bluuebunny/crossref_metadata_2025 huggingface dataset:
Alpha‐enolase 1 knockdown facilitates the proliferation and invasion of villous trophoblasts by upregulating COX‐2
Authors: Tang Huaiyun , Pan Linqing , Tang Lisha , Liu Jiayin
Published: June 2023

Background

Enolase 1 (ENO1) is a metabolic enzyme which participates in pyruvate synthesis and ATP production in cells. Previously, differential expression of ENO1 was discovered in villous tissues between recurrent miscarriage and induced abortion. This study was designed to explore whether ENO1 influences the proliferation and invasion of villous trophoblasts and the related molecular mechanisms.

Methods

First, ENO1 expression in placental villus tissues collected from recurrent miscarriage (RM) patients and women for induced abortion as well as in trophoblast‐derived cell lines was detected by RT‐qPCR and western blotting. ENO1 localization and expression in villus tissues were further confirmed through immunohistochemistry staining. Then, the effects of ENO1 downregulation on trophoblast Bewo cell proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT) process were evaluated by CCK‐8 assay, transwell assay, and western blotting. As for the regulatory mechanism of ENO1, the expression of COX‐2, c‐Myc and cyclin D1 in Bewo cells after ENO1 knockdown was finally evaluated by RT‐qPCR and western blotting.

Results

ENO1 was mainly localized in the cytoplasm, with very small amounts in the nucleus of trophoblast cells. ENO1 expression in the villi tissues of RM patients was significantly increased, when compared with the villous tissues of healthy controls. Furthermore, Bewo cells, a trophoblast cell line with relatively higher expression of ENO1, was used to downregulate the ENO1 expression by ENO1‐siRNA transfection. ENO1 knockdown significantly facilitated Bewo cell growth, EMT process, migration, and invasion. ENO1 silencing markedly elevated COX‐2, c‐Myc, and cyclin D1 expression.

Conclusion

ENO1 may participate in the development of RM via suppressing the growth and invasion of villous trophoblasts via reducing the expression of COX‐2, c‐Myc, and cyclin D1.
Two regularization methods for identifying the source term of Caputo–Hadamard time‐fractional diffusion equation
Authors: Yang Fan , Cao Ying , Li Xiao‐Xiao
Published: June 2023

In this paper, the inverse problem for identifying the unknown source on time‐fractional diffusion equation with Caputo–Hadamard derivative is considered. This problem is ill‐posed, and two regularization methods are used to solve it. Firstly, we prove that the problem is ill‐posed and give the conditional stability and the optimal error bound. Secondly, the error estimates of the fractional Landweber iterative regularization method and the fractional Tikhonov regularization method under a priori and a posteriori parameter selection rules are given, respectively. Finally, numerical examples are given to illustrate the effectiveness of two regularization methods.
Incremental retraining, clinical implementation, and acceptance rate of deep learning auto‐segmentation for male pelvis in a multiuser environment
Authors: Duan Jingwei , Vargas Carlos E. , Yu Nathan Y. , Laughlin Brady S. , Toesca Diego Santos , Keole Sameer , Rwigema Jean Claude M. , Wong William W. , Schild Steven E. , Feng Xue , Chen Quan , Rong Yi
Published: June 2023

Background

Deep learning auto‐segmentation (DLAS) models have been adopted in the clinic; however, they suffer from performance deterioration owing to the clinical practice variability. Some commercial DLAS software provide an incremental retraining function that enables users to train a custom model using their institutional data to account for clinical practice variability.

Purpose

This study was performed to evaluate and implement the commercial DLAS software with the incremental retraining function for definitive treatment of patients with prostate cancer in a multi‐user environment.

Methods

CT‐based target organs and organs‐at‐risk (OAR) delineation of 215 prostate cancer patients were utilized. The performance of three commercial DLAS software built‐in models was validated with 20 patients. A retrained custom model was developed using 100 patients and evaluated on the remaining data (n = 115). Dice similarity coefficient (DSC), Hausdorff distance (HD), mean surface distance (MSD), and surface DSC (SDSC) were utilized for quantitative evaluation. A multi‐rater qualitative evaluation was blindly performed with a five‐level scale. Visual inspection was performed in consensus and non‐consensus unacceptable cases to identify the failure modes.

Results

Three commercial DLAS vendor built‐in models achieved sub‐optimal performance in 20 patients. The retrained custom model had a mean DSC of 0.82 for prostate, 0.48 for seminal vesicles (SV), and 0.92 for rectum, respectively. This represents a significant improvement over the built‐in model with DSC of 0.73, 0.37, and 0.81 for the corresponding structures. Compared to the acceptance rate of 96.5% and consensus unacceptable rate (i.e., both reviewers rated as unacceptable) of 3.5% achieved by manual contours, the custom model achieved a 91.3% acceptance rate and 8.7% consensus unacceptable rate. The failure modes of retrained custom model were attributed to the following: cystogram (n = 2), hip prosthesis (n = 2), low dose rate brachytherapy seeds (n = 2), air in endorectal balloon(n = 1), non‐iodinated spacer (n = 2), and giant bladder(n = 1).

Conclusion

The commercial DLAS software with the incremental retraining function was validated and clinically adopted for prostate patients in a multi‐user environment. AI‐based auto‐delineation of the prostate and OARs is shown to achieve improved physician acceptance, overall clinical utility, and accuracy.
Motion‐corrected model‐based reconstruction for 2D myocardial T1 mapping
Authors: Kerkering Kirsten Miriam , Schulz‐Menger Jeanette , Schaeffter Tobias , Kolbitsch Christoph
Published: June 2023

Purpose

To allow for T1 mapping of the myocardium within 2.3 s for a 2D slice utilizing cardiac motion‐corrected, model‐based image reconstruction.

Methods

Golden radial data acquisition is continuously carried out for 2.3 s after an inversion pulse. In a first step, dynamic images are reconstructed which show both contrast changes due to T1 recovery and anatomical changes due to the heartbeat. An image registration algorithm with a signal model for T1 recovery is applied to estimate non‐rigid cardiac motion. In a second step, estimated motion fields are applied during an iterative model‐based T1 reconstruction. The approach was evaluated in numerical simulations, phantom experiments and in in‐vivo scans in healthy volunteers.

Results

The accuracy of cardiac motion estimation was shown in numerical simulations with an average motion field error of 0.7 ± 0.6 mm for a motion amplitude of 5.1 mm. The accuracy of T1 estimation was demonstrated in phantom experiments, with no significant difference (p = 0.13) in T1 estimated by the proposed approach compared to an inversion‐recovery reference method. In vivo, the proposed approach yielded 1.3 × 1.3 mm T1 maps with no significant difference (p = 0.77) in T1 and SDs in comparison to a cardiac‐gated approach requiring 16 s scan time (i.e., seven times longer than the proposed approach). Cardiac motion correction improved the precision of T1 maps, shown by a 40% reduced SD.

Conclusion

We have presented an approach that provides T1 maps of the myocardium in 2.3 s by utilizing both cardiac motion correction and model‐based T1 reconstruction.
Lung T2* mapping using 3D ultrashort TE with tight intervals δTE
Authors: Malis Vadim , Kassai Yoshimori , Vucevic Diana , Bae Won C. , Ohno Yoshiharu , Yen Andrew , Miyazaki Mitsue
Published: June 2023

Purpose

To develop 3D ultrashort‐TE (UTE) sequences with tight TE intervals (δTE), allowing for accurate mapping of lungs under free breathing.

Methods

We have implemented a four‐echo UTE sequence with δTE (< 0.5 ms). A Monte‐Carlo simulation was performed to identify an optimal number of echoes that would result in a significant improvement in the accuracy of the fit within an acceptable scan time. A validation study was conducted on a phantom with known short values (< 5 ms). The scanning protocol included a combination of a standard multi‐echo UTE with six echoes (2.2‐ms intervals) and a new four‐echo UTE (TE < 2 ms) with tight TE intervals δTE. The human imaging was performed at 3 T on 6 adult volunteers. mapping was performed with mono‐exponential and bi‐exponential models.

Results

The simulation for the proposed 10‐echo acquisition predicted over 2‐fold improvement in the accuracy of estimating the short compared with the regular six‐echo acquisition. In the phantom study, the was measured up to three times more accurately compared with standard six‐echo UTE. In human lungs, maps were successfully obtained from 10 echoes, yielding average values  = 1.62 ± 0.48 ms for mono‐exponential and  = 1.00 ± 0.53 ms for bi‐exponential models.

Conclusion

A UTE sequence using δTE was implemented and validated on short phantoms. The sequence was successfully applied for lung imaging; the bi‐exponential signal model fit for human lung imaging may provide valuable insights into the diseased human lungs.
Material point method‐based simulation of dynamic process of soil landslides considering pore fluid pressure
Authors: Wu Fengyuan , Sun Wei , Li Xinchao , Guan Yongping , Dong Manman
Published: June 2023

In this study, the dynamic process of soil landslides is investigated using the material point method (MPM). A basal friction algorithm is developed based on the MPM, and the pore water pressure is considered for calculating the basal friction. A large‐scale debris flow experiment is performed to validate the effectiveness of the MPM in simulating the dynamic process of soil landslides. The calculated depths of the debris flow using the MPM are consistent with the experimental results. The effects of the basal friction angle and internal friction angle on the debris flow depths are discussed. Moreover, a landslide case is simulated using the MPM, and the calculation results are consistent with the measured results. The horizontal velocity, vertical velocity, velocity direction, and kinetic energy of the landslide are analyzed. Finally, a case involving a different slope near a landslide is evaluated using the MPM. The distributions of velocity in different directions and changes in the average velocity, kinetic energy, and sliding distance are analyzed. By setting a retaining wall, the accumulation height of a landslide accumulated at the retaining wall and the normal force on the retaining wall can be estimated.
A phenotypic approach to obesity treatment
Authors: Zandvakili Inuk , Pulaski Marya , Pickett‐Blakely Octavia
Published: June 2023

Obesity is a chronic disease that increases morbidity and mortality and adversely affects quality of life. The rapid rise of obesity has outpaced the development and deployment of effective therapeutic interventions, thereby creating a global health crisis. The presentation, complications, and response to obesity treatments vary, yet lifestyle modification, which is the foundational therapeutic intervention for obesity, is often “one size fits all.” The concept of personalized medicine uses genetic and phenotypic information as a guide for disease prevention, diagnosis, and treatment and has been successfully applied in diseases such as cancer, but not in obesity. As we gain insight into the pathophysiologic mechanisms of obesity and its phenotypic expression, specific pathways can be targeted to yield a greater, more sustained therapeutic impact in an individual patient with obesity. A phenotype‐based pharmacologic treatment approach utilizing objective measures to classify patients into predominant obesity mechanism groups resulted in greater weight loss (compared with a non–phenotype‐based approach) in a recent study by Acosta and colleagues. In this review, we discuss the application of lifestyle modifications, behavior therapy and pharmacotherapy using the obesity phenotype–based approach as a framework.
Micronutrient deficiencies in patients with gastrointestinal cancer: To treat or not to treat
Authors: Turkiewicz Joanna , Garcia Michael , Li Zhaoping , Surampudi Vijaya
Published: June 2023

Nutrition supplements are widely used among patients with cancer. The general public perceives supplements as more natural anticancer and antitoxicity agents, and often supplements are used without the knowledge of the treating physician. In the clinical setting, there are concerns that supplements may decrease effectiveness of chemotherapy and/or radiotherapy and, as a result, supplementation is avoided. There is a body of literature evaluating micronutrient deficiencies, supplementation, and cancer risk; however, little is known about the risks of treatment of micronutrient deficiencies in specific cancers. Of the types of cancers, patients with gastrointestinal cancers are at high risk of developing malnutrition and, subsequently, possible micronutrient deficiencies. This review aims to evaluate the effects of supplementation of specific micronutrients in patients with cancer of the digestive tract.
A mixed three‐field total Lagrangian material point method for phase‐field fracture modeling of nearly incompressible rubber‐like solids
Authors: Zhang Zijian , Hu Zhiqiang , Ye Hongfei , Zhang Hongwu , Zheng Yonggang
Published: June 2023

The rubber‐like solids, as commonly observed materials in nature and engineering areas, often show high extensibility and weak compressibility, which lead to difficulties for modeling the fracture behavior of these materials. In this paper, we propose a mixed three‐field total Lagrangian material point method (TLMPM) to deal with the fracture of nearly incompressible rubber‐like solids. In this method, the phase‐field method combining with perturbed Lagrangian approach is developed to describe the fracture of nearly incompressible materials. Based on the Lagrangian equation, the governing equations of the displacement, pressure and phase fields are derived for the system considering dynamic effect. Then, a mixed three‐field TLMPM discrete formulation with a remapping strategy is then built to solve the problem involving large deformation. Besides, a staggered solving scheme with explicit time integration is developed for the three‐field problem. The accuracy and capabilities of the proposed method for dealing with the fracture of incompressible materials are demonstrated by modeling several quasi‐static and dynamic numerical problems and comparing the results with other numerical methods and experiments. Moreover, the applicability of the method is further proved by an out‐of‐plane tearing case.
Influencing factors of sleep disorders and sleep quality in healthcare workers during the COVID‐19 pandemic: A systematic review and meta‐analysis
Authors: Lv Qian , Zhou Wenguang , Kong Yue , Chen Silu , Xu Baoling , Zhu Fangfang , Shen Xianying , Qiu Zhaojun
Published: June 2023

Aim

The aim of this study was to identify the influencing factors of sleep disorders and sleep quality in healthcare workers during the COVID‐19 pandemic.

Design

Systematic review and meta‐analysis of observational research.

Methods

The databases of the Cochrane Library, Web of Science, PubMed, Embase, SinoMed database, CNKI, Wanfang Data, and VIP were systematically searched. The quality of studies was assessed using the Agency for Healthcare Research and Quality evaluation criteria and the Newcastle–Ottawa scale.

Results

A total of 29 studies were included, of which 20 were cross‐sectional studies, eight were cohort studies, and 1 was a case–control study; 17 influencing factors were finally identified. Greater risk of sleep disturbance was associated with female gender, single relationship status, chronic disease, insomnia history, less exercise, lack of social support, frontline work, days served in frontline work, department of service, night shift, years of work experience, anxiety, depression, stress, received psychological assistance, worried about being infected, and degree of fear with COVID‐19.

Conclusions

During the COVID‐19 pandemic, healthcare workers did have worse sleep quality than the general population. The influencing factors of sleep disorders and sleep quality in healthcare workers are multifaceted. Identification and timely intervention of resolvable influencing factors are particularly important for preventing sleep disorders and improving sleep.

Patient or Public Contribution

This is a meta‐analysis of previously published studies so there was no patient or public contribution.
Prognostic factors of sepsis in children with acute leukemia admitted to the pediatric intensive care unit
Authors: Wu Li , Jin Ming , Wang Ruiqing , Yang Lihua , Lai Xiaorong , Yu Lihua , Lin Danna , Huang Lulu , Zhang Yajie , Zhang Jingxin , Liao Xu , Zi Juan , Yuan Yuting , Zeng Yinghua , Cheng Ming , Tao Shaohua
Published: June 2023

Objective

To analyze the prognostic factors of sepsis in children with acute leukemia admitted to the pediatric intensive care unit (PICU) and to compare the efficacy of different scoring systems for predicting the outcome of children.

Methods

Patients with an acute leukemia diagnosis admitted to a tertiary care university hospital PICU due to sepsis during chemotherapy between May 2015 and August 2022 were retrospectively analyzed through an electronic medical record system.

Results

During this period, 693 children with acute leukemia initially diagnosed were admitted to the center, and 155 (22.3%) of them were transferred to PICU due to deterioration of the disease during treatment. Total 109 (70.3%) patients were transferred to PICU due to sepsis. Here, 17 patients was excluded (prior treatment from another hospital; referring from other hospitals; discontinued treatment; incomplete medical record). Of the 92 patients studied, the mortality rate was 35.9%. Multivariate analysis revealed that remission status, lactate level, invasive mechanical ventilation (IMV), and inotropic support within 48 hours after PICU transfer were independent risk factors for PICU mortality. The pediatric sequential organ failure assessment (PSOFA) score had the greatest predictive validity for hospital mortality (area under the receiver operating characteristic curve [AUROC]: 0.83, 95% confidence intervals [CI]: 0.74–0.92), followed by the pediatric early warning score (PEWS) (0.82, 0.73–0.91) and pediatric critical illness score (PCIS) (0.79, 0.69–0.88).

Conclusion

The mortality rate among children with acute leukemia complicated with sepsis is high after being transferred to the PICU. Various scoring systems can be used to monitor the clinical status of patients, identify sepsis early, detect critical illness, and determine the optimal time for transfer to the PICU for supportive treatment, thereby improving the prognosis of these patients.
Convergent validity of the Behavior Observation of Students in Schools for elementary school students with disruptive behaviors
Authors: Alperin Alexander , Dudek Christopher M. , Reddy Linda A. , Glover Todd A. , Wiggs Nicole B. , Bronstein Briana
Published: June 2023

Systematic direct observations (SDOs) and behavior rating scales are integral to multimethod behavioral assessment approaches. The present study investigated the convergent validity of the Behavior Observation of Students in Schools (BOSS) form, a widely utilized SDO system, with the most frequently used teacher rating scales in schools, the Behavioral Assessment System for Children, Third Edition (BASC‐3) and the Behavioral and Emotional Screening System, third edition (BESS‐3). Specifically, the present study compared independent observer data collection of student on‐task and disruptive behaviors on the BOSS with teachers' ratings of behavioral problems on the BASC‐3 and BESS‐3. Data come from a sample of 136 teachers and 349 students with or at risk of disruptive behavior disorders (DBDs). Pearson correlations were computed between BOSS and teacher ratings on the BASC‐3 and BESS‐3. Findings demonstrated significant, small to moderate correlations. Results indicate evidence of convergent validity for the BOSS and BASC3 assessments and highlight multimethod behavioral assessment's utility in supporting students with or at risk of DBDs.
Fast proteomics with dia‐PASEF and analytical flow‐rate chromatography
Authors: Szyrwiel Lukasz , Gille Christoph , Mülleder Michael , Demichev Vadim , Ralser Markus
Published: June 2023

Increased throughput in proteomic experiments can improve accessibility of proteomic platforms, reduce costs, and facilitate new approaches in systems biology and biomedical research. Here we propose combination of analytical flow rate chromatography with ion mobility separation of peptide ions, data‐independent acquisition, and data analysis with the DIA‐NN software suite, to achieve high‐quality proteomic experiments from limited sample amounts, at a throughput of up to 400 samples per day. For instance, when benchmarking our workflow using a 500‐μL/min flow rate and 3‐min chromatographic gradients, we report the quantification of 5211 proteins from 2 μg of a mammalian cell‐line standard at high quantitative accuracy and precision. We further used this platform to analyze blood plasma samples from a cohort of COVID‐19 inpatients, using a 3‐min chromatographic gradient and alternating column regeneration on a dual pump system. The method delivered a comprehensive view of the COVID‐19 plasma proteome, allowing classification of the patients according to disease severity and revealing plasma biomarker candidates.
Plastic bronchitis during childhood: Diversity of presentation, etiology, treatment, and outcomes
Authors: Nayır Büyükşahin Halime , Emiralioglu Nagehan , Sekerel Bulent E. , Soyer Tutku , Oguz Berna , Güzelkaş Ismail , Sunman Birce , Alboğa Didem , Akgül Erdal Meltem , Yalcın Ebru , Doğru Deniz , Ozcelik Ugur , Kiper Nural
Published: June 2023

Objective

Plastic bronchitis (PB) is a rare disease in children, and reliable data are scarce. Here, we aimed to analyze the clinical features, management, and outcomes in children with PB.

Methods

The medical data of patients who were followed up with a diagnosis of PB between January 2010 and March 2022 were retrospectively analyzed.

Results

The median age of 15 patients was 9 (interquartile range: 4–10) years with a male/female ratio of 12/3. Initial symptoms included recurrent pneumonia (33.3%), persistent atelectasis (33.3%), cast expectoration (26.6%), and intense, persistent cough (6.6%). The most common underlying diagnosis was asthma (n = 12, 80%), and six of the patients were newly diagnosed. The most common radiological findings were atelectasis as a consequence of major airway obstruction on chest X‐ray or computed tomography. Five patients, all diagnosed as having asthma, had recurrent PB and required multiple airway procedures for treatment and diagnosis. During a median 7‐year follow‐up of five patients, occasionally cast expectoration was observed in one patient with asthma who had poor compliance with inhaled corticosteroids.

Conclusion

PB is a common reflection of the different underlying etiologies in the pediatric age group, and treatment and outcomes are closely related to these. It should be kept in mind that asthma can be a predisposing factor for the development of PB.
Template‐guided method for protein–ligand complex structure prediction: Application to CASP15 protein–ligand studies
Authors: Xu Xianjin , Duan Rui , Zou Xiaoqin
Published: June 2023

Critical Assessment of Structure Prediction 15 (CASP15) added a new category of ligand prediction to promote the development of protein/RNA‐ligand modeling methods, which have become important tools in modern drug discovery. A total of 22 targets were released, including 18 protein–ligand targets and 4 RNA‐ligand targets. We applied our recently developed template‐guided method to the protein–ligand complex structure predictions. The method combined a physicochemical, molecular docking method, and a bioinformatics‐based ligand similarity method. The Protein Data Bank was scanned for template structures containing the target protein, homologous proteins, or proteins sharing a similar fold with the target protein. The binding modes of the co‐bound ligands in the template structures were used to guide the complex structure prediction for the target. The CASP assessment results show that the overall performance of our method was ranked second when the top predicted model was considered for each target. Here, we analyzed our predictions in detail, and discussed the challenges including protein conformational changes, large and flexible ligands, and multiple diverse ligands in a binding pocket.
Antimicrobial stewardship: Prescribing across the primary care health professions
Authors: Hollingworth Samantha A. , McGuire Treasure , Van Driel Mieke , Begum Nelufa , Ford Pauline J. , Hawley Glenda , Walsh Laurence J.
Published: June 2023

We examined the patterns of antibiotic prescribing by medical and non‐medical prescribers (dentists, nurse practitioners, and midwives) in Australia. We explored trends in the dispensed use of antibiotics (scripts and defined daily dose [DDD] per 1000 population/day) by Australian prescribers over the 12‐year period, 2005–2016. We obtained data on dispensed prescriptions of antibiotics from registered health professionals subsidized on the Pharmaceutical Benefits Scheme (PBS). There were 216.2 million medical and 7.1 million non‐medical dispensed prescriptions for antibiotics over 12 years. The top four antibiotics for medical prescribers were doxycycline; amoxicillin, amoxicillin plus clavulanic acid, and cefalexin, constituting 80% of top 10 use in 2005 and 2016; the top three for non‐medical were amoxicillin, amoxicillin plus clavulanic acid and metronidazole (84% of top 10 use in 2016). The proportional increase in antibiotic use was higher for non‐medical than medical prescribers. While medical prescribers preferentially prescribed broad‐spectrum and non‐medical prescribers moderate‐spectrum antibiotics, there was a large increase in the use of broad‐spectrum antibiotics over time by all prescribers. One in four medical prescriptions were repeats. Overprescribing of broad‐spectrum antibiotics conflicts with national antimicrobial stewardship initiatives and guidelines. The proportional higher increase in antibiotic use by non‐medical prescribers is a concern. To reduce inappropriate use of antibiotics and antimicrobial resistance, educational strategies targeted at all medical and non‐medical prescribers are needed to align prescribing with current best practice within the scope of practice of respective prescribers.
Racial residential segregation and child mortality in the southern United States at the turn of the 20th century
Authors: Karbeah J'Mag , Hacker J. David
Published: June 2023

A growing body of research considers racial residential segregation to be a form of systemic racism and a fundamental cause of persistent racial disparities in health and mortality. Historical research examining the impact of segregation on health and mortality, however, is limited to a few studies with poor data and inconsistent results. In this study, we examine the association between racial residential segregation and child mortality in the South at the turn of the 20th century. We rely on the new IPUMS 1900 and 1910 complete‐count databases to estimate child mortality in the 5 years before each census and construct segregation measures at the census enumeration district (ED), the lowest level of geography consistently available in the census. We calculate the proportion of households headed by Black individuals in each ED, and the Sequence Index of Segregation (SIS), which is based on the racial sequencing of household heads within each district. We construct models of child mortality for rural and urban areas, controlling for a wide variety of demographic and socioeconomic variables. The results indicate thatproportion BlackandSISwere strongly and positively associated with the mortality of Black children in most models and in both rural and urban areas.Proportion Blackwas also positively but more moderately correlated with the mortality of White children, whileSISwas not correlated or negatively correlated. These results suggest that racial segregation was a long‐standing fundamental cause of race disparities in health and mortality in the United States.
Thymoquinone induces apoptosis and protective autophagy in gastric cancer cells by inhibiting the PI3K/Akt/mTOR pathway
Authors: He Pengzhan , He Yang , Ma Jingjing , Liu Yinghui , Liu Chuan , Baoping Yu , Dong Weiguo
Published: June 2023

Gastric cancer (GC) is often diagnosed in the advanced stages with a poor prognosis. Thymoquinone (TQ) is known for its antitumor activity; however, the specific mechanism in GC remains unknown. In our study, TQ inhibited GC cell proliferation and induced apoptosis and autophagy in a concentration‐dependent manner. Transmission electron microscopy showed increased autophagosome formation in GC cells treated with TQ. Meanwhile, the LC3B puncta and LC3BII protein levels were significantly increased in GC cells, while p62 expression was significantly decreased. The autophagy inhibitor, Bafilomycin A1 enhanced TQ‐inhibited proliferation and TQ‐induced apoptosis, suggesting that TQ‐induced autophagy has a protective effect on GC cells. Furthermore, TQ decreased the phosphorylation levels of phosphatidylinositol‐4,5‐bisphosphate 3 kinase (PI3K), protein kinase B (Akt), and mechanistic target of rapamycin (mTOR). The PI3K agonist partially rescued TQ‐induced autophagy and apoptosis. Finally, in vivo experiments showed that TQ could inhibit tumor growth and promote apoptosis and autophagy. This study provides new insights into the specific mechanism for the anti‐GC effect of TQ. TQ inhibits the proliferation of GC cells and induces apoptosis and protective autophagy by inhibiting the PI3K/Akt/mTOR pathway. The results suggest that the combination of TQ and autophagy inhibitors might be a potential chemotherapeutic strategy for GC.
Tuberculosis control in the face of emerging infectious diseases: Highlights from the 7th South African Tuberculosis Conference
Authors: Ma'aruf Shamsuddeen Yusuf , Smith Tayla , du Plessis Su‐Mari , Obasa Zimvo
Published: June 2023

Tuberculosis (TB) remains a disease of global concern caused by the pathogen Mycobacterium tuberculosis. In the face of emerging infectious diseases, such as COVID‐19, dengue fever, Lassa fever, and Ebola, attention to the control of TB is losing its place as a priority in public and global health initiatives. Recently, after a hiatus enforced by the COVID‐19 pandemic, scientists, public health experts, and other stakeholders met in Durban, South Africa (SA) for the 7th South Africa Tuberculosis Conference to share, discuss, and recommend strategies to regain TB control. In this paper, we summarized and captured key plenary sessions and presentations by scientists and other stakeholders at the conference, which focused on various themes: pathogenesis of TB—pathogen and host, drugs/vaccine/diagnostics, implementation/health systems, and social and community aspects of TB. The current policy and effort to control TB have declined in recent times. We suggested a critical and inclusive engagement of funders, researchers, policymakers, and the civil society toward regaining TB control. Additional investigation into this paper may make it easier to identify control strategies to help realize the End TB Strategy.
African Medicines Agency: How it will change the landscape of medicines in Africa
Authors: Ogbodum Molly Unoh , Shomuyiwa Deborah Oluwaseun , Lucero‐Prisno Don Eliseo , Gutu Comfort Tanaka , Bouali Hajar , Bangura Buya Nabie , Fofana Moussa , Musa Mohamed Babiker , Daoud Hassan Ali , Owusu‐Mensah Priscilla , Fiagan David Do Céu , Danquah Cynthia Amaning , Samai Mohamed
Published: June 2023

The African continent, with a population of about 1.2 billion, faces limited access to safe, high‐quality and effective medicine, resulting in a disproportionate disease burden. However, the scarcity of pharmaceuticals has been a significant problem for decades. The need to scale up local production of medicines in Africa is apparent, as over 70% of drugs available in the continent are imported. Africa's pharmaceutical manufacturing industry capacity is subpar due to inadequate production equipment and substandard operations. Inadequate pharmaceutical supplies encouraged the circulation of fake drugs, and the COVID‐19 pandemic highlighted the dangers of the continent's reliance on foreign supplies. Africa's porous borders create ease for drug counterfeiting, with little likelihood of detection once in the supply chain. The African Medicines Agency (AMA) was founded to model the European Medicines Agency to enhance regional drug production, regulation and patient access. The African Union's AMA is a specialized health organization tasked with enhancing regulatory harmonization of medicines, particularly in pharmaceutical production, to increase access to high‐quality medications across the continent. Africa's healthcare industry, particularly domestic pharmaceutical manufacturing, will be a significant economic engine for the continent over the next 5 years. The establishment of AMA is a call to action for governments and regulators to enable Africa to manufacture 60% of the vaccines needed on the continent by 2040.
Achieving COVID‐19 herd immunity in Bangladesh
Authors: Mary Rabeya Mashferat , Alam Falguni , Miranda Adriana Viola , Lucero‐Prisno Don Eliseo , Bulbul Md. Mofijul Islam
Published: June 2023

Achieving herd immunity against COVID‐19 through vaccination is a global target, including in lower resource settings. Despite the challenges and limitations, Bangladesh has achieved its target of vaccinating 70% of its population, with good vaccine coverage among refugees, remote population, and women. This can be attributed to the evidence‐informed adaptability and collaborative approaches of the program. Yet some challenges remain, including dependence on donors and the need to ramp up vaccination among the underserved communities. This article discusses the factors contributing to the achievements of the COVID‐19 vaccination program of Bangladesh and the remaining challenges that should be addressed by the government to ensure the sustainability of the program and inform future vaccination efforts.
Is iron deficiency caused by BMPR2 mutations or dysfunction in pulmonary arterial hypertension patients?
Authors: Theobald Vivienne , Grünig Ekkehard , Benjamin Nicola , Seyfarth Hans‐Jürgen , Halank Michael , Schneider Marc A. , Richtmann Sarah , Kazdal Daniel , Hinderhofer Katrin , Xanthouli Panagiota , Egenlauf Benjamin , Harutyunova Satenik , Hoeper Marius M. , Jonigk Danny , Sparla Richard , Muckenthaler Martina U. , Eichstaedt Christina A.
Published: June 2023

Iron deficiency is common in idiopathic and heritable pulmonary arterial hypertension patients (I/HPAH). A previous report suggested a dysregulation of the iron hormone hepcidin, which is controlled by BMP/SMAD signaling involving the bone morphogenetic protein receptor 2 (BMPR‐II). Pathogenic variants in the BMPR2 gene are the most common cause of HPAH. Their effect on patients' hepcidin levels has not been investigated. The aim of this study was to assess whether iron metabolism and regulation of the iron regulatory hormone hepcidin was disturbed in I/HPAH patients with and without a pathogenic variant in the gene BMPR2 compared to healthy controls. In this explorative, cross‐sectional study hepcidin serum levels were quantified by enzyme‐linked immunosorbent assay. We measured iron status, inflammatory parameters and hepcidin modifying proteins such as IL6, erythropoietin, and BMP2, BMP6 in addition to BMPR‐II protein and mRNA levels. Clinical routine parameters were correlated with hepcidin levels. In total 109 I/HPAH patients and controls, separated into three groups, 23 BMPR2 variant‐carriers, 56 BMPR2 noncarriers and 30 healthy controls were enrolled. Of these, 84% had iron deficiency requiring iron supplementation. Hepcidin levels were not different between groups and corresponded to the degree of iron deficiency. The levels of IL6, erythropoietin, BMP2, or BMP6 showed no correlation with hepcidin expression. Hence, iron homeostasis and hepcidin regulation was largely independent from these parameters. I/HPAH patients had a physiologically normal iron regulation and no false elevation of hepcidin levels. Iron deficiency was prevalent albeit independent of pathogenic variants in the BMPR2 gene.
A systematic review of widening participation: Exploring the effectiveness of outreach programmes for students in second‐level schools
Authors: Ní Chorcora Eilís , Bray Aibhín , Banks Joanne
Published: June 2023

A major challenge for universities across the globe is to address the lack of diversity within higher education. Widening participation (WP) programmes can vary between in‐reach and outreach programmes. Some initiatives focus on either pre‐entry stage (primary or secondary schools) or post‐entry stage (helping students adapt to university life). This systematic literature review provides an analysis of the effectiveness of widening participation outreach programmes, a topic that is relatively unexplored, particularly at school level education. By examining empirical studies of widening participation interventions, the paper allows for the investigation of the educational outcomes measured in these programmes. A total of 19 studies were included, which analysed quantitative or mixed‐method data. The findings indicate a growth in the evidence base for widening participation programmes for second‐level students over the last decade. Interventions identified in the literature were categorised by their approach, which included guidance‐based interventions, multidimensional interventions or pedagogical interventions. The findings confirm some positive effects for widening participation outreach programmes on a range of outcomes including students' college readiness, educational aspirations and college enrolment. The review argues for consistency in the way in which educational outcomes are measured, as well as the need for cross‐collaboration and sharing of data between schools and universities, to enable more effective measurement of widening participation programmes in future research.

Context and implication

Rationale for this study

This study gives an up‐to‐date synthesis of outreach interventions in secondary schools which aim to widen participation at higher education. A review of its kind has not been conducted in the last decade.

Why the new findings matter

Findings highlight the most effective new interventions, as well as, the challenges in defining success, research design and collecting accurate data across secondary and tertiary educational institutions.

Implications for educational researchers and policy makers

This systematic review provides an overview for widening participation WP practitioners of what types of outreach interventions are out there, offering templates and ideas for introducing these kinds of initiatives in other universities and partnership schools. The paper highlights to policy makers, the need to create policies that enable cross‐collaboration and sharing of data between schools and universities. Implications for researchers include discussion around how success is being defined, what outcomes are being measured, the need for longitudinal studies with larger sample sizes as well as the collection of baseline data of participants.
Composite event‐triggered H∞ control for nonlinear switched singular systems with a mode‐dependent triggering strategy
Authors: Yang Anqing , Zhao Zhenli , Shi Hongpeng , Ma Shuping
Published: June 2023

This paper considers the event‐triggered control problem of nonlinear switched singular systems (NSSSs) with incremental quadratic constraints (IQCs) via a mode‐dependent hybrid triggering strategy. First, impulsive control is introduced to reduce the effect of impulse caused by switching, and the closed‐loop system is modeled as an impulsive NSSS. Then, a novel mode‐dependent hybrid event‐triggering strategy (ETS) consisting of disturbance‐influenced ETS and Lyapunov‐function‐dependent ETS is constructed to avoid Zeno behavior and asynchronous phenomena. Based on this ETS and admissible edge‐dependent average dwell time (AED‐ADT) method, some new sufficient conditions in terms of linear matrix inequalities (LMIs) are derived to ensure that the closed‐loop system is regular, impulse‐free, has a unique solution, and is globally uniformly asymptotically stable (GUAS) with a weighted performance. Further, Zeno behavior is excluded by calculating the minimum lower bound of inter‐event time. Finally, a numerical example and a practical application are proposed to demonstrate the validity of the results.
A sensor‐based assistive technology for lower‐limb‐disabled agricultural workers and abled female workers for tractor clutch and brake operation
Authors: Hota Smrutilipi , Tewari V. K. , Dhruw Laxmi Kant , Chandel Abhilash K.
Published: June 2023

Agricultural mechanization although reduces the food demand and supply gap through improved and smart technologies, it also risks the lower‐limb disability of workers due to accidents that restrict them to participate in agricultural operations due to the unavailability of appropriate assistive technologies. The lack of use of ergonomics further minimizes the inclusion of female workers in farming operations. Therefore, this study is focused on the development of a sensor‐based wireless hand control system for tractor clutch and brake operation to assist lower‐limb‐disabled agricultural workers and abled females in tractor operation. Actuation force and speed of conventional clutch and brake pedals were evaluated using an integrated foot transducer and used as a reference for the design of the system (clutch: 92–310 N, 36–43 mm/s; brake: 106–329 N, 57–63 mm/s). The hand control system consists of a transmitter and a receiver node incorporating a single‐board computer, matrix keypad, voltage regulators, relay switches, wireless communication through radio frequency modules, and electric linear actuators connected with the pedals through L‐shaped clips, nuts, bolts, and chains. The response time of the developed system was determined as 100 ms and the stopping distance of the tractor using the hand control system ranged from 44.0 to 190.7 cm at a forward speed of 2.1–7.9 km/h. The ergonomic evaluation measured using the K4b2 oxygen analyzer identified the foot control usage in tractors as high energy consuming (9.7–15.1 kJ/min) compared with the hand control usage (7.3–14.1 kJ/min). Electromyography‐root mean square (EMG‐RMS) of upper limb muscle, extension digitorum was found to be highest (14.76–45.29 µV) and was significantly affected by forward speed, gender, subjects, and type of control (p < 0.01) whereas, EMG‐RMS of other selected upper limb muscles, middle deltoid, flexor carpi radialis, and brachioradialis was not significantly affected by the type of control (foot or hand). Muscle workload of all the muscles was observed within the recommended limit (<30%) during the tractor operation with the developed hand control system. The developed hand control system provides options to bypass foot‐based actuation requirement for lower limb disabled as well as female workers. The novel design requires minimal workplace and operating forces and is inclusive of operator ergonomics.
Development of a real‐time work‐related postural risk assessment system of farm workers using a sensor‐based artificial intelligence approach
Authors: Singh Lakhwinder Pal , Kumar Praveen , Lohan Shiv Kumar
Published: June 2023

In recent years, the promotion of farm mechanization has been directed toward reducing the human discomfort and fatigue associated with various agricultural work‐related activities. During these activities, many factors (like force, awkward posture, vibration, repetition, etc.) play a significant role in causing musculoskeletal disorders. Second, ergonomic risk assessment of physical work is conventionally conducted through observation and direct/indirect physiological measurements. However, these methods are time‐consuming and require human subjects to perform the motion to obtain detailed body movement data. In the present study, a semiautomatic rapid entire body assessment (REBA) evaluation tool is developed for real‐time assessment of agricultural work‐related musculoskeletal disorders risk of farm workers using Kinect V2 sensor‐based artificial intelligence approach. It allows the investigator speedy detect of awkward postures leading to critical conditions and to reduce subjective bias. It is useful to analyze online as well as offline posture analysis, it detects the critical areas of the body posture, which may lead to the musculoskeletal disorders of agricultural workers, and suggest aptly to correct the posture. The Kinect V2 REBA assessment score was found with a factual significant match with the reference expert evaluation as reflected by the Landis and Koch scale k = 0.673 (p < 0.001), 95% confidence interval (CI) for the left side, and k = 0.644 (p < 0.001), 95% CI for the right side of the body respectively.
Climate and environmental data contribute to the prediction of grain commodity prices using deep learning
Authors: Wang Zilin , French Niamh , James Thomas , Schillaci Calogero , Chan Faith , Feng Meili , Lipani Aldo
Published: June 2023

Background

Grain commodities are important to people's daily lives and their fluctuations can cause instability for households. Accurate prediction of grain prices can improve food and social security.

Methods & Materials

This study proposes a hybrid Long Short‐Term Memory (LSTM)‐Convolutional Neural Network (CNN) model to forecast weekly oat, corn, soybean and wheat prices in the United States market. The LSTM‐CNN is a multivariate model that uses weather data, macroeconomic data, commodities grain prices and snow factors, including Snow Water Equivalent (SWE), snowfall and snow depth, to make multistep ahead forecasts.

Results

Of all the features, the snow factor is used for the first time for commodity price forecasting. We used the LSTM‐CNN model to evaluate the 5, 10, 15 and 20 weeks ahead forecasting and this hybrid model had the lowest Mean Squared Error (MSE) at 5, 10 and 15 weeks ahead of prediction. In addition, Shapley values were calculated to analyse the feature contribution of the LSTM‐CNN model when forecasting the testing set. Based on the feature contribution, SWE ranked third, fifth and seventh in feature importance in the 5‐week ahead forecast for corn, oats and wheat, respectively, and 7–8 places higher than total precipitation, indicating the potential use of SWE in grain price forecasting.

Conclusion

The hybrid multivariate LSTM‐CNN model outperformed other models and the newly involved climate data, SWE, showed the research potential of using snow as an input variable to predict grain prices over a multistep ahead time horizon.