bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Distancing, Health Care Disruptions, Telemedicine Use, and Treatment Interruption During the COVID‐19 Pandemic in Patients With or Without Autoimmune Rheumatic Disease
Authors: George Michael D. , Baker Joshua F. , Banerjee Shubhasree , Busch Howard , Curtis David , Danila Maria I. , Gavigan Kelly , Kirby Daniel , Merkel Peter A. , Munoz George , Nowell William Benjamin , Stewart Patrick , Sunshine William , Venkatachalam Shilpa , Xie Fenglong , Curtis Jeffrey R.
Published: May 2021

Background

We aimed to compare concerns, social distancing, health care disruptions, and telemedicine use in patients with autoimmune rheumatic disease (ARD) and non‐ARD and to evaluate factors associated with immunomodulatory medication interruptions.

Methods

Patients in a multistate community rheumatology practice network completed surveys from April 2020 to May 2020. Adults with common ARD (rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus) or non‐ARD (gout, osteoarthritis, osteoporosis) were evaluated. Concerns about coronavirus disease 2019 (COVID‐19), social distancing, health care disruptions, and telemedicine use were compared in patients with ARD versus non‐ARD, adjusting for demographics, rural residence, and zipcode‐based measures of socioeconomic status and COVID‐19 activity. Factors associated with medication interruptions were assessed in patients with ARD.

Results

Surveys were completed by 2319/36 193 (6.4%) patients with non‐ARD and 6885/64 303 (10.7%) with ARD. Concerns about COVID‐19 and social distancing behaviors were similar in both groups, although patients receiving a biologic or Janus kinase (JAK) inhibitor reported greater concerns and were more likely to avoid friends/family, stores, or leaving the house. Patients with ARD were less likely to avoid office visits (45.2% vs. 51.0%, odds ratio [OR] 0.79 [0.70‐0.89]) with similar telemedicine use. Immunomodulatory medications were stopped in 9.7% of patients with ARD, usually (86.9%) without a physician recommendation. Compared with patients with an office visit, the likelihood of stopping medication was higher for patients with a telemedicine visit (OR 1.54 [1.19‐1.99]) but highest for patients with no visits (OR 2.26 [1.79‐2.86]).

Conclusion

Patients with ARD and non‐ARD reported similar concerns about COVID‐19 and similar social distancing behaviors. Missed office visits were strongly associated with interruptions in immunomodulatory medication.
The Association of Diuretics and Proton Pump Inhibitors With Chondrocalcinosis
Authors: Felson David T. , Rabasa Gabriela , Chen Xiaoyang , LaValley Michael , Jafarzadeh S. Reza , Lewis Cora E. , Torner James , Nevitt Michael C. , Misra Devyani
Published: May 2021

Objective

Hypomagnesemia increases the risk of chondrocalcinosis and calcium pyrophosphate disease. We examined whether the use of drugs that can cause hypomagnesemia, diuretics and proton pump inhibitors (PPIs), increases the risk of chondrocalcinosis.

Methods

Participants in the Multicenter Osteoarthritis (MOST) Study obtained weight‐bearing knee radiographs, and their medication use was recorded at baseline and 30‐, 60‐, 84‐, and 144‐month examinations. We read radiographs serially for chondrocalcinosis and characterized incident chondrocalcinosis when it first appeared. We classified diuretic use as thiazide, loop, and other. To test drug effects on incident chondrocalcinosis at each interval (eg, 30‐60 months), we excluded persons with chondrocalcinosis at the interval’s beginning. For each drug, we evaluated exposure at the beginning and end of the interval. We conducted knee‐based analyses using Bayesian mixed‐effects discrete time survival models adjusted for age, sex, body mass index, radiographic osteoarthritis, race, and clinic site.

Results

Of 5272 knees, 196 developed chondrocalcinosis. Thiazide use (21.7% of examinations) and PPI use (13.7%) were common. Neither loop nor other diuretic use was associated with incident chondrocalcinosis. Thiazide use at the beginning and end of the interval of incidence conferred a high risk (hazard ratio [HR] = 2.18; 95% confidence interval [CI] 1.23‐3.89), but use at the beginning of the interval was not associated with risk (HR = 1.04). PPI use at the interval’s beginning increased risk of chondrocalcinosis (HR = 2.29; 95% CI 1.37‐3.79).

Conclusion

Thiazide diuretics, but not other diuretics, and PPI use probably increase the risk of chondrocalcinosis. These findings may have important clinical implications.
Understanding the Mechanism of PbCl2 Additive for MAPbI3‐Based Perovskite Solar Cells
Authors: Xie Yulin , Duan Jiashun , Peng Liping , Arramel  , Li Neng
Published: May 2021

PbCl2 additive engineering is an effective method to decrease the charge accumulation in devices. Herein, the influence of PbCl2 additive on the charge transport properties of inverted planar MAPbI3 perovskite devices is investigated by capacitance–voltage (C–V) spectroscopy. The C–V curves show that the ΔVpeak of the MAPbI3−xClx‐based device is decreased compared to the undoped device, indicating that the introduction of chloride ions effectively mitigates charge accumulation at the interface. Simultaneously, it is proposed that the introduction of chloride ions into the perovskite lattice can decrease the trap density, which promotes charge carrier separation/transport at the electrode interfaces/absorber interface, as evidenced by photoluminescence measurements. The findings of this study clarify that trap states and charge accumulation in the MAPbI3 perovskite solar cell have a considerable influence on carrier separation/transport, enhancing the device performance to ultimately achieve power conversion efficiency (PCE) from 12.3% to 15.5%. Accordingly, this work paves the way for further improving the efficiency of perovskite solar cells.
The Emergence and Evolution of Borophene
Authors: Ou Meitong , Wang Xuan , Yu Liu , Liu Chuang , Tao Wei , Ji Xiaoyuan , Mei Lin
Published: May 2021

Neighboring carbon and sandwiched between non‐metals and metals in the periodic table of the elements, boron is one of the most chemically and physically versatile elements, and can be manipulated to form dimensionally low planar structures (borophene) with intriguing properties. Herein, the theoretical research and experimental developments in the synthesis of borophene, as well as its excellent properties and application in many fields, are reviewed. The decade‐long effort toward understanding the size‐dependent structures of boron clusters and the theory‐directed synthesis of borophene, including bottom‐up approaches based on different foundations, as well as up‐down approaches with different exfoliation modes, and the key factors influencing the synthetic effects, are comprehensively summarized. Owing to its excellent chemical, electronic, mechanical, and thermal properties, borophene has shown great promise in supercapacitor, battery, hydrogen‐storage, and biomedical applications. Furthermore, borophene nanoplatforms used in various biomedical applications, such as bioimaging, drug delivery, and photonic therapy, are highlighted. Finally, research progress, challenges, and perspectives for the future development of borophene in large‐scale production and other prospective applications are discussed.
circFAT1 Promotes Cancer Stemness and Immune Evasion by Promoting STAT3 Activation
Authors: Jia Lingfei , Wang Yilun , Wang Cun‐Yu
Published: May 2021

Cancer stemness and immune evasion are closely associated, and play critical roles in tumor development and resistance to immunotherapy. However, little is known about the underlying molecular mechanisms that coordinate this association. Here, it is reported that elevated circular RNA FAT1 (circFAT1) in squamous cell carcinoma (SCC) unifies and regulates the positive association between cancer stemness and immune evasion by promoting STAT3 activation. circFAT1 knockdown (KD) reduces tumorsphere formation of SCC cells in vitro and tumor growth in vivo. Bioinformatic analysis reveals that circFAT1 KD impairs the cancer stemness signature and activates tumor cell‐intrinsic immunity. Mechanistically, circFAT1 binding to STAT3 in the cytoplasm prevents STAT3 dephosphorylation by SHP1 and promotes STAT3 activation, resulting in inhibition of STAT1‐mediated transcription. Moreover, circFAT1 KD significantly enhances PD1 blockade immunotherapy by promoting CD8+ cell infiltration into tumor microenvironment. Taken together, the results demonstrate that circFAT1 is an important regulator of cancer stemness and antitumor immunity.
Optically Induced Static Magnetization in Metal Halide Perovskite for Spin‐Related Optoelectronics
Authors: Wang Miaosheng , Xu Hengxing , Wu Ting , Ambaye Haile , Qin Jiajun , Keum Jong , Ivanov Ilia N. , Lauter Valeria , Hu Bin
Published: May 2021

Understanding the feasibility to couple semiconducting and magnetic properties in metal halide perovskites through interface design opens new opportunities for creating the next generation spin‐related optoelectronics. In this work, a fundamentally new phenomenon of optically induced magnetization achieved by coupling photoexcited orbital magnetic dipoles with magnetic spins at perovskite/ferromagnetic interface is discovered. The depth‐sensitive polarized neutron reflectometry combined with in situ photoexcitation setup, constitutes key evidence of this novel effect. It is demonstrated that a circularly polarized photoexcitation induces a stable magnetization signal within the depth up to 7.5 nm into the surface of high‐quality perovskite (MAPbBr3) film underneath a ferromagnetic cobalt layer at room temperature. In contrast, a linearly polarized light does not induce any detectable magnetization in the MAPbBr3. The observation reveals that photoexcited orbital magnetic dipoles at the surface of perovskite are coupled with the spins of the ferromagnetic atoms at the interface, leading to an optically induced magnetization within the perovskite’s surface. The finding demonstrates that perovskite semiconductor can be bridged with magnetism through optically controllable method at room temperature in this heterojunction design. This provides the new concept of utilizing spin and orbital degrees of freedom in new‐generation spin‐related optoelectronic devices.
Recent Advance in Ionic‐Liquid‐Based Electrolytes for Rechargeable Metal‐Ion Batteries
Authors: Zhou Wenjun , Zhang Meng , Kong Xiangyue , Huang Weiwei , Zhang Qichun
Published: May 2021

From basic research to industry process, battery energy storage systems have played a great role in the informatization, mobility, and intellectualization of modern human society. Some potential systems such as Li, Na, K, Mg, Zn, and Al secondary batteries have attracted much attention to maintain social progress and sustainable development. As one of the components in batteries, electrolytes play an important role in the upgrade and breakthrough of battery technology. Since room‐temperature ionic liquids (ILs) feature high conductivity, nonflammability, nonvolatility, high thermal stability, and wide electrochemical window, they have been widely applied in various battery systems and show great potential in improving battery stability, kinetics performance, energy density, service life, and safety. Thus, it is a right time to summarize these progresses. In this review, the composition and classification of various ILs and their recent applications as electrolytes in diverse metal‐ion batteries (Li, Na, K, Mg, Zn, Al) are outlined to enhance the battery performances.
Hypermethylation of Hepatic Mitochondrial ND6 Provokes Systemic Insulin Resistance
Authors: Cao Ke , Lv Weiqiang , Wang Xueqiang , Dong Shanshan , Liu Xuyun , Yang Tielin , Xu Jie , Zeng Mengqi , Zou Xuan , Zhao Daina , Ma Qingqing , Lin Mu , Long Jiangang , Zang Weijin , Gao Feng , Feng Zhihui , Liu Jiankang
Published: May 2021

Mitochondrial epigenetics is rising as intriguing notion for its potential involvement in aging and diseases, while the details remain largely unexplored. Here it is shown that among the 13 mitochondrial DNA (mtDNA) encoded genes, NADH‐dehydrogenase 6 (ND6) transcript is primarily decreased in obese and type 2 diabetes populations, which negatively correlates with its distinctive hypermethylation. Hepatic mtDNA sequencing in mice unveils that ND6 presents the highest methylation level, which dramatically increases under diabetic condition due to enhanced mitochondrial translocation of DNA methyltransferase 1 (DNMT1) promoted by free fatty acid through adenosine 5’‐monophosphate (AMP)‐activated protein kinase (AMPK) activation. Hepatic knockdown of ND6 or overexpression of Dnmt1 similarly impairs mitochondrial function and induces systemic insulin resistance both in vivo and in vitro. Genetic or chemical targeting hepatic DNMT1 shows significant benefits against insulin resistance associated metabolic disorders. These findings highlight the pivotal role of ND6 epigenetic network in regulating mitochondrial function and onset of insulin resistance, shedding light on potential preventive and therapeutic strategies of insulin resistance and related metabolic disorders from a perspective of mitochondrial epigenetics.
POU2F2‐IL‐31 Autoregulatory Circuit Converts Hepatocytes into the Origin Cells of Hepatocellular Carcinoma
Authors: Yuan Chunwang , Pang Lijun , Wang Wenjing , Ouyang Yabo , Guo Xianghua , Liu Kai
Published: May 2021

Hepatocellular carcinoma (HCC) originates from fully differentiated hepatocytes, but the decisive events for converting hepatocytes to the cells of origin for HCC are still unclear. Liver cancer stem cells (LCSCs) cause HCC but are not bona fide cells of origin. Here, the expressions of POU2F2 and IL‐31 are identified in macroscopically normal livers of diethylnitrosamine‐challenged mice. An autoregulatory circuit formed by mutual induction between POU2F2 and IL‐31 drives hepatocytes to progress to LCSCs by acquiring stemness, as well as stimulates them to in vivo grow and malignantly progress. The development of the autoregulatory circuit is a decisive event for converting hepatocytes into the cells of origin, since hepatocytes expressing the circuit have acquired tumorigenic potential before progressing to LCSCs. Nonetheless, acquiring stemness is still required for the cells of origin to initiate hepatocarcinogenesis. The circuit also occurs in human cirrhotic tissues, partially elucidating how premalignant lesions progress to HCC.
Topological Encoded Vector Beams for Monitoring Amyloid‐Lipid Interactions in Microcavity
Authors: Gong Chaoyang , Qiao Zhen , Yuan Zhiyi , Huang Shih‐Hsiu , Wang Wenjie , Wu Pin Chieh , Chen Yu‐Cheng
Published: May 2021

Lasers are the pillars of modern photonics and sensing. Recent advances in microlasers have demonstrated its extraordinary lasing characteristics suitable for biosensing. However, most lasers utilized lasing spectrum as a detection signal, which can hardly detect or characterize nanoscale structural changes in microcavity. Here the concept of amplified structured light‐molecule interactions is introduced to monitor tiny bio‐structural changes in a microcavity. Biomimetic liquid crystal droplets with self‐assembled lipid monolayers are sandwiched in a Fabry–Pérot cavity, where subtle protein‐lipid membrane interactions trigger the topological transformation of output vector beams. By exploiting Amyloid β (Aβ)‐lipid membrane interactions as a proof‐of‐concept, it is demonstrated that vector laser beams can be viewed as a topology of complex laser modes and polarization states. The concept of topological‐encoded laser barcodes is therefore developed to reveal dynamic changes of laser modes and Aβ‐lipid interactions with different Aβ assembly structures. The findings demonstrate that the topology of vector beams represents significant features of intracavity nano‐structural dynamics resulted from structured light‐molecule interactions.
High Performance, Fully Bio‐Based, and Optically Transparent Wood Biocomposites
Authors: Montanari Céline , Ogawa Yu , Olsén Peter , Berglund Lars A.
Published: May 2021

The sustainable development of engineering biocomposites has been limited due to a lack of bio‐based monomers combining favorable processing with high performance. Here, the authors report a novel and fully bio‐based transparent wood biocomposite based on green synthesis of a new limonene acrylate monomer from renewable resources. The monomer is impregnated and readily polymerized in a delignified, succinylated wood substrate to form optically transparent biocomposites. The chemical structure of the limonene acrylate enables diffusion into the cell wall, and the polymer phase is both refractive index‐matched and covalently linked to the wood substrate. This results in nanostructured biocomposites combining an excellent optical transmittance of 90% at 1.2 mm thickness and a remarkably low haze of 30%, with a high mechanical performance (strength 174 MPa, Young's modulus 17 GPa). Bio‐based transparent wood holds great potential towards the development of sustainable wood nanotechnologies for structural applications, where transparency and mechanical performance are combined.
Green Algorithms: Quantifying the Carbon Footprint of Computation
Authors: Lannelongue Loïc , Grealey Jason , Inouye Michael
Published: May 2021

Climate change is profoundly affecting nearly all aspects of life on earth, including human societies, economies, and health. Various human activities are responsible for significant greenhouse gas (GHG) emissions, including data centers and other sources of large‐scale computation. Although many important scientific milestones are achieved thanks to the development of high‐performance computing, the resultant environmental impact is underappreciated. In this work, a methodological framework to estimate the carbon footprint of any computational task in a standardized and reliable way is presented and metrics to contextualize GHG emissions are defined. A freely available online tool, Green Algorithms (www.green‐algorithms.org) is developed, which enables a user to estimate and report the carbon footprint of their computation. The tool easily integrates with computational processes as it requires minimal information and does not interfere with existing code, while also accounting for a broad range of hardware configurations. Finally, the GHG emissions of algorithms used for particle physics simulations, weather forecasts, and natural language processing are quantified. Taken together, this study develops a simple generalizable framework and freely available tool to quantify the carbon footprint of nearly any computation. Combined with recommendations to minimize unnecessary CO2 emissions, the authors hope to raise awareness and facilitate greener computation.
Microporous 3D Graphene‐Like Carbon as Iodine Host for Zinc‐Based Battery–Supercapacitor Hybrid Energy Storage with Ultrahigh Energy and Power Densities
Authors: Park Hongjun , Bera Raj Kumar , Ryoo Ryong
Published: May 2021

Zinc (Zn)‐based aqueous battery‐supercapacitor hybrid (BSH) devices are considered promising energy storage devices benefiting from their high energy and power densities, low‐cost, safety, and environmental benignity. However, challenges remain in the development of efficient BSH electrodes due to poor reversibility in battery electrodes and lack of efficient supercapacitor electrodes to solve the problems of low power and energy densities. Herein, the loading of iodine (I2) in the nanopores of 3D graphene‐like carbon (3DGC) for the fabrication of BSH electrodes and their device application with Zn are reported. The uniform micropores of 3DGC serve as nanocages to stabilize I2, the high surface area of 3DGC maximizes the dispersion, and the high conductivity of 3DGC provides a path for fast electron transfer. The resultant I2‐loaded 3DGC (I2/3DGC) is applied to evaluate Zn‐based battery and BSH performance. The I2/3DGC‐based electrode exhibits excellent performance with ultrahigh energy and power densities resulting from the high reversibility of I2 and supercapacitance of 3DGC. The device exhibits high cyclic stability in both battery and supercapacitor modes due to the confinement of I2 in the micropores. It is demonstrated that this combination of 3DGC with I2 provides an easy way to fabricate durable and economical BSH electrodes.
Apple tree adaptation to shade in agroforestry: an architectural approach
Authors: Pitchers Benjamin , Do Frédéric C. , Pradal Christophe , Dufour Lydie , Lauri Pierre‐Éric
Published: May 2021

PREMISE

The expression of shade adaptation traits is expected to be stronger in low light and can be detrimental to flowering and yield. Our study focused on the expression of shade adaptation traits of apple trees (Malus domestica Borkh. ‘Dalinette’) in an agroforestry system.

METHODS

The architecture of 45 apple trees in their third and fourth year was extensively described and analyzed at the tree scale and compared depending on the light quantity received during the growing season. Flower cluster phenology and the relation between leaf area and floral initiation were also investigated.

RESULTS

The number of growing shoots and the leaf area were reduced by shade even if specific leaf area increased with increasing shade. Shade did not modify primary growth but did decrease secondary growth, so that apple tree shoots in shade were slender, with a lower taper and reduced number and proportion of flower clusters. The correlation between floral initiation and leaf area was high both in full and moderate light but not for apple trees in low light. Shade did not impact the date of bud burst and the early phenological stages of flower clusters, but it reduced the number of days at full bloom.

CONCLUSIONS

Our results suggest that while the architecture of apple trees is modified by a reduction in light intensity, it is not until a reduction of 65% that the capability to produce fruit is impeded. These results could help optimize the design of apple‐tree‐based agroforestry systems.
Variability of extracorporeal cardiopulmonary resuscitation practice in patients with out‐of‐hospital cardiac arrest from the emergency department to intensive care unit in Japan
Authors: Hifumi Toru , Inoue Akihiko , Takiguchi Toru , Watanabe Kazuhiro , Ogura Takayuki , Okazaki Tomoya , Ijuin Shinichi , Zushi Ryosuke , Arimoto Hideki , Takada Hiroaki , Shiraishi Shinichirou , Egawa Yuko , Kanda Jun , Nasu Michitaka , Kobayashi Makoto , Sakuraya Masaaki , Naito Hiromichi , Nakao Shunichiro , Otani Norio , Takeuchi Ichiro , Bunya Naofumi , Shimizu Takafumi , Sawano Hirotaka , Takayama Wataru , Kushimoto Shigeki , Shoko Tomohisa , Aoki Makoto , Otani Takayuki , Matsuoka Yoshinori , Homma Koichiro , Maekawa Kunihiko , Tahara Yoshio , Fukuda Reo , Kikuchi Migaku , Nakagami Takuo , Hagiwara Yoshihiro , Kitamura Nobuya , Sugiyama Kazuhiro , Sakamoto Tetsuya , Kuroda Yasuhiro ,   SAVE‐J II Study Group
Published: May 2021

Aim

A lack of known guidelines for the provision of extracorporeal cardiopulmonary resuscitation (ECPR) to patients with out‐of‐hospital cardiac arrest (OHCA) has led to variability in practice between hospitals even in the same country. Because variability in ECPR practice has not been completely examined, we aimed to describe the variability in ECPR practice in patients with OHCA from the emergency department (ED) to the intensive care units (ICU).

Methods

An anonymous online questionnaire to examine variability in ECPR practice was completed in January 2020 by 36 medical institutions who participated in the SAVE‐J II study. Institutional demographics, inclusion and exclusion criteria, initial resuscitation management, extracorporeal membrane oxygenation (ECMO) initiation, initial ECMO management, intra‐aortic balloon pumping/endotracheal intubation/management during coronary angiography, and computed tomography criteria were recorded.

Results

We received responses from all 36 institutions. Four institutions (11.1%) had a hybrid emergency room. Cardiovascular surgery was always involved throughout the entire ECMO process in only 14.7% of institutions; 60% of institutions had formal inclusion criteria and 50% had formal exclusion criteria. In two‐thirds of institutions, emergency physicians carried out cannulation. Catheterization room was the leading location of cannulation (48.6%) followed by ED (31.4%). The presence of formal exclusion criteria significantly increased with increasing ECPR volume (P for trend <0.001). Intra‐aortic balloon pumping was routinely initiated in only 25% of institutions. Computed tomography was routinely carried out before coronary angiography in 25% of institutions.

Conclusions

We described the variability in ECPR practice in patients with OHCA from the ED to the ICU.
Influence of high‐dose antithrombin on platelet function and blood coagulation
Authors: Miike Toru , Sakamoto Yuichiro , Narumi Shougo , Yoshitake Kunimasa , Sakurai Ryota , Nakayama Kento , Inoue Satoshi
Published: May 2021

Aim

In healthy adults, there are sufficient amounts of antithrombin in the blood to regulate thrombin. However, the effects of high concentrations of antithrombin on dose‐dependent anticoagulation and platelet function have not been reported. In this study, we assessed platelet function and blood coagulation following high‐dose antithrombin supplementation in vitro.

Methods

Blood samples were collected from 10 healthy volunteers, and samples with different antithrombin concentrations were prepared by adding an antithrombin agent (Neuart). Blood coagulation was assessed by the Thrombus‐Formation Analysis System (T‐TAS) and Rotational Thromboelastometry (ROTEM) using whole blood samples.

Results

The data obtained by the platelet chip, exclusively representing platelet function, revealed that the onset of thrombus formation was significantly delayed in a dose‐dependent manner (100%–200%, P = 0.021; 100%–500%, P = 0.011; 200%–500%, P = 0.047). In measurements using the atheroma chip, which enables assessment of blood coagulation, the thrombus formation ability was found to be reduced (100%–200%, P = 0.022; 100%–500%, P = 0.05). In the ROTEM measurements, clotting time was prolonged in a dose‐dependent manner (100%–200%: P = 0.203, 200%–500%: P = 0.005, 500%–1000%: P = 0.022), except when comparing with 100% and 200%. Although antithrombin is reportedly saturated in healthy blood, its anticoagulant ability appears to be enhanced depending on its concentration. Furthermore, data obtained from the platelet chip showed that antithrombin might reduce platelet function.

Conclusions

Antithrombin suppressed platelet function and blood coagulation in a dose‐dependent manner.
Early endotracheal intubation improves neurological outcome following witnessed out‐of‐hospital cardiac arrest in Japan: a population‐based observational study
Authors: Nakagawa Koshi , Sagisaka Ryo , Tanaka Shota , Takyu Hiroshi , Tanaka Hideharu
Published: May 2021

Aim

It is unclear whether endotracheal intubation in the prehospital setting improves outcomes following out‐of‐hospital cardiac arrest. The purpose of this study was to evaluate the association between endotracheal intubation time (time from patient contact to endotracheal intubation) and favorable neurological outcomes on out‐of‐hospital cardiac arrest.

Methods

We extracted patients who underwent endotracheal intubation on the scene from a nationwide out‐of‐hospital cardiac arrest database registered between 2014 and 2017 in Japan. We included 14,969 witnessed and intubated adult out‐of‐hospital cardiac arrest cases. Patients were divided into Shockable (n = 1,102) and Non‐shockable (n = 13,867) cohorts. We first drew the logistic curve due to predicting the association between endotracheal intubation time and favorable neurological outcome defined as Cerebral Performance Category (CPC) 1 or 2. Secondary, multivariable logistic regressions were used to estimate the association between the endotracheal intubation time (1‐min unit increase), CPC 1 or 2.

Results

The logistic curve for CPC 1 or 2 showed similar shapes and indicated a decreasing outcome over time. From the results of multivariable logistic regression, in the Shockable cohort, endotracheal intubation time delay was correlated with decreasing favorable outcomes: CPC 1 or 2 (adjusted odds ratio, 0.89; 95% confidence interval, 0.82–0.87). Results were the same for the Non‐shockable cohort: CPC 1 or 2 (adjusted odds ratio, 0.94; 95% confidence interval, 0.89–0.99).

Conclusion

Early endotracheal intubation was correlated with favorable neurological outcome. Training for intubation skills and improving protocols are needed for carrying out early endotracheal intubation.
Comparison of Systemic Inflammatory Response Syndrome and quick Sequential Organ Failure Assessment scores in predicting bacteremia in the emergency department
Authors: Furuta Katsuyuki , Akamatsu Hiroaki , Sada Ryuichi , Miyamoto Kyohei , Teraoka Shunsuke , Hayata Atsushi , Ozawa Yuichi , Nakanishi Masanori , Koh Yasuhiro , Yamamoto Nobuyuki
Published: May 2021

Aim

The emergency department requires simple and useful clinical indicators to identify bacteremia. This retrospective study explored the Systemic Inflammatory Response Syndrome (SIRS) and quick Sequential Organ Failure Assessment (qSOFA) scores for predicting bacteremia.

Methods

Between April and September 2017, we assessed blood cultures of 307 patients in our emergency department. We calculated the SIRS and qSOFA scores for these patients and evaluated their correlation with bacteremia.

Results

Of 307 patients, 66 (21.5%) had bacteremia, 237 (77.2%) were SIRS‐positive, and 123 (40.0%) were qSOFA‐positive. The sensitivity and specificity of the SIRS score for predicting bacteremia were 87.9% and 25.7%, respectively. The sensitivity and specificity of the qSOFA score were 47.0% and 61.8%, respectively. Multivariate analysis revealed that body temperature (odds ratio, 2.16; 95% confidence interval, 1.22–3.84; P = 0.009) and blood pressure (odds ratio, 2.72; 95% confidence interval, 1.39–5.35; P = 0.004) significantly associated with bacteremia.

Conclusions

The SIRS score was a more sensitive indicator than the qSOFA score for predicting bacteremia.
Adequacy of hand positioning by medical personnel during chest compression in a simulation study
Authors: Koyama Yasuaki , Matsuyama Tasuku , Kainoh Takako , Hoshino Tetsuya , Nakao Junzo , Shimojo Nobutake , Inoue Yoshiaki
Published: May 2021

Aim

During chest compressions (CCs), the hand position at the lower half of the sternum is not strictly maintained, unlike depth or rate. This study was conducted to determine whether medical staff could adequately push at a marked location on the lower half of the sternum, identify where the inappropriate hand position was shifted to, and correct the inappropriate hand position.

Methods

This simulation‐based, prospective single‐center study enrolled 44 medical personnel. Pressure and hand position during CC were ascertained using a flexible pressure sensor. The participants were divided into four groups by standing position and the hand in contact with the sternum: right–left (R–l), right–right (R–r), left–right (L–r), and left–left (L–l). We compared the groups and the methods: the manual method (MM), the thenar method, and the hypothenar method (HM).

Results

Among participants using the MM, 80% did not push adequately at the marked location on the lower half of the sternum; 60%–90% of the inadequate positions were shifted to the hypothenar side. CCs with the HM facilitated stronger pressure, and the position was minimally shifted to the hypothenar side.

Conclusion

Medical staff could not push at an appropriate position during CCs. Resuscitation courses should be designed to educate personnel on the appropriate position for application of maximal pressure while also evaluating the position during CCs.
Modeling life‐cycle inventory for multi‐product biorefinery: tracking environmental burdens and evaluation of uncertainty caused by allocation procedure
Authors: Obydenkova Svetlana V , Kouris Panos D , Smeulders David M J , Boot Michael D , van der Meer Yvonne
Published: May 2021

Life‐cycle inventory (LCI) is a fundamental phase in the quantification of the environmental performance of products. However, when it comes to the LCI of a multi‐product system, discussions about the choice of the appropriate methodology to allocate environmental impacts still continue. A further system subdivision and the implementation of a mechanism allowing environmental burdens to be tracked would help to improve model accuracy. This study focuses on the LCI modeling of a lignocellulosic biorefinery producing ethanol, lignin oligomers, and electricity, and demonstrates the application of the matrix‐based approach for detailed system subdivision and environmental burden tracking. Forty scenarios utilizing process‐specific allocation methods were tested to account for the global warming potential of outputs. The main findings of the paper are: (i) the importance of specific allocation methods applied to combined heat and power plants that stress the key role of internal energy supply in carrying environmental burdens; (ii) a negligible effect of allocation methods applied to wastewater treatment facilities; (iii) the inconsistency of results obtained via two allocation methods, one based on the total mass and the second based on the dry mass allocation, which raises questions about the validity of water accounting in the allocation procedure of related products; (iv) the role of upstream greenhouse gas (GHG) emissions in lignin‐derived outputs, which emphasizes the importance of a proper allocation methodology to be applied to this residue; and (v) an important role of the biomass pretreatment and lignin solvolysis processes in the accumulation of emissions, which highlights the importance of decreasing the amount of solids and methanol content in the processes discussed here. © 2021 The Authors. Biofuels, Bioproducts and Biorefining published by Society of Industrial Chemistry and John Wiley & Sons Ltd.
Using peer code review to improve computational thinking in a blended learning environment: A randomized control trial
Authors: Lin Xuefen , Ma Yanghui , Ma Weifeng , Liu Yang , Tang Wei
Published: May 2021

Although the importance of computational thinking (CT) has been widely recognized, we still poorly understand how to effectively teach this skill. The aim of this study is to investigate whether peer code review (PCR) could affect CT, learning engagement, and learning satisfaction in a blended learning environment. To achieve this, we carried out a randomized control trial study involving 84 first‐year undergraduates (second semester) from different majors. There was no difference in CT before this experiment and after the experiment, general CT, specific CT, learning engagement, and satisfaction were measured. An independent sample t test showed that students learning with code peer review showed better performance on computational concepts, computational perspectives, learning engagement, and learning satisfaction (p < .001). Bayesian t test further showed substantial or strong evidence for the improvement of computational concepts, learning engagement, learning satisfaction, and computational perspectives. Moreover, the absolute values of Cohen's effect sizes of computational concept, computational perspectives, emotional engagement, behavior engagement, learning engagement, learning satisfaction were all above 0.4, which is viewed as educationally meaningful. Although there was no difference in the general CT, we still saw evidence of improvement over the course of the experiment. Overall, our findings suggest instructors to use PCR reasonably to further improve CT, learning engagement, and satisfaction in programming courses.
Establishment of a prognostic model of four genes in gastric cancer based on multiple data sets
Authors: Zhou Liqiang , Li Shi H. , Wu You , Xin Lin
Published: May 2021

Gastric cancer (GC) is a kind of malignancy with a high mortality and recurrence. An effective prediction model based on ideal biomarkers to assess prognosis could benefit patients for optimization of treatment. Bioinformatics has played an increasingly important role in the study of cancer diseases. Therefore, this study started with bioinformatics to establish a reliable prognostic model of gastric cancer. The gene expression data and clinical data of GC tissues and normal tissues were obtained from the Gene Expression Omnibus (GEO), Genotype‐Tissue Expression (GTEx), and The Cancer Genome Atlas (TCGA) profile database. We finally identified a four gene signature and constructed a prognostic model. The results of internal and external validation showed that the model is highly reliable. In addition, we also constructed a nomogram based on the model, which was verified by a calibration curve to show its predicted accuracy. Comprehensive analysis indicated that the four genes in the model are related to the occurrence and development of tumors, perhaps they are potential targets for tumor treatment. Generally, this prognostic model can bring potential benefits to patients with gastric cancer.
Fzd7/Wnt7b signaling contributes to stemness and chemoresistance in pancreatic cancer
Authors: Zhang Zhongbo , Xu Yuanhong , Zhao Chenghai
Published: May 2021

Mining databases and data obtained from assays on human specimens had shown that Fzd7 is closely associated with Wnt7b, that Fzd7/Wnt7b expression is upregulated in pancreatic cancer tissues compared with normal tissues, and its expression is negatively correlated with survival. Fzd7/Wnt7b knockdown in Capan‐2 and Panc‐1 cells reduced the proliferative capacity of pancreatic cancer stem cells (PCSCs), reduced drug resistance, decreased the percentage of CD24+CD44+ subset of cells and the levels of ABCG2, inhibited cell‐sphere formation, and reduced gemcitabine (GEM) resistance. In contrast, Fzd7/Wnt7b overexpression increased the percentage of the CD24+CD44+ subset of cells, and increased the levels of ABCG2 detected in cell spheroids. The gem‐resistant cells exhibited higher levels of Fzd7/Wnt7b expression, an increased percentage of CD24+CD44+ cells, and higher levels of ABCG2 compared with the parental cells. Taken together, Fzd7/Wnt7b knockdown can reduce PDAC cell stemness and chemoresistance by reducing the percentage of CSCs. Mechanistically, Fzd7 binds with Wnt7b and modulates the levels of β‐catenin, and they may exert their role via modulation of the canonical Wnt pathway.
Risk factors of cervical cancer after a negative cytological diagnosis in Polish cervical cancer screening programme
Authors: Macios Anna , Didkowska Joanna , Wojciechowska Urszula , Komerska Katarzyna , Glińska Patrycja , Kamiński Michał F. , Nowakowski Andrzej
Published: May 2021

Risk factors of cervical cancer (CC) development are well investigated, however, those influencing the risk of a potential false negative cytology preceding diagnosis of an invasive CC are not. We have aimed to explore these factors according to the data from Organised Cervical Cancer Screening Programme (OCCSP) in Poland. A total of 2.36 million of Pap tests sampled in 2010–2012 within OCCSP were merged with the Polish National Cancer Registry to identify CC cases after abnormal cytology and after normal cytology within 3 years of screening. Of 1460 invasive CCs, 1025 were preceded by abnormal and 399 by normal cytology result. Multivariate logistic analysis indicated that the presence of microorganisms in the Pap (OR = 2.18, 95% CI 1.65–2.87), evaluation by smaller (below 9000 slides processed per year) laboratories (OR = 1.60, 95% CI 1.22–2.09) and non‐squamous histology of cancer increased the odds for a potential false negative result (OR = 3.39, 95% CI 2.37–4.85 for adenocarcinoma, OR = 1.99, 95% CI 1.11–3.55 for other types of carcinoma), whereas cervical ectropion, other macroscopic changes on the cervix and smoking decrease the odds for a potential false negative Pap test result preceding CC (OR = 0.61, 95% CI 0.45–0.82, OR = 0.41, 95% CI 0.25–0.67, OR = 0.60, 95% CI 0.46–0.78, respectively). Proper triage of women with microscopic signs of microorganisms in the Pap smear should be reconsidered and cytology should be assessed in laboratories processing over 9000 slides annually to decrease the odds for negative Pap test result in 2 years before CC diagnosis. Information on macroscopic changes on the cervix provided to cytomorphologist may reduce the risk of a potential false negative cytology result.
The low expression of NUP62CL indicates good prognosis and high level of immune infiltration in lung adenocarcinoma
Authors: Ren Shiqi , Wang Wei , Zhang Chenlin , Sun Yidan , Sun Mengjing , Wang Yingjing , Zhang Xiaojing , Lu Bing , Yao Lanlan
Published: May 2021

A primary factor in tumor morbidity and mortality, lung adenocarcinoma (LUAD) is known to be a major subtype of lung cancer, having the lowest survival rate among all other cancers. Using The Cancer Genome Atlas (TCGA) database the relationship between the immune infiltrate and the NUP62CL was explored and the value of the NUP62CL expression in the prognosis and diagnosis LUAD was examined. Using the logistic regression and the Wilcoxon signed‐rank test the relationship between the NUP62CL and the clinico‐pathological features was analyzed. There was a significant correlation between the clinical stage (p = 0.005), the N (p = 0.004), and the decreased expression of NUP62CL. The prognosis of LUAD with high NUP62CL expression was revealed to be worse than that with low NUP62CL expression (p < 0.001) by the Kaplan‐Meier survival analysis. The potentiality of NUP62CL to be a significant factor of prognosis for LUAD was indicated by the analyses of the multivariate and the univariate Cox regression models. In LUAD, the crucial role of recombination and maintenance of telomere as a significant pathway for NUP62CL was suggested by the Gene Set Enrichment Analysis (GSEA). To analyze the correlation between the genes and the tumor infiltrating immune cells the CIBERSORT was used. Moreover the positive correlation with the NUP62CL expression in LUAD of the infiltration level of the tumor infiltrating B lymphocytes and memory CD4+ T cells was exhibited by CIBERSORT. Therefore, NUP62CL may be a new valuable prognostic indicator for LUAD.
The addition of chemotherapy to adjuvant radiation is associated with inferior survival outcomes in intermediate‐risk HPV‐negative HNSCC
Authors: Tasoulas Jason , Lenze Nicholas R. , Farquhar Douglas , P. Schrank Travis , Shen Colette , Shazib M. Ali , Singer Bart , Patel Shetal , Grilley Olson Juneko E. , Hayes David N. , Gulley Margaret L. , Chera Bhishamjit S. , Hackman Trevor , Olshan Andrew F. , Weiss Jared , Sheth Siddharth
Published: May 2021

Background

Only high‐risk tumors with extranodal extension (ENE) and/or positive surgical margins (PSM) benefit from adjuvant therapy (AT) with concurrent chemoradiation (CRT) compared to radiation therapy (RT) in locally advanced head and neck squamous cell carcinoma (HNSCC). Optimal treatment for intermediate‐risk tumors remains controversial. We categorized patients based on their surgical pathologic risk factors and described AT treatment patterns and associated survival outcomes.

Methods

Patients were identified from CHANCE, a population‐based study, and risk was classified based on surgical pathology review. High‐risk patients (n = 204) required ENE and/or PSM. Intermediate‐risk (n = 186) patients had pathological T3/T4 disease, perineural invasion (PNI), lymphovascular invasion (LVI), or positive lymph nodes without ENE. Low‐risk patients (n = 226) had none of these features.

Results

We identified 616 HPV‐negative HNSCC patients who received primary surgical resection with neck dissection. High‐risk patients receiving AT had favorable OS (HR 0.50, p = 0.013) which was significantly improved with the addition of chemotherapy compared to RT alone (HR 0.47, p = 0.021). When stratified by node status, the survival benefit of AT in high‐risk patients persisted only among those who were node‐positive (HR: 0.17, p < 0.0005). On the contrary, intermediate‐risk patients did not benefit from AT (HR: 1.26, p = 0.380) and the addition of chemotherapy was associated with significantly worse OS compared to RT (HR: 1.76, p = 0.046).

Conclusion

In high‐risk patients, adjuvant chemoradiotherapy improved OS compared to RT alone. The greatest benefit was in node‐positive cases. In intermediate‐risk patients, the addition of chemotherapy to RT increased mortality risk and therefore should only be used cautiously in these patients.
A novel five‐gene signature predicts overall survival of patients with hepatocellular carcinoma
Authors: Wang Zhigang , Pan Leyu , Guo Deliang , Luo Xiaofeng , Tang Jie , Yang Weihua , Zhang Yuxian , Luo Anni , Gu Yang , Pan Yuxuan
Published: May 2021

Hepatocellular carcinoma (HCC) is one of the most common public health challenges, worldwide. Because of molecular complexity and tumor heterogeneity, there are no effective predictive models for prognosis of HCC. This underlines the unmet need for accurate prognostic models for HCC. Analysis of GSE14520 data from gene omnibus (GEO) database identified multiple differentially expressed mRNAs (DEMs) between HCC and normal tissues. After randomly stratifying the patients into the training and testing groups, we performed univariate, lasso, and multivariable Cox regression analyses to delineate the prognostic gene signature in training set. We then used Kaplan–Meier plot, time‐dependent receiver operating characteristic (ROC), multivariable Cox regression analysis of clinical information, nomogram, and decision curve analysis (DCA) to evaluate the predictive and overall survival value of a novel five‐gene signature (CNIH4, SOX4, SPP1, SORBS2, and CCL19) within and across sets, separately and combined. We also validated the prognostic value of the five‐gene signature using The Cancer Genome Atlas—Liver Hepatocellular Carcinoma (TCGA‐LIHC), GSE54236 and International Cancer Genome Consortium (ICGC) sets. Multivariable Cox regression analysis revealed that the five‐gene signature and tumor node metastasis (TNM) stage were independent prognostic factors for overall survival of HCC patients in GSE14520 and TCGA‐LIHC. Combining TNM stage clinical pathological parameters and nomogram greatly improved the prognosis prediction of HCC. Further gene set enrichment analysis (GSEA) revealed enrichment of KEGG pathways related to cell cycle in the high‐risk group and histidine metabolism in the low‐risk group. Finally, all these five mRNAs are overexpressed between 12 pairs of HCC and adjacent normal tissues by quantitative real‐time PCR validation. In brief, a five‐gene prognostic signature and a nomogram were identified and constructed, respectively, and further validated for their HCC prognostic value. The five‐gene risk score together with TNM stage models could aid in rationalizing customized therapies in HCC patients.