bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylation-based Cell-free DNA Signature for Early Detection of Pancreatic Cancer
Authors: Ying Lee , Sharma Anup , Chhoda Ankit , Ruzgar Nensi , Hasan Nesrin , Kwak Ruby , Wolfgang Christopher L. , Wang Tza Huei , Kunstman John W. , Salem Ronald R. , Wood Laura D. , Iacobuzio-Donahue Christine , Schneider Eric B. , Farrell James J. , Ahuja Nita 
Published: December 2021

Objectives
The potential of DNA methylation alterations in early pancreatic cancer (PC) detection among pancreatic tissue cell-free DNA seems promising. This study investigates the diagnostic capacity of the 4-gene methylation biomarker panel, which included ADAMTS1, BNC1, LRFN5, and PXDN genes, in a case-control study.

Methods
A genome-wide pharmacoepigenetic approach identified ADAMTS1, BNC1, LRFN5, and PXDN genes as putative targets. Tissue samples including stage I–IV PC (n = 44), pancreatic intraepithelial neoplasia (n = 15), intraductal papillary mucinous neoplasms (n = 24), and normal pancreas (n = 8), and cell-free DNA, which was acquired through methylation on beads technology from PC (n = 22) and control patients (n = 10), were included. The 2−∆ct was the outcome of interest and underwent receiver operating characteristic analysis to determine the diagnostic accuracy of the panel.

Results
Receiver operating characteristic analysis revealed an area under the curve of 0.93 among ADAMTS1, 0.76 among BNC1, 0.75 among PXDN, and 0.69 among LRFN5 gene. The combination gene methylation panel (ADAMTS1, BNC1, LRFN5, and PXDN) had an area under the curve of 0.94, with a sensitivity of 100% and specificity of 90%.

Conclusions
This methylation-based biomarker panel had promising accuracy for PC detection and warranted further validation in prospective PC surveillance trials.
Borderline Resectable and Locally Advanced Pancreatic Cancers
Authors: Khachfe Hussein H. , Habib Joseph R. , Nassour Ibrahim , Al Harthi Salem , Jamali Faek R. 
Published: December 2021

Abstract
Locally advanced and borderline resectable pancreatic cancers are being increasingly recognized as a result of significant improvements in imaging modalities. The main tools used in diagnosis of these tumors include endoscopic ultrasound, computed tomography, magnetic resonance imaging, and diagnostic laparoscopy. The definition of what constitutes a locally advanced or borderline resectable tumor is still controversial to this day. Borderline resectable tumors have been treated with neoadjuvant therapy approaches that aim at reducing tumor size, thus improving the chances of an R0 resection. Both chemotherapy and radiotherapy (solo or in combination) have been used in this setting. The main chemotherapy agents that have shown to increase resectability and survival are FOLFORINOX (a combination of folinic acid, fluorouracil, irinotecan, and oxaliplatin) and gemcitabine–nab-paclitaxel. Surgery on these tumors remains a significantly challenging task for pancreatic surgeons. More studies are needed to determine the best agents to be used in the neoadjuvant and adjuvant settings, biologic markers for prognostic and operative predictions, and validation of previously published retrospective results.
Transient End‐Tidal Carbon Dioxide Elevation During Pediatric Upper Endoscopy With Carbon Dioxide Insufflation
Authors: Dike Chinenye R. , Bishop Warren P. , Titler Sarah S. , Rahhal Riad 
Published: December 2021

ABSTRACTBackground:Endoscopic insufflation, long performed using air, is being replaced by carbon dioxide (CO2) at many pediatric centers, despite limited published data on its use in children. We have previously demonstrated that CO2 use during esophagogastroduodenoscopy (EGD) in non‐intubated children is associated with transient elevations of end‐tidal CO2 (EtCO2). This observation raised concerns about possible CO2 inhalation and systemic absorption. Here, we investigate this concern by concurrently measuring both EtCO2 and transcutaneous CO2 (tCO2) during upper endoscopic procedures in children.Aim:To determine if elevations in EtCO2 levels seen in non‐intubated children undergoing CO2 insufflation during EGD are associated with elevated systemic CO2 levels.Methods:Double‐blinded, prospective, randomized clinical trial. Children were randomized 1:1 to receive either CO2 or air for endoscopic insufflation. EtCO2 was sampled with a CO2‐sampling nasal cannula and tCO2 was monitored using the Radiometer transcutaneous monitoring device.Results:Fifty nine patients were enrolled; 30 patients in the CO2 insufflation group and 29 in the air group. All patients underwent a procedure involving an EGD. Transient elevations in EtCO2 (defined as >60 mmHg) were observed only in the CO2 insufflation group. This contrasted with the similar elevations of tCO2 between the CO2 and air insufflation groups. None of these events were of clinically significant magnitude or duration.Conclusion:This study demonstrates that the observed transient elevations in EtCO2 seen during EGD in non‐intubated children receiving CO2 insufflation are most likely measurements of eructated CO2 without evidence of excessive systemic absorption of CO2.
Unmet Birth Expectations and Birth Trauma among Adolescents
Authors: Anderson Cheryl A. , Akinmade Faith 
Published: December 2021

Abstract

Purpose:
To assess and compare birth expectations of younger and older age adolescents and explore if unmet expectations predict psychological birth trauma (PBT).

Study Design and Methods:
This secondary analysis expands findings of a previous study (N = 303) which classified adolescents' perceptions of birth into four main themes. The previous study used a mixed-methods approach providing data related to birth expectations. For the current study, expectations were determined by themes as met or unmet by three reviewers. Of 116 useable written narrations, responses of younger (ages 13-17) versus older (ages 18-19) adolescents were compared and explored for impact on PBT.

Results:
Birth expectations for both age groups were more often unmet than met. Despite a smaller cohort, younger adolescents provided more remarks than older adolescents. There were no differences between groups on unmet birth expectations (p = .16). Unmet expectations most often related to pain with older adolescents more inclined to state poor pain management. Younger adolescents more often feared dying. Unmet expectations did not predict PBT.

Clinical Implications:
Comprehensive prenatal care can allow for early, open conversations to assess labor knowledge and misconceptions, fear of birth, existing supports, and overall birth expectations, with a premier focus on expected labor pain and pain management. Multiparous adolescents should receive prenatal assessments of posttraumatic stress (PTS) symptoms (a recognized predictor of posttraumatic stress syndrome) potentially originating from a previous traumatic birth. Following birth, symptoms of acute stress and PTS should be assessed of all adolescents, especially if experienced numerous unmet labor expectations.
Mechanical testing of cephalomedullary nail lag screws after the addition of hydroxyapatite substitutes
Authors: Nakajima Takayuki , Aoki Yasuchika , Watanabe Atsuya , Inoue Masahiro , Yamaguchi Satoshi , Nakamura Junichi , Matsuura Yusuke , Hagiwara Shigeo , Himeno Daisuke , Ohtori Seiji 
Published: December 2021

Abstract

Objective:
To compare the effects of 3 implant designs, with and without hydroxyapatite reinforcement, on push/pull-out strength and rotational torque.

Methods:
Three implant designs (Gamma 3, INTERTAN, and PFNA-II) were selected for comparison. A hydroxyapatite cylinder (NEOBRACE) was used to reinforce the interface between the femoral head and the lag screw. Maximum push-out strength, maximum pull-out strength, and peak rotational torque were measured in cellular blocks mimicking osteoporotic cancellous bone, with and without NEOBRACE.

Results:
In the push-out test, INTERTAN produced a significantly higher push-out strength in osteoporotic bone density cellular blocks than the other lag screws and blades (P < .05). With the addition of NEOBRACE, push-out strength was significantly higher for INTERTAN and PFNA-II (P < .05) than for the non-NEOBRACE group. In the pull-out test, INTERTAN produced a significantly higher pull-out strength in the osteoporotic bone density cellular blocks than did the other lag screws and blades (P < .05). With the addition of NEOBRACE, the pull-out strengths of INTERTAN and Gamma 3 versus those of the non-NEOBRACE group significantly increased (P < .05). In the rotational torque test, INTERTAN produced significantly greater rotational torque in the osteoporotic cellular blocks than the other lag screws and blades (P < .05). The addition of NEOBRACE resulted in a significant increase in rotational torque only for INTERTAN (P < .05).

Conclusion:
The use of NEOBRACE supported an increase in push/pull-out strength and rotational torque, especially in systems with a relatively increased bone or implant interface area.

Level of Evidence: Level V
Sectoral Sparing Associated With a Cilioretinal Artery in Arteritic Anterior Ischemic Optic Neuropathy
Authors: Gaier Eric D. , Rasool Nailyn , Rizzo Joseph F. 
Published: December 2021

Abstract:
Giant cell arteritis (GCA) is a life-threatening vasculitis occurring in older adults that can cause blindness by ischemia of the choroid, retina, and optic nerve. We report a case of a patient who presented with “occult” GCA with severe anterior ischemic optic neuropathy affecting both optic nerves, delayed choroidal filling, and a concomitant cilioretinal artery occlusion in the left eye. The retinal territory supplied by the affected cilioretinal artery was hypoperfused, yet this retinal territory at least partially corresponded to the only preserved visual field in that eye. The sector of the optic disc corresponding to the emergence of the cilioretinal artery was the only sector spared by pallid edema. This pattern of sectoral sparing associated with a cilioretinal artery has been observed in other patients with GCA and in animal models of posterior ciliary artery occlusion. This case serves as a clear example of an incompletely understood phenomenon in posterior pole circulation in vascular occlusive disease that deserves further study.
Added diagnostic accuracy after [18F]flutemetamol PET scanning in young patients with dementia in an academic memory clinic setting
Authors: Handels Ron L.H. , Zwan Marissa D. , Pelkmans Wiesje , Biessels Geert Jan , van Domburg Peter , Hoff Erik , Roks Gerwin , Schoonenboom Niki , Verweij Niek , van Berckel Bart N.M. , van der Flier Wiesje M. , Verhey Frans , Scheltens Philip , Bouwman Femke H. 
Published: December 2021

ABSTRACTIntroductionA timely diagnosis of Alzheimer’s Disease (AD) in an early stage of dementia is important to support timely access to treatment, advice, and care. The aim of this study was to estimate the diagnostic accuracy of [18F]flutemetamol PET in addition to the usual diagnostic workup for the diagnosis of AD in a memory clinic population with young onset dementia by means of a panel reference-based etiology diagnosis.Methodsin an academic memory clinic early onset dementia cohort (n=211) the nosological diagnosis was set by usual diagnostic workup and after including [18F]flutemetamol amyloid PET in a stepwise approach. To assess the change in proportion correctly diagnosed, the diagnosis with and without [18F]flutemetamol PET was related to a panel-based reference standard, serving as gold standard, consisting of 3 neurologists who relied on available clinical information over 2-year follow-up (n=152; blinded for PET).ResultsThe panel majority nosology was set as a reference diagnosis in 122 participants, leaving 30 (20%) participants with no majority reached. In 107 (88%) cases post-PET was in line with the reference, and in 103 (84%) the pre-PET diagnosis was in line with the reference. The difference was 3.3% (95% CI -3.5% to 10.1%; p=0.424).Discussion[18F]flutemetamol PET did not significantly improve the diagnostic accuracy in young patients with dementia in an academic memory clinic setting. The secondary analyses provided several indications for future research in a narrower subsample of persons with (very) high diagnostic uncertainty and to assess patient relevant health outcomes.
One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: relation to chromosomal dosage
Authors: Vione Beatrice , Ramacieri Giuseppe , Zavaroni Giacomo , Piano Angela , La Rocca Giorgia , Caracausi Maria , Vitale Lorenza , Piovesan Allison , Gori Caterina , Pirazzoli Gian Luca , Strippoli Pierluigi , Cocchi Guido , Corvaglia Luigi , Locatelli Chiara , Pelleri Maria Chiara , Antonaros Francesca 
Published: December 2021

AbstractDown syndrome (DS) is the most common chromosomal disorder and it is caused by trisomy of chromosome 21 (Hsa21). Subjects with DS show a large heterogeneity of phenotypes and the most constant clinical features present are typical facies and intellectual disability (ID). Several studies demonstrated that trisomy 21 causes an alteration in the metabolic profile, involving among all one-carbon cycle. We performed enzyme-linked immunosorbent assays (ELISAs) to identify the concentration of 5 different intermediates of the one-carbon cycle in plasma samples obtained from a total of 164 subjects with DS compared to 54 euploid subjects. We investigated: tetrahydrofolate (THF; DS n=108, control n=41), 5-methyltetrahydrofolate (5-methyl-THF; DS n=140, control n=34), 5-formyltetrahydrofolate (5-formyl-THF; DS n=80, control n=21), S-adenosyl-homocysteine (SAH; DS n=94, control n=20) and S-adenosyl-methionine (SAM; DS n=24, control n=15). Results highlight specific alterations of THF with a median concentration ratio DS/control of 2:3, a decrease of a necessary molecule perfectly consistent with a chromosomal dosage effect. Moreover, SAM and SAH show a ratio DS/control of 1.82:1 and 3.6:1, respectively. The relevance of these results for the biology of intelligence and its impairment in trisomy 21 is discussed, leading to the final proposal of 5-methyl-THF as the best candidate for a clinical trial aimed at restoring the dysregulation of one-carbon cycle in trisomy 21, possibly improving cognitive skills of subjects with DS.
Regional Topological Aberrances of White Matter- and Gray Matter-based Functional Networks for Attention Processing may Foster Traumatic Brain Injury-Related Attention Deficits in Adults
Authors: Wu Ziyan , Cao Meng , Di Xin , Wu Kai , Gao Yu , Li Xiaobo 
Published: December 2021

ABSTRACTTraumatic brain injury (TBI) is highly prevalent in adults. TBI-related functional brain alterations have been linked with common post-TBI neurobehavioral sequelae, with unknown neural sub-strates. This study examined the systems-level functional brain alterations in white matter (WM) and gray matter (GM) for visual sustained attention processing, their interactions, and contribution to post-TBI attention deficits. Task-based functional MRI data were collected from 42 adults with TBI and 43 group-matched normal controls (NCs), and analyzed using the graph theoretic tech-nique. Global and nodal topological properties were calculated and compared between the two groups. Correlation analyses were conducted between the neuroimaging measures that showed significant between-group differences and the behavioral symptom measures in attention domain in the groups of TBI and NCs, respectively. Significantly altered nodal efficiency and/or degree in several WM and GM nodes were reported in the TBI group, including the posterior corona radiata (PCR), posterior thalamic radiation (PTR), postcentral gyrus (PoG), and superior temporal sulcus (STS). Subjects with TBI also demonstrated abnormal systems-level functional synchronization between the PTR and STS in the right hemisphere, hypo-interaction between PCR and PoG in the left hemisphere; as well as the involvement of systems-level functional aberrances in PCR in TBI-related behavioral impairments in the attention domain. Findings of the current study suggest that TBI-related systems-level functional alterations associated with these two major association WM tracts and their anatomically connected GM regions may play critical role in TBI-related behavioral deficits in attention domain.
Rethinking Margin of Stability: Incorporating Step-To-Step Regulation to Resolve the Paradox
Authors: Kazanski Meghan , Cusumano Joseph P. , Dingwell Jonathan B. 
Published: December 2021

ABSTRACTDerived from inverted pendulum dynamics, mediolateral Margin of Stability (MoSML) is a mechanically-grounded measure of instantaneous stability. However, average MoSML measures yield paradoxical results. Gait pathologies or perturbations often induce larger (supposedly “more stable”) average MoSML, despite clearly destabilizing factors. However, people do not walk “on average” – they walk (and sometimes lose balance) one step at a time. We assert the paradox arises because averaging discards step-to-step dynamics. We present a framework unifying the inverted pendulum with Goal-Equivalent Manifold (GEM) analyses. We identify in the pendulum’s center-of-mass dynamics constant-MoSML manifolds, including one candidate “stability GEM” signifying the goal to maintain some constant . We used this framework to assess step-to-step MoSML dynamics of humans walking in destabilizing environments. While goal-relevant deviations were readily corrected, humans did not exploit equifinality by allowing deviations to persist along this GEM. Thus, maintaining a constant is inconsistent with observed step-to-step fluctuations in center-of-mass states. Conversely, the extent to which participants regulated fluctuations in foot placements strongly predicted regulation of center-of-mass fluctuations. Thus, center-of-mass dynamics may arise indirectly as a consequence of regulating mediolateral foot placements. To resolve the paradox caused by averaging MoSML, we present a new statistic, Probability of Instability (PoIL), to predict instability likelihood. Participants exhibited increased PoIL when destabilized (p = 9.45×10−34), despite exhibiting larger (“more stable”) average MoSML (p = 1.70×10−15). Thus, PoIL correctly captured people’s increased risk of losing lateral balance, whereas average MoSML did not. PoIL also explains why peoples’ average MoSML increased in destabilizing contexts.
Benchmarking Geometric Deep Learning for Cortical Segmentation and Neurodevelopmental Phenotype Prediction
Authors: Fawaz Abdulah , Williams Logan Z. J. , Alansary Amir , Bass Cher , Gopinath Karthik , da Silva Mariana , Dahan Simon , Adamson Chris , Alexander Bonnie , Thompson Deanne , Ball Gareth , Desrosiers Christian , Lombaert Hervé , Rueckert Daniel , Edwards A. David , Robinson Emma C. 
Published: December 2021

AbstractThe emerging field of geometric deep learning extends the application of convolutional neural networks to irregular domains such as graphs, meshes and surfaces. Several recent studies have explored the potential for using these techniques to analyse and segment the cortical surface. However, there has been no comprehensive comparison of these approaches to one another, nor to existing Euclidean methods, to date. This paper benchmarks a collection of geometric and traditional deep learning models on phenotype prediction and segmentation of sphericalised neonatal cortical surface data, from the publicly available Developing Human Connectome Project (dHCP). Tasks include prediction of postmenstrual age at scan, gestational age at birth and segmentation of the cortical surface into anatomical regions defined by the M-CRIB-S atlas. Performance was assessed not only in terms of model precision, but also in terms of network dependence on image registration, and model interpretation via occlusion. Networks were trained both on sphericalised and anatomical cortical meshes. Findings suggest that the utility of geometric deep learning over traditional deep learning is highly task-specific, which has implications for the design of future deep learning models on the cortical surface. The code, and instructions for data access, are available from https://github.com/Abdulah-Fawaz/Benchmarking-Surface-DL.
Sex-dependent changes in murine striatal dopamine release, sleep, and behavior during spontaneous Δ-9-tetrahydrocannabinol abstinence
Authors: Kesner Andrew J. , Mateo Yolanda , Abrahao Karina P. , Ramos-Maciel Stephanie , Pava Matthew J. , Gracias Alexa L. , Paulsen Riley T. , Carlson Hartley B. , Lovinger David M. 
Published: December 2021

AbstractWithdrawal symptoms are observed upon cessation of cannabis use in humans. Although animal studies have examined withdrawal symptoms following exposure to delta-9-tetrahydrocannabinol (THC), difficulties in obtaining objective measures of spontaneous withdrawal using paradigms that mimic cessation of use in humans have slowed research. The neuromodulator dopamine (DA) is known to be affected by chronic THC treatment and plays a role in many behaviors related to human THC withdrawal symptoms. These symptoms include sleep disturbances that often drive relapse, and emotional behaviors, e.g., irritability and anhedonia. We examined THC withdrawal-induced changes in striatal DA release and the extent to which sleep disruption and behavioral maladaptation manifest during withdrawal in a mouse chronic cannabis exposure model. Using a THC treatment regimen known to produce tolerance we measured electrically elicited DA release in acute brain slices from different striatal subregions during early and late THC abstinence. Long-term polysomnographic recordings from mice were used to assess vigilance state and sleep architecture before, during, and after THC treatment. We additionally assessed how behaviors that model human withdrawal symptoms are altered by chronic THC treatment in early and late abstinence. We detected altered striatal DA release, sleep disturbances that mimic clinical observations, and behavioral maladaptation in mice following tolerance inducing THC treatment. Sex differences were observed in nearly all metrics. Altered striatal DA release, sleep and affect-related behaviors associated with spontaneous THC abstinence were more consistently observed in male mice. To our knowledge these findings provide the first model of directly translatable non-precipitated cannabis withdrawal symptoms, in particular, sleep disruption.
Delta variant with P681R critical mutation revealed by ultra-large atomic-scale ab initio simulation: Implications for the fundamentals of biomolecular interactions
Authors: Adhikari Puja , Jawad Bahaa , Rao Praveen , Podgornik Rudolf , Ching Wai-Yim 
Published: December 2021

ABSTRACTSARS-CoV-2 Delta variant is emerging as a globally dominant strain. Its rapid spread and high infection rate are attributed to a mutation in the spike protein of SARS-CoV-2 allowing the virus to invade human cells much faster and with increased efficiency. Particularly, an especially dangerous mutation P681R close to the furin cleavage site has been identified as responsible for increasing the infection rate. Together with the earlier reported mutation D614G in the same domain, it offers an excellent instance to investigate the nature of mutations and how they affect the interatomic interactions in the spike protein. Here, using ultra large-scale ab initio computational modeling, we study the P681R and D614G mutations in the SD2-FP domain including the effect of double mutation and compare the results with the wild type. We have recently developed a method of calculating the amino acid-amino acid bond pairs (AABP) to quantitatively characterize the details of the interatomic interactions, enabling us to explain the nature of mutation at the atomic resolution. Our most significant find is that the mutations reduce the AABP value, implying a reduced bonding cohesion between interacting residues and increasing the flexibility of these amino acids to cause the damage. The possibility of using this unique mutation quantifiers in a machine learning protocol could lead to the prediction of emerging mutations.