bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison Between Manual and Automated Analyses in Multichannel Intraluminal Impedance: pH Monitoring for Laryngopharyngeal Reflux
Authors: Kang Hee Jin , Park Jung Min , Choi Soo Young , Kim Su Il , Lee Young Chan , Eun Young‐Gyu , Ko Seong‐Gyu 
Published: April 2021

ObjectiveTo evaluate differences between manual and automated analyses of 24‐hour multichannel intraluminal impedance–pH monitoring for diagnosis of laryngopharyngeal reflux.Study DesignCase series with planned data collection.SettingAcademic center outpatient clinic.MethodsThe study group comprised 127 patients with symptoms suspicious of laryngopharyngeal reflux, who underwent 24‐hour multichannel intraluminal impedance–pH monitoring. Automated and manual analyses were performed for each patient. The following parameters were compared between analyses: number of proximal reflux episodes, proximal exposure time, symptom index, and symptom association probability.ResultsThe number of proximal reflux episodes detected by manual analysis was significantly lower than that detected by automated analysis, except in acid reflux cases. The false positive of automated analysis was 39.8%. In addition, the proximal exposure time for manual analysis was significantly lower than that for automated analysis, except in cases of acid reflux. Symptom index and symptom association probability values based on manual analysis were significantly lower than in automated analysis, except in heartburn cases.ConclusionsAutomated analysis demonstrated a tendency of excessive reflux measurement when compared with manual analysis. It is necessary to increase the accuracy of laryngopharyngeal reflux diagnosis through manual analysis.
The pathophysiology of “happy” hypoglycemia
Authors: Loeb Thomas , Ozguler Anna , Baer Geraldine , Baer Michel 
Published: April 2021

Abstract
Background
Hypoglycemia usually includes various neurological symptoms, which are the consequence of neuroglycopenia. When it is severe, it is associated with altered mental status, even coma.

Case presentation
We report the case of a patient with severe hypoglycemia, completely asymptomatic, due to the increase of lactate production in response to tissue hypoperfusion following a hemorrhagic shock. This illustrates that lactate can substitute glucose as an energy substrate for the brain. It is also a reminder that this metabolite, despite its bad reputation maintained by its role as a marker of severity in critical care patients, has a fundamental role in our metabolism.

Conclusions
Following the example of the “happy hypoxemia” recently reported in the literature describing asymptomatic hypoxemia in COVID-19 patients, we describe a case of “happy hypoglycemia.”
A systematic review to identify biomarkers of intake for fermented food products
Authors: Li Katherine J. , Brouwer-Brolsma Elske M. , Burton-Pimentel Kathryn J. , Vergères Guy , Feskens Edith J. M. 
Published: April 2021

Abstract
Background
Fermented foods are ubiquitous in human diets and often lauded for their sensory, nutritious, and health-promoting qualities. However, precise associations between the intake of fermented foods and health have not been well-established. This is in part due to the limitations of current dietary assessment tools that rely on subjective reporting, making them prone to memory-related errors and reporting bias. The identification of food intake biomarkers (FIBs) bypasses this challenge by providing an objective measure of intake. Despite numerous studies reporting on FIBs for various types of fermented foods and drinks, unique biomarkers associated with the fermentation process (“fermentation-dependent” biomarkers) have not been well documented. We therefore conducted a comprehensive, systematic review of the literature to identify biomarkers of fermented foods commonly consumed in diets across the world.

Results
After title, abstract, and full-text screening, extraction of data from 301 articles resulted in an extensive list of compounds that were detected in human biofluids following the consumption of various fermented foods, with the majority of articles focusing on coffee (69), wine (69 articles), cocoa (62), beer (34), and bread (29). The identified compounds from all included papers were consolidated and sorted into FIBs proposed for a specific food, for a food group, or for the fermentation process. Alongside food-specific markers (e.g., trigonelline for coffee), and food-group markers (e.g., pentadecanoic acid for dairy intake), several fermentation-dependent markers were revealed. These comprised compounds related to the fermentation process of a particular food, such as mannitol (wine), 2-ethylmalate (beer), methionine (sourdough bread, cheese), theabrownins (tea), and gallic acid (tea, wine), while others were indicative of more general fermentation processes (e.g., ethanol from alcoholic fermentation, 3-phenyllactic acid from lactic fermentation).

Conclusions
Fermented foods comprise a heterogeneous group of foods. While many of the candidate FIBs identified were found to be non-specific, greater specificity may be observed when considering a combination of compounds identified for individual fermented foods, food groups, and from fermentation processes. Future studies that focus on how fermentation impacts the composition and nutritional quality of food substrates could help to identify novel biomarkers of fermented food intake.
Hydrological and biogeochemical controls on temporal variations of dissolved carbon and solutes in a karst river, South China
Authors: Liu Jing , Zhong Jun , Chen Shuai , Xu Sen , Li Si-Liang 
Published: April 2021

Abstract
Background
Understanding the responses of riverine dissolved carbon dynamics and chemical weathering processes to short-term climatic variabilities is important to understand the Surface-Earth processes under ongoing climate change. Temporal variations of solutes and stable carbon isotope of dissolved inorganic carbon (δ13CDIC) were analysed during a hydrological year in the Guijiang River, South China. We aimed to unravel the chemical weathering processes and carbon dynamics in karst areas under ongoing climate changes.

Results
Significant positive relationships were found between weathering rates and climatic factors (i.e. temperature and discharge) over the hydrological year. The total flux of CO2 consumption (760.4 × 103 mol/km2/year) in the Guijiang River was much higher than the global mean flux, with a higher CO2 consumption capacity in the Guijiang River relative to most other global rivers. Chemical weathering fluxes in this karst area showed high sensitivity to global climate change. CO2 evasion during the warm–wet seasons was much lower than those during cold–dry seasons. Light δ13CDIC values occurred under high-flow conditions, corresponding with the high temperatures in high-flow seasons. IsoSource modelling revealed that biological carbon could account for 53% of all dissolved inorganic carbon (DIC), controlling the temporal carbon variabilities.

Conclusion
This study quantitatively evaluated the temporal variations in CO2 fluxes and carbon cycling of karstic river systems and demonstrated that riverine carbon cycling will have a higher sensibility to ongoing global climate change. High discharges accelerate solutes transport, with relatively large quantities of 13C-depleted carbon being flushed into rivers. Meanwhile, high temperatures also accelerate organic carbon mineralisation, producing high content of soil CO2, whose influx can shift the 13C-depleted values in the high-flow seasons. Taken together, biological carbon influx should be responsible for the temporal carbon dynamics.
Insights from macroevolutionary modelling and ancestral state reconstruction into the radiation and historical dietary ecology of Lemuriformes (Primates, Mammalia)
Authors: Fulwood Ethan L. , Shan Shan , Winchester Julia M. , Kirveslahti Henry , Ravier Robert , Kovalsky Shahar , Daubechies Ingrid , Boyer Doug M. 
Published: April 2021

AbstractBackgroundLemurs once rivalled the diversity of rest of the primate order despite thier confinement to the island of Madagascar. We test the adaptive radiation model of Malagasy lemur diversity using a novel combination of phylogenetic comparative methods and geometric methods for quantifying tooth shape.ResultsWe apply macroevolutionary model fitting approaches and disparity through time analysis to dental topography metrics associated with dietary adaptation, an aspect of mammalian ecology which appears to be closely related to diversification in many clades. Metrics were also reconstructed at internal nodes of the lemur tree and these reconstructions were combined to generate dietary classification probabilities at internal nodes using discriminant function analysis. We used these reconstructions to calculate rates of transition toward folivory per million-year intervals. Finally, lower second molar shape was reconstructed at internal nodes by modelling the change in shape of 3D meshes using squared change parsimony along the branches of the lemur tree. Our analyses of dental topography metrics do not recover an early burst in rates of change or a pattern of early partitioning of subclade disparity. However, rates of change in adaptations for folivory were highest during the Oligocene, an interval of possible forest expansion on the island.ConclusionsThere was no clear phylogenetic signal of bursts of morphological evolution early in lemur history. Reconstruction of the molar morphologies corresponding to the ancestral nodes of the lemur tree suggest that this may have been driven by a shift toward defended plant resources, however. This suggests a response to the ecological opportunity offered by expanding forests, but not necessarily a classic adaptive radiation initiated by dispersal to Madagascar.
Health-related quality of life in patients with recurrent pericarditis: results from a phase 2 study of rilonacept
Authors: Lin David , Klein Allan , Cella David , Beutler Anna , Fang Fang , Magestro Matt , Cremer Paul , LeWinter Martin M. , Luis Sushil Allen , Abbate Antonio , Ertel Andrew , Litcher-Kelly Leighann , Klooster Brittany , Paolini John F. 
Published: April 2021

Abstract
Background
Impact of recurrent pericarditis (RP) on patient health-related quality of life (HRQoL) was evaluated through qualitative patient interviews and as an exploratory endpoint in a Phase 2 trial evaluating the efficacy and safety of rilonacept (IL-1α/IL-1β cytokine trap) to treat RP.

Methods
Qualitative interviews were conducted with ten adults with RP to understand symptoms and HRQoL impacts, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS GH) v1.2 was evaluated to determine questionnaire coverage of patient experience. The Phase 2 trial enrolled participants with active symptomatic RP (A-RP, n = 16) and corticosteroid-dependent participants with no active recurrence at baseline (CSD-RP, n = 9). All participants received rilonacept weekly during a 6-week base treatment period (TP) plus an optional 18-week extension period (EP). Tapering of concomitant medications, including corticosteroids (CS), was permitted during EP. HRQoL was assessed using the PROMIS GH, and patient-reported pain and blood levels of c-reactive protein (CRP) were collected at Baseline and follow-up periods. A secondary, descriptive analysis of the Phase 2 trial efficacy results was completed using HRQoL measures to characterize both the impact of RP and the treatment effect of rilonacept.

Results
Information from qualitative interviews demonstrated that PROMIS GH concepts are relevant to adults with RP. From the Phase 2 trial, both participant groups showed impacted HRQoL at Baseline (mean PROMIS Global Physical Health [GPH] and Global Mental Health [GMH], were lower than population norm average). In A-RP, GPH/MPH improved by end of base TP and were sustained through EP (similar trends were observed for pain and CRP). Similarly, in CSD-RP, GPH/MPH improved by end of TP and further improved during EP, during CS tapering or discontinuation, without disease recurrence (low pain scores and CRP levels continued during the TP and EP).

Conclusion
This is the first study demonstrating impaired HRQoL in RP. Rilonacept treatment was associated with HRQoL improvements using PROMIS GH scores. Maintained/improved HRQoL during tapering/withdrawal of CS without recurrence suggests that rilonacept may provide an alternative to CS.
Trial registration: ClinicalTrials.Gov; NCT03980522; 5 June 2019, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03980522.
Translation of the updated clinical frailty scale 2.0 into Danish and implications for cross-sectoral reliability
Authors: Fournaise Anders , Nissen Søren Kabell , Lauridsen Jørgen T. , Ryg Jesper , Nickel Christian H. , Gudex Claire , Brabrand Mikkel , Poulsen Lone Musaeus , Andersen-Ranberg Karen 
Published: April 2021

AbstractThe Clinical Frailty Scale, which provides a common language about frailty, was recently updated to version 2.0 to cater for its increased use in areas of medicine usually involved in the care and treatment of older patients. We have previously translated the Clinical Frailty Scale 1.2 into Danish and found inter-rater-reliability to be excellent for primary care physicians, community nurses, and hospital doctors often involved in cross-sectoral collaborations. In this correspondence we present the Danish translation and cultural adaption of the Clinical Frailty Scale 2.0. Our recent findings on cross-sectoral inter-rater reliability for the Clinical Frailty Scale 1.2 are likely also applicable for the Clinical Frailty Scale 2.0.
DNA methylation of tumor associated calcium signal transducer 2 (TACSTD2) loci shows association with clinically aggressive renal cell cancers
Authors: Katzendorn Olga , Peters Inga , Dubrowinskaja Natalia , Tezval Hossein , Tabrizi Pouriya Faraj , von Klot Christoph A. , Hennenlotter Jörg , Lafos Marcel , Kuczyk Markus A. , Serth Jürgen 
Published: April 2021

Abstract
Background
DNA methylation is frequently observed in the development and progression of many human tumors as well as renal cell cancer (RCC). Tumor Associated Calcium Signal Transducer 2 (TACSTD2) participates in cell cycle progression through MAPK signalling pathway activation. Moreover, tumor-specific hypermethylation and association with aggressive cancer characteristics has been found for lung adenocarcinoma, hepatocellular carcinoma and cholangiocarcinoma. Whether TACSTD2 is tumor specifically hypermethylated in RCC or shows association of methylation with adverse clinicopathological parameters and survival of patients has not been investigated at yet.

Methods
Quantitative methylation-specific PCR (qMSP) analysis of a locus in the intron 1 region of TACSTD2 gene was carried out in a cross-sectional study of 127 paired RCC and normal samples. In silico analysis of TACSTD2 methylation in the TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset of 280 patients served as validation cohort. Statistical analyses were carried out using the two-sided paired t-test for matched tumor and normal sample comparisons, logistic regression for subgroup comparisons, Cox regression for analysis of recurrence free survival (RFS) and Pearson correlation analysis for correlation of TACSTD2 methylation and TACSTD2 mRNA in KIRC data.

Results
Higher methylation levels in RCC were significantly associated with advanced disease (p < 0.001), high tumor stage (p = 0.003), tumor differentiation (p = 0.033) and presence of lymph node (p = 0.021) or distant metastases (p = 0.008). TACSTD2 hypermethylation was associated with a shorter RFS of patients and demonstrate statistical independency from clinical parameters as state of metastasis, tumor stage, grade and state of advanced disease. In silico validation using TCGA KIRC data also demonstrated association of TACSTD2 loci with adverse clinicopathology and shortened RFS of patients. In addition, in silico analyses of TCGA KIRC data showed an inverse correlation between DNA methylation levels of TACSTD2 and mRNA expression.

Conclusions
Our results suggest an association between TACSTD2 methylation and disease progression and clinical course of RCC.
Clinically relevant dual probe difference specimen imaging (DDSI) protocol for freshly resected breast cancer specimen staining
Authors: House Broderick J. , Kwon Marcus J. , Schaefer Jasmin M. , Barth Connor W. , Solanki Allison , Davis Scott C. , Gibbs Summer L. 
Published: April 2021

Abstract
Background
Re-excision rates following breast conserving surgery (BCS) remain as high as ~ 35%, with positive margins detected during follow-up histopathology. Additional breast cancer resection surgery is not only taxing on the patient and health care system, but also delays adjuvant therapies, increasing morbidity and reducing the likelihood of a positive outcome. The ability to precisely resect and visualize tumor margins in real time within the surgical theater would greatly benefit patients, surgeons and the health care system. Current tumor margin assessment technologies utilized during BCS involve relatively lengthy and labor-intensive protocols, which impede the surgical work flow.

Methods
In previous work, we have developed and validated a fluorescence imaging method termed dual probe difference specimen imaging (DDSI) to accurately detect benign and malignant tissue with direct correlation to the targeted biomarker expression levels intraoperatively. The DDSI method is currently on par with touch prep cytology in execution time (~ 15-min). In this study, the main goal was to shorten the DDSI protocol by decreasing tissue blocking and washing times to optimize the DDSI protocol to < 10-min whilst maintaining robust benign and malignant tissue differentiation.

Results
We evaluated the utility of the shortened DDSI staining methodology using xenografts grown from cell lines with varied epidermal growth factor receptor (EGFR) expression levels, comparing accuracy through receiver operator characteristic (ROC) curve analyses across varied tissue blocking and washing times. An optimized 8-min DDSI methodology was developed for future clinical translation.

Conclusions
Successful completion of this work resulted in substantial shortening of the DDSI methodology for use in the operating room, that provided robust, highly receptor specific, sensitive diagnostic capabilities between benign and malignant tissues.
Th cytokine profile in childhood-onset systemic lupus erythematosus
Authors: Quan Wei , An Jingnan , Li Gang , Qian Guanghui , Jin Meifang , Feng Chenxi , Li Si , Li Xiaozhong , Xu Yunyun , Hu Xiaohan 
Published: April 2021

Abstract
Background
Childhood-onset systemic lupus erythematosus (cSLE) is a kind of chronic inflammatory disease characterized by a highly abnormal immune system. This study aimed to detect the serum levels of Th (T helper) cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ and TNF-α) in cSLE and healthy controls, and then to elucidate their association with clinical manifestations, disease activity and laboratory parameters. In order to provide clues for early diagnosis and timely intervention treatment of cSLE patients.

Methods
A total of 33 children with cSLE and 30 healthy children were enrolled in this study. Children in the cSLE group were classified into the inactive or active cSLE group according to their SLE disease activity index 2000 (SLEDAI-2 K) score. Th cytokine profiles in the peripheral blood were detected and analysed.

Results
Levels of IL-2, IL-10 and IL-21 in the cSLE group were significantly higher than those in the healthy control group (P < 0.05, P < 0.01 and P < 0.01, respectively). Expression of IL-2, IL-10 and IL-21 in the active cSLE group was significantly higher than that in the healthy control group (P < 0.05, P < 0.01 and P < 0.05, respectively), but that of IL-22 expression was markedly lower in the active cSLE group than in the healthy control group (P < 0.001). IL-21 in the inactive SLE group was significantly higher than that in the healthy control group (P < 0.05), and levels of IL-2 and IL-10 in the active cSLE group were significantly higher than those in the inactive cSLE group (P < 0.01 and P < 0.05). In-depth analysis showed that after excluding age, gender and drug interference, the levels of IL-2 (P < 0.05), IL-6 (P < 0.05) and IL-10 (P < 0.05) were still positively correlated with SLEDAI-2 K scores. However, the levels of IL-6 (P < 0.05) and IFN- γ (P < 0.05) were still negatively correlated with CD4+/CD8+, and the concentration of IL-6 (P < 0.05) was still positively correlated with the occurrence of nephritis.

Conclusion
This study provides a theoretical basis for the discovery of effective methods to regulate imbalance in T lymphocyte subsets in cSLE, which may lead to new approaches for the diagnosis of cSLE.
Economic gradient of onset of disability in India
Authors: Mishra Radhe Shyam , Mohanty Sanjay K. , Cordes Jack , Sahoo Umakanta , Singh Rajeev R. , Subramanian S. V. 
Published: April 2021

Abstract
Background
Disability in India is associated with increasing non-communicable diseases, rising longevity, and increasing accidents and injuries. Though studies have examined prevalence, patterns, and socioeconomic correlates of disability, no attempt has been made in estimating age of onset of disability in India.

Objective
This paper investigates the economic gradient of age of onset of locomotor, visual, hearing, speech, mental retardation, mental illness, and other disabilities in India.

Method
We use nationally representative data of 106,894 disabled individuals from the 76th round of National Sample Survey (NSS), 2018. Descriptive statistics, kernel density, Kaplan-Meier survival curves, and linear regression models are used in the analysis.

Result
The disability rate in India was 2184 per 100,000 persons. The disability rate was highest for locomotor (1353) followed by hearing (296), visual (234), speech (228), mental retardation (158), and mental illness (131). Over 85% of mental retardation and 80% of speech disabilities occur at birth, while 82% of locomotor and 81% of visual disabilities occur after birth. Among those who had disability after birth, the median age for mental retardation was 2 years followed by mental illness (28 years), speech (29 years), locomotor (42 years), visual (55 years), and 56 years for hearing disability. Adjusting for socioeconomic covariates, the age of onset of locomotor and speech disabilities among the poorest individuals were 7 and 11 years earlier than the richest, respectively.

Conclusion
The economic gradient of onset of locomotive and speech disabilities are strong. The age of onset of disability was earliest for mental retardation followed by mental illness and speech disability.