bluuebunny/crossref_metadata_2025 huggingface dataset:
Controllable Doping in 2D Layered Materials
Authors: Wang Zhen , Xia Hui , Wang Peng , Zhou Xiaohao , Liu Chunsen , Zhang Qinghua , Wang Fang , Huang Menglin , Chen Shiyou , Wu Peisong , Chen Yunfeng , Ye Jiafu , Huang Shenyang , Yan Hugen , Gu Lin , Miao Jinshui , Li Tianxin , Chen Xiaoshuang , Lu Wei , Zhou Peng , Hu Weida
Published: September 2021

For each generation of semiconductors, the issue of doping techniques is always placed at the top of the priority list since it determines whether a material can be used in the electronic and optoelectronic industry or not. When it comes to 2D materials, significant challenges have been found in controllably doping 2D semiconductors into p‐ or n‐type, let alone developing a continuous control of this process. Here, a unique self‐modulated doping characteristic in 2D layered materials such as PtSSe, PtS0.8Se1.2, PdSe2, and WSe2 is reported. The varying number of vertically stacked‐monolayers is the critical factor for controllably tuning the same material from p‐type to intrinsic, and to n‐type doping. Importantly, it is found that the thickness‐induced lattice deformation makes defects in PtSSe transit from Pt vacancies to anion vacancies based on dynamic and thermodynamic analyses, which leads to p‐ and n‐type conductance, respectively. By thickness‐modulated doping, WSe2 diode exhibits a high rectification ratio of 4400 and a large open‐circuit voltage of 0.38 V. Meanwhile, the PtSSe detector overcomes the shortcoming of large dark‐current in narrow‐bandgap optoelectronic devices. All these findings provide a brand‐new perspective for fundamental scientific studies and applications.
Impact of the Buffer/Absorber Interface on the Metastability of Fill Factor Temperature Coefficients in CIGSSe Solar Cells
Authors: Ahmed Hamsa , Solovyeva Vita , Gonzalez Marco A. , Elshabasi Mohamed , Richter Michael , Pareek Devendra , Heise Stephan J. , Stölzel Marko , Weber Alfons , Dalibor Thomas , Schäfer Sascha , Parisi Jürgen
Published: September 2021

The metastable behavior of the fill factor temperature coefficient (βFF,rel) in Cu(In,Ga)(S,Se)2 solar cells is investigated for absorbers with a different Ga content in the front surface, and for different buffer materials. The buffer/absorber interface region is suggested to be the location which causes the metastability in βFF,rel. Temperature dependent current–voltage curves, light‐biased external quantum efficiency, and low temperature capacitance–voltage measurements are performed to characterize the electrical properties and metastable defects in the investigated solar cell devices. The presence of Ga in the absorber front surface, together with the buffer layer material plays a significant role in the metastable behavior. Additionally, energy dispersive X‐ray spectroscopy indicates that the InxSy buffer layers allow for elemental interdiffusion from absorbers with a Ga‐richer front surface, whereas a Zn(O,S) buffer shows to be rather resilient to atomic diffusion. The elemental interdiffusion between the buffer and absorber layers is proposed to be the cause of the defects causing the observed βFF,rel metastability.
Anomalous Electronic and Protonic Conductivity of 2D Titanium Oxide and Low‐Temperature Power Generation Using Its Protonic Conduction
Authors: Lee Sang Eun , Jung Sung Yeb , Seo Jun , Joo Jong Hoon , Lee Jaekwang , Kim Young‐Min , Lee Kyu Hyoung , Kim Yong In , Park Hee Jung
Published: September 2021

In this study, a titanium‐oxide film is fabricated by stacking 2D nanosheets with a thickness of 1 nm layer‐by‐layer. The electrical properties of the titanium‐oxide film are investigated under various temperatures (25–300 °C) and a water vapor atmosphere. As a result, it is found that protonic conduction is dominant at low temperatures (<100 °C), while electronic conduction is highest at high temperatures (>200 °C). The electrical conductivity is about one billion times higher than that of conventional 3D titanium‐oxide. Protons, dominant charge carriers at low temperature, are transported along the pathway between layers of nanosheets. The protonic conductivity is as high as 10−4−5 S cm−1 due to the increased interfacial density of the film. This anomalous electronic and protonic conduction is expected to be available in various applications. In this study, the developed 2D titanium‐oxide with high protonic conductivity is employed in the solid electrolyte of a solid oxide fuel cell using water as a fuel. A competitive power density of ≈0.22 mW cm−2 is obtained at low temperature (75 °C) under a water concentration gradient.
Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged Skin
Authors: Sun Xiaoyan , Xiang Jiangbing , Chen Runkai , Geng Zhijun , Wang Lintao , Liu Yiqiong , Ji Shuaifei , Chen Huating , Li Yan , Zhang Cuiping , Liu Peng , Yue Tao , Dong Lei , Fu Xiaobing
Published: September 2021

Restoration of sweat glands (SwGs) represents a great issue in patients with extensive skin defects. Recent methods combining organoid technology with cell fate reprogramming hold promise for developing new regenerative methods for SwG regeneration. Here, a practical strategy for engineering functional human SwGs in vitro and in vivo is provided. First, by forced expression of the ectodysplasin‐A in human epidermal keratinocytes (HEKs) combined with specific SwG culture medium, HEKs are efficiently converted into SwG cells (iSwGCs). The iSwGCs show typical morphology, gene expression pattern, and functions resembling human primary SwG cells. Second, by culturing the iSwGCs in a special 3D culturing system, SwG organoids (iSwGOs) that exhibit structural and biological features characteristic of native SwGs are obtained. Finally, these iSwGOs are successfully transplanted into a mouse skin damage model and they develop into fully functioning SwGs in vivo. Regeneration of functional SwG organoids from reprogrammed HEKs highlights the great translational potential for personalized SwG regeneration in patients with large skin defects.
Sox2 regulates globose basal cell regeneration in the olfactory epithelium
Authors: Li Zhexuan , Wei Ming , Shen Wenjuan , Kulaga Heather , Chen Mengfei , Lane Andrew P.
Published: September 2021

Background

In the olfactory epithelium, mitotically active globose basal cells (GBCs) continuously replenish olfactory sensory neurons (OSNs) lost throughout life. Although an essential role of the transcription factor Sox2 in expanding olfactory progenitors/stem cells has been shown, its precise role in olfactory GBCs remain incompletely understood.

Methods

We characterized the Sox2 expression in olfactory GBCs in normal conditions and in a lesion‐regeneration model using a Lgr5EGFP‐IRES‐creERT2 strain. During GBC‐mediated regeneration, genetic deletion of sox2 and lineage tracing experiments were performed to examine the function of Sox2 in the progeny of Lgr5‐EGFP+ GBCs.

Results

Over 95% of Lgr5‐EGFP+ GBCs express Sox2 in normal or regeneration conditions. Loss of Sox2 dramatically reduces the cell number in each lineage traced cluster. In the progeny of Lgr5‐EGFP+ GBCs, loss of Sox2 significantly decreased the portion of OMP+ OSNs. However, the generation of sustentacular cells was unchanged.

Conclusions

Our observations support an essential role of Sox2 in adult olfactory regeneration, likely acting on neuronal‐lineage GBCs.
Predictive value of clinical characteristics in eosinophilic chronic rhinosinusitis with nasal polyps: A cross‐sectional study in the Chinese population
Authors: Yu Longgang , Jiang Yan , Yan Bing , Fang Gaoli , Wang Chengshuo , Zhang Luo
Published: September 2021

Background

Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a refractory subtype of chronic rhinosinusitis with nasal polyps (CRSwNP), with clinical characteristics differing from those of non‐ECRSwNP. We aimed to explore the predictive value of clinical characteristics, including medical history, symptoms, and signs, prior to ECRSwNP diagnosis, and to develop a nomogram for use in clinical practice.

Methods

A total of 502 patients with CRSwNP were enrolled. Based on the degree of eosinophilic infiltration in nasal polyps (NPs), patients were classified as ECRSwNP or non‐ECRSwNP group. Participants’ demographic characteristics, asthma history, severity of nasal symptoms (nasal obstruction, rhinorrhea, hyposmia, and facial pain/headache) according to the visual analog scale, and nasal polyp scores based on polyp scoring system were recorded. Logistic regression analysis was performed to screen for independent risk factors, and a model nomogram was constructed.

Results

The percentage of asthmatic patients and the hyposmia, rhinorrhea, and total nasal symptom scores were significantly higher in ECRSwNP patients than that in non‐ECRSwNP patients. The nasal polyp score was lower in the eosinophilic group than that in the non‐eosinophilic group. Logistic regression analysis revealed that asthma history and hyposmia, rhinorrhea and nasal polyp scores were independent predictors of ECRSwNP. A nomogram consisting of these four independent risk factors was constructed, and its C‐index was 0.808 (95% CI, 0.771 to 0.846).

Conclusions

The nomogram based on asthma history and olfactory, rhinorrhea, and nasal polyp scores could help predict ECRSwNP, providing a simple, fast, and practical way to distinguish ECRSwNP from non‐ECRSwNP cases in clinical practice.
Associations of amyloid and neurodegeneration plasma biomarkers with comorbidities
Authors: Syrjanen Jeremy A. , Campbell Michelle R. , Algeciras‐Schimnich Alicia , Vemuri Prashanthi , Graff‐Radford Jonathan , Machulda Mary M. , Bu Guojun , Knopman David S. , Jack Clifford R. , Petersen Ronald C. , Mielke Michelle M.
Published: September 2021

Introduction

Blood‐based biomarkers of amyloid pathology and neurodegeneration are entering clinical use. It is critical to understand what factors affect the levels of these markers.

Methods

Plasma markers (Aβ42, Aβ40, NfL, T‐tau, Aβ42/40 ratio) were measured on the Quanterix Simoa HD‐1 analyzer for 996 Mayo Clinic Study of Aging (MCSA) participants, aged 51 to 95 years. All other data were collected during in‐person MCSA visits or abstracted from the medical record.

Results

Among cognitively unimpaired (CU) participants, all plasma markers correlated with age. Linear regression models revealed multiple relationships. For example, higher Charlson Comorbidity Index and chronic kidney disease were associated with higher levels of all biomarkers. Some relationships differed between mild cognitive impairment and dementia participants.

Discussion

Multiple variables affect plasma biomarkers of amyloid pathology and neurodegeneration among CU in the general population. Incorporating this information is critical for accurate interpretation of the biomarker levels and for the development of reference ranges.
Effects of I3− Electrolyte Additive on the Electrochemical Performance of Zn Anodes and Zn/MnO2 Batteries
Authors: Liu Siying , Shang Wenshuo , Yang Yaxin , Kang Dongjian , Li Changsheng , Sun Buting , Kang Litao , Yun Shan , Jiang Fuyi
Published: September 2021

While delivering the highest energy density among low‐cost aqueous batteries, the practical implement of rechargeable Zn‐ion batteries (ZIBs) is still seriously restricted by the dynamic parasitic reactions on the metallic Zn anodes including dendrite growth, H2 evolution and corrosion reactions. Modulating electrolyte is identified as a facile and effective approach to restrain these detrimental processes by various chemical mechanisms. Herein, we report a new strategy to improve the performance of Zn anodes and ZIBs by simply adding I3− species into the electrolytes. The I3− can react with the surface Zn and passivate the growth hotspots of Zn dendrites, prolonging the cycling lifetime of the electrodes. As a competitive reaction, it can also suppress the H2O‐derived corrosion and H2 evolution process. The I3− is regenerable by oxidizing reactions on cathode surface, and can therefore long‐term persist its beneficial effects in ZIBs, as demonstrated in the classic Zn/MnO2 battery. However, the I3− additive seems failed in evolving into a dense interfacial protective layer, and may be useful as a supplementary measure to prevent shorting failure of Zn‐based batteries.
Quantification of serum thyroid hormones using tandem mass spectrometry in patients with Down syndrome
Authors: Iwano Reiko , Toki Machiko , Hanakawa Junko , Asakura Yumi , Adachi Masanori , Tanaka Yukichi , Muroya Koji
Published: September 2021

Thyroid dysfunction is common in patients with Down syndrome (DS), the most common chromosomal disorder. Thyroid hormones (THs) are important for normal growth, neurodevelopment, and metabolism, highlighting the importance of quantifying the levels in patients with DS. However, current methods possess cross‐reactivity that results in inaccuracies in quantification. We aimed at developing a new analytical method for quantifying the total 3,3′,5‐triiodo‐l‐thyronine (TT3), total 3,3′,5,5′‐tetraiodo‐l‐thyronine (TT4), 3,3′,5′‐triiodo‐l‐thyronine, and reverse T3 (rT3) levels using LC–MS/MS. Repeatability and reproducibility with coefficient of variation values of 2–9 and 3–13%, respectively, were acceptable, suggesting that the assay was suitable for measuring serum THs. We measured the serum TH levels of patients with DS but without thyroid dysfunction (age, 3–20 years) and compared the levels to those of controls (patients with idiopathic short stature; age, 3–17 years). When TH levels were summarized by age group, the serum TT4 concentrations were not significantly different between the controls and patients with DS across all age groups. Meanwhile, the serum TT3 concentrations differed according to age. In addition, the serum rT3 concentrations were significantly higher in patients with DS than in controls, except for those in the 12–14 age group. We also calculated the T3/T4 and rT3/T4 ratios to elucidate the reason for the higher rT3 in patients with DS; however, no useful findings were obtained. Thus, further investigation is needed to clarify our findings.
(Mis)managing overstock in luxury: Burning inventory and brand trust to the ground
Authors: Lee Park Camila , Fracarolli Nunes Mauro , Paiva Ely Laureano
Published: September 2021

Traditionally associated with demands for superior quality and social status, luxury consumption is expected to undergo important transformations in the coming decades. Following a series of societal changes, the environmental impacts generated by companies have become decisive factors in purchasing decisions. Authors have also been stressing the effect of sustainability performance on assorted dimensions of B2C relationships, thereby putting pressure on companies to incorporate these trends. While luxury brands have sought to adapt their business models, a series of unsustainable practices continue to be part of their day‐to‐day operations. Among the most controversial is the burning of unsold products as a way of preserving brand value. In addition to attracting unwanted attention from the media, the destruction of fully functional products often triggers harsh reactions from environmentalists, as well as from consumers who are more sensitive to these issues. The prospect of growing demands for environmental responsibility, coupled with the perception that any failure in this regard represents a risk to the reputational assets of luxury companies, makes the investigation of inventory burning in relation to stakeholders' perceptions an urgent task. Aiming to offer new insights into the future of sustainable luxury consumption, we assess the impact of this practice on two key components of consumer perception. Through two scenario‐based experiments with a total sample of 492 participants, we investigate the effects of inventory burning on consumer trust and avoidance of luxury brands. Our results indicate the need for luxury brands to further incorporate environmental demands as they seek to serve increasingly demanding eco‐conscious consumers.
Development and validation of a predictive model for bleeding after peripheral vascular intervention: A report from the National Cardiovascular Data Registry Peripheral Vascular Interventions Registry
Authors: Salisbury Adam C. , Safley David M. , Kennedy Kevin F. , Bhardwaj Bhaskar , Aronow Herbert D. , Jones William Schuyler , Feldman Dmitriy N. , Secemsky Eric , Tsai Thomas T. , Attaran Robert R. , Spertus John A.
Published: September 2021

Objectives

To develop a model to predict risk of in‐hospital bleeding following endovascular peripheral vascular intervention.

Background

Peri‐procedural bleeding is a common, potentially preventable complication of catheter‐based peripheral vascular procedures and is associated with increased mortality. We used the National Cardiovascular Data Registry (NCDR) Peripheral Vascular Interventions (PVI) Registry to develop a novel risk‐prediction model to identify patients who may derive the greatest benefit from application of strategies to prevent bleeding.

Methods

We examined all patients undergoing lower extremity PVI at 76 NCDR PVI hospitals from 2014 to 2017. Patients with acute limb ischemia (n = 1600) were excluded. Major bleeding was defined as overt bleeding with a hemoglobin (Hb) drop of ≥ 3 g/dl, any Hb decline of ≥ 4 g/dl, or a blood transfusion in patients with pre‐procedure Hb ≥ 8 g/dl. Hierarchical multivariable logistic regression was used to develop a risk model to predict major bleeding. Model validation was performed using 1000 bootstrapped replicates of the population after sampling with replacement.

Results

Among 25,382 eligible patients, 1017 (4.0%) developed major bleeding. Predictors of bleeding included age, female sex, critical limb ischemia, non‐femoral access, prior heart failure, and pre‐procedure hemoglobin. The model demonstrated good discrimination (optimism corrected c‐statistic = 0.67), calibration (corrected slope = 0.98, intercept of −0.04) and range of predicted risk (1%–18%).

Conclusions

Post‐procedural PVI bleeding risk can be predicted based upon pre‐ and peri‐procedural patient characteristics. Further studies are needed to determine whether this model can be utilized to improve procedural safety through developing and targeting bleeding avoidance strategies.
Effect of thiamethoxam seed treatment in peanut
Authors: Monfort Scott , Culbreath Albert , Abney Mark , Brandenburg Rick , Royals Brian , Jordan David , Herbert Ames , Taylor Sally , Malone Sean
Published: September 2021

Tobacco thrips (Frankliniella fusca) and tomato spotted wilt (TSW) orthotospovirus (family Tospoviridae, genus Orthotospovirus) can reduce peanut (Arachis hypogaea L.) yield. Systemic insecticides are applied in the seed furrow at planting and to peanut foliage to reduce injury from tobacco thrips and decrease incidence of TSW. Research was conducted in Georgia, North Carolina, South Carolina, and Virginia in 2013 and 2014 to compare the effect of the following treatments on tobacco thrips feeding injury and expression of TSW in peanut: thiamethoxam seed treatment, thiamethoxam seed treatment followed by acephate 3 weeks after planting, phorate applied in the seed furrow at planting, and a nontreated check. Tobacco thrips feeding injury and TSW incidence were significantly higher in thiamethoxam and thiamethoxam followed by acephate‐treated peanut than peanut treated with phorate. Thiamethoxan seed treatment followed by acephate resulted in significantly lower tobacco thrips feeding injury compared to thiamethoxam seed treatment alone. Yield of Virginia market type cultivars was greater when thiamethoxam was followed by acephate applied to peanut foliage or when phorate was applied compared with nontreated peanut or the seed treatment alone. Runner market type cultivars yielded higher when phorate was applied compared with nontreated peanut while peanut treated with thiamethoxam with or with acephate yielded similar to both of these treatments.
Appearance of microtubules at the cytokinesis to interphase transition in Arabidopsis thaliana
Authors: Lucas Jessica R.
Published: September 2021

Microtubule arrays drastically reorganize during the cell cycle to facilitate specific events. Many cells contain a centrosome that dictates the assembly and organization of microtubule arrays. However, plant cells and many others do not contain centrosomes or discrete microtubule organizing centers. In plants, microtubules nucleate and polymerize from gamma‐tubulin‐containing complexes in the interphase cell cortex. During plant cell division, microtubules nucleate near nuclei to form the mitotic spindle and plant‐specific phragmoplast required for cytokinesis. Therefore, during the plant cell cycle, microtubule nucleation shifts from cell cortex to the perinuclear region. While it is unclear how this shift occurs, previous studies observed microtubules that appeared to extend from nuclei into the cortex as cells transitioned into interphase in small cells. These data led to the hypothesis that microtubule nucleation complexes move from the nuclear surface to the cortex at the transition from cytokinesis into interphase. Here we document GFP labeled microtubules in living plant cells during the transition from cytokinesis to interphase. We observed apparent groups of microtubules spanning between the nucleus and cell cortex in large, vacuolated epidermal leaf cells. We also observed microtubules in the cell cortex that appeared separate from perinuclear‐associated microtubules. While these cortical microtubules were not always seen, when present they were apparent before cytokinesis was complete and/or before nuclear‐associated microtubules were obvious. These data add to and deepen the knowledge of microtubule reorganization at this cell cycle transition.
Tracking Reaction Pathways by a Modular Flow Reactor Coupled to Electrospray Ionization Mass Spectrometry
Authors: Tripodi Guilherme L. , Derks Max T. G. M. , Rutjes Floris P. J. T. , Roithová Jana
Published: September 2021

Invited for this month's cover is the group of Jana Roithová at the Radboud University (The Netherlands). The cover picture shows a mini‐plant for automated monitoring of chemical reactions. Flow chemistry enables screening of chemical reactions under well‐defined conditions that can  systematically vary. Mass spectrometry couples it with the detection of low abundant reaction intermediates. Therefore, this platform allows tracking reaction pathways, monitoring reaction kinetics of intermediates and is set for a discovery of novel chemical transformations in future. Read the full text of their Full Paper at 10.1002/cmtd.202100046.
Monitoring Aqueous Phase Reactions by Operando ATR‐IR Spectroscopy at High Temperature and Pressure: A Biomass Conversion Showcase
Authors: Khalili Khaled N. M. , de Peinder Peter , Bruijnincx Pieter C. A. , Weckhuysen Bert M.
Published: September 2021

Invited for this month's cover is the group of Bert M. Weckhuysen at the Utrecht University (The Netherlands). The cover picture shows an attenuated Total Reflection Infrared spectroscopy (ATR‐IR) probe monitoring a chemical reaction in the liquid phase, particularly water, at demanding conditions. The light penetrates few microns deep in proximity of the ATR‐IR probe and thus any IR‐active entity in that range is probed. This research systematically addresses the challenges associated with acquiring operando ATR‐IR spectra for liquid/aqueous phase reactions, which is essential for better understanding of chemical reactions in the liquid phase. Read the full text of their Full Paper at 10.1002/cmtd.202100041.
Nanocellulose: Production and Processing for Biomedical Applications
Authors: Brenes Ricardo Gonzalo Ramírez , Grieco Maria Angela Bernardes , Bojorge Ninoska , Pereira Nei
Published: September 2021

Nanocellulose (NC) is a unique and promising natural material derived from native cellulose. It has attracted much attention for its versatility in construction composites, which have improved chemical and mechanical properties. This review covers the type of biomass used and NC production methods, emphasizing biotechnological routes, which promote their biological properties (biocompatibility, biodegradability and low toxicity), fundamental for medical applications. NC has many hydroxyl groups on its surface, enabling its structure to be modifiable, adaptable and viable for various fields. Furthermore, NC‐based biosensors are suitable for food quality control, monitoring environmental analytes, and particularly in health diagnostics, such as COVID19 detection. The developed analytical devices were described in a table, including information about the sensor molecule, reading system, analyte, range, detection limit, sensitivity and analytical performance.
Efficient Photo‐Thermo‐Electric Conversion Using Polyoxovanadate in Ionic Liquid for Low‐Grade Heat Utilization
Authors: Wang Yan , Liu Congyan , Wang Yang , Zhu Chaofeng , Chen Xihai , Liu Bo
Published: September 2021

A large fraction of energy, including solar energy, is dissipated into ambient atmosphere as low‐grade waste heat. Efficient utilization of such energy is critical to address the current energy crisis and global warming issue. Herein, the efficient near‐IR (NIR)‐photothermal, thermoelectric, and thus photo‐thermo‐electric conversion of polyoxovanadate compound {[Ni(1,10‐phenanthroline)3][V14O34Cl]Cl, NiV14} in ionic liquid was achieved. The solution displayed a NIR‐photothermal efficiency of 16.04 and 23.43 % at 808 and 1064 nm, respectively. Taking advantage of the synergetic thermodiffusive and thermogalvanic effects of various ion species in NiV14 solution, an open circuit voltage of approximately 0.45 V was obtained at ΔT=70 K generated by physical heating or NIR irradiation, indicating a large Seebeck coefficient of 6.38 mV K−1 and an optimized thermal power at 1.2 W m−2. The polyoxovanadate‐ionic liquid system offers a new platform for efficiently utilizing not only low‐grade thermal energy but also solar energy for electricity generation.
IgM and IgA augmented autoantibody signatures improve early‐stage detection of colorectal cancer prior to nodal and distant spread
Authors: Roney Md Saiful Islam , Lanagan Catharine , Sheng Yong Hua , Lawler Karen , Schmidt Christopher , Nguyen Nam‐Trung , Begun Jakob , Kijanka Gregor Stefan
Published: September 2021

Objectives

Tumor‐associated autoantibodies (AAbs) in individuals with cancer can precede clinical diagnosis by several months to years. The objective of this study was to determine whether the primary immune response in form of IgM and gut mucosa‐associated IgA can aid IgG AAbs in the detection of early‐stage colorectal cancer (CRC).

Methods

We developed a novel protein array comprising 492 antigens seropositive in CRC. The array was used to profile IgG, IgM and IgA antibody signatures in 99 CRC patients and 99 sex‐ and age‐matched non‐cancer controls. A receiver operating curve (ROC), Kaplan–Meier survival analysis and univariate and multivariate Cox regression analyses were conducted.

Results

We identified a panel of 16 multi‐isotype AAbs with a cumulative sensitivity of 91% and specificity of 74% (AUC 0.90, 95% CI: 0.850–0.940) across all CRC stages. IgM and IgG isotypes were conversely associated with disease stage with IgM contributing significantly to improved stage I and II sensitivity of 96% at 78% specificity (AUC 0.928, 95% CI: 0.884–0.973). A single identified IgA AAb reached an overall sensitivity of 5% at 99% specificity (AUC 0.520, 95% CI: 0.440–0.601) balanced across all CRC stages. Kaplan–Meier analysis revealed that se33‐1 (ZNF638) IgG AAbs were associated with reduced 5‐year overall survival (log‐rank test,P = 0.012), whereas cumulative IgM isotype signatures were associated with improved 5‐year overall survival (log‐rank test,P = 0.024).

Conclusion

IgM AAbs are associated with early‐stage colorectal cancer. Combining IgG, IgM and IgA AAbs is a novel strategy to improve early diagnosis of cancers.
CircIMMP2L promotes esophageal squamous cell carcinoma malignant progression via CtBP1 nuclear retention dependent epigenetic modification
Authors: Liang Yingkuan , Mao Qixing , Wang Lin , Xia Wenjie , Chen Bing , Wang Hui , Li Rutao , Xu Lin , Jiang Feng , Dong Gaochao
Published: September 2021

Background

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers. The two major lethal causes of ESCC are diagnosis at an advanced stage and lymph node metastasis (LNM). Circular RNAs (circRNAs) play critical regulatory roles in cancer progression, though, largely through unclear mechanisms. However, the character of circRNAs in the malignant progression of ESCC remains unclear.

Methods

The circRNA microarray was used to explore the circRNAs that were differentially expressed between ESCC and paired adjacent normal tissues. The function of circIMMP2L was validated by gain or loss of function assays. Pull‐down, RNA immunoprecipitation assays were used to demonstrate the biological mechanism of circIMMP2L. Tissue microarray (TMA), specimen, and paired plasma were investigated to evaluate the clinical significance of circIMMP2L.

Results

CircIMMP2L, commonly upregulated in tumor and plasma from advanced‐stage ESCC patients and LNM patients, predicts poorer patient survival. CircIMMP2L was also found to be a significant indicator for LNM, even in the T1 stage of ESCC. CircIMMP2L depletion suppressed the malignant progression of ESCC both in vitro and in vivo. Mechanistically, cytoplasmic circIMMP2L interacted with CtBP1 and facilitated the nuclear retention of CtBP1 in a CtBP2‐independent manner. Moreover, circIMMP2L promoted the interaction of CtBP1 with HDAC1 in the nucleus, which is essential for epigenetic remodeling and transcriptional suppression of E‐cadherin and p21.

Conclusions

These findings demonstrated that circIMMP2L promotes the malignant progression of ESCC mediated by CtBP1 nuclear retention and is a robust biomarker for the diagnosis, prognosis, and LNM in ESCC. Further, the findings extend our knowledge about the mechanism of circRNA regulation of gene transcription through epigenetics.
RNA N6‐methyladenosine modification in the lethal teamwork of cancer stem cells and the tumor immune microenvironment: Current landscape and therapeutic potential
Authors: Zhang Zhihui , Zhang Chaoqi , Luo Yuejun , Zhang Guochao , Wu Peng , Sun Nan , He Jie
Published: September 2021

N6‐methyladenosine (m6A), the newest and most prevalent layer of internal epigenetic modification in eukaryotic mRNA, has been demonstrated to play a critical role in cancer biology. Increasing evidence has highlighted that the interaction between cancer stem cells (CSCs) and the tumor immune microenvironment (TIME) is the root cause of tumorigenesis, metastasis, therapy resistance, and recurrence. In recent studies, the m6A modification has been tightly linked to this CSC‐TIME interplay, participating in the regulation of CSCs and TIME remolding. Interestingly, the m6A modification has also been identified as a novel decisive factor in the efficacy of immunotherapies—particularly anti‐PD‐1/PD‐L1 monotherapies—by changing the plasticity of the TIME. Given the functional importance of the m6A modification in the crosstalk between CSCs and the TIME, targeting m6A regulators will open new avenues to overcome therapeutic resistance, especially for immune checkpoint‐based immunotherapy. In the present review, we summarize the current landscape of m6A modifications in CSCs and the TIME, and also prospect the underling role of m6A modifications at the crossroads of CSCs and the TIME for the first time. Additionally, to provide the possibility of modulating m6A modifications as an emerging therapeutic strategy, we also explore the burgeoning inhibitors and technologies targeting m6A regulators. Lastly, considering recent advances in m6A‐seq technologies and cancer drug development, we propose the future directions of m6A modification in clinical applications, which may not only help to improve individualized monitoring and therapy but also provide enhanced and durable responses in patients with insensitive tumors.
A multi‐omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma
Authors: Jin Xing , Liu Lei , Wu Jia , Jin Xiaoxia , Yu Guanzhen , Jia Lijun , Wang Fengying , Shi Minxin , Lu Haimin , Liu Jibin , Liu Dan , Yang Jing , Li Hua , Ni Yan , Luo Qin , Jia Wei , Wang Wei , Chen Wen‐Lian
Published: September 2021

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with inferior prognosis. Here, we conducted comprehensive transcriptomic, proteomic, phosphoproteomic, and metabolomic characterization of human, treatment‐naive ESCC and paired normal adjacent tissues (cohort 1, n = 24) in an effort to identify new molecular vulnerabilities for ESCC and potential therapeutic targets. Integrative analysis revealed a small group of genes that were related to the active posttranscriptional and posttranslational regulation of ESCC. By using proteomic, phosphoproteomic, and metabolomic data, networks of ESCC‐related signaling and metabolic pathways that were closely linked to cancer etiology were unraveled. Notably, integrative analysis of proteomic and phosphoproteomic data pinpointed that certain pathways involved in RNA transcription, processing, and metabolism were stimulated in ESCC. Importantly, proteins with close linkage to ESCC prognosis were identified. By enrolling an ESCC patient cohort 2 (n = 41), three top‐ranked prognostic proteins X‐prolyl aminopeptidase 3 (XPNPEP3), bromodomain PHD finger transcription factor (BPTF), and fibrillarin (FBL) were verified to have increased expression in ESCC. Among these prognostic proteins, only FBL, a well‐known nucleolar methyltransferase, was essential for ESCC cell growth in vitro and in vivo. Furthermore, a validation study using an ESCC patient cohort 3 (n = 100) demonstrated that high FBL expression predicted unfavorable patient survival. Finally, common cancer/testis antigens and established cancer drivers and kinases, all of which could direct therapeutic decisions, were characterized. Collectively, our multi‐omics analyses delineated new molecular features associated with ESCC pathobiology involving epigenetic, posttranscriptional, posttranslational, and metabolic characteristics, and unveiled new molecular vulnerabilities with therapeutic potential for ESCC.
Inhibition of tumor‐associated macrophages by trabectedin improves the antitumor adaptive immunity in response to anti‐PD‐1 therapy
Authors: Belgiovine Cristina , Frapolli Roberta , Liguori Manuela , Digifico Elisabeth , Colombo Federico Simone , Meroni Marina , Allavena Paola , D'Incalci Maurizio
Published: September 2021

A considerable proportion of cancer patients are resistant or only partially responsive to immune checkpoint blockade immunotherapy. Tumor‐Associated Macrophages (TAMs) infiltrating the tumor stroma suppress the adaptive immune responses and, hence, promote tumor immune evasion. Depletion of TAMs or modulation of their protumoral functions is actively pursued, with the purpose of relieving this state of immunesuppression. We previously reported that trabectedin, a registered antitumor compound, selectively reduces monocytes and TAMs in treated tumors. However, its putative effects on the adaptive immunity are still unclear. In this study, we investigated whether treatment of tumor‐bearing mice with trabectedin modulates the presence and functional activity of T‐lymphocytes.

In treated tumors, there was a significant upregulation of T cell‐associated genes, including CD3, CD8, perforin, granzyme B, and IFN‐responsive genes (MX1, CXCL10, and PD‐1), indicating that T lymphocytes were activated after treatment. Notably, the mRNA levels of the Pdcd1 gene, coding for PD‐1, were strongly increased. Using a fibrosarcoma model poorly responsive to PD‐1‐immunotherapy, treatment with trabectedin prior to anti‐PD‐1 resulted in improved antitumor efficacy. In conclusion, pretreatment with trabectedin enhances the therapeutic response to checkpoint inhibitor‐based immunotherapy. These findings provide a good rational for the combination of trabectedin with immunotherapy regimens.
Efficient Synthesis of Cu(II)‐N‐Heterocyclic Carbene Complexes in Water and Their Activity Towards Aerobic Alcohol Oxidation
Authors: Ahmad Bhat Irshad , Avinash Iruthayaraj , Kumar Sachan Sharad , Singh Sadhana , Anantharaman Ganapathi
Published: September 2021

The majority of the copper N‐heterocyclic carbene (NHC) complexes contain Cu in a +1 oxidation state. The Cu(II)‐NHC complexes reported so far usually require strict inert atmosphere conditions. In this work, we report a very facile and quantitative preparation of a series of new Cu(II)‐NHC complexes (2 a–c) starting from the inexpensive and readily available Cu(II) salts like Cu(OAc)2 and CuCl2 ⋅ 2H2O with imidazolium salts (1 a–c), wherein 2 b and 2 c were exclusively synthesized in water under aerobic condition. It should be emphasized that this is the first example where Cu(II)‐NHC complexes have been prepared in the aqueous medium. All the complexes have manifested with a heterobidentate C, O chelate type of coordination to Cu(II) centers forming trans‐[Cu(IRpyO)2] (where R=Me, Mes, Dipp) type of complexes where 2 b forms a perfect square planar Cu(II)‐NHC complex. Complexes 2 a–c were evaluated as catalysts for the aerobic oxidation of alcohols.
A new hedging hypothesis regarding prediction interval formation in stock price forecasting
Authors: Zhu Dan , Wang Qingwei , Goddard John
Published: September 2021

We propose and test a simple hedging hypothesis for prediction interval formation in stock price forecasting. In the presence of uncertainty, forecasters hedge their forecasts by adjusting the bounds of the prediction interval in a way that reflects their forecast of the average forecast of others. This hypothesis suggests a positive relationship between the belief wedge, defined as the difference between the subject's forecast of the average forecast of others and the subject's own point forecast, and the asymmetry of the prediction interval. Empirical support for the hedging hypothesis is drawn from two in‐class surveys, an experiment, and a large survey of professional analysts' forecasts of future stock prices.
Pilot feasibility study of cognitive training exercises for Egyptian adults: Proof of concept
Authors: Tawfik Heba M. , Tsatali Marianna , Hassanin Hany I.
Published: September 2021

Objectives

Cognitive training exercises (CTE) are promising and effective interventions to enhance cognitive reserve and slowdown cognitive deterioration in people with subjective memory impairment (SCI) and mild cognitive impairment (MCI). In this pilot study, we aimed to assess the feasibility of CTE among Egyptian adults.

Methods

Eighteen participants above 40 years old were recruited. They underwent baseline neuropsychological assessment and functional assessment. However, after receiving a 6 weeks' cognitive training, eight participants (seven with MCI and one was cognitively intact) dropped out from the study. Finally, 10 participants (8 participants with MCI, 1 with SCI and 1 was cognitively intact) completed 12 weeks of CTE and undergone the post‐assessment afterward. CTE included visual, verbal, memory, executive function, visuospatial, attention, and psychokinetic exercises through onsite and home‐based sessions.

Results

For the 10 participants who completed 12 weeks of CTE, the Wilcoxon signed‐rank test showed a statistically significant change in the scores of mini‐mental state examination (Z = −2.546, p = 0.011), semantic fluency test (Z = −2.913, p = 0.004), subjective memory complaint questionnaire (Z = −2.913, p = 0.004), Consortium to Establish a Registry for Alzheimer's Disease Word List (first trial: Z = −2.641, p = 0.008; Word list recall: Z = −2.825, p = 0.005), construction abilities (immediate: Z = −2.121, p = 0.034; delayed recall: Z = −2.414, p = 0.016), and Digit span test (forward: Z = −2.724, p = 0.006; backward: Z = −2.724, p = 0.006).

Conclusions

The results of this study suggested that CTE are feasible among Egyptian adults, especially those with MCI, and potentially effective in enhancing global cognition and after 12 weeks of training. Future research should shed light on the efficacy of longitudinal CTE implementation in Arab adults' populations.
Identification of enhancer RNAs for the prognosis of head and neck squamous cell carcinoma
Authors: Feng Guanying , Wang Tianxiao , Xue Feifei , Qi Yibo , Wang Ruixia , Yuan Hua
Published: September 2021

Background

Enhancer RNAs (eRNAs) play an important role in carcinogenesis. The landscape of eRNAs in head and neck squamous cell carcinoma (HNSCC) remains largely unknown.

Methods

The eRNA expression matrix was obtained from the enhancer RNA in the cancer database. Functional enrichment analyses were performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG). Prognostic eRNAs were identified using Cox regression analysis, and a prognostic prediction model was constructed based on coefficients.

Results

KEGG analysis showed that eRNA‐related transcription factors were mainly enriched in herpes simplex virus 1 (HSV1) infection. The zinc finger (ZNF) family may play an essential role in HNSCC. ENSR00000188847, ENSR00000250663, ENSR00000313345, ENSR00000317887, and ENSR00000336429 were identified. The prediction model was robust.

Conclusions

We constructed a robust 5‐eRNA prognostic prediction model, and these eRNAs are potential biomarkers for HNSCC prognosis.
Sharing lessons learnt: Reflections on a novel approach to developing the contextual activity template
Authors: Berber Elise , Read Gemma J. M. , Simcock Gabrielle
Published: September 2021

Introduction

There have been few published applications of the second phase of Cognitive Work Analysis (CWA), Control Task Analysis, particularly the Contextual Activity Template (CAT). The current study aimed to share lessons learnt from utilizing an online survey as a novel approach to development of a CAT. The application domain was sport, specifically football goalkeeping. A secondary aim was to apply the CAT to the goalkeeping role and gain the perceptions of both goalkeeping coaches and players on the functions and situations specific to a goalkeeper during match‐play.

Methods

Ten SMEs with high‐level expertize in goalkeeping coaching and/or playing participated in an online survey including a series of demographic, Likert scale and open‐ended questions regarding goalkeeper specific functions and match‐play situations. Eight goalkeeper match‐play situations and 18 specific functions were included.

Results

A CAT model was created demonstrating the match‐play situations where specific goalkeeper functions occur. Three function groupings were identified: broad (six or more functions), moderate (between three and five functions), and specific (below three functions).

Discussion

Utilizing online surveys to develop a CAT model is a novel approach within the Human Factors and Ergonomics (HFE) literature. Further, the CAT represents a first of its kind analysis in the football performance literature. Strengths and limitations of using online surveys for the development of a CAT are discussed. In conclusion, the work suggests flexible approaches can be used to develop HFE models.
Electrodeposition of Poly‐3‐Methyl Thiophene using Pulsed Techniques: A Preliminary Study
Authors: Pereira Ibaldo Adriana
Published: September 2021

In this preliminary study poly(3‐methyl thiophene) (P3MT) films were obtained by electropolymerization on ITO substrates using as voltage excitation signal differential pulse. The P3MT films present globular morphology, which could provide an increased P3MT/electrode interfacial area. The P3MT films when part of an ITO/P3MT/Al device, present photovoltaic response. The differential pulse technique may be an alternative to prepare polythiophene films aiming polymeric thin films for optoelectronic devices and sensors.
Bone Fractures in Children and Young Adults With Type 1 Diabetes: Age Distribution, Fracture Location, and the Role of Glycemic Control
Authors: Eckert Alexander J , Semler Oliver , Schnabel Dirk , Köstner Katharina , Wurm Donald , Bechtold-Dalla Pozza Susanne , Schaaf Katja , Hörtenhuber Thomas , Hammersen Johanna , Holl Reinhard W
Published: September 2021

Type 1 diabetes (T1D) is a known risk factor for fractures, but the underlying pathophysiology is still not fully understood. This study aims to define age peaks and frequent fracture sites of children and young adults with T1D. Additionally, associations of fractures with metabolic and lifestyle factors as well as with additional complications in individuals with T1D were analyzed. A total of 750 individuals with T1D aged ≤25 years with fractures were matched to 3750 patients with T1D without fractures by demographics and insulin regimen. Hemoglobin A1c (HbA1c) values were compared using linear regression, and logistic regression was used to calculate odds ratios (OR) for fractures in individuals with acute complications and diseases. Median (Q1–Q3) age was 12.7 (9.9 to 14.9) years in individuals with fractures and 16.3 (12.6 to 17.8) years in the entire control group with 65% versus 53% males. Peak age for fractures was 7 to <15 years in males and 9 to <11 years in females, which is earlier than reported for the general population. HbA1c (%) was significantly higher in individuals with fractures than in controls (difference of estimated means: 0.26%; 95% confidence interval [CI] 0.07–0.46), especially in postpubertal females (0.68; 0.10–1.26). Significantly higher odds for fractures were observed in individuals with severe hypoglycemia (OR = 1.90; 95% CI 1.47–2.47), especially in prepubertal females (OR = 2.81; 1.21–6.52]) and postpubertal males (2.44; 1.11–5.38), celiac disease (2.02; 1.67–2.45), and with a history of smoking (1.38; 1.02–1.88). The age peak of fractures seems to be earlier in T1D than in the general population. Poor glycemic control is related to fractures, even before puberty. Associations of HbA1c and severe hypoglycemia with fractures highly depend on age and sex. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).