bluuebunny/crossref_metadata_2025 huggingface dataset:
YAP1 controls the N-cadherin-mediated tumor-stroma interaction in melanoma progression
Authors: Xio Yao , Zhou Lilni , Andl Thomas , Zhang Yuhang
Published: July 2023

Epithelial-to-mesenchymal transition (EMT) is crucial for melanoma cells to escape keratinocyte control, invade underlying dermal tissues, and metastasize to distant organs. The hallmark of EMT is the switch from epithelial cadherin (E-cadherin) to neural cadherin (N-cadherin), allowing melanoma cells to form a homotypic N-cadherin-mediated adhesion with stromal fibroblasts. However, how “cadherin switching” is initiated, maintained, and regulated in melanoma remains unknown. Here, we show that upon Yes-associated protein 1 (YAP1) ablation in cancer-associated fibroblasts (CAFs), the progression of a BRAF-mutant mouse melanoma was significantly suppressed in vivo, and overexpressing YAP1 in CAFs accelerated melanoma growth. CAFs require the YAP1 function to proliferate, migrate, remodel the cytoskeletal machinery and matrix, and promote cancer cell invasion. By RNA-Seq, N-cadherin was identified as a major downstream effector of YAP1 signaling in CAFs. YAP1 silencing led to N-cadherin downregulation in CAFs, which subsequently induced the downregulation of N-cadherin in neighboring melanoma cells. N-cadherin downregulation inhibited the PI3K-AKT signaling pathway in melanoma cells and suppressed melanoma growth in vivo, supporting the role of N-cadherin as an adhesive and signaling molecule in melanoma cells. This finding suggests that YAP1 depletion in CAFs induces the downregulation of p-AKT signaling in melanoma cells through the N-cadherin-mediated interaction between melanoma cells and CAFs. Importantly, our data underscore that CAFs can regulate N-cadherin-mediated interactions with melanoma cells. Thus, disentangling cadherin-mediated cell‒cell interactions can potentially disrupt tumor-stroma interactions and reverse the tumor cell invasive phenotype.
Influence of the low plasticity burnishing on surface quality and ultra-microhardness
Authors: de Oliveira Diogo Azevedo , Martins Augusto Moura , Santos Anderson Júnior dos , Magalhães Frederico de Castro , Abrão Alexandre Mendes
Published: July 2023

Low plasticity burnishing (LPB) is a mechanical operation that aims to improve surface quality and mechanical properties of components, as an increase on hardness and fatigue resistance. In this work, a LPB device was developed to be use on flat and complex surfaces. To evaluate is applicability on a machining center, LPB was conducted on flat surfaces of AISI 304 Stainless steel. Roughness, waviness, and microhardness were evaluated as a function of the number of passes (n) and burnishing speed (V). The burnishing tests results indicated that the device presented repeatability and stability. The number of burnishing passes influenced the microgeometric profile as well as the macrogeometric one. Considering the arithmetic mean roughness (Ra) an increase on both input parameters promoted a decrease of amplitude. Number of passes was the most significant parameter, reducing the profile amplitude by deforming the roughness peaks originated from previous passes. The increase on V also promoted a decrease on Ra. For maximum profile peak height (Rp) and maximum profile valley depth (Rv), the number of passes was the most significant parameter. The interaction between n and V was also significant. The waviness parameters also had distinct influences, for arithmetic mean waviness (Wa) only the Vn interaction was significant, for the maximum profile peak height (Wp) the main effects were significant and for maximum profile valley depth (Wv) only the interaction. The number of passes showed a more significant influence on microhardness and an increase of n resulted in higher values.
An Efficient CNN-based LSTM Approach to Detect the Rumor Prediction in COVID-19 Data using Fuzzy based Deep learning
Authors: Mukiri Raja Kumari , Burra Vijaya Babu
Published: July 2023

As the traditional rumor detection method is concerned, reduce in the data accuracy may influence the observation directivity and lack in the extraction of feature datasets. In order to overcome the above problem, here the modified rumor prediction model is proposed using deep learning with the integration of CNN in order to improve the data accuracy with the help of neural networks. First, the continuous bag of words (CBOW) model is modified to define the window context based on the definition of the weighted module. Then, CNN gets modified with the association of the attention module added along with the output of the weighted module as it helps to identify the feature incompleteness in the long sequence of online social networks. The attention module along with CNN with the function of max pooling and upsampling layer in order to extract the features in the text effectively. Then, the extracted feature is given into the softmax layer for performing text classification to identify and predict the rumor in the online social network. Based on the online samples, the analysis is conducted on the proposed model based on certain parameter such as, data accuracy, precision, recall and F1-Score as it shows better performance as compared to the other existing models like LSTM based Fuzzy deep learning, deep recurrent Q-learning and adaptive deep transfer learning.
MicroRNA-Mediated Obstruction of Stem-loop Alternative Splicing (MIMOSAS): a global mechanism for the regulation of alternative splicing
Authors: Zhai Rong , Ruan Kai , Perez German Farinas , Kubat Miroslav , Liu Jiaqi , Hofacker Ivo , Wuchty Stefan
Published: July 2023

While RNA secondary structures are critical to regulate alternative splicing of long-range pre-mRNA, the factors that modulate RNA structure and interfere with the recognition of the splice sites are largely unknown. Previously, we identified a small, non-coding microRNA that sufficiently affects stable stem structure formation of Nmnat pre-mRNA to regulate the outcomes of alternative splicing. However, the fundamental question remains whether such microRNA-mediated interference with RNA secondary structures is a global molecular mechanism for regulating mRNA splicing. We designed and refined a bioinformatic pipeline to predict candidate microRNAs that potentially interfere with pre-mRNA stem-loop structures, and experimentally verified splicing predictions of three different long-range pre-mRNAs in the Drosophila model system. Specifically, we observed that microRNAs can either disrupt or stabilize stem-loop structures to influence splicing outcomes. Our study suggests that MicroRNA-Mediated Obstruction of Stem-loop Alternative Splicing (MIMOSAS) is a novel regulatory mechanism for the transcriptome-wide regulation of alternative splicing, increases the repertoire of microRNA function and further indicates cellular complexity of post-transcriptional regulation.
Dual engagement of the nucleosomal acidic patches is essential for deposition of histone H2A.Z by SWR1C
Authors: Peterson Craig , Baier Alexander , Gioacchini Nathan , Eek Priit , Tan Song
Published: July 2023

The SWR1C chromatin remodeling enzyme catalyzes the ATP-dependent exchange of nucleosomal histone H2A for the histone variant H2A.Z, a key variant involved in a multitude of nuclear functions. How the 14-subunit SWR1C engages the nucleosomal substrate remains largely unknown. Numerous studies on the ISWI, CHD1, and SWI/SNF families of chromatin remodeling enzymes have demonstrated key roles for the nucleosomal acidic patch for remodeling activity, however a role for this nucleosomal epitope in nucleosome editing by SWR1C has not been tested. Here, we employ a variety of biochemical assays to demonstrate an essential role for the acidic patch in the H2A.Z exchange reaction. Utilizing asymmetrically assembled nucleosomes, we demonstrate that the acidic patches on each face of the nucleosome are required for SWR1C-mediated dimer exchange, suggesting SWR1C engages the nucleosome in a “pincer-like” conformation, engaging both patches simultaneously. Loss of a single acidic patch results in loss of high affinity nucleosome binding and nucleosomal stimulation of ATPase activity. We identify a conserved arginine-rich motif within the Swc5 subunit that binds the acidic patch and is key for dimer exchange activity. In addition, our cryoEM structure of a Swc5-nucleosome complex suggests that promoter proximal, histone H2B ubiquitinylation may regulate H2A.Z deposition. Together these findings provide new insights into how SWR1C engages its nucleosomal substrate to promote efficient H2A.Z deposition.
CERN-based Experiments and Monte Carlo Simulations on Focused VHEE (Very High Energy Electron) Beams For Radiotherapy
Authors: Whitmore Lucy , Mackay Ranald , Herk Marcel van , Korysko Pierre , Farabolini Wilfrid , Malyzhenkov Alexander , Corsini Roberto , Jones Roger Michael
Published: July 2023

Very High Energy Electrons (VHEEs) are a promising alternative to conventional radiotherapy due to their highly penetratingnature and their applicability as a modality for FLASH (ultra-high dose rate) radiotherapy. The dose distributions due to VHEE need to be optimised; one option is through the use of quadrupole magnets to focus the beam, reducing the dose to healthy tissue and allowing for targeted dose delivery at conventional or FLASH dose rates. This paper presents the first targeted area of focused VHEE dose delivery in air and a water phantom, obtained using six quadrupoles at fixed field strengths and adjusted by changing only the strength of one quadrupole and the beam charge at the CLEAR (CERN Linear Electron Accelerator forResearch) facility for beam energies >200 MeV. Experimental results have been verified with Monte Carlo modelling. This targeted dose delivery method in the form of a ’Spread-Out Electron Peak’ (SOEP), analogous to the Spread-Out Bragg Peak(SOBP) for protons, could potentially be used in future (FLASH) VHEE treatments. As a step towards this, the effect of the vacuum beampipe aperture size and spacings between quadrupoles were explored and optimised in Monte Carlo simulations.
Study on the correlation between intestinal flora and trimethylamine oxide on gallbladder stone formation
Authors: Zhang Yang , Wang Qi , Wang Xiaowen , Yang Jiming
Published: July 2023

In patients with gallbladder stones, there are differences in intestinal flora, oxidized trimethylamine, triglyceride and cholesterol levels compared to the healthy population. We investigated whether there is a correlation between gallbladder stones and intestinal flora and other outcomes to provide a new reference for gallbladder stone prevention and treatment. We used 40 patients with gallbladder stones who met the inclusion criteria in the Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, from January 2021 to December 2021 as a case group. During the same period, 35 medical examiners who underwent health checkups at our hospital served as the control group. We extracted blood, urine, and stool specimens from the case and control groups for the study and analysis of relevant indexes. We found no significant difference in the levels of the phylum Thick-walled Bacteroides and Bacteroides in the case and control populations at the level of bacterial phylum. In the case group population the content of Aspergillus was higher than in the control group (P<0.05). At the level of bacterial genera, the levels of Enterococcus faecalis, Eubacterium were increased in the case group compared to the control group (P<0.05). The levels of trimethylamine oxide in blood and urine were higher in the case group population than in the control group (P<0.05). In contrast, the triglyceride and cholesterol levels in both groups, were not statistically significant (P>0.05). Therefore, we conclude that the distribution of intestinal flora and the abnormalities of oxidized trimethylamine in patients with gallbladder stones suggest that there may be a correlation between these two types of factors on gallbladder stone formation.
Regional and seasonal differences of radar reflectivity slopes in lower troposphere in convective and stratiform precipitation using TRMM PR data
Authors: Kumar Shailendra
Published: July 2023

Slopes of radar reflectivity below freezing height (FZH) is a critical parameter to estimate the correct rainfall near the surface. TRMM PR based radar reflectivity slopes is presented here, during Indian and Austral summer monsoon by calculating them in lower troposphere (< 4 km). Slopes are either positive or negative, which means they are either decreasing or increasing towards the surface. In majority of cases, slopes decrease towards the surface over land, but increases towards the surface over ocean. A close similarity has been observed in the tropical oceanic areas in convective precipitation and Arabian Ocean consists of the highest fraction (89.10~%) of negative slopes, whereas Bay of Bengal has the highest fraction of positive slopes (21~%) in convective precipitation. Western Himalaya Foothills has the highest fraction of positive slope in convective precipitation and shows that ~ 76% and 83% of convective and stratiform profiles decrease towards the surface. During Austral summer monsoon Maritime Continent consists of the highest fraction of negative slopes (~ 92%%) in convective precipitation followed by Equatorial Indian Ocean. Land vs ocean and regional differences in radar reflectivity slopes are higher in convective precipitation compared to stratiform precipitation. Vertical profiles with extreme positive (> 1) slopes have higher ETH in convective precipitation over tropical ocean during both the seasons, whereas over the land higher ETHs are contributing to negative slopes.
Fetal face shape analysis from prenatal 3D ultrasound images
Authors: Sivera Raphael , Clark Anna E. , Dall'Asta Andrea , Ghi Tullio , Schievano Silvia , Lees Christoph C.
Published: July 2023

3D ultrasound imaging of fetal faces has been predominantly confined to qualitative assessment. Many genetic conditions evade diagnosis and identification could assist with parental counselling, pregnancy management and neonatal care planning. We describe a methodology to build a shape model of the third trimester fetal face from 3D ultrasound and show how it can objectively describe morphological features and gestational-age related changes of normal fetal faces. 135 fetal face 3D ultrasound volumes (117 appropriately grown, 18 growth-restricted) of 24-34 weeks gestation were included. A 3D surface model of each face was obtained using a semi-automatic segmentation workflow. Size normalisation and rescaling was performed using a growth model giving the average size at every gestation. The model demonstrated a similar growth rate to standard head circumference reference charts. A landmark-free morphometry model was estimated to characterize shape differences using non-linear deformations of an idealized template face. Advancing gestation is associated with widening/fullness of the cheeks, contraction of the chin and deepening of the eyes. Fetal growth restriction is associated with a smaller average facial size but no morphological differences. This model may eventually be used as a reference to assist in the diagnosis of congenital anomalies with characteristic facial dysmorphisms.
New Benchmarks on Demographic Disparities in Pivotal Trials Supporting FDA Approved Drugs and Biologics
Authors: Smith Zachary , Botto Emily , Johnson Otis , Getz Kenneth
Published: July 2023

Background
A lack of diversity and representation in clinical trials is an established issue in drug development, and the COVID-19 pandemic increased awareness of the problem among the general public. This awareness has led to increased pressure on drug development sponsors, as well as additional attention and regulation from federal bodies, to improve the diversity of clinical trials. This study updates existing baselines regarding demographic disparities, as well as detecting early signs that the situation may be starting to improve.
Methods
Building on an existing dataset, this study collected and analyzed pivotal trial demographic data for drugs and biologics approved by the FDA between 2007 and 2021. Demographic data were collected from applications on the FDA website and clinicaltrials.gov, and compared to indication-specific demographic data when available, or US Census estimates when they were not. Regression analyses were used to test for significant trends in reporting of demographic data and representation in pivotal trials, as well as the effect of representation on clinical trial duration and FDA review.
Results
Reporting of demographic data has improved significantly for all three demographic categories (sex, racial identity, and ethnic identity) over the observed time period (p < .0001). During this time period, overrepresentation of white participants has decreased significantly (p < .0001), and representation of Black participants has increased (p = .0003). Other racial and ethnic identities did not show significant trends. Representation of demographic subgroups were not significant predictors of trial duration except for the representation of Black participants, which was a negative correlation, indicating that as representation of Black participants increases, trial duration decreases (p = .0350).
Research on the Recyclable Design of Wooden Furniture Based on the Recyclability Evaluation
Authors: Zhang zhuoyu , Zhu Jiangang , Qi Qian
Published: July 2023

With the rapid development of the economy and the change of people's aesthetic concept, the renewal of furniture has become more and more frequent. Among the huge amount used furniture, solid wood and wood-based panel furniture account for the vast majority, but the imperfective recycling system and the insufficient recycling efforts resulting in serious waste, which is contrary to the low-carbon transition and sustainable development means. Based on the whole life cycle theory of products, the recyclable designability of wooden furniture at all stages of design, manufacturing, sales, use, recycling were researched and analyzed, and feasible suggestions to the government, enterprises and consumers were proposed respectively. In particular, an evaluation index system and evaluation model for the recyclability of wooden furniture were established with an aim to quantitatively analyze the recycling of wooden furniture, which will provide certain references not only to achieve reasonable recycling and disposal of used furniture but also to solve the furniture recycling issues from various levels.
The incidence and risk of different indwelling times of peripherally inserted central catheter-related venous thrombosis in cancer patients: a retrospective analysis of 654 patients
Authors: Tan YuQin , Chen ShiLi , Xi YuXiang , Fang JingJing , Lai DanQi , Chen YanNi , Lin ZiQi , Xie RongZhi
Published: July 2023

Purpose
The purpose of this study was to investigate the incidence of peripherally inserted central catheter-related venous thrombosis (PICC-RVT) in cancer patients with different indwelling times after PICC catheterization, and to explore the main factors related to PICC-RVT in cancer patients.
Methods
A retrospective study of a total of 654 cancer patients who underwent PICC insertion was conducted from January 2020 to December 2021 in a tertiary hospital in Guangdong Province, China. The risk factors for PICC-RVT in cancer patients were analyzed by logistic regression, including the clinical symptoms of the patients and the monitoring of asymptomatic thrombosis in combination with color Doppler ultrasonography.
Results
The incidence of PICC-RVT in cancer patients reached 24.9% (n = 163), among which the incidence of thrombosis at 1 month, 3 months, and 6 months and more was 30.6% (n = 11), 25.5% (n = 37) and 18.89% (n = 115), respectively. Multivariable analysis identified 6 variables: "age", "sex", "BMI", “with or without chemotherapy ", "different catheter indwelling duration" and "different cancer types". We observed a trend for a higher risk of PICC-RVT in cancer patients who were male (OR = 1.46, P = 0.035), were older than 69 years (OR = 1.76, P = 0.08), had a BMI < 18.5 (OR = 0.47, P = 0.015), and did not undergo chemotherapy (OR = 0.52, P = 0.048), which were determined to be independent influencing factors for PICC-RVT in cancer patients.
Conclusion
PICCs had a high incidence of thrombosis in the early indwelling period. The results suggest that patients with cancer who are male, elderly, emaciated, and not receiving chemotherapy should be monitored and treated to prevent PICC-RVT.
Web-based problem-based learning (PBL) and scenario simulation teaching in airway management for undergraduate students
Authors: Lin Yun , Wang Ting-ting , Hou Yuan-yuan , Wen Qing-ping , Lu Xin-yu , Gao Le-jun , Hersi Salad Abdirahman , Oliver Patrick J , Gao Peng
Published: July 2023

Background
This study aimed to evaluate the effectiveness of web-based combination of problem-based learning (PBL) and scenario simulation teaching in airway management course for undergraduate anesthesia students.
Methods
Sixty-five undergraduate students participated in the web-based airway management course. Both pre- and post-class quizzes were administered to assess students' knowledge. The effectiveness of the teaching modality was observed by comparing the pre- and post-class quiz scores, along with the technical skills scores and non-technical skills scores in two simulation scenarios. Additionally, an anonymous questionnaire was distributed to evaluate the students' perceptions and experiences.
Results
The results revealed a significant improvement in students' scores on the second quiz after completing the PBL combined with simulation course compared to the first quiz (p < 0.001). Moreover, during the second simulation, students demonstrated enhanced technical skills across all four simulation scenarios (p = 0.030, p = 0.037, p = 0.028, p = 0.028, respectively), as well as non-technical skills (including task management, teamwork, communication, sustained vigilance, crisis identification, decision-making, and self-confidence). The questionnaire responses indicated that students found the course enjoyable and helpful in improving their problem-solving skills. Furthermore, 97.3% of the students believed that the course enhanced their self-learning and teamwork skills, while 97.22% of students felt that it facilitated the mastery of anesthesia skills.
Conclusions
The combination of PBL and simulation-based teaching proves to be a highly effective approach in online anesthesia education. It stimulates students' interest in learning and fosters the development of critical thinking and non-technical skills.
The nexus between air pollution and the COVID-19 pandemic in Turkey: Further evidence from wavelet coherence analysis
Authors: Aladag Erdinc
Published: July 2023

The effect of the ambient air quality on the COVID-19 pandemic is a topic that has attracted much attention and still remains of current interest. The study area of Turkey is one of the countries with high case numbers, but there is no detailed investigation dealing with it in the literature. For this reason, the correlation and nexus between COVID-19 cases and deaths in Turkey with the air pollutants of PM10, PM2.5, SO2, CO, NO2 and O3 were determined between 1 April and 31 July 2021 using the statistical methods of correlation and wavelet coherence analysis. According to the findings, for the COVID-19 pandemic parameters, there were positive significant correlations with PM2.5, SO2, CO, and NO2 and an inverse significant correlation with O3. Wavelet transform coherence revealed that air pollution, which has significant effects on human life, was one of the main determinants of the spread and mortality linked to the pandemic. Additionally, it is notable that the national air quality improved during full lockdown periods in the country. The findings obtained in this study are expected to attract the attention of legislating and enforcing authorities and support more decisive steps being taken to reduce environmental pollutants and to control air pollution.
Factors Associated with Infectious Diseases Fellowship Academic Success
Authors: Khodadadi Ryan B. , Yetmar Zachary A. , Domonoske Cynthia L. , Razonable Raymund R.
Published: July 2023

Background: A multitude of factors are considered in an infectious diseases (ID) training program’s meticulous selection process of ID fellows but their correlation to pre and in-fellowship academic success as well as post-fellowship academic success and short-term outcomes is poorly understood. Our goal was to investigate factors associated with subsequent academic success in fellowship as well as post-fellowship short-term outcomes.
Methods: In 2022, we retrospectively analyzed deidentified academic records from 39 graduates of the Mayo Clinic Rochester ID Fellowship Program (July 1, 2013- June 30, 2022). Data abstracted included demographics, degrees, honor society membership, visa/citizenship status, medical school, residency training program, United States Medical Licensure Exam (USMLE) scores, letters of recommendation, in-training examination (ITE) scores, fellowship track, academic rank, career choice, number of honors, awards, and abstracts/publications prior to fellowship, during training, and within 2 years of graduation.
Results: Younger fellows had higher USMLE step 1 scores, pre and in-fellowship scholarly productivity, and higher ITE performance. Female fellows had significantly higher USMLE step 3 scores. Prior research experience translated to greater in-fellowship scholarly productivity. Higher USMLE scores were associated with higher ID ITE performance during multiple years of fellowship, but USMLE step 2 clinical knowledge and 3 scores were associated with higher pre and in-fellowship scholarly productivity and receiving an award during fellowship. USMLE step 1 score did not correlate with fellowship performance beyond year 1 and 2 ITE scores.
Conclusions: Multiple aspects of a prospective fellow’s application must be considered as part of a holistic reviewprocess for fellowship selection. USMLE step 2 CK and 3 scores may predict fellowship performance across multiple domains.
Multiphoton Spectroscopy of a Dynamical Axion Insulator
Authors: Narang Prineha , Liebman Olivia , Curtis Jonathan , Petrides Ioannis
Published: July 2023

The unusual magnetoelectric transport present in Weyl semimetals can be compactly understood as manifestations of an underlying axion field, which itself is determined by the microscopic band structure. The axion couples nonlinearly to electric and magnetic fields and possesses a signature topological magnetoelectric response, leading to a modified form of Maxwell’s equations known as axion electrodynamics. Axions are naturally present in Weyl semimetals relating to the separation of the Weyl nodes in energy and in crystal momentum. In the presence of strong interactions, charge density-wave (CDW) order may develop which serves to gap the Weyl nodes and introduces corresponding collective excitations. When the inherent chiral symmetry of Weyl semimetals is spontaneously broken by the formation of CDW order, the resultant chiral condensate is endowed with intrinsic dynamics which yields a dynamical contribution to the axion field. However, unambiguous identification of this dynamical axion mode is challenging due to its inherent nonlinear coupling to electromagnetic fields. Therefore, we propose an all-optical protocol for verifying and characterizing dynamical axion collective modes in Weyl semimetals with CDW order. First, we show that axion collective mode can be excited using two-photon excitation schemes. Following excitation, the collective axion oscillations are then diagnosed by measuring the time-resolved Kerr rotation. Our results demonstrate a pathway towards utilizing multi-photon and entangled pair spectroscopies to identify new correlated phases in quantum matter.
Growth retardation associated with a novel DNMT3A variation in a Chinese boy: A Case Report
Authors: Wang Li-Xia , Yang Wu , Zhang Hongwen
Published: July 2023

Background The human gene DNMT3A (DNA methyltransferase 3 alpha) is involved in DNA de novo methylation essential for genome regulation and development. Pathogenic variants in DNMT3A are most commonly associated with variable overgrowth (such as Tatton-Brown-Rahman Syndrome, TBRS), intellectual disability, autism spectrum disorder (ASD) and acute myeloid leukemia (AML). We identified a de novo DNMT3A variant in a Chinese boy with growth retardation. Case presentation A 2.8-year boy was hospitalized with a complaint of growth retardation for 24 months. He was born at 38 weeks of gestation. He showed obviously growth retardation since 3 months of age later, including weight and height. His motor and intellectual developmental milestone were slightly delayed. He began to rise head and turn over at 4 months, sit at 6 months, crawl at 7 months and work at 18 months, respectively. He began to speak a single word at 12 months and could speak few words at 2 years. At admission at 2.8 years of age, his weight was 9.6 kg (< P3th), height was 85.4 cm (< P3th), and head circumference was 45.2 cm (< P3th). He could run but could not jump with two feet, he could follow easy and simple instructions. Physical examination revealed no abnormal signs, especially no abnormal dysmorphic features. A de novo DNMT3A variant, c.911_913del (p.S304del), was identified using next-generation sequencing. His growth retardation was associated with DNMT3A variation. Conclusion We reported here the first case presented with growth retardation who was associated with a de novo DNMT3A variation in a Chinse boy. Our report has expanded on the clinical phenotype of the DNMT3A gene, which can also associated with growth retardation besides overgrowth.
Clinical Significance of Multi-Cancer Genome Profiling: Data from A Japan Hospital
Authors: Aoyama Rika , Nishikubo Hinano , Kawabata Kyouka , Kanei Saki , Yamamoto Yurie , Nishimura Sadaaki , Yashiro Masakazu
Published: July 2023

Aim
New hopes for “precision cancer care” hinge on the success of individualized cancer genome profiling at predicting the therapeutic efficacy of various anticancer drug treatments in eligible patients. We aimed to clarify the significance of cancer genome profiling in Japan by analyzing the clinical data from cancer genome testing of various solid cancers at our hospital.
Materials and Methods
A total of 230 patients examined by one of three tests for multi-cancer genome profiling including NCC Oncopanel, FoundationOne CDx, and FoundationOne Liquid were retrospectively enrolled. Adequate treatment for each patient was discussed at the expert panel meeting according to the results from the genome profiling tests.
Results
The most frequent cancer types enrolled in this study were pancreas cancer, bowel cancer, and biliary cancer. Druggable cases comprised 108 (47%) of 230 cases, and 21 (9.1%) of 230 cases actually received medication. Partial Response (PR) was found in 7 (33%) of the 21 cases Three cases of biliary cancer and three cases of BRCA2 mutation were included among the seven PR cases.
Conclusion
Twenty-one (9.1%) of 230 patients were medicated in accord with multi-cancer panel data. Japanese patients with biliary tumors might derive benefit from multi-cancer genome profiling.
Experimental Study and Numerical Simulation of Morphing Characteristics of Bistable Laminates Embedded with 4D Printed Shape Memory Polymers
Authors: Zhang Zheng , Yang Guoquan , Pan Baisong , Sun Min , Zhang Guang , Chai Hao , Wu Huaping , Jiang Shaofei
Published: July 2023

The morphing characteristics of bistable laminates embedded with 4D printed shape memory polymers are investigated. Bistable laminates have potential applications in soft robotics due to their two stable states and ability to deform through both snap-through and snap-back processes. For example, a bistable laminate is triggered to snap back by a pneumatic-actuated method that allows it to grip objects. By reducing the snap-back load and increasing the snap-through load, the bistable laminate can be more easily driven to deform while maintaining good stiffness in its first stable state. 4D printed shape memory polymers have shape memory and recovery, A design method for suppressing and controlling the deformation of bistable laminates using 4D printed shape memory polymers is proposed in this paper. A numerical model of viscoelasticity of the laminate is established to study its deformation characteristics, and the numerical results are compared with experimental results with good agreement. The effect of shape memory polymers on the snap load and principal curvature of bistable laminates is also investigated. Finally, the interlayer interface bonding of the bistable laminates is examined in microscopic perspective. The results demonstrate that 4D printed shape memory polymers can effectively enhance the snap-through load and reduce the snap-back load of bistable laminates, achieving deformation suppression and control while maintaining good interlaminar bonding with carbon fiber composites. This study provides new insights and practical significance for the deformation suppression and active control of bistable structures.
Screening utility and acceptability of the Kiswahili-pGALS (paediatric Gait, Arms, Legs, Spine) at a tertiary referral hospital in Kenya-A diagnostic accuracy study.
Authors: Kawishe Jacqueline Evarist , Ngugi Anthony , Luchters Stanley , Foster Helen , Migowa Angela
Published: July 2023

Background: Paediatric rheumatic diseases cause considerable disease burden to children and their families (1). Delayed diagnosis is a significant determinant of severity and mortality attributed to these conditions (2). pGALS is a simple clinical tool used to assess joints and identify musculoskeletal (MSK) conditions in school-going children to enable early referral to paediatric rheumatologists.
Objectives: This study aimed to translate and determine the diagnostic accuracy and acceptability of a Kiswahili version of the pGALS screening tool among Kiswahili-speaking children.
Methods: The pGALS screening questions were translated into Kiswahili according to the World Health Organisation (WHO) standard for translation of a tool. The validity of the Kiswahili PGALS was ascertained and acceptability rated (time taken, discomfort). Using systematic random sampling, we enrolled children aged 5–16 years presenting at the Aga Khan University Hospital’s (AKUH) emergency department in Kenya, who spoke Kiswahili and had symptoms suggestive of an MSK condition. Those already under follow-up at the paediatric rheumatology service at AKUH were excluded. MSK assessment was undertaken by two resident doctors using the newly translated Kiswahili-pGALS and findings were compared with a paediatric rheumatologist examination (‘gold-standard’) on the same day, and who was blinded to the pGALS findings. We analysed demographic details of the participants and determined the diagnostic accuracy by cross tabulation of the index test results by the results of the reference standard.
Results: One hundred children with a median age of nine years (IQR 7–11) were enrolled. The sensitivity and specificity of the Kiswahili-pGALS screening tool were 76.8% (95%CI 63.6–87.0%) and 40.0% (95%CI 23.9–57.9%), respectively. The diagnostic accuracy was 62.7% (95%CI 52.1–72.1%), area under the ROC was 0.58 (95%CI 0.48–0.68). The median time to perform the Kiswahili-pGALS was 5.0 minutes (IQR 3.5-6.0 minutes). Ninety percent of the guardians found the practice of Kiswahili-pGALS to have none, or only some discomfort.
Conclusions: The Kiswahili-pGALS’s was found to be a useful screening tool to aid early identification of MSK conditions in Kiswahili-speaking settings. However, the low specificity implies that relatively large number of false positives would still need to be reviewed by a rheumatologist if the tool is adapted for use.
Regulation of endoplasmic reticulum stress on autophagy and apoptosis of nucleus pulposus cells in intervertebral disc degeneration and its related mechanisms
Authors: Dai Jiuming , Liu Jin , Shen Yucheng , Zhang Bing , Li Chaonian , Liu Zhidong
Published: July 2023

Background
Intervertebral disc degeneration (IVDD) is a common and frequent disease in orthopedics, which seriously affects the quality of life of patients. Endoplasmic reticulum stress (ERS)-regulated autophagy and apoptosis play an important role in nucleus pulposus (NP) cells in IVDD.
Methods and Results
Hypoxia and serum deprivation were used to induce NP cells. CCK-8 assay was used to detect cell activity and immunofluorescence (IF) was applied for the appraisement of GRP78 and GFP-LC3. Cell apoptosis was detected by flow cytometry and the expression of LC3II/I was detected by western blot. NP cells under hypoxia and serum deprivation were induced by lipopolysaccharide (LPS), and intervened by ERS inhibitor (4-phenylbutyric acid, 4-PBA) and activator (Thapsigargin, TP). Then, above functional experiments were conducted again and western blot was employed for the evaluation of autophagy-, apoptosis and ERS-related proteins. Finally, NP cells under hypoxia and serum deprivation were stimulated by LPS and intervened using apoptosis inhibitor z-VAD-FMK and autophagy inhibitor 3-MA. CCK-8 assay, IF, flow cytometry and western blot were preformed again. Besides, the levels of inflammatory cytokines were measured with ELISA and the protein expressions of programmed death markers were estimated with western blot. It showed that serum deprivation induces autophagy and apoptosis. ERS was significantly activated by LPS in hypoxic and serum deprivation environment, and autophagy and apoptosis were significantly promoted.
Conclusions
ERS affects the occurrence and development of IVDD by regulating autophagy, apoptosis and other programmed death.
Assessing and harnessing updated polyketide synthase modules through combinatorial engineering
Authors: Keatinge-Clay Adrian , Ray Katherine , Lutgens Joshua , Bista Ramesh , Zhang Jie , Desai Ronak , Hirsch Melissa , Miyazawa Takeshi , Cordova Antonio
Published: July 2023

The modular nature of polyketide assembly lines and the significance of their products make them prime targets for combinatorial engineering. While short synthases constructed using the recently updated module boundary have been shown to outperform those using the traditional boundary, larger synthases constructed using the updated boundary have not been investigated. Here we describe our design and implementation of a BioBricks-like platform to rapidly construct 5 triketide, 25 tetraketide, and 125 pentaketide synthases from the updated modules of the Pikromycin synthase. Every combinatorial possibility of modules 2-6 inserted between the first and last modules of the native synthase was constructed and assayed. Anticipated products were observed from 60% of the triketide synthases, 32% of the tetraketide synthases, and 6.4% of the pentaketide synthases. Ketosynthase gatekeeping and module-skipping were determined to be the principal impediments to obtaining functional synthases. The platform was also used to create functional hybrid synthases through the incorporation of modules from the Erythromycin, Spinosyn, and Rapamycin assembly lines. The relaxed gatekeeping observed from a ketosynthase in the Rapamycin synthase is especially encouraging in the quest to produce designer polyketides.
How high is high enough? A multi-million-member ensemble analysis of future climate scenarios and their relevance
Authors: Sarofim Marcus , Smith Christopher , Malek Parker , McDuffie Erin , Hartin Corinne , Lay Claire
Published: July 2023

High end emissions and forcing scenarios used to drive climate models provide key insights into possible high-risk climate change impacts in the 21st century and beyond. Given rapid and ongoing societal changes (e.g., population growth, energy demand, technology, etc.), debates are increasing on the continued relevance of higher forcing scenarios, such as those designed to reach 8.5 W/m2 by the end of the century (e.g., RCP8.5 and SSP5-8.5). Here, we determine an updated probability of exceeding 8.5 W/m2 by 2100 by generating a multi-million-member ensemble from a newly developed database of probabilistic greenhouse gas (GHG) emissions scenarios, augmented here with improved characterization of aerosols and minor GHGs, coupled with the newest version of a reduced complexity climate model, with parameter distributions calibrated to match the IPCC 6th Assessment Report. The probability of exceeding 8.5 W/m2 this century is estimated to be less than 1%: however, we discuss important rationales for the continued use of 8.5 W/m2 scenarios, including for generating high temperature scenarios for use in calibrating damage functions, characterizing climate in the 22nd century (probability of exceeding 8.5 W/m2 increases to ~7% by 2150), and assessing low-probability/high-impact futures.
3D Electrospinning of Al2O3/ZrO2 Fibrous Aerogels for Multipurpose Thermal Insulation
Authors: Dong Shiling , Maciejewska Barbara , Millar Robert , Grobert Nicole
Published: July 2023

Ceramic aerogels are excellent ultralight-weight thermal insulators yet impractical due to their tendency towards structural degradation at elevated temperatures, under mechanical disturbances, or in humid environments. Here, we present flexible and durable alumina/zirconia fibrous aerogels (AZFA) fabricated using 3D sol-gel electrospinning - a technique enabling in situ formation of 3D fiber assemblies with significantly reduced time consumption and low processing cost compared to most existing methods. Our AZFAs exhibit ultralow density (> 3.4 mg cm-3), low thermal conductivity (> 21.6 mW m-1 K-1), excellent fire resistance, whilst remaining mechanically elastic and flexible at 1300°C, and thermally stable at 1500°C. Particularly, we investigate the underlying structure-thermal conductivity relationships, demonstrating that the macroscopic fiber arrangement dictates the solid-phase thermal conduction, while mesopores in the fiber effectively trap air hence decreasing the gas conduction. We show experimentally and theoretically that directional heat transport, i.e., anisotropic thermal conductivity, can be achieved through compressing the fiber network. We further solve the moisture sensitivity problem of common fibrous aerogels through fluorination coating. The resulting material possesses excellent hydrophobicity and self-cleaning properties, which can provide reliable thermal insulation under various conditions, including but not limited to high-temperature conditions in vehicles and aircraft, wet humid conditions in buildings, and underwater environments for oil pipelines.
Knowledge and perception of nosocomial infections among patients in a Nigerian hospital
Authors: Oni Olawale , OROK Edidiong , Lawal Zainab , Ojo Tolulope , Oluwadare Tunrayo , Bamitale Toba , Jaiyesimi Boluwaji , Akinjisola Alice , Apara Titilayo
Published: July 2023

Background
Nosocomial infections are infections that are a leading cause of morbidity and mortality among hospitalized patients, and can lead to higher healthcare costs and longer hospital stays in both developed and developing countries. The objectives of the study were to identify the level of knowledge and perception of patients on nosocomial infection, and to determine the factors affecting the knowledge and perception of patients on nosocomial infection in Federal Medical Centre, Ebute-Metta, Lagos (FMC).
Methods
A cross- sectional research design was used in carrying out the research among in-patients of FMC where an interview-based semi-structured questionnaire was used for data collection. Patients’ knowledge was categorised as good (≥ 70% score), fair (50–69%) and poor (< 50% score) while perception was grouped as positive and negative. Independent sample T-test and One-way Analysis of Variance was used to assess statistical difference in knowledge scores between categorical variables with 2 and 3 groups respectively.
Results
A total of 102 patients gave consent to participate in this study of which 46.1% were male, 27.5% were aged between 38 and 47 years and 69.6% were married. About 24% did not know what is meant by nosocomial infections while 53.9% stated that all hospital-acquired infections are preventable. 18.6% strongly disagreed that making alcohol rubs mandatory for all visitors would decrease the incidence while all strongly agreed that if left untreated can become life-threatening. Overall, 15.7% showed good knowledge while most patients (51%) showed a negative perception of nosocomial infections.
Conclusion
This study showed that most patients had fair knowledge as well as negative perception towards nosocomial infections. Factors such as gender, age, and educational qualification had an influence on patients’ perception and knowledge of nosocomial infection.
Enhanced oxidative phosphorylation, re-organized intracellular signaling, and epigenetic de-silencing as revealed by oligodendrocyte translatome analysis after contusive spinal cord injury
Authors: Forston Michael D. , Wei George , Chariker Julia H. , Stephenson Tyler , Andres Kariena , Glover Charles , Rouchka Eric C. , Whittemore Scott R , Hetman Michal
Published: July 2023

Reducing the loss of oligodendrocytes (OLs) is a major goal for neuroprotection after spinal cord injury (SCI). Therefore, the OL translatome was determined in Ribotag:Plp1-CreERT2 mice at 2, 10, and 42 days after moderate contusive T9 SCI. At 2 and 42 days, mitochondrial respiration- or actin cytoskeleton/cell junction/cell adhesion mRNAs were upregulated or downregulated, respectively. The latter effect suggests myelin sheath loss/morphological simplification which is consistent with downregulation of cholesterol biosynthesis transcripts on days 10 and 42. Various regulators of pro-survival-, cell death-, and/or oxidative stress response pathways showed peak expression acutely, on day 2. Many acutely upregulated OL genes are part of the repressive SUZ12/PRC2 operon suggesting that epigenetic de-silencing contributes to SCI effects on OL gene expression. Acute OL upregulation of the iron oxidoreductase Steap3 was confirmed at the protein level and replicated in cultured OLs treated with the mitochondrial uncoupler FCCP. Hence, STEAP3 upregulation may mark mitochondrial dysfunction. Taken together, in SCI-challenged OLs, acute and subchronic enhancement of mitochondrial respiration may be driven by axonal loss and subsequent myelin sheath degeneration. Acutely, the OL switch to oxidative phosphorylation may lead to oxidative stress that is further amplified by upregulation of such enzymes as STEAP3.