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In this paper, we propose an attention-based instance and semantic segmentation joint approach, termed ABJNet, for addressing the instance and semantic segmentation of 3D point clouds simultaneously. First, a point feature enrichment (PFE) module is used to enrich the segmentation network’s input data by indicating the relative importance of each point’s neighbors. Then, a more efficient attention pooling operation is designed to establish a novel module for extracting point cloud features. Finally, an efficient attention-based joint segmentation module (ABJS) is proposed for combining semantic features and instance features in order to improve both segmentation tasks. We evaluate the proposed attention-based joint semantic-instance segmentation neural network (ABJNet) on a variety of indoor scene datasets, including S3DIS and ScanNet V2. Experimental results demonstrate that our method outperforms the start-of-the-art method in 3D instance segmentation and significantly outperforms it in 3D semantic segmentation.

AbstractDespite considerable research efforts, pancreatic cancer is associated with a dire prognosis and a 5-year survival rate of only 10%. Early symptoms of the disease are mostly nonspecific. The premise of improved survival through early detection is that more individuals will benefit from potentially curative treatment. Artificial intelligence (AI) methodology has emerged as a successful tool for risk stratification and identification in general health care. In response to the maturity of AI, Kenner Family Research Fund conducted the 2020 AI and Early Detection of Pancreatic Cancer Virtual Summit (www.pdac-virtualsummit.org) in conjunction with the American Pancreatic Association, with a focus on the potential of AI to advance early detection efforts in this disease. This comprehensive presummit article was prepared based on information provided by each of the interdisciplinary participants on one of the 5 following topics: Progress, Problems, and Prospects for Early Detection; AI and Machine Learning; AI and Pancreatic Cancer-Current Efforts; Collaborative Opportunities; and Moving Forward-Reflections from Government, Industry, and Advocacy. The outcome from the robust Summit conversations, to be presented in a future white paper, indicate that significant progress must be the result of strategic collaboration among investigators and institutions from multidisciplinary backgrounds, supported by committed funders.

Mingqiang Gong,1,2,* Yunxia Shen,2,* Wenbin Liang,2 Zhen Zhang,3 Chunxue He,4 Mingwu Lou,2 ZiYu Xu2 1Department of Acupuncture and Moxibustion, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Department of Radiology, Longgang Central Hospital, Shenzhen, People’s Republic of China; 3Department of Radiology, The Third People’s Hospital of Longgang District, Shenzhen, People’s Republic of China; 4Department of Radiology, Shenzhen Clinical Medicine College, Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingwu Lou; ZiYu Xu, Department of Radiology, Longgang Central Hospital, No. 6082, Longgang Avenue, Longgang District, Shenzhen, 518000, People’s Republic of China, Tel +86 13808854650 ; +86 13824321925, Email mingwulou@sina.com; xuziyu82@163.comPurpose: Methamphetamine use may cause severe neurotoxicity and cognitive impairment, leading to addiction, overdose, and high rates of relapse. However, few studies have systematically focused on functional impairments detected by neuroimaging in methamphetamine abstainers (MAs) during short-term abstinence. This study aimed to investigate effective connectivity, resting-state networks, and internetwork functional connectivity in MA brains to improve clinical treatment.Methods: Twenty MAs and 27 age- and education-matched healthy controls underwent resting-state functional magnetic resonance imaging. The amplitude of low-frequency fluctuations and Granger causality were analyzed to investigate disrupted brain regions and effective connectivity, respectively. Independent component analysis and functional network connectivity were used to identify resting-state networks and internetwork functional connectivity, respectively.Results: Compared with healthy controls, MAs demonstrated abnormal amplitudes of low-frequency fluctuations in the bilateral precuneus, left posterior cingulate cortex (PCC), left middle frontal gyrus (MFG), left superior parietal lobule, left supplementary motor area (SMA), and left inferior parietal lobule (IPL). Moreover, MAs showed decreased effective connectivity from the left PCC to the left precuneus, increased effective connectivity from the left precuneus to the left MFG and from the right precuneus to the left SMA, and altered functional connectivity within the default mode network (DMN), frontoparietal network, sensorimotor network, ventral attention network, cerebellar network, and visual network. Importantly, hyperconnectivity between the DMN and ventral attention network and hypoconnectivity between the DMN and cerebellar network as well as the DMN and frontoparietal network were demonstrated in MAs.Conclusion: Our study implies that in short-term methamphetamine abstinence, disruptions to the DMN and executive network may a play key role, providing new insights for early rehabilitation.Keywords: methamphetamine, abstinence, network, Granger causality analysis, independent component analysis

Chengxiao Fu,1,2,* Qi Pei,3,* Wu Liang,4 Bo Yang,2 Wei Li,5 Jun Liu,5 Hongyi Tan,1,4 Chengxian Guo,1,4 Hao Zhang,5 Guoping Yang1,4 1Center for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2The First Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, People’s Republic of China; 3Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 4Research Center of Drug Clinical Evaluation of Central South University, Changsha, People’s Republic of China; 5Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoping Yang; Hao Zhang, Email ygp9880@126.com; zhanghaoliaoqing@163.comPurpose: Parathyroid hormone (PTH) can induce the downregulation of CYP3A in chronic kidney disease (CKD). Nevertheless, the effect of PTH on CYP3A-mediated clearance pathways from a clinical perspective remains unclear.Methods: This study employed population pharmacokinetic (PopPK) modeling to delineate potential changes in CYP3A activity in patients with CKD. Pharmacokinetic data for nifedipine, a typical CYP3A substrate, as well as covariate information, were prospectively collected from 157 patients with a total of 612 concentrations. PopPK data analysis was performed using a nonlinear mixed-effects model.Results: The pharmacokinetics of nifedipine were optimally described according to a one-compartment model with zero-order absorption and first-order elimination. The estimated population parameters (and interindividual variability) were apparent clearance (CL/F) 49.61 L/h (58.33%) and apparent volume of distribution (V/F) 2300.26 L (45.62%), and the PTH level negatively correlated with CL/F. In comparison with the reference level, it was observed that the dosage of nifedipine should be reduced with the maximum boundary value of PTH, after a Monte Carlo simulation.Conclusion: This study provides insight into the effects of PTH on CYP3A-mediated clearance pathways. Moreover, PTH could be used as a guide for the appropriate administration of CYP3A eliminated drugs in patients with CKD.Keywords: chronic kidney disease, parathyroid hormone, CYP3A, population pharmacokinetic, nifedipine

Purpose Anesthetics are required for procedures that deliver drugs/biologics, infectious/inflammatory agents, and toxicants directly to the lungs. However, the possible confounding effects of anesthesia on lung inflammation and injury are underreported. Here, we evaluated the effects of two commonly used anesthetic regimens on lung inflammatory responses to ozone in mice. Methods We tested the effects of brief isoflurane (Iso) or ketamine/xylazine/atipamezole (K/X/A) anesthesia prior to ozone exposure (4 h, 3 ppm) on lung inflammatory responses in mice. Anesthesia regimens modeled those used for non-surgical intratracheal instillations and were administered 1-2 h or 24 h prior to initiating ozone exposure. Results We found that Iso given 1-2 h prior to ozone inhibited inflammatory responses in the lung, and this effect was absent when Iso was given 23-24 h prior to ozone. In contrast, K/X/A given 1-2 h prior to ozone increased lung and systemic inflammation. Conclusion Our results highlight the need to comprehensively evaluate anesthesia as an experimental variable in the assessment of lung inflammation in response to ozone and other inflammatory stimuli., Author(s): Miranda L. Wilson [sup.1] [sup.3], Jarl A. Thysell [sup.1] [sup.2], Kristen K. Baumann [sup.1], Danny V. Quaranta [sup.1] [sup.2], W. Sandy Liang [sup.1], Michelle A. Erickson [sup.1] [sup.2] Author [...]

Nan Liu, Bo Chen, Luchuan Li, Qingdong Zeng, Lei Sheng, Bin Zhang, Weili Liang, Bin Lv Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Bin LvDepartment of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of ChinaEmail lvbin@sdu.edu.cnBackground: Recurrent laryngeal nerve injury (RLNI) still occurs in total endoscopic thyroidectomy (TET) by using intraoperative neuromonitoring (IONM). As the region where most injuries occur, more attention should be paid to RLNI near the nerve entry point (NEP) in TET.Materials and Methods: This cohort study collected retrospectively data from 415 patients who underwent TET between February 2012 and December 2019. The functions of the recurrent laryngeal nerve (RLN) in TET were recorded by IONM. The patients with RLNI near the NEP were followed up by laryngoscopies. The demographic and clinical characteristics, the mechanisms of RLNI, and the outcomes of RLNI were recorded and analyzed.Results: There were a total of 444 at-risk nerves in 405 patients were analyzed. The incidence of RLNI near the NEP was 7.9%. RLNs with extralaryngeal branches were more likely to be injured near the NEP (P = 0.037). The incidences of different types of RLNI, in order of frequency, were 68.8% for thermal injury (n = 22), 28.1% for traction/compression injury (n = 9), and 3.1% for transverse injury (n = 1). A total of 93.8% (n = 30) of RLNI patients had complete recovery of vocal cord activity function.Conclusion: The extralaryngeal branch was a risk factor for RLNI near the NEP in TET. Thermal injury caused by an ultrasonic scalpel was the most common cause of RLNI near the NEP. Most RLNIs near the NEP would eventually recover.Keywords: thyroid surgery, total endoscopic thyroidectomy, recurrent laryngeal nerve injury, intraoperative neuromonitoring, recovery time

Yonghao Xu,* Manshu Li,* Liang Zhou,* Dongdong Liu, Weiqun He, Weibo Liang, Qingwen Sun, Huadong Sun, Yimin Li, Xiaoqing Liu Department of Critical Care Medicine, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoqing LiuDepartment of Critical Care Medicine, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Street West, Guangzhou, Guangdong, 510120, People’s Republic of ChinaEmail lxq1118@126.comBackground: The coronavirus disease 2019 (COVID-19) pandemic has spread all over the world resulting in high mortality, yet no specific antiviral treatment has been recommended.Methods: A retrospective descriptive study was conducted involving 19 consecutive critically ill patients during January 27, 2020 to April 18, 2020. Ribavirin was given at 0.15g q8h orally upon ICU admission for 7 to 21 days. Here, 28-day mortality, lower respiratory tract specimens (ETA), and ribavirin side effect on the day of ICU admission (Day 1), Day 7, Day 14 and Day 21 were analyzed.Results: All the nineteen critically ill COVID-19 patients (14 males and 5 females, median age 56yr) survived through to the 28th day of observations with 6 patients (31.58%) being discharged from the ICU. The SARS-CoV-2 viral positivity in sputum/ETA was 100% (19/19) on Day 1, 73.68% (14/19) on Day 7, 57.89% (11/19) on Day 14 and 36.84% (7/19) on Day 21. Ribavirin side effect was not observed in these patients.Conclusion: Ribavirin is well tolerated in critically ill patients with COVID-19 and may benefit COVID-19 patients through increasing the virus clearance.Keywords: SARS-CoV-2, COVID-19, ribavirin, antiviral

Lei Xia,1 Wei Liang,2 Dan Que,2 Qichao Xie2 1Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing City, 400000, People’s Republic of China; 2Department of Oncology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing City, 400000, People’s Republic of ChinaCorrespondence: Qichao Xie Tel +86 23-60353465Email qichaoxieyubei@163.comBackground: The role of circRNA circ_0071662 has been studied in bladder cancer. The present study aimed to analyze its involvement in esophageal squamous cell carcinoma (ESCC).Methods: Patients with ESCC (n = 66), esophageal ulcer (EU, n = 66), or gastroesophageal reflux disease (GERD, n = 66) and healthy controls (n = 66) were enrolled in this study. Plasma samples were collected from all patients and controls. ESCC and paired non-tumor tissue samples were collected from ESCC patients. Circ_0071662 levels in these samples were determined by RT-qPCRs. Diagnostic and prognostic values of circ_0071662 for ESCC were analyzed with ROC curve and survival curve analyses.Results: Circ_0071662 level was decreased in ESCC, but not in GERN and EU compared to the controls and in ESCC tissues compared to the non-tumor tissues. Plasma circ_0071662 was closely correlated with patients’ tumor size but not with other clinical features. Decreased plasma circ_0071662 levels separated ESCC patients from GERN patients, EU patients, and healthy controls. Low plasma circ_0071662 levels were closely correlated with worse survival outcomes of ESCC patients.Conclusion: Circ_0071662 is lowly expressed in ESCC and may serve as a potential diagnostic and prognostic biomarker for ESCC.Keywords: esophageal squamous cell carcinoma, circ_0071662, diagnosis, prognosis

Dakai Xiao,1,&ast; Qiuhua Deng,1,&ast; Dongyun He,2,&ast; Ying Huang,2 Wenchi Liang,2 Fengnan Wang,2 Haihong Yang2 1Research Center forTranslational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China; 2Department of Thoracic Oncology, State Key Laboratory of Respiratory Diseases, National Clinical Research Center of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haihong YangDepartment of Thoracic Oncology, State Key Laboratory of Respiratory Diseases, National Clinical Research Center of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, 510120, People’s Republic of ChinaEmail bjrf2009@yahoo.comBackground: About 20% of patients with ALK-rearranged non-small cell lung cancer (NSCLC) develop acquired resistance to tyrosine kinase inhibitor (TKI) during the first 6 months. This study aimed to examine the molecular mechanisms of early TKI resistance and prognosis in ALK-rearranged NSCLC.Methods: Ten patients with ALK-rearranged NSCLC were included: five who developed rapid resistance to crizotinib (progression-free survival (PFS) ≤ 3 months) and five who exhibited a good response to crizotinib (PFS ≥ 36 months). The tumor specimens were subjected to whole-exome sequencing (WES). The validation cohort included 19 patients with ALK-rearranged NSCLC who received crizotinib; targeted sequencing of 43 selected genes was performed. The effect of the TP53 G245S mutation on crizotinib sensitivity was tested in H3122 cells.Results: Mutations in DNA repair-associated genes were identified in primary resistance to crizotinib. Patients with a poor response to crizotinib harbored a greater burden of somatic mutations than those with a good response [median somatic mutations, 136 (range, 72– 180) vs 31 (range, 10– 48)]. Compared with the patients carrying wild-type TP53 or TP53 exon 3 deletion, 29 patients with TP53 G245S mutation showed a shorter survival time (P < 0.05), with a median PFS of 3 (95% CI: 1.9– 4.1) months and a median overall survival of 7 (95% CI: 3.4– 10.5) months. TP53 mutation promoted the proliferation of EML4-ALK-rearranged H3122 cells by approximately 3 folds (P < 0.001). H3122 cells with TP53 mutant were more sensitive to crizotinib compared with control cells.Conclusion: A higher mutation burden and mutations in DNA repair gene, including TP53, were potentially associated with primary resistance to crizotinib in ALK-rearranged NSCLC. An immune-checkpoint inhibition strategy could be examined, which might overcome primary resistance to crizotinib in ALK-rearranged NSCLC.Keywords: ALK, non-small cell lung cancer, TKI, resistance, prognosis

Chuangkun Li,1,2,* Weiwen Liang,1,2,* Lili Chu,1,* Yingqi Wei,1,2 Xiusen Qin,1,2 Zifeng Yang,1,2 Wentai Guo,1,2 Hui Wang,1,2 Huaiming Wang,1,2 Rongkang Huang1,2 1Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huaiming WangDepartment of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, People’s Republic of ChinaEmail wanghm7@mail.sysu.edu.cnRongkang HuangDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of ChinaTel +86-134-8021-8647Email huangrk3@mail.sysu.edu.cnPurpose: Anastomotic leakage after rectal cancer surgery in elderly patients is a critical challenge. Many risk factors have been found and many interventions tried, but anastomotic leakage in elderly patients remains difficult to deal with. This study aimed to create a nomogram for predicting anastomotic leakage after rectal surgery in elderly rectal cancer patients with dysfunctional stomata.Methods: We collected data from 326 consecutive elderly patients with dysfunctional stomata after rectal cancer surgery at the Sixth Affiliated Hospital, Sun Yat-Sen University from January 2014 to December 2019. Risk factors of anastomotic leakage were identified with multivariate logistic regression and used to create a nomogram. Predictive performance was evaluated by the area under the receiver-operating characteristic (ROC) curve.Results: American Society of Anesthesiologists score ≥ 3, male sex, and neoadjuvant radiotherapy were identified as significantly associated factors that could be combined for accurate prediction of anastomotic leakage on multivariate logistic regression and development of a nomogram.The area under the ROC curve for this model was 0.645. The C-index value for this model was 0.645, indicating moderate predictive ability of the risk of anastomotic leakage.Conclusion: The nomogram showed good ability to predict anastomotic leakage in elderly patients with rectal cancer after surgery, and might be helpful in providing a reference point for selection of surgical procedures and perioperative treatment.Keywords: nomogram, rectal cancer, anastomotic leakage, elderly patients

Chronic pancreatitis is a prominent risk factor for the development of pancreatic ductal adenocarcinoma. In both conditions, the activation of myofibroblast-like pancreatic stellate cells (PSCs) plays a predominant role in the formation of desmoplastic reaction through the synthesis of connective tissue and extracellular matrix, inducing local pancreatic fibrosis and an inflammatory response. Yet the signaling events involved in chronic pancreatitis and pancreatic cancer progression and metastasis remain poorly defined. Cadherin-11 (Cad-11, also known as OB cadherin or CDH11) is a cell-to-cell adhesion molecule implicated in many biological functions, including tissue morphogenesis and architecture, extracellular matrix-mediated tissue remodeling, cytoskeletal organization, epithelial-to-mesenchymal transition, and cellular migration. In this study, we show that, in human chronic pancreatitis and pancreatic cancer tissues, Cad-11 expression was significantly increased in PSCs and pancreatic cancer cells. In particular, an increased expression of Cad-11 can be detected on the plasma membrane of activated PSCs isolated from chronic pancreatitis tissues and in pancreatic cancer cells metastasized to the liver. Moreover, knockdown of Cad-11 in cancer cells reduced pancreatic cancer cell migration. Taken together, our data underline the potential role of Cad-11 in PSC activation and pancreatic cancer metastasis.

Epidemiologic data has linked obesity to a higher risk of pancreatic cancer, but the underlying mechanisms are poorly understood. To allow for detailed mechanistic studies in a relevant model mimicking diet-induced obesity and pancreatic cancer, a high-fat, high-calorie diet (HFCD) was given to P48+/Cre;LSL-KRASG12D (KC) mice carrying a pancreas-specific oncogenic Kras mutation. The mice were randomly allocated to a HFCD or control diet (CD). Cohorts were sacrificed at 3, 6, and 9 months and tissues were harvested for further analysis. Compared to CD-fed mice, HFCD-fed animals gained significantly more weight. Importantly, the cancer incidence was remarkably increased in HFCD-fed KC mice, particularly in male KC mice. In addition, KC mice fed the HFCD showed more extensive inflammation and fibrosis, and more advanced PanIN lesions in the pancreas, compared to age-matched CD-fed animals. Interestingly, we found that the HFCD reduced autophagic flux in PanIN lesions in KC mice. Further, exome sequencing of isolated murine PanIN lesions identified numerous genetic variants unique to the HFCD. These data underscore the role of sustained inflammation and dysregulated autophagy in diet-induced pancreatic cancer development and suggest that diet-induced genetic alterations may contribute to this process. Our findings provide a better understanding of the mechanisms underlying the obesity-cancer link in males and females, and will facilitate the development of interventions targeting obesity-associated pancreatic cancer.