bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro measurement of concentration of unlabeled protein within a hyaluronic acid matrix
Authors: dos Santos Antonio C. F. , Ahmadzadegan Adib , Ximenes Eduardo , Vlachos Pavlos , Ardekani Arezoo , Kapur Shiven , Corvari Vince , Ladisch Michael R. 
Published: September 2022

AbstractThere are currently more than 560 therapeutic monoclonal antibodies (mAbs) at various stages of research and clinical testing, including candidates for administration by subcutaneous (SC) injection. Preclinical studies based on in vitro measurements of high molecular weight proteins within simulated SC matrices are assisting laboratory studies of interactions of injectable biotherapeutic proteins within the SC environment in relation to bioavailability. We report a new method for directly measuring diffusion of unlabeled, high molecular weight proteins injected into an in vitro matrix that simulates the negatively charged environment of the SC. The matrix consists of 10 mg/ml HA in a repurposed cell culture chamber. The measurement consists of pipetting triplicate 20 μl protein samples into the matrix, placing the chamber in a laboratory scanner, activating tryptophan residues in the protein at 280 nm, and imaging the resulting protein fluorescence at 384 nm over a 0.5–4 h time period thus tracking protein movement. This facile approach enables mapping of protein concentration as a function of time and distance within the matrix, and determination of diffusion coefficients, D, within ±10%. Bovine IgG and BSA gave D = 2.3 ± 0.2*10−7 and 4.6 ± 0.2*10−7 cm2/s at 24°C, respectively, for initial protein concentrations of 21 mg/mL.
A prognostic six‐gene expression risk‐score derived from proteomic profiling of the metastatic colorectal cancer secretome
Authors: Robles Javier , Pintado‐Berninches Laura , Boukich Issam , Escudero Beatriz , de los Rios Vivian , Bartolomé Rubén A , Jaén Marta , Martín‐Regalado Ángela , Fernandez‐Aceñero María Jesús , Imbaud Juan Ignacio , Casal José Ignacio 
Published: September 2022

AbstractThe necessity to accurately predict recurrence and clinical outcome in early stage colorectal cancer (CRC) is critical to identify those patients who may benefit from adjuvant chemotherapy. Here, we developed and validated a gene‐based risk‐score algorithm for patient stratification and personalised treatment in early stage disease based on alterations in the secretion of metastasis‐related proteins. A quantitative label‐free proteomic analysis of the secretome of highly and poorly metastatic CRC cell lines with different genetic backgrounds revealed 153 differentially secreted proteins (fold‐change >5). These changes in the secretome were validated at the transcriptomic level. Starting from 119 up‐regulated proteins, a six‐gene/protein‐based prognostic signature composed of IGFBP3, CD109, LTBP1, PSAP, BMP1, and NPC2 was identified after sequential discovery, training, and validation in four different cohorts. This signature was used to develop a risk‐score algorithm, named SEC6, for patient stratification. SEC6 risk‐score components showed higher expression in the poor prognosis CRC subtypes: consensus molecular subtype 4 (CMS4), CRIS‐B, and stem‐like. High expression of the signature was also associated with patients showing dMMR, CIMP+ status, and BRAF mutations. In addition, the SEC6 signature was associated with lower overall survival, progression‐free interval, and disease‐specific survival in stage II and III patients. SEC6‐based risk stratification indicated that 5‐FU treatment was beneficial for low‐risk patients, whereas only aggressive treatments (FOLFOX and FOLFIRI) provided benefits to high‐risk patients in stages II and III. In summary, this novel risk‐score demonstrates the value of the secretome compartment as a reliable source for the retrieval of biomarkers with high prognostic and chemotherapy‐predictive capacity, providing a potential new tool for tailoring decision‐making in patient care.
Telediagnosis of dental caries: Possible or impossible? A pilot cross‐sectional study
Authors: Zotti Francesca , Rosolin Luca , Simoncelli Francesco , Pappalardo Davide , Cominziolli Annalisa , Zerman Nicoletta 
Published: September 2022

AbstractObjectivesThe aims of this study were to evaluate the effectiveness of teledentistry (based on a home intraoral imaging protocol) in detecting dental caries and to assess the accuracy of this method compared to clinical examination.MethodsForty‐three patients were recruited for the study. Using a protocol for taking intraoral photographs at home with a smartphone proposed by the Dental School of Verona, a remote diagnosis of dental caries (TD) was performed by an experienced dentist. The same caries sites were also assessed by clinical diagnosis (CD) by a second experienced dentist. Ten photos were taken at home in five different perspectives, with and without flash, and emailed to one of the authors. The best five photos were selected for telediagnosis. The International Caries Detection and Assessment System (ICDAS II) score was used for caries diagnosis. Statistical tests were performed: Sensitivity and specificity of TD, the positive and negative predictive value of TD (PPV–NPV), and Spearman correlation to evaluate the relationship between the scores of TD and CD.ResultsA total of 430 photographs were submitted; TD was performed on 215 photographs and 43 patients were visited. A total of 1201 teeth were analyzed. The sensitivity of TD was 74.0, the specificity was 99.1, the PPV of TD was 91.7, and the NPV was 96.4. The Spearman correlation was 0.816, showing a very strong correlation between the values obtained with TD and CD.ConclusionsThe study showed good potential for TD, which proved to be a feasible method to combine with routine caries diagnosis in daily preventive dentistry practice.
Charge Carriers for Aqueous Dual‐Ion Batteries
Authors: Wang Shaofeng , Guan Ying , Gan Fangqun , Shao Zongping 
Published: September 2022

AbstractEnvironmental and safety concerns of energy storage systems call for application of aqueous battery systems which have advantages of low cost, environmental benignity, safety, and easy assembling. Among the aqueous battery systems, aqueous dual‐ion batteries (ADIBs) provide high possibility for achieving excellent battery performance. Compared with the “rocking chair” batteries with only one type of carrier involved in the charging and discharging, ADIBs with both cations and anions as charge carriers possess diverse selections of electrodes and electrolytes. Charge carriers are the basis of the configuration of ADIBs. In this Review, cations and anions that could be applied in ADIBs are demonstrated with corresponding electrode materials and favorable electrolytes. Some insertion mechanisms are emphasized to provide insights for the possibilities to enhance the practical performances of ADIBs.
A Prospective Life Cycle Assessment of Electrochemical CO2 Reduction to Selective Formic Acid and Ethylene
Authors: Ai Ling , Ng Sue‐Faye , Ong Wee‐Jun 
Published: September 2022

AbstractInvited for this month′s cover is the group of Prof. Dr. Wee‐Jun Ong at Xiamen University Malaysia. The image shows a model of Xiamen University and is in celebration of the 5th and 100th anniversary of Xiamen University Malaysia and Xiamen University, respectively. The cover showcases the institutes as a pillar of renewable nanotechnology research and a key player in the ever‐growing search for sustainable energy. The Research Article itself is available at 10.1002/cssc.202200857.
Immunophenotypic assessment ofPNHclones in major and minor cell lineages in the peripheral blood of patients with paroxysmal nocturnal hemoglobinuria
Authors: Richards Stephen J. , Dickinson Anita J. , Newton Darren J. , Hillmen Peter 
Published: September 2022

AbstractBackgroundFlow cytometric immunophenotyping is essential for the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). Most cases have easy to interpret flow cytometry profiles with red cells, neutrophils and monocytes showing complete deficiency of glycophosphatidylinositol (GPI) linked antigen expression. Some cases are more challenging to interpret due to the presence of multiple populations of PNH cells and variable levels of GPI antigen expression.MethodsWe studied 46 known PNH patients, many with complex immunophenotypic profiles using a novel, single tube, multi‐parameter 7‐color immunophenotyping assay that allowed simultaneous detection and assessment of PNH clones within multiple lineages of peripheral blood leucocytes. Red cell PNH clones were also assessed in total and immature (CD71+) components by CD59 expression.ResultsFor individual patients, total PNH clones in each cell lineage were highly correlated. Monocytes, eosinophils and basophils showed the highest proportions of PNH cells. Red cell PNH clones were typically smaller than monocyte and neutrophil PNH clones. In most cases, PNH clones were detectable in minor leucocyte populations where multiple populations of PNH cells were present, variability in the proportions of type II and type III cells was seen across different cell lineages, even though total PNH clones remained similar.ConclusionsThis study shows that PNH patients with multiple PNH clones do not always display the same abnormality across all cell lineages routinely tested. There is no simple explanation for this but is likely due to a combination of complex molecular, genetic and biochemical dysfunction in different blood cell types.
Combination of gait speed and grip strength to predict cognitive decline and dementia
Authors: Orchard Suzanne G. , Polekhina Galina , Ryan Joanne , Shah Raj C. , Storey Elsdon , Chong Trevor T.‐J. , Lockery Jessica E. , Ward Stephanie A. , Wolfe Rory , Nelson Mark R. , Reid Christopher M. , Murray Anne M. , Espinoza Sara E. , Newman Anne B. , McNeil John J. , Collyer Taya A. , Callisaya Michele L. , Woods Robyn L. ,   and on behalf of the ASPREE Investigator group
Published: September 2022

AbstractIntroductionTo determine whether slowed gait and weakened grip strength independently, or together, better identify risk of cognitive decline or dementia.MethodsTime to walk 3 meters and grip strength were measured in a randomized placebo‐controlled clinical trial involving community‐dwelling, initially cognitively healthy older adults (N = 19,114).ResultsOver a median 4.7 years follow‐up, slow gait and weak grip strength at baseline were independently associated with risk of incident dementia (hazard ratio [HR] = 1.44, 95% confidence interval [CI]: 1.19–1.73; and 1.24, 95% CI: 1.04–1.50, respectively) and cognitive decline (HR = 1.38, 95% CI: 1.26–1.51; and 1.04, 95% CI: 0.95–1.14, respectively) and when combined, were associated with 79% and 43% increase in risk of dementia and cognitive decline, respectively. Annual declines in gait and in grip over time showed similar results.DiscussionGait speed and grip strength are low‐cost markers that may be useful in the clinical setting to help identify and manage individuals at greater risk, or with early signs, of dementia, particularly when measured together.Highlights
Grip strength and gait speed are effective predictors and markers of dementia.
Dementia risk is greater than cognitive decline risk with declines in gait or grip.
Decline in gait speed, more so than in grip strength, predicts greater dementia risk.
Greater risk prediction results from combining grip strength and gait speed.
Risk factors for intracardiac thrombus in peripartum cardiomyopathy: a retrospective study in China
Authors: Fu Kang , Zhang Hui , Chen Naiyi , Hu Yue , Xiao Jie , Zhang Xinyu , Lin Zongwei , Lu Huixia , Ji Xiaoping 
Published: September 2022

AbstractAimsPeripartum cardiomyopathy (PPCM) are more vulnerable to intracardiac thrombus than other types of cardiomyopathies, although explicit anticoagulant strategy is not sure. Too aggressive anticoagulation therapy can lead to severe bleeding events. Hence, we want to construct a risk stratification model for intracardiac thrombus in PPCM patients.Methods and resultsA total of 159 suspected PPCM cases were initially screened, whereas 123 confirmed cases were enrolled in the final analysis. The study population was randomly assigned as derivation group (N = 83) and validation group (N = 40). The derivation cohort was utilized to develop the model, and the validation cohort was used to internal validate the discriminatory ability of the model. Formation of intracardiac thrombus was detected in 22 patients. After adjusted by multivariable logistic regression analysis, left ventricle ejection fraction (LVEF, OR 0.772, 95% CI 0.665–0.897, P = 0.001), haemoglobin levels (OR 1.050, 95% CI 1.003–1.099, P = 0.038), and thrombocyte counts (OR 1.018, 95% CI 1.006–1.029, P = 0.003) were identified as risk factors independently associated with intracardiac thrombus and were finally included in the tentative risk stratification model with a C‐indexes of 0.916 (95% CI: 0.850–0.982, P < 0.001). A score of ≤7 was regarded as low risk, 8–10 defined intermediate risk, and ≥11 defined high risk in our model. Internal validation showed good discriminatory ability of the model with a C‐indexes of 0.790 (95% CI: 0.644–0.936, P = 0.017).ConclusionsIn our retrospective study, impaired LVEF, elevated haemoglobin levels, and high thrombocyte counts were regarded as independent risk factors for intracardiac thrombus in PPCM. A risk stratification model derived from these risk factors, which was economic and easily applicable in clinical practice, could rapidly and accurately identify PPCM patients with higher‐risk of intracardiac thrombus.
Pain‐autonomic measures reveal nociceptive sensitization in complex regional pain syndrome
Authors: Scheuren Paulina S. , De Schoenmacker Iara , Rosner Jan , Brunner Florian , Curt Armin , Hubli Michèle 
Published: September 2022

AbstractBackgroundAllodynia and hyperalgesia are common signs in individuals with complex regional pain syndrome (CRPS), mainly attributed to sensitization of the nociceptive system. Appropriate diagnostic tools for the objective assessment of such hypersensitivities are still lacking, which are essential for the development of mechanism‐based treatment strategies.ObjectivesThis study investigated the use of pain‐autonomic readouts to objectively detect sensitization processes in CRPS.MethodsTwenty individuals with chronic CRPS were recruited for the study alongside 16 age‐ and sex‐matched healthy controls (HC). All individuals underwent quantitative sensory testing and neurophysiological assessments. Sympathetic skin responses (SSRs) were recorded in response to 15 pinprick and 15 noxious heat stimuli of the affected (CRPS hand/foot) and a control area (contralateral shoulder/hand).ResultsIndividuals with CRPS showed increased mechanical pain sensitivity and increased SSR amplitudes compared with HC in response to pinprick and heat stimulation of the affected (p < 0.001), but not in the control area (p > 0.05). Habituation of pinprick‐induced SSRs was reduced in CRPS compared to HC in both the affected (p = 0.018) and slightly in the control area (p = 0.048). Habituation of heat‐induced SSR was reduced in CRPS in the affected (p = 0.008), but not the control area (p = 0.053).ConclusionsThis is the first study demonstrating clinical evidence that pain‐related autonomic responses may represent objective tools to quantify sensitization processes along the nociceptive neuraxis in CRPS (e.g. widespread hyperexcitability). Pain‐autonomic readouts could help scrutinize mechanisms underlying the development and maintenance of chronic pain in CRPS and provide valuable metrics to detect mechanism‐based treatment responses in clinical trials.SignificanceThis study provides clinical evidence that autonomic measures to noxious stimuli can objectively detect sensitization processes along the nociceptive neuraxis in complex regional pain syndrome (CRPS) (e.g. widespread hyperexcitability). Pain‐autonomic readouts may represent valuable tools to explore pathophysiological mechanisms in a variety of pain patients and offer novel avenues to help guide mechanism‐based therapeutic strategies.
An international Delphi survey and consensus meeting to define the core outcome set for trigeminal neuralgia clinical trials
Authors: Venda Nova Carolina , Ni Riordain Richeal , Baker Sarah R. , Zakrzewska Joanna M. 
Published: September 2022

AbstractBackgroundTrigeminal neuralgia (TN) is an excruciating unilateral facial pain, which negatively affects patient's quality of life. Historically, it has been difficult to compare treatment efficacy due to the lack of standardized outcomes. In addition, patients' perspective has seldomly been acknowledged. The aim of this study was to reach consensus on what outcomes of treatment are important to different TN stakeholders (patients, clinicians and researchers), to identify the TN Core Outcome Set (TRINCOS).MethodsA list of outcomes identified through a systematic review and focus group work was used to develop the survey questionnaire. A three‐round Delphi was conducted. Participants were asked to score the outcomes on scale from 1 to 9 (1–3 not important;4–6 important but not critical;7–9 critical). Outcomes scored as critical by ≥70% and not important by <15% were retained, and those for which no consensus was reached were discussed at a consensus meeting.ResultsOf the 70 participants who completed the Delphi, 26 were patients, 38 were clinicians and six were researchers. Of the 40 outcomes presented, 17 were scored as critical and no consensus was met for 23 outcomes. Agreement was reached during a consensus meeting on 10 outcomes across six domains (pain, side effects, social impact, quality of life, global improvement, and satisfaction with treatment).ConclusionImplementation of TRINCOS in future clinical trials will improve homogeneity of studies' results, reduce the redundancy in the outcome assessment and effectively allow comparison of different treatments to better inform researchers, clinicians and most importantly patients, about the efficacy of the different treatments.SignificanceImplementation of a 10‐item core outcome set in trigeminal neuralgia will improve comparability between studies allowing patients to have faster access to better treatments.
Serum bile acids as a prognostic biomarker in biliary atresia following Kasai portoenterostomy
Authors: Harpavat Sanjiv , Hawthorne Kieran , Setchell Kenneth D. R. , Rivas Monica Narvaez , Henn Lisa , Beil Charlotte A. , Karpen Saul J. , Ng Vicky L. , Alonso Estella M. , Bezerra Jorge A. , Guthery Stephen L. , Horslen Simon , Loomes Kathy M. , McKiernan Patrick , Magee John C. , Merion Robert M. , Molleston Jean P. , Rosenthal Philip , Thompson Richard J. , Wang Kasper S. , Sokol Ronald J. , Shneider Benjamin L. ,   for Childhood Liver Disease Research Network (ChiLDReN)
Published: September 2022

Background and Aims:
In biliary atresia, serum bilirubin is commonly used to predict outcomes after Kasai portoenterostomy (KP). Infants with persistently high levels invariably need liver transplant, but those achieving normalized levels have a less certain disease course. We hypothesized that serum bile acid levels could help predict outcomes in the latter group.

Approach and Results:
Participants with biliary atresia from the Childhood Liver Disease Research Network were included if they had normalized bilirubin levels 6 months after KP and stored serum samples from the 6‐month post‐KP clinic visit (n = 137). Bile acids were measured from the stored serum samples and used to divide participants into ≤40 μmol/L (n = 43) or >40 μmol/L (n = 94) groups. At 2 years of age, the ≤40 μmol/L compared with >40 μmol/L group had significantly lower total bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma‐glutamyltransferase, bile acids, and spleen size, as well as significantly higher albumin and platelet counts. Furthermore, during 734 person‐years of follow‐up, those in the ≤40 μmol/L group were significantly less likely to develop splenomegaly, ascites, gastrointestinal bleeding, or clinically evident portal hypertension. The ≤40 μmol/L group had a 10‐year cumulative incidence of liver transplant/death of 8.5% (95% CI: 1.1%–26.1%), compared with 42.9% (95% CI: 28.6%–56.4%) for the >40 μmol/L group (p = 0.001).

Conclusions:
Serum bile acid levels may be a useful prognostic biomarker for infants achieving normalized bilirubin levels after KP.
Relevance and quality of implementation research proposals to face the challenges of public health in Latin‐America and the Caribbean
Authors: Alcalde‐Rabanal Jacqueline Elizabeth , Torres‐Grimaldo Alejandro , Becerril‐Montekio Victor , Garcia‐Cerde Rodrigo , Reveiz Ludovic , Torres‐Pereda Pilar 
Published: September 2022

AbstractObjectivesTo analyse the relevance and quality of the research proposals submitted to the 2016 call for proposals for the initiative Improving Programme Implementation through Embedded Research (iPIER‐2016) to address current public health challenges in Latin America and the Caribbean.MethodsWe performed a cross‐sectional study using information from 108 research proposals using quantitative and qualitative methods. We used three frameworks to analyse the relevance of the proposals: The Global Burden of Disease, the WHO Health Systems Conceptual Framework and the Sustainable Development Goals proposed in 2015 by the United Nations. We performed an index to analyse the relevance and quality of the proposals.ResultsTwenty seven percent of the proposals have very good relevance, one third of the proposals have quality flaws. This means their research questions are not related to implementation research or their methods are insufficient or inadequate to respond to the objective.ConclusionsThe response to this call is proof of health authorities' interest in research as a tool to improve the implementation of health programs in the region. However, proposals show important variations in terms of relevance and quality among countries and training health staff in programme implementation seems a central requirement.
Systemic risk in the Scandinavian banking sector
Authors: Hedström Axel Per , Uddin Gazi Salah , Rahman Md Lutfur , Sjö Bo 
Published: September 2022

AbstractThe banking sectors in the Scandinavian countries are highly concentrated, typically undercapitalised and they have suffered through several crises since the 1990s. This article analyses the systemic risk in Denmark, Norway and Sweden focusing on the co‐dependence in the tails of equity returns of an individual bank and the overall banking system. We use, partly in a new way, conditional cross‐quantilograms (CQs) for this purpose. We find that the CQs are positive and statistically significant in the low and high quantiles indicating that the Scandinavian banks are systemically linked. The low‐quantile dependence is relatively stronger compared with the magnitude of dependence in the other quantiles. These results hold even after controlling for equity market volatility and economic policy uncertainty. We further observe that the systemic risk was insignificant from the early—2000 to the outbreak of the global financial crisis (GFC). However, after the GFC and the euro zone crisis, the systemic risk has increased substantially. Finally, we find that bank size has a positive relationship with systemic risk (low‐quantile dependence) while return on asset and loan to deposit ratio exhibit a negative influence. Furthermore, these relationships are asymmetric across quantiles.