bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-related differences in the functional topography of the locus coeruleus: implications for cognitive and affective functions
Authors: Veréb Dániel , Mijalkov Mite , Canal-Garcia Anna , Chang Yu-Wei , Gomez-Ruis Emiliano , Gerboles Blanca Zufiria , Kivipelto Miia , Svenningsson Per , Zetterberg Henrik , Volpe Giovanni , Betts Mathew J. , Jacobs Heidi , Pereira Joana B.
Published: May 2023

The locus coeruleus (LC) is an important noradrenergic nucleus that has recently attracted a lot of attention because of its emerging role in cognitive and psychiatric disorders. Although previous histological studies have shown that the LC has heterogeneous connections and cellular features, no studies have yet assessed its functional topography in vivo, how this heterogeneity changes over aging and whether it is associated with cognition and mood. Here we employ a gradient-based approach to characterize the functional heterogeneity in the organization of the LC over aging using 3T resting-state fMRI in a population-based cohort aged from 18 to 88 years old (Cambridge Centre for Ageing and Neuroscience cohort, n=618). We show that the LC exhibits a rostro-caudal functional gradient along its longitudinal axis, which was replicated in an independent dataset (Human Connectome Project 7T dataset, n=184). Although the main rostro-caudal direction of this gradient was consistent across age groups, its spatial features varied with increasing age, emotional memory and emotion regulation. More specifically, a loss of rostral-like connectivity, more clustered functional topography and greater asymmetry between right and left LC gradients was associated with higher age and worse behavioral performance. Furthermore, participants with higher-than-normal Hospital Anxiety and Depression Scale ratings exhibited alterations in the gradient as well, which manifested in greater asymmetry. These results provide an in vivo account of how the functional topography of the LC changes over aging, and imply that spatial features of this organization are relevant markers of LC-related behavioral measures and psychopathology.
A positive feedback loop between ZEB2 and ACSL4 regulates lipid metabolism to promote breast cancer metastasis
Authors: Lin Jiamin , Zhang Pingping , Liu Wei , Liu Guorong , Zhang Juan , Yan Min , Duan Yuyou , Yang Na
Published: May 2023

Lipid metabolism plays a critical role in cancer metastasis. However, the mechanisms through which metastatic genes regulate lipid metabolism remain unclear. Here, we describe a new oncogenic–metabolic feedback loop between the epithelial–mesenchymal transition transcription factor ZEB2 and the key lipid enzyme ACSL4 (long-chain acyl-CoA synthetase 4), resulting in enhanced cellular lipid storage and fatty acid oxidation (FAO) to drive breast cancer metastasis. Functionally, depletion of ZEB2 or ACSL4 significantly reduced lipid droplets (LDs) abundance and cell migration. ACSL4 overexpression rescued the invasive capabilities of the ZEB2 knockdown cells, suggesting that ACSL4 is crucial for ZEB2-mediated metastasis. Mechanistically, ZEB2-activated ACSL4 expression by directly binding to the ACSL4 promoter. ACSL4 binds to and stabilizes ZEB2 by reducing ZEB2 ubiquitination. Notably, ACSL4 not only promotes the intracellular lipogenesis and LDs accumulation but also enhances FAO and adenosine triphosphate production by upregulating the FAO rate-limiting enzyme CPT1A (carnitine palmitoyltransferase 1 isoform A). Finally, we demonstrated that ACSL4 knockdown significantly reduced metastatic lung nodes in vivo. In conclusion, we reveal a novel positive regulatory loop between ZEB2 and ACSL4, which promotes LDs storage to meet the energy needs of breast cancer metastasis, and identify the ZEB2–ACSL4 signaling axis as an attractive therapeutic target for overcoming breast cancer metastasis.
How their environment influences endothelial cells
Authors: Liu Xuejing , Bouman Chen Zhen
Published: May 2023

Changes in gene expression in cultured endothelial cells can be partially reversed by simulating in vivo conditions.
Epithelial to mesenchymal transition in mammary gland tissue fibrosis and insights into drug therapeutics
Authors: Syed Mudasir Ahmad , Bhat Basharat , Wali Abiza , Saleem Afnan , Ahmad Dar Lateef , Gugjoo Mudasir Bashir , Bhat Shakil , Saleem Bhat Sahar
Published: May 2023

Background

The epithelial-mesenchymal transition (EMT) is a multi-step morphogenetic process in which epithelial cells lose their epithelial properties and gain mesenchymal characteristics. The process of EMT has been shown to mediate mammary gland fibrosis. Understanding how mesenchymal cells emerge from an epithelial default state will aid in unravelling the mechanisms that control fibrosis and, ultimately, in identifying therapeutic targets to alleviate fibrosis.

Methods

The effects of EGF and high glucose (HG) on EMT in mammary epithelial cells, MCF10A and GMECs, as well as their pathogenic role, were studied. In-silico analysis was used to find interacting partners and protein-chemical/drug molecule interactions.

Results

On treatment with EGF and/or HG, qPCR analysis showed a significant increase in the gene expression of EMT markers and downstream signalling genes. The expression of these genes was reduced on treatment with EGF+HG combination in both cell lines. The protein expression of COL1A1 increased as compared to the control in cells treated with EGF or HG alone, but when the cells were treated with EGF and HG together, the protein expression of COL1A1 decreased. ROS levels and cell death increased in cells treated with EGF and HG alone, whereas cells treated with EGF and HG together showed a decrease in ROS production and apoptosis. In-silico analysis of protein-protein interactions suggest the possible role of MAPK1, actin alpha 2 (ACTA2), COL1A1, and NFκB1 in regulating TGFβ1, ubiquitin C (UBC), specificity protein 1 (SP1) and E1A binding protein P300 (EP300). Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment suggests advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signalling pathway, relaxin signalling pathway and extra cellular matrix (ECM) receptor interactions underlying fibrosis mechanism.

Conclusion

This study demonstrates that EGF and HG induce EMT in mammary epithelial cells and may also have a role in fibrosis.
Prognostic significance of SH2D5 expression in lung adenocarcinoma and its relation to immune cell infiltration
Authors: Zhou Hao , Li Shengjun , Lin Yuansheng
Published: May 2023

Objective

Through analyzing the SH2D5 expression profiles, clinical features, and immune infiltration in lung adenocarcinoma (LUAD), the study was intended to discuss the correlations of SH2D5 with prognosis and immune infiltration in LUAD.

Methods

We downloaded transcriptome and clinical data of LUAD patients from TCGA, GEO, and CCLE databases. Sangerbox, R language, GEPIA, UALCAN, and Kaplan-Meier Plotter were adopted to analyze the SH2D5 expression patterns, prognosis, and clinical features. Spearman correlation analysis was performed to determine the association between SH2D5 expression and immune cell infiltration and immune checkpoint genes. The miRNA-SH2D5 relations were predicted by miRDB and starbase. Lastly, quantitative PCR, IHC and Western blot were implemented for validation.

Results

A prominent up-regulation of SH2D5 was noted in the LUAD group relative to the normal group, which was validated by quantitative PCR, IHC and Western blot. SH2D5 expression was inversely related to overall survival (OS) of LUAD patients as well as B cell immune infiltration. Additionally, SH2D5 expression was negatively correlated with dendritic cells resting (p < 0.001), plasma cells (p < 0.001), mast cells resting (p = 0.031) and T cells CD4 memory resting (p = 0.036) in LUAD patients with abundant SH2D5 expression correlated with poor prognosis. Furthermore, enrichment analysis suggested that SH2D5 was associated with lung cancer and immunity. Lastly, we investigated the relationship between the expression of SH2D5 and the use of antitumor drugs.

Conclusion

High SH2D5 expression shares an association with unfavorable prognosis in LUAD, and SH2D5 may also provide new ideas for immunotherapy as a potential therapeutic target.
A long non-coding RNA PelncRNA1 is involved in Phyllostachys edulis response to UV-B stress
Authors: Yu Lu , Ding Yiqian , Zhou Mingbing
Published: May 2023

Phyllostachys edulis (moso bamboo) is China’s most widespread bamboo species, with significant economic and ecological values. Long non-coding RNA (lncRNA) is a type of regulatory RNA that is longer than 200 nucleotides and incapable of encoding proteins, and is frequently involved in regulating biotic and abiotic stress and plant development. However, the biological functions of lncRNA in moso bamboo are unknown. In this study, a lncRNA (named PelncRNA1) differentially expressed following UV-B treatment was discovered in the whole transcriptome sequencing database of moso bamboo. The target genes were filtered and defined by correlation analysis of PelncRNA1 and gene expression pattern. The expression levels of PelncRNA1 and its target genes were verified using qRT-PCR. The results demonstrated that the expression levels of PelncRNA1 and its target genes increased during UV-B treatment. In Arabidopsis transgenic seedlings and moso bamboo protoplasts, PelncRNA1 was discovered to influence the expression of its target genes when overexpressed. In addition, transgenic Arabidopsis showed higher tolerance to UV-B stress. These results suggest that PelncRNA1 and its target genes are involved in the response of moso bamboo to UV-B stress. The novel findings would contribute to our understanding of how lncRNAs regulate the response to abiotic stresses in moso bamboo.
Topological feature generation for link prediction in biological networks
Authors: Temiz Mustafa , Bakir-Gungor Burcu , Güner Şahan Pınar , Coskun Mustafa
Published: May 2023

Graph or network embedding is a powerful method for extracting missing or potential information from interactions between nodes in biological networks. Graph embedding methods learn representations of nodes and interactions in a graph with low-dimensional vectors, which facilitates research to predict potential interactions in networks. However, most graph embedding methods suffer from high computational costs in the form of high computational complexity of the embedding methods and learning times of the classifier, as well as the high dimensionality of complex biological networks. To address these challenges, in this study, we use the Chopper algorithm as an alternative approach to graph embedding, which accelerates the iterative processes and thus reduces the running time of the iterative algorithms for three different (nervous system, blood, heart) undirected protein-protein interaction (PPI) networks. Due to the high dimensionality of the matrix obtained after the embedding process, the data are transformed into a smaller representation by applying feature regularization techniques. We evaluated the performance of the proposed method by comparing it with state-of-the-art methods. Extensive experiments demonstrate that the proposed approach reduces the learning time of the classifier and performs better in link prediction. We have also shown that the proposed embedding method is faster than state-of-the-art methods on three different PPI datasets.
LA COHESIÓN SOCIAL DE LOS BARRIOS DE SANTIAGO EN TIEMPOS DE PANDEMIA
Authors: Greene Margarita , Link Felipe , Fuentes Luis , Rodríguez Sebastián , Señoret Andrés , Figueroa Cristhian , Berrios Emilio
Published: May 2023

La llegada de la pandemia por covid-19 al país transformó profundamente diversos ámbitos de la vida de las personas, entre ellos, las formas en cómo nos relacionamos en comunidad y el grado de cohesión social de los barrios. Este trabajo explora los cambios en cuatro dimensiones de la cohesión social barrial en Santiago, antes y durante la pandemia.
Gross Congenital Anomalies at Birth in Northeast India- A Retrospective Observational Study
Authors: Das Mrinalini , Bhoktiari Monalisa , Rahman Mahibur , Kotoky Nishigandha , Basumatary Lakshya J , Kashyap Manash Pratim
Published: May 2023

Introduction: Congenital Anomalies (CA) are a significant cause of neonatal mortality both in developed and developing nations. Congenital abnormalities can have different patterns, prevalence rates, and risk factors across time and across different geographic regions. Aim: To find out the incidence of CA occurring among institutional live births and to study the associated maternal and perinatal risk factors in Northeast region of India. Materials and Methods: This retrospective observational study was carried out in the Neonatal Intensive Care Unit (NICU) at a Tertiary Care Hospital, Guwahati, Assam, India. The duration of the study was from January 2019 to December 2019. All newborns with CA during this period were included. Maternal and labour ward records were obtained. Data of maternal and antenatal factors such as age, parity, history of consanguinity, family history of congenital abnormality and mode of delivery were collected. The data were analysed using Microsoft Excel and Statistical Package for Social Sciences (SPSS) version 26.0 (IBM SPSS Statistics for Windows, Armonk, NY, USA). Proportion was calculated and the association was tested with Chi-square test and Fisher’s-exact test. p<0.05 was considered to be statistically significant. Multivariate regression analysis was done to find the independent factor(s) for congenital anomaly. Results: During this study, there were 13530 deliveries, which include 13290 (98.2%) live births and 240 (1.8%) stillbirths. Out of 13290 newborns, 349 had one or more CA accounting for an incidence of 2.6%. The Gastrointestinal (GIT) System was the most commonly affected (33.8%), followed by the Central Nervous System (CNS) (20.9%) and craniofacial (11.7%) system. Cases of the congenital anomaly were found in 2.7% of multiparas, whereas in primiparas, the proportion was only 2.3%. In univariate analysis birth weight, gender, gestational age, maternal age, parity and mode of delivery showed significant association with incidence of congenital anomaly p<0.05*. Regression analysis showed three variables were significantly affecting the occurrence of CAs: gender Odd's Ratio (OR) (OR=0.341), gestational age (OR=32.7) and parity (OR=0.016). Conclusion: This study highlights the prevalence of GIT, CNS and craniofacial anomalies in this region. The major determinants for CAs were gestational age, gender and parity.
Oral Morphine versus Rectal Ketamine in Pain Management during Burn Wound Dressing: An Open Label Randomized Clinical Trial
Authors: Atai Alice Gertrude , Andrew Kwikiriza , Okobi Okelue Edwards , Ekpa Queen Lutina-Oloom , Ekrebe Oghenekevwe , Koroyin Mercy Oyeinbrakemi , Dick Anthony I. , Bolaji Kafayat Oluwatoyin , Adedoye Enoobong Aderonke , Abubakar Aisha M. T. , Okobi Emeka Kenneth , Evbayekha Endurance O.
Published: May 2023

Background: Oral morphine has been widely used to manage children’s pain during burn wound dressing. Rectal ketamine may also be safely administered to children.

Objective: To evaluate and compare the efficacy of oral morphine vs. rectal racemic ketamine in management of pain during burn wound dressing in a pediatric population in a rural study population.

Methods: This was a randomized open-label clinical trial done in a rural hospital in Uganda. Study participants were randomly assigned to one of the treatment groups, either oral morphine or rectal ketamine, with a ratio of 1:1. Overall, we enrolled 44 participants, with 22 in each treatment arm.

Assessment of baseline vital signs, including pulse rate, blood pressure, respiratory rate, temperature, oxygen saturation (SPO2), pain assessment (using Face Legs Activity Cry Consolability [FLACC]), and sedation scores (using Richmond’s agitation and sedation scale [RASS]) among others was done. Study participants were followed up hourly for 8 hours for outcomes of interest: adequate pain management/adverse events.

Results: The mean age of the study participants was 2.56 (±1.59) years. The overall mean intra-procedural pain difference score for children who received oral morphine was 2.7 (SD±2.2) compared to 0 (SD±0) among those who received rectal ketamine, and the mean difference of 2.7 was statistically significant (p < 0.0001). Sialorrhea (hyper-salivation) was the only significant adverse event, with more occurrence in the rectal Ketamine treatment arm (n= 8, 36.3%) compared to 1 (5%) in the oral Morphine treatment arm, p = 0.009. There were no significant adverse effects noted in either treatment arm.

Conclusion: The study showed the non-inferiority of rectal ketamine over oral morphine and concluded that administration of rectal ketamine was better at pain management and safety compared to oral morphine. Rectal ketamine is associated with an increased incidence of sialorrhea compared to oral morphine.
Unusual Clinical Presentation of Cutaneous Squamous Cell Carcinoma: a Retrospective Study in Al Baha Region, Southern Saudi Arabia
Authors: Alghamdi Mohammad A.
Published: May 2023

Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer, and it accounts for 20% of all skin cancers. It occurs typically on parts of the skin exposed to sunlight and begins as firm erythematous papules or nodules that enlarge over a period of months in most cases. This study investigates the unusual presentation of cSCC with the goal of raising awareness of rare presentations and promoting accurate diagnostic tools. It is a five-year retrospective study retrieving patient data to study the demographic, clinical and histological features of cSCC with unusual presentations that were clinically unsuspected. It was carried out in Al Baha Province, southern Saudi Arabia. A total of 25 cases were included; males predominated (60%), and the mean age of the cohort was 59.8 years. However, three patients were <50 years old and the most prevalent site of the cSCC was the nose. Tumor size ranged from 5 to 50 mm with a mean size of 14.6 mm. Tumor size was uncorrelated with a clinical suspicion of malignancy. The clinical presentation of cSCC varies from tan nodules in most cases (28%) to warty lesions in 4% of cases; the clinical diagnosis of such lesions also varied from highly malignant lesions (melanoma) to a simple inflammatory disease. Histologically, most cases (96%) were keratinizing squamous cell carcinomas. A clinical suspicion of cSCC is not always accurate, and histopathology is the most accurate tool for diagnosis. Abdominal wall, perianal and finger sites are not immune to cSCC, and young individuals are also at risk.
Trends in Deaths From Falls Among Adults Aged 65 Years or Older in the US, 1999-2020
Authors: Santos-Lozada Alexis R.
Published: May 2023

This study examines trends in deaths from falls among adults aged 65 years or older by sex and by race and ethnicity between 1999 and 2020 in the US.
Membership in the Council of Teaching Hospitals and Health Systems Among Emergency Medicine Residency Program–Sponsoring Institutions, 2001-2020
Authors: Bennett Christopher L. , Boggs Krislyn M. , Gettel Cameron J. , Sun Wendy W. , Venkatesh Arjun K. , Camargo Carlos A.
Published: May 2023

This cross-sectional study identifies US institutions sponsoring residency programs and examines whether Council of Teaching Hospitals and Health Systems membership is associated with institution characteristics.
Workplace Psychosocial Resources and Risk of Sleep Disturbances Among Employees
Authors: Xu Tianwei , Rugulies Reiner , Vahtera Jussi , Stenholm Sari , Pentti Jaana , Magnusson Hanson Linda L. , Kecklund Göran , Mathisen Jimmi , Nordentoft Mads , Kivimäki Mika , Rod Naja Hulvej
Published: May 2023

Importance

Workplace psychosocial resources naturally tend to cluster in some work teams. To inform work-related sleep health promotion interventions, it is important to determine the associations between clustering of workplace resources and sleep disturbances when some resources are high while others are low and to mimic an actual intervention using observational data.

Objective

To examine whether clustering of and changes in workplace psychosocial resources are associated with sleep disturbances among workers.

Design, Setting, and Participants

This population-based cohort study used data from the Swedish Longitudinal Occupational Survey of Health (2012-2018), the Work Environment and Health in Denmark study (2012-2018), and the Finnish Public Sector Study (2008-2014), collected biennially. Statistical analysis was conducted from November 2020 to June 2022.

Exposure

Questionnaires were distributed measuring leadership quality and procedural justice (ie, vertical resources) as well as collaboration culture and coworker support (ie, horizontal resources). Resources were divided into clusters of general low, intermediate vertical and low horizontal, low vertical and high horizontal, intermediate vertical and high horizontal, and general high.

Main Outcomes and Measures

Odds ratios (ORs) and 95% CIs were reported from logistic regression models for the associations between the clustering of resources and concurrent and long-term sleep disturbances. Sleep disturbances were measured by self-administered questionnaires.

Results

The study identified 114 971 participants with 219 982 participant-observations (151 021 [69%] women; mean [SD] age, 48 [10] years). Compared with participants with general low resources, other groups showed a lower prevalence of sleep disturbances, with the lowest observed in the general high group concurrently (OR, 0.38; 95% CI, 0.37-0.40) and longitudinally after 6 years (OR, 0.52; 95% CI, 0.48-0.57). Approximately half of the participants (27 167 participants [53%]) experienced changes in resource clusters within 2 years. Improvements in vertical or horizontal dimensions were associated with reduced odds of persistent sleep disturbances, and the lowest odds of sleep disturbances was found in the group with improvements in both vertical and horizontal dimensions (OR, 0.53; 95% CI, 0.46-0.62). A corresponding dose-response association with sleep disturbances was observed for decline in resources (eg, decline in both dimensions: OR, 1.74; 95% CI, 1.54-1.97).

Conclusions and Relevance

In this cohort study of workplace psychosocial resources and sleep disturbances, clustering of favorable resources was associated with a lower risk of sleep disturbances.
Comparison of Metabolic Response to Colonic Fermentation in Lean Youth vs Youth With Obesity
Authors: Galuppo Brittany , Umano Giuseppina Rosaria , Li Zhongyao , Van Name Michelle , Samuels Stephanie L. , Kien C. Lawrence , Cline Gary W. , Wagner David A. , Barbieri Emiliano , Tricò Domenico , Santoro Nicola
Published: May 2023

Importance

Pediatric obesity is a growing health care burden. Understanding how the metabolic phenotype of youth with obesity may modify the effect of intestinal fermentation on human metabolism is key to designing early intervention.

Objective

To assess whether adiposity and insulin resistance in youth may be associated with colonic fermentation of dietary fibers and its production of acetate, gut-derived hormone secretion, and adipose tissue lipolysis.

Design, Setting, and Participants

Cross-sectional study of youths aged 15 to 22 years with body mass index in the 25th to 75th percentile or higher than the 85th percentile for age and sex throughout the New Haven County community in Connecticut. Recruitment, studies, and data collection occurred from June 2018 to September 2021. Youths were assigned to a lean, obese insulin sensitive (OIS), or obese insulin resistant (OIR) group. Data were analyzed from April 2022 to September 2022.

Exposure

Participants consumed 20 g of lactulose during a continuous 10-hour sodium d3-acetate intravenous infusion to measure the rate of appearance of acetate in plasma.

Main Outcomes and Measures

Plasma was obtained hourly to measure acetate turnover, peptide tyrosine tyrosine (PYY), ghrelin, active glucagon-like peptide 1 (GLP-1), and free fatty acids (FFA).

Results

A total of 44 youths participated in the study (median [IQR] age, 17.5 [16.0-19.3] years; 25 [56.8%] were female; 23 [52.3%] were White). Consequent to lactulose ingestion, there was a reduction of plasma FFA, an improvement of adipose tissue insulin sensitivity index, an increase in colonic acetate synthesis, and an anorexigenic response characterized by an increased plasma concentration of PYY and active GLP-1 and a reduction of ghrelin in the subgroups. Compared with the lean and OIS groups, the OIR group showed a less marked median (IQR) rate of acetate appearance (OIR: 2.00 [−0.86 to 2.69] μmol × kg−1 × min−1; lean: 5.69 [3.04 to 9.77] μmol × kg−1 × min−1; lean vs OIR P = .004; OIS: 2.63 [1.22 to 4.52] μmol × kg−1 × min−1; OIS vs OIR P = .09), a blunted median (IQR) improvement of adipose insulin sensitivity index (OIR: 0.043 [ 0.006 to 0.155]; lean: 0.277 [0.220 to 0.446]; lean vs OIR P = .002; OIS: 0.340 [0.048 to 0.491]; OIS vs OIR P = .08), and a reduced median (IQR) PYY response (OIR: 25.4 [14.8 to 36.4] pg/mL; lean: 51.3 [31.6 to 83.3] pg/mL; lean vs OIR P = .002; OIS: 54.3 [39.3 to 77.2] pg/mL; OIS vs OIR P = .011).

Conclusions and Relevance

In this cross-sectional study, lean, OIS, and OIR youth demonstrated different associations between colonic fermentation of indigestible dietary carbohydrates and the metabolic response, with OIR youth showing minimal metabolic modifications as compared with the other 2 groups.

Trial Registration

ClinicalTrials.gov Identifier: NCT03454828
CCR4‐IL2 bispecific immunotoxin is more effective than brentuximab for targeted therapy of cutaneous T‐cell lymphoma in a mouse CTCL model
Authors: Wang Zhaohui , Ma Jihong , Zhang Huiping , Ramakrishna Rashmi , Mintzlaff Danielle , Mathes David W. , Pomfret Elizabeth A. , Lucia M. Scott , Gao Dexiang , Haverkos Bradley M. , Wang Zhirui
Published: May 2023

Cutaneous T‐cell lymphoma (CTCL) encompasses two main subtypes: mycosis fungoides and Sezary syndrome. Global response rates for the systemic treatment of mycosis fungoides and Sezary syndrome are approximately 30%, and none of these treatments are thought to be curative. C–C chemokine receptor type 4 (CCR4) and CD25 are encouraging targets for the treatment of CTCL and are individually targeted by mogamulizumab and denileukin diftitox, respectively. We developed a novel CCR4‐IL2 bispecific immunotoxin (CCR4‐IL2 IT) targeting both CCR4 and CD25. CCR4‐IL2 IT demonstrated superior efficacy against CCR4+CD25+CD30+ CTCL in an immunodeficient NSG mouse tumor model. Investigative New Drug‐enabling studies of CCR4–IL2 IT are ongoing, including Good Manufacturing Practice production and toxicology studies. In this study, we compared the in vivo efficacy of CCR4‐IL2 IT versus the US Food and Drug Administration–approved drug, brentuximab, using an immunodeficient mouse CTCL model. We demonstrated that CCR4–IL2 IT was significantly more effective in prolonging survival than brentuximab, and combination treatment of CCR4–IL2 IT and brentuximab was more effective than brentuximab or CCR4–IL2 IT alone in an immunodeficient NSG mouse CTCL model. Thus, CCR4–IL2 IT is a promising novel therapeutic drug candidate for CTCL treatment.
In Situ Artificial Hybrid SEI Layer Enabled High‐Performance Prelithiated SiOx Anode for Lithium‐Ion Batteries
Authors: Sun Yi , Zhang Kuanxin , Chai Run , Wang Yueda , Rui Xianhong , Wang Kang , Deng Huaxia , Xiang Hongfa
Published: May 2023

Considered the promising anode material for next‐generation high‐energy lithium‐ion batteries, SiOx has been slow to commercialize due to its low initial Coulombic efficiency (ICE) and unstable solid electrolyte interface (SEI) layer, which leads to reduced full‐cell energy density, short cycling lives, and poor rate performance. Herein, a novel strategy is proposed to in situ construct an artificial hybrid SEI layer consisting of LiF and Li3Sb on a prelithiated SiOx anode via spontaneous chemical reaction with SbF3. In addition to the increasing ICE (94.5%), the preformed artificial SEI layer with long‐term cycle stability and enhanced Li+ transport capability enables a remarkable improvement in capacity retention and rate capability for modified SiOx. Furthermore, the full cell using Li(Ni0.8Co0.1Mn0.1)O2 and a pre‐treated anode exhibits high ICE (86.0%) and capacity retention (86.6%) after 100 cycles at 0.5 C. This study provides a fresh insight into how to obtain stable interface on a prelithiated SiOx anode for high energy and long lifespan lithium‐ion batteries.
Biomimetic Liquid Metal Mechatronic Devices
Authors: Wang Yushu , Chang Hao , Wang Shengnan , Wang Dawei , Xue Mianqi , Liu Jing , Rao Wei
Published: May 2023

Perceiving mechanical stimuli and converting them into bioelectric signals to complete sensing information transmission and computation is a fundamental mechanism for survival and evolution of natural animals. This leads to a variety of intelligent behaviors, such as processing, learning, judgment, feedback, and so on when tackling complex and changeable environmental challenges. Until now, the realization of a bionic system to mimic the above activities has long been an important goal which is mainly based on the integration of distributed functional units, lacking the coordination between functional units and the whole systems. Herein, based on the mechano‐electronic coupling effect of liquid metals and by following the basic principle of perception and transduction of piezo proteins, a biomimetic functional liquid metal mechatronic device is proposed with the switching behavior via establishing the reversible charge gradient. Owing to flexible features of liquid metals, this all‐soft mechatronic device exhibits excellent compliance with the whole system. Based on electrochemical characteristics of liquid metals, the passive intelligent device demonstrates versatile behaviors, such as self‐energy supply, encoding, computation, sensing, information identification, communicating, and controlling functions etc. which can only possibly be achieved by living animals. This work opens a new strategy for developing intelligent mechatronic systems.
Scalable Synthesis of High‐Quality Core/Shell Quantum Dots With Suppressed Blinking
Authors: Tao Chen‐Lei , Ma Jinling , Wei Changting , Xu Dan , Xie Zhuoyi , Jiang Zhengfei , Ge Feiyue , Zhang Han , Xie Mingcai , Ye Zhiliang , Cheng Fang , Xu Bo , Tian Yuxi , Wu Xue‐Jun
Published: May 2023

A facile and reproducible method for scalable synthesis of high‐quality core/shell quantum dots (QDs) is a prerequisite to facilitate their versatile applications. Herein, a seed‐mediated heat‐up approach is developed for the preparation of high‐quality core/shell QDs with variable shell composition and continuously tunable shell thickness by selection of conventional salts as the precursors. The method is very simple and highly reproducible and, therefore, can be easily scaled up to get gram‐level product. The as‐obtained CdSe/CdS and CdSe/ZnCdS core/shell QDs exhibit intriguing optical properties, that is a narrow photoluminescence (PL) emission peak and near‐unity PL quantum yield. Importantly, the CdSe/ZnCdS core/shell QDs with a size of 11.4 nm exhibit obviously suppressed blinking behavior, and the fraction of nonblinking QDs (defined by an on‐time fraction ≥ 0.95) can reach as high as 96.0% on the measurement of more than 200 QDs. Moreover, quantum‐dot light‐emitting diodes (QLEDs) based on CdSe/ZnCdS core/shell QDs show a peak external quantum efficiency of 14.8% and low efficiency roll‐off at luminance ranging from 1000 to 25 000 cd·m−2. It is anticipated that the presented work will pave a novel way for the large‐scale production of high‐quality QDs and further boost their applications in light‐emitting diodes, lasing, and biological imaging.
CD44 and HAP‐Conjugated hADSCs as Living Materials for Targeted Tumor Therapy and Bone Regeneration
Authors: Xia He , Hao Min , Li Kaiwen , Chen Xin , Yu Liyang , Qiu Jichuan , Zhang Hongyu , Li Haijun , Sang Yuanhua , Liu Hong
Published: May 2023

Combining targeted tumor therapy with tissue regeneration represents a promising strategy for synergistic tumor therapy. In this study, a multifunctional living material is constructed with human‐derived adipose stem cells (hADSCs) and antibody‐modified hydroxyapatite nanorods (nHAP) for targeted drug delivery and bone regeneration following surgery. The living material delivers the therapeutics to the tumor site efficiently based on the strength of the inherent tumor tropism of hADSCs. The bioconjugation of nHAP with hADSCs via specific antibody modification is found to be biocompatible, even when loaded with the chemotherapeutic drug doxorubicin (Dox). The endocytosis of nHAP stimulates the osteogenic differentiation of hADSCs, promoting bone tissue regeneration. Moreover, the antibody‐modified nHAP‐hADSC conjugate exhibits targeted tumor delivery, which is further facilitated by pH‐triggered release of Dox, inducing apoptosis of tumor cells with low toxicity to healthy tissues. Therefore, the present study provides a general strategy for engineering living materials to achieve targeted tumor therapy and bone tissue regeneration after surgery, which can be extended to other disease types.
Prevalent stroke, age of its onset, and post‐stroke lifestyle in relation to dementia: A prospective cohort study
Authors: Zhong Wansi , Chen Hui , Gong Xiaoxian , Tong Lusha , Xu Xin , Zong Geng , Yuan Changzheng , Lou Min
Published: May 2023

INTRODUCTION

The association of age at stroke onset with dementia and the role of post‐stroke lifestyle on dementia risk remains unclear.

METHODS

We leveraged data of 496,251 dementia‐free participants from UK Biobank and explored the relationship between age at stroke onset and incident dementia. Among 8328 participants with stroke history, we further investigated the association of a healthy lifestyle with risk of dementia.

RESULTS

Participants with stroke history had a higher risk of dementia (hazard ratio [HR], 2.02). The association was stronger among participants with stroke onset at a younger age (≤50: HR, 2.63) compared with those at the age > 50 years (50–60: HR, 2.17; ≥60: HR, 1.58). Among participants with stroke history, a favorable lifestyle was associated with a lower risk of incident dementia.

DISCUSSION

Stroke onset in earlier life stage predicted a higher risk for dementia, but a favorable post‐stroke lifestyle may protect against dementia.
Blue light transurethral resection and biopsy of bladder cancer with hexaminolevulinate: Histopathological characteristics and recurrence rates in a single UK centre study
Authors: Chan Kimberley , Hampson Alexander , Hayes John , Rabinowitz Joshua , Vasdev Nikhil
Published: May 2023

Introduction

Blue light cystoscopy with hexaminolevulinate (HAL) during transurethral resection of bladder cancer (TURBT) has been shown to improve detection, thereby reducing bladder cancer recurrence compared with white light cystoscopy.

Methods

Single‐centred UK (United Kingdom) study on 101 patients who underwent blue light cystoscopy between July 2017 and November 2020, performed by a single surgeon. Our study was divided into two arms; the primary arm had no prior diagnosis of bladder malignancy (N = 41), whereas secondary re‐resection arm had (N = 57). Three patients with non‐urothelial bladder cancer were excluded. Patients were followed up for 24 months. Data were collected on biopsy quality, histopathological characteristics and recurrence. The end points of the study were recurrence rate at 24 months in both arms and detection of CIS in patients who undergo TURBT or biopsy after initial white light study in the secondary, re‐resection arm. This was analysed with Fisher's exact test.

Results

Of 98 patients, 39 had malignancy in their first blue light TURBT/biopsy: primary arm (10/41, 24.4%) and secondary arm (29/57, 50.9%), with detrusor present in 80.5% and 80.7%, respectively. In the secondary arm, blue light re‐resection TURBT detected significantly more CIS (20.7% vs 51.7%, p = 0.0277) compared with white light with 3.4% upstaged to muscle invasive bladder cancer (G3pT2). Median time to re‐resection was 3.06 months. Recurrence rate was 33.3% in the primary arm and 37.5% in the secondary arm after 24 months of follow‐up.

Conclusion

Our data confirm that blue light TURBT with HAL provides superior detection and diagnosis of CIS in patients with previous white light cystoscopy.
The effect of thioredoxin‐1 in a rat model of traumatic brain injury depending on diurnal variation
Authors: Noriega‐Navarro Roxana , Martínez‐Tapia Ricardo Jesús , González‐Rivera Rubén , Ochoa‐Sánchez Alicia , Abarca‐Magaña Julio César , Landa‐Navarro Lucía , Rodríguez‐Mata Verónica , Ugalde‐Muñiz Perla , Pérez‐Torres Armando , Landa Abraham , Navarro Luz
Published: May 2023

Introduction

Traumatic brain injury (TBI) is a public health concern with limited treatment options because it causes a cascade of side effects that are the leading cause of hospital death. Thioredoxin is an enzyme with neuroprotective properties such as antioxidant, antiapoptotic, immune response modulator, and neurogenic, among others; it has been considered a therapeutic target for treating many disorders.

Methods

The controlled cortical impact (CCI) model was used to assess the effect of recombinant human thioredoxin 1 (rhTrx1) (1 μg/2 μL, intracortical) on rats subjected to TBI at two different times of the light‐dark cycle (01:00 and 13:00 h). We analyzed the food intake, body weight loss, motor coordination, pain perception, and histology in specific hippocampus (CA1, CA2, CA3, and Dental Gyrus) and striatum (caudate‐putamen) areas.

Results

Body weight loss, reduced food intake, spontaneous pain, motor impairment, and neuronal damage in specific hippocampus and striatum regions are more evident in rats subjected to TBI in the light phase than in the dark phase of the cycle and in groups that did not receive rhTrx1 or minocycline (as positive control). Three days after TBI, there is a recovery in body weight, food intake, motor impairment, and pain, which is more pronounced in the rats subjected to TBI at the dark phase of the cycle and those that received rhTrx1 or minocycline.

Conclusions

Knowing the time of day a TBI occurs in connection to the neuroprotective mechanisms of the immune response in diurnal variation and the usage of the Trx1 protein might have a beneficial therapeutic impact in promoting quick recovery after a TBI.
Altered resting‐state hippocampal functional connectivity in breast cancer survivors with chemotherapy‐induced amenorrhea
Authors: Zhuang Yingying , Guo Lili , Huang Wei , Bo Genji , Zhang Jiandong , Zhu Zhaohuan , Feng Yun
Published: May 2023

Introduction

Amenorrhea induced decrease of hormones is associated with cognitive impairment. This study aimed to evaluate hippocampal functional connectivity patterns in chemotherapy‐induced amenorrhea (CIA) breast cancer (BC) patients, to evaluate the relationship between the functional connectivity features and hormone levels.

Method

Neuropsychological test, functional magnetic resonance imaging, and assessment of hormone levels were conducted in 21 premenopausal BC patients before chemotherapy (t0) and 1 week after completing chemotherapy (t1). Twenty matched healthy controls (HC) were also included and underwent the same assessments at similar time intervals. Mixed effect analysis and paired t‐test were used to compare differences in brain functional connectivity.

Results

Voxel‐based paired t‐tests revealed increased functional connectivity of the right and left hippocampus with the left fusiform gyrus, inferior and middle temporal gyrus, inferior occipital gyrus, left lingual gyrus, and parahippocampal gyrus after chemotherapy (p < .001) in CIA patients. Repeated measures analysis revealed significant group‐by‐time interactions in the left hippocampus with the bilateral fusiform gyrus, right parahippocampal gyrus, left inferior temporal gyrus, and left inferior occipital gyrus (p < .001). Premenopausal BC patients had no significant differences in cognitive function compared with HC at baseline. However, the CIA patients had high levels of self‐rating depression scale, self‐rating anxiety scale, total cholesterol, and triglycerides. Further, the CIA patients showed significant differences in hormone and fasting plasma glucose levels and cognitive performances between t0 and t1 (p < .05). Functional connectivity changes between the left hippocampus and the left inferior occipital gyrus was negatively correlated with E2 and luteinizing hormone changes (p < .05).

Conclusion

The CIA patients had cognitive dysfunction mainly in memory and visual mobility. Chemotherapy may affect hippocampal‐posterior cortical circuit which mediates visual processing in CIA patients. Moreover, E2 may be involved in this process.
Total neoadjuvant treatment to increase the clinical complete response rate for distal locally advanced rectal cancer (TESS): A study protocol of a prospective, open‐label, multicenter, single‐arm, phase 2 trial
Authors: Liu Shuang , Wang XiaoZhong , Zhuang YeZhong , Bai ShouMin , Wu XiaoJun , Ye YiJing , Luo HuiLong , Yu HaiNa , Wang QiaoXuan , Chang Hui , Zeng ZhiFan , Cai PeiQiang , Pan ZhiZhong , Gao YuanHong , Chen Gong , Xiao WeiWei
Published: May 2023

Background

Standard treatment of locally advanced rectal cancer (LARC) was neoadjuvant chemoradiotherapy (CRT), followed by total mesorectal excision (TME). Total neoadjuvant treatment (TNT), a new concept, attempts to deliver both systemic chemotherapy and neoadjuvant CRT prior to surgery. Patients treated with neoadjuvant chemotherapy were more likely to show higher tumor regression. The objective of this trial was to increase complete clinical rate (cCR) for LARC patients by optimizing tumor response, using TNT regimen as compared to conventional chemoradiotherapy. TESS, a prospective, open‐label, multicenter, single‐arm, phase 2 study, is underway.

Methods

Main inclusion criteria include cT3‐4aNany or cT1‐4aN+ rectal adenocarcinoma aged 18‐70y; Eastern Cooperative Oncology Group (ECOG) performance 0–1; location ≤5 cm from anal verge. Ninety‐eight patients will receive 2 cycles of neoadjuvant chemotherapy Capeox (capecitabine + oxaliplatin) before, during, and after radiotherapy 50Gy/25 fractions, before TME (or other treatment decisions, such as Watch and Wait strategy) and adjuvant chemotherapy capecitabine 2 cycles. Primary endpoint is the cCR rate. Secondary endpoints include ratio of sphincter preservation strategy; pathological complete response rate and tumor regression grade distribution; local recurrence or metastasis; disease‐free survival; locoregional recurrence‐free survival; acute toxicity; surgical complications; long‐term anal function; late toxicity; adverse effect, ECOG standard score, and quality of life. Adverse events are graded per Common Terminology Criteria for Adverse Events V5.0. Acute toxicity will be monitored during antitumor treatment, and late toxicity will be monitored for 3 years from the end of the first course of antitumor treatment.

Discussion

The TESS trial aims to explore a new TNT strategy, which is expected to increase the rate of cCR and sphincter preservation rate. This study will provide new options and evidence for a new sandwich TNT strategy in patients with distal LARC.
Risk factor analysis of thymoma resection and its value in guiding clinical treatment
Authors: Du Xin , Cui Jian , Yu Xin‐tao , Yu Lei
Published: May 2023

Background

In this study, relationships between clinicopathologic characteristics and progression‐free survival (PFS) of patients after thymomectomy were analyzed to provide valuable suggestions regarding the treatment of thymoma.

Methods

Data from 187 thymoma patients undergoing surgery at Beijing Tongren Hospital between January 1, 2006, and December 31, 2015, were retrospectively reviewed. We explored the risk factors for PFS among sex, age, thymoma‐associated MG, completeness of resection, histologic type and TNM stage, and investigated their interrelationship.

Results

Among the 187 patients, 18 patients (9.63%) had tumor recurrence/metastasis, and all of whom had in situ recurrence or pleural metastasis, and most of them (10 of 18 patients) had MG symptoms that reappeared or were aggravated. Fifteen patients (8.02%) died, and myasthenic crisis was a leading cause. Based on Cox regression analysis, only age (HR = 3.16; 95% CI: 1.44–6.91;p = 0.004) and the completeness of resection (HR = 9.03; 95% CI: 2.58–31.55;p = 0.001) were independent risk factors for PFS. Furthermore, we found that the completeness of resection was related to the histologic type (p = 0.009) and TNM stage (p < 0.001) by Fisher's exact test.

Conclusions

The results of this cohort study remind us that we should pay attention to the reappearance or aggravation of MG after thymoma resection, because it is the leading cause of death and may indicate tumor progression. Furthermore, completeness of resection was related to the histologic type and TNM stage, but it was the independent risk factors of thymoma. Therefore, R0 resection is critical to the prognosis of thymoma.
preHAZOP: Graph‐Based Safety Analysis for Early Integration into Automated Engineering Workflows
Authors: Oeing Jonas , Holtermann Tim , Welscher Wolfgang , Severins Christian , Vogel Marius , Kockmann Norbert
Published: May 2023

The increasing digitalization and standardization within the process industry lead to a high availability of digital, machine‐readable processes and plant descriptions. In particular, the publication of the DEXPI standard provides a digital representation of plant topologies including a complete description of all specifications. In early planning phases, this can be used as the basis for an automated safety assessment since digital availability significantly simplifies accessibility for smart search algorithms. This paper presents the preHAZOP search algorithm, which was developed to analyze P&IDs in DEXPI format and to detect safety‐critical deviations regarding their risk according to a classical HAZOP analysis. The preHAZOP is of particular interest in early process development stages and can be easily integrated into modern, digital engineering workflows.
Energierückgewinnung mit MTP‐fähigem Volumenexpander
Authors: Pilous Yannick , Humer Matthias
Published: May 2023

In einem gemeinsamen Projekt der Firmen Stumer, Avibia und Iotech wurde eine intelligente Dampfdruck‐Reduzierstation als Package Unit entwickelt, die hierbei abfallende Energie ins Stromnetz speist und sich dank einer standardisierten MTP‐Schnittstelle mit geringem Integrationsaufwand nachrüsten lässt.
Aus der Digitalisierung mit KI mehr Nutzen ziehen
Authors: Gandert Etwina , Oestreich Volker
Published: May 2023

KI kann ein Schlüssel werden, um aus der Digitalisierung deutlich mehr Nutzen zu ziehen, als nur Sensordaten zu verwalten. Axel Lorenz, CEO Process Automation, Dr. Hartmut Klocker, Segment Lead Automation and Engineering Systems und Dr. Jürgen Spitzer, General Manager Measurement Intelligence, erläutern im Interview mit CITplus, wo und wie aus der Digitalisierung und dem Einsatz von KI ein Mehrwert für Prozesssteuerung und Instandhaltung zu ziehen ist, wie weit Siemens bei der Entwicklung von APL‐fähigen Geräten ist und welche Chancen 5G bieten kann.
Funktionale Sicherheit im digitalisierten Anlagenbau
Authors: Sieber Peter , Schäfer Bernd
Published: May 2023

Sichere, flexible und anwendungsspezifische Programmierlösungen für die Funktionale Sicherheit einer Prozessanlage können zu langen Entwicklungszykluszeit führen, wenn beispielsweise langwierige Prüfprozesse den Anlagenbau ausbremsen. Ein modularer Ansatz kann diesen Prozess beschleunigen. Hier zeigt sich der Nutzen der Digitalisierung.
Technologien für die Digitalisierung is in die Feldebene
Authors: Hennecke Andreas , Rauscher Benedikt
Published: May 2023

Im Lebenszyklus einer Prozessanlage ermöglicht die Digitalisierung, Risiken zu minimieren, den Anlagenbau zu beschleunigen sowie Produktion und Qualität zu optimieren. Wesentliche Voraussetzung sind eine robuste Infrastruktur für das Feld der Prozessanlage sowie eine digitale Architektur und Beschreibung für alle Anlagenassets – und beides bestenfalls standardisiert.