bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Diagnostic Recommendations from Individual Physicians versus the Collective Intelligence of Multiple Physicians in Ambulatory Cases Referred for Specialist Consultation
Authors: Khoong Elaine C. , Nouri Sarah S. , Tuot Delphine S. , Nundy Shantanu , Fontil Valy , Sarkar Urmimala 
Published: August 2021

Background Studies report higher diagnostic accuracy using the collective intelligence (CI) of multiple clinicians compared with individual clinicians. However, the diagnostic process is iterative, and unexplored is the value of CI in improving clinical recommendations leading to a final diagnosis. Methods To compare the appropriateness of diagnostic recommendations advised by individual physicians versus the CI of physicians, we entered actual consultation requests sent by primary care physicians to specialists onto a web-based CI platform capable of collecting diagnostic recommendations (next steps for care) from multiple physicians. We solicited responses to 35 cases (12 endocrinology, 13 gynecology, 10 neurology) from ≥3 physicians of any specialty through the CI platform, which aggregated responses into a CI output. The primary outcome was the appropriateness of individual physician recommendations versus the CI output recommendations, using recommendations agreed upon by 2 specialists in the same specialty as a gold standard. The secondary outcome was the recommendations’ potential for harm. Results A total of 177 physicians responded. Cases had a median of 7 respondents (interquartile range: 5–10). Diagnostic recommendations in the CI output achieved higher levels of appropriateness (69%) than recommendations from individual physicians (45%; χ2 = 5.95, P = 0.015). Of the CI recommendations, 54% were potentially harmful, as compared with 41% of individuals’ recommendations (χ2 = 2.49, P = 0.11). Limitations Cases were from a single institution. CI was solicited using a single algorithm/platform. Conclusions When seeking specialist guidance, diagnostic recommendations from the CI of multiple physicians are more appropriate than recommendations from most individual physicians, measured against specialist recommendations. Although CI provides useful recommendations, some have potential for harm. Future research should explore how to use CI to improve diagnosis while limiting harm from inappropriate tests/therapies.
Assessing Interventions That Prevent Multiple Infectious Diseases: Simple Methods for Multidisease Modeling
Authors: Claypool Anneke L. , Goldhaber-Fiebert Jeremy D. , Brandeau Margaret L. 
Published: August 2021

Background Many cost-effectiveness analyses (CEAs) only consider outcomes for a single disease when comparing interventions that prevent or treat 1 disease (e.g., vaccination) to interventions that prevent or treat multiple diseases (e.g., vector control to prevent mosquito-borne diseases). An intervention targeted to a single disease may be preferred to a broader intervention in a single-disease model, but this conclusion might change if outcomes from the additional diseases were included. However, multidisease models are often complex and difficult to construct. Methods We present conditions for when multiple diseases should be considered in such a CEA. We propose methods for estimating health outcomes and costs associated with control of additional diseases using parallel single-disease models. Parallel modeling can incorporate competing mortality and coinfection from multiple diseases while maintaining model simplicity. We illustrate our approach with a CEA that compares a dengue vaccine, a chikungunya vaccine, and mosquito control via insecticide and mosquito nets, which can prevent dengue, chikungunya, Zika, and yellow fever. Results The parallel models and the multidisease model generated similar estimates of disease incidence and deaths with much less complexity. When using this method in our case study, considering only chikungunya and dengue, the preferred strategy was insecticide. A broader strategy—insecticide plus long-lasting insecticide-treated nets—was not preferred when Zika and yellow fever were included, suggesting the conclusion is robust even without the explicit inclusion of all affected diseases. Limitations Parallel modeling assumes independent probabilities of infection for each disease. Conclusions When multidisease effects are important, our parallel modeling method can be used to model multiple diseases accurately while avoiding additional complexity.
Prevalence and Correlates of Suicidal Ideation and Deliberate Self-harm in Canadian Adolescents During the Coronavirus Disease 2019 Pandemic
Authors: Turner Brianna J. , Robillard Christina L. , Ames Megan E. , Craig Stephanie G. 
Published: August 2021

Objective In light of recent evidence that the coronavirus disease 2019 (COVID-19) pandemic has resulted in marked increases in depression, anxiety, substance use, and other mental health concerns among Canadian adolescents, we investigated the rates of self-harm thoughts and behaviours in this population. Specifically, this study explored: (1) the demographic and geographic distributions of suicidal ideation (SI) and deliberate self-harm (DSH), and (2) the associations of mental health and substance use with SI and DSH. Method A total of 809 Canadian adolescents, aged 12–18 years, completed an online survey between June 17, 2020 and July 31, 2020. Results 44% of adolescents reported experiencing SI since the pandemic began, while 32% reported engaging in DSH. SI and DSH were more common among youth who: identified as transgender, non-binary or gender fluid; who did not reside with both parents; and who reported psychiatric concerns or frequent cannabis use. Conclusion Canadian adolescents appear to be experiencing higher rates of self-harm thoughts and behaviours relative to before the COVID-19 pandemic. It is important for adults who are likely to interact with distressed youth to be aware of potential warning signs that a youth is struggling with self-harm, and to refer youth to specialty mental health services where appropriate.
Antibacterial properties of a novel nano-silver loaded poly(styrene-co-acrylic) composites
Authors: Cao Ruge , Zhai Xuqing , Li Xueyang , Zhao Xiaoyu 
Published: August 2021

To prevent microbial contamination in foods and medical tools, we prepared a novel antibacterial material nano-silver loaded poly(styrene-co-acrylic) (nAg-PSA) composites by in situ reductions. The nAg-PSA was characterized by scanning electron microscope, transmission electron microscopy, energy dispersive X-ray spectroscopy and thermogravimetric analysis. The antibacterial properties of nAg-PSA against Escherichia coli and Staphylococcus aureus were systematically evaluated, and the underlying mechanism was investigated. Results showed that the silver nanoparticles were successfully loaded onto PSA microspheres, highly dispersed on the surface of nAg-PSA nanoparticles. The nAg-PSA nanoparticles all showed significant antibacterial effects, among which nAg-PSA4 had maximum diameters of inhibition zones against the Gram-negative E. coli (1.18 mm) and the Gram-positive S. aureus (1.29 mm), respectively, which closely related to the size and density of silver nanoparticles covered on the surface.
Online and Intellectual Awareness of Executive Functioning in Daily Life among Adolescents with and without ADHD
Authors: Fisher Orit , Berger Itai , Grossman Ephraim S. , Maeir Adina 
Published: August 2021

Objective Executive function deficits (EFD) are a central mechanism underlying negative outcomes in ADHD. This study examined awareness of EFD manifested in “real-time” task performance (Online Awareness) and in general self-knowledge of daily activities, outside the context of a specific task (Intellectual Awareness) among adolescents with and without ADHD. Methods 102 adolescents with ( n = 52) and without ( n = 50) ADHD were administered Weekly Calendar Planning Activity (WCPA) and Behavior Rating Inventory of Executive Function (BRIEF). Parents completed the BRIEF parent version. Awareness was defined using the discrepancy paradigm: performance versus estimation on WCPA for online awareness; self versus parent report on the BRIEF for intellectual awareness. Results Adolescents with ADHD overestimated their performance on the WCPA and underestimated their EFD on the BRIEF compared to parent’s ratings. The discrepancy scores in both types of awareness were significantly larger among ADHD than controls ( p < .005). Conclusions Adolescents with ADHD demonstrate significantly lower rates of online and intellectual awareness of EFD compared to controls.
Screening of Glypican-6 Expression in Benign, Primary and Metastatic Colon Cancers
Authors: Al-Saraireh Yousef M , Alshammari Fatemah OFO , Youssef Ahmed MM , Al-Sarayreh Sameeh , Al-Sarayra Yahya M , Aborajooh Emad , Al-Shuneigat Jehad , Alrawashdeh Hamzeh M 
Published: August 2021

Background: The development of colon cancer has been described as a multistep process of carcinogenesis. Understanding molecular and cellular changes underlying this process is required to determine potential biomarkers and therapeutic targets in colon cancers. Several molecular entities, including glypicans, are implicated in cancer development. Among these is glypican-6, which is overexpressed in a limited number of cancers. This study aims to characterise the glypican-6 expression in different types of colon cancer. Methods: Immunohistochemistry was used to characterise glypican-6 expression in a panel of archived formalin-fixed, paraffin-embedded colon tissue types. These types included 39 normal colon tissues, 10 colon tubular adenomas, 60 colon adenocarcinomas without metastasis and 60 colon adenocarcinomas with metastasis. Glypican-6 expression relation to demographic and clinicopathologic features was also examined. Results: Glypican-6 was strongly expressed in benign, primary and metastatic colon tumours. Normal tissue samples exhibited low to undetectable levels of glypican-6. A significantly high glypican-6 expression was displayed in colon cancers with lymph node metastasis, high depth of invasion, distant metastasis, high histological grades and late stages of the disease ( P < 0.05). Importantly, a significant differential in glypican-6 expression was found between normal tissues and different types of colon cancer tissues. Moreover, the highest glypican-6 expression was more frequently found in metastatic tumours, followed by primary tumours and the least in benign tumours ( P < 0.05). Conclusions: Selective expression of glypican-6 may establish a basis for potential use as a tissue biomarker or as a novel therapeutic target in treatment of colon cancer.
Volume changes of thalamus, hippocampus and cerebellum are associated with specific CSF profile in MS
Authors: Bajrami Albulena , Magliozzi Roberta , Pisani Anna I , Pizzini Francesca B , Crescenzo Francesco , Marastoni Damiano , Calabrese Massimiliano 
Published: August 2021

Background: The underlying pathogenesis of surface-in grey matter abnormalities in MS, demonstrated by both neuropathology and advanced MRI analyses, is under investigation and it might be related to CSF-mediated mechanism of inflammation and/or damage. Objective: To examine the link of CSF inflammatory profile with the damage of three regions early-involved in MS and bordering with CSF: thalamus, hippocampus and cerebellum. Methods: In this longitudinal, prospective study, we evaluated, in 109 relapsing–remitting MS patients, at diagnosis and after 2-year follow-up, the association between the baseline CSF level of 19 inflammatory mediators and the volume changes of thalamus, hippocampus, cerebellar cortex and control regions (globus pallidus, putamen). Results: The multivariable analysis showed that the CXCL13 and sCD163 CSF levels at baseline were independent predictors of thalamus ([Formula: see text]; p < 0.001) and hippocampus ([Formula: see text]; p < 0.001) volume change after 2-year follow-up. These molecules, plus CCL25, IFN-γ and fibrinogen, were independent predictors of the cerebellar cortex volume loss ([Formula: see text]; p < 0.001). No independent predictors of volume changes of the control regions were found. Conclusion: Our results indicate an association between the CSF inflammatory profile and grey matter volume loss of regions anatomically close to CSF boundaries, thus supporting the hypothesis of a surface-in GM damage in MS.
Structural and functional hippocampal alterations in Multiple sclerosis and neuromyelitis optica spectrum disorder
Authors: Zheng Fenglian , Li Yuxin , Zhuo Zhizheng , Duan Yunyun , Cao Guanmei , Tian Decai , Zhang Xinghu , Li Kuncheng , Zhou Fuqing , Huang Muhua , Li Haiqing , Li Yongmei , Zeng Chun , Zhang Ningnannan , Sun Jie , Yu Chunshui , Han Xuemei , Hallar Sven , Barkhof Frederik , Liu Yaou 
Published: August 2021

Background: Hippocampal involvement may differ between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Objective: To investigate the morphometric, diffusion and functional alterations in hippocampus in MS and NMOSD and the clinical significance. Methods: A total of 752 participants including 236 MS, 236 NMOSD and 280 healthy controls (HC) were included in this retrospective multi-center study. The hippocampus and subfield volumes, fractional anisotropy (FA) and mean diffusivity (MD), amplitude of low frequency fluctuation (ALFF) and degree centrality (DC) were analyzed, and their associations with clinical variables were investigated. Results: The hippocampus showed significantly lower volume, FA and greater MD in MS compared to NMOSD and HC ( p < 0.05), while no abnormal ALFF or DC was identified in any group. Hippocampal subfields were affected in both diseases, though subiculum, presubiculum and fimbria showed significantly lower volume only in MS ( p < 0.05). Significant correlations between diffusion alterations, several subfield volumes and clinical variables were observed in both diseases, especially in MS ( R = −0.444 to 0.498, p < 0.05). FA and MD showed fair discriminative power between MS and HC, NMOSD and HC (AUC > 0.7). Conclusions: Hippocampal atrophy and diffusion abnormalities were identified in MS and NMOSD, partly explaining how clinical disability and cognitive impairment are differentially affected.
Impaired motion perception is associated with functional and structural visual pathway damage in multiple sclerosis and neuromyelitis optica spectrum disorders
Authors: Ayadi Noah , Oertel Frederike C , Asseyer Susanna , Rust Rebekka , Duchow Ankelien , Kuchling Joseph , Bellmann-Strobl Judith , Ruprecht Klemens , Klistorner Alexander , Brandt Alexander U , Paul Friedemann , Zimmermann Hanna G 
Published: August 2021

Background: Decreased motion perception has been suggested as a marker for visual pathway demyelination in optic neuritis (ON) and/or multiple sclerosis (MS). Objectives: To examine the influence of neuro-axonal damage on motion perception in MS and neuromyelitis optica spectrum disorders (NMOSD). Methods: We analysed motion perception with numbers-from-motion (NFM), visual acuity, (multifocal (mf)) VEP, optical coherence tomography in patients with MS ( n = 38, confirmatory cohort n = 43), NMOSD ( n = 13) and healthy controls ( n = 33). Results: NFM was lower compared with controls in MS ( B = −12.37, p < 0.001) and NMOSD ( B = −34.5, p < 0.001). NFM was lower in ON than in non-ON eyes ( B = −30.95, p = 0.041) in NMOSD, but not MS. In MS and NMOSD, lower NFM was associated with worse visual acuity ( B = −139.4, p < 0.001/ B = −77.2, p < 0.001) and low contrast letter acuity ( B = 0.99, p = 0.002/ B = 1.6, p < 0.001), thinner peripapillary retinal nerve fibre layer ( B = 1.0, p < 0.001/ B = 0.92, p = 0.016) and ganglion cell/inner plexiform layer ( B = 64.8, p < 0.001/ B = 79.5, p = 0.006), but not with VEP P100 latencies. In the confirmatory MS cohort, lower NFM was associated with thinner retinal nerve fibre layer ( B = 1.351, p < 0.001) and increased mfVEP P100 latencies ( B = −1.159, p < 0.001). Conclusions: Structural neuro-axonal visual pathway damage is an important driver of motion perception impairment in MS and NMOSD.
CONCERTO: A randomized, placebo-controlled trial of oral laquinimod in relapsing-remitting multiple sclerosis
Authors: Comi Giancarlo , Dadon Yuval , Sasson Nissim , Steinerman Joshua R , Knappertz Volker , Vollmer Timothy L , Boyko Alexey , Vermersch Patrick , Ziemssen Tjalf , Montalban Xavier , Lublin Fred D , Rocca Maria A , Volkinshtein Rita , Rubinchick Svetlana , Halevy Nitsan , Filippi Massimo 
Published: August 2021

Background: Interventions targeting the adaptive immune response are needed in multiple sclerosis (MS). Objective: Evaluate laquinimod’s efficacy, safety, and tolerability in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: CONCERTO was a randomized, double-blind, placebo-controlled, phase-3 study. RRMS patients were randomized 1:1:1 to receive once-daily oral laquinimod 0.6 or 1.2 mg or placebo for ⩽24 months ( n = 727, n = 732, and n = 740, respectively). Primary endpoint was time to 3-month confirmed disability progression (CDP). The laquinimod 1.2-mg dose arm was discontinued (1 January 2016) due to cardiovascular events at high doses. Safety was monitored throughout the study. Results: CONCERTO did not meet the primary endpoint of significant effect with laquinimod 0.6-mg versus placebo on 3-month CDP (hazard ratio: 0.94; 95% confidence interval: 0.67–1.31; p = 0.706). Secondary endpoint p values were nominal and non-inferential. Laquinimod 0.6 mg demonstrated 40% reduction in percent brain volume change from baseline to Month 15 versus placebo ( p < 0.0001). The other secondary endpoint, time to first relapse, and annualized relapse rate (an exploratory endpoint) were numerically lower (both, p = 0.0001). No unexpected safety findings were reported with laquinimod 0.6 mg. Conclusion: Laquinimod 0.6 mg demonstrated only nominally significant effects on clinical relapses and magnetic resonance imaging (MRI) outcomes and was generally well tolerated. Clinical trial registration number: ClinicalTrials.gov (NCT01707992).
White matter microstructural differences in children and genetic risk for multiple sclerosis: A population-based study
Authors: de Mol C Louk , Neuteboom Rinze F , Jansen Philip R , White Tonya 
Published: August 2021

Background: MS patients show abnormalities in white matter (WM) on brain imaging, with heterogeneity in the location of WM lesions. The “pothole” method can be applied to diffusion-weighted images to identify spatially distinct clusters of divergent brain WM microstructure. Objective: To investigate the association between genetic risk for MS and spatially independent clusters of decreased or increased fractional anisotropy (FA) in the brain. In addition, we studied sex- and age-related differences. Methods: 3 Tesla diffusion tensor imaging (DTI) data were collected in 8- to 12-year-old children from a population-based study. Global and tract-based potholes (lower FA clusters) and molehills (higher FA clusters) were quantified in 3047 participants with usable DTI data. A polygenic risk score (PRS) for MS was calculated in genotyped individuals ( n = 1087) and linear regression analyses assessed the relationship between the PRS and the number of potholes and molehills, correcting for multiple testing using the False Discovery Rate. Results: The number of molehills increased with age, potholes decreased with age, and fewer potholes were observed in girls during typical development. The MS-PRS was positively associated with the number of molehills (β = 0.9, SE = 0.29, p = 0.002). Molehills were found more often in the corpus callosum (β = 0.3, SE = 0.09, p = 0.0003). Conclusion: Genetic risk for MS is associated with spatially distinct clusters of increased FA during childhood brain development.
The Cancers-Specific Survival of Metastatic Pulmonary Carcinoids and Sites of Distant Metastasis: A Population-Based Study
Authors: Zhang Jiandong , Yu Qiongjie , He Yi , Hu Tingting , Chen Kun , Yang Zhihao , Zhang Xingbo , Cheng Dezhi , He Zhifeng 
Published: August 2021

Background: Lung cancer is the leading cause of cancer-related deaths and pulmonary carcinoids (PCs) account for almost 2% of all pulmonary malignancies. However, few published articles have reported prognosis and related factors of pulmonary carcinoid patients. Material and Method: The Surveillance, Epidemiology, and End Results (SEER) database was used to collect data of patients diagnosed with metastatic PCs from 2010 to 2016. The prognosis and survival of these patients were compared by employing Cox proportional hazards and the Kaplan-Meier survival analysis. Results: A total of 1763 patients were analyzed. The liver (668, 25.6%) was shown to be the most common metastatic site in the isolated organ metastasis cohort, followed by the lung (636, 24.4%), bone (562, 21.6%), and brain (460, 17.6%). Among the patients, the tumor metastasized to a single distant site included the liver, bone, lung, and brain. Cancer-specific survival (CSS) in metastatic PCs is determined by the site of metastasis and the total number of such sites. Pulmonary carcinoid patients with isolated liver metastasis manifested more favorable survival rates in comparison to patients having isolated metastasis in the lung, brain, or bone. The median CSS was 45, 7, 6, 5 months ( P = 0.011). The number of distant metastatic sites and the location of distant metastasis were found to be independent risk factors for CSS. For patients with distant isolated metastasis, liver metastasis ( P < 0.0001) had better CSS in comparison to those with bone metastasis. When compared to patients whose carcinoids had metastasized to the bones, patients with a brain ( P = 0.273) or lung ( P = 0.483) metastasis had the same CSS. Conclusion: Cancer-specific survival in metastatic PCs depends on the site of metastasis and the total number of such locations. PC patients with isolated liver metastasis manifested more favorable survival in comparison to patients with isolated metastasis in the lung, brain, or bone.
Idiopathic intracranial hypertension – a wider spectrum than headaches and blurred vision
Authors: Urbach H , Duman IE , Altenmüller DM , Fung C , Lützen N , Elsheikh S , Beck J 
Published: August 2021

Background The purpose of this study was to analyse less known clinical scenarios associated with idiopathic intracranial hypertension. Methods The study involved analysis of magnetic resonance imaging signs of idiopathic intracranial hypertension in patients with spontaneous rhinoliquorrhoea ( n = 7), in patients with temporal lobe epilepsy and surgically treated antero-inferior temporal lobe meningo-encephaloceles (n = 15), and in patients who developed clinical signs of idiopathic intracranial hypertension following the treatment of spontaneous intracranial hypotension ( n = 7). Results Three of six patients with spontaneous rhinoliquorrhoea and six of 15 operated patients with temporal lobe epilepsy due to temporal lobe meningo-encephaloceles showed magnetic resonance imaging signs of idiopathic intracranial hypertension and had a body mass index >30 kg/m2. Rebound high pressure headaches and sings of idiopathic intracranial hypertension occurred in seven of 44 surgically treated spontaneous intracranial hypotension patients. Conclusions Magnetic resonance imaging findings should guide the clinician to consider (idiopathic) intracranial hypertension when patients develop spontaneous rhinoliquorrhoea, temporal lobe epilepsy secondary to temporal lobe meningoencephaloceles or high pressure headaches in spontaneous intracranial hypotension. Whether idiopathic intracranial hypertension must be regarded as a differential diagnosis or as a cause, or whether there are common pathophysiological pathways that lead to signs of idiopathic intracranial hypertension in this wider spectrum of disease is the focus of further study.