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Abstract DEAD-box RNA helicase 3 (DDX3) and its homologs play a vital role in translation initiation by unwinding secondary structures of selected mRNAs. The human DDX3 gene is located on the sex chromosomes, so there are DDX3X and DDX3Y. DDX3X is ubiquitously expressed in almost all tissues and critical for embryonic development, whereas DDX3Y is only expressed in the testis and essential for male fertility. Drosophila belle (bel) is the single ortholog of DDX3, and mutations in bel cause male and female infertility. Using Drosophila bel mutants and Ddx3x conditional knockout (cKO) mice, we confirmed the pivotal role of DDX3 in female fertility and ovarian development. Drosophila bel mutants exhibited female infertility and immature egg chambers. Consistently, oocyte-specific Ddx3x knockout in mice resulted in female infertility and impaired oogenesis. We further found that immature egg chambers in Drosophila bel mutants and impaired follicular development in oocyte-specific Ddx3x cKO mice were caused by excessive apoptosis. We also identified a set of DDX3 target genes involved in oocyte meiosis and maturation and demonstrated that DDX3 is involved in their translation in human cells. Our results suggest that DDX3 is critical for female fertility via translational control in oogenesis.

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 The microvascular free fibula (MFF) flap is a reliable treatment modality for mandibular reconstruction and is suitable for dental implant placement after oncologic surgery. The most common issue with the MFF flap is its limited bone height, which typically results in excessive interarch space and complicates prosthodontic therapy. Overcoming the physical limitations from tumor excision and reducing the treatment time for prosthodontic rehabilitation to improve quality of life are critical clinical challenges. Case Presentation A 64-year-old male with lower left gum and bilateral buccal cancer received a single-layer microvascular MFF flap to reconstruct a mandibular defect post-tumor excision. He underwent a bilateral modiolus Z-plasty combined with a skin flap debulking procedure to relieve oral contracture, achieving adequate mouth opening for prosthodontic rehabilitation. Scar tissue bands on the bilateral cheeks significantly affected retention and stability, hampering dental impression performance. The patient sought prosthodontic rehabilitation to enhance his chewing function and quality of life promptly. Prosthodontic rehabilitation with all-on-4 implant therapy, utilizing computer-aided design and computer-assisted manufacturing (CAD/CAM), was completed within one month. Conclusion This case utilized the all-on-4 implant system to address the insufficient fibular height for conventional dental implant placements. Dental CAD/CAM was employed to mill custom prosthetic abutments and a large titanium framework for the implant bar overdenture, compensating for the excessive interarch space between the grafted fibula and maxilla. This treatment approach successfully shortened the prosthodontic rehabilitation time and overcame anatomical limitations.

Abstract The prognostic value of central pathology review in upper urinary tract cancer (UTUC) remains inadequately addressed in existing literature. In this study, we conducted an extensive central pathology review and presented its influence on multi-center UTUC studies. We conducted a retrospective review of patients who underwent radical nephroureterectomy or segmental resection for UTUC to determine eligibility for central pathology review. In the Taiwan UTUC Collaboration cohort, 377 cases met the criteria for pathology review. We assessed agreement between pathologists using both the total percentage of agreement and simple kappa statistics. The prognostic implications of original and review pathology for various parameters were examined using the Cox regression model. This study included 209 female and 168 male participants. Pathology review revealed substantial interobserver variability in pT staging, with a particularly high rate of pT2 cases being upgraded to pT3 upon central review (17/70 pT2 stage made by local pathologists were finally confirmed as pT3 disease by the review pathologist). The local pathologist cohort identified fewer significant histological predictors in survival models compared to the review pathology cohort. Advanced pT stage, perineural invasion (PNI), and positive surgical margin were independent predictors of poorer overall survival and cancer-specific survival. PNI, lymphatic vascular invasion, and positive surgical margin were independent predictors of disease recurrence. Substantial interobserver variability in histological assessment underscores the importance of centralized pathology review for both multi-center studies and accurate post-operative management of UTUC patients. Advanced stage, perineural invasion, and margin status were significant histological predictors of oncological outcomes.

Background: Congenital pseudoarthrosis of the tibia (CPT) is a rare pathological disease associated with neurofibromatosis type 1 (NF1). It presents with tibial bowing and can progress into a nonhealing fracture. Treatment options include conservative approaches such as serial bracing or various surgical options.Surgically, the aims are to achieve long-term bone union, prevent limb length discrepancies (LLDs), and avoid mechanical axis deviation, soft tissue lesions, nearby joint stiffness, and pathological fracture.The purpose of our study is to highlight our experience with both the conservative approach and the use of vascularized free fibula reconstruction of these deformities, including the challenges encountered with a long-term follow-up until skeletal maturity. Methods: We present a retrospective analysis of a total of nine (9) patients consisting of three (3) girls and six (6) boys. Six (6) children were treated with a vascularized fibula flap, and the other three (3) were treated conservatively. Outcomes measured included fractures, LLD, ankle valgus deformity, donor site morbidity, and number of surgical corrections. Results: All patients had flap survival. Three (3) of six children had a previous failed surgery with intramedullary nail and bone graft prior to performing a vascularized free fibula reconstruction. The follow-up period ranged from 8 months to 200 months. The complications included stress fractures (50%), LLD (66.6%), and ankle valgus (33.3%). During growth phases, these children required multiple corrective surgeries. Conclusions: Fibula free flap is a good treatment option for CPT even in patients with prior surgical failures with variable results.Level of Evidence - Level 4 - Case series Therapeutic Studies—Investigating the Results of Treatment.

Background: Advanced non-small-cell lung cancer (NSCLC) can be treated with novel targeted therapies that are tailored to the genetic characteristics of malignancy. While tissue-based genomic testing is considered the gold standard for the detection of oncogenic driver mutations, several challenges like inadequate tissue availability, the invasiveness of procuring tumors, and prolonged turnaround time of analysis are encountered. Considering these limitations, guidelines have recognized liquid biopsies using circulating cell-free DNA (cfDNA) as a useful tool to complement conventional tissue testing. Even though cfDNA next-generation sequencing (NGS) can have high sensitivity and specificity, optimal patient benefit requires the interpretation of the molecular profiling results in the context of clinical and diagnostic features to achieve the best outcomes. Case Descriptions: In this case series, we present six patients with advanced NSCLC whose plasma or tissue biopsy samples were analyzed with commercially available comprehensive NGS assays that elucidate the role of testing at various time points in the treatment journey. In all six cases, comprehensive genomic profiling (CGP) provided clinically useful information to guide treatment decisions. Conclusion: Adding to the existing real-world evidence, this case series reinforces that CGP-driven treatment strategies in advanced NSCLC, coupled with other available clinical information, can optimize treatment decisions.

Purpose:. According to the National Comprehensive Cancer Network guidelines, segmental ureterectomy (SU) of upper tract urothelial carcinoma (UTUC) is a considerable option for selected mid- and distal ureteral urothelial carcinoma (UC). As a UTUC endemic area, Taiwan lacks treatment outcome analysis of SU. Materials and methods:. This study retrospectively reviewed the treatment outcomes of SU for clinically localized UTUCs. Patients with biopsy or washing cytology-confirmed UTUCs who underwent open, laparoscopic, or robot-assisted management with curative intent were retrospectively reviewed for the eligibility of analysis. Cox regression was applied for univariable and multivariable analyses. Results:. A total of 161 patients who underwent SU were reviewed and analyzed. The median follow-up period was 44.5 (interquartile range, 21.6–84.9) months. After SU, 56/161 (34.8%) patients were free of UTUCs after the follow-up, 25/161 (15.5%) patients had local recurrence, and 35/161 (21.7%) had lymph node or distant metastasis. Surgical margin involvement was a risk factor associated with worse cancer-specific survival. Higher bladder recurrence and local recurrence rates were observed with concurrent bladder UC. Lymphovascular invasion and previous radical nephroureterectomy (RNU) for UC were related to higher local recurrence rates. Patients with pathological T3/T4 stage and end-stage renal disease tended to have higher metastasis rates. For the management of local recurrence, 19 patients received salvage RNU and 25 patients had adjuvant chemotherapy. However, 26/161 (16.1%) patients died of UTUCs and 2/161 (1.2%) patients died of surgery-related complications. Conclusion:. SU provides acceptable oncological outcomes if the surgeons select candidates carefully. SU is not recommended if the patient has T3 or higher stage or comorbidity of end-stage renal disease. Concurrent bladder UC is a risk factor for worse bladder recurrence-free survival and local recurrence-free survival. Lymphovascular invasion and previous RNU for UC were related to higher local recurrence rates. After SU, periodic follow-up is mandatory because the local recurrence rate is higher than radical surgery.

Abstract Background While surgery remains the primary treatment for oral squamous cell carcinoma (OCSCC), induction chemotherapy (IC) can be used as a bridging or neoadjuvant therapy. This nationwide study in Taiwan examines the survival outcomes of OCSCC patients who received IC before surgery. Methods We analyzed data from 29,891 patients with OCSCC. Of these, 29,058 initially underwent surgery (OP group), whereas 833 received IC before surgery (IC + OP group). A propensity score (PS)‐matched analysis (4, 1 ratio, 3260 vs. 815 patients) was performed considering tumor subsite, sex, age, Charlson comorbidity index, clinical T1–T4b tumors, clinical N0–3 disease, and clinical stage I–IV. Results In the PS‐matched cohort, the 5‐year disease‐specific survival (DSS) and overall survival (OS) rates were 65% and 57%, respectively. When comparing the OP and IC + OP groups, the 5‐year DSS rates were 66% and 62%, respectively (p = 0.1162). Additionally, the 5‐year OS rates were 57% and 56%, respectively (p = 0.9917). No significant intergroup differences in survival were observed for specific subgroups with cT4a tumors, cT4b tumors, cN3 disease, pT4b tumors, and pN3 disease. However, for patients with pT4a tumors, the OP group demonstrated superior 5‐year outcomes compared to the IC + OP group, with a DSS of 62% versus 52% (p = 0.0006) and an OS of 53% versus 44% (p = 0.0060). Notably, patients with cT2–3, cN1, and c‐Stage II disease in the IC + OP group were significantly more likely to achieve pT0–1 status (p

Abstract Background Elective tracheotomy is commonly performed in resected oral squamous cell carcinoma (OCSCC) to maintain airway patency. However, the indications for this procedure vary among surgeons. This nationwide study evaluated the impact of tracheotomy on both the duration of in‐hospital stay and long‐term survival outcomes in patients with OCSCC. Methods A total of 18,416 patients with OCSCC were included in the analysis, comprising 7981 patients who underwent elective tracheotomy and 10,435 who did not. The primary outcomes assessed were 5‐year disease‐specific survival (DSS) and overall survival (OS). To minimize potential confounding factors, a propensity score (PS)‐matched analysis was performed on 4301 patients from each group. The duration of hospital stay was not included as a variable in the PS‐matched analysis. Results Prior to PS matching, patients with tracheotomy had significantly lower 5‐year DSS and OS rates compared to those without (71% vs. 82%, p

Objective Open tibial fractures are frequently encountered in high‐energy traumas and can result in significant complications such as nonunion, osteomyelitis, and even amputation. Among open tibial fractures, Gustilo type IIIC cases are particularly challenging due to the concomitant occurrence of neurovascular injuries and soft tissue defects. This study aimed to assess factors that affect union time and complications in Gustilo IIIC tibial fractures. Methods Patients who presented at our center with IIIC open tibial fractures from January 2000 to October 2020 were eligible for this retrospective analysis. Patient demographics, fracture characteristics, and the timing, number, and type of surgical intervention were documented. Outcomes of interest included union time, occurrence of osteomyelitis, and amputation. We performed univariate analyses including chi‐squared test, Fischer's exact test, analysis of variance, and Kruskal–Wallis test based on the normality of the data and multivariate analyses including Cox proportional hazards model and logistic regression analyses. Results Fifty‐eight patients were enrolled and grouped by fracture healing time; eight had timely union (13.8%); 27 had late union (46.6%); eight had delayed union (13.8%); three had nonunion (5.2%); and 12 underwent amputation (20.7%). Nine fractures (15.5%) were complicated by osteomyelitis. Union time was prolonged in cases of triple arterial injury, distal third fractures, multiple trauma with injury severity score (ISS) ≥ 16 points, and increased bone defect length. Additionally, a bone gap >50 mm, diabetes mellitus, low body mass index, and triple arterial injury in the lower leg were significant risk factors for amputation. A time from injury to definitive soft tissue coverage of more than 22 days was the major risk factor for osteomyelitis. A scoring system to predict union time was devised and the predicted probability of union within 2 years was stratified based on this score. Conclusion IIIC tibial fractures involving the distal third of the tibia, fractures with bone defects, triple arterial injury, and multiple trauma with ISS ≥16 points demonstrated delayed union, and an effective prediction system for union time was introduced in this study. Early soft tissue coverage can reduce the risk of osteomyelitis. Finally, diabetes and severe bone and soft tissue defects pose a higher risk of amputation.

AbstractLaryngeal hemangiomas are benign tumors and are categorized into two types—infantile and adult. Adult-type vocal cord hemangiomas are very rare and uncommon in clinical practice. A 71-year-old man came to medical attention because of blood-tinged sputum and hoarseness for 1-month duration. Endoscopic examination revealed a well-demarcated vegetative lesion attached to the right vocal cord. The lesion was superficially located, and therefore amenable to complete surgical excision. Post-operation followed up showed improved symptoms and without evidence of local recurrence. Based on the histopathological features, a diagnosis of cavernous hemangioma of the vocal cord was rendered. Currently, there is no clear and unequivocal treatment and management modality in adult-type hemangioma, we reported a case with adult-type laryngeal hemangioma using cold instrument microlaryngoscopic excision technique with satisfied result.

Abstract Background To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1−2N0M0 oral cavity squamous cell carcinoma (OCSCC). Methods Between 2011 and 2019, we analyzed data for 13,542 cT1−2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well‐balanced study groups (initial surgery, n = 580; definitive RT, n = 145). Results Before PS matching, the 5‐year disease‐specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5‐year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5‐year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p

Abstract Background The current NCCN guidelines recommend considering elective neck dissection (END) for early‐stage oral cavity squamous cell carcinoma (OCSCC) with a depth of invasion (DOI) exceeding 3 mm. However, this DOI threshold, determined by evaluating the occult lymph node metastatic rate, lacks robust supporting evidence regarding its impact on patient outcomes. In this nationwide study, we sought to explore the specific indications for END in patients diagnosed with OCSCC at stage cT2N0M0, as defined by the AJCC Eighth Edition staging criteria. Methods We examined 4723 patients with cT2N0M0 OCSCC, of which 3744 underwent END and 979 were monitored through neck observation (NO). Results Patients who underwent END had better 5‐year outcomes compared to those in the NO group. The END group had higher rates of neck control (95% vs. 84%, p

Esophageal cancer ranks among the ten most common cancers worldwide. Despite the adoption of neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by surgery as the standard treatment approach in recent years, the local recurrence rate remains high. In this study, we employed RNA-seq to investigate distinctive gene expression profiles in esophageal squamous cell carcinoma (ESCC) with or without recurrence following a standard treatment course. Our findings indicate that recurrent ESCC exhibits heightened keratinizing and epidermis development activity compared to non-recurrent ESCC. We identified TP63 as a potential candidate for distinguishing clinical outcomes. Furthermore, immunohistochemistry confirmed the trend of TP63 overexpression in ESCC recurrence. Patients with elevated TP63 expression had poorer overall survival and lower 3-year recurrence-free survival. This study underscores the potential of TP63 as a biomarker for detecting cancer recurrence and suggests its role in guiding future treatment options.

Abstract Background The prognostic significance of the relapse interval in patients with resected oral cavity squamous cell carcinoma (OCSCC) is a matter of ongoing debate. In this large-scale, registry-based, nationwide study, we examined whether the time interval between surgery and the first disease relapse may affect survival outcomes in Taiwanese patients with OCSCC. Methods Data made available by the Taiwan Health Promotion Administration as of 2004 were obtained. The study cohort consisted of patients who were included in the registry between 2011 and 2017. Disease staging was performed according to the American Joint Committee on Cancer (AJCC) Staging Manual, Eight Edition. We retrospectively reviewed the clinical records of 13,789 patients with OCSCC who received surgical treatment. A total of 2327 (16.9%) patients experienced a first disease relapse. The optimal cutoff value for the relapse interval was 330 days when both 5-year disease-specific survival (DSS) and overall survival (OS) (≤ 330/>330 days, n = 1630/697) were taken into account. In addition, we undertook a propensity score (PS)-matched analysis of patients (n = 654 each) with early (≤ 330 days) versus late (> 330 days) relapse. Results The median follow-up time in the entire study cohort was 702 days (433 and 2001 days in the early and late relapse groups, respectively). Compared with patients who experienced late relapse, those with early relapse showed a higher prevalence of the following adverse prognostic factors: pT4, pN3, pStage IV, poor differentiation, depth of invasion ≥ 10 mm, and extra-nodal extension. Multivariable analysis revealed that early relapse was an independent adverse prognostic factor for both 5-year DSS and OS (average hazard ratios [AHRs]: 3.24 and 3.91, respectively). In the PS-matched cohort, patients who experienced early relapse showed less favorable 5-year DSS: 58% versus 30%, p

Abstract Background Gustilo type III tibial fractures commonly involve extensive soft tissue and bony defects, requiring complex reconstructive operations. Although several methods have been proposed, no research has elucidated the efficacies and differences between vascular bone graft (VBG) and the Masquelet technique (MT) to date. We aimed to evaluate and compare the clinical effectiveness of VBG and the MT for the reconstruction of Gustilo type III tibial fractures. Methods This retrospective cohort study enrolled patients who underwent reconstruction for Gustilo type III tibial fractures using VBG or the MT in a single center from January 2000 to December 2020. The patients’ demographics, injury characteristics, and surgical interventions were documented for analysis. The clinical outcomes including union status, time to union, postoperative infections, and the causes of union failure were compared between the two groups. Results We enrolled 44 patients: 27 patients underwent VBG, and 17 underwent MT. The average union time was 20.5 ± 15.4 and 15.1 ± 9.0 months in the VBG and MT groups, respectively (p = 0.232). The postoperative deep infection rates were 70.4% and 47.1% in the VBG and MT groups (p = 0.122), respectively. Though not statistically significant, the VBG group had a shorter union time than did the MT group when the bone defect length was > 60 mm (21.0 ± 17.0 versus 23.8 ± 9.4 months, p = 0.729), while the MT group had a shorter union time than did the VBG group when the bone defect was length

Objectives: Perineural invasion (PNI) was quantitatively analyzed in oral squamous cell carcinoma (OSCC) specimens obtained by radical surgery to correlate with survival outcomes. Methods: This is a retrospective study that reviewed the Cancer registry data between 2009 and 2015. Inclusion criteria were oral cavity cancer, treatment by radical surgery, presence of PNI, and available pathologic samples for S100 staining. Patients with M1 disease and those with synchronous or metachronous cancer during staging work-up were excluded. All pathologic samples were reviewed to confirm PNI status and processed by immunohistochemical staining for S100 to quantify PNI. Pathologic information and staging results were also reviewed, and clinical outcomes were analyzed. Results: The retrospective study included 92 patients; 63 had intratumoral PNI (IPNI) and 29 had extratumoral PNI (EPNI). The average number of PNI foci (APNI) was higher in the EPNI group than in the IPNI group (6.7 vs 3.8, t -test 2-tail significance = 0.021). The 3-year overall survival (OS) and time-to-recurrence (TTR) rates of all patients were 82.5% and 81.2%, respectively. Univariate analysis showed that pathological T4 or N2-3 stage correlated with poor OS, whereas APNI ≥4 correlated with poor TTR. In multivariate analysis, only the pathological N2-3 stage was significantly correlated with poor OS, whereas only APNI ≥ 4 was an independent factor of poor TTR. The 3-year TTR rates were 92.4% and 65.6% for diseases with APNI

Footbath therapy is effective for health and wellness. We compared the effects of hot water footbaths (HFB), contrast water footbaths (CFB), and warm water footbaths (WFB) using physiological parameters, including blood pressure, calf volume, flexibility, and meridian energy for six weeks. Significant differences in diastolic blood pressure and calf volume were observed from the third to fifth week, and CFB showed the best effect. CFB and WFB demonstrated improvements in meridian energy, while HFB had no effect. These findings highlighted the effectiveness of CFB in managing stress and promoting health and well-being.

Allograft rejection is one of the obstacles in achieving a successful vascularized composite allotransplantation (VCA). Treatments of graft rejection with lifelong immunosuppression (IS) subject the recipients to a lifelong risk of cancer development and opportunistic infections. Cell therapy has recently emerged as a promising strategy to modulate the immune system, minimize immunosuppressant drug dosages, and induce allograft tolerance. In this review, the recent works regarding the use of cell therapy to improve allograft outcomes are discussed. The current data supports the safety of cell therapy. The suitable type of cell therapy in allotransplantation is clinically dependent. Bone marrow cell therapy is more suitable for the induction phase, while other cell therapies are more feasible in either the induction or maintenance phase, or for salvage of allograft rejection. Immune cell therapy focuses on modulating the immune response, whereas stem cells may have an additional role in promoting structural regenerations, such as nerve regeneration. Source, frequency, dosage, and route of cell therapy delivery are also dependent on the specific need in the clinical setting.

Abstract Aims/Introduction We aimed to study the predictive ability of visit‐to‐visit variability in albuminuria for changes in renal function in patients with type 2 diabetes mellitus. Materials and Methods The cohort study was carried out in a single medical center. In the model development cohort of 1008 subjects, we developed the albuminuria variability score (AVS) to evaluate the visit‐to‐visit variability in albuminuria, which was the percentage of the number of changes in the urine albumin : creatinine ratio ≥3.39 mg/mmol among all visit‐to‐visit urine albumin : creatinine ratio differences within an individual. Multivariate logistic regression was applied to predict the influence of AVS levels on the occurrence of study end‐points. In another independent validation cohort of 310 participants, survival analysis was carried out to evaluate the ability of AVS in predicting the study end‐point. Results In the model development cohort, a higher AVS was associated with higher adjusted odds of having a declined or rapidly declined estimated glomerular filtration rate (eGFR) trajectory (1.84, 95% confidence interval 1.23–2.76 and 5.70, 95% confidence interval 2.28–14.25, respectively), a resultant eGFR 40% decline in eGFR from baseline (6.44, 95% confidence interval 2.15–19.26). In the validation cohort, a higher AVS independently predicted a 5‐year decrease of >40% in eGFR to

BackgroundPediatric hypertension contributes to adulthood hypertension and target organ damage. Obesity is a well-known predictor for pediatric hypertension; however, the relationship between physical fitness and blood pressure (BP) is unclear among children. This study aimed to compare the differences in demographics, anthropometrics, and physical fitness across BP subgroups and investigate whether physical fitness was related to pediatric hypertension independent of weight status.MethodsThis quantitative, cross-sectional study investigated demographic, anthropometric, physical fitness, and BP measures among 360 healthy school-aged children. Continuous variables were compared across BP subgroups with the one-way analysis of variance. Mediation and moderation analyses were used to explore the mechanism. Multivariable regression models were used to assess independent associations for hypertension.ResultsThere were 177 (49.2%), 37 (10.3%), and 146 (40.6%) children in the normotensive, elevated BP, and hypertensive subgroups, respectively. The hypertensive subgroup had higher body mass index (BMI) and waist/height ratio percentiles and performed worse in 800-m run, standing long jump (SLJ), and 1-min sit-ups than the normotensive subgroup. Furthermore, the 800-m run percentile (total effect: β = 0.308, standard error = 0.044, p < 0.001) and sit and reach percentile (total effect: β = 0.308, standard error = 0.044, p < 0.001) mediated the relationship between the BMI percentile and systolic BP percentile; the SLJ percentile was directly associated with the diastolic BP percentile (β,−0.197, 95% confidence interval,−0.298−0.097; p < 0.001). The parsimonious model of multivariable regression models revealed that the SLJ percentile (adjusted exp (β), 0.992, 95% confidence interval, 0.985–0.999; p = 0.042) and BMI percentile (adjusted exp (β), 1.024, 95% confidence interval, 1.016–1.032; p < 0.001) were two independent predictors for pediatric hypertension.ConclusionPhysical fitness mediates the relationship between anthropometric and BP measures. The SLJ percentile is associated with pediatric hypertension independent of the BMI percentile. Proactive screening and health promotion for not only healthy weight status but also good physical fitness may be beneficial for BP control among school-aged students.

During the worldwide pandemic of coronavirus disease 2019 (COVID-19 pandemic), online learning is increasingly vital for students to learn at home, and online learning platforms provide learning opportunities to students. The Junyi Academy online platform is an online learning platform that both helps lower-achieving students review lessons and helps teachers in Taiwan do differentiated instruction. Several studies have shown the relationships between students’ attention and their academic achievements for students’ self-learning, but how to best use these platforms to help students learn by themselves is unclear. Therefore, this study investigates the relationships between students’ attention and their academic achievements with two online learning environments. A total of 38 upper secondary students in Taiwan to participate in this study, and these students were divided between a Khan-style video lecture (VL) group and an online practice (OP) group. This study adopted an experimental design with data collected by an electroencephalogram (EEG). The results show that students’ attention in the VL group was higher than in the OP group. Furthermore, their attention in three stages differed between the two groups. Student attention was similar in the two groups for the first stage, but the VL group had higher attention for the second and third stages was than did the OP group. In addition, there was no relationship between students’ attention and their academic achievements in the VL and OP groups. Finally, this study raised some suggestions the future research.

IntroductionVascularized bone marrow (VBM) is essential in tolerance induction through chimerism. We hypothesized that the inclusion of VBM contributes to the induction of mystacial pad allotransplantation tolerance.MethodIn this study, 19 VBM, nine mystacial pad, and six sequential VBM and mystacial pad allografts were transplanted from Brown Norway (BN) rats to Lewis (LEW) rats to test our hypothesis. The VBM recipients were divided into antilymphocyte serum (ALS) monotherapy group (two doses of ALS on day 3 pretransplantation and day 1 posttransplantation), immunosuppressant group [a week of 2 mg/kg/day tacrolimus (Tac) and 3 weeks of 3 mg/kg/day rapamycin (RPM)], and combined therapy group. The mystacial pad recipients were divided into VBM and non-VBM transplantation groups, and both groups were treated with an immunosuppression regimen that consists of ALS, Tac, and RPM. For the recipients of sequential VBM and mystacial pad allotransplantations, additional Tac was given 1 week after mystacial pad transplantation. Allograft survival, donor-specific tolerance, and chimerism level were evaluated.ResultsWith the administration of ALS and short-term Tac and RPM treatments, VBM recipients demonstrated long-term graft survival (>120 days) with persistent chimerism for 30 days. CD3+ T cells from tolerant rats showed donor-specific hyporesponsiveness and tolerance to donor skin grafts but not to third-party counterparts. Furthermore, mystacial pad graft recipients with VBM transplantation exhibited a higher allograft survival rate than those without VBM transplantation [median survival time (MST) >90 days vs. 70 days, p < 0.05].ConclusionThis study demonstrated that VBM transplantation is an efficient strategy to induce and maintain donor-specific tolerance for an osseous-free allograft.

Abstract Methods We sought to compare the prognostic impact of tumor differentiation with respect to adverse risk factors (RFs) identified by the National Comprehensive Cancer Network (NCCN) guidelines––including extranodal extension (ENE), positive/close margins, perineural invasion, lymphatic invasion, and vascular invasion––in patients with locally advanced oral cavity squamous cell carcinoma (OCSCC). Results Between 1996 and 2018, 1179 consecutive patients with first primary pT3–4 OCSCC were included. A three‐level grading system was adopted––in which the final classification was assigned according to the most prevalent tumor grade. We identified 382/669/128 patients with well/moderately/poorly differentiated tumors, respectively. Compared with well/moderately differentiated tumors, poorly differentiated OCSCC had a higher prevalence of the following variables: female sex (4%/6%/11%), ENE, (14%/36%/61%), positive margins (0.5%/2%/4%), close margins (10%/14%/22%), perineural invasion (22%/50%/63%), lymphatic invasion (2%/9%/17%), vascular invasion (1%/4%/10%), and adjuvant therapy (64%/80%/87%). The 5‐year rates of patients with well/moderately/poorly differentiated OCSCC were as follows: local control (LC, 85%/82%/84%, p = 0.439), neck control (NC, 91%/83%/70%, p

Abstract Background We compared the clinical outcomes of patients with oral cavity squamous cell carcinoma (OCSCC) with cN+pN0 versus cN0pN0 disease. Methods A total of 1309 OCSCC patients with pN0 disease were included. Of them, 1019 and 290 cases had cN0pN0 and cN+pN0 disease, respectively. For comparison purposes, we also examined 799 patients with pN+disease (cN0pN+/cN+pN+, n = 239/560). Subgroup analysis was performed in a propensity score‐matched cohort with cN0pN0 and cN+pN0 disease (n = 284 each). Results Compared with cN0pN0, patients with cN+pN0 had a higher prevalence of the following variables: betel chewing, pT3−4, depth ≥10 mm, perineural invasion, and treatment with surgery and adjuvant therapy. The prognosis of patients with cN+pN0 (mean: 52 nodes) and cN0pN0 (mean: 39 nodes) disease was similar both in the original cohort and after propensity score matching. However, the 5‐year outcomes were more favorable for cN+pN0/cN0pN0 compared with cN0pN+/cN+pN+ (local control, 88%/88%/83%/81%; neck control, 94%/93%/82%/76%; distant metastases, 4%/3%/13%/31%; disease‐free survival, 84%/83%/68%/52%; disease‐specific survival, 92%/92%/77%/57%; overall survival, 81%/82%/59%/42%; all p values 0.05). cN+pN0 disease (vs. cN0pN0) was not significantly associated with local control, neck control, distant metastases, and survivals either in univariable or multivariable analyses. Conclusions Despite a higher risk factor burden, the prognosis of patients with cN+pN0 disease did not differ from that of cases with cN0pN0. The higher nodal yield and the more frequent use of adjuvant therapy in cN+pN0 disease may explain the lack of significant differences in terms of neck control compared with cN0pN0 disease.

In Taiwan, numerous crops are threatened by Xanthomonas diseases such as citrus bacterial canker caused by X. citri subsp. citri and tomato bacterial spot mainly caused by X. euvesicatoria pv. perforans. Foliar sprays of copper-based bactericides have been frequently used for control of plant bacterial diseases. However, in Taiwan not much attention was paid on copper-resistant (CuR) Xanthomonas spp. and their impact on disease control efficacy of copper-based bactericides. In this study, CuR Xanthomonas isolates were collected from citrus and tomato in Taiwan. Compared with the pronounced effect on the copper sensitive isolate, spraying of copper hydroxide at the recommended rate of 0.5 kg/ha could not protect tomato plants against bacterial spot caused by the CuR isolate. Phylogenetic analysis of concatenated copper resistance genes, copL, copA, and copB, indicate that the Taiwanese CuR isolates belong to the worldwide clade. In addition to the three previously reported variants of the copB gene, analysis of complete copB sequences from xanthomonads associated with citrus and solanaceous hosts revealed the other three variants of copB and their global distribution. Copper-resistant Xanthomonas isolates from Taiwan have the two unreported variants of copB genes which differ from the other three previously reported types in the sizes and structures. The information provided here reveals the necessity to develop and include alternative measures rather than relying on foliar sprays of copper bactericides for sustainable control of tomato bacterial spot in Taiwan.

BackgroundIn the treatment of oral cavity squamous cell carcinoma (OCSCC), surgical quality measures which are expected to affect outcomes, including the achievement of a clear margin, are surgeon-dependent but might not be invariably associated with hospital volume. Our objective was to explore surgical margin variations and survival differences of OCSCC between two highest-volume hospitals in Taiwan.Materials and methodsA total of 2009 and 1019 patients with OCSCC who were treated at the two highest-volume Taiwanese hospitals (termed Hospital 1 and Hospital 2, respectively) were included. We examined how a pathological margin

BackgroundTo assess the prognostic significance of different nodal parameters [i.e., number of pathologically positive nodes, log odds of positive lymph nodes, lymph node ratio (LNR), and extra-nodal extension (ENE)] in Taiwanese patients with oral cavity squamous cell carcinoma (OCSCC), and to devise an optimized pN classification system for predicting survival in OCSCC.MethodsA total of 4287 Taiwanese patients with first primary OCSCC and nodal metastases were enrolled. Cox proportional hazards regression analysis with the spline method was applied to identify the optimal cut-off values for LNR, log odds of positive lymph nodes, and number of pathologically positive nodes.ResultsOn multivariable analysis, we identified a LNR ≥0.078/0.079, the presence of at least three pathologically positive nodes, and ENE as independent prognosticators for 5-year disease-specific survival (DSS) and overall survival (OS) rates. We therefore devised a four-point prognostic scoring system according to the presence or absence of each variable. The 5-year DSS and OS rates of patients with scores of 0−3 were 70%/62%/50%/36% (p

Background: The literature emphasizes the importance of matching the demand and supply of endocrinology and metabolism (EM) specialists. This study analyzed the current status of EM specialists in Taiwan. The gender effects on the workplace of EM specialists were also evaluated. Methods: The number of internal medicine (IM) specialists was obtained from the websites of the Ministry of Health and Welfare. Data about EM specialists were retrieved from the database of the Endocrine Society of the Republic of China (ESROC; Taiwan). Differences in age distribution and workplace levels or locations between female and male EM specialists were analyzed. Results: Since 1988, 809 physicians were certified as EM specialists. The average age of 739 EM specialists (509 male, 230 female) who remained as active members of the ESROC was 49.9 ± 11.1 years. The age distribution (p

Eosinophilic pustular folliculitis (EPF) is classified into Ofuji disease, immunosuppression-associated EPF, and infancy-associated EPF. The association of EPF with Demodex infestation is rarely reported. We report five cases of EPF with Demodex overgrowth. All patients were young females presenting with recurrent, itchy papulopustules on the face for 2 months to 2 years. Laboratory tests revealed eosinophilia (n = 2) and iron deficiency anemia (n = 1). Skin biopsy of papulopustular lesions was performed in each patient, and all revealed folliculocentric infiltration with eosinophils. Infundibular pustules containing Demodex mites were found in two patients. All patients had high Demodex densities examined by superficial needle-scraping method (7–18 mites/5 pustules) and/or thumbnail-squeezing method (37–255 mites/cm2). Based on the clinical and laboratory findings, the patients were either first treated as having demodicosis or as having EPF. According to the treatment responses, the cases might represent Demodex-induced EPF or EPF-like reaction (Cases 1–3) or demodicosis superimposed on EPF (Cases 4 and 5). In sum, we report five cases of EPF with Demodex overgrowth (demodicosis). These cases illustrate that the possibility of Demodex overgrowth should be considered in cases of EPF with incomplete treatment response to indomethacin and/or oral corticosteroids. Conversely, EPF should be considered in cases of demodicosis with incomplete responses to antiparasitic treatment.

The cuttlefish is a commercially important marine species across the world; however, due to the lack of appropriate artificial feed, there is limited future aquaculture development of the cuttlefish. We proposed a novel process comprising (1) feed preference tests and (2) progressive training programs. Through this process, artificial diets can become more suitable for pharaoh cuttlefish (Sepia pharaonis). Feed preference tests (based on vision, touch, and smell) revealed that pharaoh cuttlefish preferred rod-shaped feed to flat rod-shaped or ball-shaped feed, moist feed over dry feed (DF), and DF with agar coating to DF without agar coating. Without olfactory training, some cuttlefish refused to eat artificial feed and eventually died. Through progressive training programs (3- and 6-week programs), a survival rate of >80% was achieved. Although the artificial diets examined in this study resulted in a lower conversion ratio for S. pharaonis than for fresh shrimp, available artificial feed can potentially be adopted for cuttlefish aquaculture through the use of our progressive training program.

Background: The main objective of this study was to investigate the safety of bedside percutaneous dilational tracheostomy (PDT) by pulmonologists in critically ill patients, and the factors associated with complications resulting from PDT. Methods: We retrospectively enrolled critically ill patients who had undergone bedside PDT in the intensive care units (ICUs) and respiratory care center from February 2016 to December 2018. Results: A total of 312 patients were included for analysis, with a mean age of 69.6 ± 17.7 years. Two hundred and eight of the patients were male (66.7%). The mean acute physiology and chronic health evaluation II score was 25.3 ± 6.3, and the mean body mass index was 22.4 ± 4.2. Most of the patients were intubated due to respiratory disorders (51.3%). Fifty-six patients (17.9%) received antiplatelet agents or an anticoagulant regularly prior to PDT. All enrolled patients were undergone bedside PDT successfully. The total complication rate of PDT was 14.4%. Patients who took antiplatelet agents or anticoagulants regularly before PDT had a higher risk of bleeding than patients who went without (26.8% versus 7.0%, adjusted odds ratio 4.93 [95% f 2.16–11.25], p

Abstract This report describes the case of a 17‐year‐old man who developed mediastinal growing teratoma syndrome following two cycles of chemotherapy, after an initial diagnosis of primary mediastinal nonseminomatous germ cell tumor. The large, rapidly‐growing mediastinal tumor was completely resected in conjunction with right pneumonectomy, using simultaneous clamshell thoracotomy and median sternotomy. The salvage surgery with perioperative management involved in mediastinal growing teratoma syndrome is presented here. Key points Significant findings of the study The diagnosis and surgical management are challenging for patients with mediastinal growing teratoma syndrome. Nevertheless, with proper operative planning, favorable outcomes can be attained with complete resection despite the characteristic rapid growth and massive size of these neoplasms. What this study adds In spite of postoperative sternal dehiscence, we believe that a simultaneous clamshell thoracotomy with median sternotomy approach remains a viable option for an extremely large mediastinal growing teratoma, when tumor size prevents safe resection using other approaches due to limited visualization.

Despite multidisciplinary therapy, the prognosis is poor for esophageal squamous cell carcinoma (ESCC). In the locally advanced stage, neoadjuvant chemoradiotherapy (nCRT) followed by surgery could provide survival benefits to some patients. Here, we aimed to identify for tumor therapy response a biomarker based on RNA sequencing. We collected endoscopic biopsies of 32 ESCC patients, who were divided according to nCRT response, into two groups: the complete response group (n = 13) and the non-complete response group (n = 19). RNA-sequencing data showed that 464 genes were differentially expressed. Increased in non-complete response group, 4 genes increased expressions were AGR2 (anterior gradient 2), GADD45B (growth arrest and DNA damage inducible beta), PPP1R15A (protein phosphatase 1 regulatory subunit 15A) and LRG1 (leucine rich alpha-2-glycoprotein 1). The areas under the curve (AUC) of the AGR2 gene was 0.671 according to read counts of RNA-seq and therapy response of nCRT. In vitro study showed that apoptosis cell was significantly increased in the AGR2-knockdown TE-2 cell line treated with cisplatin and 5-Fluorouracil (5-FU), when compared with si-control. Results suggest that in ESCC, the AGR2 gene is a promising and predictive gene marker for the response to anti-tumor therapy.

Abstract Background To explore the diagnostic performance of triggered angiography non-contrast-enhanced magnetic resonance imaging (TRANCE-MRI) for the evaluation of venous pathology of the lower extremity. Methods This was a single-centre prospective cohort study of 25 patients with suspected venous disease in the lower extremities. Each patient received Doppler ultrasonography (for venous evaluation) before the scheduled TRANCE-MRI (for venous and arterial evaluations) on a 1.5 T MR scanner (Philips Ingenia, Philips Healthcare, Best, the Netherlands), followed by lymphography and computed tomography angiography that were arranged according to the diagnostic indications. Results The sensitivity, specificity and accuracy of TRANCE-MRI were 85.7%, 88/9 and 88%, respectively. The inter-rater agreement for deep vein thrombosis (DVT) of the thigh between the ultrasonography and TRANCE-MRI results was substantial agreement (Cohen’s kappa κ, 0.72). In ultrasonography-negative cases, TRANCE-MRI detected four additional cases (16%, 4/25) of DVT; three cases (12%, 3/25) of venous compression caused by pelvic lymphadenopathy, hip prosthesis or knee joint effusion; one case (4%, 1/25) of vena cava anomaly; two cases (8%, 2/25) of occult peripheral artery disease (PAD); and one case (4%, 1/25) of an occluded bypass graft. Conclusion TRANCE-MRI can be used as an alternative and objective tool for assessing lower extremity diseases, especially suspected venous pathology. Compared with ultrasonography, TRANCE-MRI plays a better role in assessing varicose veins of the lower extremities and deep veins of the pelvis and abdomen. However, false-positive results may occur in the left common iliac vein of elderly patients. Finally, occult PAD rarely occurs in patients with suspected lower extremity venous disease. Therefore, we recommend performing the TRANCE-MRV protocol instead of the full protocol (MRV + MRA) in the clinical setting in patients with venous scenarios.

PurposePathology reviews for upper urinary tract cancer (UTUC) remained scarce in the literature. Here, we reported the interobserver variation among the review and local pathologies of featured histologic characteristics for UTUC.MethodsPatients who underwent definitive surgical treatments for UTUC were retrospectively reviewed for eligibility of pathology review. In the Taiwan UTUC Collaboration cohort, 212 cases were reviewed, of which 154 cases were eligible for pathology review. Agreement between original pathology and review pathology was measured by the total percentage of agreement and by simple kappa statistics. The prognostic impact was analyzed by the Cox regression model with the estimation of hazard ratios (HR) and 95% confidence intervals.ResultsThere were 80 women and 74 men enrolled in this study, and the median age at treatment was 71.7 years. The agreement is moderate agreement for surgical margin status (87.7%; κ = 0.61), tumor grade (82.5%; κ = 0.43), tumor invasiveness (76.6%; κ = 0.45), lymphovascular invasion (70.8%; κ = 0.42) and T stage (67.5%; κ = 0.52). The interobserver agreements for perineural invasion and variant histology identification were slight. Kaplan–Meier analysis for disease-free survival revealed comparable results in local and review pathology for localized (Tis, Ta, T1–2) or advanced T stage (T3–4).ConclusionsPathology review of UTUC had minimal impact on clinical practice based on current available disease treatment guidelines. However, significant interobserver variations were observed in featured adverse histopathological characters.

Perivascular epithelioid cell tumour (PEComa) is an extremely rare neoplasm with distinctive morphology and specific expression of immunohistochemical markers. The lesion is typically diagnosed in middle-aged women, with few reports of paediatric cases, and there is no standardized treatment for the tumour type. Here, the case of a 17-year-old female, who presented with painless haematochezia for 2 days and was diagnosed with gastrointestinal PEComa of the sigmoid colon with regional lymph node metastasis after serial examination, is presented. She was treated by surgical resection of the tumour and cytotoxic chemotherapy comprising 900 mg/m 2 gemcitabine and 100 mg/m 2 docetaxel every 3 weeks for six cycles. Haematochezia did not recur, and complete response was achieved, with progression-free survival at the 24-month follow-up examination. Surgical resection with adjuvant conventional cytotoxic chemotherapy may be considered as an option for treating gastrointestinal PEComa.

Background: Desmoid tumor and leiomyoma are abdominal wall tumors with similar clinical, radiographic, and histological features. However, differentiation between these two diseases is important because each may be linked to different systemic diseases, and their managements are entirely different. We proposed that misdiagnosis is possible in some cases. Patients and Methods: Between 1983 and 2010, patients with a history of uterine surgeries and diagnosed with either abdominal wall desmoid tumors or leiomyomas were studied. All the images reviewed by an independent radiologist and surgical specimen were reexamined by immunohistochemistry (IHC) techniques as a standard method to confirm the diagnoses. Results: Fifteen female patients (desmoid tumors, n = 10; leiomyomas, n = 5) were included. The diagnosis of IHC revealed that two cases initially thought to be leiomyomas were desmoid tumors, whereas the remaining 13 cases maintained their initial diagnoses. The accuracy of hematoxylin and eosin staining was 86.7%. All tumors excised without complications, except for one desmoid tumor that recurred and underwent another excision. Conclusion: Preoperative magnetic resonance imaging (MRI) can be considered to differentiate the two diseases, as well as the elimination of other associated systemic diseases should be performed routinely. If MRI is inaccessible or unavailable, preoperative fine-needle biopsy is recommended. Optional IHC staining is required if the primary histological assessment is equivocal or inconclusive.

Although viscous sediment environments along the coast strongly attenuate waves, the attenuation dynamics and physical mechanism governing the attenuation process remain relatively unknown. Extremely complex interactions between muddy seabed have become increasingly important for wave evolution studies pertaining to coastal areas. The coastal protection function of mangroves was confirmed during the 2004 South Asian tsunami. Nevertheless, most research has been limited to macro-qualitative analyses, including those on variations in the transmission coefficient Kt and reflection coefficient Kr, and subsequent comparisons. However, determining the micro-physical characteristics is challenging, similar to coastal vegetation analyses with respect to mangrove vegetation characteristics. This study aims to quantify the attenuation difference in the wave energy owing to the coastal vegetation structure, under different layout conditions and combinations. Particle image velocimetry (PIV) technology is used to explore the variations in the velocity field and velocity distribution during the interaction process and calculate the wave-induced kinetic energy before and after setting up the vegetation structure. The research results emphasize that the resistance and frictional effects generated by vegetation are inversely proportional to the size of the stem, and the variation of kinetic energy determined from the velocity distribution and the thickness of the vegetation stem is mainly due to the larger frictional resistance of dense vegetation, relative to the fast flow velocity above the vegetation. Different vegetation heights slightly affect the short-period waves; however, the impact on energy reduction was smaller. For long-period waves, vegetation height significantly reduces wave kinetic energy.

Antrodia cinnamomea exhibits anti-inflammatory, antioxidant, and immunomodulatory activities. We aimed to explore the antipsoriatic potential of 2,4-dimethoxy-6-methylbenzene-1,3-diol (DMD) derived from A. cinnamomea. The macrophages activated by imiquimod (IMQ) were used as the cell model for examining the anti-inflammatory effect of DMD in vitro. A significantly high inhibition of IL-23 and IL-6 by DMD was observed in THP-1 macrophages and bone marrow-derived mouse macrophages. The conditioned medium of DMD-treated macrophages could reduce neutrophil migration and keratinocyte overproliferation. DMD could downregulate cytokine/chemokine by suppressing the phosphorylation of mitogen-activated protein kinases (MAPKs) and NF-κB. We also observed inhibition of GDAP1L1/Drp1 translocation from the cytoplasm to mitochondria by DMD intervention. Thus, mitochondrial fission could be a novel target for treating psoriatic inflammation. A psoriasiform mouse model treated by IMQ showed reduced scaling, erythema, and skin thickening after topical application of DMD. Compared to the IMQ stimulation only, the active compound decreased epidermal thickness by about 2-fold. DMD diminished the number of infiltrating macrophages and neutrophils and their related cytokine/chemokine production in the lesional skin. Immunostaining of the IMQ-treated skin demonstrated the inhibition of GDAP1LI and phosphorylated Drp1 by DMD. The present study provides insight regarding the potential use of DMD as an effective treatment modality for psoriatic inflammation.

The acid sphingomyelinase (ASM) converts sphingomyelin into ceramide. Recent work has advanced the ASM/ceramide system as a major player in the pathogenesis of major depressive disorder (MDD). Indeed, ASM activity is enhanced in MDD patients and antidepressant drugs like fluoxetine act as functional inhibitors of ASM. Here, we employed the specific ASM inhibitor ARC39 to explore the acute effects of the enzyme on hippocampal synaptic transmission and cell excitability in adult mouse brain slice preparations. In both field potential and whole-cell recordings, ARC39 (1–3 μM) enhanced excitatory synaptic input onto ventral hippocampal CA1 pyramidal cells. The specificity of drug action was demonstrated by its lacking effect in slices from ASM knockout mice. In control condition, ARC39 strongly reduced firing in most CA1 pyramidal cells, together with membrane hyperpolarization. Such pronounced inhibitory action of ARC39 on soma excitability was largely reversed when GABAA receptors were blocked. The idea that ARC39 recruits GABAergic inhibition to dampen cell excitability was further reinforced by the drug’s ability to enhance the inhibitory synaptic drive onto pyramidal cells. In pyramidal cells that were pharmacologically isolated from synaptic input, the overall effect of ARC39 on cell firing was inhibitory, but some neurons displayed a biphasic response with a transient increase in firing, suggesting that ARC39 might alter intrinsic firing properties in a cell-specific fashion. Because ARC39 is charged at physiological pH and exerted all its effects within minutes of application, we propose that the neurophysiological actions reported here are due to the inhibition of secretory rather than lysosomal ASM. In summary, the ASM inhibitor ARC39 reveals a tonic control of the enzyme over ventral hippocampal excitability, which involves the intrinsic excitability of CA1 pyramidal cells as well as their excitatory and inhibitory synaptic inputs.

Despite the known advantages of virtual surgical planning and three-dimensional (3D) printing, translation of virtual planning to actual operation is a challenge, especially in secondary mandibular reconstruction. Patients who underwent secondary microvascular mandibular reconstruction were retrospectively reviewed and categorized into three categories as follows: (i) defect not crossing the midline (category I); (ii) defects crossing the midline with availability of previous imaging data (category II) and; (iii) defects crossing the midline with unavailability of previous imaging data (category III). The resulting 3D printed models were used as an effective guide for plate bending during secondary reconstruction surgery. Accuracy of the reconstruction was evaluated by superimposing post-operative images over virtual plan. Out of eleven patients, five were category I, three were category II, and three were category III. The mean linear discrepancy between the planned and post-operative position was measured. A Mann-Whitney U test was conducted to compare mean discrepancy among the groups showed no significant difference between group I and group II (p > 0.05) whereas comparison of groups I and II with group III showed a significant difference (p < 0.01). The proposed algorithm for the generation of defect template for manual plate bending during secondary reconstruction of mandibular defects is valid with acceptable accuracy in various defect configurations.

Five liquid crystal epoxy resins and composites containing flat boron nitride (f-BN) and spherical boron nitride (s-BN) were successfully synthesized. The chemical structures, crystal diffraction, and thermal conductivity of the liquid crystal (LC) epoxy composites were measured using Nuclear Magnetic Resonance (NMR), Differential Scanning Calorimetry (DSC), X-ray, and Discovery Xenon Flash. In this study, the molecular arrangement of five LC epoxy resins and the thermal conductivity of their composites were carefully discussed. Several different amounts of flat boron nitride and spherical boron nitride were added to the five LC epoxy resins. The influence of nano-scale ceramic materials, f-BN, and s-BN, on the thermal conductivity of the LC epoxy resins, was studied. It is worth noting that the thermal conductivity of the spherical boron nitride composite demonstrated a better result than that of the flat boron nitride composite. In simpler terms, the thermal conductivity of the composites is closely related to the molecular arrangement of the LC resin and the amount of BN added. The results demonstrate that the SBPDAE/s-BN (60%) composite shows the highest thermal conductivity of 9.36 W/mK in the vertical direction. These data prove that the LC alignment of the matrix will greatly enhance the thermal conductivity of the composites.

Abstract Background Neurofibromatosis type 1 (NF1) is a dominantly inherited tumor predisposition syndrome that targets the peripheral nervous system. It is caused by mutations of the NF1 gene which serve as a negative regulator of the cellular Ras/MAPK (mitogen-activated protein kinases) signaling pathway. Owing to the complexity in some parts of clinical diagnoses and the need for better understanding of its molecular relationships, a genetic characterization of this disorder will be helpful in the clinical setting. Methods In this study, we present a customized targeted gene panel of NF1/KRAS/BRAF/p53 and SPRED1 genes combined with Multiple Ligation-Dependent Probe Amplification analysis for the NF1 mutation screening in a cohort of patients clinically suspected as NF1. Results In this study, we identified 73 NF1 mutations and two BRAF novel variants from 100 NF1 patients who were suspected as having NF1. These genetic alterations are heterogeneous and distribute in a complicated way without clustering in either cysteine–serine-rich domain or within the GAP-related domain. We also detected fifteen multi-exon deletions within the NF1 gene by MLPA Analysis. Conclusions Our results suggested that a genetic screening using a NGS panel with high coverage of Ras–signaling components combined with Multiple Ligation-Dependent Probe Amplification analysis will enable differential diagnosis of patients with overlapping clinical features.

Purpose: Excessive ultraviolet B (UVB) exposure causing corneal endothelium injury, including apoptosis, is a serious condition. Therefore, drugs that can inhibit apoptosis in corneal endothelial cells represent an effective strategy. Simvastatin is widely used as a specific inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase, can reduce levels of low density lipoprotein (LDL) cholesterol, and exerts anti-inflammatory effects. However, the protective effect of simvastatin on corneal endothelial cells remains unclear. Therefore, the aim of this study was to elucidate whether UVB promotes the initiation of apoptosis in corneal endothelial cells and injury reversible by simvastatin treatment. Methods: We detected the cell viability, subG1 population, and caspase-3 activity. Results: Results showed that simvastatin alleviates UVB-induced cell death, cell apoptosis, and caspase-3 activity. Conclusion: Our findings indicated that simvastatin alleviated UVB-induced corneal endothelial cell apoptosis via caspase-3 activity.

Cowden syndrome (CS) is a rare genetic disease which puts patients at an increased risk of developing mucocutaneous lesion, multiple hamartomas, breast cancer, thyroid cancer, and Lhermitte–Duclos disease (LDD). This article reviews the role of LDD in the diagnosis of CS. It is important for all clinicians to identify these patients due to the high risk of other associated malignancies.