bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Intelligence of Things-Based Optimal Finite-Time Terminal Attractor and Its Application to Maximum Power Point Tracking of Photovoltaic Arrays in Smart Cities
Authors: Chang En-Chih , Cheng Chun-An , Wu Rong-Ching
Published: April 2022

The combination of artificial intelligence of things (AIoT) and photovoltaic power generation can save energy and reduce carbon emissions and further promote the development of smart cities. In order to obtain the maximum power output from photovoltaic (PV) arrays, we can use optimal maximum power point tracking (MPPT) technique with AIoT sensing to improve system efficiency. The optimal MPPT technique is the finite-time terminal attractor (FTTA) based on the gradient particle swarm optimization (GPSO), which can be applied to track the maximum power of a PV array system. The FTTA not only provides fast finite-time convergence but also attenuates steady-state errors, making it ideal for nonlinear system applications. The GPSO is used to search the control parameters of the FTTA, which is able to find the global best solution. This avoids unmodeled dynamic behavior of the system excited by the quiver, which slows down the control convergence and prematurely traps the system into a local optimum. The MATLAB computer software is used to simulate the proposed PV maximum power point tracking system. The results show that more accurate and better tracking control of the PV array can be produced under partial shading conditions and then improve the steady-state and transient performance.
Design of the Online Learning System for College Physical Education Teaching Based on the BP Neural Network
Authors: Li Bin , Wang Shaofen
Published: April 2022

The popularization of the campus network provides the possibility for the realization of online sports teaching. Based on the current situation of college physical education, the existing electronic textbooks, individual technical education software, educational videos, and other resources are neatly integrated. It builds a sports network education platform that is helpful for students to learn and realizes open interactive education. Nowadays, with the development of the Internet, artificial intelligence technology has solved many problems for people. The learning model combining artificial intelligence and online education has also become a new trend of educational informatization. This paper is based on the BP neural network in artificial intelligence to explore the design of the college sports teaching system in school. The purpose of this paper is at developing an online learning system suitable for college sports, so as at improving the learning efficiency and learning experience of college sports students. This paper firstly introduces the background and research significance of online learning, the BP neural network. Then, it introduces the design of the BP neural network and online system; in this paper, a series of introductions are given to its structure, function, and recommendation algorithm. Afterwards, this paper tests the performance of the designed system and finds that the average response time of the system is 0.978 s. Finally, this paper does a questionnaire survey to the users of the learning system. It is found that both in the recognition and in the liking sections, the satisfaction of students and teachers is relatively high.
Empirical Investigation for Predicting Depression from Different Machine Learning Based Voice Recognition Techniques
Authors: Punithavathi R. , Sharmila M. , Avudaiappan T. , Raj I. Infant , Kanchana S. , Mamo Samson Alemayehu
Published: April 2022

Over the past few decades, the rate of diagnosing depression and mental illness among youths in both genders has been emerging as a challenging issue in the present society. Adequate numbers of cases that have been prevailing had unheard of symptoms linked to mental depression that are able to be detected using their voice recordings and their messages in social media websites. Due to the wide spread usage of mobile phones, services and social sites emotion prediction and analyzing have been an indispensable part of providing vital care for the eminence of youth’s life. In addition to dynamicity and popularity of mobile applications and services, it is really a challenge to provide an emotion prediction system that can collect, analyze, and process emotional communications in real time and as well as in a highly accurate manner with minimal computation time. Few depression prediction researchers have analyzed and examined that various social networking sites and its activities may be merged to low self-confidence, particularly in young people and adolescents. Moreover, the researchers suggest that several objective voice acoustic measures affected by depression can be detected reliably over the smart phones. And also in some observational study, it is stated that speech samples of patients from the telephone were obtained each week using an IVR system, and voice recording files from smart phones have been under process for predicting the depression. Such that several telephonic standards for obtaining voice data were identified as a crucial factor influencing the reliability and eminence of speech data. Hence, this article investigates on different process applied in different machine learning algorithms in recognizing voice signals which in turn will be used for scrutinizing the techniques for detecting depression levels in future. This will make a blooming change in the youth’s life and solve the social unethical issues in hand.
Design and Synthesis of Conducting Polymer Bio-Based Polyurethane Produced from Palm Kernel Oil
Authors: Munir Muhammad Abdurrahman , Badri Khairiah Haji , Heng Lee Yook , Inayatullah Ahlam , Badrul Hamid Alkhair , Emelda Emelda , Dwinta Eliza , Kusumawardani Nurul , Wulandari Ari Susiana , Aprilia Veriani , Supriyono Rachmad Bagas Yahya
Published: April 2022

Polyurethane (PU) is a unique polymer that has versatile processing methods and mechanical properties upon the inclusion of selected additives. In this study, a freestanding bio-based polyurethane film the screen-printed electrode (SPE) was prepared by the solution casting technique, using acetone as solvent. It was a one-pot synthesis between major reactants, namely, palm kernel oil-based polyol and 4,4-methylene diisocyanate. The PU has strong adhesion on the SPE surface. The synthesized bio-based polyurethane was characterized using thermogravimetry analysis, differential scanning calorimetry, Fourier-transform infrared spectroscopy (FTIR), surface area analysis by field emission scanning electron microscope, and cyclic voltammetry. Cyclic voltammetry was employed to study electrocatalytic properties of SPE-polyurethane towards oxidation of PU. Remarkably, SPE-PU exhibited improved anodic peak current as compared to SPE itself using the differential pulse voltammetry method. Furthermore, the formation of urethane linkages (-NHC(O) backbone) after polymerization was analyzed using FTIR and confirmed by the absence of peak at 2241 cm-1 attributed to the sp-hydridized carbons atoms of C≡C bonds. The glass transition temperature of the polyurethane was detected at 78.1°C.
Role of Butylphthalide in Immunity and Inflammation: Butylphthalide May Be a Potential Therapy for Anti-Inflammation and Immunoregulation
Authors: Zhang Yiliu , Ren Yijun , Chen Xiqian , Deng Shuwen , Lu Wei
Published: April 2022

Inflammation and immunity play an essential role in disease pathogenesis. 3-N-Butylphthalide (NBP), a group of compounds extracted from seeds of Apium graveolens (Chinese celery), has been demonstrated as an efficient and effective therapy for ischemic stroke. The amount of research on NBP protective effect is increasing at pace, such as microcircular reconstruction, alleviating inflammation, ameliorating brain edema and blood-brain barrier (BBB) damage, mitochondrial function protection, antiplatelet aggregation, antithrombosis, decreasing oxidative damage, and reducing neural cell apoptosis. There has been increasing research emphasizing the association between NBP and immunity and inflammation in the past few years. Hence, it is aimed at reviewing the related literature and summarizing the underlying anti-inflammatory and immunoregulatory function of NBP in various disorders.
The Effect of Starch and Magnetite on the Physicochemical Properties of Polyurethane Composites for Hyperthermia Treatment
Authors: Paprota Natalia , Szatkowski Piotr , Szlachta Monika , Piekarczyk Wojciech , Pielichowska Kinga
Published: April 2022

In this study, modified polyurethanes (PUs) with starch and magnetite were synthesized in the form of scaffolds for potential applications in orthopedics. Polyurethanes were synthesized using a one-step method. PU synthesis was carried out using poly(ε-caprolactone) 2000 as soft segments and 4,4

′

-methylenediphenyl diisocyanate (MDI). Various molar ratios of starch and 1,5-pentanediol (PDO) as crosslinker/chain extender were applied, and the effects of incorporating different amounts of magnetite, as well as the role of PDO to starch ratio, were studied. The use of the additive in the form of magnetic particles was to feature the polyurethane materials for use in hyperthermia. The prepared polyurethanes were investigated using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetry (TG), and dynamic mechanical analysis (DMA) methods. Scanning electron microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDX) analysis and preliminary bioactivity assessment were also performed. The addition of magnetic particles did not cause significant changes in the properties of the obtained materials compared to starch. The tested materials have the potential to be used to fill or replace bone defects in orthopedics, where they can undergo hyperthermia treatment.
Experimental and Numerical Analysis on the Damage and Failure Characteristics of Bituminous Coal under Multilevel Cyclic Loads
Authors: Gong Shuang , Wang Chaofei , Zhou Lei , Xi Furui , Yao Shibin , Li Xiaojun , Liu Juan , Wang Wen
Published: April 2022

The coal mining process is often accompanied by periodic disturbance of the surrounding rock mass around the coal mining face. Therefore, it is of great theoretical and engineering value to investigate the damage pattern of bituminous coal under cyclic loading and unloading conditions and analyze its damage precursors. The experiments of uniaxial multistage cyclic loading and unloading of bituminous coal were carried out, and the loading and unloading response ratios were extracted using the elastic modulus variation to describe the damage characteristics and damage precursors of bituminous coal. Based on the accumulated acoustic emission ringing counts, the response ratios were defined, and the internal damage evolution characteristics and damage laws during the damage of bituminous coal were analyzed. The CT scan images of the internal structure of the coal sample before and after the experiment were used to analyze the damage characteristics of the coal sample and the influence of the number of simulation units on the results using the inverse modeling simulation analysis method. The research shows that the response ratio of bituminous coal under uniaxial cyclic loading has three stages of variation, and it is characterized by periodic “W”-type variation at each level of stress. In addition, the inverse modeling and simulation can better characterize the damage evolution of the coal specimen.
Artemisinin Alleviates Cerebral Ischemia/Reperfusion Injury via Regulation of the Forkhead Transcription Factor O1 Signaling Pathway
Authors: Yang Xiaogang , Wu Ke
Published: April 2022

The effect and mechanism of artemisinin therapy on cerebral ischemia-reperfusion injury (CIRI) was analyzed in this work. 100 healthy male C57BL/6 mice were selected and randomly divided into the sham group (no treatment), CIRI model group (IR), IR + artemisinin posttreatment group (IR + Arte), EX527 + IR group (EX527 + IR), and EX527 + IR + artemisinin posttreatment group (EX527 + IR + Arte), with 20 mice in each group. The cerebral infarct volumes of mice in different groups were measured by the 2,3,5-triphenyltetrazolium chloride (TTC) staining method. The neurological function scores and oxidative stress levels of mice in different groups were measured and compared. In addition, the expressions of silent information regulator 1 (SIRT1), forkhead transcription factor O1 (FOXO1), and p53 protein in brain tissue were detected. The results showed that the contents of reactive oxygen species (ROS) and malondialdehyde (MDA) in the EX527 + IR group and EX527 + IR + Arte group were significantly higher than those in the IR + Arte group (

P
<
0.05

). The expressions of SIRT1 protein in the brain tissue of the IR group and EX527 + IR group were much lower than that of the sham group (

P
<
0.01

); compared with the IR + Arte group, the expression of the X527 + IR group in the brain tissue was greatly reduced (

P
<
0.05

). The expression levels of FOXO1 protein and p53 protein in the brain tissue of mice in the IR group and EX527 + IR group were higher than those in the sham group (

P
<
0.01

). It was concluded that artemisinin treatment can reduce oxidative stress damage and alleviate CIRI through the SIRT1/FOXO1 signaling pathway, thereby achieving neuroprotective effects.
Research on the Design of Intelligent Music Teaching System Based on Virtual Reality Technology
Authors: Chen Wei
Published: April 2022

With the continuous development and innovation of artificial intelligence technology, its application in the field of music education is also increasing, music classroom has accepted and applied a more efficient and intelligent teaching system. In the reform of teaching, virtual reality (VR) technology has gradually become a new means which occupies a place in the field of education and scientific research. The teaching system based on virtual reality has been focused in all kinds of teaching. Therefore, in this paper, VR is used to build a music teaching system based on model embedding, bread capture, packing capture and camera establishment, so as to implement the music teaching platform based on VR. Through the construction of different virtual elements, it can better achieve the goals of public participation and can effectively stimulate the singer's sensory organs.
Diagnostic Test to Identify Parkinson’s Disease from the Blood Sera of Chinese Population: A Cross-Sectional Study
Authors: Tong Guangan , Zhang Pingping , Hu Wenbin , Zhang Kun , Chen Xianwen
Published: April 2022

Background. Parkinson’s disease (PD) is a neurodegenerative disease, a hallmark by the formation of misfolded and aggregated α-synuclein proteins. The expression of potential microRNA (miRNA) candidates isolated from serum and cerebrospinal fluid (CSF) exosomes of PD patients was assessed for their diagnostic value and their potential role as biomarkers for PD was explored. In this study, we characterize the expression level of miRNAs in the exosomes of blood sera and cerebrospinal fluid and explore their potential role as biomarkers for PD. Materials and Methods. A total of 209 patients having an onset of PD, along with 60 neurodegenerative (ND) disorders and 50 healthy controls were enrolled. Blood samples and CSF samples were collected and exosomes were isolated. The isolated exosomes were characterized using CD63 detection and exosomal RNA was extracted. Serum miRNA profiling was carried out by synthesizing cDNA from the purified RNA and miRNA transcripts were determined by qRT-PCR using SYBR Green PremixScript. microRNA profiling strategy was employed for extracting the exosomal miRNAs from the exosomes. Results. Five common miRNAs viz. miR-151a-5p, miR-24, mir-485-5p, mir-331-5p, and mir-214 were found to be upregulated with statistical significance in both the serum exosome and CSF exosomes. The investigation revealed that serum and CSF exosomal miRNA molecules are definitive biomarkers for PD with proper specificity and sensitivity. Conclusions. The significant level of miR-151a-5p, miR-24, mir-485-5p, mir-331-5p, and mir-214 was observed in the serum and CSF which may be established as a biomarker for the diagnosis of PD.
AIM2 Promotes Gastric Cancer Cell Proliferation via the MAPK Signaling Pathway
Authors: Feng Xiaojia , Song Zaozhi , Huang Qihui , Jia Jianguang , Zhang Lingmei , Zhu Mengqi , Qian Jun
Published: April 2022

Background. Gastric cancer (GC) is a highly prevalent tumor type. The dysregulated expression of melanoma deficiency factor 2 (AIM2) has been observed in a range of tumor types. Herein, we explore the role of AIM2 in the regulation of GC progression. Methods. Gastric cancer cells BGC-823 and MGC-803 in logarithmic growth phase were divided into blank group (control), Control group (NC) and SH-AIM2 group, respectively. Control group and SH-AIM2 group were transfected with AIM2 NC and SH-AIM2, respectively. Nude mice were divided into blank group (control) and SH-AIM2 group, and the treatment methods were the same as above. Differential AIM2 expression in GC tissues was assessed via bioinformatics analyses, after which western blotting was used for analyzing the AIM2 levels in tumor and paracancerous tissues from five stomach cancer patients. In addition, qPCR and protein imprinting were used to assess AIM2 expression levels in GC cells, and AIM2 knockdown was conducted in MGC-803 and BGC-823cells, after which colony formation and EdU incorporation assay were utilized to assess cell proliferation. The oncogenic role of AIM2 was then assessed in mice and validated through immunohistochemical analyses. Results. GC tissues and cell lines exhibited marked AIM2 overexpression. AIM2 knockdown significantly impaired GC cell proliferation and migration, as confirmed through in vitro assays. In vivo experiments showed that both the increment ability and invasion and migration ability of AIM2 knockdown group were significantly lower than that of control and NC the change of AIM2 protein level would affect the change of MAPK pathway related protein level. Conclusions. AIM2 knockdown markedly suppresses the proliferation, migration, as well as invasion of GC cells via the inhibition of MAPK signaling, thereby slowing tumor progression. Overall, these results suggest that further analyses of AIM2 may offer clinically valuable insights that can aid in the treatment of human GC.
Effects of Single and Mixture Probiotic Supplements on Growth, Digestive Activity, Antioxidative Status, Immune and Growth-Related Genes, and Stress Response of Juvenile Red Sea Bream (Pagrus Major)
Authors: Shadrack Ronick Spenly , Manabu Ishikawa , Koshio Shunsuke , Yokoyama Saichiro , Zhang Yukun , Mzengereza Kumbukani , El Basuini Mohammed Fouad , Dawood Mahmoud A. O.
Published: April 2022

A 50-day feeding trial was conducted to evaluate the efficiency of single and mixed strains of probiotic bacteria supplements on juvenile red sea bream (Pagrus major). The study investigated the growth, digestibility, hemato-biochemistry, antioxidant, immune, immune, and growth gene expression and stress responses of P. major. Three hundred juvenile P. major (

21.56
±
0.09

 g) were randomly distributed into fifteen 200-L polyethylene tanks (20 fish per tank) in triplicate of 5 treatments designated as D1 = the basal diet; Streptococcus faecalis (SF)

T
−
110
 
5
×
106

cfu/g diet and Bacillus amyloliquefaciens (BA)

TOA
5001
 
5
×
105

cfu/g diet in the second group (D2) at 0.2%; mix SF

T
−
110
 
1
×
106

cfu/g diet, Lactobacillus plantarum (LP)

TO
−
A
 
4
×
105

cfu/g diet, Bacillus mesentericus (BM)

TO
−
A
 
1
×
102

cfu/g diet, BA

TOA
5001
 
5
×
105

cfu/g diet in the third group (D3) at 1%; mix SF

T
−
110
 
1
×
106

cfu/g diet, LP

TO
−
A
 
4
×
105

cfu/g diet, and BM

TO
−
A
 
1
×
102

cfu/g diet in fourth group (D4) at 0.5%; and single strain BA TOA5001 5×105 cfu/g diet in the fifth group (D5) at 0.5% of dietary proportion. Results showed that D2 and D3 fish groups exhibit better performance, followed by D4, D5, and control group D1. This finding demonstrated that the use of BA in mix strain probiotic bacteria diet (D2, D3) had improved immune response, antioxidant enzymes, immunity (TNF-a, IL-1b), and growth-related (IGF-1, IGF-2) mRNA expression of juvenile P. major compared to the mix strain D4, single strain D5, and the control D1. Furthermore, single strain D5 and mix strain D4 also exhibit relatively better immune responses in P. major than in control D1. Considering the overall fish performances, mix strain SF+BA (D2) and mix strain SF+BM+LP+BA (D3) were the recommended potential mix strain probiotic bacteria supplement for P. major and may be useful also for other related aquatic species.
Cutaneous Pseudoepitheliomatous Hyperplasia from a Displaced Metallic Orthopedic Implant
Authors: Blum Franklin R. , D’Souza Logan S.
Published: April 2022

While rare, cutaneous SCC in patients with darker Fitzpatrick skin types is essential to identify and investigate early and can have a myriad of clinical presentations. While clinical history-taking of suspicious skin lesions is often symptom-driven, other key patient history components, such as surgical history, are often overlooked. Differentiating, prioritizing, and risk-stratifying hyperkeratotic, verrucous papules in patients with darker Fitzpatrick skin types is an essential clinical skill for clinicians to develop to serve an increasingly diverse patient population. This original report presents the case of a displaced orthopedic screw causing pseudoepitheliomatous hyperplasia that was initially misdiagnosed as squamous cell carcinoma. This case highlights the importance of careful consideration of surgical history, choice of biopsy method, and skin type when examining lesions concerning for squamous cell carcinoma.
Using Chitosan‐Coated Polymeric Nanoparticles‐Thermosensitive Hydrogels in association with Limonene as Skin Drug Delivery Strategy
Authors: Campos Estefânia V. R. , Proença Patrícia L. F. , da Costa Tais G. , de Lima Renata , Fraceto Leonardo F. , de Araujo Daniele R.
Published: April 2022

Topical delivery of local anesthetics (LAs) is commonly used to decrease painful sensations, block pain throughout procedures, and alleviate pain after surgery. Dermal and/or transdermal delivery of LAs has other advantages, such as sustained drug delivery and decreased systemic adverse effects. This study reports the development of poly(D,L‐lactide‐co‐glycolide) (PLGA) nanoparticles coated with chitosan for the sustained release and topicality of benzocaine (BZC) and topical delivery. BZC PLGA nanoparticles or nonencapsulated drugs were further incorporated into Poloxamer hydrogels (Pluronic™ F‐127). The nanoparticles showed a mean diameter of 380 ± 4 nm, positive zeta potential after coating with chitosan (23.3 ± 1.7 mV), and high encapsulation efficiency (96.7 ± 0.02%). Cellular viability greater than 70% for both fibroblasts and keratinocytes was observed after treatment with nanoparticles, which is in accordance with the preconized guidelines for biomedical devices and delivery systems. Both the nanoparticles and hydrogels were able to modulate BZC delivery and increase drug permeation when compared to the nonencapsulated drug. Furthermore, the incorporation of limonene into hydrogels containing BZC‐loaded nanoparticles increased the BZC permeation rates. Non‐Newtonian and pseudoplastic behaviors were observed for all hydrogel nanoformulations with or without nanoparticles. These results demonstrate that the hydrogel‐nanoparticle hybrids could be a promising delivery system for prolonged local anesthetic therapy.
Consanguineous Marriages and Dental Anomalies: A Cross-Sectional Analytical Study
Authors: Abbas Beenish , Abbas Sana , Malik Saadia Muneer , Rahim Majida , Umair Muhammad , Khurshid Zohaib
Published: April 2022

Objective. To determine the correlation between consanguineous marriages and dental anomalies. Study Design. A cross-sectional analytical study. Materials and Methods. This cross-sectional analytical multicentered study was carried out at Foundation University College of Dentistry after approval of the Ethical Research Committee (ERC) from September 2021 to November 2021 in Pakistan. All pediatric patients (4–10 years old) with dental malformations undergoing dental procedures or examinations and born with spontaneous vaginal delivery and uncomplicated cesarean section participated in the study. First, second, and third-degree relatives’ marriages of parents were used to define consanguinity. The Basic Pay Scale was the reference of estimation of socioeconomic status. Participants with a history of orofacial trauma, pertinent parental history (infertility, hormonal treatment, or infectious diseases during pregnancy, conception with assisted reproductive techniques, prolonged complicated labor, premature deliveries, and twin births), and prolonged hospital admission immediately after birth were excluded from the study. Results. The mean maternal and paternal age was recorded to be 23.86 ± 5.4 and 27.07 ± 9.6, respectively, whereas the mean age of participants was 6.60 ± 1.67. There were 297 children with congenital abnormalities, with 203 (68.4%) males and 94 (31.6%) females. The prevalence of consanguineous marriage was found to be in 210 (70.7%) participants. Congenital dental anomalies correlation was found to be significant with consanguineous marriages (p value <0.001). Consanguineous marriages were more frequent in the lower socioeconomic group when compared with the middle and upper socioeconomic groups, respectively (74.7% vs. 8.1% vs. 17.2%, p value 0.007). Conclusion. Congenital dental anomalies were significantly prevalent in consanguineous marriages with greater incidence in lower socioeconomic groups. Consanguineous marriages have the propensity to transmute population conformation, but due to religious and social beliefs, literature is hesitant to ascribe congenital dental anomalies persuasive relevance with consanguinity.
The Genomics of Colorectal Cancer in Populations with African and European Ancestry
Authors: Myer Parvathi A. , Lee Jessica K. , Madison Russell W. , Pradhan Kith , Newberg Justin Y. , Isasi Carmen R. , Klempner Samuel J. , Frampton Garrett M. , Ross Jeffery S. , Venstrom Jeffrey M. , Schrock Alexa B. , Das Sudipto , Augenlicht Leonard , Verma Amit , Greally John M. , Raj Srilakshmi M. , Goel Sanjay , Ali Siraj M.
Published: April 2022

Black people have a higher incidence of colorectal cancer and worse survival rates when compared with white people. Comprehensive genomic profiling was performed in 46,140 colorectal adenocarcinoma cases. Ancestry-informative markers identified 5,301 patients of African descent (AFR) and 33,770 patients of European descent (EUR). AFR were younger, had fewer microsatellite instability–high (MSI-H) tumors, and had significantly more frequent alterations in KRAS, APC, and PIK3CA. AFR had increased frequency of KRAS mutations, specifically KRASG12D and KRASG13. There were no differences in rates of actionable kinase driver alterations (HER2, MET, NTRK, ALK, ROS1, and RET). In patients with young-onset colorectal cancer (<50 years), AFR and EUR had a similar frequency of MSI-H and tumor mutational burden–high (TMB-H) tumors, and strikingly different trends in APC mutations by age, as well as differences in MAPK pathway alterations. These findings inform treatment decisions, impact prognosis, and underscore the need for model systems representative of the diverse U.S. population.

Significance:

KRAS (particularly KRASG12D/G13), APC, and PIK3CA were more frequently altered in AFR who had a lower frequency of MSI-H tumors. There were no differences in actionable kinase driver alterations. In young-onset colorectal cancer, both ancestries had a similar frequency of MSI-H/TMB-H tumors, but strikingly different trends in APC.

See related commentary by Eng and Holowatyj, p. 1187.

This article is highlighted in the In This Issue feature, p. 1171
Genomic and Single-Cell Landscape Reveals Novel Drivers and Therapeutic Vulnerabilities of Transformed Cutaneous T-cell Lymphoma
Authors: Song Xiaofei , Chang Shiun , Seminario-Vidal Lucia , de Mingo Pulido Alvaro , Tordesillas Leticia , Song Xingzhi , Reed Rhianna A. , Harkins Andrea , Whiddon Shannen , Nguyen Jonathan V. , Segura Carlos Moran , Zhang Chaomei , Yoder Sean , Sayegh Zena , Zhao Yun , Messina Jane L. , Harro Carly M. , Zhang Xiaohui , Conejo-Garcia José R. , Berglund Anders , Sokol Lubomir , Zhang Jianhua , Rodriguez Paulo C. , Mulé James J. , Futreal Andrew P. , Tsai Kenneth Y. , Chen Pei-Ling
Published: April 2022

Cutaneous T-cell lymphoma (CTCL) is a rare cancer of skin-homing T cells. A subgroup of patients develops large cell transformation with rapid progression to an aggressive lymphoma. Here, we investigated the transformed CTCL (tCTCL) tumor ecosystem using integrative multiomics spanning whole-exome sequencing (WES), single-cell RNA sequencing, and immune profiling in a unique cohort of 56 patients. WES of 70 skin biopsies showed high tumor mutation burden, UV signatures that are prognostic for survival, exome-based driver events, and most recurrently mutated pathways in tCTCL. Single-cell profiling of 16 tCTCL skin biopsies identified a core oncogenic program with metabolic reprogramming toward oxidative phosphorylation (OXPHOS), cellular plasticity, upregulation of MYC and E2F activities, and downregulation of MHC I suggestive of immune escape. Pharmacologic perturbation using OXPHOS and MYC inhibitors demonstrated potent antitumor activities, whereas immune profiling provided in situ evidence of intercellular communications between malignant T cells expressing macrophage migration inhibitory factor and macrophages and B cells expressing CD74.

Significance:

Our study contributes a key resource to the community with the largest collection of tCTCL biopsies that are difficult to obtain. The multiomics data herein provide the first comprehensive compendium of genomic alterations in tCTCL and identify potential prognostic signatures and novel therapeutic targets for an incurable T-cell lymphoma.

This article is highlighted in the In This Issue feature, p. 1171
ZNF384 Fusion Oncoproteins Drive Lineage Aberrancy in Acute Leukemia
Authors: Dickerson Kirsten M. , Qu Chunxu , Gao Qingsong , Iacobucci Ilaria , Gu Zhaohui , Yoshihara Hiroki , Backhaus Emily A. , Chang Yunchao , Janke Laura J. , Xu Beisi , Wu Gang , Papachristou Evangelia K. , D'Santos Clive S. , Roberts Kathryn G. , Mullighan Charles G.
Published: April 2022

ZNF384-rearranged fusion oncoproteins (FO) define a subset of lineage ambiguous leukemias, but their mechanistic role in leukemogenesis and lineage ambiguity is poorly understood. Using viral expression in mouse and human hematopoietic stem and progenitor cells (HSPC) and a Ep300::Znf384 knockin mouse model, we show that ZNF384 FO promote hematopoietic expansion, myeloid lineage skewing, and self-renewal. In mouse HSPCs, concomitant lesions, such as NRASG12D, were required for fully penetrant leukemia, whereas in human HSPCs, expression of ZNF384 FO drove B/myeloid leukemia, with sensitivity of a ZNF384-rearranged xenograft to FLT3 inhibition in vivo. Mechanistically, ZNF384 FO occupy a subset of predominantly intragenic/enhancer regions with increased histone 3 lysine acetylation and deregulate expression of hematopoietic stem cell transcription factors. These data define a paradigm for FO-driven lineage ambiguous leukemia, in which expression in HSPCs results in deregulation of lineage-specific genes and hematopoietic skewing, progressing to full leukemia in the context of proliferative stress.

Significance:

Expression of ZNF384 FO early in hematopoiesis results in binding and deregulation of key hematopoietic regulators, skewing of hematopoiesis, and priming for leukemic transformation. These results reveal the interplay between cell of origin and expression of ZNF384 FO to mediate lineage ambiguity and leukemia development.

This article is highlighted in the In This Issue feature, p. 171
Silencing of FSTL1 Alleviated LPS-Induced Inflammatory Damage and Oxidative Damage in Human Bronchial Epithelial Cells via BMP4/KLF4 Axis
Authors: Zhang Yi , Yan Liping , Yang Jiao , Li Xiangni
Published: April 2022

Introduction: Childhood asthma is a common chronic inflammatory lung disease in children, among which airway inflammation is the main driving factor of asthma symptoms. Follistatin-like protein 1 (FSTL1) is involved in multiple inflammatory processes, but its role in airway inflammation has not been fully elucidated. Methods: We used lipopolysaccharide (LPS) to stimulate human primary bronchial epithelial (BEAS-2B) cells to establish an in vitro airway inflammation model. The expression of FSTL1 was detected by qPCR. Cell Counting Kit-8 and Annexin V-PI double staining was used to analyze the viability and apoptosis of BEAS-2B. The content of IL-6, IL-8 and TNF-α was determined by ELISA kit. Western blot was used to detect the protein expression level of the bone morphogenetic protein 4 (BMP4) and KLF4. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and malondialdehyde were measured to assess oxidative stress. Results: The mRNA expression of FSTL1 was significantly increased in LPS-treated BEAS-2B cells. Silencing of FSTL1 inhibited the release of IL-6, IL-8, TNF-α, and cell apoptosis as well as enhanced the activities of SOD, CAT, and GSH-Px. Silencing of FSTL1 reversed the inflammatory state of cells by upregulating BMP4 and increasing the expression level of KLF4. Conclusion: Silencing of FSTL1 reduced LPS-induced BEAS-2B cell damage by regulating the BMP4/KLF4 axis. FSTL1 may be a potential target for the treatment of asthma.
Mirizzi-Induced Bouveret’s Syndrome: Revelations of Timely Surgical Intervention
Authors: Stenberg Daniel , Jamal Mazen M. , Kaur Harpreet , Arcerito Massimo
Published: April 2022

Bouveret’s syndrome is an unusual clinical presentation of gastric-outlet obstruction and is the most infrequent variant of gallstone ileus with just over 300 cases in the literature. A 73-year-old female presented with innocuous constitutional symptoms and was found to have Mirizzi type Vb, a cholecystoduodenal fistula with obstruction. Esophago-gastroduodenoscopy-attempted dislodgement was unsuccessful. A gastric-jejunal bypass was the only option due to friability of the tissue. On post-op day 5, the patient developed acute abdominal pain and was found to have gallstone ileus. This case emphasizes the importance of early surgical intervention in cases of acute on chronic cholecystitis.
Elderly Patients with Moderate-To-Severe Ulcerative Colitis Are More Likely to Have Treatment Failure and Adverse Outcome
Authors: Zhang Mengmeng , Lv Hong , Yang Hong , Zhang Huimin , Bai Xiaoyin , Qian Jiaming
Published: April 2022

Background and Aim: The aim of this study was to compare therapeutic responses and prognosis between elderly and nonelderly ulcerative colitis (UC) patients with moderate-to-severe activity. Methods: 148 UC patients with moderate-to-severe activity hospitalized between 2000 and 2019 were enrolled consecutively, including 74 patients with the age of diagnosis over 60 years and 74 patients diagnosed less than 60 years. Patients were matched by gender, duration (±15%), disease activity, and admission time (±1 year). They were followed up until the latest medical record or December 2019. The primary outcome was UC-related colectomy or death. Results: 148 patients were followed over median 37.5 months. For steroid use, 76.8% of elderly UC patients were responsive, lower than that in adult group (85.7%). A decreased level of clinical activity index (2.0 [−1.5 to 4.00] vs. 6.0 [3.0–8.0], p < 0.001), reduction of C-reactive protein (23.9 [3.5–65.5] vs. 27.8 [9.7–58.1] mg/L), and erythrocyte sedimentation rate (9.0 [−1.3 to 30.5] vs. 15.5 [3.8–36.5] mm/h) at 4 weeks after steroid induction was less obvious in the elderly. More elderly patients manifested steroid dependence and resistance. 28.4% of elderly UC patients took colectomy, remarkably more than adult patients (12.2%), which also occurred earlier (8.0 [0.5–44.75] vs. 39.5 [12–57.38] months, p = 0.001). Aging (hazard ratio [HR] 2.868, 95% confidence interval [CI]: 1.290–6.375, p = 0.01), male, steroid resistance, and occurrence of complications were independently related to colectomy. The rate of serious infections was significantly higher in the elderly (55.4% vs. 35.1%, p = 0.013), mainly including cytomegalovirus infection, bacterial infection, and extraintestinal infection. Aging (odds ratio [OR] 2.774, 95% CI: 1.355–5.675, p = 0.015), extensive colonic involvement, steroid resistance, and biologics usage were independently associated with a high risk of concomitant infections. Conclusion: Elderly patients with moderate-to-severe UC experienced more treatment failure and increased risk of UC-related colectomy, mortality, and severe infections, predicting demand for more strict and individualized management.
What Stops us From Asking More About Food Insecurity While Advising on a Healthy Diet (Adequate and Balanced)?
Authors: Dikmen Derya
Published: April 2022

Inadequate diet is the leading risk factor for morbidity and mortality worldwide. However, approaches to identifying inadequate diets in clinical practice remain inconsistent, and dietary interventions (on both individual and public health policy levels) frequently focus on facilitating ‘healthy choices’, with limited emphasis on structural constraints. We examine the ethical implications of introducing a routine question in the medical history about ability to access food. Not collecting data on food security means that clinicians are unable to identify people who may benefit from support on an individual level, unable to consider relevant dietary risk factors for disease and disease progression and unable to monitor population trends and inequalities in dietary access in order to design effective policy interventions. We argue that the current lack of routine screening for food insecurity is inconsistent with our approach to other health behaviours (eg, smoking and alcohol use), as well as with doctors’ frequent informal role as gatekeepers to the food aid system, and recent calls for governmental action on food insecurity and health inequalities from individual clinicians and professional bodies. Potential ethical barriers to asking patients about food security are addressed, including concerns about stigma, limiting autonomy, fair resource allocation, unclear professional remits and clinicians’ ability to offer effective interventions. We suggest that there is an ethical imperative for doctors to ask patients about their ability to access healthy food. Gathering this data provides a valuable first step in re-framing the social determinants of health as modifiable risks, rather than inevitable inequities.
Trilogy of COVID-19: Infection, Vaccination, and Immunosuppression
Authors: Mohanraj Dinesh , Whitelegg Alison
Published: April 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative respiratory pathogen responsible for coronavirus disease 2019 (COVID-19). In 2020, the power of open science was visible to all, as novel vaccinology led to rapid establishment of vaccine clinical trials, and subsequent authorization of SARS-CoV-2 at an unprecedented pace. This evoked rapid deployment of SARS-CoV-2 vaccines and booster doses to keep with the ever-changing landscape of SARS-CoV-2. In this review, we provide an overview of vaccine efficacy studies, which have been well characterized in healthy individuals. Nevertheless, vaccine efficacy within the immunosuppressed is less well characterized, as these individuals were omitted from initial efficacy studies. Consequently, vaccine-induced responses in this group are relatively unknown. Currently, limited evidence investigating vaccine efficacy within the immunosuppressed is available. Here, we provide an overview of SARS-CoV-2 infection and associated pathogenesis. Furthermore, we undertake a critical analysis of observed vaccine responses from clinical studies, conducted in healthy and immunosuppressed populations. Whilst vaccine deployment has curbed mortality, there are significant challenges that lie ahead. This includes correlating vaccine responses with protective immunity and ensuring that global vaccine equity is met.
Exacerbaciones agudas de la EPOC: Efectos del tratamiento antibiótico
Authors: Acuña-Kaldman Moisés
Published: April 2022

Background: Although antibiotic treatment is recommended for acute exacerbations of chronic obstructive pulmonary disease (AECOPD), its value in real-world settings is still controversial. Objectives: This study aimed to evaluate the short- and long-term effects of antibiotic treatment on AECOPD outpatients. Methods: A cohort study was conducted under the PharmLines Initiative. We included participants with a first recorded diagnosis of COPD who received systemic glucocorticoid treatment for an AECOPD episode. The exposed and reference groups were defined based on any antibiotic prescription during the AECOPD treatment. The short-term outcome was AECOPD treatment failure within 14–30 days after the index date. The long-term outcome was time to the next exacerbation. Adjustment for confounding was made using propensity scores. Results: Of the 1,105 AECOPD patients, antibiotics were prescribed to 518 patients (46.9%) while 587 patients (53.1%) received no antibiotics. The overall antibiotic use was associated with a relative risk reduction of AECOPD treatment failure by 37% compared with the reference group (adjusted odds ratio [aOR] 0.63 [95% CI: 0.40–0.99]). Protective effects were similar for doxycycline, macrolides, and co-amoxiclav, although only the effect of doxycycline was statistically significant (aOR 0.53 [95% CI: 0.28–0.99]). No protective effect was seen for amoxicillin (aOR 1.49 [95% CI: 0.78–2.84]). The risk of and time to the next exacerbation was similar for both groups. Conclusion: Overall, antibiotic treatment, notably with doxycycline, supplementing systemic glucocorticoids reduces short-term AECOPD treatment failure in real-world outpatient settings. No long-term beneficial effects of antibiotic treatment on AECOPD were found for the prevention of subsequent exacerbations.
Patients with Non-Muscle-Invasive Bladder Cancer Previously Treated with Nephroureterectomy Have a High Risk of Recurrence after Bacillus Calmette-Guérin Intravesical Instillation Therapy
Authors: Maeyama Ryota , Ikeda Masaomi , Shimura Soichiro , Amano Noriyuki , Murakami Yasukiyo , Yamada Yasufumi , Koguchi Dai , Tachibana Takashi , Kawamura Mizuho , Sakata Yusuke , Hagiwara Masahiro , Matsumoto Kazumasa , Iwamura Masatsugu
Published: April 2022

Background: There is a high incidence of intravesical recurrence after transurethral resection of bladder tumor for non-muscle-invasive bladder cancer (NMIBC). Intravesical instillation of bacillus Calmette-Guérin (BCG) is widely used to prevent recurrence and progression. There are two types of NMIBC: primary NMIBC and subsequent NMIBC after radical nephroureterectomy (RNU). We compared the clinical outcomes of BCG intravesical instillation therapy between the two types of NMIBC. Patients and Methods: This study included a total of 357 patients, who received BCG intravesical instillation therapy to prevent recurrence of NMIBC (pTa/pT1) between 1991 and 2019. Among them, 34 patients had subsequent NMIBC after RNU, and the remaining 323 patients had primary NMIBC. This retrospective study analyzed 68 patients extracted by propensity score matching. Survival curves were estimated using the Kaplan-Meier method, and independent prognostic factors for survival were examined by the Cox proportional hazards model. Results: The 3-year recurrence-free survival (RFS) rates in patients with primary NMIBC and subsequent NMIBC after RNU were 70.7% and 54.8%, respectively (p = 0.036). However, there were no significant differences between the two groups in progression-free survival and cancer-specific survival. Multivariate analysis of RFS showed that only a previous history of upper tract urothelial carcinoma was an independent prognostic and predictive factor. Conclusion: Patients with subsequent NMIBC after RNU treated with BCG intravesical instillation therapy have a higher risk of recurrence than those with primary NMIBC. Thus, stringent follow-up is necessary for patients with subsequent NMIBC after RNU.
Psychological Care of Children and Families with Variations or Differences in Sex Development
Authors: Alderson Julie , Hamblin Rachel P. , Crowne Elizabeth C.
Published: April 2022

The paediatric clinical psychology literature provides applicable evidence for use in specialist healthcare settings and services. The general approach of psychological care of children and families with paediatric conditions is recognizable as preventative and destigmatizing, aimed to maximize personal agency with shared responsibility for achieving best outcomes via multi-professional teamwork. Recent commentaries regarding healthcare for children with differences in sex development (DSD) have noted service-level pitfalls, including poor teamwork and underuse of early and integrated psychological intervention. Psychological research regarding the variously termed DSD, variations in sex development, variation in sex characteristics, or intersex has historically centred around the assessment of sex differences, gender identity, and the impact of including hormone influences on brain and behaviour. Psychological research in this specialist area has not focussed on the evaluation of specific clinical interventions or psychotherapeutic models but has investigated psychological aspects of multi-professional healthcare provision. There are new goals for psychological care of children with variations or differences in sex development (V/DSD). These require a framework of good communication to enable those receiving care to come to know and articulate their own hopes for treatment and support. Paediatric psychological intervention studies involving larger clinical groups such as diabetes provide evidence applicable to DSD populations. A risk of stigma is recognized as inherent to some physical interventions within routine paediatric care of people with V/DSD. Psychological care and intervention should be aimed at minimizing these risks via questioning and examining their assumed need. Psychological approaches can provide a foundation for ethical and rights-based multi-professional care of children with V/DSD.