bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic passaging of NRAS-mutant melanoma influences adhesive properties and metastatic pattern
Authors: Dietsch Bianca , Weller Céline , Sticht Carsten , de la Torre Carolina , Kramer Martin , Goerdt Sergij , Géraud Cyrill , Wohlfeil Sebastian A. 
Published: May 2023

AbstractBackgroundLiver metastasis is a poor prognostic factor for treatment of advanced cutaneous melanoma with either immunotherapy or targeted therapies. In this study we focused onNRASmutated melanoma, a cohort with high unmet clinical need.MethodsWT31 melanoma was repeatedly passaged over the liver after intravenous injections five times generating the subline WT31_P5IV. The colonization of target organs, morphology, vascularization and the gene expression profiles of metastases were analyzed.ResultsAfter intravenous injection lung metastasis was significantly decreased and a trend towards increased liver metastasis was detected for WT31_P5IV as compared to parental WT31. Besides, the ratio of lung to liver metastases was significantly smaller. Histology of lung metastases revealed reduced proliferation of WT31_P5IV in relation to WT31 while both size and necrotic areas were unaltered. Liver metastases of both sublines showed no differences in vascularization, proliferation or necrosis. To identify tumor-intrinsic factors that altered the metastatic pattern of WT31_P5IV RNA sequencing was performed and revealed a differential regulation of pathways involved in cell adhesion. Ex vivo fluorescence imaging confirmed that initial tumor cell retention in the lungs was significantly reduced in WT31_P5IV in comparison to WT31.ConclusionThis study demonstrates that tumor-intrinsic properties influencing the metastatic pattern ofNRASmutated melanoma are strongly affected by hepatic passaging and the hematogenous route tumor cells take. It has implications for the clinical setting as such effects might also occur during metastatic spread or disease progression in melanoma patients.
Biological evaluation of novel gemcitabine analog in patient-derived xenograft models of pancreatic cancer
Authors: Inkoom Andriana , Ndemazie Nkafu Bechem , Smith Taylor , Frimpong Esther , Bulusu Raviteja , Poku Rosemary , Zhu Xue , Han Bo , Trevino Jose , Agyare Edward 
Published: May 2023

AbstractGemcitabine (Gem) has been a standard first-line drug for pancreatic cancer (PCa) treatment; however, Gem's rapid metabolism and systemic instability (short half-life) limit its clinical outcome. The objective of this study was to modify Gem into a more stable form called 4-(N)-stearoyl-gemcitabine (4NSG) and evaluate its therapeutic efficacy in patient-derived xenograft (PDX) models from PCa of Black and White patients.Methods 4NSG was synthesized and characterized using nuclear magnetic resonance (NMR), elemental analysis, and high-performance liquid chromatography (HPLC). 4NSG-loaded solid lipid nanoparticles (4NSG-SLN) were developed using the cold homogenization technique and characterized. Patient-derived pancreatic cancer cell lines labeled Black (PPCL-192, PPCL-135) and White (PPCL-46, PPCL-68) were used to assess the in vitro anticancer activity of 4NSG-SLN. Pharmacokinetics (PK) and tumor efficacy studies were conducted using PDX mouse models bearing tumors from Black and White PCa patients.Results 4NSG was significantly stable in liver microsomal solution. The effective mean particle size (hydrodynamic diameter) of 4NSG-SLN was 82 ± 6.7 nm, and the half maximal inhibitory concentration (IC50) values of 4NSG-SLN treated PPCL-192 cells (9 ± 1.1 µM); PPCL-135 (11 ± 1.3 µM); PPCL-46 (12 ± 2.1) and PPCL-68 equaled to 22 ± 2.6 were found to be significantly lower compared to Gem treated PPCL-192 (57 ± 1.5 µM); PPCL-135 (56 ± 1.5 µM); PPCL-46 (56 ± 1.8 µM) and PPCL-68 (57 ± 2.4 µM) cells. The area under the curve (AUC), half-life, and pharmacokinetic clearance parameters for 4NSG-SLN were 3–fourfold higher than that of GemHCl. For in-vivo studies, 4NSG-SLN exhibited a two-fold decrease in tumor growth compared with GemHCl in PDX mice bearing Black and White PCa tumors.Conclusion 4NSG-SLN significantly improved the Gem's pharmacokinetic profile, enhanced Gem's systemic stability increased its antitumor efficacy in PCa PDX mice bearing Black and White patient tumors.
Early resection of a rare congenital pulmonary airway malformation causing severe progressive respiratory distress in a preterm neonate: a case report and review of the literature
Authors: Ottomeyer Megan , Huddleston Charles , Berkovich Rachel M. , Brink David S. , Koenig Joyce M. , Sobush Kurtis T. 
Published: May 2023

Abstract
Background
Congenital pulmonary airway malformations (CPAMs) are a heterogenous collection of congenital lung malformations, often diagnosed prenatally. The Stocker Type III CPAM is a rare CPAM sub-type, and, when large, may be associated with hydrops. Furthermore, reports of CPAM management which may include surgical resection in extreme preterm infants are limited.

Case presentation
We report a case of a female neonate born at 28 weeks of gestation with severe respiratory distress and diffuse pulmonary opacification on the right concerning for a large congenital lung lesion. This lesion was not detected on routine antenatal imaging, and she did not have clinical findings of associated hydrops. Her respiratory status improved dramatically after surgical resection of a mass at 12 day of age. The mass was consistent pathologically with a Stocker Type III CPAM. Lung expansion showed subsequent improvement at 16 months of age.

Conclusions
Our case describes a preterm neonate with severe respiratory distress that was found postnatally to have a large, unilateral congenital lung lesion despite a normal prenatal ultrasound. Additionally, this lesion required excision early in life due to severity of respiratory compromise. This case highlights that rare congenital lung lesions, like this rare sub-type of CPAM, should remain a diagnostic consideration in neonates with severe respiratory distress. Early lung resection for CPAM in preterm infants is not well described and the favorable outcomes of this case help expand perspectives on potential management strategies.
Efficacy and safety of duloxetine in chronic musculoskeletal pain: a systematic review and meta-analysis
Authors: Ma Xuezhi , Zhou Shijie , Sun Wenyuan , Sun Jie , Li Guangguang , Wang Lining , Guo Yang 
Published: May 2023

Abstract
Background
Chronic musculoskeletal pain (CMP) is a complex condition that is mainly treated with analgesic drugs. However, antidepressant intervention is also an important factor in the treatment of CMP. Duloxetine is an effective treatment option for patients with CMP as its antidepressant effect. The purpose of this article is to evaluate the efficacy and safety of duloxetine in treating CMP.

Databases and data treatment
We searched PubMed, Web of Science, Embase, Cochrane Library from inception to May, 2022. Randomized controlled trials (RCTs) evaluating the efficacy and safety of duloxetine versus placebo in patients with CMP were included. We identified 13 articles and studied a population of 4201 participants in 4 countries.

Results
This meta-analysis showed that the duloxetine has statistically significant compared with the placebo control, benefits on 24-hour average pain, living quality, physical function, and global impressions and there was no difference in the incidence of serious adverse event. In general, duloxetine can improve mood and pain level at the same time.

Conclusions
This review shows a significant contribution of duloxetine to CMP symptom relief. This meta-analysis improved that duloxetine can significantly reduce the pain level of patients, improve depressive symptoms and global impression, and has no obvious serious adverse reactions. However, additional studies are required to confirm the relationship between psychological diseases and chronic pain and explore their internal links.
How are health technology assessment bodies responding to the assessment challenges posed by cell and gene therapy?
Authors: Drummond Michael , Ciani Oriana , Fornaro Giulia , Jommi Claudio , Dietrich Eva Susanne , Espin Jaime , Mossman Jean , de Pouvourville Gerard 
Published: May 2023

Abstract
Background
The aims of this research were to provide a better understanding of the specific evidence needs for assessment of clinical and cost-effectiveness of cell and gene therapies, and to explore the extent that the relevant categories of evidence are considered in health technology assessment (HTA) processes.

Methods
A targeted literature review was conducted to identify the specific categories of evidence relevant to the assessment of these therapies. Forty-six HTA reports for 9 products in 10 cell and gene therapy indications across 8 jurisdictions were analysed to determine the extent to which various items of evidence were considered.

Results
The items to which the HTA bodies reacted positively were: treatment was for a rare disease or serious condition, lack of alternative therapies, evidence indicating substantial health gains, and when alternative payment models could be agreed. The items to which they reacted negatively were: use of unvalidated surrogate endpoints, single arm trials without an adequately matched alternative therapy, inadequate reporting of adverse consequences and risks, short length of follow-up in clinical trials, extrapolating to long-term outcomes, and uncertainty around the economic estimates.

Conclusions
The consideration by HTA bodies of evidence relating to the particular features of cell and gene therapies is variable. Several suggestions are made for addressing the assessment challenges posed by these therapies. Jurisdictions conducting HTAs of these therapies can consider whether these suggestions could be incorporated within their existing approach through strengthening deliberative decision-making or performing additional analyses.
Improving the quality of care in nursing home organizations with urgent quality issues: design and effectiveness of a Dutch government-funded support programme
Authors: Vermunt Paulien , Reijmer Yael , van Biessum Clariska , de Groot Valerie , van den Berg Bellis , Nies Henk 
Published: May 2023

Abstract
Background
Various societal developments are currently challenging the ability of European nursing home organizations to meet quality standards. To support nursing home organizations throughout the Netherlands in quality improvement (QI), the Dutch government launched a nationwide programme in 2016 entitled ‘Dignity and pride’ (D&p). As part of this programme, participating nursing home organizations followed a tailored trajectory centred around intensive, on-site support from external expert coaches. For this study, we evaluated to what extent quality improvements were realized in the programme, paying particular attention to the role of the expert coaches.

Methods
Thirty-six nursing home organizations were included. At the start of D&p, the majority of these organizations (78%) had major quality issues as determined by the Health Care Inspectorate. Information on quality of care at the start versus end of the programme was obtained from improvement plans and final evaluation reports. Quality of person-centred care (PCC) and resident safety were quantified using a standardized assessment tool based on national guidelines, with improvements analysed using two-sided paired-sample T-tests. In addition, semi-structured interviews were conducted with 14 coaches and 29 healthcare professionals, focusing on the greatest benefits of programme participation and on the added value of the expert coaches.

Results
After completion of the programme, 60% of the organizations scored a 4 (= good) on PCC and resident safety, and none scored a 2 or less (average improvement on a 5-point scale for both themes: 1.9 points, p < 0.001). Interviewees confirmed that the quality of care had both improved and become more person-centred. The expert coaches were credited with substantially contributing to the QI process by offering an outsider’s perspective, bringing in experience and expertise, and helping the organization stay committed and focused.

Conclusions
Our study results suggest that the D&p programme was associated with improved quality of care in nursing home organizations with urgent quality issues. However, offering on-site tailored support through a nationally coordinated, government-funded programme is both time- and labour-intensive, and therefore not feasible in every healthcare setting. Nevertheless, the findings provide valuable insights for future QI support strategies.
A small protein coded within the mitochondrial canonical gene nd4 regulates mitochondrial bioenergetics
Authors: Kienzle Laura , Bettinazzi Stefano , Choquette Thierry , Brunet Marie , Khorami Hajar Hosseini , Jacques Jean-François , Moreau Mathilde , Roucou Xavier , Landry Christian R. , Angers Annie , Breton Sophie 
Published: May 2023

Abstract
Background
Mitochondria have a central role in cellular functions, aging, and in certain diseases. They possess their own genome, a vestige of their bacterial ancestor. Over the course of evolution, most of the genes of the ancestor have been lost or transferred to the nucleus. In humans, the mtDNA is a very small circular molecule with a functional repertoire limited to only 37 genes. Its extremely compact nature with genes arranged one after the other and separated by short non-coding regions suggests that there is little room for evolutionary novelties. This is radically different from bacterial genomes, which are also circular but much larger, and in which we can find genes inside other genes. These sequences, different from the reference coding sequences, are called alternatives open reading frames or altORFs, and they are involved in key biological functions. However, whether altORFs exist in mitochondrial protein-coding genes or elsewhere in the human mitogenome has not been fully addressed.

Results
We found a downstream alternative ATG initiation codon in the + 3 reading frame of the human mitochondrial nd4 gene. This newly characterized altORF encodes a 99-amino-acid-long polypeptide, MTALTND4, which is conserved in primates. Our custom antibody, but not the pre-immune serum, was able to immunoprecipitate MTALTND4 from HeLa cell lysates, confirming the existence of an endogenous MTALTND4 peptide. The protein is localized in mitochondria and cytoplasm and is also found in the plasma, and it impacts cell and mitochondrial physiology.

Conclusions
Many human mitochondrial translated ORFs might have so far gone unnoticed. By ignoring mtaltORFs, we have underestimated the coding potential of the mitogenome. Alternative mitochondrial peptides such as MTALTND4 may offer a new framework for the investigation of mitochondrial functions and diseases.
Spanish validation of the Pediatric Quality of Life Inventory (PedsQL™ 4.0) for parent report for toddlers (ages 2–4)
Authors: Martínez-Shaw Melissa Liher , del Río Francisco Javier , Sánchez-Sandoval Yolanda 
Published: May 2023

Abstract
Background/objective
Health-related quality of life is a concept that includes aspects about physical, emotional and social well-being. The aim of the study was to validate the PedsQL for parent report for toddlers in Spain and provide reference data in a Spanish population.

Method
The sample included 478 parents (89.5% mothers) of children aged 18–36 months (M = 26.75 months). Sociodemographic data were gathered, and the PedsQL and Kiddy-KINDL-R were completed by the participants.

Results
The fit of the original structure of the PedsQL was acceptable (CFI = 0.93; TLI = 0.92; RMSEA = 0.06), and the results showed good internal consistency (α = 0.85). The items about nursery school were excluded, since not all the toddlers attended this type of educational centre. Significant differences were found in physical health and activities and in the total mean in terms of parent education level, and in social activities regarding gender. For the normative interpretation of the PedsQL, the first, second and third quartiles corresponded to 77.78, 84.72 and 90.28, respectively.

Conclusions
This instrument is not only useful to individually evaluate the quality of life of a child with respect to his/her group, but also to measure the efficacy of a possible intervention.
Haploidentical transplants deliver equal outcomes to matched sibling transplants: a propensity score-matched analysis
Authors: Wu Hengwei , Zhao Yeqian , Gao Fei , Shi Jimin , Luo Yi , Yu Jian , Lai Xiaoyu , Liu Lizhen , Fu Huarui , Qian Pengxu , Huang He , Zhao Yanmin 
Published: May 2023

AbstractThe success of allogeneic hematopoietic stem cell transplant for hematological malignancies is heavily dependent on the availability of suitable donors. Haploidentical donor (HID) and matched sibling donor (MSD) are two important donor options providing faster and easier sources of stem cells, however, due to confounding factors present in most retrospective studies, the validity of comparing outcomes between these two donor types remains uncertain. We conducted a post-hoc analysis of a prospective clinical trial (trial registration: Chinese Clinical Trial Registry; #ChiCTR-OCH-12002490; registered 22 February 2012; https://www.chictr.org.cn/showproj.aspx?proj=7061) to compare outcomes of HID versus MSD peripheral blood stem cell-derived transplants in patients with hematologic malignancies between 2015 and 2022. All HID-receiving patients had antithymocyte globulin-based conditioning. Propensity score matching was employed to minimize potential confounding factors between the two cohorts. A total of 1060 patients were initially reviewed and then 663 patients were ultimately included in the analysis after propensity score matching. The overall survival, relapse-free survival, non-relapse mortality rate and cumulative incidence of relapse were similar between HID and MSD cohorts. Subgroup analysis revealed that patients with positive measurable residual disease in first complete remission may have better overall survival with an HID transplant. The present demonstrated that haploidentical transplants can provide outcomes comparable to conventional MSD transplants, and HID should be recommended as one of the optimal donor choices for patients with positive measurable residual disease in first complete remission.
Proteomics and cytokine analyses distinguish myalgic encephalomyelitis/chronic fatigue syndrome cases from controls
Authors: Giloteaux Ludovic , Li Jiayin , Hornig Mady , Lipkin W. Ian , Ruppert David , Hanson Maureen R. 
Published: May 2023

AbstractBackgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, heterogenous disease characterized by unexplained persistent fatigue and other features including cognitive impairment, myalgias, post-exertional malaise, and immune system dysfunction. Cytokines are present in plasma and encapsulated in extracellular vesicles (EVs), but there have been only a few reports of EV characteristics and cargo in ME/CFS. Several small studies have previously described plasma proteins or protein pathways that are associated with ME/CFS.MethodsWe prepared extracellular vesicles (EVs) from frozen plasma samples from a cohort of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) cases and controls with prior published plasma cytokine and plasma proteomics data. The cytokine content of the plasma-derived extracellular vesicles was determined by a multiplex assay and differences between patients and controls were assessed. We then performed multi-omic statistical analyses that considered not only this new data, but extensive clinical data describing the health of the subjects.ResultsME/CFS cases exhibited greater size and concentration of EVs in plasma. Assays of cytokine content in EVs revealed IL2 was significantly higher in cases. We observed numerous correlations among EV cytokines, among plasma cytokines, and among plasma proteins from mass spectrometry proteomics. Significant correlations between clinical data and protein levels suggest roles of particular proteins and pathways in the disease. For example, higher levels of the pro-inflammatory cytokines Granulocyte-Monocyte Colony-Stimulating Factor (CSF2) and Tumor Necrosis Factor (TNFα) were correlated with greater physical and fatigue symptoms in ME/CFS cases. Higher serine protease SERPINA5, which is involved in hemostasis, was correlated with higher SF-36 general health scores in ME/CFS. Machine learning classifiers were able to identify a list of 20 proteins that could discriminate between cases and controls, with XGBoost providing the best classification with 86.1% accuracy and a cross-validated AUROC value of 0.947. Random Forest distinguished cases from controls with 79.1% accuracy and an AUROC value of 0.891 using only 7 proteins.ConclusionsThese findings add to the substantial number of objective differences in biomolecules that have been identified in individuals with ME/CFS. The observed correlations of proteins important in immune responses and hemostasis with clinical data further implicates a disturbance of these functions in ME/CFS.
Dual trajectories of antiretroviral therapy adherence and polypharmacy in women with HIV in the United States
Authors: Elbur Abubaker Ibrahim , Ghebremichael Musie , Konkle-Parker Deborah , Jones Deborah L , Collins Shelby , Adimora Adaora A. , Schneider Michael F. , Cohen Mardge H. , Tamraz Bani , Plankey Michael , Wilson Tracey , Adedimeji Adebola , Haberer Jessica E. , Jacobson Denise L. 
Published: May 2023

Abstract
Background
Polypharmacy, using five or more medications, may increase the risk of nonadherence to prescribed treatment. We aimed to identify the interrelationship between trajectories of adherence to antiretroviral therapy (ART) and polypharmacy.

Methods
We included women with HIV (aged ≥ 18) enrolled in the Women’s Interagency HIV Study in the United States from 2014 to 2019. We used group-based trajectory modeling (GBTM) to identify trajectories of adherence to ART and polypharmacy and the dual GBTM to identify the interrelationship between adherence and polypharmacy.

Results
Overall, 1,538 were eligible (median age of 49 years). GBTM analysis revealed five latent trajectories of adherence with 42% of women grouped in the consistently moderate trajectory. GBTM identified four polypharmacy trajectories with 45% categorized in the consistently low group.

Conclusions
The joint model did not reveal any interrelationship between ART adherence and polypharmacy trajectories. Future research should consider examining the interrelationship between both variables using objective measures of adherence.
Molecular mechanisms involved in regulating protein activity and biological function of MST3
Authors: Qiu Jing , Xiong Junzhi , Jiang Lu , Wang Xinmin , Zhang Kebin , Yu Hua 
Published: May 2023

AbstractMammalian sterile 20-like (Ste20-like) protein kinase 3 (MST3) or serine/threonine-protein kinase 24 (STK24) is a serine/threonine protein kinase that belongs to the mammalian STE20-like protein kinase family. MST3 is a pleiotropic protein that plays a critical role in regulating a variety of events, including apoptosis, immune response, metabolism, hypertension, tumor progression, and development of the central nervous system. The MST3-mediated regulation is intricately related to protein activity, post-translational modification, and subcellular location. Here, we review the recent progress on the regulatory mechanisms against MST3 and its-mediated control of disease progression.