bluuebunny/crossref_metadata_2025_split huggingface dataset:
COT-11 Administration of Bevacizumab for patients who failed to complete Stupp regimen after glioblastoma surgery
Authors: Kon Takashi , Imaizumi Yoichi , Kobayashi Yusuke , Sato Yosuke , Shimizu Katsuyoshi , Mizutani Tohru 
Published: November 2020

Abstract
Stupp regimen is widely used as the standard treatment after glioblastoma surgery, but in some cases treatment must be discontinued for various reasons. We experienced Bevacizumab in two patients who were unable to continue treatment in the Stupp regimen, and report our experience with literature review. First patient is a man in his 60s. Resection of glioblastoma of the left cerebral hemisphere was performed, and postoperatively right hemiparesis and aphasia remained. Irradiation and administration of Temozolomide were performed, but Temozolomide was unable to continue because of side effects. After systemic management, Bevacizumab was administered, and reduction of residual tumor and peripheral edema were observed, and the patient began to speak. After 12 cycles of administration, the tumor regrew, and he died. Second patient is a woman in her 80s. Craniotomy was performed for hemorrhagic infarction of the left cerebral hemisphere, postoperatively, aphasia, right hemiparesis remained, bedridden, and was unable to eat. Four months after initial surgery, a tumor was found in left parietal lobe and was resected. The pathological diagnosis was glioblastoma. For the treatment of recurrence, the patient was unable to be transferred for radiochemotherapy, so the patient was treated with Temozolomide and Bevacizumab. The patient’s condition became better, eat by herself, and could play in rehabilitation facility on the wheelchair. After 12 cycles of bevacizumab, the tumor subsequently enlarged, and died. Although the effect is limited, there are some cases in which Bevacizumab administration could maintain patient’s condition by controlling tumor growth for a certain period of time. From the experience of these patients, it seems that even in patients with postoperative poor Karnofsky Performance Status (KPS)and elderly people, Bevacizumab administration would be an option before transitioning to end-of-life care.
COT-12 The role of clinical research professional in the registration study of pediatric solid tumor in Japan Children’s Cancer Group
Authors: Furukawa Keiko , Makino Yasuhide , Mineharu Yohei , Umeda Katsutsugu , Takita Junko , Arakawa Yoshiki 
Published: November 2020

Abstract
A larger scale prospective registration study for pediatric solid tumor has been conducted nationwide in Japan since 2011 in Japan Children’s Cancer Group (JCCG). In the study, the clinical data and surgical specimen are collected into the National Center for Child Health. Kyoto University Hospital has participated in the study since IRB approval in 2011. We reviewed our patients registered to the study and assessed the role of clinical research professional in the registration study. Fifty-one patients with pediatric brain tumors participated in this study from 2011 to 2020. There were 17 intracranial germ cell tumors, 9 medulloblastomas, 14 gliomas and ependymomas in 5 diffuse midline gliomas, 9 pilocytic astrocytoma, and 2 other types of tumor. Forty surgical specimens were collected for central review. The status of clinical data entry was complete in 33 patients. The registrations and sending of clinical data and specimens have remarkably increased without exceptions since a clinical research professional supported the study in 2018. The study collecting and analyzing pathological diagnosis, molecular diagnosis, treatment, and clinical information in patients with pediatric brain tumor are important to realize the current status. The clinical research professional plays an important role to register patients and to send the specimens and clinical data into the study.
Sources of Dynamism in Modern Administrative Law
Authors: Bell Joanna 
Published: November 2020

Abstract
The list of recognised grounds of judicial review has remained constant in England and Wales for several decades. Modern administrative law may therefore appear to be characterised by high levels of stability or perhaps stagnancy. The essays in The Frontiers of Public Law are, however, an important reminder of three important sources of dynamism across modern administrative law. First, legislation can change regularly in this field, generating novel legal questions. Secondly, internal administrative practices are not static but evolving, creating questions about the adequacy of existing doctrinal structures. Thirdly, principles can emerge within sub-branches of judicial review, giving rise to questions about whether and how those same principles apply elsewhere. These sources of dynamism make modern administrative law ripe territory for novel and important legal issues.
The Early Impact of COVID-19 on Chronic Pain: A Cross-Sectional Investigation of a Large Online Sample of Individuals with Chronic Pain in the United States, April to May, 2020
Authors: Mun Chung Jung , Campbell Claudia M , McGill Lakeya S , Aaron Rachel V 
Published: November 2020

Abstract

Objective
Individuals with chronic pain are uniquely challenged by the COVID-19 pandemic, as increased stress may exacerbate chronic pain, and there are new barriers to receiving chronic pain treatment. In light of this, using a large online sample in the United States, we examined 1) the early impact of COVID-19 on pain severity, pain interference, and chronic pain management; and 2) variables associated with perceived changes in pain severity and pain interference.

Design
A cross-sectional study.

Methods
Online survey data for 1,453 adults with chronic pain were collected via Amazon’s Mechanical Turk platform.

Results
Although a large proportion of participants reported no perceived changes in their pain severity and pain interference since the outbreak, approximately 25–30% of individuals reported exacerbation in these domains. Individuals identifying as Black and of non-Hispanic origin, who experienced greater disruptions in their mood and sleep quality, were more likely to report worsened pain interference. The majority of participants reported engaging in self-management strategies as usual. However, most appointments for chronic pain treatment were either postponed or canceled, with no future session scheduled. Furthermore, a notable proportion of participants had concerns about or difficulty accessing prescription opioids due to COVID-19.

Conclusions
We may expect to see a long-term exacerbation of chronic pain and related interference in functioning and chronic pain management among individuals most impacted by the pandemic. These individuals may benefit from remotely delivered intervention to effectively mitigate COVID-19–related exacerbations in chronic pain and interruptions in face-to-face treatment.
The Use of the Seattle Angina Questionnaire in Patients Who Underwent Spinal Cord Stimulation for Refractory Angina Pectoris
Authors: Langford Brendan , Hunt Christine , Lerman Amir , Mauck William D 
Published: November 2020

Abstract

Background
The Seattle Angina Questionnaire (SAQ) is a self-administered questionnaire used in cardiac patients to quantify angina based on five scales: physical limitation scale, anginal stability scale, anginal frequency scale, treatment satisfaction scale, and the disease perception scale. Here we report the use of the SAQ to assess angina symptoms in 18 patients who underwent spinal cord stimulation (SCS) for refractory angina pectoris (RAP) at the Mayo Clinic.

Methods
Electronic health records were searched to find patients who underwent SCS for the treatment of RAP at a single institution from 2003 to 2018. Eligible patients were asked to participate in a phone survey that included the SAQ.

Results
Out of 13 patients who still had their implant, six (46%) had minimal physical limitations. Ten patients (76.9%) had favorable anginal frequency scores, defined as minimal or mild. Out of the five patients who had their device removed, one (20%) had minimal physical limitations and three (60%) had favorable anginal frequency scores. There was a high treatment satisfaction score for both those with their implant in place and those with the device removed.

Conclusion
The SAQ is useful as a comprehensive measure specific to patients with RAP assessing function, pain, and satisfaction. The utilization of this tool pre- and post-operatively may provide additional information to analyze the effectiveness of SCS for RAP.
Regeneration of critical-sized defects, in a goat model, using a dextrin-based hydrogel associated with granular synthetic bone substitute
Authors: Pereira Isabel , Pereira José Eduardo , Maltez Luís , Rodrigues Alexandra , Rodrigues Catarina , Oliveira Manuela , Silva Dina M , Caseiro Ana Rita , Prada Justina , Maurício Ana Colette , Santos José Domingos , Gama Miguel 
Published: November 2020

AbstractThe development of injectable bone substitutes (IBS) have obtained great importance in the bone regeneration field, as a strategy to reach hardly accessible defects using minimally invasive techniques and able to fit to irregular topographies. In this scenario, the association of injectable hydrogels and bone graft granules is emerging as a well-established trend. Particularly, in situ forming hydrogels have arisen as a new IBS generation. An in situ forming and injectable dextrin-based hydrogel (HG) was developed, aiming to act as a carrier of granular bone substitutes and bioactive agents. In this work, the HG was associated to a granular bone substitute (Bonelike®) and implanted in goat critical-sized calvarial defects (14 mm) for 3, 6 and 12 weeks. The results showed that HG improved the handling properties of the Bonelike® granules and did not affect its osteoconductive features, neither impairing the bone regeneration process. Human multipotent mesenchymal stromal cells from the umbilical cord, extracellular matrix hydrolysates and the pro-angiogenic peptide LLKKK18 were also combined with the IBS. These bioactive agents did not enhance the new bone formation significantly under the conditions tested, according to micro-computed tomography and histological analysis.
Strontium ranelate incorporated 3D porous sulfonated PEEK simulating MC3T3-E1 cell differentiation
Authors: Sun Yingxiao , Liu Xingdan , Tan Ji , Lv Dan , Song Wengang , Su Rui , Li Ling , Liu Xuanyong , Ouyang Liping , Liao Yun 
Published: November 2020

Abstract
Polyetheretherketone (PEEK) has been used as an implant material because it has similar mechanical properties to natural bone. However, inferior osseointegration and bioinertness hamper the clinical application of PEEK. In this study, the surfaces of sulfonated three-dimensional (3D) PEEK porous structures were loaded with different concentrations of strontium ranelate, a compound commonly used in the treatment or prevention of osteoporosis by promoting bone formation and inhibiting bone resorption. Field-emission scanning electron microscopy was used to characterize the topography of the structures, elemental carbon, oxygen and strontium contents were measured by X-ray photoelectron spectroscopy, and surface zeta potentials and water-contact angle were also measured. The results indicated that strontium ranelate was successfully loaded onto the 3D porous structures. In vitro cellular results showed that strontium ranelate-treated sulfonated PEEK (SP-SR) strengthened the adhesion of MC3T3-E1 cells. The activity of alkaline phosphatase, collagen secretion and extracellular matrix mineralization deposition of MC3T3-E1 cells were also improved on the surface of SP-SR. These results indicate that SP-SR could serve a new implant candidate for surgical treatment.
A Multimodal Sepsis Quality-Improvement Initiative Including 24/7 Screening and a Dedicated Sepsis Response Team-Reduced Readmissions and Mortality
Authors: Alnababteh Muhtadi H. , Huang Sean Shenghsiu , Ryan Andrea , McGowan Kevin M. , Yohannes Seife 
Published: November 2020

Objectives:
To evaluate if a hospitalwide sepsis performance improvement initiative improves compliance with the Centers for Medicare and Medicaid Services-mandated sepsis bundle interventions and patient outcomes.

Study Design:
Retrospective analysis comparing 6 months before and 14 months after intervention.

Setting:
Tertiary teaching hospital in Washington, DC.

Subjects:
Patients admitted with a diagnosis of sepsis to a tertiary hospital.

Interventions:
Implementation of a multimodal quality-improvement initiative.

Measurements and Main Results:
A total of 4,102 patients were diagnosed with sepsis, severe sepsis, or septic shock during the study period, 861 patients (21%) were diagnosed during a 6-month preintervention period, and 3,241 (79%) were diagnosed in a 13-month postintervention period. Adjusted for patient case-mix, the prevalence of simple sepsis increased by 12%, but it decreased for severe sepsis and septic shock by 5.3% and 6.9%, respectively. Compliance with all sepsis bundle interventions increased by 31.1 percentage points (p < 0.01). All-cause hospital readmission and readmission due to infection were both reduced by 1.6% and 1.7 percentage points (p < 0.05). Death from any sepsis diagnosis was reduced 4.5% (p < 0.01). Death from severe sepsis and septic shock both was reduced by 5% (p < 0.01) and 6.5% (p < 0.01), respectively.

Conclusions:
After the implementation of multimodal sepsis performance initiatives, we observed a higher prevalence of sepsis secondary to screening but a lower prevalence of severe sepsis and septic shock, an improvement in compliance with the sepsis bundle interventions bundle, as well as reduction in hospital readmission and all- cause mortality rate.
The Unyvero Hospital-Acquired pneumonia panel for diagnosis of secondary bacterial pneumonia in COVID-19 patients
Authors: Tellapragada Chaitanya , Giske Christian G. 
Published: November 2020

AbstractThe study was undertaken to evaluate the performance of Unyvero Hospitalized Pneumonia Panel (HPN) Application, a multiplex PCR based method for the detection of bacterial pathogens from lower respiratory tract (LRT) samples, obtained from COVID-19 patients with suspected secondary hospital-acquired pneumonia. Residual LRT samples obtained from critically ill COVID-19 patients with predetermined microbiological culture results were tested using the Unyvero HPN Application. Performance evaluation of the HPN Application was carried out using the standard-of-care (SoC) microbiological culture findings as the reference method. Eighty-three LRT samples were used in the evaluation. The HPN Application had a full concordance with SoC findings in 59/83 (71%) samples. The new method detected additional bacterial species in 21 (25%) and failed at detecting a bacterial species present in lower respiratory culture in 3 (3.6%) samples. Overall the sensitivity, specificity, positive and negative predictive values of the HPN Application were 95.1% (95%CI: 96.5-98.3%); 98.3% (95% CI: 97.5-98.9%); 71.6% (95% CI: 61.0-80.3%) and 99.8% (95% CI: 99.3-99.9%) respectively. In conclusion, the HPN Application demonstrated higher diagnostic yield in comparison with the culture and generated results within 5 hours.
Clonal hematopoiesis is associated with risk of severe Covid-19
Authors: Bolton Kelly L. , Koh Youngil , Foote Michael B. , Im Hogune , Jee Justin , Sun Choong Hyun , Safonov Anton , Ptashkin Ryan , Moon Joon Ho , Lee Ji Yeon , Jung Jongtak , Kang Chang Kyung , Song Kyoung-Ho , Choe Pyeong Gyun , Park Wan Beom , Kim Hong Bin , Oh Myoung-don , Song Han , Kim Sugyeong , Patel Minal , Derkach Andriy , Gedvilaite Erika , Tkachuk Kaitlyn A. , Braunstein Lior Z. , Gao Teng , Papaemmanuil Elli , Babady N. Esther , Pessin Melissa S. , Kamboj Mini , Diaz Luis A. , Ladanyi Marc , Rauh Michael J. , Natarajan Pradeep , Machiela Mitchell J. , Awadalla Philip , Joseph Vijai , Offit Kenneth , Norton Larry , Berger Michael F , Levine Ross L , Kim Eu Suk , Kim Nam Joong , Zehir Ahmet 
Published: November 2020

ABSTRACTAcquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival.1–4 These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH.2,5,6 A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19.7,8 Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 515 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we found that CH was associated with severe Covid-19 outcomes (OR=1.9, 95%=1.2-2.9, p=0.01). We further explored the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH was significantly associated with risk of Clostridium Difficile (HR=2.0, 95% CI: 1.2-3.3, p=6×10−3) and Streptococcus/Enterococcus infections (HR=1.5, 95% CI=1.1-2.1, p=5×10−3). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.
Can machine learning aid in identifying disease genes? The case of autism spectrum disorder
Authors: Gunning Margot , Pavlidis Paul 
Published: November 2020

AbstractDiscovering genes involved in complex human genetic disorders is a major challenge. Many have suggested that machine learning (ML) algorithms using gene networks can be used to supplement traditional genetic association-based approaches to predict or prioritize disease genes. However, questions have been raised about the utility of ML methods for this type of task due to biases within the data, and poor real-world performance. Using autism spectrum disorder (ASD) as a test case, we sought to investigate the question: Can machine learning aid in the discovery of disease genes? We collected thirteen published ASD gene prioritization studies and evaluated their performance using known and novel high-confidence ASD genes. We also investigated their biases towards generic gene annotations, like number of association publications. We found that ML methods which do not incorporate genetics information have limited utility for prioritization of ASD risk genes. These studies perform at a comparable level to generic measures of likelihood for the involvement of genes in any condition, and do not out-perform genetic association studies. Future efforts to discover disease genes should be focused on developing and validating statistical models for genetic association, specifically for association between rare variants and disease, rather than developing complex machine learning methods using complex heterogeneous biological data with unknown reliability.
Infection-Induced Extracellular Vesicles Evoke Neuronal Transcriptional and Epigenetic Changes
Authors: Tedford Ellen , Badya Norhidayah Binti , Laing Conor , Asaoka Nozomi , Kaneko Shuji , Filippi Beatrice Maria , McConkey Glenn Alan 
Published: November 2020

ABSTRACTInfection with the protozoanToxoplasma gondiiinduces changes in neurotransmission, neuroinflammation, and behavior, yet it remains elusive how these changes come about. In this study we investigated how norepinephrine levels are altered by infection. TINEV (Toxoplasma-induced neuronal extracellular vesicles) isolated from infected noradrenergic cells down-regulated dopamine β-hydroxylase (DBH) gene expression in human and rodent cells. Here we report that intracerebral injection of TINEVs into the brain is sufficient to induceDBHdown-regulation and distrupt catecholaminergic signalling. Further, TINEV treatment induced hypermethylation upstream of the DBH gene. An antisense lncRNA toDBHwas found in purified TINEV preparations. Paracrine signalling to induce transcriptional gene silencing and DNA methylation may be a common mode to regulate neurologic function.
Spatial heterogeneity of glioblastoma cells reveals sensitivity to NAD+ depletion at tumor edge
Authors: Yamashita Daisuke , Botta Davide , Cho Hee Jin , Guo Xiaoxian , Ozaki Saya , Flanary Victoria L , Sirota Inna , Gao Mu , Yamaguchi Shinobu , Nakano Mayu A , Zhou Fen , Zhou Hongyi , Kondo Toru , Kunieda Takeharu , Crossman David K , Kornblum Harley I , Gorospe Myriam , Nam Do-Hyun , Zamboni Nicola , Skolnick Jeffrey , Gu Zhenglong , Lund Frances E , Nakano Ichiro 
Published: November 2020

ABSTRACTEven after total resection of glioblastoma core lesions by surgery and aggressive post-surgical treatments, life-threatening tumors inevitably recur. A characteristic obstacle in effective treatment is high intratumoral heterogeneity, both longitudinally and spatially. Recurrence occurs predominantly at the brain parenchyma-tumor core interface, a region termed tumor edge. Given the difficulty of accessing it surgically, the composition of the tumor edge, harboring both cancerous and non-cancerous cells, remains largely unknown. Here, to identify phenotypic diversity among heterogeneous glioblastoma core and edge lesions, we uncovered the existence of three phenotypically-distinct clonal subpopulations within individual tumors from glioblastoma patients. Clones from the tumor core shared the same phenotype, exclusively generating tumor-core cells. In contrast, two distinct clonal subtypes were identified at the tumor edge: one generated only edge-lesion cells and the other expanded more broadly to establish both edge- and core-lesions. Using multiple xenograft experimental models in mouse brains, tumor edge development was found to require that both somatic and tumor cells express the NADase CD38, combinedly elevating glioblastoma malignancy. In vitro data suggested that intracellular NADase activity at the edge was provoked through intercellular communication between edge clones and normal astrocytes. Systemic treatment of tumor-bearing mice with 78c, a small-molecule CD38 inhibitor, attenuated the formation of glioblastoma edge lesions, suggesting its clinical potential to pharmacologically eliminate tumor-edge lesions. Collectively, these findings provide novel phenotypic and mechanistic insights into clonal heterogeneity within glioblastoma, particularly in the surgically unresectable, currently understudied tumor edge.
Integrated Ligand and Structure based approaches towards developing novel Janus Kinase 2 inhibitors for the treatment of myeloproliferative neoplasms
Authors: Ambili Unni.P , Pillai Girinath G. , Sajitha Lulu.S 
Published: November 2020

AbstractMyeloproliferative neoplasms (MPNs) are a group of diseases affecting hematopoiesis in humans. Types of MPNs include Polycythemia Vera (PV), Essential Thrombocythemia (ET) and myelofibrosis. JAK2 gene mutation at 617thposition act as a major causative factor for the onset and progression of MPNs. So, JAK2 inhibitors are widely used for the treatment of MPNs. But, increased incidence of adverse drug reactions associated with JAK2 inhibitors acts as a paramount challenge in the treatment of MPNs. Hence, there exists an urgent need for the identification of novel lead molecules with enhanced potency and bioavailability. We employed ligand and structure-based approaches to identify novel lead molecules which could act as JAK2 inhibitors. The dataset for QSAR modeling (ligand-based approach) comprised of 49 compounds. We have developed a QSAR model, which has got statistical as well as biological significance. Further, all the compounds in the dataset were subjected to molecular docking and bioavailability assessment studies. Derivative compounds with higher potency and bioavailability were identified for the best lead molecule present in the dataset by employing chemical space exploration. Dataset and models are available athttps://github.com/giribio/agingdataAbstract FigureGraphical abstract