bluuebunny/crossref_metadata_2025_split huggingface dataset:
Line-of-Sight Pursuit in Monotone and Scallop Polygons
Authors: Berry Lindsay , Beveridge Andrew , Butterfield Jane , Isler Volkan , Keller Zachary , Shine Alana , Wang Junyi 
Published: May 2020

We study a turn-based game in a simply connected polygonal environment [Formula: see text] between a pursuer [Formula: see text] and an adversarial evader [Formula: see text]. Both players can move in a straight line to any point within unit distance during their turn. The pursuer [Formula: see text] wins by capturing the evader, meaning that their distance satisfies [Formula: see text], while the evader wins by eluding capture forever. Both players have a map of the environment, but they have different sensing capabilities. The evader [Formula: see text] always knows the location of [Formula: see text]. Meanwhile, [Formula: see text] only has line-of-sight visibility: [Formula: see text] observes the evader’s position only when the line segment connecting them lies entirely within the polygon. Therefore [Formula: see text] must search for [Formula: see text] when the evader is hidden from view. We provide a winning strategy for [Formula: see text] in two families of polygons: monotone polygons and scallop polygons. In both families, a straight line [Formula: see text] can be moved continuously over [Formula: see text] so that (1) [Formula: see text] is a line segment and (2) every point on the boundary [Formula: see text] is swept exactly once. These are both subfamilies of strictly sweepable polygons. The sweeping motion for a monotone polygon is a single translation, and the sweeping motion for a scallop polygon is a single rotation. Our algorithms use rook’s strategy during its pursuit phase, rather than the well-known lion’s strategy. The rook’s strategy is crucial for obtaining a capture time that is linear in the area of [Formula: see text]. For both monotone and scallop polygons, our algorithm has a capture time of [Formula: see text], where [Formula: see text] is the number of polygon vertices.
Pattern of Invasion in Human Pancreatic Cancer Organoids Is Associated with Loss of SMAD4 and Clinical Outcome
Authors: Huang Wenjie , Navarro-Serer Bernat , Jeong Yea Ji , Chianchiano Peter , Xia Limin , Luchini Claudio , Veronese Nicola , Dowiak Cameron , Ng Tammy , Trujillo Maria A. , Huang Bo , Pflüger Michael J. , Macgregor-Das Anne M. , Lionheart Gemma , Jones Danielle , Fujikura Kohei , Nguyen-Ngoc Kim-Vy , Neumann Neil M. , Groot Vincent P. , Hasanain Alina , van Oosten A. Floortje , Fischer Sandra E. , Gallinger Steven , Singhi Aatur D. , Zureikat Amer H. , Brand Randall E. , Gaida Matthias M. , Heinrich Stefan , Burkhart Richard A. , He Jin , Wolfgang Christopher L. , Goggins Michael G. , Thompson Elizabeth D. , Roberts Nicholas J. , Ewald Andrew J. , Wood Laura D. 
Published: May 2020

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by extensive local invasion and systemic spread. In this study, we employed a three-dimensional organoid model of human pancreatic cancer to characterize the molecular alterations critical for invasion. Time-lapse microscopy was used to observe invasion in organoids from 25 surgically resected human PDAC samples in collagen I. Subsequent lentiviral modification and small-molecule inhibitors were used to investigate the molecular programs underlying invasion in PDAC organoids. When cultured in collagen I, PDAC organoids exhibited two distinct, morphologically defined invasive phenotypes, mesenchymal and collective. Each individual PDAC gave rise to organoids with a predominant phenotype, and PDAC that generated organoids with predominantly mesenchymal invasion showed a worse prognosis. Collective invasion predominated in organoids from cancers with somatic mutations in the driver gene SMAD4 (or its signaling partner TGFBR2). Reexpression of SMAD4 abrogated the collective invasion phenotype in SMAD4-mutant PDAC organoids, indicating that SMAD4 loss is required for collective invasion in PDAC organoids. Surprisingly, invasion in passaged SMAD4-mutant PDAC organoids required exogenous TGFβ, suggesting that invasion in SMAD4-mutant organoids is mediated through noncanonical TGFβ signaling. The Rho-like GTPases RAC1 and CDC42 acted as potential mediators of TGFβ-stimulated invasion in SMAD4-mutant PDAC organoids, as inhibition of these GTPases suppressed collective invasion in our model. These data suggest that PDAC utilizes different invasion programs depending on SMAD4 status, with collective invasion uniquely present in PDAC with SMAD4 loss.

Significance:
Organoid models of PDAC highlight the importance of SMAD4 loss in invasion, demonstrating that invasion programs in SMAD4-mutant and SMAD4 wild-type tumors are different in both morphology and molecular mechanism.
Medium-throughput Drug Screening of Patient-derived Organoids from Colorectal Peritoneal Metastases to Direct Personalized Therapy
Authors: Narasimhan Vignesh , Wright Josephine A. , Churchill Michael , Wang Tongtong , Rosati Rachele , Lannagan Tamsin R.M. , Vrbanac Laura , Richardson Anne B. , Kobayashi Hiroki , Price Timothy , Tye Gayle X.Y. , Marker Julie , Hewett Peter J. , Flood Michael P. , Pereira Shalini , Whitney G. Adam , Michael Michael , Tie Jeanne , Mukherjee Siddhartha , Grandori Carla , Heriot Alexander G. , Worthley Daniel L. , Ramsay Robert G. , Woods Susan L. 
Published: May 2020

AbstractPurpose:Patients with colorectal cancer with peritoneal metastases (CRPMs) have limited treatment options and the lowest colorectal cancer survival rates. We aimed to determine whether organoid testing could help guide precision treatment for patients with CRPMs, as the clinical utility of prospective, functional drug screening including nonstandard agents is unknown.Experimental Design:CRPM organoids (peritonoids) isolated from patients underwent parallel next-generation sequencing and medium-throughput drug panel testing ex vivo to identify specific drug sensitivities for each patient. We measured the utility of such a service including: success of peritonoid generation, time to cultivate peritonoids, reproducibility of the medium-throughput drug testing, and documented changes to clinical therapy as a result of the testing.Results:Peritonoids were successfully generated and validated from 68% (19/28) of patients undergoing standard care. Genomic and drug profiling was completed within 8 weeks and a formal report ranking drug sensitivities was provided to the medical oncology team upon failure of standard care treatment. This resulted in a treatment change for two patients, one of whom had a partial response despite previously progressing on multiple rounds of standard care chemotherapy. The barrier to implementing this technology in Australia is the need for drug access and funding for off-label indications.Conclusions:Our approach is feasible, reproducible, and can guide novel therapeutic choices in this poor prognosis cohort, where new treatment options are urgently needed. This platform is relevant to many solid organ malignancies.
Ablation of Reentry-Vulnerable Zones Determined by Left Ventricular Activation From Multiple Directions: A Novel Approach for Ventricular Tachycardia Ablation
Authors: Anter Elad , Neuzil Petr , Reddy Vivek Y. , Petru Jan , Park Kyoung-Min , Sroubek Jakub , Leshem Eran , Zimetbaum Peter J. , Buxton Alfred E. , Kleber Andre G. , Shen Changyu , Wit Andrew L. 
Published: May 2020

Background:
The optimal method to identify the arrhythmogenic substrate of scar-related ventricular tachycardia (VT) is unknown. Sites of activation slowing during sinus rhythm (SR) often colocalize with the VT circuit. However, the utility and limitations of such approach for guiding ablation are unknown.

Methods:
We conducted a multicenter study in patients with infarct-related VT. The left ventricular (LV) was mapped during activation from 3 directions: SR (or atrial pacing), right ventricular, and LV pacing at 600 ms. Ablation was applied selectively to the cumulative area of slow activation, defined as the sum of all regions with activation times of ≥40 ms per 10 mm. Hemodynamically tolerated VTs were mapped with activation or entrainment. The primary outcome was a composite of appropriate implanted cardioverter-defibrillator therapies and cardiovascular death.

Results:

In 85 patients, the LV was mapped during activation from 2.4±0.6 directions. The direction of LV activation influenced the location and magnitude of activation slowing. The spatial overlap of activation slowing between SR and right ventricular pacing was 84.2±7.1%, between SR and LV pacing was 61.4±8.8%, and between right ventricular and LV pacing was 71.3±9.6% (
P
<0.05 between all comparisons). Mapping during SR identified only 66.2±8.2% of the entire area of activation slowing and 58% critical isthmus sites. Activation from other directions by right ventricular and LV stimulation unmasked an additional 33% of slowly conducting zones and 25% critical isthmus sites. The area of maximal activation slowing often corresponded to the site where the wavefront first interacted with the infarct. During a follow-up period of 3.6 years, the primary end point occurred in 14 out of 85 (16.5%) patients.

Conclusions:
The spatial distribution of activation slowing is dependent on the direction of LV activation with the area of maximal slowing corresponding to the site where the wavefront first interacts with the infarct. This data may have implications for VT substrate mapping strategies.
Accelerated Early Vascular Aging Among Adolescents With Obesity and/or Type 2 Diabetes Mellitus
Authors: Ryder Justin R. , Northrop Elise , Rudser Kyle D. , Kelly Aaron S. , Gao Zhiqian , Khoury Philip R. , Kimball Thomas R. , Dolan Lawrence M. , Urbina Elaine M. 
Published: May 2020

Background
The normal rate of subclinical vascular aging from adolescence to young adulthood has not been well‐characterized. We conducted a 5‐year longitudinal study among adolescents with normal‐weight, obesity, and/or type 2 diabetes mellitus to examine trajectories of early vascular aging.

Methods and Results

Adolescents (mean [SD] age 17.6 [3.5]; 35.3% male) had either normal weight (n=141), obesity (n=156), or type 2 diabetes mellitus (n=151) at baseline. Primary metrics used for early vascular aging included measures of vascular structure (carotid intima‐media thickness [cIMT]; common, internal, and bulb) and arterial stiffness (carotid‐femoral pulse wave velocity, and augmentation index). Longitudinal (5‐year) outcomes were examined using generalized estimating equations adjusting for baseline value, sex, race, and age. Compared with participants with normal weight, those with obesity had greater positive change in common cIMT (0.05 mm [0.03, 0.06];
P
<0.001), bulb cIMT (0.02 mm [0.00, 0.05];
P
=0.033), internal cIMT (0.03 mm [0.01, 0.05];
P
<0.001), and pulse wave velocity carotid‐femoral (0.38 m/sec [0.14, 0.61];
P
=0.001), and those with type 2 diabetes mellitus had greater positive change in common cIMT (0.05 mm [0.04, 0.07];
P
<0.001), bulb cIMT (0.06 mm [0.04, 0.09];
P
<0.001), internal cIMT (0.04 mm [0.02, 0.07];
P
<0.001), augmentation index (4.67% [2.20, 7.13];
P
<0.001), and pulse wave velocity carotid‐femoral (0.74 m/sec [0.46, 1.02];
P
<0.001). Higher baseline systolic blood pressure was associated with greater positive change in common cIMT (0.007 mm [0.003, 0.011];
P
<0.001), bulb cIMT (0.009 mm [0.002, 0.016];
P
=0.01), internal cIMT (0.008 mm [0.003, 0.013];
P
=0.001), and pulse wave velocity carotid‐femoral (0.066 m/sec [0.002, 0.130];
P
=0.042).

Conclusions
These longitudinal data support the hypothesis that the presence of obesity, type 2 diabetes mellitus, and elevated baseline systolic blood pressure in early life accelerates the progression of risk factors key in the development of early vascular aging.
Ownership and Productivity in Vertically Integrated Firms: Evidence from the Chinese Steel Industry
Authors: Brandt Loren , Jiang Feitao , Luo Yao , Su Yingjun 
Published: May 2020

AbstractWe study productivity differences in vertically integrated steel facilities using equipment-level information on inputs and output for each of the main stages in the value chain. We obtain stage-level productivity estimates by estimating a multistage production system and then integrate them into estimates for integrated facilities. At this level, we do not find statistically significant differences in productivity by ownership. This conceals important differences upstream and downstream in the value chain: private firms outperform in pig iron and steelmaking but lag in sintering. Inferior access to higher-quality raw materials and use of less automated technology are likely sources of these differences.
Rhythms of nutag
Authors: Namsaraeva Sayana 
Published: May 2020

Abstract
While Henri Lefebvre used his rhythmanalysis for analysing urban spaces and the effects of those rhythms on the inhabitants of those spaces, I attempt to apply it to a more rural and non-European environment, the comparatively small and familiar space of a Mongolian nutag. Case studies based on oral and written Buryat and Barga Mongols’ accounts demonstrate that entering the spiritually thick atmosphere of the nutag (crossing its borders) requires a certain slowing down and tactical deceleration to adjust to local rhythms. To examine the hierarchy of the various contingent forces that influence people and their movement either in their own or in khari nutag [foreign land], I elaborate host–guest relations into a triangulated arrangement of relations between ezed masters, guests and the locals. To borrow an expression from physics to add to our analytical vocabulary of writing on slowness and deceleration, each nutag appears to be a sort of a ‘viscous medium’ with different rhythms and fluids creating more drag on objects (people) moving through it.
The effectiveness of Kinesio Taping® for mobility and functioning improvement in knee osteoarthritis: a randomized, double-blind, controlled trial
Authors: Donec Venta , Kubilius Raimondas 
Published: May 2020

Objective: To evaluate the effectiveness of the Kinesio Taping® method for mobility and functioning improvement for patients with knee osteoarthritis (KO). Design: Randomized, double-blinded, controlled trial. Setting: Outpatient rehabilitation department. Subjects: A total of 187 subjects with symptomatic I–III grade KO participated; of these, 157 subjects were included in the analyses (intervention group, n = 81 (123 knees); control group, n = 76 (114 knees). Intervention: The intervention group received a specific Kinesio Taping application, and the control group received non-specific knee taping for a month. Main measures: Changes in Knee injury and Osteoarthritis Outcome Scores (KOOS), knee active range of motion, 10-Meter Walk, and the five times sit to stand tests (5xSST) were assessed at baseline, after four weeks of taping, and a month post taping intervention. Subjective participants’ experiences and opinions on the effect of knee taping were evaluated. The chosen level of significance was p < 0.05. Results: The mean age of participants was 68.7 ± 9.9 in intervention group and 70.6 ± 8.3 in control group ( p > 0.05). The change from baseline in gait speed in the intervention group after taping month was +0.04 ± 0.1 m/s, at follow-up +0.06 ± 0.1 m/s; in control group +0.07 ± 0.1 m/s, and +0.09 ± 0.1 m/s; the change in time needed to accomplish 5xSST was –2.2 ± 3.2 seconds, at follow-up –2.4 ± 3.1 seconds; in control group –2.8 ± 3.6 seconds, and –2.4 ± 4 seconds. Improved knee flexion and enhancement in functioning assessed by KOOS were noticed in both groups, with lasting improvement to follow up. No difference in the change in the above-mentioned outcomes was found between groups ( p > 0.05). Fewer subjects (6.2% (5) vs. 21.1% (16), χ2 = 7.5, df = 2, p = 0.024) from Kinesio Taping group were unsure if taping alleviated their mobility and more intervention group patients indicated higher subjective satisfaction with the effect of knee taping to symptom and mobility alleviation than control group ( p < 0.005). Conclusion: Investigated Kinesio Taping technique did not produce better results in mobility and functioning improvement over non-specific knee taping; however, it had higher patient-reported subjective value for symptom attenuation and experienced mobility enhancement.
Effects of pain neuroscience education and dry needling for the management of patients with chronic myofascial neck pain: a randomized clinical trial
Authors: Valiente-Castrillo Pedro , Martín-Pintado-Zugasti Aitor , Calvo-Lobo César , Beltran-Alacreu Hector , Fernández-Carnero Josué 
Published: May 2020

Objectives The aim of this study was to observe the medium-term effects on pain, disability, and psychological factors of a combination of myofascial trigger point (MTrP) dry needling (DN) with pain neuroscience education (PNE) versus DN alone versus control care as usual (CUC) in patients with chronic neck pain. Methods A total of 60 patients were randomly selected in a Spanish National Health Service Public Hospital and divided into three groups: 6 sessions of DN with 3 sessions of PNE (TrPDN + PNE group, n = 21), 6 sessions of DN alone (TrPDN group, n = 20), or 10 sessions of usual care (CUC group, n = 19). The primary outcome was neck pain intensity, while neck disability, medication intake, and psychological factors were secondary outcomes. These variables were measured at baseline, post-treatment, and at 1 month and 3 months after treatment. Results TrPDN + PNE and DN alone were associated with greater reductions in pain intensity and disability compared to CUC (p < 0.01). TrPDN + PNE resulted in greater improvements in kinesiophobia, pain anxiety, and pain-related beliefs than DN alone and CUC (p < 0.01). No differences between groups were observed in medication intake, quality of life, catastrophizing, depression, or fear of pain (p > 0.05). Discussion Provision of PNE and DN in the management of chronic neck pain in a Spanish National Health Service Public Hospital was associated with greater improvements in psychological factors than DN therapy only. Conclusion DN alone was more effective at reducing chronic non-specific neck pain and disability than CUC at 3-month follow-up. However, the inclusion of PNE combined with DN resulted in greater improvements in kinesiophobia, pain anxiety, and pain-related beliefs. Trial registration number NCT03095365 (ClinicalTrials.gov).
An intensive form of trauma focused cognitive behaviour therapy in an acute adolescent inpatient unit: An uncontrolled open trial
Authors: Cabrera Natalie , Moffitt Gavin , Jairam Rajeev , Barton Giles 
Published: May 2020

Purpose: Post-traumatic stress disorder (PTSD) rates among hospitalised adolescents are between 21% and 32%, and there is a lack of evidence-based interventions for this population. Trauma-focused cognitive behaviour therapy (TF-CBT) is an evidence-based intervention for children and adolescents with PTSD; however, it has not been implemented in an acute adolescent inpatient unit. This study examines the implementation of an intensive form of TF-CBT in an adolescent inpatient unit. Method: An uncontrolled open trail study was conducted where 15 adolescents diagnosed with PTSD were treated with an intensive form of TF-CBT. Measures used were the University of California, Los Angeles’ (UCLA) PTSD Reaction Index for Diagnostic and Statistical Manual of Mental Disorders (4th ed., Adolescent Version; DSM-IV-Adolescent Version), the National Stressful Events Survey PTSD Short Scale (NSESSS) and the Children’s Global Assessment Scale (CGAS) Results: Adolescents received an average of nine sessions of TF-CBT over a period of 28 days. The average NSESSS on admission was 23.73 and 8.27 at discharge; the CGAS average on admission was 19 and on discharge was 48.7; both were statistically significant changes. Conclusion: Preliminary findings support the use of an intensive form of TF-CBT to treat adolescents with PTSD admitted to acute adolescent inpatient units indicating the need for further research in this area.
Evaluation of various confirmatory tests for the diagnosis of aldosterone-producing adenoma
Authors: Kidoguchi Satoshi , Sugano Naoki , Kawauchi Ruri , Nakashima Daisuke , Hayashi-Ishikawa Naomi , Tokudome Goro , Yokoo Takashi 
Published: May 2020

Introduction: Adrenal venous sampling is useful for discriminating unilateral and bilateral hypersecretion in patients with primary aldosteronism, but it is relatively invasive. To determine the site of hypersecretion more non-invasively, we evaluated predictors of unilateral hypersecretion. Materials and methods: We evaluated the baseline characteristics and the results of confirmatory tests of 123 patients with primary aldosteronism who underwent adrenal venous sampling. Results: Unilateral hypersecretion was identified in 22.0%. The plasma aldosterone concentration and aldosterone–renin ratio were significantly higher and serum potassium concentration and plasma renin activity were significantly lower in patients with unilateral hypersecretion. Plasma aldosterone concentrations after captopril challenge test, saline infusion test and rapid adrenocorticotropic hormone stimulation test were significantly higher among patients with unilateral hypersecretion. The plasma aldosterone concentration reduction ratio in saline infusion test and plasma aldosterone concentration elevation ratio during rapid adrenocorticotropic hormone stimulation test were significantly higher in patients with unilateral hypersecretion. However, areas under the curve for these parameters were not superior to the values after confirmatory tests. Conclusions: The plasma aldosterone concentration values after captopril challenge test, saline infusion test and rapid adrenocorticotropic hormone stimulation test were useful for identifying patients with unilateral hypersecretion. However, value changes or ratios during confirmatory tests are less useful for this aim.
Characteristics for a tool for timely identification of palliative needs in heart failure: The views of Dutch patients, their families and healthcare professionals
Authors: Janssen Daisy JA , Ament Stephanie MC , Boyne Josiane , Schols Jos MGA , Rocca Hans-Peter Brunner-La , Maessen José MC , van den Beuken-van Everdingen Marieke HJ 
Published: May 2020

BackgroundPalliative care can improve outcomes for patients with advanced chronic heart failure and their families, but timely recognition of palliative care needs remains challenging.AimThe aim of this study was to identify characteristics of a tool to assess palliative care needs in chronic heart failure that are needed for successful implementation, according to patients, their family and healthcare professionals in The Netherlands.MethodsExplorative qualitative study, part of the project ‘Identification of patients with HeARt failure with PC needs’ (I-HARP), focus groups and individual interviews were held with healthcare professionals, patients with chronic heart failure, and family members. Data were analysed using the Consolidated Framework for Implementation Research.ResultsA total of 13 patients, 10 family members and 26 healthcare professionals participated. Direct-content analysis revealed desired tool characteristics for successful implementation in four constructs: relative advantage, adaptability, complexity, and design quality and packaging. Healthcare professionals indicated that a tool should increase awareness, understanding and knowledge concerning palliative care needs. A tool needs to: be adaptable to different disease stages, facilitate early identification of palliative care needs and ease open conversations about palliative care. The complexity of chronic heart failure should be considered in a personalized approach.ConclusionsThe current study revealed the characteristics of a tool for timely identification of palliative care needs in chronic heart failure needed for successful implementation. The next steps will be to define the content of the tool, followed by development of a preliminary version and iterative testing of this version by the different stakeholders.