bluuebunny/crossref_metadata_2025 huggingface dataset:
Neddylation activated TRIM25 desensitizes triple-negative breast cancer to paclitaxel via TFEB-mediated autophagy
Authors: Zheng Bowen , Qian Fengyuan , Wang Xuehui , Wang Yuying , Zhou Baian , Fang Lin
Published: June 2024

Background

Paclitaxel (PTX) treatment resistance is an important factor leading to poor prognosis in triple-negative breast cancer (TNBC), therefore there is an urgent need to identify new target for combination therapy. Neddylation is a post-translational process that introduces a ubiquitin-like protein called neural precursor cell expressed developmentally downregulated protein 8 (NEDD8). Previous studies have found that neddylation is activated in multiple tumors, but its relationship with PTX chemotherapy sensitivity has not been reported.

Methods

Differences in UBC12 and NEDD8 expression levels between PTX-sensitive and PTX-insensitive TNBC tissues were validated using public databases and immunohistochemistry. The in vitro and in vivo functional experiments were used to observe the effect of neddylation inhibition combined with PTX therapy on tumor progression. Co-IP, western blot and PCR assays were used to investigate the molecular mechanisms. Molecular docking was used to simulate the protein binding of UBC12 and TRIM25. Molecular dynamics simulation was used to observe the changes in TRIM25 protein conformation.

Results

We found that in TNBC that is insensitive to PTX, NEDD8 and NEDD8 conjugating enzyme UBC12 are highly expressed. Treatment with the NEDD8-activating enzyme (NAE) inhibitor mln4924 or knockdown of UBC12 significantly increased the sensitivity of the tumor to PTX, and this increase in sensitivity is related to UBC12-mediated autophagy activation. Mechanistically, UBC12 can transfer NEDD8 to E3 ubiquitin ligase tripartite motif containing 25 (TRIM25) at K117. Molecular dynamics simulations indicate that the neddylation modification of TRIM25 reduces steric hindrance in its RING domain, facilitating the binding of TRIM25 and ubiquitylated substrates. Subsequently, TRIM25 promotes the nuclear translocation of transcription factor EB (TFEB) and transcription of autophagy related genes by increasing K63-polyubiquitination of TFEB, thereby reducing tumor sensitivity to PTX.

Conclusions

Neddylation is activated in PTX-insensitive TNBC. Specifically, autophagy gene transcriptional activation mediated by the UBC12/TRIM25/TFEB axis reduces TNBC sensitivity to PTX. Neddylation suppression combination with PTX treatment shows a synergistic anti-tumor effect.
Resolving intra-repeat variation in medically relevant VNTRs from short-read sequencing data using the cardiovascular risk gene LPA as a model
Authors: Di Maio Silvia , Zöscher Peter , Weissensteiner Hansi , Forer Lukas , Schachtl-Riess Johanna F. , Amstler Stephan , Streiter Gertraud , Pfurtscheller Cathrin , Paulweber Bernhard , Kronenberg Florian , Coassin Stefan , Schönherr Sebastian
Published: June 2024

Background

Variable number tandem repeats (VNTRs) are highly polymorphic DNA regions harboring many potentially disease-causing variants. However, VNTRs often appear unresolved (“dark”) in variation databases due to their repetitive nature. One particularly complex and medically relevant VNTR is the KIV-2 VNTR located in the cardiovascular disease gene LPA which encompasses up to 70% of the coding sequence.

Results

Using the highly complex LPA gene as a model, we develop a computational approach to resolve intra-repeat variation in VNTRs from largely available short-read sequencing data. We apply the approach to six protein-coding VNTRs in 2504 samples from the 1000 Genomes Project and developed an optimized method for the LPA KIV-2 VNTR that discriminates the confounding KIV-2 subtypes upfront. This results in an F1-score improvement of up to 2.1-fold compared to previously published strategies. Finally, we analyze the LPA VNTR in > 199,000 UK Biobank samples, detecting > 700 KIV-2 mutations. This approach successfully reveals new strong Lp(a)-lowering effects for KIV-2 variants, with protective effect against coronary artery disease, and also validated previous findings based on tagging SNPs.

Conclusions

Our approach paves the way for reliable variant detection in VNTRs at scale and we show that it is transferable to other dark regions, which will help unlock medical information hidden in VNTRs.
Effects of whole-body vibration on body composition, microbiota, cardiometabolic markers, physical fitness, and quality of life after bariatric surgery: protocol for a randomized controlled trial
Authors: Gómez-Bruton Alejandro , Irún Pilar , Matute-Llorente Angel , Lozano-Berges Gabriel , Moradell Ana , Ara-Gimeno Susana , Subias-Perie Jorge , Sánchez-Luengo Marta , Hijos-Mallada Gonzalo , García-Mateo Sandra , Arechavaleta Samantha , Palacios Fanlo María José , Lanas Angel , Casajús Jose A.
Published: June 2024

Background

Morbid obesity is a complex chronic condition characterized by a body mass index of 40 kg/m2 or higher. The incidence of the condition is on the rise in developed countries, and bariatric surgery has been proposed as a potential solution to address this trend. Nonetheless, bariatric surgery may also result in adverse effects, including a reduction in bone mineral density (BMD) and muscle mass, as well as an increased risk of fractures. The present study aims to elucidate the effects of bariatric surgery and whole-body vibration (WBV) training on body composition, microbiota, physical fitness, quality of life, and cardiometabolic markers.

Methods

Twenty-eight participants (14 females), aged 18 to 50 years, will undergo sleeve gastrectomy surgery. They will be randomly allocated into a control group or a WBV training group. The WBV group will train three times per week with increasing intensities and duration ranging from 30 to 45 min over the 4-month training period. Measurements of body composition (dual-energy X-ray absorptiometry and peripheral quantitative computed tomography), physical fitness (muscular strength, agility, cardiorespiratory fitness, and balance), gait biomechanics, cardiometabolic markers, gut microbiota, quality of life, and physical activity levels will be collected at four different time points: (1) prior to the surgery, (2) 45 days post-surgery, (3) 6 months post-surgery, and (4) 18 months post-surgery.

Discussion

Both groups are expected to experience improvements in most of the aforementioned variables. Nonetheless, we expect the WBV group to show larger improvements proving that the training is effective and safe.

Trial registration

Clinicaltrials.gov NCT05695599. Registered on January 25, 2023.
Effectiveness of a positive psychology and mindfulness-based app on mental health for parents of children with a neurodevelopmental disorder: study protocol of a pragmatic international randomized controlled trial
Authors: Tönis Kim J. M. , Drossaert Constance H. C. , ten Klooster Peter M. , Schaer Marie , Bourgeron Thomas , Buitelaar Jan K. , Sadaka Yair , Freitag Christine M. , Lapidus Keren Mayer , Chiocchetti Andreas G. , Staal Wouter G. , Bohlmeijer Ernst T.
Published: June 2024

Introduction

Parents of children with a neurodevelopmental disorder (NDD) experience more stress than parents of typically developing children. In a cocreation process with experts and parents, a low-threshold application that uses exercises based on the principles of positive psychology and mindfulness was developed. This application, called “Adappt,” aims at enhancing the ability to adapt of the parents and caregivers of children with NDDs and at supporting their mental health. This protocol describes the evaluation study of the effectiveness of Adappt, its core working mechanisms and user experiences.

Method

A pragmatic international multicenter randomized controlled trial will compare the effectiveness of Adappt with a (delayed) waitlist control condition. At least 212 parents or primary caregivers of children younger than 18 years diagnosed with or suspected of a NDD will be randomly assigned to the intervention or waitlist control condition. Participants are excluded if they have severe anxiety or depression levels or are in treatment for mental health issues. Measures will be collected online at baseline, post-intervention (1 month after baseline), and 4 and 7 months after baseline. The primary outcome is the improvement in generic sense of ability to adapt as measured with the Generic Sense of Ability to Adapt Scale (GSAAS; (Front Psychol 14:985408, 2023)) at 4-month follow-up. Secondary outcomes are mental well-being, (parental) distress, and client satisfaction with “Adappt.”

Discussion

Results of this study will contribute to knowledge on the effectiveness of a low-threshold application for parents of children with a NDD in multiple countries. If the application is found to be effective in improving mental health, recommendations will be made for implementation in health care.

Trial registration

This study is registered on clinicaltrials.gov (NCT06248762) on February 8, 2024, and the Open Science Framework (https://osf.io/5znqv).
White out hemithorax secondary to salivary gland type of lung cancer with metastasis in liver and bone: a case report
Authors: Badhe Padma V. , Sivakumar M. , Lamture Swastika , Patil Sanika , Tekriwal Khushboo , Mohammad Khalid Ahmad
Published: June 2024

Background

Salivary gland-type lung carcinomas are uncommon neoplasms of the lung, representing less than 1% of all lung tumors. The two most common among them are adenoid cystic carcinoma and mucoepidermoid carcinoma. Although they usually have an indolent behavior, adenoid cystic carcinomas can be more aggressive, with 5-year survival as low as 55%. Very few cases are reported in literature. We report a similar rare case of salivary gland type lung carcinoma that presented for the first time with unilateral opacification of left hemithorax.

Case presentation

A 38-year-old man of North Indian origin, who was a a nonsmoker, presented with complaints of shortness of breath and cough for 1 year, which has increased in the last 2 months and was associated with significant weight loss. A frontal radiograph of the chest and computed tomography of the chest were performed, which showed a mass in the left upper lobe of the lung with its epicenter in the left main bronchus. A bronchoscopic guided biopsy was performed, and histopathology confirmed the diagnosis of lung carcinoma of salivary gland type (adenoid cystic carcinoma). There was invasion of major vessels, hence the patient was offered and started on palliative management instead of surgical treatment.

In spite of palliative management of two cycles of chemotherapy and radiotherapy, the patient succumbed to the disease within 2 months from the time of diagnosis.

Conclusion

Lung carcinoma of the salivary gland type (especially adenoid cystic carcinoma) usually presents at a later stage. The resectability of the tumor depends on the involvement of the surrounding major vessels. Interestingly, these cancers have no association with smoking. The prognosis depends on the extent of the disease at the time of diagnosis. Hence, imaging plays a major role in deciding the further plan of management.
Generalized Tikhonov regularization method for an inverse boundary value problem of the fractional elliptic equation
Authors: Zhang Xiao
Published: June 2024

This research studies the inverse boundary value problem for fractional elliptic equation of Tricomi–Gellerstedt–Keldysh type and obtains a condition stability result. To recover the continuous dependence of the solution on the measurement data, a generalized Tikhonov regularization method based on ill-posedness analysis is constructed. Under the a priori and a posterior selection rules for the regularization parameter, corresponding Hölder type convergence results are obtained. On this basis, this thesis verifies the simulation effect of the generalized Tikhonov method through numerical examples. The examples show that the method performs well in dealing with the problem under consideration.
Hydration Characteristics of Slag-Ca(OH)2-Al2O3 Binder in a 60 °C Curing Environment with Brine as Mixing Water
Authors: Kang Choonghyun , Kim Taewan , Park Yong-Myung , Seo Ki-Young
Published: June 2024

Recently, research results on PC-based or alkali-activated slag cement (AASC) using seawater as mixing water have been reported. Unlike seawater, reverse osmosis brine (brine) is waste discharged into the ocean from seawater desalination plants. There is a need to develop new and effective methods of disposing or utilizing brine to reduce marine pollution, protect marine ecosystems, and increase marine plant construction. However, research on cement or concrete using brine as a mixing water is very limited. Brine has almost the same composition as seawater, and the ion concentration is 2–4 times higher. Therefore, it is believed that new methods of using brine can be investigated and developed based on existing research and experimental results on seawater. The effects of brine and aluminum oxide (AO) on activated slag with calcium hydroxide (CH) were investigated for hydration and mechanical properties. 5% and 10% of CH were used, and samples using fresh water (FC) were prepared at the same time for comparison with brine. The slag sample without CH has a low initial (1 and 3d) strength of about 10 MPa for both FC and brine, but increases rapidly from 7d. Incorporation of CH was effective in improving the mechanical performance of FC and brine samples. In addition, the brine sample exhibited higher strength than the FC sample because it formed fewer C3AH6 phases that cause volume instability than the FC sample and affected the hydration promotion of slag particles. And more calcite phases were observed in the brine samples than in the FC samples. Through this study, the possibility of using brine as a building material was confirmed. In addition, the effect of chloride ion adsorption of slag mixed with AO and CH on the physical properties and mechanical performance of the hydration reaction was confirmed.
The impact of 24-h take-home exam on language learning and teaching on the China campus of a British university
Authors: Ye Xiaomin , Yang Yilong , Qie Yi , Hu Zengbao
Published: June 2024

Take-home exam (THE) use has been reported in various disciplines, but research on THE use in language modules in higher education appears to be scarce. The current study employed surveys and interviews to examine how the shift to written THE, in place of the traditional in-class exam (ICE) during the pandemic, impacted language learning and teaching on the China campus of a British university. Additionally, correlation analyses were conducted with ranking data of students from the same cohort under THE and ICE to explore patterns in student performance under these exam conditions. In surveys and interviews, teachers reported that their teaching foci did not change under THE, while many students reported that their learning practices were different under THE and ICE. Students also exhibited a tendency to spend more time practicing skills that they expected to be assessed in the exam. Overall, both teachers and students expressed preference for ICE, with many raising concerns about fairness issues in THE. Furthermore, correlation analyses showed that, overall, for a given group of students, written ICE rankings exhibited strong correlations with each other but written THE rankings did not, suggesting relative instability of THE results. However, when written THE and oral ICE results from the same module are combined, the resultant rankings strongly correlated with pure ICE rankings. This indicates that combining ICE and THE components for assessment could help mitigate some perceived shortcomings, including the instability issue, of THE used alone.
Prediction of geothermal temperature field by multi-attribute neural network
Authors: Gao Wanli , Zhao Jingtao
Published: June 2024

Hot dry rock (HDR) resources are gaining increasing attention as a significant renewable resource due to their low carbon footprint and stable nature. When assessing the potential of a conventional geothermal resource, a temperature field distribution is a crucial factor. However, the available geostatistical and numerical simulations methods are often influenced by data coverage and human factors. In this study, the Convolution Block Attention Module (CBAM) and Bottleneck Architecture were integrated into UNet (CBAM-B-UNet) for simulating the geothermal temperature field. The proposed CBAM-B-UNet takes in a geological model containing parameters such as density, thermal conductivity, and specific heat capacity as input, and it simulates the temperature field by dynamically blending these multiple parameters through the neural network. The bottleneck architectures and CBAM can reduce the computational cost while ensuring accuracy in the simulation. The CBAM-B-UNet was trained using thousands of geological models with various real structures and their corresponding temperature fields. The method’s applicability was verified by employing a complex geological model of hot dry rock. In the final analysis, the simulated temperature field results are compared with the theoretical steady-state crustal ground temperature model of Gonghe Basin. The results indicated a small error between them, further validating the method's superiority. During the temperature field simulation, the thermal evolution law of a symmetrical cooling front formed by low thermal conductivity and high specific heat capacity in the center of the fault zone and on both sides of granite was revealed. The temperature gradually decreases from the center towards the edges.
Engineering extracellular vesicles for ROS scavenging and tissue regeneration
Authors: Abdal Dayem Ahmed , Yan Ellie , Do Minjae , Kim Yoojung , Lee Yeongseo , Cho Ssang-Goo , Kim Deok-Ho
Published: June 2024

Stem cell therapy holds promise for tissue regeneration, yet significant challenges persist. Emerging as a safer and potentially more effective alternative, extracellular vesicles (EVs) derived from stem cells exhibit remarkable abilities to activate critical signaling cascades, thereby facilitating tissue repair. EVs, nano-scale membrane vesicles, mediate intercellular communication by encapsulating a diverse cargo of proteins, lipids, and nucleic acids. Their therapeutic potential lies in delivering cargos, activating signaling pathways, and efficiently mitigating oxidative stress—an essential aspect of overcoming limitations in stem cell-based tissue repair. This review focuses on engineering and applying EVs in tissue regeneration, emphasizing their role in regulating reactive oxygen species (ROS) pathways. Additionally, we explore strategies to enhance EV therapeutic activity, including functionalization and incorporation of antioxidant defense proteins. Understanding these molecular mechanisms is crucial for optimizing EV-based regenerative therapies. Insights into EV and ROS signaling modulation pave the way for targeted and efficient regenerative therapies harnessing the potential of EVs.
Toward automated microstructure characterization of stainless steels through machine learning-based analysis of replication micrographs
Authors: Ghauri Hamza , Tafreshi Reza , Mansoor Bilal
Published: June 2024

Machine learning-driven automated replication micrographs analysis makes possible rapid and unbiased damage assessment of in-service steel components. Although micrographs captured by scanning electron microscopy (SEM) have been analyzed at depth using machine learning, there is no literature available on the technique being attempted on optical replication micrographs. This paper presents a machine-learning approach to segment and quantify carbide precipitates in thermally exposed HP40-Nb stainless-steel microstructures from batches of low-resolution optical images obtained by replication metallography. A dataset of nine micrographs was used to develop a random forest classification model to segment precipitates within the matrix (intragranular) and at grain boundaries (intergranular). The micrographs were preprocessed using background subtraction, denoising, and sharpening to improve quality. The method achieves high segmentation accuracy (91% intergranular, 97% intragranular) compared to human expert classification. Furthermore, segmented micrographs were quantified to obtain carbide size, shape, and density distribution. The correlations in the quantified data aligned with expected carbide evolution mechanisms. Results from this study are promising but necessitate validation of the method on a larger dataset representative of evolution of thermal degradation in steel, given that characterization of the evolution of microstructure components, such as precipitates, applies to broad applications across diverse alloy systems, particularly in extreme service.
A case of chronic expanding hematoma mimicking a cystic pancreatic tumor
Authors: Sakamoto Asuna , Ando Yasuhisa , Feng Dongping , Nagao Mina , Matsukawa Hiroyuki , Nishiura Bunpei , Kondo Akihiro , Suto Hironobu , Asano Eisuke , Kishino Takayoshi , Oshima Minoru , Kumamoto Kensuke , Okano Keiichi
Published: June 2024

Background

A chronic expanding hematoma is an uncommon entity described as an organized blood collection that increases in size after the initial hemorrhagic event without histological neoplastic features. The standard treatment is complete resection. To our knowledge, this is the first report of a chronic expanding hematoma mimicking a pancreatic cystic tumor that has been successfully resected utilizing a laparoscopic approach.

Case presentation

We report the case of a 32-year-old man with a 10-cm chronic expanding hematoma that was preoperatively diagnosed as a cystic pancreatic tumor. Dynamic computed tomography revealed a cyst at the inferior part of the uncinate process of the pancreas without contrast enhancement. His blood biochemical data were within normal limits. The operation initially utilized a laparoscopic approach; however, the procedure was converted to hand-assisted laparoscopic surgery due to capsule adherence to surrounding organs and finally, enucleation of the tumor was performed. Pathological findings revealed a chronic expanding hematoma in the retroperitoneal space.

Conclusion

Chronic expanding hematoma in the retroperitoneal space is so rare and sometimes adheres to the surrounding tissue. It is difficult to distinguish hematoma attaching pancreas and pancreatic cyst preoperatively. In rare cases such as this, hand-assisted laparoscopic surgery is a feasible, less invasive procedure for facilitating complete resection and preventing recurrence.
Participants’ perceived benefits from the GLA:D™ program for individuals living with hip and knee osteoarthritis: a qualitative study
Authors: Kania-Richmond Ania , Beaupre Lauren A. , Jessiman-Perreault Geneviève , Tribo Danika , Martyn Jason , Hart David A. , Robert Jill , Slomp Mel , Jones C. Allyson
Published: June 2024

Background

The Good Life with osteoArthritis: Denmark (GLA:D™), an evidence-based education and exercise program designed for conservative management of knee and hip osteoarthritis (OA), has been shown to benefit participants by reducing pain, improving function, and quality of life. Standardized reporting in the GLA:D databases enabled the measurement of self-reported and performance-based outcomes. There is a paucity of qualitative research on the participants’ perceptions of this program, and it is important to understand whether participants’ perceptions of the benefits of the program align with reported quantitative findings.

Methods

We conducted semi-structured telephone interviews with individuals who participated in the GLA:D program from January 2017 to December 2018 in Alberta, Canada. Data were analyzed using an interpretive description approach and thematic analysis to identify emergent themes and sub-themes associated with participants perceived benefits of the GLA:D program. We analyzed the data using NVivo Pro software. Member checking and bracketing were used to ensure the rigour of the analysis.

Results

30 participants were interviewed (70% female, 57% rural, 73% knee OA). Most participants felt the program positively benefited them. Two themes emerged from the analysis: wellness and self-efficacy. Participants felt the program benefited their wellness, particularly with regard to pain relief, and improvements in mobility, strength, and overall well-being. Participants felt the program benefited them by promoting a sense of self-efficacy through improving the confidence to perform exercise and routine activities, as well as awareness, and motivation to manage their OA symptoms. Twenty percent of participants felt no benefits from the program due to experiencing increased pain and feeling their OA was too severe to participate.

Discussion

The GLA:D program was viewed as beneficial to most participants, this study also identified factors (e.g., severe OA, extreme pain) as to why some participants did not experience meaningful improvements. Early intervention with the GLA:D program prior to individuals experiencing severe OA could help increase the number of participants who experience benefits from their participation.

Conclusion

As the GLA:D program expands across jurisdictions, providers of the program may consider recruitment earlier in disease progression and targeting those with mild and moderate OA.
Do board characteristics matter in the relationship between intellectual capital efficiency and firm value? Evidence from the Nigerian oil and gas downstream sector
Authors: Bala Ahmed Jinjiri , Hassan Aminu , Muhammad Muhammad Liman
Published: June 2024

Purpose

The purpose of this study is to investigate the moderating effects of board characteristics such as board size, chief executive officer duality, number of board meetings, and diversity, on the relationship between intellectual capital efficiency and firm value in the Nigerian oil and gas downstream sector.

Design/methodology/approach

We collected time-series cross-sectional data from eight (8) downstream-sector oil and gas companies quoted on the Nigerian Exchange Group for the period 2004–2020. We analysed the data using Prais–Winsten regression with panel-corrected standard errors.

Findings

Overall, our results show no significant direct relationship between the modified value-added intellectual coefficient and our two measures of firm value (Tobin’s Q and Price Earnings Ratio (PER)). However, the board size is found to moderate the intellectual capital efficiency–PER relationship significantly and negatively, whereas board diversity significantly positively moderates the association between the modified value-added intellectual coefficient and PER. Our multi-theory framework, which blends clean surplus, agency, stakeholder, and resource-based theories is found to be relevant in underpinning this study.

Research limitations/implications

The research relies on 17-year panel data for eight downstream-sector oil and gas companies. Consequently, future research within intellectual capital efficiency in Nigeria could incorporate related sectors like midstream and upstream to enable comparability and expand generalization.

Practical implication

Policymakers may adopt the study findings to serve as a robust empirical base to demand improved board diversity as a catalyst for boosting the potency of the intellectual capital efficiency-firm value relationship.

Originality/value

Firstly, to the best of our knowledge, this study is the pioneer attempt to use board characteristics as moderators of the relationship between intellectual capital efficiency and firm value. Secondly, we develop and use a novel theoretical framework that combines clean surplus, agency, stakeholder, and resource-based theories to underpin the study.
Navigating COVID-19-associated mucormycosis: endoscopic grading, radiological correlations, and treatment outcomes
Authors: Gupta Yamini , Verma Jagram , Valecha Krishna
Published: June 2024

Background

The global COVID-19 pandemic has brought forth multifaceted healthcare challenges, including the emergence of COVID-19-associated mucormycosis (CAM). This study investigates demographics, clinical presentation, endoscopic grading, radiological correlations, treatment modalities, and outcomes of CAM in Central India.

Methods

A retrospective analysis of 312 CAM patients (April-June 2021). Data included demographics, clinical profiles, endoscopic and radiological findings, laboratory results, and treatments. A novel endoscopic grading system was utilized to assess the severity of mucormycosis lesions. Statistical analysis, including chi-squared tests, was performed.

Results

Among 312 patients, 65% were male, 82% had comorbidities, and 84% presented with facial swelling. Endoscopic grading correlated with radiological manifestations (p < 0.05) and intraoperative findings. Surgical debridement and antifungal therapy were common treatments, yielding varied clinical outcomes. Mortality was 13% in advanced grades.

Conclusion

This study underscores the role of endoscopic grading in risk stratification and prognosis. Findings contribute to CAM management knowledge, underscoring tailored interventions’ significance.
Characterization of pepper (
Capsicum
spp.) germplasms based on morphological and phytochemical characters in Bangladesh
Authors: Parvin Nighat , Masuda Mst Salma , Turin Mst Tanjina Shahanaj , Jui Sohana , Amzad Mst. Anamika , Khatun Mst. Ananya , Arifuzzaman Md , Alshamrani Rahma Ibrahim , Ahmed Eakhlas Uddin
Published: June 2024

Pepper (
Capsicum
spp.) is a major spice crop around the globe. The major goal of the experiment was to evaluate the genetic diversity amongst 30 pepper germplasms for twelve morphological and phytochemical parameters. The investigation was conducted between November 2019 and April 2020 using a randomized complete block design with three replications in the experimental field of Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh. The results revealed a notable disparity across the genotypes for all studied traits. The genotype C80 displayed the highest fresh fruit weight (20.60 g) and dry fruit weight (1.20 g). Once again, the genotype YF1 had the highest chlorophyll and vitamin-C contents. The most significant correlations were revealed between fresh fruit weight and dry fruit weight (r = 0.83***) followed by between fruit diameter and dry fruit weight (r = 0.80***), and between fruit diameter and fresh fruit weight (r = 0.79***). The Wards-D method was used to cluster thirty genotypes into four clusters based on Euclidean distances. Cluster IV consisted of a maximum of 13 pepper genotypes. Cluster I yielded the greatest fresh fruit weight, measuring 11.75 g, whereas cluster III contained the highest Vitamin-C content, measuring 23.61 mg/ 100 g. The clusters I and III had the highest inter-cluster distances (6.45), while cluster I had the highest intra-cluster distance (2.36). PC1 and PC2 explained 32.8% and 18.3% of the total variances, respectively. In the biplot, the genotypes C54 and C80 favored fresh and dry fruit weights as well as fruit diameters, while the genotypes C29 and YF1 positively favored chlorophyll and vitamin-C contents. Therefore, the diverse pepper genotypes C54, C80 from cluster I and C29 and YF1 from cluster III could be included in future hybridization of pepper breeding.
The qP- and qSV-wave separation in 2D vertically transversely isotropic media and their applications in elastic reverse time migration
Authors: Fan Na , Xie Xiao-Bi , Zhao Lian-Feng , Yao Zhen-Xing
Published: June 2024

Compressional and shear wave separation is an important step in anisotropic elastic reverse time migration (ERTM). With separated wavefields, we can generate images between different wave types and reveal more subsurface physical properties, as well as remove unwanted crosstalk and improve image quality. Traditional Helmholtz decomposition based on divergence and curl operations for isotropic media cannot be directly extended to vertically transversely isotropic (VTI) media. Wave-mode separation methods, similar to the nonstationary spatial filter and Poynting vector, cannot preserve the phase and amplitude information of the original coupled wavefield, thus limiting their application in ERTM. Currently, the anisotropic wavefield decomposition methods include the wavenumber-domain approach, the low-rank approximation, and other separation approaches based on different approximations, e.g., weak or elliptical anisotropy. These methods are either computationally intensive or involve large separation errors, especially in models with strong heterogeneities and anisotropy. The VTI wavefield separation operator is essentially defined in a mixed space-wavenumber domain. We introduce scalar operators to transfer operations from this mixed space-wavenumber domain to the space domain. The local wave propagation direction in the scalar operators is estimated using the Poynting vector, which is highly computationally efficient in the space domain. When we apply the wave separation method to ERTM, we not only obtain the vectorized qP and qSV waves but also retrieve the scalar qP wavefield. The scalar and vector wavefields preserve the amplitude and phase information in the original coupled wavefield. For anisotropic ERTM, we suggest using the scalar imaging condition to generate the PP image and the magnitude- and sign-based vector imaging condition to produce the PS image, both having higher image accuracy than the dot-product imaging condition. Numerical examples are used to validate our anisotropic wavefield separation method and the related ERTM workflow.
Impact of complete cytogenetic response on survival in patients with myelodysplastic syndromes.
Authors: Urrutia Samuel , Sasaki Koji , Kantarjian Hagop M. , Jabbour Elias , Chien Kelly Sharon , Hammond Danielle , Bueso-Ramos Carlos E. , Khoury Joseph , Patel Keyur P. , Montalban-Bravo Guillermo , Wei Yue , Colla Simona , Short Nicholas James , Daver Naval Guastad , Borthakur Gautam , Kadia Tapan M. , Pierce Sherry , Wierda William G. , Garcia-Manero Guillermo
Published: June 2024

6567

Background: Response to therapy prolongs survival in patients with myelodysplastic syndromes (MDS). The aim of this study is to evaluate the impact of complete cytogenetic response (CCyR) on survival in patients with MDS and abnormal cytogenetics. Methods: We reviewed 2311 consecutive patients with MDS and cytogenetic abnormalities who were treated at our institution from 2006 to 2023. Results: CCyR was observed in 330 patients (14%), complete response (CR) in 208 (9%), CR with bilineage recovery (CRbi) in 255 (11%), CR with unilineage recovery (CRuni) in 151 (7%), CR with incomplete hematologic recovery (CRh) in 4 (0.2%), and non-CR in 1363 (59%). With a median follow-up of 59 months, the median overall survival (mOS) was 14 months. Ten months for non-CR, 19 months for CRh/CRbi/CRuni, 21 months for CR, and 26 months for patients with CCyR (p < 0.001). With stem cell transplant (SCT) censoring, mOS was 15 months. Eleven months in non-CR, 19 months in CRh/CRbi/CRuni, 19 months in CR, and 27 months for patients with CCyR (p < 0.001). In low-risk MDS by the International Prognostic Scoring System (IPSS), mOS with SCT censoring was 87 months for CCyR, compared to 40 months for non-CR, 38 months for CRh/CRbi/CRuni, and 36 months for CR (p < 0.001). In intermediate/high-risk MDS mOS with SCT censoring mOS was 25 months in CCyR, compared to 9 months in non-CR, 15 months in CRh/CRbi/CRuni, and 17 months in CR (p < 0.001). In a multivariate regression analysis, age > 75 years (HR 3.1, p < 0.001), complex karyotype (HR 2.15, p < 0.001) performance status 3-4 (HR 1.48, p < 0.001), hemoglobin < 8 g/dL (HR 1.48, p=0.003), creatinine > 1.3 g/dL (HR 1.44, p < 0.001), therapy-related AML (HR 1.41, p < 0.001), infection at diagnosis (HR 1.34, p =0.003), white blood cells > 50 x109/L (HR 1.31, p <0.001), cardiac comorbidities (HR 1.26, p < 0.001), platelets < 20 x109/L (HR 1.26, p=0.001), pneumonia at diagnosis (1.22, p =0.006), and core-binding factor cytogenetics (HR 0.48, p < 0.001) were independently prognostic for survival in this select group. Conclusions: Achievement of CCyR in patients with MDS and abnormal cytogenetic abnormalities leads to improved survival. Given poor outcomes in older patients with MDS, CCyR can be used as a valid surrogate for long-term outcomes.
J-TAIL-2: A prospective observational study of atezolizumab (atezo) combination therapy in patients (pts) with non-small cell lung cancer (NSCLC) in Japan.
Authors: Watanabe Yasutaka , Nishio Makoto , Ohashi Kadoaki , Osoegawa Atsushi , Kikuchi Eiki , Kimura Hideharu , Goto Yasushi , Shimizu Junichi , Miyauchi Eisaku , Yoshioka Hiroshige , Yoshino Ichiro , Misumi Toshihiro , Yamaguchi Masafumi , Yoshimori Kouzou , Seike Masahiro , Yoshida Hironori , Nishino Kazumi , Miwa Asako , Tanaka Misa , Gemma Akihiko
Published: June 2024

8573

Background: The IMpower130 (West et al. Lancet Oncol 2018), IMpower132 (Nishio et al. JTO 2021) and IMpower150 (1) trials led to the approval of first-line atezo combination therapies for NSCLC. As data remain limited in Japanese pts, J-TAIL-2 (NCT04501497) is evaluating the efficacy and safety of 3 atezo combination therapies for NSCLC in the clinical setting in Japan. Methods: Japanese pts had unresectable advanced or recurrent NSCLC, were ≥20 y old, and were scheduled to start atezo combination therapy in clinical practice. Pts received atezo + carboplatin and nab-paclitaxel (atezo + CnP), atezo + carboplatin or cisplatin + pemetrexed (atezo + PP) or atezo + bevacizumab + carboplatin + paclitaxel (atezo + bev + CP). The primary endpoint was 12-mo OS rate. Secondary endpoints included OS and safety. Efficacy and safety were analyzed in the IMpower-unlike (did not meet the main eligibility criteria of each IMpower study) and IMpower-like subgroups. Geriatric assessment (G8) was done in pts ≥70 y old at baseline; a score < median vs ≥ median indicated poorer health status. Results: From Aug 21, 2020, to data cut off (Feb 3, 2023), 814 pts were enrolled at 150 sites (atezo + CnP, n=217; atezo + PP, n=211; atezo + bev + CP, n=386). Baseline characteristics in the efficacy analysis population (n=791) are shown (Table). The IMpower-unlike group included pts with ECOG PS ≥2, brain metastases or interstitial lung disease. Twelve-mo OS rates (95% CI) were 62.9% (55.8, 69.2), 72.1% (65.2, 77.9) and 68.3% (63.2, 72.9), and median OS was 19.7, 23.5 and 17.3 mo with atezo + CnP, atezo + PP and atezo + bev + CP, respectively. OS HRs (95% CI) in the IMpower-unlike vs -like subgroups were 1.36 (0.91, 2.05), 1.08 (0.70, 1.68) and 1.49 (1.09, 2.06), respectively. The median G8 score for all evaluable pts was 13; in pts with a G8 score < median vs ≥ median, OS HRs (95% CI) were 2.10 (1.22, 3.61), 3.53 (1.95, 6.37) and 2.04 (1.22, 3.40) with atezo + CnP, atezo + PP and atezo + bev + CP, respectively. In the safety analysis population (n=800), Grade ≥3 AEs occurred in 60.4% of pts and Grade 5 AEs in 1.3%. Conclusions: In Japanese pts, the efficacy and safety of each atezo combination therapy were comparable to those seen in the relevant IMpower studies and largely consistent in pts who would have been ineligible for the trials. Pts aged ≥70 y with a G8 score < median vs ≥ median had poorer efficacy and safety outcomes. 1. Socinski et al. NEJM 2018. Clinical trial information: NCT04501497 . [Table: see text]
Health insurance plans offered at NCI-designated cancer centers.
Authors: Moore Vanessa Ann , Xing Jiazhang , Bouvette Max Joseph , Lam Anh B. , Jiang Changchuan , Nipp Ryan David , Choradia Nirmal
Published: June 2024

9052

Background: The health insurance landscape in the US represents an expensive and complex challenge to patients and physicians alike. Little is known about health insurance plans (HIPs) offered to physicians, particularly at NCI-designated cancer centers, which represent centers seeking to meet the highest standards. Methods: We collected data on the HIPs offered to physicians at NCI-designated cancer centers by reviewing institution websites from 11/2023 - 01/2024. We abstracted data on the insurance premium, deductible, out-of-pocket (OOP) maximum, and coinsurance for hospitalizations, limited to three HIPs per institution. We derived estimates using the lowest charge. We calculated inpatient stay costs based on standard hospital stay costs ($2,883 per day over an average of 4.5 days). We compared HIPs between public and private cancer centers. We used US Census Bureau population density data and regression models to explore associations among population density and OOP costs. Results: Among 65 NCI-designated cancer centers reviewed, 61 (93.8%) had readily available information about HIPs provided. Most institutions provided HIPs for all hospital employees, while 2 institutions only covered physicians. On average, each cancer center offered 3.67 HIPs, involving 1.67 insurers (54.1% offered a single insurer). Among 153 HIPs overall, 51.6% were preferred provider organization (PPOs) and one-third (33.3%) were health maintenance organization (HMOs). Only 22.9% of HIPs were high-deductible health plans (HDHP). The majority of cancer centers offered PPO plans (75.4%), HMO plans (57.4%), HDHP plans (55.7%), and some (24.6%) offered other plans, such as point of service and exclusive provider organization. Average costs for different kinds of HIPs are presented in the Table. A higher percentage of public cancer centers provided HMOs (60.5% vs. 50.0%, p=0.76) and PPOs (84.3% vs. 60.5%, p=0.09) than private centers, yet differences did not reach significance. Centers located in regions with higher state population density were more likely to have higher HMO OOP costs (beta=2.72; p=.006) and lower PPO OOP costs (beta=-2.98; p=.012). Conclusions: We found that most NCI-designated cancer centers had readily available information about HIPs provided to physicians. For these centers, physicians had limited HIP options offered, particularly in private institutions, which offered fewer HMO and PPO plans. We also demonstrated associations among state population density and OOP max in HMO and PPO plans. Our study provides a current synopsis of HIPs and identifies disparities among them, contributing to a foundation for future research. [Table: see text]
Looking Beyond the Usual Suspects: A Rare Case of Teriparatide-Induced Gynecomastia
Authors: Ramchandani Bhanvi , Mirza Faryal Sardar
Published: June 2024

Teriparatide, an osteoanabolic agent, is a biosynthetic analogue of the 1-34 amino acids of human parathyroid hormone (PTH) used for the treatment of osteoporosis. It is typically well-tolerated; common side effects include headaches, arthralgias, nausea, and dizziness. In this report, we present a case of gynecomastia occurring shortly after initiating teriparatide therapy, associated with nipple sensitivity and breast tenderness. Secondary workup for various causes of gynecomastia was unremarkable. Finally, a decision was made to discontinue teriparatide due to the patient’s concerns. The nipple sensitivity started improving shortly afterward, with complete resolution of gynecomastia 4 months later. Although this unusual side effect has been reported as a possibility in postmarketing studies, a chronological report on the occurrence of teriparatide-induced gynecomastia and its complete resolution after discontinuing teriparatide has not yet been published in the literature.
Cauldron, Copper, Cash: Medieval Bronze in Motion and Flux
Authors: Moser Jeffrey
Published: June 2024

Medieval Chinese thinkers conceptualized ancient bronzes in anthropocentric terms—as mute, inert objects that required the engagement of a perspicacious human subject for their value to become apparent. They also regarded bronzes as animate things that had the capacity to act independently of direct human manipulation, and they situated bronzes within frameworks of material vitalism that parallel many aspects of the “new materialism” associated with contemporary theorists like Karen Barad and Jane Bennett. This article interprets both of these understandings as containment strategies designed to rein in and constrain bronze's ever-present capacity for liquefaction. As with other metals, bronze was forever oscillating between solidity, in the form of discrete, functional objects, and liquidity, as a mutable substance of tremendous potency. Both states spawned different metaphors. Tracing this tension between solidity and liquidity, from the casting of the Nine Cauldrons and the origin myths of Chinese civilization through the medieval challenge of adapting a metallist currency regime to an expanding economy, this article explores how the cultural logics and natural tendencies of bronze were intertwined.
Η συμβολή τεχνολογικά εμπλουτισμένων εκπαιδευτικών παιχνιδιών στην ενίσχυση του καταστασιακού ενδιαφέροντος στο μάθημα της μουσικής στην πρωτοβάθμια εκπαίδευση
Authors: Ματζίρης Χρήστος
Published: June 2024

Πρόσφατες έρευνες επισημαίνουν τον σημαντικό ρόλο του ενδιαφέροντος στην εκπαιδευτική διαδικασία. Το ενδιαφέρον συμβάλλει θετικά στην προσοχή και τη μάθηση και ενεργοποιείται από την προγενέστερη γνώση και το απροσδόκητο περιεχόμενο. Επιπλέον, η χρήση παιχνιδιών ως εργαλείων μάθησης προάγει την κριτική σκέψη, την ανάληψη ρίσκου, ενισχύει την προσοχή των μαθητών, τους εκπαιδεύει να εργάζονται υπό πίεση, να διασκεδάζουν, να σέβονται τους κανόνες και να διαχειρίζονται καλύτερα τη νίκη ή την ήττα σε ένα απόλυτα ασφαλές περιβάλλον. Η παρούσα έρευνα δράσης είχε ως στόχο την ενίσχυση του καταστασιακού ενδιαφέροντος των μαθητών Γ΄ και Δ΄ Δημοτικού Γενικής Παιδείας στο διδακτικό αντικείμενο της μουσικής. Για το σκοπό αυτό σχεδιάστηκαν και εφαρμόστηκαν τρία τεχνολογικά εμπλουτισμένα εκπαιδευτικά παιχνίδια, δηλαδή παιχνίδια που συνδυάζουν τη χρήση φυσικών αντικειμένων (όπως ζάρια, καρτέλες και μουσικά όργανα) με τη χρήση ενός εικονικού υπολογιστικού περιβάλλοντος πλήρως ελεγχόμενου από τον εκπαιδευτικό. Μέσα από μία μικτή ερευνητική προσέγγιση τριών φάσεων που περιλάμβανε ερωτηματολόγια ανοιχτού και κλειστού τύπου, συνεντεύξεις και παρατήρηση διερευνήθηκε το καταστασιακό ενδιαφέρον των μαθητών πριν, κατά τη διάρκεια και μετά την εφαρμογή τριών τεχνολογικά εμπλουτισμένων εκπαιδευτικών παιχνιδιών. Επίσης διερευνήθηκαν καταστάσεις και δραστηριότητες που ενίσχυσαν ή μείωσαν το ενδιαφέρον των μαθητών, στοιχεία που λήφθηκαν υπόψη στον αναστοχασμό και τον σχεδιασμό της κάθε φάσης. Τα αποτελέσματα της έρευνας έδειξαν ότι υπήρξε ενίσχυση του περιστασιακού/ καταστασιακού ενδιαφέροντος κατά τη διάρκεια και μετά την υλοποίηση του παιχνιδιού, κάνοντας το μάθημα της μουσικής ελκυστικότερο και ενισχύοντας τα θετικά συναισθήματα των μαθητών. Η παρούσα διατριβή επιβεβαιώνει προγενέστερες μελέτες οι οποίες ασχολούνται με στρατηγικές μάθησης που ενισχύουν το περιστασιακό/ καταστασιακό ενδιαφέρον, όπως η παροχή επιλογών, η ομαδική εργασία, η ενσωμάτωση στοιχείων παιχνιδιού καθώς και η χρήση καινοτομιών και ποικιλίας στη μαθησιακή διαδικασία.
Μαθηματικές ιδιότητες της γραμμικής ελαστικότητας
Authors: Λαμπροπούλου Δήμητρα
Published: June 2024

Η μηχανική των συνεχών μέσων και η θεωρία της ελαστικότητας είναι βασικές για την επιστήμη και την τεχνολογία. Η παρούσα διατριβή μελετά τις βασικές ιδιότητες της γραμμικής ισότροπης και ανισότροπης ελαστικότητας, αναπτύσσοντας αναλυτικές λύσεις. Αρχίζοντας από τα ισότροπα υλικά, η γραμμική ισότροπη ελαστικότητα περιγράφεται από τους νόμους του Hooke και του Newton, οδηγώντας στη γενικευμένη εξίσωση Navier. Η σφαιρική γεωμετρία χρησιμοποιείται για την επίλυση προβλημάτων ελαστικότητας, παράγοντας βασικές συναρτήσεις σε σφαιρικές συντεταγμένες. Η ανισότροπη ελαστικότητα εξετάζει υλικά με ιδιότητες που αλλάζουν με τον προσανατολισμό, εφαρμόζοντας τη θεωρία στον νόμο του Newton και του Hooke, καθώς και τον τελεστή δυσκαμψίας. Η μελέτη επικεντρώνεται στο κυβικό σύστημα, χρησιμοποιώντας έναν τροποποιημένο τελεστή κλίσης για την περιγραφή της συμπεριφοράς ανισότροπων υλικών. Υπολογίζονται θεωρητικά ανισότροπες αρμονικές συναρτήσεις και χρησιμοποιούνται για την επίλυση του νόμου του Newton χωρίς σωματικές δυνάμεις, παράγοντας πολυωνυμικές λύσεις για ισότροπα και ανισότροπα υλικά. Η αξιοπιστία της μεθοδολογίας επιβεβαιώνεται μέσω των αποτελεσμάτων από τον ανισότροπο στον ισότροπο χώρο, με εφαρμογή σε ένα αντιπροσωπευτικό πρόβλημα.