bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mononuclear cells from patients with rhupus are influenced by TNF in their production of gp130/sIL-6Rb and APRIL
Authors: Amezcua-Guerra Luis M , Sánchez-Muñoz Fausto , Guzmán-García Santiago , Márquez-Velasco Ricardo , Becerril-Villanueva Enrique , Vázquez-Panchos Yadira , Juárez-Vicuña Yaneli 
Published: October 2023

ObjectiveRhupus is a rare disease that shares characteristics of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). While several studies have explored the clinical and immunological profiles of patients with rhupus, the underlying cause of the disease remains unknown due to its complex pathogenesis. The objective of this study was to investigate the role of tumour necrosis factor (TNF) in the production of inflammatory molecules by peripheral blood mononuclear cells (PBMCs) from patients with rhupus.MethodsThe study involved five healthy controls, seven patients with rhupus and seven patients with SLE. PBMCs were obtained from each participant and stimulated with recombinant human TNF for 24 hours. The levels of various molecules secreted by the cells, such as cytokines and chemokines, were measured using immunobead-based assays on xMAP technology.ResultsThe production levels of some molecules were higher in TNF-stimulated PBMCs from patients with rhupus and SLE than in unstimulated cells. In addition, the levels of certain molecules, including gp130/sIL-6Rb, a proliferation-inducing ligand (APRIL), interferon-β, matrix metalloproteinase-3 and interleukin (IL)-12, were higher in PBMCs from patients with rhupus even without TNF stimulation. Similarly, the levels of gp130/sIL-6Rb and APRIL were higher in TNF-stimulated PBMCs from patients with rhupus than in healthy controls. These results were further validated against patients with RA using enzyme-linked immunosorbent assay.ConclusionsThese findings suggest that the spontaneous production of molecules by cells from patients with rhupus may contribute to the development of the disease, and that TNF may play a role in this process by regulating the secretion of gp130/sIL-6Rb and APRIL.
Phase II Clinical Trial of Pembrolizumab and Chemotherapy Reveals Distinct Transcriptomic Profiles by Radiologic Response in Metastatic Triple-Negative Breast Cancer
Authors: Wilkerson Avia D. , Parthasarathy Prerana Bangalore , Stabellini Nickolas , Mitchell Carley , Pavicic Paul G. , Fu Pingfu , Rupani Amit , Husic Hana , Rayman Patricia A. , Swaidani Shadi , Abraham Jame , Budd G. Thomas , Moore Halle , Al-Hilli Zahraa , Ko Jennifer S. , Baar Joseph , Chan Timothy A. , Alban Tyler , Diaz-Montero C. Marcela , Montero Alberto J. 
Published: October 2023

Abstract

Purpose:
A single arm, phase II trial of carboplatin, nab-paclitaxel, and pembrolizumab (CNP) in metastatic triple-negative breast cancer (mTNBC) was designed to evaluate overall response rate (ORR), progression-free survival (PFS), duration of response (DOR), safety/tolerability, overall survival (OS), and identify pathologic and transcriptomic correlates of response to therapy.

Patients and Methods:
Patients with ≤2 prior therapies for metastatic disease were treated with CNP regardless of tumor programmed cell death-ligand 1 status. Core tissue biopsies were obtained prior to treatment initiation. ORR was assessed using a binomial distribution. Survival was analyzed via the Kaplan–Meier method. Bulk RNA sequencing was employed for correlative studies.

Results:
Thirty patients were enrolled. The ORR was 48.0%: 2 (7%) complete responses (CR), 11 (41%) partial responses (PR), and 8 (30%) stable disease (SD). The median DOR for patients with CR or PR was 6.4 months [95% confidence interval (CI), 4–8.5 months]. For patients with CR, DOR was &gt;24 months. Overall median PFS and OS were 5.8 (95% CI, 4.7–8.5 months) and 13.4 months (8.9–17.3 months), respectively. We identified unique transcriptomic landscapes associated with each RECIST category of radiographic treatment response. In CR and durable PR, IGHG1 expression was enriched. IGHG1high tumors were associated with improved OS (P = 0.045) and were concurrently enriched with B cells and follicular helper T cells, indicating IGHG1 as a promising marker for lymphocytic infiltration and robust response to chemo-immunotherapy.

Conclusions:
Pretreatment tissue sampling in mTNBC treated with CNP reveals transcriptomic signatures that may predict radiographic responses to chemo-immunotherapy.
Activation of KrasG12D in Subset of Alveolar Type II Cells Enhances Cellular Plasticity in Lung Adenocarcinoma
Authors: Chaudhary Priyanka , Xu Xia , Wang Guangfang , Hoj Jacob P. , Rampersad Rishi R. , Asselin-Labat Marie-Liesse , Ting Stephanie , Kim William , Tamayo Pablo , Pendergast Ann Marie , Onaitis Mark W. 
Published: October 2023

Abstract

We have previously identified alveolar type II cell as the cell-of-origin of KrasG12D-induced lung adenocarcinoma using cell lineage–specific inducible Cre mouse models. Using gain-of-function and loss-of-function genetic models, we discovered that active Notch signaling and low Sox2 levels dictate the ability of type II cells to proliferate and progress into lung adenocarcinoma upon KrasG12D activation. Here, we examine the phenotype of type II cells after Kras activation and find evidence for proliferation of cells that coexpress type I and type II markers. Three-dimensional organoid culture and transplantation studies determine that these dual-positive cells are highly plastic and tumor initiating in vivo. RNA sequencing analysis reveals that these dual-positive cells are enriched in Ras/MAPK, EGFR, and Notch pathways. Furthermore, the proliferation of these cells requires active Notch signaling and is inhibited by genetic/chemical Sox2 upregulation. Our findings could provide new therapeutic strategies to target KRAS-activated lung adenocarcinomas.

Significance:
Identification of progenitor like tumor-initiating cells in KRAS-mutant lung adenocarcinoma may allow development of novel targeted therapeutics.
SIX4 Controls Anti-PD-1 Efficacy by Regulating STING Expression
Authors: Liang Beiyuan , Zhang Evan H. , Ye Zhen , Storts Hayden , Jin Wei , Zheng Xinru , Hylton Hannah , Zaleski Olivia , Xing Xuanxuan , Miles Wayne , Wang Jing J. 
Published: October 2023

Abstract

The cGAS/STING cytosolic DNA-sensing pathway plays a significant role in antitumor immunity. Expression of STING is tightly regulated and commonly reduced or defective in many types of cancer. We have identified SIX4 as a significant regulator of STING expression in colon cancer cells. We showed that knockout of SIX4 decreased STING expression at the mRNA and protein levels while ectopic expression of SIX4 increased STING expression. Depletion of SIX4 led to attenuated STING activation and downstream signaling. Reexpression of SIX4 or ectopic expression of STING in SIX4 knockout cells reversed the effect. Ectopic expression of SIX4 enhanced DMXAA and cGAMP-induced STING activation and downstream signaling. Importantly, decrease of SIX4 expression substantially decreased tumor infiltration of CD8+ T cells and reduced the efficacy of PD-1 antibodies to diminish tumor growth in immune competent mice in vivo. Finally, analysis of The Cancer Genome Atlas colon cancer dataset indicated that tumors with high SIX4 expression were significantly enriched in the Inflammatory Response pathway. SIX4 expression also correlated with expression of multiple IFN-stimulated genes, inflammatory cytokines, and CD8A. Taken together, our results implicate that SIX4 is a principal regulator of STING expression in colon cancer cells, providing an additional mechanism and genetic marker to predict effective immune checkpoint blockade therapy responses.

Significance:
Our studies demonstrate that SIX4 is an important regulator of STING expression, providing a genetic marker or a therapeutic target to predict or enhance immune checkpoint blockade therapy responses in colon cancer.
Um café com a Medusa, Ana Martins Marques e Hélène Cixous
Authors: Gelmini Juliana dos Santos 
Published: October 2023

Ana Martins Marques (Belo Horizonte, 1977) é uma das vozes protagonistas na cena da poesia brasileira contemporânea. Meu objetivo neste artigo é investigar a reescrita da figura feminina Medusa, a partir da leitura crítico-interpretativa do poema “Um café com a Medusa”, publicado no livro Risque esta palavra (2021), tomando por base a crítica feminista de Hélène Cixous, em O riso da Medusa. Neste poema, vemos o deslocamento da representação da personagem feminina da condição de objeto para sujeito do discurso, como pretendia Beauvoir, no livro considerado como fundador do feminismo O segundo sexo. Para nós, com Ana Martins Marques e Cixous, “basta olhar a Medusa de frente para vê-la: ela não é mortal. Ela é bela, e ela ri” (CIXOUS, 2022, p. 62).
Beariz Sarlo, professora (um comentário sobre o método)
Authors: Kremer Natan Schmitz , Fernandez Vaz Alexandre 
Published: October 2023

Resenha de SARLO, Beatriz. Clases de literatura argentina: Facultad de Filosofía y Letras, UBA, 1984-1988. Editado por Sylvia Saítta. Buenos Aires: Siglo XXI, 2022
Qual o lugar das neurociências na educação?
Authors: Louzada Fernando , Moreno-Louzada Luca 
Published: October 2023

Nas últimas décadas surgiram inúmeras iniciativas com o objetivo de estabelecer uma ponte entre neurociências e educação. Algumas destas iniciativas tentaram precipitar o surgimento de novas disciplinas, como por exemplo a neuroeducação, criando a ideia de que neurociência poderia ser prescritiva para a educação. Neste artigo, discordamos dessa ideia e apresentamos quais as contribuições que a neurociência pode trazer para a educação diante dos desafios de se aproximar áreas de conhecimento tão distintas.
Imaging of Angiogenesis in White Matter Hyperintensities
Authors: Ding Lingling , Hou Bo , Zang Jie , Su Tong , Feng Feng , Zhu Zhaohui , Peng Bin 
Published: October 2023

Background
White matter hyperintensities (WMHs) are areas of increased signal intensity on T2‐weighted magnetic resonance imaging (MRI). WMH penumbra may be a potential target for early intervention in WMHs. We explored the relationship between angiogenesis and WMH penumbra in patients with WMHs.

Methods and Results

Twenty‐one patients with confluent WMHs of Fazekas grade ≥2 were included. All the participants underwent
68
Ga‐NOTA‐PRGD2 positron emission tomography/magnetic resonance imaging. WMH penumbra was analyzed with masks created for the WMH and 7 normal‐appearing white matter layers; each layer was dilated away from the WMH by 2 mm. Angiogenesis array and ELISA were used to detect the serum levels of angiogenic factors, inflammatory factors, HIF‐1 alpha, and S100B. Fourteen patients with increased
68
Ga‐NOTA‐PRGD2 maximum standardized uptake (>0.17) were classified into group 2. Seven patients with maximum standardized uptake ≤0.17 were classified as group 1. WMH volume and serum levels of integrin αvβ3, vascular endothelial growth factor receptor 22, and interleukin‐1β tended to be higher in group 2 than in group 1. In group 2,
68
Ga‐NOTA‐PRGD2 uptake was significantly increased at the border between the WMH and normal‐appearing white matter than in WMHs (
P
=0.004). The structure penumbra, defined by fractional anisotropy, was wider in group 2 (8 mm) than in group 1 (2 mm). The cerebral blood flow penumbra was 12 mm in both groups. Angiogenesis showed a correlation with reduced cerebral blood flow and microstructure integrity.

Conclusions
Our study provides evidence that angiogenesis occurs in the WMH penumbra. Further studies are warranted to verify the effect of angiogenesis on WMH growth.
Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study
Authors: Shah Ravi V. , Hwang Shih‐Jen , Murthy Venkatesh L. , Zhao Shilin , Tanriverdi Kahraman , Gajjar Priya , Duarte Kevin , Schoenike Mark , Farrell Robyn , Brooks Liana C. , Gopal Deepa M. , Ho Jennifer E. , Girerd Nicholas , Vasan Ramachandran S. , Levy Daniel , Freedman Jane E. , Lewis Gregory D. , Nayor Matthew 
Published: October 2023

Background
While exercise impairments are central to symptoms and diagnosis of heart failure with preserved ejection fraction (HFpEF), prior studies of HFpEF biomarkers have mostly focused on resting phenotypes. We combined precise exercise phenotypes with cardiovascular proteomics to identify protein signatures of HFpEF exercise responses and new potential therapeutic targets.

Methods and Results

We analyzed 277 proteins (Olink) in 151 individuals (N=103 HFpEF, 48 controls; 62±11 years; 56% women) with cardiopulmonary exercise testing with invasive monitoring. Using ridge regression adjusted for age/sex, we defined proteomic signatures of 5 physiological variables involved in HFpEF: peak oxygen uptake, peak cardiac output, pulmonary capillary wedge pressure/cardiac output slope, peak pulmonary vascular resistance, and peak peripheral O
2
extraction. Multiprotein signatures of each of the exercise phenotypes captured a significant proportion of variance in respective exercise phenotypes. Interrogating the importance (ridge coefficient magnitude) of specific proteins in each signature highlighted proteins with putative links to HFpEF pathophysiology (eg, inflammatory, profibrotic proteins), and novel proteins linked to distinct physiologies (eg, proteins involved in multiorgan [kidney, liver, muscle, adipose] health) were implicated in impaired O
2
extraction. In a separate sample (N=522, 261 HF events), proteomic signatures of peak oxygen uptake and pulmonary capillary wedge pressure/cardiac output slope were associated with incident HFpEF (odds ratios, 0.67 [95% CI, 0.50–0.90] and 1.43 [95% CI, 1.11–1.85], respectively) with adjustment for clinical factors and B‐type natriuretic peptides.

Conclusions
The cardiovascular proteome is associated with precision exercise phenotypes in HFpEF, suggesting novel mechanistic targets and potential methods for risk stratification to prevent HFpEF early in its pathogenesis.
Serum Cholesterol and Impact of Age on Coronary Heart Disease Death in More Than 4 Million Veterans
Authors: Nguyen Xuan‐Mai T. , Ho Yuk‐Lam , Li Yanping , Song Rebecca J. , Leung Kenneth H. , Rahman Saad Ur , Orkaby Ariela R. , Vassy Jason L. , Gagnon David R. , Cho Kelly , Gaziano J. Michael , Wilson Peter W. F. 
Published: October 2023

Background
The lipid hypothesis postulates that lower blood cholesterol is associated with reduced coronary heart disease (CHD) risk, which has been challenged by reports of a U‐shaped relation between cholesterol and death in recent studies. We sought to examine whether the U‐shaped relationship is true and to assess the impact of age on this association.

Method and Results
We conducted a prospective cohort study of 4 467 942 veterans aged >18 years, with baseline outpatient visits from 2002 to 2007 and follow‐up to December 30, 2018, in the Veterans Health Administration electronic health record system. We observed a J‐shaped relation between total cholesterol (TC) and CHD mortality after a comprehensive adjustment of confounding factors: flat for TC <180 mg/dL, and greater risk was present at higher cholesterol levels. Compared with veterans with TC between 180 and 199 mg/dL, the multiadjusted hazard ratios (HRs) for CHD death were 1.03 (95% CI, 1.02–1.04), 1.07 (95% CI, 1.06–1.09), 1.15 (95% CI, 1.13–1.18), 1.25 (95% CI, 1.22–1.28), and 1.45 (95% CI, 1.42–1.49) times greater among veterans with TC (mg/dL) of 200 to 219, 220 to 239, 140 to 259, 260 to 279 and ≥280, respectively. Similar J‐shaped TC‐CHD mortality patterns were observed among veterans with and without statin use at or before baseline.

Conclusions
The cholesterol paradox, for example, higher CHD death in patients with a low cholesterol level, was a reflection of reverse causality, especially among older participants. Our results support the lipid hypothesis that lower blood cholesterol is associated with reduced CHD. Furthermore, the hypothesis remained true when TC was low due to use of statins or other lipid‐lowering medication.
Rurality and Atrial Fibrillation: Patient Perceptions of Barriers and Facilitators to Care
Authors: Mann Harnoor K. , Streiff Meg , Schultz Kevan C. , Halpern David V. , Ferry Danielle , Johnson Amber E. , Magnani Jared W. 
Published: October 2023

Background
Patients experience atrial fibrillation (AF) as a complex disease given its adversity, chronicity, and necessity for long‐term treatments. Few studies have examined the experience of rural individuals with AF. We conducted qualitative assessments of patients with AF residing in rural, western Pennsylvania to identify barriers and facilitators to care.

Methods and Results
We conducted 8 semistructured virtual focus groups with 42 individuals living in rural western Pennsylvania using contextually tailored questions to assess participant perspectives. We inductively analyzed focus group transcripts using paragraph‐by‐paragraph and focused coding to identify themes with the qualitative description approach. We used Krippendorff α scoring to determine interreviewer reliability. We harnessed investigator triangulation to augment the reliability of our findings. We reached thematic saturation after coding 8 focus groups. Participants were 52.4% women, with a median age of 70.9 years (range, 54.5–82.0 years), and most were White race (92.9%). Participants identified medication costliness, invisibility of AF to others, and lack of emergent transportation as barriers to care. Participants described interpersonal support and use of technology as important for AF self‐care, and expressed ambivalence about how relationships with health care providers affected AF care.

Conclusions
Focus group participants described multiple social and structural barriers to care for AF. Our findings highlight the complexity of the experience of individuals with AF residing in rural western Pennsylvania.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT 04076020.
Ecumenism Begins at Home: Orthodoxy and the Romanian Greek Catholic Church
Authors: Ladouceur Paul 
Published: October 2023

Abstract
This article examines the relations of the Romanian Orthodox Church (RoOC) towards the Romanian Greek Catholic Church (rgcc), a Byzantine rite church formed around 1700. Until World War ii, the rgcc was a substantial ecclesial entity, but in 1948 the new communist leaders of Romanian dissolved the ugcc and seized its properties, allowing the RoOC the use of most religious properties. Former rgcc clergy who did not join the RoOC were persecuted, but the church survived underground, emerging in 1989 with considerably fewer adherents than in 1948. Attempts by the rgcc to recover properties seized in 1948 were met with strong resistance by RoOC hierarchy and parishes. Notwithstanding the involvement of the RoOC in ecumenical undertakings, it has not acted in accordance with Christian principles and in conflict with its commitment to ecumenism, by supporting the dissolution of the rgcc, and its opposition to the restoration of seized properties.
Shikhat, Nashat and (Un)serious Theory
Authors: El Maarouf Moulay Driss , Belghazi Taieb , El Maarouf Farouk 
Published: October 2023

Abstract
In nashat-loaded circles, the shikha, claiming the center of her pedestal, asks the question: ‘al-hlawa fin kayna?’ (sweetness, where is it?). She pauses tantalizingly and looks around, but no one offers an answer. She inquires again with a smile. As she proceeds, what seems like mere initiation into eroticism and sensuality becomes a deeply philosophical pursuit of the rather far-flung meanings of the female and her body. While the shikha is no academician, she constructs through dance and lyrics a body of thought that navigates across a constellation of dialectics: female prevailing/alternative realities, gaming/thinking, play/seriousness and representation/agency. This article discusses female performers not as the embodiment of the carnivalesque, parodism, playfulness, profanity and voyeurism but as potential theorists in the domain of nashat where speculations on the existence of sweetness can easily become about its absence, deficiency and lack. It also addresses shikhat as potential theory-makers and proto-philosophers oscillating between epistemic margins and centers while leading the popular musical and performative scenes with primordial advice, guidance, teaching and wisdom.
The Changing Landscape of Medieval Chinese Customs: Focusing on Sitting Positions
Authors: Gu Tao 
Published: October 2023

Abstract
From the Wei-Jin through Tang-Song periods, social structures and customs in China underwent great change. In the case of sitting positions, these periods saw a shift from the “floor-sitting era” prior to the Qin to the “era of raised sitting” following the Tang and Song dynasties. In the interim, there was a period where the seated squat (juzuo 踞坐) made an appearance. This position is depicted in the “Man seated on foreign stool” detail of the scroll painting, Bei Qi jiaoshu tu 北齊校 書圖. During the Liu Song dynasty, monks at the Qihuan Temple ate in a seated squat and were vehemently lambasted by scholar-officials led by Fan Tai, instigating political debate around the sitting position. From a Confucian point of view, sitting positions are divided into two categories based on whether the calves or the bottoms of one’s feet touch the ground: the first includes kneeling, the sitting kneel, and the lotus positions, while the second includes squatting, sitting with legs outstretched, and the seated squat positions. Shifts in sitting positions reflect not only subtle changes taking place across various aspects of Chinese social customs and daily life, but also structural change on a systemic level. On the ideological front, obscure learning of the Wei and Jin dynasties exposed abuses of Confucian ethics. Compounded with the onslaught of foreign cultural influences such as Buddhism, it is no wonder, in this context of great historical upheaval, that efforts to preserve Confucianism would end in failure.
Song Dynasty Family Rituals and the Reconstruction of Confucian Daily Life
Authors: Lu Minzhen 
Published: October 2023

Abstract
The reconstruction of Confucianism during the Song dynasty is an important issue in the history of Chinese thought. Song scholar-officials not only introduced ideological innovations and founded the new type of Confucianist “School of Universal Principle” known as “Neo-Confucianism,” but also, in their reconstruction of Confucianism, attended to the specific rituals and introduced the concepts and values of the school into people’s daily life and habits. The observance of ritual privately at home – using ritual to “instruct” and “admonish” the family – became the way for scholar-officials to embody Confucian values effectively in daily life. Song family rituals developed differences from previous eras with respect to text, structure, and meaning. However, as rituals that comprehensively arranged the order of Confucian daily life, they were not merely a static Neo-Confucian text and system. Rather, scholar-officials’ ritual activities were always the concrete, dynamic aspect of the Confucian revival movement. Therefore, we must begin the discussion of family rituals from a wider perspective, first by exploring the motivation and goals of scholar-officials’ rituals. We will then discover how frustrated and compromised scholar-officials of the period felt when the pattern of daily life they had created proved difficult to accommodate to the real world. We will finally take note of the value system that this pattern was meant to demonstrate.
Two new species of Phalangium (Opiliones: Phalangiidae) from Turkey
Authors: KURT KEMAL , ERDEK MELEK , KURT PINAR 
Published: October 2023

Two new harvestmen species, Phalangium nalanae sp. n. and Phalangium taylani sp. n., are described, diagnosed and illustrated based on male material from Hakkari Province, Turkey. Also, the differences between two new species and similar species of the genus Phalangium are discussed.