bluuebunny/crossref_metadata_2025_split huggingface dataset:
Demonstration of a superconducting diode-with-memory, operational at zero magnetic field with switchable nonreciprocity
Authors: Golod Taras , Krasnov Vladimir M. 
Published: June 2022

AbstractDiode is one of the basic electronic components. It has a nonreciprocal current response, associated with a broken space/time reversal symmetry. Here we demonstrate prototypes of superconducting diodes operational at zero magnetic field. They are based on conventional niobium planar Josephson junctions, in which space/time symmetry is broken by a combination of self-field effect from nonuniform bias and stray fields from a trapped Abrikosov vortex. We demonstrate that nonreciprocity of critical current in such diodes can reach an order of magnitude and rectification efficiency can exceed 70%. Furthermore, we can easily change the diode polarity and switch nonreciprocity on/off by changing the bias configuration and by trapping/removing of a vortex. This facilitates a memory functionality. We argue that such a diode-with-memory can be used for a future generation of in-memory superconducting computers.
Osteocyte CIITA aggravates osteolytic bone lesions in myeloma
Authors: Liu Huan , He Jin , Bagheri-Yarmand Rozita , Li Zongwei , Liu Rui , Wang Zhiming , Bach Duc-hiep , Huang Yung-hsing , Lin Pei , Guise Theresa A. , Gagel Robert F. , Yang Jing 
Published: June 2022

AbstractOsteolytic destruction is a hallmark of multiple myeloma, resulting from activation of osteoclast-mediated bone resorption and reduction of osteoblast-mediated bone formation. However, the molecular mechanisms underlying the differentiation and activity of osteoclasts and osteoblasts within a myelomatous microenvironment remain unclear. Here, we demonstrate that the osteocyte-expressed major histocompatibility complex class II transactivator (CIITA) contributes to myeloma-induced bone lesions. CIITA upregulates the secretion of osteolytic cytokines from osteocytes through acetylation at histone 3 lysine 14 in the promoter of TNFSF11 (encoding RANKL) and SOST (encoding sclerostin), leading to enhanced osteoclastogenesis and decreased osteoblastogenesis. In turn, myeloma cell–secreted 2-deoxy-D-ribose, the product of thymidine catalyzed by the function of thymidine phosphorylase, upregulates CIITA expression in osteocytes through the STAT1/IRF1 signaling pathway. Our work thus broadens the understanding of myeloma-induced osteolysis and indicates a potential strategy for disrupting tumor-osteocyte interaction to prevent or treat patients with myeloma bone disease.
Warming-induced increase in carbon uptake is linked to earlier spring phenology in temperate and boreal forests
Authors: Gu Hongshuang , Qiao Yuxin , Xi Zhenxiang , Rossi Sergio , Smith Nicholas G. , Liu Jianquan , Chen Lei 
Published: June 2022

AbstractUnder global warming, advances in spring phenology due to rising temperatures have been widely reported. However, the physiological mechanisms underlying the advancement in spring phenology still remain poorly understood. Here, we investigated the effect of temperature during the previous growing season on spring phenology of current year based on the start of season extracted from multiple long-term and large-scale phenological datasets between 1951 and 2018. Our findings indicate that warmer temperatures during previous growing season are linked to earlier spring phenology of current year in temperate and boreal forests. Correspondingly, we observed an earlier spring phenology with the increase in photosynthesis of the previous growing season. These findings suggest that the observed warming-induced earlier spring phenology is driven by increased photosynthetic carbon assimilation in the previous growing season. Therefore, the vital role of warming-induced changes in carbon assimilation should be considered to accurately project spring phenology and carbon cycling in forest ecosystems under future climate warming.
Cellular automaton simulation and experimental validation of eutectic transformation during solidification of Al-Si alloys
Authors: Gu Cheng , Moodispaw Michael P. , Luo Alan A. 
Published: June 2022

AbstractThe morphology of eutectic silicon in solidification microstructure is critical to the performance of Al-Si-based alloys. Simulating eutectic Si phase formation has been a challenge in ICME (integrated computational materials engineering) based design and manufacturing of solidification products of Al-Si-based alloys. In this study, our previous three-dimensional (3-D) cellular automaton (CA) model for α-Al dendritic growth was extended to include eutectic (α-Al + Si) transformation in multi-dendrite domains, providing a complete solidification simulation of critically important Al-Si based alloys. The quantitative results of the Si phase in the eutectic microstructure were experimentally validated using scanning electron microscopy and deep etching techniques. The simulation results show a good agreement with the experimental observations and calculations by the Scheil model and lever rule. This 3-D CA model is useful for predicting and optimizing the solidification microstructure including eutectic transformation during solidification processing such as casting, potentially welding, and additive manufacturing.
Empirical evidence for biometal dysregulation in Parkinson’s disease from a systematic review and Bradford Hill analysis
Authors: Abdeen Amr H. , Trist Benjamin G. , Double Kay L. 
Published: June 2022

AbstractThe Bradford Hill model evaluates the causal inference of one variable on another by assessing whether evidence of the suspected causal variable aligns with a set of nine criteria proposed by Bradford Hill, each representing fundamental tenets of a causal relationship. The aim of this study was to use the Bradford Hill model of causation to assess the level of empirical evidence supporting our hypotheses that alterations to iron and copper levels, and iron- and copper-associated proteins and genes, contribute to Parkinson’s disease etiology. We conducted a systematic review of all available articles published to September 2019 in four online databases. 8437 articles matching search criteria were screened for pre-defined inclusion and exclusion criteria. 181 studies met study criteria and were subsequently evaluated for study quality using established quality assessment tools. Studies meeting criteria for moderate to high quality of study design (n = 155) were analyzed according to the Bradford Hill model of causation. Evidence from studies considered of high quality (n = 73) supported a causal role for iron dysregulation in Parkinson’s disease. A causal role for copper dysregulation in Parkinson’s disease was also supported by high quality studies, although substantially fewer studies investigated copper in this disorder (n = 25) compared with iron. The available evidence supports an etiological role for iron and copper dysregulation in Parkinson’s disease, substantiating current clinical trials of therapeutic interventions targeting alterations in brain levels of these metals in Parkinson’s disease.
Error measurements for a quantum annealer using the one-dimensional Ising model with twisted boundaries
Authors: Chancellor Nicholas , Crowley Philip J. D. , Durić Tanja , Vinci Walter , Amin Mohammad H. , Green Andrew G. , Warburton Paul A. , Aeppli Gabriel 
Published: June 2022

AbstractA finite length ferromagnetic chain with opposite spin polarization imposed at its two ends is one of the simplest frustrated spin models. In the clean classical limit the domain wall inserted on account of the boundary conditions resides with equal probability on any one of the bonds, and the degeneracy is precisely equal to the number of bonds. If quantum mechanics is introduced via a transverse field, the domain wall will behave as a particle in a box, and prefer to be nearer the middle of the chain rather than the ends. A simple characteristic of a real quantum annealer is therefore which of these limits obtains in practice. Here we have used the ferromagnetic chain with antiparallel boundary spins to test a real flux qubit quantum annealer and discover that contrary to both expectations, the domain walls found are non-uniformly distributed on account of effective random longitudinal fields present notwithstanding tuning carried out to zero out such fields when the couplings between qubits are nominally zero. We present a simple derivation of the form of the distribution function for the domain walls, and show also how the effect we have discovered can be used to determine the strength of the effective random fields (noise) characterizing the annealer. The noise measured in this fashion is smaller than what is seen during the single-qubit tuning process, but nonetheless qualitatively affects the outcome of the simulation performed by the annealer.
Clonal structure, stability and dynamics of human memory B cells and circulating plasmablasts
Authors: Phad Ganesh E. , Pinto Dora , Foglierini Mathilde , Akhmedov Murodzhon , Rossi Riccardo L. , Malvicini Emilia , Cassotta Antonino , Fregni Chiara Silacci , Bruno Ludovica , Sallusto Federica , Lanzavecchia Antonio 
Published: June 2022

AbstractMemory B cells persist for a lifetime and rapidly differentiate into antibody-producing plasmablasts and plasma cells upon antigen re-encounter. The clonal relationship and evolution of memory B cells and circulating plasmablasts is not well understood. Using single-cell sequencing combined with isolation of specific antibodies, we found that in two healthy donors, the memory B cell repertoire was dominated by large IgM, IgA and IgG2 clonal families, whereas IgG1 families, including those specific for recall antigens, were of small size. Analysis of multiyear samples demonstrated stability of memory B cell clonal families and revealed that a large fraction of recently generated plasmablasts was derived from long-term memory B cell families and was found recurrently. Collectively, this study provides a systematic description of the structure, stability and dynamics of the human memory B cell pool and suggests that memory B cells may be active at any time point in the generation of plasmablasts.
Assessment of the frequency of coughing and sneezing triggered by nasopharyngeal swabbing in the pandemic setting
Authors: Cismaru Cosmin Andrei , Chira Sergiu , Cismaru Gabriel Laurentiu , Nutu Andreea Mihaela , Netea Mihai Gheorghe , Berindan-Neagoe Ioana 
Published: June 2022

AbstractA variety of medical procedures are classified as aerosol generating. However there is no consensus on whether some procedures such as nasopharyngeal swabbing can generate aerosols. During specimen collection, the contact of the nasopharyngeal swab with the respiratory mucosa often triggers defense reflexes such as sneezing and coughing, which generate airborne particles. The accumulation and persistence of a viral load from infectious aerosols for hours after their generation can represent a threat for increased spread of infection. Prospective observational cohort study in individuals tested for RT-PCR SARS-CoV-2 from July to October 2020. Participants were evaluated for the prevalence of aerosol generating events (AGEs) triggered by the nasopharyngeal swabbing. We used descriptive statistics to analyze the data set and the chi-square test for AGE comparison between sexes. Among 1239 individuals, we reported 264 in which AGEs were triggered by the specimen collection. 97 individuals tested positive for SARS-CoV-2, of which 20 presented AGEs. There were no significant differences in the occurrence of AGEs by age, but significant differences have been identified between sex and the occurrence of AGEs both in the SARS-CoV-2 negative and SARS-CoV-2 positive individuals. The prevalence of coughing or sneezing triggered by the nasopharyngeal swabbing was high among tested individuals. Testing facilities should ensure adequate availability of personal protective equipment (PPE) for the testing personnel, ensure appropriate ventilation of the rooms, and develop additional strategies to limit the risk of contamination of other participants to the testing session from potentially infectious and persistent aerosols.
Tyramide-conjugated DNA barcodes enable signal amplification for multiparametric CODEX imaging
Authors: Simonson Paul D. , Valencia Itzel , Patel Sanjay S. 
Published: June 2022

AbstractMultiparametric imaging allows researchers to measure the expression of many biomarkers simultaneously, allowing detailed characterization of cell microenvironments. One such technique, CODEX, allows fluorescence imaging of >30 proteins in a single tissue section. In the commercial CODEX system, primary antibodies are conjugated to DNA barcodes. This modification can result in antibody dysfunction, and development of a custom antibody panel can be very costly and time consuming as trial and error of modified antibodies proceeds. To address these challenges, we developed novel tyramide-conjugated DNA barcodes that can be used with primary antibodies via peroxidase-conjugated secondary antibodies. This approach results in signal amplification and imaging without the need to conjugate primary antibodies. When combined with commercially available barcode-conjugated primary antibodies, we can very quickly develop working antibody panels. We also present methods to perform antibody staining using a commercially available automated tissue stainer and in situ hybridization imaging on a CODEX platform. Future work will include application of the combined tyramide-based and regular CODEX approach to image specific tumors with their immune cell infiltrates, including biomarkers that are currently difficult to image by regular CODEX.
Impaired oxygen-sensitive regulation of mitochondrial biogenesis within the von Hippel–Lindau syndrome
Authors: Li Shuijie , Li Wenyu , Yuan Juan , Bullova Petra , Wu Jieyu , Zhang Xuepei , Liu Yong , Plescher Monika , Rodriguez Javier , Bedoya-Reina Oscar C. , Jannig Paulo R. , Valente-Silva Paula , Yu Meng , Henriksson Marie Arsenian , Zubarev Roman A. , Smed-Sörensen Anna , Suzuki Carolyn K. , Ruas Jorge L. , Holmberg Johan , Larsson Catharina , Christofer Juhlin C. , von Kriegsheim Alex , Cao Yihai , Schlisio Susanne 
Published: June 2022

AbstractMitochondria are the main consumers of oxygen within the cell. How mitochondria sense oxygen levels remains unknown. Here we show an oxygen-sensitive regulation of TFAM, an activator of mitochondrial transcription and replication, whose alteration is linked to tumours arising in the von Hippel–Lindau syndrome. TFAM is hydroxylated by EGLN3 and subsequently bound by the von Hippel–Lindau tumour-suppressor protein, which stabilizes TFAM by preventing mitochondrial proteolysis. Cells lacking wild-type VHL or in which EGLN3 is inactivated have reduced mitochondrial mass. Tumorigenic VHL variants leading to different clinical manifestations fail to bind hydroxylated TFAM. In contrast, cells harbouring the Chuvash polycythaemia VHLR200W mutation, involved in hypoxia-sensing disorders without tumour development, are capable of binding hydroxylated TFAM. Accordingly, VHL-related tumours, such as pheochromocytoma and renal cell carcinoma cells, display low mitochondrial content, suggesting that impaired mitochondrial biogenesis is linked to VHL tumorigenesis. Finally, inhibiting proteolysis by targeting LONP1 increases mitochondrial content in VHL-deficient cells and sensitizes therapy-resistant tumours to sorafenib treatment. Our results offer pharmacological avenues to sensitize therapy-resistant VHL tumours by focusing on the mitochondria.
One-Year Neurodevelopmental Outcomes After Neonatal Opioid Withdrawal Syndrome: A Prospective Cohort Study
Authors: Benninger Kristen L. , Richard Celine , Conroy Sara , Newton Julia , Taylor H. Gerry , Sayed Alaisha , Pietruszewski Lindsay , Nelin Mary Ann , Batterson Nancy , Maitre Nathalie L. 
Published: June 2022

Purpose:
The aims of this study were, in a cohort of children with neonatal opioid withdrawal syndrome (NOWS), (a) to report 1-year neurodevelopmental outcomes and specifically characterize speech, language, and hearing outcomes and (b) to report the prevalence of cleft lip and/or cleft palate.

Method:

This prospective observational cohort study includes newborns with confirmed in utero opioid exposure who received pharmacological treatment for NOWS. During 1-year-old developmental visits, we administered standardized assessments (Bayley Scales of Infant and Toddler Development–Third Edition [Bayley-III] or Developmental Assessment of Young Children–Second Edition [DAYC-2]—due to COVID-19 restrictions). We compared Bayley-III scores to standardized population means using one-sample
z
tests. We report estimates, 95% confidence intervals, and two-sided
p
values.

Results:
We enrolled 202 infants (October 2018 to March 2020). Follow-up at 1-year was 80%. Infants with NOWS had lower Bayley-III scores at 1 year compared to published norms for cognitive, language, and motor domains. One infant with NOWS was diagnosed with isolated cleft palate and Pierre Robin sequence. All infants passed the newborn hearing screen, and 7.5% had a formal hearing evaluation after neonatal intensive care unit discharge, with 40% having abnormal or inconclusive results; middle ear effusion was the leading cause of abnormal hearing (66.7%). Ten percent of children received a speech-language pathology referral prior to 2 years of age. Infants born to mothers with mental health conditions were more likely to have Bayley-III or DAYC-2 scores below 95 in language or motor domains.

Conclusions:
Infants with pharmacologically treated NOWS have significantly lower cognitive, language, and motor scores on standardized developmental testing compared to population means at 1 year of age. Early speech-language pathology referral is frequently necessary to promote optimal development in this population.

Supplemental Material:

https://doi.org/10.23641/asha.20044403
Thymoquinone Potentiates Methotrexate Mediated-Apoptosis in Saos-2 Osteosarcoma Cell Line
Authors: khyavi Payam Ali , Valizadeh Amir , Shanehbandi Dariush , Yousefi Bahman , Soleimanpour Jafar 
Published: June 2022

AbstractIntroduction Recently, various studies have concentrated on the therapeutic potential of thymoquinone (TQ), a natural polyphenol, in various human malignancies, including osteosarcoma. However, the underlying mechanisms in TQ-mediated anti-cancer effects are not yet fully understood. Therefore, the present study investigated the effect of TQ on methotrexate (MTX)-induced apoptosis in Saos-2 cells.Methods Saos-2 cells were treated with MTX, TQ, and a combination of both, and cell viability was assessed by MTT assay. mRNA expression of apoptotic markers, including Bax, Bcl-2, and caspase-3, was assessed using quantitative real-time polymerase chain reaction (qRT-PCR).Results MTX resulted in significant inhibition of cell proliferation in a dose-dependent manner. The combination of TQ and MTX inhibited proliferation compared to single treatments (P<0.05). TQ also induced apoptosis by regulating pro-apoptotic markers including Bax and caspase-3 and reducing anti-apoptotic mediators including Bcl-2. In addition, TQ increased MTX-induced apoptosis in Saos-2 cells.Conclusion The findings of the present study highlight new insights into understanding the role of TQ as a potential therapeutic agent in osteosarcoma by increasing MTX-induced apoptosis.
Clinical Presentation, Treatment Outcomes, and Resistance-related Factors in South American Women with Low-risk Postmolar Gestational Trophoblastic Neoplasia
Authors: Ramírez Luz Angela Correa , Maestá Izildinha , Bianconi María Inés , Jankilevich Gustavo , Otero Silvina , Mejía Carlos Raúl Villegas , Cortés-Charry Rafael , Elias Kevin M. , Horowitz Neil S. , Seckl Michael , Berkowitz Ross S. 
Published: June 2022

Abstract
Objective There are few multinational studies on gestational trophoblastic neoplasia (GTN) treatment outcomes in South America. The purpose of this study was to assess the clinical presentation, treatment outcomes, and factors associated with chemoresistance in low-risk postmolar GTN treated with first-line single-agent chemotherapy in three South American centers.
Methods Multicentric, historical cohort study including women with International Federation of Gynecology and Obstetrics (FIGO)-staged low-risk postmolar GTN attending centers in Argentina, Brazil, and Colombia between 1990 and 2014. Data were obtained on patient characteristics, disease presentation, and treatment response. Logistic regression was used to assess the relationship between clinical factors and resistance to first-line single-agent treatment. A multivariate analysis of the clinical factors significant in univariate analysis was performed.
Results A total of 163 women with low-risk GTN were included in the analysis. The overall rate of complete response to first-line chemotherapy was 80% (130/163). The rates of complete response to methotrexate or actinomycin-D as first-line treatment, and actinomycin-D as second-line treatment postmethotrexate failure were 79% (125/157), 83% (⅚), and 70% (23/33), respectively. Switching to second-line treatment due to chemoresistance occurred in 20.2% of cases (33/163). The multivariate analysis demonstrated that patients with a 5 to 6 FIGO risk score were 4.2-fold more likely to develop resistance to first-line single-agent treatment (p = 0.019).
Conclusion 1) At presentation, most women showed clinical characteristics favorable to a good outcome, 2) the overall rate of sustained complete remission after first-line single-agent treatment was comparable to that observed in developed countries, 3) a FIGO risk score of 5 or 6 is associated with development of resistance to first-line single-agent chemotherapy.
Computed Tomographic Measurements of the Sulcus Angle of the Femoral Trochlea in Small-Breed Dogs with and without Medial Patellar Luxation
Authors: Sasaki Akari , Hidaka Yuki , Mochizuki Manabu , Honnami Muneki 
Published: June 2022

AbstractTrochleoplasty is often performed in dogs with medial patellar luxation (MPL); however, the current guidelines on when to perform a trochleoplasty in dogs are vague. The sulcus angle (SA) is used to assess the femoral trochlear morphology in humans. The aim of this study is to describe a method to measure the SA and other parameters of trochlea morphology in dogs using computed tomography. First, we searched for a suitable measuring location for the SA. Transverse images of the femurs were obtained as perpendicular planes to the tangent of the femoral trochlea which was 0 to 60 degrees (every 5 degrees) to the anatomical axis of the femur. The deepest point of the femoral trochlea was found in the transverse images perpendicular to the tangent of the femoral trochlea which was at 15 degrees to the anatomical axis of the femur. The SA and the other parameters of femoral trochlea morphology were measured at the deepest point of the femoral trochlea. The SA of the stifle joints with grade 3 and 4 MPL was significantly higher than the SA of stifle joints not affected by MPL. There was no significant difference in the SA between dogs affected by grade 1 and 2 MPL and dogs not affected by MPL. Further studies are needed to establish whether the SA can be used as selection criteria for trochleoplasty.