bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uma interpretação rawlsiana da Constituição: considerações agonísticas sobre a democracia brasileira
Authors: Schargel Sergio , Leal João Gabriel Ribeiro Pessanha 
Published: December 2022

Na concepção de John Rawls, o consenso sobreposto consiste na formulação de uma instância de tolerância mútua que torna democracias possíveis. Entendimento de que para uma democracia funcionar é necessário que os agentes políticos respeitem direitos de seus oponentes, ainda que discordem de suas crenças, uma noção que dialoga com a ideia de Chantal Mouffe sobre democracia agonística. A democracia agonística, casando as ideias de Rawls com as de Bobbio e Mouffe, depende do respeito pelo consenso sobreposto, pela própria existência da democracia. É pertinente utilizar as reflexões teóricas desses autores para perceber suas absorções pela Constituição Federal de 1988, em especial as noções rawlsianas. Da mesma forma, perceber a fragilização das noções dos princípios de justiça e do consenso sobreposto conforme sucessivas crises – política, saúde, econômica – colocam a própria Constituição em cheque. Assim, a proposta deste trabalho é deslocar a teoria de John Rawls para compreender seus diálogos com a Constituição de 1988, ante a hipótese de que a fragilização democrática brasileira, seguida da eleição de um nacionalista autoritário em 2018, erode essas próprias noções por dentro. Destarte, através do diálogo entre a base teórica e o objeto apreendido, será possível contribuir para o estado da arte ao alargar os conceitos rawlsianos para a interpretação de um objeto periférico na academia, e permitindo, em última instância, perceber a essencialidade das concepções de Rawls para a existência de uma democracia liberal saudável e estável.
ANDRADE, Everaldo de Oliveira (Org.). Economia socialista: experiências históricas de planificação econômica e debates sobre transição hoje. São Paulo: Maria Antônia, 2022. 295 p.
Authors: Paulino Davi Luiz 
Published: December 2022

Resenha do livro ANDRADE, Everaldo de Oliveira (Org.). Economia socialista: experiências históricas de planificação econômica e debates sobre transição hoje. São Paulo: Maria Antônia, 2022. 295 p.
Bicuspid Aortic Valve–Associated Regulatory Regions Reveal
GATA4
Regulation and Function During Human-Induced Pluripotent Stem Cell–Based Endothelial-Mesenchymal Transition—Brief Report
Authors: Huang Tingting , Cheng Jiaxi , Feng Hao , Zhou Wei , Qiu Ping , Zhou Dong , Yang Dongshan , Zhang Jifeng , Willer Cristen , Chen Y. Eugene , Mizrak Dogukan , Yang Bo 
Published: December 2022

Background:
The endothelial-mesenchymal transition (EndoMT) is a fundamental process for heart valve formation and defects in EndoMT cause aortic valve abnormalities. Our previous genome-wide association study identified multiple variants in a large chromosome 8 segment as significantly associated with bicuspid aortic valve (BAV). The objective of this study is to determine the biological effects of this large noncoding segment in human induced pluripotent stem cell (hiPSC)-based EndoMT.

Methods:

A large genomic segment enriched for BAV-associated variants was deleted in hiPSCs using 2-step CRISPR/Cas9 editing. To address the effects of the variants on
GATA4
expression, we generated CRISPR repression hiPSC lines (CRISPRi) as well as hiPSCs from BAV patients. The resulting hiPSCs were differentiated to mesenchymal/myofibroblast-like cells through cardiovascular-lineage endothelial cells for molecular and cellular analysis. Single-cell RNA sequencing was also performed at different stages of EndoMT induction.

Results:

The large deletion impaired hiPSC-based EndoMT in multiple biallelic clones compared with their isogenic control. It also reduced
GATA4
transcript and protein levels during EndoMT, sparing the other genes nearby the deletion segment. Single-cell trajectory analysis revealed the molecular reprogramming during EndoMT. Putative GATA-binding protein targets during EndoMT were uncovered, including genes implicated in endocardial cushion formation and EndoMT process. Differentiation of cells derived from BAV patients carrying the rs117430032 variant as well as CRISPRi repression of the rs117430032 locus resulted in lower
GATA4
expression in a stage-specific manner. TWIST1 was identified as a potential regulator of
GATA4
expression, showing specificity to the locus tagged by rs117430032.

Conclusions:

BAV-associated distal regions regulate
GATA4
expression during hiPSC-based EndoMT, which in turn promotes EndoMT progression, implicating its contribution to heart valve development.
The Serum- and Glucocorticoid-Inducible Kinase 1 (SGK1) as a Novel Therapeutic Target in Mantle Cell Lymphoma
Authors: Li Jiao , Yu Hui , Wang Xing , Ye Yingying , Fang Wei , Ding Ning , Mi Lan , Ping Lingyan , Wang Xiaogan , Song Yuqin , Zhu Jun 
Published: December 2022

Introduction Mantle cell lymphoma (MCL) is an aggressive and incurable B-cell-derived malignant disease. MCL is treated using general chemotherapy; however, disease progression and relapse are common; thus, the development of novel therapeutic targets for treatment of MCL is urgently required. Serum- and glucocorticoid-inducible kinase 1 (SGK1) is involved in various cellular activities, and its dysregulation contributes to the pathogenesis of multiple types of cancer. However, little is known regarding its functional roles and associated molecular mechanisms in MCL. Methods SGK1 inhibition mediated by either shRNA or treatment with SGK1 inhibitor (GSK650394) was conducted in MCL cell lines. Western blotting analysis was performed to figure out the expression of related proteins. MCL-cell-derived xenograft models were constructed to evaluate the anti-tumor effects of SGK1 inhibition or/and Bruton’s tyrosine kinase (BTK) inhibition in vivo. Results In this study, it was shown that inhibition of SGK1 significantly reduced cell proliferation, invasion and migration, increased apoptosis and blocked cell cycle progression in MCL cells. Furthermore, SGK1 inhibition significantly reduced the activation of ERK, AKT/mTOR, JAK2/STAT3 and the NF-κB signaling pathways. Using MCL-cell-derived xenograft mice models, SGK1 inhibition decreased tumor cell proliferation and tumor growth. Importantly, SGK1 overexpression significantly promoted xenograft tumor growth. Moreover, simultaneous inhibition of SGK1 and Bruton tyrosine kinase (BTK) resulted in synergistic anti-tumor effects on MCL both in vitro and in vivo. Conclusion SGK1 may be a novel candidate therapeutic target and simultaneous inhibition of SGK1 and BTK may be a promising therapeutic strategy for MCL patients. Further pre-clinical and even clinical studies of SGK1 inhibitor or combination with BTK inhibitor are essential.
Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas
Authors: Lynch Ryan C. , Poh Christina , Ujjani Chaitra S. , Warren Edus H. , Smith Stephen D. , Shadman Mazyar , Morris Karolyn , Lee Sydney , Rasmussen Heather , Ottemiller Susan , Shelby Megan , Keo Sarith , Verni Kaitlin , Kurtz David M. , Alizadeh Ash A. , Chabon Jacob J. , Hogan Gregory J. , Schulz Andre , Gooley Ted , Voutsinas Jenna M. , Gopal Ajay K. 
Published: December 2022

Abstract
The POLARIX trial demonstrated the superiority of polatuzumab vedotin (Pola) over vincristine in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) regimen for large B-cell lymphomas, but it is unknown whether Pola can be safely incorporated into intensified regimens (eg, dose-adjusted [DA]–EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab]) typically used for the highest risk histologies. This was a single-center, open-label, prospective clinical trial of 6 cycles of Pola-DA-EPCH-R (vincristine omitted) in aggressive large B-cell lymphomas. The primary end point was to estimate the safety of Pola-DA-EPCH-R as measured by the rate of dose-limiting toxicities (DLTs) in the first 2 cycles with prespecified suspension rules. Secondary and exploratory end points included efficacy and correlation with circulating tumor DNA (ctDNA) levels. We enrolled 18 patients on study, and with only 3 DLTs observed, the study met its primary end point for safety. There were 5 serious adverse events, including grade 3 febrile neutropenia (3, 17%), grade 3 colonic perforation in the setting of diverticulitis, and grade 5 sepsis/typhlitis. Among 17 evaluable patients, the best overall response rate was 100%, and the complete response rate was 76%. With a median follow-up of 12.9 months, 12-month event-free survival was 72%, and 12-month overall survival was 94%. No patient with undetectable ctDNA at the end of treatment has relapsed to date. Using Pola to replace vincristine in the DA-EPOCH-R regimen met its primary safety end point. These data support the further evaluation and use of this approach in histologies where the potential benefit of both an intensified regimen and Pola may be desired. This trial was registered at www.clinicaltrials.gov as #NCT04231877.
Improved Subthreshold Characteristics by Back-Gate Coupling on Ferroelectric ETSOI FETs
Authors: Zhang Zhaohao , Li Yudong , Xu Jing , Tang Bo , Xiang Jinjuan , Li Junjie , Zhang Qingzhu , Wu Zhenhua , Yin Huaxiang , Luo Jun , Wang Wenwu 
Published: December 2022

AbstractIn this work, extremely thin silicon-on-insulator field effective transistors (ETSOI FETs) are fabricated with an ultra-thin 3 nm ferroelectric (FE) hafnium zirconium oxides (Hf0.5Zr0.5O2) layer. Furthermore, the subthreshold characteristics of the devices with double gate modulation are investigated extensively. Contributing to the advantages of the back-gate voltage coupling effects, the minimum subthreshold swing (SS) value of a 40 nm ETSOI device could be adjusted from the initial 80.8–50 mV/dec, which shows ultra-steep SS characteristics. To illustrate this electrical character, a simple analytical model based on the transient Miller model is demonstrated. This work shows the feasibility of FE ETSOI FET for ultra-low-power applications with dynamic threshold adjustment.
Challenges of using external data in clinical trials- an illustration in patients with COVID-19
Authors: Chevret Sylvie , Timsit Jean-François , Biard Lucie 
Published: December 2022

Abstract
Background
To improve the efficiency of clinical trials, leveraging external data on control and/or treatment effects, which is almost always available, appears to be a promising approach.

Methods
We used data from the experimental arm of the Covidicus trial evaluating high-dose dexamethasone in severely ill and mechanically ventilated COVID-19 patients, using published data from the Recovery trial as external data, to estimate the 28-day mortality rate. Primary approaches to deal with external data were applied.

Results
Estimates ranged from 0.241 ignoring the external data up to 0.294 using hierarchical Bayesian models. Some evidence of differences in mortality rates between the Covidicus and Recovery trials were observed, with an matched adjusted odds ratio of death in the Covidicus arm of 0.41 compared to the Recovery arm.

Conclusions
These indirect comparisons appear sensitive to the method used. None of those approaches appear robust enough to overcome randomized clinical trial data.

Trial registration
Covidicus Trial: NCT04344730, First Posted: 14/04/2020; Recovery trial: NCT04381936
Lipid accumulation product, visceral adiposity index and risk of chronic kidney disease
Authors: Bullen Alexander L. , Katz Ronit , Kumar Ujjala , Gutierrez Orlando M. , Sarnak Mark J. , Kramer Holly J. , Shlipak Michael G. , Ix Joachim H. , Judd Suzanne E. , Cushman Mary , Garimella Pranav S. 
Published: December 2022

Abstract
Background
Lipid accumulation product (LAP) and visceral adiposity index (VAI) are novel, non-imaging markers of visceral adiposity that are calculated by using body mass index (BMI), waist circumference (WC) and serum lipid concentrations. We hypothesized that LAP and VAI are more strongly associated with adverse kidney outcomes than BMI and WC.

Methods
Using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we used multivariable logistic regression to evaluate associations of LAP, VAI, BMI and WC with incident chronic kidney disease (CKD), (incident eGFR < 60 ml/min/1.73m2 and > 25% decline).

Results
Among the overall cohort of 27,550 participants, the mean baseline age was 65 years; 54% were women; and 41% were African American. After a median of 9.4 years (IQR 8.6, 9.9) of follow-up, a total of 1127 cases of incident CKD were observed. Each two-fold higher value of VAI (OR 1.12, 95% CI 1.04, 1.20), LAP (OR 1.21, 95% CI 1.13, 1.29), WC (OR 2.10, 95% CI 1.60, 2.76) and BMI (OR: 2.66, 95% CI 1.88, 3.77), was associated with greater odds of incident CKD.

Conclusions
LAP and VAI as measures of visceral adiposity are associated with higher odds of incident CKD but may not provide information beyond WC and BMI.
Magnetic resonance imaging negative myelopathy in Leber’s hereditary optic neuropathy: a case report
Authors: Martikainen Mika H. , Suomela Miika , Majamaa Kari 
Published: December 2022

Abstract
Background
Leber’s hereditary optic neuropathy (LHON) is a common form of mitochondrial disease. The typical clinical presentation of LHON is subacute, painless loss of vision resulting from bilateral optic nerve atrophy. Moreover, extra-ocular manifestations such as cardiac conduction abnormalities and neurological manifestations such as multiple sclerosis (MS) like disease or parkinsonism are encountered in some patients. Abnormal findings in spinal cord MR imaging or in the cerebrospinal fluid (CSF) have been observed in previous cases of LHON-associated myelopathy.

Case presentation
We report a male patient with LHON who developed symptoms of myelopathy including gait unsteadiness, enhanced deep tendon reflexes and sensory loss of the lower extremities. Imaging of the brain and spinal cord, CSF analysis, as well as neurography and electromyography did not disclose any abnormalities. The somatosensory evoked potential (SEP) findings were suggestive of dorsal column dysfunction.

Conclusions
The patient case demonstrates that myelopathy associated with LHON can present without abnormal findings in central nervous system MR imaging or in the CSF, and without evidence suggestive of multiple sclerosis or MS-like disease. The dorsal column seems to be particularly vulnerable to myelopathy changes in LHON. Evoked potential investigations may assist in confirming the diagnosis, when clinical features are in line with myelopathy but findings in CSF analysis and central nervous system imaging are normal.
Clinical-neuroimaging-pathological relationship analysis of adult onset Neuronal Intranuclear Inclusion Disease (NIID)
Authors: Mao Chenhui , Zhou Liangrui , Li Jie , Pang Junyi , Chu Shanshan , Jin Wei , Huang Xinying , Wang Jie , Liu Caiyan , Liu Qing , Hao Honglin , Zhou Yan , Hou Bo , Feng Feng , Shen Lu , Tang Beisha , Peng Bin , Cui Liying , Gao Jing 
Published: December 2022

Abstract
Background
Neuronal Intranuclear Inclusion Disease (NIID) is a degenerative disease with heterogeneous clinical manifestations. We aim to analysis the relationship between clinical manifestations, neuroimaging and skin pathology in a Chinese NIID cohort.

Methods
Patients were recruited from a Chinese cohort. Detail clinical information were collected. Visual rating scale was used for evaluation of neuroimaging. The relationship between clinical presentations and neuroimaging, as well as skin pathology was statistically analyzed.

Results
Thirty-two patients were recruited. The average onset age was 54.3 y/o. 28.1% had positive family history. Dementia, autonomic nervous system dysfunction, episodic attacks were three main presentations. CSF analysis including Aβ42 and tau level was almost normal. The most frequently involved on MRI was periventricular white matter (100%), frontal subcortical and deep white matter (96.6%), corpus callosum (93.1%) and external capsule (72.4%). Corticomedullary junction DWI high intensity was found in 87.1% patients. Frontal and external capsule DWI high intensity connected to form a “kite-like” specific image. Severity of dementia was significantly related to leukoencephalopathy (r = 0.465, p = 0.0254), but not cortical atrophy and ventricular enlargement. Grey matter lesions were significantly associated with encephalopathy like attacks (p = 0.00077) but not stroke like attacks. The density of intranuclear inclusions in skin biopsy was not associated with disease duration, severity of leukoencephalopathy and dementia.

Conclusions
Specific distribution of leukoencephalopathy and DWI high intensity were indicative. Leukoencephalopathy and subcortical mechanism were critical in pathogenesis of NIID. Irrelevant of inclusion density and clinical map suggested the direct pathogenic factor need further investigation.
Thyroid dysfunction in pregnancy - a retrospective observational analysis of a Maltese cohort
Authors: Vella Katia , Vella Sandro , Savona-Ventura C. , Vassallo J. 
Published: December 2022

AbstractBackgroundThyroid dysfunction is known to adversely affect pregnancy. This study evaluates the prevalence of thyroid disorders and explores their association with pregnancy complications/comorbidities and modes of delivery in the Maltese pregnant population over a ten year period.DesignA population based observational study.MethodWe analysed data from the National Obstetrics Information Service of the Department of Health Informations and Research (NOIS) for all births delivered in Malta between 2006 and 2016. Cases identified and recorded by NOIS to have had some form of thyroid dysfunction during pregnancy were confirmed by cross-referencing with laboratory results found in patients’ medical records and/or iSOFT® database system. Using the Statistical Package for the Social sciences (SPSS®) demographic data, past obstetric and medical history and obstetric outcomes were analysed for pregnancies with thyroid dysfunction and compared to data pertaining to pregnancies in euthyroid patients, that is those with no recorded thyroid dysfunction on NOIS. Chi square/Fisher's exact test were used to compare categorical variables while ANOVA/Mann-Whitney U test was used to compare continuous variables. Statistical significance was defined by a two-sidedpvalue <0.05.ResultsData was available for 46,283 women (mean [SD] age = 29.2 [5.4] years). 587 pregnancies (1.3%) suffered from thyroid dysfunction. Of these, 67.3% were hypothyroid, 3.2% had hyperthyroidism, 28.3% had isolated hypothyroxinaemia (IHT) while 1.2% had a history of thyroid carcinoma. Patients with IHT and hypothyroidism were older than euthyroid patients (p< 0.001). IHT and hypothyroid patients had a statistically significant higher body mass index (BMI) than euthyroid women (p=0.001 for hypothyroid women,p= 0.035 for IHT). Hypothyroid and IHT women were more likely to have had a previous lower segment caesarean section (p=0.043, and 0.006 respectively). Type 1 diabetes and gestational diabetes p= 0.012) were more common associated comorbidities in hypothyroid pregnancies. Offspring of patients with IHT had a higher birth weight than those born to euthyroid patients (p=0.009). Patients with hyperthyroidism were found to have a significantly increased risk of early preterm delivery before 34 weeks of gestation and were also more likely to have suspected intrauterine growth restriction and low mean birth weight. We report no significant differences in past history of obstetric loss, antenatal complications, mode of delivery, gestational age at delivery and postpartum haemorrhage rates across thyroid categories.ConclusionsAvailable evidence suggests that thyroid dysfunction is more likely in the setting of older age, and higher body mass index. Moreover, it impacts on neonatal birth weight, rates of early preterm delivery and intrauterine growth restriction.
Physical self-concept and ability to swim in patients born with anorectal malformation and Hirschsprung’s disease: a case control study
Authors: König Tatjana Tamara , Krude Mattis , Muensterer Oliver J. 
Published: December 2022

Abstract
Background
Children with anorectal malformation (ARM) and Hirschsprung’s Disease (HD) live with permanent urinary and bowel symptoms, possibly impairing motor development in early childhood. Not being able to swim adds an unnecessary health risk. The aim of this study was to determine the ability to swim and physical self-concept in patients with ARM and HD.

Methods
We performed an anonymous survey among the members of the national patient organization SoMA e.V. (6 through 25 years). A control group was recruited from our department. Ability to swim, symptom load according to Rintala Score and physical self-concept were recorded using validated questionnaires. Patients were matched with controls according to gender and age. Mean scores and 95%-confidence intervals (95%-CI) were calculated, χ2-test and multiple linear regression models were used as appropriate.

Results
Totally, 83 match-control-pairs were included. Patients learned to swim at a similar age and rate (6.5 years, 95%-CI: 6.1–6.9, 74.7% swimmers) compared to controls (6.4 years, 95%-CI: 6.1–6.8, 79.5% swimmers, p = 0.46). VACTERL patients had a significantly lower swimmer rate (59.1%, p = 0.048). Swimmers had a significantly higher mean Rintala Score (12.5, 95%-CI: 11.6–13.2) compared to non-swimmers (10.4, 95%-CI: 8.1–12.1, p = 0,049). In prepubertal children (6 through 12 years), no difference in physical self-concept was shown compared to controls. Adolescents and young adults with ARM/HD, especially females, had a significantly lower mean score for the subscales of flexibility, speed, endurance and sports competence, independent of bowel symptom load according to Rintala Score.

Conclusions
Patients with ARM/HD have normal swimming skills and a normal physical self-concept in childhood that decreases with age compared to peers. In adolescence, parents and health care professionals should actively promote physical activity in ARM/HD patients.