bluuebunny/crossref_metadata_2025_split huggingface dataset:
“As soon as I start trusting human beings, they disappoint me, and now I am going to get on an app that someone could hack. I really do not want to take that chance”: barriers and facilitators to digital peer support implementation into community mental health centers
Authors: Fortuna Karen L. , Divatia Shreya , Neupane Sudeep , Geiger Pamela , Bohm Andrew 
Published: July 2023

BackgroundCertified peer support specialists often use technologies such as smartphone applications to deliver digital peer support in community mental health centers. Certified peer support specialists are individuals with a mental health diagnosis, trained and accredited by their state to provide mental health support services. Digital peer support has shown promising evidence of promoting recovery, hope, social support, and medical and psychiatric self-management among patients with a diagnosis of a serious mental illness. Interest in digital peer support as part of the patient experience has grown. Understanding barriers and facilitators to the implementation process of digital peer support into community mental health centers is a critical next step to facilitate uptake.MethodsSemi-structured qualitative interviews were conducted with 27 patient participants (N = 17 persons with serious mental illness; N = 10 certified peer support specialists) from an urban community mental health center. Participants responded to open-ended questions on the barriers and facilitators of engaging with digital peer support technologies within community mental health centers. The interview guide and the responses were categorized according to the Consolidated Framework for Implementation Science Research (CFIR) constructs.ResultsNine barriers and two facilitators were identified for the implementation of digital peer support in community mental health centers. The overarching domains for the identified barriers included (1) intervention characteristics (i.e., adaptability, complexity, and cost), (2) inner settings (i.e., implementation climate, readiness for implementation, and access to knowledge and information), and (3) characteristics of individuals (i.e., knowledge and beliefs about the intervention and other personal attributes). The two facilitators identified included (1) intervention characteristics (i.e., relative advantage) and (2) outer setting (i.e., patient needs and resources).ConclusionsThe identified barriers and facilitators represent a starting point for developing or modifying digital peer support technology requirements to ease implementation in community mental health centers. Building technology requirements and implementation processes based on these findings may facilitate uptake of digital peer support technologies by people with serious mental illness and certified peer support specialists in community mental health centers.
Mendelian randomization study of thyroid function and anti-Müllerian hormone levels
Authors: Liang Zhu , Xu Zijin , Liu Jianqiao 
Published: July 2023

ObjectiveAlthough previous studies have reported an association between thyroid function and anti-Müllerian hormone (AMH) levels, which is considered a reliable marker of ovarian reserve, the causal relationship between them remains uncertain. This study aims to investigate whether thyrotropin (TSH), free thyroxine (fT4), hypo- and hyperthyroidism are causally linked to AMH levels.MethodsWe obtained summary statistics from three sources: the ThyroidOmics Consortium (N = 54,288), HUNT + MGI + ThyroidOmics meta-analysis (N = 119,715), and the most recent AMH genome-wide association meta-analysis (N = 7,049). Two-sample MR analyses were conducted using instrumental variables representing TSH and fT4 levels within the normal range. Additionally, we conducted secondary analyses to explore the effects of hypo- and hyperthyroidism. Subgroup analyses for TSH were also performed.ResultsMR analyses did not show any causality relationship between thyroid function and AMH levels, using normal range TSH, normal range fT4, subclinical hypothyroidism, subclinical hyperthyroidism and overt hypothyroidism as exposure, respectively. In addition, neither full range TSH nor TSH with individuals &lt;50 years old was causally associated with AMH levels. MR sensitivity analyses guaranteed the robustness of all MR results, except for the association between fT4 and AMH in the no-DIO1+DIO2 group.ConclusionOur findings suggest that there was no causal association between genetically predicted thyroid function and AMH levels in the European population.
Lenvatinib improves anti-PD-1 therapeutic efficacy by promoting vascular normalization via the NRP-1-PDGFRβ complex in hepatocellular carcinoma
Authors: Yang Jieying , Guo Zhixing , Song Mengjia , Pan Qiuzhong , Zhao Jingjing , Huang Yue , Han Yulong , Ouyang Dijun , Yang Chaopin , Chen Hao , Di Muping , Tang Yan , Zhu Qian , Wang Qijing , Li Yongqiang , He Jia , Weng Desheng , Xiang Tong , Xia JianChuan 
Published: July 2023

IntroductionThe limited response to immune checkpoint blockades (ICBs) in patients with hepatocellular carcinoma (HCC) highlights the urgent need for broadening the scope of current immunotherapy approaches. Lenvatinib has been shown a potential synergistic effect with ICBs. This study investigated the optimal method for combining these two therapeutic agents and the underlying mechanisms.MethodsThe effect of lenvatinib at three different doses on promoting tissue perfusion and vascular normalization was evaluated in both immunodeficient and immunocompetent mouse models. The underlying mechanisms were investigated by analyzing the vascular morphology of endothelial cells and pericytes. The enhanced immune infiltration of optimal-dose lenvatinib and its synergistic effect of lenvatinib and anti-PD-1 antibody was further evaluated by flow cytometry and immunofluorescence imaging.ResultsThere was an optimal dose that superiorly normalized tumor vasculature and increased immune cell infiltration in both immunodeficient and immunocompetent mouse models. An adequate concentration of lenvatinib strengthened the integrity of human umbilical vein endothelial cells by inducing the formation of the NRP-1-PDGFRβ complex and activating the Crkl-C3G-Rap1 signaling pathway in endothelial cells. Additionally, it promoted the interaction between endothelial cells and pericytes by inducing tyrosine-phosphorylation in pericytes. Furthermore, the combination of an optimal dose of lenvatinib and an anti-PD-1 antibody robustly suppressed tumor growth.ConclusionsOur study proposes a mechanism that explains how the optimal dose of lenvatinib induces vascular normalization and confirms its enhanced synergistic effect with ICBs.
Immunoprecipitation methods impact the peptide repertoire in immunopeptidomics
Authors: Wacker Marcel , Bauer Jens , Wessling Laura , Dubbelaar Marissa , Nelde Annika , Rammensee Hans-Georg , Walz Juliane S. 
Published: July 2023

IntroductionMass spectrometry-based immunopeptidomics is the only unbiased method to identify naturally presented HLA ligands, which is an indispensable prerequisite for characterizing novel tumor antigens for immunotherapeutic approaches. In recent years, improvements based on devices and methodology have been made to optimize sensitivity and throughput in immunopeptidomics. However, developments in ligand isolation, mass spectrometric analysis, and subsequent data processing can have a marked impact on the quality and quantity of immunopeptidomics data.MethodsIn this work, we compared the immunopeptidome composition in terms of peptide yields, spectra quality, hydrophobicity, retention time, and immunogenicity of two established immunoprecipitation methods (column-based and 96-well-based) using cell lines as well as primary solid and hematological tumor samples.ResultsAlthough, we identified comparable overall peptide yields, large proportions of method-exclusive peptides were detected with significantly higher hydrophobicity for the column-based method with potential implications for the identification of immunogenic tumor antigens. We showed that column preparation does not lose hydrophilic peptides in the hydrophilic washing step. In contrast, an additional 50% acetonitrile elution could partially regain lost hydrophobic peptides during 96-well preparation, suggesting a reduction of the bias towards the column-based method but not completely equalizing it.DiscussionTogether, this work showed how different immunoprecipitation methods and their adaptions can impact the peptide repertoire of immunopeptidomic analysis and therefore the identification of potential tumor-associated antigens.
Impact of in vitro HIV infection on human thymic regulatory T cell differentiation
Authors: Swaminathan Sharada , Scorza Tatiana , Yero Alexis , Farnos Omar , Burke Schinkel Stephanie C. , Angel Jonathan B. , Jenabian Mohammad-Ali 
Published: July 2023

BackgroundThe differentiation and function of immunosuppressive regulatory T cells (Tregs) is dictated by the master transcription factor FoxP3. During HIV infection, there is an increase in Treg frequencies in the peripheral blood and lymphoid tissues. This accentuates immune dysfunction and disease progression. Expression of FoxP3 by thymic Tregs (tTregs) is partially controlled by TGF-β. This cytokine also contributes to Treg development in the peripheral blood and lymphoid tissues. Although TGF-β mediates lymphoid tissue fibrosis and peripheral Treg differentiation in HIV-infected individuals, its role in the induction and maintenance of Tregs within the thymus during HIV infection remains unclear.MethodsThymocytes were isolated from fresh human thymic tissues obtained from pediatric patients undergoing cardiac surgery. Infection by both R5- and X4-tropic HIV-1 strains and TGF-β treatment of human thymocytes was performed in an in vitro co-culture model with OP9-DL1 cells expressing Notch ligand delta-like 1 without T cell receptor (TCR) activation.ResultsDespite high expression of CCR5 and CXCR4 by tTregs, FoxP3 +  CD3highCD8- thymocytes were much less prone to in vitro infection with R5- and X4-tropic HIV strains compared to FoxP3-CD3highCD8- thymocytes. As expected, CD3highCD4+ thymocytes, when treated with TGF-β1, upregulated CD127 and this treatment resulted in increased FoxP3 expression and Treg differentiation, but did not affect the rate of HIV infection. FoxP3 expression and Treg frequencies remained unchanged following in vitro HIV infection alone or in combination with TGF-β1.ConclusionFoxP3 expression and tTreg differentiation is not affected by in vitro HIV infection alone or the combination of in vitro HIV infection and TGF-β treatment.
The functional status of vestibular otolith and conductive pathway in patients with unilateral idiopathic sudden sensorineural hearing loss
Authors: Shen Jiali , Ma Xiaobao , Zhang Qing , Chen Jianyong , Wang Lu , Wang Wei , He Kuan , Sun Jin , Zhang Qin , Chen Xiangping , Duan Maoli , Jin Yulian , Yang Jun 
Published: July 2023

BackgroundThe cause of idiopathic sudden sensorineural hearing loss (ISSNHL) remains unknown. It has been found that the functional status of the vestibular otolith is relevant to its prognosis; however, the evaluation of the vestibular otolith (intra-labyrinth) and superior and inferior vestibular nerve pathways (retro-labyrinth) in ISSNHL patients is not well-documented.ObjectiveThis study aimed to investigate the functional status of the vestibular otolith and conductive pathway in patients with unilateral ISSNHL and analyze the correlations between vestibular evoked myogenic potentials (VEMPs) and hearing improvement after treatment.MethodsA total of 50 patients with unilateral ISSNHL underwent a battery of audio-vestibular evaluations, including pure tone audiometry, middle ear function, air-conducted sound-cervical VEMP (ACS-cVEMP), ACS-ocular VEMP (ACS-oVEMP), galvanic vestibular stimulation-cervical VEMP (GVS-cVEMP), and GVS-ocular VEMP (GVS-oVEMP). The results of auditory and VEMPs were retrospectively analyzed.ResultsThe abnormal rates of ACS-cVEMP, ACS-oVEMP, GVS-cVEMP, and GVS-oVEMP in affected ears were 30, 52, 8, and 16%, respectively. In affected ears, the abnormal rate of ACS-oVEMP was significantly higher than that of ACS-cVEMP (p = 0.025), while it was similar between GVS-cVEMP and GVS-oVEMP (p = 0.218). Compared with GVS-cVEMP, affected ears presented with a significantly higher abnormal rate of ACS-cVEMP (p = 0.005), and the abnormal rate of ACS-oVEMP was significantly higher than that of GVS-oVEMP (p &lt; 0.001). No significant difference existed in latency and amplitude between affected and unaffected ears in ACS-VEMPs or GVS-VEMPs (p &gt; 0.05). The abnormal rate of VEMPs in the poor recovery group was significantly higher than that of the good recovery group (p = 0.040). The abnormality percentages of ACS-oVEMP and GVS-oVEMP in the poor recovery group were significantly higher than that of the good recovery group (p = 0.004 and 0.039, respectively). The good hearing recovery rates were 76.47% in the normal VEMPs group, 58.33% in the intra-labyrinth lesion group, and 22.22% in the retro-labyrinth lesion group. Hearing recovery worsened as a greater number of abnormal VEMPs was presented.ConclusionBesides Corti's organ, the impairment of otolithic organs was prominent in patients with ISSNHL. The normal VEMPs group had the highest rate of good recovery, followed by the intra-labyrinth lesion group and the retro-labyrinth lesion group presented with the lowest recovery rate. Abnormalities in ACS-oVEMP and/or GVS-oVEMP were indicators of a poor prognosis.
An oxidative stress biomarkers predict prognosis in gastric cancer patients receiving immune checkpoint inhibitor
Authors: Deng Guiming , Sun Hao , Huang Rong , Pan Hongming , Zuo Yanjiao , Zhao Ruihu , Du Zhongze , Xue Yingwei , Song Hongjiang 
Published: July 2023

ObjectiveThe development and advance of gastric cancer are inextricably linked to oxidative and antioxidant imbalance. Although immunotherapy has been shown to be clinically effective, the link between oxidative stress and gastric cancer patients treated with immune checkpoint inhibitor (ICIs) remains unknown. This study aims at looking into the prognostic value of oxidative stress scores in gastric cancer patients treated with ICIs.MethodsBy taking the propagation to receiver operating characteristic (ROC) we got the best cut-off values, and divided 265 patients receiving ICIs and chemotherapy into high and low GC-Integrated Oxidative Stress Score (GIOSS) groups. We also used Kaplan-Meier and COX regression models to investigate the relationship between oxidative stress biomarkers and prognosis.ResultsThrough both univariate and multivariate analyses, it’s shown that GIOSS severs as an independent prognostic factor for progression-free survival (PFS) and Overall survival (OS). Based on GIOSS cutoff values, patients with high GIOSS levels, compared to those with low levels exhibited shorter PFS and OS, both in the high GIOSS group, which performed poorly in the ICIs subgroup and other subgroup analyses.ConclusionGIOSS is a biomarker that responds to systemic oxidative stress in the body and can predict prognosis in patients with gastric cancer who are taking ICIs. Additionally, it might come to medical professionals’ aid in making more effective or more suitable treatment plans for gastric cancer.
Supportive parent-adolescent relationships as a foundation for adolescent emotion regulation and adjustment
Authors: Ratliff Erin L. , Morris Amanda S. , Cui Lixian , Jespersen Jens E. , Silk Jennifer S. , Criss Michael M. 
Published: July 2023

IntroductionThe purpose of this investigation was to examine the influence of supportive parent-adolescent relationships on adolescent adjustment (i.e., prosocial behavior, aggression, depressive symptoms) both directly and indirectly (via adolescent emotion regulation). Scholars have posited that adolescent emotion regulation (ER) may serve as an underlying mechanism in the link between parenting and adolescent adjustment. Supportive parent-adolescent relationships (i.e., openness, acceptance, emotional responsiveness) may be a key emotion socialization mechanism influencing adolescent ER.MethodsThe sample included 206 adolescents (Age Range= 10–18years; 51% female; 70.4% ethnic minorities) and one primary caregiver (83.3% biological mothers, 38.7% single parents). Structural equation modeling (SEM) was implemented to investigate the direct and indirect (via adolescent ER) effects of supportive parent-adolescent relationships on adolescent adjustment. We also explored whether these indirect and direct effects varied by adolescent sex and age.ResultsResults suggested direct and indirect (via adolescent ER) links between supportive parent-adolescent relationships and adolescent prosocial behavior, aggressive behavior, and depressive symptoms. Moreover, evidence indicated that many of these pathways were significant for boys but not girls. No evidence of youth age as a moderator was found.DiscussionThese findings highlight the important role supportive parent-adolescent relationships play in adolescent emotional and behavioral adjustment. Parenting programs could focus on facilitating a mutually responsive parent-adolescent relationship with a specific focus on the dynamic nature of emotion socialization during adolescence.
Receipt of COVID-19 vaccine in preterm-born children aged 3-7 in China
Authors: Wang Dan , Li Li , Ma Xiaofeng , Lin Yunfeng , Chen Liping , Arigonggaowa  , Peng Xianglian , Shi Jingyun , Yang Jie , Ju Rong , Li Zhankui , Cao Jingke , Liu Changgen , Feng Zhichun , Li Qiuping 
Published: July 2023

ObjectivesTo determine the COVID-19 vaccination rate in preterm-born children aged 3–7 in China and influential factors, identify vaccination-related adverse reactions, and clarify reasons behind parental refusal of vaccination to their children.MethodsThis cross-sectional study was conducted in parents of preterm-born children aged 3–7 in different regions of China through WeChat.ResultsOf 1,924 Chinese preterm-born children aged 3–7 included in this study, 1,552 (80.7%) had been vaccinated against COVID-19, with a higher vaccination rate in eastern China. Children older than 4 years, kids in kindergartens and primary schools, children living in eastern or western China, and children whose fathers had received at least one dose of a COVID-19 vaccine tended to be vaccinated against COVID-19 after adjusting for other covariates. Conversely, children living in urban areas, children whose annual family income was &lt; 50,000 CNY or more than 300,000 CNY, premature children who underwent hospital transfers, and children with underlying diseases were less likely to get vaccinated. Adverse reactions occurred in 59/1,552 (3.8%) vaccinated children. Parents of 118/372 (31.7%) children expressed their concerns over adverse reactions to COVID-19 vaccination. Other reasons like the absence of information about the place where they could get vaccination were mentioned as well.ConclusionsCOVID-19 vaccination-related adverse reactions rarely occurred and most of them were mild among preterm-born children aged 3–7. Higher vaccination coverage can be achieved as parents are provided with more scientific data about benefits of vaccination, vaccination contraindications and precautions, and more information about vaccination sites.
Bioavailability of Macroelements from Synbiotic Sheep’s Milk Ice Cream
Authors: Kowalczyk Magdalena , Znamirowska-Piotrowska Agata , Buniowska-Olejnik Magdalena , Zaguła Grzegorz , Pawlos Małgorzata 
Published: July 2023

To determine the potential bioavailability of macroelements (Ca, Mg, P, K), probiotic ice cream samples (Lactaseibacillus paracasei L-26, Lactobacillus casei 431, Lactobacillus acidophilus LA-5, Lactaseibacillus rhamnosus and Bifidobacterium animalis ssp. lactis BB-12) from sheep’s milk with inulin, apple fiber and inulin, or apple fiber and control samples were submitted to in vitro digestion in the mouth, stomach and small intestine. The bioavailability of calcium in the ice cream samples ranged from 40.63% to 54.40%, whereas that of magnesium was 55.64% to 44.42%. The highest bioavailability of calcium and magnesium was shown for the control samples. However, adding 4% inulin reduced the bioavailability of calcium by about 3–5% and magnesium only by about 5–6%. Adding 4% apple fiber reduced the bioavailability of calcium by as much as 6–12% and magnesium by 7–8%. The highest bioavailability of calcium was determined in ice cream with L. paracasei, and the highest bioavailability of magnesium was determined in ice cream with L. casei. The bioavailability of phosphorus in ice cream ranged from 47.82% to 50.94%. The highest bioavailability of phosphorus (>50%) was in sheep ice cream fermented by B. animalis. In the control ice cream, the bioavailability of potassium was about 60%. In ice cream with inulin, the bioavailability of potassium was lower by 3–4%, and in ice cream with apple fiber, the bioavailability of potassium was lower by up to 6–9%. The bioavailability of potassium was significantly influenced only by the addition of dietary fiber. The results of the study confirmed the beneficial effect of bacteria on the bioavailability of Ca, Mg and P.
Evaluation of the relative allelic load of mutations of resistance to ibrutinib in the <i>BTK</i> gene by allele-specific PCR in patients with progression of CLL
Authors: Likold E. B. , Biderman B. V. , Fevraleva I. S. , Severina N. A. , Dmitrieva E. A. , Petrenko A. A. , Nikitin E. A. , Sudarikov A. B. 
Published: July 2023

Introduction. Currently, Ibrutinib is one of the most effective drugs for relapsed and refractory chronic lymphocytic leukemia treatment. In most patients with CLL, ibrutinib causes persistent remissions, but in some patients the disease progresses. Ibrutinib resistance in most cases is associated with the C481S mutation, which corresponds to the c.1441T>A and c.1442G>C substitutions in the BTK gene, however, other variants also exist.Aim — to evaluate variable allele fraction of the BTK gene mutations in patients with relapsed chronic lymphocytic leukemia using the in-house allele-specific real-time PCR test.Materials and methods. The study included material from 102 cases: 39 CLL patients with disease progression on ibrutinib therapy, 24 CLL patients with disease progression on the FCR/FCR-lite protocols, and 38 CLL treatment-naive patients. The control group included 118 patients with non-neoplastic hematological diseases.Results. Using in-house using AS-PCR, we detected the c.1442G>C mutation in 20 out of 39 CLL patients with progression on ibrutinib therapy. Mutation c.1442G>T was detected in 2 patients. In a single patient, two mutations were detected simultaneously: c.1441T>A and c.1442G>C. Another single patient had a combination of three mutations: c.1442G>C, c.1442G>T and c.1442G>A. In 15 patients with progression on ibrutinib therapy, mutations in the BTK gene were not detected. In treatment-naive CLL patients, in the group treated with FCR/FCR-lite regimens, and in the control group of patients with nonneoplastic diseases, mutations in the BTK gene were not detected.Conclusion. Variable allele fraction of exon 15 BTK gene mutations in the patients with CLL progression was successfully determined using in-house AS-PCR test: 50 % of patients had one mutation, 5 % had two mutations, and 2.5 % had three mutations in the BTK gene. Timely detection of these mutations before clinical recurrence may facilitate effective treatment strategy. Since clinical manifestations of ibrutinib resistance appear after an average of 1–2 years, we suggest monitoring BTK mutation load every 3 months in patients with CLL before relapse during treatment with ibrutinib.