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Abstract Nonlinear friction, system uncertainty, and external disturbances have a significant impact on the performance of high-precision servo feed systems. In order to achieve higher tracking accuracy, a sliding mode controller based on a generalized extended state observer with the double critic deep deterministic policy gradient algorithm is designed. Firstly, a flexible two mass drive model (FTMDM) is established for the two-axis differential micro-feed system (TDMS). Next, a generalized extended state observer (GESO) is designed to estimate matched interference and mismatched interference. And it is proved that the observation error of GESO is bounded. A sliding mode controller based on GESO is further proposed. The stability of the controller has been proven through Lyapunov theory, and the error is bounded and converges to zero in finite time. The tuning process of controller parameters is simplified by using quadratic optimal control principle. Furthermore, a double critic deep deterministic policy gradient algorithm (DCDDPG) is proposed to achieve dynamic optimization of parameters about GESO. The simulation results show that GESO with DCDDPG can reduce the observation error of step signal and sinusoidal signal, and improve the observation accuracy of nonlinear friction significantly. Finally, experimental results show that the proposed control method achieves more accurate position tracking performance on TDMS.

Four previously described species of Argopistes are recognized and redescribed from Japan and Taiwan: A. biplagiatus Motschulsky, 1860, A. rufus Chen, 1934, A. tsekooni Chen, 1934, and A. unicolor Jacoby, 1885. Three new species from Taiwan, A. jungchani sp. nov., A. tsoui sp. nov., and A. yuae sp. nov., are described. Descriptions of species include illustrations of aedeagi, antennae, gonocoxae, abdominal ventrite VIII, and spermathecae. Argopistes rufus Chen, 1934, stat. nov. is raised to species status from a variety of A. biplagiatus Motschulsky, 1860. Argopistes coccinelliformis Csiki, 1940, syn. nov. and A. ryukyuensis Shigetoh & Suenaga, 2022, syn. nov. are proposed as junior synonyms of A. rufus Chen, 1934 Lectotypes are designated for A. undecimmaculata Jacoby, 1885, A. unicolor Jacoby, 1885, and A. biplagiatus var. rufus Chen, 1934.

Abstract Background Research indicates a positive association between short-term diurnal temperature range (DTR) exposure and hypertension. However, the impact of long-term DTR exposure has not been thoroughly studied in population-based cohort research. Methods This study conducted cross-sectional (including 16,690 participants) and longitudinal analyses (including 9,650 participants) based on the China Health and Retirement Longitudinal Study (CHARLS). Daily temperature data was sourced from the National Scientific Data of the Qinghai-Tibet Plateau. We calculated the moving average of DTR exposure of all the participants in CHARLS with exposure windows of 30-day, 60-day, 180-day, 1-year, and 2-year before the interview month of CHARLS Wave1 (2011). Logistic regression and age-stratified Cox proportional hazards models were employed in our analysis. Results In the cross-sectional study, 6,572 (39.4%) participants had hypertension. We found higher DTR is associated with a higher prevalence of hypertension across different exposure windows. The effect was strongest when the exposure window of DTR was 180-day, with an adjusted odds ratio (OR) of 1.261 (95% confidence interval (CI): 1.124–1.416 [highest tertile DTR vs. lowest tertile DTR]). In the cohort study, 3,020 (31.3%) participants developed hypertension during 83 months of follow-up. A higher level of DTR (hazard ratio (HR): 1.224, 95% CI: 1.077–1.391) was associated with a higher risk of incident hypertension. We found significant interactions between DTR and age (P interaction:

Abstract Background Intracranial artery stenosis (ICAS) and cerebral small vessel disease (CSVD) are associated with a heavy socioeconomic burden; however, their longitudinal changes remain controversial. Methods We conducted a longitudinal analysis on 756 participants of Shunyi Cohort who underwent both baseline and follow-up brain magnetic resonance imaging (MRI) and MR angiography in order to investigate the risk factors for ICAS and CSVD progression in community population. Incident ICAS was defined as new stenosis occurring in at least one artery or increased severity of the original artery stenosis. CSVD markers included lacunes, cerebral microbleeds (CMB), and white matter hyperintensities (WMH). Results After 5.58 ± 0.49 years of follow-up, 8.5% of the 756 participants (53.7 ± 8.0 years old, 65.1% women) had incident ICAS. Body mass index (BMI) (OR = 1.09, 95% CI = 1.01–1.17, p = 0.035) and diabetes mellitus (OR = 2.67, 95% CI = 1.44–4.93, p = 0.002) were independent risk factors for incident ICAS. Hypertension was an independent risk factor for incident lacunes (OR = 2.12, 95% CI = 1.20–3.77, p = 0.010) and CMB (OR = 2.32, 95% CI = 1.22–4.41, p = 0.011), while WMH progression was primarily affected by BMI (β = 0.108, SE = 0.006, p = 0.002). A higher LDL cholesterol level was found to independently protect against WMH progression (β = −0.076, SE = 0.027, p = 0.019). Conclusions Modifiable risk factor profiles exhibit different in patients with ICAS and CSVD progression. Controlling BMI and diabetes mellitus may help to prevent incident ICAS, and antihypertensive therapy may conduce to mitigate lacunes and CMB progression. LDL cholesterol may play an inverse role in large arteries and small vessels.

Tumor organoids, derived from tumor tissues, are three-dimensional structures created in vitro to mimic in vivo tumor growth. They possess comparable genetic lineage and pathological characteristics to the original tumor, making them a promising research platform for studying tumor biology. In recent years, significant advancements in techniques such as microfluidics, cell co-culture and vascularization have greatly promoted the development of Organ-on-a-Chip (OoC) and expanded the applications of tumor organoid models in both basic and clinical translational research. These advancements include leveraging tumor organoid models to investigate drug resistance mechanisms, perform drug screening, and facilitate clinical trials of precisional therapy. However, current organoid models still face several limitations, including the instability of cell culture quality, low cost-effectiveness, and the inability to accurately replicate the complex tumor microenvironment and spatial structures. Further research is needed to overcome these technical bottlenecks and improve the application of organoid models in cancer research, thereby further enhancing the depth of tumor research. This review summarized the development history and latest progress of tumor organoids. In terms of the latest applications of tumor organoids, this article reviewed disease modeling, research and development of innovative tumor drugs, and their application in personalized treatment. It also summarized the recent clinical researches of organoids; In addition, this review provided a detailed introduction to the technological progress of tumor organoids, including the development of novel culture devices, simulation of tumor microenvironment, and induction of angiogenesis. In summary, this review explored the latest developments, defects and future directions in the research of tumor organoids, aiming to provide reference for the study of tumor organoids.

Abstract The proinflammatory properties of high‐mobility group box protein 1 (HMGB1) in sepsis have been extensively studied. This study aimed to investigate the impact of HMGB1 on ferroptosis and its molecular mechanism in sepsis‐induced acute lung injury (ALI). A septic mouse model was established using the cecal ligation and puncture method. Blocking HMGB1 resulted in improved survival rates, reduced lung injury, decreased levels of ferroptosis markers (reactive oxygen species, malondialdehyde, and Fe2+), and enhanced antioxidant enzyme activities (superoxide dismutase and catalase) in septic mice. In addition, knockdown of HMGB1 reduced cellular permeability, ferroptosis markers, and raised antioxidant enzyme levels in lipopolysaccharide (LPS)‐stimulated MLE‐12 cells. Silencing of HMGB1 led to elevations in the expressions of ferroptosis core‐regulators in LPS‐treated MLE‐12 cells, such as solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member A2 (SLC3A2), and glutathione peroxidase 4. Furthermore, blocking HMGB1 did not alter ferroptosis, oxidative stress‐related changes, and permeability in LPS‐treated MLE‐12 cells that were pretreated with ferrostatin‐1 (a ferroptosis inhibitor). HMGB1 inhibition also led to elevated expressions of nuclear factor erythroid 2‐related factor 2 (Nrf2) and its downstream targets, heme oxygenase‐1 (HO‐1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) in LPS‐treated MLE‐12 cells and lung tissues from septic mice. The Nrf2‐specific inhibitor ML385 reversed the effects of HMGB1 silencing on ferroptosis and cell permeability in LPS‐treated MLE‐12 cells. Our findings indicated that the inhibition of HMGB1 restrains ferroptosis and oxidative stress, thereby alleviating sepsis‐induced ALI through the activation of Nrf2 signaling.

Abstract Bacteria extracellular vesicles (BEVs), characterized as the lipid bilayer membrane-surrounded nanoparticles filled with molecular cargo from parent cells, play fundamental roles in the bacteria growth and pathogenesis, as well as facilitating essential interaction between bacteria and host systems. Notably, benefiting from their unique biological functions, BEVs hold great promise as novel nanopharmaceuticals for diverse biomedical potential, attracting significant interest from both industry and academia. Typically, BEVs are evaluated as promising drug delivery platforms, on account of their intrinsic cell-targeting capability, ease of versatile cargo engineering, and capability to penetrate physiological barriers. Moreover, attributing to considerable intrinsic immunogenicity, BEVs are able to interact with the host immune system to boost immunotherapy as the novel nanovaccine against a wide range of diseases. Towards these significant directions, in this review, we elucidate the nature of BEVs and their role in activating host immune response for a better understanding of BEV-based nanopharmaceuticals’ development. Additionally, we also systematically summarize recent advances in BEVs for achieving the target delivery of genetic material, therapeutic agents, and functional materials. Furthermore, vaccination strategies using BEVs are carefully covered, illustrating their flexible therapeutic potential in combating bacterial infections, viral infections, and cancer. Finally, the current hurdles and further outlook of these BEV-based nanopharmaceuticals will also be provided. Graphical Abstract

Nisotra chrysomeloides Jacoby, 1885, N. dohertyi (Maulik, 1926), N. gemella (Erichson, 1834), and Nisotra nigripes Jacoby, 1894 are redescribed with illustrations of aedeagi, antennae, gonocoxae, abdominal ventrite VIII, and spermathecae. Nisotra nigripes is recorded for the first time from Taiwan. The immature stages and life history of N. gemella were studied in the laboratory using a novel rearing design. Four synonyms previously proposed are confirmed: Sphaeroderma javana de Motschulsky, 1866, S. orbiculata de Motschulsky, 1866, Nisotra bowringi Baly, 1876, and Podagrica hibisci Bryant, 1941 with N. gemella (Erichson, 1834). Lectotypes are designated for Haltica gemella Erichson, 1834, N. chrysomeloides Jacoby, 1885, N. bowringi Baly, 1876, and Podagrica hibisci Bryant, 1941.

Abstract Background About 13–25% of cerebral venous thrombosis (CVT) cases lack clear etiology, which may be associated with underlying genetic factors. This study aims to investigate genetic factors in CVT patients using whole exome sequencing (WES). Methods Thirty-eight CVT patients hospitalized underwent WES. 977 subjects with WES data from a community cohort study --the Shunyi cohort were as the control group. Using bioinformatics analysis, differential genes with rare damaging variants between two groups were filtered (P A, CBS c.949 A > G; F2 c.1787G > A; SERPINC1 c.409-11G > T. Comparing the WES data of two groups, a total of 179 different genes with rare damaging variants were screened (P

Abstract Background/purpose(s) The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. Methods We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. Results Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. Conclusion Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies. Graphical Abstract

Background: Cytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. Methods: This retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. Results: There were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P

Background: Patients with hematological malignancies (HM) were at a high risk of developing severe disease from coronavirus disease 2019 (COVID-19). We aimed to assess the clinical outcome of COVID-19 in hospitalized patients with HM. Methods: Adult patients with HM who were hospitalized with a laboratory-confirmed COVID-19 between May, 2021 and November, 2022 were retrospectively identified. Primary outcome was respiratory failure requiring mechanical ventilation or mortality within 60 days after hospitalization. We also analyzed associated factors for de-isolation (defined as defervescence with a consecutive serial cycle threshold value > 30) within 28 days. Results: Of 152 eligible patients, 22 (14.5%) developed respiratory failure or mortality in 60 days. Factors associated with developing respiratory failure that required mechanical ventilation or mortality included receipt of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) (adjusted hazards ratio [aHR], 5.10; 95% confidence interval [CI], 1.64–15.85), type 2 diabetes mellitus (aHR, 2.47; 95% CI, 1.04–5.90), lymphopenia at admission (aHR, 6.85; 95% CI, 2.45–19.15), and receiving

BackgroundThe differentiation of hematopoietic cells is significantly affected by cell metabolic activity. However, despite increasing interest in this field, there has been no comprehensive investigation of the metabolic functions of human hematopoietic cells during specific phases of differentiation. Thus, this study was conducted to develop a method for comparing hematopoietic cell lineage differentiation based on the metabolic functions of the cell. The metabolic activity of human umbilical cord-derived hematopoietic cells was examined during various phases of differentiation, specifically, hematopoietic stem cells (HSCs), hematopoietic progenitor cells, and differentiated blood cells. This approach was used to develop comprehensive metabolic maps corresponding to the different stages.ResultsHSCs were found to have robust fatty acid (FA) synthesis, FA oxidation, pentose phosphate pathway (PPP) activity, and glucose uptake, shown by their significantly higher expression of ACAC, CPT1A, G6PD, and GLUT1 as compared to differentiated pluripotent progenitor cells, common myeloid progenitors, megakaryocyte erythroid progenitors, lympho-myeloid primed progenitors, and granulocyte-macrophage progenitor cell populations. In monocytic differentiation, higher levels of ACAC, ASS1, ATP5A, CPT1A, G6PD, GLUT1, IDH2, PRDX2, and HK1 protein expression were evident in classical and intermediate monocytes relative to non-classical monocytes, consistent with high anabolic and catabolic levels. Compared with myelocytes and mature cells, the meta-myelocyte and pro-myelocyte populations of granulocytes show significantly elevated levels of ACAC, ASS1, ATP5A, CPT1A, G6PD, IDH2, PRDX2, and HK. In contrast to naïve and regulatory B cells, pro-B cells had higher levels of oxidative phosphorylation, while regulatory B cells showed greater PPP activity, glucose uptake, and tricarboxylic acid cycle activity. The analyses of T cells also indicated significantly higher ACAC, ASS1, ATP5A, CPT1A, G6PD, GLUT1, IDH2, PRDX2, and HK1 expression levels in CD4+ populations compared with CD8+ populations.ConclusionsThe results provide comprehensive analytical methods and reference values for future systematic studies into the metabolic functions of various cord blood-derived hematopoietic cell populations in different pathological or physiological conditions. These findings could also contribute to research on the connection between cellular metabolism and cancer or aging.

Abstract Objectives To investigate the risk factors and underlying causes of pregnancy-related cerebral venous thrombosis (PCVT). Methods A retrospective cohort of 16 patients diagnosed with CVT during pregnancy and postpartum (within six weeks after delivery) in a comprehensive hospital in China between 2009 and 2022 were carefully reviewed, focusing on demographic, clinical, and etiological characteristics, especially underlying causes. We matched 16 PCVT patients with 64 pregnant and puerperal women without PCVT to explore risk factors and clinical susceptibility to PCVT. Results PCVT occurred commonly during the first trimester (43.75%) and the puerperium (37.5%). The frequency of anemia, thrombocytosis and thrombocytopenia during pregnancy, dehydration, and pre-pregnancy anemia was significantly higher in women with PCVT than in those without PCVT (P A (p. Met406Ile), heterozygous PROS1 c.301C > T (p. Arg101Cys), composite heterozygous mutation in the F8 gene (c.144-1259C > T; c.6724G > A (p. Val2242Met)) and homozygous MTHFR c.677C > T (p. Ala222Val). Conclusions The occurrence of anemia, thrombocytopenia and thrombocytosis during pregnancy, dehydration and pre-pregnancy anemia suggested a greater susceptibility to PCVT. For confirmed PCVT patients, autoimmune diseases, hereditary thrombophilia, and hematological disorders were common causes. Screening for potential etiologies should be paid more attention, as it has implications for treatment and long-term management.

Abstract Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Studies have indicated that immune dysfunction plays a central role in the pathogenesis of sepsis. Dendritic cells (DCs) play a crucial role in the emergence of immune dysfunction in sepsis. The major manifestations of DCs in the septic state are abnormal functions and depletion in numbers, which are linked to higher mortality and vulnerability to secondary infections in sepsis. Apoptosis is the most widely studied pathway of number reduction in DCs. In the past few years, there has been a surge in studies focusing on regulated cell death (RCD). This emerging field encompasses various forms of cell death, such as necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death (ADCD). Regulation of DC’s RCD can serve as a possible therapeutic focus for the treatment of sepsis. Throughout time, numerous tactics have been devised and effectively implemented to improve abnormal immune response during sepsis progression, including modifying the functions of DCs and inhibiting DC cell death. In this review, we provide an overview of the functional impairment and RCD of DCs in septic states. Also, we highlight recent advances in targeting DCs to regulate host immune response following septic challenge. Graphical Abstract

Abstract Background Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. Results A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. Conclusion Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.

Abstract Mitochondria are the centers of energy and material metabolism, and they also serve as the storage and dispatch hubs of metal ions. Damage to mitochondrial structure and function can cause abnormal levels and distribution of metal ions, leading to cell dysfunction and even death. For a long time, mitochondrial quality control pathways such as mitochondrial dynamics and mitophagy have been considered to inhibit metal-induced cell death. However, with the discovery of new metal-dependent cell death including ferroptosis and cuproptosis, increasing evidence shows that there is a complex relationship between mitochondrial quality control and metal-dependent cell death. This article reviews the latest research results and mechanisms of crosstalk between mitochondrial quality control and metal-dependent cell death in recent years, as well as their involvement in neurodegenerative diseases, tumors and other diseases, in order to provide new ideas for the research and treatment of related diseases.

Abstract Background Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. Methods The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58 hep−/− . The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). Results Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. Conclusions This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

Abstract Background Narrative medicine demonstrated positive impact on empathy in medicine and nursing students. However, this pedagogical approach had not been evaluated in pharmacy education. This study sought to apply and evaluate the narrative medicine approach in extending empathy in Asian undergraduate pharmacy students. Methods Narrative medicine was applied through workshops which used narratives of people with different experiences and perspectives. First-year undergraduate pharmacy students who volunteered and attended these workshops formed the intervention group (N = 31) and the remaining first-year cohort formed the control group (N = 112). A sequential explanatory mixed methods approach was adopted in which quantitative methods were first used to measure impact on pharmacy students’ empathy using the Jefferson Scale of Empathy– Health Professions Student (JSE-HPS), and qualitative methods (i.e. group interviews) were then used to assess pharmacy students’ emotional responses to narratives, and the perspectives of pharmacy students and faculty of this pedagogical approach. Results There was no difference in JSE-HPS scores between intervention and control groups across baseline (i.e. upon matriculation), pre-intervention, and post-intervention timepoints. Pharmacy students in the intervention group had lower scores in Factor 3 (“Standing in People’s Shoes”) following the intervention. Five themes, guided by internal and external factors in cognition, emerged from the Group Interviews: (1) incongruence between students’ motivation and faculty’s perception, (2) learning context, (3) academic context, (4) cognitive system, and (5) affective system. Themes 1, 4 and 5 referred to internal factors such as students’ motivation, perceived learnings, and feelings. Themes 2 and 3 referred to external factors including workshop materials, activities, content, and facilitation. Conclusion This study is the first to demonstrate that pharmacy students engaged with the narrative medicine approach as narratives elicited emotional responses, exposed them to diverse perspectives, and deepened their appreciation of the importance of empathy and complexities of understanding patients’ perspectives. Scaffolded educational interventions using narratives and real-life patient encounters, alongside longitudinal measurements of empathy, are necessary to bring about meaningful and sustained improvements in empathy.

Cancer-induced bone pain (CIBP) significantly impacts the quality of life and survival of patients with advanced cancer. Despite the established role of neurexins in synaptic structure and function, their involvement in sensory processing during injury has not been extensively studied. In this study using a rat model of CIBP, we observed increased neurexin 2 expression in spinal cord neurons. Knockdown of neurexin 2 in the spinal cord reversed CIBP-related behaviors, sensitization of spinal c-Fos neurons, and pain-related negative emotional behaviors. Additionally, increased acetylation of neurexin 2 mRNA was identified in the spinal dorsal horn of CIBP rats. Decreasing the expression of N-acetyltransferase 10 (NAT10) reduced neurexin 2 mRNA acetylation and neurexin 2 expression. In PC12 cells, we confirmed that neurexin 2 mRNA acetylation enhanced its stability, and neurexin 2 expression was regulated by NAT10. Finally, we discovered that the NAT10/ac4C-neurexin 2 axis modulated neuronal synaptogenesis. This study demonstrated that the NAT10/ac4C-mediated posttranscriptional modulation of neurexin 2 expression led to the remodeling of spinal synapses and the development of conscious hypersensitivity in CIBP rats. Therefore, targeting the epigenetic modification of neurexin 2 mRNA ac4C may offer a new therapeutic approach for the treatment of nociceptive hypersensitivity in CIBP.

Abstract This study introduces a novel image capture and lighting techniques using a cutting-edge hybrid MEMS scanner system designed for compact microscopic imaging. The scanner comprises a tapered optical fiber waveguide and innovative aerosol-jet printed PZT (lead zirconate titanate) bimorph push-pull actuators on a stainless-steel substrate, effectively addressing issues that are commonly associated with PZT on silicon substrates such as fracture and layer separation. By leveraging nonlinear vibration, the scanner achieves a spiral scan pattern from a single signal input, in addition to the expected two-dimensional scanning and target illumination from two phase-shifted inputs. This capability is further enhanced by a novel process to taper the optical fiber, which reduces illumination scattering and tunes the fiber to the resonant frequencies of the scanner. The precisely tapered tip enables large fields of view while maintaining independent 2-axis scanning through one-degree-of-freedom actuation. Experimental validation showcases the successful generation of a spiral scan pattern with a 60 μm diameter scan area and a 10 Hz frame rate, effectively reconstructing scanned images of 5 μm lines, cross patterns (15 μm in length with a 5 μm gap), and structures of a Psychodidae wing.

International guidelines and standards for human protection from electromagnetic fields have been revised recently. The epithelial/absorbed power density (APD) has been used as a new physical quantity for local exposure to frequencies > 6 GHz, related to the temperature rise in the superficial layer. The assessment methods of APD for practical exposure scenarios are crucial for realistic exposures. This study investigates averaging methods for APD in nonplanar skin models for local electromagnetic field exposure from 10 to 90 GHz. Eight research groups compared the calculated APDs using distinct numerical approaches and postprocessing techniques. The intercomparison aimed to clarify the primary causes of variations in aspects, such as APD averaging methods, skin model structure, and types of exposure antennas. Statistical analyses reveal that the maximum differences in relative confidence intervals (RCI) due to different average methods and skin models are within 9.4% and 5.1%, respectively. In contrast, when the distance between the antenna and skin is set to 5 mm, the discrepancy attributed to the exposure antenna reaches 59.4% at 10 GHz. This difference does not exceed 9.2% under other computational conditions. Additionally, the spatially averaged APD appears to have a linear relationship with the maximum skin surface temperature elevation, based on regression analysis. The findings indicate that the variances in the spatially averaged APD are largely independent of both the APD averaging methods and skin model structures. However, they slightly depend on the antenna types used as exposure sources.

Abstract Acute myeloid leukemia (AML) with CEBPA bZIP in-frame mutations (CEBPA bZIP-inf) is classified within the favorable-risk group by the 2022 European LeukemiaNet (ELN-2022). However, heterogeneous clinical outcomes are still observed in these patients. In this study, we aimed to investigate the mutation profiles and transcriptomic patterns associated with poor outcomes in patients with CEBPA bZIP-inf. One hundred and thirteen CEBPA bZIP-inf patients were identified in a cohort of 887 AML patients homogeneously treated with intensive chemotherapy. Concurrent WT1 or DNMT3A mutations significantly predicted worse survival in AML patients with CEBPA bZIP-inf. RNA-sequencing analysis revealed an enrichment of interferon (IFN) signaling and metabolic pathways in those with a shorter event-free survival (EFS). CEBPA bZIP-inf patients with a shorter EFS had higher expression of IFN-stimulated genes (IRF2, IRF5, OAS2, and IFI35). Genes in mitochondrial complexes I (NDUFA12 and NDUFB6) and V (ATP5PB and ATP5IF1) were overexpressed and were associated with poorer survival, and the results were independently validated in the TARGET AML cohort. In conclusion, concurrent WT1 or DNMT3A mutations and a dysregulated immune and metabolic state were correlated with poor survival in patients with CEBPA bZIP-inf, and upfront allogeneic transplantation may be indicated for better long-term disease control.

Abstract Introduction We investigated the safety and efficacy of percutaneous facial nerve pulsed radiofrequency combined with drug injection for treatment of intractable facial paralysis of herpes zoster. The authors provide a detailed description of percutaneous facial nerve pulsed radiofrequency combined with steroid injection for treatment of intractable facial paralysis after herpes zoster, and they examine its clinical efficacy. This is the first time in the literature to our knowledge that this procedure has been applied in facial paralysis after herpes zoster. Methods A total of 43 patients with a history of facial paralysis after herpes zoster for > 1 month were enrolled in this retrospective study. The patients were subjected to percutaneous stylomastoid foramen pulsed radiofrequency of the facial nerve under computed tomography (CT) guidance combined with drug injection. The House-Brackmann grades and NRS (Numerical Rating Scale) data collection were performed at different time points (preoperatively, 1 day post-procedure, and 2, 4, and 12 weeks postoperatively). The occurrence of complications was also assessed. Results The 43 participants successfully completed the CT-guided percutaneous stylomastoid foramen pulsed radiofrequency of the facial nerve combined with drug injection. Both approaches [posterior approach of the ear (7 cases) and anterior approach of the ear (36 cases)] were efficacious and safe. The House-Brackmann grades (I, II, III, IV, V, VI) were 4 (3–4), 2 (2–3), 1 (1–2), and 1 (0–2) at different operation times (T0, T1, T2, T3, T4); patients felt significant recovery at T1 after operation and had gradually recovered at each time point but had no significant recovery after T3. The NRS scores at different operation times were 2.690 ± 2.213, 0.700 ± 0.939, 0.580 ± 1.006, 0.440 ± 0.908, and 0.260 ± 0.759, respectively. Differences in NRS scores between T0 and T1/2/3/4 were significant while differences between T1 and T2/3/4 were not significant. Six patients developed mild numbness, nine patients exhibited muscle tension, while one patient exhibited facial stiffness. During surgery, there was no intravascular injection of drugs, no nerve injury was reported, and there was no local anesthetic poisoning or spinal anesthesia. Conclusions Percutaneous stylomastoid foramen pulsed radiofrequency combined with drug injection of the facial nerve for treatment of intractable facial paralysis after herpes zoster is a minimally invasive technique with high rates of success, safety, and effective outcomes. It is a potential therapeutic option for cases of facial paralysis of herpes zoster with a > 1 month history even for those with severe facial paralysis and whose treatment has failed after oral medication and physiotherapy.

Abstract Background Extrachromosomal circular DNAs (eccDNAs) exist in human blood and somatic cells, and are essential for oncogene plasticity and drug resistance. However, the presence and impact of eccDNAs in type 2 diabetes mellitus (T2DM) remains inadequately understood. Methods We purified and sequenced the serum eccDNAs obtained from newly diagnosed T2DM patients and normal control (NC) subjects using Circle-sequencing. We validated the level of a novel circulating eccDNA named sorbin and SH3‐domain‐ containing‐1circle97206791–97208025 (SORBS1circle) in 106 newly diagnosed T2DM patients. The relationship between eccDNA SORBS1circle and clinical data was analyzed. Furthermore, we explored the source and expression level of eccDNA SORBS1circle in the high glucose and palmitate (HG/PA)-induced hepatocyte (HepG2 cell) insulin resistance model. Results A total of 22,543 and 19,195 eccDNAs were found in serum samples obtained from newly diagnosed T2DM patients and NC subjects, respectively. The T2DM patients had a greater distribution of eccDNA on chromosomes 1, 14, 16, 17, 18, 19, 20 and X. Additionally, 598 serum eccDNAs were found to be upregulated, while 856 eccDNAs were downregulated in T2DM patients compared with NC subjects. KEGG analysis demonstrated that the genes carried by eccDNAs were mainly associated with insulin resistance. Moreover, it was validated that the eccDNA SORBS1circle was significantly increased in serum of newly diagnosed T2DM patients (106 T2DM patients vs. 40 NC subjects). The serum eccDNA SORBS1circle content was positively correlated with the levels of glycosylated hemoglobin A1C (HbA1C) and homeostasis model assessment of insulin resistance (HOMA-IR) in T2DM patients. Intracellular eccDNA SORBS1circle expression was significantly enhanced in the high glucose and palmitate (HG/PA)-induced hepatocyte (HepG2 cell) insulin resistance model. Moreover, the upregulation of eccDNA SORBS1circle in the HG/PA-treated HepG2 cells was dependent on generation of apoptotic DNA fragmentation. Conclusions These results provide a preliminary understanding of the circulating eccDNA patterns at the early stage of T2DM and suggest that eccDNA SORBS1circle may be involved in the development of insulin resistance.

Abstract Introduction Zoster-associated pain (ZAP) treatment and management is still inadequate. Repeated intervention protocol is often applied to manage ZAP. This study aimed to retrospectively investigate the effect of repeated applications of pulsed radiofrequency therapy on controlling acute/subacute ZAP. Methods From March 2019 to December 2021, 150 patients with acute/subacute ZAP who underwent repeated application of pulsed radiofrequency treatment (R-PRF) and pulsed radiofrequency combined paravertebral block interventions (PRF + PVB) in the Pain Department of the affiliated Hospital of Jiaxing University were enrolled. Patients were grouped by intervention protocol and received at least 12 months of follow-up assessments using the Numerical Rating Scale score (NRSs), Pittsburg Sleep Quality Index (PSQI), Simple McGill Pain Questionnaire-2 score (SF-MPQ-2s), and follow-up interventions. Results Both groups experienced a reduction in the incidence of clinically meaningful ZAP after the intervention therapy. In the R-PRF group, there were 36 cases of clinically meaningful ZAP within the first month post-treatment, while the PRF + PVB group had 38 cases. The incidence of clinically meaningful ZAP, as determined by multivariable generalized estimating equations, was 42.86% in the R-PRF group and 57.58% in the PRF + PVB group during the first month of follow-up. There was a significant difference in the incidence of clinically meaningful ZAP between the two groups after 1 month of treatment (adjusted odds ratio: 0.40; 95% confidence interval: 0.18–0.91; p = 0.03). Conclusions Both R-PRF and PRF + PVB treatments effectively relieve pain in patients with acute/subacute ZAP. However, R-PRF may have superior efficacy compared to PRF + PVB in reducing the incidence of clinically meaningful ZAP 1 month after treatment.

Abstract Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is considered for patients with high‐risk B‐cell lymphoma and relapsed or refractory disease. This study aimed to analyze the long‐term follow‐up data of patients who underwent allo‐HSCT in Taiwan. This was a retrospective observational study using data from the Taiwan Society of Blood and Marrow Transplantation database. A total of 105 patients who underwent allo‐HSCT because of high‐risk, relapsed, or refractory disease between 2010 and 2019 were included. Forty‐five percent of the patients previously underwent autologous stem cell transplantation (ASCT). The median follow‐up duration was 18.6 months. The probability of 3‐year progression‐free survival and overall survival (OS) was 34.5% and 37%, respectively. The probability of 1‐year non‐relapse mortality was 31.4%, and the major cause was infection (75.8%). The multivariable analysis showed that not in remission at the time of transplantation and the absence of graft‐versus‐host disease (GVHD) were factors associated with inferior OS. The probability of 3‐year OS in patients with diffuse large B‐cell lymphoma who underwent allo‐HSCT and allo‐HSCT after ASCT was 40.2% and 25.2%, respectively. Allo‐HSCT could be a salvage therapeutic option for relapsed or refractory B‐cell lymphoma. Complete remission at the time of allo‐HSCT and the presence of GVHD are independent variables for overall survival.