bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Models of Genetic Education and Testing for Pancreatic Cancer Interception: Preliminary Results from the GENERATE Study
Authors: Furniss C. Sloane , Yurgelun Matthew B. , Ukaegbu Chinedu , Constantinou Pamela E. , Lafferty Catherine C. , Talcove-Berko Eliana R. , Schwartz Alison N. , Stopfer Jill E. , Underhill-Blazey Meghan , Kenner Barbara , Nelson Scott H. , Okumura Sydney , Law Sherman , Zhou Alicia Y. , Coffin Tara B. , Rodriguez Nicolette J. , Uno Hajime , Ocean Allyson J. , McAllister Florencia , Lowy Andrew M. , Lippman Scott M. , Klein Alison P. , Madlensky Lisa , Petersen Gloria M. , Garber Judy E. , Goggins Michael G. , Maitra Anirban , Syngal Sapna 
Published: October 2021

Abstract

Up to 10% of patients with pancreatic ductal adenocarcinoma (PDAC) carry underlying germline pathogenic variants in cancer susceptibility genes. The GENetic Education Risk Assessment and TEsting (GENERATE) study aimed to evaluate novel methods of genetic education and testing in relatives of patients with PDAC. Eligible individuals had a family history of PDAC and a relative with a germline pathogenic variant in APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, or TP53 genes. Participants were recruited at six academic cancer centers and through social media campaigns and patient advocacy efforts. Enrollment occurred via the study website (https://GENERATEstudy.org) and all participation, including collecting a saliva sample for genetic testing, could be done from home. Participants were randomized to one of two remote methods that delivered genetic education about the risks of inherited PDAC and strategies for surveillance. The primary outcome of the study was uptake of genetic testing. From 5/8/2019 to 5/6/2020, 49 participants were randomized to each of the intervention arms. Overall, 90 of 98 (92%) of randomized participants completed genetic testing. The most frequently detected pathogenic variants included those in BRCA2 (N = 15, 17%), ATM (N = 11, 12%), and CDKN2A (N = 4, 4%). Participation in the study remained steady throughout the onset of the Coronavirus disease (COVID-19) pandemic. Preliminary data from the GENERATE study indicate success of remote alternatives to traditional cascade testing, with genetic testing rates over 90% and a high rate of identification of germline pathogenic variant carriers who would be ideal candidates for PDAC interception approaches.

Prevention Relevance:
Preliminary data from the GENERATE study indicate success of remote alternatives for pancreatic cancer genetic testing and education, with genetic testing uptake rates over 90% and a high rate of identification of germline pathogenic variant carriers who would be ideal candidates for pancreatic cancer interception.
Amyloid Deposits and Fibrosis on Left Ventricular Endomyocardial Biopsy Correlate With Extracellular Volume in Cardiac Amyloidosis
Authors: Pucci Angela , Aimo Alberto , Musetti Veronica , Barison Andrea , Vergaro Giuseppe , Genovesi Dario , Giorgetti Assuero , Masotti Silvia , Arzilli Chiara , Prontera Concetta , Pastormerlo Luigi Emilio , Coceani Michele Alessandro , Ciardetti Marco , Martini Nicola , Palmieri Cataldo , Passino Claudio , Rapezzi Claudio , Emdin Michele 
Published: October 2021

Background
The relative contribution of amyloid and fibrosis to extracellular volume expansion in cardiac amyloidosis (CA) has never been defined.

Methods and Results

We included all patients diagnosed with amyloid light‐chain (AL) or transthyretin cardiac amyloidosis at a tertiary referral center between 2014 to 2020 and undergoing a left ventricular endomyocardial biopsy. Patients (n=37) were more often men (92%), with a median age of 72 years (interquartile range, 68–81). Lambda‐positive AL was found in 14 of 19 AL cases (38%) and kappa‐positive AL in 5 of 19 (14%), while transthyretin was detected in the other 18 cases (48%). Amyloid deposits accounted for 15% of tissue sample area (10%–30%), without significant differences between AL and transthyretin amyloidosis. All patients displayed myocardial fibrosis, with a median extent of 15% of tissue samples (10%–23%; range, 5%–60%), in the absence of spatial overlap with amyloid deposits. Interstitial fibrosis was often associated with mild and focal subendocardial fibrosis. The extent of fibrosis or the combination of amyloidosis and fibrosis did not differ significantly between transthyretin amyloidosis and AL subgroups. In 20 patients with myocardial T1 mapping at cardiac magnetic resonance, the combined amyloid and fibrosis extent displayed a modest correlation with extracellular volume (
r
=0.661,
P
=0.001). The combined amyloid and fibrosis extent correlated with high‐sensitivity troponin T (
P
=0.035) and N‐terminal pro‐B‐type natriuretic peptide (
P
=0.002) serum levels.

Conclusions
Extracellular spaces in cardiac amyloidosis are enlarged to a similar extent by amyloid deposits and fibrotic tissue. Their combination can better explain the increased extracellular volume at cardiac magnetic resonance and circulating biomarkers than amyloid extent alone.
Efficacy and Safety of Vorapaxar by Intensity of Background Lipid‐Lowering Therapy in Patients With Peripheral Artery Disease: Insights From the TRA2P‐TIMI 50 Trial
Authors: Gilchrist Ian C. , Morrow David A. , Creager Mark A. , Olin Jeffrey W. , Scirica Benjamin M. , Goodrich Erica L. , Bonaca Marc P. 
Published: October 2021

Background
Patients with peripheral artery disease are at increased risk of both major adverse cardiovascular events (MACEs) and limb events. The pathobiology of limb events is likely multifactorial. Observational studies suggest a benefit of statin therapy for reducing the risk of limb ischemic events while randomized trials demonstrate a benefit with more potent antithrombotic therapies, particularly those targeting thrombin. Whether the effects of these therapeutic pathways are independent and complementary is not known.

Methods and Results

The TRA 2°P‐TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events–Thrombolysis in Myocardial Infarction 50) trial demonstrated that vorapaxar significantly reduced MACEs and limb events. The purpose of the current analysis was to evaluate the association of statin use and intensity and the occurrence of MACEs and limb events in 5845 patients with symptomatic peripheral artery disease randomized in TRA 2°P‐TIMI 50 and then to understand whether statin use modified the benefits of vorapaxar for MACEs or limb ischemic events. We found that statin therapy was associated with significantly lower risk of MACEs (hazard ratio [HR], 0.77; 95% CI, 0.66–0.89;
P
<0.001) and limb ischemic events (HR, 0.73; 95% CI, 0.60–0.89;
P
=0.002). The benefit of vorapaxar for reducing MACEs and limb events was consistent regardless of background statin (
P
‐interaction=0.715 and 0.073, respectively). Event rates were lowest in patients receiving the combination of statin therapy and vorapaxar.

Conclusions
In conclusion, statin use and intensity is associated with significantly lower rates of MACEs and limb ischemic events. Thrombin inhibition with vorapaxar is effective regardless of background statin therapy. These results suggest that targeting both lipid and thrombotic risk in peripheral artery disease is necessary in order to optimize outcomes.
Large-Scale Multivariate Analysis to Interrogate an Animal Model of Stroke: Novel Insights Into Poststroke Pathology
Authors: Zhang Shenpeng R. , Kim Hyun Ah , Chu Hannah X. , Lee Seyoung , Evans Megan A. , Li Xia , Ma Henry , Drummond Grant R. , Sobey Christopher G. , Phan Thanh G. 
Published: October 2021

Background and Purpose:
Preclinical stroke studies endeavor to model the pathophysiology of clinical stroke, assessing a range of parameters of injury and impairment. However, poststroke pathology is complex and variable, and associations between diverse parameters may be difficult to identify within the usual small study designs that focus on infarct size.

Methods:
We have performed a retrospective large-scale big data analysis of records from 631 C57BL/6 mice of either sex in which the middle cerebral artery was occluded by 1 of 5 surgeons either transiently for 1 hour followed by 23-hour reperfusion (transient middle cerebral artery occlusion [MCAO]; n=435) or permanently for 24 hours without reperfusion (permanent MCAO; n=196). Analyses included a multivariate linear mixed model with random intercept for different surgeons as a random effect to reduce type I and type II errors and a generalized ordinal regression model for ordinal data when random effects are low.

Results:

Analyses indicated that brain edema volume was associated with infarct volume at 24 hours (β, 0.52 [95% CI, 0.45–0.59]) and was higher after permanent MCAO than after transient MCAO (
P
<0.05). A more severe clinical score was associated with a greater infarct volume but not with the animal’s age or edema volume. Further, a more severe clinical score was observed for a given brain infarct volume after transient MCAO versus permanent MCAO. Remarkably the animal’s age, which corresponded with the period of young adulthood (6–40 weeks; equivalent to ≈18–35 years in humans), was positively associated with severity of lung infection (β, 0.65 [95% CI, 0.42–0.88]) and negatively with spleen weight (β, −0.36 [95% CI, −0.63 to −0.09]).

Conclusions:
Large-scale analysis of preclinical stroke data can provide researchers in our field with insight into relationships between variables not possible if individual studies are analyzed in isolation and has identified hypotheses for future study.
Using an Artificial Neural Network to improve operational wind prediction in a small unresolved valley
Authors: CHINYOKA SINCLAIR , STEENEVELD GERT-JAN , HEDDE THIERRY 
Published: October 2021

AbstractThis study improves surface wind predictions in an unresolved valley using an artificial neural network (ANN). Forecasting winds in complex terrain with a mesoscale model is challenging. This study assesses the quality of 3-km wind forecasts by the Weather Research and Forecasting (WRF) model and the potential of post-processing by an ANN within the 1-2 km wide Cadarache Valley in southeast France. Operational wind forecasts for 110m above ground level and the near-surface vertical potential temperature gradient with a lead time of 24-48h were used as ANN input. Observed horizontal wind components at 10m within the valley were used as targets during ANN training. We use the Directional ACCuracy (DACC45, wind direction error ≤ 45°) and mean absolute error to evaluate the WRF direct model output and the ANN results. By post-processing, the score for DACC45 improves from 56% in the WRF direct model output to 79% after applying the ANN. Furthermore, the ANN performed well during the day and night, but poorly during the morning and afternoon transitions. The ANN improves the DACC45 at 10m even for poor WRF forecasts (direction bias ≥ 45°) from 42% to 72%. A shorter lead time and finer grid spacing (1 km) showed negligible impact which suggests that a 3 km grid spacing and a 24-48h lead time is effective and relatively cheap to apply. We find that WRF performs well in near-neutral conditions and poorly in other atmospheric stability conditions. The ANN post-treatment consistently improves the wind forecast for all stability classes to a DACC45 of about 80%. The study demonstrates the ability to improve Cadarache valley wind forecasts using an ANN as post-processing for WRF daily forecasts.
Percutaneous cholecystostomy for acute cholecystitis after stent insertion in patients with malignant biliary obstruction: clinical outcomes of 107 patients
Authors: Choi Woosun , Gwon Dong Il , Kim Jong Woo , Kim Jin Hyoung , Shin Ji Hoon , Ko Gi-Young , Hur Joonho 
Published: October 2021

Background The outcome of percutaneous cholecystostomy (PC) in malignant patients with acute cholecystitis (AC) after biliary stent insertion has not been investigated in a large group. Purpose To evaluate the clinical outcomes of PC for AC after stent insertion in patients with malignant biliary obstruction. Material and Methods From April 2007 to February 2019, 107 patients (57 men, 52 women; mean age = 67.5 years; age range = 27–93 years) who had undergone PC for AC after biliary stent insertion were retrospectively evaluated. Of the 107 patients, 86 underwent biliary stent insertion by the endoscopic approach and the remaining 21 patients by the percutaneous approach. All patients were classified into three groups: those with stent-induced AC; those with cancer-induced AC; and those with AC without mechanical cause (biliary stent, GB stone, or cancer invasion). The mean survival time, recurrence rate, symptom improvement, and cystic duct patency in each patient group were analyzed. Results Stent-induced AC (n = 40, 37.4%) developed with a mean onset time of six days (range = 0–14 days), AC without mechanical cause (n = 27, 25.2%), 87 days (range = 15–273 days), and cancer-induced AC (n = 40, 37.4%), 137 days (range = 15–447 days) after stent insertion. Symptom resolution and significant improvement in laboratory test values were achieved in 95 patients (88.8%) within four days after PC. Conclusion PC is a technically safe and effective method for the treatment of AC after biliary stent insertion in patients with malignant biliary obstruction.
Acta Radiologica 2003–2017: a 15-year overview
Authors: Skjennald Arnulf 
Published: October 2021

This review article is written as a contribution to the special issue presented in conjunction with the 100th anniversary of Acta Radiologica. An overview is given of what has happened with and in the journal during the 15 years from 2003 to 2017 and a resume is provided concerning the handling and flow of manuscripts, manuscript publication, scientific prizes awarded by the journal, and finally the process leading up to establishing the new open-access journal Acta Radiologica Short Reports/Acta Radiologica Open.
A rare case of Panophthalmitis due to cobra bite
Authors: Ganesan Suganeswari , Agarwal Aditi Ashok Kumar , Subramanian Krishnakumar 
Published: October 2021

Purpose Ocular manifestations of snake bite are rare, ranging from direct injury to the eye from snake venom or indirect injury due to antivenom. We report a rare case of cobra bite causing panophthalmitis due to indirect injury as a result of snake venom toxin related tissue necrosis and susceptibility to secondary infections. Methods Observational case report. External photographs, slit lamp photos, ultrasonography of the eye and histopathology of the eviscerated eye were used to characterize and describe the clinical findings. Thirty-nine-years-old male farmer presented with history of cobra snake bite on his right index finger and developed right eye sudden onset pain and redness 3 days later. On examination, features were suggestive of panophthalmitis and the eye had to be eviscerated with scleral excision. Conclusion It is important for ophthalmologist to be aware of such grave consequences of snake bite to be prepared for the emergency management of such cases.
Development of lung diffusion to adulthood following extremely preterm birth
Authors: Satrell Emma , Clemm Hege , Røksund Ola Drange , Hufthammer Karl Ove , Thorsen Einar , Halvorsen Thomas , Vollsæter Maria 
Published: October 2021

BackgroundGas exchange in extremely preterm (EP) infants must take place in fetal lungs. Childhood lung diffusing capacity of the lung for carbon monoxide (DLCO) is reduced; however, longitudinal development has not been investigated. We describe the growth ofDLCOand its subcomponents to adulthood in EP compared with term-born subjects.MethodsTwo area-based cohorts born at gestational age ≤28 weeks or birthweight ≤1000 g in 1982–1985 (n=48) and 1991–1992 (n=35) were examined twice, at ages 18 and 25 years and 10 and 18 years, respectively, and compared with matched term-born controls. Single-breathDLCOwas measured at two oxygen pressures, with subcomponents (membrane diffusion (DM) and pulmonary capillary blood volume (VC)) calculated using the Roughton–Forster equation.ResultsAge-, sex- and height-standardised transfer coefficients for carbon monoxide (KCO) andDLCOwere reduced in EP compared with term-born subjects, and remained so during puberty and early adulthood (p-values for all time-points and both cohorts ≤0.04), whereas alveolar volume (VA) was similar. Development occurred in parallel to term-born controls, with no signs of pubertal catch-up growth nor decline at age 25 years (p-values for lack of parallelism within cohorts 0.99, 0.65, 0.71, 0.94 and 0.44 for z-DLCO, z-VA, z-KCO,DMandVC, respectively). Split by membrane and blood volume components, findings were less clear; however, membrane diffusion seemed most affected.ConclusionsPulmonary diffusing capacity was reduced in EP compared with term-born subjects, and development from childhood to adulthood tracked in parallel to term-born subjects, with no signs of catch-up growth nor decline at age 25 years.
Transendothelial migration induces differential migration dynamics of leukocytes in tissue matrix
Authors: van Steen Abraham C. I. , Kempers Lanette , Schoppmeyer Rouven , Blokker Max , Beebe David J. , Nolte Martijn A. , van Buul Jaap D. 
Published: October 2021

ABSTRACT
Leukocyte extravasation into inflamed tissue is a complex process that is difficult to capture as a whole in vitro. We employed a blood-vessel-on-a-chip model in which human endothelial cells were cultured in a tube-like lumen in a collagen-1 matrix. The vessels are leak tight, creating a barrier for molecules and leukocytes. Addition of inflammatory cytokine TNF-α (also known as TNF) caused vasoconstriction, actin remodelling and upregulation of ICAM-1. Introducing leukocytes into the vessels allowed real-time visualization of all different steps of the leukocyte transmigration cascade, including migration into the extracellular matrix. Individual cell tracking over time distinguished striking differences in migratory behaviour between T-cells and neutrophils. Neutrophils cross the endothelial layer more efficiently than T-cells, but, upon entering the matrix, neutrophils display high speed but low persistence, whereas T-cells migrate with low speed and rather linear migration. In conclusion, 3D imaging in real time of leukocyte extravasation in a vessel-on-a-chip enables detailed qualitative and quantitative analysis of different stages of the full leukocyte extravasation process in a single assay.
This article has an associated First Person interview with the first authors of the paper.
PKC-ε regulates vesicle delivery and focal exocytosis for efficient IgG-mediated phagocytosis
Authors: D'Amico Anna E. , Wong Alexander C. , Zajd Cheryl M. , Zhang Xuexin , Murali Ananya , Trebak Mohamed , Lennartz Michelle R. 
Published: October 2021

ABSTRACT
Protein kinase C (PKC)-ε is required for membrane addition during IgG-mediated phagocytosis, but its role in this process is ill defined. Here, we performed high-resolution imaging, which reveals that PKC-ε exits the Golgi and enters phagosomes on vesicles that then fuse. TNF and PKC-ε colocalize at the Golgi and on vesicles that enter the phagosome. Loss of PKC-ε and TNF delivery upon nocodazole treatment confirmed vesicular transport on microtubules. That TNF+ vesicles were not delivered in macrophages from PKC-ε null mice, or upon dissociation of the Golgi-associated pool of PKC-ε, implies that Golgi-tethered PKC-ε is a driver of Golgi-to-phagosome trafficking. Finally, we established that the regulatory domain of PKC-ε is sufficient for delivery of TNF+ vesicles to the phagosome. These studies reveal a novel role for PKC-ε in focal exocytosis – its regulatory domain drives Golgi-derived vesicles to the phagosome, whereas catalytic activity is required for their fusion. This is one of the first examples of a PKC requirement for vesicular trafficking and describes a novel function for a PKC regulatory domain.
This article has an associated First Person interview with the first author of the paper.
Sport-Specific Increased Risk of Anterior Cruciate Ligament Injury Following a Concussion in Collegiate Female Lacrosse
Authors: Lutz Robert H. , DeMoss Deidra J. , Roebuck Emily H. , Mason Tommy , Eiler Brian A. 
Published: October 2021

Abstract
Poor neurocognitive performance has been associated with a greater risk of musculoskeletal injury, and anterior cruciate ligament (ACL) injury prevention protocols include exercises to improve neuromuscular control. Research shows that a concussion elevates the risk for subsequent lower-extremity injury, because concussions lead to lower neurocognitive performance. Studies have been conducted using data within individual male sports, such as football and rugby, or across collegiate sports in aggregate; no study has focused on women's sports. Using 7 years of data collected by athletic training staff at Davidson College, this paper evaluates preconcussive versus postconcussive lower-extremity injury risk across five collegiate women's sports: field hockey, soccer, basketball, volleyball, and lacrosse. Using incidence rate ratios, lacrosse athletes had a five-fold increase in ACL injury risk within 365 d following a concussion. Recognizing that postconcussive ACL tear risk varies across different women's sports is important in informing sport-specific concussion return to play protocols.
Femoral Injury Over the Site of Spontaneous Regression of an Osteochondroma in a Teenage Athlete
Authors: Le Hung M. , Schwartz Richard B. , Corrado Gianmichel 
Published: October 2021

Abstract
The spontaneous regression of an osteochondroma is extremely rare. We report a case of medial femoral condyle impaction fracture over the site of spontaneous regression of a pedunculated osteochondroma discovered on advanced imaging after an acute injury in a 16-year-old male American football athlete. Although spontaneous regression of an osteochondroma has been described, the case presented reveals questions regarding resultant architectural changes to the bone after resorption, leaving it prone to injury. This is the first case that describes increased injury risk potential at the site of osteochondral regression.