bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transglutaminase-2 mediates acquisition of neratinib resistance in metastatic breast cancer
Authors: Shinde Aparna , Kulkoyluoglu Cotul Eylem , Chen Hao , Smith Andrew , Libring Sarah , Solorio Luis , Wendt Michael K. 
Published: June 2022

AbstractAcquisition of resistance to targeted therapies remains a major clinical obstacle for the HER2+ subtype of breast cancer. Using an isogeneic progression series of HER2+ breast cancer metastasis we demonstrate that metastatic cells have an increased capacity to acquire resistance to the covalent, pan-ErbB inhibitor, neratinib. RNA sequencing analyses comparing parental and metastatic cells identified upregulation of transglutaminase 2 (TG2). Genetic depletion and overexpression approaches established that TG2 is both necessary and sufficient for acquisition of neratinib resistance. Mechanistically, we describe a pathway in which TG2-mediates activation of NF-κB signaling leading to upregulation of IL-6 in metastatic cells. This autocrine expression of IL-6 functions to maintain enhanced levels of TG2 via JAK:STAT3 signaling. This drug persistence feedback loop can be interrupted through the use of the JAK1/2 inhibitor ruxolitinib. In vivo application of ruxolitinib had no effect on tumor growth under non-treated conditions, but effectively prevented acquisition of resistance, leading to tumor regression upon coadministration with neratinib. Overall, our studies reveal a mechanism in metastatic breast cancer cells that predisposes them to acquisition of resistance to ErbB-targeted therapeutics. Clinically, immediate application of ruxolitinib could prevent acquisition of resistance and improve patient responses to HER2-targeted therapies.
Timing of surgery and elective perioperative management of patients with previous SARS-CoV-2 infection: a SIAARTI expert consensus statement
Authors: Cortegiani Andrea , Tripodi Vincenzo Francesco , Castioni Carlo Alberto , Esposito Clelia , Galdieri Nicola , Monzani Roberta , Rispoli Marco , Simonini Alessandro , Torrano Vito , Giarratano Antonino , Gratarola Angelo 
Published: June 2022

Abstract
Background
The appropriate timing of surgery and perioperative management of patients with previous SARS-CoV-2 infection are open issues. The purpose of this document is to support the clinical decision-making process regarding the patient with previous Sars-CoV-2 infection to undergo elective surgery. The recipients of this document are physicians, nurses, healthcare personnel, and other professionals involved in the patient’s surgical process.

Methods
The Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) selected 11 experts to reach a consensus on key aspects of this theme in adult and pediatric population. The methods of this process document were in accordance to the principles of rapid review of the scientific literature and modified Delphi method. The experts produced statements and supporting reasons in the form of an informative text. The overall list of statements was subjected to a vote in order to express the degree of consent.

Results
Patients should not undergo elective surgery within 7 weeks of infection unless there is the risk of a negative evolution of the disease. To mitigate the risk of postsurgical mortality, a multidisciplinary approach seemed useful in addition to the use of validated algorithms to estimate the risk of perioperative morbidity and mortality; the risk related to SARS-CoV-2 infection should be added. The risk of potential nosocomial contagion from a positive patients should also be considered when deciding to proceed with surgery. Most of the evidence came from previous SARS-CoV-2 variants, so the evidence should be considered indirect.

Conclusion
A balanced preoperative multidisciplinary risk–benefit evaluation is needed in patients with previous infection by SARS-CoV-2 for elective surgery.
Genome-wide association studies in non-anxiety individuals identified novel risk loci for depression
Authors: Cheng Bolun , Qi Xin , Meng Peilin , Cheng Shiqiang , Yang Xuena , Liu Li , Yao Yao , Jia Yumeng , Wen Yan , Zhang Feng 
Published: June 2022

AbstractBackgroundDepression is a debilitating mental disorder that often coexists with anxiety. The genetic mechanisms of depression and anxiety have considerable overlap, and studying depression in non-anxiety samples could help to discover novel gene. We assess the genetic variation of depression in non-anxiety samples, using genome-wide association studies (GWAS) and linkage disequilibrium score regression (LDSC).MethodsThe GWAS of depression score and self-reported depression were conducted using the UK Biobank samples, comprising 99,178 non-anxiety participants with anxiety score <5 and 86,503 non-anxiety participants without self-reported anxiety, respectively. Replication analysis was then performed using two large-scale GWAS summary data of depression from Psychiatric Genomics Consortium (PGC). LDSC was finally used to evaluate genetic correlations with 855 health-related traits based on the primary GWAS.ResultsTwo genome-wide significant loci for non-anxiety depression were identified: rs139702470 (p = 1.54 × 10−8, OR = 0.29) locate in PIEZO2, and rs6046722 (p = 2.52 × 10−8, OR = 1.09) locate in CFAP61. These associated genes were replicated in two GWAS of depression from PGC, such as rs1040582 (preplication GWAS1 = 0.02, preplication GWAS2 = 2.71 × 10−3) in CFAP61, and rs11661122 (preplication GWAS1 = 8.16 × 10−3, preplication GWAS2 = 8.08 × 10−3) in PIEZO2. LDSC identified 19 traits genetically associated with non-anxiety depression (p < 0.001), such as marital separation/divorce (rg = 0.45, SE = 0.15).ConclusionsOur findings provide novel clues for understanding of the complex genetic architecture of depression.
Genetic Analysis of Pheochromocytoma and Paraganglioma Complicating Cyanotic Congenital Heart Disease
Authors: Ogasawara Tatsuki , Fujii Yoichi , Kakiuchi Nobuyuki , Shiozawa Yusuke , Sakamoto Ryuichi , Ogawa Yoshihiro , Ootani Katsuki , Ito Etsuro , Tanaka Tomoaki , Watanabe Kenichiro , Yoshida Yusaku , Kimura Noriko , Shiraishi Yuichi , Chiba Kenichi , Tanaka Hiroko , Miyano Satoru , Ogawa Seishi 
Published: June 2022

Abstract

Context
Pheochromocytoma and paraganglioma (PPGL) may appear as a complication of cyanotic congenital heart disease (CCHD-PPGL) with frequent EPAS1 mutations, suggesting a close link between EPAS1 mutations and tissue hypoxia in CCHD-PPGL pathogenesis.

Objective
Our aim is to further investigate the role of EPAS1 mutations in the hypoxia-driven mechanism of CCHD-PPGL pathogenesis, particularly focusing on metachronous and/or multifocal CCHD-PPGL tumors.

Methods
We performed whole-exome sequencing (WES) for somatic and germline mutations in 15 PPGL samples from 7 CCHD patients, including 3 patients with metachronous and/or multifocal tumors, together with an adrenal medullary hyperplasia (AMH) sample.

Results
We detected EPAS1 mutations in 15 out of 16 PPGL/AMH samples from 7 cases. Conspicuously, all EPAS1 mutations in each of 3 cases with multifocal or metachronous tumors were mutually independent and typical examples of parallel evolution, which is suggestive of strong positive selection of EPAS1-mutated clones. Compared to 165 The Cancer Genome Atlas non–CCHD-PPGL samples, CCHD-PPGL/AMH samples were enriched for 11p deletions (13/16) and 2p amplifications (4/16). Of particular note, the multiple metachronous PPGL tumors with additional copy number abnormalities developed 18 to 23 years after the resolution of hypoxemia, suggesting that CCHD-induced hypoxic environments are critical for positive selection of EPAS1 mutants in early life, but may no longer be required for development of PPGL in later life.

Conclusion
Our results highlight a key role of activated hypoxia-inducible factor 2α due to mutated EPAS1 in positive selection under hypoxic environments, although hypoxemia itself may not necessarily be required for the EPAS1-mutated clones to progress to PPGL.
T Cells Mediate Kidney Tubular Injury via Impaired PDHA1 and Autophagy in Type 1 Diabetes
Authors: Wang Chung-Hsing , Lu Wen-Li , Chiang Shang-Lun , Tsai Tsung-Hsun , Liu Su-Ching , Hsieh Chia-Hung , Su Pen-Hua , Huang Chih-Yang , Tsai Fuu-Jen , Lin Yu-Jung , Huang Yu-Nan 
Published: June 2022

Abstract

Context
Nephropathy is a severe complication of type 1 diabetes (T1DM). However, the interaction between the PDHA1-regulated mechanism and CD4+ T cells in the early stage of kidney tubular injury remains unknown.

Objective
To evaluate the role of PDHA1 in the regulation of tubular cells and CD4+ T cells and further to study its interaction in tubular cell injury in T1DM.

Methods
Plasma and total RNA were collected from T cells of T1DM patients (n = 35) and healthy donors (n = 33) and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, PDHA1, and biomarkers of CD4+ T cells including T helper 1 cells (Th1) and regulatory T cells (Treg) markers. HK-2 cells cocultured with CD4+ T cells from T1DM patients or healthy donors (HDs) to evaluate the interaction with CD4+ T cells.

Results
Increased PDHA1 gene expression levels in CD4+ T cells were positively associated with the plasma level of NGAL in T1DM patients and HDs. Our data demonstrated that the Th1/Treg subsets skewed Th1 in T1DM. Knockdown of PDHA1 in kidney tubular cells decreased ATP/ROS production, NAD/NADH ratio, mitochondrial respiration, and cell apoptosis. Furthermore, PDHA1 depletion induced impaired autophagic flux. Coculture of tubular cells and T1DM T cells showed impaired CPT1A, upregulated FASN, and induced kidney injury.

Conclusion
Our findings indicate that Th1 cells induced tubular cell injury through dysregulated metabolic reprogramming and autophagy, thereby indicating a new therapeutic approach for kidney tubular injury in T1DM.
Circ-CCNB1 Modulates Trophoblast Proliferation and Invasion in Spontaneous Abortion by Regulating miR-223/SIAH1 axis
Authors: Jing Meng-yu , Xie Lai-di , Chen Xi , Zhou Ying , Jin Meng-meng , He Wei-hua , Wang Di-min , Liu Ai-xia 
Published: June 2022

Abstract

Context
Spontaneous abortion (SA) is a common disorder in early pregnancy. Circular RNAs (circRNAs) have been reported to exert important regulatory effects on trophoblast function and embryo development.

Objective
The aim of this study was to explore whether and how circRNAs regulate trophoblast function in SA during early pregnancy.

Methods
Cell proliferation, 5-bromo-2-deoxyuridine (BrdU) staining, Transwell, immunofluorescence, Western blot, RNA pull-down, and dual luciferase reporter assays were performed to investigate the effect of circRNA cyclin B1 (circ-CCNB1) on trophoblast function in HTR-8/SVneo and JEG-3 cells.

Results
An in vitro study demonstrated that upregulation of circ-CCNB1 significantly inhibited trophoblast proliferation and invasion compared with the controls using HTR-8/SVneo and JEG-3 cells, respectively. Moreover, miR-223 was downregulated in the villous tissues of patients with SA and was further predicted and shown to negatively interact with circ-CCNB1, which is involved in trophoblast proliferation and invasion. Using bioinformatics tools and subsequent RNA pull-down and dual luciferase assays, we found that miR-223 directly targets seven in absentia homolog-1 (SIAH1) and that upregulation of miR-223 decreased circ-CCNB1-induced SIAH1 expression levels in HTR-8/SVneo cells. Interestingly, upregulation of circ-CCNB1 suppressed trophoblast proliferation and invasion through inhibition of CCNB1 nuclear translocation induced by SIAH1. Downregulation of SIAH1 enhanced circ-CCNB1-suppressed CCNB1 nuclear protein expression in trophoblast cells.

Conclusion
Circ-CCNB1 served as a modulator of trophoblast proliferation and invasion by sponging miR-223, thus forming a regulatory network of circ-CCNB1/miR-223/SIAH1 in modulating CCNB1 nuclear translocation, which enabled us to elucidate the molecular mechanisms involved in normal embryo implantation or in SA.
Zhang Dongsun
Authors: Liu Jianmei 
Published: June 2022

Abstract
This article contributes to the study of the cultural politics of Thirdspace in modern China, which exerted a far-reaching influence on Chinese intellectual history, literature, and culture. Although the term the third space was coined by Homi K. Bhabha, the leading figure in postcolonial theoretical studies, as a new form of discourse to go beyond dualistic categories such as the colonizer/colonized opposition, it has much broader cultural meanings in the modern Chinese context. One of the prominent Chinese intellectuals, Zhang Dongsun, intentionally created a critical interface of Thirdspace through which to ensure a spirit of tolerance, independence of individuals, and freedom of criticism. The article investigates Zhang Dongsun's philosophical system, his political thought and commentary, and his cultural criticism in the Republic of China, discussing the motivations that compelled him to undertake the third route, as he attempted to transcend binary oppositions, which ultimately led to his downfall in the New China. The case of Zhang Dongsun, who exemplifies a group of liberal Chinese intellectuals, not only indicates the predicament of the discourse of Thirdspace in modern China but also adds new insights to our understanding of the divergent spiritual journeys that Chinese intellectuals have taken in response to the national crisis.
Leveraging the Human–Dog Bond to Support Physical Activity across the Life Span
Authors: Potter Katie , Chase Colleen J. 
Published: June 2022

Apply It!
• Do you work with clients or patients who love dogs? Learn about the unique benefits of physical activity in the company of dogs and ways to leverage the human–dog bond to increase physical activity in people of all ages.
• Think through considerations to ensure dog walking and play are safe and enjoyable for both people and pets.
Men, The Missing Link In Gender-equitable Family Planning: A Scoping Review
Authors: Seth Kuhika , Nanda Sharmishtha , Sahay Aishwarya , Verma Ravi , Achyut Pranita 
Published: June 2022

Background: Across societies, gender norms often allow men to hold key decision-making power within relationships, households and communities. This extends to almost all domains, consisting of family planning (FP) as well. FP programs have largely engaged men as clients and rarely as equal partners or influencers although across lower- and middle-income countries (LMICs), and especially in South Asia, men hold key decision-making power on the domain of family planning. The objective of this article is to explore couple dynamics through the lens of spousal communication and decision-making and unpack male engagement and spousal dynamics in family planning. Methods: This review presents a synthesis of evidence from two peer-reviewed databases, PubMed and Jstor, and and insights from programmatic documents to shed light on gender equitable engagement of young married men in family planning. Inclusion and exclusion criteria for both these databases was set and search strategies were finalized. This was followed by title and abstract screening, data extraction, synthesis and analysis. Results: Study participants included unmarried men (16%, n=8), married men (19%, n=9), married women (19%, n=9), married couples (25%, n=12) or more than two respondent categories (21%, n=10). Almost three quarters (71%, n=34) of the studies selected had FP as the primary area of inquiry. Other prominent thematics on which the studies reported were around norms (n=9, 16%), couple dynamics and intimacy (n=12, 22%). Conclusions: The evidence presented provides sufficient impetus to expand on gender-equitable male engagement, viewing men as equal and supportive partners for informed, equitable and collaborative contraceptive uptake and FP choices by couples.
A Digital Image Correlation (DIC) prototype system for crack propagation monitoring in aircraft assemblies
Authors: Hack Erwin , Luan LiKang , Crosbie Liam , Michel Silvain 
Published: June 2022

Background: In the Clean Sky 2 project DIMES, the cyclic loading of a section of an A320 wing with pre-existing damage was carried out. Methods: We present a Digital Image Correlation (DIC) prototype system to monitor crack propagation in the aircraft wing. This system includes a mount for easy installation and adjustment in a confined space. Results: Strain localization and evaluation due to crack propagation was successfully observed in the Region-of-Interest (ROI) during cyclic fatigue loading. The results from the DIC prototype system were supported by conventional contact Resistance Strain Gauge (RSG) sensors acting as a far-field monitor. Conclusions: Future improvements, the combination of two DIC modules for a stereo DIC system and the potential of the DIC system for ground-based tests and Structural Health Monitoring (SHM) applications are also discussed.
High index core flat fiber surface plasmon resonance bio-sensor
Authors: Alkhateeb Abdulhameed Fouad , Islam Md. Shofiqul , Ali Md. Yeakub , Usha Rownok Jahan , Tasnim Sanjida , Alghamdi Sami , Mollah Md. Aslam 
Published: June 2022

Due to tremendous design flexibility and ease of light control capability, the photonic crystal fiber offers efficient, flexible, and miniaturized plasmonic biosensors with attractive features. In this work, a high index (

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doped silica) core flat fiber is proposed and analyzed for RI sensing ranging from 1.53 to 1.60. A rectangular analyte channel is created on top of a flat fiber to better handle the liquid analyte. To introduce the plasmonic effect,

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and gold are deposited to the analyte channel. The sensing performance is carried out for two operating wavelengths, as two peaks are obtained for each analyte. The second operating wavelength shows better sensing performance than the first one. However, the proposed sensor offers average wavelength sensitivity of 5000 nm/RIU with a sensor resolution of

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RIU. In addition, the proposed sensor shows identical linearity, which is quite rare in prior sensors. Moreover, the proposed flat sensor provides outstanding detection accuracy of

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, detection limit of 79.28 nm, signal to noise ratio of

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, and figure of merit of

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. Owing to outstanding sensing performance and a unique detection range, this sensor can be effectively used in biological and organic analyte sensing applications.
Relative humidity sensing using THz metasurfaces combined with polyvinyl alcohol
Authors: Gu Jialin , Qin Jinyuan , Han Zhanghua 
Published: June 2022

Relative humidity (RH) plays an important role in almost every industrial field. Thus, the detection of RH is of great significance in these fields. Terahertz (THz) waves are extremely sensitive to the changes in RH because water absorbs strongly in this electromagnetic band. In this paper, a RH sensor based on THz metasurfaces combined with polyvinyl alcohol (PVA) is proposed. Different from the conventional metasurface sensor, our sensor includes a PVA layer that is sandwiched between the metal structure and the substrate. The improved design is able to enhance the interaction between the electric field and the water molecules absorbed in the PVA layer, and the sensitivity of the humidity sensor can reach 0.34 GHz/%RH, which is more than twice that of the conventional metasurface sensor. These results show that the proposed sensor can be used for the detection of RH with high reliability and high sensitivity, which open a new, to the best of our knowledge, avenue for RH sensing using THz spectroscopy.
Environmental barriers matter from the early stages of functional decline among older adults in France
Authors: Laborde Caroline , Ankri Joël , Cambois Emmanuelle 
Published: June 2022

Background
The adaptation of living environments can preserve functional independence among older people. A few studies have suggested that this would only benefit the most impaired. But conceptual models theorize that environmental pressure gradually increases with functional decline.

Objectives
We examined (1) how far different environmental barriers increased difficulties and favoured resort to assistance; (2) at what stage in functional decline environmental barriers begin to matter.

Methods
We used the French cross-sectional survey CARE (2015), including 7,451 participants (60+) with at least one severe functional limitation (FL). Multinomial logistic regressions models were used to compare predicted probabilities for outdoor activities of daily living (OADL) difficulties (no OADL difficulties; difficulties but without assistance; use of assistance) among individuals with and without environmental barriers (self-reported or objective), in relation to the number of FLs.

Results
Poor-quality pedestrian areas and lack of places to rest were associated with a higher probability of experiencing OADL difficulties, whatever the number of FLs; the association increased with the number of FLs. Up to 6 FLs, individuals with these barriers were more likely to report difficulties without resorting to assistance, with a decreasing association. Living in cities/towns with high diversity of food outlets was associated with a lower probability of reporting assistance, whatever the number of FLs, but with a decreasing association.

Discussion
Overall, the results suggest that environmental barriers increasingly contribute to OADL difficulties with the number of FLs. Conclusions differed as to whether they tended to favour resort to assistance, but there was a clear association with food outlets, which decreased with impairment severity. The adaptation of living environments could reduce difficulties in performing activities from the early stages of decline to the most severe impairment. However, the most deteriorated functional impairments seem to generate resort to assistance whatever the quality of the environment.
DAS DECISÕES MANIPULATIVAS: UM OLHAR CRÍTICO AO PAPEL CRIATIVO DOS TRIBUNAIS FRENTE AO ATIVISMO JUDICIÁRIO
Authors: Oliveira Volante Joaquim Pedro de , Scremin Neto Ferdinando , Smolarek Dias Bruno 
Published: June 2022

No presente artigo busca-se compreender, por meio de análise doutrinária, jurisprudencial e legal, o papel ultrapassado do Tribunal Constitucional como Legislador negativo, no âmbito de recentes decisões manipulativas, uma vez que o Supremo Tribunal Federal, além de exercer o papel de legislador negativo, também exerce atividade hermenêutica da Lei, podendo adicionar, substituir ou retrair parte do texto de lei visando a conformação constitucional. Será analisado, a partir da doutrina, a linha tênue entre a decisão manipulativa e o ativismo judicial, a partir da fundamentação da decisão manipulativa, demonstrando uma brecha potencialmente danosa ao Estado Democrático de Direito.
Detection of Anal Intraepithelial Neoplasia and Anal Squamous Cell Carcinoma on Colonoscopy
Authors: Voss Jordan K. , Kurdi Ahmed T. , Neto Manuel Braga , Wang Xiao Jing , Chedid Victor G. 
Published: June 2022

ABSTRACT
The purpose of this case series is to review the endoscopic detection of anal intraepithelial neoplasia and anal squamous cell carcinoma including the role of rectal retroflexion and narrow-band imaging. Four cases of anal intraepithelial neoplasia were incidentally discovered in women aged 55–71 years. Anal lesions identified included sessile polyps, nodular mucosa, and circumferential polyps. A fifth patient, who presented with abdominal pain, was found to have a 3 cm anal squamous cell carcinoma on diagnostic colonoscopy, despite a negative colonoscopy 21 months earlier. In the absence of contraindications, retroflexion should be performed on all patients. Suspicious anal mucosa warrants biopsy.