bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personalized tumor antigen-pulsed dendritic cell therapy synergizes with simultaneous blockade of PD-1/TIM-3 to treat lung cancer
Authors: Chen Chen , Huang Jingyu , Wang Yujin , Wang Qingwen , Hu Liwen , Guo Zixin , Li Sheng , Hu Weidong 
Published: April 2022

Abstract
Background
Immunotherapy has become a promising innovation in human cancer treatment. However, only a minority of patients were benefited from immunotherapy, including PD-1/PD-L1 blockade, dendritic cell vaccine. Why these novel therapies failed and how to improve their therapeutic efficacy in cancer patients, particularly those with lung cancers, remain elusive.
Methods
The function of dendritic cells (DCs) was analyzed by various ex vivo and in vivo assays. Bone marrow were exploited in vitro to drive DCs to load whole tumor antigens (thereafter named Ag-DC) for T cell priming in vitro and in vivo. In both syngeneic and endogenous lung tumor models, the therapeutic effect, underlying mechanisms and acquired resistance of Ag-DC therapy were examined. Finally, the safety and efficacy of combination therapy of Ag-DC and simultaneous blockade of PD-1 and TIM-3 were investigated.
Results
The function of DCs is repressed with respect to phagocytosis of tumor cells and antigen-dependent T cell priming in lung tumor microenvironment. DCs derived from bone marrow in vitro are able to stimulate tumor antigen-specific T cell activation and subsequent killing of tumor cells. Local or systemic administration of whole tumor antigen-pulsed DCs (Ag-DCs) elicits potent T cell activation, enriched tumor-infiltrating lymphocytes, and increased memory T cells, contributing to fewer and smaller lung tumors. In addition, Ag-DC therapy induces expression of immune checkpoint molecules PD-1 and TIM-3 on T cells, which rationalizes the great synergistic efficacy of combination therapy of Ag-DC and simultaneous blockade of PD-1 and TIM-3.
Conclusions
These findings suggest that bone marrow derived DCs in vitro loaded with whole tumor antigens can inhibit lung tumor initiation and progression by triggering strong T-cell antitumor activity, pulmonary recruitment, and tumor infiltration. Simultaneous blockade of PD-1 and TIM-3 synergizes with Ag-DC therapy in lung cancer treatment, representing a novel combination therapy for lung cancer.
“How do I keep this live in my mind?” Allied Health Professionals’ perspectives of barriers and enablers to implementing Good Clinical Practice in research: A qualitative exploration guided by behaviour change theory
Authors: Wenke Rachel , Roberts Shelley , Angus Rebecca , Owusu Maame Amma , Weir Kelly 
Published: April 2022

Abstract
BACKGROUND
Allied health professionals (AHPs) engaged in research are encouraged to comply with Good Clinical Practice (GCP) principles to protect participant safety and wellbeing and enhance data integrity. Currently, there is limited exploration into health professionals’ perceptions of implementing and adhering to GCP standards in research. Such knowledge is vital to guide future interventions to increase GCP adherence.
METHODS
This qualitative descriptive study, guided by behaviour change theory, aimed to identify the barriers and enablers AHPs experience when applying GCP principles to research conduct in a public hospital and health service, as well as their perceived support needs. AHPs currently undertaking ethically approved research within a public health service in Queensland, Australia were interviewed to explore barriers and enablers to GCP adherence and support needs, with interview questions guided by the Theoretical Domains Framework.
RESULTS
Ten AHPs across six professions were interviewed. Participants identified several enablers to implementing GCP. These included strong beliefs about the importance of GCP in increasing research rigour and participant safety; existing clinical skills and personal attributes they can apply when implementing, available training and support; and alignment with their moral sense to ‘do the right thing’. Barriers to GCP implementation were generally less commonly reported but included reduced time to implement GCP and a sense of ‘red tape’, a lack of knowledge of GCP principles and a fear of making mistakes, and varying relevance to individual projects. Several suggestions for support were identified beyond training, such as physical resources (e.g., prescriptive checklists, templates and scripts), additional time, and regular one-on-one mentoring support.
CONCLUSIONS
This study provides important insights into AHP experiences of implementing GCP principles in research, to guide the development of targeted interventions. Findings suggest clinicians require support beyond standard GCP training to implement GCP on a practical basis and adapt relevant principles to their research designs. Other strategies to enhance GCP implementation and adherence should be further investigated.
Correlations between diet quality and early childhood caries among 2- to 5-year-old Chinese children：A cross-sectional study
Authors: Wang Xinfeng , Ma Zhe , Lei Min , Zhao Caiyun , Lin Xiuyan , Cao Fengdi , Shi Hong 
Published: April 2022

Abstract
Background: Early childhood caries (ECC) is one of the most common chronic diseases among children. Diet quality assessment is better than single food or specific nutrient assessment in predicting the risk of ECC. This study is aimed to explore the correlations between diet quality and ECC among 2- to 5-year-old Chinese children. Methods: Totally 150 two- to five-year-old children were selected in this study. The decayed, missing or filled surface (dmfs) of each child was examined and recorded. Then the children were divided by ages and dmfs scores into the caries-free group, ECC group, and severe ECC (SECC) group respectively. The information of 24-h dietary intake from each child was captured via a mobile APP. The diet quality of each child was assessed by calculating the Chinese diet balance index for preschool children (DBI_C) indicators scores, high bound score (HBS), low bound score (LBS) and diet quality distance (DQD). Correlations of HBS, LBS, DQD and scores of 10 food group indicators with ECC were evaluated using rank sum test and logistic regression analysis.Results: The probabilities of ECC and SECC are positively correlated with HBS (OR: ECC=1.102, SECC=1.098) and with DQD (OR: ECC=1.117, SECC=1.114), but not correlated with LBS (P>0.05) among the 2- to 5-year-old children. The severity of caries among the 2- to 5-year-old children are positively correlated with the score of Grains (OR: ECC=1.322, SECC=2.929) and negatively with the score of Food diversity (OR: ECC=0.378, SECC=0.034), but not correlated with other indicators. Conclusions: The possibilities of ECC and SECC among the 2- to 5-year-old children are positively correlated with the degree of excessive dietary intake and dietary imbalance. The severity of caries among the 2- to 5-year-old children is positively correlated with grains intake and negatively with food diversity.
Excess Escherichia elicits mild autism spectrum disorder in young subjects via disturbing the balance of gut microbial GABA metabolism
Authors: Wang Dilong , Zhu Wenhui , Pan Yihang , Wang Tao , Jiang Youheng , Liang Liyang , Fan Shilu , Yan Hui , Costa Clive Da , Zhang Xuesong , Li Huiliang , He Yulong , Li Ningning 
Published: April 2022

Abstract
Background: Accumulating clinical evidence demonstrated that gut microbiota (GM) transfer substantially ameliorated autistic symptoms, implying a role of GM in autism spectrum disorder (ASD). Continuous investigation reported GM alteration in ASD individuals, while inconsistency also persists in the abundance of bacterial taxon, as well as their metabolites. Due to deficiencies of stringent study designs, multi-omics assessment, and even animal tests, such data heterogeneity is yet to be addressed, which impedes establishing a causal effect of a specific microbiome-metabolome axis on pathogenesis of ASD.Results: We developed a participant recruitment and sampling procedure that fully considered possible intergroup and intragroup confounders, including age, diet, severity of ASD, and stool consistency. To tease out biological features of ASD from an overarching investigation on metabolome, composition and function of GM, we compared faecal samples collected from 123 children with either mild ASD (n=56) or typical development (TD) (n=67). Metabolite profiling of targeted metabolomics screened and validated a significantly higher ratio of gamma-aminobutyric acid (GABA) to glutamate (Glu) as a metabolic signature of ASD. Linked to autistic symptomatology, the microbial GABA/Glu ratio independently distinguished ASD from TD subjects, particularly at 3-5 years. The 16S rRNA gene sequencing displayed substantially declined GM richness but over-presented genus Escherichia in ASD, which was profoundly associated with the increased GABA/Glu ratio. Metagenomics confirmed both structural and metabolic dysbiosis of GM via revealing consistent changes in microbial components and Escherichia abundance, and highlighting overall hypofunction of the GM and imbalanced GABA/Glu synthesis in ASD. We further identified a series of E. coli-specific adhesins that linked Escherichia colonization with GABA production. Quantitative PCR validation supported increment of Escherichia-specific glutamate decarboxylase, promoting GABA synthesis. Further, challenge of healthy weaning mice with gut commensal E. coli induced significant social deficiency, but not abnormalities in repetitive, locomotor, recognition memory- and anxiety-related behaviors. Conclusions: Our multi-omics study elucidated a microbe-metabolite axis out of GM dysbiosis in mild ASD, characterized by over-presented Escherichia and concomitant GABA/Glu imbalance, which were well-marked features of ASD-linked GM at an early age, and potential causal factors of autistic symptomology. Our study provided insight into importance of microbial excitatory/inhibitory neurotransmitters imbalance in diagnosis and therapeutic treatment of ASD.
Detection of blood plasma concentration using SPR-based biosensor employing black phosphor layers and different metals
Authors: Almawgani Abdulkarem H. M. , Daher Malek G. , Taya Sofyan A. , Olaimat Melad M. , Alhawari Adam R. H. , Colak Ilhamic 
Published: April 2022

Abstract
The main role of blood plasma is to transport proteins, hormones and nutrients to certain parts of the body. All blood constituents are carried by blood plasma through the circulatory system. Cells get rid of waste products into the plasma. In this paper, we present a surface plasmon resonance (SPR) biosensor based on a black phosphor (BP) layer to improve the sensor performance. The black phosphor layer is employed as an interacting medium with the sensing medium for the improvement of the sensor sensitivity. The sensor is employed for the detection of blood plasma. Four metals are used: silver (Ag), gold (Au), copper (Cu) and aluminum (Al). We found that structures with the BP layer have better performance than those without a BP layer. Cu-structure has shown the highest sensitivity while the Ag-structure has shown the highest quality factor and detection accuracy and the lowest FWHM. As the concentration of the plasma increases, the sensitivity can be enhanced.
Frequency and predictors of post-stroke cognitive impairment in Ethiopian stroke survivors: A cross-sectional study
Authors: Zewde Yared Z. , Alem Atalay , Seeger Susanne K. 
Published: April 2022

Abstract
Background: Stroke is emerging as a public health threat to sub-Saharan African countries. Even though cognitive impairment is increasingly being recognized as a major cause of disability in stroke survivors there is no data on the burden of stroke related cognitive dysfunction from Ethiopia. In this study, we aimed to assess the frequency and predictors of post-stroke cognitive impairment in Ethiopian stroke survivors.Methods: Participants were adult stroke survivors who came for follow-up at least 3 months after the last stoke. Demographic and clinical data were collected using a structured questionnaire. We employed the Montreal Cognitive Assessment Scale-Basic (MOCA-B), modified Rankin Scale (mRS) and Patient Health Questionnaire-9 (PHQ-9) to assess post-stroke cognition, functional recovery, and depression, respectively.Results: Among 67 stroke survivors (mean age: 52.1 ± 12.7 years, females: 40.3%, low or no education: 41.8%, median stroke duration: 3 years), 28 (41.8%) had post-stroke cognitive impairment. Of these, 20 (30%) had mild cognitive impairment and 8 (12%) had post-stroke dementia. On multivariate analysis, increased age [AOR=0.24, 95% CI (0.07,0.83)], lower education [AOR=4.02, 95% CI (1.13,14.32)] and poor function recovery (mRS ³3) [AOR=0.27, 95% CI (0.08-0.81)] were independently associated with post-stroke cognitive impairment.Conclusion:Cognitive impairment is frequent among Ethiopian stroke survivors. We found that increased age, low educational attainment, and poor recovery on physical function were independently associated with cognitive decline. Although causality cannot be inferred, physical rehabilitation and better education might play a significant role in building cognitive resilience among stroke survivors.
Caregivers in anorexia nervosa: Is grief underlying parental burden?
Authors: Duclos Jeanne , Piva Giulia , Riquin Elise , Lalanne Christophe , Meilleur Dominique , Blondin Soline , Cook-Darzens Solange , Godart Nathalie 
Published: April 2022

Abstract
Purpose. Anorexia Nervosa (AN) is a severe chronic disorder and parents’ experience of caregiving is usually marked by emotional distress and burden. Severe chronic psychiatric disorders are known to be linked with the concept of grief. Grief has not been investigated in AN. The aim of this study was to examine parents’ and adolescents’ characteristics that underlie parental burden and grief in AN, and the link between these two dimensions. Methods. Eighty mothers, 55 fathers and their adolescents (N=84) hospitalized for AN participated in this study. Evaluations of clinical characteristics of the adolescent’s illness were completed, as well as self-evaluations of adolescent and parental emotional distress (anxiety, depression, alexithymia). Levels of parental burden were evaluated with the Experience Caregiving Inventory and levels of parental grief with the Mental Illness Version of the Texas Revised Inventory of Grief.Results. Main findings indicated that burden was higher in parents of adolescents with a more severe AN; fathers’ burden was also significantly and positively related to their own level of anxiety. Parental grief was higher when adolescents’ clinical state was more severe. Paternal grief was related to higher anxiety and depression, while in mothers, grief was correlated to higher alexithymia and depression. Paternal burden was explained by father’s anxiety and grief, and maternal burden by mother’s grief and her child’s clinical state.Conclusion. Parents of adolescents suffering from AN experienced high levels of burden, emotional distress and grief. These perceptions (that are also inter-related) should be specific targets for intervention aimed at supporting parents. Our results sustained the extensive literature on the need to assist fathers and mothers in their caregiving role. This in turn may improve both their mental health and their abilities as caregivers of their suffering child.ClinicalTrials.gov Identifier: NCT00910169grief; burden; caregiving; parents; anorexia nervosa; gender roleLevel of evidence III
Prevalence of AmpC and Extended-Spectrum Beta-Lactamase Producing E. coli and Klebsiella spp. in Sewage Effluents of Dharan, Nepal
Authors: Dahal Prashant , Rai Rojina , Sharma Madhav Raj , Chaudhary Lalit Narayan , Chaudhary Prabha Nand , Khadka Niku , poudel Mausam , Rai Rabin 
Published: April 2022

Abstract
Background
The prevalence of extended-spectrum \(\beta\)-lactamase (ESBL) and AmpC \(\beta\)-lactamase (ABL) producing Enterobacteriaceae is increasing rapidly across the world. Members of Enterobacteriaceae like E. coli and Klebsiella spp. exhibit antimicrobial resistance mainly due to the production of beta-lactamase enzymes like extended-spectrum βlactamases, AmpC β-lactamases, and carbapenemases. These bacteria are frequently reported in sewage effluents of hospital and municipal sewerage systems indicating sewage as a promising source for dissemination of such drug-resistant pathogens. However, in most of the developing countries including Nepal, the major portion of sewage is discharged in water sources without proper treatment and disinfection. This study was undertaken to access the prevalence of ESBL and ABL producing E. coli and Klebsiella spp. in sewage effluents of Dharan, Nepal.
Results
A total of 235 bacteria were isolated, out of which 103 (43.83%) were E. coli and 132 (56.17%) were Klebsiella spp. ESBL production was seen in 157 (66.81%) isolates. Among them, 89 (56.69%) were Klebsiella spp. and 68 (43.31%) were E. coli. 66.02% of total isolated E. coli and 67.42% of total isolated Klebsiella spp. showed production of ESBL enzymes. ABL production was seen in 133 (56.59%) isolates. Among them, 54 (40.60%) were E. coli and 79 (59.40%) were Klebsiella spp. 52.43% of the isolated E. coli and 59.85% of isolated Klebsiella spp. were found producing ABL enzyme.
Conclusions
The results indicate that there is a high prevalence of ESBL and ABL producing E. coli and Klebsiella spp. in sewage effluents of Dharan. Effective treatment of sewage effluents must be ensured before discharging the sewage into the environment. National guidelines for discharging the municipal sewage must be immediately amended and an effective treatment system before discharge must be implemented. Dissemination of such drug-resistant bacteria in the human population leading to severe public health emergency is likely to occur from sewage contamination, so further study and surveillance and effective prevention and control measures are necessary.
Artificial bone graft substitutes for curettage of benign and low-grade malignant bone tumors: clinical and radiological experience with Cerasorb
Authors: Wittig Ulrike S. , Friesenbichler Jörg , Liegl-Atzwanger Bernadette , Igrec Jasminka , Bergovec Marko , Leithner Andreas , Scheipl Susanne 
Published: April 2022

Abstract
Artificial bone graft substitutes (ABGS) for curettage of bone tumors are becoming increasingly popular. The aim of this retrospective analysis was to determine the efficacy of the ABGS Cerasorb (Curasan-AG, Kleinostheim, Germany), a beta-tricalcium phosphate (beta-TCP), concerning resorption profile, bone healing and remodeling after surgery and to evaluate potential complications. 43 patients suffering from benign and low-grade malignant bone tumors were treated with curettage and refilling of the bony cavity using the ABGS Cerasorb between 2018 and 2021 and included in the final analysis. Clinical follow-up exams with x-rays in two planes were performed six weeks, three months, six months and one year after surgery. After a mean follow-up period of 14.6 months, radiological consolidation following curettage was observed in all patients. Total resorption was observed in 16.3% of patients; in the other 83.7%, resorption was partial. In four patients, of whom two had a tumor in the distal femur and two in the humeral diaphysis, fractures occurred within six weeks after primary surgery. In conclusion, the beta-TCP Cerasorb seems to be a reliable bone graft substitute with low complication rates and is a suitable alternative to autologous bone grafts or allografts. Nonetheless, it shows a tendency of delayed resorption.
Enhanced root growth of the Arabidopsis abi5 mutant under high salinity is associated with reduced NO levels in Arabidopsis seedlings
Authors: Le Quang Tri , Truong Hai An , Nguyen Dinh Thanh , Lee Ye Ji , Chung Eui-Hwan , Lee Hojoung 
Published: April 2022

Abstract
Many environmental factors and stresses influence plant growth and development. High salt stress is expected to have a damaging effect on more than 50% of fully arable land by 2050. Understanding the response of plants to excessive use of nitrogen fertilisers and salt stress is vital for increasing crop productivity. However, the effect of excessive nitrate application on plant growth is controversial and not well-understood; therefore, we investigated the effect of a high nitrate supply and high salt stress on plant growth performance. We showed that abi5-7 plants exhibited tolerance to adverse environmental conditions of high nitrate and high salinity stress. Particularly, abi5-7 plants showed lower endogenous nitric oxide levels than Col-0 plants because of their lower nitrate reductase activity, resulting from the decreased transcript levels of NIA2 , a gene encodes nitrate reductase. The supply of excess nitrate reduced the plant's salt stress tolerance, in which nitric oxide appeared to play a crucial role. Therefore, discovering regulators, such as ABI5, that can regulate nitrate reductase activity and understanding the molecular functions of these regulators are important for implementing gene-editing techniques to modulate transcription factor activities, leading to the optimal accumulation of nitric oxide to increase the productivity of crops exposed to various stress environments.
Clinicians’ Prediction of Survival and Prognostic Confidence in Patients with Far- Advanced Cancer in Three East Asian Countries
Authors: Lee Eon Sook , Hiratsuka Yusuke , Suh Sang-Yeon , Won Seon Hye , Kim Sun-Hyun , Yoon Seok-Joon , Choi Sung-Eun , Choi Hana , Ahn Hong-Yup , Kim Yoonjoo , Hui David , Cheng Shao-Yi , Chen Ping-Jen , Wu Chien-Yi , Mori Masanori , Morita Tatsuya , Yamaguchi Takashi , Tsuneto Satoru 
Published: April 2022

Abstract
Purpose: This study aims to examine accuracy of CPS for 7-, 21-, and 42-day survival of inpatients with far-advanced cancer in 37 palliative care units in Japan, Korea, and Taiwan and its association with prognostic confidence.Methods: In this study, discrimination of CPS was investigated through sensitivity, specificity, overall accuracy, and area under the receiver operating curves (AUROCs) according to 7-, 21-, and 42-day survival. The accuracies of CPS were compared with those of Performance Status-based Palliative Prognostic Index (PS-PPI) in three timeframe prediction. Clinicians were instructed to rate confidence level for each prediction on a 0–10-point scale.Results: A total of 2,571 patients were analyzed. Among the three time-frames, the specificity was highest at 93.2–100.0% for the 7-day CPS and sensitivity was highest at 71.5–86.8% for the 42-day CPS. The AUROCs of the 7-day CPS were 0.88, 0.94, and 0.89 while those of PS-PPI were 0.77, 0.69, and 0.69 for JP, KR, and TW, respectively. In all timeframe, CPS was more accurate than the PS-PPI. As for 42-day prediction, sensitivities of PS-PPI were higher than those of CPS. Clinicians’ confidence was strongly associated with the accuracy of prediction in all three countries (all p values <0.01). Conclusions: CPS accuracies were highest (0.88 -0.94) for the 7-day survival prediction. CPS was more accurate than PS-PPI in all timeframe prediction. Meanwhile, PS-PPI can be a screening tool in 42-day survival prediction which may be supplementary to CPS. Prognostic confidence was significantly associated with the accuracy of CPS.