophysiology in AD remains unclear. In this review, we summarized the studies that evaluated the associations between WMH and AD pathophysiology (Aβ and tau). We found that the evidence supporting the association of WMH with Aβ was mixed, and this may be explained by the relative contributions of WMH due to its differential load and anatomical distribution. More studies are also needed to determine the association of WMH with tau pathology. Future longitudinal studies with harmonized methodologies to quantify WMH and account for the anatomical differences of WMH are required to validate the relationship between WMH and AT(N) biomarkers. This will allow a clearer understanding of the utility of WMH as a vascular biomarker in the AT(N) framework. Novel CVD biomarkers will also have the potential to further elucidate the contributions of CVD to the AD pathophysiology., Competing Interests: The authors report no disclosures.

Background: Williams syndrome (WS) is a multisystem neurodevelopmental disorder caused by microdeletions in 7q11.23. This study aims to characterize the clinical phenotypes of Chinese children with WS to help for the early diagnosis and intervention of this disease., Methods: 231 children diagnosed with WS were retrospectively recruited to the study. Clinical data were analyzed to obtain the incidence of different clinical phenotypes. The occurrence of phenotypes and the influence of gender and age on the incidence of different phenotypes were analyzed., Results: All WS exhibited facial dysmorphism (100.0%). The majority had neurodevelopmental disorder (91.8%), hoarseness (87.4%) and cardiovascular anomalies (85.7%). The incidence of short stature (46.9%), inguinal hernia (47.2%), hypercalciuria (29.10%), hypercalcemia (9.1%), subclinical hypothyroidism (26.4%) and hypothyroidism (7.4%) were relatively higher. Gender differences were found in supravalvular aortic stenosis (SVAS, p < .001), ventricular septal defect (VSD, p < .05), inguinal hernia (p < .001), superior pulmonary stenosis (SVPS, p < .05) and neurodevelopmental disorder (p < .05). The incidence of neurodevelopmental disorder in WS increased with age (p < .05) while cardiovascular anomalies (p < .001), short stature (p < .001), hypercalciuria (p < .001) and hypercalcemia (p < .01) decreased with age., Conclusions: Facial dysmorphism, neurodevelopmental disorder, hoarseness and cardiovascular anomalies were the most common phenotypes. Genetic testing should be suggested to confirm the diagnosis for children with the above abnormalities. Gender and age should be taken into account when making diagnosis and intervention., (© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Objective: To clarify the epidemiological characteristics and spatiotemporal clustering dynamics of COVID-19 in Shanghai in 2022. Methods: The COVID-19 data presented on the official websites of Municipal Health Commissions of Shanghai during March 1, 2022 and May 31, 2022 were collected for a spatial autocorrelation analysis by GeoDa software. A logistic growth model was used to fit the epidemic situation and make a comparison with the actual infection situation. Results: Pudong district had the highest number of symptomatic and asymptomatic infectants, accounting for 29.30% and 35.58% of the total infectants. Differences in cumulative attack rates and infection rates among 16 districts ( P <0.001) were significant. The rates were significantly higher in Huangpu district than in other districts. The attack rate of COVID-19 from March 1, 2022 to May 31, 2022 had a global spatial positive correlation ( P <0.05). Spatial distribution of COVID-19 attack rate was different at different periods. The global autocorrelation coefficient from March 16 to March 29, April 6 to April 12 and May 18 to May 24 had no statistical significance ( P >0.05). Our local autocorrelation analysis showed that 22 high-high clustering areas were detected in eight periods.The high-risk hot-spot areas have experienced a "less-more-less" change process. The growth model fitting results were consistent with the actual infection situation. Conclusion: There was a clear spatiotemporal correlation in the distribution of COVID-19 in Shanghai. The comprehensive prevention and control measures of COVID-19 epidemic in Shanghai have effectively prohibited the growth of the epidemic, not only curbing the spatially spread of high-risk epidemic areas, but also reducing the risk of transmission to other cities.

Background: Keloids represent the dysregulation of cutaneous wound healing caused by aberrant fibroblast activities. Adipose-derived stem cells have been recognized as a promising treatment for keloids. However, the molecular mechanisms have not been fully elucidated. Objectives: to explicitly demonstrate the relationship between adipose-derived stem cells alleviating keloids and alterations of Col-1, Col-3, CTGF, and P-4-HB. Methods: Skin biopsies were obtained from 10 keloid patients and 9 healthy volunteers. Fibroblasts isolated from all samples were divided into two groups, one co-cultured with adipose-derived stem cells and the other grown independently. We compared the wound-healing rates, fibroblast survival rates, apoptosis rates, mRNA expressions, and protein levels of Col-1, Col-3, CTGF, and P-4-HB between separated groups. Results: We found no significant differences between normal fibroblasts and keloid fibroblasts in terms of wound-healing rate, survival rate, or apoptosis rate at the baseline. With adipose-derived stem cells, wound-healing rate and survival rate of normal fibroblasts were promoted, whereas in keloid fibroblasts, they were reduced. The apoptosis rate of normal fibroblasts and keloid fibroblasts were restrained, with the restraint in keloid fibroblasts being more evident. The protein levels of Col-3, CTGF, and P-4-HB were lower in keloid fibroblasts co-cultured with adipose-derived stem cells than in normal fibroblasts under similar conditions. Conclusions: Adipose-derived stem cells strongly suppressed keloid fibroblasts' proliferative and invasive behavior. However, adipose-derived stem cells negatively regulated keloid fibroblast apoptosis. Adipose-derived stem cells can be a potential keloid therapy worth further investigation., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objectives: Polypharmacy is common in home health care (HHC). This study examined the prevalence of medications associated with geriatric syndromes (MAGS), its predictors, and association with subsequent hospitalization in HHC., Design: Analysis of HHC electronic medical records, the Outcome and Assessment Information Set (OASIS), and Medicare HHC claims., Setting and Participants: A total of 6882 adults ≥65 years old receiving HHC in 2019 from a large, not-for-profit home health agency serving multiple counties in New York State., Measures: MAGS use was identified from active medications reconciled during HHC visits (HHC electronic medical records). MAGS use was operationalized as count and in quartiles. Hospitalization during the HHC episode was operationalized as a time-to-event variable (ie, number of days from HHC admission to hospitalization). We used regression analyses to identify predictors of MAGS use, and survival analyses to examine the association between MAGS and hospitalization., Results: Nearly all (98%) of the HHC patients used at least 1 MAGS and 41% of all active medications used by the sample were MAGS. More MAGS use was found in HHC patients who were community-referred, taking more medications, and having more diagnoses, depressive symptoms, and functional limitations. Adjusted for covariates, higher MAGS quartiles were not independently associated with the risk of hospitalization, but higher MAGS quartiles combined with multimorbidity (ie, having ≥10 diagnoses) were associated with a 2.3-fold increase in hospitalization risk (hazard ratio 2.24; 95% confidence interval: 1.61-3.13; P < .001), relative to the lowest quartile of MAGS use and having <10 diagnoses., Conclusions and Implications: More than 40% of medications taken by HHC patients are MAGS. Multimorbidity and MAGS use collectively increased the risk of hospitalization by up to 2.3 times. HHC clinicians should carefully review patients' medications and use information about MAGS to facilitate discussion about deprescribing with patients and their prescribers., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)