bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of algorithms to identify individuals with Neurofibromatosis type 1 within administrative data and electronic medical records in Ontario, Canada
Authors: Barnett Carolina , Candido Elisa , Chen Branson , Pequeno Priscila , Parkin Patricia C. , Tu Karen 
Published: August 2022

AbstractBackgroundThere is limited population-based data on Neurofibromatosis type 1 (NF1) in North America. We aimed to develop and validate algorithms using administrative health data and electronic medical records (EMRs) to identify individuals with NF1 in Ontario, Canada.MethodsWe conducted an electronic free-text search of 15 commonly-used terms related to NF1 in the Electronic Medical Records Primary Care Database. Records were reviewed by two trained abstractors who classified them as confirmed, possible, and not NF1. An investigator with clinical expertise performed final NF1 classification. Patients were classified as confirmed if there was a documented diagnosis, meeting NIH criteria. Patients were classified as possible if (1) NF1 was recorded in the cumulative patient profile, but no clinical information to support the diagnosis; (2) only one criterion for diagnosis (e.g. child of confirmed case) but no further data to confirm or rule out. We tested different combinations of outpatient and inpatient billing codes, and applied a free-text search algorithm to identify NF1 cases in administrative data and EMRs, respectively.ResultsOf 273,440 eligible patients, 2,058 had one or more NF1 terms in their medical records. The terms “NF”, “café-au-lait”, or “sheath tumour” were constrained to appear in combination with another NF1 term. This resulted in 837 patients: 37 with possible and 71 with confirmed NF1. The population prevalence ranged from 1 in 3851 (confirmed NF1) to 1 in 2532 (possible and confirmed NF1). Billing code algorithms had poor performance, with overall low PPV (highest being 71%). The accuracy of the free-text EMR algorithm in identifying patients with NF1 was: sensitivity 85% (95% CI 74–92%), specificity 100% (95% CI 100–100%), positive predictive value 80% (95% CI 69–88%), negative predictive value 100% (95% CI 100–100%), and false positive rate 20% (95% CI 11–33%). Of false positives, 53% were possible NF1.ConclusionsA free-text search algorithm within the EMR had high sensitivity, specificity and predictive values. Algorithms using billing codes had poor performance, likely due to the lack of NF-specific codes for outpatient visits. While NF1 ICD-9 and 10 codes are used for hospital admissions, only ~ 30% of confirmed NF1 cases had a hospitalization associated with an NF1 code.
Increased serum IL-6 is predictive of long-term cardiovascular events in high-risk patients submitted to coronary angiography: an observational study
Authors: Mossmann Márcio , Wainstein Marco Vugman , Mariani Stéfani , Machado Guilherme Pinheiro , de Araújo Gustavo Neves , Andrades Michael , Gonçalves Sandro Cadaval , Bertoluci Marcello Casaccia 
Published: August 2022

Abstract
Background
Interleukin-6 (IL-6) is an inflammation-related cytokine associated with an elevated risk of cardiovascular events. In a previous study, we demonstrated that increased IL-6 was predictive of sub-clinical atherosclerotic coronary disease in intermediate-risk patients undergoing coronary angiography. In the present study, we investigated whether increased serum IL-6 is predictive of cardiovascular events in high-risk patients.

Methods
In this observational study, consecutive patients referred for elective coronary angiography due to stable chest pain/myocardial ischemia had IL-6 measured immediately before the procedure. Long-term follow-up was performed by phone call or e-mail, and their clinical registries were revised. The primary outcome was a composite of new myocardial infarction, new ischemic stroke, hospitalization due to heart failure, new coronary revascularization, cardiovascular death, and death due to all causes.

Results
From 141 patients submitted to coronary angiography and IL-6 analysis, 100 had complete follow-up data for a mean of 5.7 years. The median age was 61.1 years, 44% were men, and 61% had type-2 diabetes. The median overall time-to-event for the primary outcome was 297 weeks (95% confidence interval [CI] 266.95–327.16). A receiver operator characteristic curve defined the best cut-off value of baseline serum IL-6 (0.44 pg/mL) with sensitivity (84.37%) and specificity (38.24%) to define two groups. High (> 0.44 pg/mL) IL-6 levels were predictive of cardiovascular events. (p for interaction = 0.015) (hazard ratio = 2.81; 95% CI 1.38–5.72, p = 0.01). Subgroup analysis did not find interactions between patients with or without diabetes, obesity, or hypertension.

Conclusion
In conclusion, an interleukin-6 level higher than 0.44 pg/mL, obtained just before elective coronary angiography, was associated with a poorer prognosis after a mean of 5,7-year. A pre-procedure IL-6 below 0.44 pg/mL, on the other hand, has a very good negative predictive value, suggesting a good prognosis, and may be useful to better indicate coronary angiography in high-risk patients.
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Increased plasma and brain immunoglobulin A in Alzheimer’s disease is lost in apolipoprotein E ε4 carriers
Authors: Pocevičiūtė Dovilė , Nuñez-Diaz Cristina , Roth Bodil , Janelidze Shorena ,   The Netherlands Brain Bank, Giannisis Andreas , Hansson Oskar , Wennström Malin 
Published: August 2022

AbstractBackgroundAlzheimer’s disease (AD) is foremost characterized by β-amyloid (Aβ)-extracellular plaques, tau-intraneuronal fibrillary tangles (NFT), and neuroinflammation, but over the last years it has become evident that peripheral inflammation might also contribute to the disease. AD patients often demonstrate increased levels of circulating proinflammatory mediators and altered antibody levels in the blood. In our study, we investigated the plasma Immunoglobulin A (IgA) levels in association with apolipoprotein E (APOE)ε4status and Aβ pathology.MethodsIgA levels in antemortem-collected (cohort I) and postmortem-collected (cohort II) plasma samples from AD patients (n= 30 in cohort I andn= 16 in cohort II) and non-demented age-matched controls (NC) (n= 42 in cohort I andn= 7 in cohort II) were measured using ELISA. Hippocampal sections from cohort II were immunostained against IgA, and the IgA area fraction as well as the number of IgA positive (IgA+) cells in the cornu ammonis region were analysed using ImageJ. The relationship between plasma IgA levels and cognition, C-reactive protein (CRP), and cerebrospinal fluid (CSF) AD biomarkers in cohort I as well as neuropathology, IgA+ cell number, and IgA area fraction in cohort II was analysed before and after grouping the cohorts intoAPOEε4carriers andAPOEε4non-carriers.ResultsPlasma IgA levels were higher in AD patients compared to NC in both cohorts. Also, AD patients demonstrated higher IgA area fraction and IgA+ cell number compared to NC. WhenAPOEε4status was considered, higher plasma IgA levels in AD patients were only seen inAPOEε4non-carriers. Finally, plasma IgA levels, exclusively inAPOEε4non-carriers, were associated with cognition, CRP, and CSF Aβ levels in cohort I as well as with IgA area fraction, IgA+ cell number, and Aβ, Lewy body, and NFT neuropathology in cohort II.ConclusionsOur study suggests that AD pathology and cognitive decline are associated with increased plasma IgA levels in anAPOEallele-dependent manner, where the associations are lost inAPOEε4carriers.
Idiopathic remitting seronegative symmetrical synovitis with pitting edema syndrome mimicking symptoms of polymyalgia rheumatica: a case report
Authors: Tarasiuk-Stanislawek Katarzyna , Dumusc Alexandre , Favrat Bernard , Kokkinakis Ioannis 
Published: August 2022

Abstract
Background
Remitting seronegative symmetrical synovitis with pitting edema is a rare rheumatic condition of the elderly population that is well described but whose mechanisms remain little studied. This syndrome is characterized by symmetrical swelling located mainly on the dorsal part of the hands and the feet. Because of possible heterogeneous clinical presentation, it can easily mimic the onset of other rheumatic diseases or appear associated with them. Here we report a case of a patient who developed remitting seronegative symmetrical synovitis with pitting edema with preexisting shoulder and hip girdle pain associated with progressive fatigue, indicating a possible differential diagnosis of polymyalgia rheumatica. We reviewed and compared classification for remitting seronegative symmetrical synovitis with pitting edema and polymyalgia rheumatica and discussed other differential diagnoses.

Case presentation
An 84-year-old Caucasian woman presented to our General Medicine Unit with acute onset of symmetrical hands and feet edema, leading to functional limitation due to pain and stiffness. Additionally, she was complaining about neck, shoulder, and pelvic girdle pain present for about 2 months associated with worsening asthenia. Blood tests showed an elevated level of C-reactive protein and erythrocyte sedimentation rate, as well as absence of anti-cyclic citrullinated peptide antibodies and rheumatoid factor. As all criteria of remitting seronegative symmetrical synovitis with pitting edema syndrome were present, the patient was treated with low-dose prednisone, with a rapid and complete resolution of symptoms. She remains asymptomatic without treatment 2 years after the onset of symptoms, without any evident oncologic etiology.

Conclusions
This case is an example of a classic representation of remitting seronegative symmetrical synovitis with pitting edema syndrome with clinical elements suggesting a concomitant existing early stage of polymyalgia rheumatica. These two entities, classified in the group of seronegative arthritis, can coexist (up to 10% of cases), with remitting seronegative symmetrical synovitis with pitting edema appearing as an initial or late manifestation of polymyalgia rheumatica. It is essential to remind that remitting seronegative symmetrical synovitis with pitting edema is associated with a higher risk of cancer (30%). A proper diagnosis allows the clinician to precisely define the appropriate therapy duration to limit its side effects in the elderly and remain aware of the potential risk of underlying malignancy.
Include or not to include conference abstracts in systematic reviews? Lessons learned from a large Cochrane network meta-analysis including 585 trials
Authors: Hackenbroich Samantha , Kranke Peter , Meybohm Patrick , Weibel Stephanie 
Published: August 2022

Abstract
Background
Systematic reviews attempt to gather all available evidence. Controversy exists regarding effort and benefit of including study results presented at conferences only. We recently published a Cochrane network meta-analysis (NMA) including 585 randomized controlled trials comparing drugs for prevention of postoperative nausea and vomiting (PONV). Studies published as conference abstracts only were excluded. This study aimed to include all eligible studies published as abstracts only, assessing their added value regarding reporting quality and effect on the review’s interpretation.

Methods
Conference abstracts were searched in the review’s excluded studies and conference proceedings of anaesthesiologic societies. We assessed their reporting quality regarding review’s eligibility criteria, Cochrane ‘risk of bias’ assessment tool 1.0, and adherence to CONSORT (Consolidated Standards of Reporting Trials) for abstracts. Abstracts were included in sensitivity NMA, and impact on the NMA structure was investigated.

Results
We identified 90 abstracts. A total of 14% (13/90) were eligible. A total of 86% (77/90) are awaiting classification due to insufficient reporting of review’s eligibility criteria. In abstracts awaiting classification, sufficient information was missing on standardization of anaesthesia in 71% (55/77), age of participants in 56% (43/77), and outcome details in 46% (36/77). A total of 73% (66/90) of abstracts lacked sufficient information on 15/25 data extraction items. Reported study characteristics of abstracts were comparable to included studies of the review. A total of 62% (56/90) of abstract trials were assessed as overall high risk of bias due to poor reporting. Median adherence to CONSORT for abstracts was 24% (IQR, 18 to 29%). Six of the 13 eligible abstracts reported relevant outcome data in sufficient detail for NMA on seven outcomes of the Cochrane review. Inclusion of abstracts did not substantially change the network structure, network effect estimates, ranking of treatments, or the conclusion. Certainty of evidence for headache on palonosetron use was upgraded from very low to low.

Conclusions
Most conference abstracts on PONV were insufficiently reported regarding review’s narrow inclusion criteria and could not be included in NMA. The resource-intensive search and evaluation of abstracts did not substantially extent the full-text evidence base of the review, given the few adequately reported abstracts. Conferences should oblige authors to adhere to CONSORT for abstracts.
A global meta-analysis of woody plant responses to elevated CO2: implications on biomass, growth, leaf N content, photosynthesis and water relations
Authors: Mndela Mthunzi , Tjelele Julius T. , Madakadze Ignacio C. , Mangwane Mziwanda , Samuels Igshaan M. , Muller Francuois , Pule Hosia T. 
Published: August 2022

Abstract
Background
Atmospheric CO2 may double by the year 2100, thereby altering plant growth, photosynthesis, leaf nutrient contents and water relations. Specifically, atmospheric CO2 is currently 50% higher than pre-industrial levels and is projected to rise as high as 936 μmol mol−1 under worst-case scenario in 2100. The objective of the study was to investigate the effects of elevated CO2 on woody plant growth, production, photosynthetic characteristics, leaf N and water relations.

Methods
A meta-analysis of 611 observations from 100 peer-reviewed articles published from 1985 to 2021 was conducted. We selected articles in which elevated CO2 and ambient CO2 range from 600–1000 and 300–400 μmol mol−1, respectively. Elevated CO2 was categorized into < 700, 700 and > 700 μmol mol−1 concentrations.

Results
Total biomass increased similarly across the three elevated CO2 concentrations, with leguminous trees (LTs) investing more biomass to shoot, whereas non-leguminous trees (NLTs) invested to root production. Leaf area index, shoot height, and light-saturated photosynthesis (Amax) were unresponsive at < 700 μmol mol−1, but increased significantly at 700 and > 700 μmol mol−1. However, shoot biomass and Amax acclimatized as the duration of woody plants exposure to elevated CO2 increased. Maximum rate of photosynthetic Rubisco carboxylation (Vcmax) and apparent maximum rate of photosynthetic electron transport (Jmax) were downregulated. Elevated CO2 reduced stomatal conductance (gs) by 32% on average and increased water use efficiency by 34, 43 and 63% for < 700, 700 and > 700 μmol mol−1, respectively. Leaf N content decreased two times more in NLTs than LTs growing at elevated CO2 than ambient CO2.

Conclusions
Our results suggest that woody plants will benefit from elevated CO2 through increased photosynthetic rate, productivity and improved water status, but the responses will vary by woody plant traits and length of exposure to elevated CO2.
Regiospecific C–H amination of (−)-limonene into (−)-perillamine by multi-enzymatic cascade reactions
Authors: Ge Yue , Huang Zheng-Yu , Pan Jiang , Li Chun-Xiu , Zheng Gao-Wei , Xu Jian-He 
Published: August 2022

Abstract
Background
(−)-Limonene, one of cyclic monoterpenes, is an important renewable compound used widely as a key building block for the synthesis of new biologically active molecules and fine chemicals. (−)-Perillamine, as derived from (−)-limonene, is a highly useful synthon for constructing more complicated and functionally relevant chemicals.

Aim
We aimed to report a more sustainable and more efficient method for the regiospecific C–H amination of (−)-limonene into (−)-perillamine.

Results
Here, we report an artificial penta-enzymatic cascade system for the transformation of the cheap and easily available (−)-limonene into (−)-perillamine for the first time. This system is composed of cytochrome P450 monooxygenase, alcohol dehydrogenase and w-transaminase for the main reactions, as well as formate dehydrogenase and NADH oxidase for cofactor recycling. After optimization of the multi-enzymatic cascade system, 10 mM (−)-limonene was smoothly converted into 5.4 mM (−)-perillamine in a one-pot two-step biotransformation, indicating the feasibility of multi-enzymatic C7-regiospecific amination of the inert C–H bond of (−)-limonene. This method represents a concise and efficient route for the biocatalytic synthesis of derivatives from similar natural products.
Improved accuracy of S-value-based dosimetry: a guide to transition from Cristy–Eckerman to ICRP adult phantoms
Authors: Subramanian Shalini , He Bin , Frey Eric , Jokisch Derek W. , Bolch Wesley , Sgouros George 
Published: August 2022

AbstractBackgroundIn 2016, the International Commission on Radiological Protection (ICRP) published the results of Monte Carlo simulations performed using updated and anatomically realistic voxelized phantoms. The resulting specific absorbed fractions are based on more realistic human anatomy than those computed in the stylized, geometrical Cristy–Eckerman (CE) phantom. Despite this development, the ICRP-absorbed fractions have not been widely adopted for radiopharmaceutical dosimetry. To help make the transition, we have established a correspondence between source and target tissues defined in the CE phantom and those defined in the ICRP phantoms.ResultsThe ICRP phantom has 79 source regions and 43 target regions in comparison with the 23 source and 18 target tissue regions defined in the CE phantom. The ICRP phantom provides tissue regions with greater anatomical detail. Some of this additional detail is focused on radiation protection and dosimetry of inhaled/ingested radioactivity. Some, but not all, of this detail is useful and appropriate for radiopharmaceutical therapy. We have established the correspondence between CE and ICRP phantom source and target regions and attempted to highlight the ICRP source tissues relevant to radiopharmaceutical therapy (RPT). This paper provides tables and figures highlighting the correspondences established.ConclusionThe results provide assistance in transitioning from CE-stylized phantoms to the anatomically accurate voxelized ICRP phantoms. It provides specific guidance for porting the total absorbed activity for regions as defined in the CE phantom to regions within the ICRP phantoms.
Development of a cypovirus protein microcrystal-encapsulated Bacillus thuringiensis UV-tolerant and mosquitocidal δ-endotoxin
Authors: Ibuki Takumi , Iwasawa Satoshi , Lian Ai Ai , Lye Ping Ying , Maruta Rina , Asano Shin-ichiro , Kotani Eiji , Mori Hajime 
Published: August 2022

Abstract
The δ-endotoxin Cry4Aa from Bacillus thuringiensis israelensis (Bti) has insecticidal characteristics specific to insects of the order Diptera. Although Cry4Aa has shown potential as an effective proteinaceous pesticide against mosquitoes, it has an ultraviolet (UV)-intolerant property that limits its outdoor use. Our previous research showed that protein microcrystal polyhedra from Bombyx mori cypovirus can encapsulate diverse foreign proteins and maintain long-term protein activity under hostile environmental conditions, including UV irradiation. In this study, we report the development of polyhedra encapsulating the Cry4Aa insecticidal activity domain by using a modified baculovirus expression system. We confirmed the oral intake of recombinant polyhedra introduced into the experimental environment by the larvae of a mosquito, Aedes albopictus, and delivery of encapsulated proteins into the digestive tract. The polyhedra encapsulating partial Cry4Aa showed mosquito larvicidal activity during incubation of larvae with 50% lethal-dose value of 23.717×104 cubes for 10 Aedes albopictus larvae in 1 ml water. In addition, polyhedra showed a specific property to reduce the impact of UV-C irradiation on the activity of encapsulated partial Cry4Aa, thus demonstrating the effectiveness of encapsulating Bti δ-endotoxins inside polyhedra to increase the availability of proteinaceous pesticides for outdoor use for mosquito control.
Automated morphologic analysis of intracranial and extracranial arteries using convolutional neural networks
Authors: Wan Liwen , Li Haoxiang , Zhang Lei , Su Shi , Wang Cheng , Zhang Baochang , Liang Dong , Zheng Hairong , Liu Xin , Zhang Na 
Published: August 2022

Objective: To develop an automated method for 3D magnetic resonance (MR) vessel wall image analysis to facilitate morphologic quantification of intra- and extracranial arteries, including vessel centerline tracking, vessel straightening and reformation, vessel wall segmentation based on convoluted neural networks (CNNs), and morphological measurement. Methods: MR vessel wall images acquired using DANTE-SPACE sequences and corresponding time-of-flight-MRA images of 67 subjects (including 47 healthy volunteers and 20 patients with atherosclerosis) were included in this study. The centerline of the vessel was firstly extracted from the MRA images and copyed to the 3D MR vessel wall images through the registration relationship between the MRA images and the MR vessel wall images to extract, straighten, and reconstruct interested vessel segments into 2D slices. Then a complete CNN-based Unet-like method was used to automatically segment the vessel wall to obtain quantitative morphological measurements such as maximum wall thicknesses and normalized wall index (NWI). Results: The proposed automatic segmentation network was trained and validated with 11,735 slices and tested on 2517 slices. The method showed satisfactory agreement with manual segmentation method. The Dice coefficients of intracranial arteries were 0.90 for lumen and 0.78 for vessel wall, while the Dice coefficients of extracranial arteries were 0.90 for lumen and 0.82 for vessel wall. The maximum wall thickness and NWI obtained from the proposed automatic method were slightly larger than those obtained from the manual method for both intra- and extracranial arteries. However, there was no significant difference of the quantitative measurements between the two methods (p > 0.05). In addition, the automatically measured NWI of plaque slice was significantly larger than that of normal slice. Conclusion: We propose an automatic analysis method of MR vessel wall images, which can realize automatic segmentation of intra- and extracranial vessel wall. It is expected to facilitate large-scale arterial vessel wall morphological quantification. Advances in knowledge: We have proposed an automatic method for analysis of intra- and extracranial MR vessel wall images simultaneously based on CNN, which can facilitate large-scale quantitative analyses of vessel walls.