bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR4: Modulation of integrin CD11b as a novel therapeutic strategy against lung cancer
Authors: Geraghty Terese D. , Rajagopalan Anugraha , Aslam Rabail , Gupta Vineet 
Published: March 2020

Abstract
Lung cancer is the leading cause of cancer-related deaths in the United States. With a 5-year survival rate at 19%, lung cancer patients are urgently in need of new therapeutic options. A major problem facing cancer therapy is the immune suppression by the tumor and its subsequent escape from the immune response, which is mediated by the tumor microenvironment. Tumors have large numbers of myeloid-derived suppressor cells (MDSCs), which suppress the adaptive immune response, increase neovascularization of the tumor, and promote tumor survival. Integrin heterodimer CD11b/CD18 (aka Mac-1 or αMβ2) is highly expressed on MDSCs and plays an important role in innate cell recruitment and other biologic functions. GB1275 (previously known as ADH503) is a novel small-molecule CD11b allosteric modulator. In experimental models of pancreatic cancer, GB1275 reduces MDSC infiltration and M2 macrophage polarization leading to tumor growth inhibition. GB1275 is currently in phase 1/2 clinical development in patients with pancreatic, esophageal, gastric/GEJ, triple-negative breast, castration-resistant prostate, or microsatellite stable colorectal cancer. To investigate the impact of CD11b modulation in the context of lung cancer, GB1275 treatment effects on tumor growth and immune infiltrates were assessed in the Lewis Lung Carcinoma (LLC) syngeneic tumor model, propagated in C57BL/6 wild-type (WT) mice. Additionally, we developed a transgenic CD11b knockin (KI) mouse that renders CD11b in a partially active state. CD11b KI mice were engineered to express partially active CD11b by introducing a point mutation at position 332 causing an isoleucine to glycine switch (I332G). We studied LLC tumor growth in CD11b KI mice as an orthogonal approach to test the mechanism of action. We will present data showing that pharmacologic modulation of CD11b with GB1275 significantly reduces LLC tumor growth. Concomitantly, we will present our studies with the CD11b KI mice that show a significant reduction in both the size and the rate of LLC tumor growth, as compared to the WT mice, mimicking treatment effects with GB1275. Our comprehensive pharmacologic and genetic studies show that CD11b activation reprograms MDSCs to enhance the adaptive immune response and is a novel strategy against lung cancer.
This abstract is also being presented as Poster B71.
Citation Format: Terese D. Geraghty, Anugraha Rajagopalan, Rabail Aslam, Vineet Gupta. Modulation of integrin CD11b as a novel therapeutic strategy against lung 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 PR4.
Abstract PR6: Disrupting enhancers within the core epigenetic program of exhaustion improves T-cell responses and enhances tumor control
Authors: Sen Debattama R. , Weiss Sarah A. , Miller Brian C. , Tonnerre Pierre , Abosy Rose Al , Yates Kathleen B. , Bi Kevin , Lafleur Martin W. , Wolski David , Georg Lauer , Sharpe Arlene H. , Haining W. Nicholas 
Published: March 2020

Abstract
T-cell exhaustion describes an acquired dysfunction common in settings of cancer and chronic viral infection. Despite clinical efforts to rescue exhaustion, the fundamental mechanisms specifying this state, and the potential for reprogramming exhausted T cells, remain poorly understood. We profiled accessible chromatin in chronic viral infection to show that exhausted CD8+ cells acquire a state-specific landscape of enhancers that profoundly differs from functional memory. Critically, CD8+ tumor-infiltrating lymphocytes shared significant epigenetic and transcriptional features with chronic viral infection, suggesting that T-cell exhaustion is a fundamental adaptation to settings of chronic stimulation. Comparison of mouse cells to those isolated from patients infected with HCV or HIV showed that the core epigenetic program of exhaustion is conserved across species. Importantly, curative therapy, which reduces viral antigen load, as well as anti-PD-1 immunotherapy, which reduces inhibitory T-cell signaling, failed to reverse the exhausted epigenetic profile. T-cell exhaustion is therefore a stable epigenetic state that is not rescued by common treatment modalities. We then sought new strategies to modulate T-cell exhaustion. We used Cas9-mediated genome editing to generate a novel mouse strain with germline deletion of a core exhaustion-associated enhancer near PD-1. We observed 2- to 3-fold enrichment in vivo of PD-1 enhancer-null cells over control cells in chronic infection, suggesting that CD8+ T cells in these mice might be less prone to exhaustion. PD-1 enhancer-null mice also exhibited slower tumor growth and increased survival when challenged with B16-ova melanoma. The establishment of a core program of T-cell exhaustion and increased insight into its epigenetic modulation has crucial implications for the future of immunotherapy and rational engineering of T cells for clinical use.
This abstract is also being presented as Poster A3.
Citation Format: Debattama R. Sen, Sarah A. Weiss, Brian C. Miller, Pierre Tonnerre, Rose Al Abosy, Kathleen B. Yates, Kevin Bi, Martin W. Lafleur, David Wolski, Lauer Georg, Arlene H. Sharpe, W. Nicholas Haining. Disrupting enhancers within the core epigenetic program of exhaustion improves T-cell responses and enhances tumor control [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 PR6.
Additions of woody climbers (Lianas) to the flora of Manipur, India
Authors: Chanu Longjam Malemnganbee , Bhattacharyya Debjyoti 
Published: March 2020

Five species of woody climbers—Ampelopsis rubifolia (Wall.) Planch. (Vitaceae), Argyreia wallichii Choisy (Convolvulaceae), Combretum sundaicum Miq. (Combretaceae), Jasminum lanceolaria Roxb. (Oleaceae), and Tetrastigma obovatum Gagnep. (Vitaceae)—are reported here as new distribution records of lianas for the state flora of Manipur, India.
Mating behavior of the Yellow-throated Marten Martes flavigula (Mammalia: Carnivora: Mustelidae)
Authors: Parida Abinash , Murthy Meesala Krishna , Solanki G.S. 
Published: March 2020

In this study, we report the mating behavior of Yellow-throated Marten Martes_flavigula. A pair was observed mating on a Sterculia villosa tree at the Tuilut anti-poaching camp situated near the core of Dampa Tiger Reserve at 05.35h on 25 November 2018. Copulation between the pair was observed 14 times with successive coupling rhythms approximately four minutes apart.
The insect fauna of Tenompok Forest Reserve in Sabah, Malaysia
Authors: Chung Arthur Y.C. , Paul Viviannye , Bosuang Steven 
Published: March 2020

The insect fauna in Tenompok Forest Reserve, adjacent to Mount Kinabalu in Sabah was surveyed. Nocturnal insect diversity was moderately high, compared to other forest reserves surveyed earlier. Species richness, however, was moderate, with an average of 73 species from 84 individuals recorded from a 1m2 area of the light-trapping cloth. At least 20 Bornean endemic insect species were recorded from this rapid biodiversity assessment, which include 19 moth species and one beetle species. The endemics and other insects of conservation interest recorded during the survey provide salient information to enhance the conservation effort of this forest which connects Kinabalu Park and the Crocker Range Park. Such information provides inputs towards recommendations on high conservation value (HCV) of the area that would be incorporated in the formulation of the forest management plan. Issues affecting the insect fauna and recommendations on insect diversity enhancement and conservation are highlighted in this paper.
Analysis of stereotypic behaviour and enhanced management in captive Northern Giraffe Giraffa camelopardalis housed at Zoological Garden Alipore, Kolkata
Authors: Kulkarni Tushar Pramod 
Published: March 2020

In the wild, giraffes live complex social lives exhibiting fission-fusion social systems. They have sophisticated communication which likely forms a crucial component regulating subgroup dynamics. They spend a large part of their day browsing and traveling over large distances. In captivity, lack of continuous browsing opportunities and limited space can lead to various abnormal and stereotypic behaviours. These stereotypic behaviours can have cascading detrimental health consequences. A behavioural analysis of stereotypic behaviours in giraffes under human care was conducted to evaluate sources of variation within a population and provide management recommendations. The aim of this investigation was threefold: 1. to examine current behaviour of giraffes in Zoological Garden Alipore, Kolkata to advise on their enhanced management; 2. to highlight any behavioural abnormalities and recommend enrichment mechanisms; and 3. to compare the observed stereotypic behaviours with behaviour described in other zoological institutions and in the wild to provide a focal trajectory in the development of guidelines. Four individuals (two adult males, one adult female, and one male calf) were observed outdoors for seven days, three times a day for 30 minutes by instantaneous scan sampling method. During the observation period, the giraffe exhibited oral stereotypy more than any other behaviour recorded, though this was recorded disproportionally between individuals. The giraffe spent a larger amount of time exhibiting oral stereotypy compared to feeding/foraging activities. The study suggests incorporating diet and feeding strategies with provision of natural browse as well as offering enrichment methods to increase the foraging time using various time-engaged feeding devices to mitigate the observed abnormal stereotypic behaviour. Additionally, recommendations are made for expanding the size of the open enclosure to meet guidelines by the Central Zoo Authority, as a minimum.
Stent performance in palliative transhepatic treatment of malignant biliary obstruction: a randomized study comparing covered versus uncovered stents
Authors: Elkilany Aboelyazid , Alwarraky Mohamed , Geisel Dominik , Maaly Mohamed A , Denecke Timm 
Published: March 2020

Background Considering the limitations in both uncovered self-expandable metallic stents (USEMS) and covered self-expandable metallic stents (CSEMS), it is difficult to make a general recommendation for their application in percutaneous decompression of malignant biliary obstruction (MBO). Purpose To compare percutaneous transhepatic CSEMSs versus USEMSs for the palliative treatment of MBO in terms of technical success, clinical success, stent patency, patient survival, complications, and stent dysfunction. Material and Methods This prospective randomized study included 66 patients with unresectable MBO. CSEMSs were inserted in 31 patients (26 men, 5 women; mean age = 63.8 ± 7.96 years) and USEMSs were inserted in 35 patients (26 men, 9 women; mean age = 62.3 ± 11.7 years). Results Mean primary stent patency duration was 138 ± 92.7 days in CSEMSs versus 150 ± 77.9 days in USEMSs ( P = 0.578). Tumor overgrowth occurred exclusively in one patient with CSEMS ( P = 0.470) and tumor ingrowth exclusively in two patients with USEMS ( P = 0.494). Stent migration occurred in two patients with CSEMSs versus one patient with USEMSs ( P = 0.579). Hemobilia occurred in five patients with CSEMSs versus three patients with USEMSs while bile leakage occurred in one patient in each group despite the larger introducer sheath caliber with CSEMSs (9 F vs. 6–7 F). There was no significant difference regarding patient survival ( P = 0.969). Conclusion In our cohort of patients with rather poor life expectancy, there was no significant difference between covered and uncovered stents for the palliative treatment of MBO. However, considering the higher cost of CSEMs and the larger introducer diameter necessary for their placement, USEMSs can be preferred.
Value of multi-detector computed tomography during intra-arterial infusion of contrast medium for locating insulinomas
Authors: Song Peng , Yan Jie-Yu , Wang Yan , Li Xiao 
Published: March 2020

Objective This study aimed to evaluate the accuracy of multi-detector computed tomography (CT) during intra-arterial infusion of contrast medium (MDCT-IA) for locating insulinomas. Methods This retrospective study included patients with insulinomas who underwent surgery at the Chinese PLA General Hospital in 2013 to 2014. The patients’ case notes and investigation results were reviewed. Preoperative tumor localization was carried out by MDCT-IA and noninvasive methods including MDCT, magnetic resonance imaging (MRI), and contrast-enhanced ultrasound (CEUS). Insulinoma localization using these methods was compared with the histologically confirmed location following surgical excision. Results Twelve insulinomas were identified in 12 patients, all of which were treated surgically. All patients received MDCT-IA (100%), 11 patients also underwent MRI (91.7%), seven underwent CT (58.3%), and all 12 underwent CEUS (100%). Tumor localization was determined successfully in 12/12 patients by MDCT-IA (100%), in 9/11 by MRI (81.8%), 4/7 by CT (57.1%), and 7/12 by CEUS (58.3%). Overall, MDCT-IA correctly localized 100% of the lesions. Conclusions MDCT-IA can be used to determine the preoperative localization of insulinomas.
Regression from prediabetes to normal glucose regulation: State of the science
Authors: Sallar Anthony , Dagogo-Jack Samuel 
Published: March 2020

Prediabetes, an intermediate stage between normal glucose regulation and type 2 diabetes, is diagnosed based on documentation of impaired fasting glucose, impaired glucose tolerance, or a hemoglobin A1c level of 5.7–6.4%. Individuals with prediabetes have increased risks for the development of type 2 diabetes and multiple vascular complications. Randomized controlled trials have demonstrated the feasibility of preventing progression from prediabetes to type 2 diabetes, using lifestyle or pharmacological interventions. Lifestyle modification has a sustained effect on diabetes prevention, whereas medications lose efficacy when discontinued. Few studies have pre-specified reversal of prediabetes as the primary outcome. There is emerging evidence that reversal of prediabetes (i.e. restoration of normal glucose regulation) confers significant protection from future diabetes and complications, including premature death, during long-term follow-up. Current lifestyle intervention protocols have been more effective in preventing progression from prediabetes to type 2 diabetes than restoring normal glucose regulation; thus, interventions that prevent type 2 diabetes in people with prediabetes do not always reverse prediabetes. Given the compelling benefits of restoration of normal glucose regulation, specific protocols for reversal of prediabetes need to be developed and tested. The design of such protocols requires a deeper understanding of the pathobiology of prediabetes and early glucose dysregulation. The present review focuses on those studies that have assessed the impact of interventions on regression of the prediabetes state and restoration of normal glucose regulation. Furthermore, we discuss alterations in adiposity, glucoregulatory mechanisms, metabolomics, inflammatory markers, and other factors that predict the initial escape from normoglycemia. Such knowledge could inform the future development of novel, refined, and targeted interventions for the reversal prediabetes/early dysglycemia and restoration of normal glucose regulation. Impact statement Prediabetes increases the risks of future type 2 diabetes (T2D) and vascular complications, risks that can be prevented by restoring normal glucose regulation (NGR). Few studies have pre-specified reversal of prediabetes and restoration of NGR as primary outcome, and current approaches that prevent T2D in people with prediabetes do not always reverse the prediabetes. The present review focuses on studies that have assessed reversal of the prediabetes, and discusses known and emerging predictors of prediabetes. We argue that fuller knowledge of such predictors could inform the discovery of novel, targeted interventions for reversing prediabetes.
A randomized controlled trial of real versus sham acupuncture for basal thumb joint arthritis
Authors: Barnard Anna , Jansen Victoria , Swindells Mark G. , Arundell Melanie , Burke Frank D. 
Published: March 2020

We report a single-blinded randomized controlled trial comparing acupuncture to sham (non-penetrating) needling for relief of symptoms of basal thumb joint arthritis. Seventy acupuncture naive patients with basal thumb joint arthritis were randomized to receive true acupuncture or sham needling with 35 patients in each arm. Blinded baseline and post-treatment assessments included visual analogue pain scores for different grips and movement. Function was assessed using the Nelson questionnaire. Both groups showed statistically and clinically significant improvements in pain at week one post-treatment compared with baseline, but there was no difference between the treatment groups. The pain relief was comparable with published data for some standard treatments. Acupuncture did not perform better than sham needling in this study, indicating that pain relief may have been achieved through non-specific mechanisms. Level of evidence: I
Skeletal Deformity in Patients With Unilateral Coronal Craniosynostosis: Perceptions of the General Public
Authors: Robertson Emilie , Kwan Peter , Louie Gorman , Boulanger Pierre , Aalto Daniel 
Published: March 2020

Study Design: A two-alternative forced choice design was used to gather perceptual data regarding unicoronal synostosis (UCS). Objective: Cranial vault remodeling aims at improving the aesthetic appearance of infants with UCS by reshaping the forehead and reducing the potential for psychosocial discrimination. People's perception of craniofacial deformity plays a role in the stigma of deformity. The purpose of this study is to examine the relationship between objective skull deformity in UCS patients and laypersons’ perception of skull normality. Methods: Forty layperson skull raters were recruited from the general public. Skull raters were asked to categorize 45 infant skull images as normal or abnormal. Twenty-one of the images were UCS skulls, and 24 were normal skulls. Skulls were displayed briefly on a computer to simulate a first impression scenario and generate a perceptual response. A χ 2 analysis and mixed-effects regression model were used to analyze the response data. Results: Members of the general public were good at distinguishing between skull groups, χ 2 (1) = 281.97, P < .001. In addition, skull raters’ responses were predicted by the severity of deformity in the UCS skulls ( b = −0.10, z = −2.6, P = .010, CI: −0.18, −0.02). A skull with a deformity value of 2.8 mm (CI: 1.8, 4.1) was equally likely to be rated normal or abnormal. Conclusions: This is the first study to investigate the relationship between objective skull deformity in UCS and public perception. Laypersons were good at distinguishing the difference between normal and UCS skulls, and their perceptions of normality were predicted by the degree of skull deformity.
Iterative four-phase development of a theory-based digital behaviour change intervention to reduce occupational sedentary behaviour
Authors: Stephenson Aoife , Garcia-Constantino Matias , McDonough Suzanne M , Murphy Marie H , Nugent Chris D , Mair Jacqueline L 
Published: March 2020

Introduction As high amounts of occupational sitting have been associated with negative health consequences, designing workplace interventions to reduce sedentary behaviour (SB) is of public health interest. Digital technology may serve as a cost-effective and scalable platform to deliver such an intervention. This study describes the iterative development of a theory-based, digital behaviour change intervention to reduce occupational SB. Methods The behaviour change wheel and The Behaviour Change Technique Taxonomy were used to guide the intervention design process and form a basis for selecting the intervention components. The development process consisted of four phases: phase 1 – preliminary research, phase 2 – consensus workshops, phase 3 – white boarding and phase 4 – usability testing. Results The process led to the development and refinement of a smartphone application – Worktivity. The core component was self-monitoring and feedback of SB at work, complemented by additional features focusing on goal setting, prompts and reminders to break up prolonged periods of sitting, and educational facts and tips. Key features of the app included simple data entry and personalisation based on each individual’s self-reported sitting time. Results from the ‘think-aloud’ interviews ( n=5) suggest Worktivity was well accepted and that users were positive about its features. Conclusion This study led to the development of Worktivity, a theory-based and user-informed mobile app intervention to reduce occupational SB. It is the first app of its kind developed with the primary aim of reducing occupational SB using digital self-monitoring. This paper provides a template to guide others in the development and evaluation of technology-supported behaviour change interventions.
Reverse Total Shoulder Arthroplasty for Treatment of 3- and 4-Part Proximal Humeral Fractures: Clinical and Radiological Analysis With Minimum Follow-Up of 2 Years
Authors: Barbosa Luis , Pires Luis , Rego Paulo , Alonso Raul 
Published: March 2020

Background: Hemiarthroplasty has been associated with inferior and unpredictable outcomes when used in the treatment of complex proximal humeral fractures in elderly patients. In this age-group, reverse shoulder arthroplasty is gaining popularity due to the promising results presented in recent evidence. Our aim is to analyze the cases of complex proximal humeral fractures treated by reverse shoulder arthroplasty, regarding functional results and complications. Materials and Methods: Thirty-five fractures from 33 patients with the mean age of 73.5 (65-81) years were treated with reverse shoulder arthroplasty for complex fractures of the proximal humerus. These patients were followed for a mean of 38.3 months (24-68) and analyzed regarding clinical outcomes and complications. Results: The average Quick-Disabilities of the Arm, Shoulder and Hand and American Shoulder and Elbow Surgeons scores were 6.8 points and 78.3%, respectively. The mean Constant score on the affected side was 64.4 points, 19.5% less than the nonoperated side. The mean active elevation was 123°, abduction 109°, external rotation 38°, and internal rotation 41°. The radiographic tuberosity healing rate was 85.7%. There were no significant differences in outcomes, between patient with healed and reabsorbed tuberosities. Inferior scapular notching was seen in 8 patients. The global complication rate was 12.8%. Conclusion: Reverse shoulder arthroplasty yields good and reproductive results with acceptable complication rates in selected elderly patients with complex proximal humeral fractures.