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Abstract Fifth generation (5G) new radio (NR) fiber-wireless integrated systems using polarization multiplexing-multiband technique and self-polarization diversity scheme are successfully implemented. Polarization multiplexing-multiband technique is an effectual method to enhance the transmission capacity and spectral efficiency of systems. Self-polarization diversity scheme is an efficient scheme for polarization demultiplexing, in which an x-polarized (y-polarized) optical carrier with multiple x-polarized (y-polarized) optical signals can be detected using single-ended photodiodes. The transmission of 5G NR sub-terahertz (THz) signals through fiber-wireless integrated systems holds promise to afford high-speed and long-haul wired-wireless communications. It shows the robustness to achieve high aggregate data rates and lays the foundation to meet the evolving demands of future communication systems. Through an integrated medium of 20 km single-mode fiber, 1.6 km optical wireless, and 4/8/12 m 5G NR wireless, four 5G sub-THz 32-quadrature amplitude modulation-orthogonal frequency-division multiplexing signals at x- and y-polarizations are transmitted with good transmission performance in terms of low bit error rates and error vector magnitudes. The successful transmission of sub-THz signals at different carrier frequencies and polarizations over fiber-wireless integrated systems proves system’s ability to support cutting-edge 5G NR fiber-wireless integrated systems.

Background Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator-activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Abstract Numerous plant taxa are threatened by habitat destruction or overexploitation. To overcome these threats, new methods are urgently needed for rescuing threatened and endangered plant species. Here, we review the genetic consequences of threats to species populations. We highlight potential advantages of genome editing for mitigating negative effects caused by new pathogens and pests or climate change where other approaches have failed. We propose solutions to protect threatened plants using genome editing technology unless absolutely necessary. We further discuss the challenges associated with genome editing in plant conservation to mitigate the decline of plant diversity.

Abstract Background The evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE. Methods A retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted. Results Multivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p

Abstract Background Nephroureterectomy with bladder cuff excision is the standard treatment for high-risk upper urinary tract urothelial carcinoma (UTUC). The role of minimally invasive surgery in treating locally advanced UTUC remains controversial. This study aimed to compare the outcomes of open, laparoscopic, and robotic surgeries for managing locally advanced UTUC. Methods We retrospectively reviewed 705 patients with locally advanced UTUC from multiple institutions throughout Taiwan. Perioperative outcomes and oncological outcomes, such as cancer-specific survival, overall survival, disease-free survival and bladder-free survival, were compared between the open, laparoscopic and robotic groups. Results The minimally invasive group had better overall and cancer-specific survival (CSS) rates. The 2-year CSS rates of the open, laparoscopic and robotic groups were 71%, 83%, and 77% respectively (p

Abstract The integration of fiber-optical wireless convergence with fifth generation new radio is crucial in building high-performance access networks. This approach not only provides high-transmission-rates but also ensures broad coverage, which is vital for future networks. Here we report fifth generation new radio fiber-wireless converged systems by injection locking multi-optical carrier into directly-modulated lasers. Data rates of 10 Gb/s, 20 Gb/s, and 40 Gb/s are achieved by direct modulation on directly-modulated lasers using 16-quadrature amplitude modulation-orthogonal frequency-division multiplexing signal. Through 25-km single-mode fiber, 1.5-km optical wireless, and 12-/22-/33-m millimeter-wave/sub-terahertz wireless integrated-media, 10-Gb/s/20-GHz, 20-Gb/s/60-GHz, and 40-Gb/s/100-GHz signals are transmitted with acceptably low bit error rates and error vector magnitudes, as well as distinct constellations. The successful transport of fifth generation new radio millimeter-wave and sub-terahertz signals at different carrier frequencies through fiber-wireless convergence demonstrates the potential of the system to meet the evolving requirement of next-generation communications.

Abstract To establish normal reference ranges for fetal right ventricular modified myocardial performance index (RV Mod-MPI) using automatic synchronization of the RV inflow and outflow images (MPI+TM). Additionally, we aimed to clinically apply RV Mod-MPI to investigate its changes in fetal right congenital diaphragmatic hernia (CDH) compared to normal fetuses. This prospective study included uncomplicated singleton pregnancies between 16 and 38 weeks of gestational age. Cases with any maternal or fetal complications that developed during the enrollment period were excluded. Two experienced operators measured the RV Mod-MPI using the automated and manual methods. The intraclass correlation coefficients (ICC) were calculated for intra- and inter-operator reproducibility. The mean differences between the manual and automated measurements were also compared. The RV Mod-MPI was then compared between the right CDH fetuses and normal fetuses. Seventy normal fetuses were analyzed for the feasibility of an automated system, and 364 examinations from 272 fetuses were analyzed for developing the normal references. The automated system showed significantly higher intra- and inter-operator reproducibility of Mod-MPI than those of manual measurements (ICC = 0.962 vs. 0.913 and 0.961 vs. 0.889, respectively). The mean difference in Mod-MPI between the manual and automated method was 0.0002 ± 0.0586 with a 95% confidence interval of -0.0095–0.0099. The Mod-MPI and isovolumetric relaxation time increased throughout the gestational weeks. The isovolumetric contraction time increased until 24 weeks of gestation and then slightly decreased afterwards, and the ejection time also increased until 31 weeks of gestation and then decreased. There was no significant difference in the Mod-MPI between right CDH and normal fetuses. The automated system showed high inter- and intra-operator reproducibility. Furthermore, the normal reference values of Mod-MPI for each gestational age were established. Our results suggest that the automated system might be clinically feasible for evaluating fetal cardiac function.

Abstract The proximity-effect, whereby materials in contact appropriate each other’s electronic-properties, is widely used to induce correlated states, such as superconductivity or magnetism, at heterostructure interfaces. Thus far however, demonstrating the existence of proximity-induced charge-density-waves (PI-CDW) proved challenging. This is due to competing effects, such as screening or co-tunneling into the parent material, that obscured its presence. Here we report the observation of a PI-CDW in a graphene layer contacted by a 1T-TaS2 substrate. Using scanning tunneling microscopy (STM) and spectroscopy (STS) together with theoretical-modeling, we show that the coexistence of a CDW with a Mott–gap in 1T-TaS2 coupled with the Dirac-dispersion of electrons in graphene, makes it possible to unambiguously demonstrate the PI-CDW by ruling out alternative interpretations. Furthermore, we find that the PI-CDW is accompanied by a reduction of the Mott gap in 1T-TaS2 and show that the mechanism underlying the PI-CDW is well-described by short-range exchange-interactions that are distinctly different from previously observed proximity effects.

Abstract In hospitals, the deterioration of a patient's condition leading to death is often preceded by physiological abnormalities in the hours to days beforehand. Several risk‐scoring systems have been developed to identify patients at risk of major adverse events; however, such systems often exhibit low sensitivity and specificity. To identify the risk factors associated with in‐hospital cardiac arrest (IHCA), we conducted a retrospective cohort study at a tertiary medical center in Taiwan. Four machine learning algorithms were employed to identify the factors most predictive of IHCA. The support vector machine model was discovered to be the most effective at predicting IHCA. The ten most critical physiological parameters at 8 h prior to the event were pulse rate, age, white blood cell count, lymphocyte count, body temperature, body mass index, systolic and diastolic blood pressure, platelet count, and use of central nervous system‐active medication. Using these parameters, we can enhance early warning and rapid response systems in our hospital, potentially reducing the incidence of IHCA in clinical practice.

Abstract This study investigates predictors of unsatisfactory outcomes in female overactive bladder (OAB) patients treated with oral monotherapy by analyzing skin sympathetic nerve activity (SKNA) using a novel “neuECG” method. The study included 55 newly diagnosed female patients with idiopathic OAB, autonomic function was evaluated using neuECG before treatment initiation, and validated OAB questionnaires and urodynamic studies were administered. Initial monotherapy was administered for the first 4 weeks, with non‐responders defined as patients not achieving satisfactory symptom relief and requiring further treatment. Responders (n = 32) and non‐responders (n = 23) had no significant differences in baseline characteristics or urodynamic parameters; however, non‐responders exhibited significantly higher baseline average SKNA (aSKNA) (1.36 ± 0.49 vs. 0.97 ± 0.29 μV, p = 0.001), higher recovery aSKNA (1.28 ± 0.46 vs. 0.97 ± 0.35 μV, p = 0.007), and a lower stress/baseline ratio of aSKNA (1.05 ± 0.42 vs. 1.26 ± 0.26, p = 0.029). Baseline aSKNA had the highest predictive value for monotherapy refractoriness in OAB (AUROC = 0.759, p = 0.001), with an optimal cut‐off point of >1.032 μV. These findings suggest that elevated pre‐treatment aSKNA can predict resistance to oral monotherapy in OAB, warranting close monitoring and proactive treatment strategies for patients with high aSKNA.

Abstract Background To investigate the outcomes of bilateral implantation of enhanced monofocal intraocular lenses (IOLs, ICB00) with a − 2.00 diopter (D) target in patients with moderate to high myopia and to compare the clinical outcomes of a − 2.00 D binocular target with an emmetropia target in patients who underwent cataract surgery. Methods In this retrospective study, we reviewed the medical records of patients who underwent uncomplicated phacoemulsification with ICB00 IOL implantation. Emmetropia (Group 1) and − 2.00 D (Group 2) were targeted in 60 and 20 eyes of 30 and 10 patients, respectively. Three months after surgery, uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), and uncorrected near visual acuity (UNVA) were measured. Defocus curves were measured under the photopic condition by intervals of 0.50 D from + 0.50 D to − 4.00 D. Results The postoperative binocular logMAR UDVA, UIVA, and UNVA were 0.01 ± 0.03, 0.08 ± 0.11, and 0.33 ± 0.15 in Group 1 and 0.31 ± 0.13, 0.04 ± 0.05, and 0.11 ± 0.07 in Group 2, respectively. Group 2 showed a significantly superior postoperative binocular UNVA (P = 0.027) and inferior binocular UDVA (P = 0.003) than Group 1. Binocular UIVA and CDVA did not significantly differ between the groups although UIVA was better in Group 2 than in Group 1. Near glasses were needed by 66% of Group 1 and 0% of Group 2. Conclusions Bilateral implantation of ICB00 IOL with − 2.00 D of residual myopia is suitable for patients with moderate to high myopia to improve UDVA, UIVA, and UNVA.

Abstract Aims Social culture concerns and betel quid (BQ) dependence may be the potential reasons for BQ chewing. This study’s purpose was to identify the correlates of reasons for male BQ chewing. Methods We adopted a mixed-methods design. The study was conducted between October 2021 and August 2023 at a medical center of northern Taiwan. The Reasons for Betel-Quid Chewing Scale, Numeric Rating Scale, and Betel Quid Dependence Scale were used to quantitatively assess reasons for BQ chewing, stress, and BQ dependence, respectively. Semi-structured questions were used to interview for qualitative data. Results Among 150 BQ users, the most common reasons for BQ chewing were stimulation, reinforcement, and social/cultural factors. Chewers who reported more pressure to chew were more likely to be younger, have less educational level, be employed, have greater stress, and have more BQ dependence. Content analysis of qualitative data showed three themes: physical and psychological demands, peer pressure, and perceived greater effectiveness. Conclusion Employment was the factor most commonly associated with reasons for BQ chewing and with each construct. Study findings can help healthcare professionals understand reasons for BQ chewing, thereby helping them educate chewers to cope with withdrawal symptoms and successfully quit.

Fluconazole-resistant clade 4 Candida tropicalis causing candidemia in humans has been detected in tropical/subtropical areas, including those in China, Singapore, and Australia. We analyzed 704 individual yeasts isolated from fruits, soil, water, and farmers at 80 orchards in Taiwan. The most common pathogenic yeast species among 251 isolates recovered from farmers were Candida albicans (14.7%) and C. parapsilosis (11.6%). In contrast, C. tropicalis (13.0%), C. palmioleophila (6.6%), and Pichia kudriavzevii (6.0%) were prevalent among 453 environmental isolates. Approximately 18.6% (11/59) of C. tropicalis from the environment were resistant to fluconazole, and 81.8% (9/11) of those belonged to the clade 4 genotype. C. tropicalis susceptibility to fluconazole correlated with susceptibilities to the agricultural azole fungicides, difenoconazole, tebuconazole, and triadimenol. Tandem gene duplications of mutated ERG11 contributed to azole resistance. Agriculture environments are a reservoir for azole-resistant C. tropicalis; discontinuing agricultural use of azoles might reduce emergence of azole-resistant Candida spp. strains in humans.

Background: The partial pectoralis major transfer for the treatment of serratus anterior deficiency and modified Eden-Lange/Triple Tendon Transfer for trapezius deficiency result in improvement in pain and shoulder function. However, athletic function following these procedures is unknown. The purpose of this study is to determine the outcomes and return to military duty and athletic tasks following partial pectoralis major transfer and Tripler Tendon Transfer. Methods: A retrospective review of prospectively gathered data was performed for all patients surgically treated for medial and lateral scapular winging at two military medical centers. Preoperative patient-reported outcomes collected included the Single Assessment Numeric Evaluation (SANE), Visual Analog Scale (VAS), and American Shoulder and Elbow Surgeons (ASES). Patients were excluded if they had less than 1 year follow-up, no postoperative patient-reported outcomes or return to military duty data. Results: Eleven patients were surgically treated for scapular winging, 7 patients for serratus anterior deficiency and 4 patients for trapezius deficiency and were available for follow-up at a mean of 28 months. The mean preoperative outcome scores were SANE 40.9%, VAS 4.4 and ASES 54.4. Significant improvement in SANE 77.4% (P = .001), VAS 1.8 (P = .017) and ASES 75.7 (P = .008) was identified. Five of the 9 (55.6%) active-duty service members were able to meet their fitness requirements and remain on active-duty status. Conclusion: The split pectoralis major transfer for serratus anterior deficiency and the Triple Tendon Transfer for trapezius deficiency are excellent treatment options in patients who have high physical demands.

Ollier's disease is a rare sporadic nonhereditary condition associated with mutations in the IDH1 and IDH2 genes, that manifests in early age of life. It is characterized by widespread enchondromas, predominantly affecting one side of the body. Diagnosis is based on clinical and radiological evaluations, and interval assessment for Ollier's disease is important as enchondromas are at risk of malignant transformation into chondrosarcomas. This case report aims to discuss the role of bone scan and plain X-ray in managing multiple enchondromas of a 25-year-old male patient with swellings over the left chest wall and left acromial regions.

Distinguishing lupus nephritis (LN) from other glomerulopathies, such as immunoglobulin A nephropathy (IgAN), poses a diagnostic challenge owing to overlapping clinical and histopathologic findings. Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare and potentially fatal disorder characterized by the presence of lupus anticoagulant and acquired factor II deficiency. We report a pediatric case of LN with LAHPS, which was initially diagnosed as IgAN. An 8-year-old girl presented with gross hematuria with nephrotic syndrome. Based on the kidney biopsy results, treatment for IgAN with membranoproliferative pattern was initiated. Two months later, she developed left upper extremity swelling with multiple vein thromboses requiring anticoagulation; treatment led to remission, allowing discontinuation of immunosuppressants within 8 months. Gross hematuria recurred 10 months later and was accompanied by hypocomplementemia; positive antinuclear, anti-double stranded DNA, and triple antiphospholipid antibodies; and factor II deficiency, prompting revision of the diagnosis to LN and LAHPS. Initial delay in LN diagnosis was attributed to the patient’s young age, nonspecific symptoms, and inconclusive laboratory and histopathological findings. Immunosuppressive therapy for IgAN partially improved LN, further complicating the diagnosis. This case emphasized the importance of clinical suspicion; integrating clinical, serological, and histopathological data; and considering LAHPS in differential diagnosis of glomerulonephritis with coagulopathy.

Abstract Advanced pancreatic ductal adenocarcinomas (PDACs) respond poorly to all therapies, including the first-line treatment, chemotherapy, the latest immunotherapies, and KRAS-targeting therapies. Despite an enormous effort to improve therapeutic efficacy in late-stage PDAC patients, effective treatment modalities remain an unmet medical challenge. To change the status quo, we explored the key signaling networks underlying the universally poor response of PDAC to therapy. Here, we report a previously unknown chemo-induced symbiotic signaling circuit that adaptively confers chemoresistance in patients and mice with advanced PDAC. By integrating single-cell transcriptomic data from PDAC mouse models and clinical pathological information from PDAC patients, we identified Yap1 in cancer cells and Cox2 in stromal fibroblasts as two key nodes in this signaling circuit. Co-targeting Yap1 in cancer cells and Cox2 in stroma sensitized PDAC to Gemcitabine treatment and dramatically prolonged survival of mice bearing late-stage PDAC, whereas simultaneously inhibiting Yap1 and Cox2 only in cancer cells was ineffective. Mechanistically, chemotherapy triggers non-canonical Yap1 activation by nemo-like kinase in 14-3-3ζ-overexpressing PDAC cells and increases secretion of CXCL2/5, which bind to CXCR2 on fibroblasts to induce Cox2 and PGE2 expression, which reciprocally facilitate PDAC cell survival. Finally, analyses of PDAC patient data revealed that patients who received Statins, which inhibit Yap1 signaling, and Cox2 inhibitors (including Aspirin) while receiving Gemcitabine displayed markedly prolonged survival compared to others. The robust anti-tumor efficacy of Statins and Aspirin, which co-target the chemo-induced adaptive circuit in the tumor cells and stroma, signifies a unique therapeutic strategy for PDAC.

Abstract It remains unclear whether pulmonary fibrosis-like changes differ in patients with different SARS-CoV-2 variants. This study aimed to compare pulmonary fibrotic changes between two SARS-CoV-2 variant periods (delta vs. pre-delta) in critically ill patients with SARS-CoV-2 pneumonia. Clinical data and chest CT images of patients with SARS-CoV-2 pneumonia receiving mechanical ventilation were collected from 10 hospitals in South Korea over two periods: delta (July-December, 2021; n = 64) and pre-delta (February, 2020-June, 2021; n = 120). Fibrotic changes on chest CT were evaluated through visual assessment. Of 184 patients, the mean age was 64.6 years, and 60.5% were ale. Fibrosis-like changes on chest CT (median 51 days from enrollment to follow up CT scan, interquartile range 27–76 days) were identified in 75.3%. Delta group showed more fibrosis-like changes (≥ 2) (69.8% vs. 43.1%, P = 0.001) and more frequent reticulation and architectural distortion+/-parenchymal band than pre-delta group. Even after propensity score matching with clinical variables, delta group had more severe (≥ 2) fibrosis-like changes (71.4% vs. 38.8%, P = 0.001), and more frequent reticulation and architectural distortion+/-parenchymal band than pre-delta group. Our data suggest that critically ill patients with SARS-CoV-2 in delta period had more severe pulmonary fibrosis-like changes than those in pre-delta period.

Abstract Despite the intensive research on gut microbiome-associated diseases over the past 20 years, pharmacological methods for effectively eliminating pathobionts remain unsatisfactory. This study investigated the therapeutic potential of bacteriophages against Enterococcus faecalis, in which bacterial tyrosine decarboxylase (TDC) converts orally administered levodopa (L-DOPA) to dopamine, in an MPTP mouse model of Parkinson’s disease (PD). E. faecalis bacteriophages PBEF62, PBEF66, and PBEF67 (4 × 1010 PFU total/200 µl/day), and E. faecalis cells (2 × 109 CFU/200 µl/day) were orally administered at 2-h intervals before every MPTP (i.p.) and/or L-DOPA (p.o.) treatments for 13 days. The relative abundances of E. faecalis cells and bacteriophages in the feces peaked at 4 and 12 h after administration and gradually decreased by 12 and 48 h, respectively. While the administration of E. faecalis cells eliminated the beneficial effect of L-DOPA on MPTP-induced behavioral deficits, as assessed by cylinder and rotarod tests, the co-administration of bacteriophages with bacterial cells restored this effect. The modulating effects of L-DOPA, E. faecalis, and bacteriophages on PD behavior were closely associated with choline acetyltransferase expression levels in the striatum but not with tyrosine hydroxylase in the substantia nigra of each group. Recurrence and extinction of PD behaviors following treatment with E. faecalis and/or bacteriophages were also coincident with the dopamine levels in the blood and brain tissues of PD mice. The effectiveness of L-DOPA was restored after the three types of E. faecalis bacteriophages selectively eliminated E. faecalis cells, along with the TDC gene copies and transcripts responsible for converting L-DOPA to dopamine in the gastrointestinal tract. In conclusion, a combination of bacteriophages PBEF62, PBEF66, and PBEF67 targeting E. faecalis demonstrates potential as a valuable supplement to L-DOPA therapy for PD.

Abstract By investigating the correlation between the injection rate and pressure of subretinal tissue plasminogen activator (tPA) and air using a standard Viscous Fluid Control (VFC) system with a 38-gauge cannula, we aimed to establish guidelines for stable injections. We fabricated a retina mimicking model (RMM) with 0.25% agarose solution and an aluminum plate, and substituted submacular hemorrhage (SMH) and tPA with blood-mimicking fluid (BMF) and balanced salt solution (BSS), respectively. The diameter of the pre-bleb mimicking SMH in RMM was 1.30 ± 0.16 cm, increasing to 1.98 ± 0.24 cm and 1.83 ± 0.22 cm after bleb propagation with BSS and air, respectively. BSS injection rates were 2.86 ± 0.04 µl/sec, 6.74 ± 0.48 µl/sec and 8.55 ± 0.16 µl/sec at 8, 12, and 16 psi, respectively. Air injection rates were 37.98 ± 3.11 µl/sec, 79.01 ± 5.13 µl/sec and 156.06 ± 13.72 µl/sec at 2, 3 and 4 psi, respectively. By experimenting with different pressures in the RMM, we found 12 psi to be the minimum for proper BSS injection and 2 psi for air. These findings provide crucial parameters for safer surgery to prevent irreversible damage.

Abstract Purpose This study aimed to develop a novel model that combines both clinical and image-based parameters to predict early recovery of urinary incontinence after robotic-assisted radical prostatectomy (RARP) more easily and precisely. Materials and methods We retrospectively enrolled data from patients who underwent RARP performed by a single surgeon. Clinical parameters were collected through medical chart review. All patients received cystography one week after RARP to evaluate the anastomosis healing condition. All cystography images were analyzed by a single radiologist who was blinded to the clinical status of the patients. Multivariate analysis was performed to select significant predictors for early post-prostatectomy incontinence (PPI) recovery, defined as being pad-free within four weeks after surgery. Results A total of 293 patients were enrolled in this study. Among them, 26.7% experienced immediate dryness after surgery, while 47.6% achieved being pad-free within one month. The overall continence rate was over 90% six months after surgery. In univariate analysis, factors associated with early PPI recovery were BMI, T stage, NVB preservation, surgical margin status, downward bladder neck, and bladder neck angle on cystography. BMI, NVB preservation, and downward bladder neck remained significant in multivariate analysis (p-values = 0.041, 0.027, and 0.023, respectively). A nomogram model was established based on these three predictors. Conclusion This is the first model to combine preoperative clinical factors, peri-surgical factors, and postoperative image-based factors to predict PPI recovery after RARP. This model can assist clinicians in taking optimal actions for PPI and also reduce patient anxiety.

Abstract Charge density waves (CDWs) are pervasive orders in solids that usually enhance the effective mass (m*) and reduce the Fermi velocity ( $${v}_{{{{\rm{F}}}}}$$ v F ) of carriers. Here, we report on the inverse — a reduced m* and an enhanced $${v}_{{{{\rm{F}}}}}$$ v F correlated with the growth of the CDW order in CuTe with gapped, practically linearly dispersing bands — reminiscent of emergent CDW-gapped topological semimetals. Using momentum-dependent electron energy-loss spectroscopy (q-EELS), we simultaneously capture m* and $${v}_{{{{\rm{F}}}}}$$ v F of the CDW-related, practically linearly dispersing electrons by plasmon dispersions across the transition (335 K, TCDW), with m* of 0.28 m0 (m0, the electron rest mass) and $${v}_{{{{\rm{F}}}}}$$ v F of ~ 0.005c (c, the speed of light) at 300 K. With the growth of the CDW order-parameter strength toward 100 K, the electrons become lighter and move faster by ~ 20%. Thorough inspection below TCDW unveils the essential role of the increasing opening of the CDW gap. CuTe is a rich platform for the exploration of CDW/correlation physics with q-EELS established as a useful probe for this type of physics.

Abstract Background Motor-sparing local infiltration analgesia (LIA) enhances recovery after total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, LIA can induce local anesthetic systemic toxicity (LAST), sometimes necessitating rescue lipid emulsion therapy. Our institute initiated a pilot study to pretreat patients with lipid emulsion (SMOFlipid®) to test its efficacy in mitigating LIA-induced LAST events. Methods This retrospective study enrolled 1,621 adult patients who received LIA with bupivacaine (2–3 mg/kg, maximum 300 mg) for unilateral primary THA or TKA under general anesthesia between January 2020 and April 2022. A total of 439 patients received lipid pretreatment, while 1,182 did not. Demographics, surgical and anesthesia profiles, along with LAST events affecting the neurological, cardiovascular, and respiratory systems, were compared after propensity score matching for age, sex, body mass index (BMI), and surgery type. Results The incidence of severe LAST events requiring rescue lipid emulsion slightly decreased after lipid pretreatment (from 2.54 to 2.28 per 1000). Lipid pretreatment significantly reduced the incidence of bradycardia and new-onset arrhythmia (odds ratio: 0.13, adjusted p-value: 0.024) but increased postoperative opioid requirement (odds ratio: 1.71, adjusted p-value: 0.032) after Benjamini-Hochberg correction for multiplicity. Conclusions The efficacy of lipid pretreatment (SMOFlipid® 1.5 ml/kg, maximum 100 ml) in mitigating LIA-induced LAST remains controversial. While lipid pretreatment reduced the incidence of new-onset arrhythmia, it showed no clear benefits for neurologic and respiratory outcomes. Additionally, lipid pretreatment might hinder postoperative recovery by increasing the need for rescue opioid analgesia. Further prospective pharmacokinetic studies are required to assess plasma bupivacaine concentrations following LIA and lipid pretreatment, examine their relationship to LAST events, and establish the efficacy and safety of lipid pretreatment.

Abstract In the post-pandemic world, open educational resources (OER) have the potential to ensure educational equity by providing all students with access to learning materials and by supporting teachers’ instructional practices through readily available, adaptable resources. However, the quality of OER continues to be a concern. Therefore, this study explored the use of (1) GeoGebra and scaffolding strategies to develop OER for secondary school mathematics teaching and (2) formative evaluation techniques to enhance the quality of the OER. A GeoGebra expert and a total of 40 frontline teachers participated in three review cycles of the OER development in the project. The feedback from each cycle informed the application of scaffolding strategies in the development of OER for the subsequent cycles. In Cycles 2 and 3, teachers rated the OER and provided feedback through surveys for further improvement. The results indicated that teacher ratings were significantly higher in Cycle 3 (n = 40, Mdn = 5) than in the previous cycle (n = 21, Mdn = 4) regarding the appropriateness of the OER for students with different learning preferences, z = − 2.87, p

Objective: An elevated risk of acute type B aortic dissection exists in patients with Marfan syndrome after the David procedure. This study explores hemodynamic changes in the descending aorta postsurgery. Methods: A single-center retrospective review identified 5 patients with Marfan syndrome who experienced acute type B aortic dissection within 6 years after the David procedure, alongside 5 matched patients with Marfan syndrome without dissection more than 6 years postsurgery. Baseline and postoperative computed tomography and magnetic resonance scans were analyzed for aortic geometry reconstruction. Computational fluid dynamic simulations evaluated preoperative and postoperative hemodynamics. Results: Patients with acute type B aortic dissection showed lower blood flow velocities, increased vortices, and altered velocity profiles in the proximal descending aorta compared with controls. Preoperatively, median time-averaged wall shear stress in the descending aorta was lower in patients with acute type B aortic dissection (control: 1.76 [1.50-2.83] Pa, dissection: 1.16 [1.06-1.30] Pa, P = .047). Postsurgery, neither group had significant time-averaged wall shear stress changes (dissection: P = .69, control: P = .53). Localized analysis revealed surgery-induced time-averaged wall shear stress increases near the subclavian artery in the dissection group (range, +0.30 to +1.05 Pa, each comparison, P

Most cases of high blood pressure have no identifiable cause, termed essential hypertension; however, in approximately 15% of cases, hypertension occurs due to secondary causes. Primary aldosteronism (PA) and pheochromocytoma and paraganglioma (PPGL) are representative endocrine hypertensive diseases. The differentiation of endocrine hypertension provides an opportunity to cure and prevent target organ damage. PA is the most common cause of secondary hypertension, which significantly increases the risk of cardiovascular disease compared to essential hypertension; thus, patients with clinical manifestations suggestive of secondary hypertension should be screened for PA. PPGL are rare but can be fatal when misdiagnosed. PPGL are the most common hereditary endocrine tumors; therefore, genetic testing using next-generation sequencing panels is recommended. Herein, we aimed to summarize the characteristic clinical symptoms of PA and PPGL and when and how diagnostic tests and treatment strategies should be performed.

Plexiform schwannomas representing a rare subset, comprise 5% of all schwannomas. However, their occurrence in the thyroid gland is exceptionally rare. A 32-year-old male presented with an incidentally discovered, asymptomatic thyroid mass. Imaging revealed an approximately 5 cm heterogeneous solid mass on the right thyroid lobe extending to the upper mediastinum and directly invading the upper trachea. Under the suspicion of thyroid malignancy, the patient underwent right thyroidectomy. Histological examination confirmed a plexiform schwannoma with S100-positive spindle cells. Currently, the patient is undergoing outpatient follow-up, with no reported complications. To our knowledge, this is the first documented case of plexiform schwannoma of the thyroid gland within the English literature. This case highlights the diverse and unpredictable clinical manifestations of thyroid masses, emphasizing the importance of a multidisciplinary approach for diagnosing and managing rare entities, such as thyroid gland schwannomas.

Background: Valve-sparing root replacement (VSRR) requires a unique skill set. This study aimed to examine the influence of surgeon's procedural volume on outcomes of VSRR. Methods: This retrospective study included 1697 patients from 2 large, high-volume aortic centers who underwent aortic root replacement (ARR) between 2004 and 2021 and were potentially eligible for VSRR. Surgeons were classified as performing

Background We explored the utility of a small multi-gene DNA panel for assessing molecular profiles of thyroid nodules and influencing clinical decisions by comparing outcomes between tested and untested nodules. Methods Between April 2022 and May 2023, we prospectively performed fine-needle aspiration (FNA) with gene testing via DNA panel of 11 genes (BRAF, RAS [NRAS, HRAS, KRAS], EZH1, DICER1, EIF1AX, PTEN, TP53, PIK3CA, TERT promoter) in 278 consecutive nodules (panel group). Propensity score-matching (1:1) was performed with 475 nodules that consecutively underwent FNA without gene testing between January 2021 and December 2021 (control group). Results In the panel group, positive call rate for mutations was 41.7% (BRAF 16.2%, RAS 12.6%, others 11.5%, double mutation 1.4%) for all nodules, and 40.0% (BRAF 4.3%, RAS 19.1%, others 15.7%, double mutation 0.9%) for indeterminate nodules. Benign call rate was 69.8% for all nodules, and 75.7% for indeterminate nodules. In four nodules, additional TP53 (in addition to BRAF or EZH1) or PIK3CA (in addition to BRAF or TERT) mutations were co-detected. Sensitivity, specificity, positive predictive value, and negative predictive value were 80.0%, 53.3%, 88.1%, 38.1% for all nodules, and 78.6%, 45.5%, 64.7%, 62.5% for indeterminate nodules, respectively. Panel group exhibited lower surgical resection rates than the control group for all nodules (27.0% vs. 52.5%, P

Background We examined the impact of gout on the end-stage renal disease (ESRD) risk in patients with type 2 diabetes mellitus (T2DM) and determined whether this association differs according to chronic kidney disease (CKD) status. Methods Using the Korean National Health Insurance Service, this nationwide cohort study enrolled 847,884 patients with T2DM who underwent health checkups in 2009. Based on the presence of CKD (estimated glomerular filtration rate

Non-Down syndrome pediatric acute megakaryoblastic leukemia (AMKL) may be classified according to the presence of recurrent genetic abnormalities with prognostic relevance. In this case study, we report on a girl with AMKL, 32 months old at the time of diagnosis, in whom we confirmed the presence of the cryptic, poor prognosis NUP98::KDM5A fusion. The patient achieved complete remission (CR) with the first course of chemotherapy, underwent haploidentical family donor hematopoietic stem cell transplantation (HSCT) without event, but relapsed 5 months after HSCT. Through this case report, we emphasize the good initial response to chemotherapy, and the early relapse despite undergoing HSCT in first CR. We review the limited literature on NUP98::KDM5A (+) pediatric AML, and underscore the need for further study to improve the outcome of patients with this rare AML subtype.

Abstract Purpose To compare long-term intraocular lens (IOL) decentration and tilt following femtosecond laser-assisted cataract surgery (FLACS) and conventional surgery using swept-source anterior segment ocular coherence tomography (SS-ASOCT). Methods In this retrospective cross-sectional study, all patients underwent FLACS or conventional cataract surgery. Those with a minimum of 12-months follow-up since surgery were included. Patients with surgical complications were excluded. Demographics, preoperative ocular measurements (axial length, anterior chamber depth), and postoperative measurements [corrected distance visual acuity (CDVA), autorefraction, keratometry, IOL type] were collected. Postoperative IOL tilt and decentration were compared using SS-ASOCT between patients with FLACS and conventional cataract surgery. Subgroup analysis was conducted to analyze tilt and decentration by haptic type (single-piece vs. three-piece). Results A total of 188 eyes were included [110 (58.5%) in the FLACS group and 78 (41.5%) in the conventional group]. No differences were observed between the FLACS and conventional groups regarding preoperative parameters. FLACS resulted in less IOL decentration compared to conventional cataract surgery (170 μm vs. 240 μm, p = 0.002). No statistically significant differences were observed between the FLACS and conventional groups in the magnitude and axis of IOL tilt. Both groups had a trend of IOL tilt toward the inferotemporal aspects. Moreover, no difference regarding postoperative CDVA, spherical equivalent, and keratometric astigmatism was observed. Conclusions FLACS resulted in significantly better long-term IOL centration than conventional surgery with manual capsulotomy. No significant difference in IOL tilt or postoperative CDVA was observed between FLACS and conventional cataract surgery.

Abstract Dynamic contrast-enhanced MRI (DCE-MRI) is increasingly used to non-invasively image blood-brain barrier leakage, yet its clinical utility has been hampered by issues such as noise and partial volume artifacts. In this retrospective study involving 306 adult patients with diffuse glioma, we applied deep learning-based super-resolution and denoising (DLSD) techniques to enhance the signal-to-noise ratio (SNR) and resolution of DCE-MRI. Quantitative analysis comparing standard DCE-MRI (std-DCE) and DL-enhanced DCE-MRI (DL-DCE) revealed that DL-DCE achieved significantly higher SNR and contrast-to-noise ratio (CNR) compared to std-DCE (SNR, 52.09 vs 27.21; CNR, 9.40 vs 4.71; P < 0.001 for all). Diagnostic performance assessed by the area under the receiver operating characteristic curve (AUROC) showed improved differentiation of WHO grades based on a pharmacokinetic parameter $$\hbox {V}_{{e}}$$ (AUC, 0.88 vs 0.83, P = 0.02), while remaining comparable to std-DCE in other parameters. Analysis of arterial input function (AIF) reliability demonstrated that $$\hbox {AIF}_{{DL}}$$ exhibited superior agreement compared to $$\hbox {AIF}_{{std}}$$ , as indicated by mostly higher intraclass correlation coefficients (Time to peak, 0.79 vs 0.43, P < 0.001). In conclusion, DLSD significantly enhances both the image quality and reliability of DCE-MRI in patients with diffuse glioma, while maintaining or improving diagnostic performance.

Abstract Although several studies have demonstrated the cardiovascular (CV) implication of hypoalbuminemia and arterial calcification among hemodialysis patients, little is known regarding their cardiac correlates and relevant CV outcomes in asymptomatic individuals. We assessed the potential CV interrelation between serum albumin (SA) and aortic calcification. Among 2,723 asymptomatic individuals underwent cardiovascular health check-up, we assessed serum albumin (SA) level, thoracic aortic calcification (TAC) and coronary artery calcification (CAC) by multi-detector computed tomography, and ultrasound-determined carotid plaque burden. We related these measures to cardiac structure/function and CV outcomes. Lower SA level was associated with higher TAC score and volume rather than carotid plaque or coronary calcification burden in fully adjusted models. By categorizing the study population into 4 groups by SA (>, ≤ 4.6 mg/dL) and presence of TAC, subjects classified into low SA/TAC(+) category were oldest with highest prevalent CV disease. Both lower SA and TAC(+) were independently associated with impaired myocardial systolic/diastolic mechanics and higher CV events during a median of 6.6 years (IQR: 5.1, 6.8 years) follow-up. Participants classified into low SA/TAC(+) category showed highest risk for CV events (adjusted HR: 3.78 [95% CI: 2.11, 6.77], high SA/TAC[-] as reference) in fully adjusted Cox model. Among symptom-free individuals, TAC was closely associated with low SA concentration in relation to unfavorable cardiac mechanics and may serve as a useful prognosticator for adverse CV events.

Abstract Colon polyp detection and removal via colonoscopy are essential for colorectal cancer screening and prevention. This study aimed to develop a colon polyp detection program based on the RetinaNet algorithm and verify its clinical utility. To develop the AI-assisted program, the dataset was fully anonymized and divided into 10 folds for 10-fold cross-validation. Each fold consisted of 9,639 training images and 1,070 validation images. Video data from 56 patients were used for model training, and transfer learning was performed using the developed still image-based model. The final model was developed as a real-time polyp-detection program for endoscopy. To evaluate the model’s performance, a prospective randomized controlled trial was conducted at six institutions to compare the polyp detection rates (PDR). A total of 805 patients were included. The group that utilized the AI model showed significantly higher PDR and adenoma detection rate (ADR) than the group that underwent colonoscopy without AI assistance. Multivariate analysis revealed an OR of 1.50 for cases where polyps were detected. The AI-assisted polyp-detection program is clinically beneficial for detecting polyps during colonoscopy. By utilizing this AI-assisted program, clinicians can improve adenoma detection rates, ultimately leading to enhanced cancer prevention.

Abstract NO previous studies have examined the simultaneous effects of obstructive sleep apnea (OSA), hypertension, and the SNP rs68430822 on stroke. We aimed to explore whether these elements together, play a role as risk factors for stroke. Data was obtained from the Taiwan Biobank and the National Health Insurance database. We used logistic regression analysis to investigate the effect of OSA and hypertension as a risk factor for stroke in different genotypes. We found that OSA and hypertension was associated with stroke in those with the rs6843082 genotype. People with OSA and hypertension together with the rs6843082 genotype (GA + AA) showed a statistically significant difference as a risk for stroke (OR,2.57; 95% CI,1.53 to 4.33). However, there was no statistically significant difference in those people with OSA but without hypertension (OR, 0.53; 95% CI,0.13 to 2.25). After further stratification by combination of OSA and hypertension, those with genotype rs6843082 (GG) had higher risk odds than those with OSA and those with hypertension alone (OR,5.46, 95% CI,3.46 to 8.60). Individuals with genotype rs6843082(GA + AA), OSA and hypertension together had the highest risk for stroke (OR,6.25, 95% CI,3.63 to 10.76) and those with OSA and no hypertension (OR,0.57, 95% CI,0.14 to 2.36) had no significant risk. Our findings showed that people with genotype rs6843082 (GG), with or without hypertension had OSA as a risk factor for stroke. For individuals with the genotype rs6843082 (GA + AA), those with hypertension, OSA is a risk factor for stroke, and for those without hypertension, OSA is not associated with stroke.

Abstract The high mutation rate of RNA viruses provides viral populations with the ability to adapt to new environments but also makes them vulnerable to extinction due to the deleterious effects of mutations, which is the conceptual basis for the antiviral activity of RNA mutagens. However, there are still gaps in the quantitative understanding of the dynamics between the mutations induced by an RNA mutagen and its effects on viral fitness. To address this, we used Venezuelan Equine Encephalitis Virus (VEEV) and the potent RNA mutagen β-d-N4-hydroxycytidine (NHC) as a model to analyze virus replication competency and mutation frequency following treatment in the total and replication-competent viral populations separately. We found that NHC induced transition mutations in a concentration dependent manner in the total population, while the replication-competent population maintained itself within an increased, yet narrow, mutation spectrum. The incorporation of NHC mainly happened during the positive sense RNA synthesis of VEEV. A growth kinetic analysis of VEEV population treated with NHC pointed to a lower but more diverse distribution in mutational fitness, demonstrating that NHC-induced mutations negatively and broadly affect the fitness of the virus. Together, our study provides mechanistic insight into how RNA mutagens affect viral population landscape and the potential of RNA mutagens as an antiviral strategy for alphaviruses.

Abstract Connexin 36 (Cx36) forms interneuronal gap junctions, establishing electrical synapses for rapid synaptic transmission. In disease conditions, inhibiting Cx36 gap junction channels (GJCs) is beneficial, as it prevents abnormal synchronous neuronal firing and apoptotic signal propagation, mitigating seizures and progressive cell death. Here, we present cryo-electron microscopy structures of human Cx36 GJC in complex with known channel inhibitors, such as mefloquine, arachidonic acid, and 1-hexanol. Notably, these inhibitors competitively bind to the binding pocket of the N-terminal helices (NTH), inducing a conformational shift from the pore-lining NTH (PLN) state to the flexible NTH (FN) state. This leads to the obstruction of the channel pore by flat double-layer densities of lipids. These studies elucidate the molecular mechanisms of how Cx36 GJC can be modulated by inhibitors, providing valuable insights into potential therapeutic applications.

Abstract Background The increasing trend of patients with mental health conditions seeking emergency care is a global phenomenon. Numerous studies have emphasized the importance of emergency physicians' ability to recognize and manage psychiatric emergencies, both for patient well-being and societal safety nets. With the growing demand for emergency care related to mental health conditions, it is crucial to assess whether emergency physicians possess sufficient confidence and capabilities to adapt to these changes. Against this backdrop, our study aimed to explore the factors influencing emergency physicians' management of acute psychiatric emergencies and to critically evaluate whether current training programs adequately align with societal expectations for psychiatric emergency care. Methods A cross-sectional survey, disseminated online by the Taiwan Society of Emergency Medicine, targeted 936 attending physicians and 449 residents in 43 Resident Review Committee approved training hospitals in winter 2021. The questionnaire covered participant demographics, skill requirements, and confidence in managing acute psychiatric patients independently. Statistical analyses included descriptive statistics, chi-square tests, medians (IQRs), and Wilcoxon rank-sum tests. Results Out of 229 participants, 63.8% were attending physicians, and 81.7% were affiliated with medical centers. Psychiatrists led 69.9% of emergency psychiatric training curricula, and 66.8% reported that their clinical psychiatric training outcomes were assessed by psychiatrists. Clinical seniority, training hospital level, and the average number of patients with an acute psychiatric presentation seen in a daily shift influenced physicians' self-reported confidence in managing acute psychiatric patients independently. Medical center training improved capability in managing psychiatric emergencies in the elderly, while encountering a higher average number of patients with an acute psychiatric presentation seen in a daily EM shift was associated with better performance, especially in managing specific populations. Conclusions Our nationwide study highlights how clinical seniority, training hospital level, and patient volume per shift influence emergency physicians' confidence in managing acute psychiatric patients. However, there remains room for improvement, particularly in addressing the needs of specific patient populations. These findings underscore the importance of refining training curricula to bridge these gaps and enhance the quality of psychiatric emergency patient care.

Abstract Background There is a lack of evidence of the diagnosis and treatment-related epidemiological studies of symptomatic discoid meniscus. This study analyzed the national epidemiological data for discoid meniscus in South Korea. Methods From 2011 to 2019, data related to the diagnosis and procedure codes of discoid meniscus were obtained from the Korean Health Insurance Review and Assessment Service database. All patients encoded as discoid meniscus were included. Data were extracted and further analyzed as follows: (1) the total number and the incidence (cases per 100,000) of discoid meniscus diagnosis per year, (2) sex distribution, (3) age distribution, (4) discoid meniscus ratio (total discoid meniscus coding per total meniscus injury coding), and (5) surgical procedures after discoid meniscus injury. Results The total number of discoid meniscus diagnosed was 4576 in 2011 and increased to 6639 in 2019, representing a 45.1% increase. The incidence was 9.5 in 2011 and increased to 13.0 in 2019. Concerning sex, discoid meniscus was more common in females (55%) than in males (45%) over the study period. Regarding age, the peak age of discoid meniscus in 2011 was “under 19,” whereas in 2019, the peak age was observed in the 50s. The discoid meniscus ratio range was 2.12–2.60% from 2011 to 2019. The total number of meniscectomy increased by 20% from 2000 in 2011 to 2475 in 2014. However, the total number of meniscus repairs was 318 in 2011 and increased to 502 in 2019, indicating an increase of 58%. Conclusions The total number and incidence of symptomatic discoid as well as the discoid meniscus ratio and the incidence of total discoid meniscus repair steadily increased from 2011 to 2019. The number of meniscus repair procedures increased more rapidly than that of meniscectomy. The current study helps understand the epidemiology of symptomatic discoid meniscus, its prevention, and cost-saving measures in South Korea.

Abstract In South Korea, the snowy season spans from October to April, and the annual average snowfall varies significantly depending on specific regions, latitudes, and elevations, ranging from 0 to 260 cm. The average annual snowfall in South Korea is 25.1 cm. Despite of the relatively shallow snowfall depth, over the past decade, South Korea has experienced approximately 120 million dollars in damages attributed to snow-related incidents. In this study, the DPSIR (Driver-Pressure-State-Impact-Response) framework was employed to consider the meteorological and socioeconomic factors to calculate the snow damage vulnerability. A total of 17 indicators were taken into account to comprehend meteorological conditions, socioeconomic factors, and historical damage records from 1994 to 2020. However, due to the limited availability of meteorological observatories and changes in greenhouse design standards, accurately estimating the snow damage amount poses challenges. Therefore, based on the vulnerability, the risk levels were classified into four categories and estimated snow damage generated by the categorized models was compared with those of the model constructed using the entire dataset. The categorized models offer improved estimation results, as the meteorological and socioeconomic characteristics within each category differ and should be addressed separately in modeling. Among the categorized models, the Green zone exhibited the best results, primarily because it did not include outlier snow damage incidents. The developed model in this study could be utilized to mitigate the impact of heavy snowfall and prioritize snow removal regions.

Abstract Background Arginine deprivation was previously shown to inhibit retinoblastoma cell proliferation and induce cell death in vitro. However, the mechanisms by which retinoblastoma cells respond to arginine deprivation remain to be elucidated. Methods The human-derived retinoblastoma cell lines Y79 and WERI-Rb-1 were subjected to arginine depletion, and the effects on inhibiting cell growth and survival were evaluated. This study investigated potential mechanisms, including autophagy, cell cycle arrest and apoptosis. Moreover, the roles of the general control nonderepressible 2 (GCN2) and mechanistic target of rapamycin complex 1 (mTORC1) signaling pathways in these processes were examined. Results We demonstrated that arginine deprivation effectively inhibited the growth of retinoblastoma cells in vitro. This treatment caused an increase in the autophagic response. Additionally, prolonged arginine deprivation induced G2 cell cycle arrest and was accompanied by an increase in early apoptotic cells. Importantly, arginine depletion also induced the activation of GCN2 and the inhibition of mTOR signaling. We also discovered that the activation of SLC7A11 was regulated by GCN2 upon arginine deprivation. Knockdown of SLC7A11 rendered retinoblastoma cells partially resistant to arginine deprivation. Furthermore, we found that knockdown of GCN2 led to a decrease in the autophagic response in WERI-Rb-1 cells and arrested more cells in S phase, which was accompanied by fewer apoptotic cells. Moreover, knockdown of GCN2 induced the constant expression of ATF4 and the phosphorylation of 70S6K and 4E-BP1 regardless of arginine deprivation. Conclusions Collectively, our findings suggest that the GCN2‒SLC7A11 axis regulates cell growth and survival upon arginine deprivation through coordinating autophagy, cell cycle arrest, and apoptosis in retinoblastoma cells. This work paves the way for the development of a novel treatment for retinoblastoma.

Abstract Background This study aims to assess the joint and independent effects of self-reported physical activity and sedentary behavior on mortality in older persons. Methods A prospective community-based cohort study was conducted to examine physical activity (PA) level and sitting time (ST) in relation to mortality among 1,786 older persons aged 65 years and above. PA was assessed by a checklist of 26 self-reported items about PA and hours per week, and the metabolic equivalent hours/week was derived, and ST was measured by a self-reported item asking the average number of hours spent sitting per day. The participants were divided into four combination groups of PA and ST based on WHO guideline and values found in literature: high PA/short ST group, high PA/long ST group, low PA/long ST group, and low PA/short ST group. Data on death ascertainment were obtained through linkage with the national death datasets and expanded cardiovascular disease (CVD) included cardiovascular disease, diabetes, and chronic kidney disease. Results After follow-up for a median 11.1 years, 599 mortality cases were recorded, giving a crude all-cause mortality of 32.5/1,000 person-years, CVD mortality of 8.6/1,000 person-years, expanded CVD mortality of 11.9/1,000 person-years, and nonexpanded CVD mortality of 20.8/1,000 person-years. For all-cause, and expanded CVD, the hazards ratios (HRs) for the low PA/long ST group remained significant compared with that for the high PA/short ST group after all covariates were considered [HRs for all-cause mortality: 1.4 [95% confidence interval (CI) 1.1, 1.8]; and expanded CVD mortality: 1.7 (95% CI 1.1, 2.4). Conclusions The independent effect of PA and the joint effects of PA and ST are associated with all-cause and expanded CVD death risks. Expanded CVD mortality may be minimized by engaging in PA and reducing sedentary behaviors.

Abstract Background To evaluate the feasibility and safety of the superficial circumflex iliac perforator flap (SCIP) for maxillary reconstruction with intraoral anastomosis, pedicle elongation, and super-microsurgery techniques to overcome its anatomical shortcomings due to the attractive merits of the flap. Methods Patients who underwent reconstruction of maxillary defects with SCIPs from July 2020 to December 2022 were included. Intraoral anastomosis, pedicle elongation, and super-microsurgery were performed during surgery with or without a neck incision. The sizes, pedicle lengths, inner calibres of vessels, complications and flap survival statuses were recorded. Results A total of 12 patients were included, with 3 males and 9 females, and the median age was 45 years, ranging from 14 to 74 years. There were 5 class IIa and 7 class IIb defects, 6 cases underwent maxillary defect reconstruction via SCIPs with intraoral anastomosis, and the other 6 cases with distally design and/or de-epidermis pedicle elongation. Super-microsurgery interventions were needed in 5 patients. The size ranged from 3 cm×4 cm to 6 cm×8 cm. The pedicle length ranged from 4 cm to 12 cm, with a median of 6 cm. The inner caliber of the arteries ranged from 0.7 mm to 2 mm, with a median of 1 mm, and the veins ranged from 1.5 mm to 4 mm, with a median of 2.5 mm. All the flaps survived, and no donor site complications occurred. Conclusion Superficial circumflex iliac perforator flaps can be regarded as feasible and safe choices for maxillary defects with the support of intraoral anastomosis, pedicle elongation and super-microsurgery.

Abstract Background Checkpoint immunotherapy unleashes tumor control by T cells, but it is undermined in non-immunogenic tumors, e.g. with low MHC class I expression and low neoantigen burden, such as neuroblastoma (NB). Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an enzyme that trims peptides before loading on MHC class I molecules. Inhibition of ERAP1 results in the generation of new antigens able of inducing potent anti-tumor immune responses. Here, we identify a novel non-toxic combinatorial strategy based on genetic inhibition of ERAP1 and administration of the HDAC inhibitor (HDACi) entinostat that increase the immunogenicity of NB, making it responsive to PD-1 therapy. Methods CRISPR/Cas9-mediated gene editing was used to knockout (KO) the ERAP1 gene in 9464D NB cells derived from spontaneous tumors of TH-MYCN transgenic mice. The expression of MHC class I and PD-L1 was evaluated by flow cytometry (FC). The immunopeptidome of these cells was studied by mass spectrometry. Cocultures of splenocytes derived from 9464D bearing mice and tumor cells allowed the assessment of the effect of ERAP1 inhibition on the secretion of inflammatory cytokines and activation and migration of immune cells towards ERAP1 KO cells by FC. Tumor cell killing was evaluated by Caspase 3/7 assay and flow cytometry analysis. The effect of ERAP1 inhibition on the immune content of tumors was analyzed by FC, immunohistochemistry and multiple immunofluorescence. Results We found that inhibition of ERAP1 makes 9464D cells more susceptible to immune cell-mediated killing by increasing both the recall and activation of CD4+ and CD8+ T cells and NK cells. Treatment with entinostat induces the expression of MHC class I and PD-L1 molecules in 9464D both in vitro and in vivo. This results in pronounced changes in the immunopeptidome induced by ERAP1 inhibition, but also restrains the growth of ERAP1 KO tumors in vivo by remodelling the tumor-infiltrating T-cell compartment. Interestingly, the absence of ERAP1 in combination with entinostat and PD-1 blockade overcomes resistance to PD-1 immunotherapy and increases host survival. Conclusions These findings demonstrate that ERAP1 inhibition combined with HDACi entinostat treatment and PD-1 blockade remodels the immune landscape of a non-immunogenic tumor such as NB, making it responsive to checkpoint immunotherapy.

Background: The calcaneal enthesis, an osseous footprint where the Achilles tendon seamlessly integrates with the bone, represents a complex interface crucial for effective force transmission. Bone adapts to mechanical stress and remodels based on the applied internal and external forces. This study explores the relationship between the elasticity of the Achilles tendon enthesis and the bone microstructure in the calcaneal crescent. Methods: In total, 19 calcaneal-enthesis sections, harvested from 10 fresh-frozen human cadaveric foot-ankle specimens (73.8 ± 6.0 years old, seven female), were used in this study. Indentation tests were performed at the enthesis region, and Hayes’ elastic modulus was calculated for each specimen. Micro-CT scanning was performed at 50-micron voxel size to assess trabecular bone microstructure within six regions of interest (ROIs) and the cortical bone thickness along the calcaneal crescent. Results: Significant Spearman correlations were observed between the enthesis elastic modulus and trabecular bone thickness in the distal entheseal (ROI 3) and proximal plantar (ROI 4) regions (R = 0.786 and 0.518, respectively). Conclusion: This study highlights the potential impacts of Achilles tendon enthesis on calcaneal bone microstructure, which was pronounced in the distal calcaneal enthesis, suggesting regional differences in load transfer mechanism that require further investigation.

Background. Hurdling is a dynamic and technically demanding sport within athletics. It requires a unique combination of speed, agility, coordination, and strength to support good technique and achievement. The ability to excel in this sport depends on the athlete’s mastery of these components, making it an interesting subject for sports science research. Objectives. This study aimed to evaluate existing research on sports biomechanics as it relates to improving hurdling performance. Materials and methods. The study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology of the relevant literature. A total of 15 articles published between 1990 and 2023 were identified as relevant to the focus of the study and selected for in-depth analysis. Results. The findings showed that sports biomechanics research in hurdling training has mainly concentrated on the following key areas: kinematics analysis, the application of technology, and the potential injury studies. Although significant progress has been made in understanding the biomechanics of hurdling training, this study suggests the need for further and more comprehensive research. The research mentioned should delve deeper into the biomechanical factors influencing performance in order to develop optimal training methods and injury prevention strategies. Conclusions. This review underscores the importance of continued research in this area, as it has the potential to enhance training approaches and improve athletic performance in hurdling.

Abstract Cytomegalovirus (CMV) commonly infects immunocompromised individuals, such as cancer patients. We present a case involving a 60‐year‐old male with Stage 3A lung adenocarcinoma and chronic obstructive pulmonary disease (COPD) diagnosed with CMV tracheobronchitis, initially suspected as cancer progression. Treatment with ganciclovir led to partial improvement in symptoms of shortness of breath and cough, as well as bronchoscopic findings. However, due to ganciclovir‐induced neutropenia, the therapy was switched to foscarnet. Distinguishing between cancer progression and infectious tracheobronchitis through physical examination and chest CT scans remains challenging. In lung cancer patients presenting with airway and bronchial narrowing along with ulcerative mucosal lesions, CMV infection should be considered. A bronchoscopic biopsy is crucial for accurate diagnosis and determining the appropriate treatment in these patients.