bluuebunny/crossref_metadata_2025 huggingface dataset:
Adolescentes com Transtornos por Uso de Substâncias: perfil, autoestima e transtornos mentais
Authors: Pereira Jefferson Luiz , Ramos Denise Gimenez , Ulisses Sofia Marques Viana
Published: June 2023

Objetivo: caracterizar o perfil do uso de substâncias,indicadores de transtornos mentais e a autoestima emadolescentes com diagnóstico de Transtorno por Uso deSubstâncias (TUS) internados em um hospital psiquiátrico(Grupo com TUS – GT), comparando-os a um grupo deadolescentes sem diagnóstico (Grupo de Comparação – GC).Metodologia: estudo descritivo, quantitativo e transversal,participaram 82 adolescentes do sexo masculino, entre 12 e18 anos. O perfil do uso de substâncias, os indicadores detranstornos mentais e a autoestima foram avaliados pormeio dos instrumentos: Alcohol, Smoking and SubstanceInvolvement Screening Test, Self-Reporting Questionnairee Escala de Autopercepção de Harter para Adolescentes.Resultados: o GT mostrou um alto nível de evasão escolar,envolvimento em atos infracionais e indicadores de humore pensamentos depressivos expressivamente superioresao GC. O uso de substâncias foi significativamente superiorno GT, excetuando-se o uso de álcool, que teve característicassemelhantes nos dois grupos. A autoestima global mostrou-serebaixada nos adolescentes do GT. Conclusão: foi possívelcaracterizar o perfil do uso de substâncias de adolescentes comTUS e as variáveis associadas a esse fenômeno. O tratamentode TUS nessa população deve ocorrer de forma multidisciplinare contextualizada, ressaltando-se a importância do cuidadocom os fatores de risco e as comorbidades.
Terapia ocupacional e a armadilha neoliberal progressista: desafios para uma práxis antiopressiva
Authors: Farias Magno Nunes , Lopes Roseli Esquerdo
Published: June 2023

Compreendendo as contradições que envolvem o neoliberalismo, e suas pretensões progressistas, é preciso se interrogar sobre as possíveis armadilhas que essas configurações sociais podem “construir” para disfarçar a sua malvadez, inviabilizando uma práxis terapêutico-ocupacional radicalmente antiopressiva, que não se deixe enganar pelas narrativas hegemônicas que tudo tentam cooptar. Parte dessas armadilhas, para nós, se desenha em relação com o fenômeno do identitarismo. De forma mais explícita, esses movimentos articulados – neoliberalismo progressista e identitarismo – representam um risco para a ação profissional contemporânea, reduzindo a compreensão dos sujeitos ao imediato, ao visível, ao individual e ao subjetivismo, por uma ação que lê o caminho do reconhecimento da identidade (colocada como fixa e separada das dinâmicas sociais) via, exclusivamente, o empoderamento individual/vazio/simbólico, podendo reafirmar um discurso meritocrata. Logo, é urgente empreender as lutas pelo reconhecimento das identidades em diálogo com a leitura do sujeito social em uma estrutura desigual e conjuntamente às lutas por redistribuição. Assim, a dimensão social objetiva e concreta, que se consolida na estrutura social, toma lugar na práxis terapêutico-ocupacional e vai de encontro aos movimentos que tentam negar (pela força ou pelo consenso) nossa ação comprometida com a antiopressão e com a transformação social.
Ang II Promotes ET-1 Production by Regulating NOX2 Activity Through Transcription Factor Oct-1
Authors: Kamhieh-Milz Julian , Chen Lei , Goettsch Claudia , Pfefferkorn Anna Maria , Hofmann Anja , Brunssen Coy , Müller Gregor M. , Walther Thomas , Ashraf Muhammad Imtiaz , Moll Guido , Morawietz Henning , Witowski Janusz , Catar Rusan
Published: June 2023

BACKGROUND:

Increasing evidence suggests that superoxide ions produced by NOX (nicotinamide adenine dinucleotide phosphate oxidases) mediate vascular effects of Ang II (angiotensin II) evoked by atherogenic diets. Here, we analyzed the mechanism by which NOX2 contributes to Ang II–induced ET-1 (endothelin 1) production in human microvascular endothelial cells.

METHODS:

The effects of high-fat diet were compared between WT (wild type) and
Nox2
(
mouse NOX2 gene
)-deficient mice. ET-1 production and NOX2 expression by human microvascular endothelial cells in vitro were analyzed by ELISA, reverse transcription quantitative polymerase chain reaction, electrophoretic mobility shift assay, promoter deletions, RNA interference, and pharmacological inhibition. Production of superoxide anions was visualized by fluorescent cell labeling.

RESULTS:

Feeding mice high-fat diet for 10 weeks increased cardiac expression and plasma levels of Ang II and ET-1 in WT but not in
Nox2
-deficient animals. Exposure of human microvascular endothelial cells to Ang II resulted in increased ET-1 production, which could be blocked by silencing
NOX2
(
human NOX2 gene
). Ang II promoted
NOX2
expression through induction of the Oct-1 (human/mouse octamer binding transcription factor 1 protein) and activation of the
NOX2
promoter region containing Oct-1–binding sites. Stimulation of
NOX2
expression by Ang II was associated with increased production of superoxide anions. Inhibition of Oct-1 by small interfering RNA reduced Ang II–induced
NOX2
expression and superoxide anion production, and neutralization of superoxide by SOD (superoxide dismutase) abolished Ang II–stimulated
ET1
(
human ET-1 gene
) promoter activity, ET1 mRNA expression, and ET-1 release.

CONCLUSIONS:

Ang II may promote ET-1 production in the endothelium in response to atherogenic diets through a mechanism that involves the transcription factor Oct-1 and the increased formation of superoxide anions by NOX2.
Localized Prox1 Regulates Aortic Valve Endothelial Cell Diversity and Extracellular Matrix Stratification in Mice
Authors: O’Donnell Anna , Gonzalez Brittany A. , Mukherjee Shreyasi , Wilson Ruby , Alfieri Christina M. , Swoboda Casey O. , Millay Douglas P. , Zorn Aaron M. , Yutzey Katherine E.
Published: June 2023

BACKGROUND:

Specialized valve endothelial cell (VEC) populations are localized oriented to blood flow in developing aortic and mitral valves, but their roles in valve development and disease are unknown. In the aortic valve (AoV), a population of VECs on the fibrosa side expresses the transcription factor Prox1 together with genes found in lymphatic ECs. In this study, we examine Prox1’s role in regulating a lymphatic-like gene network and promoting VEC diversity required for the development of the stratified trilaminar extracellular matrix (ECM) of murine AoV leaflets.

METHODS:

To determine whether disruption of Prox1 localization affects heart valve development, we generated mice (

NFATc1
enCre

Prox1
gain-of-function) in which Prox1 is overexpressed on the ventricularis side of the AoV beginning in embryonic development. To identify potential targets of Prox1, we performed cleavage under targets and release using nuclease on wild-type and

NFATc1
enCre

Prox1
gain-of-function AoVs with validation by colocalization in vivo using RNA in situ hybridization in

NFATc1
enCre

Prox1
gain-of-function AoVs. Natural induction of Prox1 and target gene expression was evaluated in myxomatous AoVs in a mouse model of Marfan syndrome (

Fbn1
C1039G/+

).

RESULTS:

The overexpression of Prox1 is sufficient to cause enlargement of AoVs by postnatal day (P)0, as well as a decrease in ventricularis-specific gene expression and disorganized interstitial ECM layers at P7. We identified potential targets of Prox1 known to play roles in lymphatic ECs including
Flt1
,
Efnb2
,
Egfl7
, and
Cx37
. Ectopic Prox1 colocalized with induced
Flt1
,
Efnb2
, and
Cx37
expression in

NFATc1
enCre

Prox1
gain-of-function AoVs. Moreover, in Marfan syndrome myxomatous AoVs, endogenous Prox1, and its identified targets, were ectopically induced in ventricularis side VECs.

CONCLUSIONS:

Our results support a role for Prox1 in localized lymphatic-like gene expression on the fibrosa side of the AoV. Furthermore, localized VEC specialization is required for development of the stratified trilaminar ECM critical for AoV function and is dysregulated in congenitally malformed valves.
Clinical Variation in the Treatment Practices for Patients With Type 2 Diabetes: A Cross‐Sectional Patient Simulation Study Among Primary Care Physicians and Cardiologists
Authors: De Belen Enrico , Ganesan Divya , Paculdo David , Gill Rosalynn , Peabody John W.
Published: June 2023

Background

Cardiovascular disease risk stratification is necessary and critically important in patients with type 2 diabetes. Despite its known benefits to guide treatment and prevention, we hypothesized that providers do not routinely incorporate this into their diagnostic and treatment decisions.

Methods and Results

The QuiCER DM (QURE CVD Evaluation of Risk in Diabetes Mellitus) study enrolled 161 primary care physicians and 80 cardiologists. Between March 2022 and June 2022, we measured the care variation in risk determination among these providers caring for simulated patients with type 2 diabetes. We found a wide variation in the overall assessment of cardiovascular disease in patients with type 2 diabetes. Participants performed half of the necessary care items with quality‐of‐care scores, ranging between 13% and 84%, averaging 49.4±12.6%. Participants did not assess cardiovascular risk in 18.3% of cases and incorrectly stratified risk in 42.8% of cases. Only 38.9% of participants arrived at the correct cardiovascular risk stratification. Those who correctly identified a cardiovascular risk score were significantly more likely to order nonpharmacologic treatments, advising on their patients' nutrition (38.8% versus 29.9%,
P
=0.013) and the correct glycated hemoglobin target (37.7% versus 15.6%,
P
<0.001). Pharmacologic treatments, however, did not vary between those who correctly specified risk and those who did not.

Conclusions

Physician participants struggled to determine the correct cardiovascular disease risk and specify the appropriate pharmacologic interventions in simulated patients with type 2 diabetes. Additionally, there was a wide variation in the quality of care regardless of risk level, indicating opportunities to improve risk stratification.
Left Ventricular Physiology and Ventricular‐Vascular Interactions in Young Patients After Heart Transplantation
Authors: Latus Heiner , Raap Ramona , Klingel Karin , Happel Christoph , Moysich Axel , Khalil Markus , Kerst Gunter , Milla Jakob , Skrzypek Susanne , Thul Josef , Jux Christian , Schranz Dietmar , Apitz Christian
Published: June 2023

Background

In patients after heart transplantation, systemic arterial hypertension and enhanced central aortic stiffness contribute to increased ventricular afterload, which might lead to graft dysfunction. The aim of our study was to characterize systemic arterial elastance and its impact on left ventricular function and ventriculo‐arterial coupling in a cohort of children, adolescents, and young adults after heart transplantation using invasive conductance catheter technique.

Methods and Results

Thirty patients who had heart transplants (age, 20.0±6.5 years, 7 female) underwent invasive cardiac catheterization including pressure‐volume loop analysis. Load‐independent parameters of systolic (ventricular elastance [Ees]) and diastolic (ventricular compliance) function as well as systemic arterial elastance (Ea, end‐systolic pressure/stroke volume) and ventriculo‐arterial coupling (Ea/Ees) were assessed at baseline level and during dobutamine infusion (10 μg/kg/min). Ees showed an appropriate increase under inotropic stimulation from 0.43 (0.11–2.52) to 1.00 (0.20–5.10) mm Hg/mL/m
2
(
P
<0.0001), whereas ventricular compliance remained rather unchanged (0.16±0.10 mm Hg/mL/m
2
to 0.12±0.07 mm Hg/mL/m
2
;
P
=0.10). Ventriculo‐arterial coupling Ea/Ees was abnormal at rest and did not improve significantly under dobutamine (1.7 [0.6–6.7] to 1.3 [0.5–4.9],
P
=0.70) due to a simultaneous rise in Ea from 0.71 (0.37–2.82) to 1.10 (0.52–4.03) mm Hg/mL/m
2
(
P
<0.0001). Both Ees and ventricular compliance were significantly associated with Ea at baseline and under dobutamine infusion.

Conclusions

Patients who underwent heart transplantation show impaired ventriculo‐arterial coupling at rest and under inotropic stimulation despite preserved left ventricular contractile reserve. An abnormal response in vascular function resulting in increased afterload seems to represent an important factor that may play a role for the development of late graft failure.
Pupil Size Encodes Uncertainty during Exploration
Authors: Fan Haoxue , Burke Taylor , Sambrano Deshawn Chatman , Dial Emily , Phelps Elizabeth A. , Gershman Samuel J.
Published: June 2023

Exploration is an important part of decision making and is crucial to maximizing long-term rewards. Past work has shown that people use different forms of uncertainty to guide exploration. In this study, we investigate the role of the pupil-linked arousal system in uncertainty-guided exploration. We measured participants' (n = 48) pupil dilation while they performed a two-armed bandit task. Consistent with previous work, we found that people adopted a hybrid of directed, random, and undirected exploration, which are sensitive to relative uncertainty, total uncertainty, and value difference between options, respectively. We also found a positive correlation between pupil size and total uncertainty. Furthermore, augmenting the choice model with subject-specific total uncertainty estimates decoded from the pupil size improved predictions of held-out choices, suggesting that people used the uncertainty estimate encoded in pupil size to decide which option to explore. Together, the data shed light on the computations underlying uncertainty-driven exploration. Under the assumption that pupil size reflects locus coeruleus-norepinephrine neuromodulatory activity, these results also extend the theory of the locus coeruleus-norepinephrine function in exploration, highlighting its selective role in driving uncertainty-guided random exploration.
Rural Administration, Tax-Farming, and the mutadarriks in Egypt from the Late 14th to the Early 16th Centuries
Authors: Igarashi Daisuke
Published: June 2023

This paper focuses on the category of Egyptian provincial officials called mutadarrik who emerged in the late 14th century, to understand the relationship between the government and rural areas, and the state of rural society in late medieval Egypt. After the mid-14th century, the iqṭāʿ land system underwent a major transformation. Amidst repeated plagues, declining agricultural production, rampant political instability, and the rise of Arab tribes in the provinces, the financial and local administrations of the Mamluk Sultanate underwent a substantial process of restructuring. This paper shows that the emergence of the mutadarrik was closely related to these changes in the administration as well as in rural society.
Place without an Owner: Urban Modernization and Waqf Property in post-Ottoman Niš
Authors: Radovanović Jelena
Published: June 2023

This article takes the example of post-Ottoman Niš to argue that the transformation of post-Ottoman cities was not a local, nationalism-induced architectural phenomenon, as suggested by the studies of “de-Ottomanization,” but rather a global development which was made possible through the dismantling of the local Ottoman legal regime of urban property. Focusing on the waqf as a quintessential Ottoman form of urban property, this article examines how war and displacement of the Muslim population on the one hand, and new associations between the modern city and particular forms of property on the other together contributed to the destruction of the waqf despite its protection by international law.
‘Do You Not Bow before Heaven?’: The First Qing- Durrānī Encounter, the Tributary Non-relationship, and Disorder on a Shared Frontier
Authors: Eijk Juul , Khan Timur
Published: June 2023

In 1763, Aḥmad Shāh Durrānī sent an embassy to the Qianlong emperor. The envoy caused offence by refusing to prostrate himself. Still, the Qing court fêted his embassy. It seemed the beginning of a promising relationship, but the two empires never had contact again. The Qing court presented the embassy as a tributary mission, but in the pragmatic world of Qing frontier policy, contact with the Durrānīs was deliberately avoided. Why did no relationship develop? This attitude stemmed from Qianlong’s distrust of Central Asian rulers, and his understanding of the Afghans not as a tributary, but a rival imperial power.
Twig-assisted masturbation in Balinese long-tailed macaques
Authors: Cenni Camilla , Wandia I Nengah , Leca Jean-Baptiste
Published: June 2023

We documented evidence of idiosyncratic but repeated twig-assisted genital stimulation by Balinese long-tailed macaques (Macaca fascicularis), living in Ubud, Indonesia. This population is known to customarily engage in genital stone-tapping/-rubbing, a behaviour expressed by males and females of different age classes as part of a broader cultural repertoire of stone-directed and overall playful actions known as stone handling. However, genital stimulation using other objects has never been reported in this population and species. We observed repeated and extensive twig-assisted genital stimulation in one adult female and one adult male. We also recorded three instances of twig-assisted genital stimulation in three additional individuals. Our results indicate that this behaviour is not accidental and may be sexually motivated; that is, it may be another form of tool-assisted masturbation in this primate population. This report provides a valuable addition to the increasing literature on tool-assisted behavioural innovations pertaining to self-care and possibly pleasure.
“Strictness is a Virtue” – Social Determination of Authoritarian Parenting and Political Authoritarianism
Authors: Zhussipbek Galym , Nagayeva Zhanar
Published: June 2023

Parenting and children’s rights are intimately related. The parenting styles characterised by low responsiveness to children’s needs, including authoritarian-paternalistic and those of neglect, are harmful to child’s development and contradict the main principles of children’s rights. The slow development of children’s rights in Kazakhstan and, in general, in the Eurasian1 context, derives from the social norms justifying authoritarian-paternalistic parenting, specifically, the widespread belief that “strictness is a virtue”. This article proposes and discusses the concepts of “social determination of authoritarian parenting” and “social determination of political authoritarianism”. The former concept denotes an embodiment of social norms that shape the parenting styles with low responsiveness to children’s needs, especially authoritarian-paternalistic. The latter suggests that authoritarianism is a product of social and cultural contexts, including parenting. These concepts, being mutually supportive phenomena, create the vicious circle of the persistency of authoritarianism in both politics and in child-rearing.
Redefining Inclusive Education for Autistic Children in International and European Law
Authors: Ducarre Lucie Margot
Published: June 2023

This paper focuses on the legal concept of inclusive education, and the challenges that its current interpretation raises, especially for autistic children. Centring on European and international law, it first analyses the sources and genesis of the current interpretation of inclusive education as full mainstream inclusion. It then proceeds critically to examine the conceptual and legal limitations this interpretation involves, before developing arguments for a more neurodiverse and rights-based alternative. Under this new interpretation, states would be required not only to render mainstream education more inclusive, but also to provide alternative educational offers for when mainstream education is not able to provide a neurodiverse and rights-based inclusive education.
The Future of Fixed-term Employment in India
Authors: Jain Kanupriya , Ghosh Piyali , Misra Shankha Shuvra
Published: June 2023

The industrial relations (IR) environment in India and its labour market, have been undergoing significant transformations in multiple domains for around two decades after the economic liberalization. Gillan and Lambert (2013) observe several restructurings at the workplace level in the country. These include, among others, farming out job functions or services to any third party through outsourcing, engaging contract labour in the organized sector, the tendency among managers to avoid acknowledging the right of trade unions to collectively bargain and the prevalence of voluntary retirement schemes for having numerical flexibility of the workforce.
Research on control strategy of an active magnetorheological fluid bearing based on improved gray wolf optimization approach
Authors: Peng Lai , Hua Dezheng , Liu Xinhua , Andriukaitis Darius , Królczyk Grzegorz , Li Zhixiong
Published: June 2023

In order to address the problems of insufficient load capacity and rotor vibration, an active fluid-film bearing lubricated with magnetorheological fluid (MRF) is proposed. First, the geometry of the MRF fluid-film bearing is designed and its intelligent lubrication mechanism is analyzed to clarify its advantages. In addition, mathematical model of MRF fluid-film bearing-rotor system is derived, and FEM model is utilized to obtain stiffness and damping coefficients to supplement mathematical model. Moreover, an improved gray wolf optimization (IGWO) algorithm is developed to tune the PID controller parameters. The validity of the proposed method is verified by numerical simulation. Furthermore, the simulation results show that with the increasing of current magnitude, the orbits of shaft center decrease. Under the presence of magnetic fields, the shaft center orbits of the MRF bearing can converge to a point, and therefore this bearing has ability to suppress rotor vibration. Finally, IGWO-PID controller has better response characteristics than GWO, PSO, and GA algorithms, and hence the IGWO algorithm can find the more appropriate PID controller parameters, that the validity of the improved algorithm is further proved. Therefore, the active bearing and its research findings provide new reference for MRF vibration control in the field of journal bearing lubrication.
Disruptiveness of COVID-19: Differences in Course Engagement, Self-Appraisal, and Learning
Authors: Ober Teresa M. , Cheng Ying , Carter Matthew F. , Liu Cheng
Published: June 2023

We investigated how the transition to remote instruction during the COVID-19 pandemic affected students’ engagement, self-appraisals, and learning in advanced placement (AP) Statistics courses. Participants included 681 (Mage=16.7 years, SDage=.90; %female=55.4) students enrolled in the course during 2017–2018 (N=266), 2018–2019 (N=200), and the pandemic-affected 2019–2020 (N=215) school years. Students enrolled during the pandemic-affected year reported a greater improvement in affective engagement but a decrease in cognitive engagement in the spring semester relative to a previous year. Females enrolled in the pandemic-affected year experienced a greater negative change in affective and behavioral engagement. Students enrolled during the pandemic-affected year reported a greater decrease in their anticipated AP exam scores and received lower scores on a practice exam aligned with the AP exam compared to a prior year. Although students were resilient in some respects, their self-appraisal and learning appear to have been negatively affected by pandemic circumstances.
Groundwater–rock interactions in crystalline rocks: evidence from SIMS oxygen isotope data
Authors: Yardley Bruce W.D. , Milodowski Antoni E. , Field Lorraine P. , Wogelius Roy A. , Metcalfe Richard , Norris Simon
Published: June 2023

The diffusive exchange of dissolved material between fluid flowing in a fracture and the enclosing wallrocks (rock matrix diffusion) has been proposed as a mechanism by which radionuclides derived from a radioactive waste repository may be removed from groundwater and incorporated into the geosphere. To test the effectiveness of diffusive exchange in igneous and metamorphic rocks, we have carried out an investigation of veins formed at low temperatures (<100°C), comparing the oxygen isotopic composition of vein calcite with that of secondary calcite in the wallrocks. Two examples of veins from the Borrowdale Volcanic Group, Cumbria, and one from the Mountsorrel Granodiorite, Leicestershire, UK, have remarkably similar vein calcite compositions, ca. +20‰(SMOW) or greater, substantially heavier than the probable compositions of the host rocks, and these vein calcite compositions are inferred to reflect the infiltrating fluid and the temperature of vein formation. Calcites from the wallrocks are similar to those in veins, with little evidence for exchange with the wallrocks. The results support existing models for this type of vein which suggest low-temperature growth from formation brines originally linked to Permian or Triassic evaporites. The results are consistent with flow through fractures being attenuated through a damage zone adjacent to the fracture and provide no evidence of diffusional exchange with pore waters from wallrocks.
Endogenous testosterone density associates with predictors of tumor upgrading and disease progression in the low through favorable intermediate prostate cancer risk categories: analysis of risk factors and clinical implications
Authors: Porcaro Antonio B. , Bianchi Alberto , Gallina Sebastian , Ditonno Francesco , Ornaghi Paola I. , Serafin Emanuele , Tafuri Alessandro , Panunzio Andrea , Cerrato Clara , Vidiri Stefano , D’Aietti Damiano , Mazzucato Giovanni , Rizzetto Riccardo , Amigoni Nelia , De Marco Vincenzo , Migliorini Filippo , Zecchini Antoniolli Stefano , Brunelli Matteo , Siracusano Salvatore , Cerruto Maria Angela , Antonelli Alessandro
Published: June 2023

Background

The study aimed to test the hypothesis that endogenous testosterone density (ETD), in the low through favorable intermediate PCa risk classes patients undergoing surgery, might be associated with disease progression.

Materials and methods

ETD, PSAD, and percentage of biopsy positive cores density (BPCD) were calculated in relation to prostate volume (PV). Tumor load density (TLD) was estimated as the tumor load (TL) ratio to prostate weight. ET was considered low if < 230 ng/dL. Tumor upgrading (ISUP > 2), upstaging (pT > 2) and their related features were investigated.

Results

433 patients were included, 249 (57.5%) from the favorable intermediate-risk class. Upgrading occurred in 168 (38.8%) cases and upstaging in 62 (14.3%). ETD above the median (9.9 ng/(dL x mL)), was discriminated by PSAD (AUC = 0.719; 95% CI: 0.671–0.766; p < 0.0001), BPCD (AUC = 0.721; 95% CI: 0.673–0.768; p < 0.0001), TLD (AUC = 0.674; 95% CI: 0.624–0.724; p < 0.0001) with accuracy improved by the multivariable model (AUC = 0.798; 95% CI: 0.724–0.811; p < 0.0001). In linear multivariable models as ETD increased, so did TLD (rc = 0.019; 95% CI: 0.014; 0.025; p < 0.0001), further increased by low ET (rc = 0.097; 95% CI: 0.017; 0.176; p = 0.017). After adjusting for clinical and pathological features, ETD correlated with TLD above the first quartile. Disease progression occurred in 43 (11.9%) patients, independently predicted by PSAD (hazard ratio, HR = 99.906; 95% CI: 6.519–1531.133; p = 0.001) and tumor upgrading (HR = 3.586; 95% CI: 3.586–6.863; p < 0.0001).

Conclusions

ETD was associated with unfavorable PCa, and men with tumor upgrading were at increased risk of disease progression. ETD was related to predictors of PCa progression and could provide pivotal biological information about aggressive disease.
Comprehensive analysis of KLF2 as a prognostic biomarker associated with fibrosis and immune infiltration in advanced hepatocellular carcinoma
Authors: Chen Xue-Qin , Ma Jie , Xu Di , Xiang Zuo-Lin
Published: June 2023

Purpose

Most Hepatocellular carcinoma (HCC) patients are in advanced or metastatic stage at the time of diagnosis. Prognosis for advanced HCC patients is dismal. This study was based on our previous microarray results, and aimed to explore the promising diagnostic and prognostic markers for advanced HCC by focusing on the important function of KLF2.

Methods

The Cancer Genome Atlas (TCGA), Cancer Genome Consortium database (ICGC), and the Gene Expression Comprehensive Database (GEO) provided the raw data of this study research. The cBioPortal platform, CeDR Atlas platform, and the Human Protein Atlas (HPA) website were applied to analyze the mutational landscape and single-cell sequencing data of KLF2. Basing on the results of single-cell sequencing analyses, we further explored the molecular mechanism of KLF2 regulation in the fibrosis and immune infiltration of HCC.

Results

Decreased KLF2 expression was discovered to be mainly regulated by hypermethylation, and indicated a poor prognosis of HCC. Single-cell level expression analyses revealed KLF2 was highly expressed in immune cells and fibroblasts. The function enrichment analysis of KLF2 targets indicated the crucial association between KLF2 and tumor matrix. 33-genes related with cancer associated fibroblasts (CAFs) were collected to identify the significant association of KLF2 with fibrosis. And SPP1 was validated as a promising prognostic and diagnostic marker for advanced HCC patients. CXCR6 CD8+ T cells were noted as a predominant proportion in the immune microenvironment, and T cell receptor CD3D was discovered to be a potential therapeutic biomarker for HCC immunotherapy.

Conclusion

This study identified that KLF2 is an important factor promoting HCC progression by affecting the fibrosis and immune infiltration, highlighting its great potential as a novel prognostic biomarker for advanced HCC.
Multiomics data analyses to identify SLC25A17 as a novel biomarker to predict the prognosis and immune microenvironment in head and neck squamous cell carcinoma
Authors: Shi Yunbin , Huang Juntao , Hu Yi , Shen Yi
Published: June 2023

Objective

This study aims to explore the predictive value of SLC25A17 in the prognosis and tumor microenvironment (TME) of patients with head and neck squamous cell carcinoma (HNSCC) and to provide ideas for individual clinical treatment.

Methods

A pancancer analysis of the differential expression of SLC25A17 among different tumors was first conducted via the TIMER 2.0 database. Subsequently, the expression of SLC25A17 and related clinical information of HNSCC patients were obtained from the TCGA database, and patients were divided into two groups according to the median value of SLC25A17 expression. K‒M survival analysis was conducted to compare the overall survival (OS) and progression-free survival (PFS) between the groups. The Wilcoxon test was used to compare the distribution of SLC25A17 in different clinical characteristics, and univariate Cox and multivariate Cox analyses were performed to analyze independent prognostic factors to establish a predictive nomogram. Calibration curves were generated to verify the reliability of predicting 1-year, 3-year and 5-year survival rates and another cohort (GSE65858) was used for external validation. Gene set enrichment analysis was conducted to compare the enriched pathways, and the immune microenvironment was assessed using the CIBERSORT and estimate packages. Furthermore, the expression levels of SLC25A17 in immune cells were also analyzed with single-cell RNA-seq via the TISCH. Moreover, the immunotherapeutic response and chemotherapy drug sensitivity were compared between the two groups to guide precise treatment. The TIDE database was applied to predict the possibility of immune escape in the TCGA-HNSC cohort.

Results

Compared with normal samples, the expression of SLC25A17 was much higher in HNSCC tumor samples. For patients with high SLC25A17 expression, the OS and PFS were shorter than those with low SLC25A17 expression, indicating a worse prognosis. The expression of SLC25A17 varied in different clinical features. Univariate Cox and multivariate COX analyses showed that SLC25A17, age, and lymph node metastasis are independent prognostic risk factors for HNSCC, and the survival prediction model based on these factors had reliable predictive value. Patients in the low-expression group exhibited more immune cell infiltration, higher TME scores, higher IPS scores and lower TIDE scores than those in the high-expression groups, suggesting better immunotherapeutic response with lower SLC25A17 expression. Moreover, patients in the high-expression group were more sensitive to chemotherapy.

Conclusions

SLC25A17 can effectively predict the prognosis of HNSCC patients and could be a precise individual-targeted indicator for the treatment of HNSCC patients.
The complete chloroplast genome of Ulmus mianzhuensis with insights into structural variations, adaptive evolution, and phylogenetic relationships of Ulmus (Ulmaceae)
Authors: Lin Nan , Liu Rui , Wang Yakun , Guo Peng , Wang Yihan , Liu Yanpei , Shang Fude
Published: June 2023

Background

Ulmus mianzhuensis is an endemic tree species in China with high ornamental and economic value. Currently, little is known regarding its genomic architecture, phylogenetic position, or adaptive evolution. Here, we sequenced the complete chloroplast genome (cp genome) of U. mianzhuensis and further compared the variations in gene organization and structure within Ulmus species to define their genomic evolution, then reconstructed the phylogenomic relationship of 31 related Ulmus species to explore the systematic position of U. mianzhuensis and the utility of cp genome for resolving phylogenetics among Ulmus species.

Results

Our results revealed that all the Ulmus species exhibited a typical quadripartite structure, with a large single copy (LSC) region of 87,170 − 88,408 bp, a small single copy (SSC) region of 18,650 − 19,038 bp and an inverted repeat (IR) region of 26,288 − 26,546 bp. Within Ulmus species, gene structure and content of cp genomes were highly conserved, although slight variations were found in the boundary of SC/IR regions. Moreover, genome-wide sliding window analysis uncovered the variability of ndhC-trnV-UAC, ndhF-rpl32, and psbI-trnS-GCU were higher among 31 Ulmus that may be useful for the population genetics and potential DNA barcodes. Two genes (rps15 and atpF) were further detected under a positive selection of Ulmus species. Comparative phylogenetic analysis based on the cp genome and protein-coding genes revealed consistent topology that U. mianzhuensis is a sister group to U. parvifolia (sect. Microptelea) with a relatively low-level nucleotide variation of the cp genome. Additionally, our analyses also found that the traditional taxonomic system of five sections in Ulmus is not supported by the current phylogenomic topology with a nested evolutionary relationship between sections.

Conclusions

Features of the cp genome length, GC content, organization, and gene order were highly conserved within Ulmus. Furthermore, molecular evidence from the low variation of the cp genome suggested that U. mianzhuensis should be merged into U. parvifolia and regarded as a subspecies of U. parvifolia. Overall, we demonstrated that the cp genome provides valuable information for understanding the genetic variation and phylogenetic relationship in Ulmus.
A scoping review of statistical methods in studies of biomarker-related treatment heterogeneity for breast cancer
Authors: Sollfrank L , Linn SC , Hauptmann M , Jóźwiak K
Published: June 2023

Background

Many scientific papers are published each year and substantial resources are spent to develop biomarker-based tests for precision oncology. However, only a handful of tests is currently used in daily clinical practice, since development is challenging. In this situation, the application of adequate statistical methods is essential, but little is known about the scope of methods used.

Methods

A PubMed search identified clinical studies among women with breast cancer comparing at least two different treatment groups, one of which chemotherapy or endocrine treatment, by levels of at least one biomarker. Studies presenting original data published in 2019 in one of 15 selected journals were eligible for this review. Clinical and statistical characteristics were extracted by three reviewers and a selection of characteristics for each study was reported.

Results

Of 164 studies identified by the query, 31 were eligible. Over 70 different biomarkers were evaluated. Twenty-two studies (71%) evaluated multiplicative interaction between treatment and biomarker. Twenty-eight studies (90%) evaluated either the treatment effect in biomarker subgroups or the biomarker effect in treatment subgroups. Eight studies (26%) reported results for one predictive biomarker analysis, while the majority performed multiple evaluations, either for several biomarkers, outcomes and/or subpopulations. Twenty-one studies (68%) claimed to have found significant differences in treatment effects by biomarker level. Fourteen studies (45%) mentioned that the study was not designed to evaluate treatment effect heterogeneity.

Conclusions

Most studies evaluated treatment heterogeneity via separate analyses of biomarker-specific treatment effects and/or multiplicative interaction analysis. There is a need for the application of more efficient statistical methods to evaluate treatment heterogeneity in clinical studies.
Do outcomes for patients with hospital-acquired Acute Kidney Injury (H-AKI) vary across specialties in England?
Authors: Magadi Winnie , Peracha Javeria , McKane William S , Savino Manuela , Braddon Fiona , Steenkamp Retha , Nitsch Dorothea
Published: June 2023

Background

Acute Kidney Injury (AKI) is a common and serious clinical syndrome. There is increasing recognition of heterogeneity in observed AKI across different clinical settings. In this analysis we have utilised a large national dataset to outline, for the first time, differences in burden of hospital acquired AKI (H-AKI) and mortality risk across different treatment specialities in the English National Health Service (NHS).

Methods

A retrospective observational study was conducted using a large national dataset of patients who triggered a biochemical AKI alert in England during 2019. This dataset was enriched through linkage with NHS hospitals administrative and mortality data. Episodes of H-AKI were identified and attributed to the speciality of the supervising consultant during the hospitalisation episode in which the H-AKI alert was generated. Associations between speciality and death in hospital or within 30 days of discharge (30-day mortality) was modelled using logistic regression, adjusting for patient age, sex, ethnicity, socioeconomic status, AKI severity, season and method of admission.

Results

In total, 93,196 episodes of H-AKI were studied. The largest number of patients with H-AKI were observed under general medicine (21.9%), care of the elderly (18.9%) and general surgery (11.2%). Despite adjusting for differences in patient case-mix, 30-day mortality risk was consistently lower for patients in surgical specialities compared to general medicine, including general surgery (OR 0.65, 95% CI 0.61 to 0.7) and trauma and orthopaedics (OR 0.52, 95% CI 0.48 to 0.56). Mortality risk was highest in critical care (OR 1.78, 95% CI 1.56 to 2.03) and oncology (OR 1.74, CI 1.54 to 1.96).

Conclusions

Significant differences were identified in the burden of H-AKI and associated mortality risk for patients across different specialities in the English NHS. This work can help inform future service delivery and quality improvement activity for patients with AKI across the NHS.
Comparing the effects of mHealth app use and face-to-face training on the clinical and laboratory parameters of dietary and fluid intake adherence in hemodialysis patients: a randomized clinical trial
Authors: Torabikhah Mohsen , Farsi Zahra , Sajadi Seyedeh Azam
Published: June 2023

Background

Numerous factors are likely to result in poor treatment adherence, which is one of the important factors contributing to increased complications and the low efficacy of hemodialysis (HD), particularly inadequate knowledge of patients. This study aimed to compare the effects of a mobile health (mHealth) app (the Di Care app) use and face-to-face training on the clinical and laboratory parameters of dietary and fluid intake adherence in patients undergoing HD.

Methods

This single-blinded, two-stage/two-group randomized clinical trial was fulfilled in 2021-22 in Iran. Seventy HD patients were recruited, using the convenience sampling method, and were then randomized into two groups: mHealth (n = 35) and face-to-face training (n = 35). ​ The patients in both groups received the same educational materials via the Di Care app and face-to-face training for one month. Before and 12 weeks after the intervention, the mean interdialytic weight gain (IDWG), potassium (K), phosphorus (P), total cholesterol (TC), triglyceride (TG), albumin (AL), and ferritin (FER) levels were measured and compared. The data were analyzed using the SPSS via descriptive statistics (mean, SD, frequency, and percentage) and analytical tests (independent-samplest-test, paired-samplest-test, Wilcoxon signed-rank test, Mann-Whitney U test, Chi-square test, and Fisher’s exact test).

Results

​Prior to the intervention, the mean IDWG and the K, P, TC, TG, AL, and FER levels, were not significantly different in both groups (p > 0.05). The mean IDWG (p < 0.0001), and the K (p = 0.001), P (p = 0.003), TC/TG (p < 0.0001), and FER (p = 0.038) levels in the HD patients in the mHealth group decreased. ​As well, the mean IDWG (p < 0.0001), and the K (p < 0.0001) and AL (p < 0.0001) levels showed a descending trend in the face-to-face group. The fall in the mean IDWG (p = 0.001) and the TG level (p = 0.034) in the patients in the mHealth group was significantly greater than that in the face-to-face group.

Conclusions

The Di Care app use and the face-to-face training could improve dietary and fluid intake adherence in patients. However, mHealth could have more effect on the laboratory parameters than face-to-face training, largely reducing the IDWG.

Trial registration

This study was registered in the Iranian Registry of Clinical Trials (No. ID IRCT20171216037895N5).
The associations of ferritin, serum lipid and plasma glucose levels across pregnancy in women with gestational diabetes mellitus and newborn birth weight
Authors: Ji Jing , Wu Pei , Li Guohua , He Zhangya , Wang Shanshan , Yu Wenlu , Li Chao , Mi Yang , Luo Xiaoqin
Published: June 2023

Background

Women with gestational diabetes mellitus (GDM) are at greater risk of abnormal birth weight. Since the level of biochemical indicators could often affect the intrauterine growth and development of the fetus, it is of great practical significance to understand the changes of biochemical levels across pregnancy in women with GDM and to find out the indicators that play an important role in predicting birth weight.

Methods

The data source of this study was from the Xi'an Longitudinal Mother–Child Cohort study (XAMC), in which women with GDM with normal and high pre-pregnancy body mass index (BMI) and their newborns between January 1st and March 31st in 2018 were included. The data of ferritin, serum lipid profile and fasting plasma glucose (FPG) of mothers in the three trimesters of pregnancy, as well as birth weight of newborns were all collected from medical records. Multiple linear regression and multivariate logistic regression analyses were used to explore the association of the biochemical indexes and birth weight. A P value < 0.05 was considered statistically significant.

Results

A total of 782 mother-infant pairs were finally included and divided into normal weight group (NG) (n = 530, 67.8%) and overweight/obesity group (OG) (n = 252, 32.2%) according to maternal pre-pregnancy BMI. The level of ferritin in both NG and OG decreased during pregnancy (P for trend < 0.001 for all), whereas the levels of total cholesterol (TC), high density cholesterol (HDL-C), low density cholesterol (LDL-C) and triglycerides (TG) all showed an upward trend (P for trend < 0.05 for all). The levels of FPG in the two groups remained in a relatively stable during the whole pregnancy even though it was higher in OG during the 2nd and 3rd trimesters, whilst HbAlc levels in NG women increased (P for trend = 0.043) during pregnancy. Meanwhile, the risk of macrosomia and large-for-gestational-age (LGA) increased with the increase of FPG level (P for trend < 0.05). Multivariate logistic regression analyses results showed that only FPG level in the 3rd trimester was correlated with birth weight, with birth weight increased by 44.9 g for each SD increase in FPG level.

Conclusion

Maternal FPG in the 3rd trimester is an independent predictor of newborn birth weight, and a higher level of that is associated with an increased risk of macrosomia and LGA.
The coagulation-related genes for prognosis and tumor microenvironment in pancreatic ductal adenocarcinoma
Authors: Wang Di , Cui Song-ping , Chen Qing , Ren Zhang-yong , Lyu Shao-cheng , Zhao Xin , Lang Ren
Published: June 2023

Background

Pancreatic ductal adenocarcinoma (PDAC) is a malignancy characterized by challenging early diagnosis and poor prognosis. It is believed that coagulation has an impact on the tumor microenvironment of PDAC. The aim of this study is to further distinguish coagulation-related genes and investigate immune infiltration in PDAC.

Methods

We gathered two subtypes of coagulation-related genes from the KEGG database, and acquired transcriptome sequencing data and clinical information on PDAC from The Cancer Genome Atlas (TCGA) database. Using an unsupervised clustering method, we categorized patients into distinct clusters. We investigated the mutation frequency to explore genomic features and performed enrichment analysis, utilizing Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) to explore pathways. CIBERSORT was used to analyze the relationship between tumor immune infiltration and the two clusters. A prognostic model was created for risk stratification, and a nomogram was established to assist in determining the risk score. The response to immunotherapy was assessed using the IMvigor210 cohort. Finally, PDAC patients were recruited, and experimental samples were collected to validate the infiltration of neutrophils using immunohistochemistry. In addition, and identify the ITGA2 expression and function were identified by analyzing single cell sequencing data.

Results

Two coagulation-related clusters were established based on the coagulation pathways present in PDAC patients. Functional enrichment analysis revealed different pathways in the two clusters. Approximately 49.4% of PDAC patients experienced DNA mutation in coagulation-related genes. Patients in the two clusters displayed significant differences in terms of immune cell infiltration, immune checkpoint, tumor microenvironment and TMB. We developed a 4-gene prognostic stratified model through LASSO analysis. Based on the risk score, the nomogram can accurately predict the prognosis in PDAC patients. We identified ITGA2 as a hub gene, which linked to poor overall survival (OS) and short disease-free survival (DFS). Single-cell sequencing analysis demonstrated that ITGA2 was expressed by ductal cells in PDAC.

Conclusions

Our study demonstrated the correlation between coagulation-related genes and the tumor immune microenvironment. The stratified model can predict the prognosis and calculate the benefits of drug therapy, thus providing the recommendations for clinical personalized treatment.