bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in Cancer Phenotypes Among Frequent CHEK2 Variants and Implications for Clinical Care—Checking CHEK2
Authors: Bychkovsky Brittany L. , Agaoglu Nihat B. , Horton Carolyn , Zhou Jing , Yussuf Amal , Hemyari Parichehr , Richardson Marcy E. , Young Colin , LaDuca Holly , McGuinness Deborah L. , Scheib Rochelle , Garber Judy E. , Rana Huma Q.
Published: September 2022

Importance

Germline CHEK2 pathogenic variants (PVs) are frequently detected by multigene cancer panel testing (MGPT), but our understanding of PVs beyond c.1100del has been limited.

Objective

To compare cancer phenotypes of frequent CHEK2 PVs individually and collectively by variant type.

Design, Setting, and Participants

This retrospective cohort study was carried out in a single diagnostic testing laboratory from 2012 to 2019. Overall, 3783 participants with CHEK2 PVs identified via MGPT were included. Medical histories of cancer in participants with frequent PVs, negative MGPT (wild type), loss-of-function (LOF), and missense were compared.

Main Outcomes and Measures

Participants were stratified by CHEK2 PV type. Descriptive statistics were summarized including median (IQR) for continuous variables and proportions for categorical characteristics. Differences in age and proportions were assessed with Wilcoxon rank sum and Fisher exact tests, respectively. Frequencies, odds ratios (ORs), 95% confidence intervals were calculated, and P values were corrected for multiple comparisons where appropriate.

Results

Of the 3783 participants with CHEK2 PVs, 3473 (92%) were female and most reported White race. Breast cancer was less frequent in participants with p.I157T (OR, 0.66; 95% CI, 0.56-0.78; P<.001), p.S428F (OR, 0.59; 95% CI. 0.46-0.76; P<.001), and p.T476M (OR, 0.74; 95% CI, 0.56-0.98; P = .04) PVs compared with other PVs and an association with nonbreast cancers was not found. Following the exclusion of p.I157T, p.S428F, and p.T476M, participants with monoallelic CHEK2 PV had a younger age at first cancer diagnosis (P < .001) and were more likely to have breast (OR, 1.83; 95% CI, 1.66-2.02; P < .001), thyroid (OR, 1.63; 95% CI, 1.26-2.08; P < .001), and kidney cancer (OR, 2.57; 95% CI, 1.75-3.68; P < .001) than the wild-type cohort. Participants with a CHEK2 PV were less likely to have a diagnosis of colorectal cancer (OR, 0.62; 95% CI, 0.51-0.76; P < .001) compared with those in the wild-type cohort. There were no significant differences between frequent CHEK2 PVs and c.1100del and no differences between CHEK2 missense and LOF PVs.

Conclusions and Relevance

CHEK2 PVs, with few exceptions (p.I157T, p.S428F, and p.T476M), were associated with similar cancer phenotypes irrespective of variant type. CHEK2 PVs were not associated with colorectal cancer, but were associated with breast, kidney, and thyroid cancers. Compared with other CHEK2 PVs, the frequent p.I157T, p.S428F, and p.T476M alleles have an attenuated association with breast cancer and were not associated with nonbreast cancers. These data may inform the genetic counseling and care of individuals with CHEK2 PVs.
Association of QTc Formula With the Clinical Management of Patients With Cancer
Authors: Richardson Daniel R. , Parish P. Christopher , Tan Xianming , Fabricio Julia , Andreini Cami L. , Hicks Charles H. , Jensen Brian C. , Muluneh Benyam , Zeidner Joshua F.
Published: September 2022

Importance

Monitoring of the corrected QT interval (QTc) for patients with cancer receiving chemotherapy is not standardized. Selection of QTc formula may be associated with adverse event grading and chemotherapy delivery.

Objective

To describe the association of QTc formula selection with adverse event grading and chemotherapy delivery.

Design, Setting, and Participants

This retrospective observational cohort study used data from January 2010 to April 2020 and included adult patients seen at the University of North Carolina Cancer Hospital who had an electrocardiogram (ECG) performed.

Exposures

Adjusted QTc using the Bazett, Fridericia, and Framingham formulae.

Main Outcomes and Measures

The main outcome was QTc prolongation using the Common Terminology Criteria for Adverse Events (CTCAE). Consistency between formulae was evaluated. Subsequently, appropriateness of clinical management due to prolonged QTc was assessed for a subset of patients being treated with chemotherapy agents associated with a prolonged QT interval. We hypothesized that use of the Bazett formula would be associated with higher rates of QTc prolongation and inappropriate modifications to chemotherapy.

Results

A total of 19 955 ECGs from 6881 adult patients (3055 [44.4%] women, 3826 [55.6%] men; median [IQR] age at first ECG, 60 [47-68] years) were analyzed. The percentage of ECGs with grade 3 QTc prolongation differed by formula (all patients: Framingham, 1.8%; Fridericia, 2.8%; and Bazett, 9.0%; patients receiving QT-prolonging chemotherapy [2340 ECGs]: Framingham, 2.7%; Fridericia, 4.5%; and Bazett, 12.5%). The Bazett formula resulted in a median QTc value 26.4 milliseconds higher than Fridericia and 27.8 milliseconds higher than Framingham. Of the 1786 ECGs classified as grade 3 by Bazett, 1446 (81.0%) were grade 2 or less by either Fridericia or Framingham. A total of 5 of 28 (17.9%) evaluated clinical changes associated with prolonged QTc were deemed inappropriate when using either Fridericia or Framingham formula.

Conclusions and Relevance

Findings of this cohort study suggest that the Bazett formula resulted in higher QTc values associated with a 3-fold increase in grade 3 CTCAE toxic effects compared with other common formulae. Use of the Bazett formula likely was associated with inappropriate changes in clinical management. These data support the use of a standard QTc formula (such as Fridericia or Framingham) for QTc correction in oncology.
Avoiding Definitive Conclusions in Meta-analysis of Heterogeneous Studies With Small Sample Sizes
Authors: Zhou Shouhao , Shen Chan
Published: September 2022

This Viewpoint argues for caution when interpreting the findings of meta-analyses of heterogenous studies with small samples.
Unraveling the Mechanism of Different Kinetics Performance between Ether and Carbonate Ester Electrolytes in Hard Carbon Electrode
Authors: Yi Xiaoli , Li Xinhai , Zhong Jing , Wang Siwu , Wang Zhixing , Guo Huajun , Wang Jiexi , Yan Guochun
Published: September 2022

Ether electrolytes exhibit better rate kinetics than carbonate ester electrolytes when used in several kinds of anode materials, especially in hard carbon (HC) for sodium‐ion batteries (SIBs). However, the mechanism causing the remarkable kinetics difference is still unclear. Here, a three‐electrode system is used first to eliminate the influence of polarization from the Na counter electrode. Then, there is systematic exploration from three steps of the electrode reaction process (Na+storage in HC; de‐solvation; Na+migration through solid electrolyte interphase (SE), and the underlying mysteries are uncovered. For Na+storage in the bulk of the HC, it is found that two systems show the same storage mechanism and Na metallic nanoparticles will appear when discharged to 0.1 V. In addition, faster de‐solvation of the ether electrolyte is uncovered by three‐electrode temperature‐dependent EIS and solvation free energies calculation. Moreover, the difference of the SEI layers is unraveled by X‐ray photoelectron spectroscopy etching, scanning electron microscopy, and differential electrochemical mass spectrometry. Most importantly, by discriminating the impacts of the SEI layers and de‐solvation behavior, it can be concluded that the de‐solvation process is the rate‐controlling step of the electrode reaction process and is the main factor causing the kinetics differences between the two electrolytes. The research provides a clear mechanism to illuminate fast kinetics for ether electrolytes, which will promote its application in SIBs.
Electron‐Transport Layers Employing Strongly Bound Ligands Enhance Stability in Colloidal Quantum Dot Infrared Photodetectors
Authors: Zhang Yangning , Vafaie Maral , Xu Jian , Pina Joao M. , Xia Pan , Najarian Amin M. , Atan Ozan , Imran Muhammad , Xie Ke , Hoogland Sjoerd , Sargent Edward H.
Published: September 2022

Solution‐processed photodetectors based on colloidal quantum dots (CQDs) are promising candidates for short‐wavelength infrared light sensing applications. Present‐day CQD photodetectors employ a CQD active layer sandwiched between carrier‐transport layers in which the electron‐transport layer (ETL) is composed of metal oxides. Herein, a new class of ETLs is developed using n‐type CQDs, finding that these benefit from quantum‐size effect tuning of the band energies, as well as from surface ligand engineering. Photodetectors operating at 1450 nm are demonstrated using CQDs with tailored functionalities for each of the transport layers and the active layer. By optimizing the band alignment between the ETL and the active layer, CQD photodetectors that combine a low dark current of ≈1 × 10−3 mA cm−2 with a high external quantum efficiency of ≈66% at 1 V are reported, outperforming prior reports of CQD photodetectors operating at >1400 nm that rely on metal oxides as ETLs. It is shown that stable CQD photodetectors rely on well‐passivated CQDs: for ETL CQDs, a strongly bound organic ligand trans‐4‐(trifluoromethyl)cinnamic acid (TFCA) provides improved passivation compared to the weakly bound inorganic ligand tetrabutylammonium iodide (TBAI). TFCA suppresses bias‐induced ion migration inside the ETL and improves the operating stability of photodetectors by 50× compared to TBAI.
Optical Fourier Volumes: A Revisiting of Holographic Photopolymers and Photoaddressable Polymers
Authors: Kim Kwangjin , Lim Yongjun , Son Heeju , Hong Seung Jae , Shin Chang‐Won , Baek Dongjae , Kim Hyeon Ho , Kim Nam , Bang Joona , Lee Seungwoo
Published: September 2022

To avoid mixing of the undesired frequencies in a free‐space, the point sources of gratings, defined by a spatially varying refractive index, should be sinusoidally rather than binarily arranged. This long‐lasting but gold standard lesson attainable from a classical Fourier optics, however, is underutilized in the practical materialization of gratings, mainly because most of the fabrication methods, developed thus far, are intrinsically compatible with a binary rather than sinusoidal grating. Recently, such design concept of optical Fourier elements has been implemented into the real surface gratings (referred to as optical Fourier surfaces) by taking advantage of advanced nanofabrication, whereas their volumetric equivalents (optical Fourier volumes, OFVs) have yet to be conceptually and experimentally elucidated. In this work, the key characteristics of OFVs and their structural requirements are systematically exploited with the assistance of analytical and numerical calculations. Especially, the dynamic range and thickness of volume gratings, required for OFVs, are newly defined. Given these theoretical blueprints, both the holographic photopolymers and photoaddressable polymers are then revisited and they are experimentally validated as easy‐to‐craft mediums of OFVs. The landscape of volume gratings is extended by providing an integrative pipeline of OFVs across their theoretical design and practical materialization.
A n‐type, Stable Electrolyte Gated Organic Transistor Based on a Printed Polymer
Authors: Viola Fabrizio Antonio , Melloni Filippo , Molazemhosseini Alireza , Modena Francesco , Sassi Mauro , Beverina Luca , Caironi Mario
Published: September 2022

Electrolyte‐gated organic transistors (EGOTs) are promising and versatile devices for next‐generation biosensors, neuromorphic systems, and low‐voltage electronics. They are particularly indicated for applications where stable operation in aqueous environment and cost‐effective manufacturing are required. Indeed, EGOTs can be fabricated through low‐cost, large area, and scalable techniques, such as printing, from a large portfolio of solution processable organic materials, which are often able to stably operate in water or physiological solutions. Despite a large number of solution processable EGOTs have been reported in the literature so far, only a few are based on printed semiconductors, with no examples of digitally printed, i.e., inkjet printed, n‐type devices, which would easily enable complementary architectures. In this work, we propose the first example of a n‐type electrolyte gated organic transistor based on an inkjet printed polymer. The proposed device shows a high stability when operated in water and requires only 3 hours of conditioning to produce a stable response, a much faster dynamic than in the case of printed polymers currently tested for p‐type EGOTs. As a proof‐of‐concept, the proposed printed n‐type EGOT is successfully integrated with a printed single‐walled carbon‐nanotubes based p‐type device in a logic inverter, demonstrating the possibility to build simple water‐gated digital electronic circuits.
Alternatives to Water Photooxidation for Photoelectrochemical Solar Energy Conversion and Green H2 Production
Authors: Ta Xuan Minh Chau , Daiyan Rahman , Nguyen Thi Kim Anh , Amal Rose , Tran‐Phu Thanh , Tricoli Antonio
Published: September 2022

Photoelectrochemical (PEC) water splitting is considered a promising technology to produce renewable hydrogen, a clean fuel or energy carrier to replace conventional carbon‐based fossil‐fuel sources. Nevertheless, the overall solar‐to‐hydrogen efficiency and the cost‐effectiveness of this technology are still unsatisfactory for practical implementation. This can be primarily attributed to the sluggish kinetics of the anodic oxygen evolution reaction (OER) and the relatively low economic value of cogenerated O2 production. Over the past decades, there are extensive efforts to explore more kinetically favorable photooxidation reactions, which coupled with hydrogen evolution reaction (HER) can simultaneously improve H2 production yield and produce higher valuable alternatives to conventional O2. This review aims to present recent progress on the alternative anodic choices to OER. Here, the fundamental of PEC water splitting and the critical components required for this system are first shortly summarized. Then the benefits and issues of alternative photooxidation reactions including photooxidation of water to hydrogen peroxide, chlorine, alcohol, 5‐hydroxymethylfurfural, or urea oxidation when combined with the concurrent HER, are reviewed and analyzed. This review is concluded by presenting a critical evaluation of the challenges and opportunities of these alternative HER‐coupled photooxidation reactions for solar energy production and environmental treatment.
Intriguing interactions of triazolyl organosilane with copper (II) ion, blue copper protein, and silica nanoparticles: Spectral and theoretical approach
Authors: Singh Gurjaspreet , Kaur Jashan Deep , Pawan  , Priyanka  , Mohit  , Devi Anita , Gupta Sofia , Thakur Yamini , Singh Kamal Nain
Published: September 2022

In this manuscript, a concise library of 2‐Amino‐4‐chlorophenol‐based organosilanes 5(a‐c) was designed and synthesized by employing a multistep strategy and characterized with the help of NMR (1H and 13C) spectroscopic and mass spectrometry techniques. The silica nanoparticles loaded with 5a have been successfully synthesized and confirmed with the help of various techniques. Further, the interaction of probes 5a and its hybrid silica nanoparticles (A‐NPs) have been investigated towards various metal ions and exhibited favorable selectivity towards Cu2+ ions over other common metal ions in methanol with both colorimetric and fluorimetric read‐outs. The binding of probes 5a and A‐NPs with Cu2+ can be monitored by change of color in daylight and also by turn‐off fluorescence response in UV light. The sensing mechanism is ascribed to paramagnetic nature of Cu2+ ion leading to ligand to metal charge transfer and, hence, shows chelation enhanced fluorescence quenching (CHEQ) effect in the vicinity of ligands 5a and A‐NPs. The results demonstrated that the hybrid nanocomposites (A‐NPs) has even lower limit of detection and higher binding affinity as compared to probe 5a. The possible mechanism of 1:1 binding of 5a with Cu2+ could be substantiated by the density functional theory. Thus, this facile and appropriate sensing strategy may serve as a promising tool for selective and sensitive detection of Cu2+ ions. Moreover, the molecular docking studies provide valuable information regarding the interaction of compound 5a with the blue copper protein (plastocyanin). Hence, the current investigation provides a new avenue to design more potent organosilane analogs.
Concepts and Emerging Trends for Structural Battery Electrolytes
Authors: Tan Ming Yan , Safanama Dorsasadat , Goh Shermin S. , Lim Jason Y. C. , Lee Chih‐Hung , Yeo Jayven Chee Chuan , Thitsartarn Warintorn , Srinivasan Madhavi , Fam Derrick Wen Hui
Published: September 2022

The structural battery is a multifunctional energy storage device that aims to address the weight and volume efficiency issues that conventional batteries face, especially in electric transportation. By combining the functions of mechanical load bearing and energy storage, structural batteries can reduce the reliance on, or even eventually replace the main power source in an electric vehicle or a drone. However, one of the key challenges to be addressed before achieving multifunctionality in structural batteries would be the design of a suitable multifunctional structural battery electrolyte. The structural battery electrolyte is the constituent that provides mechanical integrity under flexural loads or impact and hence determines the electrochemical and much of the mechanical performance of a structural battery device. This concept paper aims to cover the key considerations and challenges facing the design of structural battery electrolytes. In addition, the main approaches to surmount these challenges are highlighted, keeping design aspects like sustainability and recyclability in view.
Exploring brainstem auditory evoked potentials and mental development index as early indicators of autism spectrum disorders in high‐risk infants
Authors: Wang Xiaoyan , Carroll Xianming , Zhang Ping , du Prel Jean‐Baptist , Wang Hong , Xu Haiqing , Leeper‐Woodford Sandra
Published: September 2022

This study of infants from Hubei Province, China examined brainstem auditory evoked potentials (BAEP) and mental development index (MDI) as possible early indicators associated with autism spectrum disorders (ASD). The 34 ASD cases and 102 controls who had recovered from perinatal conditions were matched for age, sex, gestational age, birth weight and maternal age. BAEP absolute latencies (AL) I, III, V and interpeak latencies (IPL) I‐III, III‐V, I‐V were compared in ASD cases and controls at ages 1, 3 and 6 months. MDI scores were compared in these infants from 1 month to 2 years old. Multiple logistic regression analysis was performed to test associations among ASD, BAEP and MDI. Results showed BAEP AL I, V and IPL III‐V prolonged in the ASD group (p < 0.001), and MDI scores in ASD cases sharply declining from 12 to 24 months (p < 0.001). Regression analysis revealed odds ratios (OR) indicating that ASD was likely associated with abnormal values of BAEP AL I at 1 and 3 months (ORAL I: 4.27; ORAL I: 4.13), and AL V at 6 months (ORAL V: 7.85). Lower MDI scores (MDI < 80) in infants at 1, 3, and 6 months were likely associated with ASD (ORMDI: 2.58; ORMDI: 3.83; ORMDI: 4.87). These data show that abnormal BAEP values and low MDI scores are independent factors associated with ASD, and that monitoring of BAEP and MDI during infancy might facilitate screening for ASD development.
Enhancing estimation methods for integrating probability and nonprobability survey samples with machine‐learning techniques. An application to a Survey on the impact of the COVID‐19 pandemic in Spain
Authors: Rueda María del Mar , Pasadas‐del‐Amo Sara , Rodríguez Beatriz Cobo , Castro‐Martín Luis , Ferri‐García Ramón
Published: September 2022

Web surveys have replaced Face‐to‐Face and computer assisted telephone interviewing (CATI) as the main mode of data collection in most countries. This trend was reinforced as a consequence of COVID‐19 pandemic‐related restrictions. However, this mode still faces significant limitations in obtaining probability‐based samples of the general population. For this reason, most web surveys rely on nonprobability survey designs. Whereas probability‐based designs continue to be the gold standard in survey sampling, nonprobability web surveys may still prove useful in some situations. For instance, when small subpopulations are the group under study and probability sampling is unlikely to meet sample size requirements, complementing a small probability sample with a larger nonprobability one may improve the efficiency of the estimates. Nonprobability samples may also be designed as a mean for compensating for known biases in probability‐based web survey samples by purposely targeting respondent profiles that tend to be underrepresented in these surveys. This is the case in the Survey on the impact of the COVID‐19 pandemic in Spain (ESPACOV) that motivates this paper. In this paper, we propose a methodology for combining probability and nonprobability web‐based survey samples with the help of machine‐learning techniques. We then assess the efficiency of the resulting estimates by comparing them with other strategies that have been used before. Our simulation study and the application of the proposed estimation method to the second wave of the ESPACOV Survey allow us to conclude that this is the best option for reducing the biases observed in our data.
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

There 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

The 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

Objectives

The 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.

Methods

Forty‐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.

Results

A 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.

Conclusions

The 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

Environmental 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

Invited 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

Background

Flow 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.

Methods

We 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.

Results

For 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.

Conclusions

This 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

Introduction

To determine whether slowed gait and weakened grip strength independently, or together, better identify risk of cognitive decline or dementia.

Methods

Time 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).

Results

Over 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.

Discussion

Gait 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.
Borohydride Ammoniate Solid Electrolyte Design for All‐Solid‐State Mg Batteries
Authors: Pang Yuepeng , Nie Zhengfang , Xu Fen , Sun Lixian , Yang Junhe , Sun Dalin , Fang Fang , Zheng Shiyou
Published: September 2022

Searching for novel solid electrolytes is of great importance and challenge for all‐solid‐state Mg batteries. In this work, we develop an amorphous Mg borohydride ammoniate, Mg(BH4)2·2NH3, as a solid Mg electrolyte that prepared by a NH3 redistribution between 3D framework‐γ‐Mg(BH4)2 and Mg(BH4)2·6NH3. Amorphous Mg(BH4)2·2NH3 exhibits a high Mg‐ion conductivity of 5 × 10−4 S cm−1 at 75 °C, which is attributed to the fast migration of abundant Mg vacancies according to the theoretical calculations. Moreover, amorphous Mg(BH4)2·2NH3 shows an apparent electrochemical stability window of 0–1.4 V with the help of in‐situ formed interphases, which can prevent further side reactions without hindering the Mg‐ion transfer. Based on the above superiorities, amorphous Mg(BH4)2·2NH3 enables the stable cycling of all‐solid‐state Mg cells, as the critical current density reaches 3.2 mA cm−2 for Mg symmetrical cells and the reversible specific capacity reaches 141 mAh g−1 with a coulombic efficiency of 91.7% (first cycle) for Mg||TiS2 cells.
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

Aims

Peripartum 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 results

A 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).

Conclusions

In 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

Background

Allodynia 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.

Objectives

This study investigated the use of pain‐autonomic readouts to objectively detect sensitization processes in CRPS.

Methods

Twenty 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).

Results

Individuals 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).

Conclusions

This 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.

Significance

This 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

Background

Trigeminal 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).

Methods

A 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.

Results

Of 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).

Conclusion

Implementation 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.

Significance

Implementation 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

Objectives

To 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.

Methods

We 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.

Results

Twenty 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.

Conclusions

The 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

The 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.
Vaccine‐induced binding and neutralizing antibodies against Omicron 6 months after a homologous BNT162b2 booster
Authors: Favresse Julien , Gillot Constant , Bayart Jean‐Louis , David Clara , Simon Germain , Wauthier Loris , Closset Mélanie , Dogné Jean‐Michel , Douxfils Jonathan
Published: September 2022

Evidence about the long‐term persistence of the booster‐mediated immunity against Omicron is mandatory for pandemic management and deployment of vaccination strategies. A total of 155 healthcare professionals (104 COVID‐19 naive and 51 with a history of SARS‐CoV‐2 infection) received a homologous BNT162b2 booster. Binding antibodies against the spike protein and neutralizing antibodies against Omicron were measured at several time points before and up to 6 months after the booster. Geometric mean titers of measured antibodies were correlated to vaccine efficacy (VE) against symptomatic disease. Compared to the highest response, a significant 10.2‐ and 11.5‐fold decrease in neutralizing titers was observed after 6 months in participants with and without history of SARS‐CoV‐2 infection. A corresponding 2.5‐ and 2.9‐fold decrease in binding antibodies was observed. The estimated T1/2 of neutralizing antibodies in participants with and without history of SARS‐CoV‐2 infection was 42 (95% confidence interval [CI]: 25–137) and 36 days (95% CI: 25–65). Estimated T1/2 were longer for binding antibodies: 168 (95% CI: 116–303) and 139 days (95% CI: 113–180), respectively. Both binding and neutralizing antibodies were strongly correlated to VE (r = 0.83 and 0.89). However, binding and neutralizing antibodies were modestly correlated, and a high proportion of subjects (36.7%) with high binding antibody titers (i.e., >8434 BAU/ml) did not have neutralizing activity. A considerable decay of the humoral response was observed 6 months after the booster, and was strongly correlated with VE. Our study also shows that commercial assays available in clinical laboratories might require adaptation to better predict neutralization in the Omicron era.