bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncologic Outcomes of Laparoscopic Radical Hysterectomy Using the No-Look No-Touch Technique for Early Stage Cervical Cancer: A Propensity Score-Adjusted Analysis
Authors: Fusegi Atsushi , Kanao Hiroyuki , Ishizuka Naoki , Nomura Hidetaka , Tanaka Yuji , Omi Makiko , Aoki Yoichi , Kurita Tomoko , Yunokawa Mayu , Omatsu Kohei , Matsuo Koji , Miyasaka Naoyuki
Published: December 2021

We evaluated oncologic outcomes of laparoscopic radical hysterectomy using the no-look no-touch technique (NLNT). We analyzed patients with early stage (IA2, IB1, and IIA1, FIGO2008) cervical cancer treated between December 2014 and December 2019. The primary endpoint was disease-free survival (DFS). We compared the outcomes of the abdominal radical hysterectomy (ARH) and NLNT groups using a Cox model with inverse probability of treatment weighting (IPTW), according to propensity scores. We also evaluated NLNT’s non-inferiority to ARH using an evaluation of heterogeneity between the results of the Laparoscopic Approach to Cervical Cancer (LACC) trial and our study. ARH and NLNT were performed in 118 and 113 patients, respectively. The median follow-up duration was 3.2 years. After IPTW adjustment, the 3-year DFS rates (NLNT 92.4%; ARH 94.0%) and overall survival rates did not differ significantly between the groups. Furthermore, the 3-year DFS rates for patients with tumor sizes ≥ 2 cm in the NLNT (85.0%) and ARH (90.3%) groups did not differ significantly. No significant heterogeneity was observed between the LACC trial and our study (I2 = 60.5%, p = 0.111), although there was a trend toward a lower hazard ratio in our study. Laparoscopic radical hysterectomy using NLNT provides a favorable prognosis for early stage cervical cancer.
PCAT6 May Be a Whistler and Checkpoint Target for Precision Therapy in Human Cancers
Authors: Jiang Feng , Lv Qiaoyi , Hu Cexun , Li Zhanghui , Wu Haojie , Gao Shujun , Wang Hui , Zhao Yangjing , Shao Qixiang
Published: December 2021

LncRNAs are involved in the occurrence and progressions of multiple cancers. Emerging evidence has shown that PCAT6, a newly discovered carcinogenic lncRNA, is abnormally elevated in various human malignant tumors. Until now, PCAT6 has been found to sponge various miRNAs to activate the signaling pathways, which further affects tumor cell proliferation, migration, invasion, cycle, apoptosis, radioresistance, and chemoresistance. Moreover, PCAT6 has been shown to exert biological functions beyond ceRNAs. In this review, we summarize the biological characteristics of PCAT6 in a variety of human malignancies and describe the biological mechanisms by which PCAT6 can facilitate tumor progression. Finally, we discuss its diagnostic and prognostic values and clinical applications in various human malignancies.
The Role of Long Non-Coding RNAs (lncRNAs) in Female Oriented Cancers
Authors: Naz Faiza , Tariq Imran , Ali Sajid , Somaida Ahmed , Preis Eduard , Bakowsky Udo
Published: December 2021

Recent advances in molecular biology have discovered the mysterious role of long non-coding RNAs (lncRNAs) as potential biomarkers for cancer diagnosis and targets for advanced cancer therapy. Studies have shown that lncRNAs take part in the incidence and development of cancers in humans. However, previously they were considered as mere RNA noise or transcription byproducts lacking any biological function. In this article, we present a summary of the progress on ascertaining the biological functions of five lncRNAs (HOTAIR, NEAT1, H19, MALAT1, and MEG3) in female-oriented cancers, including breast and gynecological cancers, with the perspective of carcinogenesis, cancer proliferation, and metastasis. We provide the current state of knowledge from the past five years of the literature to discuss the clinical importance of such lncRNAs as therapeutic targets or early diagnostic biomarkers. We reviewed the consequences, either oncogenic or tumor-suppressing features, of their aberrant expression in female-oriented cancers. We tried to explain the established mechanism by which they regulate cancer proliferation and metastasis by competing with miRNAs and other mechanisms involved via regulating genes and signaling pathways. In addition, we revealed the association between stated lncRNAs and chemo-resistance or radio-resistance and their potential clinical applications and future perspectives.
Association between Body Mass Index and Immune-Related Adverse Events (irAEs) among Advanced-Stage Cancer Patients Receiving Immune Checkpoint Inhibitors: A Pan-Cancer Analysis
Authors: Zhang Dongyu , Shah Neil , Cook Michael , Blackburn Matthew , Serzan Michael , Advani Shailesh , Potosky Arnold , Madhavan Subha , Belouali Anas , Atkins Michael , Braithwaite Dejana
Published: December 2021

Evidence regarding the association between body mass index (BMI) and immune-related adverse events (irAEs) among cancer patients receiving immune checkpoint inhibitors (ICIs) is limited. Here, we use cross-sectional hospital-based data to explore their relationship. Pre-treatment BMI was treated as an ordinal variable (<25, 25 to ≤30, ≥30 kg/m2). The outcome of interest was irAEs after ICI initiation. A multivariable logistic regression model estimated the adjusted odds ratio (aOR) and 95% confidence interval (CI) of BMI. A total of 684 patients with stage III or IV cancer were included in the study (lung: 269, melanoma: 204, other: 211). The mean age at the first dose of ICI was 64.1 years (SD = 13.5), 394 patients (57.6%) were male, and over one-third (N = 260, 38.0%) were non-White. Overall, 52.9% of patients had BMI ≥ 25 kg/m2 (25 to ≤30: 217, ≥30: 145) and 288 (42.1%) had irAEs after ICI treatment. Patients with higher BMI tended to have a higher rate of irAEs (<25: 35.7%, 25 to ≤30: 47.0%, ≥30: 49.0%). The multivariable logistic regression yielded consistent results (BMI ≥ 30 vs. BMI < 25: aOR = 1.47, 95% CI = 0.96–2.23; 25 ≤ BMI < 30 vs. BMI < 25: aOR = 1.46, 95% CI = 1.02–2.11, p-trend = 0.04). In conclusion, among patients with advanced cancer receiving ICIs, the rate of irAEs appears to be higher among those with higher BMI.
Preferred Lung Cancer Screening Modalities in China: A Discrete Choice Experiment
Authors: Zhao Zixuan , Du Lingbin , Wang Le , Wang Youqing , Yang Yi , Dong Hengjin
Published: December 2021

This study aimed to identify preferred lung cancer screening modalities in a Chinese population and predict uptake rates of different modalities. A discrete choice experiment questionnaire was administered to 392 Chinese individuals aged 50–74 years who were at high risk for lung cancer. Each choice set had two lung screening options and an option to opt-out, and respondents were asked to choose the most preferred one. Both mixed logit analysis and stepwise logistic analysis were conducted to explore whether preferences were related to respondent characteristics and identify which kinds of respondents were more likely to opt out of any screening. On mixed logit analysis, attributes that were predictive of choice at 1% level of statistical significance included the screening interval, screening venue, and out-of-pocket costs. The preferred screening modality seemed to be screening by low-dose computed tomography (LDCT) + blood test once a year in a general hospital at a cost of RMB 50; this could increase the uptake rate by 0.40 compared to the baseline setting. On stepwise logistic regression, those with no endowment insurance were more likely to opt out; those who were older and housewives/househusbands, and those with a health check habit and with commercial endowment insurance were less likely to opt out from a screening programme. There was considerable variance between real risk and self-perceived risk of lung cancer among respondents. Lung cancer screening uptake can be increased by offering various screening modalities, so as to help policymakers further design the screening modality.
NDRG2 Expression in Breast Cancer Cells Downregulates PD-L1 Expression and Restores T Cell Proliferation in Tumor-Coculture
Authors: Lee Aram , Lim Soyoung , Oh Juyeong , Lim Jihyun , Yang Young , Lee Myeong-Sok , Lim Jong-Seok
Published: December 2021

(1) Background: The aim of the present study was to evaluate the effect of NDRG2 expression in regulating PD-L1 or PD-L2 on malignant breast cancer cells. (2) Methods: Overexpression and knockdown of the NDRG2 gene in human and mouse cancer cells were applied and quantitative real-time PCR and Western blot analysis were performed. T cell proliferation and TCGA analysis were conducted to validate negative correlation of the PD-L1 expression with the NDRG2 expression. (3) Results: We found that NDRG2 overexpression inhibits PD-L1 expression in human breast cancer cells through NF-κB signaling. NDRG2 overexpression in 4T1 mouse breast cancer cells followed by PD-L1 downregulation could block the suppressive activity of cancer cells on T cell proliferation and knockdown of NDRG2 expression enhanced the expression of PD-L1, leading to the inhibition of T cell proliferation by tumor cell coculture. Finally, we confirmed from TCGA data that PD-L1 expression in basal and triple-negative breast cancer patients was negatively correlated with the expression of NDRG2. Intriguingly, linear regression analysis using TNBC cell lines showed that the PD-L1 level was negatively associated with the NDRG2 expression level. (4) Conclusions: Our findings demonstrate that NDRG2 expression is instrumental in suppressing PD-L1 expression and restoring PD-L1-inhibited T cell proliferation activity in TNBC cells.
Object Detection Improves Tumour Segmentation in MR Images of Rare Brain Tumours
Authors: Chegraoui Hamza , Philippe Cathy , Dangouloff-Ros Volodia , Grigis Antoine , Calmon Raphael , Boddaert Nathalie , Frouin Frédérique , Grill Jacques , Frouin Vincent
Published: December 2021

Tumour lesion segmentation is a key step to study and characterise cancer from MR neuroradiological images. Presently, numerous deep learning segmentation architectures have been shown to perform well on the specific tumour type they are trained on (e.g., glioblastoma in brain hemispheres). However, a high performing network heavily trained on a given tumour type may perform poorly on a rare tumour type for which no labelled cases allows training or transfer learning. Yet, because some visual similarities exist nevertheless between common and rare tumours, in the lesion and around it, one may split the problem into two steps: object detection and segmentation. For each step, trained networks on common lesions could be used on rare ones following a domain adaptation scheme without extra fine-tuning. This work proposes a resilient tumour lesion delineation strategy, based on the combination of established elementary networks that achieve detection and segmentation. Our strategy allowed us to achieve robust segmentation inference on a rare tumour located in an unseen tumour context region during training. As an example of a rare tumour, Diffuse Intrinsic Pontine Glioma (DIPG), we achieve an average dice score of 0.62 without further training or network architecture adaptation.
Therapeutic Efficacy of Variable Biological Effectiveness of Proton Therapy in U-CH2 and MUG-Chor1 Human Chordoma Cell Death
Authors: Singh Prerna , Eley John , Mahmood Nayab , Bhandary Binny , Dukic Tijana , Tu Kevin J. , Polf Jerimy , Lamichhane Narottam , Mahmood Javed , Vujaskovic Zeljko , Shukla Hem D.
Published: December 2021

Background: Chordoma is a cancer of spinal cord, skull base, and sacral area. Currently, the standard of care to treat chordoma is resection followed by radiation therapy. Since, chordoma is present in the spinal cord and these are very sensitive structures and often complete removal by surgery is not possible. As a result, chordoma has a high chance of recurrence and developing resistance to radiation therapy. In addition, treatment of chordoma by conventional radiation therapy can also damage normal tissues surrounding chordoma. Thus, current therapeutic options to treat chordoma are insufficient and novel therapies are desperately needed to treat locally advanced and metastatic chordoma. (2) Methods: In the present investigation, human chordoma cell lines of sacral origin MUG-Chor1 and U-CH2 were cultured and irradiated with Proton Beam Radiation using the clinical superconducting cyclotron and pencil-beam (active) scanning at Middle and End of the Spread-Out Bragg Peak (SOBP). Proton radiation was given at the following doses: Mug-Chor1 at 0, 1, 2, 4, and 8 Gy and U-CH2 at 0, 4, 8, 12, and 16 Gy. These doses were selected based on a pilot study in our lab and attempted to produce approximate survival fractions in the range of 1, 0.9, 0.5, 0.1, and 0.01, respectively, chosen for linear quadratic model fitting of the dose response. (3) Results: In this study, we investigated relative biological effectiveness (RBE) of proton radiation at the end of Spread Out Bragg Peak assuming that the reference radiation is a proton radiation in the middle of the SOBP. We observed differences in the survival of both Human chordoma cell lines, U-CH2 and MUG-Chor1. The data showed that there was a significantly higher cell death at the end of the Bragg peak as compared to middle of the Bragg peak. Based on the linear quadratic (LQ) fit for cell survival we calculated the RBE between M-SOBP and E-SOBP at 95% CI level and it was observed that RBE was higher than 1 at E-SOBP and caused significantly higher cell killing. Proton field at E-SOBP caused complex DNA damage in comparison to M-EOBP and the genes such as DNA topoisomerase 1, GTSE1, RAD51B were downregulated in E-SOBP treated cells. Thus, we conclude that there seems to be substantial variation in RBE (1.3–1.7) at the E-SOBP compared with the M-SOBP.
Combining an Autophagy Inhibitor, MPT0L145, with Abemaciclib Is a New Therapeutic Strategy in GBM Treatment
Authors: Hsieh Tsung-Han , Liang Muh-Lii , Zheng Jia-Huei , Lin Yu-Chen , Yang Yu-Chen , Vo Thanh-Hoa , Liou Jing-Ping , Yen Yun , Chen Chun-Han
Published: December 2021

Glioblastoma multiforme (GBM) is the most malignant brain tumor in the world, only 25% of GBM patients were alive one year after diagnosis. Although Temozolamide combined with radiation therapy more effectively prolonged the survival rate than radiation alone, the overall survival rate is still dismal. Therefore, a new therapeutic strategy is urgently needed. CDK4/6 inhibitors are newly FDA-approved agents to treat HR-positive, HER2-negative advanced, and metastatic breast cancers, and preclinical results showed that CDK4/6 inhibitors significantly reduced cell proliferation and tumor growth. However, several studies have suggested that CDK4/6 inhibitor-induced non-genetic changes caused treatment failure, including autophagy activation. Therefore, this study aimed to combine an autophagy inhibitor, MPT0L145, with abemaciclib to improve therapeutic efficiency. The use of abemaciclib effectively inhibited cell proliferation via suppression of RB phosphorylation and induced autophagy activation in GBM cancer cells. MPT0L145 treatment alone not only blocked autophagy activation, but also induced generation of ROS and DNA damage in a concentration-dependent manner. Importantly, MPT0L145 had a comparable penetration ability to TMZ in our blood brain barrier permeability assay. Combined MPT0L145 with abemaciclib significantly reduced cell proliferation, suppressed RB phosphorylation, and increased ROS production. In conclusion, the data suggested that blocking autophagy by MPT0L145 synergistically sensitized GBM cancer cells to abemaciclib and represents a potential therapeutic strategy for treating GBM in the future.
Sample Preparation Approach Influences PAM50 Risk of Recurrence Score in Early Breast Cancer
Authors: Lien Tonje , Ohnstad Hege , Lingjærde Ole , Vallon-Christersson Johan , Aaserud Marit , Sveli My , Borg Åke , OSBREAC on , Garred Øystein , Borgen Elin , Naume Bjørn , Russnes Hege , Sørlie Therese
Published: December 2021

The PAM50 gene expression subtypes and the associated risk of recurrence (ROR) score are used to predict the risk of recurrence and the benefits of adjuvant therapy in early-stage breast cancer. The Prosigna assay includes the PAM50 subtypes along with their clinicopathological features, and is approved for treatment recommendations for adjuvant hormonal therapy and chemotherapy in hormone-receptor-positive early breast cancer. The Prosigna test utilizes RNA extracted from macrodissected tumor cells obtained from formalin-fixed, paraffin-embedded (FFPE) tissue sections. However, RNA extracted from fresh-frozen (FF) bulk tissue without macrodissection is widely used for research purposes, and yields high-quality RNA for downstream analyses. To investigate the impact of the sample preparation approach on ROR scores, we analyzed 94 breast carcinomas included in an observational study that had available gene expression data from macrodissected FFPE tissue and FF bulk tumor tissue, along with the clinically approved Prosigna scores for the node-negative, hormone-receptor-positive, HER2-negative cases (n = 54). ROR scores were calculated in R; the resulting two sets of scores from FFPE and FF samples were compared, and treatment recommendations were evaluated. Overall, ROR scores calculated based on the macrodissected FFPE tissue were consistent with the Prosigna scores. However, analyses from bulk tissue yielded a higher proportion of cases classified as normal-like; these were samples with relatively low tumor cellularity, leading to lower ROR scores. When comparing ROR scores (low, intermediate, and high), discordant cases between the two preparation approaches were revealed among the luminal tumors; the recommended treatment would have changed in a minority of cases.
Receptor Activator of NF-κB (RANK) Confers Resistance to Chemotherapy in AML and Associates with Dismal Disease Course
Authors: Clar Kim , Weber Lisa , Schmied Bastian , Heitmann Jonas , Marconato Maddalena , Tandler Claudia , Schneider Pascal , Salih Helmut
Published: December 2021

Although treatment options of acute myeloid leukemia (AML) have improved over the recent years, prognosis remains poor. Better understanding of the molecular mechanisms influencing and predicting treatment efficacy may improve disease control and outcome. Here we studied the expression, prognostic relevance and functional role of the tumor necrosis factor receptor (TNFR) family member Receptor Activator of Nuclear Factor (NF)-κB (RANK) in AML. We conducted an experimental ex vivo study using leukemic cells of 54 AML patients. Substantial surface expression of RANK was detected on primary AML cells in 35% of the analyzed patients. We further found that RANK signaling induced the release of cytokines acting as growth and survival factors for the leukemic cells and mediated resistance of AML cells to treatment with doxorubicin and cytarabine, the most commonly used cytostatic compounds in AML treatment. In line, RANK expression correlated with a dismal disease course as revealed by reduced overall survival. Together, our results show that RANK plays a yet unrecognized role in AML pathophysiology and resistance to treatment, and identify RANK as “functional” prognostic marker in AML. Therapeutic modulation of RANK holds promise to improve treatment response in AML patients.
Comparing Characteristics of Endometrial Cancer in Women of South Asian and White Ethnicity in England
Authors: Mohammed Seid , Polymeros Konstantinos , Wickham-Joseph Rochelle , Luqman Iqra , Charadva Creana , Morris Thomas , Collins Anna , Barber Shaun , Khunti Kamlesh , Moss Esther L.
Published: December 2021

Differences in patient demographic and tumour characteristics between patients of South Asian and White ethnicity diagnosed with an endometrial cancer (EC) and currently living in England are not well described. We undertook a retrospective study of EC cases diagnosed at the University Hospitals of Leicester, UK. A total of 1884 cases were included, with 13% of the patients being of South Asian ethnicity. South Asian women were diagnosed at a significantly younger age (mean age of 60.3 years) compared to women of White ethnicity (mean age of 66.9 years) with a mean difference of 6.6 years (95% CI 5.1 to 8.1, p < 0.001). Rising body mass index (BMI) in the White patient group was significantly correlated with younger age at diagnosis (p < 0.001); however, this association was not seen in South Asian patients. A linear regression that adjusted for diabetes status, BMI, and the interaction terms of diabetes status with BMI and ethnicity with BMI, highlighted a younger age of diagnosis in South Asian patients with a BMI less than 45 kg/m2. The difference was greatest at lower BMIs for both non-diabetics and diabetics. Further investigation is needed to explain these differences and to determine their impact on suspected cancer referral criteria.
A Guide for Water Bolus Temperature Selection for Semi-Deep Head and Neck Hyperthermia Treatments Using the HYPERcollar3D Applicator
Authors: Drizdal Tomas , van Rhoon Gerard C. , Verhaart Rene F. , Fiser Ondrej , Paulides Margarethus M.
Published: December 2021

During hyperthermia cancer treatments, especially in semi-deep hyperthermia in the head and neck (H&N) region, the induced temperature pattern is the result of a complex interplay between energy delivery and tissue cooling. The purpose of this study was to establish a water bolus temperature guide for the HYPERcollar3D H&N applicator. First, we measured the HYPERcollar3D water bolus heat-transfer coefficient. Then, for 20 H&N patients and phase/amplitude settings of 93 treatments we predict the T50 for nine heat-transfer coefficients and ten water bolus temperatures ranging from 20–42.5 °C. Total power was always tuned to obtain a maximum of 44 °C in healthy tissue in all simulations. As a sensitivity study we used constant and temperature-dependent tissue cooling properties. We measured a mean heat-transfer coefficient of h = 292 W m−2K−1 for the HYPERcollar3D water bolus. The predicted T50 shows that temperature coverage is more sensitive to the water bolus temperature than to the heat-transfer coefficient. We propose changing the water bolus temperature from 30 °C to 35 °C which leads to a predicted T50 increase of +0.17/+0.55 °C (constant/temperature-dependent) for targets with a median depth < 20 mm from the skin surface. For deeper targets, maintaining a water bolus temperature at 30 °C is proposed.
A Network-Based Approach to Glioma Surgery: Insights from Functional Neurosurgery
Authors: Samuel Nardin , Vetkas Artur , Pancholi Aditya , Sarica Can , Loh Aaron , Germann Jurgen , Harmsen Irene E. , Tasserie Jordy , Milano Vanessa , Yamamoto Kazuaki , Kalia Suneil K. , Kongkham Paul N. , Lozano Andres M.
Published: December 2021

The evaluation and manipulation of structural and functional networks, which has been integral to advancing functional neurosurgery, is beginning to transcend classical subspecialty boundaries. Notably, its application in neuro-oncologic surgery has stimulated an exciting paradigm shift from the traditional localizationist approach, which is lacking in nuance and optimization. This manuscript reviews the existing literature and explores how structural and functional connectivity analyses have been leveraged to revolutionize and individualize pre-operative tumor evaluation and surgical planning. We describe how this novel approach may improve cognitive and neurologic preservation after surgery and attenuate tumor spread. Furthermore, we demonstrate how connectivity analysis combined with neuromodulation techniques can be employed to induce post-operative neuroplasticity and personalize neurorehabilitation. While the landscape of functional neuro-oncology is still evolving and requires further study to encourage more widespread adoption, this functional approach can transform the practice of neuro-oncologic surgery and improve the care and outcomes of patients with intra-axial tumors.
Phosphoproteomics Sample Preparation Impacts Biological Interpretation of Phosphorylation Signaling Outcomes
Authors: Sampadi Bharath , Mullenders Leon H. F. , Vrieling Harry
Published: December 2021

The influence of phosphoproteomics sample preparation methods on the biological interpretation of signaling outcome is unclear. Here, we demonstrate a strong bias in phosphorylation signaling targets uncovered by comparing the phosphoproteomes generated by two commonly used methods—strong cation exchange chromatography-based phosphoproteomics (SCXPhos) and single-run high-throughput phosphoproteomics (HighPhos). Phosphoproteomes of embryonic stem cells exposed to ionizing radiation (IR) profiled by both methods achieved equivalent coverage (around 20,000 phosphosites), whereas a combined dataset significantly increased the depth (>30,000 phosphosites). While both methods reproducibly quantified a subset of shared IR-responsive phosphosites that represent DNA damage and cell-cycle-related signaling events, most IR-responsive phosphoproteins (>82%) and phosphosites (>96%) were method-specific. Both methods uncovered unique insights into phospho-signaling mediated by single (SCXPhos) versus double/multi-site (HighPhos) phosphorylation events; particularly, each method identified a distinct set of previously unreported IR-responsive kinome/phosphatome (95% disparate) directly impacting the uncovered biology.
Changes in Epigenetic Patterns Related to DNA Replication in Vicia faba Root Meristem Cells under Cadmium-Induced Stress Conditions
Authors: Żabka Aneta , Gocek Natalia , Winnicki Konrad , Szczeblewski Paweł , Laskowski Tomasz , Polit Justyna Teresa
Published: December 2021

Experiments on Vicia faba root meristem cells exposed to 150 µM cadmium chloride (CdCl2) were undertaken to analyse epigenetic changes, mainly with respect to DNA replication stress. Histone modifications examined by means of immunofluorescence labeling included: (1) acetylation of histone H3 on lysine 56 (H3K56Ac), involved in transcription, S phase, and response to DNA damage during DNA biosynthesis; (2) dimethylation of histone H3 on lysine 79 (H3K79Me2), correlated with the replication initiation; (3) phosphorylation of histone H3 on threonine 45 (H3T45Ph), engaged in DNA synthesis and apoptosis. Moreover, immunostaining using specific antibodies against 5-MetC-modified DNA was used to determine the level of DNA methylation. A significant decrease in the level of H3K79Me2, noted in all phases of the CdCl2-treated interphase cell nuclei, was found to correspond with: (1) an increase in the mean number of intranuclear foci of H3K56Ac histones (observed mainly in S-phase), (2) a plethora of nuclear and nucleolar labeling patterns (combined with a general decrease in H3T45Ph), and (3) a decrease in DNA methylation. All these changes correlate well with a general viewpoint that DNA modifications and post-translational histone modifications play an important role in gene expression and plant development under cadmium-induced stress conditions.
Comparative Genomics and Physiological Investigation of a New Arthrospira/Limnospira Strain O9.13F Isolated from an Alkaline, Winter Freezing, Siberian Lake
Authors: Misztak Agnieszka E. , Waleron Malgorzata , Furmaniak Magda , Waleron Michal M. , Bazhenova Olga , Daroch Maurycy , Waleron Krzysztof F.
Published: December 2021

Cyanobacteria from the genus Arthrospira/Limnospira are considered haloalkalotolerant organisms with optimal growth temperatures around 35 °C. They are most abundant in soda lakes in tropical and subtropical regions. Here, we report the comprehensive genome-based characterisation and physiological investigation of the new strain O9.13F that was isolated in a temperate climate zone from the winter freezing Solenoye Lake in Western Siberia. Based on genomic analyses, the Siberian strain belongs to the Arthrospira/Limnospira genus. The described strain O9.13F showed the highest relative growth index upon cultivation at 20 °C, lower than the temperature 35 °C reported as optimal for the Arthrospira/Limnospira strains. We assessed the composition of fatty acids, proteins and photosynthetic pigments in the biomass of strain O9.13F grown at different temperatures, showing its potential suitability for cultivation in a temperate climate zone. We observed a decrease of gamma-linolenic acid favouring palmitic acid in the case of strain O9.13F compared to tropical strains. Comparative genomics showed no unique genes had been found for the Siberian strain related to its tolerance to low temperatures. In addition, this strain does not possess a different set of genes associated with the salinity stress response from those typically found in tropical strains. We confirmed the absence of plasmids and functional prophage sequences. The genome consists of a 4.94 Mbp with a GC% of 44.47% and 5355 encoded proteins. The Arthrospira/Limnospira strain O9.13F presented in this work is the first representative of a new clade III based on the 16S rRNA gene, for which a genomic sequence is available in public databases (PKGD00000000).
P2Y12 Inhibition in Murine Myocarditis Results in Reduced Platelet Infiltration and Preserved Ejection Fraction
Authors: Schmidt Sarah , Reichardt Wilfried , Kaufmann Beat , Wadle Carolin , von Elverfeldt Dominik , Stachon Peter , Hilgendorf Ingo , Wolf Dennis , Heidt Timo , Duerschmied Daniel , Peter Karlheinz , Bode Christoph , von zur Mühlen Constantin , Maier Alexander
Published: December 2021

Previous mouse studies have shown the increased presence of platelets in the myocardium during early stages of myocarditis and their selective detection by MRI. Here, we aimed to depict early myocarditis using molecular contrast-enhanced ultrasound of activated platelets, and to evaluate the impact of a P2Y12 receptor platelet inhibition. Experimental autoimmune myocarditis was induced in BALB/c mice by subcutaneous injection of porcine cardiac myosin and complete Freund adjuvant (CFA). Activated platelets were targeted with microbubbles (MB) coupled to a single-chain antibody that binds to the “ligand-induced binding sites” of the GPIIb/IIIa-receptor (=LIBS-MB). Alongside myocarditis induction, a group of mice received a daily dose of 100 g prasugrel for 1 month. Mice injected with myosin and CFA had a significantly deteriorated ejection fraction and histological inflammation on day 28 compared to mice only injected with myosin. Platelets infiltrated the myocardium before reduction in ejection fraction could be detected by echocardiography. No selective binding of the LIBS-MB contrast agent could be detected by either ultrasound or histology. Prasugrel therapy preserved ejection fraction and significantly reduced platelet aggregates in the myocardium compared to mice without prasugrel therapy. Therefore, P2Y12 inhibition could be a promising early therapeutic target in myocarditis, requiring further investigation.
When Down Is Up: Heterochromatin, Nuclear Organization and X Upregulation
Authors: Makki Reem , Meller Victoria H.
Published: December 2021

Organisms with highly differentiated sex chromosomes face an imbalance in X-linked gene dosage. Male Drosophila solve this problem by increasing expression from virtually every gene on their single X chromosome, a process known as dosage compensation. This involves a ribonucleoprotein complex that is recruited to active, X-linked genes to remodel chromatin and increase expression. Interestingly, the male X chromosome is also enriched for several proteins associated with heterochromatin. Furthermore, the polytenized male X is selectively disrupted by the loss of factors involved in repression, silencing, heterochromatin formation or chromatin remodeling. Mutations in many of these factors preferentially reduce male survival or enhance the lethality of mutations that prevent normal recognition of the X chromosome. The involvement of primarily repressive factors in a process that elevates expression has long been puzzling. Interestingly, recent work suggests that the siRNA pathway, often associated with heterochromatin formation and repression, also helps the dosage compensation machinery identify the X chromosome. In light of this finding, we revisit the evidence that links nuclear organization and heterochromatin to regulation of the male X chromosome.
First Glimpse at the Diverse Aquaporins of Amphipod Crustaceans
Authors: Desiderato Andrea , Mamos Tomasz , Rewicz Tomasz , Burzynski Artur , Mucciolo Serena
Published: December 2021

The importance of aquaporins (AQPs) in the transport of water and solutes through cell membranes is well recognized despite being relatively new. To date, despite their abundance, diversity, and presence in disparate environments, amphipods have only been mentioned in studies about the AQPs of other animals and have never been further investigated. In this work, we aimed to recover from public data available AQPs of these crustaceans and reconstruct phylogenetic affinities. We first performed BLAST searches with several queries of diverse taxa against different NCBI databases. Then, we selected the clades of AQPs retrieving the amphipod superfamily Gammaroidea as monophyletic and ran phylogenetic analyses to assess their performances. Our results show how most of the AQPs of amphipods are similar to those of other crustaceans, despite the Prip-like displayed different paralogs, and report for the first time a putative Aqp8-like for arthropods. We also found that the candidate genes of Prip-like, Bib-like, Aqp12-like, and Glp-like help solve deeper relationships in phylogenies of amphipods while leaving uncertainties in shallower parts. With our findings, we hope to increase attention to the study of amphipods as models for AQP functioning and evolution.
Transcriptomic Mapping of Neural Diversity, Differentiation and Functional Trajectory in iPSC-Derived 3D Brain Organoid Models
Authors: Kiaee Kiavash , Jodat Yasamin A. , Bassous Nicole J. , Matharu Navneet , Shin Su Ryon
Published: December 2021

Experimental models of the central nervous system (CNS) are imperative for developmental and pathophysiological studies of neurological diseases. Among these models, three-dimensional (3D) induced pluripotent stem cell (iPSC)-derived brain organoid models have been successful in mitigating some of the drawbacks of 2D models; however, they are plagued by high organoid-to-organoid variability, making it difficult to compare specific gene regulatory pathways across 3D organoids with those of the native brain. Single-cell RNA sequencing (scRNA-seq) transcriptome datasets have recently emerged as powerful tools to perform integrative analyses and compare variability across organoids. However, transcriptome studies focusing on late-stage neural functionality development have been underexplored. Here, we combine and analyze 8 brain organoid transcriptome databases to study the correlation between differentiation protocols and their resulting cellular functionality across various 3D organoid and exogenous brain models. We utilize dimensionality reduction methods including principal component analysis (PCA) and uniform manifold approximation projection (UMAP) to identify and visualize cellular diversity among 3D models and subsequently use gene set enrichment analysis (GSEA) and developmental trajectory inference to quantify neuronal behaviors such as axon guidance, synapse transmission and action potential. We showed high similarity in cellular composition, cellular differentiation pathways and expression of functional genes in human brain organoids during induction and differentiation phases, i.e., up to 3 months in culture. However, during the maturation phase, i.e., 6-month timepoint, we observed significant developmental deficits and depletion of neuronal and astrocytes functional genes as indicated by our GSEA results. Our results caution against use of organoids to model pathophysiology and drug response at this advanced time point and provide insights to tune in vitro iPSC differentiation protocols to achieve desired neuronal functionality and improve current protocols.
Core-Shell Iron-Nickel Hexacyanoferrate Nanoparticle-Based Sensors for Hydrogen Peroxide Scavenging Activity
Authors: Vokhmyanina Darya V. , Shcherbacheva Elizaveta V. , Daboss Elena V. , Karyakina Elena E. , Karyakin Arkady A.
Published: December 2021

To access hydrogen peroxide scavenging activity, we propose a sensor based on core-shell iron-nickel hexacyanoferrate nanoparticles. On the one hand, the sensor preparation procedure is simple: syringing the nanoparticles suspension with subsequent annealing. On the other hand, the sensor demonstrates a stable response to 0.05 mM of H2O2 within one hour, which is sufficient for the evaluation of antioxidant activity (AO). The analytical performance characteristics of the sensor (0.5–0.6 A M−1 cm−2, detection limit 1.5 × 10−7 M and linear dynamic range 1–1000 µM) are leads to advantages over the sensor based on Prussian Blue films. The pseudo-first-order constant of hydrogen peroxide scavenging was chosen as a characteristic value of AO. The latter for trolox (standard antioxidant) was found to be linearly dependent on its concentration, thus allowing for the evaluation of antioxidant activity in trolox equivalents. The approach was validated by analyzing real beverage samples. Both the simplicity of sensor preparation and an expressiveness of analytical procedure would obviously provide a wide use of the proposed approach in the evaluation of antioxidant activity.
Parenting during the COVID-19 Lockdown in Portugal: Changes in Daily Routines, Co-Parenting Relationships, Emotional Experiences, and Support Networks
Authors: Antunes Ana P. , Martins Silvana , Magalhães Laura , Almeida Ana T.
Published: December 2021

The COVID-19 pandemic challenged parental resources pertinent to coping with lockdowns. The main objective of this work was to study parenting during the COVID-19 lockdown. Specifically at focus were parental behaviors concerning key domains for the family (daily routine, co-parenting, emotional experience, and support network) and changes related to the pandemic and associated with the parents’ employment statuses. An online survey was carried out through an ad hoc questionnaire where participants completed questions about their sociodemographic data and rated how much their family routines, their co-parenting relationship, their emotional experiences, and the support available in the family network varied on a 5-point scale. The participants included 1384 parents, of which 286 responded to open questions regarding impactful experiences during the lockdown. The results showed differences in daily routine, co-parenting, emotional experience, and support network according to the parents’ employment statuses. Between-group comparisons showed that at-home parents caring for children with governmental aids generally revealed more positive parenting behavior changes, while at-home parents who were teleworking reported more difficulties in parent-child activities and co-parenting. Furthermore, the content analysis of the data confirmed how important themes such as family dynamics, professional activities, and the relationship with the school community were throughout the participants’ accounts of gains and losses. Overall, parents’ employment statuses are associated with diverse experiences during lockdown. The COVID-19 pandemic highlighted the importance of family resources and parental resilience, particularly during circumstances jeopardizing the ever-sensitive work-family balance.
The Impact of Nutritional and Lifestyle Changes on Body Weight, Body Composition and Cardiometabolic Risk Factors in Children and Adolescents during the Pandemic of COVID-19: A Systematic Review
Authors: Karatzi Kalliopi , Poulia Kalliopi-Anna , Papakonstantinou Emilia , Zampelas Antonis
Published: December 2021

The coronavirus (COVID-19) pandemic and the measures taken by most countries to curb virus transmission, such as social distancing, distance learning, population, home confinement and disruption of all organized activities, has affected children and adolescents worldwide. The aim of this review was to assess the role of diet and lifestyle changes due to COVID-19 measures on body weight/composition and cardiometabolic risk factors in children and adolescents. An electronic search was conducted in PUBMED, COCHRANE, Google Scholar and SCOPUS databases up to 31 October 2021. 15 eligible studies were identified. According to the studies included in the analysis, COVID-19 measures seem to have had a negative impact on the diets and lifestyles of children and adolescents, with a consequent increase in body weight and central fat accumulation. On the other hand, the parental presence and control resulted in better glycaemic control in children with diabetes mellitus (DM) Type 1, but the effect of the pandemic in the glycaemic control of children with DM2 2 is controversial. Finally, diet and lifestyle changes had a differential impact on children’s hypertension prevalence. These findings point to the need for public policy measures to prevent obesity and its complications, to and improve diet and lifestyle during the continuing and yet unresolved COVID-19 epidemic.
Level of Adherence to the Mediterranean Diet and Weight Status among Adolescent Female Gymnasts: A Cross-Sectional Study
Authors: Kontele Ioanna , Grammatikopoulou Maria G. , Vassilakou Tonia
Published: December 2021

Adolescent female gymnasts are a vulnerable population in terms of their diet, as their nutritional needs are higher due to their growth and high daily training demands. The Mediterranean diet (MD) is a well-known dietary pattern that is associated with a greater nutritional adequacy and a lower prevalence of overweight. The aim of this cross-sectional study was to evaluate the degree of adherence to the MD among adolescent female athletes who participated in all disciplines of gymnastics in Greece, as well as to explore the potential correlations between MD adherence, body weight, and body mass index (BMI). A total of 269 female gymnasts (between 11–18 years old) completed the Mediterranean Diet Quality Index (KIDMED) and reported their weight and height. Approximately 10% of the participants were underweight and a mere 5.6% were classified as overweight. A high adherence to the MD was reported by 34.9% of the sample and this was correlated with a healthier BMI. Moreover, specific eating habits, such as eating nuts 2–3 times per week and eating fast-food less than once-weekly, were also associated with BMI. Athletes, parents, and coaches of gymnastics should be informed and educated regarding balanced nutrition habits. Future studies could evaluate adherence to MD, as well as the factors that influence the eating behaviors of adolescent female and male athletes in various sports.
Spontaneous Closure of the Arterial Duct after Transcatheter Closure Attempt in Preterm Infants
Authors: Méot Mathilde , Haddad Raymond N. , Patkai Juliana , Abu Zahira Ibrahim , Di Marzio Anna , Szezepanski Isabelle , Bajolle Fanny , Kermorvant Elsa , Lapillonne Alexandre , Bonnet Damien , Malekzadeh-Milani Sophie
Published: December 2021

(1) Background: Transcatheter closure of the patent arterial duct (TCPDA) in preterm infants is an emerging procedure. Patent arterial duct (PDA) spontaneous closure after failed TCPDA attempts is seen but reasons and outcomes are not reported; (2) Methods: We retrospectively included all premature infants <2 kg with abandoned TCPDA procedures from our institutional database between September 2017 and August 2021. Patients’ data and outcomes were reviewed; (3) Results: The procedure was aborted in 14/130 patients referred for TCPDA. Two patients had spasmed PDA upon arrival in the catheterization laboratory and had no intervention. One patient had ductal spasm after guidewire cross. Four patients had unsuitable PDA size/shape for closure. In seven patients, device closure was not possible without causing obstruction on adjacent vessels. Among the 12 patients with attempted TCPDA, five had surgery on a median of 3 days after TCPDA and seven had a spontaneous PDA closure within a median of 3 days after the procedure. Only the shape of the PDA differed between the surgical ligation group (short and conical) and spontaneous closure group (F-type); (4) Conclusions: In the case of TCPDA failure, mechanically induced spontaneous closure may occur early after the procedure. Surgical ligation should be postponed when clinically tolerated.
Homogeneous–Heterogeneous Chemical Reactions of Radiation Hybrid Nanofluid Flow on a Cylinder with Joule Heating: Nanoparticles Shape Impact
Authors: Alarabi Taghreed H. , Rashad Ahmed M. , Mahdy A.
Published: December 2021

The current analysis aims to exhibit the nanoparticles of Al2O3 + Cu-water hybrid nanofluid flow for Darcy–Forchheimer with heterogeneous–homogeneous chemical reactions and magnetic field aspects past a stretching or shrinking cylinder with Joule heating. This paper performed not only with the hybrid nanofluid but also the shape of Al2O3 and Cu nanoparticles. The model of single-phase hybrid nanofluid due to thermophysical features is utilized for the mathematical formulation. In the present exploration equal diffusions factors for reactants and auto catalyst are instituted. The system of governing equations has been simplified by invoking the similarity transformation. The numerical computations are invoked due to the function bvp4c of Matlab, with high non-linearity. Numerical outcomes illustrated that; sphere shape nanoparticles presented dramatic performance on heat transfer of hybrid nanofluid movement; an opposite behavior is noticed with lamina shape. The local Nusselt number strengthens as the transverse curvature factor becomes larger. In addition, the homogeneous–heterogeneous reactions factors lead to weaken concentration fluctuation.
Enhanced Piezoresponse and Dielectric Properties for Ba1-XSrXTiO3 Composition Ultrathin Films by the High-Throughput Method
Authors: Zhang Nana , Wang Di , Wang Jie , Fang Hong , He Bin , Guo Jinrui , Han Yue , Zhang Peng , Shi Chaoqun , Chen Yanan , Wang Qixiang , Ren Miaojuan , Lü Weiming
Published: December 2021

The stacked single-unit cell Ba1-xSrxTiO3 (BSTO) thin film designed by the high-throughput method is fabricated by layer-by-layer deposition by laser molecular beam epitaxy, and its ferroelectric and dielectric characteristics as a function of Sr concentration are comprehensively investigated. The permittivity of BSTO exhibits a monotonous increase by Sr with a plateau in the region of 14% < Sr < 85%. Meanwhile, at the low Sr doping regime, the piezoelectric response has been discovered, and the maximum piezoresponse and d33 can reach approximately 139.05 pm and 88 pm/V once an appropriate Ba/Sr ratio is formed, exhibiting a coexistence of a dielectric property and giant piezoresponse. This effective piezoelectric constant d33 value is significantly larger than the conventional chemical doping scenarios, suggesting that the intra-plane interaction is crucial for designing future promising dielectric and ferroelectric thin films via high-throughput technologies.