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BACKGROUND/PURPOSE Decorin is a small leucine-rich proteoglycan rich in extracellular matrix with potential antitumor activity. However, the role of decorin in hematological malignancies remains unclear, especially in the case of multiple myeloma (MM), a bone marrow (BM) stroma-dependent plasma cell neoplasm. METHODS We measured decorin levels in BM plasma samples from 270 patients with newly diagnosed MM (NDMM) using enzyme-linked immunosorbent assays. RESULTS Patients were divided into high decorin (H-DCN, > 18.99 ng/mL) and low decorin (L-DCN

Our aim is to investigate the association of cerebral deep medullary veins (DMVs) with white matter microstructural integrity and regional brain atrophy in MRI. In a community-based cohort of 979 participants (mean age 55.4 years), DMVs were identified on susceptibility-weighted imaging. Brain structural measurements including gray matter and hippocampus volumes, as well as diffusion tensor metrics, were evaluated. The mean (SD)number of DMVs was 19.0 (1.7). A fewer number of DMVs was related to lower fractional anisotropy and higher mean diffusivity in multiple voxels on the white matter skeleton (threshold-free cluster enhancement corrected p

Background/purpose Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the curative therapy for acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS), but advanced age with multiple comorbidities limits the eligibility for allo-HSCT. We conducted a retrospective study to investigate the comorbidities assessments and prognostic factors that predict outcomes for these patients. Methods Clinical data of patients older than 50 years who had received diagnoses of AML or MDS and underwent allo-HSCT were obtained. Information on patient characteristics, including age, gender, allogeneic transplant type, conditioning regimens, Charlson comorbidity index (CCI), and presence of acute graft-versus-host disease (GVHD) or chronic GVHD, were collected and analyzed. Results Two hundred fifty-five elderly patients with a median age at allo-HSCT of 57 years were included. The significant prognostic factors associated with worse overall survival (OS) were CCI ≥3 (hazard ratio: 1.88) and grade III–IV acute GVHD (3.18). Similar findings were noted in the non-relapse mortality analysis. To investigate the effects of chronic GVHD on patient outcomes, OS analysis was performed for those with survival >100 days after transplantation. The results revealed CCI ≥3 (1.88) and grade III–IV acute GVHD (2.73) remained poor prognostic factors for OS, whereas mild chronic GVHD (0.43) was associated with better OS. Conclusion This cohort study suggests that CCI ≥3 predicts poor outcomes, primarily due to a higher NRM risk. Careful management of GVHD after transplantation could improve outcomes in elderly patients with AML or MDS after allo-HSCT.

MXene aerogels with a porous microstructure are a promising electromagnetic interference (EMI) shielding material due to its low density and excellent electrical conductivity, which has attracted widespread attention. Compared with traditional EMI shielding materials that rely on reflection as the primary mechanism, MXene aerogels with absorption as the dominant mechanism have greater potential for development as a novel EMI shielding material because of its ability to reduce environmental contamination from reflected electromagnetic (EM) waves from materials. In this study, a novel Ti3C2Tx MXene/PEDOT:PSS hybrid aerogel was presented by freeze-drying and thermal annealing using few-layered Ti3C2Tx MXene and the conductive polymer poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS). PEDOT:PSS not only improved the gelling ability of Ti3C2Tx but also successfully established a conductive bridge between MXene nanosheets. The experimental results demonstrated that the hybrid aerogel exhibited an obvious porous microstructure, which was beneficial for the multiple scattering of EM waves within the materials. The EMI shielding effectiveness and specific shielding effectiveness reached up to 59 dB and 10,841 dB·cm2·g-1, respectively, while the SER/SET ratio value was only 0.05, indicating superior wave absorption performance. Furthermore, the good impedance matching, due to the electrical conductance loss and polarization loss effect of the composites, plays a critical role in their excellent wave absorption and EMI shielding performance. Therefore, this work provides a practical approach for designing and fabricating lightweight absorption-dominated EMI shielding materials.

BACKGROUND Resistant hypertension (RH) has always been a difficult problem in clinical diagnosis and treatment. At present, there is no recognized safe and effective minimally invasive treatment. CASE SUMMARY An 80-year-old woman was admitted to hospital due to trigeminal neuralgia (TN). The patient had a history of RH for more than 10 years and her blood pressure (BP) was not well-controlled. Before the treatment for TN, we decided to perform chemical renal sympathetic denervation with ethanol in the Pain Department of our hospital. One year after the operation, she stopped taking antihypertensive drugs, and her BP was satisfactorily controlled within 4 years after surgery. CONCLUSION Computed tomography-guided chemical renal sympathetic modulation may be a feasible method for the treatment of RH.

The outbreak of coronavirus disease 2019 (COVID‐19) has globally strained medical resources and caused significant mortality. This study was aimed to develop and validate a prediction model based on clinical features to estimate the risk of patients with COVID‐19 at admission progressing to critical patients. Patients admitted to the hospital between January 16, 2020, and March 10, 2020, were retrospectively enrolled, and they were observed for at least 14 days after admission to determine whether they developed into severe pneumonia. According to the clinical symptoms, all patients were divided into four groups: mild, normal, severe, and critical. A total of 390 patients with COVID‐19 pneumonia were identified, including 212 severe patients and 178 nonsevere patients. The least absolute shrinkage and selection operator (LASSO) regression reduced the variables in the model to 6, which are age, number of comorbidities, computed tomography severity score, lymphocyte count, aspartate aminotransferase, and albumin. The area under curve of the model in the training set is 0.898, and the specificity and sensitivity were 89.7% and 75.5%. The prediction model, nomogram might be useful to access the onset of severe and critical illness among COVID‐19 patients at admission, which is instructive for clinical diagnosis.

There has been a surge of emphasis on polarimetric imaging modalities recently, in which Mueller matrix polarimetry (MMP) is at the heart of our understanding of polarization properties of an imaged sample. However, the historiography of MMP, predominantly undertaken in optics, largely lost sight of the potential of terahertz radiation on interactions with the imaged samples, especially biological ones. In addition, studies of MMP are generally concerned with intensity-only measurements requiring at least 16 polarization combinations, which dramatically add to the time cost in the process of measurements. The proposed study sets out to examine the complete 4 × 4 MMP from 0.2 to 1 THz using only orthogonal polarizations for two-dimensional (2-D) and 3-D imaging on leaf. A modified THz time domain spectrometer with self-designed linear polarizers is utilized for measurements and data acquisition. The Mueller matrix polar decomposition and Mueller matrix transform are employed to facilitate extraction of polarization characteristics of the imaged leaf. The time-of-flight technique is adopted to assist in the 3-D reconstruction of the leaf. The results demonstrate the effectiveness and feasibility of the novel measurement synthesis approach and the modified system for accurate characterization of the sample. Meanwhile, the findings indicate that MMP is superior in feature extraction as well as contrast enhancement of the sample. The insights gained from this article may be of assistance to the characterization of biological samples with MMP at higher frequencies for future research.

In this work, a fully integrated phased array using multi‐layer printed circuit board (PCB) fabrication technologies is presented. This array is directly fed by 50 Ω coaxial cables, without balanced‐to‐unbalanced transitions. An asymmetric dipole is used to achieve stable input impedance. Furthermore, to broaden the operating bandwidth, a coupling patch is designed beneath the asymmetric dipole , which also eliminates the common‐mode resonance and decreases the array profile. In addition, three wide‐angle impedance matching (WAIM) layers with different structures are utilised to improve the scan range in all scanning planes. Infinite array simulations indicate that the proposed array can operate over a 5.1:1 bandwidth (2.4 ∼ 12.2 GHz) with an active voltage standing wave ratio below 3 while scanning up to ± 60° in H plane and ±75° in the E plane. Furthermore, the proposed antenna, whose cross‐polarization levels remain below −35 and −7.5 dB when scanning up to 75° in the E plane and 60° in the D plane, demonstrates the merits of high polarization purity. Array simulations are verified by the measurements of a 12 × 12 prototype, and good agreement is observed.

In this letter, an appropriate approach is proposed for modeling the electromagnetic (EM) scattering from composite rough surfaces made up of wake due to a submerged body and wind-driven sea waves. The computational fluid dynamics (CFD) method is used to extract the air–seawater surface wake generated by an underwater moving body at different speeds and depths. Then, the wake is superimposed on the randomly rough wind-driven sea surfaces that obey the Pierson–Moskowitz power spectrum. The small slope approximation (SSA) method is adopted to calculate the EM scattering by the composite surfaces. The simulation results are obtained and justified.

Background: Few studies have investigated the association between cognition and brain volume associated with cerebral small vessel disease (CSVD). Objective: We investigated the association between cognition and brain volume and neuroimaging markers of CSVD in a community-dwelling population. Methods: Participants (n = 993, age≥35 years) from the community-based Shunyi Study were included to investigate the association between neuroimaging markers and cognition cross-sectionally. Magnetic resonance imaging markers included brain volume measurements of the total cerebrum, white matter, gray matter, and CSVD imaging markers. Cognitive performance was assessed using neuropsychological tests of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Fuld Object Memory, digit span, Trail Making Test (TMT)-A, and TMT-B. Results: For brain volume measurement, subcortical white matter fraction was positively associated with MMSE score (β= 0.034, p = 0.0062) and MoCA score (β= 0.034, p = 0.0174), and negatively associated with TMT-A and TMT-B completion time (β= –2.319, p = 0.0002; β= –2.827, p = 0.0073, respectively). For evaluation of CSVD imaging markers, the presence of lacunes was positively associated with TMT-B completion time (β= 17.241, p = 0.0028). Conclusion: In community-dwelling populations, reduced white matter volumes, as a consequence of aging and vascular damage, are associated with worse global cognition and executive function. Our findings provide potential insights into the correlation between cognition and CSVD-associated subcortical white matter injury.

The mutant burden of FLT3-ITD modulates its prognostic impact on patients with acute myeloid leukemia (AML). However, for patients with low allelic ratio (AR) FLT3-ITD (FLT3-ITDlow, AR

Purpose To evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety of single and multiple doses of PF-06881894 (pegfilgrastim-apgf; Nyvepria™), a biosimilar to reference pegfilgrastim (Neulasta®), in women with non-distantly metastatic breast cancer. Methods In Phase I (Cycle 0) of this Phase I/II study, the PD response (absolute neutrophil count [ANC]; CD34 + count), PK profile, and safety of a single 3- or 6-mg subcutaneous dose of PF-06881894 were assessed in chemotherapy-naïve patients before definitive breast surgery. In Phase II (Cycles 1–4), the PD response (duration of severe neutropenia [DSN, Cycle 1], ANC [Cycles 1 and 4]) and PK profile (Cycles 1 and 4) of single and multiple 6-mg doses of PF-06881894 concomitant with chemotherapy and after definitive breast surgery were assessed. Results Twenty-five patients (mean age 59 years) were enrolled (Cycle 0, n = 12; Cycles 1–4, n = 13). In Cycle 0, PD responses and PK values were lower with 3-mg versus 6-mg PF-06881894. In Cycles 1 and 4, mean DSN was 0.667 days after single or multiple 6-mg doses of PF-06881894, respectively. In Cycle 4 versus Cycle 1, PD responses were more robust; PK values (mean area under the curve, maximum concentration) were lower; and clearance values were higher. The safety profile of PF-06881894 was similar to that for reference pegfilgrastim. Conclusion PF-06881894 as a single 3- or 6-mg dose prior to definitive surgery, or multiple 6-mg/cycle doses postoperatively, with/without myelosuppressive chemotherapy, was consistent with the clinical pharmacology and safety profile of reference pegfilgrastim. Trial registration October 2017. ClinicalTrials.gov Identifier: NCT02650193. EudraCT Number: 2015-002057-35.

Introduction Histopathological characteristics of cytomegalovirus (CMV) lymphadenitis have been well described. Rare studies have reported the immune status and clinical features. Clinically, experts believed that CMV lymphadenitis develops in immunocompromised and immunocompetent patients. Infectious mononucleosis (IM)-like syndrome is the most well-known clinical presentation. Methods We reviewed archived CMV immunohistochemical stains on lymphoid tissues. The clinicopathological features of CMV-positive cases were studied. Results For lymph nodes, we detected CMV in 29% (5/17) allogeneic peripheral blood hematopoietic stem cell transplantation (PBSCT) recipients, 29% (4/14) post-autologous PBSCT patients, 13% (6/47) patients treated with intravenous chemotherapy, and 9% (9/96) immunocompetent patients. We detected CMV in 7% (2/24) of tonsils but not in the nasopharynx, tongue base, or spleen specimens. The patients with iatrogenic immunodeficiency ranged from 37 to 76 years old. CMV infections developed a few years after lymphoma treatment (median duration after allogeneic PBSCT, 932 days; after autologous PBSCT, 370 days; and after chemotherapy, 626 days). The most common clinical presentation was neck mass (13/25, 42%), followed by asymptomatic image finding (10/25, 40%). Positron emission tomography/computed tomography (PET/CT) scan showed increased uptake compared to the liver in all patients (11/11, 100%). Of 10 lymphoma patients, 8 (80%) had a Deauville score of 4–5; they accounted for 30% (8/27) of lymphoma patients with false-positive PET/CT scan results. All cases were self-limiting. 96% (23/25) cases had Epstein–Barr virus coinfection, and EBER-positive cells were predominantly in a few germinal centers. Conclusions Cytomegalovirus (CMV) lymphadenitis and tonsillitis were subclinical infections, not primary CMV infection with IM-like syndrome. The lymphadenopathy typically developed a few years after lymphoma treatments in the middle-aged and the elderly. The lesions mimicked lymphoma relapse in PET scans. Therefore, recognizing CMV infection in lymphoid tissues is of clinical importance. Graphic abstract

Background We externally validated Fujimoto's post-transplant lymphoproliferative disorder (PTLD) scoring system for risk prediction by using the Taiwan Blood and Marrow Transplant Registry Database (TBMTRD) and aimed to create a superior scoring system using machine learning methods. Materials and Methods Consecutive allogeneic hematopoietic cell transplant (HCT) recipients registered in the TBMTRD from 2009 to 2018 were included in this study. The Fujimoto PTLD score was calculated for each patient. The machine learning algorithm, least absolute shrinkage and selection operator (LASSO), was used to construct a new score system, which was validated using the fivefold cross-validation method. Results We identified 2,148 allogeneic HCT recipients, of which 57 (2.65%) developed PTLD in the TBMTRD. In this population, the probabilities for PTLD development by Fujimoto score at 5 years for patients in the low-, intermediate-, high-, and very-high–risk groups were 1.15%, 3.06%, 4.09%, and 8.97%, respectively. The score model had acceptable discrimination with a C-statistic of 0.65 and a near-perfect moderate calibration curve (HL test p = .81). Using LASSO regression analysis, a four–risk group model was constructed, and the new model showed better discrimination in the validation cohort when compared with The Fujimoto PTLD score (C-statistic: 0.75 vs. 0.65). Conclusion Our study demonstrated a more comprehensive model when compared with Fujimoto's PTLD scoring system, which included additional predictors identified through machine learning that may have enhanced discrimination. The widespread use of this promising tool for risk stratification of patients receiving HCT allows identification of high-risk patients that may benefit from preemptive treatment for PTLD. Implications for Practice This study validated the Fujimoto score for the prediction of post-transplant lymphoproliferative disorder (PTLD) development following hematopoietic cell transplant (HCT) in an external, independent, and nationally representative population. This study also developed a more comprehensive model with enhanced discrimination for better risk stratification of patients receiving HCT, potentially changing clinical managements in certain risk groups. Previously unreported risk factors associated with the development of PTLD after HCT were identified using the machine learning algorithm, least absolute shrinkage and selection operator, including pre-HCT medical history of mechanical ventilation and the chemotherapy agents used in conditioning regimen.

Mesenchymal stromal/stem cells (MSCs) have a great potential to proliferate, undergo multi‐directional differentiation, and exert immunoregulatory effects. There is already much enthusiasm for their therapeutic potentials for respiratory inflammatory diseases. Although the mechanism of MSCs‐based therapy has been well explored, only a few articles have summarized the key advances in this field. We hereby provide a review over the latest progresses made on the MSCs‐based therapies for four types of inflammatory respiratory diseases, including idiopathic pulmonary fibrosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and asthma, and the uncovery of their underlying mechanisms from the perspective of biological characteristics and functions. Furthermore, we have also discussed the advantages and disadvantages of the MSCs‐based therapies and prospects for their optimization., The dominant functions of MSCs in IPF, ARDS, COPD and Asthma.

Deep learning is applied to assist the joint inversion for audio-magnetotelluric and seismic travel time data. More specifically, deep residual convolutional neural networks (DRCNNs) are designed to learn both structural similarity and resistivity–velocity relationships according to prior knowledge. During the inversion, the unknown resistivity and velocity are updated alternatingly with the Gauss–Newton method, based on the reference model generated by the trained DRCNNs. The workflow of this joint inversion scheme and the design of the DRCNNs are explained in detail. Compared with describing the resistivity–velocity relationship using empirical equations, this method can avoid the necessity in modeling the correlations in rigorous mathematical forms and extract more hidden prior information embedded in the training set, meanwhile preserving the structural similarity between different inverted models. Numerical tests show that the inverted resistivity and velocity have similar profiles, and their relationship can be kept consistent with the prior joint distribution. Furthermore, the convergence is faster, and final data misfits can be lower than separate inversion.

This study was performed to investigate the relationship between the aspartate transaminase and/or alanine transaminase ratio (DRR) and long-term mortality of patients diagnosed with sepsis or septic shock.We conducted a retrospective study among adult septic patients who were admitted to the surgical intensive care unit (ICU) of the Chinese People's Liberation Army (PLA) General Hospital from January 2014 to December 2018. Baseline characteristics were compared between survivors and non survivors. We performed univariate and multivariate Cox regression analyses to evaluate the relation of DRR with 180-day mortality. The potential prognostic value of DRR in predicting mortality rate was assessed by receiver operating characteristic (ROC) curve analysis. In addition, we conducted subgroup analysis by the optimal DRR cutoff value.We included a total of 183 patients in the current study, and 44 (24%) patients died within 180 days of hospitalization. Univariate and multivariate Cox analyses revealed that DRR was an independent predictor of 180-day mortality (hazard ratio [HR] 1.421, 95% confidence interval [CI] 1.073-1.883, P = 0.014). The predictive accuracy of DRR for 180-day mortality was presented as an ROC curve, which had an area under the curve (AUC) of 0.708 (95% CI 0.629-0.786, P0.001). After we stratified all enrolled patients into two groups by using the optimal cutoff value of 1.29, we observed a significantly higher mortality in patients with a relatively high DRR.An elevated DRR was associated with higher 180-day mortality among septic patients, and DRR might be an optimal marker for predicting the long-term mortality of sepsis. More prospective and randomized trials are needed to confirm the prognostic value of DRR.

Background To comprehensively analyze the risk factors, clinical characteristics, outcomes, and prognostic factors of Cytomegalovirus (CMV) enteritis. Methods This retrospective cohort study enrolled patients who had undergone pathological examinations for CMV enteritis. They were divided into CMV and non-CMV groups according to immunohistochemistry staining results. The risk factors, clinical presentations, endoscopic features, treatments, outcomes, and prognostic factors of CMV enteritis were then analyzed. Results Forty-two patients (18 CMV, 24 non-CMV group) were included in the study. Major clinical presentations in the CMV group included gastrointestinal bleeding (72.2%), abdominal pain (55.6%), and fever (33.3%); ulcers (72.2%) were the most common endoscopic findings. In-hospital and overall mortality rates were 27.8% and 38.9%, respectively; and longer hospital stays and higher overall mortality rates were observed. Radiotherapy and C-reactive protein levels were prognostic factors for in-hospital mortality. The risk factors for CMV enteritis included immunocompromised status (p = 0.013), steroid use (p = 0.014), shock (p = 0.031), concurrent pneumonia (p = 0.01), antibiotic exposure (p Conclusions Physicians should pay attention to the characteristics of CMV enteritis in high-risk patients to make an early diagnosis and potentially improve the clinical outcome.

Background Intestinal perforations and fistulas are common complications of Crohn’s disease. However, chronic perforation with peritoneal space to rectal and vaginal fistulas have not been previously reported. Case presentation A 38-year-old female suffered from progressive lower abdominal pain, diarrhea and weight loss. Terminal ileal chronic perforation with intra-abdominal abscess, peritoneal space to rectal and vaginal fistulas were noted. The patient received surgical resection of the cecum and terminal ileum, and then vedolizumab treatment. Three months later, she had complete fistula closure, and her body mass index had increased from 13 to 22. Conclusion Vedolizumab combined with stool diversion is effective at treating Crohn’s disease with chronic perforation and complex peritoneal space to rectal and vaginal fistulas.

Next-generation sequencing (NGS) has been applied to measurable/minimal residual disease (MRD) monitoring after induction chemotherapy in patients with acute myeloid leukemia (AML), but the optimal time point for the test remains unclear. In this study, we aimed to investigate the clinical significance of NGS MRD at 2 different time points. We performed targeted NGS of 54 genes in bone marrow cells serially obtained at diagnosis, first complete remission (first time point), and after the first consolidation chemotherapy (second time point) from 335 de novo AML patients. Excluding DNMT3A, TET2, and ASXL1 mutations, which are commonly present in individuals with clonal hematopoiesis of indeterminate potential, MRD could be detected in 46.4% of patients at the first time point (MRD1st), and 28.9% at the second time point (MRD2nd). The patients with detectable NGS MRD at either time point had a significantly higher cumulative incidence of relapse and shorter relapse-free survival and overall survival. In multivariate analysis, MRD1st and MRD2nd were both independent poor prognostic factors. However, the patients with positive MRD1st but negative MRD2nd had a similar good prognosis as those with negative MRD at both time points. The incorporation of multiparameter flow cytometry and NGS MRD revealed that the presence of NGS MRD predicted poorer prognosis among the patients without detectable MRD by multiparameter flow cytometry at the second time point but not the first time point. In conclusion, the presence of NGS MRD, especially after the first consolidation therapy, can help predict the clinical outcome of AML patients.

Background: In this study, we investigated the relationship between long-chain non-coding RNAs (lncRNAs) and respiratory syncytial virus (RSV)- exacerbated asthma. Methods: Transcriptome microarray was used to detect differentially expressed lncRNAs in dendritic cells (DCs) co-cultured with RSV-infected human airway epithelial cells and DCs infected with RSV. The identified downregulation of lncRNA n337374 was validated using fluorescence RT-qPCR. LncRNA n337374-overexpressing DCs and RSV-exacerbated asthmatic mouse models were established. Airway hyperreactivity and bronchoalveolar lavage fluid (BALF) were examined, and pathological changes in lung tissues were observed in mice. Surface molecules in DCs were detected by flow cytometry and RT-qPCR and the expression of CD86 and mitogen-activated protein kinases was determined by western blot. Results: In an RSV-exacerbated asthmatic mouse model, the airway wall was thickened, luminal stenosis was observed, a large number of inflammatory cells were infiltrated in the lung tissue, lung function was impaired, and counts of inflammatory cells in the BALF were increased. The overexpression of lncRNA n337374 ameliorated these pathological changes and improved impaired lung function and inflammation in an asthmatic mouse model. In DCs co-cultured with RSV-infected human airway epithelial cells, CD86 expression was promoted and ERK was markedly phosphorylated. When lncRNA n337374-overexpressing DCs were used in the co-cultures, the expression of CD86 and phosphorylated ERK was decreased. Conclusion: The results suggest that lncRNA n337374 overexpression may suppress DC maturation by downregulating the CD86 and ERK pathway, subsequently relieving the symptoms of RSV-induced asthma. LncRNA n337374 may be a promising target in the treatment of RSV infection-induced asthma.

Background and purposeThis study aimed to investigate the association of metabolic syndrome (MetS) with both intracranial atherosclerotic stenosis (ICAS) and imaging markers of cerebral small vessel disease (CSVD) in a community-based sample.MethodsThis study included 943 participants (aged 55.6±9.2 years, 36.1% male) from the community-based Shunyi cohort study. MetS was defined according to the joint interim criteria and quantified by the MetS severity Z-score. ICAS was evaluated by brain magnetic resonance angiography. The MRI markers of CSVD, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVS), were assessed. Multiple regression models were used to investigate the association of MetS severity Z-score with ICAS and these CSVD markers.ResultsWe found that risk of ICAS (OR=1.75, 95% CI 1.39 to 2.21, pConclusionsOur findings suggest that WMH and lacunes share risk factors with atherosclerosis of the cerebral artery, whereas the impact of glucose and lipid metabolic disorder to CMB or EPVS might be weak.

Background: Mechanisms through which arterial stiffness impacts cognitive function are crucial for devising better strategies to prevent cognitive decline. Objective: To examine the associations of arterial stiffness with white matter integrity and cognition in community dwellings, and to investigate whether white matter injury was the intermediate of the associations between arterial stiffness and cognition. Methods: This study was a cross-sectional analysis on 952 subjects (aged 55.5±9.1 years) who underwent diffusion tensor imaging and measurement of brachial-ankle pulse wave velocity (baPWV). Both linear regression and tract-based spatial statistics were used to investigate the association between baPWV and white matter integrity. The association between baPWV and global cognitive function, measured as the mini-mental state examination (MMSE) was evaluated. Mediation analysis was performed to assess the influence of white matter integrity on the association of baPWV with MMSE. Results: Increased baPWV was significantly associated with lower mean global fractional anisotropy (β= –0.118, p

Objectives This study aimed to explore the novel biomarkers for immune checkpoint inhibitor (ICI) responses in non‐small cell lung cancer (NSCLC) by integrating genomic profiling, tumor mutational burden (TMB), and expression of programmed death receptor 1 ligand (PD‐L1). Materials and Methods Tumor and blood samples from 637 Chinese patients with NSCLC were collected for targeted panel sequencing. Genomic alterations, including single nucleotide variations, insertions/deletions, copy number variations, and gene rearrangements, were assessed and TMB was computed. TMB‐high (TMB‐H) was defined as ≥10 mutations/Mb. PD‐L1 positivity was defined as ≥1% tumor cells with membranous staining. Genomic data and ICI outcomes of 240 patients with NSCLC were derived from cBioPortal. Results EGFR‐sensitizing mutations, ALK, RET, and ROS1 rearrangements were associated with lower TMB and PD‐L1+/TMB‐H proportions, whereas KRAS, ALK, RET, and ROS1 substitutions/indels correlated with higher TMB and PD‐L1+/TMB‐H proportions than wild‐type genotypes. Histone‐lysine N‐methyltransferase 2 (KMT2) family members (KMT2A, KMT2C, and KMT2D) were frequently mutated in NSCLC tumors, and these mutations were associated with higher TMB and PD‐L1 expression, as well as higher PD‐L1+/TMB‐H proportions. Specifically, patients with KMT2C mutations had higher TMB and PD‐L1+/TMB‐H proportions than wild‐type patients. The median progression‐free survival (PFS) was 5.47 months (95% CI 2.5–NA) in patients with KMT2C mutations versus 3.17 months (95% CI 2.6–4.27) in wild‐type patients (p = 0.058). Furthermore, in patients with NSCLC who underwent ICI treatment, patients with TP53/KMT2C co‐mutations had significantly longer PFS and greater durable clinical benefit (HR: 0.48, 95% CI: 0.24–0.94, p = 0.033). TP53 mutation combined with KMT2C or KRAS mutation was a better biomarker with expanded population benefit from ICIs therapy and increased the predictive power (HR: 0.46, 95% CI: 0.26–0.81, p = 0.007). Conclusion We found that tumors with different alterations in actionable target genes had variable expression of PD‐L1 and TMB in NSCLC. TP53/KMT2C co‐mutation might serve as a predictive biomarker for ICI responses in NSCLC. Implications for Practice Cancer immunotherapies, especially immune checkpoint inhibitors (ICIs), have revolutionized the treatment of non‐small cell lung cancer (NSCLC); however, only a proportion of patients derive durable responses to this treatment. Biomarkers with greater accuracy are highly needed. In total, 637 Chinese patients with NSCLC were analyzed using next‐generation sequencing and IHC to characterize the unique features of genomic alterations and TMB and PD‐L1 expression. Our study demonstrated that KMT2C/TP53 co‐mutation might be an accurate, cost‐effective, and reliable biomarker to predict responses to PD‐1 blockade therapy in NSCLC patients and that adding KRAS to the biomarker combination creates a more robust parameter to identify the best responders to ICI therapy., Cancer immunotherapy, especially immune checkpoint inhibitors (ICIs), is epoch‐making in non‐small cell lung cancer (NSCLC), but only a proportion of patients can derive durable benefits from it, more accurate biomarkers are thus highly needed. Samples of 637 Chinese patients with NSCLC were analyzed through next‐generation sequencing and IHC to characterize the unique features of genomic alterations, TMB, and PD‐L1 expression. The results showed that the alteration subtypes of common driver genes including EGFR G719X, KRAS G12C, MET amplification, and SNVs/INDELs of ALK, RET, and ROS1 in NSCLC are associated with higher PD‐L1 expression or higher TMB value. Furthermore, our study first demonstrated that KMT2C/TP53 co‐mutation might be an accurate, cost‐effective, and reliable biomarker to predict the responses to PD‐1 blockade therapy in NSCLC patients, and that adding KRAS to the biomarker combination creates a more robust parameter to identify the best responders to ICI therapy.

Burnout syndrome is a condition marked by emotional exhaustion, deterioration in motivation and lack of commitment, resulting from long-lasting workplace stress, characterized by exhaustion, negative feelings towards one's work and reduced professional efficacy. Healthcare workers are at particularly high risk for burnout due to high levels of stress. Our objectives were to determine the prevalence of burnout syndrome among doctors in Sabah and factors associated with it. This multi-centre cross-sectional study was carried out among doctors working in five Sabah main hospitals. Data were collected by using self-administered questionnaires consisting of basic socio-demographic information and Copenhagen Burnout Inventory (CBI). Overall, a total of 523 doctors consented to participate in this study. The prevalence of personal burnout, work-related burnout, and patient-related burnout among doctors were 57.1%, 48.8%, and 30.4% respectively. Chi-square analysis showed factors that were associated to personal burnout and work-related burnout, were marital status, duration of service and position in the service. Duration of service was the only factor associated with patient-related burnout. The prevalence of burnout syndrome in Sabah should not to be overlooked and more researches are indicated to look into prevention of burnout syndrome in Malaysian setting.

Introduction Gastric cancer (GC) has a high incidence and mortality rate, especially in East Asians, and about 90% of GCs are adenocarcinomas. Histological and etiological heterogeneity and ethnic diversity make molecular subtyping of GC complicated, thus making it difficult to determine molecular division systems and standard treatment modalities. Limited cohorts from South Korea, Singapore, Australia, and Japan have been studied; however, the mutational landscape of gastric adenocarcinomas in Chinese patients is still unknown. Methods We performed a targeted sequencing panel focusing on cancer‐related genes and tumor‐associated microorganisms of 529 gastric adenocarcinoma samples with matched blood controls. We identified 449 clinically relevant gene mutations. Results Approximately 47.1% of Chinese patients with GC harbored at least one actionable mutation. The top somatic mutations were TP53, ARID1A, LRP1B, PIK3CA, ERBB2, CDH1, KRAS, FAT4, CCNE1, and KMT2D. Truncation mutations of ARID1A, KMT2D, RNF43, TGFBR2, and CIC occurred in patients with high tumor mutational burden. Gene amplifications of ERBB2, CCNE1, CDK12, and CCND1 were detected in patients with low tumor mutational burden. Pathway analysis revealed common gene alterations in the Wnt and PI3K/Akt signaling pathways. The ratio of patients with high microsatellite instability was significantly lower than other cohorts, and high microsatellite instability and Epstein‐Barr virus (EBV)–positive features seemed mutually inclusive in Chinese patients with GC. In 44 (8.3%) patients, 45 germline mutations were identified, among which SPINK1 mutations, all SPINK1 c.194 + 2T > C, were present in 15.9% (7/44) of patients. Microorganisms found in Chinese patients with GC included Helicobacter pylori, EBV, hepatitis B virus, and human papillomavirus types 16 and 18. Conclusion Identification of varied molecular features by targeted next‐generation sequencing provides more insight into patient stratification and offers more possibilities for both targeted therapies and immunotherapies of Chinese patients with GC. Implications for Practice This study investigated the genomic alteration profile of 529 Chinese patients with gastric adenocarcinoma by deep targeting sequencing, which might be the largest Chinese cohort on the genomic research of gastric adenocarcinoma up to now., Novel molecular targeted therapies for gastric cancer are urgently needed. This article explores the mutational landscape covering somatic, germline, and microorganisms among a cohort of Chinese patients with gastric cancer. Findings provide insight on patient stratification and potential molecular targets, and for developing new treatment strategies for patients in China and worldwide.

Background Fistula and intraabdominal fistula are common complications of Crohn's disease (CD), but complex rectal fistula with abscess formation is rare. Tumor necrosis factor antagonists combined with percutaneous drainage or surgical intervention is optimal treatment for fistulizing CD with intraabdominal abscess. There is no study show the efficacy of vedolizumab in such complicated condition. Case summary A 47-year-old man has decompensated liver cirrhosis, child B. He suffered from abdominal pain, bloody diarrhea, fever, and body weight loss. CD with rectoprostatic fistula, rectopresacral fistula, pre-sacral abscess and cyto-megalovirus (CMV) infection were noted. He received antibiotics, anti-viral therapy, transverse colostomy and vedolizumab treatment. Six months later, he had deep remission and complete fistula tracts closure. Conclusion Early vedolizumab and stool diversion are effective and safe in treating CD with complex rectal fistula with abscess formation.

Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related angiitis. Acute or subacute onset of cognitive decline or behavioral changes is the most common symptom of CAA-RI. Rapid progressive dementia, headache, seizures, or focal neurological deficits, with patchy or confluent hyperintensity on T2 or fluid-attenuated inversion recovery sequences and evidence of strictly lobar microbleeds or cortical superficial siderosis on susceptibility-weighted imaging imply CAA-RI. The gold standard for diagnosis is autopsy or brain biopsy. However, biopsy is invasive; consequently, most clinically diagnosed cases have been based on clinical and radiological data. Other diagnostic indexes include the apolipoprotein E ε4 allele, Aβ and anti-Aβ antibodies in cerebral spinal fluid and amyloid positron emission tomography. Many diseases with similar clinical manifestations should be carefully ruled out. Immunosuppressive therapy is effective both during initial presentation and in relapses. The use of glucocorticoids and immunosuppressants improves prognosis. This article reviews the pathology and pathogenesis, clinical and imaging manifestations, diagnostic criteria, treatment, and prognosis of CAA-RI, and highlights unsolved problems in the existing research.

Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers, can be divided into head and body/tail cancers anatomically. We previously reported a prognostic relevance of tumour location in resectable PDAC. This study aimed to further explore the mechanism underlying the molecular diversity between the head and body/tail of PDACs. We detected tumour genomes in 154 resectable (surgery) and non‐resectable (biopsy) PDACs using a next‐generation sequencing panel. Wilcoxon's rank test or Fisher's exact test was used for evaluating associations between clinical characteristics, mutation frequency and survival probability between the two cohorts. Compared with pancreatic head cancers, pancreatic body/tail cancers showed significantly more enriched genomic alterations in KRAS (97.1% vs 82.4%, P = 0.004) and SMAD4 (42.0% vs 21.2%, P = 0.008). At early stages (I‐II), the SMAD4 mutation rate was significantly higher in pancreatic body/tail cancers than pancreatic head cancers (56.0% vs 26.5%, P = 0.021). At late stages (III‐IV), pancreatic body/tail cancers presented significantly higher KRAS mutation rate (100.0% vs 75.8%, P = 0.001), higher frequency of MAPK pathway mutation (100% vs 87.8%, P = 0.040) and lower rates of druggable genomic alterations (30.8% vs 57.6%, P = 0.030) than pancreatic head cancers. Our work points out that pancreatic body/tail cancer seems to be more malignant than pancreatic head cancer at late stages.

Sepsis is a systemic inflammatory response caused by infection and is a major cause of neonatal death. This study explored the miR-455-5p in neonatal sepsis, and further investigated the diagnostic and prognostic value of miR-455-5p in neonatal sepsis (NS). The levels of serum miR-455-5p in 88 healthy controls and 90 NS patients were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Pearson correlation coefficient was used to evaluate the correlation between miR-455-5p and clinical features. Receiver operating characteristic (ROC) curve analysis was performed for the diagnostic evaluation on miR-455-5p. The prognostic value of miR-455-5p in NS was analyzed by Kaplan–Meier survival curve and multivariate Cox regression. The expression of serum miR-455-5p in NS patients was highly expressed in comparison to healthy controls (P, GRAPHICAL ABSTRACT

Aims: The relationship between central arterial stiffness and aging-related intracranial arteriopathy is not well investigated in the general population. In a population-based study, we investigated arterial stiffness in relation to intracranial atherosclerotic stenosis and intracranial arterial dolichoectasia. Methods: This study was a cross-sectional analysis on 1,123 subjects (aged 56.0 ± 9.3 years, 37.9% men) of the population-based Shunyi study in China. Arterial stiffness was assessed by measuring brachial-ankle pulse wave velocity (baPWV). Intracranial atherosclerotic stenosis and intracranial arterial dolichoectasia were evaluated via brain magnetic resonance angiography. Multivariate regression models were constructed to investigate the association between baPWV and intracranial large artery diseases. Results: Increased baPWV was significantly associated with higher prevalence of intracranial atherosclerotic stenosis (odds ratio for the highest quartile of baPWV compared with the lowest quartile, 3.66 [95% confidence interval, 1.57–8.54]), after adjustment for cardiovascular risk factors in multivariate analysis. BaPWV was not associated with the presence of basilar artery dolichoectasia and dilation of basilar artery and internal carotid artery. When the diameters of intracranial arteries were regarded as continuous variables, increased baPWV was inversely related to the internal carotid artery diameter in fully adjusted models (β ± SE, −0.083 ± 0.042, p = 0.047). Conclusions: This population-based study demonstrates that arterial stiffness was more likely associated with intracranial stenotic arteriopathy other than intracranial dilative arteriopathy.

Background: Primary intestinal lymphomas (PILs) are rare, and this study compared the clinical outcomes of aggressive primary intestinal B-cell lymphomas (aB-PILs) and T/natural killer-cell lymphomas (T/NK-PILs). Methods: The clinical information of patients diagnosed with aggressive PILs at our institution between 1995 and 2015 were retrospectively investigated. Pathological subtypes were confirmed according to the 2016 revision of the World Health Organization classification. The correlation between clinicopathological features and overall survival (OS) was determined using univariate and multivariate analyses. Results: Cases of T/NK-PILs had higher initial bowel perforation incidence (67% vs. 7%, P

Background/aims This study aimed to analyze the data of 24 cases of multiple perforation or obstruction of the digestive tract caused by accidental ingestion of magnetic beads, to improve the understanding of its harmfulness to children and explore the best treatment. Materials and methods In total, 24 cases were collected and retrospectively analyzed. These patients were divided into two groups: perforation group and non-perforation group. The medical history, number of magnetic beads, white blood cell (WBC) count, and C-reactive protein (CRP) were analyzed. Results There was no significant difference in age, gender, medical history, number of magnetic beads, and WBC count between the perforation group and non-perforation group, but there was a significant difference in CRP. After the diagnosis, 70% of the cases underwent laparotomy and perforation repair. All cases recovered smoothly after the operation, and no complications occurred during the follow-up. Conclusion This study offers diagnosis and treatment methods for the perforation or obstruction of the digestive tract caused by accidental ingestion of magnetic beads and raises the awareness regarding the harmfulness of the presence of foreign bodies in the digestive tract.

Introduction: Pleural fluid adenosine deaminase (pfADA) is a simple, rapid and inexpensive surrogate marker for tuberculous pleural effusion (TPE). A nationwide cut-off of 40 U/L is currently used based on overseas data. There is a need to optimise the diagnostic utility of pfADA by establishing a local cut-off value. In this study, we aimed to describe the demographics and clinical characteristics of patients with TPE and non-TPE; determine the sensitivity and specificity of current pfADA of 40 U/L; and establish a new local pfADA cut-off for TPE. Methods: We conducted a single-centre, observational, prospective study of patients with exudative pleural effusion and pfADA measured from 1 October 2019 to 30 April 2020 at Queen Elizabeth Hospital, Malaysia. Results: The diagnosis of analysed patients ( n = 93) included TPE ( n = 41), malignancy ( n = 28), parapneumonic effusion ( n = 12) and other causes ( n = 12). The mean pfADA was 51.15 U/L (standard deviation (SD) = 13.77) among TPE group and 18.86 U/L (SD = 12.33) among non-TPE. When analysis was restricted to TPE patients, the local pfADA cut-off is 29.6 U/L, with a sensitivity of 97.6% and specificity of 90.4%. The current pfADA of 40 U/L has a sensitivity of 87.8% and specificity of 92.3%. Conclusion: We established a local pfADA cut-off of 29.6 U/L for TPE. Optimising the utility of pfADA helps to enhance clinicians’ treatment confidence of TPE when initial work-up is inconclusive.

The likelihood of advanced or synchronous neoplasms is significantly higher in fecal immunochemical test (FIT)-positive individuals than in the general population. The magnitude of the colonoscopy-related complication rate in FIT-positive individuals remains unknown. This study aimed to elucidate the colonoscopy-related complication rate after a positive FIT result and compare it with the rate when colonoscopy was performed for other purposes.Information regarding colonoscopy-related severe complications after a positive FIT result (FIT-colonoscopy) and ordinary colonoscopy during 2010-2014 was collected from the Taiwanese Colorectal Cancer Screening Program Database and National Health Insurance Research Database. Severe complications included significant bleeding, perforation, and cardiopulmonary events ≤ 14 days after colonoscopy. The number of events per 1000 procedures was used to quantify complication rates. Multivariate analysis was conducted to assess the association of various factors with severe complications associated with FIT-colonoscopy compared with ordinary colonoscopy.319 114 FIT-colonoscopies (214 955 patients) were identified, 51 242 (16.1 %) of which included biopsy and 94 172 (29.5 %) included polypectomy. Overall, 2125 significant bleedings (6.7 ‰) and 277 perforations (0.9 ‰) occurred ≤ 14 days after FIT-colonoscopy. Polypectomy, antiplatelet use, and anticoagulant use were associated with higher risk of complications (adjusted odds ratio [aOR] 4.41, 95 % confidence interval [CI] 4.05-4.81); aOR 1.35, 95 %CI 1.12-1.53; aOR 1.88, 95 %CI 0.61-5.84, respectively). Compared with ordinary colonoscopy, FIT-colonoscopy involved significantly higher risk of significant bleeding (aOR 3.10, 95 %CI 2.90-3.32).FIT-colonoscopy was associated with a more than two-fold risk of significant bleeding, especially when polypectomy was performed.The likelihood of advanced or synchronous neoplasms is significantly higher in fecal immunochemical test (FIT)-positive individuals than in the general population. The magnitude of the colonoscopy-related complication rate in FIT-positive individuals remains unknown. This study aimed to elucidate the colonoscopy-related complication rate after a positive FIT result and compare it with the rate when colonoscopy was performed for other purposes.Information regarding colonoscopy-related severe complications after a positive FIT result (FIT-colonoscopy) and ordinary colonoscopy during 2010–2014 was collected from the Taiwanese Colorectal Cancer Screening Program Database and National Health Insurance Research Database. Severe complications included significant bleeding, perforation, and cardiopulmonary events ≤ 14 days after colonoscopy. The number of events per 1000 procedures was used to quantify complication rates. Multivariate analysis was conducted to assess the association of various factors with severe complications associated with FIT-colonoscopy compared with ordinary colonoscopy.319 114 FIT-colonoscopies (214 955 patients) were identified, 51 242 (16.1 %) of which included biopsy and 94 172 (29.5 %) included polypectomy. Overall, 2125 significant bleedings (6.7 ‰) and 277 perforations (0.9 ‰) occurred ≤ 14 days after FIT-colonoscopy. Polypectomy, antiplatelet use, and anticoagulant use were associated with higher risk of complications (adjusted odds ratio [aOR] 4.41, 95 % confidence interval [CI] 4.05–4.81); aOR 1.35, 95 %CI 1.12–1.53; aOR 1.88, 95 %CI 0.61–5.84, respectively). Compared with ordinary colonoscopy, FIT-colonoscopy involved significantly higher risk of significant bleeding (aOR 3.10, 95 %CI 2.90–3.32).FIT-colonoscopy was associated with a more than two-fold risk of significant bleeding, especially when polypectomy was performed.

Caustic substance ingestion is frequently life-threatening, and its pathological mechanisms of tissue damage are well documented. However, few studies have assessed the combined effects of pH and the ingested dose on patient outcomes. Additionally, the miscellaneous chemical properties are not immediately available for providing predictive insights to physicians. This study aimed to provide a new perspective of the risk assessment of caustic substance ingestion based on the pH and dose.The retrospective study analyzed adults treated for caustic substance ingestion at Chang Gung Memorial Hospital between January 1999 and December 2018. Uniformly strict inclusion/exclusion criteria and a double-checked process during chart review were adopted. All patients underwent urgent esophagogastroduodenoscopy (EGD) within 24 h. Caustic mucosal damage was graded using Zargar's modified endoscopic classification. The pH and ingested dose of caustic substances were clearly recorded. Statistical analyses were conducted using IBM SPSS, version 22.Based on the 468 enrolled cases, the pH and dose were valuable predictors of the extent of gastrointestinal tract injury, commonly encountered complications, and long-term overall survival outcomes. Risks of mortality and perforation were dose-dependent for acids and pH-dependent for alkalis. The severe EGD findings (grade ≥ 2b) in this study were pH-dependent for both substances and additionally dose-dependent for acids.Combining pH and dose, we proposed a new perspective for the risk assessment of caustic substance ingestion. Such findings may provide predictive insights for resolving clinical uncertainty before the availability of examination results. "Large doses of acids" and "high pH of alkalis" deserve special attention. This new perspective with a retrospective nature requires further validation.

Background Kirsten rat sarcoma vial oncogene (KRAS) is one of the most prevalent oncogenes in multiple cancer types, but the incidence is different between the Asian and non-Asian populations. The recent development of KRAS G12C targeting drug has shown great promise. It is thus important to understand the genomic landscape of KRAS G12C in a specific population. Methods Sequencing data of 11,951 tumor samples collected from 11/2016 to 7/2019 from multiple centres in China were analyzed for KRAS mutation status. Concomitant genomic aberrations were further analyzed in tumors with KRAS G12C mutations, which were sequenced with comprehensive cancer panel including over 450 cancer-related genes. Smoking status and its correlation with KRAS were analyzed in 2,235 lung cancer cases within this cohort. Results KRAS mutations were identified in 1978 (16.6%) patient samples. Specifically, KRAS G12C accounted for 14.5% (n=286) of all KRAS mutations. G12C was most commonly seen in lung cancer (4.3%), followed by colorectal cancer (2.5%) and biliary cancer (2.3%). Almost all patients (99.6%) with G12C mutations had concomitant genomic aberrations. These were most commonly associated with the RAS/RTK pathway including BRAF and PI3KCA mutations. Moreover, KRAS mutation was positively correlated with smoking status in lung adenocarcinomas. Conclusions The overall incidence of KRAS G12C mutations remains low in the Chinese population. The most common tumor types harboring KRAS G12C mutations are in patients suffering from lung, colorectal and biliary cancers.

The fall armyworm (FAW), Spodoptera frugiperda (Smith), is a major pest native to the Americas. A recent invasion of FAWs from Africa eastward to South Asia, the Indochina Peninsula, and mainland China has received much attention due to the considerable economic losses in agriculture. FAWs can rapidly colonise a new area, likely due to the wide range of host plants, good flying capability, and high egg production. Therefore, a convenient, quick, and accurate tool for FAW identification is urgently required to establish a FAW invasion management strategy. In this study, FAW-specific primers were designed to recognise FAWs on the basis of internal transcribed spacer 1 (ITS1). The results revealed the accurate FAW recognition of the three congeneric species and eight common corn lepidopteran pests, especially at their larval stage. Furthermore, species-specific primers have confirmed their efficacy by using 69 FAW specimens from Taiwan, Thailand, and the United States, with a 96% success rate, excluding 3 decayed specimens. By using the simple, reliable, and convenient FAW-specific primers, a pest management programme can be developed not only to reduce sequencing costs and experimental time from 2 days to 4 h, but eradicate the FAW as soon as it enters a new area.

Polyimide film is a practicable alternative to the conventional substrates utilized in conformal antennas. Due to its flexibility, the antennas based on the polyimide film can be easily conformed to the platform surface. An eight-element linear-phased array operating at the P-band with a wide scan angle is investigated in this letter, which is constructed by the dipoles printed on the polyimide film. The antenna surface is mounted on the front wing of an unmanned aerial vehicle (UAV). Strong coupling is observed between the array elements when the beam scans. Therefore, decoupling structures are loaded in the array elements to broaden the scan angle. To satisfy the requirement of the radar system, directors and reflectors are also employed on the surface of the front wing to narrow the main lobe beamwidth in the elevation plane. The proposed phased array achieves a fractional bandwidth of 16.7% when scanning up to ±60° in the E-plane. The validity of this design is verified by the simulation and measurements of a 1 × 8 array prototype.

Background Drug resistance is a major obstacle to effective cancer therapy. In order to detect the change in tumor genomic states under drug selection pressure, we use next-generation sequencing technology to investigate the underlying potential mechanisms of drug resistance. Methods In our study, we presented a bladder cancer patient who had been a bona fide responder to first-line gemcitabine plus cisplatin regimen and second-line pazopanib (tyrosine kinase inhibitor (TKI) for FGFR3-TACC3 fusion) but finally had disease progression as an ideal case for showing genomic alteration during drug resistance. We applied whole-exome sequencing and ultra-deep target sequencing to the patient pre- and post- pazopanib resistance. Protein-protein interaction (PPI) network and Gene Ontology (GO) analyses were used to analysis protein interactions and genomic alterations. Patient-derived xenograft (PDX) model was built to test drug sensitivity. Results Twelve mutations scattered in 12 genes were identified by WES pre- pazopanib resistance, while 63 mutations in 50 genes arose post- pazopanib resistance. PPI network showed proteins from multiple epigenetic regulator families were involved post- pazopanib resistance, including subunits of chromatin remodeler SWI/SNF complex ARID1A/1B and SMARCA4, histone acetylation writers CREBBP, histone methylation writer NSD1 and erasers KDM6A/5A. GO enrichment analysis showed pazopanib resistance genes were prominently tagged for chromatin modification, transcription, as well as gland development, leaving genes with the best adaptive FGFR TKI-coping mechanisms. In addition, significantly elevated tumor mutational burden suggested possible utility of immunotherapy. Intriguingly, PDX model suggested that, sensitivity to original chemotherapy regimen (cisplatin) was restored in patient tumor post-pazopanib. Conclusions Epigenetic regulation may play a role in acquired TKI resistance. Our study traced the complete tumor genomic variation course from chemo-resistant but TKI-sensitive to TKI-resistant but chemo-(re) sensitive, revealing the potential complex dynamic drug-driven mechanisms of resistance.

Purpose High prevalence of psychiatric comorbidities (PCs) has been widely documented in caustic substance ingestion cases. However, their effect on the clinical features and prognostic outcomes remains unclear due to the paucity of discussion. We report on detailed clinical courses with long-term multifaceted outcomes and review the association between caustic ingestion and each specific PC. Patients and methods The retrospective chart review included 396 adults (median follow-up, 16.6 months) with and 377 without (control group) PCs treated between 1999 and 2018 at Chang Gung Memorial Hospital. All PCs were diagnosed/confirmed by psychiatrists through face-to-face interviews. Results The PCs predicted serious esophagogastroduodenoscopy grading, higher rates of admission/surgery/intensive care unit stay, increments of systemic/gastrointestinal complications, and poorer 5-year overall survival rates. The poor survival among patients with PCs was highly consistent with their baseline characteristics. Significantly advanced age, more non-PCs, alcoholism, illicit drug abuse, and baseline unhealthy status resulted in statistically higher risks of severe complications and limited recovery. Conclusion PCs changed clinical patterns and had critical roles in the survival outcomes of caustic injury victims. Clinical awareness achieves benefit by limiting injuries in mild cases or allowing emergent interventions in severe cases. Future studies based on worldwide populations are essential for realizing geographic differences.

BACKGROUND AND PURPOSE: Previous studies have shown that diffusion tensor imaging suggests a diffuse loss of white matter integrity in people with white matter hyperintensities or lacunes. The purpose of this study was to investigate whether the presence of cerebral microbleeds and their distribution are related to the integrity of white matter microstructures. MATERIALS AND METHODS: The study comprised 982 participants who underwent brain MR imaging to determine microbleed status. The cross-sectional relation between microbleeds and the microstructural integrity of the white matter was assessed by 2 statistical methods: a multilinear regression model based on the average DTI parameters of normal-appearing white matter and Tract-Based Spatial Statistics analysis, a tract-based voxelwise analysis. Fiber tractography was used to spatially describe the microstructural abnormalities along WM tracts containing a cerebral microbleed. RESULTS: The presence of cerebral microbleeds was associated with lower mean fractional anisotropy and higher mean diffusivity, axial diffusivity, and radial diffusivity, and the association remained when cardiovascular risk factors and cerebral small-vessel disease markers were further adjusted. Tract-Based Spatial Statistics analysis indicated strictly lobar cerebral microbleeds associated with lower fractional anisotropy, higher mean diffusivity, and higher radial diffusivity in the internal capsule and corpus callosum after adjusting other cerebral small-vessel disease markers, while only a few voxels remained associated with deep cerebral microbleeds. Diffusion abnormalities gradients along WM tracts containing a cerebral microbleed were not found in fiber tractography analysis. CONCLUSIONS: Cerebral microbleeds are associated with widely distributed changes in white matter, despite their focal appearance on SWI.

This letter proposes a novel deep learning (DL) approach to resolve the electromagnetic inverse scattering (EMIS) problems. The conventional approaches of resolving EMIS problems encounter assorted difficulties, such as high contrast, high computational cost, inevitable intrinsic nonlinearity, and strong ill-posedness. To surmount these difficulties, a novel DL approach is proposed based on a novel complex-valued deep fully convolutional neural network structure. The proposed complex-valued deep learning model for solving EMIS problems composes of an encoder network and its corresponding decoder network, followed by a final pixel-wise regression layer. The complex-valued encoder network extracts feature fragments from received scattered field data, while the role of the complex-valued decoder network is mapping the feature fragments to retrieve the final contrasts (permittivities) of dielectric scatterers. Hence, the proposed deep learning model functions as an “heterogeneous” transformation process, where measured scattering field data is converted into the corresponding contrasts of scatterers. As a consequence, the EMIS problem could be resolved accurately even for extremely high-contrast targets. Numerical benchmarks have illustrated the feasibility and accuracy of our proposed approach. The proposed approach opens a novel path for the deep learning-based real-time quantitative microwave imaging for high-contrast scatterers.

Background There is no current standard rescue treatment for dual drug-resistant strains of Helicobacter pylori (H. pylori). This aim of this study was to investigate the efficacy of rifabutin-based triple therapy for patients infected with dual drug-resistant strains to clarithromycin and levofloxacin. Methods After 2 or 3 H. pylori treatment failures, patients underwent upper endoscopy with tissue biopsies. Phenotypic and genotypic resistances were determined using agar dilution test and polymerase chain reaction with direct sequencing, respectively. Patients infected with dual drug-resistant (clarithromycin and levofloxacin) strains and receiving rifabutin-based triple therapy (rifabutin 150 mg bid, amoxicillin 1 g bid and esomeprazole 40 mg bid for 10 days) were enrolled. Eradication status was determined by 13C-urea breath test 4 weeks after treatment completion. Results A total of 39 patients infected with dual drug-resistant strains were enrolled in this study, with a mean age of 55.9 years. The eradication rate was 79.5% (31/39) (95% confidence intervals: 54.96% ~ 111.40%). Adverse event was reported in 23.1% (9/39) of patients but they were mild and tolerable. In univariate analysis, no factor was identified as an independent predictor of eradication failure. Conclusions Our current study demonstrated that rifabutin-based triple therapy was well tolerated and yielded an acceptable eradication rate for patients infected with dual drug-resistant strains of H. pylori.

Previous studies have indicated that long non-coding RNAs (lncRNAs) were closely related to diabetes. In this study, we aimed to explore the possible role and mechanism of lncRNA MEG3 in the occurrence and development of type 2 diabetes mellitus (T2DM) and its vascular complications. A case–control study involving 115 subjects was conducted, including 53 T2DM patients (37 patients with vascular complication and 16 patients without vascular complications) and 62 healthy subjects. We performed real-time polymerase chain reaction (RT-PCR) analysis of the lncRNA MEG3 and miR-146a levels in peripheral blood mononuclear cells (PBMCs) in the 115 samples. We found that the expression of lncRNA MEG3 was upregulated in the T2DM patients with vascular complication (DC group) compared with T2DM patients without vascular complication (D group) (P

PF-06881894 is a proposed biosimilar to pegfilgrastim (Neulasta®). This study evaluated the pharmacodynamic/pharmacokinetic (PD/PK) equivalence, immunogenicity, and safety of PF-06881894 vs pegfilgrastim reference products (US- and EU-Neulasta®) in healthy volunteers. A phase 1, open-label, randomized, crossover study was conducted to assess the pharmacologic equivalence and safety of a single 6-mg dose of PF-06881894, pegfilgrastim-US, and pegfilgrastim-EU. The primary PD endpoints were area under the effect-versus-time curve for absolute neutrophil count (ANC) from dose administration to 288 h postdose, and maximum observed ANC value among subjects confirmed negative for anti-pegfilgrastim antibodies. Primary PK variables included area under the serum pegfilgrastim-versus-time curve from the time of dose administration to time infinity and maximum observed serum pegfilgrastim concentration. A second phase 1, open-label, randomized (1:1), parallel-group, non-inferiority study was conducted to assess the immunogenicity and safety of multiple 6-mg doses of PF-06881894 versus pegfilgrastim-US. The primary endpoint for the immunogenicity study was the proportion of subjects with both negative baseline and confirmed positive postdose anti-pegfilgrastim antibodies at any time during the study. Across the single- and multiple-dose studies (N = 153 and N = 420 treated subjects, respectively), demographics for age (18–65 years), male gender (n = 264/573), and white race (n = 423/573) were similar. Three-way PD/PK equivalence of PF-06881894, pegfilgrastim-US, and pegfilgrastim-EU was demonstrated with the primary PD endpoints and primary PK variables being completely contained within the predefined 90% confidence interval acceptance limits (80–125%). The non-inferiority of PF-06881894 versus pegfilgrastim-US in terms of immunogenicity was established according to the prespecified non-inferiority margin (≤10%). Overall, there were no clinically meaningful differences in safety profiles among or between study groups. Single-dose PF-06881894 demonstrated PD/PK equivalence and comparable safety with US- and EU-pegfilgrastim reference products. Multiple-dose PF-06881894 demonstrated immunogenicity non-inferiority to pegfilgrastim-US with comparable safety. Both studies contributed to the totality of evidence supporting biosimilarity. ClinicalTrials.gov identifiers: NCT02629289 (C1221001); NCT03273842 (C1221005).

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma often with extranodal involvement at diagnosis, and yet how this feature correlates with survival awaits elucidation. To address this issue, a correlative analysis between clinical features of 127 MCL patients and their overall survival (OS) was conducted. In this cohort, the median age at MCL diagnosis was 62 years and 81% were males. Eighty-four percent of patients were Ann Arbor stage 4, and 15% were blastoid variants. In patients with gastrointestinal MCL, approximately 40% had gastric involvement. In treatment, CHOP-based induction chemotherapy was given to 61.1% of patients. One-third of patients undertook autologous stem cell transplant (SCT), and 4.7% had allogeneic SCT. The median OS was 82 months and well-stratified in MIPI risk groups. In the multivariate analysis for OS, blastoid variants and gastric involvement were both independent risk factors whereas auto-SCT had a protective effect. Overall, this study corroborated with the current understandings and international therapeutic standards for MCL. Auto-SCT associated with a better OS while allo-SCT remained an option for blastoid variants and those who failed Auto-SCT. Interestingly, patients with gastric involvement tended to have worse survival, a finding that spawns more studies to investigate the mechanism.

Although ring finger protein 2 (RNF2) serves an important role in the occurrence, development and regulation of various types of cancer, RNF2 expression in skin squamous cell carcinoma (SCC) remains unknown. The aim of the present study was to investigate the role of RNF2 expression in SCC and adjacent tissues from patients. The protein and gene expression levels of RNF2 in SCC and adjacent tissues were detected by immunohistochemistry (IHC), western blot analysis and semi-quantitative reverse transcription (RT) PCR. Single factor analysis was used to study the association between RNF2 expression level and the clinicopathological characteristics of patients with SCC. Multifactor Cox survival analysis was used to examine the association between RNF2 expression and the overall survival rate of postoperative patients with SCC. The results from IHC staining demonstrated that the positive expression rate of RNF2 was 84.68% (210/248) and 56.05% (139/248) in SCC and in adjacent tissues, respectively. Furthermore, results from western blot analysis demonstrated that RNF2 protein expression in SCC tissues was significantly higher compared with that in the adjacent tissues (P