bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic expression assay testing among American Indian and Alaska Native women with breast cancer
Authors: Marmor Schelomo , Longacre Colleen F. , Altman Ariella M. , Hui Jane Y. C. , Jensen Eric H. , Tuttle Todd M. 
Published: September 2020

BackgroundBreast cancer is one of the most common causes of cancer mortality for all women, including American Indian and Alaska Native (AI/AN) women. The use of the 21‐gene recurrence score (RS) appears to be predictive of the benefit of chemotherapy for women with estrogen receptor (ER)–positive breast cancer. The objective of the current study was to compare RS testing between AI/AN and non‐Hispanic White (NHW) women with breast cancer.MethodsThe Surveillance, Epidemiology, and End Results program was used to identify women with ER‐positive breast cancer from 2004 through 2015. Multivariable logistic regression was used to evaluate factors associated with RS use, with high‐risk RS, and with chemotherapy use among those with a high‐risk RS.ResultsA total of 363,387 NHW patients and 1951 AI/AN patients with ER‐positive breast cancer were identified. AI/AN women were found to be less likely to undergo RS testing and, when tested, were more likely to have a high‐risk RS. In the multivariable logistic regression analysis, AI/AN women were found to be significantly more likely to have a high‐risk RS (odds ratio,1.28; 95% confidence interval, 1.01‐1.66). Among untested women, chemotherapy use was higher for AI/AN women; however, the use of chemotherapy was not found to be significantly different between the groups with a high‐risk RS. Using Cox proportional hazards models, AI/AN race was found to be significantly associated with worse overall survival.ConclusionsAI/AN women were less likely to undergo RS testing compared with NHW women and were more likely to have a high‐risk RS. Reversing the disparity in genomic expression assay testing is critical to ensure guideline‐based breast cancer treatment and improve survival rates for AI/AN women with breast cancer.
The diencephalon of two carnivore species: The feliform banded mongoose and the caniform domestic ferret
Authors: Pillay Sashrika , Bhagwandin Adhil , Bertelsen Mads F. , Patzke Nina , Engler Gerhard , Engel Andreas K. , Manger Paul R. 
Published: September 2020

AbstractThis study provides an analysis of the cytoarchitecture, myeloarchitecture, and chemoarchitecture of the diencephalon (dorsal thalamus, ventral thalamus, and epithalamus) of the banded mongoose (Mungos mungo) and domestic ferret (Mustela putorius furo). Using architectural and immunohistochemical stains, we observe that the nuclear organization of the diencephalon is very similar in the two species, and similar to that reported in other carnivores, such as the domestic cat and dog. The same complement of putatively homologous nuclei were identified in both species, with only one variance, that being the presence of the perireticular nucleus in the domestic ferret, that was not observed in the banded mongoose. The chemoarchitecture was also mostly consistent between species, although there were a number of minor variations across a range of nuclei in the density of structures expressing the calcium‐binding proteins parvalbumin, calbindin, and calretinin. Thus, despite almost 53 million years since these two species of carnivores shared a common ancestor, strong phylogenetic constraints appear to limit the potential for adaptive evolutionary plasticity within the carnivore order. Apart from the presence of the perireticular nucleus, the most notable difference between the species studied was the physical inversion of the dorsal lateral geniculate nucleus, as well as the lateral posterior and pulvinar nuclei in the domestic ferret compared to the banded mongoose and other carnivores, although this inversion appears to be a feature of the Mustelidae family. While no functional sequelae are suggested, this inversion is likely to result from the altricial birth of Mustelidae species.
Enhancement of total lipid production in vegetative tissues of alfalfa and sainfoin using chemical mutagenesis
Authors: Wijekoon Champa P , Singer Stacy D. , Weselake Randall J , Petrie James R. , Singh Surinder , Jayawardhane Kethmi N. , Shah Saleh , Chen Guanqun , Eastmond Peter J. , Acharya Surya N 
Published: September 2020

AbstractAlfalfa (Medicago sativa L.) and sainfoin (Onobrychis viciifoila Scop.) are two key forage legumes for the western Canadian cattle industry. Despite the high protein content, drawbacks to their use exist, including inefficient protein digestibility and energy use efficiency in the ruminant system, leading to economic losses and negative environmental impacts. Increasing the proportion of lipids in the diet of cattle is known to mitigate greenhouse gas emissions; however, the above two forage legumes possess only trace quantities of lipids in the shoot tissues used by the ruminants. In the current study, chemical mutagenesis was used as a conventional breeding approach to enhance lipid levels in the vegetative tissues of alfalfa and sainfoin. The mutagenesis procedures for these two forages need to be firmly established. We developed protocols for ethyl methanesulfonate (EMS)‐mediated mutagenesis by optimizing mutagen concentration and seed soaking duration. The EMS‐treated populations were assessed for morphological variants and total shoot lipid content (TSLC). Fatty acid composition was examined in a subset of plants with increased TSLC. Within 24 mo, the screening process identified mutagenized plants with significant increases in TSLC (3–5% on a dry weight basis), and a subset of these also displayed alterations in fatty acid composition in both species. These genotypes provide a novel source of germplasm for the future improvement of these two forage species.
Hyperprogression: A novel response pattern under immunotherapy
Authors: Han Xue‐jiao , Alu Aqu , Xiao Yi‐nan , Wei Yu‐quan , Wei Xia‐wei 
Published: September 2020

AbstractCheckpoint blockade therapy has shown significant therapeutic benefits and resulted in durable responses in patients with various tumors. However, accumulating evidence has demonstrated that 4‐29% of all patients with cancers with various histologies may suffer from tumor flare following such therapy. This novel tumor response pattern, termed hyperprogression, is a potentially deleterious side effect of checkpoint blockade therapy that accelerates disease progression in a subset of patients. In this review, we describe possible immune checkpoint blockade biomarkers and the epidemiology, different definitions, and predictors of hyperprogression based on the research findings and further present the available evidence supporting pathophysiological hypotheses that might explain hyperprogression during checkpoint blockade therapy. We also compare hyperprogression and pseudoprogression. Finally, we discuss areas requiring further study.
Evaluation of B‐cell intracellular signaling by monitoring the PI3K‐Akt axis in patients with common variable immunodeficiency and activated phosphoinositide 3‐kinase delta syndrome
Authors: del Pino‐Molina Lucía , Torres Canizales Juan M. , Rodríguez‐Pena Rebeca , López‐Granados Eduardo 
Published: September 2020

AbstractBackgroundPrimary antibody deficiencies (PADs) are characterized by hypogammaglobulinemia and impaired B‐cell differentiation. Patients with common variable immunodeficiency (CVID) present severe reductions in at least 2 serum immunoglobulins and impaired terminal differentiation of B cells. Most patients with CVID do not appear to present monogenic defects. Activated phosphoinositide 3‐kinase delta syndrome (APDS), caused by gain‐of‐function mutations in the PIK3CD gene (p110δ), can present in patients with a CVID‐like phenotype. Memory B‐cell differentiation requires the orchestrated activation of numerous intracellular signaling pathways, which promote transcriptional programs required for long‐term B‐cell survival. The aim of this study was to develop a flow cytometry assay to trace the PI3K‐Akt‐mTOR pathway, a critical component of B‐cell homeostasis, and analyze its status in PADs.MethodsWe analyzed the intracellular expression of Akt and S6 by flow cytometry and their phosphorylation status in both baseline conditions and upon B‐cell receptor activation with anti‐IgM in various primary B‐cell subsets of patients with CVID and APDS.ResultsB cells from CVID patients showed reduced phosphorylation in Akt and S6 proteins after anti‐IgM stimulation. Constitutive high baseline B‐cell levels of Akt and S6 phosphorylation in a patient with APDS were reduced once m‐TOR inhibition therapy was initiated.ConclusionsIntracellular flow cytometry can be routinely employed to explore alterations in the PI3K‐Akt‐mTOR pathway in B cells from patients with PADs. AKT and S6 phosphorylation levels are informative biomarkers that could be employed as mTOR inhibitors for monitoring therapies targeting this pathway.
Temperature, topography, soil characteristics, and NDVI drive habitat preferences of a shade‐tolerant invasive grass
Authors: Bowen Anna K. M. , Stevens Martin H. H. 
Published: September 2020

AbstractAimDespite the large literature documenting the negative effects of invasive grasses, we lack an understanding of the drivers of their habitat suitability, especially for shade‐tolerant species that do not respond positively to canopy disturbance. We aimed to understand the environmental niche and potential spatial distribution of a relatively new invasive species, wavyleaf basketgrass (Oplismenus undulatifolius(Ard.) Roem. & Schult, WLBG) by leveraging data available at two different spatial scales.LocationMid‐Atlantic region of the United States.MethodsMaximum entropy modeling (Maxent) was used to predict the habitat suitability of WLBG at the regional scale and the landscape scale. Following variable evaluation, model calibration, and model evaluation, final models were created using 1,000 replicates and projected to each study area.ResultsAt the regional scale, our best models show that suitability for WLBG was driven by relatively high annual mean temperatures, low temperature seasonality and monthly range, low slope, and high cumulative Normalized Difference Vegetation Index (NDVI). At the landscape scale, suitability was highest near roads and streams, far from trails, at low elevations, in sandy, moist soil, and in areas with high NDVI.Main ConclusionsWe found that invasion potential of this relatively new invader appears high in productive, mesic habitats at low slope and elevations. At the regional scale, our model predicted areas of suitable habitat far outside areas where WLBG has been reported, including large portions of Virginia and West Virginia, suggests serious potential for spread. However, large portions of this area carry a high extrapolation risk and should therefore be interpreted with caution. In contrast, at the landscape level, the suitability of WLBG is largely restricted to areas near current presence points, suggesting that the expansion risk of this species within Shenandoah National Park is somewhat limited.
The impact of parental contact upon cortical noxious‐related activity in human neonates
Authors: Jones Laura , Laudiano‐Dray Maria Pureza , Whitehead Kimberley , Meek Judith , Fitzgerald Maria , Fabrizi Lorenzo , Pillai Riddell Rebecca 
Published: September 2020

AbstractBackgroundNeonates display strong behavioural, physiological and cortical responses to tissue‐damaging procedures. Parental contact can successfully regulate general behavioural and physiological reactivity of the infant, but it is not known whether it can influence noxious‐related activity in the brain. Brain activity is highly dependent upon maternal presence in animal models, and therefore this could be an important contextual factor in human infant pain‐related brain activity.MethodsGlobal topographic analysis was used to identify the presence and inter‐group differences in noxious‐related activity in three separate parental contexts. EEG was recorded during a clinically required heel lance in three age and sex‐matched groups of neonates (a) while held by a parent in skin‐to‐skin (n = 9), (b) while held by a parent with clothing (n = 9) or (c) not held at all, but in individualized care (n = 9).ResultsThe lance elicited a sequence of 4–5 event‐related potentials (ERPs), including the noxious ERP (nERP), which was smallest for infants held skin‐to‐skin and largest for infants held with clothing (p=0.016). The nERP was then followed by additional and divergent long‐latency ERPs (> 750 ms post‐lance), not previously described, in each of the groups, suggesting the engagement of different higher level cortical processes depending on parental contact.ConclusionsThese results show the importance of considering contextual factors in determining infant brain activity and reveal the powerful influence of parental contact upon noxious‐related activity across the developing human brain.SignificanceThis observational study found that the way in which the neonatal brain processes a noxious stimulus is altered by the type of contact the infant has with their mother. Specifically, being held in skin‐to‐skin reduces the magnitude of noxious‐related cortical activity. This work has also shown that different neural mechanisms are engaged depending on the mother/infant context, suggesting maternal contact can change how a baby's brain processes a noxious stimulus.
Overactivity assessment in chronic pain: The development and psychometric evaluation of a multifaceted self‐report assessment
Authors: Andrews Nicole E. , Chien Chi‐Wen , Ireland David , Varnfield Marlien 
Published: September 2020

AbstractBackgroundOveractivity in the context of chronic pain (i.e. activity engagement that significantly exacerbates pain) is an important clinical issue that has gained empirical attention in the last decade. Current assessment concepts of overactivity tend to focus on frequency to quantify the severity of the pain behaviour. This study aimed to develop and validate a more comprehensive self‐assessment, the Overactivity in Persistent Pain Assessment (OPPA).MethodsA sample of 333 individuals with chronic pain completed the OPPA. A subset of 202 individuals also completed a set of existing measures of pain‐related outcomes and activity patterns. The remaining 131 participants were provided with a second copy of the OPPA to fill in one week following their initial assessment.ResultsA principal component analysis confirmed that the OPPA items were best represented by a single construct. The OPPA was found to correlate with pain‐related measures in an expected way that is supported by both theory and qualitative data. When compared to existing overactivity measures, the OPPA was the only measure to contribute significantly to the regression models predicting higher levels of pain severity, more pain interference and lower levels of activity participation after controlling for age, gender and activity avoidance. In addition, the OPPA scale exhibited acceptable internal consistency and good test–retest reliability.ConclusionThe results of this study reinforce the potentially important role of overactivity in the maintenance of pain‐related suffering and supports a corresponding assessment tool with preliminary psychometric evidence for clinical and research applications.SignificanceThis study deconstructs the overactivity concept and develop a corresponding assessment based on five quantifiable severity features: severity of pain exacerbation, maladaptive coping strategies used, impact on occupational performance, recovery time and frequency. Results of the psychometric evaluation indicate that this comprehensive assessment of overactivity severity features may be necessary to understand the impact of overactivity on pain severity and physical functioning from both a clinical and research perspective.
Drive for thinness provides an alternative, more meaningful, severity indicator than the DSM‐5 severity indices for eating disorders
Authors: Krug Isabel , Binh Dang An , Granero Roser , Agüera Zaida , Sánchez Isabel , Riesco Nadine , Jimenez‐Murcia Susana , Menchón Jose M. , Fernandez‐Aranda Fernando 
Published: September 2020

AbstractObjectiveTo assess an alternative trans‐diagnostic indicator for severity based on drive for thinness (DT) for anorexia nervosa (AN), bulimia nervosa (BN), binge‐eating disorder (BED), and other specified feeding or eating disorder (OSFED), and to compare this new approach to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) severity categories for EDs.MethodA total of 2,811 ED [428 AN‐restrictive (AN‐R), 313 AN‐binge purging (AN‐BP), 1,340 BN, 329 BED, 154 OSFED/atypical AN (AT), and 223 OSFED/purging disorder (PD)] patients were classified using: (a) The DSM‐5 severity categories and (b) a DT categorisation. These severity classifications were then compared based on ED symptoms, general psychopathology, personality, and impulsive behaviours.ResultsFor the DSM‐5 categories, most ED patients fell into the ‘mild’ to ‘moderate’ categories. Using the DT categories, AN patients were mainly represented in the ‘low’ DT category, and BN, OSFED/AT, and PD in the ‘high’ DT category. The clinically significant findings were stronger for the DT than the DSM‐5 severity approach (medium‐to‐large effect sizes). AN‐BP and AN‐R provided the most pronounced effects.ConclusionOur findings question the clinical value of the DSM‐5 severity categorisation, and provide initial support for an alternative DT severity approach for AN.Highlights
This study assessed an alternative trans‐diagnostic drive for thinness (DT) severity.
Category for all eating disorder (ED) sub‐types, and then compared this to the Diagnostic and Statistical Manual of Mental Disorders‐5 (DSM‐5) severity indices for EDs.
ED symptoms, general psychopathology, personality, and impulsive behaviours were assessed using both classifications in a total of 2,811 female patients diagnosed with EDs.
Clinically significant findings were stronger for the DT than the DSM‐5 severity category (medium‐to‐large effect sizes); there was differentiation of the anorexia nervosa (AN) patients into mainly ‘low’ DT, and bulimia nervosa (BN) spectrum patients into mainly ‘high’ DT, vs. most patients were clustered in the ‘mild‐to‐moderate’ DSM‐5 categories.
Our findings provide initial support for an alternative trans‐diagnostic DT severity category that may be more clinically meaningful than the DSM‐5 severity indices for EDs.
Prediagnostic circulating levels of sex hormones and survival in esophageal adenocarcinoma
Authors: Xie Shao‐Hua , Ness‐Jensen Eivind , Langseth Hilde , Gislefoss Randi E. , Mattsson Fredrik , Lagergren Jesper 
Published: September 2020

AbstractSex hormonal differences may contribute to the strong male predominance in esophageal adenocarcinoma (EAC), but whether sex hormone levels influence survival in EAC is unstudied. Our study aimed to assess associations between prediagnostic sex hormone levels and survival in EAC. In a population‐based cohort study, 244 male EAC patients from the Janus Serum Bank Cohort in Norway were followed up through 2018. Associations between prediagnostic serum levels of 12 sex hormone measures and disease‐specific mortality were assessed using multivariable Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, body mass index, tobacco smoking, physical activity and surgical resection. Higher levels of sex hormone‐binding globulin (SHBG) indicated decreased disease‐specific mortality (HR 0.68, 95% CI 0.44‐1.07, highest vs lowest tertile). In stratified analyses by surgery, such associations remained in nonoperated patients (HR 0.58, 95% CI 0.35‐0.96, highest vs lowest tertile), but not in operated patients. Higher levels of follicle‐stimulating hormone (FSH) were associated with increased disease‐specific mortality in an exposure‐response pattern; HRs for the middle and highest tertiles vs the lowest tertile were 1.35 (95% CI 0.89‐2.05) and 1.61 (95% CI 1.06‐2.43), respectively. No clear associations were observed with serum levels of dehydroepiandrosterone sulfate, luteinizing hormone, prolactin, testosterone, 17‐OH‐progesterone, progesterone, estradiol, androstenedione, testosterone:estradiol ratio or free testosterone index. These findings suggest that higher endogenous levels of SHBG and lower levels of FSH may increase the survival in EAC. The other 10 examined sex hormone measures may not influence the survival.
Impact of DNA damage repair defects and aggressive variant features on response to carboplatin‐based chemotherapy in metastatic castration‐resistant prostate cancer
Authors: Slootbeek Peter H. J. , Duizer Marleen L. , van der Doelen Maarten J. , Kloots Iris S. H. , Kuppen Malou C. P. , Westgeest Hans M. , Uyl‐de Groot Carin A. , Pamidimarri Naga Samhita , Ligtenberg Marjolijn J. L. , van Oort Inge M. , Gerritsen Winald R. , Schalken Jack A. , Kroeze Leonie I. , Bloemendal Haiko J. , Mehra Niven 
Published: September 2020

AbstractPlatinum‐based chemotherapy is not standard of care for unselected or genetically selected metastatic castration‐resistant prostate cancer (mCRPC) patients. A retrospective assessment of 71 patients was performed on platinum use in the Netherlands. Genetically unselected patients yielded low response rates. For a predefined subanalysis of all patients with comprehensive next‐generation sequencing, 30 patients were grouped based on the presence of pathogenic aberrations in genes associated with DNA damage repair (DDR) or aggressive variant prostate cancer (AVPC). Fourteen patients (47%) were DDR deficient (DDRd), of which seven with inactivated BRCA2 (BRCA2mut). Six patients classified as AVPC. DDRd patients showed beneficial biochemical response to carboplatin, largely driven by all BRCA2mut patients having >50% prostate‐specific antigen (PSA) decline and objective radiographic response. In the wild‐type BRCA2 subgroup, 35% had a >50% PSA decline (P = .006) and 16% radiographic response (P < .001). Median overall survival was 21 months for BRCA2mut patients vs 7 months (P = .041) for those with functional BRCA2. AVPC patients demonstrated comparable responses to non‐AVPC, including a similar overall survival, despite the poor prognosis for this subgroup. In the scope of the registration of poly‐(ADP)‐ribose polymerase inhibitors (PARPi) for mCRPC, we provide initial insights on cross‐resistance between PARPi and platinum compounds. By combining the literature and our study, we identified 18 patients who received both agents. In this cohort, only BRCA2mut patients treated with platinum first (n = 4), responded to both agents. We confirm that BRCA2 inactivation is associated with meaningful responses to carboplatin, suggesting a role for both PARPi and platinum‐based chemotherapy in preselected mCRPC patients.