bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of heat stress on proliferation, synthesis of steroids, and gene expression of duck granulosa cells
Authors: Yang Chen , Huang Xue‐bing , Chen Shi‐jian , Li Xiu‐jin , Fu Xin‐liang , Xu Dan‐ning , Tian Yun‐bo , Liu Wen‐jun , Huang Yun‐mao 
Published: August 2021

AbstractGranulosa cells (GCs) play an important role in the development of follicles. In this study, we investigate the impact of heat stress at 41°C and 43°C on duck GCs' proliferation and steroids secretion. And, the transcriptomic responses to heat treatment were examined using RNA‐sequencing analysis. Digital gene expression profiling was used to screen and identify differentially expressed genes (fold change ≥ 2 and Q value < 0.05). Further, the differential expression genes (DEGs) were classified into GO categories and KEGG pathways. The results show that duck GCs blocked in the G1 phase were increased on exposure to heat stress. Meanwhile, the expression of proliferative genes, which were essential for the transition from G1 to S phase, was inhibited. At the same time, heat stress inhibited the estradiol synthesis of GCs by decreasing CYP11A1 and CYP19A1 gene expression. A total of 241 DEGs including 181 upregulated and 60 downregulated ones were identified. Transcriptome result shows that heat shock protein and CXC chemokines gene were significantly activated during heat stress. While collagenases (MMP1 and MMP13) and strome lysins (MMP3) were downregulated. And, the hedgehog signaling pathway may be a prosurvival adaptive response under heat stress. These results offer a basis for better understanding the molecular mechanism underlying lay‐eggs‐less in ducks under heat stress.
Binacox: automatic cut‐point detection in high‐dimensional Cox model with applications in genetics
Authors: Bussy Simon , Alaya Mokhtar Z. , Jannot Anne‐Sophie , Guilloux Agathe 
Published: August 2021

AbstractWe introduce binacox, a prognostic method to deal with the problem of detecting multiple cut‐points per feature in a multivariate setting where a large number of continuous features are available. The method is based on the Cox model and combines one‐hot encoding with the binarsity penalty, which uses total‐variation regularization together with an extra linear constraint, and enables feature selection. Original nonasymptotic oracle inequalities for prediction (in terms of Kullback–Leibler divergence) and estimation with a fast rate of convergence are established. The statistical performance of the method is examined in an extensive Monte Carlo simulation study, and then illustrated on three publicly available genetic cancer data sets. On these high‐dimensional data sets, our proposed method outperforms state‐of‐the‐art survival models regarding risk prediction in terms of the C‐index, with a computing time orders of magnitude faster. In addition, it provides powerful interpretability from a clinical perspective by automatically pinpointing significant cut‐points in relevant variables.
Stratigraphic forward modelling of distributive fluvial systems based on the Huesca System, Ebro Basin, northern Spain
Authors: Snieder Swiad , Griffiths Cedric M. , Owen Amanda , Hartley Adrian J. , Howell John A. 
Published: August 2021

AbstractTo better understand the stratigraphic development of sedimentary systems, it is necessary to link the controls on sedimentary processes to the resulting deposits, which in turn allows predictions of stratigraphic architectures at a range of scales. We use a stratigraphic forward model to link the governing parameters to the distribution of deposits within a distributive fluvial system (DFS). The numerical model has been validated against outcrop observations to establish how the depositional processes needed to form the specific sedimentary system have been reproduced. We chose the previously studied Oligocene to Miocene Huesca DFS in northern Spain to investigate and calibrate the model. Additionally, downstream profiles from modern DFS in northern India, and hydrological measurements from the High Island Creek, Minnesota, USA, were used as input parameters for the model in addition to the outcrop data from the Huesca DFS. The resulting model adequately reproduced the real‐world system. Once validated, the analysis of the modelled DFS led to key findings, which expand our understanding of DFS stratigraphic architecture. Reservoir characteristics in radial DFS are dependent on the angle away from the meridian (straight line from the source through the apex to the distal zone of the DFS). The greater the angle is, the coarser the average grain size in the proximal zone is but the finer the average grain size in the medial and distal zones. Lateral variability of net to gross, sandbody thickness and number, and amalgamation ratio is greatest at the transition between the proximal and medial zone and is still significant in the distal part of the DFS. Stratigraphic forward modelling enhanced our understanding of DFS, which leads to reducing risk associated with exploration, production and storage of fluids in subsurface DFS.
The prevalence of oropharyngeal squamous cell carcinoma in patients admitted with symptoms of peritonsillar abscess or cellulitis: A retrospective multicentre study
Authors: Lau Andrew S. , Milinis Kristijonas , Roode Mila , Williams Stephen P. , Cook Colette , Walijee Hussein , Zammit Matthew , Siau Richard , Emerson Hannah , Wright Rosanna , Hampton Thomas 
Published: August 2021

AbstractObjectivesAnecdotal evidence suggests that oropharyngeal squamous cell carcinoma (OPSCC) should be suspected in patients presenting with symptoms of peritonsillar abscess (PTA) or cellulitis (PTC). The aim of this study was to estimate the prevalence of OPSCC in patients presenting with symptoms of PTA/PTC.Method, Setting and ParticipantsWe retrospectively identified all adults with a coded diagnosis of PTA or PTC who presented between 2012 and 2016 inclusive, across six ENT units in Merseyside. Records were compared to that of the centralised regional head and neck cancer database. The clinical records of a subset of patients were reviewed for the purposes of data validation.ResultsA total of 1975 patients with PTA/PTC were identified. Three patients were subsequently diagnosed with OPSCC. None of the three actually had an objective underlying diagnosis of PTA/PTC on the same side. The prevalence of OPSCC in patients admitted with symptoms of PTA/PTC was 0.15% or approximately 1:650 admissions. The records of 510 patients who presented over a one‐year period (2016) were reviewed in even greater detail. There were 298 patients with PTA (59.4%) and 151 with PTC (29.1%) and 61 had an alternative diagnosis (11.9%). High‐risk features (age ≥40, tonsillar asymmetry or tonsillar lesion) were present in 106 patients (24%). Urgent follow‐up was expedited for 77 patients (73%).ConclusionThis study estimates the risk of OPSCC in patients with peritonsillar symptoms. The prevalence is low, even in a region with a relatively heavy disease burden. Clinicians should, however, retain a high level of suspicion in patients with persistent symptoms.
An open‐label, nonrandomized, phase Ib feasibility study of cusatuzumab in patients with nasopharyngeal carcinoma
Authors: De Meulenaere Astrid , Vermassen Tijl , Creytens David , De Keukeleire Stijn , Delahaye Tim , Deron Philippe , Duprez Fréderic , Fung Samson , Pauwels Patrick , Ferdinande Liesbeth , Rottey Sylvie 
Published: August 2021

AbstractCD70 is expressed in up to 80% of nasopharyngeal carcinoma (NPC) cases. Cusatuzumab is a humanized anti‐CD70 monoclonal antibody, with dual action mechanisms: induction of cytotoxicity against CD70+ tumor cells and reduction in CD70‐CD27 signaling mediated immune evasion. The aim of this study was to assess the safety, pharmacokinetic profile, immunogenicity, pharmacodynamic profile, and preliminary activity of cusatuzumab in advanced NPC. Eleven patients were enrolled: one patient was assigned to arm A (adjuvant cusatuzumab monotherapy after curative chemoradiation), nine patients to arm B (cusatuzumab monotherapy; noncurative setting), and one patient to arm C (cusatuzumab + chemotherapy; noncurative setting); irrespective of tumoral CD70 expression. Both patients in arms A and C completed the study. All patients in arm B discontinued at an early stage. Five patients experienced grade greater than or equal to 3 nondrug related treatment‐emergent adverse events, most commonly fatigue and pneumonia (18%). An infusion‐related reaction was observed in two of 11 patients. Laboratory results showed no trend over time. Seven patients were eligible for response evaluation. No objective response to cusatuzumab was observed with stable disease being the best response. The current study indicates that the safety profile of cusatuzumab (with or without concurrent chemotherapy) is manageable in patients with advanced NPC, which is consistent with known safety profile. Limited activity of cusatuzumab in advanced NPC was observed. Combination therapies of cusatuzumab and other types of therapy should be explored for the improvement of activity in NPC and other CD70‐expressing malignancies.
How can real‐world evidence aid decision making during the life cycle of nonprescription medicines?
Authors: Csoke Emese , Landes Sabine , Francis Matthew J. , Ma Larry , Teotico Pohlhaus Denise , Anquez‐Traxler Christelle 
Published: August 2021

AbstractReal‐world evidence (RWE) is an emerging scientific discipline which is being increasingly utilized for decision making on prescription‐only medicines. However, there has been little focus to date on the application of RWE within the nonprescription sector. This paper reviews the existing and potential applications of RWE for nonprescription medicines, using the nonprescription medicine life cycle as a framework for discussion. Relevant sources of real‐world data (RWD) are reviewed and compared with those available for prescribed medicines. Existing life‐cycle data gaps are identified where RWE is required or where use of RWE can complement data from randomized controlled trials. Published RWE examples relating to nonprescription medicines are summarized, and potential relevant future sources of RWD discussed. Challenges and limitations to the use of RWE on nonprescription medicines are discussed, and recommendations made to promote optimal and appropriate use of RWE in this sector. Overall, RWE currently plays a key role in specific phases of the nonprescription medicine life cycle, including reclassification and postmarketing safety surveillance. The increasing availability of patient‐generated health data is likely to further increase the utilization of RWE to aid decision making on nonprescription medicines.
Avoidant/restrictive food intake disorder and autism spectrum disorder: clinical implications for assessment and management
Authors: Farag Fadila , Sims Annemarie , Strudwick Katy , Carrasco Janette , Waters Amy , Ford Vicki , Hopkins Julia , Whitlingum Gabriel , Absoud Michael , Kelly Veronica B 
Published: August 2021

AimWe examined clinical and neurodevelopmental presentations of children with avoidant/restrictive food intake disorder (ARFID) to inform clinical assessment and management.MethodFive hundred and thirty‐six patients (mean age 6y 10mo, SD 3y 5mo, range 10mo–20y; 401 males, 135 females) seen by the tertiary multidisciplinary feeding service at the Evelina London Children’s Hospital between January 2013 and June 2019 were included in this case–control study. These children experienced significant feeding difficulties impacting nutrition, development, and psychosocial functioning requiring tertiary specialized input. Data on ARFID diagnosis, demographics, comorbidity, and nutrition was extracted from electronic patient records.ResultsForty‐nine per cent of children met ARFID criteria. The remaining participants had other difficulties including feeding, medical, and/or neurodevelopmental conditions. ARFID is more prevalent among younger patients (4–9 years) and in children with comorbid autism spectrum disorder (ASD). Younger age, comorbid ASD, and male sex significantly predicted ARFID. Diet range and male sex significantly predicted nutritional inadequacy, while comorbid ASD did not. A trend was seen between younger age and nutritional inadequacy.InterpretationYoung children with ARFID should raise suspicion for ASD. Although significant nutritional deficiencies are common in children with comorbid ARFID and ASD, they are correctable with nutritional supplementation. Specialty perspective potentially limits generalizability of findings to community feeding services. We also emphasize the importance of early identification of nutritional deficits and management.
Lipohypertrophy Monitoring Study (LIMO): Effect of single use of 4 mm pen needles combined with education on injection site rotation on glycaemic control: Confirmation of an unpleasant truth
Authors: Bochanen Niels , Decochez Katelijn , Heleu Els , Cuypers Joke , Vercammen Chris , Coremans Peter , Vanhaverbeke Gerd , Shadid Samyah , Keymeulen Bart , Bolsens Nancy , De Block Christophe 
Published: August 2021

AbstractAimsTo investigate whether single use of 4 mm needles combined with education about injection technique and lipohypertrophy affects HbA1c, hypoglycaemia and glucose variability.MethodsInsulin‐injecting people with diabetes recruited from nine Belgian diabetes centres were prospectively followed for 6 months. They were provided 4 mm pen needles and education concerning injection technique using an online platform (BD and Me™) based on the international Forum for Injection Technique & Therapy Recommendations focused on avoidance of lipohypertrophy zones and reduction of needle reuse.ResultsA total of 171 people with diabetes were included of which 146 completed the study. At baseline, lipohypertrophy was present in 63.0% of those who completed the study, with 51.4% injecting in zones of lipohypertrophy, 37.0% incorrectly rotating and 95.9% reusing needles. After the intervention, 7.5% still injected in a lipohypertrophy zone, 4.1% rotated incorrectly and needle reuse decreased to 21.2%. The number of participants with severe hypoglycaemias (from 15.8% to 4.1%, p < 0.001), unexplained hypoglycaemias (from 46.6% to 16.4%, p < 0.001) and high glucose variability (from 64.4% to 29.5%, p < 0.001) was significantly reduced. HbA1c and total daily insulin dose remained stable.ConclusionThe combination of 4 mm pen needles and online education on injection techniques significantly reduced the number of people with severe hypoglycaemic episodes, unexplained hypoglycaemia and high glucose variability but did not improve HbA1c control nor lower insulin needs.Trial registration: ClinicalTrials.gov NCT04659330.
Acquisition of IDH2 mutations in relapsed/refractory AML is associated with worse patient outcomes
Authors: Song Amy , Altabbakh Omar , Sallman David A. , Padron Eric , Talati Chetasi , Hussaini Mohammad O. 
Published: August 2021

AbstractObjectivesThe presence of targeted therapy, Enasidenib, for IDH2‐mutated AML underscores the importance of understanding the clonal dynamics of IDH2 mutations, which has not been elucidated. In the largest study of IDH2 clonal dynamics, we detail the IDH2‐evolutionary patterns and their clinical significance.MethodsWe analyzed ~6000 patients with NGS results to identify 120 AML patients with IDH2 mutations and longitudinal NGS testing. IDH2 mutation status was recorded at diagnosis, remission, relapse, and persistent disease.ResultsOne hundred and five patients were IDH2‐positive at the initial diagnosis, and 15 acquired the mutation later. Of those 15 patients, 7 patients gained the mutation during persistent disease, 6 during relapse, and 2 at remission. Twenty‐one patients (18%) who were IDH2‐positive in a prior test remained IDH2‐positive in remission. Twenty‐four patients with IDH2‐positive AML were IDH2‐positive at relapse. IDH2‐positive at diagnosis had better survival than IDH2 mutation acquired later in disease (P = .024). Patients who were IDH2‐negative in remission had significantly improved survival (P = .002). Also, loss‐of‐IDH2 mutation with persistent disease had better OS (P = .035).ConclusionsThere are 70% that clear IDH2 in disease remission. 12% gain IDH2 mutation later, usually in the setting of refractory/relapsed AML. These patients fared worse. Longitudinal IDH2 testing may be helpful in prognostic stratification.
Serial DaT‐SPECT imaging in asymptomatic carriers of LRRK2 G2019S mutation: 8 years’ follow‐up
Authors: Sánchez‐Rodríguez Antonio , Martínez‐Rodríguez Isabel , Sánchez‐Juan Pascual , Sierra María , González‐Aramburu Isabel , Rivera‐Sánchez María , Andrés‐Pacheco Javier , Gutierrez‐González Ángela , García‐Hernández Adrián , Madera Jorge , Delgado‐Alvarado Manuel , Infante Jon 
Published: August 2021

AbstractBackgroundCarriers of the G2019S mutation of LRRK2 provide a great opportunity to investigate the premotor stages of Parkinson’s disease (PD). We have studied by serial clinical and dopamine transporter single photon emission computed tomography (DaT‐SPECT) evaluations a cohort of asymptomatic carriers of the LRRK2‐G2019S mutation in order to evaluate the usefulness of these tools as biomarkers. Here we report the results of the extended follow‐up of this cohort at 8 years.MethodsSeventeen participants, of the 25 available from the 4‐year evaluation, completed the 8‐year assessment. UPDRS‐III, UPSIT test and DaT‐SPECT imaging (123I‐ioflupane) were performed. We used repeated‐measures linear mixed effects models to examine the changes in DaT binding over time.ResultsThree carriers had converted to PD at 4 years. One additional carrier converted at 8 years. PD‐converters had lower striatal DaT binding at baseline than non‐converters. There was a significant decline of DaT binding over time, with a mean annual rate of 3.5%, with somewhat inter‐individual and intra‐individual variability and comparable between PD‐converters and non‐converters. No carrier with DAT binding ratio above an undefined threshold between 0.5 and 0.8 developed PD symptoms. The age‐adjusted UPSIT score did not change significantly over time.ConclusionsThe rate of conversion to PD at 8 years in this cohort aged ~58 years at baseline was 16%. The observed decline of DaT binding over time and its association with the phenotype render DaT‐SPECT a potentially useful tool for monitoring the premotor stage of the disease, although at the individual level its ability to predict phenoconversion is limited.
Add‐on cannabidiol in patients with Dravet syndrome: Results of a long‐term open‐label extension trial
Authors: Scheffer Ingrid E. , Halford Jonathan J. , Miller Ian , Nabbout Rima , Sanchez‐Carpintero Rocio , Shiloh‐Malawsky Yael , Wong Matthew , Zolnowska Marta , Checketts Daniel , Dunayevich Eduardo , Devinsky Orrin 
Published: August 2021

AbstractObjectiveAdd‐on cannabidiol (CBD) reduced seizures associated with Dravet syndrome (DS) in two randomized, double‐blind, placebo‐controlled trials: GWPCARE1 Part B (NCT02091375) and GWPCARE2 (NCT02224703). Patients who completed GWPCARE1 Part A (NCT02091206) or Part B, or GWPCARE2, were enrolled in a long‐term open‐label extension trial, GWPCARE5 (NCT02224573). We present an interim analysis of the safety, efficacy, and patient‐reported outcomes from GWPCARE5.MethodsPatients received a pharmaceutical formulation of highly purified CBD in oral solution (100 mg/ml), titrated from 2.5 to 20 mg/kg/day over a 2‐week period, added to their existing medications. Based on response and tolerance, CBD could be reduced or increased to 30 mg/kg/day.ResultsOf the 330 patients who completed the original randomized trials, 315 (95%) enrolled in this open‐label extension. Median treatment duration was 444 days (range = 18–1535), with a mean modal dose of 22 mg/kg/day; patients received a median of three concomitant antiseizure medications. Adverse events (AEs) occurred in 97% patients (mild, 23%; moderate, 50%; severe, 25%). Commonly reported AEs were diarrhea (43%), pyrexia (39%), decreased appetite (31%), and somnolence (28%). Twenty‐eight (9%) patients discontinued due to AEs. Sixty‐nine (22%) patients had liver transaminase elevations >3 × upper limit of normal; 84% were on concomitant valproic acid. In patients from GWPCARE1 Part B and GWPCARE2, the median reduction from baseline in monthly seizure frequency assessed in 12‐week periods up to Week 156 was 45%–74% for convulsive seizures and 49%–84% for total seizures. Across all visit windows, ≥83% patients/caregivers completing a Subject/Caregiver Global Impression of Change scale reported improvement in overall condition.SignificanceWe show that long‐term CBD treatment had an acceptable safety profile and led to sustained, clinically meaningful reductions in seizure frequency in patients with treatment‐resistant DS.
Wealth and urbanization shape medium and large terrestrial mammal communities
Authors: Magle Seth B. , Fidino Mason , Sander Heather A. , Rohnke Adam T. , Larson Kelli L. , Gallo Travis , Kay Cria A. M. , Lehrer Elizabeth W. , Murray Maureen H. , Adalsteinsson Solny A. , Ahlers Adam A. , Anthonysamy Whitney J. B. , Gramza Ashley R. , Green Austin M. , Jordan Mark J. , Lewis Jesse S. , Long Robert A. , MacDougall Brandon , Pendergast Mary E. , Remine Katie , Simon Kelly Conrad , St. Clair Colleen C. , Shier Catherine J. , Stankowich Theodore , Stevenson Cassondra J. , Zellmer Amanda J. , Schell Christopher J. 
Published: August 2021

AbstractUrban biodiversity provides critical ecosystem services and is a key component to environmentally and socially sustainable cities. However, biodiversity varies greatly within and among cities, leading to human communities with changing and unequal experiences with nature. The “luxury effect,” a hypothesis that predicts a positive correlation between wealth, typically measured by per capita income, and species richness may be one indication of these inequities. While the luxury effect is well studied for some taxa, it has rarely been investigated for mammals, which provide unique ecosystem services (e.g., biological pest control) and exhibit significant potential for negative human–wildlife interactions (e.g., nuisances or conflicts). We analyzed a large dataset of mammal detections across 20 North American cities to test whether the luxury effect is consistent for medium‐ to large‐sized terrestrial mammals across diverse urban contexts. Overall, support for the luxury effect, as indicated by per capita income, was inconsistent; we found evidence of a luxury effect in approximately half of our study cities. Species richness was, however, highly and negatively correlated with urban intensity in most cities. We thus suggest that economic factors play an important role in shaping urban mammal communities for some cities and species, but that the strongest driver of urban mammal diversity is urban intensity. To better understand the complexity of urban ecosystems, ecologists and social scientists must consider the social and political factors that drive inequitable human experiences with nature in cities.