bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Analysis of the Blade Coating Process Using Non‐Newtonian Nanofluid with Magnetohydrodynamic (MHD) and Slip Effects
Authors: Javed Muhammad Asif , Ghaffari Abuzar , Khan Sami Ullah , Elattar Ehab
Published: April 2024

The coating process is widely used in various industries to enhance the production quality and efficiency. This study gives a comprehensive analysis of non‐isothermal blade coating of non‐Newtonian nanofluid incorporating magnetic, thermophoresis, and Brownian effects. The mathematical equations derived from mass, momentum, and energy conservation laws are initially streamlined by means of lubrication approximation theory (LAT). Subsequently, these dimensionless equations are solved in dimensionless form numerically using fourth order Runge–Kutta and Newton–Raphson methods. This study includes the effects of the slip parameter, magnetohydrodynamic (MHD) and other material parameters on the coating thickness (), blade load, velocity, temperature, concentration, and pressure profiles through graphs and tables. The velocity of molten polymer increases near the substrate while it decreases near the blade surface as the slip parameter increases. The temperature distribution increases as the Brinkman number rises, with the maximum temperature occurring in the nip region of the flow. The coating thickness and load‐carrying force for both plane and exponential coater increase with higher values of the magnetohydrodynamic (MHD) parameter.
Benzo[a]pyrene promotes an epithelial‐to‐mesenchymal transition process in MCF10A cells and mammary tumor growth and brain metastasis in female mice
Authors: Castillo‐Sanchez Rocio , Garcia‐Hernandez Alejandra , Torres‐Alamilla Pablo , Cortes‐Reynosa Pedro , Candanedo‐Gonzales Fernando , Salazar Eduardo Perez
Published: April 2024

Breast cancer is the most frequent neoplasia in developed countries and the leading cause of death in women worldwide. Epithelial‐to‐mesenchymal transition (EMT) is a cellular process through which epithelial cells decrease or lose their epithelial characteristics and gain mesenchymal properties. EMT mediates tumor progression, because tumor cells acquire the capacity to execute the multiple steps of invasion and metastasis. Benzo[a]pyrene (B[a]P) is an environmental organic pollutant generated during the burning of fossil fuels, wood, and other organic materials. B[a]P exposition increases the incidence of breast cancer, and induces migration and/or invasion in MDA‐MB‐231 and MCF‐7 breast cancer cells. However, the role of B[a]P in the induction of an EMT process and metastasis of mammary carcinoma cells has not been studied in detail. In this study, we demonstrate that B[a]P induces an EMT process in MCF10A mammary non‐tumorigenic epithelial cells. In addition, B[a]P promotes the formation of larger tumors in Balb/cJ mice inoculated with 4T1 cells than in untreated mice and treated with dimethyl sulfoxide (DMSO). B[a]P also increases the number of mice with metastasis to brain and the total number of brain metastatic nodules in Balb/cJ mice inoculated with 4T1 cells compared with untreated mice and treated with DMSO. In conclusion, B[a]P induces an EMT process in MCF10A cells and the growth of mammary tumors and metastasis to brain in Balb/cJ mice inoculated with 4T1 cells.
Four and a half LIM domains 2 (FHL2) attenuates tumorigenesis of gastrointestinal stromal tumors (GISTs) by negatively regulating KIT signaling
Authors: Zhang Shaoting , Zhang Liangying , Zhang Dan , Guo Yue , Gao Yisha , Jiang Zongying , Li Shujing , Liu Anbu , Cao Xu , Tian Jinhai , Zhao Sien , Yu Yuanyuan , Yang Wei , Bai Ru , Huang Ling , Yan Hongli , Zhao Hui , Sun Jianmin
Published: April 2024

Gastrointestinal stromal tumors (GISTs) are predominately induced by KIT mutants. In this study, we found that four and a half LIM domains 2 (FHL2) was highly expressed in GISTs and KIT signaling dramatically increased FHL2 transcription while FHL2 inhibited KIT transcription. In addition, our results showed that FHL2 associated with KIT and increased the ubiquitination of both wild‐type KIT and primary KIT mutants in GISTs, leading to decreased expression and activation of KIT although primary KIT mutants were less inhibited by FHL2 than wild‐type KIT. In the animal experiments, loss of FHL2 expression in mice carrying germline KIT/V558A mutation which can develop GISTs resulted in increased tumor growth, but increased sensitivity of GISTs to imatinib treatment which is used as the first‐line targeted therapy of GISTs, suggesting that FHL2 plays a role in the response of GISTs to KIT inhibitor. Unlike wild‐type KIT and primary KIT mutants, we further found that FHL2 didn't alter the expression and activation of drug‐resistant secondary KIT mutants. Taken together, our results indicated that FHL2 acts as the negative feedback of KIT signaling in GISTs while primary KIT mutants are less sensitive and secondary KIT mutants are resistant to the inhibition of FHL2.
On the jerk and snap in motion along non‐lightlike curves in Minkowski 3‐space
Authors: Elsharkawy Ayman , Cesarano Clemente , Alhazmi Hadil
Published: April 2024

In this paper, we study the jerk vector that is the rate of change of the acceleration vector over time. In three‐dimensional space, the decomposition of the jerk vector is a new concept in the field. This decomposition expresses the jerk vector as the sum of three unique components in specific directions: the tangential direction, the radial direction in the osculating plane, and the radial direction in the rectifying plane. The snap vector is the rate of change of the jerk vector over time. In this paper, the authors examine non‐relativistic particles moving along non‐lightlike Frenet curves at low speeds compared to the speed of light in Minkowski 3‐space. They resolve the jerk and snap vectors using Frenet–Serret frames. Additionally, the cases for motion along non‐lightlike Frenet planar curves in the Minkowski 3‐space are given as corollaries. To help understand these results, the paper provides some illustrative examples
High gain D‐band hybrid integrated on‐chip antenna based on low‐cost printed circuit board packaging technology
Authors: Wang Yanjun , Yi Xiang , Che Wenquan , Xue Quan
Published: April 2024

A high gain D‐band hybrid integrated on‐chip antenna (OCA) based on a low‐cost printed circuit board (PCB) packaging technology is analyzed and designed in a standard 40‐nm CMOS process in this paper. The proposed OCA is a hybrid structure of a slotted patch OCA with off‐chip PCB ground and off‐chip dielectric resonator (DR). The proposed OCA exhibits a simulated gain of 3.5 dBi and 53% radiation efficiency at 150 GHz. The simulated impedance bandwidth is 20 GHz. The radiation performance and impedance bandwidth of the OCA are observably improved with the proposed techniques. The proposed OCA occupies 0.52 × 0.56 mm2, and addresses the highly desirable yet challenging overall design of future low‐cost integrated millimeter‐wave (mm‐Wave) and terahertz (THz) systems, which hit the mark on cost and compatibility.
Age estimation and validation in otoliths, spines, and fin rays from four central Texas fishes
Authors: Pfennig Meredith B. , Crane Derek P. , Smith Nate G. , Buckmeier Dave L.
Published: April 2024

Objective

Age estimation methods have not been validated for many species. Thus, we focused this age estimation study on four species from central Texas: the Guadalupe Bass Micropterus treculii, Channel Catfish Ictalurus punctatus, Gray Redhorse Moxostoma congestum, and Redbreast Sunfish Lepomis auritus. Our objectives for each species were to (1) investigate whether increments form annually in otoliths, fin rays, or spines; (2) determine the seasonal timing of zone deposition in each calcified structure; and (3) compare age estimates between otoliths and fin rays or spines.

Methods

Fish were sampled from central Texas waters and injected with oxytetracycline (OTC) quarterly in 2021. In July 2022, otoliths and fin rays or spines were collected to determine whether the increments formed annually and to estimate age.

Result

On average, two readers identified the correct number of annuli after the OTC mark in at least 95% of Gray Redhorse, Guadalupe Bass, and Redbreast Sunfish otoliths but in only 69% of Channel Catfish otoliths. However, the more experienced reader identified the correct number of annuli in at least 95% of otoliths from age-2–4 Channel Catfish. Compared to otoliths, the correct number of annuli after the OTC mark was identified in a smaller percentage of fin rays or spines (47–62%). The probability of identifying the correct number of annuli after the OTC mark differed between the two readers for all spines and fin rays. Age difference plots revealed that age estimates based on fin rays or spines were either overestimated or underestimated compared to otolith-based ages for all species.

Conclusion

We consider annual increment formation in otoliths to be validated for all age-classes of Gray Redhorse, Guadalupe Bass, and Redbreast Sunfish examined and for ages 2–4 of Channel Catfish. Differences in correctness between readers were most likely due to differences in age estimation experience. Given the level of error observed in our study, caution is advised if using age estimates from unvalidated structures and species.
Work experience of breastfeeding nurses returning to work after maternity leave in Liaoning Province of China: A qualitative study
Authors: Wan Xin‐li , Yang Jia‐yi , Pan Ying‐li
Published: April 2024

Aim

With the implementation of China's three‐child policy in 2021, the nurse population faces an increase in the number of breastfeeding nurses returning to work after maternity leave. This study aims to describe the work experience of breastfeeding nurses returning to work after maternity leave.

Design

A qualitative descriptive design.

Methods

The data were collected through semi‐structured interviews with eight nurses and analysed through Braun and Clarke's thematic analysis.

Results

Three themes and nine sub‐themes emerged from the analysis of the interviews: changes in nurses (emotional changes, physical changes and changes in work); needs for an improving work environment (needs for a supportive workplace and nurse shortage); support for breastfeeding nurses (support from coworkers, support from the manager, support from the organisation and own need for work).

Public Contribution

This study highlighted that breastfeeding nurses need an adjustment period when they return to work after maternity leave. Successful breastfeeding requires support from coworkers, managers and the organisation. In addition, workplace support for breastfeeding and management for nurses needs to be improved.
RAF1 gene fusions are recurrent driver events in infantile fibrosarcoma‐like mesenchymal tumors
Authors: Motta Marialetizia , Barresi Sabina , Pizzi Simone , Bifano Delfina , Lopez Marti Jennifer , Garrido‐Pontnou Marta , Flex Elisabetta , Bruselles Alessandro , Giovannoni Isabella , Rotundo Giovannina , Fragale Alessandra , Tirelli Valentina , Vallese Silvia , Ciolfi Andrea , Bisogno Gianni , Alaggio Rita , Tartaglia Marco
Published: April 2024

Infantile fibrosarcomas (IFS) and congenital mesoblastic nephroma (CMN) are rare myofibroblastic tumors of infancy and early childhood commonly harboring the ETV6::NTRK3 gene fusion. IFS/CMN are considered as tumors with an ‘intermediate prognosis’ as they are locally aggressive, but rarely metastasize, and generally have a favorable outcome. A fraction of IFS/CMN‐related neoplasms are negative for the ETV6::NTRK3 gene rearrangement and are characterized by other chimeric proteins promoting MAPK signaling upregulation. In a large proportion of these tumors, which are classified as IFS‐like mesenchymal neoplasms, the contributing molecular events remain to be identified. Here, we report three distinct rearrangements involving RAF1 among eight ETV6::NTRK3 gene fusion‐negative tumors with an original histological diagnosis of IFS/CMN. The three fusion proteins retain the entire catalytic domain of the kinase. Two chimeric products, GOLGA4::RAF1 and LRRFIP2::RAF1, had previously been reported as driver events in different cancers, whereas the third, CLIP1::RAF1, represents a novel fusion protein. We demonstrate that CLIP1::RAF1 acts as a bona fide oncoprotein promoting cell proliferation and migration through constitutive upregulation of MAPK signaling. We show that the CLIP1::RAF1 hyperactive behavior does not require RAS activation and is mediated by constitutive 14‐3‐3 protein‐independent dimerization of the chimeric protein. As previously reported for the ETV6::NTRK3 fusion protein, CLIP1::RAF1 similarly upregulates PI3K‐AKT signaling. Our findings document that RAF1 gene rearrangements represent a recurrent event in ETV6::NTRK3‐negative IFS/CMN and provide a rationale for the use of inhibitors directed to suppress MAPK and PI3K‐AKT signaling in these cancers. © 2024 The Pathological Society of Great Britain and Ireland.
ΔNp73 and its effector targets promote colorectal peritoneal carcinosis and predict survival
Authors: Pastor‐Morate Daniel , Amigo‐Morán Lidia , Garranzo‐Asensio María , Rejas‐González Raquel , Carnicero Patricia , Rodríguez Nuria , Pérez‐Robledo Juan Pedro , Barderas Rodrigo , Prieto‐Nieto Isabel , Domínguez Gemma
Published: April 2024

Peritoneal metastasis of colorectal origin appears in ~10–15% of patients at the time of diagnosis and in 30–40% of cases with disease progression. Locoregional spread through the peritoneum is considered stage IVc and is associated with a poor prognosis. The development of a regional therapeutic strategy based on cytoreductive surgery, and hyperthermic intra‐abdominal chemotherapy has significantly altered the course of the disease. Although recent evidence supports the benefits of cytoreductive surgery, the benefits of hyperthermic intra‐abdominal chemotherapy are, however, still a matter of debate. Understanding the molecular alterations underlying the disease is crucial for developing new therapeutic strategies. Here, we evaluated the involvement in peritoneal dissemination of the oncogenic isoform of TP73, ΔNp73, and its effector targets in in vitro and mouse models, and in 30 patients diagnosed with colorectal peritoneal metastasis. In an orthotopic mouse model, we observed that tumor cells overexpressing ΔNp73 present a higher avidity for the peritoneum and that extracellular vesicles secreted by ΔNp73‐upregulating tumor cells enhance their dissemination. In addition, we identified that tumor cells overexpressing ΔNp73 present with dysregulation of genes associated with an epithelial/mesothelial‐to‐mesenchymal transition (MMT) and that mesothelial cells exposed to the conditioned medium of tumor cells with upregulated ΔNp73 present a mesenchymal phenotype. Lastly, ΔNp73 and its effector target RNAs were dysregulated in our patient series, there were positive correlations between ΔNp73 and its effector targets, and MSN and ITGB4 (ΔNp73 effectors) predicted patient survival. In conclusion, ΔNp73 and its effector targets are involved in the peritoneal dissemination of colorectal cancer and predict patient survival. The promotion of the EMT/MMT and modulation of the adhesion capacity in colorectal cancer cells might be the mechanisms triggered by ΔNp73. Remarkably, ΔNp73 protein is a druggable protein and should be the focus of future studies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Event‐free survival in relapsed and refractory rhabdomyosarcoma treated on cooperative group phase II trials: A report from the Children's Oncology Group
Authors: Metts Jonathan , Xue Wei , Gao Zhengya , Oberoi Sapna , Weiss Aaron R. , Venkatramani Rajkumar , Harrison Douglas J.
Published: April 2024

Background

Novel therapies are needed for relapsed and refractory rhabdomyosarcoma (RRMS). Phase II clinical trials in RRMS have typically utilized radiologic response as the primary activity endpoint, an approach that poses several limitations in RRMS. In this analysis, we aimed to estimate an event‐free survival (EFS) endpoint for RRMS that could be used as a benchmark for future studies.

Procedure

We performed a retrospective study of patients with RRMS enrolling on 13 single‐agent phase II Children's Oncology Group and legacy group trials from 1997 to 2016. All included trials used radiographic response as their primary activity endpoint. Six‐month EFS was estimated from time of trial enrollment with 95% confidence intervals. Clinical characteristics, including trial of enrollment, sex, age, race, histology, number of prior chemotherapies, and radiographic response were evaluated for their impact on 6‐month EFS.

Results

We identified 175 patients across 13 trials. The 6‐month EFS was 16.8% (11.6%–22.8%). No differences were seen in 6‐month EFS based on age, sex, race, or histology. There were nonsignificant trends toward improved 6‐month EFS for patients with less than or equal to two prior lines of therapy versus higher than two, for patients enrolled on trials that achieved their primary radiographic response endpoint versus trials that did not, and for patients who achieved complete or partial response compared to those achieving stable disease.

Conclusions

The prognosis of RRMS enrolled on single‐agent phase II trials is poor. This pooled 6‐month EFS of RRMS on single‐agent trials may be used as a RRMS‐specific benchmark for future single‐agent phase II trials.
Updated core competencies in pharmacoepidemiology to inform contemporary curricula and training for academia, government, and industry
Authors: Osborne Vicki , Goodin Amie , Brown Joshua , Winterstein Almut G. , Bate Andrew , Cohet Catherine , Pont Lisa , Moeny David , Klungel Olaf , Pinheiro Simone , Seeger John , Chan K. Arnold , Edlavitch Stanley , Tilson Hugh , Layton Deborah
Published: April 2024

Purpose

The first paper to specify the core content of pharmacoepidemiology as a profession was published by an ISPE (International Society for Pharmacoepidemiology) workgroup in 2012 (Jones JK et al. PDS 2012; 21[7]:677–689). Due to the broader and evolving scope of pharmacoepidemiology, ISPE considers it important to proactively identify, update and expand the list of core competencies to inform curricula of education programs; thus, better positioning pharmacoepidemiologists across academic, government (including regulatory), and industry positions. The aim of this project was to update the list of core competencies in pharmacoepidemiology.

Methods

To ensure applicability of findings to multiple areas, a working group was established consisting of ISPE members with positions in academia, industry, government, and other settings. All competencies outlined by Jones et al. were extracted from the initial manuscript and presented to the working group for review. Expert‐based judgments were collated and used to identify consensus. It was noted that some competencies could contribute to multiple groups and could be directly or indirectly related to a group.

Results

Five core domains were proposed: (1) Epidemiology, (2) Clinical Pharmacology, (3) Regulatory Science, (4) Statistics and data science, and (5) Communication and other professional skills. In total, 55 individual competencies were proposed, of which 25 were new competencies. No competencies from the original work were dropped but aggregation or amendments were made where considered necessary.

Conclusions

While many core competencies in pharmacoepidemiology have remained the same over the past 10 years, there have also been several updates to reflect new and emerging concepts in the field.
Applying structural equation modeling to examine the role of teacher beliefs and practices in differentiated instruction in physical education: Multiple mediation analyses
Authors: Wen Qingyun , Cai Juan
Published: April 2024

Differentiated instruction remains one of the most important frameworks for the global education community to achieve sustainable educational development goals and inclusive education. It is also one of the most critical challenges for teachers in different subjects. This study used structural equation modeling to examine the role of teachers' practices and beliefs in implementing differentiated instruction in physical education. Using a sample of 527 preservice teachers, we found that a growth mindset was the strongest predictor of differentiated instruction, followed by flexible grouping and differentiating the curriculum. In addition, multiple mediation analyses revealed that differentiating the curriculum and flexible grouping mediated the relationship between a growth mindset and differentiated instruction. We also guide teacher educators to develop teachers' growth mindsets and help teachers better understand differentiated instruction in physical education.
Characterization of a chromatin‐associated TCF7L1 complex in human embryonic stem cells
Authors: Vuong Linh M. , Pan Songqin , Sierra Robert A. , Waterman Marian L. , Gershon Paul D. , Donovan Peter J.
Published: April 2024

Human embryonic stem cells (hESCs) resemble the pluripotent epiblast cells found in the early postimplantation human embryo and represent the “primed” state of pluripotency. One factor that helps primed pluripotent cells retain pluripotency and prepare genes for differentiation is the transcription factor TCF7L1, a member of a small family of proteins known as T cell factors/Lymphoid enhancer factors (TCF/LEF) that act as downstream components of the WNT signaling pathway. Transcriptional output of the WNT pathway is regulated, in part, by the activity of TCF/LEFs in conjunction with another component of the WNT pathway, β‐CATENIN. Because TCF7L1 plays an important role in regulating pluripotency, we began to characterize the protein complex associated with TCF7L1 when bound to chromatin in hESCs using rapid immunoprecipitation of endogenous proteins (RIME).  Data are available via ProteomeXchange with identifier PXD047582. These data identify known and new partners of TCF7L1 on chromatin and provide novel insights into how TCF7L1 and pluripotency itself might be regulated.
Tracheostomy and inpatient outcomes among children with congenital central hypoventilation syndrome: A kids' inpatient database study
Authors: Tsou Po‐Yang , Tapia Ignacio E.
Published: April 2024

Study Objectives

Congenital central hypoventilation syndrome (CCHS) is a rare disease predisposing children to respiratory failure due to abnormal ventilatory drive. Variability in hypoventilation and respiratory support need have been reported. We aim to identify clinical variables associated with incident tracheostomy and common etiologies of hospitalization among children with CCHS.

Methods

Hospital discharge records were obtained for children (<21 years) with CCHS hospitalized between 2006 and 2019 from the Kid's Inpatient Database. Primary diagnostic categories for hospitalizations with CCHS were summarized. Multivariable logistic regression models were used to explore risk factors associated with incident tracheostomy.

Results

Among 2404 hospitalizations with CCHS, 133 (5.5%) had incident tracheostomy, 1230 (51.2%) had established tracheostomy, and 1041 (43.3%) had no tracheostomy. Compared with children without tracheostomy, those with incident tracheostomy were younger, had a history of prematurity, congenital heart disease, laryngeal, glottic, and subglottic stenosis (LGSS), congenital airway anomalies, neuromuscular weakness, gastroesophageal reflux disease. Children without tracheostomy had higher mortality than those with tracheostomy status (2.19% vs. 0.66%). Multivariable‐adjusted analyses showed that incident tracheostomy was associated with infancy (0–1 years), neuromuscular weakness, and congenital heart disease. Most common diagnostic categories include (1) diseases of the respiratory system (30.23%), (2) injury and poisoning (9.35%), and (3) diseases of the nervous system and sense organs (6.71%).

Conclusions

Children with CCHS who received incident tracheostomy are more likely to be younger and with LGSS, neuromuscular weakness and congenital heart disease. Clinicians should be aware of these risk factors representing more severe CCHS with earlier manifestation needing tracheostomy. Higher mortality among nontracheostomy group highlights the need for considering tracheostomy in caring for children with CCHS.
Cystic fibrosis in Iceland and the high prevalence of the N1303K variant
Authors: Elidottir Helga , Bjarnadottir Selma R. , Baldursson Olafur , Jonsdottir Brynja
Published: April 2024

Background

Cystic fibrosis (CF) is most common in populations of Northern European ancestry where the F508del variant predominates. In 2020, Iceland became a member of the European Cystic Fibrosis Society Patient Registry, and we launched an epidemiological study of CF in Iceland. The study aimed to determine the prevalence and the genetic variants present in the country. Furthermore, we aimed to describe the previous and the current situation regarding lung function, infections, complications, treatment, and follow‐up to understand the strengths and weaknesses of CF care in Iceland.

Methods

This retrospective study included all individuals in Iceland with a confirmed CF diagnosis between 1955 and 2021. We conducted a medical records search for CF diagnosis codes and found 30 people with CF who were included in the study. Two hundred sixteen clinical variables were registered. A descriptive analysis of these was performed.

Results

The prevalence of CF in Iceland is 0.372:10,000 inhabitants. The F508del is the most common CF transmembrane conductance regulator (CFTR) variant (46.4%), closely followed by N1303K (44.6%). Staphylococcus aureus was the most common airway pathogen, followed by Pseudomonas aeruginosa. Nasal polyps and CF‐related diabetes were the most common complications. Modern CF medications, including the recent CFTR modulators, are available.

Conclusion

Even though Iceland has a relatively low prevalence of CF, it holds the highest known prevalence of the N1303K variant in Europe. Access to necessary treatment is satisfactory, but improvements are advisable for some aspects of the routine assessments by best practice guidelines.
Outcomes of 10 years of PSA screening for prostate cancer in Norwegian men with Lynch syndrome
Authors: Grindedal Eli Marie , Zucknick Manuela , Stormorken Astrid , Rønne Elin , Tandstad Nora M. , Isaacs William B. , Axcrona Karol , Mæhle Lovise
Published: April 2024

Background

Pathogenic germline variants in the mismatch repair (MMR) genes are associated with an increased risk of prostate cancer (PCa). Since 2010 we have recommended MMR carriers annual PSA testing from the age of 40. Prospective studies of the outcome of long‐term PSA screening are lacking. This study aimed to investigate the incidence and characteristics of PCa in Norwegian MMR carriers attending annual PSA screening (PSA threshold >3.0 ng/mL) to evaluate whether our recommendations should be continued.

Methods

This is a prospective observational study of 225 male MMR carriers who were recommended annual PSA screening by the Section of Inherited Cancer, Oslo University Hospital from 2010 and onwards. Incidence and tumor characteristics (age, PSA at diagnosis, Gleason score, TNM score) were described. IHC and MSI‐analyses were done on available tumors. Standardized incidence ratio (SIR) was calculated based on data from the Cancer Registry of Norway.

Results

Twenty‐two of 225 (9.8%) had been diagnosed with PCa, including 10/69 (14.5%) MSH2 carriers and 8/61 (13.1%) MSH6 carriers. Ten of 20 (50%) tumors had Gleason score ≥4 + 3 on biopsy and 6/11 (54.5%) had a pathological T3a/b stage. Eight of 17 (47.1%) tumors showed abnormal staining on IHC and 3/13 (23.1%) were MSI‐high. SIR was 9.54 (95% CI 5.98–14.45) for all MMR genes, 13.0 (95% CI 6.23–23.9) for MSH2 and 13.74 for MSH6 (95% CI 5.93–27.08).

Conclusions

Our results indicate that the MMR genes, and especially MSH2 and MSH6, are associated with a significant risk of PCa, and a high number of tumors show aggressive characteristics. While the impact of screening on patient outcomes remains to be more firmly established, the high SIR values we observe provide support for continued PSA screening of MSH2 and MSH6 carriers. Studies are needed to provide optimal recommendations for PSA‐threshold and to evaluate whether MLH1 and PMS2 carriers should not be recommended screening.
Detection and recognition of the invasive species, Hylurgus ligniperda, in traps, based on a cascaded convolution neural network
Authors: Zhang Xiahui , Li Zhengyi , Ren Lili , Liu Xuanxin , Zeng Tian , Tao Jing
Published: April 2024

BACKGROUND

Hylurgus ligniperda, an invasive species originating from Eurasia, is now a major forestry quarantine pest worldwide. In recent years, it has caused significant damage in China. While traps have been effective in monitoring and controlling pests, manual inspections are labor‐intensive and require expertise in insect classification. To address this, we applied a two‐stage cascade convolutional neural network, YOLOX‐MobileNetV2 (YOLOX‐Mnet), for identifying H. ligniperda and other pests captured in traps. This method streamlines target and non‐target insect detection from trap images, offering a more efficient alternative to manual inspections.

RESULTS

Two cascade convolutional neural network models were employed in two stages to detect both target and non‐target insects from images captured in the same forest. Initially, You Only Look Once X (YOLOX) served as the target detection model, identifying insects and non‐insects from the collected images, with non‐insect targets subsequently filtered out. In the second stage, MobileNetV2, a classification network, classified the captured insects. This approach effectively reduced false positives from non‐insect objects, enabled the inclusion of additional classification terms for multi‐class insect classification models, and utilized sample control strategies to enhance classification performance.

CONCLUSION

Application of the cascade convolutional neural network model accurately identified H. ligniperda, and Mean F1‐score of all kinds of insects in the trap was 0.98. Compared to traditional insect classification, this method offers great improvement in the identification and early warning of forest pests, as well as provide technical support for the early prevention and control of forest pests. © 2024 Society of Chemical Industry.
Salivary proteins NlSP5 and NlSP7 are required for optimal feeding and fitness of the brown planthopper, Nilaparvata lugens
Authors: Liu Xin‐Yang , Cai Xin‐Yu , Wu Hui‐Jie , Wan Yi , Wei Sheng‐Fei , Xu Hai‐Jun
Published: April 2024

BACKGROUND

Saliva has a crucial role in determining the compatibility between piercing–sucking insects and their hosts. The brown planthopper (BPH) Nilaparvata lugens, a notorious pest of rice in East and Southeast Asia, secretes gelling and watery saliva when feeding on rice sap. Nlsalivap‐5 (NlSP5) and Nlsalivap‐7 (NlSP7) were identified as potential planthopper‐specific gelling saliva components, but their biological functions remain unknown.

RESULTS

Here, we showed by transcriptomic analyses that NlSP5 and NlSP7 were biasedly expressed in the salivary glands of BPHs. Using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9‐mediated genome‐editing system, we constructed NlSP5 and NlSP7 homozygous mutants (NlSP5−/− and NlSP7−/−). Electrical penetration graph assay showed that NlSP5−/− and NlSP7−/− mutants exhibited abnormal probing and feeding behaviors. Bioassays revealed that the loss‐of‐function of NlSP5 and NlSP7 significantly reduced the fitness of BPHs, with extended developmental duration, shortened lifespan, reduced weight, and impaired fecundity and hatching rates.

CONCLUSION

These findings deepen our understanding of the BPH–host interaction and may provide potential targets for the management of rice planthoppers. © 2024 Society of Chemical Industry.
The pyrexia channel remodels egg‐laying of Liriomyza huidobrensis in response to temperature change
Authors: Wu Yaxi , Wang Huimin , Hu Zhihao , Pan Mengchen , Wu Yanan , Guo Xiaojiao , Ge Jin , Wang Zhengjun , Yang Meiling
Published: April 2024

BACKGROUND

The pea leafminer, Liriomyza huidobrensis, is one of the most important insect pests on vegetables and ornamentals. The survival and egg‐laying behavior of leafminers are markedly affected by the environment temperature. However, the mechanisms underlying the relationship between egg‐laying and temperature are still largely unknown.

RESULTS

Here, we find that leafminers have evolved an adaptive strategy to overcome the stress from high or low temperature by regulating oviposition‐punching plasticity. We further show that this oviposition‐punching plasticity is mediated by the expression of pyx in the ovipositor when subjected to disadvantageous temperature. Specifically, down‐regulation of pyx expression in leafminers under low temperature stress led to a significant decrease in the swing numbers of ovipositor and puncture area of the egg spot, and consequently the lower amount of egg‐laying compared to leafminers at ambient temperature. Conversely, activation of pyx expression under high temperature stress increased the swing numbers and puncture area, still resulting in a reduction of egg‐laying amount.

CONCLUSION

Thereby, leafminers are able to coordinate pyx channel expression level and accordingly depress the oviposition. Our study uncovers a molecular mechanism underlying the adaptive strategy in insects that can avoid disadvantageous temperature for reproducing offspring. © 2024 Society of Chemical Industry.
Tumor growth and overall survival modeling to support decision making in phase Ib/II trials: A comparison of the joint and two‐stage approaches
Authors: Marchand Mathilde , Gonçalves Antonio , Mercier François , Chanu Pascal , Jin Jin Y. , Guedj Jérémie , Bruno René
Published: April 2024

Model‐based tumor growth inhibition (TGI) metrics are increasingly used to predict overall survival (OS) data in Phase III immunotherapy clinical trials. However, there is still a lack of understanding regarding the differences between two‐stage or joint modeling methods to leverage Phase I/II trial data and help early decision‐making. A recent study showed that TGI metrics such as the tumor growth rate constant KG may have good operating characteristics as early endpoints. This previous study used a two‐stage approach that is easy to implement and intuitive but prone to bias as it does not account for the relationship between the longitudinal and time‐to‐event processes. A relevant alternative is to use a joint modeling approach. In the present article, we evaluated the operating characteristics of TGI metrics using joint modeling, assuming an OS model previously developed using historical data. To that end, we used TGI and OS data from IMpower150—a study investigating atezolizumab in over 750 patients suffering from non‐small cell lung cancer—to mimic randomized Phase Ib/II trials varying in terms of number of patients included (40 to 15 patients per arm) and follow‐up duration (24 to 6 weeks after the last patient included). In this context, joint modeling did not outperform the two‐stage approach and provided similar operating characteristics in all the investigated scenarios. Our results suggest that KG geometric mean ratio could be used to support early decision‐making provided that 30 or more patients per arm are included and followed for at least 12 weeks.
Comparing various Bayesian random‐effects models for pooling randomized controlled trials with rare events
Authors: Yao Minghong , Jia Yulong , Mei Fan , Wang Yuning , Zou Kang , Li Ling , Sun Xin
Published: April 2024

The meta‐analysis of rare events presents unique methodological challenges owing to the small number of events. Bayesian methods are often used to combine rare events data to inform decision‐making, as they can incorporate prior information and handle studies with zero events without the need for continuity corrections. However, the comparative performances of different Bayesian models in pooling rare events data are not well understood. We conducted a simulation to compare the statistical properties of four parameterizations based on the binomial‐normal hierarchical model, using two different priors for the treatment effect: weakly informative prior (WIP) and non‐informative prior (NIP), pooling randomized controlled trials with rare events using the odds ratio metric. We also considered the beta‐binomial model proposed by Kuss and the random intercept and slope generalized linear mixed models. The simulation scenarios varied based on the treatment effect, sample size ratio between the treatment and control arms, and level of heterogeneity. Performance was evaluated using median bias, root mean square error, median width of 95% credible or confidence intervals, coverage, Type I error, and empirical power. Two reviews are used to illustrate these methods. The results demonstrate that the WIP outperforms the NIP within the same model structure. Among the compared models, the model that included the treatment effect parameter in the risk model for the control arm did not perform well. Our findings confirm that rare events meta‐analysis faces the challenge of being underpowered, highlighting the importance of reporting the power of results in empirical studies.
Using spatiotemporal information in weather radar data to detect and track communal roosts
Authors: Perez Gustavo , Zhao Wenlong , Cheng Zezhou , Belotti Maria Carolina T. D. , Deng Yuting , Simons Victoria F. , Tielens Elske , Kelly Jeffrey F. , Horton Kyle G. , Maji Subhransu , Sheldon Daniel
Published: April 2024

The exodus of flying animals from their roosting locations is often visible as expanding ring‐shaped patterns in weather radar data. The NEXRAD network, for example, archives more than 25 years of data across 143 contiguous US radar stations, providing opportunities to study roosting locations and times and the ecosystems of birds and bats. However, access to this information is limited by the cost of manually annotating millions of radar scans. We develop and deploy an AI‐assisted system to annotate roosts in radar data. We build datasets with roost annotations to support the training and evaluation of automated detection models. Roosts are detected, tracked, and incorporated into our developed web‐based interface for human screening to produce research‐grade annotations. We deploy the system to collect swallow and martin roost information from 12 radar stations around the Great Lakes spanning 21 years. After verifying the practical value of the system, we propose to improve the detector by incorporating both spatial and temporal channels from volumetric radar scans. The deployment on Great Lakes radar scans allows accelerated annotation of 15 628 roost signatures in 612 786 radar scans with 183.6 human screening hours, or 1.08 s per radar scan. We estimate that the deployed system reduces human annotation time by ~7×. The temporal detector model improves the average precision at intersection‐over‐union threshold 0.5 (APIoU = .50) by 8% over the previous model (48%→56%), further reducing human screening time by 2.3× in its pilot deployment. These data contain critical information about phenology and population trends of swallows and martins, aerial insectivore species experiencing acute declines, and have enabled novel research. We present error analyses, lay the groundwork for continent‐scale historical investigation about these species, and provide a starting point for automating the detection of other family‐specific phenomena in radar data, such as bat roosts and mayfly hatches.
Fabrication of Highly Porous and Sheet Like Fe3O4‐Carbon Nanocomposites: A Versatile Catalyst for Electrocatalytic Oxygen Evolution Reactions
Authors: Shanmugapriya S. A. T. , Kumar Anand , Afzal Mohd , Chaudhary Ratiram Gomaji , Kumar Mandari Kotesh , Mondal Aniruddha , Mondal Sudip
Published: April 2024

Fuel cells and metal‐air batteries are examples of renewable energy technologies that depend on having highly effective electrocatalysts for the oxygen evolution reaction (OER). In this study, a mesoporous nanostructure composed of Fe3O4‐Carbon nanocomposites was synthesised using a simple and economically viable approach at a relatively low temperature. The observed catalytic activity of the prepared defected Fe3O4‐Carbon nanocomposites mesoporous nanostructure was found to be remarkable. Additionally, the nanostructure exhibited a high tolerance to methanol and demonstrated durability towards the oxygen evolution reaction (OER) in alkaline media. In the course of the experiment, it was observed that the catalyst exhibited noteworthy activity in the Oxygen Evolution Reaction (OER) when compared to the commercially available RuO2 catalyst. This was evident through a more overpotential value of 325 mV at current density of 10 mA/cm2. The catalyst‘s notable capacity for high oxygen reaction activity may potentially enhance the synergistic effect resulting from the combination of defect sites and the porous structure of Fe3O4‐Carbon nanocomposites. The findings of this study indicate that the Fe3O4‐Carbon nanocomposites nanostructures exhibit promising attributes as an electrocatalyst for the oxygen evolution reaction (OER) in real‐world scenarios.
Green Synthesis of Baby Pumpkin Derived Fluorescent Carbon Dots – A Potent Label‐Free Probe for Cd2+ Determination
Authors: Liao Shihua , Hu Jing , Long Xiang , Wu Shaogui
Published: April 2024

This study demonstrates a facile solvothermal approach to synthesizing green fluorescent carbon dots (G‐CDs) using baby pumpkin as a natural precursor. The G‐CDs exhibit strong fluorescence emission at 547 nm under excitation at 467 nm, and the highest quantum yield reaching 17.5 % in acetone, making them suitable for a range of applications including sensing, bioimaging, catalysis, and drug delivery. The G‐CDs demonstrate excellent stability under various conditions, such as prolonged light exposure, high salt concentration, extended periods, and elevated temperatures. Furthermore, the G‐CDs show a good linear relationship with Cd2+ within the concentration range of 0 to 16.5 μmol/L, with a linear correlation coefficient of 0.9920. The detection limit (LOD) was calculated to be 0.68 μmol/L. The recovery rate ranges between 85.66% to 97.43%, indicating their potential for use in environmental metal ion detection. This study provides a convenient and economical method for the synthesis of G‐CDs using baby pumpkin as a precursor, offering a sustainable alternative for various applications in sensing, imaging, catalysis, and drug delivery.
Assessing the Impact of π‐Conjugation Length on Aggregation Induced Emission and Self‐Assembly Formation of α‐Cyanostilbene and Bis‐Cyanostilbene
Authors: Waghchoure Aishwarya P. , Narode Hanuman , Sangale Vijay B. , Siddiqui Zahir Ali , Sarkhel Sanchita , Pardeshi Satish K. , Jaiswal Amit , Sekar Nagaiyan , More Sandeep , Bhosale Rajesh S.
Published: April 2024

In this work, short π‐conjugated (Z)‐2‐(4‐(2‐cyano‐2‐phenylvinyl)phenoxy)‐N‐(1‐(3‐ethoxy‐4‐methoxyphenyl)‐2‐(methyl sulfonyl)ethyl)acetamide (CYS) and large π‐conjugated 2,2′‐(((1Z,1′Z)‐1,4‐phenylenebis(2‐cyanoethene‐2,1‐diyl))bis(4,1‐phenyl ene))bis(oxy))bis(N‐(1‐(3‐ethoxy‐4‐methoxyphenyl)‐2‐(methyl sulfonyl)ethyl)acetamide (BCYS) compounds were synthesized. Furthermore, the influence of π‐conjugation length on CYS and BCYS absorption, fluorescence, aggregation induced emission (AIE) characteristics, and self‐assembly was examined. The large π‐conjugated BCYS (π‐conjugation length=18.71 Å) exhibits AIE property getting on in the DMSO−Water solvent combination as the volume % of water increases and demonstrated production of self‐assembled bundle of micro fibrous structure of around 5 to 6 microns long and 200 to 500 nm wide. Short π‐conjugated CYS (π‐conjugation length=10.80 Å), on the other hand, exhibits aggregation caused quenching (ACQ) in the DMSO−Water solvent combination as the volume % of water increases and the creation of self‐assembled nanostructured crystalline asymmetrical particles. Moreover, the cytotoxicity study of CYS and BCYS revealed that BCYS had superior biocompatibility than CYS.
Discovery of Small‐Molecules as Potential GSK‐3β Inhibitors for the Treatment of Alzheimer's Disease Using Pharmacophore‐Based Virtual Screening
Authors: Jangid Kailash , Devi Bharti , Rani Pooja , Kumar Naveen , Kumar Vinay , Kumar Vinod
Published: April 2024

Glycogen synthase kinase‐3β (GSK‐3β) plays pivotal role in regulating diverse range of cellular functions. It plays negative role in cellular signaling pathways and believed to involved in the pathologies of various diseases like neurological disorders, type II diabetes, inflammation, cardiac hypertrophy, cancer and bipolar disorders. GSK‐3β is proposed as a promising target for drug discovery in treating these disease conditions. A number of structurally different chemical scaffolds including pyrimidinone derivatives have been identified as potential GSK‐3β inhibitors. In the current study, PHASE module of Schrödinger 3D QSAR was used on about 157 pyrimidinone derivatives for the development of statistically significant PLS model. Consecutively, the best pharmacophore hypothesis with features like three hydrogen bond acceptors (A1‐3), two hydrophobic regions (H1 and H2), and one aromatic ring (R1), was selected to screen ZINC and PUBCHEM databases. Molecules with matching pharmacophoric features and ROF were subjected to structure‐based virtual screening (HTVS→SP→XP) and MMGBSA. Two hits from each library were selected for MD simulation studies that showed good pharmacokinetic properties, binding score (−6.8–−8.8 kcal/mol) and ▵GMMGBSA (−55.80–−58.1 kcal/mol) as compared to the reference molecule, NP‐12. Similarly, MD simulation, and MMPBSA identified three compounds i. e. ZINC67743231, ZINC01582756, and PUBCHEM11553018 displaying stability in the binding pocket and demonstrated better binding affinity of −22.07, −27.33, and −30.61 kcal/mol, respectively, within the active site of GSK‐3β. DFT studies also demonstrated the stability of these three lead compounds with a high energy gap between HOMO and LUMO ranging between 0.14546 and 0.1718 eV.
Green Fluorescent Diamino‐Terephthalonitriles with Reactive Terminal Groups Towards Synthesis of Value‐Added Fluorophores
Authors: Raghava Tanya , Banerjee Subhadeep
Published: April 2024

We report synthesis of a library of diamino‐terephthalonitrile based single‐benzene fluorophores (SBFs). These SBFs contain a reactive terminal linker group. They open up the possibility of marrying their excellent fluorescent property with various biogenic units, leading to value‐added SBFs. The solvatofluorochromism behavior of these newly synthesized SBFs was also studied. The emission enhances and blue‐shifts in case of non‐polar solvents and vice versa in the polar solvents, implying the environmental sensitivity of these fluorophores. Photostability test was also done to test for the stability of the emission of these fluorophores with time and the fluorophores were found to be stable. We also observed time‐dependent fluorescence enhancement of one of our SBFs in presence of reactive biogenic amines. Overall, the generation of these novel molecules opens up new opportunities towards bioconjugated fluorophores.