bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterising Spectral Anomalies in Rotating Machine Sensors
Authors: Champneys Alan , Aitken Mungo , Alecio Alex , Ballu Marin , Bond Oliver , Booker Cameron , Chakraborty Abhishek , Cowley Stephen , Duff Margaret , Evans Alex , Grinfeld Michael , Hinch John , Hoffstetter Michael , Kavvadias Konstantin , Khimshashvilli George , Lefauve Adrien , Luong Karen , Machado Simon , Mavrogiannis George , Priddin Matthew , Piette Bernard , Sear Chris , Tatulea-Codrean Maria , Zahradova Katerina
Published: November 2021

Several spectral analysis algorithms have been developed to identify spectral anomalies. A careful literature analysis is undertaken of sources of nonlinearity through bearing distress and other contacts and rubs within rotor dynamics. Several different models for such contact-force or lubrication nonlinearities are synthesised from the literature. These forces are implemented within a simulation of a simple Jeffcott rotor. Reasonable parameter values are identified and results are reproduced that are qualitatively similar to both those observed by Faraday Predictive and seen in the literature. The results enable a tentative hypothesis, using the theory of Arnold tongues, about how the severity of bearing distress may be reflected in changes to the observed spectrum. Various recommendations are made as to avenues of further work to hone the algorithms, apply spectral analysis to the synthetic simulation data, and to perform more systematic parameter studies.
Effect of Supplying Rosemary (Rosmarinus officinalis L.) and Garlic (Allium sativum L.) Essential Oils to Feedlot Lambs on in vitro Ruminal Fermentation
Authors: Cavalheiro Junior Elias Rodrigues , Serafim Camila Cano , Rodrigues Erica Regina , Guerra Geisi Loures , do Carmo João Pedro Monteiro , dos Santos Tayna Fernandes , Simonelli Sandra Maria , Poveda Parra Angela Rocio , Mizubuti Ivone Yurika , Prado Calixto Odimári Pricila
Published: November 2021

The aim of this trial was to evaluate the ruminal degradation kinetics of carbohydrates in diets with different roughage:concentrate ratios and dosages of garlic and rosemary essential oils, in order to find the most suitable dosage to supply feedlot lambs. Three roughage:concentrate ratios (50:50, 40:60, and 20:80) and six dosages of garlic and rosemary essential oils (0.0, 0.10, 0.25, 1.0, 1.50, and 2.0 g L−1) were tested. Kinetic parameters for carbohydrate breakdown were estimated using a semi-automated in vitro gas production technique. Ruminal degradation parameters were subjected to variance analysis and then regression analysis at a 5% significance level. There was no interaction between the roughage:concentrate ratios and the dosage of rosemary essential oil. The roughage:concentrate ratios in diets with rosemary oil affected the non-fiber carbohydrate degradation rate (Kdnfc), colonization time (L), gas volume and breakdown rate from the degradation of fiber carbohydrates (Vfc and Kdfc, respectively), and final gas volume of both fiber and non-fiber carbohydrates (Vfinal). Rosemary dosages affected Vnfc and Vfc, which presented a quadratic response with a peak at 0.71 g L−1 and a nip at 1.17 g L−1, respectively. Bacterial colonization time was quadratic, reaching a maximum value at 1.18 g L−1. Vfinal showed a decreasing linear trend, such that each gram of rosemary essential oil added to the diet could reduce gas production by 30.312 mL. Therefore, rosemary essential oil has an effect on carbohydrate degradation kinetics. There was no interaction between roughage:concentrate ratios and different garlic oil dosages, except for colonization time. Roughage:concentrate ratios with garlic oil had affected the Vnfc, Kdnfc, and L. Garlic oil dosages affected Vfc and Vfinal in a quadratic manner, with the lowest values of gas production at 1.35 and 1.54 g L−1, respectively. L was affected by the garlic oil dosage and roughage:concentrate ratios in a decreasing linear trend for a 50:50 ratio and quadratic response for a 40:60 ratio, peaking at 0.14 g L−1. Based on these in vitro results, a ruminal content of 1.0 g L−1 is recommended for both rosemary and garlic essential oils.
Saccade and Fixation Eye Movements During Walking in People With Mild Traumatic Brain Injury
Authors: Lirani-Silva Ellen , Stuart Samuel , Parrington Lucy , Campbell Kody , King Laurie
Published: November 2021

Background: Clinical and laboratory assessment of people with mild traumatic brain injury (mTBI) indicate impairments in eye movements. These tests are typically done in a static, seated position. Recently, the use of mobile eye-tracking systems has been proposed to quantify subtle deficits in eye movements and visual sampling during different tasks. However, the impact of mTBI on eye movements during functional tasks such as walking remains unknown.

Objective: Evaluate differences in eye-tracking measures collected during gait between healthy controls (HC) and patients in the sub-acute stages of mTBI recovery and to determine if there are associations between eye-tracking measures and gait speed.

Methods: Thirty-seven HC participants and 67individuals with mTBI were instructed to walk back and forth over 10-m, at a comfortable self-selected speed. A single 1-min trial was performed. Eye-tracking measures were recorded using a mobile eye-tracking system (head-mounted infra-red Tobbii Pro Glasses 2, 100 Hz, Tobii Technology Inc. VA, United States). Eye-tracking measures included saccadic (frequency, mean and peak velocity, duration and distance) and fixation measurements (frequency and duration). Gait was assessed using six inertial sensors (both feet, sternum, right wrist, lumbar vertebrae and the forehead) and gait velocity was selected as the primary outcome. General linear model was used to compare the groups and association between gait and eye-tracking outcomes were explored using partial correlations.

Results: Individuals with mTBI showed significantly reduced saccade frequency (p = 0.016), duration (p = 0.028) and peak velocity (p = 0.032) compared to the HC group. No significant differences between groups were observed for the saccade distance, fixation measures and gait velocity (p > 0.05). A positive correlation was observed between saccade duration and gait velocity only for participants with mTBI (p = 0.025).

Conclusion: Findings suggest impaired saccadic eye movement, but not fixations, during walking in individuals with mTBI. These findings have implications in real-world function including return to sport for athletes and return to duty for military service members. Future research should investigate whether or not saccade outcomes are influenced by the time after the trauma and rehabilitation.
Current Status of Breast Organoid Models
Authors: Mohan Srivarshini Cherukupalli , Lee Tian-Yu , Giuliano Armando E. , Cui Xiaojiang
Published: November 2021

Breast cancer (BC) is the most frequently diagnosed malignancy among women globally. Although mouse models have been critical in advancing the knowledge of BC tumorigenesis and progression, human breast models comprising the breast tissue microenvironment are needed to help elucidate the underlying mechanisms of BC risk factors. As such, it is essential to identify an ex vivo human breast tissue mimetic model that can accurately pinpoint the effects of these factors in BC development. While two-dimensional models have been invaluable, they are not suitable for studying patient-specific tumor biology and drug response. Recent developments in three-dimensional (3D) models have led to the prominence of organized structures grown in a 3D environment called “organoids.” Breast organoids can accurately recapitulate the in vivo breast microenvironment and have been used to examine factors that affect signaling transduction, gene expression, and tissue remodeling. In this review, the applications, components, and protocols for development of breast organoids are discussed. We summarize studies that describe the utility of breast organoids, including in the study of normal mammary gland development and tumorigenesis. Finally, we provide an overview of protocols for development of breast organoids, and the advantages and disadvantages of different techniques in studies are described. The included studies have shown that breast organoids will continue to serve as a crucial platform for understanding of progression of BC tumors and the testing of novel therapeutics.
TEMPO-Oxidized Cellulose Nanofiber-Alginate Hydrogel as a Bioink for Human Meniscus Tissue Engineering
Authors: Lan Xiaoyi , Ma Zhiyao , Szojka Alexander R. A. , Kunze Melanie , Mulet-Sierra Aillette , Vyhlidal Margaret J. , Boluk Yaman , Adesida Adetola B.
Published: November 2021

Objective: The avascular inner regions of the knee menisci cannot self-heal. As a prospective treatment, functional replacements can be generated by cell-based 3D bioprinting with an appropriate cell source and biomaterial. To that end, human meniscus fibrochondrocytes (hMFC) from surgical castoffs of partial meniscectomies as well as cellulose nanofiber-alginate based hydrogels have emerged as a promising cell source and biomaterial combination. The objectives of the study were to first find the optimal formulations of TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl)-oxidized cellulose nanofiber/alginate (TCNF/ALG) precursors for bioprinting, and then to use them to investigate redifferentiation and synthesis of functional inner meniscus-like extracellular matrix (ECM) components by expanded hMFCs.

Methods: The rheological properties including shear viscosity, thixotropic behavior recovery, and loss tangent of selected TCNF/ALG precursors were measured to find the optimum formulations for 3D bioprinting. hMFCs were mixed with TCNF/ALG precursors with suitable formulations and 3D bioprinted into cylindrical disc constructs and crosslinked with CaCl2 after printing. The bioprinted constructs then underwent 6 weeks of in vitro chondrogenesis in hypoxia prior to analysis with biomechanical, biochemical, molecular, and histological assays. hMFCs mixed with a collagen I gel were used as a control.

Results: The TCNF/ALG and collagen-based constructs had similar compression moduli. The expression of COL2A1 was significantly higher in TCNF/ALG. The TCNF/ALG constructs showed more of an inner meniscus-like phenotype while the collagen I-based construct was consistent with a more outer meniscus-like phenotype. The expression of COL10A1 and MMP13 were lower in the TCNF/ALG constructs. In addition, the immunofluorescence of human type I and II collagens were evident in the TCNF/ALG, while the bovine type I collagen constructs lacked type II collagen deposition but did contain newly synthesized human type I collagen.
Bioprinting of Collagen Type I and II via Aerosol Jet Printing for the Replication of Dense Collagenous Tissues
Authors: Gibney Rory , Ferraris Eleonora
Published: November 2021

Collagen has grown increasingly present in bioprinting, however collagen bioprinting has mostly been limited to the extrusion printing of collagen type I to form weak collagen hydrogels. While these weak collagen hydrogels have their applications, synthetic polymers are often required to reinforce gel-laden constructs that aim to replicate dense collagenous tissues foundin vivo. In this study, aerosol jet printing (AJP) was used to print and process collagen type I and II into dense constructs with a greater capacity to replicate the dense collagenous ECM found in connective tissues. Collagen type I and II was isolated from animal tissues to form solutions for printing. Collagen type I and II constructs were printed with 576 layers and measured to have average effective elastic moduli of 241.3 ± 94.3 and 196.6 ± 86.0 kPa (±SD), respectively, without any chemical modification. Collagen type II solutions were measured to be less viscous than type I and both collagen type I and II exhibited a drop in viscosity due to AJP. Circular dichroism and SDS-PAGE showed collagen type I to be more vulnerable to structural changes due to the stresses of the aerosol formation step of aerosol jet printing while the collagen type II triple helix was largely unaffected. SEM illustrated that distinct layers remained in the aerosol jet print constructs. The results show that aerosol jet printing should be considered an effective way to process collagen type I and II into stiff dense constructs with suitable mechanical properties for the replication of dense collagenous connective tissues.
Insight on Diagnosis and Treatment From Over a Decade of Research Through the University of Chicago Monogenic Diabetes Registry
Authors: Bowden Tiana L. , Letourneau-Freiberg Lisa R. , Kandasamy Balamurugan , Sanyoura May , Tian Persephone , Harris Anastasia G. , Bell Graeme I. , Philipson Louis H. , Naylor Rochelle N. , Greeley Siri Atma W.
Published: November 2021

Monogenic diabetes is a category of diabetes mellitus caused by a single gene mutation or chromosomal abnormality, usually sub-classified as either neonatal diabetes or maturity-onset diabetes of the young (MODY). Although monogenic diabetes affects up to 3.5% of all patients with diabetes diagnosed before age 30, misdiagnosis and/or improper treatment occurs frequently. The University of Chicago Monogenic Diabetes Registry, established in 2008, offers insight into the diagnosis, treatment, and natural history of individuals known or suspected to have monogenic diabetes. Those interested in participating in the Registry begin by completing a secure web-based registration form found on our website (http://monogenicdiabetes.uchicago.edu/registry/). Participants are then screened for eligibility and consented either by phone, video call, or in person. Relevant medical and family history is collected at baseline and then annually via surveys through our secure Research Electronic Data Capture (REDCap) database. The University of Chicago Monogenic Diabetes Registry has enrolled over 3800 participants from over 2000 families. Participants represent all 50 states and more than 20 different countries. To date, over 1100 participants have a known genetic cause of diabetes. While many Registry participants reported being referred through their diabetes care provider (54%), a large portion also learned about the Registry through web searching (24%), friends/family (18%), or other sources (13%). Around two-thirds of those with a known genetic cause had research-based genetic testing completed rather than clinical testing due to insurance coverage difficulties. Of those who were found to have monogenic diabetes, significant delays in diagnosis were identified, which highlights the need for increased access to clinical genetic testing covered by insurance companies specifically within the United States. Among genes that cause a MODY phenotype, GCK mutations were the most common (59%) followed by HNF1A mutations (28%), while mutations in KCNJ11 were the most common among genes that cause neonatal diabetes (35%) followed by INS (16%). Over the last decade, improvements in data collection for the University of Chicago Monogenic Diabetes Registry have resulted in increased knowledge of the natural history of monogenic diabetes, as well as a better understanding of the most effective treatments. The University of Chicago Monogenic Diabetes Registry serves as a valuable resource that will continue to provide evidence to support improved clinical care and patient outcomes in monogenic diabetes.
Integrin β3 Induction Promotes Tubular Cell Senescence and Kidney Fibrosis
Authors: Li Shen , Jiang Song , Zhang Qingyan , Jin Bo , Lv Daoyuan , Li Wenju , Zhao Min , Jiang Chunming , Dai Chunsun , Liu Zhihong
Published: November 2021

Tubular cell senescence is a common biologic process and contributes to the progression of chronic kidney disease (CKD); however, the molecular mechanisms regulating tubular cell senescence are poorly understood. Here, we report that integrin β3 (ITGB3) expression was increased in tubular cells and positively correlated with fibrosis degree in CKD patients. ITGB3 overexpression could induce p53 pathway activation and the secretion of TGF-β, which, in turn, resulted in senescent and profibrotic phenotype change in cultured tubular cells. Moreover, according to the CMAP database, we identified isoliquiritigenin (ISL) as an agent to inhibit ITGB3. ISL treatment could suppress Itgb3 expression, attenuate cellular senescence, and prevent renal fibrosis in mice. These results reveal a crucial role for integrin signaling in cellular senescence, potentially identifying a new therapeutic direction for kidney fibrosis.
Targeting Mechanosensitive Piezo1 Alleviated Renal Fibrosis Through p38MAPK-YAP Pathway
Authors: Fu Yuanyuan , Wan Pengzhi , Zhang Jie , Li Xue , Xing Jia , Zou Yu , Wang Kaiyue , Peng Hui , Zhu Qizhuo , Cao Liu , Zhai Xiaoyue
Published: November 2021

Renal fibrosis is the most common pathological manifestation of a wide variety of chronic kidney disease. Increased extracellular matrix (ECM) secretion and enhanced microenvironment stiffening aggravate the progression of renal fibrosis. However, the related mechanisms remain unclear. Here, we evaluated the mechanism by which ECM stiffness aggravates renal fibrosis. In the present study, renal mesangial cells (MCs) were cultured on polyacrylamide hydrogels with different stiffness accurately detected by atomic force microscope (AFM), simulating the in vivo growth microenvironment of MCs in normal kidney and renal fibrosis. A series of in vitro knockdown and activation experiments were performed to establish the signaling pathway responsible for mechanics-induced MCs activation. In addition, an animal model of renal fibrosis was established in mice induced by unilateral ureteral obstruction (UUO). Lentiviral particles containing short hairpin RNA (sh RNA) targeting Piezo1 were used to explore the effect of Piezo1 knockdown on matrix stiffness-induced MCs activation and UUO-induced renal fibrosis. An in vitro experiment demonstrated that elevated ECM stiffness triggered the activation of Piezo1, which increased YAP nuclear translocation through the p38MAPK, and consequently led to increased ECM secretion. Furthermore, these consequences have been verified in the animal model of renal fibrosis induced by UUO and Piezo1 knockdown could alleviate UUO-induced fibrosis and improve renal function in vivo. Collectively, our results for the first time demonstrate enhanced matrix stiffness aggravates the progression of renal fibrosis through the Piezo1-p38MAPK-YAP pathway. Targeting mechanosensitive Piezo1 might be a potential therapeutic strategy for delaying the progression of renal fibrosis.
Natural Products for the Management of Castration-Resistant Prostate Cancer: Special Focus on Nanoparticles Based Studies
Authors: Singla Rajeev K. , Sai Chandragiri Siva , Chopra Hitesh , Behzad Sahar , Bansal Himangini , Goyal Rajat , Gautam Rupesh K. , Tsagkaris Christos , Joon Shikha , Singla Shailja , Shen Bairong
Published: November 2021

Prostate cancer is the most common type of cancer among men and the second most frequent cause of cancer-related mortality around the world. The progression of advanced prostate cancer to castration-resistant prostate cancer (CRPC) plays a major role in disease-associated morbidity and mortality, posing a significant therapeutic challenge. Resistance has been associated with the activation of androgen receptors via several mechanisms, including alternative dehydroepiandrosterone biosynthetic pathways, other androgen receptor activator molecules, oncogenes, and carcinogenic signaling pathways. Tumor microenvironment plays a critical role not only in the cancer progression but also in the drug resistance. Numerous natural products have shown major potential against particular or multiple resistance pathways as shown by in vitro and in vivo studies. However, their efficacy in clinical trials has been undermined by their unfavorable pharmacological properties (hydrophobic molecules, instability, low pharmacokinetic profile, poor water solubility, and high excretion rate). Nanoparticle formulations can provide a way out of the stalemate, employing targeted drug delivery, improved pharmacokinetic drug profile, and transportation of diagnostic and therapeutic agents via otherwise impermeable biological barriers. This review compiles the available evidence regarding the use of natural products for the management of CRPC with a focus on nanoparticle formulations. PubMed and Google Scholar search engines were used for preclinical studies, while ClinicalTrials.gov and PubMed were searched for clinical studies. The results of our study suggest the efficacy of natural compounds such as curcumin, resveratrol, apigenin, quercetin, fisetin, luteolin, kaempferol, genistein, berberine, ursolic acid, eugenol, gingerol, and ellagic acid against several mechanisms leading to castration resistance in preclinical studies, but fail to set the disease under control in clinical studies. Nanoparticle formulations of curcumin and quercetin seem to increase their potential in clinical settings. Using nanoparticles based on betulinic acid, capsaicin, sintokamide A, niphatenones A and B, as well as atraric acid seems promising but needs to be verified with preclinical and clinical studies.
Endolymphatic Hydrops is a Marker of Synaptopathy Following Traumatic Noise Exposure
Authors: Badash Ido , Quiñones Patricia M. , Oghalai Kevin J. , Wang Juemei , Lui Christopher G. , Macias-Escriva Frank , Applegate Brian E. , Oghalai John S.
Published: November 2021

After acoustic trauma, there can be loss of synaptic connections between inner hair cells and auditory neurons in the cochlea, which may lead to hearing abnormalities including speech-in-noise difficulties, tinnitus, and hyperacusis. We have previously studied mice with blast-induced cochlear synaptopathy and found that they also developed a build-up of endolymph, termed endolymphatic hydrops. In this study, we used optical coherence tomography to measure endolymph volume in live CBA/CaJ mice exposed to various noise intensities. We quantified the number of synaptic ribbons and postsynaptic densities under the inner hair cells 1 week after noise exposure to determine if they correlated with acute changes in endolymph volume measured in the hours after the noise exposure. After 2 h of noise at an intensity of 95 dB SPL or below, both endolymph volume and synaptic counts remained normal. After exposure to 2 h of 100 dB SPL noise, mice developed endolymphatic hydrops and had reduced synaptic counts in the basal and middle regions of the cochlea. Furthermore, round-window application of hypertonic saline reduced the degree of endolymphatic hydrops that developed after 100 dB SPL noise exposure and partially prevented the reduction in synaptic counts in the cochlear base. Taken together, these results indicate that endolymphatic hydrops correlates with noise-induced cochlear synaptopathy, suggesting that these two pathologic findings have a common mechanistic basis.
Papillary Thyroid Carcinoma Landscape and Its Immunological Link With Hashimoto Thyroiditis at Single-Cell Resolution
Authors: Pan Jun , Ye Fang , Yu Chengxuan , Zhu Qinsheng , Li Jiaqi , Zhang Yaohui , Tian Hedi , Yao Yunjin , Zhu Minjie , Shen Yibin , Zhu Feng , Wang Yingying , Zhou Xinhui , Guo Guoji , Wu Yijun
Published: November 2021

The tumor microenvironment heterogeneity of papillary thyroid cancer (PTC) is poorly characterized. The relationship between PTC and Hashimoto thyroiditis (HT) is also in doubt. Here, we used single-cell RNA sequencing to map the transcriptome landscape of PTC from eight PTC patients, of which three were concurrent with HT. Predicted copy number variation in epithelial cells and mesenchymal cells revealed the distinct molecular signatures of carcinoma cells. Carcinoma cells demonstrated intertumoral heterogeneity based onBRAFV600E mutation or lymph node metastasis, and some altered genes were identified to be correlated with disease-free survival in The Cancer Genome Atlas datasets. In addition, transcription factor regulons of follicular epithelial cells unveil the different transcription activation state in PTC patients with or without concurrent HT. The immune cells in tumors exhibited distinct transcriptional states, and the presence of tumor-infiltrating B lymphocytes was predominantly linked to concurrent HT origin. Trajectory analysis of B cells and plasma cells suggested their migration potential from HT adjacent tissues to tumor tissues. Furthermore, we revealed diverse ligand–receptor pairs between non-immune cells, infiltrating myeloid cells, and lymphocytes. Our results provided a single-cell landscape of human PTC. These data would deepen the understanding of PTC, as well as the immunological link between PTC and HT.
Deciphering the Intercellular Communication Network of Peripartum Decidua that Orchestrates Delivery
Authors: Huang Jingrui , Zhang Weishe , Zhao Yanhua , Li Jingzhi , Xie Mingkun , Lu Yang , Peng Qiaozhen , Zhang Jiejie , Li Ping , Dai Lei
Published: November 2021

Intercellular communication in the decidua plays important roles in relaying information between the maternal and fetal systems in the maintenance of pregnancy and the transition to labor. To date, several studies have explored cell-cell communications in the decidua during different periods of pregnancy, but studies systematically decoding the intercellular communication network, its internal cascades, and their involvement in labor are still lacking. In this study, we reconstructed a decidual cell-cell communication network based on scRNA-seq of peripartum decidua via the CellCall method. The results showed that endometrial cells (EECs) and extravillous trophoblasts relayed most of the common intercellular signals in the decidua both before delivery (DBD) and after delivery (DAD). Endothelial cells and EECs controlled many WNT-signaling-related intercellular communication factors that differed between DBD and DAD, some of which could be candidate biomarkers for the diagnosis of labor. Analysis of intercellular communications related to T cells identified abundant maternal-fetal immune-tolerance-related communication, such as TNFSF14-TNFRSF14/LTBR and FASLG-FAS signalings. We further explored the characteristics of the B cell receptor (BCR) and T cell receptor (TCR) repertoires by single-cell BCR/TCR sequencing. The results showed no significant differences in clonal expansion of B/T cells between DAD and DBD, indicating there was no significant change to adaptive immunity at the maternal-fetal interface during delivery. In summary, the findings provide a comprehensive view of the intercellular communication landscape in the peripartum decidua and identified some key intercellular communications involved in labor and maternal-fetal immune tolerance. We believe that our study provides valuable clues for understanding the mechanisms of pregnancy and provides possible diagnostic strategies for the onset of labor.
Programmed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration
Authors: Wang Ruirui , Huang Fujing , Wei Wei , Zhou Yu , Ye Zi , Yu Liya , Hu Junyuan , Cai Cheguo
Published: November 2021

Programmed cell death ligand 1 (PD-L1) is widely expressed in a variety of human tumors, and inhibition of the PD-L1/PD-1 pathway represents one of the most promising therapy for many types of cancer. However, the physiological function of PD-L1 in tissue development is still unclear, although PD-L1 mRNA is abundant in many tissues. To address this puzzle, we investigated the function of PD-L1 in mammary gland development. Interestingly, we found that PD-L1 is enriched in protein C receptor (Procr)-expressing mammary stem cells (MaSCs), and PD-L1-expressing mammary basal cells (PD-L1+ basal cells) exhibit robust mammary regeneration capacity in transplantation assay. The lineage tracing experiment showed that PD-L1+ cells can differentiate into all lineages of mammary epithelium cells, suggesting that PD-L1+ basal cells have the activities of MaSCs. Furthermore, PD-L1 deficiency significantly impairs mammary development and reduces mammary regeneration capacity of mammary basal cells, suggesting that PD-L1 is not only enriched in MaSCs but also improves activities of MaSCs. In summary, these results demonstrated that PD-L1 is enriched in MaSCs and promotes mammary gland development and regeneration. Mechanistically, our data indicated that PD-L1 expression is induced by continuous activation of Wnt/ß-catenin signaling. In conclusion, these results demonstrated that PD-L1 is a marker of MaSCs, and PD-L1 is essential for mammary development. Our study provides novel insight into the physiological functions of PD-L1 in tissue development.
Comparing a Novel Malformation Syndrome Caused by Pathogenic Variants in FBRSL1 to AUTS2 Syndrome
Authors: Pauli Silke , Berger Hanna , Ufartes Roser , Borchers Annette
Published: November 2021

Truncating variants in specific exons of Fibrosin-like protein 1 (FBRSL1) were recently reported to cause a novel malformation and intellectual disability syndrome. The clinical spectrum includes microcephaly, facial dysmorphism, cleft palate, skin creases, skeletal anomalies and contractures, postnatal growth retardation, global developmental delay as well as respiratory problems, hearing impairment and heart defects. The function of FBRSL1 is largely unknown, but pathogenic variants in the FBRSL1 paralog Autism Susceptibility Candidate 2 (AUTS2) are causative for an intellectual disability syndrome with microcephaly (AUTS2 syndrome). Some patients with AUTS2 syndrome also show additional symptoms like heart defects and contractures overlapping with the phenotype presented by patients with FBRSL1 mutations. For AUTS2, a dual function, depending on different isoforms, was described and suggested for FBRSL1. Both, nuclear FBRSL1 and AUTS2 are components of the Polycomb subcomplexes PRC1.3 and PRC1.5. These complexes have essential roles in developmental processes, cellular differentiation and proliferation by regulating gene expression via histone modification. In addition, cytoplasmic AUTS2 controls neural development, neuronal migration and neurite extension by regulating the cytoskeleton. Here, we review recent data on FBRSL1 in respect to previously published data on AUTS2 to gain further insights into its molecular function, its role in development as well as its impact on human genetics.
Interplay of Eph-Ephrin Signalling and Cadherin Function in Cell Segregation and Boundary Formation
Authors: Wilkinson David G.
Published: November 2021

The segregation of distinct cell populations to form sharp boundaries is crucial for stabilising tissue organisation, for example during hindbrain segmentation in craniofacial development. Two types of mechanisms have been found to underlie cell segregation: differential adhesion mediated by cadherins, and Eph receptor and ephrin signalling at the heterotypic interface which regulates cell adhesion, cortical tension and repulsion. An interplay occurs between these mechanisms since cadherins have been found to contribute to Eph-ephrin-mediated cell segregation. This may reflect that Eph receptor activation acts through multiple pathways to decrease cadherin-mediated adhesion which can drive cell segregation. However, Eph receptors mainly drive cell segregation through increased heterotypic tension or repulsion. Cadherins contribute to cell segregation by antagonising homotypic tension within each cell population. This suppression of homotypic tension increases the difference with heterotypic tension triggered by Eph receptor activation, and it is this differential tension that drives cell segregation and border sharpening.
Pulsatilla chinensis Saponins Ameliorate Inflammation and DSS-Induced Ulcerative Colitis in Rats by Regulating the Composition and Diversity of Intestinal Flora
Authors: Liu Yali , Zhou Mingyue , Yang Ming , Jin Chen , Song Yonggui , Chen Jingbin , Gao Meng , Ai Zhifu , Su Dan
Published: November 2021

Pulsatilla chinensis (Bunge) Regel is a commonly used Chinese medicine for clearing away heat and detoxification, cooling blood, stopping dysentery, and anti-inflammatory effects. Pulsatilla chinensis saponins (PRS) have been identified to be responsible for producing these pharmacological activities. Studies have shown that Pulsatilla decoction has a good therapeutic effect on ulcerative colitis (UC), however, the therapeutic effect of PRS on UC has not been reported. Therefore, the purpose of this study was to investigate the possible anti-UC activity of PRS using a dextran sulfate sodium (DSS)-induced rat model, and further study the mechanism of PRS in the treatment of UC. The fecal and colon samples were collected from rats to monitor the changes in the composition and diversity of the intestinal flora, and pathological colon sections were also made to examine the mesenteric hemorheological characteristics. The results showed that PRS significantly reduced the mesenteric blood flow in UC rats and significantly alleviated the inflammatory response, which indicates that saponins are involved in the anti-UC effects of PRS. At the same time, it is also suggested that the regulation of intestinal flora by Pulsatilla chinensis saponins is an important pathway for its anti-UC activity, which may be ascribed to the increase in beneficial bacteria like norank_F_Muribaculaceae and norank_F_norank_O_Clostridia_UCG-014, and decrease in the harmful Bacteroides.
The Impact of Harsh Parenting on the Development of Obesity in Adulthood: An Examination of Epigenetic/Gene Expression Mediators Among African American Youth
Authors: Lei Man-Kit , Beach Steven R. H. , Simons Ronald L. , Ye Kaixiong
Published: November 2021

Objective: We examined the association of prospectively assessed harsh parenting during adolescence with body mass index (BMI) in young adulthood among African American youth. We also assessed the role of methylation of obesity-related genes and gene expression markers of obesity as mediators of this association, providing a pathway for the biological embedding of early harsh parenting and its long-term impact on young adult health.

Methods: Hypotheses were tested with a sample of 362 African American youth for whom harsh parenting was assessed at ages 10–15, BMI was assessed at age 10 and 29, and both DNA methylation (DNAm) and gene expression of obesity genes were assessed at age 29. Mediational analyses were conducted using bootstrap methods to generate confidence intervals.

Results: Controlling for genetic risk for obesity and health-related covariates, harsh parenting across childhood and adolescence was associated with change in BMI (Δ BMI) from ages 10–29. In addition, we found that the indirect effect of harsh parenting on Δ BMI was mediated through obesity-related DNAm and accounted for 45.3% of the total effect. Further, obesity-related DNAm mediated the effect of harsh parenting on gene expression of obesity-related genes (GEOG), and GEOG, in turn, mediated the impact of obesity-related DNAm on ΔBMI. This pathway accounted for 3.4% of the total effect. There were no gender differences in the magnitude of this indirect effect.

Conclusions: The results suggest that alterations in methylation and gene expression mediate the impact of harsh parenting on change in obesity from childhood to young adulthood, illustrating plausible biological pathways from harsh parenting to obesity and bolstering the hypothesis that harsh parenting in childhood and adolescence can become biologically embedded and contribute to obesity.
Arterial and Cardiac Remodeling Associated With Extra Weight Gain in an Isolated Abdominal Obesity Cohort
Authors: Mandry Damien , Girerd Nicolas , Lamiral Zohra , Huttin Olivier , Filippetti Laura , Micard Emilien , Ncho Mottoh Marie-Paule Bernadette , Böhme Philip , Chemla Denis , Zannad Faïez , Rossignol Patrick , Marie Pierre-Yves
Published: November 2021

Introduction: This study aims to assess the changes in cardiovascular remodeling attributable to bodyweight gain in a middle-aged abdominal obesity cohort. A remodeling worsening might explain the increase in cardiovascular risk associated with a dynamic of weight gain.

Methods: Seventy-five middle-aged subjects (56 ± 5 years, 38 women) with abdominal obesity and no known cardiovascular disease underwent MRI-based examinations at baseline and at a 6.1 ± 1.2-year follow-up to monitor cardiovascular remodeling and hemodynamic variables, most notably the effective arterial elastance (Ea). Ea is a proxy of the arterial load that must be overcome during left ventricular (LV) ejection, with increased EA resulting in concentric LV remodeling.

Results: Sixteen obese subjects had significant weight gain (>7%) during follow-up (WG+), whereas the 59 other individuals did not (WG–). WG+ and WG– exhibited significant differences in the baseline to follow-up evolutions of several hemodynamic parameters, notably diastolic and mean blood pressures (for mean blood pressure, WG+: +9.3 ± 10.9 mmHg vs. WG–: +1.7 ± 11.8 mmHg, p = 0.022), heart rate (WG+: +0.6 ± 9.4 min−1 vs. −8.9 ± 11.5 min−1, p = 0.003), LV concentric remodeling index (WG: +0.08 ± 0.16 g.mL−1 vs. WG−: −0.02 ± 0.13 g.mL−1, p = 0.018) and Ea (WG+: +0.20 ± 0.28 mL mmHg−1 vs. WG−: +0.01 ± 0.30 mL mmHg−1, p = 0.021). The evolution of the LV concentric remodeling index and Ea were also strongly correlated in the overall obese population (p < 0.001, R2 = 0.31).

Conclusions: A weight gain dynamic is accompanied by increases in arterial load and load-related concentric LV remodeling in an isolated abdominal obesity cohort. This remodeling could have a significant impact on cardiovascular risk.
The Increasing Frequency of Tropical Cyclones in the Northeastern Atlantic Sector
Authors: Lima Miguel M. , Hurduc Alexandra , Ramos Alexandre M. , Trigo Ricardo M.
Published: November 2021

North Atlantic Tropical Cyclones (TCs) are major atmospheric hazards that can cause large disruptions to coastal and near-coastal societies. Although most studies focus on those areas with highest impact (e.g., Caribbean Islands, the Gulf and western coast of United States), there is an increasing interest in characterizing changes in occurrence and impacts in areas usually less affected by TCs, particularly in the framework of a changing climate. Here we provide a long-term context evaluating changes in the frequency of TC in the Northeast Atlantic (NEA) basin during the 1978–2019 period. In the last decades, scattered information has shown an impact both from TCs and Post-Tropical Cyclones (PTC) in the NEA. We compute several complementary linear trends and show a significant (p ≤ 0.1) increase in the number of stronger storms in the entire North Atlantic basin, and the amount of TCs and PTCs that reach the NEA, in agreement with previous works. A highly significant relation (p ≤ 0.05) is found between the Atlantic Multidecadal Oscillation (AMO) index and TC activity in both the entire North Atlantic and the NEA basin. Sea surface temperature anomaly maps are produced to better encapsulate the annual variability without the multidecadal oscillation effects and, important cold (warm) pools in cyclogenesis and development zones are found in years with low (high) TC activity. It is also found that the sea surface temperature field plays a minor role in the guiding of storms into the NEA sector. Long-term trends as well as high/low seasonal activity analysis suggest that atmospheric circulation (vertical wind shear, lapse rate, mean sea level pressure and upper-level steering) is more relevant than sea surface temperature in the NEA region.
Review of Operation and Maintenance Methodologies for Solar Photovoltaic Microgrids
Authors: Keisang Ketshephaone , Bader Tobias , Samikannu Ravi
Published: November 2021

Global concerns and growth in electricity demand, especially for rural and remote settlements, has forced governments, scientists, engineers, and researchers to look for alternative solutions in the form of renewable energy sources. High global growth in solar energy technology applications has added more weight in operations and maintenance (O&M) of solar-photovoltaic (SPV) systems. SPV reliability and optimized system performance are key to ensuring success and continual adaptation of SPV technology. O&M plays a central role in ensuring sustainability and long-term availability throughout the operational lifetime of the elements of SPV systems whilst boosting confidence of ultimate consumers in solar energy. While appreciating that SPV installations intrinsically require minimal maintenance actions, the objective of this manuscript is hence to reaffirm the significance of O&M scheduling in SPV systems by reviewing the O&M approaches in SPV microgrid systems. Further discussions focus on the various maintenance strategies employed in the field with special emphasis on corrective, preventive, and predictive maintenance strategies. Because of the variation in the design and development procedures of SPV systems, there is lack of clear steps followed in the development of an O&M program for SPV systems and the evaluation of its performance. This manuscript serves to address this through a model for developing an O&M program and portrays the key elements for its success, including a management and execution approach for improved risk-return balance and savings from the O&M expenditure. Eventually, the three models of executing an O&M program (i.e., in-house O&M team, third party contract, or installation company) are analyzed.
Can Prosuming Become Perilous? Exploring Systems of Control and Domestic Abuse in the Smart Homes of the Future
Authors: Sovacool Benjamin , Furszyfer-Del Rio Dylan D , Martiskainen Mari
Published: November 2021

In what ways can new, emerging digital technologies and energy business models such as “prosuming” become intertwined with troubling patterns of domestic abuse and violence? Domestic violence entails controlling, coercive or threatening behaviours, to gain or maintain power and control between intimate partners or family members regardless of gender or sexuality. The rapid development of digital communication services, smart homes, and digitalization processes such as prosuming create surprising threats related to technology-facilitated abuse. In this empirical study, based on a nationally representative survey of householders (n= 1,032 respondents) and three focus groups with the general public in different locations around the UK (n= 18 respondents), we explore the extent that prosuming technologies, smart grids and smart systems could act as potential enablers of domestic violence or systems of control. We also explore the use of smart systems as possible deterrents and mechanisms to reduce and address domestic violence and provide victim protection and recovery. In doing so, we explore user perceptions and preferences of smart systems, in relation to trust, monitoring, tracking, and surveillance. We finally discuss our results through the themes of duality and policy and provide conclusions with recommendations for further research.
Invalid Data Rejection of Audible Noise on AC Transmission Lines Based on Moving Window Kernel Principal Component Analysis
Authors: Cheng Ziyi , Li Zhenhua , Huang Yuehua , Yao Weifang , Xie Huichun
Published: November 2021

The statistical characteristics of the nighttime noise data of 1000 kV AC transmission lines were investigated, the noise data of the Huainan-Shanghai 1000 kV AC transmission line collected at night (0:00 to 6:00) from September 25, 2015, to February 16, 2016, were statistically analyzed using the nonparametric statistical K-S test, and the outliers were detected using the moving window kernel principal component analysis (MWKPCA). The results show that after the ineffective data are removed by MWKPCA, the 5, 50, and 95% values of the data are basically unchanged. To a certain extent, the method proposed in this paper can remove the invalid audible noise (AN) data of 1000 kV AC transmission lines without affecting the subsequent study of AN, we use various machine learning algorithms to predict the A weight sound level (Awsl) before and after the invalid data rejection, and the results show that the invalid data rejection has contributed to the improvement of the transmission line AN Awsl prediction accuracy.
Case Report: De novo KLHL24 Gene Pathogenic Variants in Chinese Twin Boys With Epidermolysis Bullosa Simplex
Authors: Xu Xiaojing , Zhao Juan , Wang Chao , Qu Xiaoxuan , Ran Menglong , Ye Fang , Shen Ming , Wang Kundi , Zhang Qi
Published: November 2021

Objectives: The aim of this study was to determine the molecular etiology and clinical manifestations of a pair of Chinese twins affected with epidermolysis bullosa simplex. Pediatricians should pay attention to the early genetic diagnosis of this disease.

Methods: Histopathological examination of HE-stained skin, electron microscopy of biopsied normal skin, and whole-exome sequencing was performed to assess pathogenicity and conservation of detected mutations. Two years later, the cutaneous and extracutaneous manifestations of the twins were comprehensively evaluated.

Results:A de novo pathogenic variant c.2T>C (p.M1T) in KLHL24 (NM_017,644) was identified in both twins. The characteristics of extensive skin defects on the extremities at birth and the tendency to lesson with increasing age were confirmed. No positive sensitive markers, such as B-type natriuretic peptide, cardiac troponin I, for cardiac dysfunction were detected.

Conclusions: The de novo pathogenic variants c.2T>C (p.M1T) in KLHL24 (NM_017,644) contributes to the development of epidermolysis bullosa. Genetic diagnosis at birth or early infancy can better predict the disease prognosis and guide the treatment.
Anti-PD-1 Therapy—A Potential Treatment for Myocardial Metastasis From Nasopharyngeal Carcinoma: A Case Report
Authors: Tang Xiaowan , Zhou Weijun , Huang Danjiang , Chen Lili , Zhang Guangwen
Published: November 2021

Myocardial metastasis of nasopharyngeal carcinoma (NPC) is rarely reported in the literature. Some autopsy studies found metastases in more than 10% of cases with malignant neoplasm. However, patients are often diagnosed during the postmortem because myocardial metastasis is often asymptomatic, and its Cardiac complications tend to be severe and fatal. Patients with Cardiac metastases are often treated with chemotherapy or surgical intervention, although the prognosis is poor. Immunotherapy with anti-programmed cell death receptor-1 or ligand-1 (PD-1 or PD-L1) inhibitors has recently been reported to be therapeutically significant in multiple cancers, including melanoma, nonsmall cell lung cancer, and NPC, but the treatment of myocardial metastasis of NPC has not been reported. This study described the case of a 50-year-old male patient who presented initially with NPC and received radiotherapy as first-line therapy. For 20 years, he had recurrent Cardiac metastasis of NPC. The pathological examination suggested tPD-L1 expression. Therefore, off-label sintilimab (200 mg every 21 days) was administered. After 10 cycles of treatment, myocardial metastasis shrank and the enlarged mediastinal lymph nodes disappeared. This case report demonstrated that Cardiac metastasis of NPC expressing PD-L1 might have a sustained response to PD-L1 inhibitor–directed therapy.