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LRRK2, GBA and their interaction in the regulation of autophagy: implications on therapeutics in Parkinson’s disease

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Translational Neurodegeneration 2022年第1期11卷 869-882页

作者： Shirley Yin-Yu Pang Rachel Cheuk Nam Lo Philip Wing-Lok Ho Hui-Fang Liu Eunice Eun Seo Chang Chi-Ting Leung Yasine Malki Zoe Yuen-Kiu Choi Wing Yan Wong michelle hiu-wai kung David Boyer Ramsden Shu-Leong Ho Division of Neurology Department of MedicineQueen Mary HospitalUniversity of Hong KongHong KongChina School of Biomedical Sciences Li Ka Shing Faculty of MedicineUniversity of Hong KongHong KongChina Institute of Metabolism and Systems Research University of BirminghamBirminghamUK.

Mutations in leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA) represent two most common genetic causes of Parkinson’s disease (PD). Both genes are important in the autophagic-lysosomal pathway (ALP), defects of which are associated with α-synuclein (α-syn) accumulation. LRRK2 regulates macroautophagy via activation of the mitogen activated protein kinase/extracellular signal regulated protein kinase (MAPK/ERK) kinase (MEK) and the calcium-dependent adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathways. Phosphorylation of Rab GTPases by LRRK2 regulates lysosomal homeostasis and endosomal trafficking. Mutant LRRK2 impairs chaperone-mediated autophagy, resulting in α-syn binding and oligomerization on lysosomal membranes. Mutations in GBA reduce glucocerebrosidase (GCase) activity, leading to glucosylceramide accumulation, α-syn aggregation and broad autophagic abnormalities. LRRK2 and GBA influence each other: GCase activity is reduced in LRRK2 mutant cells, and LRRK2 kinase inhibition can alter GCase activity in GBA mutant cells. Clinically, LRRK2 G2019S mutation seems to modify the effects of GBA mutation, resulting in milder symptoms than those resulting from GBA mutation alone. However, dual mutation carriers have an increased risk of PD and earlier age of onset compared with single mutation carriers, suggesting an additive deleterious effect on the initiation of PD pathogenic processes. Crosstalk between LRRK2 and GBA in PD exists, but its exact mechanism is unclear. Drugs that inhibit LRRK2 kinase or activate GCase are showing efficacy in pre-clinical models. Since LRRK2 kinase and GCase activities are also altered in idiopathic PD (iPD), it remains to be seen if these drugs will be useful in disease modification of iPD.

关键词： Parkinson’s disease Interaction LRRK2 GBA GCase Mutation Autophagy α-Synuclein

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Lottery Numbers and Ordered Statistics

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Applied Mathematics 2024年第4期15卷 287-291页

作者： kung-Kuen Tse Department of Mathematics Kean University Union NJ USA

The lottery has long captivated the imagination of players worldwide, offering the tantalizing possibility of life-changing wins. While winning the lottery is largely a matter of chance, as lottery drawings are typically random and unpredictable. Some people use the lottery terminal randomly generates numbers for them, some players choose numbers that hold personal significance to them, such as birthdays, anniversaries, or other important dates, some enthusiasts have turned to statistical analysis as a means to analyze past winning numbers identify patterns or frequencies. In this paper, we use order statistics to estimate the probability of specific order of numbers or number combinations being drawn in future drawings.

关键词： Lottery Order Statistics Hypergeometric Distribution Expectation Uniform

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Effects of green bonds on bioenergy development under climate change: A case study in Taiwan province, China

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Advances in Climate Change Research 2022年第1期13卷 97-106页

作者： Shan-Shan kung Hai-Ling LI Si-Ru LI Li-Guo ZHANG Chih-Chun kung College of Foreign Studies Hubei University of EconomicsWuhan 430205China Office of Postdoctoral Management Jiangxi University of Finance and EconomicsNanchang 330013China School of International Trade&Economics University of International Business&EconomicsBeijing 100021China School of Economics Jiangxi University of Finance&EconomicsNanchang 330013China

Bioenergy development improves energy security and mitigates climate *** the stable supply of agricultural resources provides a solid basis for efficient bioenergy production,the climate-induced impacts such as changes in lempeniture and precipitation that potentially alter the farming decisions and cropping patterns should be taken into *** study designs two-stage stochastic programming with recourse model to investigate the net bioenergy production and emission reduction,as well as the bioenergy producers'strategies under various market operations and climate *** results show that the net production of biopower and biofuel are relatively stable because the supply of bioenergy feedstocks could remain at a constant level,but the farming decisions,cropping pattern,and resource utilization are likely to be altered by climate-induced *** results also indicate that for efficient bioenergy production,approximately 41.5 billion TWD(9.65 billion CNY)and 33.6 billion TWD(7.81 billion CNY)of bond principal should be invested in crop-based and residual-based technology,*** the face of strict environmental regulations and emission management,biopower technology becomes more competitive,and under such a circumstance,more than 98.3%of the low-cost bond should be invested in biopower development to achieve development efficiency.

关键词： Climate change mitigation Financial mechanism Renewable energy Sustainable development

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Targeting PP2A for cancer therapeutic modulation

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Cancer Biology & Medicine 2022年第10期19卷 1428-1439页

作者： Halle Ronk Jared S.Rosenblum Timothy kung Zhengping Zhuang Neuro-Oncology Branch National Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA

Protein phosphatases play essential roles as negative regulators of kinases and signaling cascades involved in cytoskeletal *** phosphatase 2A(PP2A)is highly conserved and is the predominant serine/threonine phosphatase in the nervous system,constituting more than 70%of all neuronal ***2A is involved in diverse regulatory functions,including cell cycle progression,apoptosis,and DNA *** PP2A has historically been identified as a tumor suppressor,inhibition of PP2A has paradoxically demonstrated potential as a therapeutic target for various ***100,a water-soluble,small-molecule competitive inhibitor of PP2A,has shown particular promise as a chemo-and radio-sensitizing *** success has led to a profusion of clinical trials on LB100 adjuvant therapies,including a phase I trial in extensive-stage small-cell lung cancer,a phase I/II trial in myelodysplastic syndrome,a phase II trial in recurrent glioblastoma,and a completed phase I trial assessing the safety of LB100 and docetaxel in various relapsed solid ***,we review the development of LB100,the role of PP2A in cancer biology,and recent advances in targeting PP2A inhibition in immunotherapy.

关键词： Chemo-sensitization clinical trials colorectal cancer glioblastoma immunotherapy LB100 protein phosphatase 2A PP2A inhibition radio-sensitization small molecule inhibitor

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Idiopathic colopleural fistula presenting with lung abscess and refractory empyema:A case report

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World Journal of Gastrointestinal Surgery 2023年第4期15卷 740-744页

作者： Chun-Li Wang kung-Chuan Cheng Division of Colorectal Surgery Department of SurgeryKaohsiung Chang Gung Memorial HospitalKaohsiung 833Taiwan

BACKGROUND Colopleural fistula is a rare condition,and only a limited number of cases have been ***,we report a case of idiopathic colopleural fistula in an adult without any known predisposing *** patient presented with a lung abscess and refractory empyema and was successfully treated with surgical *** SUMMARY A 47-year-old man with a history of lung tuberculosis,which had been completely cured 4 years ago,presented to our emergency department with a productive cough and fever for 3 *** his history,he had undergone left lower lobe segmentectomy of the left lung due to lung abscess one year ago at another ***,he developed refractory empyema postoperatively despite surgical intervention including decortication and flap *** admission,we reviewed his previous medical images and noted a fistula tract between the left pleural cavity and splenic *** addition,according to his medical records,bacterial culture of the thoracic drainage showed growth of Escherichia coli and Bacteroides *** lower gastrointestinal series and colonoscopy confirmed the diagnosis of colopleural *** patient underwent a left hemicolectomy,splenectomy,and distal pancreatectomy,and the diaphragm was repaired under our *** further empyema recurrence was noted during *** Indicative signs of colopleural fistula include refractory empyema accompanied by the growth of colonic flora in the pleural fluid.

关键词： Colopleural fistula Lung abscess Empyema Colonic flora Case report

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Role of locoregional therapies in the management of patients with hepatocellular carcinoma

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Hepatoma Research 2022年第1期8卷 106-126页

作者： Janet Wui Cheung kung Kelvin Kwok Chai Ng Department of Surgery The Chinese University of Hong KongHong Kong 999077China

Hepatocellular carcinoma(HCC)was the sixth most common cancer and the third cause of cancer-related deaths worldwide in *** resection and transplantation remain the cornerstone for patients with early-stage disease and represent the only option for potential cure in ***,fewer than 10%of patients are considered suitable for surgery at the time of *** therapies,defined as minimally invasive image-guided liver tumour-directed procedures,are integral to in the management of *** review discusses the role of locoregional therapies in HCC management in the emergence of immune and systemic treatments.

关键词： Locoregional therapy hepatocellular carcinoma ablation transarterial embolization radiation therapy

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Sensor Networking: Concepts, Applications, and Challenges

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自动化学报 2006年第6期32卷 839-845页

作者： YAO kung Electrical Engineering Department University of California Los Angeles 90095 - 1594 USA

Sensor network has experienced world-wide explosive interests in recent years. It combines the technology of modern microelectronic sensors, embedded computational processing systems, and modern computer and wireless networking methodologies. In this overview paper, we first provide some rationales for the growth of sensor networking. Then we discuss various basic concepts and hardware issues. Four basic application cases in the US. National Science Foundation funded Ceneter for Embedded Networked Sensing program at UCLA are presented. Finally, six challenging issues in sensor networks are discussed. Numerous references including relevant papers, books, and conferences that have appeared in recent years are given.

关键词： Sensor networks wireless communication embedded processing information processing environmental monitoring health care system robotics automated manufacturing

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Surgical outcomes and quality of life following exercise-based prehabilitation for hepato-pancreatico-biliary surgery:A systematic review and meta-analysis

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Hepatobiliary & Pancreatic Diseases International 2022年第3期21卷 207-217页

作者： Andy Deprato Kevin Verhoeff Kieran Purich Janice Y kung David L Bigam Khaled Z Dajani University of Alberta 116 St&85 AveEdmontonAlberta T6G 2R3Canada Department of Surgery University of Alberta Hospital8440112 Street NWEdmontonAlberta T6G 2B7Canada John W.Scott Health Sciences Library University of Alberta Hospital8440112 Street NWEdmontonAlberta T6G 2B7Canada Department of Surgery Division of General SurgeryHPB Transplant and OncologyUniversity of Alberta Hospital8440112 Street NWEdmontonAlberta T6G 2B7Canada

Background:Hepato-pancreatico-biliary(HPB)patients experience significant risk of preoperative *** assessing preventative prehabilitation in HPB populations are *** systematic review and meta-analysis evaluates outcomes for HPB patients treated with exercise *** sources:A comprehensive search of MEDLINE(via Ovid),Embase(Ovid),Scopus,Web of Science Core Collection,Cochrane Library(Wiley),Pro Quest Dissertations,Theses Global,and Google Scholar was conducted with review and extraction following PRISMA *** studies evaluated more than 5 adult HPB patients undergoing≥7-day exercise *** primary outcome was postoperative length of stay(LOS);secondary outcomes included complications,mortality,physical performance,and quality of ***:We evaluated 1778 titles and abstracts and selected 6(randomized controlled trial,n=3;prospective cohort,n=1;retrospective cohort,n=2)that included 957 *** those,536 patients(56.0%)underwent exercise prehabilitation and 421(44.0%)received standard *** in both groups were similar with regards to important demographic *** was associated with a 5.20-day LOS reduction(P=0.03);when outliers were removed,LOS reduction decreased to 1.85 days and was non-statistically significant(P=0.34).Postoperative complications(OR=0.70;95%CI:0.39 to 1.26;P=0.23),major complications(OR=0.83;95%CI:0.60 to 1.14;P=0.24),and mortality(OR=0.67;95%CI:0.17 to 2.70;P=0.57)were *** was associated with improved strength,cardiopulmonary function,quality of life,and alleviated ***:Exercise prehabilitation may reduce LOS and morbidity following HPB *** with well-defined exercise regimens are needed to optimize exercise prehabilitation outcomes.

关键词： Exercise-based prehabilitation Preoperative exercise Hepatobiliary Pancreaticoduodenectomy Hepatic resection Pancreatectomy

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Vascular resections in minimally invasive surgery for pancreatic cancer

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Laparoscopic, Endoscopic and Robotic Surgery 2022年第1期5卷 3-9页

作者： Janet W.C.kung Rowan W.Parks Division of HBP Surgery Prince of Wales HospitalShatinHong KongChina Department of Surgery The Chinese University of Hong KongHong KongChina HPB Surgery Royal Infirmary of EdinburghEdinburghUnited Kingdom Department of Clinical Surgery University of EdinburghEdinburghUnited Kingdom

Pancreatic ductal adenocarcinoma(PDAC)is characterised by poor oncological outcome and is the seventh cause of cancer-related deaths *** the advances in surgical technology,oncological treatment,and critical care,extended pancreatic resections including vascular resections have become more frequently performed in specialised ***,the boundaries of resectability continue to be pushed in order to achieve a potentially curative approach in selected patients in combination with neoadjuvant and adjuvant treatment *** review gives an overview on the current state of venous and arterial resections in PDAC surgery with particular attention given to the minimally invasive approach.

关键词： Pancreatic adenocarcinoma Minimally invasive surgery Extended pancreatic resection Vascular resection Vascular reconstruction Neoadjuvant therapy

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Laparoscopic common bile duct exploration to treat choledocholithiasis in situs inversus patients:A technical review

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World Journal of Clinical Cases 2023年第9期11卷 1939-1950页

作者： Bo-Ya Chiu Shu-Hung Chuang Shih-Chang Chuang kung-Kai Kuo School of Post-baccalaureate Medicine College of MedicineKaohsiung Medical UniversityKaohsiung 80708Taiwan Division of General and Digestive Surgery Department of SurgeryKaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiung 80708Taiwan School of Medicine College of MedicineKaohsiung Medical UniversityKaohsiung 80708Taiwan

Situs inversus(SI)is a rare congenital condition characterized by a mirror-image transposition of the major visceral *** the 1990s,more than one hundred SI patients have been reported to have successfully undergone laparoscopic *** these cases,the major problem is to overcome is the left-right condition for right-handed *** common bile duct exploration(LCBDE),an alternative to treat patients with bile duct stones,has shown equivalent efficacy and is less likely to cause pancreatitis than endoscopic retrograde *** updated meta-analyses revealed that a shorter postoperative hospital stay,fewer procedural interventions,cost-effectiveness,a higher stone clearance rate,and fewer perioperative complications are additional advantages of ***,the technique is technically demanding,even for skilled laparoscopic *** LCBDE in patients with difficult situations,such as SI,is more complex than *** herein review published SI patients with choledocholithiasis treated by LCBDE,including our own experience,and this paper focuses on the technical aspects.

关键词： Choledocholithiasis Choledochotomy Laparoscopic common bile duct exploration Single incision Situs inversus Transcystic

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