bluuebunny/crossref_metadata_2025_split huggingface dataset:
The absolute percent deviation of IGHV mutation rather than a 98% cut‐off predicts survival of chronic lymphocytic leukaemia patients treated with fludarabine, cyclophosphamide and rituximab
Authors: Jain Preetesh , Nogueras González Graciela M. , Kanagal‐Shamanna Rashmi , Rozovski Uri , Sarwari Nawid , Tam Constantine , Wierda William G. , Thompson Philip A. , Jain Nitin , Luthra Rajyalakshmi , Quesada Andres , Sanchez‐Petitto Gabriela , Ferrajoli Alessandra , Burger Jan , Kantarjian Hagop , Cortes Jorge , O'Brien Susan , Keating Michael J. , Estrov Zeev 
Published: November 2017

SummaryThe degree of somatic hypermutation, determined as percent deviation of immunoglobulin heavy chain gene variable region sequence from the germline (IGHV%), is an important prognostic factor in chronic lymphocytic leukaemia (CLL). Currently, a cut‐off of 2% deviation or 98% sequence identity to germline in IGHV sequence is routinely used to dichotomize CLL patients into mutated and unmutated groups. Because dissimilar IGHV% cut‐offs of 1–5% were identified in different studies, we wondered whether no cut‐off should be applied and IGHV% treated as a continuous variable. We analysed the significance of IGHV% in 203 CLL patients enrolled on the original frontline fludarabine, cyclophosphamide and rituximab (FCR) trial with a median of 10 years follow‐up. Using the Cox Proportional Hazard model, IGHV% was identified as a continuous variable that is significantly associated with progression‐free (PFS) and overall survival (OS) (P < 0·001). Furthermore, we validated this finding in 323 patients treated with FCR off‐protocol and in the total cohort (n = 535). Multivariate analysis revealed a continuous trend. Higher IGHV% levels were incrementally associated with favorable PFS and OS in both FCR‐treated cohorts (P < 0·001, both cohorts). Taken together, our data suggest that IGHV% is a continuous variable in CLL patients treated with FCR.
Considerations in fertility preservation in cases of testicular trauma
Authors: Starmer Benjamin Z. , Baird Andrew , Lucky Marc A. 
Published: November 2017

ObjectiveTo perform a review of the literature to assess the options for preserving fertility in patients with fertility threatening testicular injuries and their effectiveness to help guide surgeons who encounter these patients in the future.Materials and methodsMedline, Embase and Cochrane library databases were searched using the keywords ‘treatment’, ‘therapy’, ‘management’, ‘scrotal trauma/injury’, ‘testicular trauma/injury/amputation’, ‘fertility’, and ‘fertility preservation’. The inclusion criteria were studies reporting fertility preserving techniques with a history of testicular trauma with loss of one, both, or nearly all testicular parenchymal tissue.ResultsTwo cases of testicular sperm extraction (TESE), eight cases of testicular replantation, and one case of cryopreservation after injury were identified. Presence of viable sperm after surgery was found in five of 11 patients. Common reasons for failure of replantation were prolonged ischaemic time and extensive crush injury to the vascular supply of the testis. Both cases of TESE and the single cryopreservation case obtained viable sperm.ConclusionScrotal trauma with threat to fertility is rare. It is important that urologists should consider fertility in any situation where complete or a large amount of testicular tissue loss is at risk of occurring and offer fertility preservation options as locally available.
Mechanism of doxorubicin cardiotoxicity evaluated by integrating multiple molecular effects into a biophysical model
Authors: Fernandez‐Chas M , Curtis M J , Niederer S A 
Published: November 2017

Background and PurposeDoxorubicin (DOX) is an effective cancer therapeutic agent but causes therapy‐limiting cardiotoxicity. The effects of DOX and its metabolite doxorubicinol (DOXL) on individual channels have been well characterized in isolation. However, it is unknown how the action and interaction of affected channels combine to generate the phenotypic cardiotoxic outcome. We sought to develop an in silico model that links drug effects on channels to action potential duration (APD) and intracellular Ca2+ concentration in order to address this gap in knowledge.Experimental ApproachWe first propose two methods to obtain, from published values, consensus drug effects on the currents of individual channels, transporters and pumps. Separately, we obtained equivalent values for APD and Ca2+ concentration (the readouts used as surrogates for cardiotoxicity). Once derived, the consensus effects on the currents were incorporated into established biophysical models of the cardiac myocyte and were refined adjusting the sarcoplasmic reticulum Ca2+ leak current (ILeak) until the consensus effects on APD and Ca2+ dynamics were replicated. Using factorial analysis, we then quantified the relative contribution of each channel to DOX and DOXL cardiotoxicity.Key ResultsThe factorial analysis identified the rapid delayed rectifying K+ current, the L‐type Ca2+ current and the sarcoplasmic reticulum ILeak as the targets primarily responsible for the cardiotoxic effects on APD and Ca2+ dynamics.Conclusions and ImplicationsThis study provides insight into the mechanisms of DOX‐induced cardiotoxicity and a framework for the development of future diagnostic and therapeutic strategies.
Microtopographic specialization and flexibility in tropical peat swamp forest tree species
Authors: Freund Cathryn A. , Harsanto Fransiskus A. , Purwanto Ari , Takahashi Hidenori , Harrison Mark E. 
Published: November 2017

AbstractTropical tree species distributions are determined by a wide range of biotic and abiotic factors, including topography and hydrology. Tropical peat swamp forests (TPSFs) are characterized in part by small‐scale variations in topography (‘hummocks’ and ‘hollows’) that create distinct microhabitats and thus may contribute to niche diversification among TPSF tree species. Using tree elevations calibrated to daily peat water levels collected using a data logger and a permutation test, we evaluated topographical microhabitat preferences for 21 tree species in a relatively undisturbed TPSF in Central Kalimantan, Indonesia, to determine whether these species show preferential association with hummocks or hollows and to quantify the prevalence of microhabitat specialization among them. Only one species, Tetractomia tetrandrum, emerged as a hollow specialist, with no hummock specialists among the species tested. The remaining 20 species, including Psydrax dicoccos, which had the lowest mean observed elevation, and Maasia hypoleuca, which had the highest mean observed elevation, showed no clear microtopographic preference. This suggests that many TPSF species may be resilient to the natural hydrologic variations that occur in relatively intact peat swamp forests. Such studies of microtopographic preferences of tree species in TPSF and other wetland forest ecosystems can inform selection of tree species for reforestation projects, and potentially also provide information on how future climate change may impact these habitats and their resident tree species.
Back‐to‐back colon capsule endoscopy and optical colonoscopy in colorectal cancer screening individuals
Authors: Kobaek‐Larsen M. , Kroijer R. , Dyrvig A.‐K. , Buijs M. M. , Steele R. J. C. , Qvist N. , Baatrup G. 
Published: November 2017

AbstractAimThe aim was to determine the polyp detection rate and per‐patient sensitivity for polyps > 9 mm of colon capsule endoscopy (CCE) compared with colonoscopy as well as the diagnostic accuracy of CCE.MethodIndividuals who had a positive immunochemical faecal occult blood test during screening had investigator blinded CCE and colonoscopy. Participants underwent repeat endoscopy if significant lesions detected by CCE were considered to have been missed by colonoscopy.ResultsThere were 253 participants. The polyp detection rate was significantly higher in CCE compared with colonoscopy (P = 0.02). The per‐patient sensitivity for > 9 mm polyps for CCE and colonoscopy was 87% (95% CI: 83–91%) and 88% (95% CI: 84–92%) respectively. In participants with complete CCE and colonoscopy examinations (N = 126), per‐patient sensitivity of > 9 mm polyps in CCE (97%; 95% CI: 94–100%) was superior to colonoscopy (89%; 95% CI: 84–94%). A complete capsule endoscopy examination (N = 134) could detect patients with intermediate or greater risk (according to the European guidelines) with an accuracy, sensitivity, specificity and positivity rate of 79%, 93%, 69% and 58% respectively, using a cut‐off of at least one polyp > 10 mm or more than two polyps.ConclusionCCE is superior to colonoscopy in polyp detection rate and per‐patient sensitivity to > 9 mm polyps, but only in complete CCE examinations. The rate of incomplete CCE examinations must be improved.
Pre‐operative features of non‐invasive follicular thyroid neoplasms with papillary‐like nuclear features: An analysis of their cytological, Gene Expression Classifier and sonographic findings
Authors: Song S. J. , LiVolsi V. A. , Montone K. , Baloch Z. 
Published: November 2017

ObjectiveTo investigate the corresponding cytological diagnoses, Gene Expression Classifier (GEC) results and ultrasound features of thyroid nodules diagnosed as non‐invasive follicular thyroid neoplasms with papillary‐like nuclear features (NIFTP), as well as any coexisting pathology.MethodsWe performed a retrospective review of thyroid nodules histologically diagnosed as NIFTP at our institution between 1st April 2016 and 1st April 2017. The following data points were collected: demographics, nodule size, ultrasound features, cytological diagnosis, GEC results, origin of sample (in‐house vs outside hospital) and any additional pathology identified in the resection specimen.ResultsThe case cohort included 87 nodules diagnosed as NIFTP (size range: 1‐7 cm, mean: 2.5 cm) from 82 patients (age range: 22‐82, mean age: 50.4, M:F—1:4.1). Corresponding FNA results were available for 72 nodules (82.8%) and were categorised as follows: benign (n = 5, 6.9%), atypia of unknown significance/follicular lesion of undetermined significance (n = 29, 40.3%), follicular neoplasm/suspicious for follicular neoplasm/follicular neoplasm with oncocytic features (n = 27, 37.5%), suspicious for papillary thyroid carcinoma (n = 6, 8.3%) and malignant (n = 5, 6.9%). GEC results were available for 32 (44.4%) nodules, with the majority of cases classified as suspicious (81.3%). On ultrasound, most of the nodules were predominantly solid (81.8%), vascular (93.8%), non‐calcified (86.5%), and either hypoechoic (44.9%) or isoechoic (38.8%). In addition to NIFTP and other benign findings in the background thyroid, 75 separate malignant tumours were identified in 38 (46.3%) patients, many of which were papillary thyroid microcarcinomas (86.5%) with lymph node metastases present in two cases.ConclusionsThe majority of thyroid nodules histologically diagnosed as NIFTP have indeterminate cytology (77.8%) and are classified as suspicious (81.3%) by GEC testing. Taken together, these findings can guide clinicians toward a more conservative therapeutic approach.
Suicidal ideation in individuals at ultra‐high risk for psychosis and its association with suspiciousness independent of depression
Authors: Bang Minji , Park Jin Young , Kim Kyung Ran , Lee Su Young , Song Yun Young , Kang Jee In , Lee Eun , An Suk Kyoon 
Published: November 2017

AimPsychotic experiences, including delusions and hallucinations, and their attenuated forms have been recently suggested as a significant but under‐recognized marker of suicide risk. However, the relationship between attenuated positive symptoms and suicide has not yet been clearly demonstrated in individuals at ultra‐high risk (UHR) for psychosis. Here, we investigated the effect of attenuated positive symptoms on suicidal ideation in UHR individuals.MethodsFifty‐three healthy controls (HCs) and 74 UHR individuals participated in the present study. All participants were assessed for the intensity of suicidal ideation and depressive symptoms at baseline. The effect of attenuated positive symptoms on suicidal ideation in the UHR group was examined using a multiple linear regression analysis after adjustment for concurrent depressive symptoms.ResultsUHR participants were found to have significantly greater suicidal ideation and more severe depressive symptoms compared to those of HCs. The regression model demonstrated that suspiciousness significantly increased suicidal ideation in UHR participants, independent of the severity of depressive symptoms.ConclusionThe findings of the present study suggest that suspiciousness may serve as a risk indicator for suicide in clinical practice for UHR individuals. It is crucial to focus on the risk of suicide in the UHR population, as they require sufficient clinical attention and proper management for crises related to their unusual and confusing experiences.
Effect of sensor installation on the accurate measurement of soil water content
Authors: Iwata Y. , Miyamoto T. , Kameyama K. , Nishiya M. 
Published: November 2017

SummaryWe evaluated the effects of different methods of installing a capacitance soil moisture sensor on the sensor's output with six soil types and three methods of sensor installation. For Method 1, the sensor was first placed in a container and then buried. For Method 2, the entire sensor (including prongs and circuitry) was inserted into a prepacked soil sample. For Method 3, the sensor prongs were installed directly into a prepacked soil sample, and then soil was placed around the circuitry. The sensor outputs of Method 1 were significantly smaller for the volumetric soil water content (θ) of most of the soil types compared with the sensor outputs of the other two methods. Large differences in sensor outputs were observed in relation to the installation method, which resulted in a large estimation error when using a soil moisture sensor. For example, the difference in θ values calculated by the calibration equation obtained by Methods 1 and 2 was 0.076 m3 m−3, a maximum for the Andisol sample. We observed a significant linear relation between the maximum differences in θ (which might result from the different sensor installation methods) and the coarse pore volume determined from soil water characteristic curves. Compaction around the sensor induced by sensor installation, which might be considerable for soil with many coarse pores, was considered the main reason for an increase in the soil moisture sensor's output value. For the sensor installed by Methods 2 or 3, a second‐order polynomial equation could be used to translate sensor output to θ accurately except for soils with > 40% clay content or very low bulk density.Highlights
An appropriate calibration equation is important to monitor soil water content precisely.
Effects of different sensor installation methods on calibration equations have not been determined.
Method of installation considerably affected output values of a capacitance sensor.
Soil compaction by sensor installation increases the sensor output: more so in coarse pore soil.
Habitat‐specific capture timing of deer mice (Peromyscus maniculatus) suggests that predators structure temporal activity of prey
Authors: Connolly Brian M. , Orrock John L. 
Published: November 2017

AbstractTiming is an essential component of the choices that animals make: The likelihood of successful resource capture (and predator avoidance) depends not just on what an animal chooses to do, but when it chooses to do it. Despite the importance of activity timing, our ability to understand the forces that constrain activity timing has been limited because this aspect of animal behavior is shaped by several factors (e.g., interspecific competitors, predators, physical conditions), and it is difficult to examine activity timing in a setting where only a single factor is operating. Using an island system that makes it possible to focus on the effect of predation risk in the absence of interspecific competition, we examine how the onset of activity of the deer mouse (Peromyscus maniculatus) varies between habitats with unique predation risks (i.e., minimal‐shrub cover versus abundant‐shrub cover sites). Using capture time to assess the timing of mouse activity, we found that mice in habitats with minimal shrub cover were captured 1.7 hr earlier than mice in habitats with abundant shrub cover. This difference in timing between habitats was likely a direct response to differences in predation risk between the two habitats: There were no differences in thermal conditions between the two habitats, and the difference in activity timing disappeared during a night when overcast skies reduced island‐wide predation risk. Our results demonstrate that predation risk, independent of interspecific competition, can generate significant changes in animal activity timing. Our work suggests that habitat structure that provides safety (i.e., refuge habitats) plays a direct role in the timing of prey activity and that habitat modification that alters refuge availability (e.g., shrub dominance) may alter the timing of animal activity.
Toward a socially acceptable gentrification: A review of strategies and practices against displacement
Authors: Ghaffari Leila , Klein Juan‐Luis , Angulo Baudin Wilfredo 
Published: November 2017

AbstractThis article offers a systematic review of available studies on gentrification and displacement with the primary goal of identifying the few (relative to the number of publications) solutions or strategies being suggested for mitigating displacement. We categorize these strategies into 3 types: tenants' protection, controlling ownership and development, and community empowerment. Each strategy is accompanied by various tools which may differ from one context to another. Finally, proposing that displacement can be controlled, the article concludes that counteracting the negative effects of gentrification requires more than just reducing displacement. In other words, we believe that there are several issues beyond physical displacement to be considered in order to make gentrification socially acceptable.
Quantifying Isotopic Heterogeneity of Candidate Reference Materials at the Picogram Sampling Scale
Authors: Ramsey Michael H. , Wiedenbeck Michael 
Published: November 2017

We propose a method for quantifying the in situ heterogeneity of solid materials at the picogram test portion scale, illustrating its use by investigating the oxygen isotope ratio (18O−/16O−) of four quartz samples. Using secondary ion mass spectrometry, we could estimate the intrinsic heterogeneity using a large number (~ 100) of closely spaced duplicated measurements. An analysis of variance was then applied to these large data sets to extract the measurement repeatability (typically 0.10–0.15‰, 1s) from the total variability, thereby revealing a variability ranging from 0.18‰ to 2.3‰, which can be attributed to the genuine isotope ratio heterogeneities. A small proportion of outlying values were either rejected manually after inspection, or were accommodated using robust statistics. We also evaluated two distinct approaches for estimating and correcting instrumental drift; the use of a sub‐area of the test material (if shown to have sufficiently low heterogeneity) is judged to be preferable to using a piece of unrelated silicate glass that we believe to be homogeneous. We also compared three approaches for estimating measurement repeatability, from which we show that the ‘duplicate method’ applied to the reference material is preferable to using other methods based either on the drift monitoring material or on assessing residuals of the drift monitoring material after drift correction. Finally, here we propose a strategy for predicting the number of measurements on individual fragments of a material that would be required to achieve a specified target uncertainty.
Capturing and missing the patient's story through outcome measures: A thematic comparison of patient‐generated items in PSYCHLOPS with CORE‐OM and PHQ‐9
Authors: Sales Célia MD , Neves Inês TD , Alves Paula G. , Ashworth Mark 
Published: November 2017

AbstractBackgroundThere is increasing interest in individualized patient‐reported outcome measures (I‐PROMS), where patients themselves indicate the specific problems they want to address in therapy and these problems are used as items within the outcome measurement tool.ObjectiveThis paper examined the extent to which 279 items reported in an I‐PROM (PSYCHLOPS) added qualitative information which was not captured by two well‐established outcome measures (CORE‐OM and PHQ‐9).DesignComparison of items was only conducted for patients scoring above the “caseness” threshold on the standardized measures.Setting and patients107 patients were participating in therapy within addiction and general psychiatric clinical settings.Main resultsAlmost every patient (95%) reported at least one item whose content was not covered by PHQ‐9, and 71% reported at least one item not covered by CORE‐OM.DiscussionResults demonstrate the relevance of individualized outcome assessment for capturing data describing the issues of greatest concern to patients, as nomothetic measures do not always seem to capture the whole story.
Immune correlates of clinical outcome in melanoma
Authors: Pawelec Graham 
Published: November 2017

SummaryMelanoma has long been recognized as a potentially immunogenic tumour, but only recently has it become clear that the reason for this resides in its many ultraviolet (UV)‐induced mutations and expression of multiple autoantigens which can be targeted by the immune system. The first successful applications of immune‐based treatments included passive immunotherapy using high‐dose interleukin (IL)‐2 and/or adoptive transfer of natural killer (NK)‐cells, as well as active immunotherapy using whole cell‐derived or peptide vaccines. In the intervening decades, it has become clear that these approaches can lead to durable responses in stage III/IV melanoma, and even to functional cures – but only in a vanishingly small fraction of patients. With the advent of immune checkpoint blockade first with anti‐cytotoxic T‐lymphocyte 4 (CTLA‐4), then with anti‐programmed cell death 1 (PD‐1) antibodies, and combinations thereof, the small percentage of responding patients may be increased to half, a major accomplishment in this refractory disease. Improved techniques for identifying mutation‐derived neoantigens and thus more sophisticated active immunotherapies, probably combined with checkpoint blockade, currently hold great promise for further increasing the fraction of responding patients. As additional immunomodulatory antibodies and therapies become available, it will be increasingly important to develop diagnostic tools to determine which particular therapy is likely to elicit the best response for the individual patient. Practically speaking, therapy selection and efficacy monitoring on the basis of the results of a blood test would be most desirable. The purpose of this review is to consider the feasibility of identifying ‘immune signatures’ for predicting responses and determining mechanisms responsible for success or failure of these immunotherapies.