bluuebunny/crossref_metadata_2025_split huggingface dataset:
Foveal avascular zone morphology and parafoveal capillary perfusion in sickle cell retinopathy
Authors: Lynch Giselle , Scott Adrienne W , Linz Marguerite O , Han Ian , Andrade Romo Jorge S , Linderman Rachel E , Carroll Joseph , Rosen Richard B , Chui Toco Y 
Published: July 2019

Background/aimsTo assess foveal avascular zone (FAZ) morphology and parafoveal capillary perfusion in patients with various stages of sickle cell retinopathy (SCR) using optical coherence tomography angiography (OCT-A).MethodsThis is a multi-institutional retrospective study of patients with various stages of SCR compared with healthy controls. Parafoveal OCT-A images obtained using a commercial spectral domain-OCT system were reviewed. Foveal-centred 3×3 mm full vascular slab OCT-As were used for image processing and data analysis. FAZ area, perimeter, and acircularity index were determined on the OCT-A image after manual delineation of the FAZ border. Quadrant-based parafoveal capillary density and per cent area deviating from normal distribution were also measured.ResultsFifty-two patients with SCR (33 non-proliferative and 19 proliferative) and 20 age and race-matched healthy controls were included. One randomly selected eye per study participant was analysed. FAZ perimeter and acircularity index were significantly greater in SCR eyes when compared with the controls. While parafoveal capillary density was significantly lower, per cent area deviated from normal distribution was significantly higher in SCR eyes than that of the control. However, no statistically significant difference between the two SCR stages was observed. In quadrant-based analysis, the temporal quadrant showed greater parafoveal capillary dropout due to SCR, with the most profound effect in patients with proliferative SCR.ConclusionsAbnormal FAZ morphology and altered parafoveal capillary perfusion were found in patients with SCR. Our customised OCT-A image analysis method uniquely highlights significant quantitative alterations in perfusion density mapping in a qualitative display, with minimal obscuration of OCT-A image detail.
White-Box vs. Black-Box Complexity of Search Problems
Authors: Komargodski Ilan , Naor Moni , Yogev Eylon 
Published: July 2019

Ramsey theory assures us that in any graph there is a clique or independent set of a certain size, roughly logarithmic in the graph size. But how difficult is it to find the clique or independent set? If the graph is given explicitly, then it is possible to do so while examining a linear number of edges. If the graph is given by a black-box, where to figure out whether a certain edge exists the box should be queried, then a large number of queries must be issued. But what if one is given a program or circuit for computing the existence of an edge? This problem was raised by Buss and Goldberg and Papadimitriou in the context of TFNP, search problems with a guaranteed solution.
We examine the relationship between black-box complexity and white-box complexity for search problems with guaranteed solution such as the above Ramsey problem. We show that under the assumption that collision-resistant hash function exists (which follows from the hardness of problems such as factoring, discrete-log, and learning with errors) the white-box Ramsey problem is hard and this is true even if one is looking for a much smaller clique or independent set than the theorem guarantees. This is also true for the colorful Ramsey problem where one is looking, say, for a monochromatic triangle.
In general, one cannot hope to translate all black-box hardness for TFNP into white-box hardness: we show this by adapting results concerning the random oracle methodology and the impossibility of instantiating it.
Another model we consider is that of succinct black-box, where the complexity of an algorithm is measured as a function of the description size of the object in the box (and no limitation on the computation time). In this case, we show that for all TFNP problems there is an efficient algorithm with complexity proportional to the description size of the object in the box times the solution size. However, for promise problems this is not the case.
Finally, we consider the complexity of graph property testing in the white-box model. We show a property that is hard to test even when one is given the program for computing the graph (under the appropriate assumptions such as hardness of Decisional Diffie-Hellman). The hard property is whether the graph is a two-source extractor.
A Systematic Review and Meta-analysis of Associations between Clinical Prostatitis and Prostate Cancer: New Estimates Accounting for Detection Bias
Authors: Langston Marvin E. , Horn Mara , Khan Saira , Pakpahan Ratna , Doering Michelle , Dennis Leslie K. , Sutcliffe Siobhan 
Published: July 2019

Abstract

Background:
Previous meta-analyses have estimated summary positive associations between clinical prostatitis and prostate cancer. However, none have accounted for detection bias, the possibility for increased prostate cancer screening and detection in men with clinical prostatitis, in their pooled estimates.

Methods:
We searched for studies that investigated the relation between clinical prostatitis and prostate cancer through November 2018. Random effects meta-analysis was used to calculate summary odds ratios (OR) among all studies and in strata defined by methods used to reduce detection bias.
Results: Although an increased odds of prostate cancer was seen among men with a history of clinical prostatitis in all 38 eligible studies combined [OR, 2.05; 95% confidence interval (CI), 1.64–2.57], this estimate attenuated to null among studies that performed the most rigorous analyses to limit detection bias (OR, 1.16; 95% CI, 0.77–1.74).

Conclusions:
Our findings indicate that previously reported positive associations between clinical prostatitis and prostate cancer are likely due to detection bias.

Impact:
Studies using rigorous detection bias methods are warranted to replicate these findings, as well as to examine the possible relation between prostate inflammation and prostate cancer directly, rather than indirectly through the diagnosis of “prostatitis,” which includes a large proportion of men without evidence of prostate inflammation.
Clinical and Molecular Predictors of Response to Immune Checkpoint Inhibitors in Patients with Advanced Esophagogastric Cancer
Authors: Greally Megan , Chou Joanne F. , Chatila Walid K. , Margolis Matthew , Capanu Marinela , Hechtman Jaclyn F. , Tuvy Yaelle , Kundra Ritika , Daian Foysal , Ladanyi Marc , Kelsen David P. , Ilson David H. , Berger Michael F. , Tang Laura H. , Solit David B. , Diaz Luis A. , Schultz Nikolaus , Janjigian Yelena Y. , Ku Geoffrey Y. 
Published: July 2019

AbstractPurpose:Immune checkpoint inhibitors (ICI) are effective in only a minority of patients with esophagogastric cancer (EGC). Here, we aimed to identify predictors of durable clinical benefit to ICI in EGC.Experimental Design:Patients with advanced EGC treated with ICIs at Memorial Sloan Kettering Cancer Center (New York, NY) were identified. Clinicopathologic variables were assessed. In patients profiled by MSK-IMPACT–targeted sequencing, outcomes were correlated with tumor genomic features.Results:One-hundred sixty-one patients were treated with ICIs (110 with anti–PD-1/PD-L1 antibodies and 51 with anti–CTLA-4 and PD-1/PD-L1 antibodies). The median progression-free survival (PFS) and overall survival (OS) were 1.7 and 4.9 months, respectively. Greater number of disease sites (≥3), liver metastases, treatment with ≥3 prior therapies and ECOG performance status ≥2 were associated with poorer PFS and OS. Patients treated with combination ICI and those with PD-L1–positive tumors had improved outcomes. There was no difference in outcomes between patients treated with antibiotics during or in the 2 months preceding ICI treatment versus those who were not. Occurrence of irAEs was associated with improved OS. In genomically profiled tumors (n = 89), survival was associated with increasing tumor mutation burden (TMB). However, in multivariable analyses and when microsatellite unstable (MSI) patients were excluded, a significant association was no longer observed.Conclusions:In patients with advanced EGC, heavily pretreated patients, those with high-volume disease and/or poor PS were less likely to benefit from ICI. irAEs were associated with improved OS. TMB correlated with improved survival, but this association was not observed when MSI-high patients were excluded.
Phase I and Pharmacology Study of Ropidoxuridine (IPdR) as Prodrug for Iododeoxyuridine-Mediated Tumor Radiosensitization in Advanced GI Cancer Undergoing Radiation
Authors: Kinsella Timothy , Safran Howard , Wiersma Susan , DiPetrillo Thomas , Schumacher Andrew , Rosati Kayla , Vatkevich John , Anderson Lawrence W. , Hill Kimberly D. , Kunos Charles , Collins Jerry M. 
Published: July 2019

AbstractPurpose:Iododeoxyuridine (IUdR) is a potent radiosensitizer; however, its clinical utility is limited by dose-limiting systemic toxicities and the need for prolonged continuous infusion. 5-Iodo-2-pyrimidinone-2′-deoxyribose (IPdR) is an oral prodrug of IUdR that, compared with IUdR, is easier to administer and less toxic, with a more favorable therapeutic index in preclinical studies. Here, we report the clinical and pharmacologic results of a first-in-human phase I dose escalation study of IPdR + concurrent radiation therapy (RT) in patients with advanced metastatic gastrointestinal (GI) cancers.Patients and Methods:Adult patients with metastatic GI cancers referred for palliative RT to the chest, abdomen, or pelvis were eligible for study. Patients received IPdR orally once every day × 28 days beginning 7 days before the initiation of RT (37.5 Gy in 2.5 Gy × 15 fractions). A 2-part dose escalation scheme was used, pharmacokinetic studies were performed at multiple time points, and all patients were assessed for toxicity and response to Day 56.Results:Nineteen patients were entered on study. Dose-limiting toxicity was encountered at 1,800 mg every day, and the recommended phase II dose is 1,200 mg every day. Pharmacokinetic analyses demonstrated achievable and sustainable levels of plasma IUdR ≥1 μmol/L (levels previously shown to mediate radiosensitization). Two complete, 3 partial, and 9 stable responses were achieved in target lesions.Conclusions:Administration of IPdR orally every day × 28 days with RT is feasible and tolerable at doses that produce plasma IUdR levels ≥1 μmol/L. These results support the investigation of IPdR + RT in phase II studies.
β8 Integrin Mediates Pancreatic Cancer Cell Radiochemoresistance
Authors: Jin Sha , Lee Wei-Chun , Aust Daniela , Pilarsky Christian , Cordes Nils 
Published: July 2019

Abstract

Pancreatic ductal adenocarcinoma (PDAC) stroma, composed of extracellular matrix (ECM) proteins, promotes therapy resistance and poor survival rate. Integrin-mediated cell/ECM interactions are well known to control cancer cell survival, proliferation, and therapy resistance. Here, we identified β8 integrin in a high-throughput knockdown screen in three-dimensional (3D), ECM-based cell cultures for novel focal adhesion protein targets as a critical determinant of PDAC cell radiochemoresistance. Intriguingly, β8 integrin localizes with the golgi apparatus perinuclearly in PDAC cells and resection specimen from PDAC patients. Upon radiogenic genotoxic injury, β8 integrin shows a microtubule-dependent perinuclear-to-cytoplasmic shift as well as strong changes in its proteomic interactome regarding the cell functions transport, catalysis, and binding. Parts of this interactome link β8 integrin to autophagy, which is diminished in the absence of β8 integrin. Collectively, our data reveal β8 integrin to critically coregulate PDAC cell radiochemoresistance, intracellular vesicle trafficking, and autophagy upon irradiation.

Implications:
This study identified β8 integrin as an essential determinant of PDAC cell radiochemosensitivity and as a novel potential cancer target.
Parasite-induced colour alteration of intermediate hosts increases ingestion by suitable final host species
Authors: Thünken Timo , Baldauf Sebastian A. , Bersau Nicole , Frommen Joachim G. , Bakker Theo C.M. 
Published: July 2019

Abstract
Parasites with complex life cycles often alter the phenotypic appearance of their intermediate hosts in order to facilitate ingestion by the final host. However, such manipulation can be costly as it might increase ingestion by less suitable or dead-end hosts as well. Species-specific parasitic manipulation is a way to enhance the transmission to suitable final hosts. Here, we experimentally show that the altered body colouration of the intermediate host Gammarus pulex caused by its acanthocephalan parasite Pomphorhynchus laevis differently affects predation by different fish species (barbel, perch, ruffe, brown trout and two populations of three-spined stickleback) depending on their suitability to act as final host. Species that were responsive to colour manipulation in a predation experiment were more susceptible to infection with P. laevis than unresponsive species. Furthermore, three-spined stickleback from different populations responded to parasite manipulation in opposite directions. Such increased ingestion of the intermediate host by preferred and suitable hosts suggests fine-tuned adaptive parasitic manipulation and sheds light on the ongoing evolutionary arms race between hosts and manipulative parasites.
Development and outcome of intrasexual contests in males and females of Chalcides viridanus (Fam. Scincidae) along breeding period
Authors: Sánchez-Hernández P. , Molina-Borja M. 
Published: July 2019

Abstract
Morphological and behavioural traits influence contest development and outcome. We analysed morphological and behavioural traits in male and female staged contests of Chalcides viridanus along breeding time. There was no significant difference in any morphologic trait for winner and looser male contenders; larger hind-limbs and heads were significantly associated to winner females. ‘Approach’ was positively while ‘flee’ negatively associated to winner males. ‘Tongue-flick’ and ’approach’ were positively associated to female winners and ‘flee’ to losers. Contest intensity was higher in male than in female contests. For males it was higher in May than in March or April but for females in April and May than in March. Contest intensity was positively related to head width in loser males, suggesting fitting to a pure self-assessment model. For females there was no significant association. For the first time we have shown that skink female contests are as complex as those of males.
A Social Imagination of Forgiveness
Authors: Forster Dion 
Published: July 2019

Abstract
This article studies the complexity of understandings of forgiveness among a sample of Black and White South Africans within the context of an empirical intercultural Bible reading process. We will first focus on the foundation upon which the study is predicated—namely that the social imagination of forgiveness is deeply contested among South Africans. Next, we will discuss the approach that the study took to gather the necessary data, and analyse the theological views of forgiveness among the participants in the study. Finally, we shall discuss some of the primary findings of the study. These show that social identity plays a significant role in shaping theological hermeneutics. Black and White participants hold diverse, and even conflicting, expressions and expectations for forgiveness. These are characterised as predominantly social and political for the Black participants, and predominantly individual and spiritual for the White participants.
New Kids on the Block
Authors: Pacholska Magdalena 
Published: July 2019

Abstract
One of the most contentious issues of the “Identification of Customary International Law”, a topic the International Law Commission has recently finalized its work on, concerns the extent to which international organizations (IOs) play a part in the creation of customary norms. Conclusion 4(2) of the 2018 draft provides that “[i]n certain cases, the practice of international organizations also contributes to the formation, or expression, of rules of customary international law.” The official commentary recognizes two such cases: i) when States “have transferred exclusive competences to the [IOs]”, and ii) when States “have conferred competences upon the [IOs] that are functionally equivalent to powers exercised by States.” After questioning the utility of the Commission’s approach, this contribution outlines an alternative analytical framework for IOs’ participation in the creation of customary rules grounded in the principle of speciality and premised on the ratione personae applicability of the rule to be identified.
Decomposition of Future Moisture Flux Changes over the Tibetan Plateau Projected by Global and Regional Climate Models
Authors: Zhang Hongwen , Gao Yanhong , Xu Jianwei , Xu Yu , Jiang Yingsha 
Published: July 2019

AbstractTo meet the requirement of high-resolution datasets for many applications, a dynamical downscaling approach using a regional climate model (the WRF Model) driven by a global climate model (CCSM4) has been adopted. This study focuses on projections of future moisture flux changes over the Tibetan Plateau (TP). First, the downscaling results for the historical period (1980–2005) are evaluated for precipitation P, evaporation E, and precipitation minus evaporation P − E against Global Land Data Assimilation System (GLDAS) data. The mechanism of P − E changes is analyzed by decomposition into dynamic, thermodynamic, and transient eddy components. Whether the historical period changes and mechanisms continue into the future (2010–2100) is investigated using the WRF and CCSM model projections under the RCP4.5 and RCP8.5 scenarios. Compared with coarse-resolution forcing, downscaling was found to better reproduce the historical spatial patterns and seasonal mean of annual average P, E, and P − E over the TP. WRF projects a diverse spatial variation of P − E changes, with an increase in the northern TP and a decrease in the southern TP, compared with the uniform increase in CCSM. The dynamic component dominates P − E changes for the historical period in both the CCSM and WRF projections. In the future, however, the thermodynamic component in CCSM dominates P − E changes under RCP4.5 and RCP8.5 from the near-term (2010–39) to the long-term (2070–99) future. Unlike the CCSM projections, the WRF projections reproduce the mechanism seen in the historical period—that is, the dynamic component dominates P − E changes. Furthermore, future P − E changes in the dynamical downscaling are less sensitive to warming than its coarse-resolution forcing.
Comparison between different non-destructive techniques methods to detect and characterize impact damage on composite laminates
Authors: Papa I , Ricciardi MR , Antonucci V , Langella A , Tirillò J , Sarasini F , Pagliarulo V , Ferraro P , Lopresto V 
Published: July 2019

This paper aims to investigate the ability of ultrasonic and electronic speckle pattern interferometry to analyse the low-velocity impact internal damage mechanisms on basalt composite laminates and to provide information on the shape and the extent of the delamination in non-destructive way. Basalt/epoxy composites with different thicknesses have been realised and characterised by mechanical tests to investigate both fibre-dominated (tensile and flexural behaviour) and matrix-dominated properties (interlaminar shear strength). Specimens were impacted at penetration and at increasing energy values, to explore the damage onset and propagation. The results showed that the damage was concentrated under the impactor–material contact point and that the composite with intermediate thickness had the best balance between the different kinds of impact damages: delamination and indentation. Further, a good agreement was found between the overall data obtained by the two non-destructive techniques, confirming the capability of both techniques to examine the composite impact damage.
Throwing Injuries in Youth Baseball Players: Can a Prevention Program Help? A Randomized Controlled Trial
Authors: Sakata Jun , Nakamura Emi , Suzuki Tatsuhiro , Suzukawa Makoto , Akeda Masaki , Yamazaki Tetsuya , Ellenbecker Todd S. , Hirose Norikazu 
Published: July 2019

Background: Throwing injuries of the shoulder and elbow are common among youth baseball players. Hypothesis: A prevention program will reduce the incidence of throwing injuries of the shoulder and elbow by 50% among youth baseball players. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: The authors block randomized 16 youth baseball teams consisting of 237 players aged 9 to 11 years into an intervention group (8 teams, 117 players) and a control group (8 teams, 120 players). The intervention program consisted of 5 stretching, 2 dynamic mobility, and 2 balance training exercises performed during warm-up. Both groups were followed up for 12 months, during which the incidence of shoulder and elbow injuries was recorded. In addition, ball speed during pitching as a performance-related factor and variables of physical function (passive range of motion of the elbow, shoulder and hip, dynamic balance, and thoracic kyphosis angle) were assessed during the pre- and postintervention periods. Results: The incidence of shoulder and elbow injuries in the intervention group (1.7 per 1000 athlete-exposures) was significantly lower than that in the control group (3.1 per 1000 athlete-exposures) (hazard ratio, 1.940; 95% CI, 1.175-3.205; P = .010). The factors related to pitching performance, as assessed by ball speed, tended to increase in the intervention group as compared with the control group ( P = .010). The program also improved shoulder horizontal adduction deficits on the dominant side, hip internal rotation on the nondominant side, and the thoracic kyphosis angle. Conclusion: A prevention program decreases throwing injuries of the shoulder and elbow and enhances the parameter of pitching performance in youth baseball players.
Domain integration of ADAM family proteins: Emerging themes from structural studies
Authors: Seegar Tom CM , Blacklow Stephen C 
Published: July 2019

ADAM (a disintegrin and metalloproteinase) proteins are type-1 transmembrane and secreted proteins that function in cell adhesion and signal transduction. Here we review the structural features of ADAM proteins that direct their biological functions in ectodomain shedding and cell adhesion. Impact statement Recent structural advances have provided a deeper appreciation for interdomain relationships that modulate the activity of ADAM proteins in ectodomain shedding and cellular adhesion. Our review covers these new findings, and places them into historical context. The new results make clear that the metalloproteinase domain works in combination with its ancillary domains to execute its biological function. The ADAM ectodomain is dynamic, and accesses conformations that require interdomain movements during its enzymatic “lifecycle.” Fundamental questions about ADAM activation and substrate selection, however, still remain unanswered. Elucidating the biochemical and structural basis for ADAM regulation will be an exciting avenue of future research that should greatly advance our understanding of ADAM function in biology and human pathogenesis.