bluuebunny/crossref_metadata_2025 huggingface dataset:
Controversial Flow Cytometry Monitoring of a Relapse Case of Pediatric T Cell Acute Lymphoblastic Leukemia: A Case Report
Authors: Popa Delia Codruţa , Şerbănică Andreea , Obrisca Radu , Şerbănică Ionut , Radu Letiţia , Jercan Cristina , Marcu Andra , Bica Ana , Asan Minodora , Petran Mădălina , Dragomir Mihaela , Jardan Cerasela , Ţică Valeria , Gheorghe Anca , Stoian Irina , Coriu Daniel , Coliţă Anca , Coliţă Andrei
Published: March 2022

Acute lymphoblastic leukemia (ALL) is the most frequent childhood cancer, with 80–85% represented by B cell ALL and only 15% by T cell ALL. T Cell ALL (T-ALL) carries a more reserved prognosis compared to B Cell ALL (B-ALL) with regard to response to treatment, risk of relapse, and overall survival. Progress made in current monitoring protocols such as via flow cytometry immunophenotyping (FCM) and by PCR-based amplification of antigen-receptor genes led to improved management of patients with ALL and superior rates of survival. Nevertheless, challenges remain in some clinical cases. This manuscript describes a unique case of T-ALL and raises awareness of such clinical challenges. The article presents an overview of the flow cytometry immunophenotyping at diagnosis and during treatment of a pediatric patient with T-ALL from Fundeni Clinical Institute. In this case, in spite of various therapeutic measures such as first-line chemotherapy for high risk group, salvage chemotherapy (FLAG), conditioning regimen (FLU-BU-TT-ATG), and stem cell transplant, a chemoresistance clone continued to be present.
A Novel Noninvasive Diagnostic Model of HBV-Related Inflammation in Chronic Hepatitis B Virus Infection Patients With Concurrent Nonalcoholic Fatty Liver Disease
Authors: Tao Xuemei , Chen Lin , Zhao Youfei , Liu Yonggang , Shi Ruifang , Jiang Bei , Mi Yuqiang , Xu Liang
Published: March 2022

Background and Aims

Patients with chronic hepatitis B virus infection (CBI) with concurrent nonalcoholic fatty liver disease (NAFLD) is becoming increasingly common in clinical practice, and it is quite important to identify the etiology when hepatitis occurs. A noninvasive diagnostic model was constructed to identify patients who need antihepatitis B virus (HBV) therapies [histologic activity index (HAI) ≥ 4] in patients with CBI with concurrent NAFLD by analyzing clinical routine parameters.

Approach and Results

In total, 303 out of 502 patients with CBI with concurrent NAFLD proven by liver biopsy from January 2017 to December 2020 in the Tianjin Second People's Hospital were enrolled and they were divided into the HBV-related inflammation (HBV-I) group (HAI ≥ 4,176 cases) and the non-HBV-I group (HAI < 4,127 cases) according to hepatic pathology. The univariate analysis and multivariate logistic regression analysis were performed on the two groups of patients, and then the HBV-I model of patients with CBI with concurrent NAFLD was constructed. The areas under receiver operating characteristic curves (AUROCs) were used to evaluate the parameters of the regression formula. Another 115 patients with CBI with concurrent NAFLD proven by liver biopsy from January 2021 to January 2022 were enrolled as the validation group. There were some statistical differences in demographic data, biochemical indicators, immune function, thyroid function, virology indicator, and blood routine indicators between the two groups (P < 0.05) and liver stiffness measurement (LSM) in the HBV-I group was significantly higher than those in the non-HBV-I group (P < 0.05). While controlled attenuation parameters (CAP) in the HBV-I group were lower than those in the non-HBV-I group (P < 0.05); (2) We developed a novel model by logistic regression analysis: HBV-I = −0.020 × CAP + 0.424 × LSM + 0.376 × lg (HBV DNA) + 0.049 × aspartate aminotransferase (AST) and the accuracy rate was 82.5%. The area under the receiver operating characteristic (AUROC) is 0.907, the cutoff value is 0.671, the sensitivity is 89.30%, the specificity is 77.80%, the positive predictive value is 90.34%, and the negative predictive value is 81.89%; (3) The AUROC of HBV-I in the validation group was 0.871 and the overall accuracy rate is 86.96%.

Conclusion

Our novel model HBV-I [combining CAP, LSM, lg (HBV DNA), and AST] shows promising utility for predicting HBV-I in patients with CBI with concurrent NAFLD with high sensitivity, accuracy, and repeatability, which may contribute to clinical application.
Toxic Effects of Copper Nanoparticles on Paramecium bursaria–Chlorella Symbiotic System
Authors: Tan Bingyu , Wang Yiwen , Gong Zhiwei , Fan Xinpeng , Ni Bing
Published: March 2022

Although many reports have demonstrated that nanoparticles can have a negative effect on aquatic organisms, the toxic effects on symbiotic organisms remain poorly understood. The present study conducts ultrastructure, enzyme activity, and transcriptomics to assess the toxic effects to the Paramecium bursaria–Chlorella symbiotic system from exposure to copper nanoparticles (CuNPs) for 24 h. We found that in both the host and symbiotic algae, CuNP exposure induced high reactive oxygen species level, which leads to oxidative damage and energy metabolism disorder. Moreover, transmission electron micrographs (TEMs) showed that the symbiotic algae in the cytoplasm of P. bursaria were enveloped in the digestive vacuole and digested, and the level of acid phosphatase activity increased significantly within 24 h, which indicated that the stability of the symbiotic system was affected after CuNP exposure. We speculated that the increased energy demand in the host and symbiotic algae resulted from oxidative stress, precipitating the decrease of the photosynthetic products provided to the host, the digestion of the symbiont, and the destruction of the stable symbiotic relationship. The study provides the first insight into the mechanisms of nanoparticles’ toxicity to the symbiotic relationship in the ecosystem, which may help to understand the environmental effects and toxicological mechanisms of nanoparticles.
Enzyme Characterization of Pro-virulent SntA, a Cell Wall-Anchored Protein of Streptococcus suis, With Phosphodiesterase Activity on cyclic-di-AMP at a Level Suited to Limit the Innate Immune System
Authors: Cabezas Alicia , Costas María Jesús , Canales José , Pinto Rosa María , Rodrigues Joaquim Rui , Ribeiro João Meireles , Cameselle José Carlos
Published: March 2022

Streptococcus suis and Streptococcus agalactiae evade the innate immune system of the infected host by mechanisms mediated by cell wall-anchored proteins: SntA and CdnP, respectively. The former has been reported to interfere with complement responses, and the latter dampens STING-dependent type-I interferon (IFN) response by hydrolysis of bacterial cyclic-di-AMP (c-di-AMP). Both proteins are homologous but, while CdnP has been studied as a phosphohydrolase, the enzyme activities of SntA have not been investigated. The core structure of SntA was expressed in Escherichia coli as a GST-tagged protein that, after affinity purification, was characterized as phosphohydrolase with a large series of substrates. This included 3′-nucleotides, 2′,3′-cyclic nucleotides, cyclic and linear dinucleotides, and a variety of phosphoanhydride or phosphodiester compounds, most of them previously considered as substrates of E. coli CpdB, a periplasmic protein homologous to SntA and CdnP. Catalytic efficiency was determined for each SntA substrate, either by dividing parameters kcat/KM obtained from saturation curves or directly from initial rates at low substrate concentrations when saturation curves could not be obtained. SntA is concluded to act as phosphohydrolase on two groups of substrates with efficiencies higher or lower than ≈ 105 M–1 s–1 (average value of the enzyme universe). The group with kcat/KM ≥ 105 M–1 s–1 (good substrates) includes 3′-nucleotides, 2′,3′-cyclic nucleotides, and linear and cyclic dinucleotides (notably c-di-AMP). Compounds showing efficiencies <104 M–1 s–1 are considered poor substrates. Compared with CpdB, SntA is more efficient with its good substrates and less efficient with its poor substrates; therefore, the specificity of SntA is more restrictive. The efficiency of the SntA activity on c-di-AMP is comparable with the activity of CdnP that dampens type-I IFN response, suggesting that this virulence mechanism is also functional in S. suis. SntA modeling revealed that Y530 and Y633 form a sandwich with the nitrogen base of nucleotidic ligands in the substrate-binding site. Mutants Y530A-SntA, Y633A-SntA, and Y530A+Y633A-SntA were obtained and kinetically characterized. For orientation toward the catalytic site, one tyrosine is enough, although this may depend on the substrate being attacked. On the other hand, both tyrosines are required for the efficient binding of good SntA substrates.
Sensor Measurements Can Characterize Fluctuations and Wearing Off in Parkinson’s Disease and Guide Therapy to Improve Motor, Non-motor and Quality of Life Scores
Authors: Farzanehfar Parisa , Woodrow Holly , Horne Malcolm
Published: March 2022

Objectives

The aim was to examine the role of sensor measurement in identifying and managing fluctuations in bradykinesia of Parkinson’s Disease.

Method

Clinical scales and data from wearable sensors obtained before and after optimization of treatment from 107 participants who participated in a previous study was used. Fluctuators were identified by a levodopa response or wearing off in their sensor data and were subdivided according to whether the sensor’s bradykinesia scores were in target range, representing acceptable bradykinesia for part of the dose (Controlled Fluctuator: n = 22) or above target for the whole dose period (Uncontrolled Fluctuator; n = 28). Uncontrolled Non-fluctuators (n = 24) were cases without a levodopa response or wearing-off and sensor bradykinesia scores above target throughout the day (un-controlled). Controlled Non-fluctuators (n = 33) were below target throughout the day (controlled) and used as a reference for good control (MDS-UPDRS III = 33 ± 8.6 and PDQ39 = 28 ± 18).

Results

Treating Fluctuators significantly improved motor and quality of life scores. Converting fluctuators into Controlled Non-fluctuators significantly improved motor, non-motor and quality of life scores and a similar but less significant improvement was obtained by conversion to a Controlled Fluctuator. There was a significantly greater likelihood of achieving these changes when objective measurement was used to guide management.

Conclusions

The sensor’s classification of fluctuators bore a relation to severity of clinical scores and treatment of fluctuation improved clinical scores. The sensor measurement aided in recognizing and removing fluctuations with treatment and resulted in better clinical scores, presumably by assisting therapeutic decisions.
Nanocontainers Against Biofouling and Corrosion Degradation of Materials: A Short Review With Prospects
Authors: Kordas George
Published: March 2022

The current state of the art in active corrosion prevention is based on the use of macromolecular containers that can store and release corrosion inhibitors particularly to the surface when corrosion develops. These corrosion inhibitor-containing nano- or microcontainers are subsequently infused into coatings, allowing them to self-heal. Especially, nanocontainers for self-healing coatings with controlled corrosion inhibitors, energy storage, cement fracture repair, and antifouling metal protection have recently been developed. Incorporating these nanocontainers into materials in small amounts (e.g., 5–10 wt% in paints) provided anticorrosion protection that was incomparably better than the current approaches. Furthermore, the materials developed had multifunctional properties, including self-healing, antibacterial, and antimicrobial properties. The primary goal of this review was to compile the different research studies that have been published in a variety of publications so that the reader may better understand the potential of these new types of nanotechnology and the prospects for nanocontainers.
Prevalence and Risk Factors for Unruptured Intracranial Aneurysms in the Population at High Risk for Aneurysm in the Rural Areas of Tianjin
Authors: Liu Jie , Zou Xuan , Zhao Yan , Jin Zhangning , Tu Jun , Ning Xianjia , Li Jidong , Yang Xinyu , Wang Jinghua
Published: March 2022

Although the prevalence of unruptured intracranial aneurysm (UIA) lies between 2 and 5%, the consequences of aneurysm rupture are fatal. The burden of UIA is considerable in stroke patients. However, the best prevention and management strategy for UIA is uncertain among patients with a family history of stroke. Therefore, this study aimed to determine the epidemiological characteristics and risk factors for UIA based on a population with a family history of stroke. This study used random sampling to recruit participants with a family history of stroke among rural residents in Jixian, Tianjin, China. All participants underwent a questionnaire survey, physical examination, and cervical computed tomography angiography (CTA). CTA data were used to determine whether the subjects had UIA. The relationship between relevant factors and UIA was assessed using logistic regression analysis. A total of 281 residents were recruited in this study, with a mean age of 50.9 years. The prevalence of UIA in those with a family history of stroke was 10.3% overall (9.8% among men and 10.9% among women). Moreover, with each unit increase in body mass index (BMI), the prevalence of UIA decreased by 12.5%. Particularly among non-obese men, BMI had a stronger protective effect (OR: 0.672; 95%CI: 0.499–0.906; P = 0.009), and among non-obese men, an increase in low-density lipoprotein (LDL) was associated with an increased prevalence of UIA (OR: 3.638; 95%CI: 1.108–11.947; P = 0.033). Among the non-obese with a family history of stroke, BMI may be protective against UIA, especially in men. It is crucial to strictly control the LDL level in non-obese people to reduce the burden of UIA.
Is Virtual Reality Training More Effective Than Traditional Physical Training on Balance and Functional Mobility in Healthy Older Adults? A Systematic Review and Meta-Analysis
Authors: Liu Meng , Zhou Kaixiang , Chen Yan , Zhou Limingfei , Bao Dapeng , Zhou Junhong
Published: March 2022

Objective

The studies showed the benefits of virtual reality training (VRT) for functional mobility and balance in older adults. However, a large variance in the study design and results is presented. We, thus, completed a systematic review and meta-analysis to quantitatively examine the effects of VRT on functional mobility and balance in healthy older adults.

Methods

We systematically reviewed the publications in five databases. Studies that examine the effects of VRT on the measures of functional mobility and balance in healthy older adults were screened and included if eligible. Subgroup analyses were completed to explore the effects of different metrics of the intervention design (e.g., session time) on those outcomes related to functional mobility and balance.

Results

Fifteen studies of 704 participants were included. The quality of these studies was good. Compared to traditional physical therapy (TPT), VRT induced greater improvement in TUG (MD = −0.31 s, 95% CI = −0.57 to −0.05, p = 0.02, I2 = 6.34%) and one-leg stance with open eyes (OLS-O) (MD = 7.28 s, 95% CI = 4.36 to 10.20, p = 0.00, I2 = 36.22%). Subgroup analyses revealed that immersive VRT with more than 800 min of total intervention time over 8 weeks and at least 120 min per week and/or designed by the two motor-learning principles was optimal for functional mobility and balance.

Conclusion

Virtual reality training can significantly improve functional mobility and balance in healthy older adults compared to TPT, and the findings provided critical knowledge of the optimized design of VRT that can inform future studies with more rigorous designs.

Systematic Review Registration

[https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021297085].
Consciousness as the Temporal Propagation of Information
Authors: Revach Daniel , Salti Moti
Published: March 2022

Our ability to understand the mind and its relation to the body is highly dependent on the way we define consciousness and the lens through which we study it. We argue that looking at conscious experience from an information-theory perspective can help obtain a unified and parsimonious account of the mind. Today’s dominant models consider consciousness to be a specialized function of the brain characterized by a discrete neural event. Against this background, we consider subjective experience through information theory, presenting consciousness as the propagation of information from the past to the future. We examine through this perspective major characteristics of consciousness. We demonstrate that without any additional assumptions, temporal continuity in perception can explain the emergence of volition, subjectivity, higher order thoughts, and body boundaries. Finally, we discuss the broader implications for the mind-body question and the appeal of embodied cognition.
Physicochemical and Functional Properties of Membrane-Fractionated Heat-Induced Pea Protein Aggregates
Authors: Asen Nancy D. , Aluko Rotimi E.
Published: March 2022

This study was carried out to investigate the effect of heat pre-treatment of pea proteins at different pH values on the formation of functional protein aggregates. A 10% (w/v) aqueous mixture of pea protein concentrate (PPC) was adjusted to pH 3.0, 5.0, 7.0, or 9.0 followed by heating at 100°C for 30 min, cooled and centrifuged. The supernatant was sequentially passed through 30 and 50 kDa molecular weight cut-off membranes to collect the <30, 30–50, and >50 kDa fractions. The >50 kDa fractions from pH 3.0 (FT3), 5.0 (FT5), 7.0 (FT7), and 9.0 (FT9) treatments had >60% protein content in contrast to the ≤20% for the <30 and 30–50 kDa fractions. Therefore, the >50 kDa fractions were collected and then compared to the untreated PPC for some physicochemical and functional properties. Protein aggregation was confirmed as the denaturation temperature for FT3 (124.30°C), FT5 (190.66oC), FT7 (206.33oC) and FT9 (203.17oC) was significantly (p < 0.05) greater than that of PPC (74.45oC). Scanning electron microscopy showed that FT5 had a compact structure like PPC while FT3, FT7, and FT9 contained a more continuous network. In comparison to PPC, the >50 kDa fractions showed improved solubility (>60%), oil holding capacity (~100%), protein content (~7%), foam capacity (>10%), foam stability (>7%), water holding capacity (>16%) and surface hydrophobicity (~50%). Least gelation concentration of PPC (18%), FT3 (25%), FT5 (22%), FT7 (22%), and FT9 (25%) was improved to 16, 18, 20, 16, and 18%, respectively, after addition of NaCl.
Can CCRT/RT Achieve Favorable Oncologic Outcome in Rectal Cancer Patients With High Risk Feature After Local Excision?
Authors: Kim Seijong , Huh Jung Wook , Lee Woo Yong , Yun Seong Hyeon , Kim Hee Cheol , Cho Yong Beom , Park Yoon Ah , Shin Jung Kyong
Published: March 2022

Purpose

The oncologic outcome of concurrent chemoradiotherapy (CCRT) after local excision in patients with high-risk early rectal cancer as compared with radical operation has not been reported. The aim of this study is to compare the oncologic outcome between radical operation and adjuvant CCRT after local excision for high-risk early rectal cancer.

Materials and Methods

From January 2005 to December 2015, 266 patients diagnosed with early rectal cancer and treated with local excision who showed high-risk characteristics were retrospectively analyzed. Propensity score matching was applied in a ratio of 1:4, comparing the CCRT/radiotherapy (RT) (n = 34) and radical operation (n = 91) groups. Univariate and multivariate analyses were performed to identify prognostic factors for survival.

Results

The median follow-up period was 112 months. The 5-year disease-free survival rate and the 5-year overall survival of the radical operation group were significantly higher than those of the CCRT/RT group after propensity score matching (96.7% vs. 70.6%,p <0.001; 100% vs. 91.2%,p= 0.005, respectively). In a multivariate analysis, salvage therapy type and preoperative carcinoembryonic antigen (CEA) were prognostic factors for 5-year disease-free survival (p <0.001 andp= 0.021, respectively). The type of salvage therapy, the preoperative CEA, and the pT were prognostic factors for 5-year overall survival (p= 0.009,p= 0.024, andp= 0.046, respectively).

Conclusions

Patients who undergo radical operations after local excision with a high-risk early rectal cancer had better survival than those treated with adjuvant CCRT/RT. Therefore, radical surgery may be recommended to high-risk early rectal cancer patients who have undergone local excision for more favorable oncologic outcomes.
Magnetic Resonance Imaging Correlates of Immune Microenvironment in Glioblastoma
Authors: Salvalaggio Alessandro , Silvestri Erica , Sansone Giulio , Pinton Laura , Magri Sara , Briani Chiara , Anglani Mariagiulia , Lombardi Giuseppe , Zagonel Vittorina , Della Puppa Alessandro , Mandruzzato Susanna , Corbetta Maurizio , Bertoldo Alessandra
Published: March 2022

Background

Glioblastoma (GBM) is the most commonly occurring primary malignant brain tumor, and it carries a dismal prognosis. Focusing on the tumor microenvironment may provide new insights into pathogenesis, but no clinical tools are available to do this. We hypothesized that the infiltration of different leukocyte populations in the tumoral and peritumoral brain tissues may be measured by magnetic resonance imaging (MRI).

Methods

Pre-operative MRI was combined with immune phenotyping of intraoperative tumor tissue based on flow cytometry of myeloid cell populations that are associated with immune suppression, namely, microglia and bone marrow-derived macrophages (BMDM). These cell populations were measured from the central and marginal areas of the lesion identified intraoperatively with 5-aminolevulinic acid-guided surgery. MRI features (volume, mean and standard deviation of signal intensity, and fractality) were derived from all MR sequences (T1w, Gd+ T1w, T2w, FLAIR) and ADC MR maps and from different tumor areas (contrast- and non-contrast-enhancing tumor, necrosis, and edema). The principal components of MRI features were correlated with different myeloid cell populations by Pearson’s correlation.

Results

We analyzed 126 samples from 62 GBM patients. The ratio between BMDM and microglia decreases significantly from the central core to the periphery. Several MRI-derived principal components were significantly correlated (p <0.05, r range: [−0.29, −0.41]) with the BMDM/microglia ratio collected in the central part of the tumor.

Conclusions

We report a significant correlation between structural MRI clinical imaging and the ratio of recruited vs. resident macrophages with different immunomodulatory activities. MRI features may represent a novel tool for investigating the microenvironment of GBM.
Comprehensive Analysis of the Carcinogenic Process, Tumor Microenvironment, and Drug Response in HPV-Positive Cancers
Authors: Yu Xiaorong , Xu Jiankai , Xu Dahua , Bi Xiaoman , Wang Hong , Lu Yanda , Cao Meng , Wang Wenxiang , Xu Zhizhou , Zheng Dehua , Chen Liyang , Zhang Xiaodian , Zheng Shaojiang , Li Kongning
Published: March 2022

Human papillomavirus (HPV) is a common virus, and about 5% of all cancers worldwide is caused by persistent high-risk HPV infections. Here, we reported a comprehensive analysis of the molecular features for HPV-related cancer types using TCGA (The Cancer Genome Atlas) data with HPV status. We found that the HPV-positive cancer patients had a unique oncogenic process, tumor microenvironment, and drug response compared with HPV-negative patients. In addition, HPV improved overall survival for the four cancer types, namely, cervical squamous cell carcinoma (CESC), head and neck squamous cell carcinoma (HNSC), stomach adenocarcinoma (STAD), and uterine corpus endometrial carcinoma (UCEC). The stronger activity of cell-cycle pathways and lower driver gene mutation rates were observed in HPV-positive patients, which implied the different carcinogenic processes between HPV-positive and HPV-negative groups. The increased activities of immune cells and differences in metabolic pathways helped explain the heterogeneity of prognosis between the two groups. Furthermore, we constructed HPV prediction models for different cancers by the virus infection score (VIS) which was linearly correlated with HPV load and found that VIS was associated with drug response. Altogether, our study reveals that HPV-positive cancer patients have unique molecular characteristics which help the development of precision medicine in HPV-positive cancers.
Incidence and Survival of Multiple Primary Cancers in US Women With a Gynecologic Cancer
Authors: Corey Logan , Ruterbusch Julie , Shore Ron , Ayoola-Adeola Martins , Baracy Michael , Vezina Alex , Winer Ira
Published: March 2022

Objectives

To evaluate risk of a second cancer and associated survival times in United States women with diagnosis of cancer.

Methods

The Surveillance Epidemiology and End Results (SEER) database was queried for 2 cohorts of women aged 18 - 89 with either an index gynecologic or non-gynecologic cancer diagnosed between 1992 – 2017. Index cases were followed to determine if a second primary cancer was subsequently diagnosed; defined according to SEER multiple primary and histology coding rules. Standard Incident Ratios (SIR) and latency intervals between index diagnosis and second primary diagnosis were evaluated. Among those who developed a second primary cancer, median survival times from diagnosis of second primary cancer were also calculated.

Results

Between 1992 – 2017, 227,313 US women were diagnosed with an index gynecological cancer and 1,483,016 were diagnosed with an index non-gynecologic cancer. Among patients with index gynecologic cancer, 7.78% developed a non-gynecologic subsequent primary cancer. The risk of developing any non-gynecologic cancer following an index gynecologic cancer was higher than the risk in the general population (SIR 1.05, 95% CI 1.04 - 1.07). Organs especially at risk were Thyroid (SIR 1.45), Colon and Rectum (SIR 1.23), and Urinary System (SIR 1.33). Among women diagnosed with an index non-gynecologic cancer, 0.99% were diagnosed with a subsequent gynecologic cancer. The risk of developing a gynecologic cancer following a non-gynecologic cancer was also elevated compared to the average risk of the general population (SIR 1.05, 1.03 - 1.07), with uterine cancer having the highest SIR of 1.13.

Conclusion

The risk of a developing a second primary cancer and the corresponding survival time is based on the order and site of the index and subsequent cancer. Surveillance guidelines should be examined further to optimize survivorship programs.
Case Report: Mucocele-Like Tumor of the Breast Associated With Ductal Carcinoma In Situ
Authors: Jiang Ying , Chai Li , Dong Dandan , Chughtai Aamer Rasheed , Kong Weifang
Published: March 2022

Mucocele-like tumor of the breast is histologically characterized as mucin-containing cysts with mucin leaking to the stroma. It could be associated with atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). We report a case of mucocele-like tumor of the breast associated with DCIS confirmed by paraffin section. We review the literature and discuss the imaging features, pathology, and clinical management of the lesion. These lesions demonstrate characteristic imaging features, and we especially highlight the MR characteristics, as they have not been well documented. Performing a diagnostic fine-needle aspiration cytology (FNAC) of mucocele-like tumor carries a risk of tumor underestimation; therefore, excision for all mucocele-like tumors is suggested to be the best approach. However, some recent reports recommend close follow-up for patients with low-risk factors who have mucocele-like tumor without atypia on FNAC.
Case Report: Novel Splicing Variant in SH2D1A in a Patient With X-Linked Lymphoproliferative Syndrome Type 1
Authors: Kwon Won Kyung , Kim Jee Ah , Park Jong-Ho , Kim Doo Ri , Park Su Eun , Kim Yae Jean , Yoo Keon Hee , Jang Ja-Hyun , Kang Eun Suk
Published: March 2022

X-linked lymphoproliferative disease type 1 (XLP1), an X-linked recessive genetic disorder, is associated with primary immunodeficiency. Patients with XLP1 are susceptible to Epstein–Barr virus (EBV) infection. SH2D1A gene is known as the causative gene. We found a novel hemizygous variant of SH2D1A, c.162_201+31delinsTACAAGGACATATACA, from a 5-year-old male patient who had been diagnosed with EBV infection and Hodgkin's lymphoma. In targeted next-generation sequencing (NGS), complex variants at exon 2 were not consistently identified with two software programs. They showed a soft-clipped read pattern. The variant had a 71-bp deletion and a 16-bp insertion across exon 2 as confirmed by direct sequencing. As the variant was located within the exon–intron boundary, two aberrant transcripts were shown by RNA study. Although NGS method has a limitation in detecting large deletion/duplication variants, proper bioinformatics pipeline and careful review of data might enable the detection of complex variants.
High Anal Canal Pressure and Rectal Washouts Contribute to the Decrease of Anal Basal Pressure After Botulinum Toxin Injections in Paediatric Patients With Chronic Constipation
Authors: Sun Ge , Trzpis Monika , Broens Paul M. A.
Published: March 2022

Introduction

Chronic constipation can be treated by injecting botulinum toxin into the anal sphincter to decrease anal basal pressure. To assess the effect of botulinum toxin, we investigated the factors that contribute to changes in anal basal pressure after injection.

Methods

This was a retrospective study conducted in a tertiary hospital in the Netherlands. We included children with chronic constipation treated with botulinum toxin injections and measured anal basal pressure before and after each injection. Multivariable linear regression analyses were used.

Results

We investigated 30 cases with idiopathic constipation. Their median age was 20.5 (7.75–53.25) months. Anal basal pressure decreased after injection in 20 cases. The mean decrease of anal basal pressure after injection was 18.17 ± 35.22 mmHg. The anal basal pressure change was linearly correlated with preinjection pressure (R2 = 0.593, P < 0.001). A significant decrease of pressure was observed in patients with preinjection pressure > 70 mmHg. Preinjection anal basal pressure (β = −0.913, P < 0.001) and rectal washouts (β = −21.015, P = 0.007) contributed significantly to pressure changes. Changes in anal basal pressure were also significantly associated with patients' weights (β = 0.512, 95% CI, 0.011–1.013) and sex (β = 22.971, 95% CI, 9.205–36.736).

Conclusions

Botulinum toxin significantly decreases anal basal pressure when preinjection pressure is higher than 70 mmHg. In patients with severely elevated anal basal pressure, we recommend rectal washouts to promote the decrease of anal basal pressure.
Transcriptome Analysis of Liver Cancer Cell Huh-7 Treated With Metformin
Authors: Li Chun-Qing , Liu Zhi-Qin , Liu Sha-Sha , Zhang Gao-Tao , Jiang Li , Chen Chuan , Luo Du-Qiang
Published: March 2022

Metformin is a kind of widely used antidiabetic drug that regulates glucose homeostasis by inhibiting liver glucose production and increasing muscle glucose uptake. Recently, some studies showed that metformin exhibits anticancer properties in a variety of cancers. Although several antitumor mechanisms have been proposed for metformin action, its mode of action in human liver cancer remains not elucidated. In our study, we investigated the underlying molecular mechanisms of metformin's antitumor effect on Huh-7 cells of hepatocellular carcinoma (HCC) in vitro. RNA sequencing was performed to explore the effect of metformin on the transcriptome of Huh-7 cells. The results revealed that 4,518 genes (with log2 fold change > 1 or < −1, adjusted p-value < 0.05) were differentially expressed in Huh-7 cells with treatment of 25-mM metformin compared with 0-mM metformin, including 1,812 upregulated and 2,706 downregulated genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses identified 54 classical pathways that were significantly enriched, and 16 pathways are closely associated with cancer, such as cell cycle, DNA replication, extracellular matrix–receptor interaction, and so on. We selected 11 differentially expressed genes, which are closely associated with HCC, to validate their differential expressions through a quantitative real-time reverse transcription-polymerase chain reaction. The result exhibited that the genes of fatty acid synthase, mini-chromosome maintenance complex components 6 and 5, myristoylated alanine-rich C-kinase substrate, fatty acid desaturase 2, C-X-C motif chemokine ligand 1, bone morphogenetic protein 4, S-phase kinase-associated protein 2, kininogen 1, and proliferating cell nuclear antigen were downregulated, and Dual-specificity phosphatase-1 is significantly upregulated in Huh-7 cells with treatment of 25-mM metformin. These differentially expressed genes and pathways might play a crucial part in the antitumor effect of metformin and might be potential targets of metformin treating HCC. Further investigations are required to evaluate the metformin mechanisms of anticancer action in vivo.
Empagliflozin Ameliorates Preeclampsia and Reduces Postpartum Susceptibility to Adriamycin in a Mouse Model Induced by Angiotensin Receptor Agonistic Autoantibodies
Authors: Zhai Ruonan , Liu Yuan , Tong Jiahao , Yu Ying , Yang Lin , Gu Yong , Niu Jianying
Published: March 2022

Preeclampsia (PE) is the leading cause of maternal and perinatal morbidity and mortality and also is a risk factor for cardiovascular and kidney disease later in life. PE is associated with oversecretion of autoantibodies against angiotensin II type 1 receptor (AT1-AA) by the placenta into the maternal circulation. Here, we sought to determine the therapeutic value of the sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin (EMPA) in mice with AT1-AA-induced preeclampsia. Pregnant mice were injected with AT1-AA at gestation day (GD) 13 and treated daily with EMPA until GD 19, at which point some of the maternal mice were sacrificed and assessed. The other maternal mice were labored on time and challenged with adriamycin (ADR) at 12 weeks postpartum; their offspring were assessed for fetal outcomes. We showed that EMPA treatment significantly relieved high systolic blood pressure and proteinuria and ameliorated kidney injury in PE mice without affecting fetal outcomes. EMPA also ameliorated podocyte injury and oxidative stress, reduced the expression of SGLT2 and activated the AMPK/SIRT1 signaling pathway in vivo and in vitro. Remarkably, EMPA treatment during pregnancy reduced ADR-induced kidney and podocyte injury postpartum. These findings suggest that EMPA could be a potential pharmacological agent for PE.
Biomass Allocation Responses to Root Interactions in Wheat Cultivars Support Predictions of Crop Evolutionary Ecology Theory
Authors: Zhu Yong-He , Weiner Jacob , Jin Yi , Yu Ming-Xi , Li Feng-Min
Published: March 2022

The goal of agriculture is to optimize the population yield, but natural selection has produced active competition among plants, which decreases population performance. Therefore, cultivar breeding should be based on group selection, increasing yield by weakening individual competitive responses. We hypothesize that this has occurred inadvertently to some degree, so modern cultivars have weakened competitive traits and responses, such as reduced root proliferation in response to neighboring roots. We conducted a field experiment with eight cultivars of spring wheat that have been released over the last hundred years, which we grew at two densities. Two contrasting wheat cultivars, a landrace and a modern cultivar, were used in a second field experiment on competition within and between the two cultivars to quantify their competitiveness. Finally, a greenhouse experiment was conducted with these two cultivars gown (a) in mixture and monoculture, (b) at four densities, (c) two watering levels, and (d) with permeable vs. non-permeable soil dividers, to study root proliferation responses to competition. Results of field experiment 1 showed that the population aboveground biomass (AGB) had increased, while belowground biomass had decreased over the course of breeding, so that the root to shoot ratio (R/S) was negatively correlated with the release year of the cultivar. The landrace had stronger competitiveness than the modern cultivar in the field experiment 2. There was clear evidence of root proliferation and a resultant reduction in AGB in response to neighboring roots in the greenhouse experiment, and the modern variety showed less root proliferation in response to neighbors. We conclude that the newer cultivar was a weaker competitor but higher-yielding in two ways: (1) it had higher reproductive effort and therefore less allocation to structures that increase competitive ability, and (2) it had reduced root proliferation in response to the roots of neighboring plants. Our results show that wheat plants change their biomass allocation in response to resource levels and the presence of neighboring roots. The presence of root proliferation in the modern cultivar, albeit less than in the landrace, suggests that further increases in yield via group selection are possible.
Blended Online Intervention to Reduce Digital Transformation Stress by Enhancing Employees’ Resources in COVID-19
Authors: Makowska-Tłomak Ewa , Bedyńska Sylwia , Skorupska Kinga , Paluch Julia
Published: March 2022

Generally, the solutions based on information and communication technologies (ICT) provide positive outcomes for both companies and employees. However, the process of digital transformation (DT) can be the cause of digital transformation stress (DTS), when the work demands caused by fast implementation of ICT are elevated and employees’ resources are limited. Based on the Job Demand-Resources (JD-R) Model we claim that DT, rapidly accelerating in the COVID-19 pandemic, can increase the level of DTS and general stress at work. To reduce these negative effects of DTS, we propose the online intervention aimed to strengthen employees’ resources, such as self-efficacy. In this article we evaluate the effectiveness of the blended intervention, based on cognitive behavioral therapy (CBT) and social cognitive therapy, composed of a prototyped online training (e-stressless) and series of interactive online workshops. In a longitudinal study, we examined the change in DTS, perceived stress at work, attitudes toward DT, self-efficacy and burnout in two time points, before and after the intervention. We compared five groups of participants (558 in total), three groups not qualified (n= 417), and two groups qualified to intervention (n= 141). Our results revealed that the designed blended intervention decreased DTS and one of the dimensions of burnout, namely disengagement. More specifically, the results showed that in the group of active participants of the blended intervention DTS significantly decreased [MT1= 3.23,MT2= 3.00,t(432) = 1.96,p= 0.051], and in the group of ineligible participants DTS significantly increased [MT1= 1.76,MT2= 2.02,t(432) = 4.17,p< 0.001]. This research paves way for the creation of blended online intervention which could help in addressing employee digital transformation stress before it starts having adverse effects on employee performance and well-being.
Reflection in the Context of the Epidemic: Does Death Anxiety Have a Positive Impact? The Role of Self-Improvement and Mental Resilience
Authors: Luo Yang , Guo Rui , Huang Chaohua , Xiong Yan , Zhou Fei
Published: March 2022

Public health emergencies can trigger individual death anxiety. Most previous studies focus on the negative effects of death anxiety via the Western materialistic view, neglecting both the positive aspects of death anxiety within the Chinese cultural background and the positive effects of death anxiety upon environmental consumption. By implementing the unique Chinese cultural background for the concepts of justice and interests, this study explores the positive influence of individual death anxiety on altruistic environmental consumption during the COVID-19 crisis by analyzing personal life reviews and other sources. The results show that (1) under the guidance of the correct concept of justice and benefit, individuals with high death anxiety during the epidemic period not only enhance their self-esteem through positive self-perception and social evaluation, but they are more inclined to benefit from other environmental consumption behaviors and attain a symbolic self-survival; and (2) during the epidemic period, mental resilience, as a transformation mechanism of external defense and the internal growth of death psychology, can directly affect altruistic environmental consumption by consumers without relying on external standards. In the context of the Chinese culture’s concept of justice and interests, this study enriches the knowledge of fear management theory and the positive impact of death anxiety on environmental consumption. The introduction of mental resilience as a boundary condition has important theoretical and practical significance within the study of consumer behavior in public health emergencies and post-epidemic economic recovery.
Current State and Future Directions of Technologies for Music Instrument Pedagogy
Authors: Acquilino Alberto , Scavone Gary
Published: March 2022

Technological advances over the past 50 years or so have resulted in the development of a succession of hardware and software systems intended to improve the quality and effectiveness of Western music instrument pedagogy during classroom instruction or individual study. These systems have aimed to provide evaluation or visualization of single or combined technical aspects by analyzing performance data collected in real time or offline. The number of such educational technologies shows an ever-increasing trend over time, aided by the wide diffusion and availability of mobile devices. However, we believe there are unrealized opportunities for modern technologies to help music students in their technical development and assist them during their practice sessions in between visits to their teachers. The ubiquity of PCs and mobile devices with built-in microphones, speakers, and cameras has inspired the development of media technologies in support of music pedagogy. They offer an attractive potential for implementing audio signal processing algorithms addressing different technical skills of the performer, providing real-time feedback, collecting data over time, and applying statistical models. Despite this potential, most available software for music instrument pedagogy remains very limited in functionality. This study provides a survey of music edTech software available, together with the methods of use, addressed technical skills, commonalities, and limitations. Results show that most current software is based on the metronome and tuner, with only a few systems that have limited abilities to follow a performance in real-time and compare it to a given score to monitor correctness of notes, intonation, and rhythm. The survey also highlights a high and under-exploited potential regarding the monitoring of other more specific technical skills, which are more instrument-dependent, but no less important, such as the control of dynamic range and clarity of the attack. This article ends with a discussion of possible directions for future development of technologies to support the practice of music students at different levels, with some consideration for the corresponding signal processing methods that can be utilized or that need advancement. By helping students to more efficiently achieve a high level of proficiency of their instruments with assistive technologies, we hope to minimize stress and afford better enjoyment of the music performance experience for all.
Trajectories of Sexual Risk Behaviors and the Associated Factors Among Young Men Who Have Sex With Men in China
Authors: Wei Liqing , Tian Jiawei , Guo Menglan , Zhu Biao , Jiang Qingqing , Yu Bin , Yan Hong
Published: March 2022

Background

Young men who have sex with men (YMSM) are at high risk of HIV infection that accounts for an increasing proportion of new human immunodeficiency virus (HIV) infections in China. However, little is known about the trajectories of sexual risk behaviors in this population. The study aimed to investigate longitudinal patterns of sexual risk behaviors among YMSM in China.

Methods

Study data were collected from a prospective cohort study among 460 YMSM from 2017 to 2020. Based on the predicted HIV infection risk scores, distinct sexual risk behaviors trajectories of YMSM were estimated and plotted using the group-based censored normal model to identify the predictors of trajectories change over time.

Results

Three sexual risk behaviors trajectories were identified: a decreasing low-risk group (7.6%), an intermediate-risk group (67.4%), and an ascending high-risk group (25.0%).

Compared to the decreasing low-risk group, intermediate-risk group membership was associated with being from rural areas, current smoker and higher depressive symptoms; ascending high-risk group membership was associated with an education level of high school or lower, being from rural areas, younger age at sex debut with a man, current smoker, higher depressive symptoms and sexual minority stress.

Conclusions

Sexual risk behaviors among YMSM changed over time within different trajectories. Identifying YMSM belonging to high-risk trajectories before HIV infection is vital for the intervention and may reduce HIV transmission.
Learning to Centralize Dual-Arm Assembly
Authors: Alles Marvin , Aljalbout Elie
Published: March 2022

Robotic manipulators are widely used in modern manufacturing processes. However, their deployment in unstructured environments remains an open problem. To deal with the variety, complexity, and uncertainty of real-world manipulation tasks, it is essential to develop a flexible framework with reduced assumptions on the environment characteristics. In recent years, reinforcement learning (RL) has shown great results for single-arm robotic manipulation. However, research focusing on dual-arm manipulation is still rare. From a classical control perspective, solving such tasks often involves complex modeling of interactions between two manipulators and the objects encountered in the tasks, as well as the two robots coupling at a control level. Instead, in this work, we explore the applicability of model-free RL to dual-arm assembly. As we aim to contribute toward an approach that is not limited to dual-arm assembly but dual-arm manipulation in general, we keep modeling efforts at a minimum. Hence, to avoid modeling the interaction between the two robots and the used assembly tools, we present a modular approach with two decentralized single-arm controllers, which are coupled using a single centralized learned policy. We reduce modeling effort to a minimum by using sparse rewards only. Our architecture enables successful assembly and simple transfer from simulation to the real world. We demonstrate the effectiveness of the framework on dual-arm peg-in-hole and analyze sample efficiency and success rates for different action spaces. Moreover, we compare results on different clearances and showcase disturbance recovery and robustness when dealing with position uncertainties. Finally, we zero-shot transfer policies trained in simulation to the real world and evaluate their performance. Videos of the experiments are available at the project website (https://sites.google.com/view/dual-arm-assembly/home).