bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors for red blood cell alloimmunization in the Recipient Epidemiology and Donor Evaluation Study (REDS‐III) database
Authors: Karafin Matthew S. , Westlake Matt , Hauser Ronald G. , Tormey Christopher A. , Norris Philip J. , Roubinian Nareg H. , Wu Yanyun , Triulzi Darrell J. , Kleinman Steve , Hendrickson Jeanne E. ,   NHLBI Recipient Epidemiology and Donor Evaluation Study‐III (REDS‐III)
Published: April 2018

SummaryDespite the significance of red blood cell (RBC) alloimmunization, the lack of standardized registries in the US has prevented the completion of large studies. Data from 3·5 years of the Recipient Epidemiology and Donor Evaluation Study‐III (REDS‐III) recipient database, containing information from 12 hospitals, were studied. A RBC alloantibody responder had an antibody identified at any point during the study, and a non‐responder had a negative antibody screen at least 15 days post‐RBC transfusion. Demographics, blood type, ICD9/10 codes, and other potential correlates were evaluated. Of 319 177 (2·07%) screened patients, 6597 had a total of 8892 clinically significant RBC alloantibodies identified, with 75% being in the Rh or Kell families. Alloimmunization was more common in females (2·38%) than males (1·68%), and in RhD negative (2·82%) than RhD positive (1·94%) patients. Age, sex, RhD status and race were associated with being a responder, and certain diagnoses (including sickle cell disease or trait, systemic lupus erythematosus, rheumatoid arthritis and myelodysplastic syndrome) were more common among responders than non‐responders. Data collected in this multi‐centre recipient database provide the largest RBC alloimmunized patient cohort studied in the US, with previously known demographic and disease associations of responder status confirmed, and new associations identified.
Resistance to proteasome inhibitors and other targeted therapies in myeloma
Authors: Wallington‐Beddoe Craig T. , Sobieraj‐Teague Magdalena , Kuss Bryone J. , Pitson Stuart M. 
Published: April 2018

SummaryThe number of novel therapies for the treatment of myeloma is rapidly increasing, as are the clinical trials evaluating them in combination with other novel and established therapies. Proteasome inhibitors, immunomodulatory agents and monoclonal antibodies are the most well known and studied classes of novel agents targeting myeloma, with histone deacetylase inhibitors, nuclear export inhibitors and several other approaches also being actively investigated. However, in parallel with the development and clinical use of these novel myeloma therapies is the emergence of novel mechanisms of resistance, many of which remain elusive, particularly for more recently developed agents. Whilst resistance mechanisms have been best studied for proteasome inhibitors, particularly bortezomib, class effects do not universally apply to all class members, and within‐class differences in efficacy, toxicity and resistance mechanisms have been observed. Although immunomodulatory agents share the common cellular target cereblon and thus resistance patterns relate to cereblon expression, the unique cell surface antigens to which monoclonal antibodies are directed means these agents frequently exhibit unique within‐class differences in clinical efficacy and resistance patterns. This review describes the major classes of novel therapies for myeloma, highlights the major clinical trials within each class and discusses known resistance mechanisms.
Ethnic disparity in primary cutaneous CD30+ T‐cell lymphoproliferative disorders: an analysis of 1496 cases from the US National Cancer Database
Authors: Su Chang , Nguyen Kevin A. , Bai Harrison X. , Zogg Cheryl K. , Cao Ya , Karakousis Giorgos , Zhang Paul J. , Zhang Guiying , Xiao Rong 
Published: April 2018

SummaryPrimary cutaneous CD30+ T cell lymphoproliferative disorders (PCLPD), the second most common type of primary cutaneous T cell lymphomas, accounts for approximately 25–30% of cutaneous T‐cell lymphoma cases. However, only small retrospective studies have been reported. We aimed to identify prognostic factors and evaluate the overall survival (OS) of patients with PCLPD stratified by ethnicity. We identified 1496 patients diagnosed with PCLPD between 2004 and 2014 in the US National Cancer Database. Chi‐square test and anova were used to evaluate differences in demographic and disease characteristics, socioeconomic factors and treatments received. OS was evaluated with the log‐rank test, Cox proportional hazard regression analysis, and propensity score matching. The study included 1267 Caucasians, 153 African Americans (AA), 43 Asians, and 33 of other/unknown ethnicity. Older age, higher Charlson‐Deyo score, higher clinical stage and receipt of chemotherapy were predictors of shorter OS. Primary disease site on a lower extremity was associated with shorter OS, while a head and neck location was associated with longer OS. AA patients had shorter OS when compared to Caucasian patients on multivariate analysis. This ethnic disparity persisted on propensity‐score matched analysis and after matching Caucasian and AA patients on demographic and disease characteristics, socioeconomic factors and treatments received, and age and gender‐matched relative survival analyses.
Systematic patient involvement for homebased outpatient administration of complex chemotherapy in acute leukemia and lymphoma
Authors: Fridthjof Katrine S. , Kampmann Peter , Dünweber Anne , Gørløv Jette S. , Nexø Connie , Friis Lone S. , Nørskov Kristina H. , Welinder Pernille C. , Moser Claus , Kjeldsen Lars , Møller Tom 
Published: April 2018

SummaryBased on experience with comprehensive patient involvement, we present data from implementation of portable, programmable infusion pumps (PPP) for home‐based chemotherapy administration in patients with acute leukaemia and in lymphoma patients receiving (carmustine, etoposide, cytarabine, melphalan) BEAM regimen. Data from 84 patients, receiving 177 cycles of PPP administered chemotherapy, showed convincing safety with minor equipment errors encountered and with high patient satisfaction. In‐hospital days could be reduced with 52% out of a total of 1197 treatment days. Homebased PPP has several advantages from a patient perspective and furthermore frees up in‐hospital beds for patients in need of them.
Rapid identification of BCR/ABL1‐like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time‐polymerase chain reaction: clinical, prognostic and therapeutic implications
Authors: Chiaretti Sabina , Messina Monica , Grammatico Sara , Piciocchi Alfonso , Fedullo Anna L. , Di Giacomo Filomena , Peragine Nadia , Gianfelici Valentina , Lauretti Alessia , Bareja Rohan , Martelli Maria P. , Vignetti Marco , Apicella Valerio , Vitale Antonella , Li Loretta S. , Salek Cyril , Elemento Olivier , Inghirami Giorgio , Weinstock David M. , Guarini Anna , Foà Robin 
Published: April 2018

SummaryBCR/ABL1‐like acute lymphoblastic leukaemia (ALL) is a subgroup of B‐lineage acute lymphoblastic leukaemia that occurs within cases without recurrent molecular rearrangements. Gene expression profiling (GEP) can identify these cases but it is expensive and not widely available. Using GEP, we identified 10 genes specifically overexpressed by BCR/ABL1‐like ALL cases and used their expression values – assessed by quantitative real time‐polymerase chain reaction (Q‐RT‐PCR) in 26 BCR/ABL1‐like and 26 non‐BCR/ABL1‐like cases to build a statistical “BCR/ABL1‐like predictor”, for the identification of BCR/ABL1‐like cases. By screening 142 B‐lineage ALL patients with the “BCR/ABL1‐like predictor”, we identified 28/142 BCR/ABL1‐like patients (19·7%). Overall, BCR/ABL1‐like cases were enriched in JAK/STAT mutations (P < 0·001), IKZF1 deletions (P < 0·001) and rearrangements involving cytokine receptors and tyrosine kinases (P = 0·001), thus corroborating the validity of the prediction. Clinically, the BCR/ABL1‐like cases identified by the BCR/ABL1‐like predictor achieved a lower rate of complete remission (P = 0·014) and a worse event‐free survival (P = 0·0009) compared to non‐BCR/ABL1‐like ALL. Consistently, primary cells from BCR/ABL1‐like cases responded in vitro to ponatinib. We propose a simple tool based on Q‐RT‐PCR and a statistical model that is capable of easily, quickly and reliably identifying BCR/ABL1‐like ALL cases at diagnosis.
The Complexity of Loss During a Forced Termination: A Case Illustration
Authors: Aafjes‐Van Doorn Katie , Wooldridge Tom 
Published: April 2018

The end of a therapeutic relationship is experienced in a unique way by each patient and triggers complex feelings relating to early attachment issues, losses and traumas. It is an immense rupture: a process of attachment and separation, intimacy and loss that is an emotionally intense experience for both participants. This case illustration provides insight into the difficulties experienced during the process of forced termination in an analytic community‐training clinic. Following a 2‐year treatment, Peter, a patient who had been severely traumatized in youth, had to tolerate the pain of another loss; having to say goodbye to a therapist. We describe the therapist's initiation and engagement of the termination phase. A series of measurements of patient personality, therapist attachment, and change in alliance and outcomes provide information on the impact of Peter's history and the therapeutic relationship. Clinical illustrations highlight different parts of the decision‐making process in terms of the patient's sensitivity to loss, as well as the therapist's uncertainty around self‐disclosure. We suggest ways therapists may facilitate endings by addressing positive and negative feelings, providing a good‐enough attachment experience, and stimulating an internalization of the therapeutic relationship. Implications for clinical practice, research and supervision are discussed.
The natural history of asymptomatic calyceal stones
Authors: Darrad Maitrey P. , Yallappa Sachin , Metcalfe John , Subramonian Kesavapillai 
Published: April 2018

ObjectivesTo evaluate the outcomes of patients with incidentally detected asymptomatic calyceal stones on active surveillance, and to identify risk factors for stone‐related adverse events (AEs).Patients and MethodsIn this retrospective case series, we identified all renal units with non‐contrast computed tomography diagnosed asymptomatic calyceal stones in a single reference centre between August 2005 and August 2016. Primary endpoints were spontaneous stone passage and need for stone‐related surgical intervention. The secondary endpoints were stone‐related symptoms and AEs. Cox proportional hazards models were used.ResultsWe identified 301 renal units from 238 adult patients. The median average age of the study group was 56 years, with two‐thirds consisting of males. The mean average cumulative stone size was 10.8 mm. At the end of the study, 58.8% of renal units with stones remained on surveillance with a median follow‐up of 63 months. Overall, 26.6% of patients proceeded to surgical intervention with the majority secondary to pain with no stone relocation (30%) or stone relocation to the ureter with or without pain (25%). Over the 5‐year period, 14.6% of stones passed spontaneously. On analysis of the secondary endpoints, 39.5% had a stone‐related AE (either symptoms and/or need for surgical intervention). Younger patients (aged <50 years), and those with stone growth >1 mm annually were significantly more likely to have an AE (P = 0.012 and P = 0.006, respectively). The risk of an AE during surveillance at 1, 3, and 5 years was 3.4%, 18.9%, and 30.7% respectively.ConclusionsLong‐term conservative approaches for asymptomatic renal stones are an effective management option with ~60% of renal units remaining on active surveillance in >5 years of follow‐up. Appropriate counselling with careful patient selection is advocated, as younger patients and those with evidence of stone growth were found to be at greatest risk of an adverse outcome.
Host plant distributions and climate interact to affect the predicted geographic distribution of a Neotropical termite
Authors: da Cunha Hélida F. , Ferreira Érica D. , Tessarolo Geiziane , Nabout João C. 
Published: April 2018

AbstractSpecies distribution models (SDMs) have been widely used in the scientific literature. The majority of SDMs use climate data or other abiotic variables to forecast the potential distribution of a species in geographic space. Biotic interactions can affect the predicted spatial distribution of a species in many ways across multiple spatial scales, and incorporating these predictors in an SDM is a current topic in the scientific literature. Constrictotermes cyphergaster is a widely distributed termite in the Neotropics. This termite species nests in plants and more frequently nests in some arboreal species. Thus, this species is an excellent model to evaluate the influence of biotic interactions in SDMs. We evaluate the influences of climate and the geographic distribution of host plants on the potential distribution of C. cyphergaster. Three correlative models (MaxEnt) were built to predict the geographic distribution of the termite: (1) climate data, (2) biotic data (i.e., the geographic distribution of host plants), and (3) climate and biotic data. The models that were generated indicate that the potential geographic distribution of C. cyphergaster is concentrated in the Cerrado and Caatinga regions. In addition, path analysis and multiple regression revealed the importance of the direct effects of biological interactions in the geographic distribution of the termite, while climate affected the distribution of the termite mainly through indirect effects by influencing the geographic distributions of host plants. The current study endorses the importance of including biological interactions in SDMs. We recommend using biotic predictors in SDM studies of insect species, mainly because insects have important environmental services and biotic interaction data can improve the macroecological studies of this group.
New insights into the phenotypes of atopic dermatitis linked with allergies and asthma in children: An overview
Authors: Amat F. , Soria A. , Tallon P. , Bourgoin‐Heck M. , Lambert N. , Deschildre A. , Just J. 
Published: April 2018

SummaryAtopic dermatitis (AD) is a complex disease with multiple causes and complex mechanistic pathways according to age of onset, severity of the illness, ethnic modifiers, response to therapy and triggers. A group of difficult‐to‐manage patients characterized by early‐onset AD and severe lifelong disease associated with allergic asthma and/or food allergy (FA) has been identified. In this study, we focus on these severe phenotypes, analysing their links with other atopic comorbidities, and taking into account the results from recent cohort studies and meta‐analyses. The main hypothesis that is currently proposed to explain the onset of allergic diseases is an epithelial barrier defect. Thus, the atopic march could correspond to an epithelial dysfunction, self‐sustained by a secondary allergenic sensitization, explaining the transition from AD to allergic asthma. Furthermore, AD severity seems to be a risk factor for associated FA. Results from population‐based, birth and patient cohorts show that early‐onset and severe AD, male gender, parental history of asthma, and early and multiple sensitizations are risk factors leading to the atopic march and the development of asthma. The importance of environmental factors should be recognized in these high‐risk children and prevention programs adapted accordingly. Effective targeted therapies to restore both barrier function and to control inflammation are necessary; early emollient therapy is an important approach to prevent AD in high‐risk children. Clinicians should also keep in mind the specific risk of atopic comorbidities in case of filaggrin loss‐of‐function mutations and the rare phenotypes of orphan syndromes due to heritable mutations in skin barrier components.
Rapidly changing myeloma epidemiology in the general population: Increased incidence, older patients, and longer survival
Authors: Turesson Ingemar , Bjorkholm Magnus , Blimark Cecilie Hveding , Kristinsson Sigurdur , Velez Ramon , Landgren Ola 
Published: April 2018

AbstractThe incidence of multiple myeloma is characterized by a steep increase with advancing age. Dramatic improvements in survival have been reported in clinical trials; however, elderly patients are generally underrepresented in these. The aims of this study are to review patterns of incidence and survival in multiple myeloma in the general population. We searched PubMed for population‐based studies on trends in incidence and survival published between January 1, 2000 and June 30, 2017 and based on regional or national cancer registries and report the following results of the review. The age‐adjusted incidence of multiple myeloma has increased during the second half of the twentieth century in some countries but remained stable in areas with high case ascertainment and access to universal medical care. The crude incidence is increasing globally due to an aging population. Survival rates have improved, and 5‐year relative survival rates are now around 50% and over 60% in patients 65‐70 years or younger. Preliminary data suggest a 3‐fold increase in the prevalence of multiple myeloma. We conclude that the number of multiple myeloma patients is increasing in the general population due to (i) aging populations and (ii) more patients living longer due to modern drugs.
The biphasic effect of extracellular glucose concentration on carbachol‐induced fluid secretion from mouse submandibular glands
Authors: Terachi Momomi , Hirono Chikara , Kitagawa Michinori , Sugita Makoto 
Published: April 2018

Cholinergic agonists evoke elevations of the cytoplasmic free‐calcium concentration ([Ca2+]i) to stimulate fluid secretion in salivary glands. Salivary flow rates are significantly reduced in diabetic patients. However, it remains elusive how salivary secretion is impaired in diabetes. Here, we used an ex vivo submandibular gland perfusion technique to characterize the dependency of salivary flow rates on extracellular glucose concentration and activities of glucose transporters expressed in the glands. The cholinergic agonist carbachol (CCh) induced sustained fluid secretion, the rates of which were modulated by the extracellular glucose concentration in a biphasic manner. Both lowering the extracellular glucose concentration to less than 2.5 mM and elevating it to higher than 5 mM resulted in decreased CCh‐induced fluid secretion. The CCh‐induced salivary flow was suppressed by phlorizin, an inhibitor of the sodium–glucose cotransporter 1 (SGLT1) located basolaterally in submandibular acinar cells, which is altered at the protein expression level in diabetic animal models. Our data suggest that SGLT1‐mediated glucose uptake in acinar cells is required to maintain the fluid secretion by sustaining Cl− secretion in real‐time. High extracellular glucose levels may suppress the CCh‐induced secretion of salivary fluid by altering the activities of ion channels and transporters downstream of [Ca2+]i signals.
Population assignment and local adaptation along an isolation‐by‐distance gradient in Pacific cod (Gadus macrocephalus)
Authors: Drinan Daniel P. , Gruenthal Kristen M. , Canino Michael F. , Lowry Dayv , Fisher Mary C. , Hauser Lorenz 
Published: April 2018

AbstractThe discernment of populations as management units is a fundamental prerequisite for sustainable exploitation of species. A lack of clear stock boundaries complicates not only the identification of spatial management units, but also the assessment of mixed fisheries by population assignment and mixed stock analysis. Many marine species, such as Pacific cod, are characterized by isolation by distance, showing significant differentiation but no clear stock boundaries. Here, we used restriction‐site‐associated DNA (RAD) sequencing to investigate population structure and assess power to genetically assign Pacific cod to putative populations of origin. Samples were collected across the species range in the eastern Pacific Ocean, from the Salish Sea to the Aleutian Islands. A total of 6,425 putative biallelic single nucleotide polymorphisms were identified from 276 individuals. We found a strong isolation‐by‐distance signal along coastlines that mirrored previous microsatellite results and pronounced genetic differentiation between coastal samples and those from the inland waters of the Salish Sea, with no evidence for hybridization between these two populations. Individual assignment success based on two methods was high overall (≥84%) but decreased from south to north. Assignment to geographic location of origin also was successful, with average distance between capture and assignment location of 220 km. Outlier analyses identified more loci potentially under selection along the coast than between Salish Sea and coastal samples, suggesting more diverse adaptation to latitudinal environmental factors than inshore vs. offshore environments. Our results confirm previous observations of sharp genetic differentiation of the Salish Sea population and isolation by distance along the coast, but also highlight the feasibility of using modern genomic techniques to inform stock boundaries and fisheries management in a low FST marine species.
Growth rate variability of larval European eels (Anguilla anguilla) across the extensive eel spawning area in the southern Sargasso Sea
Authors: Ayala Daniel Jiro , Munk Peter 
Published: April 2018

AbstractThe European eel (Anguilla anguilla) spawns in the Sargasso Sea, and the leptocephalus larvae are distributed in the Subtropical Convergence Zone (STCZ), covering an area approximately 500 × 2,000 km in extent. The STCZ is hydrographically diverse and highly dynamic, which is likely to impact growth and survival opportunities of the larvae. Here we investigate the temporal and spatial growth rate variability of larvae collected along seven sampling transects across the STCZ during March–April 2014. Scanning electron microscopic analyses of otolith ring‐formations were used to estimate larval age‐at‐length, initial growth and growth trajectories. Analyzed larvae averaged 14 mm in length and 30 days of age. Age estimation indicated that the larvae were spawned during one continuous period, extending from mid‐February to late‐March, and that spawning had peaked during the new moon of 4 March. Growth estimates (average: 0.38 mm/day, ~6% weight increase/day) showed substantial variability among individuals. There were no apparent spatial trends in this variability, and no linkage to measures of temperature and salinity, while earlier‐spawned leptocephali showed slightly higher growth rates than later‐spawned larvae. The variability in growth rates at single sampling sites was as great as variability across the entire area of distribution. This indicates that individual growth opportunities are strongly impacted by variable conditions in the immediate environment while average conditions for larval growth and survival are basically the same throughout the immense area of larval distribution.