bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of CYP11A1 recovers cell cycle distribution in renal cell carcinoma Caki-1
Authors: Ong Hien Thi My , Kim Tae-Hun , Ates Eda , Pyun Jae-Chul , Kang Min-Jung 
Published: October 2022

Abstract
Background
Clear cell renal carcinoma is commonly known for its metastasis propensity to outspread to other organs and is asymptomatic in the early stage. Recent studies have shown that deficiencies in CYP11A1 expression can lead to fatal adrenal failure if left untreated and are associated with downstream regulation in various cancer types. However, the molecular mechanisms of CYP11A1 and kidney cancer proliferation remain unclear.

Methods
Normal and renal carcinoma cell lines (HEK293 and Caki-1) were transfected with plasmid encoding CYP11A1 to overexpress the P450scc protein. Cell cycle distribution was investigated using flow cytometry. The expression of proteins related to C-Raf/ERK/JNK/p38 signaling pathways was examined using western blot.

Results
We observed that CYP11A1 overexpression suppressed the cyclin B1 and cell-division cycle 2 expression while cyclin-dependent kinases 2 and 4 were unaffected. Cancer cell migration and invasion were suppressed along with epithelial-intermediate metastatic markers Snail and Vimentin. In addition, in CYP11A1-overexpressing Caki-1 cells, cdc2/cyclinB1 was downregulated while the phosphorylation of cdc25c, a G2/M arrest-related upstream signal, was increased. The intrinsic-mitochondrial apoptosis markers were not significantly altered. We also identified that the C-Raf/ERK/JNK/p38 pathway is an important pro-apoptotic mechanism in CYP11A1-overexpressing cell-based models. Our results suggest that CYP11A1 overexpression recovered the disturbed cell cycle arrest distribution in renal carcinoma cell line Caki-1 through G2/M arrest and C-Raf/ERK/JNK pathway.

Conclusions
Our findings may suggest promising new therapeutic targets to suppress kidney cancer proliferation without affecting normal cells, eventually improving the survival of patients with cancer.
Dual-dynamic-bond cross-linked injectable hydrogel of multifunction for intervertebral disc degeneration therapy
Authors: Yang Linjun , Yu Congcong , Fan Xuhui , Zeng Tianni , Yang Wentao , Xia Jiechao , Wang Jianle , Yao Litao , Hu Chuan , Jin Yang , Zhu Yutao , Chen Jiaxin , Hu Zhijun 
Published: October 2022

AbstractDeveloping smart hydrogels with integrated and suitable properties to treat intervertebral disc degeneration (IVDD) by minimally invasive injection is of high desire in clinical application and still an ongoing challenge. In this work, an extraordinary injectable hydrogel PBNPs@OBG (Prussian blue nanoparticles@oxidized hyaluronic acid/borax/gelatin) with promising antibacterial, antioxidation, rapid gelation, and self-healing characteristics was designed via dual-dynamic-bond cross-linking among the oxidized hyaluronic acid (OHA), borax, and gelatin. The mechanical performance of the hydrogel was studied by dynamic mechanical analysis. Meanwhile, the swelling ratio and degradation level of the hydrogel was explored. Benefiting from its remarkable mechanical properties, sufficient tissue adhesiveness, and ideal shape-adaptability, the injectable PBNPs containing hydrogel was explored for IVDD therapy. Astoundingly, the as-fabricated hydrogel was able to alleviate H2O2-induced excessive ROS against oxidative stress trauma of nucleus pulposus, which was further revealed by theoretical calculations. Rat IVDD model was next established to estimate therapeutic effect of this PBNPs@OBG hydrogel for IVDD treatment in vivo. On the whole, combination of the smart multifunctional hydrogel and nanotechnology-mediated antioxidant therapy can serve as a fire-new general type of therapeutic strategy for IVDD and other oxidative stress-related diseases.
Huc-MSC-derived exosomes modified with the targeting peptide of aHSCs for liver fibrosis therapy
Authors: Lin Yan , Yan Mengchao , Bai Zhongtian , Xie Ye , Ren Longfei , Wei Jiayun , Zhu Dan , Wang Haiping , Liu Yonggang , Luo Junqian , Li Xun 
Published: October 2022

Abstract
Background
Effective therapeutics to stop or reverse liver fibrosis have not emerged, because these potential agents cannot specifically target activated hepatic stellate cells (aHSCs) or are frequently toxic to parenchymal cells. Human umbilical cord mesenchymal stem cell (Huc-MSC)-derived exosomes show promise in nanomedicine for the treatment of liver fibrosis. However, systemic injection showed that unmodified exosomes were mainly taken up by the mononuclear phagocyte system. The discovery of ligands that selectively bind to a specific target plays a crucial role in clinically relevant diagnostics and therapeutics. Herein, we aimed to identify the targeting peptide of aHSCs by screening a phage-displayed peptide library, and modify Huc-MSC-derived exosomes with the targeting peptide.

Results
In this study, we screened a phage-displayed peptide library by biopanning for peptides preferentially bound to HSC-T6 cells. The identified peptide, HSTP1, also exhibited better targeting ability to aHSCs in pathological sections of fibrotic liver tissues. Then, HSTP1 was fused with exosomal enriched membrane protein (Lamp2b) and was displayed on the surface of exosomes through genetic engineering technology. The engineered exosomes (HSTP1-Exos) could be more efficiently internalized by HSC-T6 cells and outperformed both unmodified exosomes (Blank-Exos) and Lamp2b protein overexpressed exosomes (Lamp2b + Exos) in enhancing the ability of exosomes to promote HSC-T6 reversion to a quiescent phenotype. In vivo results showed HSTP1-Exos could specifically target to the aHSC region after intravenous administration, as demonstrated by coimmunofluorescence with the typical aHSCs marker α-SMA, and enhance the therapeutic effect on liver fibrosis.

Conclusion
These results suggest that HSTP1 is a reliable targeting peptide that can specifically bind to aHSCs and that HSTP1-modified exosomes realize the precise treatment for aHSCs in complex liver tissue. We provide a novel strategy for clinical liver fibrosis therapy.

Graphical Abstract
“I don’t go to funerals anymore”: how people who use opioids grieve drug-related death in the US overdose epidemic
Authors: Schlosser Allison V. , Hoffer Lee D. 
Published: October 2022

AbstractBackgroundOpioid-related overdose death is a public health epidemic in much of the USA, yet little is known about how people who use opioids (PWUO) experience overdose deaths in their social networks. We explore these experiences through a qualitative study of opioid-related overdose death bereavement among PWUO.MethodsWe recruited 30 adults who inject opioids from a syringe service program in the Midwestern USA and interviewed them using a semi-structured guide that addressed experiences of opioid use, opioid-related overdose, and overdose reversal via the medication naloxone. Interviews were transcribed verbatim and analyzed thematically.FindingsParticipants described overdose death as ever-present in their social worlds. Most (approximately 75%) reported at least one overdose death in their social network, and many came to consider death an inevitable end of opioid use. Participants described grief shaped by complex social relations and mourning that was interrupted due to involvement with social services and criminal legal systems. They also reported several ways that overdose deaths influenced their drug use, with some increasing their use and others adopting safer drug use practices. Despite the high prevalence of overdose deaths in their social networks, only one participant reported receiving grief support services.DiscussionFindings underscore the need for interventions that not only maintain life, such as naloxone distribution, but also improve quality of life by attending to grief related to overdose death bereavement. We discuss policies and practices with the potential to address the unique psychological, social, and structural challenges of grief for this population.
Does the neighborhood built environment moderate the effectiveness of a weight-loss intervention for mothers with overweight or obesity? Findings from the Healthy Eating and Active Living Taught at Home (HEALTH) study
Authors: Gilbert Amanda S. , Salvo Deborah , Tabak Rachel G. , Haire-Joshu Debra 
Published: October 2022

Abstract
Background
Women of childbearing age are vulnerable to weight gain and experience a high prevalence of obesity due to pregnancy and stressors of parenthood. Lifestyle interventions such as the Healthy Eating and Active Living Taught at Home (HEALTH) study have been effective for weight loss; however, little is known about how the built environment (parks, transit, grocery stores, fast food, walkability etc.), where participants live might modify intervention effectiveness. This study examined whether characteristics of the neighborhood built environment modified effectiveness of the HEALTH study on weight loss.

Methods
Secondary data analysis was conducted using data from HEALTH. Using GIS, buffers were built around participant addresses to capture distance to and availability of food (grocery store, convenience store, fast food) and urban design and transit (parks, street connectivity, transit) built environment characteristics. Built environment characteristics were dichotomized into low and high density and distance. Likelihood ratio tests for interaction were conducted to determine if built environment characteristics modified intervention effectiveness on Body mass index (BMI) and waist circumference (WC). Mixed effects linear regression models were then run to estimate the effect of the HEALTH intervention on weight outcomes at 24-months across both strata of built environment characteristics.

Results
The analytic sample (n = 151) had baseline mean BMI 34.9 (SD = 5.8) and mean WC 46.0 cm (SD4.9). All urban design and transit and all food environment characteristics modified HEALTH effectiveness on one or both weight outcomes. The built environment modified the HEALTH intervention such that it was mostly effective for mothers residing in neighborhoods with low transit access, low street connectivity, high park access, and low access to grocery stores, convenience stores, and fast food.

Conclusions
Result show the HEALTH was most effective for women residing neighborhoods with built environment characteristics suggestive of suburban neighborhood typology. To maximize impact for mothers residing in all types of neighborhoods, future research should explore scaling up HEALTH in suburban settings, while adapting HEALTH to maximize effectiveness in compact neighborhoods most likely, urban core neighborhoods.
miR-1297 sensitizes glioma cells to temozolomide (TMZ) treatment through targeting adrenomedullin (ADM)
Authors: He Zongze , Cheng Meixiong , Hu Junting , Liu Lingtong , Liu Ping , Chen Longyi , Cao Deqian , Tang Jian 
Published: October 2022

AbstractBackgroundGliomas account for about 80% of all malignant brain and other central nervous system (CNS) tumors. Temozolomide (TMZ) resistance represents a major treatment hurdle. Adrenomedullin (ADM) has been reported to induce glioblastoma cell growth.MethodsCell viability was measured using the CCK-8 assay. The apoptosis analysis was performed using the Annexin V-FITC Apoptosis Detection Kit. The mitochondrial membrane potential was determined by JC-1 staining. A nude mouse tumor assay was used to detect tumor formation. Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were performed in tissue sections. Activation of Akt and Erk and expression of apoptosis-related proteins were determined by immunoblotting.ResultsADM expression has been found upregulated in TMZ -resistant glioma samples based on bioinformatics and experimental analyses. Knocking down ADM in glioma cells enhanced the suppressive effects of TMZ on glioma cell viability, promotive effects on cell apoptosis, and inhibitory effects on mitochondrial membrane potential. Moreover, ADM knockdown also enhanced TMZ effects on Bax/Bcl-2, Akt phosphorylation, and Erk1/2 phosphorylation. Bioinformatics and experimental investigation indicated that miR-1297 directly targeted ADM and inhibited ADM expression. miR-1297 overexpression exerted similar effects to ADM knockdown on TMZ-treated glioma cells. More importantly, under TMZ treatment, inhibition of miR-1297 attenuated TMZ treatment on glioma cells; ADM knockdown partially attenuated the effects of miR-1297 inhibition on TMZ-treated glioma cells.ConclusionsmiR-1297 sensitizes glioma cells to TMZ treatment through targeting ADM. The Bax/Bcl-2, Akt, and Erk1/2 signaling pathways, as well as mitochondrial functions might be involved.
Transitioning patients with juvenile idiopathic arthritis to adult care: the Nordic experience
Authors: Mikola Katriina , Rebane Katariina , Arnstad Ellen Dalen , Berntson Lillemor , Fasth Anders , Glerup Mia , Herlin Troels , Kautiainen Hannu , Nielsen Susan , Nordal Ellen , Peltoniemi Suvi , Rygg Marite , Rypdal Veronika , Zak Marek , Aalto Kristiina 
Published: October 2022

Abstract
Background
With juvenile idiopathic arthritis (JIA), there are several protocols and practices used worldwide for the transition from paediatric to adult care. In this study, we examined the transferral rates and disease activity after transition, as well as the disease- and health-related outcomes. We also introduce the transition practices employed in the Nordic countries.

Methods
The study population comprised 408 participants with a disease onset from 1997 to 2000 who attended an 18-year follow-up visit in this population-based Nordic JIA cohort study. The patients were retrospectively divided into three subgroups: Patients transferred directly from paediatric care to adult rheumatology care, patients referred there later, and patients never transferred during the 18-year follow-up period.

Results
One hundred and sixty-three (40%) JIA patients had been directly transferred to an adult clinic. The cumulative transition rate was 52%, but there were significant differences between the participating centres. Fifty patients had later been referred to an adult clinic. Among the 195 patients who had never been transferred, 39% were found to have disease activity at the study visit.

Conclusion
This study highlights the need to reconsider transition practices to avoid our undesirable finding of patients with disease activity in JIA, but no appropriate health care follow-up.
Required sample size to detect mediation in 3-level implementation studies
Authors: Williams Nathaniel J. , Preacher Kristopher J. , Allison Paul D. , Mandell David S. , Marcus Steven C. 
Published: October 2022

Abstract
Background
Statistical tests of mediation are important for advancing implementation science; however, little research has examined the sample sizes needed to detect mediation in 3-level designs (e.g., organization, provider, patient) that are common in implementation research. Using a generalizable Monte Carlo simulation method, this paper examines the sample sizes required to detect mediation in 3-level designs under a range of conditions plausible for implementation studies.

Method
Statistical power was estimated for 17,496 3-level mediation designs in which the independent variable (X) resided at the highest cluster level (e.g., organization), the mediator (M) resided at the intermediate nested level (e.g., provider), and the outcome (Y) resided at the lowest nested level (e.g., patient). Designs varied by sample size per level, intraclass correlation coefficients of M and Y, effect sizes of the two paths constituting the indirect (mediation) effect (i.e., X→M and M→Y), and size of the direct effect. Power estimates were generated for all designs using two statistical models—conventional linear multilevel modeling of manifest variables (MVM) and multilevel structural equation modeling (MSEM)—for both 1- and 2-sided hypothesis tests.

Results
For 2-sided tests, statistical power to detect mediation was sufficient (≥0.8) in only 463 designs (2.6%) estimated using MVM and 228 designs (1.3%) estimated using MSEM; the minimum number of highest-level units needed to achieve adequate power was 40; the minimum total sample size was 900 observations. For 1-sided tests, 808 designs (4.6%) estimated using MVM and 369 designs (2.1%) estimated using MSEM had adequate power; the minimum number of highest-level units was 20; the minimum total sample was 600. At least one large effect size for either the X→M or M→Y path was necessary to achieve adequate power across all conditions.

Conclusions
While our analysis has important limitations, results suggest many of the 3-level mediation designs that can realistically be conducted in implementation research lack statistical power to detect mediation of highest-level independent variables unless effect sizes are large and 40 or more highest-level units are enrolled. We suggest strategies to increase statistical power for multilevel mediation designs and innovations to improve the feasibility of mediation tests in implementation research.
Documenting manifestations and impacts of autosomal recessive spastic ataxia of Charlevoix–Saguenay to develop patient-reported outcome
Authors: Tremblay Marjolaine , Girard-Côté Laura , Brais Bernard , Gagnon Cynthia 
Published: October 2022

AbstractBackgroundAutosomal recessive cerebellar ataxias (ARCA) are a group of rare inherited disorders characterized by degeneration or abnormal development of the cerebellum. Autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS) is one of the most prevalent in Europe.ObjectivesThe aim of this study is to provide a better understanding of the manifestations and impacts of ARSACS.MethodsA systematic review of the literature was conducted, followed by a qualitative study using semistructured interviews and discussion groups to obtain the experience of people affected.ResultsAccording to the PROMIS framework, the results show manifestations and impacts in three components of health: physical, mental, and social. Fatigue and struggles with balance and dexterity are the physical manifestations of the disease most often cited by participants. Negative affects such as frustration and depression are among the mental health impacts with some loss in cognitive abilities. Social health is the least documented component; nonetheless, people with the disease report significant impacts in terms of social relationships, activities and work.ConclusionsThese findings shed new light on the experience of people with recessive ataxia and identify key aspects to assess to improve their overall health.
Cognitive functioning and mental health in children with a primary mitochondrial disease
Authors: van de Loo Kim F. E. , Custers José A. E. , de Boer Lonneke , van Lieshout Marloes , de Vries Maaike C. , Janssen Mirian C. H. , Verhaak Christianne M. 
Published: October 2022

Abstract
Background
Studies regarding cognitive and mental health functioning in children with mitochondrial disease (MD) are scarce, while both are important issues given their impact on QoL. Knowledge on these aspects of functioning and its relationship with disease parameters is essential to gather more insight in working mechanisms and provide recommendations for future research and patientcare. The aim of this study was to map the cognitive functioning and mental health in children with MD in relation to disease specific factors.

Methods
Pediatric patients (< 18 year) with a genetically confirmed MD were included. Demographic and disease specific factors (International Paediatric Mitochondrial Disease Scale) were assessed, as well as cognitive functioning (intelligence, attention, working memory (WM)), and mental health (psychological functioning and quality of life). Individual patient data was described.

Results
Thirty-three children with MD were included. Intellectual functioning ranged from a clinically low IQ (36% of the patients, N = 12/33) to an average or above average IQ (39%, N = 13/33). A higher verbal versus performance IQ was observed (36% N = 5/14), a lower processing speed (43%, N = 6/14), attentional problems (50%, N = 7/14), and verbal WM problems (11%, N = 2/18). Regarding mental health, general behavioral problems were reported (45%, N = 10/22), and on subscale level, attention problems (45%, N = 10), withdrawn/depressed (36%, N = 8/22) and anxious/depressed behavior (14%, N = 3/22). Furthermore, QoL impairments were reported (42%, N = 5/12). The specific intelligence profiles, cognitive impairments, behavioral problems and QoL impairments occurred in every intelligence subgroup. Children with an average or above general intellectual functioning had a generally lower and less variability in IPMDS scores, less frequently epilepsy, vision and hearing problems, and a relatively later age of onset, as compared to patients with a clinically low intellectual functioning.

Conclusions
Despite considerable heterogeneity, overall results showed a high rate of impairments in both cognitive and mental health functioning. Also in children with an average or above level of intellectual functioning, specific cognitive impairments were observed. Children with a clinically low intellectual functioning more often had disease related impairments compared to children with a higher intellectual functioning. The importance of structural assessment of cognitive functioning and mental health is warranted, also in children with mild disease related symptoms.
BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: mechanisms and clinical studies
Authors: Alu Aqu , Lei Hong , Han Xuejiao , Wei Yuquan , Wei Xiawei 
Published: October 2022

AbstractBruton’s tyrosine kinase (BTK) is an essential component of multiple signaling pathways that regulate B cell and myeloid cell proliferation, survival, and functions, making it a promising therapeutic target for various B cell malignancies and inflammatory diseases. Five small molecule inhibitors have shown remarkable efficacy and have been approved to treat different types of hematological cancers, including ibrutinib, acalabrutinib, zanubrutinib, tirabrutinib, and orelabrutinib. The first-in-class agent, ibrutinib, has created a new era of chemotherapy-free treatment of B cell malignancies. Ibrutinib is so popular and became the fourth top-selling cancer drug worldwide in 2021. To reduce the off-target effects and overcome the acquired resistance of ibrutinib, significant efforts have been made in developing highly selective second- and third-generation BTK inhibitors and various combination approaches. Over the past few years, BTK inhibitors have also been repurposed for the treatment of inflammatory diseases. Promising data have been obtained from preclinical and early-phase clinical studies. In this review, we summarized current progress in applying BTK inhibitors in the treatment of hematological malignancies and inflammatory disorders, highlighting available results from clinical studies.