bluuebunny/crossref_metadata_2025 huggingface dataset:
Acoustic properties of piezoelectric cubic crystals
Authors: Ballato Arthur , Ballato John
Published: July 2023

This paper is offered as a complementary adjunct to the many treatments of the electronic and photonic properties of cubic III–V and II–VI compounds appearing in the literature. These crystals typically exhibit piezoelectricity, due to the molecular dissymmetry, thereby allowing the inclusion of classical mechanical/acoustic features along with the quantum. We discuss the history of this modality and then illustrate its use by applying it to an electro‐elastic problem that has the estimable virtues of having an exact solution, along with wide practical applicability: determination of the piezocoupling values governing the excitation of thickness vibrations in thin cubic films or plates of arbitrary crystallographic orientation by electric fields directed either along, or lateral to, the thickness. Explicit results are given for orientations along the great‐circle paths connecting the principal directions [100], [110], and [111]. The formalism is then applied to GaAs as an example; it is further demonstrated that various results, such as the orientational variations of piezocoupling factors, are generally applicable to other members of the III–V and II–VI families by scaling. Ancillary aspects, such as errors due to misorientations, nonlinearities, and equivalent circuit representations, are described and discussed. This work is dedicated to Gerald W. Farnell (1925–2015), Prof. Emeritus, McGill University, Montréal, Canada.
Microwave‐Assisted One Pot Cascade Conversion of Furfural to γ‐Valerolactone over Sc(OTf)3
Authors: Li Fukun , Yang Ronghe , Tian Zheng , Du Ziting , Dai Jinhang , Wang Xingmin , Li Ning , Zhang Jie
Published: July 2023

γ‐Valerolactone (GVL) is considered as a star biochemical which can be used as a green solvent, fuel additive and versatile organic intermediate. In this study, metal triflate (M(OTf)n) was utilized as the catalyst for one‐pot transformation of furfural (FF) to GVL in alcohol media under microwave irradiation. Alcohol plays multiple functions including solvent, hydrogen donor and alcoholysis reagent in this cascade reaction process. And process efficiency of GVL production from FF upgrading is strongly related to the effective charge density of selected catalyst and the reduction potential of selected alcohol. Complex (OTf)n‐M−O(H)R, presenting both Brønsted acid and Lewis acid, is the real catalytic active species in this cascade reaction process. Among various catalysts, Sc(OTf)3 exhibited the best catalytic activity for GVL production. Various reaction parameters including the Sc(OTf)3 amount, reaction temperature and time were optimized by the response surface methodology with the central composite design (RSM‐CCD). Up to 81.2 % GVL yield and 100 % FF conversion were achieved at 143.9 °C after 8.1 h in the presence of 0.16 mmol catalyst. This catalyst exhibits high reusability and can be regenerated by oxidative degradation of humins. In addition, a plausible cascade reaction network was proposed based on the distribution of product.
Water‐Dispersible Carbon Nano‐Test Tubes as a Container for Concentrated DNA Molecules
Authors: Hoshikawa Yasuto , Kanno Yasuyuki , Tawata Hanako , Sagae Takuya , Ishii Takafumi , Imoto Shuhei , Hagihara Shinya , Wada Takehiko , Nagatsugi Fumi , Aziz Alex , Nishihara Hirotomo , Kyotani Takashi , Itoh Tetsuji
Published: July 2023

Water‐dispersible carbon nano‐test tubes (CNTTs) with an inner and outer diameter of about 25 and 35 nm, respectively, were prepared by the template technique and then their inner carbon surface was selectively oxidized to introduce carboxy groups. The adsorption behavior of DNA molecules on the oxidized CNTTs (Ox‐CNTTs) was examined in the presence of Ca2+ cations. Many DNA molecules are attracted to the inner space of Ox‐CNTTs based on the Ca2+‐mediated electrostatic interaction between DNA phosphate groups and carboxylate anions on the inner carbon surface. Moreover, the total net charge of the DNA adsorbed was found to be equal to the total charge of the carboxylate anions. This selective adsorption into the interior of Ox‐CNTTs can be explained from the fact that the electrostatic interaction onto the inner concave surface is much stronger than that on the outer convex surface. On the other hand, the desorption of DNA easily occurs whenever Ca2+ cations are removed by washing with deionized water. Thus, each of Ox‐CNTTs works well as a nano‐container for a large amount of DNA molecules, thereby resulting in the occurrence of DNA enrichment in the nanospace.
The holo beta‐lactoglobulin lozenge reduces symptoms in cat allergy—Evaluation in an allergen exposure chamber and by titrated nasal allergen challenge
Authors: Bergmann Karl‐Christian , Raab Jennifer , Graessel Anke , Zwingers Thomas , Becker Sylvia , Kugler Sebastian , Zuberbier Torsten , Roth‐Walter Franziska , Kramer Matthias F. , Jensen‐Jarolim Erika
Published: July 2023

Background

The allergists´ tool box in cat allergy management is limited. Clinical studies have shown that holo beta‐lactoglobulin (holoBLG) can restore micronutritional deficits in atopic immune cells and alleviate allergic symptoms in a completely allergen‐nonspecific manner. With this study, we aimed to provide proof of principle in cat allergy.

Methods

A novel challenge protocol for cat allergy in a standardized ECARF allergen exposure chamber (AEC) was developed. In an open pilot study (NCT05455749), patients with clinically relevant cat allergy were provoked with cat allergen for 120 min in the AEC before and after a 3‐month intervention phase (holoBLG lozenge 2x daily). Nasal, conjunctival, bronchial, and pruritus symptoms were scored every 10 min– constituting the total symptom score (TSS). Peak nasal inspiratory flow (PNIF) was measured every 30 min. In addition, a titrated nasal provocation test (NPT) was performed before and after the intervention. Primary endpoint was change in TSS at the end of final exposure compared to baseline. Secondary endpoints included changes in PNIF, NPT, and occurrence of late reactions up to 24 h after exposure.

Results

35 patients (mean age: 40 years) completed the study. Compared to baseline, holoBLG supplementation resulted in significant improvement in median TSS of 50% (p < 0.001), as well as in median nasal flow by 20 L/min (p = 0.0035). 20% of patients reported late reactions after baseline exposure, but 0% after the final exposure.

Conclusions

Cat allergic patients profited from targeted micronutrition with the holoBLG lozenge. As previously seen in other allergies, holoBLG supplementation also induced immune resilience in cat allergies, resulting in significant symptom amelioration.
Facile Access to Structurally Diverse Antimalarial Indoles Using a One‐Pot A3 Coupling and Domino Cyclization Approach
Authors: da Silva Gustavo , Luz André F. S. , Duarte Denise , Fontinha Diana , Silva Vera L. M. , Almeida Paz Filipe A. , Madureira Ana M. , Simões Sandra , Prudêncio Miguel , Nogueira Fátima , Silva Artur M. S. , Moreira Rui
Published: July 2023

A multistep and diversity‐oriented synthetic route aiming at the A3 coupling/domino cyclization of o‐ethynyl anilines, aldehydes and s‐amines is described. The preparation of the corresponding precursors included a series of transformations, such as haloperoxidation and Sonogashira cross‐coupling reactions, amine protection, desilylation and amine reduction. Some products of the multicomponent reaction underwent further detosylation and Suzuki coupling. The resulting library of structurally diverse compounds was evaluated against blood and liver stage malaria parasites, which revealed a promising lead with sub‐micromolar activity against intra‐erythrocytic forms of Plasmodium falciparum. The results from this hit‐to‐lead optimization are hereby reported for the first time.
Digital Therapeutics as a New Therapeutic Modality: A Review from the Perspective of Clinical Pharmacology
Authors: Ribba Benjamin , Peck Richard , Hutchinson Lucy , Bousnina Imein , Motti Dario
Published: July 2023

The promise of transforming digital technologies into treatments is what drives the development of digital therapeutics (DTx), generally known as software applications embedded within accessible technologies—such as smartphones—to treat, manage, or prevent a pathological condition. Whereas DTx solutions that successfully demonstrate effectiveness and safety could drastically improve the life of patients in multiple therapeutic areas, there is a general consensus that generating therapeutic evidence for DTx presents challenges and open questions. We believe there are three main areas where the application of clinical pharmacology principles from the drug development field could benefit DTx development: the characterization of the mechanism of action, the optimization of the intervention, and, finally, its dosing. We reviewed DTx studies to explore how the field is approaching these topics and to better characterize the challenges associated with them. This leads us to emphasize the role that the application of clinical pharmacology principles could play in the development of DTx and to advocate for a development approach that merges such principles from development of traditional therapeutics with important considerations from the highly attractive and fast‐paced world of digital solutions.
The LongitudinAl Nationwide stuDy on Management And Real‐world outComes of diabetes in India over 3 years (LANDMARC trial)
Authors: Das Ashok K. , Kalra Sanjay , Joshi Shashank , Mithal Ambrish , Kumar K. M. Prasanna , Unnikrishnan A. G. , Thacker Hemant , Sethi Bipin , Chowdhury Subhankar , Sugumaran Amarnath , Satpathy Ashwini , Gadekar Arvind , Menon Shalini K. , Neogi Renuka , Chodankar Deepa , Trivedi Chirag , Wangnoo S. K. , Zargar A. H. , Rais Nadeem ,   LANDMARC study group
Published: July 2023

Introduction

LANDMARC (CTRI/2017/05/008452), a prospective, observational real‐world study, evaluated the occurrence of diabetes complications, glycemic control and treatment patterns in people with type 2 diabetes mellitus (T2DM) from pan‐India regions over a period of 3 years.

Methods

Participants with T2DM (≥25 to ≤60 years old at diagnosis, diabetes duration ≥2 years at the time of enrollment, with/without glycemic control and on ≥2 antidiabetic therapies) were included. The proportion of participants with macrovascular and microvascular complications, glycemic control and time to treatment adaptation over 36 months were assessed.

Results

Of the 6234 participants enrolled, 5273 completed 3 years follow‐up. At the end of 3‐years, 205 (3.3%) and 1121 (18.0%) participants reported macrovascular and microvascular complications, respectively. Nonfatal myocardial infarction (40.0%) and neuropathy (82.0%) were the most common complications. At baseline and 3‐years, 25.1% (1119/4466) and 36.6% (1356/3700) of participants had HbA1c <7%, respectively. At 3‐years, population with macrovascular and microvascular complications had higher proportion of participants with uncontrolled glycemia (78.2% [79/101] and 70.3% [463/659], respectively) than those without complications (61.6% [1839/2985]). Over 3‐years, majority (67.7%–73.9%) of the participants were taking only OADs (biguanides [92.2%], sulfonylureas [77.2%] and DPP‐IV inhibitors [62.4%]). Addition of insulin was preferred in participants who were only on OADs at baseline, and insulin use gradually increased from 25.5% to 36.7% at the end of 3 years.

Conclusion

These 3‐year trends highlight the burden of uncontrolled glycemia and cumulative diabetes‐related complications, emphasizing the importance of optimizing diabetes management in India.
Optimization of multi‐response biodiesel fueled diesel engine parameters using Taguchi grey relational analysis and analytical hierarchy process
Authors: Warkhade Ganesh S. , Katam Ganesh Babu , Veeresh Babu A.
Published: July 2023

Compression ignition engines are currently optimized to run on petrodiesel fuel, but due to its increasing demand and depletion of fossil fuel reserves, alternative fuels must be utilized. In this article, an attempt was made to optimize the operating parameters of an unmodified compression ignition engine fueled with linseed methyl ester biodiesel. The input parameters were compression ratio, load, and fuel blend, while output responses included brake‐specific fuel consumption (BSFC), brake thermal efficiency (BTE), and exhaust gas temperature (EGT), peak cylinder pressure (PCP), the rate of pressure rise (RPR), and net heat release rate (NHR), hydrocarbon (HC), carbon monoxide (CO), NOx, and Smoke. The aim was to determine the optimal combination of input parameters for minimal emissions and better performance and combustion parameters, with a minimum number of experiments. The study used Taguchi's L9 orthogonal array with a grey relational analysis approach (GRA) to obtain the optimum combination of input parameters. The study found that fuel blend B10, CR 18, and load 100% were the optimal input parameter combinations using the TGRA method. The S/N ratio analysis of grey relational grade (GRG) showed the optimal input factor levels to be fuel B10, CR 16, and load 100%, which was confirmed by the AHP method. The analysis of variance (ANOVA) showed that the load was the most influential factor, followed by CR and fuel. The confirmatory results showed an improvement of 56.1%, indicating that biodiesel can be efficiently used in an unmodified compression ignition engine by varying these influencing factors.
Fire resistance of austenitic stainless steel beams with rectangular hollow sections
Authors: Lopes N. , Arrais F. , Vila Real P. , Alves M. , Mesquita L. , Piloto P. , Pinho da Cruz J.
Published: July 2023

This paper presents a study on the structural behaviour of stainless steel profiles under fire conditions. An experimental campaign of three‐point bending tests on rectangular hollow section beams of the grade 1.4301 (also known as 304) were conducted, considering both steady‐state and transient state conditions. Prior to those tests, the mechanical characterization of the stainless steel was investigated. The constitutive laws obtained by tensile tests at high temperatures are compared with those recommended in Eurocode 3, whose respective material models were recently proposed for modifications, still requiring complete validation. In addition, numerical modelling of the bending tests has been performed afterwards achieving close approximation to the observed experimental results. Finally, analytical methods to predict the load‐deflection behaviour are also presented. Good agreement between the considered methodologies was attained validating their application on the prediction of the fire behaviour of stainless steel beams.
Downdraft energy tower for negative emissions: Analysis on methane removal and other co‐benefits
Authors: Tao Tao , Wang Yuyin , Ming Tingzhen , Mu Liwen , de Richter Renaud , Li Wei
Published: July 2023

The downdraft energy tower is proposed in research as a new technology for green electricity in recent years. In this work, it is analyzed as an emerging greenhouse gas removal technology against climate change that provides multiple co‐benefits for the environment, in addition to green electricity. Compared to other negative emission technologies, DET might be able to remove atmospheric methane (CH4) without adding additional equipment, materials or costs. In multiple case studies, the DET offers at least 15% increase in profit thanks to CH4 removal in addition to green electricity generation. © 2023 The Authors. Greenhouse Gases: Science and Technology published by Society of Chemical Industry and John Wiley & Sons Ltd.
Microglia are involved in regulating histamine‐dependent and non‐dependent itch transmissions with distinguished signal pathways
Authors: Yang Yuxiu , Mou Bin , Zhang Qi‐Ruo , Zhao Hong‐Xue , Zhang Jian‐Yun , Yun Xiao , Xiong Ming‐Tao , Liu Ying , Liu Yong U. , Pan Haili , Ma Chao‐Lin , Li Bao‐Ming , Peng Jiyun
Published: July 2023

Although itch and pain have many similarities, they are completely different in perceptual experience and behavioral response. In recent years, we have a deep understanding of the neural pathways of itch sensation transmission. However, there are few reports on the role of non‐neuronal cells in itch. Microglia are known to play a key role in chronic neuropathic pain and acute inflammatory pain. It is still unknown whether microglia are also involved in regulating the transmission of itch sensation. In the present study, we used several kinds of transgenic mice to specifically deplete CX3CR1+ microglia and peripheral macrophages together (whole depletion), or selectively deplete microglia alone (central depletion). We observed that the acute itch responses to histamine, compound 48/80 and chloroquine were all significantly reduced in mice with either whole or central depletion. Spinal c‐fos mRNA assay and further studies revealed that histamine and compound 48/80, but not chloroquine elicited primary itch signal transmission from DRG to spinal Npr1‐ and somatostatin‐positive neurons relied on microglial CX3CL1‐CX3CR1 pathway. Our results suggested that microglia were involved in multiple types of acute chemical itch transmission, while the underlying mechanisms for histamine‐dependent and non‐dependent itch transmission were different that the former required the CX3CL1‐CX3CR1 signal pathway.
Empowering general practitioners in dementia care: The ANTISTIGMA education intervention in Europe
Authors: Cartz‐Piver Leslie , Calvet Benjamin , Mehrabian‐Spassova Shima , Raycheva Margarita , Rejdak Kondrad , Papuk Ewa , Leperre‐Desplanques Armelle , Krolak‐Salmon Pierre
Published: July 2023

Background

There is a well‐documented lack or delay of diagnosis of dementia in all countries, including in Europe. Most general practitioners (GPs) have acquired adequate academic and scientific information about dementia but avoid using it in practice because of stigma.

Objectives

To persuade GPs of their role in dementia detection, an Antistigma education intervention was designed, with teaching objectives focusing on “Why” and “How” to diagnosis and manage dementia, based on ethical and practical content, as opposed to classical training centered on teaching “What”, with mainly academic content.

Methods

During the European Joint Action “ACT ON DEMENTIA”, the Antistigma education intervention was implemented in four Universities: Lyon and Limoges (France), Sofia (Bulgaria) and Lublin (Poland). General data, including information about training and experience in dementia, was collected. Specific scales measured Dementia Negative Stereotypes DNS and Dementia Clinical Confidence D‐CO before and after training.

Results

134 GPs and 58 residents R completed the training. The participants were mainly women (74%), and the mean age was 42.8 ± 13.2. Before training, participants expressed difficulties in defining GPs role and worries about inflicting Stigma, Risks of diagnosis, Lack of benefit and Communication difficulties. Participants' D‐CO was significantly higher for Diagnosis process (64%) than for other clinical situations. After training, total NS was reduced from 34.2% to 29.9% (p < 0.001), and stereotypes were improved: GPs' role (40.1% reduced to 35.9%; p < 0.001), Stigma (38.7% reduced to 35.5%; p < 0.001), Risks of diagnosis (39.0% reduced to 33.3%; p < 0.001), Lack of Benefit (29.3% reduced to 24.6%; p < 0.001) and Communication difficulties (19.9% reduced to 16.9%; p < 0.001). After training, D‐CO was significantly increased in all the clinical situations (p < 0.001), but stayed highest for Diagnosis Process. There was no significant difference between the universities. Participants who benefited best from the Antistigma education intervention were those without training in Geriatrics and those working in nursing homes (who reduced the most D‐NS), as well younger participants and those who managed less than five people living with dementia per week (who increased the most D‐CO).

Conclusion

The Antistigma program is based on the idea that most often GPs and R have acquired adequate academic and scientific information about dementia but avoid using it in practice because of stigma. These results outline the importance of addressing ethical issues and practical management situations in dementia education, to empower GPs in dementia care.
Chronic myeloid leukemia kinase domain mutations: A retrospective descriptive study on the therapeutic and prognostic significance in patients at King Edward VIII Hospital, KwaZulu‐Natal, South Africa
Authors: Benjamin Caryn , Murugan Stephanie , Hoosen Siddeeq , Rapiti Nadine
Published: July 2023

Background

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that harbors the Philadelphia chromosome. Tyrosine kinase inhibitor (TKI) therapy has dramatically improved the survival of patients with CML. Nevertheless, 20%–40% of CML patients require changes in TKI therapy due to intolerance or drug resistance. A total of 30%–60% of resistant cases result from kinase domain (KD) mutations. There is currently no published data on CML KD mutations in South Africa.

Methods

This retrospective, descriptive study collected data from 206 CML patients attending the King Edward Hospital Hematology clinic. Patient‐based and mutation‐based factors were analyzed using descriptive statistical analysis and Kaplan–Meier curves for survival analysis.

Results

KD mutations were detected in 29.1% (n = 60 of 206). A total of 40 different KD mutations were detected, with unknown responses to TKI therapy in 65% (n = 26 of 40). A total of 57.7% (n = 15 of 26) of mutations with an unknown response, showed a response to specific TKIs in our study. Four patients had A399T mutations, of which two showed good responses to Nilotinib. Patients with I293N and V280M mutations showed good responses to Imatinib. G250E was most frequently detected. Despite M351T being one of six most commonly reported KD mutations globally, this mutation was not detected in our patient cohort. A total of 20.9% (n = 43 of 206) human immunodeficiency virus (HIV) positive patients were identified, of which 25.6% (n = 11 of 43) had KD mutations. HIV status showed no significant effect on mutational status or overall survival.

Conclusion

The predicted response to TKI therapy was unknown in more than half of the KD mutations detected in our patient population. Additionally, eight patients with mutations with known responses to TKIs showed responses discordant to that expected. HIV status and KD mutations had no statistically significant effect on overall survival. Although some data were comparable to international publications, few notable differences warrant further investigation.
Psychological impact of COVID‐19 pandemic and lockdown among the population involved in tourism sector in Lakeside of Pokhara: A qualitative study
Authors: Paudel Rajesh , Khadka Seema , Rai Jeetendra , Singh Rakesh
Published: July 2023

Background and Aims

The COVID‐19 pandemic has exerted a substantial influence on every sector of people's lives worldwide, including Nepal. The tourism industry is not exceptional. Lakeside Pokhara is one of the country's major tourist hubs and relies both on national and international visitors. The people residing in this area who depend on tourism‐related businesses to regulate their daily living faced numerous stressors and psychological impacts due to the pandemic. This study aimed to explore the COVID‐19 pandemic‐related stressors and their psychological impact among people dependent on the tourism business in the Lakeside of Pokhara, located in the Gandaki Province of Nepal.

Method

Via the qualitative approach, semi‐structured in‐depth interviews were conducted to collect the data from 20 individuals related to tourism business stakeholders in Lakeside of Pokhara. Thematic analysis was performed to analyze the data.

Results

The study found business‐related stressors among the people dependent on the tourism businesses, and these stressors were found to increase the experiences of psychological issues, including suicidal ideation. The pandemic has not only affected their economy but has also had an impact on their personal, familial, and social life. However, to combat the problems most of the study participants were found to be utilizing positive coping mechanisms, whereas some respondents were observed to consume more alcohol as a negative coping strategy.

Conclusions

People indulging in the tourism sectors were at greater risk of vulnerability in the future pandemic. Tourism business stakeholders struggled to combat the numerous stressors and psychological impacts carried out by the COVID‐19 pandemic and lockdown. Therefore, there is a growing need for government bodies to implement favorable business‐related policies, and Mental Health and Psychosocial Support (MHPSS) related programs to these stakeholders.
Panitumumab plus trifluridine/tipiracil as anti‐EGFR rechallenge therapy in patients with refractory RAS wild‐type metastatic colorectal cancer: Overall survival and subgroup analysis of the randomized phase II VELO trial
Authors: Napolitano Stefania , Ciardiello Davide , De Falco Vincenzo , Martini Giulia , Martinelli Erika , Della Corte Carminia Maria , Esposito Lucia , Famiglietti Vincenzo , Di Liello Alessandra , Avallone Antonio , Cardone Claudia , De Stefano Alfonso , Montesarchio Vincenzo , Zampino Maria Giulia , Fazio Nicola , Di Maio Massimo , Del Tufo Sara , De Vita Ferdinando , Altucci Lucia , Marrone Francesca , Ciardiello Fortunato , Troiani Teresa
Published: July 2023

The randomized phase II VELO trial showed that the addition of panitumumab to trifluridine/tipiracil significantly improves progression‐free survival (PFS) as compared to trifluridine/tipiracil in third‐line therapy in patients with refractory RAS wild‐type (WT) metastatic colorectal cancer (mCRC). With longer follow‐up, final overall survival results and posttreatment subgroup analysis are presented. Sixty‐two patients with refractory RAS WT mCRC were randomly assigned to receive, as third‐line therapy, trifluridine/tipiracil alone (arm A) or in combination with panitumumab (arm B). Primary endpoint was PFS; secondary endpoints included overall survival (OS) and overall response rate (ORR). Median OS was 13.1 months (95% CI 9.5‐16.7) in arm A compared to 11.6 months (95% CI 6.3‐17.0) in arm B (HR: 0.96, 95% CI 0.54‐1.71, P = .9). To evaluate the impact of subsequent lines of treatment, subgroup analysis was performed for the 24/30 patients in arm A, that received fourth‐line therapy after disease progression. Median PFS was 4.1 months (95% CI 1.44‐6.83) for 17 patients treated with anti‐EGFR rechallenge as compared to 3.0 months (95% CI 1.61‐4.31) for seven patients that received other therapies (HR: 0.29, 95% CI 0.10‐0.85, P = .024). Median OS from the start of fourth‐line treatment was 13.6 months (95% CI 7.2‐20), and 5.1 months (95% CI 1.8‐8.3) for patients treated with anti‐EGFR rechallenge vs other therapies, respectively (HR: 0.30, 95% CI 0.11‐0.81, P = .019). Final results of the VELO trial support the role of anti‐EGFR rechallenge in the continuum of care of patients with RAS/BRAF WT mCRC.
Grading of steatosis, fibrosis, lobular inflammation, and ballooning from liver pathology images using pre‐trained convolutional neural networks
Authors: Zamanian Hamed , Shalbaf Ahmad
Published: July 2023

This study aims to automatically detect the degree of pathological indices as a reference method for detecting the severity and extent of various liver diseases from pathological images of liver tissue with the help of deep learning algorithms. Grading is done using a collection of pre‐trained convolutional neural networks, including DenseNet121, ResNet50, inceptionv3, MobileNet, EfficientNet‐b1, EfficientNet‐b4, Xception, NASNetMobile, and Vgg16. These algorithms are performed by fine‐tuning the trainable layers of the networks. The results showed that compared to other methods, the EfficientNet‐b1 network provides a better response to grade the stage of liver disease among all indicators from pathological images, due to its structural features. This classification accuracy was 97.26% for fibrosis, 94.1% for steatosis, 90.2% for lobular inflammation, and 98.0% for ballooning. Consequently, this fully automated framework can be very useful in clinical methods and be considered as an assistant or an alternative to the diagnosis of experienced pathologists.
Organoid and organoid extracellular vesicles for osteoporotic fractures therapy: Current status and future perspectives
Authors: Liu Han , Su Jiacan
Published: July 2023

Osteoporosis is a systemic and degenerative disease characterized by low bone mass and fragile microarchitecture, which predispose patients to fragility fractures, also known as osteoporotic fractures (OPF). OPF have become a major social problem that threaten the health of the elderly. Over the past decade, organoids and organoids extracellular vesicles (OEVs) play a significant role in OPF repair. Organoids have been widely used for fractures treatment. Moreover, EVs are promising nanocarriers due to their cell‐free system, stable drug loading capacity, nanometer size, and good biocompatibility. Importanly, compared with traditional EVs, OEVs have more quantity, better physiological effects, and better therapeutic effects. Therefore, the development of organoid and OEVs in the treatment of OPF is of great significance. Here, we summarize the current status and future perspectives of organoids and OEVs, which will provide innovative solutions to OPF repair.
CircDUS2L (circ_0039908) promotes lung adenocarcinoma progression by upregulating PGAM1 by acting as a miR‐590‐5p molecular sponge
Authors: Tian Qing , Guo Ying , Liu Jinfeng , Pang Chao , Wang Qiang , Xie Qi , Li Jianke
Published: July 2023

Lung adenocarcinoma (LUAD) is usually found at the metastatic stage. Circular RNA dihydrouridine synthase 2‐like (DUS2L) (circDUS2L) has been discovered to be upregulated in LUAD. Nevertheless, the function of circDUS2L in LUAD has not been verified. Levels of circDUS2L, microRNA‐590‐5p (miR‐590‐5p), and phosphoglycerate mutase 1 (PGAM1) mRNA were analyzed using quantitative real‐time polymerase chain reaction (RT‐qPCR). Cell proliferation, apoptosis, metastasis, and invasion were assessed by 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide (MTT), colony formation, 5‐ethynyl‐2′‐deoxyuridine (Edu), flow cytometry, and transwell assays. Protein levels were detected by western blotting. Cell glycolysis was analyzed by measuring cell glucose consumption, lactate production, and extracellular acidification rate (ECAR). The regulatory mechanism of circDUS2L in LUAD cells was analyzed by bioinformatics analysis, dual‐luciferase reporter, RNA pull‐down, and RNA immunoprecipitation (RIP) assays. Xenograft assay was conducted to confirm the function of circDUS2L in vivo. CircDUS2L was highly expressed in LUAD tissues and cells. CircDUS2L silencing constrained xenograft tumor growth in vivo. CircDUS2L knockdown induced apoptosis, repressed viability, colony formation, proliferation, metastasis, invasion, and glycolysis of LUAD cells in vitro by releasing miR‐590‐5p via functioning as a miR‐590‐5p sponge. MiR‐590‐5p was lowly expressed in LUAD tissues and cells, and miR‐590‐5p mimic curbed malignant behaviors and glycolysis of LUAD cells by targeting PGAM1. PGAM1 was overexpressed in LUAD tissues and cells, and circDUS2L sponged miR‐590‐5p to regulate PGAM1 expression. CircDUS2L elevated PGAM1 expression through functioning as a miR‐590‐5p sponge, thus driving malignant behaviors and glycolysis of LUAD cells.
Posttraumatic sleep disturbances in veterans: A pilot randomized controlled trial of cognitive behavioral therapy for insomnia and imagery rehearsal therapy
Authors: Prguda Emina , Evans Justine , McLeay Sarah , Romaniuk Madeline , Phelps Andrea J. , Lewis Kerri , Brown Kelly , Fisher Gina , Lowrie Fraser , Saunders‐Dow Elise , Dwyer Miriam
Published: July 2023

Objectives

Posttraumatic stress disorder (PTSD) is associated with sleep disturbances including insomnia and nightmares. This study compared cognitive behavioral therapy for insomnia (CBT‐I) with CBT‐I combined with imagery rehearsal therapy (IRT) for nightmares to evaluate if the combined treatment led to greater reductions in trauma‐related sleep disturbances in Australian veterans.

Methods

Veterans with diagnosed PTSD, high insomnia symptom severity, and nightmares (N = 31) were randomized to eight group CBT‐I sessions or eight group CBT‐I + IRT sessions. Self‐reported sleep, nightmare, and psychological measures (primary outcome: Pittsburgh Sleep Quality Index), and objective actigraphy data were collected; the effect of obstructive sleep apnea (OSA) risk on treatment outcomes was also examined.

Results

No treatment condition effects were detected for the combined treatment compared to CBT‐I alone, and no moderating effect of OSA risk was detected. On average, participants from both groups improved on various self‐report measures over time (baseline to 3 months posttreatment). Despite the improvements, mean scores for sleep‐specific measures remained indicative of poor sleep quality. There were also no significant differences between the groups on the actigraphy indices.

Conclusions

The findings indicate that there is potential to optimize both treatments for veterans with trauma‐related sleep disturbances.
How communication mediums shape the message
Authors: Oba Demi , Berger Jonah
Published: July 2023

Communication is an integral part of everyday life. Consumers chat with friends, search for information, and complain to customer service. Salespeople pitch products, employees answer questions, and market researchers ask them. But communication does not occur in a vacuum. Modalities (e.g., speaking or writing), channels (e.g., text, phone call, or email), and devices (e.g., smartphone or computer) are the mediums through which communicators communicate. While these mediums often seem incidental, might they impact what gets communicated? And if so, how? This paper offers a comprehensive framework for understanding how mediums shape the message. Specifically, we argue that modality, devices, and channels all shape communication through the same two key drivers: deliberation and audience salience. As a result, the mediums communicators use to communicate impact everything from the thoughtfulness and concreteness of communicated content to the degree to which it is self‐enhancing or honest. This work sheds light on the psychology of content production, provides insight into the drivers and consequences of communication, and highlights how emerging technologies may shape communication in the future.
Intended and unintended impacts of nitrogen‐fixing microorganisms and microbial inhibitors on nitrogen losses in contrasting maize cropping systems
Authors: Souza Emerson F. C. , Rosen Carl J. , Venterea Rodney T. , Tahir Muhammad
Published: July 2023

Efforts to mitigate the nitrogen (N) footprint of maize production include using N‐fixing microbes (NFM) and/or microbial inhibitors. We quantified the effects of NFM, the nitrification inhibitor (NI) 2‐(N‐3,4‐dimethyl‐1H‐pyrazol‐1‐yl) succinic acid isomeric mixture, and the urease inhibitor (UI) N‐(n‐butyl) thiophosphoric triamide, each applied by itself or paired with another additive, on nitrous oxide (N2O) emissions, nitrate (NO3−) leaching, and crop performance in contrasting irrigated and rainfed maize systems over two growing seasons. We also used published emission factors to estimate indirect N2O emissions from leached NO3− that can be converted to N2O. Agronomic effects were relatively small; the NI + NFM treatment increased N use efficiency and grain yield and protein content in some cases by 11%–14% relative to a treatment receiving only urea. Most of the additive treatments reduced direct (in‐field) N2O emissions, most consistently for treatments that contained NI which reduced emissions by 24%–77%. However, these beneficial effects were counteracted by increased NO3− leaching, which occurred most consistently with UI or NFM applied as single additives or with NI. In these treatments, NO3− leaching increased during at least one growing season, and at both sites, by factors of 2–7. In three site‐years, increased NO3− leaching with NFM and NI + NFM offset large reductions in direct N2O, such that total direct + indirect N2O emissions were not different from that in the urea only treatment. These unintended effects may have resulted from unfavorable rainfall timing, varying crop N demand, and declining additive effectiveness. Use of these soil additives requires caution and further study.
GRIK1‐AS1 deficiency accelerates endometriosis progression by boosting DNMT1‐dependent SFRP1 promoter methylation in endometrial stromal cells
Authors: Liu Wei , Hu Bin , Wang Xiaoli , Huang Erqing , Chen Xuexing , Chen Lijuan
Published: July 2023

Background

Endometriosis, a gynecological disease that affects up to 10% of women, is a major cause of pain and infertility. Deregulation of the epigenome is accountable for the onset and progression of endometriosis, although its exact mechanism is unknown. The purpose of the current study is to examine the role of the long non‐coding RNA (lncRNA) GRIK1‐AS1 in the epigenetic regulation of endometrial stromal cell proliferation and the development of endometriosis.

Methods

Endometriosis datasets were screened to identify GRIKI‐AS1 as dramatically declining in endometriosis. Gain or loss of function endometrial stromal cell (ESC) models were established. The anti‐proliferation phenotype was investigated using in vitro and in vivo experiments. Epigenetic regulatory network analyses were conducted to suggest the intrinsic molecular mechanism.

Results

With bioinformatic and clinical data, we observed that GRIK1‐AS1 and SFRP1 were expressed at low levels in endometriosis. Overexpressed GRIK1‐AS1 inhibited ESC proliferation, while SFRP1 knockdown rescued the antiproliferative ability of GRIK1‐AS1. Specifically, methylation‐dependent expression inhibition of SFRP1 was revealed in ESCs. Mechanistically, GRIK1‐AS1 hampers the occupancy of DNMT1 in SRFP1 promoter, leading to hypomethylation of SFRP1 and upregulated SFRP1 expression, thereby potentially suppressing Wnt signaling and its adverse proliferative effect. Therapeutically, lentivirus‐mediated upregulation of GRIK1‐AS1 inhibited endometriosis disease progression in vivo.

Conclusions

Our study is a proof‐of‐concept demonstration for GRIKI‐AS1‐associated endometriosis pathogenesis and highlights a potential intervention target.
Identification of the shared gene signatures and molecular pathways in systemic lupus erythematosus and diffuse large B‐cell lymphoma
Authors: Li Haoguang , Zhou Jie , Zhou Lu , Zhang Xiuling , Shang Jingjing , Feng Xueqin , Yu Le , Fan Jie , Ren Jie , Zhang Rongwei , Duan Xinwang
Published: July 2023

Background

Diffuse large B‐cell lymphoma (DLBCL) incidence is higher in systemic lupus erythematosus (SLE) patients than the general population, but the molecular mechanisms behind this link remain ambiguous. The aim of this study was to investigate shared gene signatures and molecular pathways between SLE and DLBCL.

Methods

We procured expression profiles of SLE and DLBCL from public databases and identified common differentially expressed genes (DEGs). Functional pathway enrichment and protein–protein interaction (PPI) analyses were performed on these shared genes. The molecular complex detection technology (MCODE) and eXtreme Gradient Boosting (XGBoost) machine learning algorithm were used to select core shared genes, followed by Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis.

Results

We identified 54 DEGs as shared genes, among which CD177, CEACAM1, GPR84 and IFIT3 were identified as core shared genes. These genes showed strong associations with inflammatory and immune response pathways. We found a significant positive correlation between GPR84 and IFIT3 expression levels and the immune microenvironment. Decreased expression levels of GPR84 and IFIT3 were linked to enhanced immune therapy sensitivity, potentially due to lower dysregulation scores during low expression. We also discovered that TP53 mutations might elevate CD177 and GPR84 expression and that reduced expression levels of GPR84 and IFIT3 were linked with better overall survival and progression‐free survival in DLBCL patients.

Conclusions

Our study provides valuable insights into the shared molecular mechanisms underpinning the pathogenesis of SLE and DLBCL. These findings could potentially offer new biomarkers and therapeutic targets for SLE and DLBCL.
Regioselective synthesis and computational calculation studies of some new pyrazolyl‐pyridine and bipyridine derivatives
Authors: Farag Ahmad M. , Kheder Nabila A. , Fahim Asmaa M. , Dawood Kamal M.
Published: July 2023

Starting from 3‐oxo‐N‐(3‐pyridyl)butanamide, as key intermediate, the title compounds were synthesized in good yields. Reaction of the pyridine‐carboxamide 1 with hydrazonoyl chlorides 3a,b and with triethyl orthoformate afforded the corresponding pyrazole‐carboxamides 6a,b, and the bis‐pyridine 7, respectively. Coupling of the pyridine‐carboxamide 1 with 3‐phenylpyrazole‐5‐diazonium chloride gave the hydrazone 10 which upon heating in pyridine afforded the pyrazolo[5,1‐c]‐1,2,4‐triazine derivative 11. Reaction of the pyridine‐carboxamide 1 with arylmethylenepropanedinitrile derivatives afforded 1,3′‐bipyridines 13a–c. Structure elucidation of the newly synthesized compounds was carried out using IR, NMR spectroscopy, and mass spectrometry. The extensive theoretical and experimental mechanical studies of the pyrazole derivative 6a were in accordance with its elemental analysis, FT‐IR, NMR, and MS spectral data. Moreover, computer analyses indicated that the pyridine derivatives 13a,b predominated over the pyran derivatives 14a,b as the adducts. In addition, the optimization of compounds utilized the HF/6‐31G(d) and DFT/B3LYP/6‐31G(d) basis sets. Furthermore, the physical descriptors of these compounds demonstrated their stability, and NMR correlation investigations were also carried out.
Deep Learning Nomogram for the Identification of Deep Stromal Invasion in Patients With Early‐Stage Cervical Adenocarcinoma and Adenosquamous Carcinoma: A Multicenter Study
Authors: Xiao Mei Ling , Qian Ting , Fu Le , Wei Yan , Ma Feng Hua , Gu Wei Yong , Li Hai Ming , Li Yong Ai , Qian Zhao Xia , Cheng Jie Jun , Zhang Guo Fu , Qiang Jin Wei
Published: July 2023

Background

Deep stromal invasion (DSI) is one of the predominant risk factors that determined the types of radical hysterectomy (RH). Thus, the accurate assessment of DSI in cervical adenocarcinoma (AC)/adenosquamous carcinoma (ASC) can facilitate optimal therapy decision.

Purpose

To develop a nomogram to identify DSI in cervical AC/ASC.

Study Type

Retrospective.

Population

Six hundred and fifty patients (mean age of 48.2 years) were collected from center 1 (primary cohort, 536), centers 2 and 3 (external validation cohorts 1 and 2, 62 and 52).

Field Strength/Sequence

5‐T, T2‐weighted imaging (T2WI, SE/FSE), diffusion‐weighted imaging (DWI, EPI), and contrast‐enhanced T1‐weighted imaging (CE‐T1WI, VIBE/LAVA).

Assessment

The DSI was defined as the outer 1/3 stromal invasion on pathology. The region of interest (ROI) contained the tumor and 3 mm peritumoral area. The ROIs of T2WI, DWI, and CE‐T1WI were separately imported into Resnet18 to calculate the DL scores (TDS, DDS, and CDS). The clinical characteristics were retrieved from medical records or MRI data assessment. The clinical model and nomogram were constructed by integrating clinical independent risk factors only and further combining DL scores based on primary cohort and were validated in two external validation cohorts.

Statistical Tests

Student's t‐test, Mann–Whitney U test, or Chi‐squared test were used to compare differences in continuous or categorical variables between DSI‐positive and DSI‐negative groups. DeLong test was used to compare AU‐ROC values of DL scores, clinical model, and nomogram.

Results

The nomogram integrating menopause, disruption of cervical stromal ring (DCSRMR), DDS, and TDS achieved AU‐ROCs of 0.933, 0.807, and 0.817 in evaluating DSI in primary and external validation cohorts. The nomogram had superior diagnostic ability to clinical model and DL scores in primary cohort (all P < 0.0125 [0.05/4]) and CDS (P = 0.009) in external validation cohort 2.

Data Conclusion

The nomogram achieved good performance for evaluating DSI in cervical AC/ASC.

Level of Evidence

3

Technical Efficacy

Stage 2
How Crisis May Generate and Sustain Creative Cycles: The Role of Problem Persistence
Authors: Villanova Ana Luisa , Pina e Cunha Miguel , Carlsen Arne
Published: July 2023

We performed an inductive study to advance theory on how a crisis can inspire individuals to be persistently creative in successive cycles. We draw from rich data of 17 volunteer projects in the Tech4Covid movement, a Portuguese organization of entrepreneurs who gathered online to develop digital solutions to help society during the COVID‐19 pandemic. This empirical context is uniquely suited to study how interactions with intended beneficiaries during crises can encourage creators to initiate and continue creative work. Our results allowed us to extend the knowledge of crisis‐induced creative processes in two ways. First, we noticed that throughout the creative process, creators might switch the primary focus of their work from outside beneficiaries to their own benefit. These changes can serve as a trigger to reinforce creators' motivations to continue their creative work beyond the first set of creative outputs. Second, we propose that the nature of the problem to be solved influences the continuity of creative processes: while momentary problems induced by the crisis may stimulate episodic ideas, their transitory nature may prevent creators from having time to fully develop their ideas further. Thus, it is primarily persistent problems that favor the progress of ideas in successive creative cycles.
Composite lipid emulsion use and essential fatty acid deficiency in pediatric patients with intestinal failure with high parenteral nutrition dependence: A retrospective cohort study
Authors: Belza Christina , Courtney‐Martin Glenda , Wong‐Sterling Sylvia , Garofalo Elizabeth , Silva Carina , Yanchis Dianna , Avitzur Yaron , Wales Paul W.
Published: July 2023

Background

Reports of essential fatty acid deficiency (EFAD) in patients receiving parenteral nutrition (PN) and a composite lipid (mixed oil intravenous lipid emulsion [MO ILE]) are predominantly when managed by lipid restriction. The objective of this study was to determine the prevalence of EFAD in patients with intestinal failure (IF) who are PN dependent without lipid restriction.

Methods

We retrospectively evaluated patients, ages 0–17 years, followed by our intestinal rehabilitation program between November 2020 and June 2021 with PN dependency index (PNDI) of >80% on a MO ILE. Demographic data, PN composition, PN days, growth, and plasma fatty acid profile were collected. A plasma triene‐tetraene (T:T) ratio >0.2 indicated EFAD. Summary statistics and Wilcoxon rank sum test evaluated to compare between PNDI category and ILE administration (grams/kilograms/day). P < 0.05 was considered significant.

Results

Twenty‐six patients (median age, 4.1 years [interquartile range (IQR) = 2.4–9.6]) were included. The median duration of PN was 1367 days (IQR = 824–3195). Sixteen patients had a PNDI of 80%–120% (61.5%). Fat intake for the group was 1.7 g/kg/day (IQR = 1.3–2.0). The median T:T ratio was 0.1 (IQR = 0.1–0.2) with no values >0.2. Linoleic and arachidonic acid were low in 85% and 19% of patients, respectively; however, Mead acid was normal in all patients.

Conclusion

This report is the largest to date on the EFA status of patients with IF on PN. These results suggest that, in the absence of lipid restriction, EFAD is not a concern when using MO ILEs in children receiving PN for IF.