bluuebunny/crossref_metadata_2025 huggingface dataset:
Solvation and Ion‐Pairing Effects of Choline Acetate Electrolyte in Protic and Aprotic Solvents Studied by NMR Titrations
Authors: Veroutis Emmanouil , Merz Steffen , Eichel Rüdiger‐A. , Granwehr Josef
Published: October 2021

Choline‐based electrolytes have been proposed as environmentally friendly and low‐cost alternatives for secondary zinc air batteries. Choline acetate [Ch]+[OAc]− in protic (D2O) and aprotic (DMSO‐d6) solvents has been studied by means of concentration‐dependent 1H NMR, viscosity, and density measurements. The viscosities have been calculated on the basis of the Jones‐Dole equation and showed that the dominant contribution originates from short‐range ion‐solvent interactions. Site‐specific association affinities were assigned from NMR chemical shift titrations. In DMSO‐d6, the hydroxyl group of choline was found to have the smallest dissociation constant followed by the methyl group of acetate. The corresponding Gibbs energies at low concentration were found to be in agreement with a solvent‐separated ion pair (2SIP) configuration, whereas at concentrations above 300 mM, a solvent‐shared ion pair (SIP) configuration was assigned. For [Ch]+[OAc]− in D2O, association effects were found to be weaker, attributed to the high dielectric constant of the solvent. On time scales on the order of 100 ms, NMR linewidth perturbations indicated a change in the local rotational dynamics of the ions, attributed to short‐range cation‐solvent interactions and not to solvent viscosity. At 184 mM,
40 % of the cations in DMSO‐d6 and
10 % in D2O were found to exhibit short‐range interactions, as indicated by the linewidth perturbations. It was found that at about 300 mM, the ions in DMSO‐d6 exhibit a transition from free to collective translational dynamics on time scales on the order of 400 ms. In DMSO‐d6, both ions were found to be almost equally solvated, whereas in D2O solvation of acetate was stronger, as indicated by the obtained effective hydrodynamic radii. For [Ch]+[OAc]− in DMSO‐d6, the results suggest a solvent‐shared ion association with weak H‐bonding interactions for concentrations between 0.3–1 M. Overall, the extent of ion association in solvents such as DMSO is not expected to significantly limit charge transport and hinder the performance of choline‐based electrolytes.
Joint subcarrier and power allocation with proportional fairness in multicarrier nonorthogonal multiple access systems
Authors: Ding Hongwen , Li Li
Published: October 2021

In this paper, we investigate joint subcarrier and power allocation in multicarrier nonorthogonal multiple access (MC‐NOMA) systems aims to guarantee rate proportional fairness among all users. To this end, we adopt the sum logarithmic rate function as the objective and formulate a resource optimization problem which is a mixed‐integer nonlinear programming (MINLP) problem. Based on variable relaxation and replacement, we convert this problem into a convex optimization problem. On this basis, the expressions of joint subcarrier and power allocation solutions are obtained by using convex optimization theory and the Karush–Kuhn–Tucker (KKT) condition. However, power and subcarrier allocation solutions are highly coupled, and it is difficult to derive both solutions simultaneously. Fortunately, when the subcarrier allocation strategy is given, the optimal power allocation solution can be derived by solving the equations. Furthermore, we develop an iterative resource allocation algorithm to implement joint subcarrier and power allocation among users. Numerical results reveal that the proposed algorithm is effective in general multiuser and multicarrier scenarios, and a substantial performance improvement can be achieved by the proposed algorithm in contrast with the traditional orthogonal multiple access (OMA) schemes. In specific, the proposed algorithm achieves 63% and 59% gains in terms of utility and fairness performance, respectively.
Prevalence and genotype distribution of high‐risk human papillomavirus infection among women with cervical cytological abnormalities in Chongqing, China, 2014–2020
Authors: Luo Qinli , Lang Lin , Han Na , Liang Ling , Shen Lianjun , Zhang Haiyan
Published: October 2021

Background

Persistent infection with high‐risk human papillomavirus (HR‐HPV) is the main leading cause of cervical precancerous lesions and cervical cancer. This study aims to explore the epidemiological characteristics of HR‐HPV genotypes and their correlation with the ThinPrep cytological test (TCT) results among women in Chongqing, in China.

Methods

In this retrospective study, cervical exfoliations of 14,548 women who visited Chongqing university cancer hospital were collected for detecting HR‐HPV genotypes and TCT.

Results

Overall, the rate of HR‐HPV infection was 14.26%. The three most common HR‐HPV genotypes are HPV52 (4.39%), HPV58 (2.21%), and HPV16 (1.94%). In this study, the positive rate of cervical TCT was 4.54%. Atypical squamous cells of undetermined significance (ASC‐US), atypical squamous cells that could not exclude high‐grade squamous intraepithelial lesion (ASU‐H), low‐grade squamous intraepithelial lesions (LSIL), high‐grade squamous intraepithelial lesions (HSIL), and atypical glandular cells of undetermined significance (AGC) were 2.99%, 0.20%, 0.92%, 0.29%, and 0.14%, respectively. Among the several types of cytological lesions, the HR‐HPV infection rates of ASC‐US, ASC‐H, LSIL, HSIL, and (AGC) were 24.82%, 41.38%, 64.18%, 95.24%, and 23.81%, respectively.

Conclusions

HPV52, HPV 58, and HPV16 are the most common infection subtypes in Chongqing. When implementing HPV vaccine programs in Chongqing, HPV58 and HPV52 should be attached importance as HPV16 and HPV18.
Site fidelity and behavioral plasticity regulate an ungulate’s response to extreme disturbance
Authors: Kreling Samantha E.S. , Gaynor Kaitlyn M. , McInturff Alex , Calhoun Kendall L. , Brashares Justin S.
Published: October 2021

With rapid global change, the frequency and severity of extreme disturbance events are increasing worldwide. The ability of animal populations to survive these stochastic events depends on how individual animals respond to their altered environments, yet our understanding of the immediate and short‐term behavioral responses of animals to acute disturbances remains poor. We focused on animal behavioral responses to the environmental disturbance created by megafire. Specifically, we explored the effects of the 2018 Mendocino Complex Fire in northern California, USA, on the behavior and body condition of black‐tailed deer (Odocoileus hemionus columbianus). We predicted that deer would be displaced by the disturbance or experience high mortality post‐fire if they stayed in the burn area. We used data from GPS collars on 18 individual deer to quantify patterns of home range use, movement, and habitat selection before and after the fire. We assessed changes in body condition using images from a camera trap grid. The fire burned through half of the study area, facilitating a comparison between deer in burned and unburned areas. Despite a dramatic reduction in vegetation in burned areas, deer showed high site fidelity to pre‐fire home ranges, returning within hours of the fire. However, mean home range size doubled after the fire and corresponded to increased daily activity in a severely resource‐depleted environment. Within their home ranges, deer also selected strongly for patches of surviving vegetation and woodland habitat, as these areas provided forage and cover in an otherwise desolate landscape. Deer body condition significantly decreased after the fire, likely as a result of a reduction in forage within their home ranges, but all collared deer survived for the duration of the study. Understanding the ways in which large mammals respond to disturbances such as wildfire is increasingly important as the extent and severity of such events increases across the world. While many animals are adapted to disturbance regimes, species that exhibit high site fidelity or otherwise fixed behavioral strategies may struggle to cope with increased climate instability and associated extreme disturbance events.
Permafrost response to temperature rise in carbon and nutrient cycling: Effects from habitat‐specific conditions and factors of warming
Authors: Gao Wenlong , Sun Weimin , Xu Xingliang
Published: October 2021

Permafrost is experiencing climate warming at a rate that is two times faster than the rest of the Earth's surface. However, it is still lack of a quantitative basis for predicting the functional stability of permafrost ecosystems in carbon (C) and nutrient cycling. We compiled the data of 708 observations from 89 air‐warming experiments in the Northern Hemisphere and characterized the general effects of temperature increase on permafrost C exchange and balance, biomass production, microbial biomass, soil nutrients, and vegetation N dynamics through a meta‐analysis. Also, an investigation was made on how responses might change with habitat‐specific (e.g., plant functional groups and soil moisture status) conditions and warming variables (e.g., warming phases, levels, and timing). The net ecosystem C exchange (NEE) was found to be downregulated by warming as a result of a stronger sensitivity to warming in respiration (15.6%) than in photosynthesis (6.2%). Vegetation usually responded to warming by investing more C to the belowground, as belowground biomass increased much more (30.1%) than aboveground biomass (2.9%). Warming had a minor effect on microbial biomass. Warming increased soil ammonium and nitrate concentrations. What's more, a synthesis of 70 observations from 11 herbs and 9 shrubs revealed a 2.5% decline of N in green leaves. Compared with herbs, shrubs had a stronger response to respiration and had a decline in green leaf N to a greater extent. Not only in dry condition did green leaf N decline with warming but also in wet conditions. Warming in nongrowing seasons would negatively affect soil water, C uptake, and biomass production during growing seasons. Permafrost C loss and vegetation N decline may increase with warming levels and timing. Overall, these findings suggest that besides a positive C cycling–climate feedback, there will be a negative feedback between permafrost nutrient cycling and climate warming.
Implantation of ventricular assist devices in hypertrophic cardiomyopathy with left ventricular systolic dysfunction
Authors: Yagi Nobuichiro , Seguchi Osamu , Mochizuki Hiroki , Kuroda Kensuke , Nakajima Seiko , Watanabe Takuya , Yanase Masanobu , Tadokoro Naoki , Fukushima Satsuki , Fujita Tomoyuki , Fukushima Norihide
Published: October 2021

Aims

The outcomes of patients with hypertrophic cardiomyopathy with left ventricular systolic dysfunction (HCM‐LVSD) undergoing left ventricular assist device (LVAD) implantation remain unclear. We retrospectively evaluated the clinical impact of LVAD implantation on clinical outcomes, including haemodynamics and brain natriuretic peptide (BNP) levels, in patients with HCM‐LVSD, in comparison with those with dilated cardiomyopathy (DCM).

Methods and results

In this retrospective, single‐centre, observational study conducted in Japan, the medical records of patients who underwent LVAD implantation in the National Cerebral and Cardiovascular Center between 2011 and 2020 were reviewed. We enrolled 96 patients with DCM (average age: 43.5 years; 73 men) and 24 patients with HCM‐LVSD (average age: 48.3 years; 16 men). The HCM‐LVSD group had smaller left ventricles with thicker ventricular walls than the DCM group, which became more prominent after LVAD implantation. Preoperatively, BNP values were comparable between both groups; however, 3 months post‐implantation, they were significantly higher in the HCM‐LVSD group. Pulmonary artery pulsatility index, right ventricular stroke work index, and cardiac index were lower, and right atrial pressure was higher, in the HCM‐LVSD group, suggesting subclinical impairment of right ventricular function. The HCM‐LVSD group demonstrated equivalent outcomes, including overall survival, cerebrovascular accidents, right ventricular failure, LVAD‐related infections, arrhythmia, and aortic insufficiency, post‐implantation.

Conclusions

Despite a decreased right ventricular function with higher BNP values, patients with HCM‐LVSD and DCM showed comparable outcomes post‐LVAD implantation.
PDGFRα‐lineage origin directs monocytes to trafficking proficiency to support peripheral immunity
Authors: Li Yu‐Tung , Yamazaki Sho , Takaki Eiichi , Ouchi Yuya , Kitayama Tomomi , Tamai Katsuto
Published: October 2021

Multiple embryonic precursors give rise to leukocytes in adults while the lineage‐based functional impacts are underappreciated. Mesodermal precursors expressing PDGFRα appear transiently during E7.5‐8.5 descend to a subset of Lin–Sca1+Kit+ hematopoietic progenitors found in adult BM. By analyzing a PDGFRα‐lineage tracing mouse line, we here report that PDGFRα‐lineage BM F4/80+SSClo monocytes/macrophages are solely Ly6C+LFA‐1hiMac‐1hi monocytes enriched on the abluminal sinusoidal endothelium while Ly6C–LFA‐1loMac‐1lo macrophages are mostly from non‐PDGFRα‐lineage in vivo. Monocytes with stronger integrin profiles outcompete macrophages for adhesion on an endothelial monolayer or surfaces coated with ICAM‐1‐Fc or VCAM‐1‐Fc. Egress of PDGFRα‐lineage‐rich monocytes and subsequent differentiation to peripheral macrophages spatially segregates them from non‐PDGFRα‐lineage BM‐resident macrophages and allows functional specialization since macrophages derived from these egressing monocytes differ in morphology, phenotype, and functionality from BM‐resident macrophages in culture. Extravasation preference for blood PDGFRα‐lineage monocytes varies by tissues and governs the local lineage composition of macrophages. More PDGFRα‐lineage classical monocytes infiltrated into skin and colon but not into peritoneum. Accordingly, transcriptomic analytics indicated augmented inflammatory cascades in dermatitis skin of BM‐chimeric mice harbouring only PDGFRα‐lineage leukocytes. Thus, the PDGFRα‐lineage origin biasedly generates monocytes predestined for BM exit to support peripheral immunity following extravasation and macrophage differentiation.
Synthesis of Large [2+3] Salicylimine Cages with Embedded Metal‐Salphen Units
Authors: Uhrmacher Fabian , Elbert Sven M. , Rominger Frank , Mastalerz Michael
Published: October 2021

Metal salphen containing complexes have found a broad variety of applications in catalysis as well as material science. Most of these materials are either mono‐nuclear complexes or polymeric network materials. Discrete macromolecular polynuclear salphens are still rare and mostly two‐dimensional structures. Here we present three‐dimensional trinuclear Ni(II)‐ and Pt(II)‐cage compounds with a covalently bound [2+3] salicylimine cage backbone. The solubility of the cages allowed their investigation by spectroscopic methods. Furthermore, the Pt(II) derivative was investigated by single crystal X‐ray structure analysis revealing that the presented cage compounds possess the largest intrinsic void of metal salphen cages reported till date.
Solid–Liquid Phase Behaviors of Binary Mixtures of Various Partial Acylglycerols by Differential Scanning Calorimetry
Authors: Seniorita Latifa , Minami Eiji , Kawamoto Haruo
Published: October 2021

Monoacylglycerol (MAG), diacylglycerol (DAG), and triacylglycerol (TAG) are impurities in biodiesel and a major cause of precipitation. Understanding the behavior of such acylglycerols is essential for predicting biodiesel cold flow properties (CFPs). The previous study on MAG/MAG binary mixtures shows that they tend to solidify by forming molecular compounds. In contrast, TAG/TAG mixtures, which have been studied extensively, are commonly eutectic or monotectic systems, in which each component solidifies separately. The present study focuses on binary mixtures of DAG/DAG and different acylglycerol pairs (MAG/DAG, TAG/MAG, and DAG/TAG), and determination of their solid–liquid phase behavior by differential scanning calorimetry. These mixtures are found to behave as eutectic or monotectic systems with no sign of compound formation. As DAG and TAG have lower contents than MAG in biodiesel and they are unlikely to form molecular compounds with MAG, it is suggested that DAG and TAG have little effect on the biodiesel CFPs.

Practical Applications: Biodiesel has attracted much interest because its blending with conventional fossil diesel has become more standard with biofuel mandates. From an energy perspective, the solid–liquid phase behavior of acylglycerols will contribute to building prediction models for biodiesel CFPs.
The Concept of Photozymes: Short Peptides with Photoredox Catalytic Activity for Nucleophilic Additions to α‐Phenyl Styrenes
Authors: Sack Daniel , Wagenknecht Hans‐Achim
Published: October 2021

Conventional photoredox catalytic additions of alcohols to olefins require additives, like thiophenol, to promote back electron transfer. The concept of “photozymes” assumes that forward and backward electron transfer steps in a photoredox catalytic cycle are controllable by substrate binding to photocatalytically active peptides. Accordingly, we synthesized a short tripeptide modified with 1,7‐dicyano‐perylene‐3,4 : 9,10‐tetracarboxylic acid bisimide as photoredox catalyst. This peptide undergoes an unconventional photoredox catalytic cycle with the radical anion and dianion of the perylene bisimide‐peptide as intermediates. The photoredox catalytic reactions with α‐phenyl styrenes as substrates require remarkably low catalyst loadings (0.5 mol%) and give the methoxylation products in high yields. The concept of “photozymes” for photoredox catalysis has significant potential for other photocatalytic reactions, in particular with respect to enantioselective photocatalysis.
Formal [2+2+2] Cycloaddition Reaction of 1,3,5‐Triazinanes with diethyl acetylene dicarboxylate: Approach to Tetrahydropyrimidines
Authors: Shi Ruijie , Gao Limei , Chen Weiji , Shi Yangqing , Cao Zhixing , Zheng Yongsheng , Liu Jikai
Published: October 2021

An unprecedented [2+2+2] cycloaddition reaction of 1,3,5‐triazinanes with diethyl acetylene dicarboxylate is disclosed. This catalyst free reaction provided an efficient and mild approach to synthesize a variety of functionalized tetrahydropyrimidines in moderate to excellent yields (up to 99 % yield). Preliminary mechanistic investigation has been conducted to elucidate the reaction process.
A novel top‐k key node query problem in subgraph matching and its greedy strategy
Authors: Xue Zhengyuan
Published: October 2021

Top‐k node selection in graph data is an essential problem in computer science and applications. In view of an important issue in the field of graph data, subgraph matching issue, we define the problem and propose its method for the top‐k key node query w.r.t. the subgraph matching. Unlike the general top‐k query problem, we aim to find out k nodes that make the matching subgraphs in data graph G that are covered by the k nodes as more as possible. This is a problem of the maximum coverage of subgraph matching, which belongs to the NP‐hard problem. We study the problem based on a greedy algorithm and give an intuitive solution. Considering the characteristics of the top‐k problem, we propose an improved and more efficient greedy algorithm. Experiments on real social network graph data set (Twitter) show that the related results represent the key nodes that can better reveal the essential characteristics of the query graph in the data graph G. The key node query problem in subgraph matching proposed in this article may have extensive applications in reality, such as the assessment of the influence of specific group members in social network, the detection of abnormal communication in a computer communication network, the road traffic evaluation and load balance problem in a road traffic network, and so on.
Data‐Driven Temporal Charging Patterns of Electric Vehicles in China
Authors: Li Xuefang , Zhang Qiang , Chibane Hicham , Cavallucci Denis , Tang Xiaoan , Zuo Jian , Song Hao
Published: October 2021

Users of electric vehicles (EVs) have different preferences for the temporal charging patterns. The analysis of temporal charging patterns can aid in the decision‐making of EV‐related stakeholders, including policymakers, grid operators, and automobile companies. Herein, a recognition and factor analysis framework of temporal charging patterns for EVs’ usage improvement is proposed. A Gaussian mixture model (GMM) is used to obtain temporal charging patterns by considering characteristics related to the charging session and time of parking period. A multinomial logit model is used for the factor analysis of the temporal charging patterns. An experiment is conducted with the proposed framework using data of private electric vehicles (PEVs) and carsharing electric vehicles (CSEVs) collected between 2018 and 2019 in China. The data are statistically analyzed, and then six types of temporal charging patterns are obtained by the GMM. A comparison of the pattern distributions over time shows that they are obviously different between PEVs and CSEVs. The analysis of the patterns’ influencing factors of PEVs and CSEVs shows that the PEVs have more influencing factors than the CSEVs.
Self‐Supported Fluorine‐Doped Boron Carbonitride Porous Aerogels for High‐Performance Supercapacitors
Authors: Liu Shengfu , Shi Dong , Tu Huayao , Yao Xiaogang , Deng Lequan , Xu Deqin , Shao Yongliang , Wu Yongzhong , Hao Xiaopeng
Published: October 2021

Carbon materials have long been extensively used in supercapacitors. However, the practical application of carbon‐based supercapacitors has been severely limited by their low charge storage capacity. Rational construction of carbon materials with heteroatom doping and high specific surface area can effectively improve the performance of supercapacitors. Therefore, a self‐supported fluorine‐doped boron carbonitride (F‐BCN) aerogel material for the application of supercapacitors is designed. The introduction of heteroatoms increases the defect density of the carbon skeleton, expands the interlayer spacing, and generates abundant electrochemical active sites, thereby promoting the diffusion of ions in the electrode. The specific capacitance of F‐BCN‐3 is 524.9 F g−1 at a specific current of 1 A g−1, with which the assembled symmetric supercapacitor exhibits a maximum energy density of 11.75 W h kg−1. The symmetric supercapacitor can maintain a specific capacitance of 83% after 5000 charge and discharge cycles, showing good electrochemical cycle stability. The design concept provides a promising guide for further applications of carbon materials in energy storage devices.
Resolving the “muddle in the middle”: The case for Homo bodoensis sp. nov.
Authors: Roksandic Mirjana , Radović Predrag , Wu Xiu‐Jie , Bae Christopher J.
Published: October 2021

Recent developments in the field of palaeoanthropology necessitate the suppression of two hominin taxa and the introduction of a new species of hominins to help resolve the current nebulous state of Middle Pleistocene (Chibanian) hominin taxonomy. In particular, the poorly defined and variably understood hominin taxa Homo heidelbergensis (both sensu stricto and sensu lato) and Homo rhodesiensis need to be abandoned as they fail to reflect the full range of hominin variability in the Middle Pleistocene. Instead, we propose: (1) introduction of a new taxon, Homo bodoensis sp. nov., as an early Middle Pleistocene ancestor of the Homo sapiens lineage, with a pan‐African distribution that extends into the eastern Mediterranean (Southeast Europe and the Levant); (2) that many of the fossils from Western Europe (e.g. Sima de los Huesos) currently assigned to H. heidelbergensis s.s. be reassigned to Homo neanderthalensis to reflect the early appearance of Neanderthal derived traits in the Middle Pleistocene in the region; and (3) that the Middle Pleistocene Asian fossils, particularly from China, likely represent a different lineage altogether.
Whose mental health declines during economic downturns?
Authors: Black Nicole , Jackson Angela , Johnston David W.
Published: October 2021

Prior research shows that economic downturns are associated with increases in mental illness. However, we know little about whose mental health is most negatively affected. Is it the young or old, men or women, employed or non‐employed, rich or poor? Using an 18‐year panel dataset of Australians, we contribute to this understanding by estimating the impact of changes in unemployment on mental health, separately by population subgroups. Our mental health measure captures psychological distress and emotional difficulties, which are often missed by infrequent event indicators such as suicides. We find that young women suffer most during economic downturns. Men and women of older ages are not significantly affected. The effects for young women are driven by those in insecure employment, and those from low socioeconomic backgrounds. Our results suggest that public health programs should emphasize the mental health of young women during economic downturns.
Role of metronomic therapy for advanced oral cancers and predictors of response: Multi‐institutional feasibility study
Authors: Sultania Mahesh , Imaduddin Mohammed , S. V. Deo Suryanarayana , Kar Madhabananda , K. Muduly Dillip , Kumar Sunil , Sharma Atul , Mishra Ashutosh , K. D. Majumdar Saroj , K. Adhya Amit , K. Parida Dilip
Published: October 2021

Background

In an era of targeted therapies, patients with cancer in resource‐constraint countries continue to struggle to find affordable care.

Methods

The present study is a multicenter prospective single‐arm study. Patients with expected delay in surgery, unresectable or metastatic cancers, and patients not suitable for surgery or conventional chemotherapy were included. Oral methotrexate 15 mg/m2 once a week and oral celecoxib 200 mg twice daily was used for metronomic therapy.

Results

At 8 weeks, a clinically complete response was seen in 2.5%, partial response in 46.6%, stable disease in 39.8%, and disease progression in 11%. Size less than 4 cm, alveolobuccal subsite, and well‐differentiated histology were significantly associated with no disease progression.

Conclusion

Constraint‐adapted approach of using methotrexate and celecoxib is economical with good compliance, minimal toxicity, and good efficacy. It is feasible for use in diverse settings. Individualized selection of patients based on response predictors may maximize metronomic therapy's benefit.
Effect of corticosteroid dosing on outcomes in high‐grade immune checkpoint inhibitor hepatitis
Authors: Li Michael , Wong Danny , Vogel Alexander S. , Sack Jordan S. , Rahma Osama E. , Hodi F. Stephen , Zucker Stephen D. , Grover Shilpa
Published: October 2021

Background and Aims

Consensus guidelines recommend high‐dose corticosteroids (1–2 mg/kg/day methylprednisolone equivalents) for treating grade ≥3 immune checkpoint inhibitor (ICI) hepatitis. We examined the effect of corticosteroid dosing on time to alanine aminotransferase (ALT) normalization, need for additional immunosuppression, and steroid‐related complications.

Approach and Results

We conducted a retrospective cohort study of 215 ICI‐treated patients from 2010 to 2020 who developed grade ≥3 (ALT > 200 U/L) ICI hepatitis. Patients were grouped by initial corticosteroid dose (≥1.5 mg/kg or <1.5 mg/kg methylprednisolone equivalents). Propensity scores were calculated predicting the risk of receiving the higher steroid dose and used in inverse probability of treatment weighted (IPTW) logistic or Cox regression. The 87 patients in the ≥1.5 mg/kg group received higher initial (2.0 vs. 0.8 mg/kg/day, p < 0.001) and maximum (2.0 vs. 1.0 mg/kg/day, p < 0.001) steroid doses than the 128 patients in the <1.5 mg/kg group. There was no difference between the higher versus lower‐dose groups in development of steroid‐refractory hepatitis (OR 1.22, 95% CI 0.79–1.89, p = 0.365) on IPTW‐logistic regression. In patients with steroid‐responsive disease, there was no difference between the two groups in time to ALT normalization using either standard Cox regression (HR 1.02, 95% CI 0.72–1.45, p = 0.903) or IPTW‐Cox regression (HR 1.09, 95% CI 0.78–1.51, p = 0.610). The ≥1.5 mg/kg group had longer exposure to corticosteroids (median 60 vs. 44 days, p = 0.005) and higher incidences of infection (18.4% vs. 7.0%, relative risk [RR] 2.6, 95% CI 1.2–5.6, p = 0.011) and hyperglycemia requiring treatment (23.3% vs. 7.8%, RR 3.0, 95% CI 1.5‐6.0, p = 0.001).

Conclusions

In patients with high‐grade ICI hepatitis, initial treatment with 1 mg/kg/day methylprednisolone equivalents provides similar hepatitis outcomes with reduced risk of steroid‐related complications when compared with higher‐dose regimens.
SARS‐CoV‐2 Infections Among Patients With Liver Disease and Liver Transplantation Who Received COVID‐19 Vaccination
Authors: Moon Andrew M. , Webb Gwilym J. , García‐Juárez Ignacio , Kulkarni Anand V. , Adali Gupse , Wong David K. , Lusina Beth , Dalekos George N. , Masson Steven , Shore Brandon M. , Barnes Eleanor , Barritt A. Sidney , Marjot Thomas
Published: October 2021

Many safe and effective severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccinations dramatically reduce risks of coronavirus disease 2019 (COVID‐19) complications and deaths. We aimed to describe cases of SARS‐CoV‐2 infection among patients with chronic liver disease (CLD) and liver transplant (LT) recipients with at least one prior COVID‐19 vaccine dose. The SECURE‐Liver and COVID‐Hep international reporting registries were used to identify laboratory‐confirmed COVID‐19 in CLD and LT patients who received a COVID‐19 vaccination. Of the 342 cases of lab‐confirmed SARS‐CoV‐2 infections in the era after vaccine licensing, 40 patients (21 with CLD and 19 with LT) had at least one prior COVID‐19 vaccination, including 12 who were fully vaccinated (≥2 weeks after second dose). Of the 21 patients with CLD (90% with cirrhosis), 7 (33%) were hospitalized, 1 (5%) was admitted to the intensive care unit (ICU), and 0 died. In the LT cohort (n = 19), there were 6 hospitalizations (32%), including 3 (16%) resulting in mechanical ventilation and 2 (11%) resulting in death. All three cases of severe COVID‐19 occurred in patients who had a single vaccine dose within the last 1‐2 weeks. In contemporary patients with CLD, rates of symptomatic infection, hospitalization, ICU admission, invasive ventilation, and death were numerically higher in unvaccinated individuals. Conclusion: This case series demonstrates the potential for COVID‐19 infections among patients with CLD and LT recipients who had received the COVID‐19 vaccination. Vaccination against SARS‐CoV‐2 appears to result in favorable outcomes as attested by the absence of mechanical ventilation, ICU, or death among fully vaccinated patients.
Recent Progress in the Simulation of Chiral Systems with Real Time Propagation Methods
Authors: Mattiat Johann , Luber Sandra
Published: October 2021

In this brief review, an overview about recent efforts to simulate the spectroscopic signatures of chiral molecules is given with focus on real time propagation approaches to solve the time‐dependentSchrödingerequation. In particular the simulation of electric circular dichroism spectra and vibrationalRamanoptical activity is discussed. In comparison to linear absorption spectra, where only the response of the electric dipole moment is necessary, the response of the magnetic dipole moment and electric quadrupole moment is more intricate. Issues such as gauge origin dependence, basis set dependence, non‐local potentials and the dipole approximation are addressed.
An ensemble model of convolution and recurrent neural network for skin disease classification
Authors: Ahmad Belal , Usama Mohd , Ahmad Tanvir , Khatoon Shabnam , Alam Chaudhary Maqbool
Published: October 2021

Skin cancer is one of the rapidly growing diseases in the world. Especially, millions of cases are reported every year by all types of skin cancer in America. Early detection of skin cancer using dermoscopy, the light source, and the magnification device are used to inspect the skin lesions. A dermatologist observed hypodermic structures are normally invisible. However, accurate and effective skin disease classification by humans is not straightforward and requires a long time of practice. Furthermore, it is often inaccurate and difficult to reproduce, being unable to completely use the long‐term dependence connection between specific image key features and image labels even for experienced dermatologists. Therefore, it needs to develop a computer‐aided diagnostic system for reliable skin cancer diagnosis. Classical methods focus on designing and combining hand‐craft features from input data and face vanishing or exploding of loss gradient problem, whereas the bidirectional long short term memory (BLSTM) network does not need any prior knowledge or pre‐designing, and it is an expert in keeping the associated information in both directions. Thus, to improve the classification performance for handling these problems, we proposed a hybrid classification method based on the deep convolutional neural network and stacked BLSTM network. Firstly, deep features are extracted from input skin disease facial images. Next, the sequential features among input data are learned using a dual BLSTM network, where dual BLSTM through max‐pooling, the forward and backward long short term memory (LSTM) hidden states of both the feature matrix and its transpose concatenates for inputting into a dense, fully connected (FC) layer. Finally, the softmax function is used to classify skin disease images. To improve the generalization capability, we evaluate our method on two skin disease image datasets and compare their local image descriptors. The proposed method achieved the best mean accuracy of 91.73%, which shows significant improvements in skin disease classification compared with state‐of‐the‐art skin disease classification methods.
Small world: Narrow, wide, and long replication of Goyal, van der Leij and Moraga‐Gonzélez (JPE 2006) and a comparison of EconLit and Scopus
Authors: Rose Michael E.
Published: October 2021

I undertake a narrow, wide, and long replication of Goyal, van der Leij and Moraga‐Gonzélez (2006, https://doi.org/10.1086/500990). Using social network analysis, they show that the Economics profession gradually evolved into a small world. Small worlds (or small world networks) have unique information transmission capabilities. The trend is explained by the emergence of frequently publishing researchers with many distinct co‐authors. In a social network, they resemble stars. The original results are robust to the usage of (I) another software, (II) a recent version of the originally used data, and (III) another database and a more sophisticated author disambiguation.
NADPH oxidases regulate endothelial inflammatory injury induced by PM2.5 via AKT/eNOS/NO axis
Authors: Zou Lingyue , Xiong Lilin , Wu Tianshu , Wei Tingting , Liu Na , Bai Changcun , Huang Xiaoquan , Hu Yuanyuan , Xue Yuying , Zhang Ting , Tang Meng
Published: October 2021

Fine particulate matter (PM2.5)‐induced detrimental cardiovascular effects have been widely concerned, especially for endothelial cells, which is the first barrier of the cardiovascular system. Among potential mechanisms involved, reactive oxidative species take up a crucial part. However, source of oxidative stress and its relationship with inflammatory response have been rarely studied in PM2.5‐induced endothelial injury. Here, as a key oxidase that catalyzes redox reactions, NADPH oxidase (NOX) was investigated. Human umbilical vein endothelial cells (EA.hy926) were exposed to Standard Reference Material 1648a of urban PM2.5 for 24 h, which resulted in NOX‐sourced oxidative stress, endothelial dysfunction, and inflammation induction. These are manifested by the up‐regulation of NOX, increase of superoxide anion and hydrogen peroxide, elevated endothelin‐1 (ET‐1) and asymmetric dimethylarginine (ADMA) level, reduced nitric oxide (NO) production, and down‐regulation of phosphorylation of endothelial NO synthase (eNOS) with increased levels of inducible NO synthase, as well as the imbalance between tissue‐type plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI‐1), and changes in the levels of pro‐inflammatory and anti‐inflammatory factors. However, administration of NOX1/4 inhibitor GKT137831 alleviated PM2.5‐induced elevated endothelial dysfunction biomarkers (NO, ET‐1, ADMA, iNOS, and tPA/PAI‐1), inflammatory factors (IL‐1β, IL‐10, and IL‐18), and adhesion molecules (ICAM‐1, VCAM‐1, and P‐selectin) and also passivated NOX‐dependent AKT and eNOS phosphorylation that involved in endothelial activation. In summary, PM2.5‐induced NOX up‐regulation is the source of ROS in EA.hy926, which activated AKT/eNOS/NO signal response leading to endothelial dysfunction and inflammatory damage in EA.hy926 cells.
Multiple pathways are responsible to the inhibitory effect of butorphanol on OGD/R‐induced apoptosis in AC16 cardiomyocytes
Authors: Wu Qiaoling , Liu Feifei , Shen Tu , Zhang Wei
Published: October 2021

Ischemic heart disease is the leading cause of cardiovascular mortality, which is related to cardiac myocyte apoptosis. Butorphanol is an opioid receptor agonist with potential cardioprotective function. The purpose of this work is to explore the function and mechanism of butorphanol in oxygen and glucose deprivation/reperfusion (OGD/R)‐induced cardiomyocyte apoptosis. The overlapping targets of ischemic heart disease and butorphanol were analyzed according to GeneCards, ParmMapper, Cytoscape, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Human cardiomyocyte AC16 cells were incubated with butorphanol and then stimulated with OGD/R. Cell injury was investigated by Cell Counting Kit‐8, lactate dehydrogenase (LDH) assay kit, TUNEL staining, caspase‐3 activity assay kit, and Western blotting. The proteins in signaling pathways were measured using Western blotting. A total of 93 overlapping targets of ischemic heart disease and butorphanol were obtained. Pathway analysis exhibited that these targets might be involved in multiple signaling pathways. Butorphanol alone showed little cytotoxicity to cardiomyocytes, and it protected against OGD/R‐induced viability inhibition, LDH release, cell apoptosis, and increase of caspase‐3 activity and expression levels of cleaved caspase‐3 and Bim. Butorphanol promoted the activation of the phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt)/forkhead box O (FoxO) and hypoxia‐inducible factor‐1α (HIF‐1α)/vascular endothelial growth factor (VEGF) pathways and attenuated the activation of the mitogen‐activated protein kinase (MAPK) signaling in OGD/R‐treated cardiomyocytes. In conclusion, butorphanol prevents OGD/R‐induced cardiomyocyte apoptosis through activating the PI3K/Akt/FoxO and HIF‐1α/VEGF pathways and inactivating the MAPK pathway.
The lower expression of circulating miR‐210 and elevated serum levels of HIF‐1α in ischemic stroke; Possible markers for diagnosis and disease prediction
Authors: Rahmati Mina , Ferns Gordon A. , Mobarra Naser
Published: October 2021

Background

Stroke, either due to ischemia or hemorrhage, causes acute neurological damages to the brain. There is shortage of reliable biomarkers for ischemic stroke (IS), and we therefore investigated the serum concentrations of microRNA‐210 (miR‐210) and hypoxia inducible factor‐1α (HIF‐1α), as possible diagnostic and/or prognostic markers for IS.

Methods

Serum samples were acquired from 52 IS patients and their healthy counterparts at five time points: upon admission, 24 and 48 h after admission, upon discharge and 3 months later. Serum levels of miR‐210 and HIF‐1α were respectively analyzed using real time RT‐PCR and ELISA. Diagnostic and prognostic accuracy tests were performed to assess the value of suggested biomarkers.

Results

IS patients demonstrated higher levels of serum HIF‐1α and lower miR‐210 in comparison to the healthy subjects. MiR‐210 was suggested to be a weak diagnostic biomarker at the time of admission (AUC = 0.61; p = 0.05), while HIF‐1α was an acceptable diagnostic marker for IS (AUC = 0.73; p < 0.0001). The higher expression of miR‐210 and lower levels of HIF‐1α were associated with better survivals in IS patients.

Conclusions

Serum miR‐210 is a weak diagnostic marker of IS. Serum HIF‐1α is a better biomarker in diagnosing IS patients but further work in larger groups, including those with hemorrhagic stroke is necessary to confirm its diagnostic utility. Similarly, the prognostic potentiality of miR‐210 and HIF‐1α was acceptable but needs bigger sample size and longer follow‐up to be statistically confirmed.
miR‐125a‐5p promotes gastric cancer growth and invasion by regulating the Hippo pathway
Authors: Li Ruixin , Hu Zhihao , Wang Zhuoyin , Zhu Tianyu , Wang Guojun , Gao Bulang , Wang Jingtao , Deng Xiumei
Published: October 2021

Objective

This study was carried out to explore the potential involvement of miR‐125a‐5p in the oncogenic effects of EphA2, TAZ, and TEAD2 and the activity of the Hippo signaling pathway in gastric cancer progression.

Methods

In vitro transfection of miR‐125a‐5p mimics or inhibitors, qRT‐PCR, colony formation assays, and cell invasion assays were used to assess the effect of miR‐125a‐5p on the growth and invasion in gastric cancer (GC). Male nude mice bearing tumors derived from human GC cells were used for evaluating the effects of miR‐125a‐5p on tumor growth. Luciferase reporter assay, immunofluorescence, immunohistochemistry, qRT‐PCR, and immunoblotting were performed to explore the role of miR‐125a‐5p in the epithelial‐mesenchymal transition (EMT) and association among miR‐125a‐5p, EphA2, TAZ, and TEAD2 in GC cells.

Results

MiR‐125a‐5p enhanced GC cell viability and invasion in vitro, whereas inhibition of miR‐125a‐5p using a specific inhibitor and antagomir suppressed cancer cell invasion and tumor growth. Moreover, inhibition of miR‐125a‐5p reversed EMT in vitro. miR‐125a‐5p upregulated the expression of EphA2, TAZ, and TEAD2, promoted TAZ nuclear translocation, and induced changes in the activity of the Hippo pathway by enhancing the expression of TAZ target genes. Finally, miR‐125a‐5p was overexpressed in late‐stage GCs, and positive correlations were observed with its targets EphA2, TAZ, and TEAD2.

Conclusion

miR‐125a‐5p can promote GC growth and invasion by upregulating the expression of EphA2, TAZ, and TEAD2.
Inhibition of FABP4 attenuates hyperoxia‐induced lung injury and fibrosis via inhibiting TGF‐β signaling in neonatal rats
Authors: Huang Liang‐Ti , Chou Hsiu‐Chu , Chen Chung‐Ming
Published: October 2021

Bronchopulmonary dysplasia (BPD) is a chronic lung disease characterized by interrupted alveologenesis and alveolar simplification caused by oxygen therapy in premature infants. Metabolic dysfunction is involved in the pathogenesis of BPD. Fatty acid‐binding protein 4 (FABP4) is significantly increased in specific lung tissues in patients with BPD. Therefore, we investigated whether BMS309403, an FABP4 inhibitor that can mitigate tissue fibrosis, can regulate pulmonary fibrotic processes in newborn rats exposed to hyperoxia. Newborn rat pups were exposed to room air (RA; 21% O2) or 85% O2 from 5 to 14 days of age and were then allowed to recover in RA until 29 days of age. They received intraperitoneal injection with placebo (phosphate‐buffered saline [PBS]) or BMS 309403 (0.5 mg or 1.0 mg kg−1 d−1) every other day from 4 to 14 days of age then were divided into O2 plus PBS or low dose or high dose and RA plus PBS or low dose or high dose groups. We assessed lung histology and evaluated lung collagen I, FABP4 as well as TGF‐β1 expression at 14 and 29 days of age. In the hyperoxia injury‐recovery model, prophylactic BMS309403 treatment reduced mean linear intercept values and FABP4 expression (p < 0.001). Prophylactic BMS309403 treatment mitigated pulmonary fibrosis and TGF‐β1 expression immediately after hyperoxia exposure (p < 0.05). The attenuation of hyperoxia‐induced alveolar developmental impairment and pulmonary fibrosis by FABP4 inhibition indicated that such inhibition has potential clinical and therapeutic applications.
Population Pharmacokinetics and Exposure‐Response Modeling of Daratumumab Subcutaneous Administration in Patients With Light‐Chain Amyloidosis
Authors: Luo Man (Melody) , Zhu Peijuan (Penny) , Nnane Ivo , Xiong Yuan , Merlini Giampaolo , Comenzo Raymond L , Kastritis Efstathios , Wechalekar Ashutosh D. , Weiss Brendan M. , Tran NamPhuong , Qin Xiang , Vermeulen Jessica , Sharma Amarnath , Sun Yu‐Nien , Zhou Honghui
Published: October 2021

The purpose of this study is to characterize the population pharmacokinetics (popPK) of subcutaneous (SC) daratumumab in combination with bortezomib, cyclophosphamide, and dexamethasone and explore the relationship between daratumumab systemic exposure and selected efficacy and safety end points in patients with newly diagnosed systemic amyloid light‐chain amyloidosis. The popPK analysis included pharmacokinetic and immunogenicity data from patients receiving daratumumab SC in combination with bortezomib, cyclophosphamide, and dexamethasone in the ANDROMEDA study (AMY3001; safety run‐in, n = 28; randomized phase, n = 183). Nonlinear mixed‐effects modeling was used to characterize the popPK and quantify the impact of potential covariates. The exposure‐response (E‐R) analysis included data from all patients in the randomized phase of ANDROMEDA (n = 388). Logistic regression and survival analysis were used to evaluate the relationships between daratumumab systemic exposure and efficacy end points. The E‐R analysis on safety was conducted using quartile comparison and logistic regression analysis. The observed concentration‐time data of daratumumab SC were well described by a 1‐compartment popPK model with first‐order absorption and parallel linear and nonlinear Michaelis‐Menten elimination pathways. None of the investigated covariates were determined to be clinically meaningful. Daratumumab systemic exposure was generally similar across subgroups that achieved different levels of hematologic response, and there was no apparent relationship between daratumumab systemic exposure and the investigated safety end points. In conclusion, the popPK and E‐R analyses supported the selected 1800‐mg flat dose of daratumumab SC in combination with the bortezomib, cyclophosphamide, and dexamethasone regimen for the treatment of light‐chain amyloidosis. No dose adjustment was recommended for investigated covariates.
MDMA‐Assisted Psychotherapy for Treatment of Posttraumatic Stress Disorder: A Systematic Review With Meta‐Analysis
Authors: Smith Kimberly W. , Sicignano Dakota J. , Hernandez Adrian V. , White C. Michael
Published: October 2021

This article discusses current literature on the use of 3,4‐methylenedioxymethamphetamine (MDMA)‐assisted psychotherapy in the treatment of posttraumatic stress disorder (PTSD). MDMA, the intended active ingredient in illicit Ecstasy or Molly products, is a psychedelic that causes an elevated mood, feeling of bonding, and increased energy. In MDMA‐assisted psychotherapy, patients are subjected to 2 or 3 multihour sessions of therapy with a team of psychiatrists. The dosing of MDMA is used to allow the therapist to probe the underlying trauma without causing emotional distress. The use of MDMA‐assisted psychotherapy treatment reduced patient's Clinician‐Administered PTSD Scale (CAPS) scores from baseline more than control psychotherapy (–22.03; 95%CI, –38.53 to –5.52) but with high statistical heterogeneity. MDMA‐assisted psychotherapy enhanced the achievement of clinically significant reductions in CAPS scores (relative risk, 3.65; 95%CI, 2.39‐5.57) and CAPS score reductions sufficient to no longer meet the definition of PTSD (relative risk, 2.10; 95%CI, 1.37‐3.21) with no detected statistical heterogeneity. While therapy was generally safe and well tolerated, bruxism, anxiety, jitteriness, headache, and nausea are commonly reported. While MDMA‐assisted psychotherapy has been shown to be an effective therapy for patients with PTSD with a reasonable safety profile, use of unregulated MDMA or use in the absence of a strongly controlled psychotherapeutic environment has considerable risks.