bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective noncovalent proteasome inhibiting activity of trifluoromethyl‐containinggem‐quaternary aziridines
Authors: Ielo Laura , Patamia Vincenzo , Citarella Andrea , Schirmeister Tanja , Stagno Claudio , Rescifina Antonio , Micale Nicola , Pace Vittorio
Published: April 2023

The ubiquitin‐proteasome pathway (UPP) represents the principal proteolytic apparatus in the cytosol and nucleus of all eukaryotic cells. Nowadays, proteasome inhibitors (PIs) are well‐known as anticancer agents. However, although three of them have been approved by the US Food and Drug Administration (FDA) for treating multiple myeloma and mantel cell lymphoma, they present several side effects and develop resistance. For these reasons, the development of new PIs with better pharmacological characteristics is needed. Recently, noncovalent inhibitors have gained much attention since they are less toxic as compared with covalent ones, providing an alternative mechanism for solid tumors. Herein, we describe a new class of bis‐homologated chloromethyl(trifluoromethyl)aziridines as selective noncovalent PIs. In silico and in vitro studies were conducted to elucidate the mechanism of action of such compounds. Human gastrointestinal absorption (HIA) and blood–brain barrier (BBB) penetration were also considered together with absorption, distribution, metabolism, and excretion (ADMET) predictions.
Data‐driven dissection of the fever effect in autism spectrum disorder
Authors: Muller Efrat , Shalev Ido , Bachmat Eitan , Eran Alal
Published: April 2023

Some individuals with autism spectrum disorder (ASD) demonstrate marked behavioral improvements during febrile episodes, in what is perhaps the only present‐day means of modulating the core ASD phenotype. Understanding the nature of this so‐calledfever effectis therefore essential for leveraging this natural temporary relief of symptoms to a sustained efficacious intervention. Toward this goal, we used machine learning to analyze the rich clinical data of the Simons Simplex Collection, in which one out of every six children with ASD was reported to improve during febrile episodes, across multiple ASD domains. Reported behavioral improvements during febrile episodes were associated with maternal infection in pregnancy (OR = 1.7, 95% CI = [1.42, 2.03], P = 4.24 × 10−4) and gastrointestinal (GI) dysfunction (OR = 1.46, 95% CI = [1.15, 1.81], P = 1.94 × 10−3). Family members of children reported to improve when febrile have an increased prevalence of autoimmune disorders (OR = 1.43, 95% CI = [1.23, 1.67],P = 3.0 × 10−6), language disorders (OR = 1.63, 95% CI = [1.29, 2.04],P = 2.5 × 10−5), and neuropsychiatric disorders (OR = 1.59, 95% CI = [1.34, 1.89],P < 1 × 10−6). Since both GI abnormalities and maternal immune activation have been linked to ASD via proinflammatory cytokines, these results might suggest a possible involvement of immune dysregulation in the fever effect, consistent with findings in mouse models. This work advances our understanding of the fever‐responsive ASD subtype and motivates the future studies to directly test the link between proinflammatory cytokines and behavioral modifications in individuals with ASD.
Machine Learning in Lithium‐Ion Battery Cell Production: A Comprehensive Mapping Study
Authors: Haghi Sajedeh , Hidalgo Marc Francis V. , Niri Mona Faraji , Daub Rüdiger , Marco James
Published: April 2023

With the global quest for improved sustainability, partially realized through the electrification of the transport and energy sectors, battery cell production has gained ever‐increasing attention. An in‐depth understanding of battery production processes and their interdependence is crucial for accelerating the commercialization of material developments, for example, at the volume predicted to underpin future electric vehicle production. Over the last five years, machine learning approaches have shown significant promise in understanding and optimizing the battery production processes. Based on a systematic mapping study, this comprehensive review details the state‐of‐the‐art applications of machine learning within the domain of lithium‐ion battery cell production and highlights the fundamental aspects, such as product and process parameters and adopted algorithms. The compiled findings derived from multi‐perspective comparisons demonstrate the current capabilities and reveal future research opportunities in this field to further accelerate sustainable battery production.
SALL4 correlates with proliferation, metastasis, and poor prognosis in prostate cancer by affecting MAPK pathway
Authors: Zhou Jie , Peng Shengmeng , Fan Huiyang , Li Jin , Li Zean , Wang Ganping , Zeng Lexiang , Guo Zhenghui , Lai Yiming , Huang Hai
Published: April 2023

Background

The mechanism involved in prostate cancer (PCa) metastasis is still poorly understood, and several oncogenes are known to regulate this process. However, the role of spalt‐like transcription factor 4 (SALL4) in PCa metastasis remains unclear.

Methods

We performed RNA‐sequencing to compare the mRNA expression profiles of seven localized PCa tissues and six metastatic PCa tissues. SALL4 was then identified and compared in the localized PCa and metastatic PCa. Immunohistochemical studies, qRT‐PCR, and Western blot were performed to analyze the expression of SALL4 in PCa patients and cell lines. SALL4 expression and its relevance to clinical traits and prognosis were further explored in the TCGA database and in our 68 clinical samples. Subsequently, we knocked down SALL4 in DU145 and PC3 cells and performed a series of functional assays to explore the effect of SALL4 on PCa progression. Finally, protein levels of SALL4 and core components of the MAPK pathway were measured by Western blot, and cells were treated with PD0325901 to observe proliferation and metastasis.

Results

Significantly higher expression of SALL4 was found in metastatic PCa than in localized PCa. In addition, high SALL4 expression was significantly associated with high pathological T stage, N stage, Gleason score, and poor disease‐free survival in TCGA database and in our clinical samples. Functional studies indicated that knockdown of SALL4 in DU145 and PC3 inhibited proliferation, migration, and angiogenesis. Furthermore, the ERK and P38 protein phosphorylation significantly reduced after knockdown of SALL4 in DU145 and PC3, indicating the inactivation of the MAPK signaling pathway. Finally, the proliferation and migration ability of DU145 and PC3 cells were significantly decreased after PD0325901 treatment.

Conclusions

SALL4 predicts unfavorable outcome and is closely associated with PCa progression, suggesting that SALL4 may be a promising prognostic marker and potential therapeutic target for PCa.
A systematic review with evidence mapping of supportive care interventions for melanoma patients and caregivers
Authors: Thompson Jake R. , Salam Rehana A. , Hanna Sarah , Dieng Mbathio , Saw Robyn P. M. , Bartula Iris
Published: April 2023

Aim

We conducted a systematic review and evidence gap mapping to explore the existing supportive care interventions and their impact on well‐being outcomes for melanoma patients and caregivers.

Methods

We searched MEDLINE, Embase, Web of Science Index Medicus, CINAHL, Lilacs, CENTRAL (Cochrane Library) and PsycINFO in December 2022, including interventional studies assessing the effectiveness of any supportive care intervention among melanoma patients and/or their caregivers.

Findings

Twenty studies were included in this review. These studies consisted of randomised controlled trials (n = 11, 55%), pre‐post studies (n = 7, 35%) and quasi‐experimental trials (n = 2, 10%). All studies originated from high‐income countries and focused primarily on melanoma patients, with no studies identified that focused solely on caregivers. Educational interventions were the most common (n = 7, 35%), followed by psychoeducational interventions (n = 6, 30%) and psychotherapeutic interventions (n = 4, 20%). Nearly all included studies (n = 18, 90%) reported a positive effect of the intervention on the primary outcome of interest; however, most studies (n = 17, 85%) were judged to be at moderate or high risk of bias. Due to heterogeneity of study designs, intervention characteristics and outcome measures, meta‐analysis was not conducted.

Implications

Supportive care interventions have positive impacts on melanoma patient well‐being outcomes, while being acceptable and feasible to conduct. More research is needed regarding supportive care interventions for melanoma caregivers. Future research should focus on eliminating sources of bias through rigorous methodology, with the development of standardised outcome measures for psychosocial outcomes to facilitate future meta‐analyses.
Controlled E. coli Aggregation Mediated by DNA and XNA Hybridization
Authors: Gasse Cécile , Srivastava Puneet , Schepers Guy , Jose Joachim , Hollenstein Marcel , Marlière Philippe , Herdewijn Piet
Published: April 2023

Chemical cell surface modification is a fast‐growing field of research, due to its enormous potential in tissue engineering, cell‐based immunotherapy, and regenerative medicine. However, engineering of bacterial tissues by chemical cell surface modification has been vastly underexplored and the identification of suitable molecular handles is in dire need. We present here, an orthogonal nucleic acid‐protein conjugation strategy to promote artificial bacterial aggregation. This system gathers the high selectivity and stability of linkage to a protein Tag expressed at the cell surface and the modularity and reversibility of aggregation due to oligonucleotide hybridization. For the first time, XNA (xeno nucleic acids in the form of 1,5‐anhydrohexitol nucleic acids) were immobilized via covalent, SNAP‐tag‐mediated interactions on cell surfaces to induce bacterial aggregation.
A highly stable and low‐cost 12T radiation hardened SRAM cell design for aerospace application
Authors: Liu Zhongyang , Xie Yuqiao , Xu Tao , Liu Qing , Bi Dawei , Hu Zhiyuan , Zou Shichang , Zhang Zhengxuan
Published: April 2023

In this paper, a highly stable and low‐cost 12T (HSLC12T) radiation hardened static‐random‐access‐memories (SRAM) cell is proposed in 55 nm CMOS technology. Based on polarity reversal design and read/write separation structure, the proposed HSLC12T cell can recover from any single event upsets (SEUs) induced at all its sensitive nodes and even single event double‐node‐upsets (SEDNUs) induced at its internal storage node pair Q‐QN, while also having the maximum read static noise margin (RSNM) and lower static hold power, as well as excellent write speed and write‐ability. Though the HSLC12T cell exhibits a larger read delay, it has the best overall performance of all other cells. This is proven by having the highest electrical quality metric (EQM) value, thus making the proposed HSLC12T cell a better choice for aerospace applications.
Immediate major dynamic changes in the T‐ and NK‐cell subset composition after cardiac transplantation
Authors: Iske Jasper , Wiegmann Bettina , Ius Fabio , Chichelnitskiy Evgeny , Ludwig Kristina , Kühne Jenny F. , Hitz Anna Maria , Beushausen Kerstin , Keil Jana , Iordanidis Susanne , Rojas Sebastián V. , Sommer Wiebke , Salman Jawad , Haverich Axel , Warnecke Gregor , Falk Christine S
Published: April 2023

Early kinetics of lymphocyte subsets involved in tolerance and rejection following heart transplantation (HTx) are barely defined. Here, we aimed to delineate the early alloimmune response immediately after HTx. Therefore, blood samples from 23 heart‐transplanted patients were collected before (pre‐), immediately (T0), 24 hours (T24), and 3 weeks (3 wks) after HTx. Immunophenotyping was performed using flow cytometry. A significant increase was detected for terminally differentiated (TEMRA) CD4+ or CD8+ T cells and CD56dimCD16+ NK cells immediately after HTx linked to a decrease in naïve CD8+ and CM CD4+ T as well as CD56brightCD16− NK cells, returning to baseline levels at T24. More detailed analyses revealed increased CD69+CD25− and diminished CD69−CD25−CD4+ or CD8+ T‐cell proportions at T0 associated with decreasing S1PR1 expression. Passenger T and NK cells were found at low frequencies only in several patients at T0 and did not correlate with lymphocyte alterations. Collectively, these results suggest an immediate, transient shift toward memory T and NK cells following HTx. Opposite migratory properties of naïve versus memory T and NK cells occurring in the early phase after HTx could underlie these observations and may impinge on the development of allo‐specific immune responses.
MHC class II‐deficient mice allow functional human CD4+ T‐cell development
Authors: Läderach Fabienne , Zdimerova Hana , Rieble Lisa , Schuhmachers Patrick , Engelmann Christine , Valencia‐Camargo Alma Delia , Kirchmeier Daniel , Böni Michelle , Münz Christian
Published: April 2023

Humanized mouse models have been developed to study cell‐mediated immune responses to human pathogens in vivo. How immunocompetent human T cells are selected in a murine thymus in such humanized mice remains poorly explored. To gain insights into this mechanism, we investigated the differentiation of human immune compartments in mouse MHC class II‐deficient immune‐compromised mice (humanized Ab0 mice). We observed a strong reduction in human CD4+ T‐cell development but despite this reduction Ab0 mice had no disadvantage during Epstein–Barr virus (EBV) infection. Viral loads were equally well controlled in humanized Ab0 mice compared to humanized NSG mice, and improved T‐cell recognition of autologous EBV‐transformed B cells was observed, especially with respect to cytotoxicity. MHC class II blocking experiments with CD4+ T cells from humanized Ab0 mice demonstrated MHC class II restriction of lymphoblastoid cell line recognition. These findings suggest that a small number of CD4+ T cells in humanized mice can be solely selected on human MHC class II molecules, presumably expressed by reconstituted human immune cells, leading to improved effector functions.
Experimental study on the dynamic responses of the end‐anchored floating bridge subjected to joint actions of earthquakes and water waves
Authors: Yan Jialei , Liu Jiabin , Liu Zhichao , Li Hui , Guo Anxin
Published: April 2023

This study experimentally investigates a dynamic behavior of an end‐anchored floating bridge under the joint actions of earthquakes and water waves. A truncated model with a geometrical scale of 1:100 was utilized for the hydrodynamic test, and an actuator was used to generate the earthquake input. A series of trials were conducted for the floating bridge model under the combined action of two different sea states and three earthquake inputs with increasing intensity based on the concept of the incremental dynamic analysis method. For comparison, the dynamic responses of the floating bridge model under earthquake action in still water and pure wave action were also conducted. Based on the test data, the dynamic responses, particularly focused on the sway, heave, roll, and pitch motions of the pontoons, of the test model were experimentally analyzed. The experimental results showed that earthquake excitation along the longitudinal axis of the bridge girder would induce noticeable oscillation of the bridge pontoons in still water. The magnitude of the coupled effects of earthquakes and water waves is dependent on the intensity of the earthquake inputs and the sea state.
Procalcitonin levels in pregnancy: A systematic review and meta‐analysis of observational studies
Authors: Prabhu Malavika , Wilkie Gianna , MacEachern Mark , LaBuda Dana , Purtell Jasmine , Rao Krishna , Riley Laura E. , Fuller Matthew , Rosser Morgan , Habib Ashraf S. , Bauer Melissa E.
Published: April 2023

Background

The utility of procalcitonin to identify obstetric sepsis is unknown.

Objective

To calculate the mean (range) procalcitonin in pregnancy among healthy women not in labor (group 1), healthy women in labor (group 2), and women with preterm prelabor rupture of membranes (PPROM) without clinical chorioamnionitis (group 3).

Search Strategy

NLM PubMed, Elsevier Embase, and Wiley Cochrane Central Register of Controlled Trials from inception to February 21, 2022.

Selection Criteria

Ten or more pregnant women with procalcitonin reported at more than 20 weeks of pregnancy, with information on labor, PPROM, and infection. Exclusions were major medical comorbidities.

Data Collection and Analysis

Each abstract and full‐text review was independently reviewed by the same two authors. Quality was reviewed using the Newcastle‐Ottawa Scale. A meta‐analysis was performed using a random effects model.

Main Results

The systematic review included 25 studies: 10 (40%) of good quality and 15 (60%) of poor quality. The meta‐analysis included 21 studies. Mean procalcitonin in group 1 was 0.092 ng/mL (range 0.036–0.049 ng/mL), in group 2 it was 0.130 ng/mL (range 0.049–0.259 ng/mL), and in group 3 it was 0.345 ng/mL (range 0.005–1.292 ng/mL).

Conclusions

Among healthy pregnant women not in labor, procalcitonin levels are comparable to those in non‐pregnant adults and may be useful in identifying infection. Procalcitonin levels in other groups overlap abnormal values of procalcitonin in non‐pregnant adults, and may not discriminate infection among women in labor or with obstetric comorbidities.

Prospero

CRD42020157376, registered 4/28/2020.
The relation of classroom climate to adolescents' countering hate speech via social skills: A positive youth development perspective
Authors: Wachs Sebastian , Valido Alberto , Espelage Dorothy L. , Castellanos Melisa , Wettstein Alexander , Bilz Ludwig
Published: April 2023

Introduction

Hate speech is a current challenge for schools around the globe. At the same time, students worldwide stand up to hate speech by countering it. Guided by a positive youth development perspective, the present study investigated the direct and indirect associations between classroom climate (environmental assets), social skills (personal assets), and countering hate speech (as a proxy of thriving) among adolescents.

Methods

The sample included 3225 students in grades 7–9 (51.7% self‐identified as female) from 40 schools in Germany (n = 1841) and Switzerland (n = 1384). Students completed self‐report questionnaires that assessed classroom climate, three facets of social skills (i.e., perspective‐taking, prosocial behavior, assertiveness), and counterspeech.

Results

The results of the 2‐(1‐1‐1)‐1 multilevel mediation analysis revealed that classroom climate (L2) and the three facets of social skills (L1) had a direct positive effect on counterspeech (L1). Furthermore, classroom climate (L2) also had a direct positive effect on the three facets of social skills (L1). Finally, classroom climate (L2) had an indirect positive effect on counterspeech (L1) via all three aspects of social skills (L1).

Conclusion

The findings highlight that successful anti‐hate speech programs may entail a combination of environmental and personal factors for increasing adolescents' active contribution to an inclusive and discrimination‐free classroom environment where hate speech is not tolerated.
Toward developing a valid and reliable assessment of adults' nature of engineering views
Authors: Kaya Erdogan , Deniz Hasan , Yesilyurt Ezgi
Published: April 2023

Background

Pre‐college engineering education reform documents aim to help students develop engineering literacy. Helping students develop sophisticated epistemological views about engineering makes a significant contribution toward developing engineering‐literate citizenry. Despite these widely recognized benefits, research on students' and teachers' epistemological views about engineering, commonly termed nature of engineering (NOE) views, has remained stagnant due to the absence of an open‐ended questionnaire whose collected evidence of validity indicates its appropriateness for assessing students' and teachers' NOE understanding.

Purpose

The purpose of this study is threefold: (a) describing the development of a new open‐ended instrument, the Views of Nature of Engineering Questionnaire version B (VNOE‐B), (b) providing evidence in support of the VNOE‐B validity and reliability, and (c) discussing the implications of the newly developed instrument for future research.

Design/Method

We aimed to provide evidence for the content and face validity of the VNOE‐B by seeking input from a panel of science/engineering educators. Evidence for the construct validity was determined by analyzing the open‐ended questionnaire and semistructured interview responses provided by pre‐service and in‐service teachers (considered novices in this field) and experts (engineers and engineering educators).

Results

Our findings indicate that the VNOE‐B is consistently successful in differentiating between experts' and novices' NOE views. All engineering experts held sophisticated NOE views across all NOE views under study, whereas most novices held partially informed or uninformed NOE views.

Conclusion

Evidence of validity supports the appropriateness of the VNOE‐B as an open‐ended instrument for assessing adults' NOE views. Its application may guide teacher educators in determining the efficacy of teacher professional development in meeting the aim of improving in‐service teachers' NOE understanding. Additionally, VNOE‐B may potentially inform the success of pre‐service teacher training.
Simple, non‐mechanical and automatic calibration approach for axial‐scanning microscopy with an electrically tunable lens
Authors: Li Shengfu , Zhao Yu , Wen Weifent , Ma Yuncan , Liu Shouxian , Chen Guanghua , Ye Yan
Published: April 2023

We describe a simple and robust calibration approach for axial‐scanning microscopy that realizes axial focus shifts with an electrically tunable lens (ETL). We demonstrate the calibration approach based on a microscope with an ETL placed close to the rear stop of the objective lens. By introducing a target—consisted of repeating lines at one known frequency and placed at a ~45° angle to the imaging path, the calibration method captures multiple images at different ETL currents and calibrates the dependence of the axial focus shift on the ETL current by evaluating the sharpness of the captured images. It calibrates the dependence of the magnification of the microscope on the ETL current by measuring the period of the repeating lines in the captured images. The experimental results show that different from the conventional calibration procedure, the proposed scheme does not involve any mechanical scanning and can simultaneously calibrate the dependence of the axial focus shift and the magnification on the ETL current. This might facilitate imaging studies that require the measurement of fine structures in a 3D volume. We also show the calibration procedure can be used to estimate the radius of a conner‐arc sample, fabricated using laser micromachining. We believe that this easy‐to‐use calibration approach may facilitate use of ETLs for a variety of imaging platforms. It may also provide new insights for the development of novel 3D surface measurement methods.

Research Highlights

The proposed calibration scheme does not involve any mechanical scanning and can simultaneously calibrate the dependence of the axial focus shift and the magnification on the electrically tunable lens (ETL) current. It might facilitate imaging studies that require the measurement of fine structures in a 3D volume, and the use of ETLs for a variety of imaging platforms. It may also provide new insights for the development of novel 3D surface measurement methods.
Two novel homozygous variants of ATP6V0A2 and ALDH18A1 lead to autosomal recessive cutis laxa type 2 and 3 in two Pakistani families
Authors: Zaman Qaiser , Iftikhar Aiman , Rehman Gauhar , Khan Qadeem , Najumuddin  , Jan Amin , Khan Jamshid , Anas Muhammad , Laiba  , Umair Muhammad , Muthaffar Osama Yousef , Abdulkareem Angham Abdulrhman , Bibi Fehmida , Naseer Muhammad Imran , Jelani Musharraf
Published: April 2023

Background

Autosomal recessive cutis laxa type 2A (ARCL2A; OMIM: 219200) is characterized by neurovegetative, developmental and progeroid elastic skin anomalies. It is caused by biallelic variation in ATPase, H+ transporting V0 subunit A2 (ATP6V0A2; OMIM: 611716) located on chromosome 12q24.31. Autosomal recessive cutis laxa type 3A (ARCL3A; OMIM: 219150) is another subclinical type characterized by short stature, ophthalmological abnormalities and a progeria‐like appearance. The ARCL3A is caused by loss of function alterations in the aldehyde dehydrogenase 18 family member A1 (ALDH18A1; OMIM: 138250) gene located at chromosome 10q24.1.

Methods

Whole‐exome sequencing (WES), and Sanger sequencing were performed for molecular diagnosis. 3D protein modeling was performed to investigate the deleterious effect of the variant on protein structure.

Results

In this study, clinical and molecular diagnosis were performed for two families, ED‐01 and DWF‐41, which displayed hallmark features of ARCL2A and ARCL3A, respectively. Three affected individuals in the ED‐01 family (IV‐4, IV‐5 and V‐3) displayed sagging loose skin, down‐slanting palpebral fissures, excessive wrinkles on the abdomen, hands and feet, and prominent veins on the trunk. Meanwhile the affected individuals in the DWF‐41 family (V‐2 and V‐3) had progeroid skin, short stature, dysmorphology, low muscle tone, epilepsy, lordosis, scoliosis, delayed puberty and internal genitalia. WES in the index patient (ED‐01: IV‐4) identified a novel homozygous deletion (NM_012463.3: c.1977_1980del; p.[Val660LeufsTer23]) in exon 16 of the ATP6V0A2 while in DWF‐41 a novel homozygous missense variant (NM_001323413.1:c.1867G>A; p.[Asp623Asn]) in exon 15 of the ALDH18A1 was identified. Sanger validation in all available family members confirmed the autosomal recessive modes of inheritances in each family. Three dimensional in‐silico protein modeling suggested deleterious impact of the identified variants. Furthermore, these variants were assigned class 1 or “pathogenic” as per guidelines of American College of Medical Genetics 2015. Screening of ethnically matched healthy controls (n = 200 chromosomes), excluded the presence of these variations in general population.

Conclusions

To the best of our knowledge, this is the first report of ATP6V0A2 and ALDH18A1 variations in the Pakhtun ethnicity of Pakistani population. The study confirms that WES can be used as a first‐line diagnostic test in patients with cutis laxa, and provides basis for population screening and premarital testing to reduce the diseases burden in future generations.
Potential applications of Aggregation Induced Emission active heterocyclic compounds
Authors: Soltan Fady Youssef Fathy , Sayed Mostafa , Tawab Mohamed Abdul , Talloj Satish Kumar , Kamal El‐dean Adel M. , Tolba Mahmoud S. , Saddik Abdelreheem Abdelfatah
Published: April 2023

Heterocyclic compounds are used as a basic structural tool in medicinal chemistry and are very essential in our daily life. A wide range of heterocyclic compounds were reported to show in the literature with interesting biological and pharmacological properties. In their profound study on a series of several heterocyclic compounds shown to have bio applications, unfortunately, the aromatic π‐conjugated heterocyclic molecules quench the emission intensity due to aggregation caused quenching due to π–π stacking. Owing to the disadvantages, the design and function of aggregation‐induced emission (AIE) active heterocyclic materials were emerging abundantly. On the other note, AIE has often been used to further improve both the emission intensity and stability of compounds, with plenty of potential applications in chemical sensing and bioimaging. In this work, we comprehensively reviewed the recent progress in heterocyclic compounds with AIE characteristics that are effectively used in chemo‐selective and bio‐imaging or as highly selective sensors.
Value of Radiomic Analysis Combined With Diffusion Tensor Imaging in Early Diagnosis of HIV‐Associated Neurocognitive Disorders
Authors: Qi Yu , Wang Wei , Rao Bo , Yang Xue , Yu Wen , Li Jia‐ying , Sun Zhi‐chao , Zhou Feini , Li Yuan‐zhe , Guo Yi‐fan , Wang Yi , Li Hong‐jun
Published: April 2023

Background

The combination of radiomics and diffusion tensor imaging (DTI) may have potential clinical value in the early stage of HIV‐associated neurocognitive disorders (HAND).

Purpose

To investigate the value of DTI‐based radiomics in the early stage of HAND in people living with HIV (PLWH).

Study Type

Retrospective.

Population

A total of 138 male PLWH were included, including 68 with intact cognition (IC) and 70 with asymptomatic neurocognitive impairment (ANI). Seventy healthy controls (HCs) were recruited for tract‐based spatial statistics (TBSS) analysis. All PLWHs were randomly divided into training and validation cohorts at a 7:3 ratio.

Field Strength/Sequence

A 3 T, single‐shot spin–echo echo planar imaging (EPI).

Assessment

The differences between the PLWH groups were compared using TBSS and region of interest (ROI) analysis. Radiomic features were extracted from the corpus callosum (CC) on DTI postprocessed images, including fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD). The performance of the radiomic signatures was evaluated by ROC curve analysis. The radiomic signature with the highest area under the curve (AUC) was combined with clinical characteristics to construct a nomogram. Decision curve analysis (DCA) was performed to evaluate the ability of different methods in discriminating ANI.

Statistical Tests

Chi‐square test, independent‐samples t test, Kruskal–Wallis test, Mann–Whitney U test, threshold‐free cluster enhancement (TFCE), ROC curve analysis, DCA, multivariate logistic regression analysis, Hosmer–Lemeshow test. P < 0.05 with TFCE corrected and P < 0.0001 without TFCE corrected were considered statistically significant.

Results

The ANI group showed lower FA and higher AD than the IC group. In the validation cohort, the AUCs of the FA‐, AD‐, MD‐ and RD‐based radiomic signatures and the clinicoradiomic nomogram were 0.829, 0.779, 0.790, 0.864, and 0.874, respectively. DCA revealed that the nomogram was of greater clinical value than TBSS analysis, the clinical models, and the RD‐based radiomic signature.

Data Conclusion

The combination of DTI and radiomics is correlated with early stage of HAND in PLWH.

Evidence Level

3.

Technical Efficacy

Stage 2.
Percutaneouse ultrasound‐guided needle aspiration for management of breast abscesses – a review
Authors: Ghunaim Hadeel
Published: April 2023

Breast abscesses are still a common cause of morbidity among lactational females. Over the years, there has been an increase in the incidence of non‐lactational breast abscesses and a decrease in lactational breast abscesses. The management could be the use of the conventional method of surgical incision and drainage or the newer techniques of needle aspiration or suction drain or catheter in addition to the administration of antibiotics. The use of needle aspiration as the minimal‐invasive conservative technique is generally recommended for abscesses less than 3–5 cm in diameter. However, recent studies have compared the two methods for abscesses larger than 3 cm and among patients with risk factors for breast abscesses. We aim to present the clinical evidence showing the comparison between needle aspiration and incision and drainage for breast abscesses irrespective of the size of the abscesses. There is a lack of comparative information on the two treatment modalities for breast abscesses larger than 3 cm in diameter; however, needle aspiration is being tried because of its advantages like cosmetic preference, short hospital stay and healing time, and no stoppage of breastfeeding.
Secular changes (1826–2021) of human thermal stress according to UTCI in Kraków (southern Poland)
Authors: Błażejczyk Krzysztof , Twardosz Robert
Published: April 2023

The set of meteorological data from the Jagiellonian University station in Kraków is one of the longest‐recorded in central Europe. Measurement records date back to 1826. Based on the average monthly values of air temperature, total cloudiness, water vapour pressure and wind speed at 1200 UTC, the UTCI values were calculated and the occurrence of cold stress (UTCI < −13°C) and heat stress (UTCI > 32°C) was estimated. The variability of the applied measures of thermal stress conditions was studied both annually and in individual seasons (MAM, JJA, SON, DJF). Statistically significant changes in the studied characteristics of the bioclimate were found. Average annual UTCI values increased at the rate of 0.27°C/10 years. In individual seasons, the trend of UTCI changes ranged from 0.10°C/10 years in summer to 0.43°C/10 years in winter. The number of days with cold stress decreased by 1.8 days/10 years and the number of days with heat stress significantly increased (0.5 days/10 years). Two subperiods with different trends of changes were determined. The first covers the years 1826–1940, and the second, 1941–2021. The former indicates a negative UTCI trend of −0.17°C/10 years, and the latter, an increasing trend of 1.09°C/10 years. The last eight decades have brought a decrease in cold days of 6.5/10 years and an increase in heat days of 2.6/10 years.
Liming and micronutrient application improves soil properties and productivity of the groundnut‐rapeseed cropping system in an acidic Inceptisol of India's eastern Himalayas
Authors: Das Santanu , Das Anup , Idapuganti Ramkrushna Gandhiji , Layek Jayanta , Thakuria Dwipendra , Sarkar Dibyendu , Bhupenchandra Ingudam , Lal Rattan , Chowdhury Samik , Babu Subhash , Debbarma Kabir
Published: April 2023

Aluminum toxicity, nutrient imbalance, and reduced microbial activity are the most limiting factors for optimum agronomic productivity in acid soils. A field study was conducted to investigate the impact of micronutrient and liming on soil properties and productivity of groundnut‐rapeseed system in an acidic Inceptisol. The impact of six micronutrient (control or no micronutrient, Zn at 5 kg ha−1, B at 1 kg ha−1, Mo at 0.5 kg ha−1, Zn + Mo, and Zn + B + Mo) and two soil amendment (furrow liming at 500 kg ha−1and no lime addition) treatments were first tested in groundnut and theirs residual effects were assessed on soil properties of succeeding rapeseed crop. Results indicated that liming significantly improved soil pH, soil organic carbon (SOC), available N, P and K, and diethylene triamine penta acetate (DTPA)‐extractable micronutrients, soil microbial biomass C and dehydrogenase activity as compared to no‐lime. After harvesting groundnut, Mo + Zn + B treated plots maintained the highest SOC content, whereas sole B and Mo treatment had the highest SOC content after harvesting rapeseed. Further, Mo + Zn + B treated plots showed higher contents of soil DTPA‐extractable micronutrients as compared to others. The highest groundnut equivalent yield (GEY) of the cropping system (pooled data of 2 years) was obtained with Mo + Zn + B (2.12 Mg ha−1) but remained at par with Zn + Mo (2.02 Mg ha−1). Multivariate principal component analysis indicated that available P was the most prominent soil nutrient with a strong effect on GEY. The results indicated that integrated application of Zn + B + Mo along with liming improves soil properties and agronomic productivity of groundnut‐rapeseed cropping system.
Epsin Mimetic UPI Peptide Delivery Strategies to Improve Endothelization of Vascular Grafts
Authors: Changizi Shirin , Sameti Mahyar , Bazemore Gabrielle L. , Chen Hong , Bashur Chris A.
Published: April 2023

Endothelialization of engineered vascular grafts for replacement of small‐diameter coronary arteries remains a critical challenge. The ability for an acellular vascular graft to promote endothelial cell (EC) recruitment in the body would be very beneficial. This study investigated epsins as a target since they are involved in internalization of vascular endothelial growth factor receptor 2. Specifically, epsin‐mimetic UPI peptides are delivered locally from vascular grafts to block epsin activity and promote endothelialization. The peptide delivery from fibrin coatings allowed for controlled loading and provided a significant improvement in EC attachment, migration, and growth in vitro. The peptides have even more important impacts after grafting into rat abdominal aortae. The peptides prevented graft thrombosis and failure that is observed with a fibrin coating alone. They also modulated the in vivo remodeling. The grafts are able to remodel without the formation of a thick fibrous capsule on the adventitia with the 100 µg mL−1 peptide‐loaded condition, and this condition enabled the formation of a functional EC monolayer in the graft lumen after only 1 week. Overall, this study demonstrated that the local delivery of UPI peptides is a promising strategy to improve the performance of vascular grafts.
Molecular mechanisms and therapeutic perspectives of peroxisome proliferator‐activated receptor α agonists in cardiovascular health and disease
Authors: Pu Yujie , Cheng Chak Kwong , Zhang Hongsong , Luo Jiang‐Yun , Wang Li , Tomlinson Brian , Huang Yu
Published: April 2023

The prevalence of cardiovascular disease (CVD) has been rising due to sedentary lifestyles and unhealthy dietary patterns. Peroxisome proliferator‐activated receptor α (PPARα) is a nuclear receptor regulating multiple biological processes, such as lipid metabolism and inflammatory response critical to cardiovascular homeostasis. Healthy endothelial cells (ECs) lining the lumen of blood vessels maintains vascular homeostasis, where endothelial dysfunction associated with increased oxidative stress and inflammation triggers the pathogenesis of CVD. PPARα activation decreases endothelial inflammation and senescence, contributing to improved vascular function and reduced risk of atherosclerosis. Phenotypic switch and inflammation of vascular smooth muscle cells (VSMCs) exacerbate vascular dysfunction and atherogenesis, in which PPARα activation improves VSMC homeostasis. Different immune cells participate in the progression of vascular inflammation and atherosclerosis. PPARα in immune cells plays a critical role in immunological events, such as monocyte/macrophage adhesion and infiltration, macrophage polarization, dendritic cell (DC) embedment, T cell activation, and B cell differentiation. Cardiomyocyte dysfunction, a major risk factor for heart failure, can also be alleviated by PPARα activation through maintaining cardiac mitochondrial stability and inhibiting cardiac lipid accumulation, oxidative stress, inflammation, and fibrosis. This review discusses the current understanding and future perspectives on the role of PPARα in the regulation of the cardiovascular system as well as the clinical application of PPARα ligands.
New insights into X‐linked adrenal hypoplasia congenita from a novel splice‐site variant of NR0B1 and adrenal CT images
Authors: Jiang Yuqing , Peng Huifang , Zhao Rui , Chang Yina , Liu Jie , Fu Liujun , Li Liping , Ma Yujin , Li Wei , Jiang Hongwei
Published: April 2023

Background

X‐linked adrenal hypoplasia congenita (AHC) is a rare disorder, often manifesting as primary adrenal insufficiency (PAI) and hypogonadotropic hypogonadism (HH), and caused by variants of NR0B1, most of which are frame‐shifting variants, and few splice‐site variants.

Methods and Results

Here, a novel splice‐site variant of NR0B1 (NM_000475.4), c.1169‐2A>T (patient 1), and a stop‐loss variant of NR0B1 c.1411T>C (patient 2) are described in this study. We perform minigene assays for the splice‐site variant (c.1169‐2A>T) and determine that the variant causes exon 2 skipping. Moreover, the defect of NR0B1 protein may bring about the severe phenotype of the patient. Through 8 years of follow‐up, we compare the CT images from 8 years ago with the latest image, and observe the CT image change of adrenal in patient 2 (from the increased thickness of adrenal to adrenal atrophy).

Conclusion

X‐linked adrenal hypoplasia congenita is produced by variants of NR0B1. We report a case that presents a novel splice‐site variant, which has been verified that it could lead to the exon 2 skipping in the RNA splicing progress. Moreover, we report the adrenal CT image change of patient 2, which has never been referred to before, and expand the spectrum of X‐linked AHC characteristics.
Regular Consumption of Biovalorized Okara‐Containing Biscuit Improves Circulating Short‐Chain Fatty Acids and Fecal Bile Acids Concentrations by Modulating the Gut Microbiome: A Randomized Controlled Crossover Trial
Authors: Lee Delia Pei Shan , Gan Alicia Xinli , Xia Xue Juan , Toh Kate Qi Xuan , Chan Gregory , Jung Sangyong , Kim Jung Eun
Published: April 2023

Scope

Okara is a fiber‐rich food by‐product whereby biovalorization with Rhizopus oligosporus can improve its nutritional quality, generating fermentable substrates for improved gut health maintenance. This study evaluates the impact of okara‐ and biovalorized okara‐containing biscuits consumption on gut health in Singapore adults.

Methods and results

Participants consume control (C), 20% flour‐substituted okara (AOK), and 20% flour‐substituted biovalorized okara (RO) biscuits for three weeks, with assessment of gut metabolites, microbiome, and dietary intake. Fecal valeric acid is significantly higher with RO compared to AOK (p = 0.005). RO and AOK have significantly higher total serum short‐chain fatty acids (p = 0.002 and 0.018 respectively) and acetic acid (p = 0.007 and 0.030 respectively) compared to C. Higher serum propionic acid (p = 0.004) and lower fecal lithocholic acid (p = 0.009) are observed with RO. Although serum zonulin shows no significant difference amongst interventions, AOK reduces Clostridiales while RO increases Bifidobacterium.

Conclusion

Okara consumption improves serum SCFA regardless of fermentation while biovalorized okara further enhances gut metabolites by modulating gut microbiome.
Efficacy and Optimal Dose of Coenzyme Q10 Supplementation on Inflammation‐Related Biomarkers: A GRADE‐Assessed Systematic Review and Updated Meta‐Analysis of Randomized Controlled Trials
Authors: Hou Shanshan , Tian Zezhong , Zhao Dan , Liang Ying , Dai Suming , Ji Qiuhua , Fan Zhiying , Liu Zhihao , Liu Meitong , Yang Yan
Published: April 2023

Scope

Coenzyme Q10 (CoQ10) has become a popular nutritional supplement due to its wide range of beneficial biological effects. Previous meta‐analyses show that the attenuation of CoQ10 on inflammatory biomarkers remains controversial. This meta‐analysis aims to assess the efficacy and optimal dose of CoQ10 supplementation on inflammatory indicators in the general population.

Methods and results

Databases are searched up to December 2022 resulting in 6713 articles, of which 31 are retrieved for full‐text assessment and included 1517 subjects. Double‐blind randomized controlled trials (RCTs) of CoQ10 supplementation are eligible if they contain C reactive protein (CRP), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α). CoQ10 supplementation can significantly reduce the levels of circulating CRP (SMD: −0.40, 95% CI: [−0.67 to −0.13], p = 0.003), IL‐6 (SMD: −0.67, 95% CI: [−1.01 to −0.33], p < 0.001), and TNF‐α (SMD: −1.06, 95% CI: [−1.59 to −0.52], p < 0.001) and increase the concentration of circulating CoQ10.

Conclusion

This meta‐analysis provides evidence for CoQ10 supplementation to reduce the level of inflammatory mediators in the general population and proposes that daily supplementation of 300–400 mg CoQ10 show superior inhibition of inflammatory factors.
Impact of imperfection in medical imaging data on deep learning‐based segmentation performance: An experimental study using synthesized data
Authors: Güneş Ayetullah Mehdi , van Rooij Ward , Gulshad Sadaf , Slotman Ben , Dahele Max , Verbakel Wilko
Published: April 2023

Background

Clinical data used to train deep learning models are often not clean data. They can contain imperfections in both the imaging data and the corresponding segmentations.

Purpose

This study investigates the influence of data imperfections on the performance of deep learning models for parotid gland segmentation. This was done in a controlled manner by using synthesized data. The insights this study provides may be used to make deep learning models better and more reliable.

Methods

The data were synthesized by using the clinical segmentations, creating a pseudo ground‐truth in the process. Three kinds of imperfections were simulated: incorrect segmentations, low image contrast, and artifacts in the imaging data. The severity of each imperfection was varied in five levels. Models resulting from training sets from each of the five levels were cross‐evaluated with test sets from each of the five levels.

Results

Using synthesized data led to almost perfect parotid gland segmentation when no error was added. Lowering the quality of the parotid gland segmentations used for training substantially lowered the model performance. Additionally, lowering the image quality of the training data by decreasing the contrast or introducing artifacts made the resulting models more robust to data containing those respective kinds of data imperfection.

Conclusion

This study demonstrated the importance of good‐quality segmentations for deep learning training and it shows that using low‐quality imaging data for training can enhance the robustness of the resulting models.
EPR characterization of Cu/Al‐Zr‐Ce ethanol dehydrogenation catalysts: Active site development and coking control
Authors: Fionov Yuri A. , Chuklina Sofia G. , Khlusova Ksenia S. , Fionov Alexander V. , Zhukova Anna I.
Published: April 2023

Electron paramagnetic resonance (EPR) spectroscopy was applied to study structure–performance relationships for copper‐containing catalysts based on Al‐Zr‐Ce mixed oxides with various oxide support synthesis temperature. In situ EPR showed that the state of Cu2+ sites depends on the phase composition of the support, temperature, as well as the presence of the reaction medium during catalysis.
In vivo assessment of β‐hydroxybutyrate metabolism in mouse brain using deuterium (2H) MRS
Authors: Soni Narayan Datt , Swain Anshuman , Jacobs Paul , Juul Halvor , Armbruster Ryan , Nanga Ravi Prakash Reddy , Nath Kavindra , Wiers Corinde , Detre John , Reddy Ravinder
Published: April 2023

Purpose

To monitor the metabolic turnover of β‐hydroxybutyrate (BHB) oxidation using 2H‐MRS in conjunction with intravenous administration of 2H labeled BHB.

Methods

Nine‐month‐old mice were infused with [3,4,4,4]‐2H4‐BHB (d4‐BHB; 3.11 g/kg) through the tail vein using a bolus variable infusion rate for a period of 90 min. The labeling of downstream cerebral metabolites from the oxidative metabolism of d4‐BHB was monitored using 2H‐MRS spectra acquired with a home‐built 2H surface coil on a 9.4T preclinical MR scanner with a temporal resolution of 6.25 min. An exponential model was fit to the BHB and glutamate/glutamine (Glx) turnover curves to determine rate constants of metabolite turnover and to aid in the visualization of metabolite time courses.

Results

Deuterium label was incorporated into Glx from BHB metabolism through the tricarboxylic acid (TCA) cycle, with an increase in the level of [4,4]‐2H2‐Glx (d2‐Glx) over time and reaching a quasi‐steady state concentration of ∼0.6 ± 0.1 mM following 30 min of infusion. Complete oxidative metabolic breakdown of d4‐BHB also resulted in the formation of semi‐heavy water (HDO), with a four‐fold (10.1 to ∼42.1 ± 7.3 mM) linear (R2 = 0.998) increase in its concentration by the end of infusion. The rate constant of Glx turnover from d4‐BHB metabolism was determined to be 0.034 ± 0.004 min−1.

Conclusion

2H‐MRS can be used to monitor the cerebral metabolism of BHB with its deuterated form by measuring the downstream labeling of Glx. The integration of 2H‐MRS with deuterated BHB substrate provides an alternative and clinically promising MRS tool to detect neurometabolic fluxes in healthy and disease conditions.