bluuebunny/crossref_metadata_2025_split huggingface dataset:
PACS-2 deficiency in tubular cells aggravates lipid-related kidney injury in diabetic kidney disease
Authors: Zhao Chanyue , Li Li , Li Chenrui , Tang Chengyuan , Cai Juan , Liu Yu , Yang Jinfei , Xi Yiyun , Yang Ming , Jiang Na , Han Yachun , Liu Yan , Luo Shilu , Xiao Li , Sun Lin 
Published: September 2022

Abstract
Background
Lipid accumulation in tubular cells plays a key role in diabetic kidney disease (DKD). Targeting lipid metabolism disorders has clinical value in delaying the progression of DKD, but the precise mechanism by which molecules mediate lipid-related kidney injury remains unclear. Phosphofurin acidic cluster sorting protein 2 (PACS-2) is a multifunctional sorting protein that plays a role in lipid metabolism. This study determined the role of PACS-2 in lipid-related kidney injury in DKD.

Methods
Diabetes was induced by a high-fat diet combined with intraperitoneal injections of streptozotocin (HFD/STZ) in proximal tubule-specific knockout of Pacs-2 mice (PT-Pacs-2−/− mice) and the control mice (Pacs-2fl/fl mice). Transcriptomic analysis was performed between Pacs-2fl/fl mice and PT-Pacs-2−/− mice.

Results
Diabetic PT-Pacs-2−/− mice developed more severe tubule injury and proteinuria compared to diabetic Pacs-2fl/fl mice, which accompanied with increasing lipid synthesis, uptake and decreasing cholesterol efflux as well as lipid accumulation in tubules of the kidney. Furthermore, transcriptome analysis showed that the mRNA level of sterol O-acyltransferase 1 (Soat1) was up-regulated in the kidney of control PT-Pacs-2−/− mice. Transfection of HK2 cells with PACS-2 siRNA under high glucose plus palmitic acid (HGPA) condition aggravated lipid deposition and increased the expression of SOAT1 and sterol regulatory element-binding proteins (SREBPs), while the effect was blocked partially in that of co-transfection of SOAT1 siRNA.

Conclusions
PACS-2 has a protective role against lipid-related kidney injury in DKD through SOAT1/SREBPs signaling.
Targeting miR-21 in spinal cord injuries: a game-changer?
Authors: Malvandi Amir Mohammad , Rastegar-moghaddam Seyed Hamidreza , Ebrahimzadeh-Bideskan Saeede , Lombardi Giovanni , Ebrahimzadeh-Bideskan Alireza , Mohammadipour Abbas 
Published: September 2022

AbstractSpinal cord injury (SCI) is a devastating neurological state causing physical disability, psychological stress and financial burden. SCI global rate is estimated between 250,000 and 500,000 individuals every year, of which 60% of victims are young, healthy males between 15 and 35 years. A variety of pathological conditions such as neuroinflammation, mitochondrial dysfunction, apoptosis, glial scar formation, blood-spinal cord barrier disruption, and angiogenesis disruption occur after SCI leading to a limitation in recovery. MicroRNAs (miRs) are endogenous and non-coding RNAs consisting of 22 nucleotides that regulate 60% of all human genes and involve several normal physiological processes and pathological conditions. miR-21 is among the most highly expressed miRs and its expression has been shown to increase one day after SCI and this elevation is sustained up to 28 days after injury. Overexpression of miR-21 exerts many protective effects against SCI by inhibiting neuroinflammation, improving blood-spinal cord barrier function, regulating angiogenesis, and controlling glial scar formation. It also exhibits anti-apoptotic effects in SCI by down-regulating the expression of PTEN, Spry2, and PDCD4. This review provides a novel therapeutic perspective for miR-21 in SCI.
Reconstruction and analysis of potential biomarkers for hypertrophic cardiomyopathy based on a competing endogenous RNA network
Authors: Chen Jin-yan , Xie Zhang-xin , Dai Jia-zhen , Han Jun-yong , Wang Kun , Lu Li-hong , Jin Jing-jun , Xue Shi-jie 
Published: September 2022

AbstractHypertrophic cardiomyopathy (HCM) is a common heritable cardiomyopath. Although considerable effort has been made to understand the pathogenesis of HCM, the mechanism of how long noncoding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network result in HCM remains unknown. In this study, we acquired a total of 520 different expression profiles of lncRNAs (DElncRNAs) and 371 messenger RNAs (mRNA, DEGs) by microarray and 33 microRNAs (DEmiRNAs) by sequencing in plasma of patients with HCM and healthy controls. Then lncRNA–miRNA pairs were predicted using miRcode and starBase and crossed with DEmiRNAs. MiRNA–mRNA pairs were retrieved from miRanda and TargetScan and crossed with DEGs. Combined with these pairs, the ceRNA network with eight lncRNAs, three miRNAs, and 22 mRNAs was constructed. lncRNA RP11-66N24.4 and LINC00310 were among the top 10% nodes. The hub nodes were analyzed to reconstruct a subnetwork. Furthermore, quantitative real-time polymerase chain reaction results showed that LINC00310 was significantly decreased in patients with HCM. For LINC00310, GO analysis revealed that biological processes were enriched in cardiovascular system development, sprouting angiogenesis, circulatory system development, and pathway analysis in the cGMP-PKG signaling pathway. These results indicate that the novel lncRNA-related ceRNA network in HCM and LINC00310 may play a role in the mechanism of HCM pathogenesis, which could provide insight into the pathogenesis of HCM.
Long-segment spinal cord infarction complicated with multiple cerebral infarctions: a case report
Authors: Xing Weifang , Zhang Wensheng , Ma Guozhong , Ma Guofen , He Jinzhao 
Published: September 2022

Abstract
Background
Spinal cord infarction is a rare disorder, constituting only 1% to 2% of all neurological vascular emergencies (making it less frequent than ischaemic brain injury); however, it is severe. A case of long-segment spinal cord infarction complicated with multiple cerebral infarctions has not been reported to date.

Case presentation
Here, we describe one such case: a patient with spinal cord infarction from the cervical 7 (C7) to thoracic 6 (T6) vertebrae, along with anterior spinal artery syndrome and complicated by multiple cerebral infarctions. A 65-year-old farmer experienced sudden onset of severe pain in his chest, back and upper limbs while unloading heavy objects. Subsequently, both his lower limbs became weak and hypoaesthetic, and he was unable to walk. Spinal magnetic resonance imaging (MRI) revealed equal T1 and long T2 signals centred on the anterior horn of the spinal cord. The axial slice of these signals was shaped like an owl’s eye. After receiving drug treatment and active rehabilitation treatment, the patient’s ability to walk was restored.

Conclusions
Long-segment spinal cord infarction is rare and can be complicated with cerebral infarction. The specific aetiology is worth exploring.
Factors associated with duration of breastfeeding in women giving birth for the first time
Authors: Haas David M. , Yang Ziyi , Parker Corette B. , Chung Judith , Parry Samuel , Grobman William A. , Mercer Brian M. , Simhan Hyagriv N. , Silver Robert M. , Wapner Ronald J. , Saade George R. , Greenland Philip , Merz Noel Bairey , Reddy Uma M. , Pemberton Victoria L. ,   for the nuMoM2b study and the nuMoM2b Heart Health Study
Published: September 2022

Abstract
Objective
To examine maternal, psychosocial, and pregnancy factors associated with breastfeeding for at least 6 months in those giving birth for the first time.

Methods
We performed a planned secondary analysis of an observational cohort study of 5249 women giving birth for the first time. Women were contacted at least 6 months after delivery and provided information regarding breastfeeding initiation, duration, and exclusivity. Maternal demographics, psychosocial measures, and delivery methods were compared by breastfeeding groups.

Results
4712 (89.8%) of the women breastfed at some point, with 2739 (58.2%) breastfeeding for at least 6 months. Of those who breastfed, 1161 (24.7% of the entire cohort), breastfed exclusively for at least 6 months. In the multivariable model among those who ever breastfed, not smoking in the month prior to delivery (adjusted odds ratio [aOR] 2.04, 95%CI 1.19–3.45), having a Master’s degree of higher (aOR 1.89, 95%CI 1.51–2.36), having a planned pregnancy (aOR 1.48, 95%CI 1.27–1.73), older age (aOR 1.02, 95% CI, 1.01–1.04), lower BMI (aOR 0.96 95% CI 0.95–0.97), and having less anxiety measured during pregnancy (aOR 0.990, 95%CI 0.983–0.998) were associated with breastfeeding for at least 6 months. Compared to non-Hispanic White women, Hispanic women, while being more likely to breastfeed initially (aOR 1.40, 95%CI 1.02–1.92), were less likely to breastfeed for 6 months (aOR 0.72, 95%CI 0.59–0.88). While non-Hispanic Black women were less likely than non-Hispanic White women to initiate breastfeeding (aOR 0.68, 95%CI 0.51–0.90), the odds of non-Hispanic Black women of continuing to breastfeed for at least 6 months was similar to non-Hispanic White women (aOR 0.92, 95%CI 0.71–1.19).

Conclusions
In this cohort of women giving birth for the first time, duration of breastfeeding was associated with several characteristics which highlight groups at greater risk of not breastfeeding as long as currently recommended.

Trial registration
NCT01322529 (nuMoM2b) and NCT02231398 (nuMoM2b-Heart Health)
Preventing adverse events of chemotherapy for gastrointestinal cancer by educating patients about the nocebo effect: a randomized-controlled trial
Authors: Michnevich T. , Pan Y. , Hendi A. , Oechsle K. , Stein A. , Nestoriuc Y. 
Published: September 2022

Abstract
Background
Adverse events of chemotherapy may be caused by pharmacodynamics or psychological factors such as negative expectations, which constitute nocebo effects. In a randomized controlled trial, we examined whether educating patients about the nocebo effect is efficacious in reducing the intensity of self-reported adverse events.

Methods
In this proof-of-concept study, N = 100 outpatients (mean age: 60.2 years, 65% male, 54% UICC tumour stage IV) starting first-line, de novo chemotherapy for gastrointestinal cancers were randomized 1:1 to a nocebo education (n = 49) or an attention control group (n = 51). Our primary outcome was patient-rated intensity of four chemotherapy-specific and three non-specific adverse events (rated on 11-point Likert scales) at 10-days and 12-weeks after the first course of chemotherapy. Secondary outcomes included perceived control of adverse events and tendency to misattribute symptoms.

Results
General linear models indicated that intensity of adverse events differed at 12-weeks after the first course of chemotherapy (mean difference: 4.04, 95% CI [0.72, 7.36], p = .02, d = 0.48), with lower levels in the nocebo education group. This was attributable to less non-specific adverse events (mean difference: 0.39, 95% CI [0.04, 0.73], p = .03, d = 0.44) and a trend towards less specific adverse events in the nocebo education group (mean difference: 0.36, 95% CI [− 0.02, 0.74], p = .07, d = 0.37). We found no difference in adverse events at 10-days follow-up, perceived control of adverse events, or tendency to misattribute non-specific symptoms to the chemotherapy.

Conclusions
This study provides first proof-of-concept evidence for the efficacy of a brief information session in preventing adverse events of chemotherapy. However, results regarding patient-reported outcomes cannot rule out response biases. Informing patients about the nocebo effect may be an innovative and clinically feasible intervention for reducing the burden of adverse events.

Trial registration
Retrospectively registered on March 27, 2018 to the German Clinical Trial Register (ID: DRKS00009501).
Long-term treatment patterns and survival in metastatic breast cancer by intrinsic subtypes – an observational cohort study in Sweden
Authors: Lindman Henrik , Wiklund Fredrik , Andersen Klaus Kaae 
Published: September 2022

Abstract
Background
Longitudinal, real-world data on the management of metastatic breast cancer is increasingly relevant to understand breast cancer care in routine clinical practice. Yet such data are scarce, particularly beyond second- and third-line treatment strategies. This study, therefore, examined both the long-term treatment patterns and overall survival (OS) in a regional Swedish cohort of female patients with metastatic breast cancer stratified by subtype in routine clinical practice during a recent eight-year period and correlation to current treatment guidelines.

Methods
Consecutive female patients with metastatic breast cancer  clinically managed at Uppsala University Hospital, Uppsala, Sweden, during 2009–2016 and followed until the end of September, 2017 (n = 370) were included and, where possible, classified as having one of five, intrinsic subtypes: Luminal A; Luminal B; human epidermal growth factor receptor 2-positive (HER2+)/ estrogen receptor-positive (ER+); HER2+/estrogen receptor-negative (ER-); or triple negative breast cancer (TNBC). Treatment patterns and OS were estimated by subtype using time-to-event methods.

Results
A total of 352/370 patients with metastatic breast cancer (mean age 67.6 years) could be subtyped: 118 (34%) were Luminal A, 119 (34%) Luminal B, 31 (8%) HER2+/ER-, 38 (11%) HER2+/Luminal, and 46 (13%) TNBC. The median number of metastatic treatment lines was 3. Most patients were on active treatment during follow-up (80% of the observation period), except for patients with TNBC who were on treatment for 60% of the observation time. Overall, 67% of patients died whilst on treatment. Among all patients (n = 370), median OS was 32.5 months (95% CI = 28.2–35.7). The 5-year survival rate was highest for HER2+/Luminal (46%) patients, followed by Luminal B (29%), Luminal A (28%), HER2+/ER- (21%), and TNBC (7%). Increasing age and number of metastatic sites also predicted worse survival.

Conclusions
Metastatic breast cancer patients in Sweden, irrespective of subtype, generally receive active treatment until time of death. Survival varies considerably across subtypes and is also associated with patient characteristics. Regardless of differences in treatment patterns for Luminal A and B patients, long-term OS was the same.
How to deal with moral challenges around the decision-making competence in transgender adolescent care? Development of an ethics support tool
Authors: de Snoo-Trimp Janine , de Vries Annelou , Molewijk Bert , Hein Irma 
Published: September 2022

Abstract
Background
Decision-making competence is a complex concept in the care for transgender and gender diverse adolescents, since this type of care concerns one’s developing gender identity and involves treatment options that often lack international consensus. Even despite competence assessments, moral challenges arise in the decision-making process. Here, traditional forms of clinical ethics support such as moral case deliberation might not fit as these do not provide thematic guidance. This study therefore aimed to develop a practice-oriented ethics support tool to assist care providers when dealing with moral challenges around decision-making competence in transgender adolescent care.

Methods
The study followed a participatory design to develop a tool in close collaboration with care providers; they had a say in all phases of development and dissemination. Firstly, nine care providers were interviewed about experienced moral challenges and needs for ethics support. Based on this, the structure and content of the tool was constructed and discussed in two focus group meetings, after which four care providers tested the tool and additional feedback was collected from the team and an advisory board. The final tool was presented to all Dutch care providers in transgender adolescent care.

Results
Care providers expressed a need for guidance in defining and assessing decision-making competence. Main moral challenges concerned discussing fertility options with young clients, dealing with co-occurring mental health difficulties and the decision-making role of parents. The final tool, named the Competence Consultant, is an interactive pdf containing four parts: (1) Clarify information; (2) Identify doubts and moral questions; (3) Guidance for conversations and (4) Overview and Conclusions.

Discussion
Developing an ethics support tool in a controversial care setting is highly relevant as it aims to help individual care providers in defining, discussing and dealing with their moral challenges in actual practice. The ‘Competence Consultant’ for transgender care providers contributes to their moral sensitivity and moral competence. It is an example of the development of innovative and integrative forms of thematic ethics support.
Changes in sensory, postural stability and gait functions depending on cognitive decline, and possible markers for detection of cognitive status
Authors: Kostic Emilija , Kwak Kiyoung , Kim Dongwook 
Published: September 2022

Abstract
Background
Numerous people never receive a formal dementia diagnosis. This issue can be addressed by early detection systems that utilize alternative forms of classification, such as gait, balance, and sensory function parameters. In the present study, said functions were compared between older adults with healthy cognition, older adults with low executive function, and older adults with cognitive impairment, to determine which parameters can be used to distinguish these groups.

Results
A group of cognitively healthy older men was found to have a significantly greater gait cadence than both the low executive function group (113.1 ± 6.8 vs. 108.0 ± 6.3 steps/min, p = 0.032) and the cognitively impaired group (113.1 ± 6.8 vs. 107.1 ± 7.4 steps/min, p = 0.009). The group with low executive function was found to have more gait stability than the impaired cognition group, represented by the single limb support phase (39.7 ± 1.2 vs. 38.6 ± 1.3%, p = 0.027). Additionally, the healthy cognition group had significantly greater overall postural stability than the impaired cognition group (0.6 ± 0.1 vs. 1.1 ± 0.1, p = 0.003), and the low executive function group had significantly greater mediolateral postural stability than the impaired cognition group (0.2 ± 0.1 vs. 0.6 ± 0.6, p = 0.012). The low executive function group had fewer mistakes on the sentence recognition test than the cognitively impaired (2.2 ± 3.6 vs. 5.9 ± 6.4, p = 0.005). There were no significant differences in visual capacity, however, the low executive function group displayed an overall greatest ability.

Conclusions
Older adults with low executive function showcased a lower walking pace, but their postural stability and sensory functions did not differ from those of the older adults with healthy cognition. The variables concluded as good cognitive status markers were (1) gait cadence for dividing cognitively healthy from the rest and (2) single limb support portion, mediolateral stability index, and the number of mistakes on the sentence recognition test for discerning between the low executive function and cognitive impairment groups.
A novel dynamic Bayesian network approach for data mining and survival data analysis
Authors: Sheidaei Ali , Foroushani Abbas Rahimi , Gohari Kimiya , Zeraati Hojjat 
Published: September 2022

AbstractBackgroundCensorship is the primary challenge in survival modeling, especially in human health studies. The classical methods have been limited by applications like Kaplan–Meier or restricted assumptions like the Cox regression model. On the other hand, Machine learning algorithms commonly rely on the high dimensionality of data and ignore the censorship attribute. In addition, these algorithms are more sophisticated to understand and utilize. We propose a novel approach based on the Bayesian network to address these issues.MethodsWe proposed a two-slice temporal Bayesian network model for the survival data, introducing the survival and censorship status in each observed time as the dynamic states. A score-based algorithm learned the structure of the directed acyclic graph. The likelihood approach conducted parameter learning. We conducted a simulation study to assess the performance of our model in comparison with the Kaplan–Meier and Cox proportional hazard regression. We defined various scenarios according to the sample size, censoring rate, and shapes of survival and censoring distributions across time. Finally, we fit the model on a real-world dataset that includes 760 post gastrectomy surgery due to gastric cancer. The validation of the model was explored using the hold-out technique based on the posterior classification error. Our survival model performance results were compared using the Kaplan–Meier and Cox proportional hazard models.ResultsThe simulation study shows the superiority of DBN in bias reduction for many scenarios compared with Cox regression and Kaplan–Meier, especially in the late survival times. In the real-world data, the structure of the dynamic Bayesian network model satisfied the finding from Kaplan–Meier and Cox regression classical approaches. The posterior classification error found from the validation technique did not exceed 0.04, representing that our network predicted the state variables with more than 96% accuracy.ConclusionsOur proposed dynamic Bayesian network model could be used as a data mining technique in the context of survival data analysis. The advantages of this approach are feature selection ability, straightforward interpretation, handling of high-dimensional data, and few assumptions.
Malignant clonal evolution drives multiple myeloma cellular ecological diversity and microenvironment reprogramming
Authors: Liang Yuanzheng , He Haiyan , Wang Weida , Wang Henan , Mo Shaowen , Fu Ruiying , Liu Xindi , Song Qiong , Xia Zhongjun , Wang Liang 
Published: September 2022

Abstract
Background
Multiple myeloma (MM) is a heterogeneous disease with different patterns of clonal evolution and a complex tumor microenvironment, representing a challenge for clinicians and pathologists to understand and dissect the contribution and impact of polyclonality on tumor progression.

Methods
In this study, we established a global cell ecological landscape of the bone marrow (BM) from MM patients, combining single-cell RNA sequencing and single-molecule long-read genome sequencing data.

Results
The malignant mutation event was localized to the tumor cell clusters with shared mutation of ANK1 and IFITM2 in all malignant subpopulations of all MM patients. Therefore, these two variants occur in the early stage of malignant clonal origin to mediate the malignant transformation of proplasmacytes or plasmacytes to MM cells. Tumor cell stemness index score and pseudo-sequential clonal evolution analysis can be used to divide the evolution model of MM into two clonal origins: types I and IX. Notably, clonal evolution and the tumor microenvironment showed an interactive relationship, in which the evolution process is not only selected by but also reacts to the microenvironment; thus, vesicle secretion enriches immune cells with malignant-labeled mRNA for depletion. Interestingly, microenvironmental modification exhibited significant heterogeneity among patients.

Conclusions
This characterization of the malignant clonal evolution pattern of MM at the single-cell level provides a theoretical basis and scientific evidence for a personalized precision therapy strategy and further development of a potential new adjuvant strategy combining epigenetic agent and immune checkpoint blockade.