Search

The pulmonary artery catheter (PAC)-despite its invasiveness-remains the gold standard for cardiac output (CO) monitoring. The FloTrac system, a less invasive hemodynamic monitor has been developed, which estimates CO using arterial pressure waveform analysis without external calibration. Recently, an upgraded version of FloTrac system with improved algorithm to follow changes in vascular resistance was introduced into the market. The aim of this study was to assess the reliability of the CO estimated from the fourth-generation FloTrac/EV1000 system (CO

Blood pressure in patients with traumatic brain injury (TBI) is associated with clinical outcome. However, evidence of blood pressure (BP) range is scarce and the association between BP and clinical outcome is mostly controversial. We aimed to investigate the association between blood pressure and clinical outcome in TBI.This is a retrospective cohort study using the Taipei Tzu Chi Hospital trauma database from January 2009 to June 2019; totally, 13,114 patients were examined. The primary outcome of this investigation was in-hospital mortality and the secondary outcomes were intensive care unit (ICU) admission rate and prolong ICU stay (defined as stay in ICU ≥ 14 days). Subgroups analysis of Glasgow Coma Scale (GCS) and Triage SBP was also conducted.A total of 1782 traumatic adult patients with TBI (AIS score3) were finally included. The cut-off points are 130 mmHg to 149 mmHg in all TBI patients with lower odds ratio of mortality. In different TBI severity, U-shape relationship also presented and we also found that cut-off points of 130 to 149 mmHg in mild TBI and 110 to 129 mmHg in moderate TBI have lower odds ratio of mortality. The mortality is significantly increased in BP below 90 mmHg and above 190 mmHg in TBI patients.Traumatic brain injury population presented a U-shape relationship between triage SBP and in-hospital mortality. Early resuscitation and correct hypotension/hypertension in TBI population with BP below 90 mmHg and above 190 mmHg may prevent from increased mortality.

Revascularisation for peripheral artery disease (PAD) is increasingly common in dialysis patients. Patients with PAD who have undergone revascularisation are at high risk of subsequent complications. Malnutrition is an important modifiable risk factor for dialysis patients, yet few data exist on the prognostic impact of malnutrition on post-procedure long term outcomes. The objective was to assess the prevalence and prognostic association of malnutrition using the Controlling Nutritional Status (CONUT) score in a prospective cohort of dialysis patients undergoing endovascular therapy (EVT) for PAD.A total of 395 consecutive dialysis patients undergoing endovascular revascularisation for lower extremity PAD between 2005 and 2019 were examined for the primary outcome of all cause death. Secondary outcomes included major adverse limb events (MALEs), defined as acute limb ischaemia, major amputation, and clinically driven revascularisation; and major adverse cardiovascular events (MACEs). Nutritional status was assessed by CONUT score, a screening tool for malnutrition, incorporating albumin, cholesterol, and total lymphocyte count.According to the CONUT score, 40.8% of patients were moderately or severely malnourished. During a median follow up of 2.2 years, 218 (55.2%) patients died; 211 (53.4%) patients had MALEs, and MACEs occurred in 135 (34.2%) patients. Compared with normal nutritional status, severe malnutrition was associated with a significantly increased risk of all cause death (adjusted hazard ration [aHR] 4.83, 95% confidence interval [CI] 2.56 - 9.12) and MALEs (aHR 2.42, 95% CI 1.23 - 4.74) but not MACEs (aHR 1.81, 95% CI 0.74 - 4.40). Similar results were observed when the CONUT score was analysed as a continuous variable.Malnutrition is common in dialysis patients with PAD requiring endovascular therapy and is strongly associated with increased death and MALEs. Clinical trials are needed to evaluate whether nutritional interventions improve outcomes for dialysis patients after peripheral revascularisation.

Background Mortality after myocardial infarction (MI) among patients undergoing dialysis is high. However, studies investigating the use of secondary prevention medications after MI and clinical outcomes in dialysis patients are lacking. This study aimed to examine the association of the number of guideline-recommended medications (antiplatelets, β-blockers, statins and renin–angiotensin–aldosterone system inhibitors) with all-cause mortality after MI in hemodialysis (HD) patients. Methods We conducted a nationwide cohort study of incident HD patients who were admitted for MI between 1 January 2010 and 31 December 2014 and were followed up until 31 December 2015, using Taiwan's national health insurance research database. Results Of 1471 patients (mean age 68 years, 41.9% women) included in the analysis, 281 (19.1%) were treated with one cardioprotective medication, 406 (27.6%) with two, 490 (33.3%) with three and 294 (20%) with four. During a median follow-up of 1.0 years, 458 (31.1%) patients died. In a multivariable Cox model, each additional use of guideline-recommended therapies was associated with a significant 12% reduction in the risk of mortality {hazard ratio [HR] 0.88 [95% confidence interval (CI) 0.80–0.97]}. Similar results were obtained in the analysis with the inverse probability of treatment weighting [HR 0.84 (95% CI 0.77–0.92)] and in the propensity score–matched subcohort [HR 0.87 (95% CI 0.77–0.98)]. The decreased mortality risk was consistently observed across all subgroups. Conclusions The use of more evidence-based medications for secondary prevention after MI was associated with a lower risk of all-cause mortality in HD patients.

NTRK-rearranged mesenchymal neoplasms mostly affect the soft tissues of pediatric patients. Given the responsiveness to selective NTRK inhibitors, it remains critical to identify those ultra-rare cases occurring in the viscera of adults. In five females and two males aged 18-53 years, we characterized visceral mesenchymal tumors harboring TPM3-NTRK1 [uterine cervix (N = 2), pleura, prostate], LMNA-NTRK1 (lung), SQSTM1-NTRK3 (heart), and NTRK3 rearrangement with unknown fusion partner (colon/mesocolon) with RNA sequencing, FISH, RT-PCR, and immunohistochemistry. The tumors exhibited spindled to ovoid/epithelioid or pleomorphic cells, often arranged in fascicles, and were low-to-intermediate-grade and high-grade in three and four cases, respectively. Keloid-like stromal collagen and perivascular hyalinization was noted in five. Adenosarcoma-like appearances were observed in two, manifesting frond-like protrusions in one cervical tumor and phyllodes-like architecture in the prostatic tumor. Abrupt high-grade transformation into pleomorphic liposarcoma was found in another cervical tumor, while the pleural tumor contained intermixed rhabdomyoblasts. Pan-TRK immunostaining was positive in all cases. All cases expressed CD34, while five were S100-positive. CDKN2A homozygous deletion with concomitant p16 loss occurred in 4/7. Whole-exome sequencing identified TP53 mutation (c.672+2TC, involving a splice site, with concomitant protein loss) in a cervical sarcoma, limited to its heterologous liposarcomatous component. At least moderate pan-TRK immunoreactivity was present in varying proportions of potential pathologic mimics, with BCOR-positive sarcoma (56%, 5/9), undifferentiated uterine sarcoma (50%, 3/6), and spindle cell/sclerosing rhabdomyosarcoma (33%, 2/6) being among the most frequent. This underscored the unsatisfactory specificity of pan-TRK immunohistochemistry and warranted molecular confirmation in the diagnosis of adult NTRK-rearranged visceral mesenchymal neoplasms. The current report highlights the ever-expanding clinicopathologic and genetic spectrum of this entity by describing the unprecedented cardiac and pleural locations and heterologous differentiation, as well as the second NTRK-rearranged "prostatic stromal sarcoma," while substantiating CDKN2A deletion as a frequent occurrence.

Personalized treatments based on the genetic profiles of tumors can simultaneously optimize efficacy and minimize toxicity, which is beneficial for improving patient outcomes. This study aimed to integrate gene alterations associated with predictive and prognostic outcomes in patients with metastatic colorectal cancer (mCRC) with polymerase chain reaction (PCR) and in-house next-generation sequencing (NGS) to detect KRAS, NRAS, and BRAF mutations. In the present study, 41 patients with mCRC were assessed between August 2017 and June 2019 at a single institution. The overall concordance between NGS and PCR results for detecting KRAS, NRAS, and BRAF mutations was considerably high (87.8–92.7%), with only 15 discrepant results between PCR and NGS. Our companion diagnostic test analyzes KRAS, NRAS, and BRAF as a panel of CRC molecular targets; therefore, it has the advantages of requiring fewer specimens and being more time and cost efficient than conventional testing for separate analyses, allowing for the simultaneous analysis of multiple genes.

Effect of MPT0L145 on autophagosome formation.

Effect of MPT0L145 on endosomal functions.

Supplementary Fig. S1, Time-dependent effects of BGJ398 on autophagy in bladder cancer cells. Supplementary Figure. S2. In vitro inhibitory effects of MPT0L145 and SAR405 on PIK3C3 (VPS34). Supplementary Figure. S3. A and B, The potentiation of MPT0L145-increased cytotoxicity by PIK3C3 knockdown in Panc1 and A2780 cells. C and D, ROS inhibitors partially reversed MPT0L145-decreased cell viability. Supplementary Figure S4. Validation of ATG5-knockout (K.O.) RT-112 cells. Supplementary Fig. S5. A, Effect of specific CSF1R inhibitor, BLZ945, on the viability in RT-112 and RT-4 cells. B, Dual inhibition of FGFR3 signaling and autophagy by MPT0L145. C, Effect of MPT0L145 on necrosis in bladder cancer cells.

Supplementary Table S1. In vitro inhibitory effects of MPT0L145 on a panel of lipid kinases. Supplementary Table S2. Binding kinetics and affinity of MPT0L145 to wildtype and mutant PIK3C3.

Effect of MPT0L145 on endosomal functions.

Purpose: MPT0L145 has been developed as a FGFR inhibitor exhibiting significant anti-bladder cancer activity in vitro and in vivo via promoting autophagy-dependent cell death. Here, we aim to elucidate the underlying mechanisms.Experimental Design: Autophagy flux, morphology, and intracellular organelles were evaluated by Western blotting, transmission electron microscope, and fluorescence microscope. Molecular docking and surface plasmon resonance assay were performed to identify drug–protein interaction. Lentiviral delivery of cDNA or shRNA and CRISPR/Cas9-mediated genome editing was used to modulate gene expression. Mitochondrial oxygen consumption rate was measured by a Seahorse XFe24 extracellular flux analyzer, and ROS level was measured by flow cytometry.Results: MPT0L145 persistently increased incomplete autophagy and phase-lucent vacuoles at the perinuclear region, which were identified as enlarged and alkalinized late-endosomes. Screening of a panel of lipid kinases revealed that MPT0L145 strongly inhibits PIK3C3 with a Kd value of 0.53 nmol/L. Ectopic expression of PIK3C3 reversed MPT0L145-increased cell death and incomplete autophagy. Four residues (Y670, F684, I760, D761) at the ATP-binding site of PIK3C3 are important for the binding of MPT0L145. In addition, MPT0L145 promotes mitochondrial dysfunction, ROS production, and DNA damage, which may in part, contribute to cell death. ATG5-knockout rescued MPT0L145-induced cell death, suggesting simultaneous induction of autophagy is crucial to its anticancer activity. Finally, our data demonstrated that MPT0L145 is able to overcome cisplatin resistance in bladder cancer cells.Conclusions: MPT0L145 is a first-in-class PIK3C3/FGFR inhibitor, providing an innovative strategy to design new compounds that increase autophagy, but simultaneously perturb its process to promote bladder cancer cell death. Clin Cancer Res; 24(5); 1176–89. ©2017 AACR.

This work used short carbon fibers (SCFs) of different lengths to manufacture epoxy bulk mold compound (BMC) composites. Drop-weight-impact tests were performed on the intact carbon-fiber-reinforced-polymers (CFRPs) laminates to generate artificial damage. The damaged CFRP laminates were then repaired using the SCF-BMC composites. Compression after impact (CAI) tests were conducted to measure the compressive strength of the repaired laminates. Tensile properties and compressive properties of the SCF-BMC composites were also measured. The results show that 48-mm carbon fibers result in the largest tensile modulus, tensile strength, and compressive strength, while 12-mm carbon fibers result in the largest compressive modulus. CAI test results show that the compressive strength of the repaired laminate can be restored to 80.3% of that of the undamaged laminate. Therefore, SCF-BMC composites significantly contribute to repairing damaged composite laminates.

Although scoliosis is commonly seen in patients with Prader-Willi syndrome, the patterns and extent of the deformity may change along their growth. Increased body weight is another issue in these patients, and its relationship with scoliosis is still controversial. The aim of this study was to evaluate scoliosis in patients with PWS, and its relationship with BMI. This was a retrospective cohort study in which a series of radiographic images and BMI from each patient were collected, and the data were rearranged following the age at which they were recorded. These patients were subsequently labeled as non-Scoliotic (10°), Moderate (10°-39°), and Severe (≥40°) according to their final Cobb angle, also as Normal (≤85%), Overweight (86%-95%), and Obese (≥95%) according to final BMI percentage. Thirty-four patients with age from 1 to 20 years old were recruited for this study, and the mean length of follow-up was 6.6 years. The prevalence of scoliosis was 71% (24 patients in Moderate, and 9 patients in Severe), and 65.6% were either overweight (11 patients) or obese (10 patients). The mean BMI percentage in non-scoliotic patients was 93.10 ± 13.84, which was significantly higher than that of the scoliotic groups (P = 0.0180). When looking at the longitudinal change, the non-Scoliotic group had high BMI since childhood, and obese patients had less spine deformity also from early childhood. In this study, we found that the prevalence of scoliosis in Taiwanese population with PWS was 71% without gender preference. Not every patient had a high BMI, and obese patients seemed to have significantly less chance to develop scoliosis. Level III.

Inflammatory leiomyosarcoma is a rare myogenic tumor with striking inflammatory infiltrates and a specific genomic pattern of near-haploidization despite exception(s). Recent studies demonstrated that inflammatory leiomyosarcoma shares substantially overlapping features with histiocyte-rich rhabdomyoblastic tumor, including expression of rhabdomyoblastic markers such as myogenin, MyoD1, and PAX7 and a high prevalence of genomic near-haploidization, suggesting that they represent a unifying entity, for which the term inflammatory rhabdomyoblastic tumor was coined. In this study, we identified 4 pulmonary tumors histologically typical of inflammatory leiomyosarcomas, all in men (aged 26 to 49), presented as slow-growing well-defined nodules ranging from 1.4 to 3.5 cm, and following uneventful postoperative courses. All tumors were positive for desmin immunostaining, while only 1 and 2 were focally positive for smooth muscle actin and smooth muscle myosin heavy chain, respectively. They showed no expression of myogenin, MyoD1, or PAX7 by immunohistochemistry or RNA sequencing. Copy number analyses by whole-exome sequencing (N=1), OncoScan single-nucleotide polymorphism array (2), and fluorescence in situ hybridization (1) revealed/suggested diploid genomes. Together with a previously reported case, all these pulmonary "inflammatory leiomyosarcomas" seemed clinically, pathologically, and genomically alike. Despite a superficial resemblance to conventional inflammatory leiomyosarcoma in somatic soft tissues (now preferably termed inflammatory rhabdomyoblastic tumor), they differ in the lack of convincing rhabdomyoblastic differentiation and genomic near-haploidization. Therefore, we propose that these pulmonary tumors probably represent a distinct entity, for which the exact line of differentiation, and perhaps the most suitable terminology to better reflect its nature, remains to be determined. The term inflammatory rhabdomyoblastic tumor seems inappropriate for this group of tumors.

For persons with lower extremity (LE) amputation, acquisition of surface electromyography (sEMG) from within the prosthetic socket remains a significant challenge due to the dynamic loads experienced during the gait cycle. However, these signals are critical for both understanding the clinical effects of LE amputation and determining the desired control trajectories of active LE prostheses. Current solutions for collecting within-socket sEMG are generally (i) incompatible with a subject's prescribed prosthetic socket and liners, (ii) uncomfortable, and (iii) expensive. This study presents an alternative within-socket sEMG acquisition paradigm using a novel flexible and low-profile electrode. First, the practical performance of this Sub-Liner Interface for Prosthetics (SLIP) electrode is compared to that of commercial Ag/AgCl electrodes within a cohort of subjects without amputation. Then, the corresponding SLIP electrode sEMG acquisition paradigm is implemented in a single subject with unilateral transtibial amputation performing unconstrained movements and walking on level ground. Finally, a quantitative questionnaire characterizes subjective comfort for SLIP electrode and commercial Ag/AgCl electrode instrumentation setups. Quantitative analyses suggest comparable signal qualities between SLIP and Ag/AgCl electrodes while qualitative analyses suggest the feasibility of using the SLIP electrode for real-time sEMG data collection from load-bearing, ambulatory subjects with LE amputation.

Oral squamous cell carcinoma (OSCC) is an extremely common head and neck cancer with a poor 5-year survival rate, especially in cases of metastatic disease. Interleukin (IL)-11 reportedly promotes cell growth and the epithelial-mesenchymal transition process in metastasis. However, the molecular mechanisms of IL-11 in OSCC metastasis are unclear. This study found that IL-11 upregulates matrix metalloproteinase 13 (MMP-13) expression in OSCC via the IL-11 receptor alpha subunit/glycoprotein 130 receptors that activate phosphatidyl-inositol 3-kinase, Ak strain transforming, and activator protein 1 signaling, which subsequently enhance MMP-13-induced tumor metastasis. TIMER2.0 analysis revealed a positive correlation between MMP-13 and IL-11 levels (r = 0.454). Moreover, a strong positive association was observed between higher levels of IL-11 expression in OSCC tissue (p 0.01), lymph node metastasis (p = 0.0154), and clinical disease stage (p = 0.0337). IL-11 knockdown suppressed the migration of OSCC cells (p 0.05). The evidence indicates that IL-11 can serve as a new molecular therapeutic target in OSCC metastasis.

This study implemented the measurement results and administrative information obtained from the hole plate into the Digital Calibration Certificate (DCC). The DCC comprises three parts: Norms and Standards, Hierarchical Structure, and XML as Exchange Format. DCCs play a significant role in the field of metrology and statistics by ensuring data interoperability, correctness, and traceability during the conversion and transmission process. The hole plate is a length standard used for two-dimensional geometric error measurements. We evaluated the accuracy of the high-precision coordinate measuring machine (CMM) in measuring a hole plate and compared the measurement error results obtained from the hole plate with those of the laser interferometer, autocollimator, and angle square. The results show that the maximum difference in linear error is −0.30 μm, the maximum difference in angle error is −0.78″, and the maximum difference in squareness error is 4.54″. The XML is designed for machine-readability and is modeled and edited using the XMLSpy 2022 software, which is based on information published by PTB. The administrative management and measurement results tasks are presented in PDF format, which is designed for human-readability and ease of use. Overall, we implemented the measurement results and information obtained from the hole plate into the DCC.

This study investigated the mechanical properties, glass-forming ability (GFA), and microstructural evolution of ZrCuAlNi amorphous alloys with various niobium (Nb) and silver (Ag) additions under static (1 × 10–1 – 1 × 10–3 s−1) and dynamic (3 × 103 – 5 × 103 s−1) loading conditions. The x-ray diffraction (XRD) results revealed that all of the alloys had an amorphous structure, and the GFA improved with an increasing Ag content. The Zr56Cu24Al9Ni7Nb1Ag3 alloy showed the highest flow stress among the various alloys under both strain rate ranges. For all of the alloys, the fracture strain increased with an increasing Ag content. Moreover, the strain rate sensitivity increased with increasing strain rate. The scanning electron microscopy observations showed that the fracture surfaces had a dimple structure. As the Ag content increased, the dimple structure changed from a smooth to molten appearance. In addition, the dimple structure density increased with an increasing strain rate. The results present that the ductility of the ZrCuAlNi amorphous alloys could be improved by increasing the Ag element content.

Visual perceptual dysfunctions were common in children with developmental delays, and have severe adverse impacts on children’s daily activities. Recent studies have shown that technologies such as virtual reality and imaging can provide a motivating and engaging tool for remediating visual perceptual dysfunctions. This study was aimed to present the work we were conducting in experimenting with augmented reality (AR) for visual perceptual rehabilitation in children with developmental delay. Sixty participants (mean age = 7.96 ± 1.4) were equally divided into an experimental group trained with proposed KBTS (KBTS group) and a control group trained using traditional visual perceptual training (TVPT group). Each group completed an 8-week training program (two 30-minute sessions per week). Visual perceptual assessments (Test of Visual Perceptual Skill- 3rd Edition, Beery-Buktenica Developmental Test of Visual-Motor Integration- 6th Edition) and functional outcome measures (Vineland Adaptive Behavior Scale- Chinese Version, School Function Assessment- Chinese Version) were administered to investigate the effectiveness of the intervention. The KBTS group significantly outperformed the TVPT group in assessments of visual-motor integration, visual perceptual skills, and school functions. The effectiveness of the KBTS was supported by robust effect sizes for the pre- and post-intervention comparisons of visual perceptual and visual motor integrative functions between the KBTS group and the TVPT group. This study suggests that KBTS effectively improves visual-motor integration and overall visual perceptual functions in children with developmental delays. This study has discussed the ideas for incorporating several principles of game scenarios for visual perceptual rehabilitation, and the proposed KBTS still have raised a number of issues requiring further work. Enabling users to perform visual motor integrative tasks in an augmented reality world offers the potential for developing advanced visual perceptual skills which may be more easily transferable to activities of daily living than other techniques. Augmented reality has the potential to achieve entertaining and satisfying outcomes for visual perceptual rehabilitation, and making use of the potential applications of AR technologies should be considered more beneficial for the home-based rehabilitation during the current pandemic situations. Other clinical applications are discussed as well.

Bizarre parosteal osteochondromatous proliferation (BPOP, or Nora’s lesion) is a benign bone surface lesion which most commonly occurs in the digits of young patients and has a high recurrence rate. Histologically, it is composed of a mixture of disorganized bone, cartilage, and spindle cells in variable proportions and characterized by amorphous “blue bone” mineralization. Recurrent chromosomal abnormalities including t(1;17)(q32-42;q21-23) and inv(7)(q21.1-22q31.3-32) have been reported in BPOP. However, the exact genes involved in the rearrangements remain unknown. In this study, we analyzed 7 BPOP cases affecting the fingers, toe, ulna, and radius of 4 female and 3 male patients, aged 5 to 68 years. RNA sequencing on 5 cases identified genetic fusions between COL1A2 and LINC-PINT, a long non-coding RNA, in 3 cases, and COL1A1::MIR29B2CHG fusion in 1, both validated with fluorescence in situ hybridization (FISH) and reverse transcription-PCR. The remaining fusion-negative case harbored 3 COL1A1 mutations as revealed by whole exome sequencing and confirmed with Sanger sequencing. All these genetic alterations were predicted to cause frameshift and/or truncation of COL1A1/2. The chromosomal locations of COL1A2 (7q21.3), LINC-PINT (7q32.3), COL1A1 (17q21.33), and MIR29B2CHG (1q32.2) were consistent with the breakpoints identified in the previous cytogenetic studies. Subsequent screening of 2 BPOPs by FISH identified one additional case with COL1A1 rearrangement. Our findings are consistent with reported chromosomal abnormalities, and implicate the disruption of type I collagen through COL1A1/2 rearrangements or COL1A1 mutations in the tumorigenesis of BPOP. The prevalence and tumorigenic mechanisms of these COL1A1/2 alterations in BPOP require further investigation.

Oxaliplatin, a third-generation platinum derivative, has become one of the main chemotherapeutic treatments for esophagus, gastric and colorectal cancer; however, it is still unclear the potential effectiveness for pancreatic ductal adenocarcinoma (PDAC) with gemcitabine resistance. Here, we observed that PDAC tumors have low level of organic cation transporter 2 (OCT2, also known as SLC22A2) compared with non-tumor tissues and identified that OCT2 expression is positively correlated with oxaliplatin sensitivity in PDAC cells. Treatment of OCT2 inhibitors or knockdown of OCT2 expression significantly decreased the sensitivity to oxaliplatin in PANC-1 cells. In addition, bisulfite sequencing polymerase chain reaction analysis revealed that higher methylation frequency represses OCT2 expression in gemcitabine-resistant PANC-1 (PANC-1/GR) cells. Moreover, we found that treatment of DNA methyltransferase (DNMT) inhibitors, decitabine or 5-azacytidine recover OCT2 expression and oxaliplatin sensitivity in PANC-1/GR cells, and DNMT1 level has inverse correlation with OCT2 expression in PDAC cells and tumors. Our findings jointly suggest that OCT2 expression is a potential and predictive marker for evaluating oxaliplatin sensitivity and developing alternative treatments for PDAC patients with gemcitabine resistance.

The mechanical properties of aluminium–scandium alloy are investigated at strain rates ranging from 0.0005 to 2600 s−1 and a temperature of 25°C using a material testing system and split-Hopkinson ...

Polymer composite samples were prepared consisting of NC-826 epoxy and approximately 0.1–0.5 wt% aerographite nanomaterial. The compression properties of the various samples were evaluated at strain rates of 10−3–10−1 s−1 using a universal testing machine. The fracture surfaces of the tested samples were examined by scanning electron microscope. Additional composite samples consisting of NC-826 epoxy and 0.3 wt% multiwalled carbon nanotubes (MWCNTs) were prepared and tested under the same compression strain rates of approximately 10−1–10−3 s−1. In general, the results showed that the addition of aerographite nanomaterials to the resin matrix is beneficial in suppressing crack propagation under compression loads and therefore leads to an improved stress, toughness, and fracture strain compared to the pure resin sample. The results additionally showed that the use of MWCNTs as a reinforcement material yields a further small improvement in the mechanical properties of the sample.

BackgroundStroke leads to tremendous impacts on patients and the healthcare system. It is crucial to explore the potential management of rehabilitation. Acupuncture and traditional Chinese herbal medicine (TCHM) integrated with conventional rehabilitation benefit post-stroke functional recovery.MethodsWe retrospectively reviewed the medical records of all patients included in the Integrated Traditional Chinese-Western Medicine care program for stroke (ITCWM-stroke care program) in 2019 in Taipei Tzu Chi Hospital to investigate the effects of acupuncture and TCHM integrated with conventional rehabilitation on National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) scores before and after the program.ResultsA total of 255 stroke inpatients were retrieved and divided into acupuncture and acupuncture + TCHM group by hemorrhagic and ischemic stroke types, respectively. All the patients were recruited in the program at the early subacute phase after stroke onset. Of the hemorrhagic and ischemic stroke subjects, the NIHSS and BI total scores were significantly improved in the acupuncture and acupuncture + TCHM groups. The subgroup analysis results showed that in subjects with a baseline BI score ≤ 40, the acupuncture + TCHM group significantly improved BI total score better than the acupuncture group in both hemorrhagic (p < 0.05) and ischemic (p < 0.05) stroke subjects.ConclusionAcupuncture and TCHM integrated with conventional rehabilitation significantly improve stroke patients’ functional recovery at the early subacute phase. Acupuncture + TCHM contributes to better activities of daily living (ADL) improvements in stroke patients with a baseline BI score ≤ 40. We suggest integrating acupuncture and TCHM into the post-stroke rehabilitation strategy, especially for stroke patients with poor ADL function.

The clinicopathologic relevance of various gene rearrangements underlying dermatofibrosarcoma protuberans (DFSP) remains insufficiently characterized. In 188 DFSPs, we determined PDGFB, COL1A1, PDGFD, COL6A3, and EMILIN2 rearrangements by fluorescence in situ hybridization (FISH). The clinicopathologic significance of rearrangement types and factors related to recurrence and metastasis were statistically analyzed. In all, classic PDGFB rearrangement, cryptic COL1A1-PDGFB fusion, and PDGFD rearrangement were identified in 172 (91.4%), 8 (4.3%), and 8 (4.3%: 4 COL6A3-PDFGD, 4 EMILIN2-PDGFD) cases, respectively. In an index DFSP harboring the cryptic fusion, the COL1A1-PDGFB transcript was confirmed by both RNA sequencing and reverse transcription-polymerase chain reaction. In comparison with cases harboring classic PDGFB rearrangement, cryptic PDGFB-rearranged DFSPs usually exhibited higher 5'-COL1A1 copy numbers. In a combined reappraisal of published and current cases, COL6A3-PDGFD-positive DFSPs (n=16) predominated in females (n=14, 88%) and torso (n=14, 88%), especially the breast (n=7, 44%); EMILIN2-PDGFD-positive DFSPs (n=6) preferentially demonstrated near exclusively subcutaneous growth (n=5, 83%) and fibrosarcomatous transformation (n=5, 83%). In our cohort, local recurrence was related to fibrosarcomatous variant (P=0.029, odds ratio=3.478) and head and neck location (P=0.046, odds ratio=3.508). Distant metastasis only occurred in the fibrosarcomatous variant (9/73, 12.3%) but not in other cases. In conclusion, 8.6% of DFSPs are negative for PDGFB break-apart FISH, which, especially those with challenging subcutaneous and circumscribed manifestation, require complementary diagnosis by FISH assays targeting COL1A1 and PDGFD. The types of fusion gene rearrangements, head and neck location, and fibrosarcomatous transformation may account for clinicopathologic and prognostic variations in DFSPs and warrant future independent validation.

Primary intracranial ependymoma is a challenging tumor to treat despite the availability of multidisciplinary therapeutic modalities, including surgical resection, radiotherapy, and adjuvant chemotherapy. After the completion of initial treatment, when resistant tumor cells recur, salvage therapy needs to be carried out with a more precise strategy. Circulating tumor cells (CTCs) have specifically been detected and validated for patients with primary or recurrent diffused glioma. The CTC drug screening platform can be used to perform a mini-invasive liquid biopsy for potential drug selection. The validation of potential drugs in a patient-derived xenograft (PDX) mouse model based on the same patient can serve as a preclinical testing platform. Here, we present the application of a drug testing model in a six-year-old girl with primary ependymoma on the posterior fossa, type A (EPN-PFA). She suffered from tumor recurrence with intracranial and spinal seeding at 2 years after her first operation and extraneural metastases in the pleura, lung, mediastinum, and distant femoral bone at 4 years after initial treatment. The CTC screening platform results showed that everolimus and entrectinib could be used to decrease CTC viability. The therapeutic efficacy of these two therapeutic agents has also been validated in a PDX mouse model from the same patient, and the results showed that these two therapeutic agents significantly decreased tumor growth. After precise drug screening and the combination of focal radiation on the femoral bone with everolimus chemotherapy, the whole-body bone scan showed significant shrinkage of the metastatic tumor on the right femoral bone. This novel approach can combine liquid biopsy, CTC drug testing platforms, and PDX model validation to achieve precision medicine in rare and challenging tumors with extraneural metastases.

Because it is an accessible and routine image test, medical personnel commonly use a chest X-ray for COVID-19 infections. Artificial intelligence (AI) is now widely applied to improve the precision of routine image tests. Hence, we investigated the clinical merit of the chest X-ray to detect COVID-19 when assisted by AI. We used PubMed, Cochrane Library, MedRxiv, ArXiv, and Embase to search for relevant research published between 1 January 2020 and 30 May 2022. We collected essays that dissected AI-based measures used for patients diagnosed with COVID-19 and excluded research lacking measurements using relevant parameters (i.e., sensitivity, specificity, and area under curve). Two independent researchers summarized the information, and discords were eliminated by consensus. A random effects model was used to calculate the pooled sensitivities and specificities. The sensitivity of the included research studies was enhanced by eliminating research with possible heterogeneity. A summary receiver operating characteristic curve (SROC) was generated to investigate the diagnostic value for detecting COVID-19 patients. Nine studies were recruited in this analysis, including 39,603 subjects. The pooled sensitivity and specificity were estimated as 0.9472 (p = 0.0338, 95% CI 0.9009–0.9959) and 0.9610 (p < 0.0001, 95% CI 0.9428–0.9795), respectively. The area under the SROC was 0.98 (95% CI 0.94–1.00). The heterogeneity of diagnostic odds ratio was presented in the recruited studies (I2 = 36.212, p = 0.129). The AI-assisted chest X-ray scan for COVID-19 detection offered excellent diagnostic potential and broader application.

Bladder cancer (BC) is one of the most prevalent cancers worldwide. However, the recurrence rate and five-year survival rate have not been significantly improved in advanced BC, and new therapeutic strategies are urgently needed. The anticancer activity of stellettin B (SP-2), a triterpene isolated from the marine sponge Rhabdastrella sp., was evaluated with the MTT assay as well as PI and Annexin V/7-AAD staining. Detailed mechanisms were elucidated through an NGS analysis, protein arrays, and Western blotting. SP-2 suppressed the viability of BC cells without severe toxicity towards normal uroepithelial cells, and it increased apoptosis with the activation of caspase 3/8/9, PARP, and γH2AX. The phosphorylation of FGFR3 and its downstream targets were downregulated by SP-2. Meanwhile, it induced autophagy in BC cells as evidenced by LC3-II formation and p62 downregulation. The inhibition of autophagy using pharmacological inhibitors or through an ATG5-knockout protected RT-112 cells from SP-2-induced cell viability suppression and apoptosis. In addition, the upregulation of DAPK2 mRNA and protein expression also contributed to SP-2-induced cytotoxicity and apoptosis. In RT-112 cells, an FGFR3-TACC3-knockout caused the downregulation of DAPK2, autophagy, and apoptosis. In conclusion, this is the first study demonstrating that SP-2 exhibits potent anti-BC activity by suppressing the FGFR3-TACC3/Akt/mTOR pathway, which further activates a novel autophagy/DAPK2/apoptosis signaling cascade.

Background Inflammation is a potential risk factor of mental disturbance. FKBP5 that encodes FK506-binding protein 51 (FKBP51), a negative cochaperone of glucocorticoid receptor (GR), is a stress-inducible gene and has been linked to psychiatric disorders. Yet, the role of FKBP51 in the inflammatory stress-associated mental disturbance remained unclear. Methods Fkbp5-deficient (Fkbp5-KO) mice were used to study inflammatory stress by a single intraperitoneal injection of lipopolysaccharide (LPS). The anxiety-like behaviors, neuroimaging, immunofluorescence staining, immunohistochemistry, protein and mRNA expression analysis of inflammation- and neurotransmission-related mediators were evaluated. A dexamethasone drinking model was also applied to examine the effect of Fkbp5-KO in glucocorticoid-induced stress. Results LPS administration induced FKBP51 elevation in the liver and hippocampus accompanied with transient sickness. Notably, Fkbp5-KO but not wild-type (WT) mice showed anxiety-like behaviors 7 days after LPS injection (LPS-D7). LPS challenge rapidly increased peripheral and central immune responses and hippocampal microglial activation followed by a delayed GR upregulation on LPS-D7, and these effects were attenuated in Fkbp5-KO mice. Whole-brain [18F]-FEPPA neuroimaging, which target translocator protein (TSPO) to indicate neuroinflammation, showed that Fkbp5-KO reduced LPS-induced neuroinflammation in various brain regions including hippocampus. Interestingly, LPS elevated glutamic acid decarboxylase 65 (GAD65), the membrane-associated GABA-synthesizing enzyme, in the hippocampus of WT but not Fkbp5-KO mice on LPS-D7. This FKBP51-dependent GAD65 upregulation was observed in the ventral hippocampal CA1 accompanied by the reduction of c-Fos-indicated neuronal activity, whereas both GAD65 and neuronal activity were reduced in dorsal CA1 in a FKBP51-independent manner. GC-induced anxiety was also examined, which was attenuated in Fkbp5-KO and hippocampal GAD65 expression was unaffected. Conclusions These results suggest that FKBP51/FKBP5 is involved in the systemic inflammation-induced neuroinflammation and hippocampal GR activation, which may contribute to the enhancement of GAD65 expression for GABA synthesis in the ventral hippocampus, thereby facilitating resilience to inflammation-induced anxiety.

Intrahepatic cholangiocarcinoma (ICC) is characterized by fibrous stroma and clinical behavior more aggressive than that of hepatocellular carcinoma (HCC). Scirrhous HCC is a subtype of HCC with fibrous stroma, frequently has partial cholangiocytic differentiation, and is more likely to have an aggressive behavior. This study explored the interaction of liver cancer cells with the extracellular matrix.Liver cancer cells grown on collagen 1-coated plates showed upregulation of cholangiocytic marker expression but downregulation of hepatocytic marker expression. Three-dimensional sphere culture and Boyden chamber assay showed enhanced invasion and migration ability in collagen 1-conditioned liver cancer cells. Interaction with collagen 1 reduced liver cancer cell proliferation. RNA sequencing showed that in the liver cancer cells, collagen 1 upregulated cell cycle inhibitor expression and cell-matrix interaction, tumor migration, and angiogenesis pathways, but downregulated liver metabolic function pathways. Cholangiocytic differentiation and invasiveness induced by collagen 1 was mediated by the mitogen-activated protein kinase (MAPK) pathway, which was regulated by cell-matrix interaction-induced Src activation. Analysis of the Cancer Genome Atlas cohort showed that collagen 1 induced and suppressed genes were highly enriched in ICC and HCC, respectively. In HCC samples, collagen 1-regulated genes were strongly coexpressed and correlated with COL1A1 expression.Liver cancer cell-matrix interaction induces cholangiocytic differentiation and switches liver cancer cells from a proliferative to an invasive phenotype through the Src/MAPK pathway, which may partly explain the differences in the behaviors of HCC and ICC.

Aims Intracranial myxoid mesenchymal tumors (IMMTs) with fusions between EWSR1/FUS and CREB transcription factors have morphologic overlap with myxoid angiomatoid fibrous histiocytoma (mAFH) and myoepithelial tumor/carcinoma (MET/MEC). We aimed to study the clinicopathologic and genetic spectrum of extracranial IMMT-like tumors and their relationships with mAFH and MET/MEC. Methods Twelve extracranial tumors harboring EWSR1/FUS-CREB fusions across different histologic groups were characterized using RNA sequencing, FISH and/or RT-PCR. Results There were 4 IMMT-like neoplasms, 3 MET/MECs, and 5 mAFHs from the tibia (n=1), oral cavity (n=2), and soft tissues (n=9; 5 in the extremities), harboring EWSR1-ATF1 in 4 cases, FUS-CREM and EWSR1-CREM in 2 each, and EWSR1-CREB1 in 2. Multinodular growth, reticular/cording/trabecular arrangements, myxocollagenous matrix, and lymphocytic infiltrates variably prevailed among the 3 groups. mAFHs were characterized by cells with syncytial cytoplasm. IMMT-like neoplasms and MET/MECs shared cells with distinct boundaries, but only MET/MECs expressed GFAP and/or S100. MUC4 and ALK were expressed in some IMMT-like neoplasms (2/4; 2/4) and mAFH (2/5; 1/5). Pan-TRK reactivity was observed in two IMMT-like neoplasms with upregulated NTRK3 mRNA and one MEC. Local recurrences, typically ≥ 12 months postoperatively, developed in 2/3 IMMT-like neoplasms, 1/2 MET/MECs, and 0/4 mAFHs with follow-up. No definite associations were found between fusion types and histology, immunoprofile or outcome. Conclusions We demonstrated the similarities and differences among 3 extracranial myxocollagenous tumor groups sharing EWSR1/FUS-CREB fusions. Oral IMMT-like neoplasms harboring FUS-CREM or EWSR1-ATF1 and FUS-CREM-positive

Sclerosing epithelioid fibrosarcoma (SEF) is an aggressive soft tissue sarcoma, characterized by a distinctive epithelioid phenotype in a densely sclerotic collagenous stroma, that shows frequent MUC4 immunoreactivity and recurrent gene fusions, often involving EWSR1 gene. A pathogenetic link with low-grade fibromyxoid sarcoma (LGFMS) has been suggested, due to cases with hybrid morphology as well as overlapping genetic signature. However, a small subset of SEF is negative for MUC4 and lacks the canonical EWSR1/FUS gene rearrangements. Triggered by the identification of recurrent YAP1-KMT2A gene fusions by RNA sequencing in 3 index cases of MUC4-negative, EWSR1/FUS fusion-negative SEF, we further investigated a cohort of 14 similar SEF cases (MUC4-negative, EWSR1/FUS fusion-negative) by fluorescence in situ hybridization (FISH), reverse transcription-polymerase chain reaction, and/or DNA-based massively parallel sequencing (MSK-IMPACT) for abnormalities in these genes. Three additional SEFs with KMT2A gene rearrangements and one additional case with YAP1 gene rearrangements were identified by FISH. In addition, one case with YAP1-KMT2A and one with KMT2A-YAP1 fusion were detected by reverse transcription-polymerase chain reaction and MSK-IMPACT, respectively. As a control group, 24 fibromyxoid spindle cell tumors, diagnosed or suspected as fusion-negative LGFMS, were also tested for YAP1 and KMT2A abnormalities by FISH, but none were positive. The YAP1/KMT2A-rearranged SEF group affected patients ranging from 10 to 86 years old (average and median: 45) of both sexes (4 females, 5 males). The tumors involved somatic soft tissues with a wide distribution, including extremities, trunk, neck, and dura. Histologically, the tumors showed variable cellularity, with monotonous ovoid to epithelioid tumor cells and hyalinized collagenous background typical of SEF. More than half of the cases showed infiltrative borders, within fat or skeletal muscle. No LGFMS component was identified. All tumors were negative for MUC4 and had an otherwise nonspecific immunophenotype. Of the 6 cases with available follow-up information, 2 had local recurrences, and 2 developed soft tissue and/or bone metastases, including 1 of them died of the disease.

Myoepithelial tumors of soft tissue are uncommon neoplasms characterized histologically by spindle to epithelioid cells arranged in cords, nests, and/or reticular pattern with chondromyxoid to hyaline stroma, and genetically by rearrangement involving EWSR1 (among other less common genes) in about half of the cases. The diagnosis often requires immunostaining to confirm myoepithelial differentiation, most importantly the expression of epithelial markers and S100 protein and/or GFAP. However, there are cases wherein the morphology is reminiscent of myoepithelial tumors, while the immunophenotype falls short. Here, we report 2 highly similar myoepithelioma-like tumors arising in the hands of young adults. Both tumors were well-demarcated and composed of alternating cellular areas with palely eosinophilic hyaline stroma and scattered acellular zones of densely eosinophilic collagen deposition. The tumor cells were mainly epithelioid cells and arranged in cords or small nests. Vacuolated cells encircling hyaline matrix globules were focally prominent. A minor component of nonhyaline fibrous nodular areas composed of bland spindle cells and rich vasculature was also observed. Perivascular concentric spindle cell proliferation and perivascular hyalinization were present in some areas. The tumor cells were positive for CD34 and epithelial membrane antigen (focal) by immunostaining, while largely negative for cytokeratin, S100, GFAP, p63, GLUT1, and claudin-1. By RNA sequencing, a novel OGT-FOXO3 fusion gene was identified in case 1 and confirmed by reverse transcription polymerase chain reaction and fluorescence in situ hybridization in both cases. Sharing the unusual clinicopathologic features and the novel fusion, these 2 cases probably represent a distinct tumor entity, whose relationship with myoepithelial tumors and tumorigenic mechanisms exerted by the OGT-FOXO3 fusion remain to be studied.

Near-field lattice spectroscopy has shown that the structure information for a lattice or periodic pattern can be obtained by measuring the diffracted spectrum of a broad-band light source at one spatial position. This technique is verified experimentally using a transmitting grating, supercontinuum white light laser, and a reflective concave mirror. The calculated grating’s period from the detected lattice spectroscopy is close to the measured period with an optical microscope, which demonstrates the validity and feasibility of this scheme.

Uterine mesenchymal tumors are genetically heterogenous; those with uniform cytomorphology, best exemplified by endometrial stromal tumors, often contain various fusion genes. Novel fusions involving ESR1 and GREB1, key factors in sex hormone pathways, have been implicated in rare uterine mesenchymal tumors. Particularly, the fusions between 5'-ESR1/GREB1 and 3'-NCOA2/NCOA3 were recently identified in 4 uterine tumors resembling ovarian sex-cord tumor (UTROSCT). By RNA sequencing, pathology review, and FISH screening, we identified 4 uterine sarcomas harboring rearranged GREB1, including GREB1-NCOA2 and the novel GREB1-NR4A3, GREB1-SS18, and GREB1-NCOA1, validated by RT-PCR and/or FISH. They occurred in the myometrium of postmenopausal women and were pathologically similar despite minor differences. Tumor cells were generally uniform and epithelioid, with vesicular nuclei and distinct to prominent nucleoli. Growth patterns included solid sheets, trabeculae/cords, nests, and fascicles. Only 1 tumor showed small foci of definitive sex-cord components featuring well-formed tubules, retiform structures, Leydig-like cells, and lipid-laden cells and exhibiting convincing immunoreactivity to sex-cord markers (calretinin, α-inhibin, and Melan-A). In contrast, all the 4 classic UTROSCT we collected occurred in premenopausal patients, consisted predominantly of unequivocal sex-cord elements, prominently expressed multiple sex-cord markers, and harbored ESR1-NCOA3 fusion. Combined with previously reported cases, GREB1-rearranged tumors involved significantly older women (P=0.001), tended to be larger and more mitotically active, showed more variable and often inconspicuous sex-cord differentiation, and appeared to behave more aggressively than ESR1-rearranged UTROSCT. Therefore, these 2 groups of tumors might deserve separate consideration, despite some overlapping features and the possibility of belonging to the same disease spectrum.

Background Type 2 diabetes mellitus (T2DM) is a condition involving several molecular mechanisms related to the intestinal microbiota for its development. Intestinal fatty acid‐binding protein (I‐FABP) is a sensitive marker to study enterocyte damage. A prebiotic is a non‐digestible food ingredient that improves host health by selectively stimulating the growth and/or activities of bacteria in the colon. We aimed to clarify the currently described effects of prebiotics in the prevention and management of T2DM. Methods In this case‐control study, we chose 68 participants with T2DM and 52 healthy participants. Both groups were further divided based on consumption of prebiotics. Forty participants with T2DM consumed prebiotics, and 28 did not; 30 healthy volunteers consumed prebiotics, and 22 did not. We used the analysis of variance to compare the inflammation levels between the case and control groups. Multiple linear regression was performed for the significantly correlated groups to estimate the influence of prebiotics on inflammation level. Results Age was a significant factor for difference in I‐FABP levels (standardized coefficient: 0.06; P = .047). The analysis of eating habits showed that vegetarian diets produced lower I‐FABP levels than non‐vegetarian diets (standardized coefficient: −2.55; P = .022). Results showed that patients with T2DM who consumed prebiotics expressed lower I‐FABP levels, reflecting an improvement in inflammation level, than the healthy volunteers who did not consume prebiotics (standardized coefficient: −3.20; P = .019). Conclusions For patients with T2DM, prebiotics supplemented produced no significant impact on serum I‐FABP levels., To evaluate effects of prebiotics in the prevention and management T2DM, totally 120 patients were recruited for the initial screening with I‐FABP. The participants in this study had no history of gastrointestinal disease and had not been treated with antibiotics or laxatives within 3 months before the experiment; all T2DM patients received dietary advice to control and treat diabetes. Blood or urine samples were collected at baseline and at 1, 3, and 6 months, followed by proper statistical analysis.