bluuebunny/crossref_metadata_2025 huggingface dataset:
On the absence or presence of 3D tuned head direction cells in rats: a review and rebuttal
Authors: Taube Jeffrey S. , Shinder Michael E.
Published: March 2020

A major question in the field of spatial cognition is how animals represent three-dimensional (3D) space. Different results have been obtained across various species and may depend on whether the species inhabits a 3D environment or is terrestrial (land dwelling). The head direction (HD) cell system is an attractive candidate to study in terms of 3D representations. HD cells fire as a function of the animal’s directional heading in the horizontal plane, independent of the animal’s location and on-going behavior. Another issue concerns whether HD cells are tuned in 3D space or tuned to the 2D horizontal plane. Shinder and Taube (Shinder ME, Taube JS. J Neurophysiol 121: 4–37, 2019) addressed this issue by manipulating a rat’s orientation in 3D space while monitoring responses from classic HD cells in the rat anterodorsal thalamus. They reported that HD cells did not display conjunctive firing with pitch or roll orientations. Direction-specific firing was primarily derived from horizontal semicircular canal information and that the gravity vector played an important role in influencing the cell’s firing rate and its preferred firing direction. Laurens and Angelaki (Laurens J, Angelaki DE. J Neurophysiol 122: 1274–1287, 2019) challenged this view by performing a mathematical analysis on the Shinder and Taube data and concluded that they would not have seen 3D tuning based on their experimental approach. We provide a historical review of these issues followed by a summary of the experiments, which includes additional analyses. We then define what it means for a HD cell to be tuned in 3D and finish by rebutting the reanalyses performed by Laurens and Angelaki.
A Harmonic Impedance Estimation Method Based on the Cauchy Mixed Model
Authors: Tang Zhirong , Li Huaqiang , Xu Fangwei , Shu Qin , Jiang Yue
Published: March 2020

In this paper, a new method without any tradition assumption to estimate the utility harmonic impedance of a point of common coupling (PCC) is proposed. But, the existing estimation methods usually are built on some assumptions, such as, the background harmonic is stable and small, the harmonic impedance of the customer side is much larger than that of utility side, and the harmonic sources of both sides are independent. However these assumptions are unpractical to modern power grid, which causes very wrong estimation. The proposed method first uses a Cauchy Mixed Model (CMM) to express the Norton equivalent circuit of the PCC because we find that the CMM can right fit the statistical distribution of the measured harmonic data for any PCC, by testing and verifying massive measured harmonic data. Also, the parameters of the CMM are determined by the expectation maximization algorithm (EM), and then the utility harmonic impedance is estimated by means of the CMM’s parameters. Compared to the existing methods, the main advantages of our method are as follows: it can obtain the accurate estimation results, but it is no longer dependent of any assumption and is only related to the measured data distribution. Finally, the effectiveness of the proposed method is verified by simulation and field cases.
Impact of Different Developmental Instars onLocusta migratoriaJumping Performance
Authors: Mo Xiaojuan , Romano Donato , Milazzo Mario , Benelli Giovanni , Ge Wenjie , Stefanini Cesare
Published: March 2020

Ontogenetic locomotion research focuses on the evolution of locomotion behavior in different developmental stages of a species. Unlike vertebrates, ontogenetic locomotion in invertebrates is poorly investigated. Locusts represent an outstanding biological model to study this issue. They are hemimetabolous insects and have similar aspects and behaviors in different instars. This research is aimed at studying the jumping performance ofLocusta migratoriaover different developmental instars. Jumps of third instar, fourth instar, and adultL.migratoriawere recorded through a high-speed camera. Data were analyzed to develop a simplified biomechanical model of the insect: the elastic joint of locust hind legs was simplified as a torsional spring located at the femur-tibiae joint as a semilunar process and based on an energetic approach involving both locomotion and geometrical data. A simplified mathematical model evaluated the performances of each tested jump. Results showed that longer hind leg length, higher elastic parameter, and longer takeoff time synergistically contribute to a greater velocity and energy storing/releasing in adult locusts, if compared to young instars; at the same time, they compensate possible decreases of the acceleration due to the mass increase. This finding also gives insights for advanced bioinspired jumping robot design.
Resolution of Inflammation in Neurodegenerative Diseases: The Role of Resolvins
Authors: Chamani Sajad , Bianconi Vanessa , Tasbandi Aida , Pirro Matteo , Barreto George E. , Jamialahmadi Tannaz , Sahebkar Amirhossein
Published: March 2020

Acute inflammation has been described as a reactive dynamic process, promoted by the secretion of proinflammatory mediators, including lipid molecules like leukotrienes and prostaglandins, and counterbalanced by proresolving mediators including omega-3 polyunsaturated fatty-acid- (PUFA-) derived molecules. The switch from the initiation to the resolution phase of acute inflammatory response is crucial for tissue homeostasis, whereas the failure to resolve early inflammation by specialized proresolving mediators leads to chronic inflammation and tissue damage. Among PUFA-derived proresolving mediators, different eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derivatives have been described, namely, resolvins (resolution phase interaction products), which exert their anti-inflammatory and immune-regulatory activities through specific G-protein-coupled receptors. In recent years, compelling evidence has shown that impairment of resolution of inflammation is a crucial pathogenic hallmark in different neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. This review summarizes current knowledge on the role of resolvins in resolution of inflammation and highlights available evidence showing the neuroprotective potential of EPA- and DHA-derived resolvins (E-series and D-series resolvins, respectively) in neurodegenerative diseases.
Late-Onset Recurrent Femoral Cyst Formation 10 Years after ACL Reconstruction: A Case Report and Literature Review
Authors: Sanchez-Munoz Enrique , Maestro Fernández Antonio , Pipa Muñiz Iván , Rodríguez García Nicolas
Published: March 2020

Synovial fistula and cyst formation after anterior cruciate ligament (ACL) reconstruction is very unusual and almost always affects the tibia. Only 3 cases originating in the femur have been reported. We present a rare case of late-onset femoral cyst formation related to ACL reconstruction. Ten years after successful ACL reconstruction surgery, effusion and pain at the lateral aspect of the lateral femoral condyle appeared. Symptoms persisted despite initial percutaneous drainage and conservative treatment. Surgery was carried out, with drainage and graft-fixation pin device removal, with recurrent cyst formation after the intervention. Total recovery of the patient was achieved after carrying out revision surgery consisting in bone tunnel filling using autologous bone graft and occlusion of cortical bone defect with local fascial flap. The development of this unusual complication was related to lack of absorption of the fixation device, bone burn due to drilling, and persistent synovial fluid in the femoral bone tunnel, combined with the absence of bone ingrowth.
Performance Evaluation of Sesame under Regulated Deficit Irrigation Application in the Low Land of Western Gondar, Ethiopia
Authors: Ambachew Mekonnen Sisay , Sintayehu Assefa
Published: March 2020

Sesame (Sesamum indicum L.) is the leading oil seed crop produced in Ethiopia. It is the second most important agricultural commodity for export market in the country. It is well suited as an alternative crop production system, and it has low crop water requirement with moderate resistance to soil moisture deficit. The low land of North Western Ethiopia is the major sesame producer in the country, and the entire production is from rainfed. The rainfall distribution in North Western Ethiopia is significantly varied. This significant rainfall variability hampers the productivity of sesame. Irrigation agriculture has the potential to stabilize crop production and mitigate the negative impacts of variable rainfall. This study was proposed to identify critical growth stages during which sesame is most vulnerable to soil moisture deficit and to evaluate the crop water productivity of sesame under deficit irrigation. The performance of sesame to stage-wise and uniform deficit irrigation scheduling technique was tested at Gondar Agricultural Research Center (Metema Station), Northern Western Ethiopia. Eight treatments, four stage-wise deficit, two uniform deficit, one above optimal, and one optimal irrigation applications, were evaluated during the 2017 irrigation season. The experiment was designed as a randomized complete block design with three replications. Plant phenological variables, grain yield and crop water productivity, were used for performance evaluation. The result showed that deficit irrigation can be applied both throughout and at selected growth stages except the midseason stage. Imposing deficit during the midseason gave the lowest yield indicating the severe effect of water deficit during flowering and capsule initiation stages. When deficit irrigation is induced throughout, a 25% uniform deficit irrigation can give the highest crop water productivity with no or little yield reduction as compared with optimal irrigation. Implementing deficit irrigation scheduling technique will be beneficial for sesame production. Imposing 75% deficit at the initial, development, late season growth stages or 25% deficit irrigation throughout whole seasons will improve sesame crop water productivity.
Design of the Supporting Structures for Large and Unusually Shaped Foundation Pit near the Yangtze River
Authors: Guo Shulan , Yan Changhong , Yu Liangchen , You Yang
Published: March 2020

A large underground transportation hub is located on the west side of the Nanjing Youth Olympic Center, which is close to the embankment of the Yangtze River. The near‐surface primarily comprises newly deposited soft soil of considerable thickness; the lower part is a riverbed‐phase sandy soil containing two confined aquifers. The foundation pit requires deep excavation and has unusual shapes of “pit in pit” and “pit leaning pit.” For the convenience and safety of excavation, the piezometric head of the upper confined aquifer, where the pit bottom is located, reached 1 m below the bottom plane through precipitation, while that of the lower confined aquifer also dewatered down to a safe water level to avoid an uplift problem. After considering the engineering geological conditions, the function and shape of the foundation pits, we divided the soil layers of the foundation pits into two areas (the NW area and the SE area) and proposed the support scheme correspondingly. The numerical simulation results and completed construction safely verified the feasibility of the support scheme.
Emergency Laparoscopic Repair of an Iatrogenic Gastric Perforation in a Hiatal Hernia following a Failed Endoscopic Closure
Authors: Reed Benjamin L. , Tabone Lawrence E. , Szoka Nova , Abunnaja Salim
Published: March 2020

Iatrogenic gastrointestinal perforation is a rare, life-threatening complication of endoscopic procedures, which requires either endoscopic or surgical repair. We report the account of an 82-year-old woman with an iatrogenic gastric perforation of a hiatal hernia secondary to an endoscopic retrograde cholangiopancreatography (ERCP) procedure. Despite immediate recognition of the complication and endoscopic closure with through-the-scope (TTS) clips, the patient developed mediastinitis, peritonitis, and sepsis. She subsequently underwent an emergency laparoscopic hiatal hernia dissection and repair of the perforation with mediastinal and peritoneal washout. Given the patient’s age and the degree of insult, subdiaphragmatic anchoring with abdominal drain placement was performed, and the hiatus was left open for additional drainage. The use of a side-viewing duodenoscope with the presence of a large hiatal hernia contributed to the risk of gastric perforation. We conclude that performing endoscopic procedures in patients with a known hiatal hernia should be carefully undertaken. If a perforation in such patients occurs, laparoscopic repair of such complications is feasible as demonstrated in this case video.
Intrahepatic Type II Gall Bladder Perforation Secondary to Acute Acalculous Cholecystitis
Authors: Koculen Vimaleswaran , Jayarajah Umesh , Ambawatte Anil P.
Published: March 2020

Gall bladder perforation is a rare but serious complication of acute cholecystitis. Gall bladder perforations commonly occur in patients with comorbidities and in association with gall stones. We report a rare occurrence of intrahepatic type II perforation of the gall bladder in a previously healthy elderly male with acalculous cholecystitis. Lack of early positive findings related to clinical assessment, laboratory workup, and imaging resulted in a challenging diagnosis. High degree of clinical suspicion and close monitoring in such patients is necessary to detect early deterioration and improve outcomes.
Effects of Saccharides from Arctium lappa L. Root on FeCl3-Induced Arterial Thrombosis via the ERK/NF-κB Signaling Pathway
Authors: Qiu Tiantian , Zhou Hailun , Li Suying , Tian Nuoya , Li Zhe , Wang Rui , Sun Pengyuan , Peng Jinyong , Du Jianling , Ma Xiaochi , Diao Yunpeng , Lv Li , Wang Li , Li Hua
Published: March 2020

Saccharides from Arctium lappa. L. root (ALR-S) is a high-purity fructosaccharide separated from the medicinal plant Arctium lappa. L. root. These compounds showed many pharmacological effects in previous studies. In the present study, the antithrombotic effects of ALR-S in arterial thrombosis via inhibiting platelet adhesion and rebalancing thrombotic and antithrombotic factor expression and secretion were found in rats and human aortic endothelial cells (HAECs). This study also showed that inhibition of oxidative stress (OS), which is closely involved in the expression of coagulation- and thrombosis-related proteins, was involved in the antithrombotic effects of ALR-S. Furthermore, studies using FeCl3-treated HAECs showed that ALR-S induced the abovementioned effects at least partly by blocking the ERK/NF-κB pathway. Moreover, U0126, a specific inhibitor of ERK, exhibited the same effects with ALR-S on a thrombotic process in FeCl3-injured HAECs, suggesting the thrombotic role of the ERK/NF-κB pathway and the antithrombotic role of blocking the ERK/NF-κB pathway by ALR-S. In conclusion, our study revealed that the ERK/NF-κB pathway is a potential therapeutic target in arterial thrombosis and that ALR-S has good characteristics for the cure of arterial thrombosis via regulating the ERK/NF-κB signaling pathway.
Morphology, Volume, and Density Characteristics of the Parotid Glands before and after Chemoradiation Therapy in Patients with Head and Neck Tumors
Authors: Santos Wellington Pereira dos , Perez Gomes João Pedro , Nussi Amanda Drumstas , João Mauricio Altemani  , Botti Rodrigues dos Santos Maria Teresa , Hasseus Bengt , Giglio Daniel , Braz-Silva Paulo Henrique , Ferreira Costa Andre Luiz
Published: March 2020

The multimodal approach for patients with head and neck cancer (HNC) includes treatment with chemoradiation therapy (CRT). A common concern regarding CRT side effects is the occurrence of structural and physiological alterations of the salivary glands due to exposure to ionizing radiation. The aim of this study is to examine the morphology, volume, and density of the parotid glands before and after CRT in HNC patients. A total of 49 HNC patients treated exclusively with CRT were included in the study. Ninety-eight parotid glands were evaluated before and after treatment by using contrast-enhanced computed tomography (CECT). Shapiro–Wilk test was performed, and the variables (pre-CRT and post-CRT) presented normal distribution. Pearson’s coefficient was used to assess the correlation between volume and density. CRT resulted in a significant decrease in the mean volume of the parotid glands (i.e., original volume reduced by 20.5%; P<0.0001). CRT induced a 30.0% (7 Hounsfield units) increase in density of the right parotid gland and a 24.9% (8 Hounsfield units) increase in density of the left parotid gland (P=0.0198 and P=0.0079, respectively). Changes in morphology and spatial configuration, increased density, and substantial loss of volume of the parotid glands were observed after CRT. There was also a difference in density (P=0.003) in the right-side parotid glands in comparison between xerostomic and nonxerostomic groups of patients. These facts lead to the need for a personalized CRT planning in order to minimize oral complications related to the treatment.
M1 Polarization but Anti‐LPS‐Induced Inflammation and Anti‐MCF‐7 Breast Cancer Cell Growth Effects of Five Selected Polysaccharides
Authors: Lin Hsiao-Chien , Lin Jin-Yuarn
Published: March 2020

Five potential polysaccharides from guava seed (GSPS), common buckwheat (CBPS), bitter buckwheat (BBPS), red Formosa lambsquarters (RFLPS), and yellow Formosa lambsquarters (YFLPS) were selected to measure their effects on mouse peritoneal macrophages in the absence or presence of lipopolysaccharide (LPS). Macrophage‐conditioned media (MCM) in the absence or presence of 5 selected polysaccharides were prepared to treat MCF‐7 cells. The cell viability was determined using 3‐(4,5‐dimethylthiazol‐2‐diphenyl)‐2,5‐tetrazolium bromide (MTT) assay. Proinflammatory (also known as M1 type) (interleukin‐ (IL‐) 1β, IL‐6 and tumor necrosis factor‐ (TNF‐) α) and anti‐inflammatory (also known as M2 type) (IL‐10) cytokines secreted by macrophages were determined using ELISA. The relationship between MCF‐7 cell growth and M1/M2 cytokine secretion profiles in the corresponding MCM were delineated. The results showed that 5 selected polysaccharides, except BBPS, significantly (P < 0.05) and dose‐dependently increased M1 (IL‐1β + IL‐6 + TNF‐α)/M2 (IL‐10) cytokine secretion ratios by macrophages in the absence of LPS, suggesting that four selected polysaccharides have M1 polarization property. However, all of 5 selected polysaccharides significantly (P < 0.05) decreased proinflammatory (IL‐1β + IL‐6 + TNF‐α)/anti‐inflammatory (IL‐10) cytokine secretion ratios by LPS‐stimulated macrophages, exhibiting that all of the 5 selected polysaccharides, particularly GSPS, have anti‐inflammatory potential. All MCM prepared with these selected polysaccharides (except YFLPS) significantly enhanced their inhibitory effects on MCF‐7 cell growth. A negative correlation was noted between MCF‐7 cell viabilities and M1/M2 cytokine secretion ratios ((IL‐6 + TNF‐α)/IL‐10) in the corresponding MCM, suggesting that increases in M1 macrophages in the tumor microenvironment might inhibit MCF‐7 cell growth. Particular polysaccharides including RFLPS, GSPS, YFLPS, and CBPS may increase the percentage of M1 macrophages in the tumor environment and further inhibit MCF‐7 cell growth via immunotherapy.
Ultrastructural Changes in Hepatocytes and Chemopreventive Effects of Short‐Term Administration of Curcuma longa L. against Oxidative Stress‐Induced Toxicity: Improvement Mechanisms of Liver Detoxification
Authors: Hasan Mohammed A.
Published: March 2020

The rhizomes of Curcuma longa L. (CL) have been widely used in herbal medicines worldwide. It has been shown to possess prophylactic effects against oxidative stress. However, there is a paucity of information regarding the protective role of CL against oxidative stress in the absence of toxic agents. The aim of the study was to elucidate the antioxidative stress pharmacodynamics of CL. Eighteen 12‐week‐old Sprague‐Dawley rats weighing about 300 ± 25 gm were divided equally into six groups. Four of the groups were supplemented with CL at 100 mg/kg b.w./day orally (P.O.) and labeled as 1st, 3rd, 5th, and 6th day groups. The PCx (positive control) group was given distilled water orally, and the NCx (negative control) group rats were provided with food and water ad libitum. Blood samples were collected, and rats were sacrificed on days 1, 3, 5, and 6 (2 h) posttreatment. The blood was used for oxidative stress enzyme analysis (SOD, GSH‐Px, and MDA) and liver (ALT) and kidney (creatinine) function assay, and the liver was dissected for histology. The results revealed that CL exhibited an antioxidative stress effect in the liver and kidneys as indicated by the low levels of ALT and creatinine. In response to antioxidant enzymes, especially that of the 3rd‐day treatment group, an increase in SOD and GSH‐Px indirectly caused an alleviation of oxidative stress, leading to a much lower level of MDA. It was concluded that treatment with CL at 100 mg/kg b.w./per day for three consecutive days demonstrated the highest efficacy in abating oxidative stress in rats.
Energy- and Resource-Aware Computation Offloading for Complex Tasks in Edge Environment
Authors: Peng Kai , Zhao Bohai , Xue Shengjun , Huang Qingjia
Published: March 2020

Mobile users typically have a series of complex tasks consisting of time-constrained workflows and concurrent workflows that need to be processed. However, these tasks cannot be performed directly locally due to resource limitations of the mobile terminal, especially for battery life. Fortunately, mobile edge computing (MEC) has been recognized as a promising technology which brings abundant resource at the edge of mobile network enabling mobile devices to overcome the resource and capacity constraints. However, edge servers, such as cloudlets, are heterogeneous and have limited resources. Thus, it is important to make an appropriate offloading strategy to maximize the utility of each cloudlet. In view of this, the time consumption and energy consumption of mobile devices and resource utilization of cloudlets have been taken into consideration in this study. Firstly, a multiconstraint workflow mode has been established, and then a multiobjective optimization mode is formulated. Technically, an improved optimization algorithm is proposed to address this mode based on Nondominated Sorting Genetic Algorithm II. Both extensive experimental evaluations and detailed theoretical analysis are conducted to show that the proposed method is effective and efficiency.
Hybrid Epithelial–Mesenchymal Phenotypes Are Controlled by Microenvironmental Factors
Authors: Selvaggio Gianluca , Canato Sara , Pawar Archana , Monteiro Pedro T. , Guerreiro Patrícia S. , Brás M. Manuela , Janody Florence , Chaouiya Claudine
Published: March 2020

Epithelial-to-mesenchymal transition (EMT) has been associated with cancer cell heterogeneity, plasticity, and metastasis. However, the extrinsic signals supervising these phenotypic transitions remain elusive. To assess how selected microenvironmental signals control cancer-associated phenotypes along the EMT continuum, we defined a logical model of the EMT cellular network that yields qualitative degrees of cell adhesions by adherens junctions and focal adhesions, two features affected during EMT. The model attractors recovered epithelial, mesenchymal, and hybrid phenotypes. Simulations showed that hybrid phenotypes may arise through independent molecular paths involving stringent extrinsic signals. Of particular interest, model predictions and their experimental validations indicated that: (i) stiffening of the extracellular matrix was a prerequisite for cells overactivating FAK_SRC to upregulate SNAIL and acquire a mesenchymal phenotype and (ii) FAK_SRC inhibition of cell–cell contacts through the receptor-type tyrosine-protein phosphatases kappa led to acquisition of a full mesenchymal, rather than a hybrid, phenotype. Altogether, these computational and experimental approaches allow assessment of critical microenvironmental signals controlling hybrid EMT phenotypes and indicate that EMT involves multiple molecular programs.

Significance:

A multidisciplinary study sheds light on microenvironmental signals controlling cancer cell plasticity along EMT and suggests that hybrid and mesenchymal phenotypes arise through independent molecular paths.
Abstract P4-13-10: An evaluation of patient reported outcomes following oncoplastic breast conserving surgery with a crescent modification of the chest wall perforated flap utilizing Breast Q
Authors: Carmichael Amtul R , Sami Amtul Shafee , Mokbel Kefah
Published: March 2020

Background: An increasing acceptance of chest wall perforator flaps has provided additional options for enhancing the cosmetic appearance of the conserved breast after breast cancer surgery. Traditional lateral intercostal anterior perforator (LICAP) flap involves a lateral chest wall scar. To enhance the cosmetic results of LICAP flap, we propose the crescent modification of the LICAP flap to conceal the scar in the inframammary crease.

Aim: The aim of our study was to investigate patient satisfaction and cosmetic outcome by using the BREAST-Q after undergoing crescent-modification of LICAP flap partial breast reconstruction.

Methods: All eighteen consecutive patients with who underwent crescent modification of LICAP flap reconstruction for partial breast reconstruction after wide local excision of breast cancer between June 2017 and July 2019 were invited to complete the BREAST-Q questionnaire. All patients were prospectively evaluated and their demographic, clinical and pathological details were recorded on a database.

Results: The median psychological, physical and sexual well-being scores were 93 (IQR 63-100), 82 (IQR 69-95) and 70 (IQR 46-96) respectively. The median satisfaction score with breast was 88 (IQR 66-100)

Conclusions: In a carefully selected group of women with breast cancer, our study demonstrates that the crescent-modification of the LICAP flap for partial breast reconstruction provides a safe and effective technique with preservation of satisfaction with breast, physical, psychological and sexual well-being.

Citation Format: Amtul R Carmichael, Amtul Shafee Sami, Kefah Mokbel. An evaluation of patient reported outcomes following oncoplastic breast conserving surgery with a crescent modification of the chest wall perforated flap utilizing Breast Q [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-13-10.
Abstract A58: TGF-beta inhibition and checkpoint blockade in mouse models for gastrointestinal cancer
Authors: Cho Kye S. , Kim Hark K.
Published: March 2020

Background: Gastrointestinal tumors are generally not responsive to checkpoint blockade unless they are hypermutated. Smad4 and p53 are frequently mutated in human gastrointestinal cancer.

Methods: We conducted the intestinal epithelium-specific knockout of Smad4 and Trp53. Transcriptomic profiles were evaluated for spontaneous tumors that formed in these genetically engineered mice.

Results: TGF-beta signaling pathway genes were overexpressed in bulk tumors formed in Villin-Cre;Smad4(F/F);Trp53(F/F). Efficacy of anti-PD-1 (10mg/kg IP BIW) and small-molecule ALK5 inhibitor (25mg/kg PO) was tested in syngeneic mice harboring heterotopic allografts of a cell line that was primarily cultured from a Smad4-null tumor. ALK5 inhibitor did not affect the growth of Smad4-null allograft as a monotherapy, but significantly enhanced the antiproliferative effect of anti-PD-1 as a combination treatment.

Conclusion: TGF-beta pathway inhibition may be a promising approach to increase the efficacy of checkpoint blockade in gastrointestinal tumors. (NCC grants 1910021/1810951.)

Citation Format: Kye S. Cho, Hark K. Kim. TGF-beta inhibition and checkpoint blockade in mouse models for gastrointestinal cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A58.
Chronic and Severe Non-Lichenoid Oral Ulcers Induced by Nivolumab – Diagnostic and Therapeutic Challenge: A Case Report
Authors: Cardona Andrés F. , Ruiz-Patiño Alejandro , Ricaurte Luisa , Zatarain-Barrón Zyanya Lucia , Barrón Feliciano , Arrieta Oscar
Published: March 2020

Due to the widespread use of immune checkpoint inhibitors and the growing research efforts in this area, immune-mediated toxicity is well recognized. Nonetheless, few severe cases of oral or upper gastrointestinal tract mucosal involvement have been documented. Early recognition and prompt treatment are key to the adequate management of these patients. We present a male 93-year-old patient with an advanced head and neck tumor treated with nivolumab who developed severe oral ulcers. After discontinuation of nivolumab, he received initial steroid treatment without any significant improvement. Histopathologic analysis of the lesions revealed a pattern similar to graft versus host disease. Extrapolating the results of colchicine mouth washing in patients with active oral ulcers and Behçet’s disease, this strategy was implemented with concomitant metronomic cyclophosphamide, achieving complete ulcer resolution. Metagenomic oral bacterial sequencing during instauration of the lesions and highest extension revealed a significant decrease in microbiomic diversity and expansion of Haemophilus parainfluenzae similar to patients with active Behçet’s disease. In conclusion, oral ulcers associated with immune checkpoint inhibitors correspond to a difficult-to-treat entity that could physiopathologically be related to both graft versus host disease and Behçet’s disease.
A Rare Case of Gastric Schwannoma: A Case Report and Literature Review
Authors: Yanagawa Senichiro , Kagemoto Kenichi , Tanji Hidehiro , Kodama Shinya , Takeshima Yukio , Sumimoto Kazuo
Published: March 2020

In general, schwannoma is a benign and slow-glowing neoplasm that rarely occurs in the gastrointestinal tract as a submucosal tumor (SMT), with the most common site being the stomach. As gastric schwannoma (GS) is a rare tumor, there is limited data in the literature about its clinical features. The diagnosis of schwannoma can only be made by pathological examination with positive staining for S-100 protein. It is necessary to obtain an accurate diagnosis to introduce optimal treatment options preoperatively. However, a precise diagnosis of GS is difficult, even with modern imaging techniques. On the other hand, a complete resection with a negative surgical margin (R0) of GS is considered the best treatment, with an excellent prognosis. We present a case of a 66-year-old female patient who underwent laparoscopic-assisted wedge gastrectomy for gastric SMT, pathologically diagnosed as GS, with positive staining for S-100 protein and negative for c-kit and CD34. At 12-month follow-up after surgery, there was no recurrence or metastasis of GS. Our treatment is appropriate and effective in case of GS exceeding 50 mm.
External Validation of a Prognostic Score for Patients with Brain Metastases: Extended Diagnosis-Specific Graded Prognostic Assessment
Authors: Nieder Carsten , Hess Sebastian , Lewitzki Victor
Published: March 2020

Purpose: The aim of our study was the external validation of an extended variant of the four-tiered diagnosis-specific graded prognostic assessment (DS-GPA) that includes more information about extracranial disease burden and blood test results, and predicts survival of patients with brain metastases. The extracranial DS-GPA (EC-GPA) includes serum albumin, lactate dehydrogenase, and number of extracranial organs involved. Originally, the score was developed in Germany. Patients and Methods: A retrospective analysis of 236 patients with brain metastases treated with primary whole-brain radiotherapy in North-Norway was performed (independent external validation cohort). Results: The four-tiered EC-GPA score showed good discrimination between all prognostic groups (log-rank test p < 0.05 for all pairwise comparisons). One-year survival was 0, 11, 30, and 100%, respectively. Median survival was 0.7 months (95% CI, 0.5–0.9) in the worst prognostic group, with a hazard ratio for death of 44.31 (95% CI, 5.78–339.50) compared to the best group. In the German database, the corresponding HR was 31.64 (median survival 0.4 months). The remaining hazard ratios in this validation study were 7.13 and 12.10, compared with 4.84 and 9.26 in the score development study. Conclusions: This study provides an independent validation of the EC-GPA, which was the best prognostic model for defining patients who did not benefit from radiation therapy of brain metastases in terms of overall survival in the original German study. The proposed modification of the established DS-GPA should undergo further validation in multi-institutional databases.
Association of a Multigenetic Pro-Inflammatory Profile with Ischaemic Stroke
Authors: Palm Frederick , Aigner Annette , Pussinen Pirkko Johanna , Urbanek Christian , Buggle Florian , Safer Anton , Becher Heiko , Grau Armin J.
Published: March 2020

Objective: A multigenetic pro-inflammatory profile may increase stroke risk. We investigated whether a higher number of pro-inflammatory genetic variants are associated with ischaemic stroke risk and whether other risk factors further elevate this risk. Methods: In a case-control study with 470 ischaemic stroke patients (cases) and 807 population controls, we investigated 23 haplotypes or alleles in 16 inflammatory genes (interleukin [IL]1A, IL1B, IL1 receptor antagonist, IL6, IL6 receptor, IL10, tumour necrosis factor-a; C-C motif chemokine ligand 2, C-C motif chemokine receptor 5, C-reactive protein (CRP), intercellular adhesion molecule 1, transforming growth factor β1, E-Selectin, selenoprotein S, cluster determinant 14, histone deacetylase 9 [HDAC9]). We constructed an extended gene score (EGS) as the sum of all individual risk alleles and analysed its effect on stroke, just as its association and interaction with cardiovascular risk factors and infectious scores (IgG antibodies against 5 respectively IgA antibodies against 4 microbial antigens). Results: Cases were less likely to carry the minor allele of IL10 rs1800872 and more likely to carry the HDAC9 allele rs11984041 and the pro-inflammatory haplotype of CRP, although the latter was not statistically significant in our study. Overall, cases tended to have more pro-inflammatory alleles and haplotypes than controls (mean ± SD 13.25 ± 2.25 and 13.04 ± 2.41, respectively). However, the EGS only slightly and not significantly increased the risk of stroke (OR 1.04, 95% CI 0.99–1.09). Its effect was neither associated with included risk factors nor with IgA and IgG infectious scores, and we found no significant interaction effects. Conclusion: A more pro-inflammatory genetic profile might increase stroke risk to some extent. This potential effect is most likely independent of established cardiovascular risk factors and the infectious burden of an individual.
Ube2v1 Positively Regulates Protein Aggregation by Modulating Ubiquitin Proteasome System Performance Partially Through K63 Ubiquitination
Authors: Xu Na , Gulick James , Osinska Hanna , Yu Yang , McLendon Patrick M. , Shay-Winkler Kritton , Robbins Jeffrey , Yutzey Katherine E.
Published: March 2020

Rationale:

Compromised protein quality control can result in proteotoxic intracellular protein aggregates in the heart, leading to cardiac disease and heart failure. Defining the participants and understanding the underlying mechanisms of cardiac protein aggregation is critical for seeking therapeutic targets. We identified Ube2v1 (ubiquitin-conjugating enzyme E2 variant 1) in a genome-wide screen designed to identify novel effectors of the aggregation process. However, its role in the cardiomyocyte is undefined.

Objective:

To assess whether Ube2v1 regulates the protein aggregation caused by cardiomyocyte expression of a mutant αB crystallin (CryAB
R120G
) and identify how Ube2v1 exerts its effect.

Methods and Results:

Neonatal rat ventricular cardiomyocytes were infected with adenoviruses expressing either wild-type CryAB (CryAB
WT
) or CryAB
R120G
. Subsequently, loss- and gain-of-function experiments were performed. Ube2v1 knockdown decreased aggregate accumulation caused by CryAB
R120G
expression. Overexpressing Ube2v1 promoted aggregate formation in CryAB
WT
and CryAB
R120G
-expressing neonatal rat ventricular cardiomyocytes. Ubiquitin proteasome system performance was analyzed using a ubiquitin proteasome system reporter protein. Ube2v1 knockdown improved ubiquitin proteasome system performance and promoted the degradation of insoluble ubiquitinated proteins in CryAB
R120G
cardiomyocytes but did not alter autophagic flux. Lys (K) 63-linked ubiquitination modulated by Ube2v1 expression enhanced protein aggregation and contributed to Ube2v1’s function in regulating protein aggregate formation. Knocking out Ube2v1 exclusively in cardiomyocytes by using AAV9 (adeno-associated virus 9) to deliver multiplexed single guide RNAs against Ube2v1 in cardiac-specific Cas9 mice alleviated CryAB
R120G
-induced protein aggregation, improved cardiac function, and prolonged lifespan in vivo.

Conclusions:

Ube2v1 plays an important role in protein aggregate formation, partially by enhancing K63 ubiquitination during a proteotoxic stimulus. Inhibition of Ube2v1 decreases CryAB
R120G
-induced aggregate formation through enhanced ubiquitin proteasome system performance rather than autophagy and may provide a novel therapeutic target to treat cardiac proteinopathies.
Comparative Effectiveness of Endovascular Treatment for Acute Ischemic Stroke: A Population‐Based Analysis
Authors: Zerna Charlotte , Rogers Edwin , Rabi Doreen M. , Demchuk Andrew M. , Kamal Noreen , Mann Balraj , Jeerakathil Tom , Buck Brian , Shuaib Ashfaq , Rempel Jeremy , Menon Bijoy K , Goyal Mayank , Hill Michael D.
Published: March 2020

Background

A heterogeneous patient population receives endovascular treatment (
EVT
) for acute ischemic stroke caused by proximal large‐vessel occlusion every day. We aimed to conduct a population‐based study of
EVT
in the province of Alberta, Canada, to understand the effectiveness in a complete population and how the magnitude of effect differs from the artificial world of clinical trials.

Methods and Results

Within a 3‐year period (April 2015 to March 2018), 576 patients fit the inclusion criteria of our study and constituted the
EVT
group of our analysis. The medical treatment group of the
ESCAPE
(Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT [Computed Tomography] to Recanalization Times) trial had 150 patients. Thus, our total sample size was 726. We captured outcomes in clinical routine using administrative data and a linked database method. Primary outcome of our study was home‐time. Home‐time refers to the number of days that the patient was back at premorbid living situation without increase in level of care within 90 days of index stroke event. Median age of patients was 70 years (interquartile range, 59–81 years), and 47.8% were women. Median National Institutes of Health Stroke Scale score was 17 (interquartile range, 13–20).
EVT
was associated with an increased 90‐day home‐time by an average of 8.5 days compared with medical treatment alone using Cragg hurdle regression (
P
=0.009). Age and higher National Institutes of Health Stroke Scale score were associated with decreased 90‐day home‐time (both
P
<0.001). Multivariable logistic regression showed no association between
EVT
and mortality at 90 days (odds ratio, 0.76; 95% CI, 0.47–1.24).

Conclusions

EVT
for acute ischemic stroke caused by proximal large‐vessel occlusion was effective in our province‐wide population‐based study and results in an increase of 90‐day home‐time by ~8.5 days.
A Conversation between Chinese Artists and Mexican Painter David
Alfaro Siqueiros
Authors: Xiangsheng Feng
Published: March 2020

In October 1956, the Mexican muralist David Siqueiros traveled Beijing and engaged in two dialogues with artists from the Chinese Artists’ Association. His visit came at an inflection point in China’s foreign and cultural policy. As Sino-Soviet relations deteriorated, China used cultural diplomacy to cultivate relationships with unaligned countries in Asia, Africa, and Latin America. China’s cultural policy mirrored this shift by relaxing its adherence to Soviet-style Socialist Realism and promoting new stylistic practices, including a revival of ink painting techniques. This policy shift re-animated a debate among Chinese artists over the best mode of representation for socialist art, with one side arguing that Soviet-style Socialist Realism was the only acceptable style, and the other advocating for the reform of Chinese ink painting techniques. Within this context, Siqueiros’s criticism of Soviet artists and his advice to follow Chinese stylistic traditions set off a rich discussion on new approaches to Socialist Realism within China.
Art and Our Surrounds: Emergent and Residual Languages
Authors: Johnson Adriana Michéle Campos
Published: March 2020

This essay undertakes a review of recent books by T.J. Demos ( Decolonizing Nature: Contemporary Art and the Politics of Ecology (2016) and Against the Anthropocene: Visual Culture and Environment Today (2017)) and Jens Andermann ( Tierras en trance: Arte y naturaleza después del paisaje (Lands Entranced: Art and Nature after Landscape, 2018)). Demos and Andermann participate in the paradigm shift taking place under the name of eco-criticism, forging connections between the debates around environmental crisis and the fields in which they have written and published previously - art criticism and visual culture and Latin American literary and cultural studies, respectively. Both authors take on the challenge of thinking through the perceptual and conceptual habits that have dominated a relationship to our environment under capitalist modernity (such as the concept of landscape) and how artistic practices might be said to rework those habits. While Demos maps recent efforts to engage ecological concerns and “decolonize nature” across the globe, Andermann looks back to the twentieth century Latin American archive, constructing a local genealogy that harbors an ecological and political thinking that anticipates what is now lived as global crisis; their projects intersect in contemporary Latin American activist art that has gained enough attention to figure as part of a global circuit. The review considers the overlapping points as well as the striking disjuncture in both projects in relation to the different knowledge formations, archives and languages from which each author speaks.
Google Books, Scopus, Microsoft Academic and Mendeley for impact assessment of doctoral dissertations: A multidisciplinary analysis of the UK
Authors: Kousha Kayvan , Thelwall Mike
Published: March 2020

A research doctorate normally culminates in publishing a dissertation reporting a substantial body of novel work. In the absence of a suitable citation index, this article explores the relative merits of alternative methods for the large-scale assessment of dissertation impact, using 150,740 UK doctoral dissertations from 2009–2018. Systematic methods for this were designed for Google Books, Scopus, Microsoft Academic, and Mendeley. Less than 1 in 8 UK doctoral dissertations had at least one Scopus (12%), Microsoft Academic (11%), or Google Books citation (9%), or at least one Mendeley reader (5%). These percentages varied substantially by subject area and publication year. Google Books citations were more common in the Arts and Humanities (18%), whereas Scopus and Microsoft Academic citations were more numerous in Engineering (24%). In the Social Sciences, Google Books (13%) and Scopus (12%) citations were important and in Medical Sciences, Scopus and Microsoft Academic citations to dissertations were rare (6%). Few dissertations had Mendeley readers (from 3% in Science to 8% in the Social Sciences) and further analysis suggests that Google Scholar finds more citations, but does not report information about all dissertations within a repository and is not a practical tool for large-scale impact assessment
Distinctions and Differentiations between Medicine and Religion
Authors: Killinger Katrin , Kleine Christoph , Triplett Katja
Published: March 2020

This special section of Asian Medicine brings together three scholars of the history of healing practices and medicine in premodern Asian societies to explore whether and how emic boundaries between religion and medicine were drawn in different historical contexts. In this introduction, we use the example of ancient Japan in an attempt to show how first steps towards a separation of religion and medicine can be identified, even when they have not yet been clearly differentiated institutionally or distinguished conceptually as distinct fields of action. By doing so, we operationalize the macro-sociological question central to the ‘multiple secularities’ approach, namely how ‘secular’ fields of action—here, curing disease—emancipate themselves from ‘religion’ in premodern ‘non-Western’ societies. We propose to look for differences in the framing and interpretation of healing activities, for the ascription of either (professional) competence or (religious) charisma to the healers, to ask whether the activities are to be interpreted as a social function or service, and to identify the sources of authority and legitimacy. This is followed by a brief summary and discussion of the contributions by Selby, Czaja, and Triplett.
Mantras and Rituals in Tibetan Medicine
Authors: Czaja Olaf
Published: March 2020

This article will explore the relationship between Tibetan medicine and Tibetan Buddhism by analyzing early Tibetan medical treatises. It will investigate mantras, meditative visualizations, and rituals that were used to prevent and to cure diseases and will study their medical context. Some of the questions addressed will be: Are these techniques employed in the case of special diseases or at particular stages of medical treatment? If so, how firmly are they established in medical texts? Are they just accessary parts and not really “medical,” or do they form an integral part of medical expertise in premodern Tibet? This article will thus question our current understanding of Tibetan medicine from an emic textual perspective on healing practices.
Pediatric Care and Buddhism in Premodern Japan: A Case of Applied “Demonology”?
Authors: Triplett Katja
Published: March 2020

The Indian idea of supernatural entities, or “demons,” that harm children found its way into Chinese translations of Buddhist texts. Through Buddhism, the idea also reached premodern Japan. Given that medicine in premodern Japan was predominantly practiced by “secular” court physicians and Buddhist monastic doctors, one might assume that court physicians focused on childhood diseases with “natural” causes, while Buddhist monastics concentrated on “supernatural” causes and ritual remedies for childhood illnesses. I aim to establish whether this was actually the case by assessing ideas and practices as well as social institutions and individuals engaged in the healing of children in premodern Japan. The wider Asian context will also be considered. I conclude that in caring for children, “demonology” was combined with ideas and practices from diverse traditions in Japan and remained alive largely outside—but not in opposition to—the Buddhist and medical institutions well into the early modern period.