bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized trial to evaluate the impact of Singapore’s forthcoming Nutri-grade front-of-pack beverage label on food and beverage purchases
Authors: Shin Soye , Puri Jyotika , Finkelstein Eric 
Published: February 2023

Abstract
Background
The epidemic of non-communicable diseases (NCDs) is a growing concern worldwide and Singapore is no exception to this global trend. As part of measures to address this concern, the Singapore government will implement a mandatory color-coded front-of-package (FOP) nutrition label for beverages, called Nutri-Grade (NG), which will complement the existing FOP label, Healthier Choice Symbol (HCS) logos, currently displayed on select food and beverage items. NG grades beverages on a four-point scale, A (healthiest) to D (least healthy), in terms of sugar and saturated fat levels. This study aimed to evaluate the effectiveness of the NG label on nutritional quality of pre-packaged beverages using a fully functional online grocery store.

Methods
We conducted a 2-arm crossover trial involving actual purchases with 138 participants randomly exposed to: 1) Control with HCS logos displayed on qualifying items; 2) Similar to Control except that all beverages displayed the NG label. The effects of the NG label were estimated using a linear mixed-effects model that addresses correlations between repeated measures and accommodates missing data.

Results
We found that the NG label encouraged consumers to choose beverages with higher ratings. This led to a reduction in sugar from beverages purchased by 1.51 g [95% CI: − 2.68, − 0.34] per serving but was not effective at reducing saturated fat purchased (− 0.009 g [95% CI: − 0.22, 0.20]) per serving or improvements in overall diet quality, measured by the weighted (by the number of servings) average Nutri-Score value ranging from 1 to 5 (− 0.024 [95% CI: − 0.13, 0.08]).

Conclusions
Results suggest that the Nutri-Grade label is likely to reduce sugar purchased from beverages. However, to improve overall diet quality in Singapore, additional measures will be needed.

Trial registration
This trial was registered on ClinicalTrials.gov under the identifier: NCT05018026 on 24th August 2021.
Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration
Authors: Khachigian Levon M. , Liew Gerald , Teo Kelvin Y. C. , Wong Tien Y. , Mitchell Paul 
Published: February 2023

AbstractNeovascular age-related macular degeneration (nAMD) is a major cause of visual impairment and blindness. Anti-vascular endothelial growth factor (VEGF) agents, such as ranibizumab, bevacizumab, aflibercept, brolucizumab and faricimab have revolutionized the clinical management of nAMD. However, there remains an unmet clinical need for new and improved therapies for nAMD, since many patients do not respond optimally, may lose response over time or exhibit sub-optimal durability, impacting on real world effectiveness. Evidence is emerging that targeting VEGF-A alone, as most agents have done until recently, may be insufficient and agents that target multiple pathways (e.g., aflibercept, faricimab and others in development) may be more efficacious. This article reviews issues and limitations that have arisen from the use of existing anti-VEGF agents, and argues that the future may lie in multi-targeted therapies including alternative agents and modalities that target both the VEGF ligand/receptor system as well as other pathways.
Predicting later categories of upper limb activity from earlier clinical assessments following stroke: an exploratory analysis
Authors: Barth Jessica , Lohse Keith R. , Bland Marghuretta D. , Lang Catherine E. 
Published: February 2023

Abstract
Background
Accelerometers allow for direct measurement of upper limb (UL) activity. Recently, multi-dimensional categories of UL performance have been formed to provide a more complete measure of UL use in daily life. Prediction of motor outcomes after stroke have tremendous clinical utility and a next step is to explore what factors might predict someone’s subsequent UL performance category.

Purpose
To explore how different machine learning techniques can be used to understand how clinical measures and participant demographics captured early after stroke are associated with the subsequent UL performance categories.

Methods
This study analyzed data from two time points from a previous cohort (n = 54). Data used was participant characteristics and clinical measures from early after stroke and a previously established category of UL performance at a later post stroke time point. Different machine learning techniques (a single decision tree, bagged trees, and random forests) were used to build predictive models with different input variables. Model performance was quantified with the explanatory power (in-sample accuracy), predictive power (out-of-bag estimate of error), and variable importance.

Results
A total of seven models were built, including one single decision tree, three bagged trees, and three random forests. Measures of UL impairment and capacity were the most important predictors of the subsequent UL performance category, regardless of the machine learning algorithm used. Other non-motor clinical measures emerged as key predictors, while participant demographics predictors (with the exception of age) were generally less important across the models. Models built with the bagging algorithms outperformed the single decision tree for in-sample accuracy (26–30% better classification) but had only modest cross-validation accuracy (48–55% out of bag classification).

Conclusions
UL clinical measures were the most important predictors of the subsequent UL performance category in this exploratory analysis regardless of the machine learning algorithm used. Interestingly, cognitive and affective measures emerged as important predictors when the number of input variables was expanded. These results reinforce that UL performance, in vivo, is not a simple product of body functions nor the capacity for movement, instead being a complex phenomenon dependent on many physiological and psychological factors. Utilizing machine learning, this exploratory analysis is a productive step toward the prediction of UL performance.
Trial registration NA
The detectable anti-interferon-γ autoantibodies in COVID-19 patients may be associated with disease severity
Authors: Chen Po-Ku , Yeo Kai-Jieh , Chang Shih-Hsin , Liao Tsai-Ling , Chou Chia-Hui , Lan Joung-Liang , Chang Ching-Kun , Chen Der-Yuan 
Published: February 2023

Abstract
Background
Neutralizing anti-interferon (IFN)-γ autoantibodies are linked to adult-onset immunodeficiency and opportunistic infections.

Methods
To explore whether anti-IFN-γ autoantibodies are associated with disease severity of coronavirus disease 2019 (COVID-19), we examined the titers and functional neutralization of anti-IFN-γ autoantibodies in COVID-19 patients. In 127 COVID-19 patients and 22 healthy controls, serum titers of anti-IFN-γ autoantibodies were quantified using enzyme-linked immunosorbent assay, and the presence of autoantibodies was verified with immunoblotting assay. The neutralizing capacity against IFN-γ was evaluated with flow cytometry analysis and immunoblotting, and serum cytokines levels were determined using the MULTIPLEX platform.

Results
A higher proportion of severe/critical COVID-19 patients had positivity for anti-IFN-γ autoantibodies (18.0%) compared with non-severe patients (3.4%, p < 0.01) or healthy control (HC) (0.0%, p < 0.05). Severe/critical COVID-19 patients also had higher median titers of anti-IFN-γ autoantibodies (5.01) compared with non-severe patients (1.33) or HC (0.44). The immunoblotting assay could verify the detectable anti-IFN-γ autoantibodies and revealed more effective inhibition of signal transducer and activator of transcription (STAT1) phosphorylation on THP-1 cells treated with serum samples from anti-IFN-γ autoantibodies-positive patients compared with those from HC (2.21 ± 0.33 versus 4.47 ± 1.64, p < 0.05). In flow-cytometry analysis, sera from autoantibodies-positive patients could also significantly more effectively suppress the STAT1 phosphorylation (median,67.28%, interquartile range [IQR] 55.2–78.0%) compared with serum from HC (median,106.7%, IQR 100.0–117.8%, p < 0.05) or autoantibodies-negative patients (median,105.9%, IQR 85.5–116.3%, p < 0.05). Multivariate analysis revealed that the positivity and titers of anti-IFN-γ autoantibodies were significant predictors of severe/critical COVID-19. Compared with non-severe COVID-19 patients, we reveal that a significantly higher proportion of severe/critical COVID-19 patients are positive for anti-IFN-γ autoantibodies with neutralizing capacity.

Conclusion
Our results would add COVID-19 to the list of diseases with the presence of neutralizing anti-IFN-γ autoAbs. Anti-IFN-γ autoantibodies positivity is a potential predictor of severe/critical COVID-19.
Effect of a suitable treatment period on the genetic transformation efficiency of the plant leaf disc method
Authors: Xia Yufei , Cao Yuan , Ren Yongyu , Ling Aoyu , Du Kang , Li Yun , Yang Jun , Kang Xiangyang 
Published: February 2023

Abstract
Background
Agrobacterium tumefaciens-mediated leaf disc genetic transformation is an important way to achieve transgenics or gene editing. Ensuring stable and efficient genetic transformation is still an important problem in modern biology. It is assumed that the difference in the development status of genetic transformation cells of receptor materials is the main reason for the difference and instability of genetic transformation efficiency; the stable and efficient genetic transformation rate can be obtained by defining the appropriate treatment period of the receptor material and applying genetic transformation in a timely manner.

Results
Based on these assumptions, we studied and established an efficient and stable Agrobacterium-mediated plant transformation system with hybrid poplar (Populus alba × Populus glandulosa, 84 K) leaves, stem segments and tobacco leaves as the research objects. There were differences in the development process of leaf bud primordial cells from different explants, and the genetic transformation efficiency was significantly related to the cell development stage of the in vitro cultured materials. Among them, the genetic transformation rate of poplar and tobacco leaves was the highest on the 3rd and 2nd day of culture, reaching 86.6% and 57.3%, respectively. The genetic transformation rate of poplar stem segments was the highest on the 4th day of culture, reaching 77.8%. The best treatment period was from the development of leaf bud primordial cells to the S phase of the cell cycle. The number of cells detected using flow cytometry and 5-ethynyl-2ʹ-deoxyuridine (EdU) staining, the expression of cell cycle-related protein CDKB1; 2, CDKD1; 1, CYCA3; 4, CYCD1; 1, CYCD3; 2, CYCD6; 1, and CYCH; 1 of explants, and morphological changes of explants can be used as indicators to determine the appropriate treatment period for genetic transformation.

Conclusions
Our study provides a new and universal set of methods and characteristics to identify the S phase of the cell cycle and apply genetic transformation treatments at the appropriate time. Our results are of great significance for improving the efficiency and stability of plant leaf disc genetic transformation.
Characteristics of subsequent contralateral proximal femoral fracture: more convenient access is needed to treat osteoporosis
Authors: Jiang Yuxuan , Zhu Yangjun , Zhang Binfei , Feng Dongxu 
Published: February 2023

Abstract
Background
Patients with proximal femoral fracture (PFF) have high mortality and many complications. Osteoporosis increases the risk of subsequent fractures, leading to subsequent contralateral PFF. This study was performed to analyze the features of individuals with subsequent PFF following surgical therapy of first PFF and to ascertain whether such patients received an examination or treatment of osteoporosis. The reasons for lack of examination or treatment were also analyzed.

Methods
This retrospective study involved 181 patients with subsequent contralateral PFF who underwent surgical treatment in Xi'an Honghui hospital from September 2012 to October 2021. The patients’ sex, age, hospital day, mechanism of injury, surgical procedure, fracture interval, fracture type, fracture classification, and Singh index of the contralateral hip at the time of the initial and subsequent fractures were recorded. Whether the patients took calcium and vitamin D supplements, used anti-osteoporosis medication, or underwent a dual X-ray absorptiometry (DXA) scan was recorded, as was the start time of each. Patients who had never undergone a DXA scan or received anti-osteoporosis medication took part in a questionnaire.

Results
The 181 patients in this study comprised 60 (33.1%) men and 121 (66.9%) women. Patients with initial PFF and subsequent contralateral PFF had a median age of 80 years (range 49–96 years) and 82 years (range 52–96 years), respectively. The median fracture interval was 24 (7–36) months. Contralateral fractures occurred at the highest incidence between 3 months and 1 year (28.7%). The Singh index was not significantly different between the two fractures. In 130 (71.8%) patients, the fracture type was the same. No significant difference was found in the fracture type or fracture stability classification. A total of 144 (79.6%) patients had never received a DXA scan or anti-osteoporosis medication. The main reason for not treating osteoporosis further was concern about the safety of drug interactions (67.4%).

Conclusions
Patients with subsequent contralateral PFF were of advanced age, had a higher proportion of intertrochanteric femoral fractures, had more severe osteoporosis, and had longer hospital stays. The difficulty managing such patients requires multidisciplinary involvement. Most of these patients were not screened or formally treated for osteoporosis. Advanced-age patients with osteoporosis need reasonable treatment and management.
Tracheobronchial tooth and dental prosthesis aspirations: 15 cases
Authors: Eliçora Aykut , Sezer Hüseyin Fatih , Topçu Salih , Çardaközü Tülay 
Published: February 2023

Abstract
Background
Tracheobronchial foreign body is uncommon in adults. Among foreign body aspirations, tooth and dental prosthesis aspiration is a very rare condition. In the literature, dental aspiration is generally found as a case report and there is no single-center case series. In this study, we aimed to present our clinical experience in 15 cases with tooth and dental prosthesis aspiration.

Methods
Data from 693 patients who presented to our hospital for foreign body aspiration between the years 2006 and 2022 were analyzed retrospectively. Fifteen cases who aspirated tooth and dental prostheses as foreign bodies were included in our study.

Results
Foreign bodies were removed by rigid bronchoscopy in 12 (80%) cases and fiberoptic bronchoscopy in 2 (13.3%) cases. In one of our cases, foreign body was expected with cough.When evaluated in terms of foreign body, partial upper anterior tooth prosthesis in 5 (33.3%) cases, partial anterior lower tooth prosthesis in 2 (13.3%) cases, dental implant screw in 2 (13.3%) cases, lower molar crown in 1 (6.6%) case, lower jaw bridge prosthesis in 1(6.6%) case, upper jaw bridge prosthesis in 1(6.6%) case, broken tooth fragment in 1(6.6%) case, upper molar tooth crown coating in 1(6.6%) case and upper lateral incisor tooth in 1(6.6%) case were observed.

Conclusion
Dental aspirations can also occur in healthy adults. Anamnesis is the most important factor in diagnosis and diagnostic bronchoscopic procedures should be performed in cases where adequate anamnesis cannot be obtained.
Contraction of human brain vascular pericytes in response to islet amyloid polypeptide is reversed by pramlintide
Authors: Nuñez-Diaz Cristina , Pocevičiūtė Dovilė , Schultz Nina ,   The Netherlands Brain Bank, Welinder Charlotte , Swärd Karl , Wennström Malin 
Published: February 2023

AbstractThe islet amyloid polypeptide (IAPP), a pancreas-produced peptide, has beneficial functions in its monomeric form. However, IAPP aggregates, related to type 2 diabetes mellitus (T2DM), are toxic not only for the pancreas, but also for the brain. In the latter, IAPP is often found in vessels, where it is highly toxic for pericytes, mural cells that have contractile properties and regulate capillary blood flow. In the current study, we use a microvasculature model, where human brain vascular pericytes (HBVP) are co-cultured together with human cerebral microvascular endothelial cells, to demonstrate that IAPP oligomers (oIAPP) alter the morphology and contractility of HBVP. Contraction and relaxation of HBVP was verified using the vasoconstrictor sphingosine-1-phosphate (S1P) and vasodilator Y27632, where the former increased, and the latter decreased, the number of HBVP with round morphology. Increased number of round HBVP was also seen after oIAPP stimulation, and the effect was reverted by the IAPP analogue pramlintide, Y27632, and the myosin inhibitor blebbistatin. Inhibition of the IAPP receptor with the antagonist AC187 only reverted IAPP effects partially. Finally, we demonstrate by immunostaining of human brain tissue against laminin that individuals with high amount of brain IAPP levels show significantly lower capillary diameter and altered mural cell morphology compared to individuals with low brain IAPP levels. These results indicate that HBVP, in an in vitro model of microvasculature, respond morphologically to vasoconstrictors, dilators, and myosin inhibitors. They also suggest that oIAPP induces contraction of these mural cells and that pramlintide can reverse such contraction.
FixItFelix: improving genomic analysis by fixing reference errors
Authors: Behera Sairam , LeFaive Jonathon , Orchard Peter , Mahmoud Medhat , Paulin Luis F. , Farek Jesse , Soto Daniela C. , Parker Stephen C. J. , Smith Albert V. , Dennis Megan Y. , Zook Justin M. , Sedlazeck Fritz J. 
Published: February 2023

AbstractThe current version of the human reference genome, GRCh38, contains a number of errors including 1.2 Mbp of falsely duplicated and 8.04 Mbp of collapsed regions. These errors impact the variant calling of 33 protein-coding genes, including 12 with medical relevance. Here, we present FixItFelix, an efficient remapping approach, together with a modified version of the GRCh38 reference genome that improves the subsequent analysis across these genes within minutes for an existing alignment file while maintaining the same coordinates. We showcase these improvements over multi-ethnic control samples, demonstrating improvements for population variant calling as well as eQTL studies.
Effects of N-acetylcysteine on systemic lupus erythematosus disease activity and its associated complications: a randomized double-blind clinical trial study
Authors: Abbasifard Mitra , Khorramdelazad Hossein , Rostamian Abdolrahman , Rezaian Mohsen , Askari Pooya Saeed , Sharifi Gholamhosein Taghipur Khajeh , Parizi Moein Kardoust , Sharifi Mobina Taghipour Khajeh , Najafizadeh Seyed Reza 
Published: February 2023

Abstract
Backgrounds
N-acetylcysteine (NAC) has broadly been used as an anti-oxidant agent in various types of diseases. This study aimed to assess the effect of NAC on the systemic lupus erythematosus (SLE) disease activity and outcome.

Methods
In this randomized, double-blind clinical trial study, 80 SLE patients were recruited that were classified into two groups: 40 patients received NAC (1800 mg/day; 3 times per day with 8-h intervals) for 3 months and 40 patients as the control group received normal therapies. Laboratory measurements and disease activity based on the British Isles Lupus Assessment Group (BILAG) and SLE Disease Activity Index (SLEDAI) were determined before the initiation of treatment and after the study time period.

Results
A statistically significant decrease in BILAG (P= 0.023) and SLEDAI (P= 0.034) scores after receiving NAC for a 3-month period was observed. BILAG (P= 0.021) and SLEDAI (P= 0.030) scores were significantly lower in NAC-receiving patients compared to the control group after 3 months. The disease activity in each organ based on BILAG score after treatment indicated a significant decrease in the NAC group compared to the baseline level in general (P=0.018), mucocutaneous (P=0.003), neurological (P=0.015), musculoskeletal (P=0.048), cardiorespiratory (P=0.047), renal (P=0.025), and vascular (P=0.048) complications. Analysis indicated a significant increase in CH50 level in the NAC group after treatment compared to the baseline level (P=0.049). No adverse event was reported by the study subjects.

Conclusions
It appears that the administration of 1800 mg/day NAC to SLE patients can decrease the SLE disease activity and its complications.
Analysis of computer-aided diagnostics in the preoperative diagnosis of ovarian cancer: a systematic review
Authors: Koch Anna H. , Jeelof Lara S. , Muntinga Caroline L. P. , Gootzen T. A. , van de Kruis Nienke M. A. , Nederend Joost , Boers Tim , van der Sommen Fons , Piek Jurgen M. J. 
Published: February 2023

Abstract
Objectives
Different noninvasive imaging methods to predict the chance of malignancy of ovarian tumors are available. However, their predictive value is limited due to subjectivity of the reviewer. Therefore, more objective prediction models are needed. Computer-aided diagnostics (CAD) could be such a model, since it lacks bias that comes with currently used models. In this study, we evaluated the available data on CAD in predicting the chance of malignancy of ovarian tumors.

Methods
We searched for all published studies investigating diagnostic accuracy of CAD based on ultrasound, CT and MRI in pre-surgical patients with an ovarian tumor compared to reference standards.

Results
In thirty-one included studies, extracted features from three different imaging techniques were used in different mathematical models. All studies assessed CAD based on machine learning on ultrasound, CT scan and MRI scan images. Per imaging method, subsequently ultrasound, CT and MRI, sensitivities ranged from 40.3 to 100%; 84.6–100% and 66.7–100% and specificities ranged from 76.3–100%; 69–100% and 77.8–100%. Results could not be pooled, due to broad heterogeneity. Although the majority of studies report high performances, they are at considerable risk of overfitting due to the absence of an independent test set.

Conclusion
Based on this literature review, different CAD for ultrasound, CT scans and MRI scans seem promising to aid physicians in assessing ovarian tumors through their objective and potentially cost-effective character. However, performance should be evaluated per imaging technique. Prospective and larger datasets with external validation are desired to make their results generalizable.