bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive and Prognostic Implications of Circulating CX3CR1+ CD8+ T Cells in Non–Small Cell Lung Cancer Patients Treated with Chemo-Immunotherapy
Authors: Abdelfatah Eihab , Long Mark D. , Kajihara Ryutaro , Oba Takaaki , Yamauchi Takayoshi , Chen Hongbin , Sarkar Joy , Attwood Kristopher , Matsuzaki Junko , Segal Brahm H. , Dy Grace K. , Ito Fumito 
Published: February 2023

Lack of reliable predictive biomarkers is a major limitation of combination therapy with chemotherapy and anti–programmed cell death protein 1/programmed death-ligand 1 (anti-PD-1/PD-L1) therapy (chemo-immunotherapy). We previously observed that the increase of peripheral blood CD8+ T cells expressing CX3CR1, a marker of differentiation, correlates with response to anti–PD-1 therapy; however, the predictive and prognostic value of T-cell CX3CR1 expression during chemo-immunotherapy is unknown. Here, we evaluated the utility of circulating CX3CR1+CD8+ T cells as a predictive correlate of response to chemo-immunotherapy in patients with non–small cell lung cancer (NSCLC). At least 10% increase of the CX3CR1+ subset in circulating CD8+ T cells from baseline (CX3CR1 score) was associated with response to chemo-immunotherapy as early as 4 weeks with 85.7% overall accuracy of predicting response at 6 weeks. Furthermore, at least 10% increase of the CX3CR1 score correlated with substantially better progression-free (P = 0.0051) and overall survival (P = 0.0138) on Kaplan–Meier analysis. Combined single-cell RNA/T-cell receptor (TCR) sequencing of circulating T cells from longitudinally obtained blood samples and TCR sequencing of tumor tissue from the same patient who received a long-term benefit from the treatment demonstrated remarkable changes in genomic and transcriptomic signatures of T cells as well as evolution of TCR clonotypes in peripheral blood containing highly frequent tumor-infiltrating lymphocyte repertoires overexpressing CX3CR1 early after initiation of the treatment despite stable findings of the imaging study. Collectively, these findings highlight the potential utility of T-cell CX3CR1 expression as a dynamic blood-based biomarker during the early course of chemo-immunotherapy and a marker to identify frequent circulating tumor-infiltrating lymphocyte repertoires.Significance:Current approaches to combined chemotherapy and anti-PD-1/PD-L1 therapy (chemo-immunotherapy) for patients with NSCLC are limited by the lack of reliable predictive biomarkers. This study shows the utility of T-cell differentiation marker, CX3CR1, as an early on-treatment predictor of response and changes in genomic/transcriptomic signatures of circulating tumor-infiltrating lymphocyte repertoires in patients with NSCLC undergoing chemo-immunotherapy.
Smooth Muscle Mineralocorticoid Receptor Promotes Hypertension After Preeclampsia
Authors: Biwer Lauren A. , Lu Qing , Ibarrola Jaime , Stepanian Alec , Man Joshua J. , Carvajal Brigett V. , Camarda Nicholas D. , Zsengeller Zsuzsanna , Skurnik Geraldine , Seely Ellen W. , Karumanchi S. Ananth , Jaffe Iris Z. 
Published: February 2023

Background:
Preeclampsia is a syndrome of high blood pressure (BP) with end organ damage in late pregnancy that is associated with high circulating soluble VEGF receptor (sFlt1 [soluble Fms-like tyrosine kinase 1]). Women exposed to preeclampsia have a substantially increased risk of hypertension after pregnancy, but the mechanism remains unknown, leaving a missed interventional opportunity. After preeclampsia, women have enhanced sensitivity to hypertensive stress. Since smooth muscle cell mineralocorticoid receptors (SMC-MR) are activated by hypertensive stimuli, we hypothesized that high sFlt1 exposure in pregnancy induces a postpartum state of enhanced SMC-MR responsiveness.

Methods:
Postpartum BP response to high salt intake was studied in women with prior preeclampsia. MR transcriptional activity was assessed in vitro in sFlt1-treated SMC by reporter assays and PCR. Preeclampsia was modeled by transient sFlt1 expression in pregnant mice. Two months post-partum, mice were exposed to high salt and then to AngII (angiotensin II) and BP and vasoconstriction were measured.

Results:
Women exposed to preeclampsia had significantly enhanced salt sensitivity of BP verses those with a normotensive pregnancy. sFlt1 overexpression during pregnancy in mice induced elevated BP and glomerular endotheliosis, which resolved post-partum. The sFlt1 exposed post-partum mice had significantly increased BP response to 4% salt diet and to AngII infusion. In vitro, SMC-MR transcriptional activity in response to aldosterone or AngII was significantly increased after transient exposure to sFlt1 as was aldosterone-induced expression of AngII type 1 receptor. Post-partum, SMC-MR-KO mice were protected from the enhanced response to hypertensive stimuli after preeclampsia. Mechanistically, preeclampsia mice exposed to postpartum hypertensive stimuli develop enhanced aortic stiffness, microvascular myogenic tone, AngII constriction, and AngII type 1 receptor expression, all of which were prevented in SMC-MR-KO littermates.

Conclusions:
These data support that sFlt1-induced vascular injury during preeclampsia produces a persistent state of enhanced sensitivity of SMC-MR to activation. This contributes to postpartum hypertension in response to common stresses and supports testing of MR antagonism to mitigate the increased cardiovascular risk in women after PE.
ITDetect: a method to detect internal tandem duplication of FMS-like tyrosine kinase (FLT3) from next-generation sequencing data with high sensitivity and clinical application
Authors: Lee Sungyoung , Sun Choong-Hyun , Jang Heejun , Kim Daeyoon , Yoon Sung-Soo , Koh Youngil , Na Seung Chan , Cho Sung Im , Kim Man Jin , Seong Moon-Woo , Byun Ja Min , Yun Hongseok 
Published: February 2023

AbstractInternal tandem duplication (ITD) of the FMS-like tyrosine kinase (FLT3) gene is associated with poor clinical outcomes in patients with acute myeloid leukemia. Although recent methods for detecting FLT3-ITD from next-generation sequencing (NGS) data have replaced traditional ITD detection approaches such as conventional PCR or fragment analysis, their use in the clinical field is still limited and requires further information. Here, we introduce ITDetect, an efficient FLT3-ITD detection approach that uses NGS data. Our proposed method allows for more precise detection and provides more detailed information than existing in silico methods. Further, it enables FLT3-ITD detection from exome sequencing or targeted panel sequencing data, thereby improving its clinical application. We validated the performance of ITDetect using NGS-based and experimental ITD detection methods and successfully demonstrated that ITDetect provides the highest concordance with the experimental methods. The program and data underlying this study are available in a public repository.
ARL9 is upregulated and serves as a biomarker for a poor prognosis in colon adenocarcinoma
Authors: Yang Hai-deng , Jin Xiu-xiu , Gu Bin-bin , Yu-Zhang  , Li Dan , Yan Ling-ling 
Published: February 2023

Abstract
Background
ARL9 is a newly identified member of the ARF family, and the clinical significance of ARL9 in colon adenocarcinoma is unknown. In this study, we aimed to explore the expression of ARL9 mRNA in colon adenocarcinoma, and its effect on the prognosis of patients with colon adenocarcinoma.

Methods
We investigated the differential expression of ARL9 between colon adenocarcinoma tissue and adjacent tissues through a bioinformatics analysis using The Cancer Genome Atlas (TCGA) database. The correlation between clinical characteristics and the mRNA expression level of ARL9 were analyzed. A survival analysis and a Cox regression analysis were used to determine the prognostic significance of ARL9. Finally, we conducted a gene set enrichment analysis (GSEA) to explore the ARL9 signaling pathways involved in the development of colon adenocarcinoma. The effect of the expression of ARL9 on the proliferation and migration of colon adenocarcinoma was analyzed by the CCK8 method and a cell scratch test, respectively.

Results
The mRNA expression of ARL9 in colon adenocarcinoma tissues was higher in comparison to the level in normal adjacent tissues (P < 0.05). The mRNA expression of ARL9 was not related to sex, tumor stage, T stage, N stage, M stage, but to age. The 5-year survival rate of colon adenocarcinoma patients with high ARL9 mRNA expression levels was significantly lower than that of patients with low ARL9 mRNA expression levels (P < 0.05). Age and the high mRNA expression of ARL9 were independent risk factors for a poor prognosis in patients with colon adenocarcinoma. The GSEA suggested that ARL9 may be able to upregulate cell adhesion, extracellular matrix receptor interactions, tumor-associated pathways, and downregulate the citrate cycle and tricarboxylic acid cycle pathway, which are involved in the development of colon adenocarcinoma. After knocking down ARL9, the proliferation and migration abilities of colon adenocarcinoma cells were decreased (P < 0.01).

Conclusion
The mRNA expression of ARL9 is upregulated in colon adenocarcinoma, and higher mRNA expression levels are associated with a poor prognosis. Knocking down ARL9 can reduce the proliferation and migration of colon adenocarcinoma cells. ARL9 mRNA can be used as a prognostic biomarker in patients with colon adenocarcinoma.
Relationship between social network and individual performance of core members from aged care services social organizations: cross-sectional study
Authors: Wang Zhengsheng , Chen Xuefei , Ji Kai , Sang Lingzhi , Bai Zhongliang , Chen Ren 
Published: February 2023

Abstract
Background
The social network of core members can affect the performance of the organization, while there is a lack of research on the relationship between the social network of core members of social organizations and individual performance in the field of aged care services. This study aimed to explore the relationship between social network and individual performance of core members from social organizations engaged in aged care services and explore measures to promote the development of aged care services.

Methods
We used a multi-stage stratified sampling method to conduct a cross-sectional study and collected the required data in six cities in Anhui Province, China. Univariate analysis and binary logistic regression were used to estimate the relationship between social network and individual performance.

Results
Our results indicated that core members with higher social network scores were more likely to yield better individual performance, including receiving awards or recognitions related to aged care services (AOR=2.534; 95% CI: 1.397-4.596). Moreover, teams led by the core members were more likely to receive awards or recognitions related to aged care services (AOR=2.930; 95% CI: 1.740-4.933). The core members or the teams led by them were more likely to be reported by the media (AOR=1.748; 95% CI: 1.030-2.966) and participate in the drafting or discussion of local aged care service standards or service specifications (AOR=2.088; 95% CI: 1.093-3.911). In addition, demographic variables such as gender, marital status, and education of core members were significantly related to their performance (P<0.05).

Conclusions
The social network of core members of aged care service social organizations has an impact on their individual performance. To improve the performance of the core members of senior citizens services and organizations, relevant measures should be taken from the government, social organizations and core members to strengthen the social network construction of core members.
Which interventions for alcohol use should be included in a universal healthcare benefit package? An umbrella review of targeted interventions to address harmful drinking and dependence
Authors: Botwright Siobhan , Sutawong Jiratorn , Kingkaew Pritaporn , Anothaisintawee Thunyarat , Dabak Saudamini Vishwanath , Suwanpanich Chotika , Promchit Nattiwat , Kampang Roongnapa , Isaranuwatchai Wanrudee 
Published: February 2023

Abstract
Background
This study aimed to identify targeted interventions for the prevention and treatment of harmful alcohol use. Umbrella review methodology was used to summarise the effectiveness across a broad range of interventions, in order to identify which interventions should be considered for inclusion within universal health coverage schemes in low- and middle-income countries.

Methods and findings
We included systematic reviews with meta-analysis of randomised controlled trials (RCTs) on targeted interventions addressing alcohol use in harmful drinkers or individuals with alcohol use disorder. We only included outcomes related to alcohol consumption, heavy drinking, binge drinking, abstinence, or alcohol-attributable accident, injury, morbidity or mortality. PubMed, Embase, PsycINFO, Cochrane Database of Systematic Reviews, and the International HTA Database were searched from inception to 3 September 2021. Risk of bias of reviews was assessed using the AMSTAR2 tool. After reviewing the abstracts of 9,167 articles, results were summarised narratively and certainty in the body of evidence for each intervention was assessed using GRADE. In total, 86 studies met the inclusion criteria, of which the majority reported outcomes for brief intervention (30 studies) or pharmacological interventions (29 studies). Overall, methodological quality of included studies was low.

Conclusions
For harmful drinking, brief interventions, cognitive behavioural therapy, and motivational interviewing showed a small effect, whereas mentoring in adolescents and children may have a significant long-term effect. For alcohol use disorder, social network approaches and acamprosate showed evidence of a significant and durable effect. More evidence is required on the effectiveness of gamma-hydroxybutyric acid (GHB), nalmefene, and quetiapine, as well as optimal combinations of pharmacological and psychosocial interventions. As an umbrella review, we were unable to identify the extent to which variation between studies stemmed from differences in intervention delivery or variation between country contexts. Further research is required on applicability of findings across settings and best practice for implementation.
Funded by the Thai Health Promotion Foundation, grant number 61–00-1812.
The CONFIDENT study protocol: a randomized controlled trial comparing two methods to increase long-term care worker confidence in the COVID-19 vaccines
Authors: Stevens Gabrielle , Johnson Lisa C. , Saunders Catherine H. , Schmidt Peter , Sierpe Ailyn , Thomeer Rachael P. , Little N. Ruth , Cantrell Matthew , Yen Renata W. , Pogue Jacqueline A. , Holahan Timothy , Schubbe Danielle C. , Forcino Rachel C. , Fillbrook Branden , Sheppard Rowena , Wooten Celeste , Goldmann Don , O’Malley A. James , Dubé Eve , Durand Marie-Anne , Elwyn Glyn 
Published: February 2023

Abstract
Background
Clinical and real-world effectiveness data for the COVID-19 vaccines have shown that they are the best defense in preventing severe illness and death throughout the pandemic. However, in the US, some groups remain more hesitant than others about receiving COVID-19 vaccines. One important group is long-term care workers (LTCWs), especially because they risk infecting the vulnerable and clinically complex populations they serve. There is a lack of research about how best to increase vaccine confidence, especially in frontline LTCWs and healthcare staff. Our aims are to: (1) compare the impact of two interventions delivered online to enhanced usual practice on LTCW COVID-19 vaccine confidence and other pre-specified secondary outcomes, (2) determine if LTCWs’ characteristics and other factors mediate and moderate the interventions’ effect on study outcomes, and (3) explore the implementation characteristics, contexts, and processes needed to sustain a wider use of the interventions.

Methods
We will conduct a three-arm randomized controlled effectiveness-implementation hybrid (type 2) trial, with randomization at the participant level. Arm 1 is a dialogue-based webinar intervention facilitated by a LTCW and a medical expert and guided by an evidence-based COVID-19 vaccine decision tool. Arm 2 is a curated social media web application intervention featuring interactive, dynamic content about COVID-19 and relevant vaccines. Arm 3 is enhanced usual practice, which directs participants to online public health information about COVID-19 vaccines. Participants will be recruited via online posts and advertisements, email invitations, and in-person visits to care settings. Trial data will be collected at four time points using online surveys. The primary outcome is COVID-19 vaccine confidence. Secondary outcomes include vaccine uptake, vaccine and booster intent for those unvaccinated, likelihood of recommending vaccination (both initial series and booster), feeling informed about the vaccines, identification of vaccine information and misinformation, and trust in COVID-19 vaccine information provided by different people and organizations. Exploration of intervention implementation will involve interviews with study participants and other stakeholders, an in-depth process evaluation, and testing during a subsequent sustainability phase.

Discussion
Study findings will contribute new knowledge about how to increase COVID-19 vaccine confidence and effective informational modalities for LTCWs.

Trial registration
NCT05168800 at ClinicalTrials.gov, registered December 23, 2021.
Nurses’ reflections on caring for sexual and gender minorities pre-post stigma reduction training in Uganda
Authors: Muwanguzi Patience A. , Nabunya Racheal , Karis Victoria M. S. , Nabisere Allen , Nangendo Joan , Mujugira Andrew 
Published: February 2023

Abstract
Background
Men who have sex with men (MSM) and transgender women (TGW) have a significant HIV burden worldwide. Data from eight countries across sub-Saharan Africa found a pooled HIV prevalence of 14% among MSM and 25% among TGW. Stigma and discrimination among healthcare providers are barriers to healthcare access by these populations. We sought to explore nurses’ attitudes before and after sensitivity training to reduce stigma in HIV prevention and care provision to MSM and transgender persons in Uganda.

Methods
An explorative qualitative study comprising in-depth interviews. Nineteen nurses who underwent sensitivity training in caring for the vulnerable, priority and key populations in Uganda participated. We interviewed each participant before and after the stigma reduction training and analyzed the data with NVivo.

Results
Eight (8) themes emerged from the reflections before the training, namely, ‘the definition of MSM and transgender persons’, ‘legal concerns’, ‘mental illness’, ‘attitude in health care provision’, ‘personal perceptions’, ‘self-efficacy’, ‘insufficient training preparation’, and ‘reasons for gender or sexual orientation preference’. The post-training reflections suggested a change in knowledge and attitude. Five themes emerged for MSM: ‘stigma reduction’, ‘sexual practices and sexuality’, ‘the need for tailored health approaches’, ‘MSM and the law’ and ‘corrected misconceptions’. For transmen, ‘reproductive health needs’, ‘social needs’, ‘safety needs’, ‘Gender identity recognition’ and ‘reduced stigma, discrimination, and barriers to care’. Finally, the reflections on their attitudes towards transwomen were on five topics; Gender affirming care’, ‘Healthcare provision for transwomen’, ‘Need for further training’, ‘New knowledge acquired’, and ‘Sexual violence’.

Conclusion
Nurses’ attitudes and empathy for vulnerable and key populations improved following the training. Nursing training programs should consider incorporating sexual and gender minority (SGM) specific health training into their curricula to decrease negative attitudes. There is a need to identify best practices and conduct implementation research to provide culturally sensitive and affirming healthcare delivery in sub-Saharan Africa. Future studies should evaluate the effect of provider sensitivity training on sexual health and HIV outcomes for SGM. Furthermore, interventions targeting higher-level stigma, such as structural and policy levels, are critical because they influence interpersonal stigma reduction efforts and initiatives.
Post-traumatic growth in caregivers of children hospitalized in the PICU due to traffic accident: a qualitative study
Authors: Ni Zhi Hong , Lv Hai Tao , Wu Jin Hua , Wang Fang 
Published: February 2023

Abstract
Background
Globally, tens of millions of children are hospitalized every year for non-fatal traffic accident injuries, being confronted with an injured child can be extremely stressful for parents. Understandably, a significant level of psychological distress may ensue. Traumatic losses may lead parents to find new insights in life and develop a greater sense of spirituality and strength.

Method
Semi-structured interviews were conducted with caregivers of children who were hospitalized in the pediatric intensive care unit (PICU) with traffic accident injuries at children’s hospitals in China between January and June 2022. Caregivers were selected using a purposive sampling method until no new data were generated (n = 24).

Results
We identified eleven sub-themes and four higher-order themes based on these sub-themes: (1) changes in their life philosophy, (2) personal strength enhancement, (3) relationship improvements, and (4) effective responses. The findings of our research contribute to a better understanding of the psychological status of the caregivers of children injured by traffic accidents.

Conclusion
Professionals should guide caregivers from a positive perspective, stimulate their strengths and potential, increase personnel support and communication, promote positive coping, formulate targeted management countermeasures to improve the PTG level of caregivers, and develop strategies to maintain stable mental health and well-being.