bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of non-neurological organ dysfunction on outcomes in severe isolated traumatic brain injury
Authors: Astarabadi Mariam , Khurrum Muhammad , Asmar Samer , Bible Letitia , Chehab Mohamad , Castanon Lourdes , Ditillo Michael , Douglas Molly , Joseph Bellal 
Published: May 2020

INTRODUCTIONOrgan dysfunction following traumatic brain injury (TBI) is common and has been associated with unpredictable outcomes. The aim of our study is to describe the incidence of non-neurological organ dysfunction (NNOD) and its impact on outcomes in patients with severe TBI admitted to our intensive care unit (ICU).METHODSWe performed a 3-year (2015-2017) review of our Level 1 trauma center’s prospectively maintained TBI database and included all adult (age ≥18y) patients with isolated severe TBI (head abbreviated injury severity (AIS) ≥3 and other AIS <3) and an ICU stay >48 hours. Organ dysfunction (OD) was measured by multiple organ dysfunction scores. Organ system failure was defined as a non-neurological component score of ≥3 on any day during the ICU stay. Outcomes measured were the incidence of NNOD and its effect on outcomes. Multivariate regression analysis was performed.RESULTSA total of 285 patients were included. The mean age was 48 ± 22 years, 72% were males, median [IQR] Glasgow Coma Scale (GCS) was 8[5-10], and median Injury Severity Score (ISS) was 17[10-26]. Epidural hematoma was the most common intracranial hemorrhage (49%) followed by subdural hematoma (46%). The overall incidence of NNOD was 33%, with the most common dysfunctional organ system being the respiratory (23%) followed by the cardiovascular (12%) and hepatic system (8%). The overall in-hospital mortality rate was 19% (NNOD:36% vs. No-NNOD:9%,p< 0.01). On regression analysis, NNOD was associated with higher in-hospital mortality (aOR: 2.0 [1.6-2.7]), discharge to skilled nursing facility (SNF) (aOR: 1.8 [1.4-2.2]), and Glasgow Outcome Scale-Extended (GOS-E) ≤4 (OR: 1.7 [1.3-2.3]) andp-values <0.01.CONCLUSIONOne in every three isolated severe TBI patients develop NNOD. NNOD is independently associated with worse outcomes. Understanding the mechanisms associated with NNOD in the setting of TBI may promote prevention practices and improve outcomes in TBI.LEVEL OF EVIDENCEPrognostic, level III.
Comparative validation of the BOADICEA and Tyrer-Cuzick breast cancer risk models incorporating classical risk factors and polygenic risk in a population-based prospective cohort
Authors: Choudhury Parichoy Pal , Brook Mark N. , Wilcox Amber N. , Lee Andrew , Mulder Charlotta , Coulson Penny , Schoemaker Minouk J. , Jones Michael E. , Swerdlow Anthony J. , Chatterjee Nilanjan , Antoniou Antonis C. , Garcia-Closas Montserrat 
Published: May 2020

AbstractPurposeThe Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and the Tyrer-Cuzick breast cancer models have recently been extended to include polygenic risk scores (PRS). In addition, BOADICEA has also been extended to include reproductive and lifestyle factors, which were already part of Tyrer-Cuzick model. We conducted a comparative validation of the extended models including a recently developed 313-variant PRS in a population-based prospective cohort.MethodsWe used data from a nested case-control sample of 1,337 women of European ancestry (619 incident breast cancer cases) aged 23-75 years from the Generations Study. Models were evaluated for calibration of five-year absolute risk and risk discrimination.ResultsThe extended BOADICEA model with risk factors and PRS was well calibrated across risk deciles: expected-to-observed ratio (E/O) at the highest risk decile = 0.97 (95% Cl = 0.51 to 1.86) for women younger than 50 years and 1.09 (0.66 to 1.80) for women 50 years or older. Adding risk factors and PRS to the BOADICEA model improved discrimination modestly in younger women (Area Under the Curve (AUC): 69.7% vs. 69.1%) and substantially in older women (AUC: 64.6% vs. 56.8%). The Tyrer-Cuzick model with PRS had similar discrimination as the extended BOADICEA model for both age groups; but showed evidence of overestimation at the highest risk decile: E/O=1.54 (0.81 to 2.92) for younger and 1.73 (1.03 to 2.90) for older women.ConclusionThe extended BOADICEA model identified women in a European ancestry population at elevated breast cancer risk more accurately than the Tyrer-Cuzick model with PRS. These analyses can inform choice of risk models for risk stratified breast cancer prevention for women of European ancestry.
Rise and Regional Variations in Schedule II Stimulant Use in the United States
Authors: Vaddadi Sneha M. , Czelatka Nicholas J. , Gutierrez Belsy D. , Maddineni Bhumika C. , Torres-Teran Carlos D. , Tron Daniel N. , McCall Kenneth L. , Piper Brian J. 
Published: May 2020

AbstractObjectiveThere is a need to better understand recent trends in stimulant usage. This report compares the pharmacoepidemiology of three Schedule II stimulants in the United States from 2010 – 2017.MethodsDrug weights were extracted from the Automated Reports and Consolidated Ordering Systems (ARCOS) for amphetamine, methylphenidate, and lisdexamfetamine. Total grams per drug were averaged across all states and compared from 2010–2017. Median stimulant daily dosage per patient user was determined from electronic medical records for a regional analysis.ResultsThere was a rise in amphetamine (+67.5%) and lisdexamfetamine (+76.7%) use from 2010–2017. The change in methylphenidate (−3.0%) was modest. Regional analysis indicated that persons/day usage of stimulants in the west was lower than that of other US regions from 2014–2017. There was a negative correlation (r(48) = −0.43 to −0.65, p < .05) between the percent Hispanic population per state and the daily dose/population per stimulant.ConclusionThe increasing amphetamine and lisdexamfetamine, but not methylphenidate, use may be explained by a rise in adult ADHD diagnoses and treatment. Regional analysis indicates that the use of stimulants in the west may be distinct from that in other regions. The lower stimulant use in areas with greater Hispanic population may reflect socioeconomic factors. Further research is needed on social factors impacting stimulant use and reasons for the pronounced regional variance.
Enzyme immunoassay for SARS-CoV-2 antibodies in dried blood spot samples: A minimally-invasive approach to facilitate community- and population-based screening
Authors: McDade Thomas W. , McNally Elizabeth M. , D’Aquila Richard , Mustanski Brian , Miller Aaron , Vaught Lauren A. , Reiser Nina L. , Bogdanovic Elena , Zelikovich Aaron S. , Demonbreun Alexis R. 
Published: May 2020

AbstractBackgroundSerological testing for SARS-CoV-2 IgG antibodies is needed to document the community prevalence and distribution of the virus, particularly since many individuals have mild symptoms and cannot access molecular diagnostic testing of naso-pharyngeal swabs. However, the requirement for serum/plasma limits serological testing to clinical settings where it is feasible to collect and process venous blood. To address this problem we developed a serological test for SARS-CoV-2 IgG antibodies that requires only a single drop of capillary whole blood, collected from a simple finger prick and dried on filter paper (dried blood spot, DBS).MethodsEnzyme linked immunosorbent assay (ELISA) was optimized to detect SARS-CoV-2 IgG antibodies against the receptor-binding domain (RBD) of the spike protein. DBS samples were eluted overnight and transferred to a 96-well plate coated with antigen, and anti-human IgG-HRP was used to generate signal in proportion to bound antibody. DBS samples spiked with anti-SARS IgG antibody, and samples from known positive and negative cases, were compared to evaluate assay performance.ResultsAnalysis of samples with known concentrations of anti-SARS IgG produced the expected pattern of dose-response. Optical density (OD) values were significantly elevated for known positive cases in comparison with samples from unexposed individuals.DiscussionDBS ELISA provides a minimally-invasive alternative to venous blood collection that combines the convenience of sample collection in the home or non-clinical setting with the quantitation of ELISA in the lab. Serological testing for SARS-CoV-2 IgG antibodies in DBS samples should facilitate research across a wide range of community- and population-based settings on seroprevalence, predictors and duration of antibody responses, as well as correlates of protection from reinfection, each of which is critically important for pandemic control.
Definitive Radiation Therapy With Dose Escalation Is Beneficial For Patients With Squamous Cell Cancer Of The Esophagus
Authors: Ghosh-Laskar Sarbani , Mummudi Naveen , Kumar Saurabha , Chandre Mukesh , Mishra Shagun , Tibdewal Anil , Agarwal JP , Patil Vijay , Noronha Vanita , Prabash Kumar , Jiwnani Sabita , Karimundackal George , Pramesh CS , Patil Prachi 
Published: May 2020

ABSTRACTOBJECTIVEWe report the long term follow-up, toxicity, and outcomes of patients with localized squamous cell carcinoma of the esophagus (ESCC) who underwent definitive chemoradiotherapy (dCRT) at our institute.MATERIALS AND METHODSPatients diagnosed with carcinoma post cricoid, upper cervical and thoracic oesophagus and treated with dCRT treated between January 2000 and March 2012 were retrospectively analysed. Data was extracted from the hospital medical records and patient files. Patients deemed inoperable received upfront RT with or without concurrent chemotherapy and patients with borderline resectable and/or bulky disease received neoadjuvant chemotherapy followed by CRT or RT alone. Radiotherapy was delivered in two phases to a maximum dose of 63 Gy in daily fractions of 1.8 Gy using conventional or conformal techniques. Overall survival and progression free survival were defined from date of registration and were calculated by Kaplan-Meier method with comparisons between different subgroup performed using log rank test. All data were analyzed using SPSS Version 22.RESULTSThree hundred and fourteen patients with ESCC treated with dCRT were included in this analysis. Median age at presentation was 56 years and median Karnofsky Performance Status (KPS) at presentation was 70. Two-third of patients were treated with conformal technique alone or a combination of conventional and conformal technique. Median dose of radiation delivered was 60 Gy (range 30.6 Gy – 70 Gy). Neoadjuvant chemotherapy was administered in about 35% patients and 57% patients received concurrent chemotherapy. About 82% patients (77%) completed their planned treatment course; 10% patients required hospitalization during treatment due to complications and 7 patients did not complete treatment. Grade 1/2 dermatitis and mucositis was seen in 77% and 71% patients respectively. Grade 3 non-hematological and hematological toxicities were seen infrequently. Complete response at first follow up was observed in 56% of patients. At a median follow up of 56 months, 77 patients were alive with controlled disease. The 1-, 2- and 3-yr OS were 80%, 67% and 62% respectively. Median PFS was 28 months; 1-, 2- and 3-yr PFS were 66%, 52% and 46% respectively. A higher RT dose was found to be a significant predictor for OS and PFS on both uni- and multivariate analysis.CONCLUSIONOur study highlights that delivery of higher RT doses (≥63□Gy) is feasible in this patient group and that a higher RT dose was associated with significantly better PFS and OS.
Structural alterations in the macaque frontoparietal white matter network after recovery from prefrontal cortex lesions
Authors: Adam Ramina , Schaeffer David J. , Johnston Kevin , Menon Ravi S. , Everling Stefan 
Published: May 2020

AbstractUnilateral damage to the frontoparietal network typically impairs saccade target selection within the contralesional visual hemifield. Severity of deficits and the degree of recovery have been associated with widespread network dysfunction, yet it is not clear how these behavioural and functional changes relate with the underlying structural white matter pathways. Here, we investigated whether recovery after unilateral prefrontal cortex (PFC) lesions was associated with structural white matter remodeling in the distributed frontoparietal network. Diffusion-weighted MRI was acquired in four macaque monkeys before the lesions and at 2-4 months post-lesion, after recovery of deficits in saccade selection of contralesional targets. Probabilistic tractography was used to reconstruct inter- and intra-hemispheric frontoparietal fiber tracts: bilateral superior longitudinal fasciculus (SLF) and transcallosal fibers connecting bilateral PFC or bilateral posterior parietal cortex (PPC). After behavioural recovery, tract-specific fractional anisotropy in contralesional SLF and transcallosal PPC increased after small lesions and decreased after larger lesions compared to pre-lesion. These findings indicate that remote fiber tracts may provide optimal compensation after small PFC lesions. However, larger lesions may have induced widespread structural damage and hindered compensatory remodeling in the structural frontoparietal network.
Causal roles of frontoparietal cortical areas in feedback control of the limb
Authors: Takei Tomohiko , Lomber Stephen G. , Cook Douglas J. , Scott Stephen H. 
Published: May 2020

SummaryGoal-directed motor corrections are surprisingly fast and complex, but little is known on how they are generated by the central nervous system. Here we show that temporary cooling of dorsal premotor cortex (PMd) or parietal area 5 (A5) in behaving monkeys caused impairments in corrective responses to mechanical perturbations of the forelimb. Deactivation of PMd impaired both spatial accuracy and response speed, whereas deactivation of A5 impaired spatial accuracy, but not response speed. Simulations based on optimal feedback control demonstrated that ‘deactivation’ of the control policy (reduction of feedback gain) impaired both spatial accuracy and response speed, whereas ‘deactivation’ in state estimation (reduction of Kalman gain) impaired spatial accuracy but not response speed, paralleling the impairments observed from deactivation of PMd and A5, respectively. Furthermore, combined deactivation of both cortical regions led to additive impairments of individual deactivations, whereas reducing the amount of cooling (i.e. milder cooling) to PMd led to impairments in response speed, but not spatial accuracy, both also predicted by the model simulations. These results provide causal support that higher order motor and somatosensory regions beyond primary somatosensory and primary motor cortex are involved in generating goal-directed motor responses. As well, the computational models suggest that the distinct patterns of impairments associated with these cortical regions reflect their unique functional roles in goal-directed feedback control.
An extensive computational approach to inhibit MSP-1 ofP.vivaxelucidates further horizon in the establishment next generation therapeutics against malaria
Authors: Islam Md Ohedul , Palit Parag , Shawon Jakaria , Hasan Md Kamrul , Mahfuz Mustafa , Ahmed Tahmeed , Mondal Dinesh 
Published: May 2020

AbstractMalaria represents a life-threatening disease caused by the obligate intra-erythrocytic protozoa of thePlasmodiumgenus, exerting a sinister global health burden and accounting for approximately 660,000 deaths annually. Additionally, 219 million new cases are reported each year, most of which result from the growing issue of artemisinin resistance shown by thePlasmodiumparasite. Much of the research done for the purpose of development of therapeutics against malaria has traditionally been focused onPlasmodium falciparum, which is responsible for majority of the cases of mortality due to malaria,Plasmodium vivaxis also known to contribute greatly towards the malaria relate morbidities particularly in vivax endemic areas. In this study, we have used two different computational approaches aimed at establishing newer concepts towards the development of advanced therapeutics against vivax malaria by targeting the surface antigen, merozoite surface protein-1 (MSP-1). In-silico approach involving computational siRNA designing against MSP-1 resulted in a total of four candidate siRNAs being rationally validated following corroboration with a plethora of algorithms. Additionally, molecular docking analysis unraveled a total of three anti-parasitic peptides. These peptides namely: AP02283, AP02285 and AP00101 were found to exhibit considerable binding affinity with MSP-1 ofP.vivax, thus providing an apparent indication of their anti-malarial property and affirming their potency to be used as novel molecules for development of next generation anti-malarials. However, irrespective of the prospective magnitude of these in-silico findings, the results require extensive validation by further rigorous laboratory experiments involving both in-vitro and in-vivo approaches.
A pathway of NADPH diaphorase positivity between central canal and pial surface at anterior fissure in spinal cord: Supra fissure area with hypothesis configuring from dog, rat, monkey and pigeon
Authors: Jia Yunge , Li Yinhua , Hou Wei , Li Fuhong , Sun Haoran , Wu Xianhui , Wen Xiaoxin , Wei Zicun , Rao Chenxu , Xu Ximeng , Masse Sudirman Fakhruddin , Abulikim Kuerbanjiang , Xu Sheng-fei , Du Guang-hui , Tan Huibing 
Published: May 2020

ABSTRACTThe spinal cord is a cylinder structure in the vertebra and thought a simplified with the gray matter and white matter. Rexed lamination for the gray matter and regional sub-division for whiter matter are completely termed to date. Anterior commissure locates between the central canal and the anterior median fissure. However, some experimental data may still confront with new confined anatomical interpretation. By using NADPH diaphorase [N-d] enzyme histology, we found a vertical oriented neuronal pathway between the central canal and the anterior median fissure in the sacral spinal cord of young adult and aged dog. We used a term “supra fissure area” [SFA] to illustrate the region which consisted of the gray commissure and anterior white commissure. The N-d pathway was notably observable in aged animals. The vertical neurites revealed the cerebrospinal fluid [CSF] contacting neurites between the anterior median fissure and the central canal. We further examined the monkey, rat and pigeon in the region for better understanding of the structure and potential function. The neurodegeneration of N-d dystrophy was detected in the [SFA] in the thoracic spinal cord of the aged monkey. N-d positive fibers were detected in anterior fissure of the rat spinal cord. N-d fibrous structures were also detected in the pigeon spinal cord. These results suggested a new pathway of CSF contacting neurons and the neuronal communications about the central canal.
Heterogeneity of EEG resting-state brain networks in absolute pitch
Authors: Greber Marielle , Klein Carina , Leipold Simon , Sele Silvano , Jäncke Lutz 
Published: May 2020

AbstractThe neural basis of absolute pitch (AP), the ability to effortlessly identify a musical tone without an external reference, is poorly understood. One of the key questions is whether perceptual or cognitive processes underlie the phenomenon as both sensory and higher-order brain regions have been associated with AP. One approach to elucidate the neural underpinnings of a specific expertise is the examination of resting-state networks.Thus, in this paper, we report a comprehensive functional network analysis of intracranial resting-state EEG data in a large sample of AP musicians (n = 54) and non-AP musicians (n = 51). We adopted two analysis approaches: First, we applied an ROI-based analysis to examine the connectivity between the auditory cortex and the dorsolateral prefrontal cortex (DLPFC) using several established functional connectivity measures. This analysis is a replication of a previous study which reported increased connectivity between these two regions in AP musicians. Second, we performed a whole-brain network-based analysis on the same functional connectivity measures to gain a more complete picture of the brain regions involved in a possibly large-scale network supporting AP ability.In our sample, the ROI-based analysis did not provide evidence for an AP-specific connectivity increase between the auditory cortex and the DLPFC. In contrast, the whole-brain analysis revealed three networks with increased connectivity in AP musicians comprising nodes in frontal, temporal, subcortical, and occipital areas. Commonalities of the networks were found in both sensory and higher-order brain regions of the perisylvian area. Further research will be needed to confirm these exploratory results.
Microstimulation in the primary visual cortex: activity patterns and their relation to visual responses and evoked saccades
Authors: Oz R. , Edelman-Klapper H. , Nivinsky-Margalit S. , Slovin H. 
Published: May 2020

AbstractIntra cortical microstimulation (ICMS) in the primary visual cortex (V1) can generate the visual perception of phosphenes and evoke saccades directed to the stimulated location in the retinotopic map. Although ICMS is widely used, little is known about the evoked spatio-temporal patterns of neural activity and their relation to neural responses evoked by visual stimuli or saccade generation. To investigate this, we combined ICMS with Voltage Sensitive Dye Imaging in V1 of behaving monkeys and measured neural activity at high spatial (meso-scale) and temporal resolution. Small visual stimuli and ICMS evoked population activity spreading over few mm that propagated to extrastriate areas. The population responses evoked by ICMS showed faster dynamics and different spatial propagation patterns. Neural activity was higher in trials w/saccades compared with trials w/o saccades. In conclusion, our results uncover the spatio-temporal patterns evoked by ICMS and their relation to visual processing and saccade generation.
PTENP1-AS contributes to BRAF inhibitor resistance and is associated with adverse clinical outcome in stage III melanoma
Authors: Vidarsdottir Linda , Azimi Alireza , Sigvaldadottir Ingibjorg , Rahmanto Aldwin Suryo , Petri Andreas , Kauppinen Sakari , Ingvar Christian , Jönsson Göran , Olsson Håkan , Stolt Marianne Frostvik , Tuominen Rainer , Sangfelt Olle , Tamm Katja Pokrovskaja , Hansson Johan , Grandér Dan , Brage Suzanne Egyházi , Johnsson Per 
Published: May 2020

ABSTRACTApproximately 50% of human cutaneous melanomas carry activating mutations in the serine/threonine protein kinase BRAF. BRAF inhibitors (BRAFi) selectively target the oncogenic BRAFV600E/Kand are effective in approximately 80% of patients carrying the mutation. However, resistance to BRAFi is common and emerges within a median time of 6-7 months of treatment and is prolonged to 11 months when combined with MEK inhibitors. Better characterization of the underlying molecular processes is therefore needed to further improve treatments. Inactivation of the tumor suppressor genePTENhas been suggested to occur during melanomagenesis and drug resistance development. We recently demonstrated that transcription ofPTENis negatively regulated by an antisense RNA from the PTEN pseudogene (PTENP1-AS) and here set out to investigate the impact of this molecular pathway on the resistance to BRAFi and clinical outcome. We used a panel of BRAFi resistant A375 sublines, and observed increased levels of PTENP1-AS associated with reduced expression ofPTEN. Furthermore, this loss ofPTENexpression was correlated to increased recruitment of Enhancer of zeste homolog 2 (EZH2) and formation of the transcriptional repression mark H3K27me3 at thePTENpromoter in the resistant cells. We demonstrated that targeting of PTENP1-AS was able to re-activate the expression ofPTENand sensitize resistant melanoma cells to BRAFi. Finally, we showed that PTENP1-AS is a promising prognostic marker for clinical outcome in melanoma patients as high expression of PTENP1-AS in regional lymph node metastases from stage III melanoma patients correlated with poor survival.