bluuebunny/crossref_metadata_2025_split huggingface dataset:
First in man study: Bcl-Xl_42-CAF®09b vaccines in patients with locally advanced prostate cancer
Authors: Mørk Sofie Kirial , Kongsted Per , Westergaard Marie Christine Wulff , Albieri Benedetta , Granhøj Joachim Stoltenborg , Donia Marco , Martinenaite Evelina , Holmström Morten Orebo , Madsen Kasper , Kverneland Anders H. , Kjeldsen Julie Westerlin , Holmstroem Rikke Boedker , Lorentzen Cathrine Lund , Nørgaard Nis , Andreasen Lars Vibe , Wood Grith Krøyer , Christensen Dennis , Klausen Michael Schantz , Hadrup Sine Reker , thor Straten Per , Andersen Mads Hald , Svane Inge Marie 
Published: March 2023

BackgroundThe B-cell lymphoma-extra-large (Bcl-XL) protein plays an important role in cancer cells’ resistance to apoptosis. Pre-clinical studies have shown that vaccination with Bcl-XL-derived peptides can induce tumor-specific T cell responses that may lead to the elimination of cancer cells. Furthermore, pre-clinical studies of the novel adjuvant CAF®09b have shown that intraperitoneal (IP) injections of this adjuvant can improve the activation of the immune system. In this study, patients with hormone-sensitive prostate cancer (PC) received a vaccine consisting of Bcl-XL-peptide with CAF®09b as an adjuvant. The primary aim was to evaluate the tolerability and safety of IP and intramuscular (IM) administration, determine the optimal route of administration, and characterize vaccine immunogenicity.Patients and methodsTwenty patients were included. A total of six vaccinations were scheduled: in Group A (IM to IP injections), ten patients received three vaccines IM biweekly; after a three-week pause, patients then received three vaccines IP biweekly. In Group B (IP to IM injections), ten patients received IP vaccines first, followed by IM under a similar vaccination schedule. Safety was assessed by logging and evaluating adverse events (AE) according to Common Terminology Criteria for Adverse Events (CTCAE v. 4.0). Vaccines-induced immune responses were analyzed by Enzyme-Linked Immunospot and flow cytometry.ResultsNo serious AEs were reported. Although an increase in T cell response against the Bcl-XL-peptide was found in all patients, a larger proportion of patients in group B demonstrated earlier and stronger immune responses to the vaccine compared to patients in group A. Further, we demonstrated vaccine-induced immunity towards patient-specific CD4, and CD8 T cell epitopes embedded in Bcl-XL-peptide and an increase in CD4 and CD8 T cell activation markers CD107a and CD137 following vaccination. At a median follow-up of 21 months, no patients had experienced clinically significant disease progression.ConclusionThe Bcl-XL-peptide-CAF®09b vaccination was feasible and safe in patients with l hormone-sensitive PC. In addition, the vaccine was immunogenic and able to elicit CD4 and CD8 T cell responses with initial IP administration eliciting early and high levels of vaccine-specific responses in a higher number og patients.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT03412786.
Contribution of clinical information to the predictive performance of plasma β-amyloid levels for amyloid positron emission tomography positivity
Authors: Chun Min Young , Jang Hyemin , Kim Hee Jin , Kim Jun Pyo , Gallacher John , Allué José Antonio , Sarasa Leticia , Castillo Sergio , Pascual-Lucas María , Na Duk L. , Seo Sang Won ,   on behalf of DPUK
Published: March 2023

BackgroundEarly detection of β-amyloid (Aβ) accumulation, a major biomarker for Alzheimer’s disease (AD), has become important. As fluid biomarkers, the accuracy of cerebrospinal fluid (CSF) Aβ for predicting Aβ deposition on positron emission tomography (PET) has been extensively studied, and the development of plasma Aβ is beginning to receive increased attention recently. In the present study, we aimed to determine whether APOE genotypes, age, and cognitive status increase the predictive performance of plasma Aβ and CSF Aβ levels for Aβ PET positivity.MethodsWe recruited 488 participants who underwent both plasma Aβ and Aβ PET studies (Cohort 1) and 217 participants who underwent both cerebrospinal fluid (CSF) Aβ and Aβ PET studies (Cohort 2). Plasma and CSF samples were analyzed using ABtest-MS, an antibody-free liquid chromatography-differential mobility spectrometry-triple quadrupole mass spectrometry method and INNOTEST enzyme-linked immunosorbent assay kits, respectively. To evaluate the predictive performance of plasma Aβ and CSF Aβ, respectively, logistic regression and receiver operating characteristic analyses were performed.ResultsWhen predicting Aβ PET status, both plasma Aβ42/40 ratio and CSF Aβ42 showed high accuracy (plasma Aβ area under the curve (AUC) 0.814; CSF Aβ AUC 0.848). In the plasma Aβ models, the AUC values were higher than plasma Aβ alone model, when the models were combined with either cognitive stage (p &lt; 0.001) or APOE genotype (p = 0.011). On the other hand, there was no difference between the CSF Aβ models, when these variables were added.ConclusionPlasma Aβ might be a useful predictor of Aβ deposition on PET status as much as CSF Aβ, particularly when considered with clinical information such as APOE genotype and cognitive stage.
Systematic identification of potential key microRNAs and circRNAs in the dorsal root ganglia of mice with sciatic nerve injury
Authors: Yu Youfen , Xu Xueru , Lin Chun , Liu Rongguo 
Published: March 2023

BackgroundNeuropathic pain (NeP) is a pathological condition arising from a lesion or disease affecting the somatosensory system. Accumulating evidence has shown that circular RNAs (circRNAs) exert critical functions in neurodegenerative diseases by sponging microRNAs (miRNAs). However, the functions and regulatory mechanisms of circRNAs as competitive endogenous RNAs (ceRNAs) in NeP remain to be determined.MethodsThe sequencing dataset GSE96051 was obtained from the public Gene Expression Omnibus (GEO) database. First, we conducted a comparison of gene expression profiles in the L3/L4 dorsal root ganglion (DRG) of sciatic nerve transection (SNT) mice (n = 5) and uninjured mice (Control) (n = 4) to define the differentially expressed genes (DEGs). Then, critical hub genes were screened by exploring protein–protein interaction (PPI) networks with Cytoscape software, and the miRNAs bound to them were predicted and selected and then validated by qRT-PCR. Furthermore, key circRNAs were predicted and filtered, and the network of circRNA-miRNA-mRNA in NeP was constructed.ResultsA total of 421 DEGs were identified, including 332 upregulated genes and 89 downregulated genes. Ten hub genes, including IL6, Jun, Cd44, Timp1, and Csf1, were identified. Two miRNAs, mmu-miR-181a-5p and mmu-miR-223-3p, were preliminarily verified as key regulators of NeP development. In addition, circARHGAP5 and circLPHN3 were identified as key circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that these differentially expressed mRNAs and targeting miRNAs were involved in signal transduction, positive regulation of receptor-mediated endocytosis and regulation of neuronal synaptic plasticity. These findings have useful implications for the exploration of new mechanisms and therapeutic targets for NeP.ConclusionThese newly identified miRNAs and circRNAs in networks reveal potential diagnostic or therapeutic targets for NeP.
Facilitators and barriers associated with breastfeeding among mothers attending primary healthcare facilities in Mpumalanga, South Africa
Authors: Seabela Ethel Sekori , Modjadji Perpetua , Mokwena Kebogile Elizabeth 
Published: March 2023

IntroductionDespite the health benefits of breastfeeding for both the mother and the child, early cessation of breastfeeding remains a public health problem in South Africa, attributed to contextual barriers and facilitators. Within the context of Mpumalanga province, which is characterized by low breastfeeding rates and high infant mortality rates in children under 5 years, we explored the facilitators and barriers to breastfeeding among mothers attending the three primary health facilities in Ermelo.MethodsUsing a semi-structured interview guide suggested by the socio-ecological model, three focus group discussions and 12 in-depth interviews were conducted among mothers selected using a purposive sampling. Transcripts from audiotaped and transcribed verbatim interviews were assessed through thematic analysis using NVivo version 10.ResultsMothers were aged between 18 and 42 years and from poor sociodemographic backgrounds. At the individual level, mothers valued breastfeeding facilitated by their commitment, maintaining it, eating healthy foods, and having sufficient breast milk. However, returning to work, insufficient breast milk, misconceptions about breastfeeding, and interference with social life were the barriers for mothers to breastfeed continuously. At the interpersonal level, the family was identified as the main form of support to breastfeeding mothers; however, family interference was also identified as a barrier. At the community level, mothers shared some family beliefs and practices but were still split between societal and cultural norms and traditional beliefs as facilitators or barriers to breastfeeding. At the organizational level, most mothers valued the support provided by healthcare workers on childcare and techniques for breastfeeding at the health facilities. They did however articulate concerns on the miscommunication some healthcare workers offered regarding breastfeeding, which negatively influenced their infant feeding practices.DiscussionIntervention efforts should focus on behaviour change to educate and equip mothers to overcome the barriers that are within their control. Such interventions should further focus on family-centered education and strengthening the proficiency of healthcare workers on advising breastfeeding mothers.
Cost-effectiveness of palbociclib plus fulvestrant as second-line therapy of women with HR+/HER2- advanced breast cancer - A Chinese healthcare system perspective
Authors: Zhu Wentao , Zheng Miaomiao , Xia Panpan , Hong Wanglong , Ma Guoqiang , Shen Aizong 
Published: March 2023

AimTo evaluate the cost-effectiveness of palbociclib plus fulvestrant in the second-line treatment of women with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer based on the latest published follow-up data from the perspective of the Chinese healthcare system.MethodsIn view of the PALOMA-3 trial, a Markov model was built for this purpose, which included three health states: progression-free survival (PFS), progressed disease (PD), and death. The cost and health utilities were mainly derived from the published literature. One-way sensitivity analysis and probabilistic sensitivity analysis were carried out to verify the robustness of the model.ResultsIn the base case analysis, compared with the placebo plus fulvestrant arm, the palbociclib plus fulvestrant arm yielded an additional 0.65 quality-adjusted life years (QALYs) (2.56 QALYs vs. 1.90 QALYs) with an incremental cost of $36,139.94 ($55,482.06 vs. $19,342.12), resulting an incremental cost-effectiveness ratio (ICER) of $55,224.90/QALY, which was deeply higher than a willingness-to-pay (WTP) threshold of $34,138.28 per QALY in China. The results of one-way sensitivity analysis indicated that the utility of PFS, cost of palbociclib, and cost of neutropenia had a great influence on the ICER.ConclusionsPalbociclib plus fulvestrant is unlikely to be cost-effective in comparison with placebo plus fulvestrant as second-line therapy of women with HR+/HER2- advanced breast cancer.
The 20 years transition of clinical characteristics and metabolic risk factors in primary liver cancer patients from China
Authors: Ding Yezhou , Feng Mingyang , Ma Di , Zhao Gangde , Wang Xiaolin , An Baoyan , Xu Yumin , Lou Shike , Lin Lanyi , Xie Qing , Liu Kehui , Bao Shisan , Wang Hui 
Published: March 2023

BackgroundThe clinical characteristics of primary liver cancer (PLC) patients are changing, maybe due to hepatitis viral vaccination and lifestyle changes, etc. The linkage between these changes and outcomes among these PLCs has not yet been fully elucidated.MethodsIt was identified total of 1691 PLC cases diagnosed between 2000 ~ 2020. Cox proportional hazards models were utilized to determine the connections between the clinical presentations and their close risk factor(s) from PLC patients.ResultsThe average age of PLC patients increased gradually from 52.74 ± 0.5 years in 2000 ~ 2004 to 58.63 ± 0.44 years in 2017 ~ 2020, accompanied by an increased proportion of females from 11.11% to 22.46%, and non-viral hepatitis-related PLC was raised from 1.5% to 22.35%. 840 (49.67%) PLC patients with alpha-fetoprotein (AFP) &lt; 20ng/mL (AFP-negative). The mortality was 285 (16.85%) or 532 (31.46%) PLC patients with alanine transaminase (ALT) between 40 ~ 60 IU/L or ALT &gt; 60 IU/L. The PLC patients with pre-diabetes/diabetes or dyslipidemia also increased from 4.29% or 11.1% in 2000 ~ 2004 to 22.34% or 46.83% in 2017 ~ 2020. The survival period of the PLC patients with normoglycemia or normolipidemic was 2.18 or 3.14 folds longer than those patients with pre-diabetes/diabetes or hyperlipidemia (P&lt;0.05).ConclusionsIt was gradually increased that age, the proportion of females, non-viral hepatitis-related causes, AFP-negative, and abnormal glucose/lipids among PLC patients. Proper control of glucose/lipids or ALT may improve the prognosis of PLCs.
Concerns and priority outcomes for children with advanced cancer and their families in the Middle East: A cross-national qualitative study
Authors: Boufkhed Sabah , Yurduşen Sema , Alarjeh Ghadeer , Ahmed Fahad , Alrjoub Waleed , Guo Ping , Alajarmeh Sawsan , Şengelen Meltem , Cemaloğlu Mustafa , Aydın Burça , Alnassan Anwar , Al-Awady Shireen , Kutluk Tezer , Shamieh Omar , Harding Richard 
Published: March 2023

IntroductionPalliative care access is limited in the Middle-East, with few specialist centers and forcibly displaced migrants facing additional struggles to access care. Little is known about the specificities of providing palliative care to children and young people (CYP) with cancer. They are rarely asked directly their concerns and needs, which limits the provision of quality patient-centered care. Our study aims to identify the concerns and needs of CYP with advanced cancer and their families, in Jordan and Turkey.MethodA qualitative cross-national study in Jordan and Turkey with framework analysis was conducted two pediatric cancer centers in Jordan and Turkey. In each country, 25 CYP, 15 caregivers and 12 healthcare professionals participated (N=104). Most caregivers (70%) and healthcare professionals (75%) were women.ResultsWe identified five areas of concern: (1) Physical pain and other symptoms (e.g. mobility, fatigue); (2) Psychological concerns and needs (e.g. anger, psychological changes); (3) Spirituality, uncertainty over the future and use of “Tawakkul” (e.g. use of religion as a coping mechanism); (4) Negative impact on social life (e.g. social isolation, loss of support); (5) Burden on caregiver and their families (e.g. financial issues, siblings left behind). Psychological concerns were a priority for both CYPs and caregivers (particularly for refugee and displaced families) but often overlooked during routine care. CYP were able to share their own concerns and care priorities.ConclusionsAdvanced cancer care must ensure assessment and management of concerns across the concerns identified. Developing child- and family-centered outcomes would ensure monitoring the quality of care. Spirituality had a more important role compared to similar investigation in other regions.
Impact of lenvatinib-induced proteinuria and renal dysfunction in patients with thyroid cancer
Authors: Shibutani Yuma , Suzuki Shinya , Sagara Atsunobu , Enokida Tomohiro , Okano Susumu , Fujisawa Takao , Sato Fumiaki , Yumoto Tetsuro , Sano Motohiko , Kawasaki Toshikatsu , Tahara Makoto 
Published: March 2023

BackgroundProteinuria is the most frequent adverse event of lenvatinib use. However, the association between lenvatinib-induced proteinuria and renal dysfunction remains unclear.MethodsWe retrospectively reviewed medical records of patients with thyroid cancer without proteinuria treated with lenvatinib as a first-line systemic therapy at the initiation of treatment to assess the association between lenvatinib-induced proteinuria and renal function and the risk factors for the development of ≥3+ proteinuria on a dipstick test. Proteinuria was assessed by the dipstick test throughout the treatment in all cases.ResultsOf the 76 patients, 39 developed ≤2+ proteinuria (low proteinuria group) and 37 developed ≥3+ proteinuria (high proteinuria group). There was no significant difference in estimated glomerular filtration rate (eGFR) between high and low proteinuria groups at each time point, but there was a trend toward a significant decrease in eGFR of -9.3 ml/min/1.73 m2 in all patients after 2 years of treatment. The percentage of change in eGFR (ΔeGFR) significantly decreased in the high proteinuria group compared to that in the low proteinuria group (ΔeGFR: -6.8% vs. -17.2%, p=0.04). However, there was no significant difference in development of severe renal dysfunction with eGFR &lt;30 ml/min/1.73 m2 between the two groups. Moreover, no patients permanently discontinued treatment because of renal dysfunction in both groups. Furthermore, renal function after completion of lenvatinib was reversible.ConclusionsThere was no association between the degree of lenvatinib-induced proteinuria and renal function. Therefore, treatment should be continued with attention to renal function, regardless of the degree of proteinuria.
Risk prediction of bronchopulmonary dysplasia in preterm infants by the nomogram model
Authors: Gao Yang , Liu Dongyun , Guo Yingmeng , Cao Menghan 
Published: March 2023

Backgrounds and AimsBronchopulmonary dysplasia (BPD) has serious immediate and long-term sequelae as well as morbidity and mortality. The objective of this study is to develop a predictive model of BPD for premature infants using clinical maternal and neonatal parameters.MethodsThis single-center retrospective study enrolled 237 cases of premature infants with gestational age less than 32 weeks. The research collected demographic, clinical and laboratory parameters. Univariate logistic regression analysis was carried out to screen the potential risk factors of BPD. Multivariate and LASSO logistic regression analysis was performed to further select variables for the establishment of nomogram models. The discrimination of the model was assessed by C-index. The Hosmer-Lemeshow test was used to assess the calibration of the model.ResultsMultivariate analysis identified maternal age, delivery option, neonatal weight and age, invasive ventilation, and hemoglobin as risk predictors. LASSO analysis selected delivery option, neonatal weight and age, invasive ventilation, hemoglobin and albumin as the risk predictors. Both multivariate (AUC = 0.9051; HL P = 0.6920; C-index = 0.910) and LASSO (AUC = 0.8935; HL P = 0.7796; C-index = 0.899) - based nomograms exhibited ideal discrimination and calibration as confirmed by validation dataset.ConclusionsThe probability of BPD in a premature infant could be effectively predicted by the nomogram model based on the clinical maternal and neonatal parameters. However, the model required external validation using larger samples from multiple medical centers.
Genomic sequencing has a high diagnostic yield in children with congenital anomalies of the heart and urinary system
Authors: Allred Erika T. , Perens Elliot A. , Coufal Nicole G. , Sanford Kobayashi Erica , Kingsmore Stephen F. , Dimmock David P. 
Published: March 2023

BackgroundCongenital heart defects (CHD) and congenital anomalies of the kidney and urinary tract (CAKUT) account for significant morbidity and mortality in childhood. Dozens of monogenic causes of anomalies in each organ system have been identified. However, even though 30% of CHD patients also have a CAKUT and both organs arise from the lateral mesoderm, there is sparse overlap of the genes implicated in the congenital anomalies for these organ systems. We sought to determine whether patients with both CAKUT and CHD have a monogenic etiology, with the long-term goal of guiding future diagnostic work up and improving outcomes.MethodsRetrospective review of electronic medical records (EMR), identifying patients admitted to Rady Children's Hospital between January 2015 and July 2020 with both CAKUT and CHD who underwent either whole exome sequencing (WES) or whole genome sequencing (WGS). Data collected included demographics, presenting phenotype, genetic results, and mother's pregnancy history. WGS data was reanalyzed with a specific focus on the CAKUT and CHD phenotype. Genetic results were reviewed to identify causative, candidate, and novel genes for the CAKUT and CHD phenotype. Associated additional structural malformations were identified and categorized.ResultsThirty-two patients were identified. Eight patients had causative variants for the CAKUT/CHD phenotype, three patients had candidate variants, and three patients had potential novel variants. Five patients had variants in genes not associated with the CAKUT/CHD phenotype, and 13 patients had no variant identified. Of these, eight patients were identified as having possible alternative causes for their CHD/CAKUT phenotype. Eighty-eight percent of all CAKUT/CHD patients had at least one additional organ system with a structural malformation.ConclusionsOverall, our study demonstrated a high rate of monogenic etiologies in hospitalized patients with both CHD and CAKUT, with a diagnostic rate of 44%. Thus, physicians should have a high suspicion for genetic disease in this population. Together, these data provide valuable information on how to approach acutely ill patients with CAKUT and CHD, including guiding diagnostic work up for associated phenotypes, as well as novel insights into the genetics of CAKUT and CHD overlap syndromes in hospitalized children.