bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vivo Nitroreductase Imaging via Fluorescence and Chemical Shift Dependent 19F NMR
Authors: Chen Shizhen , Xiao Long , Li Yu , Qiu Maosong , Yuan Yaping , Zhou Rui , Li Conggang , Zhang Lei , Jiang Zhong‐Xing , Liu Maili , Zhou Xin
Published: October 2022

Nitroreductase (NTR) is an important biomarker widely used to evaluate the degree of tumor hypoxia. Although a few optical methods have been reported for detecting nitroreductase at low concentration ranges, an effective strategy for nitroreductase monitoring in vivo without limits to the imaging depth is still lacking. Herein, a novel dual‐mode NIR fluorescence and 19F MRI agent, FCy7‐NO2, is proposed for imaging tumor hypoxia. We show that FCy7‐NO2 serves as not only a rapid NIR fluorescence enhanced probe for monitoring and bioimaging of nitroreductase in tumors, but also a novel 19F MR chemical shift‐sensitive contrast agent for selectively detecting nitroreductase catalyzed reduction. Notably, integrating two complementary imaging technologies into FCy7‐NO2 enables sensitive detection of nitroreductase in a broad concentration range without tissue‐depth limit. In general, this agent has a remarkable response to nitroreductase, which provides a promising method for understanding tumor evolution and its physiological role in the hypoxic microenvironment.
Women online: A study of Common Service Centres in India using a capability approach
Authors: Rajeev Meenakshi , Bhandarkar Supriya
Published: October 2022

Income‐generating activities by women are an effective means of reducing gender‐based deprivation and disparities. In the constrained familial and community settings of developing economies, online platforms can be an appropriate means for women to carry out economic activities. In this context, important initiatives taken by the Government of India, such as the Common Service Centres scheme, are worth studying. This paper critically evaluates such revolutionary online platform–based entrepreneurial initiatives using the capability approach developed by Amartya Sen. We examine through case studies how women‐run businesses use online platforms and what determines their success, inputs, capabilities, and conversion factors. Further, national enterprise‐level data from Indiaʼs National Sample Survey Office are analysed to show that states with a higher level of gender inequality are also the regions with a lower level of information and communications technology usage by women‐run enterprises.
Invasive gibel carp (Carassius gibelio) outperforms threatened native crucian carp (Carassius carassius) in growth rate and effectiveness of resource use: Field and experimental evidence
Authors: Tapkir Sandip , Boukal David , Kalous Lukáš , Bartoň Daniel , Souza Allan T. , Kolar Vojtech , Soukalová Kateřina , Duchet Claire , Gottwald Milan , Šmejkal Marek
Published: October 2022

Invasive alien species pose a serious threat to biodiversity. They frequently compete with native species for resources, resulting in the decline or extinction of the latter.

Native crucian carp (Carassius carassius) faces a severe decline in European waters and has become critically endangered in many European countries. Possible ecological mechanisms of the rapid decline of the crucian carp attributable to resource competition with the invasive Carassius gibelio were identified. A field study was combined with a controlled experiment to compare (i) standard length–weight relationships and growth patterns in 12 Czech and Swedish ponds in which the species occur alone or in syntopy, and (ii) individual growth and food utilization under the same conditions.

The growth increment of C. gibelio was greater than that of C. carassius under the same experimental conditions (mean increase in weight: C. gibelio, 21.7%; C. carassius, 5.2%; increase in standard length: C. gibelio, 6.3%; C. carassius, 2.0%), suggesting that C. gibelio uses food resources more efficiently than C. carassius does. Moreover, larger C. carassius individuals did not grow, whereas growth of C. gibelio individuals was largely independent of standard length.

Field data suggested that C. gibelio grew faster and were heavier than C. carassius of the same standard length in four Czech ponds where they occurred together. Individual weight‐at‐length declined in C. carassius in the presence of C. gibelio, especially in more dense populations, whereas the weight‐at‐length of C. gibelio remained similar.

Taken together, these results imply that C. gibelio has better competitive abilities for food than C. carassius and provide novel support for the long‐standing hypothesis that the introduction and spread of C. gibelio causes the decline of C. carassius in European waters.
Impacts of Aeolus horizontal Line‐Of‐Sight (HLOS) wind assimilation on the Korean integrated model (KIM) forecast system
Authors: Lee Sihye , Song Hyo‐Jong , Kwon In‐Hyuk , Kang Jeon‐Ho
Published: October 2022

The Korean Integrated Model (KIM) forecast system, based on a hybrid four‐dimensional ensemble‐variational method, was extended to assimilate Horizontal Line‐Of‐Sight (HLOS) wind observations from the Atmospheric Laser Doppler Instrument (ALADIN) on board the Atmospheric Dynamic Mission Aeolus satellite. In a global cycling experiment, assimilation of Aeolus HLOS wind observations led to reductions in the average root‐mean‐square error of 0.8 and 0.5% for the zonal and meridional wind analyses when compared against European Center for Medium‐Range Weather Forecasts (ECMWF) Integrated Forecast System (IFS) analyses. Even though the observed variable is wind, there was also an overall beneficial impact on analyses of the mass variables. In the Southern Hemisphere (SH), the reduced analysis errors led to forecast skill improvements out to 72 h. In contrast, in the Northern Hemisphere (NH) there was relatively little reduction of analysis errors, but wind forecasts were nevertheless improved, and these positive impacts lasted longer – out to 120 h rather than 72 h. Experiments suggest that the relatively poor long‐range performance in the SH high latitudes was due to problems with the mass increments derived from Aeolus wind increments via the ensemble‐based part of the hybrid background error covariance (B), which eventually led to adverse effects on the wind variables as forecasts progressed in the SH. This study shows that it is necessary to estimate the ensemble B in the Antarctic region with its high elevation more accurately in order to effectively use the Aeolus observation information.
Mental health issues in parents of children with autism spectrum disorder: A multi‐time‐point study related to COVID‐19 pandemic
Authors: Wang Luxi , Zhang Huiying , Shang Chuang , Liang Huirong , Liu Wenlong , Han Bing , Xia Wei , Zou Mingyang , Sun Caihong
Published: October 2022

Given the unpredictability and challenges brought about by the 2019 novel coronavirus (COVID‐19) pandemic, this study aimed to investigate the impact trend of the prolonged pandemic on the mental health of parents of children with autism spectrum disorder (ASD). The 8112 participants included parents of children with ASD and parents of typically developing (TD) children at two sites (Heilongjiang and Fujian province, China). The parents completed a set of self‐report questionnaires covering demographic characteristics, influences related to COVID‐19, COVID‐19 concerns and perceived behaviors, as well as the Connor‐Davidson resilience scale (CD‐RISC), self‐rating anxiety scale (SAS), and self‐rating depression scale (SDS) by means of an online survey platform. Data were collected by three cross‐sectional surveys carried out in April 2020 (Time 1), October 2020 (Time 2), and October 2021 (Time 3). The results of quantitative and qualitative comparisons showed that: (i) parents of children with ASD had lower levels of resilience, and more symptoms of anxiety and depression than parents of TD children at each time point (all P < 0.05); and (ii) there were significant time‐cumulative changes in resilience, anxiety, and depression among all participants (all P < 0.05). The logistic regression analyzes after adjusting for demographic characteristics revealed that the following factors were significantly associated with poor resilience and a higher rate of anxiety and depression in parents of children with ASD: time‐point, the effect of COVID‐19 on children's emotions and parents' emotions, changes in relationships, changes in physical exercise, changes in daily diet during the COVID‐19 pandemic, and COVID‐19‐related psychological distress. In conclusions, the parents did not report improvements in resilience, anxiety, or depression symptoms from Time 1 to Time 2 or 3, indicating that cumulative mental health issues increased when, surprisingly, the COVID‐19 restrictions were eased. The psychological harm resulting from the COVID‐19 pandemic is far‐reaching, especially among parents of children with ASD.
Physiologically based pharmacokinetic model to predict drug concentrations of breast cancer resistance protein substrates in milk
Authors: Zhang Tao , Zou Peng , Fang Yingsi , Li Yanyan
Published: October 2022

Many mothers need to take some medications during breastfeeding, which may carry a risk to breastfed infants. Thus, determining the amount of a drug transferred into breast milk is critical for risk–benefit analysis of breastfeeding. Breast cancer resistance protein (BCRP), an efflux transporter which usually protects the body from environmental and dietary toxins, was reported to be highly expressed in lactating mammary glands. In this study, we developed a mechanistic lactation physiologically based pharmacokinetic (PBPK) modeling approach incorporating BCRP mediated transport kinetics to simulate the concentration–time profiles of five BCRP drug substrates (acyclovir, bupropion, cimetidine, ciprofloxacin, and nitrofurantoin) in nursing women’s plasma and milk. Due to the lack of certain physiological parameters and scaling factors in nursing women, we combine the bottom up and top down PBPK modeling approaches together with literature reported data to optimize and determine a set of parameters that are applicable for all five drugs. The predictive performance of the PBPK models was assessed by comparing predicted pharmacokinetic profiles and the milk‐to‐plasma (M/P) ratio with clinically reported data. The predicted M/P ratios for acyclovir, bupropion, cimetidine, ciprofloxacin, and nitrofurantoin were 2.48, 3.70, 3.55, 1.21, and 5.78, which were all within 1.5‐fold of the observed values. These PBPK models are useful to predict the PK profiles of those five drugs in the milk for different dosing regimens. Furthermore, the approach proposed in this study will be applicable to predict pharmacokinetics of other transporter substrates in the milk.
Rapid screening of α‐glucosidase inhibitors in Hypericum perforatum L. using bio‐affinity chromatography coupled with UPLC/MS
Authors: Dong Qi , Hu Na , Yue Huilan , Wang Honglun , Wei Yue
Published: October 2022

α‐glucosidase inhibitors (AGIs) are widely used for the treatment of type 2 diabetes, but their side effects have made it to develop novel and alternative AGIs immediately. In this study, the extract of Hypericum perforatum L. (HPE) has been confirmed to have α‐glucosidase inhibitory activity in vitro and in vivo. Seven active compounds, rutin, hyperoside, isoquercitrin, avicularin, quercitrin, quercetin, and biapigenin, were screened based on a bio‐affinity chromatography column with α‐glucosidase enzyme‐conjugated solid phase and UPLC/MS, which exhibited excellent α‐glycosidase inhibitory effects by the determined IC50 values. The mechanism of α‐glycosidase inhibitory activity of biapigenin was studied for the first time. The results showed that biapigenin was a high‐potential, reversible, and mixed enzyme inhibitor. Analysis by molecular docking further revealed that hydrophobic interactions were generated by interactions between biapigenin and amino acid residues LYS156, PHE303, PHE314, and LEU313. In addition, hydrogen bonding occurred between biapigenin and α‐glucosidase amino acid residues ASP307, SER241, and LYS156. This research identified that biapigenin could be a novel AGI and further applied to the development of potential anti‐diabetic drugs. Furthermore, our studies established a rapid in vitro screening method for AGIs from plants.
Genomic characterization reveals distinct mutation landscapes and therapeutic implications in neuroendocrine carcinomas of the gastrointestinal tract
Authors: Wu Huanwen , Yu Zicheng , Liu Yueping , Guo Lei , Teng Lianghong , Guo Lingchuan , Liang Li , Wang Jing , Gao Jie , Li Ruiyu , Yang Ling , Nie Xiu , Su Dan , Liang Zhiyong
Published: October 2022

Background

Neuroendocrine carcinomas of the gastrointestinal tract (GI‐NECs) remain a disease of grim prognosis with limited therapeutic options. Their molecular characteristics are still undefined. This study aimed to explore the underlying genetic basis and heterogeneity of GI‐NECs.

Methods

Comprehensive genomic analysis using whole‐exome sequencing was performed on 143 formalin‐fixed, paraffin‐embedded samples of surgically resected GI‐NEC with a thorough histological evaluation. Mutational signatures, somatic mutations, and copy number aberrations were analyzed and compared across anatomic locations and histological subtypes. Survival analysis was conducted to identify the independent factors.

Results

In total, 143 GI‐NECs were examined: the stomach, 87 cases (60.8%); the esophagus, 29 cases (20.3%); the colorectum, 20 cases (14.0%); and the small intestine, 7 cases (4.9%). Eighty‐three (58.0%) and 60 (42.0%) cases were subclassified into small cell and large cell subtypes, respectively. GI‐NECs showed distinct genetic alterations from their lung counterparts and non‐neuroendocrine carcinomas in the same locations. Obvious heterogeneity of mutational signatures, somatic mutations, and copy number variations was revealed across anatomic locations rather than histological subtypes. Except for tumor protein p53 (TP53) and retinoblastoma 1 (RB1), the most frequently mutated genes in the stomach, esophagus, colorectum, and small intestine were low‐density lipoprotein receptor‐related protein 1B (LRP1B), notch receptor 1 (NOTCH1), adenomatosis polyposis coli (APC), catenin beta 1 (CTNNB1), respectively. Mutations in the WNT‐β‐catenin, NOTCH and erythroblastic leukemia viral oncogene B (ERBB) pathways were prevalently identified in gastric, esophageal, and colorectal NECs, respectively. Importantly, 104 (72.7%) GI‐NECs harbored putative clinically relevant alterations, and non‐gastric location andRB1bi‐allelic inactivation with copy number alterations were identified as two independent poor prognostic factors. Furthermore, we found that tumor cells in GI‐NECs first gain clonal mutations inTP53,RB1,NOTCH1andAPC, followed by subsequent whole‐genome doubling (WGD) and post‐WGD clonal mutations inLRP1B, CUB and Sushi multiple domains 3 (CSMD3), FAT tumor suppressor homolog 4 (FAT4) and erb‐b2 receptor tyrosine kinase 4 (ERBB4), and finally develop subclonal mutations.

Conclusions

GI‐NECs harbor distinct genomic landscapes and demonstrate significant genetic heterogeneity across different anatomic locations. Moreover, potentially actionable alterations and prognostic factors were revealed for GI‐NECs.
“Okokuqala ngokuya ndandiqala kwakungekho easy”: Feeling empowered to take collective action through community engagement
Authors: Bobo Benita , Akhurst Jacqueline
Published: October 2022

Community engagement (CE) at Rhodes University (RU) and community psychology draw on similar principles: using an asset‐based community development approach; recognising and drawing on the skills, capabilities, and knowledge of all parties, which they contribute to a partnership. Working from a strategic model of engagement, mutuality is foreground in all CE activities, where both student volunteers and community partners jointly benefit from the engagement. This paper examines CE at RU and how CE principles are translated into practise, using Siyakhana@Makana (S@M) as a case study. In S@M, a 19‐week‐long volunteer programme, community partners and student volunteers are jointly involved in planning, executing, and evaluating CE activities together. This paper illustrates how being involved in such CE activities has enabled community partners to mobilise for effective change in their communities. Community partners reflect on how they have been empowered to taken on leadership roles, addressing local challenges in collaborative ways, while drawing on the skills and knowledge that they have gained through their engagements in S@M. This resonates with the social action model of community psychology, a participatory approach that seeks to mobilise people to bring about change in the contexts in which they live.
Designing, Synthesis, and Anti‐Breast Cancer Activity of a Series of New Quinazolin‐4(1H)‐one Derivatives
Authors: Madhava Reddy Manne , Desikan Rajagopal , Naik Sanjay , Kumar Sanjit , Kumar D Thirumal , Priya Doss C George , Sivaramakrishna Akella
Published: October 2022

The inhibition of phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA) protein could be a promising treatment for breast cancer. In this regard, docking studies were accomplished on various functionalized organic molecules. Among them, several derivatives of quinazolin‐4(1H)‐one exhibited anti‐breast cancer activity and satisfied the drug likeliness properties. Further, thein vitroinhibitory studies by a series of 2‐(2‐phenoxyquinolin‐3‐yl)‐2,3‐dihydroquinazolin‐4(1H)‐one molecules showed strong anti‐cancer activity than the currently available drug, wortmannin. The MTT cytotoxicity assay was used to predict the anti‐proliferative activity of these drugs against MCF‐7 cancer cells by inhibiting the PIK3CA protein. The dose‐dependent analysis showed a striking decrease in cancer cell viability at 24 h with inhibitory concentrations (IC50) of3b,3c,3d,3fand3mare 15±1, 17±1, 8±1, 10±1 and 60±1 (nanomoles), respectively. This is the first report in the literature on the inhibition of PIK3CA protein by quinazolinone derivatives that can be used in the treatment of cancer. Quinazolinone analogs have the potential to be safe and economically feasible scaffolds if they are produced using a chemical technique that is both straightforward and amenable to modification. From the cancer research perspective, this study can eventually offer better care for cancer patients.
Combined rotational atherectomy and cutting balloon angioplasty prior to drug‐eluting stent implantation in severely calcified coronary lesions: The PREPARE‐CALC‐COMBO study
Authors: Allali Abdelhakim , Toelg Ralph , Abdel‐Wahab Mohamed , Hemetsberger Rayyan , Kastrati Adnan , Mankerious Nader , Traboulsi Hussein , Elbasha Karim , Rheude Tobias , Landt Martin , Geist Volker , Richardt Gert
Published: October 2022

Objectives

To evaluate the safety and efficacy of lesion preparation using rotational atherectomy (RA) with consecutive cutting balloon angioplasty (Rota‐Cut).

Background

Whether the Rota‐Cut combination improves stent performance in severely calcified coronary lesions is unknown.

Methods

PREPARE‐CALC‐COMBO is a single‐arm prospective trial in which 110 patients were treated with a Rota‐Cut strategy before implantation of sirolimus‐eluting stents and compared with patients treated with modified balloon (MB, scoring or cutting) or RA from a historical cohort (the randomized PREPARE‐CALC trial). The study had two primary endpoints: in‐stent acute lumen gain (ALG) by quantitative angiographic analysis and stent expansion (SE) on optical coherence tomography.

Results

In‐stent ALG was significantly higher with Rota‐Cut compared to RA or MB alone (1.92 ± 0.45 mm vs. 1.74 ± 0.45 mm with MB vs. 1.70 ± 0.42 mm with RA; p = 0.001 and p < 0.001, respectively). SE was comparable between groups (75.1 ± 13.8% vs. 73.5 ± 13.3 with MB vs. 73.1 ± 12.2 with RA; p = 0.19 and p = 0.39, respectively). The Rota‐Cut combination resulted in higher minimal stent area (MSA) (7.1 ± 2.2mm2 vs. 6.1 ± 1.7mm2 with MB vs. 6.2 ± 1.9mm2 with RA; p = 0.003 and p = 0.004, respectively). In‐hospital death occurred in one patient. Target vessel failure at 9 months was low and comparable between groups (8.2% vs. 8% with MB vs. 6% with RA; p = 1 and p = 0.79, respectively).

Conclusion

Rota‐Cut combination resulted in higher ALG and larger MSA compared with historical control of RA or MB alone, but was not associated with higher SE. Despite extensive lesion preparation, this strategy is safe, feasible, and associated with favorable clinical outcome at 9 months.
COVID‐19‐related rhino‐orbital‐cerebral mucormycosis: Neurological manifestation and related risk factors in two cases
Authors: Ohadi Mohammad Amin Dabbagh , Banihashemi Gelareh , Dilmaghani Nader Akbari , Shamsi Mohammad Ali , Sharifi Guive
Published: October 2022

Mucormycosis is an opportunistic infection that has become a serious concern as a result of the immunosuppressive drugs used during COVID‐19. In this report, we describe two cases of rhino‐orbital‐cerebral mucormycosis with neurological presentation and ophthalmologic problems accompanied by a history of COVID‐19 and diabetes.
Efficacy of intraoperative fluorescence imaging using indocyanine green‐containing gauze in identifying the appropriate dissection layer in laparoscopic intersphincteric resection: A case report
Authors: Kumata Hiroyuki , Onishi Keisuke , Takayama Tetsuro , Asami Kengo , Obara Noriyuki , Sugawara Hirofumi , Haga Izumi
Published: October 2022

In laparoscopic intersphincteric resection, identifying the dissection layer near the anus is often difficult. We safely proceeded with it, using indocyanine green‐containing gauze on the anal side to remove the internal anal sphincter with indocyanine green fluorography.
Temperature Distribution in Fluidized Beds of Porous Particles with Liquid Injection
Authors: Milacic Evan , Rantong Dylan R. , Kuipers J. A. M. , Baltussen Maike. W.
Published: October 2022

Liquid injection in fluidized beds is used to add reactants or to improve the heat management in the reactor. This injection will increase the complexity of reactor due to the formation of agglomerates. In this work the effect of the injection on the particle temperature distribution in a fluidized bed of porous particles is determined experimentally using particle image velocimetry and infra‐red thermography. The main property of the porous particles influencing the distribution is the specific surface area. In addition, the porosity has a large effect on the defluidization of the fluidized bed.
The Utilization and Modeling of Photo‐Fenton Process as a Single Unit in Textile Wastewater Treatment
Authors: Sarı Bülent , Türkeş Selman , Güney Hakan , Keskinkan Olcayto
Published: October 2022

Studies on the direct application of the photo‐Fenton process (PFOP) to disinfect and decontaminate textile wastewater are rare. The output of the artificial neural network (ANN) models applied to the wastewater of a textile factory producing woven fabrics, which is used to assess the efficiency of the PFOP process, are investigated and compared with each other in this study. The highest PFOP efficiency is obtained at a pH of 3. Chemical oxygen demand (COD), suspended solids (SS) and color removal rates are 94%, 90%, and 96%, respectively. The data are modeled with ANNs and nonlinear external input autoregressive ANNs (NARX‐ANN) using the MATLAB R2020a software program. Both Levenberg–Marquardt (trainlm) and scaled conjugate gradient (trainscg) algorithms are employed in the ANN and NARX‐ANN models, whereas hyperbolic tangent sigmoid (Tansig) and logistic sigmoid (Logsig) functions are superimposed on the hidden layer in the ANN model, and Tansig functions are superimposed on the NARX‐ANN model. It is determined that the developed ANN models are more effective in estimating the PFOP efficiency. The mean squared error is 0.000 953, and the coefficient of determination (R2) is 0.96 661.
Fine‐Tuning the Photophysics of Donor‐Acceptor (D‐A3) Thermally Activated Delayed Fluorescence Emitters Using Isomerisation
Authors: L. dos Santos Paloma , de Sa Pereira Daniel , Eng Julien , Ward Jonathan S. , Bryce Martin R. , Penfold Thomas J. , Monkman Andrew P.
Published: October 2022

Here two D–A3 regioisomers, comprising three dibenzothiophene‐S,S‐dioxide acceptor units attached to a central triazatruxene core, are studied. Both molecules show thermally activated delayed fluorescence (TADF), however, the efficiency of the TADF mechanism is strongly affected by the D–A substitution position. The meta‐ substituted emitter (1 b) shows a slightly higher‐lying singlet charge transfer state and a lower‐lying triplet state than that observed in the para‐ substituted emitter (1 a), resulting in a larger singlet–triplet splitting (ΔEST) of 0.28 eV compared to only 0.01 eV found in 1 a. As expected, this ΔEST difference strongly impacts the reverse intersystem crossing (rISC) rates and the para‐ isomer 1 a exhibits a much faster delayed fluorescence emission. Calculations show that the triplet energy difference between the two isomers is due to steric hindrance variances along the donor–acceptor rotation axis in these molecules: as 1 b is less restricted, rotation of its acceptor unit leads to a lower T1 energy, further away from the region of high density of states (the region where larger vibronic coupling is found, favouring rISC). Therefore, our results show how the substitution pattern has a marked effect on triplet state energies and character, verifying the key structural designs for highly efficient TADF materials.
Corporate governance and environmental sustainability: Addressing the dual theme from a bibliometric approach
Authors: Enciso‐Alfaro Saudi‐Yulieth , García‐Sánchez Isabel‐María
Published: October 2022

Environmental sustainability represents a business challenge that draws the attention of multidisciplinary and multicultural researchers. This study presents a comprehensive picture of the most relevant research on corporate governance and environmental sustainability since 1991. Through a bibliometric analysis of 233 articles retrieved from the Scopus database, we find that 71.67% of the research that addresses the dual theme in the last 7 years appears in journals of recognized impact (e.g., Business Strategy and the Environment). Researchers in the field focus on the United States, the United Kingdom, and China; determined by total link strength, D. M. Patten, D. Cormier, and P. Berrone are the most influential authors. We also identify 11 thematic groups or subdomains notable for their size and/or validity, including green innovation, institutional factors, climate change, environmental impact, and the board. Remaining to be addressed in future research are the agrifood sector, investment and energy efficiency, and patents and invention. In addition, theoretical approaches should be incorporated with cultural nuances that enrich our understanding of corporate governance as a driving mechanism of climate change.
A comprehensive review on the history, uses, and safety of onabotulinum toxin type A (Botox)
Authors: Patel Kevin R. , Rastogi Supriya , Prather Heidi B.
Published: October 2022

OnabotulinumtoxinA (ONA), trademarked under the brand name Botox, is a widely studied botulinum neurotoxin currently used for diverse cosmetic and noncosmetic therapeutic treatments. ONA was the first in a growing market of injectable neuromodulators to be studied for medical use. First introduced to the cosmetic marketplace in 2002 by the U.S. Food and Drug Administration for clinical indication of wrinkle correction for glabellar frown lines, ONA has proven to be an invaluable tool in the armamentarium of aesthetic medicine. The most commonly approved dermatologic uses of ONA include facial rhytidosis and hyperhidrosis with ongoing phase 2B studies for masseter hypertrophy. Nondermatologic applications include temporomandibular disorders, strabismus, cervical dystonia, blepharospasm, spasticity, migraines, overactive bladder, and incontinence. Off‐label uses of ONA are well studied in skin disorders, such as rosacea, and other indications, such as Frey's syndrome, and depression. Further, multiple studies have illustrated an improvement in quality of life and self‐esteem with ONA treatment. The favorable side effect profile with minimal adverse effects reinforces that ONA is a safe and effective treatment option with a diverse portfolio of clinically accepted applications.
Fracture distribution in overburden strata induced by underground mining
Authors: Yao Wenli , Wang Enzhi , Liu Xiaoli , Zhou Ran
Published: October 2022

Coal‐mining activities give rise to a series of ecological environmental problems, such as ground settlement and groundwater pollution. In fact, they are mainly caused by mining‐induced fractures. Hence, it is necessary to study the mining‐induced fracture distribution to identify the behavior of rock mass movement. However, the fractures in overburden strata cannot be directly measured owing to the special condition. Therefore, the majority of previous studies are based on experiments or experience. For this reason, this study first used a discrete element method to simulate the shape of mining‐induced fractures in overburden strata. Then, a geophysical tool of transient electromagnetic method (TEM) was used to investigate the mining‐induced fracture distribution. Based on the low‐resistivity anomaly area, the water‐rich area in overburden strata was analyzed to be mainly caused by fracture seepage. Through the mutual authentication between numerical simulation and TEM results, the mining‐induced fractures in overburden strata were explored. This study can enhance the understanding of mining‐induced fracture distribution on the one hand and guarantee the coal mining safety on the other, thus guiding the coordinated development between coal mining and environmental protection.
Mega‐disturbances cause rapid decline of mature conifer forest habitat in California
Authors: Steel Zachary L. , Jones Gavin M. , Collins Brandon M. , Green Rebecca , Koltunov Alexander , Purcell Kathryn L. , Sawyer Sarah C. , Slaton Michèle R. , Stephens Scott L. , Stine Peter , Thompson Craig
Published: October 2022

Mature forests provide important wildlife habitat and support critical ecosystem functions globally. Within the dry conifer forests of the western United States, past management and fire exclusion have contributed to forest conditions that are susceptible to increasingly severe wildfire and drought. We evaluated declines in conifer forest cover in the southern Sierra Nevada of California during a decade of record disturbance by using spatially comprehensive forest structure estimates, wildfire perimeter data, and the eDaRT forest disturbance tracking algorithm. Primarily due to the combination of wildfires, drought, and drought‐associated beetle epidemics, 30% of the region's conifer forest extent transitioned to nonforest vegetation during 2011–2020. In total, 50% of mature forest habitat and 85% of high density mature forests either transitioned to lower density forest or nonforest vegetation types. California spotted owl protected activity centers (PAC) experienced greater canopy cover decline (49% of 2011 cover) than non‐PAC areas (42% decline). Areas with high initial canopy cover and without tall trees were most vulnerable to canopy cover declines, likely explaining the disproportionate declines of mature forest habitat and within PACs. Drought and beetle attack caused greater cumulative declines than areas where drought and wildfire mortality overlapped, and both types of natural disturbance far outpaced declines attributable to mechanical activities. Drought mortality that disproportionately affects large conifers is particularly problematic to mature forest specialist species reliant on large trees. However, patches of degraded forests within wildfire perimeters were larger with greater core area than those outside burned areas, and remnant forest habitats were more fragmented within burned perimeters than those affected by drought and beetle mortality alone. The percentage of mature forest that survived and potentially benefited from lower severity wildfire increased over time as the total extent of mature forest declined. These areas provide some opportunity for improved resilience to future disturbances, but strategic management interventions are likely also necessary to mitigate worsening mega‐disturbances. Remaining dry mature forest habitat in California may be susceptible to complete loss in the coming decades without a rapid transition from a conservation paradigm that attempts to maintain static conditions to one that manages for sustainable disturbance dynamics.
Rare and declining bee species are key to consistent pollination of wildflowers and crops across large spatial scales
Authors: Genung Mark A. , Reilly James , Williams Neal M. , Buderi Andrew , Gardner Joel , Winfree Rachael
Published: October 2022

Biodiversity promotes ecosystem function (EF) in experiments, but it remains uncertain how biodiversity loss affects function in larger‐scale natural ecosystems. In these natural ecosystems, rare and declining species are more likely to be lost, and function needs to be maintained across space and time. Here, we explore the importance of rare and declining bee species to the pollination of three wildflowers and three crops using large‐scale (72 sites across 5000 km2), multi‐year datasets. Half of the sampled bee species (82/164) were rare or declining, but these species provided only ~15% of overall pollination. To determine the number of species important to EF, we used two methods of “scaling up,” both of which have previously been used for biodiversity‐function analysis. First, we summed bee species' contributions to pollination across space and time and then found the minimum set of species needed to provide a threshold level of function across all sites; according to this method, effectively no rare and declining bee species were important to pollination. Second, we account for the “insurance value” of biodiversity by finding the minimum set of bee species needed to simultaneously provide a threshold level of function at each site in each year. The second method leads to the conclusion that 25 rare and eight declining bee species (36% and 53% of all rare and declining bee species, respectively) are included in the minimum set. Our findings provide some of the strongest evidence yet that rare and declining species are key to meeting threshold levels of EF, thereby providing a more direct link between real‐world biodiversity loss and EF.
Structures and Applications of NIR‐II AIEgens Containing Benzobisthiadiazole Derivatives
Authors: Zhang Jian‐Qing , Xu Xiao‐Yu , Cao Shu‐Qiang , Zou You‐Quan
Published: October 2022

AIEgens fluorescent molecular probes in the NIR‐II window have attracted much attention owning to their deep penetration, reduction of tissue absorption and scattering, excellent photostability, and low cytotoxicity. Among them, as strong electron‐absorbing group, benzobisthiadiazole derivatives are widely used in the construction of various NIR‐II AIEgens materials. In this review, we concluded AIEgens nanoprobes bearing benzobisthiadiazole derivatives in the NIR‐II region. Beginning with a summary of molecular design, recent advances in bioimaging and photodynamic therapy as well as insights and challenges in this thriving field were discussed. We expect that this review will provide perspectives on the potential applications of benzobisthiadiazole‐based NIR‐II AIEgens nanoprobes in biomedical field and inspire more creative progresses in this research discipline to facilitate the investigation in future clinical translation.
Fast Charging Formation of Lithium‐Ion Batteries Based on Real‐Time Negative Electrode Voltage Control
Authors: Drees Robin , Lienesch Frank , Kurrat Michael
Published: October 2022

The formation of lithium‐ion batteries is a time‐consuming and important process during manufacturing. During the formation, surface layers on the electrodes are formed that affect the cell performance. State‐of‐the‐art formation procedures consist of several slow current cycles as it is believed to guarantee good surface layer properties while preventing degradation processes. Herein, five different formation strategies with process times between 52.79 and 1.68 h for coin cells with a lithium reference electrode are assessed. The fastest method is based on a fast charging approach that prevents lithium‐plating. Based on a real‐time negative electrode voltage control to a threshold of 20 mV, lithium‐plating is successfully prevented while ensuring a fast formation process. The formation is finished after just one cycle and results to similar cell and electrode resistance, impedance, and capacity retention compared to the other strategies. The fast charging formation approach leads to the lowest degradation when storing the cells at 80% state of charge and 60 °C for 28 days. The results conclude that the fast charging formation method with real‐time control of the negative electrode voltage is a beneficial method as it leads to faster process times while ensuring durable cell properties.
Seismic performance of interior beam‐column joints using reinforced slag‐based geopolymer concrete
Authors: Mao Yuguang , Du Yunxing , Hwang Hyeon‐Jong , Su Jie , Hu Xiang , Liu Yuzhong , Shi Caijun
Published: October 2022

Although geopolymer concrete (GC) is recognized as a green and low‐carbon material, GC structural members, particularly beam‐column joints, have been rarely studied. In the present study, eight reinforced GC joints and three reinforced concrete (RC) interior beam‐column joints were tested under cyclic loading. The test parameters were the concrete type, joint shear demand‐to‐capacity ratio, and axial‐compression ratio. The structural performance, including the failure mode, crack development, cyclic behavior of reinforced GC beam‐column joints, was evaluated. The test results showed that the cyclic behavior and crack development of the reinforced GC beam‐column joints differed from those of RC beam‐column joints. The increase of axial compression ratio improved the seismic performance of reinforced GC beam‐column joints with the joint shear demand‐to‐capacity ratio of 0.96–1.01. When the joint shear demand‐to‐capacity ratio was 1.54–1.61, the increase of axial compression ratio (0.1–0.3) improved the seismic performance, while the axial compression ratio of 0.5 was unfavorable because of significant joint shear damage. The applicability of the control conditions in the current design codes to the reinforced GC joints was evaluated. The control conditions of ACI 318–19 were applicable to the seismic design of reinforced GC beam‐column joints. On the other hand, the control conditions of GB50010‐2010 were not applicable because of the overestimated upper limit value of the joint shear demand‐to‐capacity ratio and axial compression ratio.
Using the Honey Bee (Apis mellifera L.) Cell Line AmE-711 to Evaluate Insecticide Toxicity
Authors: Goblirsch Michael , Adamczyk John J.
Published: October 2022

One of the main contributors to poor productivity and elevated mortality of honey bee colonies globally is insecticide exposure. Whole-organism and colony-level studies have demonstrated the effects of insecticides on many aspects of honey bee biology and have also shown their interactions with pathogens. However, there is a need for in vitro studies using cell lines to provide greater illumination of the effects of insecticides on honey bee cellular and molecular processes. We used a continuous cell line established from honey bee embryonic tissues (AmE-711) in assays that enabled assessment of cell viability in response to insecticide exposure. We exposed AmE-711 cells to four formulations, each containing a different insecticide. Treatment of cells with the insecticides resulted in a concentration-dependent reduction in viability after a 24-h exposure, whereas long-term exposure (120 h) to sublethal concentrations had limited effects on viability. The 24-h exposure data allowed us to predict the half-maximal lethal concentration (LC50) for each insecticide using a four-parameter logistical model. We then exposed cells for 12 h to the predicted LC50 and observed changes in morphology that would indicate stress and death. Reverse transcription–quantitative polymerase chain reaction analysis corroborated changes in morphology: expression of a cellular stress response gene, 410087a, increased after an 18-h exposure to the predicted LC50. Demonstration of the effects of insecticides through use of AmE-711 provides a foundation for additional research addressing issues specific to honey bee toxicology and complements whole-organism and colony-level approaches. Moreover, advances in the use of AmE-711 in high-throughput screening and in-depth analysis of cell regulatory networks will promote the discovery of novel control agents with decreased negative impacts on honey bees. Environ Toxicol Chem 2023;42:88–99. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Making the Invisible Visible? Using Stable Isotope Analysis to Detect Indirect Toxicant Effects
Authors: Bollinger Eric , Zubrod Jochen P. , Englert Dominic , Pollitt Annika , Fuß Bastian , Schulz Ralf , Bundschuh Mirco
Published: October 2022

Although stable isotope analysis (SIA) is widely used to address ecological research questions, its application in an ecotoxicological context has been limited. Recent studies have proposed an effect of chemical stressors on an organism's isotope signature, questioning the use of SIA in food webs impacted by toxicants. Against this background, the present study investigates 1) whether trophic enrichment factors (TEFs; i.e., the offset in stable isotope signatures of a consumer to its diet) are altered by the neonicotinoid thiacloprid, and 2) whether tracking toxicant effects on an organism's diet composition (i.e., indirect effect) with SIA fits direct observations of consumption. To address the former, the amphipod Gammarus fossarum (Koch) was exposed to three levels (0, 0.75, and 5 µg L–1) of thiacloprid and fed with either black alder leaves or Baetis rhodani (Pictet) larvae over 6 weeks (n = 35). The thiacloprid-induced changes in TEFs that we found were statistically significant but small compared with other factors (e.g., resource quality, consumer, and physiological condition) and thus likely of minor importance. To address the latter issue, gammarids were exposed to two levels of thiacloprid (0 and 0.75 µg L–1) and fed with either black alder leaves, live B. rhodani larvae, or both over 2 weeks (n = 10). Dietary proportions as suggested by SIA were indeed in agreement with those derived from direct observation of consumption. The present study consequently suggests that SIA is as a robust tool to detect indirect toxicant effects especially if TEFs are assessed in parallel. Environ Toxicol Chem 2023;42:1937–1945. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Development and validation of Navier–Stokes characteristic boundary conditions applied to turbomachinery simulations using the lattice Boltzmann method
Authors: Gianoli Thomas , Boussuge Jean‐François , Sagaut Pierre , de Laborderie Jérôme
Published: October 2022

This article reports a procedure to implement as well as to validate non‐reflecting boundary conditions applied for turbomachinery simulations, using Navier–Stokes characteristic boundary conditions in a compressible lattice Boltzmann solver. The implementation of both an inlet condition imposing total pressure, total temperature, and flow angles, as well as an outlet condition imposing a static pressure profile that allows the simulation to reach a simplified radial equilibrium, is described within the context of a lattice Boltzmann approach. The treatment at the boundaries relies on the characteristic methodology to derive conditions which are non‐reflecting in terms of acoustics and is also compatible with turbulence injection at the inlet. These properties are evaluated on test cases of increasing complexity, ranging from a simple 2D periodic domain to an S‐duct stage with turbulence injection.
Serum keratin‐18 detects hepatic inflammation and predicts progression in compensated alcohol‐associated liver disease
Authors: Thorhauge Katrine Holtz , Thiele Maja , Detlefsen Sönke , Rasmussen Ditlev Nytoft , Johansen Stine , Madsen Bjørn Stæhr , Antonsen Steen , Rasmussen Lars Melholt , Lindvig Katrine Prier , Krag Aleksander
Published: October 2022

Alcohol‐associated liver fibrosis accumulates over decades, driven by hepatic inflammation and cell death. We investigated the diagnostic accuracy of keratin‐18 degradation, measured using serum M30 and M65 levels, and the ActiTest for hepatic inflammatory activity in patients with compensated alcohol‐associated liver disease (ALD). Furthermore, we evaluated the prognostic accuracy of markers for liver‐related events and all‐cause mortality. All findings were compared with routine liver function tests: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma‐glutamyltransferase. Our prospective, biopsy‐controlled, single‐center study included 265 patients with ongoing or prior excessive alcohol intake, representing the full spectrum of compensated ALD. We defined hepatic inflammatory activity as a combined score of lobular inflammation and ballooning. For severe hepatic inflammatory activity (n = 40), we found excellent diagnostic accuracy for M30 (area under the receiver operating characteristics curve [AUROC] = 0.90), M65 (AUROC = 0.86), and AST (AUROC = 0.86). Elevated M30 (M30 > 240 U/L) had the highest positive predictive value (PPV) and specificity, significantly higher than M65, ActiTest and ALT, but not AST (M30: sensitivity = 83%, specificity = 82%, positive predictive value = 45%, negative predictive value = 95%). Patients were followed up for 1445 patient‐years. All markers, except for ALT, significantly predicted liver‐related events and all‐cause mortality. After adjusting for advanced fibrosis, drinking behavior and body mass index, M30 and M65 remained significant predictors of liver‐related events, whereas M30 and AST were significant predictors of all‐cause mortality. Conclusion: M30 and AST accurately detect severe hepatic inflammatory activity in patients with compensated ALD. M30 was the only significant predictor of both liver‐related events and all‐cause mortality after adjusting for advanced fibrosis, body mass index, and drinking behavior at inclusion.