[Efficacy of alternate mucosa-submucosa clip closure in preventing postoperative complications for patients with gastric mucosal lesions after endoscopic submucosal dissection].

Objective: To analyze the efficacy of alternate titanium clip closure in preventing postoperative complications for patients with gastric mucosal lesions after endoscopic submucosal dissection (ESD). Methods: Clinical data of patients with gastric mucosal lesions who underwent ESD in the Department of Gastroenterology, Zhongda Hospital, Southeast University, were retrospectively collected from January 1, 2013 to August 31, 2023. According to the postoperative wound closure status, the patients were divided into completely closed group (complete closure of ESD wounds using alternate titanium clip closure), partially closed group (partial closure of ESD wounds), and unclosed group (without use of clips for treatment of ESD wounds). The incidence of postoperative complications as well as wound healing at 1 month and 3 months after surgery were compared among three groups, and the factors related to delayed bleeding after ESD for gastric mucosal lesions were analyzed through multiple logistic regression analysis. Results: A total of 846 patients were included, 430 cases in the completely closed group, including 300 males and 130 females, age [M (Q1, Q3)] was 65(56, 72) years old; one hundred and nine cases in unclosed group, including 78 males and 31 females, aged 66 (60, 71) years; and 307 cases in the partially closed group, including 214 males and 93 females, aged 66 (59, 71) years. The difference in the rate of delayed postoperative bleeding between the completely closed group [2.1% (9/430)] and the unclosed group [5.5% (6/109)] was not statistically significant (P=0.072), but both were lower than that of the partially closed group [9.4% (29/307), P<0.05)]. Further stratified analysis showed that, for the lesions located in the lower 1/3 of the stomach, the rate of postoperative bleeding was lower in the completely closed group than in the partially closed and unclosed groups [0.9% (2/222) vs 11.4% (4/35) vs 9.5% (7/74), respectively, P<0.001]. For lesions≥50 mm in length, the rate of postoperative bleeding was lower in the completely closed group than that in the partially closed and unclosed group[0 vs 11.8% (2/17) vs 20.5% (15/73), respectively, P=0.004]. The incidence of postoperative abdominal pain in the completely closed group [84.2% (363/430)] was lower than that in the unclosed group [97.2% (106/109)] and the partially closed group [95.4% (293/307), both P<0.001)]. The score of postoperative abdominal pain in the completely closed group [0 (0, 1)], was lower than that in the unclosed group [3 (2, 3)], and that in the partially closed group [2 (1, 3)] (both P<0.001). The wound healing rate of the completely closed group [80% (176/220)] was higher than that of the unclosed group [52.3% (33/63)] and the partially closed group [52.2% (83/159)] at 1 month postoperatively (both P<0.001); the healing rate of all three groups reached 100% at 3 months postoperatively. Multiple logistic regression analysis showed that the presence of ulcers or scars on the surface of the lesion (OR=2.930, 95%CI:1.503-5.712, P=0.002), and the diameter (OR=1.031, 95%CI:1.015-1.047,P<0.001) were related factors for postoperative bleeding. Conclusions: The alternate titanium clip closure surgery can reduce postoperative abdominal pain and shorten wound healing time in patients with gastric mucosal lesions after ESD surgery. The risk of postoperative bleeding can be reduced for lesions with a diameter≥50 mm and located in the lower 1/3 of the stomach.

Radiomics model and deep learning model based on T1WI image for acute lymphoblastic leukemia identification.

AIM: This study aimed to develop highly precise radiomics and deep learning models to accurately detect acute lymphoblastic leukemia (ALL) using a T1WI image. MATERIALS AND METHODS: A total of 604 brain magnetic resonance data of ALL group and normal children (NC) group. Two radiologists independently retrieved radiomics features after manually delineating the area of interest along the clivus at the median sagittal position of T1WI. According to the 9:1 ratio, all samples were randomly divided into the training cohort and the testing cohort. support vector machine was then used to classify the radiomics model using the features that had a correlation coefficient of greater than 0.99 in the training cohort. The Efficientnet-B3 network model received the training set images to create a deep learning model. The sensitivity, specificity, and area under the ROC curve were calculated in order to evaluate the diagnostic efficacy of the different models after the validation of two aforementioned models in the testing cohort. RESULTS: The deep learning model had a higher AUC value of 0.981 than the radiomics model's value of 0.962 in the testing cohort. Delong's test showed no statistical difference between the two models (P>0.05). The accuracy/sensitivity/specificity/negative predictive value/positive predictive value achieved 0.9180/0.9565/0.8947/0.9714/0.8462 for the radiomics model and 0.9344/0.8696/0.9737/0.9250/0.9524 for deep learning model. CONCLUSIONS: The deep learning and radiomics models showed high AUC values in the training and test cohorts. They also exhibited good diagnostic efficacy for predicting ALL.

Development and external validation of a machine learning model for prediction of survival in undifferentiated pleomorphic sarcoma.

PURPOSE: Machine learning (ML) algorithms to predict cancer survival have recently been reported for a number of sarcoma subtypes, but none have investigated undifferentiated pleomorphic sarcoma (UPS). ML is a powerful tool that has the potential to better prognosticate UPS. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for cases of histologically confirmed undifferentiated pleomorphic sarcoma (UPS) (n = 665). Patient, tumor, and treatment characteristics were recorded, and ML models were developed to predict 1-, 3-, and 5-year survival. The best performing ML model was externally validated using an institutional cohort of UPS patients (n = 151). RESULTS: All ML models performed best at the 1-year time point and worst at the 5-year time point. On internal validation within the SEER cohort, the best models had c-statistics of 0.67-0.69 at the 5-year time point. The Multi-Layer Perceptron Neural Network (MLP) model was the best performing model and used for external validation. Similarly, the MLP model performed best at 1-year and worst at 5-year on external validation with c-statistics of 0.85 and 0.81, respectively. The MLP model was well calibrated on external validation. The MLP model has been made publicly available at https://rachar.shinyapps.io/ups_app/ . CONCLUSION: Machine learning models perform well for survival prediction in UPS, though this sarcoma subtype may be more difficult to prognosticate than other subtypes. Future studies are needed to further validate the machine learning approach for UPS prognostication.

Characteristics and outcomes of cancer patients with pre-existing microscopic colitis after exposure to PD-1 and PD-L1 inhibitors.

PURPOSE: Immune checkpoint inhibitors (ICIs) are frequently associated with adverse events, often affecting the gastrointestinal tract. We conducted this study to determine the characteristics and outcomes of cancer patients with pre-existing microscopic colitis (MC) who underwent ICI treatment. METHODS: In this retrospective study, we identified 10 patients with pre-existing MC who received ICIs at our center 01/2010-06/2020. Clinical characteristics and disease outcomes were recorded. RESULTS: Of 124 screened patients with MC before ICI exposure, 10 had sufficient data to be included in the study. Melanoma (40%) and lung cancer (30%) were the most prevalent cancer types, with 70% of stage IV cancer. Patients received either anti-programmed death 1 regimen (8, 80%) or anti-programmed death ligand 1 agent (2, 20%). Six patients (60%) had collagenous colitis, and 4 (40%) had lymphocytic colitis. The median time from MC diagnosis to ICI initiation was 4 years, with 1 patient on budesonide within 2 months of ICI initiation. Eight patients (80%) developed colitis exacerbations after ICI  and required selective immunosuppression. One patient received a compassionate-use fecal transplantation. The median time from ICI to colitis exacerbation was 14 days, with 40% and 50% of patients experiencing grade 3 diarrhea and grade 2 colitis, respectively, leading to hospitalization in 3 patients. Six patients received steroids and vedolizumab with no colitis recurrence. Of 8 patients who had colitis exacerbation, 6 resumed ICI therapy afterward; with 5 receiving concomitant vedolizumab for secondary prophylaxis. CONCLUSION: Our findings suggest that ICI exposure increases the risk of exacerbation of underlying colitis necessitating and responding to potent immunosuppression therapy.

[Impact of exposure to ambient fine particulate matter-bound polycyclic aromatic hydrocarbons on blood thrombogenicity in adults].

Objective: To investigate the effects of exposure to ambient fine particulate matter-bound polycyclic aromatic hydrocarbons on blood coagulation in adults. Methods: A total of 73 adult volunteers were recruited in a cohort study and had four clinical visits from November 2014 to January 2016. Blood samples were obtained and used to measure biomarkers of blood thrombogenicity, including soluble CD40 Ligand (sCD40L), soluble P-selection (sCD62P) and Fibrinogen (FIB). White blood cell (WBC), 8-Hydroxy-2'-Deoxyguanosine (8-OHdG), matrix metalloproteinase-2 (MMP-2) and HDL cholesterol efflux capacity (HDL-CEC) were also determined. Daily concentrations of ambient fine particulate matter-bound polycyclic aromatic hydrocarbons (PAHs) were measured throughout the study period, and positive matrix factorization (PMF) approach was used to identity PAHs sources. Linear mixed-effect models including single-pollutant model, two-pollutant model and stratification analysis were constructed to estimate the effects of exposure to ambient fine particulate matter-bound PAHs on blood thrombogenicity in adults after adjusting for potential confounders. Results: The mean age of participants was (23.3±5.4) years. During the study period, the median level of PM2.5-bound PAHs was (55.29±74.99) ng/m3. Six sources of PM2.5-bound PAHs were identified by PMF, with traffic sources contributing more than 50%. The linear mixed-effect model showed that PAHs exposure had a significant effect on elevated blood thrombogenicity. Significant elevations in sCD40L, sCD62P and FIB associated with per IQR increase (60.33 ng/m3) in exposure to PAHs were 14.36% (95%CI:6.94%-22.28%), 9.33% (95%CI: 1.71%-17.51%) and 2.07% (95%CI:0.44%-2.07%) at prior 5 days, respectively. Blood thrombogenicity levels were significantly and positively correlated with source-specific PAHs, especially gasoline vehicle emissions, diesel vehicle emission and coal burning at prior 1 or 5 days. Stronger associations between PAHs and increased blood thrombogenicity were found in participants with high plaque vulnerability, reduced HDL function, and high levels of inflammation and oxidative stress. Conclusion: Acute exposure to ambient fine particulate matter-bound PAHs, especially PAHs from traffic sources may promote blood thrombogenicity in adults, and PAHs have stronger effects on participants with reduced vascular function and high levels of inflammation and oxidative stress.

Pulmonary Complications of COVID-19: A case report.

Rapid evolution of pulmonary complications associated with severe COVID-19 pneumonia often pose a management challenge to clinicians especially in the critical care setting. Serial chest imaging enable clinicians to better monitor disease progression and identify potential complications early which may decrease the mortality and morbidity associated with COVID-19. We report a 69-year-old male patient with severe COVID-19 pneumonia who presented to a tertiary referral centre in Kuala Lumpur, Malaysia, in 2020 with multiple pulmonary complications including lung cavitation, bronchopleural fistula, pneumothorax, pneumomediastinum, subcutaneous emphysema and acute pulmonary embolism. Unfortunately, the patient died one month after admission. COVID-19 patients may develop pulmonary complications due to a combination of direct viral lung damage, hypoxaemia and high stress ventilation. Awareness of COVID-19 complications can prompt early diagnosis and timely management to reduce morbidity and mortality.

Target modulation and pharmacokinetics/pharmacodynamics translation of the BTK inhibitor poseltinib for model-informed phase II dose selection.

The selective Bruton tyrosine kinase (BTK) inhibitor poseltinib has been shown to inhibit the BCR signal transduction pathway and cytokine production in B cells (Park et al. Arthritis Res. Ther. 18, 91, https://doi.org/10.1186/s13075-016-0988-z , 2016). This study describes the translation of nonclinical research studies to a phase I clinical trial in healthy volunteers in which pharmacokinetics (PKs) and pharmacodynamics (PDs) were evaluated for dose determination. The BTK protein kinase inhibitory effects of poseltinib in human peripheral blood mononuclear cells (PBMCs) and in rats with collagen-induced arthritis (CIA) were evaluated. High-dimensional phosphorylation analysis was conducted on human immune cells such as B cells, CD8 + memory cells, CD4 + memory cells, NK cells, neutrophils, and monocytes, to map the impact of poseltinib on BTK/PLC and AKT signaling pathways. PK and PD profiles were evaluated in a first-in-human study in healthy donors, and a PK/PD model was established based on BTK occupancy. Poseltinib bound to the BTK protein and modulated BTK phosphorylation in human PBMCs. High-dimensional phosphorylation analysis of 94 nodes showed that poseltinib had the highest impact on anti-IgM + CD40L stimulated B cells, however, lower impacts on anti-CD3/CD-28 stimulated T cells, IL-2 stimulated CD4 + T cells and NK cells, M-CSF stimulated monocytes, or LPS-induced granulocytes. In anti-IgM + CD40L stimulated B cells, poseltinib inhibited the phosphorylation of BTK, AKT, and PLCγ2. Moreover, poseltinib dose dependently improved arthritis disease severity in CIA rat model. In a clinical phase I trial for healthy volunteers, poseltinib exhibited dose-dependent and persistent BTK occupancy in PBMCs of all poseltinib-administrated patients in the study. More than 80% of BTK occupancy at 40 mg dosing was maintained for up to 48 h after the first dose. A first-in-human healthy volunteer study of poseltinib established target engagement with circulating BTK protein. Desirable PK and PD properties were observed, and a modeling approach was used for rational dose selection for subsequent trials. Poseltinib was confirmed as a potential BTK inhibitor for the treatment of autoimmune diseases.Trial registration: This article includes the results of a clinical intervention on human participants [NCT01765478].

Selective optogenetic stimulation of glutamatergic, but not GABAergic, vestibular nuclei neurons induces immediate and reversible postural imbalance in mice.

Glutamatergic and GABAergic neurons represent the neural components of the medial vestibular nuclei. We assessed the functional role of glutamatergic and GABAergic neuronal pathways arising from the vestibular nuclei (VN) in the maintenance of gait and balance by optogenetically stimulating the VN in VGluT2-cre and GAD2-cre mice. We demonstrate that glutamatergic, but not GABAergic VN neuronal subpopulation is responsible for immediate and strong posturo-locomotor deficits, comparable to unilateral vestibular deafferentation models. During optogenetic stimulation, the support surface dramatically increased in VNVGluT2+ mice, and rapidly fell back to baseline after stimulation, whilst it remained unchanged during similar stimulation of VNGAD2+ mice. This effect persisted when vestibular tactilo kinesthesic plantar inputs were removed. Posturo-locomotor alterations evoked in VNVGluT2+ animals were still present immediately after stimulation, while they disappeared 1 h later. Overall, these results indicate a fundamental role for VNVGluT2+ neurons in balance and posturo-locomotor functions, but not for VNGAD2+ neurons, in this specific context. This new optogenetic approach will be useful to characterize the role of the different VN neuronal populations involved in vestibular physiology and pathophysiology.

ATP8a1, an IFT27 binding partner, is dispensable for spermatogenesis and male fertility.

Intraflagellar transport 27 (IFT27) is a key regulator for spermiogenesis and male fertility in mice. ATP8a1, a protein involved in the translocation of phosphatidylserine and phosphatidylethanolamine across lipid bilayers, is the strongest binding partner of IFT27. To investigate the role of ATP8a1 in spermatogenesis and male fertility, the global Atp8a1 knockout mice were analyzed. All mutant mice were fertile, and sperm count and motility were comparable to the control mice. Examination of testis and epididymis by hematoxylin and eosin staining did not reveal major histologic defects. These observations demonstrate that ATP8a1 is not a major spermatogenesis regulator. Given that a tissue-specific paralogue of ATP8a1, ATP8a2, is present, further studies with double-knockout models are warranted to delineate any compensatory functions of the two proteins.

Mobilization of recalcitrant phosphorous and enhancement of pepper P uptake and yield by a new biocontrol and bioremediation bacterium Burkholderia cepacia CQ18.

AIMS: Phosphorus (P) is a finite resource and inoculation of phosphorus-mobilizing bacteria (PMB) is a promising approach for the enhancement of soil P availability and plant P uptake. This drives scientists to search for the microbes effective in mobilizing legacy P in soils. METHODS AND RESULTS: The current incubation and greenhouse pot experiments were conducted to investigate P mobilization and pepper P uptake as affected by a new biocontrol and bioremediation bacterium Burkholderia cepacia CQ18. This bacterium converted Ca3 (PO4 )2 , FePO4 , AlPO4 , and lecithin into soluble inorganic P in the culture solutions and increased available P (including water-soluble P and Olsen P) in the soil. There were positive correlations between the soluble inorganic phosphorus and the exudates (protons, organic acids (oxalate and gluconate), siderophores and phosphatases) in culture solutions. Pepper plant biomass, fruit yield and P uptake changed in the sequence: chemical fertilizers plus bacterial inoculant >only chemical fertilizers >only bacterial inoculant >blank control. CONCLUSIONS: Taking into account the wide spectrums of P mobilization and simultaneous production of acid, neutral and alkaline phosphatases at a given pH, B.cepacia CQ18 may be a potential PMB used in soils with wide pH ranges. The mechanisms employed by this bacterium in the solubilization of recalcitrant inorganic P could be the efflux of protons, organic acids (oxalate and gluconate) and siderophores. Phosphatases could be of utmost importance in the mineralization of the organic P. The production of siderophores and phosphatases by of B.cepacia CQ18 could thus be crucial for not only the antagonism against plant pathogens but also the mobilization of soil sparingly available P. SIGNIFICANCE AND IMPACT OF THE STUDY: Burkholderia cepacia CQ18 could be potentially developed into a biofertilizer.

Aquaporin-5 Expression Is Reduced in Lymphocytic Colitis.

OBJECTIVE: Aquaporin-5 (AQP5) is a member of a family of water channel proteins involved in the bidirectional transfer of water across cell membranes. Lymphocytic colitis (LC) and collagenous colitis (CC) are clinically similar diseases characterized by chronic watery diarrhea in patients with usually unremarkable colonic mucosa on colonoscopy. The aim of this study was to determine whether AQP5 expression in colonic epithelium is altered in LC and CC. METHODS: Sections of formalin-fixed and paraffin-embedded colorectal biopsies from three control patients (CTL), 8 patients with chronic non-bloody diarrhea with biopsies negative for active inflammation or significant distortion (CTL-D), 8 patients with LC, and 5 with CC were stained for AQP5 using immunohistochemistry. The staining intensity was scored as 3 (strong), 2 (intermediate), 1 (weak), or 0 (no staining). Statistical analysis was performed using Prism 7 Statistical Soft-ware. RESULTS: AQP5 was strongly expressed (score 3) in the epithelial cells in all three CTL cases and all 8 CTL-D cases. In the 5 cases of CC, 3(60%) had score 3 and 2(40%) had score 2, but none had a score of 1 or 0. Of the 8 LC cases, 2(25%) had score 3, 3 had score 2(37.5%), and 3 had score 1(37.5%) (p=0.0031). In the three cases of LC with markedly reduced AQP5 (score 1), enteric steroid treatment did not lead to significant improvement in diarrhea. CONCLUSIONS: Colorectal AQP5 expression is reduced in most cases of LC. Markedly reduced AQP5 expression in LC may identify a subset of patients with suboptimal response to enteric steroid treatment. Additional larger studies are needed to confirm these findings.This abstract was presented in part at Digestive Diseases Week in San Diego, CA, May 2019.

LncRNA SNHG15 promotes the proliferation of nasopharyngeal carcinoma via sponging miR-141-3p to upregulate KLF9.

OBJECTIVE: Long non-coding RNAs (lncRNAs) have been identified to exert an oncogenic or anti-tumor function in malignant tumors. LncRNA SNHG15 is verified to be an oncogene in hepatocellular carcinoma, colorectal cancer, and prostate cancer. In this paper, we mainly investigate the potential influence of SNHG15 on the progression of nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: SNHG15 levels in NPC tissues and cell lines were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation between SNHG15 level and prognosis of NPC patients was evaluated by the Kaplan-Meier method. Regulatory effects of SNHG15 on proliferative, colony formation abilities, and apoptosis of SUNE1 and CNE1 cells were assessed through a series of functional experiments. Potential miRNAs binding SNHG15 and the downstream gene of the microRNA (miRNA) were predicted by bioinformatics method, which was confirmed by Dual-Luciferase reporter gene assay and Western blot. RESULTS: SNHG15 was upregulated in NPC tissues and cells. High level of SNHG15 indicated worse survival in NPC patients. Knockdown of SNHG15 markedly suppressed proliferative ability and induced apoptosis in SUNE1 and CNE1 cells. It is verified that miR-141-3p was the direct target binding SNHG15, and KLF9 was the downstream gene of miR-141-3p. SNHG15 was demonstrated to be a ceRNA to upregulate KLF9 by competitively binding miR-141-3p. CONCLUSIONS: SNHG15 is upregulated in NPC tissues, and this aggravates the progression of NPC by absorbing miR-141-3p to upregulate KLF9.

Intestinal Spirochetosis: Case Series and Review of the Literature.

OBJECTIVE: This study aims to present the clinical, endoscopic, and histopathologic characteristics associated with intestinal spirochetosis (IS). It also serves to heighten awareness among pathologists, since the histologic appearance of spirochetosis could be subtle and easily overlooked. METHODS: Hematoxylin & eosin (H&E) slides and special stains of intestinal biopsies from six patients with a diagnosis of IS at our institution were reviewed. Clinical history, endoscopic, and histopathologic findings were obtained from electronic medical records. RESULTS: The patients presented with diverse clinical symptoms, and only one patient was asymptomatic. The most consistent symptoms were watery diarrhea and abdominal cramps. Two out of five treated patients reported symptomatic improvement after antibiotics therapy. The colonoscopy findings were not specific, ranging from normal mucosa to polyps, to mucosal ulcerations in one patient. On histologic examination, the typical "brush-like" organisms lying perpendicular to the surface epithelium are seen both on H&E stain and special stains. CONCLUSIONS: IS is usually an incidental histologic finding, and the association with symptoms is still unclear. The clinical presentation could be very diverse, hence, a long list of differential diagnosis should be ruled out. Additional clinical testing should be pursued if patients are unresponsive to antibiotic treatment.

[Risk factors of anastomotic leakage after robotic surgery for low and mid rectal cancer].

Objective: To investigate the risk factors associated with anastomotic leakage after robotic surgery in mid-low rectal cancer. Methods: A retrospective case-control study method was conducted. Inclusion criteria: (1) 18 to 80 years old; (2) pathologically confirmed rectal cancer; (3) distance <10 cm from tumor to anal margin; (4) robotic anterior rectal resection. Patients with previous history of colorectal cancer surgery, distant metastases or other malignant tumors, undergoing emergency surgery, with severe abdominal adhesions or those receiving combined organ resection were excluded. Based on the above criteria, 636 patients undergoing robotic radical sphincter-preserving surgery for mid-low rectal cancer in Zhongshan Hospital from January 2015 to December 2018 were included in this study, including 398 males (62.6%) and 238 females (37.4%) with a mean age of (61.9±11.3) years. Sixty-eight cases (10.7%) received neoadjuvant chemoradiotherapy. Amony the 636 included patients, 123(19.3%) underwent natural orifice specimen extraction surgery (NOSES) and 15 (2.3%) underwent preventive stoma. According to the cirteria developed by the International Rectal Cancer Research Group in 2010, the anastomotic leakage was classified as grade A (no requirement of intervention), B (requirement of intervention), and C (requirement of operation). Logistic regression was used to analyze the relationship between anastomotic leakage and clinicopathological factors. Factors in univariate analysis with P<0.05 were included in the multivariate analysis. Results: Anastomotic leakage occurred in 38 cases (6.0%). The grading of anastomotic leakage was grade A in 13 cases (2.0%), grade B in 19 cases (3.0%), and grade C in 6 cases (0.9%). The 3-year disease-free survival rate of patients with anastomotic leakage and without anastomotic leakage was 83.5% and 83.6% respectively (P=0.862); the 3-year overall survival rate of the two group was 85.1% and 87.5% respectively (P=0.296). The results of univariate logistic regression analysis showed that male (P=0.011), longer operation time (P=0.042), distance ≤5 cm from tumor to anal margin (P=0.012), more intraoperative blood loss (P=0.048) were associated with anastomotic leakage (all P<0.05). NOSES was not associated with anastomotic leakage (P=0.704). Multivariate analysis confirmed that male (OR=3.03, 95%CI: 1.37 to 7.14, P=0.010), operation time ≥180 minutes (OR=2.04, 95%CI: 1.03 to 3.99, P=0.040), distance ≤5 cm from tumor to anal margin (OR=2.56, 95%CI:1.28 to 5.26, P=0.008) were independent risk factors for anastomotic leakage. Conclusion: Male, short distance from tumor to anal margin, and long operation time are independent risk factors for anastomotic leakage in patients undergoing robotic mid-low rectal cancer radical surgeries. These patients need to be cautiously treated during surgery.

Effects of quorum quenching on temporal succession of activated sludge microbial community in a membrane bioreactor.

AIMS: Quorum quenching (QQ) is an attractive strategy for mitigating biofouling in membrane bioreactors (MBRs). However, the effects of QQ on the activated sludge (AS) process have not been adequately evaluated. This study investigated the long-term effects of QQ on a laboratory-scale anoxic-oxic MBR, focusing on AS performance and microbial community. METHODS AND RESULTS: Anoxic-oxic MBRs with and without QQ were operated for 91 days. QQ did not affect COD and TN removal efficiencies over the experimental period, during which its activity remained >90%. QQ reduced floc size by approximately 8% but had no effect on biomass concentration. AS microbial communities were regularly analysed using massively parallel sequencing. AS bacterial communities were temporally dynamic irrespective of QQ presence, for example, a temporal increase in bacterial diversity and a temporal decay of community similarity. QQ counteracted the temporal change in diversity and the temporal distance-community decay. Community comparison revealed that QQ changed the successional trajectory of the AS community at a late period, because it decelerated temporal changes of specific members, such as Thiothrix and Sphingomonadaceae*. Correlation networks revealed that QQ increased network clustering, complexity and density. The combined results suggest that the tighter microbial association by QQ increased the community resistance. CONCLUSIONS: QQ can enhance the diversity and stability of the AS community in MBR by counteracting the innate temporal change in community structure. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings are useful for the further advancement of QQ-based strategies in engineered microbial environments.

Efficacy of orally toxic sugar baits against contact-insecticide resistant culex quinquefasciatus.

In recent years, attractive toxic sugar bait has been used in the mosquito control in nature, and achieved good control effects. However, the current researches about toxic sugar bait did not focus on whether the wild mosquito population used for control is resistant or not. The purpose of this study was to evaluate the effectiveness of the toxic sugar bait against mosquito resistant populations to test the effects of bait on the control of mosquitoes with different levels of resistance. Boric acid, dinotefuran and deltamethrin were separately formulated into toxic sugar bait to test their anti-mosquito activity against Culex quinquefasciatus. Using the sugar baits formulated with boric acid and dinotefuran, the mortality of Cx. quinquefasciatus resistant populations was significantly higher than that of sensitive populations at the same concentration. Conversely, with the use of sugar baits formulated with deltamethrin, the mortality of Cx. quinquefasciatus resistant populations was significantly lower than that of sensitive populations at the same concentration. The results suggested that toxic sugar baits might have a good application prospect in high resistant mosquito management.

Contribution of single-gene defects to congenital cardiac left-sided lesions in the prenatal setting.

OBJECTIVES: To explore the contribution of single-gene defects to the genetic cause of cardiac left-sided lesions (LSLs), and to evaluate the incremental diagnostic yield of whole-exome sequencing (WES) for single-gene defects in fetuses with LSLs without aneuploidy or a pathogenic copy-number variant (pCNV). METHODS: Between 10 April 2015 and 30 October 2018, we recruited 80 pregnant women diagnosed with a LSL who had termination of pregnancy and genetic testing. Eligible LSLs were aortic valve atresia or stenosis, coarctation of the aorta, mitral atresia or stenosis and hypoplastic left heart syndrome (HLHS). CNV sequencing (CNV-seq) and WES were performed sequentially on specimens from these fetuses and their parents. CNV-seq was used to identify aneuploidies and pCNVs, while WES was used to identify diagnostic genetic variants in cases without aneuploidy or pCNV. RESULTS: Of 80 pregnancies included in the study, 27 (33.8%) had a genetic diagnosis. CNV-seq analysis identified six (7.5%) fetuses with aneuploidy and eight (10.0%) with pCNVs. WES analysis of the remaining 66 cases revealed diagnostic genetic variants in 13 (19.7%) cases, indicating that the diagnostic yield of WES for the entire cohort was 16.3% (13/80). KMT2D was the most frequently mutated gene (7/66 (10.6%)) in fetuses with LSL without aneuploidy or pCNVs, followed by NOTCH1 (4/66 (6.1%)). HLHS was the most prevalent cardiac phenotype (4/7) in cases with a KMT2D mutation in this cohort. An additional six (9.1%) cases were found to have potentially deleterious variants in candidate genes. CONCLUSIONS: Single-gene defects contribute substantially to the genetic etiology of fetal LSLs. KMT2D mutations accounted for approximately 10% of LSLs in our fetal cohort. WES has the potential to provide genetic diagnoses in fetuses with LSLs without aneuploidy or pCNVs. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Contribución de los defectos unigénicos a las lesiones cardíacas congénitas del lado izquierdo en el ámbito prenatal OBJETIVOS: Estudiar la contribución de los defectos unigénicos a la causa genética de las lesiones cardíacas del lado izquierdo (LCLI) y evaluar el desempeño del diagnóstico incremental de la secuenciación hologenómica (SHG) para los defectos unigénicos en los fetos con LCLI sin aneuploidía o sin variación patógena en el número de copias (pCNV, por sus siglas en inglés). MÉTODOS: Entre el 10 de abril de 2015 y el 30 de octubre de 2018 se reclutaron 80 mujeres embarazadas diagnosticadas con LCLI, las cuales se sometieron a una interrupción del embarazo y a pruebas genéticas. Las LCLI elegibles eran la atresia o estenosis de la válvula aórtica, la coartación de la aorta, la atresia o estenosis mitral y el síndrome del hemicardio izquierdo hipoplásico (SHIH). La secuenciación CNV (CNV-seq) y la SHG se realizaron de forma secuencial en muestras de estos fetos y de sus padres. La CNV-seq se utilizó para identificar las aneuploidías y las pCNV, mientras que la SHG se utilizó para identificar las variantes genéticas de diagnóstico en los casos sin aneuploidías o pCNV. RESULTADOS: De 80 embarazos incluidos en el estudio, 27 (33,8%) tuvieron un diagnóstico genético. El análisis de la CNV-seq identificó seis (7,5%) fetos con aneuploidía y ocho (10,0%) con pCNV. El análisis de la SHG de los 66 casos restantes manifestó variantes genéticas de diagnóstico en 13 (19,7%) casos, lo que indica que el comportamiento del diagnóstico del SHG para toda la cohorte fue del 16,3% (13/80). El KMT2D fue el gen que mutó más frecuentemente (7/66 (10,6%)) en los fetos con LCLI sin aneuploidía o pCNV, seguido de NOTCH1 (4/66 (6,1%)). El SHIH fue el fenotipo cardíaco más prevalente (4/7) en los casos con mutación de KMT2D en esta cohorte. En seis casos (9,1%) adicionales se encontraron variantes potencialmente perjudiciales en los genes con riesgo. CONCLUSIONES: Los defectos unigénicos contribuyen sustancialmente a la etiología genética de las LCLI fetales. Las mutaciones de KMT2D representaron aproximadamente el 10% de las LCLI en esta cohorte fetal. La SHG tiene el potencial de proporcionar diagnósticos genéticos en fetos con LCLI sin aneuploidía o sin pCNV. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Known-component metal artifact reduction (KC-MAR) for cone-beam CT.

Intraoperative cone-beam CT (CBCT) is increasingly used for surgical navigation and validation of device placement. In spinal deformity correction, CBCT provides visualization of pedicle screws and fixation rods in relation to adjacent anatomy. This work reports and evaluates a method that uses prior information regarding such surgical instrumentation for improved metal artifact reduction (MAR). The known-component MAR (KC-MAR) approach achieves precise localization of instrumentation in projection images using rigid or deformable 3D-2D registration of component models, thereby overcoming residual errors associated with segmentation-based methods. Projection data containing metal components are processed via 2D inpainting of the detector signal, followed by 3D filtered back-projection (FBP). Phantom studies were performed to identify nominal algorithm parameters and quantitatively investigate performance over a range of component material composition and size. A cadaver study emulating screw and rod placement in spinal deformity correction was conducted to evaluate performance under realistic clinical imaging conditions. KC-MAR demonstrated reduction in artifacts (standard deviation in voxel values) across a range of component types and dose levels, reducing the artifact to 5-10 HU. Accurate component delineation was demonstrated for rigid (screw) and deformable (rod) models with sub-mm registration errors, and a single-pixel dilation of the projected components was found to compensate for partial-volume effects. Artifacts associated with spine screws and rods were reduced by 40%-80% in cadaver studies, and the resulting images demonstrated markedly improved visualization of instrumentation (e.g. screw threads) within cortical margins. The KC-MAR algorithm combines knowledge of surgical instrumentation with 3D image reconstruction in a manner that overcomes potential pitfalls of segmentation. The approach is compatible with FBP-thereby maintaining simplicity in a manner that is consistent with surgical workflow-or more sophisticated model-based reconstruction methods that could further improve image quality and/or help reduce radiation dose.