Annals of Translational Medicine

Purpose: To analyze the effect of radiotherapy timing relative to surgery on patients' survival and mortality rates in uveal melanoma (UM). Design: Retrospective cohort study using registry data from the Surveillance, Epidemiology, and End Results (SEER) database. Subjects: A total of 1,198 patients with UM were extracted from the SEER database and divided into three groups: preoperative radiotherapy, intraoperative radiotherapy (IORT), and postoperative radiotherapy. Methods: UM cases were extracted from the SEER database. Survival curves were generated based on the Kaplan-Meier method. An extended Cox regression was used to estimate the cancer-specific and all-cause mortality. Main Outcome Measures: Overall survival (including median survival) and hazard reductions for cancer-specific and all-cause mortality. Results: Preoperative radiotherapy revealed the highest median survival (4.93 years), followed by postoperative radiotherapy (4.76 years), and IORT (4.02 years). The preoperative strategy reduced the hazard of all-cause mortality by 42%, 50%, and 60% at 5-, 7-, and 10-year follow-up, respectively, compared with IORT. Findings were consistent in the cancer-specific sensitivity analysis (45%, 53%, and 62% reductions at the same time points). However, postoperative radiotherapy did not significantly reduce the cancer-specific mortality in comparison to IORT. Conclusions: Preoperative radiotherapy was associated with higher median overall survival and lower all-cause and cancer-specific mortality than IORT over 10 years of follow-up. Postoperative radiotherapy showed intermediate outcomes that did not differ significantly from IORT. Prospective studies with more detailed data on the temporal relation of radiotherapy timing and surgery are needed to confirm these findings.

Fuchs Endothelial Corneal Dystrophy (FECD) is characterized by progressive corneal endothelial cell loss and the formation of corneal guttae. Currently, there is a global shortage of donor corneas and new strategies are needed to reduce the need for corneal transplantation. While adeno-associated viruses (AAVs) have the capacity to deliver anti-apoptotic genes to human corneal endothelial cells (CECs), this has not been fully explored as a therapeutic strategy for FECD. In this study, we evaluated the transduction efficiency of self-complementary (sc-) and single-stranded (ss-) AAV2 serotypes in human CECs and ex vivo tissues and assessed whether AAV-mediated expression of Bcl-xL could attenuate apoptosis in FECD. Seventeen scAAV2 serotypes were screened for transduction efficiency in normal human CECs via green fluorescent protein (GFP) expression. The top 4 AAV2 serotypes were further evaluated in FECD cell lines, healthy cadaveric donor specimens, and FECD patient specimens. FECD cell lines were transduced with anti-apoptotic ssAAV2/5-Bcl-xL (AAV2/5-CAG-eGFP-P2A-BCLXL) and treated with etoposide to induce apoptosis. We found that scAAV2/5 demonstrated high transduction efficiency across all normal and FECD cell lines and tissues. We observed that ssAAV2/5-mediated expression of Bcl-xL provided significant protection against etoposide-induced apoptosis in FECD CECs (71.68%{+/-}0.69 vs 23.96%{+/-}8.88%, p=0.018). Our findings show that AAVs have the potential for therapeutic gene delivery to the human corneal endothelium, and that targeting the Bcl-xL mediated apoptotic pathway can be further explored as a therapeutic for FECD.

Background: Pulmonary arterial hypertension (PAH) is a serious disease with poor prognosis, especially in infants or preterm babies and there is still no optimal treatment for this disease. Noradrenalin (NE) is a vasoactive mediator which is released by sympathetic ganglion. According to previous studies, NE/1-adrenoreceptors is not only in regulating normal physiologic responses, but also in the pathogenesis of PAH. However, the mechanisms of NE in PAH are not fully understood. Methods: Human PASMC (PASMC) was used in this study. Cell viability assay and Wound healing assay were used to evaluate the proliferation and migration of PASMC. Immunoprecipitation and western blots analysis were used to investigate the mechanisms which involved in NE-induced PASMC proliferation. Results: We investigated that NE could induce human PASMC proliferation and migration. Furthermore, we first find that endothelin 1 (ET-1) signaling pathway plays an important role in NE-induced PASMC proliferation. ET1 is a critical molecular which is known for regulating cell growth and migration. We investigated that NE could increase NE-1 secretion, further enhancing ET-1 bind to its receptors. For further clarifying the downstream signals in NE/ET-1 induced PASMC proliferation, we detected the phosphorylation and expression levels of ERK and JNK. Conclusions: By combining the results from ours and previous studies, we believed that JNK/c-jun pathway may play an important role in NE-induced PASMC proliferation. Key Words: Noradrenaline; Pulmonary Arterial Hypertension; Pulmonary Artery Smooth Muscle Cells; Endothelin-1; JNK/c-Jun Signaling.

Background: Refractory and macrolide-resistant Mycoplasma pneumoniae pneumonia (MPP) has emerged as a major challenge in pediatric respiratory medicine, amplified by the post-2023 resurgence. However, a systematic overview of the research landscape specific to treatment-refractory and drugresistant disease in children remains lacking. Methods: Research articles and reviews on pediatric refractory or macrolide-resistant MPP published between 2000 and 2025 were retrieved from OpenAlex using Boolean searches. After screening, 2,286 records were quantitatively analyzed for annual output, contributing countries/institutions, thematic clusters, and citation-burst dynamics using Python. Results: Annual publications grew exponentially, with a pronounced surge after 2023 (n=378 in 2025). China produced the highest volume (45.1%) but recorded fewer citations per publication than the US, Japan, and Canada. The literature resolved into four clusters: macrolide resistance/molecular basis, epidemiology, etiology/co-infection, and refractory disease management. Burst analysis showed an evolution from earlier fronts like 23S rRNA mutations and azithromycin to recent emerging trends like pandemic-related co-circulation, genotype surveillance, and co-infection. Conclusions: Research on pediatric refractory and resistant MPP is expanding rapidly, shifting in emphasis from etiologic descriptions toward resistance mechanisms and clinical management. Standardizing the treatment of macrolide-unresponsive disease and post-pandemic epidemiological surveillance represent the principal directions for future work. Keywords: Mycoplasma pneumoniae; children; macrolide resistance; refractory pneumonia; bibliometric analysis; research trends

Ulcerative colitis (UC) and radiation enteropathy involve intestinal epithelial injury, barrier dysfunction, and inflammation, but effective treatments remain limited. This study evaluated MXC-017, a novel vimentin-targeting urea compound, in mouse models of dextran sulfate sodium (DSS)-induced colitis and radiation-induced enteropathy. Acute colitis was induced in C57BL/6 mice using 3.5% DSS for seven days, followed by regular water for seven days. Radiation enteropathy was induced by 13 Gy total abdominal irradiation. Mice received MXC-017 (150 mg/kg) or vehicle. Disease activity, intestinal permeability, inflammatory and epithelial markers, and histopathology were assessed. MXC-017's effects on cancer stem cell frequency, sphere formation, and migration were also examined in PC-3 and DU-145 prostate cancer cells. MXC-017 reduced DSS-induced colitis severity, accelerated weight recovery, lowered disease activity, partially preserved colon length, and restored barrier function. It also reduced proinflammatory cytokines, macrophage infiltration, epithelial injury, and goblet cell loss while preserving epithelial proliferation and markers of intestinal stem cell function and tight-junction integrity. Following irradiation, MXC-017 improved weight recovery, reduced intestinal permeability, preserved epithelial architecture, and partially mitigated villus shortening. Importantly, MXC-017 did not protect prostate cancer stem cells from radiation. Instead, it reduced stem cell frequency, sphere-forming capacity, and cancer cell migration. These findings support vimentin targeting with MXC-017 as a potential treatment for UC and radiation-induced intestinal toxicity and as an adjunct to radiotherapy for pelvic and abdominal malignancies.

Background: An estimated 826 million people have avoidable near vision impairment (NVI) due to lack of access to near vision glasses for presbyopia. Glasses use, uptake and replacement is essential to sustained NVI correction. Here we explore the uptake of second and subsequent pairs of near vision glasses and the willingness to pay. Methods: In this cross-sectional survey, 276 individuals who received near vision glasses through eye health screening programs in Punjab province, Pakistan from 2020 to 2022, were surveyed between February and July 2025, i.e. 3-5 years later. Results: 92.0% (n=254) of respondents were still using near vision glasses: a purchased replacement (41.3%, n=114), a free replacement (30.8%, n=85), or the original pair (19.9%, n=55). Male gender, higher age, and personal income were strongly associated with purchasing additional pairs, while women and those economically dependent on others relied more on free provision (all p values <0.05). Accessibility, indicated by shorter travel times and awareness of supply sources, also played a significant role in sustained replacement. Over 98% of participants expected to obtain (purchase or receive) a new pair of glasses in the future, and over 94% of participants expected to purchase their next pair. The mean willingness-to-pay (WTP) was 353 PKR (95% CI: 327-379) // 1.25 USD (95% CI: 1.16-1.34), while the average reported price paid was 416.67 PKR // 1.47 USD (95% CI: 351.39-481.94)). Conclusion: Sustained use of near vision glasses remained high 3-5 years after initial provision. Many recipients had purchased replacements, and willingness and ability to pay were high among participants, suggesting potential for sustained demand beyond initial subsidized distribution.

Introduction: Fighting the ventilator (FV) is characterized by a patients active counteraction of respiratory gas flow across multiple breaths during mechanical ventilation. An effective ventilation is prevented during such episodes. The objective of this exploratory study was to evaluate clinicians knowledge, perception and agreement regarding this condition. Methods: In a cross-sectional online survey, medical professionals with experience in intensive care medicine (mostly neonatal and pediatric patients) responded to 11 questions covering various clinical aspects of FV. Results: All respondents were familiar with the phenomenon and assessed it to be clinically relevant. Neonates were perceived to be predominantly affected. Promoting factors of FV included inadequate sedation and ventilation-associated factors. In clinical practice, the participants identified FV by clinical evaluation, analysis of ventilator waveforms and capnography and used both pharmacological and non-pharmacological intervention strategies. There was no consensus concerning the English terminology of the condition. Only few respondents were familiar with local guidelines to manage FV. Conclusion: Although there was consensus on the relevance of FV, diagnostics and management strategies were highly heterogeneous. Many participants agreed that poor patient-ventilator synchrony was an important cause of FV. Future work should focus on characterizing and generating evidence on FV.

Objective To evaluate the information quality, reliability, readability, and content deficits of ChatGPT, DeepSeek, and Doubao in answering frequently asked questions about bee stings. Methods Twenty-five high-frequency patient questions were selected based on Google Trends, domestic health platforms, and allergy guidelines, and submitted to the three LLMs, yielding 75 responses. Two emergency physicians independently assessed quality using GQS, mDISCERN, QAMAI, EQIP, and PEMAT-U/A. Readability was evaluated using six indices (ARI, FRES, GFI, FKGL, CLI, SMOG). Content deficits were classified qualitatively. Twenty emergency department patients evaluated the comprehensibility and credibility of AI responses. Results Significant differences were found among the three models on all quality metrics (all P < 0.01). DeepSeek achieved the highest mDISCERN score (median 21.00); ChatGPT led on QAMAI (25.00) and EQIP (75.00%); Doubao ranked lowest on all quality indicators but highest on PEMAT-U (73.00%). No model met the sixth-grade reading level standard. Eleven content deficits were identified: outdated medical advice (45.45%), omissions (36.36%), and hallucinations (18.18%). Doubao received the highest patient preference (45.0%). Conclusion The three LLMs exhibited distinct strengths: DeepSeek in source reliability, ChatGPT in overall quality, and Doubao in understandability. All models had excessively high readability levels, and outdated medical advice was the predominant content deficit. Objective To evaluate the information quality, reliability, readability, and content deficits of ChatGPT, DeepSeek, and Doubao in answering frequently asked questions about bee stings. Methods Twenty-five high-frequency patient questions were selected based on Google Trends, domestic health platforms, and allergy guidelines, and submitted to the three LLMs, yielding 75 responses. Two emergency physicians independently assessed quality using GQS, mDISCERN, QAMAI, EQIP, and PEMAT-U/A. Readability was evaluated using six indices (ARI, FRES, GFI, FKGL, CLI, SMOG). Content deficits were classified qualitatively. Twenty emergency department patients evaluated the comprehensibility and credibility of AI responses. Results Significant differences were found among the three models on all quality metrics (all P < 0.01). DeepSeek achieved the highest mDISCERN score (median 21.00); ChatGPT led on QAMAI (25.00) and EQIP (75.00%); Doubao ranked lowest on all quality indicators but highest on PEMAT-U (73.00%). No model met the sixth-grade reading level standard. Eleven content deficits were identified: outdated medical advice (45.45%), omissions (36.36%), and hallucinations (18.18%). Doubao received the highest patient preference (45.0%). Conclusion The three LLMs exhibited distinct strengths: DeepSeek in source reliability, ChatGPT in overall quality, and Doubao in understandability. All models had excessively high readability levels, and outdated medical advice was the predominant content deficit.

The lack of effective anti-JEV therapy possesses significant challenge to control JEV. {beta}-catenin, a key mediator of Wnt signaling pathway regulates different viral replication and host immune responses. However, its role in JEV infection remains to be elucidated. Thus, the current study focused on evaluating iCRT-14, a specific {beta}-catenin inhibitor, against JEV. Treatment with iCRT-14 following JEV infection resulted efficient reduction in viral progeny release, viral RNA and protein levels in Huh7 and HEK293T cells. Further, active and total {beta}-catenin, Cyclin D-1 and GSK3-{beta}, the other key pathway players were also modulated in infected and inhibitor treated cells. Moreover, iCRT-14 showed an IC of 4.56 in Huh7 cell and maximal inhibition at the early stages of the JEV life cycle. Interestingly, the overexpression of {beta}-catenin in both the cells and siRNA-mediated {beta}-catenin knockdown (in Huh7 cells) significantly abrogated JEV replication, as evidenced by decreased viral titers, viral protein expression, and viral as well as total RNA levels. Moreover, the reduction in extracellular (84%) and intracellular (60%) viral titers following iCRT-14 treatment highlights its role in impairing JEV infection. Further, in silico molecular docking and co-immunoprecipitation studies demonstrated interactions between {beta}-catenin and the JEV NS5 and E proteins. Collectively, these findings suggest that optimum level of {beta}-catenin is required for efficient JEV infection, highlighting its potential as a target for designing host-directed control strategies to regulate viral infection.

We present our Stage-1 Registered Report as a full clinical trial article with all methods in past tense and including mock results, table and figures for the primary analysis. To remind the reader that this Stage-1 article is written before data collection, we highlight in color that these mock results are only for illustrative purposes and will be replaced by the actual results in the Stage-2 Registered Report. Background In patients experiencing out-of-hospital cardiac arrest, optimization of oxygen delivery during cardiopulmonary resuscitation is a critical. Although both positive end-expiratory pressure (PEEP) and zero end-expiratory pressure (ZEEP) are employed during CPR, their respective impacts on clinically relevant outcomes is yet to be clearly established. Methods This investigator-initiated, pragmatic, registry-based, multicenter, triple-blind randomized controlled superiority trial evaluates whether applying 8 cm H2O PEEP during cardiopulmonary resuscitation improves outcomes compared with ZEEP in adults with non-traumatic, non-drowning out-of-hospital cardiac arrest. Pre-randomized CPR kits (1:1 PEEP vs. sham) were used by ambulance sites during manual ventilation throughout the resuscitation process. The primary analysis was conducted in the principal stratum of patients who received either a supraglottic airway or endotracheal tube. The primary outcome was neurological status at hospital discharge measured by a utility-weighted score on the modified Rankin Scale. Secondary outcomes included prehospital return of spontaneous circulation, 30-day survival, and 6-month quality of life. The primary safety outcome was clinically significant pneumothorax.

Background. Comparing long-term outcomes of gastric cancer surgery between hospitals requires a common reference. Risk-adjusted benchmarks depend on the model and population used to build them and are difficult for another hospital to reproduce. TNM stage is a prognostic classification already recorded for every resected gastric cancer. We report unadjusted stage-specific overall survival from a consecutive cohort with complete follow-up as reference data and propose a minimal dataset for producing comparable figures elsewhere. Methods. The cohort comprised 690 consecutive eligible patients who underwent curative-intent D2 gastrectomy for stage I to III adenocarcinoma at Ruijin Hospital, Shanghai, in 2019. All operations were performed by eight experienced, high-volume consultant surgeons. Stage followed the AJCC 8th edition: pTNM after upfront surgery (n = 570) and ypTNM after neoadjuvant chemotherapy (n = 120). Overall survival was estimated by the Kaplan-Meier method without adjustment. Results. There were 199 deaths, 181 within five years. Every survivor was followed for at least 68.1 months. After upfront surgery, five-year overall survival was 95.0% (95% CI 91.4 to 97.1) for stage I, 83.8% (76.5 to 89.0) for stage II and 56.5% (49.2 to 63.1) for stage III, and was 95.0% in IA and 95.2% in IB, falling to 26.7% in IIIC. After neoadjuvant chemotherapy, five-year survival was 78.6%, 61.9% and 31.3% for ypStage I, II and III. Pooling pTNM and ypTNM lowered stage III five-year survival to 50.2%. The proposed minimal dataset has 16 items, 13 of them recorded during the admission for gastrectomy. Conclusions. These figures are intended as a reference for comparing hospitals rather than as a standard of care. We propose 16 items, most of them routinely recorded, from which another hospital can produce the same table and compare its results by stage.

Aims: To estimate the preventable pneumococcal disease burden by 21-valent pneumococcal conjugate vaccine (PCV21) compared to PCV20 for the national immunization program for adults aged 65 years or older in Japan. Methods: Serotype distribution among isolates and the annual incidence of invasive pneumococcal disease (IPD) in adults were monitored. The numbers of IPD or pneumococcal community-acquired pneumonia (pCAP) cases preventable by immunization with PCV20 or PCV21 were estimated according to reported vaccine efficacy and duration of protection in older adults. Data from our nationwide study of adult IPD surveillance and a multicenter study of pCAP were used. Results: The mean annual incidence of adult patients with IPD caused by all serotypes among adults aged [&ge;]65 years, which declined during the COVID-19 pandemic period, recovered to 89% of the pre-pandemic level in 2025. During 2023-2025, the proportion of PCV20-non-PCV21 serotypes was 8.5% for adults aged [&ge;]65 years. At the current vaccination coverage rate of 40%, the numbers of preventable IPD cases (per person per year) by PCV20 and PCV21 were 36 and 53, respectively. The preventable numbers of pCAP cases by PCV20 and PCV21 were 2,821 and 4,765, respectively. The estimated number of preventable pCAP cases was approximately 80-90 times higher than that of preventable IPD cases. Conclusion: Our data indicate that PCV21 could prevent 1.5-1.7 times as many pneumococcal disease cases as PCV20 among adults aged [&ge;] 65 years in Japan. However, PCV20 should be considered if the incidence of adult IPD cases caused by PCV20-non-PCV21 serotypes increases.

Patients with history of neck radiation for Human Papilloma Virus (HPV)-associated head and neck cancer experience rapid progression of carotid artery stenosis. The present study sought to determine whether screening and treating asymptomatic carotid artery stenosis in patients with a history of neck radiation is cost-effective. This study is a cost-utility analysis using a probabilistic Markov model over a thirty-year time horizon assessing carotid screening and treatment to avoid neurologic consequences of neck radiation for HPV-associated head and neck cancer. A strategy of no carotid surveillance was associated with a 14.8% cumulative risk of stroke and a strategy of ultrasound surveillance and treatment with TCAR was associated with a 3.0% cumulative risk of stroke. The latter had a median incremental cost of $1.04 million USD and provided a median 39.1 additional QALYs, resulting in a median incremental cost-effectiveness ratio of $26,556 per QALY. In conclusion, this study suggests that ultrasound surveillance and treatment with TCAR for asymptomatic carotid artery stenosis is likely to be cost-effective for patients who have been successfully treated with radiation therapy for HPV-associated head and neck cancer.

Purpose: Posterior pharyngeal wall (PPW) thickening is a common structural manifestation of treatment-related internal lymphedema in patients with head and neck cancer and can be evaluated using lateral videofluoroscopic images acquired during modified barium swallow (MBS) studies. However, no standardized method currently exists for quantitative measurement. Methods: This two-phase methodological study first conducted a scoping review to characterize existing approaches to PPW thickness measurement and identify the principal factors contributing to variation in PPW thickness measurement. Eight studies were identified with variation observed across these measurement factors. An empirical reliability study was then performed using 107 MBS studies from 93 Head and Neck Cancer patients. Two independent raters annotated 10 anatomical landmarks on pre-swallow and post-swallow resting frames, and a computer-assisted algorithm quantitatively generated seven candidate PPW thickness measurements based on different vertebral reference points and measurement directions. Reliability was assessed intraclass correlation coefficients (ICCs). Results: Inter-rater reliability was highest for the measurement originating from the midpoint of C3 and extending perpendicular to the anterior C3 surface (ICC, 0.78; 95% CI, 0.72-0.83). Among the normalization references, C2-C4 vertebral length demonstrated greater reliability than C3 vertebral length, with an ICC of 0.88 (95% CI, 0.85-0.91). No significant differences were observed between pre-swallow and post-swallow PPW thickness measurements across the evaluated approaches. Conclusions: These findings provide a methodological foundation for more standardized and reliable quantification of PPW thickness, with potential to expand the role of MBS from the functional evaluation of swallowing to include quantitative characterization of pharyngeal structural abnormalities.

Background/Aims: In medical practice, the rising prevalence of infections in kidney transplant recipients (KTRs) is a notable concern. However, understanding the incidence and risk factors associated with infections in KTRs remains limited. This study aims to assess the incidence and factors associated infection among KTRs. Additionally, we also investigate the median time of each infection among KTRs. Methods: A retrospective cohort study was conducted from 1 January 2018- 31 December 2022 at Thailand's tertiary hospital. We performed univariable and multivariable logistic regression analyses to identify potential risk factors related infection and investigated for the incidence and median time of each infection among KTRs. Results: A total of 179 participants were included in this study. Our findings reveal the kidney from living donor was protective factor for infection among KTRs (aOR 0.063, 95% CI 0.005-0.792; p = 0.032). Urinary tract infections (UTIs)showed as the predominant pathogenic manifestation among KTRs (43%). The median time of UTIs, cytomegalovirus (CMV) infection and pneumocystis pneumonia (PCP) were 16, 57 and 94.5 days, respectively. Conclusions: Our study establishes that receiving a kidney from a living donor is a protective factor against post-kidney transplant infections. Particularly urinary tract infections were most common of infection. Monitoring urinary tract infections post-transplantation is recommended. Moreover, awareness of UTI, CMV infection and PCP should be concerned during 2-3 months after transplantation. However, due to a small sample size; we recommend to increase the number of particular participants in further investigations.

Abstract Background: Even though significant advances in diagnosis, treatment, and prevention strategies have been implemented, neonatal sepsis remains a common concern in clinical practice, especially in low-resource countries. It is one of the major causes of death during the first month of life. This study aimed to assess clinical outcomes and predictors of mortality among neonates with neonatal sepsis admitted to public hospitals in selected Hospitals in Addis Ababa, Ethiopia. Methods: A hospital-based prospective cohort study design was conducted among 466 neonates admitted with neonatal sepsis from September 2024 to January 2025. All neonates who were admitted to selected Hospitals of Addis Ababa city after being clinically or laboratory-diagnosed with neonatal sepsis by the attending physician were included in the study. Data were entered into EpiData 4.2 and analyzed by SPSS version 26. Bivariate and multivariate Cox regression were used to identify the relationship between dependent and independent variables. Finally, variables with p-value [&le;] 0.05 were taken as significant factors associated with poor clinical outcome. Results: The study was conducted among 466 neonates admitted with neonatal sepsis. Of all neonates admitted with neonatal sepsis, 372 (79.8%) were discharged with good outcomes, and 94 (20.2%) had a poor outcome/died. Duration of ruptured membrane being >12hr (AOR=7.02, 95 % (CI: 1.85, 26.57), marital status /divorced (AOR=3.12, 95 % (CI: 1.67, 7.45),rural residence (AOR= 6.05, 95 % (CI: 2.03-16.53), assisted instrumental delivery (AOR= 5.99, 95 % (CI: 1.46-17.11), meconium-stained amniotic fluid ((AOR= 9.48, 95 % (CI: 0.49-18.61)), no initiate exclusive breast feed within one hour (AOR= 3.20, 95 % (CI: 0.90-7.52), chest in drawing (AOR= 5.81, 95 % (CI: 1.75-11.23) were significantly associated with neonatal mortality. Conclusion: Neonatal mortality was moderately high. Meconium-stained amniotic fluid, prolonged duration of ruptured membrane (>12hr), Mode of delivery (instrumental delivery), and chest in drawing are among the predictors of neonatal mortality. Keywords: -Clinical outcome,Neonatal sepsis, Mortality, predictors, Ethiopia.

Cardiac tissue is primarily made up of cardiomyocytes, which are regulated by the autonomic nervous system. We have used and developed approaches such as patch clamping and electrical stimulation-combined calcium imaging, computer modeling, optogenetics and chemogenetics combining with video-based Short-Time Fourier transformation (STFT) method to study the physiological activities of cardiomyocytes. The action potential of cardiomyocytes was found to be synchronized with calcium signals, which can be grouped into two categories by STFT. A mathematical model was developed to simulate the changes in electrical activities within cardiomyocytes caused by energy depletion, especially for 2-deoxy-D-glucose (2DG) treatment. Optogenetic and chemogenetics tools, such as ChR2(H134R), OptoXR-{beta}2AR and hM3Dq accelerated beating, while GR, ACR1 and hM4Di inhibited cardiomyocytes beating. A video-based STFT method was developed to visualize the beating frequency during these manipulations. An in vitro co-culture method was developed to study the relationship between sympathetic neuronal firing and calcium dynamics in cardiomyocytes. In vivo, electrocardiograph (ECG) measurements showed that Clozapine N-oxide (CNO) caused heart rates increasement in cTnT-hM3Dq virus injected mouse. However, it had no impact on cTnT-hM4Di virus injected mouse. This study provides comprehensive methodologies for studying cardiomyocyte physiology and manipulating heart rates in vitro and in vivo.

Background: This systematic review and meta-analysis evaluated the prognostic value of Hippo signaling pathway biomarkers in oral squamous cell carcinoma. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, electronic database searches identified 17 eligible studies involving 1,194 patients. Associations between the immunohistochemical expression of Hippo pathway effectors, primarily YAP and TAZ, and clinicopathological characteristics were assessed. Meta-analyses using random-effects models estimated pooled hazard ratios for overall survival. Results: Predominantly nuclear expression of YAP and TAZ was consistently associated with adverse clinicopathological features, including advanced clinical stage, lymph node metastasis, and poorer histological differentiation. Meta-analysis demonstrated that YAP overexpression was associated with worse overall survival (hazard ratio, 1.918; 95% confidence interval, 1.036 to 3.549; p = 0.038). TAZ overexpression was similarly associated with poorer overall survival (hazard ratio, 2.845; 95% confidence interval, 1.682 to 4.811; p < 0.001). Although substantial between-study heterogeneity was observed, the direction of the prognostic association remained consistent across studies. Conclusions: Increased nuclear expression of YAP and TAZ is consistently associated with more aggressive disease and poorer overall survival in oral squamous cell carcinoma. These findings support the prognostic value of Hippo pathway biomarkers, although methodological heterogeneity warrants cautious interpretation.

Objective: To examine how medial plantar nerve shear wave speed (Cs) and viscosity coefficient (Vi) are associated with the severity of diabetic peripheral neuropathy (DPN), and to assess their ability to differentiate adjacent severity categories. Materials and Methods: Based on TCSS, the 113 patients with type 2 diabetes mellitus were assigned to the non-DPN (n = 33), mild DPN (n = 46), and moderate DPN (n = 34) groups. Medial plantar nerve Cs and Vi were measured using shear wave elastography and viscosity imaging. Receiver operating characteristic analysis evaluated Cs, Vi, and their logistic regression-based combination; areas under the curves (AUCs) were compared using DeLong tests. Results: Cs and Vi increased progressively across the three groups (both P < 0.001). For non-DPN versus mild DPN, the AUCs of Cs, Vi, and the combined model were 0.688 (95% CI, 0.604-0.772), 0.741 (0.660-0.822), and 0.745 (0.665-0.826), respectively, without significant pairwise differences. For mild versus moderate DPN, the corresponding AUCs were 0.707 (0.625-0.789), 0.794 (0.724-0.865), and 0.799 (0.731-0.867). The combined model outperformed Cs (P = 0.045), whereas Cs versus Vi and Vi versus the combined model did not differ significantly (P = 0.162 and 1.000, respectively). Conclusion: Medial plantar nerve Cs and Vi increased with DPN severity. Their combination improved discrimination between mild and moderate DPN compared with Cs alone but not with Vi alone. Quantitative medial plantar nerve viscoelastic assessment may complement clinical severity grading.

Background: Ionizing radiation is inherent to percutaneous coronary intervention (PCI) and may reach radiation-alert thresholds during complex procedures. Real-world data translating dose determinants into a usable planning-stage alert tool remain scarce. Aims: To determine the prevalence and predictors of radiation overexposure (RO) during PCI and to develop a pragmatic radiation-alert risk score usable before substantial dose accumulates. Methods: We analysed 10,634 consecutive PCI procedures performed between January 2008 and May 2018. Complex PCI was defined as unprotected left main, rotational atherectomy, chronic total occlusion (CTO), or bifurcation/trifurcation PCI. The composite RO endpoint was a dose-area product >500 Gy{middle dot}cm2, cumulative reference-point air kerma (AK) >5 Gy, or fluoroscopy time >60 minutes. A pragmatic score was built from early procedural variables. Results: Overall, 3,457 procedures (32.5%) were complex, and RO occurred in 99 (0.93%). Complex PCI showed higher RO rates than standard PCI (2.1% vs 0.4%; p<0.001). In multivariable analysis, body mass index (BMI), male sex, CTO, rotational atherectomy, bifurcation, and treatment of [&ge;]2 vessels independently predicted higher AK. A pragmatic score derived from early clinical and procedural variables showed good discrimination (area under the curve 0.772; 95% bootstrap CI 0.725-0.818) and was well calibrated (Brier score 0.0091; observed-to-expected ratio 0.994) for the composite RO endpoint. Conclusions: Radiation-alert thresholds were exceeded in approximately 1% of PCI procedures, but fivefold more often during complex PCI. A pragmatic, internally assessed score based on early procedural variables identified high-risk cases with good discrimination, supporting planning-stage risk stratification to activate dose-sparing strategies before substantial radiation has accumulated.