Advance Care Planning (ACP) in Medicare Beneficiaries with Heart Failure.

BACKGROUND: Heart failure is a leading cause of death in the USA, contributing to high expenditures near the end of life. Evidence remains lacking on whether billed advance care planning changes patterns of end-of-life healthcare utilization among patients with heart failure. Large-scale claims evaluation assessing billed advance care planning and end-of-life hospitalizations among patients with heart failure can fill evidence gaps to inform health policy and clinical practice. OBJECTIVE: Assess the association between billed advance care planning delivered and Medicare beneficiaries with heart failure upon the type and quantity of healthcare utilization in the last 30 days of life. DESIGN: This retrospective cross-sectional cohort study used Medicare fee-for-service claims from 2016 to 2020. PARTICIPANTS: A total of 48,466 deceased patients diagnosed with heart failure on Medicare. MAIN MEASURES: Billed advance care planning services between the last 12 months and last 30 days of life will serve as the exposure. The outcomes are end-of-life healthcare utilization and total expenditure in inpatient, outpatient, hospice, skilled nursing facility, and home healthcare services. KEY RESULTS: In the final cohort of 48,466 patients (median [IQR] age, 83 [76-89] years; 24,838 [51.2%] women; median [IQR] Charlson Comorbidity Index score, 4 [2-5]), 4406 patients had an advance care planning encounter. Total end-of-life expenditure among patients with billed advance care planning encounters was 19% lower (95% CI, 0.77-0.84) compared to patients without. Patients with billed advance care planning encounters had 2.65 times higher odds (95% CI, 2.47-2.83) of end-of-life outpatient utilization with a 33% higher expected total outpatient expenditure (95% CI, 1.24-1.42) compared with patients without a billed advance care planning encounter. CONCLUSIONS: Billed advance care planning delivery to individuals with heart failure occurs infrequently. Prioritizing billed advance care planning delivery to these individuals may reduce total end-of-life expenditures and end-of-life inpatient expenditures through promoting use of outpatient end-of-life services, including home healthcare and hospice.

Expandable-RCNN: toward high-efficiency incremental few-shot object detection.

This study aims at addressing the challenging incremental few-shot object detection (iFSOD) problem toward online adaptive detection. iFSOD targets to learn novel categories in a sequential manner, and eventually, the detection is performed on all learned categories. Moreover, only a few training samples are available for all sequential novel classes in these situations. In this study, we propose an efficient yet suitably simple framework, Expandable-RCNN, as a solution for the iFSOD problem, which allows online sequentially adding new classes with zero retraining of the base network. We achieve this by adapting the Faster R-CNN to the few-shot learning scenario with two elegant components to effectively address the overfitting and category bias. First, an IOU-aware weight imprinting strategy is proposed to directly determine the classifier weights for incremental novel classes and the background class, which is with zero training to avoid the notorious overfitting issue in few-shot learning. Second, since the above zero-retraining imprinting approach may lead to undesired category bias in the classifier, we develop a bias correction module for iFSOD, named the group soft-max layer (GSL), that efficiently calibrates the biased prediction of the imprinted classifier to organically improve classification performance for the few-shot classes, preventing catastrophic forgetting. Extensive experiments on MS-COCO show that our method can significantly outperform the state-of-the-art method ONCE by 5.9 points in commonly encountered few-shot classes.

Cancer-cell derived S100A11 promotes macrophage recruitment in ER+ breast cancer.

Macrophages are pivotal in driving breast tumor development, progression, and resistance to treatment, particularly in estrogen receptor-positive (ER+) tumors, where they infiltrate the tumor microenvironment (TME) influenced by cancer cell-secreted factors. By analyzing single-cell RNA-sequencing data from 25 ER+ tumors, we elucidated interactions between cancer cells and macrophages, correlating macrophage density with epithelial cancer cell density. We identified that S100A11, a previously unexplored factor in macrophage-cancer crosstalk, predicts high macrophage density and poor outcomes in ER+ tumors. We found that recombinant S100A11 enhances macrophage infiltration and migration in a dose-dependent manner. Additionally, in 3D models, we showed that S100A11 expression levels in ER+ cancer cells predict macrophage infiltration patterns. Neutralizing S100A11 decreased macrophage recruitment, both in cancer cell lines and in a clinically relevant patient-derived organoid model, underscoring its role as a paracrine regulator of cancer-macrophage interactions in the protumorigenic TME. This study offers novel insights into the interplay between macrophages and cancer cells in ER+ breast tumors, highlighting S100A11 as a potential therapeutic target to modulate the macrophage-rich tumor microenvironment.

Can molecular hydrogen supplementation reduce exercise-induced oxidative stress in healthy adults? A systematic review and meta-analysis.

Objective: Exercise-induced oxidative stress affects multiple neurophysiological processes, diminishing the exercise performance. Hydrogen (H2) can selectively reduce excessive free radicals, but studies observed its "dual effects" on exercise-induced oxidative stress, that is, increasing or decreasing the oxidative stress. Therefore, we here conducted a systematic review and meta-analysis to quantitatively assess the influence of H2 on exercise-induced oxidative stress in healthy adults. Methods: We conducted a systematic review of publications across five databases. The following keywords were used for search strategy: ["hydrogen"[Mesh] or "molecular hydrogen" or "hydrogen rich water" or "hydrogen-rich water" or "hydrogen rich saline"] and ["Oxidative Stress"[Mesh] or "Antioxidative Stress" or "Oxidative Damage" or "Oxidative Injury" or "Oxidative Cleavage"] and ["randomized controlled trial"[Mesh] or "randomized" or "RCT"]. We included trials reporting the effects of H2 on exercise-induced oxidative stress and potential antioxidant capacity post-exercise in healthy adults. Additionally, subgroup analyses were conducted to explore how various elements of the intervention design affected those outcomes. Results: Six studies, encompassing seven experiments with a total of 76 participants, were included in our analysis. Among these studies, hydrogen-rich water, hydrogen bathing, and hydrogen-rich gas were three forms used in H2 administration. The H2 was applied in different timing, including before, during, or after exercise only, both before and after exercise, and repeatedly over days. Single-dose, multi-dose within 1 day and/or multiple-dose over days were implemented. It was observed that compared to placebo, the effects of H2 on oxidative stress (diacron-reactive oxygen metabolites, d-ROMs) was not significant (SMD = -0.01, 95%CI-0.42 to 0.39, p = 0.94). However, H2 induced greater improvement in antioxidant potential capacity (Biological Antioxidant Potential, BAP) (SMD = 0.29, 95% CI 0.04 to 0.54, p = 0.03) as compared to placebo. Subgroup analyses revealed that H2 supplementation showed greater improvement (SMD = 0.52, 95%CI 0.16 to 0.87, p = 0.02) in the antioxidant potential capacity of intermittent exercises than continuous exercise. Conclusion: H2 supplementation can help enhance antioxidant potential capacity in healthy adults, especially in intermittent exercise, but not directly diminish the levels of exercise-induced oxidative stress. Future studies with more rigorous design are needed to examine and confirm these findings. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=364123, Identifier CRD42022364123.

The palliative care needs and experiences of patients with advanced Parkinson's disease: a qualitative scoping review.

Aim: To determine the experiences and needs of palliative care in patients with advanced Parkinson's disease (PD). Methods: A scoping literature review methodology, as described by the Joanna Briggs Institute, was employed to search for relevant literature. An electronic search of studies published in English was conducted across five databases from inception to 10 September 2023. Results: The search yielded a total of 1,205 articles, with 20 meeting the inclusion criteria. The findings were organized into four themes: (1) unmet emotional and informational needs; (2) needs for effective coordination of care; (3) planning for the future; and (4) symptom management. This scoping review highlights the intricate nature of palliative care for patients with PD and sheds light on issues within current palliative care healthcare systems. The findings emphasize the necessity for individualized interventions and services to address the diverse unmet palliative care needs of people with PD. Conclusion: The study reveals the complex landscape of palliative care for individuals with advanced PD, emphasizing the inadequacies within existing healthcare systems. The identified themes underscore the importance of tailored interventions to address the varied unmet palliative care needs of this population.

Neighborhood Racial and Ethnic Segregation and the Risk of Dementia in Older Adults Living with Kidney Failure.

BACKGROUND: Dementia disproportionately impacts older minoritized adults with kidney failure. To better understand the mechanism of this disparity, we studied the role of racial and ethnic segregation (segregation hereafter), a form of structural racism recently identified as a mechanism in numerous other health disparities. METHODS: We identified 901,065 older adults (age ≥55) with kidney failure from 2003 to 2019 using the United States Renal Data System (USRDS). We quantified dementia risk across tertiles of residential neighborhood segregation score using cause-specific hazard models, adjusting for individual and neighborhood-level factors. We included an interaction term to quantify the differential effect of segregation on dementia diagnosis by race and ethnicity. RESULTS: We identified 79,851 older adults with kidney failure diagnosed with dementia between 2003 and 2019 (median follow-up: 2.2 years). Compared to those in low-segregation neighborhoods, older adults with kidney failure in high-segregation neighborhoods had a 1.63-fold (95% confidence interval (CI):1.60-1.66) higher risk of dementia diagnosis, an association that differed by race and ethnicity (Asian: adjusted hazard ratio [aHR]=1.26, 95%CI:1.15-1.38; Black: aHR=1.66, 95%CI:1.61-1.71; Hispanic: aHR=2.05, 95%CI:1.93-2.18; White: aHR=1.59, 95%CI:1.55-1.64;Pinteraction<0.001). Notably, older Asian (aHR=1.76, 95%CI:1.64-1.89), Black (aHR=2.65, 95%CI:2.54-2.77), Hispanic (aHR=2.15, 95%CI:2.04-2.26), and White (aHR=2.20, 95%CI:2.09-2.31) adults with kidney failure residing in minority-predominant high-segregation neighborhoods had a higher risk of dementia diagnosis compared to older White adults with kidney failure in White-predominant high-segregation neighborhoods. Moreover, older adults with kidney failure receiving care at dialysis facilities located in high-segregation neighborhoods also experienced a higher risk of dementia diagnosis (aHR=1.53, 95%CI:1.50-1.56); this association differed by race and ethnicity (Pinteraction<0.001). CONCLUSIONS: Residing in or receiving care at dialysis facilities located in high-segregation neighborhoods was associated with a higher risk of dementia diagnosis among older individuals with kidney failure, particularly minoritized individuals.

Rural-urban differences in out-of-network treatment initiation and engagement rates for substance use disorders.

OBJECTIVE: To examine rural-urban disparities in substance use disorder treatment access and continuation. DATA SOURCES AND STUDY SETTING: We analyzed a 2016-2018 U.S. national secondary dataset of commercial insurance claims. STUDY DESIGN: This cross-sectional study examined individuals with a new episode of opioid, alcohol, or other drug use disorders. Treatment initiation and engagement rates, and rates of using out-of-network providers for these services, were compared between rural and urban patients. DATA COLLECTION: We included individuals 18-64 years old with continuous employer-sponsored insurance. PRINCIPAL FINDINGS: Patients in rural settings experienced lower treatment initiation rates for alcohol (36.6% vs. 38.0%, p < 0.001), opioid (41.2% vs. 44.2%, p < 0.001), and other drug (37.7% vs. 40.1%, p < 0.001) use disorders, relative to those in urban areas. Similarly, rural patients had lower treatment engagement rates for alcohol (15.1% vs. 17.3%, p < 0.001), opioid (21.0% vs. 22.6%, p < 0.001), and other drug (15.5% vs. 17.5%, p < 0.001) use disorders. Rural patients had higher out-of-network rates for treatment initiation for other drug use disorders (20.4% vs. 17.2%, p < 0.001), and for treatment engagement for alcohol (27.6% vs. 25.2%, p = 0.006) and other drug (36.1% vs. 31.1%, p < 0.001) use disorders. CONCLUSIONS: These findings indicate that individuals with substance use disorders in rural areas have lower rates of initial and ongoing treatment, and are more likely to seek care out-of-network.

Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity.

BACKGROUND: Circadian rhythm is crucial to the function of the immune system. Disorders of the circadian rhythm can contribute to inflammatory diseases such as Ulcerative colitis (UC). This Mendelian Randomization (MR) analysis applies genetic tools to represent the aggregated statistical results of exposure to circadian rhythm disorders and UC and its comorbidities, allowing for causal inferences. METHODS: Summary statistics of protein, DNA methylation and gene expression quantitative trait loci in individuals of European ancestry (pQTL, mQTL, and eQTL, respectively) were used. Genetic variants located within or near 152 circadian clock-related genes and closely related to circadian rhythm disorders were selected as instrumental variables. Causal relationships with UC and its comorbidities were then estimated through employed Summary data-based Mendelian Randomization (SMR) and Inverse-Variance-Weighted MR (IVW-MR). RESULTS: Through preliminary SMR analysis, we identified a potential causal relationship between circadian clock-related genes and UC along with its comorbidities, which was further confirmed by IVW-MR analysis. Our study identified strong evidence of positive correlation involving seven overlapping genes (CSNK1E, OPRL1, PIWIL2, RORC, MAX, PPP5C, and AANAT) through MWAS and TWAS in UC, four overlapping genes (OPRL1, CHRNB2, FBXL17, and SIRT1) in UC with PSC, and three overlapping genes (ARNTL, USP7, and KRAS) in UC with arthropathy. CONCLUSIONS: This SMR study demonstrates the causal effect of circadian rhythm disorders in UC and its comorbidities. Furthermore, our investigation pinpointed candidate genes that could potentially serve as drug targets.

Comparative efficacy and safety of Sofosbuvir/Velpatasvir and Danoprevir for the treatment of chronic hepatitis C: the real-world data in China.

BACKGROUND: Sofosbuvir/Velpatasvir (Epclusa, ECS) is the first pan-genotype direct-acting antiviral agent (DAA) for hepatitis C virus (HCV) infection, and Danoprevir (DNV) is the first DAA developed by a Chinese local enterprise, which is suitable for combined use with other drugs to treat genotype 1b chronic hepatitis C. However, previous reports have never compared the real-world data of ECS and DNV. PATIENTS AND METHODS: 178 chronic hepatitis C patients were retrospectively recruited, and 94cases were accepted with Sofosbuvir/Velpatasvir ± Ribavirin (ECS group), and others (n = 84 treated with DNV combination therapy (DNV group). The HCV genotype, virological response, adverse effects and some laboratory biochemical indexes were contrasted between above two groups in the real world study. RESULTS: DNV group had significantly lower level of alpha-fetoprotein (AFP), lower rates of decompensated cirrhosis ( P < 0.05). ECS group possessed more 6a (31.91% vs.13.10%) while DNV group was provided with more 1b (48.81% vs. 22.34%) patients. Significantly poor liver function was detected in ECS group at 4-week treatment (ALT and AST) and 12-week follow-up (AST) (all P < 0.05). The SVR12 undetectable rates of both groups were 100%, and no serious event was observed during the treatment and follow-up in both groups. CONCLUSION: In this retrospective real-world study, the efficacy of DNV combined therapy is similar to Sofosbuvir/Velpatasvir ± Ribavirin for chronic HCV infection, and the safety is comparable. DNV based therapy is a promising regimen for chronic hepatitis C.

Histone-modifying enzymes: Roles in odontogenesis and beyond.

OBJECTIVES: Odontogenesis, an intricate process initiated by epithelium-mesenchyme interaction, is meticulously regulated by a cascade of regulatory mechanisms. Epigenetic modifications, especially histone modification, have been found to exhibit spatiotemporal specificity during tooth development. However, the expression patterns and roles of enzymes associated with histone modifications have yet to be systematically explored in odontogenesis. This review aims to summarize the histone-modifying enzymes in odontogenesis and their regulation mechanism during tooth development and provide the potential theoretical basis for the clinical management and intervention of dental developmental diseases. SUBJECTS AND METHODS: This study conducted a systematic search across PubMed and Web of Science databases, utilizing the keywords "odontogenesis," "histone modification," and "enzyme" for pertinent articles. RESULTS: No doubt histone modification contributes extensively to odontogenesis regulation, and the disturbances in histone modifications can derange the odontogenesis process. CONCLUSION: Further studies are warranted to elucidate these roles and their potential downstream effects, positioning histone modifications as a pivotal focal point for unraveling the intricacies of tooth development and regeneration.

Formaldehyde Exposure Racial Disparities in Southeast Texas.

Formaldehyde (HCHO) exposures during a full year were calculated for different race/ethnicity groups living in Southeast Texas using a chemical transport model tagged to track nine emission categories. Petroleum and industrial emissions were the largest anthropogenic sources of HCHO exposure in Southeast Texas, accounting for 44% of the total HCHO population exposure. Approximately 50% of the HCHO exposures associated with petroleum and industrial sources were directly emitted (primary), while the other 50% formed in the atmosphere (secondary) from precursor emissions of reactive compounds such as ethylene and propylene. Biogenic emissions also formed secondary HCHO that accounted for 11% of the total population-weighted exposure across the study domain. Off-road equipment contributed 3.7% to total population-weighted exposure in Houston, while natural gas combustion contributed 5% in Beaumont. Mobile sources accounted for 3.7% of the total HCHO population exposure, with less than 10% secondary contribution. Exposure disparity patterns changed with the location. Hispanic and Latino residents were exposed to HCHO concentrations +1.75% above average in Houston due to petroleum and industrial sources and natural gas sources. Black and African American residents in Beaumont were exposed to HCHO concentrations +7% above average due to petroleum and industrial sources, off-road equipment, and food cooking. Asian residents in Beaumont were exposed to HCHO concentrations that were +2.5% above average due to HCHO associated with petroleum and industrial sources, off-road vehicles, and food cooking. White residents were exposed to below average HCHO concentrations in all domains because their homes were located further from primary HCHO emission sources. Given the unique features of the exposure disparities in each region, tailored solutions should be developed by local stakeholders. Potential options to consider in the development of those solutions include modifying processes to reduce emissions, installing control equipment to capture emissions, or increasing the distance between industrial sources and residential neighborhoods.

Transcutaneous electrical acupoint stimulation benefits postoperative pain relief of oocyte retrieval: A randomized controlled trial.

BACKGROUND: Transvaginal oocyte retrieval is frequently followed by adverse events related to anesthesia and the procedure. Some research showed that transcutaneous electrical acupoint stimulation (TEAS) can relieve intraoperative pain and postoperative nausea. OBJECTIVE: This study examined whether TEAS can alleviate pain and relieve adverse symptoms after oocyte retrieval. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Altogether 128 patients were randomly divided into the TEAS group and the mock TEAS group. The two groups received a 30-minute-long TEAS or mock TEAS treatment that began 30 min after oocyte retrieval. MAIN OUTCOME MEASURES: The primary outcome was the visual analog scale (VAS) pain score. Secondary outcomes were pressure pain threshold, McGill score, pain rating index (PRI), present pain intensity (PPI), VAS stress score, VAS anxiety score, and postoperative adverse symptoms. RESULTS: The baseline characteristics of the two groups were comparable (P > 0.05). The VAS pain scores of the TEAS group were lower than those of the mock TEAS group at 60 and 90 min after oocyte retrieval (P < 0.05). The McGill score, PRI and PPI in the TEAS group were significantly lower than those in the control group at 60 min after oocyte retrieval (P < 0.05). However, the two groups had equivalent beneficial effects regarding the negative emotions, such as nervousness and anxiety (P > 0.05). The TEAS group was superior to the mock TEAS group for relieving postoperative adverse symptoms (P < 0.05). CONCLUSION: TEAS treatment can relieve postoperative pain and postoperative adverse symptoms for patients undergoing oocyte retrieval. Please cite this article as: Liu LY, Su Y, Wang RR, Lai YY, Huang L, Li YT, Tao XY, Su MH, Zheng XY, Huang SC, Wu YN, Yu SY, Liang FR, Yang J. Transcutaneous electrical acupoint stimulation benefits postoperative pain relief of oocyte retrieval: A randomized controlled trial. J Integr Med. 2024; 22(1): 32-38.

The role of aryl hydrocarbon receptor in vitiligo: a review.

Vitiligo is an acquired autoimmune dermatosis characterized by patchy skin depigmentation, causing significant psychological distress to the patients. Genetic susceptibility, environmental triggers, oxidative stress, and autoimmunity contribute to melanocyte destruction in vitiligo. Due to the diversity and complexity of pathogenesis, the combination of inhibiting melanocyte destruction and stimulating melanogenesis gives the best results in treating vitiligo. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that can regulate the expression of various downstream genes and play roles in cell differentiation, immune response, and physiological homeostasis maintenance. Recent studies suggested that AhR signaling pathway was downregulated in vitiligo. Activation of AhR pathway helps to activate antioxidant pathways, inhibit abnormal immunity response, and upregulate the melanogenesis gene, thereby protecting melanocytes from oxidative stress damage, controlling disease progression, and promoting lesion repigmentation. Here, we review the relevant literature and summarize the possible roles of the AhR signaling pathway in vitiligo pathogenesis and treatment, to further understand the links between the AhR and vitiligo, and provide new potential therapeutic strategies.

Neighborhood Segregation and Access to Live Donor Kidney Transplantation.

Importance: Identifying the mechanisms of structural racism, such as racial and ethnic segregation, is a crucial first step in addressing the persistent disparities in access to live donor kidney transplantation (LDKT). Objective: To assess whether segregation at the candidate's residential neighborhood and transplant center neighborhood is associated with access to LDKT. Design, Setting, and Participants: In this cohort study spanning January 1995 to December 2021, participants included non-Hispanic Black or White adult candidates for first-time LDKT reported in the US national transplant registry. The median (IQR) follow-up time for each participant was 1.9 (0.6-3.0) years. Main Outcome and Measures: Segregation, measured using the Theil H method to calculate segregation tertiles in zip code tabulation areas based on the American Community Survey 5-year estimates, reflects the heterogeneity in neighborhood racial and ethnic composition. To quantify the likelihood of LDKT by neighborhood segregation, cause-specific hazard models were adjusted for individual-level and neighborhood-level factors and included an interaction between segregation tertiles and race. Results: Among 162 587 candidates for kidney transplant, the mean (SD) age was 51.6 (13.2) years, 65 141 (40.1%) were female, 80 023 (49.2%) were Black, and 82 564 (50.8%) were White. Among Black candidates, living in a high-segregation neighborhood was associated with 10% (adjusted hazard ratio [AHR], 0.90 [95% CI, 0.84-0.97]) lower access to LDKT relative to residence in low-segregation neighborhoods; no such association was observed among White candidates (P for interaction = .01). Both Black candidates (AHR, 0.94 [95% CI, 0.89-1.00]) and White candidates (AHR, 0.92 [95% CI, 0.88-0.97]) listed at transplant centers in high-segregation neighborhoods had lower access to LDKT relative to their counterparts listed at centers in low-segregation neighborhoods (P for interaction = .64). Within high-segregation transplant center neighborhoods, candidates listed at predominantly minority neighborhoods had 17% lower access to LDKT relative to candidates listed at predominantly White neighborhoods (AHR, 0.83 [95% CI, 0.75-0.92]). Black candidates residing in or listed at transplant centers in predominantly minority neighborhoods had significantly lower likelihood of LDKT relative to White candidates residing in or listed at transplant centers located in predominantly White neighborhoods (65% and 64%, respectively). Conclusions: Segregated residential and transplant center neighborhoods likely serve as a mechanism of structural racism, contributing to persistent racial disparities in access to LDKT. To promote equitable access, studies should assess targeted interventions (eg, community outreach clinics) to improve support for potential candidates and donors and ultimately mitigate the effects of segregation.

Five-year follow-up of sustained virological response with hepatitis C infection after direct-acting antiviral therapy: A single-center retrospective study.

In recent years, direct-acting antivirals (DAAs) have dramatically improved the sustained virological response (SVR) rates in chronic hepatitis C (CHC) patients with their favorable safety and efficacy. However, there is a lack of data on the long-term prognosis of DAA therapy for CHC patients after achieving SVR in the real world. The aim of this study was to evaluate the long-term clinical prognosis of patients with chronic hepatitis C treated by DAA after achieving SVR. This study was a single-center, retrospective, observational study that included 243 CHC patients who reached SVR after DAA treatment in the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2021, with a median follow-up period (FUP) of 24 months, to assess the long-term prognosis and clinical outcomes of CHC patients who reached SVR by DAA treatment. A total of 243 patients were enrolled in this study, 151 patients were male, the mean age of this study was 46.7 ±â€…12.3 years old, and 23.0% (n = 56) patients were cirrhosis in the baseline. At the end of follow-up, 9 patients (3.7%) progressed to hepatocellular carcinoma (HCC), and patients with cirrhosis at baseline (n = 5) had a significantly higher risk of HCC compared with noncirrhotic patients (n = 4; OR = 4.485, 95% CI: 1.162-17.318, P = .029); 2.9% patients (n = 7) relapsed at the median FUP of 12 months, and patients with genotype 3b had a significantly higher risk of relapsing than those without genotype 3b (OR = 18.48, P = .002, 95% CI: 2.866-119.169). ALT, AST, and ALB all showed improvement at the end of treatment compared with the baseline, remaining at normal levels during FUP meanwhile. The DAA-induced SVR was durable, with conspicuous improvement in clinical outcomes. Nevertheless, patients, especially patients with cirrhosis, still exist the risk of appearance of HCC after reaching SVR. Therefore, regular surveillance and monitoring is necessary even after patients reached SVR.

Genome-wide characterization and function analysis of ginger (Zingiber officinale Roscoe) ZoGRFs in responding to adverse stresses.

Growth-regulating factors (GRFs) play crucial roles in plant growth, development, hormone signaling, and stress response. Despite their significance, the roles of GRFs in ginger remain largely unknown. Herein, 31 ginger ZoGRFs were identified and designated as ZoGRF1-ZoGRF31 according to their phylogenetic relationships. All ZoGRFs were characterized as unstable, hydrophilic proteins, with 29 predicted to be located in the nucleus. Functional cis-elements related to growth and development were enriched in ZoGRF's promoter regions. RNA-seq and RT-qPCR analysis revealed that ZoGRF12, ZoGRF24, and ZoGRF28 were highly induced in various growth and development stages, displaying differential regulation under waterlogging, chilling, drought, and salt stresses, indicating diverse expression patterns of ZoGRFs. Transient expression analysis in Nicotiana benthamiana indicated that overexpressing ZoGRF28 regulated the transcription levels of salicylic acid, jasmonic acid, and pattern-triggered immunity-related genes, increased chlorophyll content and contributed to reduced disease lesions and an increased net photosynthetic rate. This research lays the foundation for further understanding the biological roles of ZoGRFs.

Protists regulate microbially mediated organic carbon turnover in soil aggregates.

Soil protists, the major predator of bacteria and fungi, shape the taxonomic and functional structure of soil microbiome via trophic regulation. However, how trophic interactions between protists and their prey influence microbially mediated soil organic carbon turnover remains largely unknown. Here, we investigated the protistan communities and microbial trophic interactions across different aggregates-size fractions in agricultural soil with long-term fertilization regimes. Our results showed that aggregate sizes significantly influenced the protistan community and microbial hierarchical interactions. Bacterivores were the predominant protistan functional group and were more abundant in macroaggregates and silt + clay than in microaggregates, while omnivores showed an opposite distribution pattern. Furthermore, partial least square path modeling revealed positive impacts of omnivores on the C-decomposition genes and soil organic matter (SOM) contents, while bacterivores displayed negative impacts. Microbial trophic interactions were intensive in macroaggregates and silt + clay but were restricted in microaggregates, as indicated by the intensity of protistan-bacterial associations and network complexity and connectivity. Cercozoan taxa were consistently identified as the keystone species in SOM degradation-related ecological clusters in macroaggregates and silt + clay, indicating the critical roles of protists in SOM degradation by regulating bacterial and fungal taxa. Chemical fertilization had a positive effect on soil C sequestration through suppressing SOM degradation-related ecological clusters in macroaggregate and silt + clay. Conversely, the associations between the trophic interactions and SOM contents were decoupled in microaggregates, suggesting limited microbial contributions to SOM turnovers. Our study demonstrates the importance of protists-driven trophic interactions on soil C cycling in agricultural ecosystems.

PDGF-BB accelerates TSCC via fibroblast lactates limiting miR-26a-5p and boosting mitophagy.

The tumor microenvironment and cancer-associated fibroblasts (CAFs) play crucial roles in tumor development, and their metabolic coupling remains unclear. Clinical data showed a positive correlation between PDGF-BB, CAFs, and glycolysis in the tumor microenvironment of oral tongue squamous cell carcinoma patients. In vitro, CAFs are derived from hOMF cells treated with PDGF-BB, which induces their formation and promotes aerobic glycolysis. Mitophagy increased the PDGF-BB-induced formation of CAF phenotypes and aerobic glycolysis, while autophagy inhibition blocked PDGF-BB-induced effects. Downregulation of miR-26a-5p was observed in CAFs; upregulation of miR-26a-5p inhibited the expression of mitophagy-related proteins ULKI, Parkin, PINK1, and LC3 and aerobic glycolysis in PDGF-BB-induced CAFs. PDGF-BB-induced CAFs promoted tumor cell proliferation, invasion, metastasis, NF-κB signaling pathway activation, and PDGF-BB secretion. Thus, PDGF-BB is associated with lactate-induced CAF formation and glucose metabolism reprogramming. These findings indicate potential therapeutic targets in oral tongue squamous cell carcinoma.

Efficacy of omalizumab in adult patients with allergic bronchopulmonary aspergillosis: a multicentre study in China.

Despite conventional glucocorticoid and antifungal therapy, acute exacerbation and hospitalization occur frequently in patients with allergic bronchopulmonary aspergillosis (ABPA). Whether omalizumab is an effective and safe treatment for adult patients with ABPA complicating asthma. Patients with ABPA complicating asthma who were treated with omalizumab from October 2019 to May 2023 were collected from five tertiary hospitals and evaluated. The frequencies of acute exacerbation and hospitalization; the number of eosinophils; the total IgE levels; and the average monthly medical dosages after 3, 6, and 12 months of omalizumab treatment were analysed, and the data before and after treatment (up to one year) were compared. The efficacy and safety of omalizumab treatment were assessed. In total, 26 patients were enrolled. The average monthly glucocorticoid dosage significantly decreased (median 0 vs. 24 mg/m) after 6 months of omalizumab treatment compared with 3 months; 73.68% of patients discontinued glucocorticoids after ≤ 12 months of treatment. Similarly, the average monthly dosage of antifungal agents was significantly decreased (median 0 vs. 3.49 g/m) after 12 months of treatment compared with 3 months. The average monthly glucocorticoid dosage (median 213.75 vs. 65.42 mg/m, P = 0.002) and the frequency of acute exacerbation (median 0.94 vs. 0.44 events, P = 0.033) were considerably reduced after omalizumab treatment. Omalizumab is effective in reducing the frequency of acute exacerbation and the necessary dosage of glucocorticoids in adult patients with ABPA complicating asthma. Patient age and BMI may affect the efficacy of treatment.