bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered gut microbiota and its metabolites correlate with plasma cytokines in schizophrenia inpatients with aggression
Authors: Deng Hongxin , He Lei , Wang Chong , Zhang Teng , Guo Hua , Zhang Hongwei , Song Yanning , Chen Bangtao 
Published: September 2022

Abstract
Background
The pathophysiological mechanisms of aggression are manifold and they may closely interconnect. Current study aimed to determine the gut microbiota and its metabolites, and clarify their correlations with inflammation, oxidation, leaky gut and clinical profiles underlying aggression in schizophrenia (ScZ).

Methods
Serum and stool specimens from ScZ inpatients with (ScZ-Ag, 25 cases) and without aggression (NScZ-Ag, 25 cases) were collected. Systemic inflammation, oxidation and leaky gut biomarkers were determined by ELISA, gut microbiota by 16S rRNA sequencing, short-chain fatty acids (SCFAs) by gas chromatography-mass spectrometry analysis and neurotransmitters by liquid chromatograph mass spectrometry analysis.

Results
Significantly higher systemic pro-inflammation, pro-oxidation and leaky gut biomarkers were observed in ScZ-Ag than NScZ-Ag group (all P<0.001). Compared to NScZ-Ag group, the alpha-diversity and evenness of fecal bacterial community were much lower, the abundance of fecal genera Prevotella was significantly increased, while that Bacteroides, Faecalibacterium, Blautia, Bifidobacterium,Collinsella and Eubacterium_coprostanoligenes were remarkably reduced in ScZ-Ag group (all corrected P<0.001). Meanwhile, 6 SCFAs and 6 neurotransmitters were much lower in ScZ-Ag group (all P<0.05). Finally, a few strongly positive or negative correlations among altered gut microbiota, SCFAs, systemic pro-inflammation, leaky gut, pro-oxidation and aggression severity were detected.

Conclusions
These results demonstrate that pro-inflammation, pro-oxidation and leaky gut phenotypes relating to enteric dysbacteriosis and microbial SCFAs feature the aggression onset or severity in ScZ individuals.
Country of birth and non-small cell lung cancer incidence, treatment, and outcomes in New South Wales, Australia: a population-based linkage study
Authors: Little Alana , Roder David , Zhao George W. , Challam Sheetal , Malalasekera Ashanya , Currow David 
Published: September 2022

Abstract
Objective
To compare treatment within 12 months of diagnosis, and survival by country of birth for people diagnosed with invasive non-small cell lung cancer (NSCLC) in New South Wales (NSW), Australia.

Design, patients, and setting
A population-based cohort study of NSW residents diagnosed with NSCLC in 2003–2016 using de-identified linked data from the NSW Cancer Registry, NSW Admitted Patient Data collection, Emergency Departments, Medicare Benefits and Pharmaceutical Benefits Scheme, and National Death Index.

Main outcome measures
Odds of receiving any treatment, surgery, systemic therapy, or radiotherapy respectively, in the 12 months following diagnosis were calculated using multivariable logistic regression. The hazard of death (all-cause) at one- and five-years following diagnosis was calculated using multivariable proportional hazards regression.

Results
27,114 People were recorded with NSCLC in the 14-year study period. Higher percentages of older males from European countries applied in the earlier years, with a shift to younger people from South East Asia, New Zealand, and the Middle East. Adjusted analyses indicated that, compared with the Australian born, people from European countries were more likely to receive treatment, and, specifically surgery. Also, people from Asian countries were more likely to receive systemic therapy but less likely to receive radiotherapy. Survival at one- and five-years following diagnosis was higher for people born in countries other than Australia, New Zealand the United Kingdom and Germany.

Conclusions
Variations exist in treatment and survival by country of birth in NSW. This may be affected by differences in factors not recorded in the NSW Registry, including use of general health services, family histories, underlying health conditions, other intrinsic factors, and cultural, social, and behavioural influences.
Color stability and surface roughness of ormocer- versus methacrylate-based single shade composite in anterior restoration
Authors: Ebaya Maha M. , Ali Ashraf I. , El-Haliem Huda Abed , Mahmoud Salah Hasab 
Published: September 2022

AbstractBackgroundThe blending ability of universal shade composites and their stability in the oral environment are of great concern in restoring anterior teeth. This study aims to evaluate and compare the color stability and surface roughness of two single-shade composite restorations, ormocer-based composite (OBC) and methacrylate resin-based composite (RBC), after storing them in different staining media.Materials and methodsIn this study, two universal shade composite restorative materials were tested: a nanohybrid OBC (Admira fusion X-tra, Voco) and a supra-nanofilled RBC (Omnichroma, Toukyama). In total, 60 cylindrical centralized cavities (diameter: 5 mm, depth: 2 mm) were prepared in sound extracted-human central incisors and divided into two equal groups according to the restorative material used (n = 30). According to the storage media, the teeth of each group were divided into three subgroups (n = 10): artificial saliva, black tea, and cola. The restoration color was evaluated for all teeth at baseline and after four weeks of storage. The color stability (∆E) was measured using a reflective spectrophotometer (X-Rite, model RM200QC, Neu-Isenburg, Germany). The surface roughness (Ra) was evaluated using three-dimensional optical profilometry (Wyko, Model NT 1100, Veeco, Tucson, USA). Additionally, the extracted data were analyzed using two-way analysis of variance (ANOVA), one-way ANOVA and Student’st-test.ResultsIn the baseline evaluation, there were no statistically significant differences with respect to color matching or surface roughness results between the two studied restorative materials. However, the differences were statistically significant after storing them in different media.ConclusionUniversal composites showed satisfactory color matching with different teeth colors and accepted surface smoothness, whereas the aging procedure exerted a negative effect on their color stability and surface characteristics.
Students’ perception and learning experience in the first medical clerkship
Authors: Gottschalk Marc , Albert Christian , Werwick Katrin , Spura Anke , Braun-Dullaeus Ruediger C. , Stieger Philipp 
Published: September 2022

Abstract
Background
The German clerkship (“Famulatur”) is the first phase in medical education, in which students learn from a physician’s perspective. According to the German Licensing Regulations for Physicians, students shall “familiarise” with providing care. However, specific learning objectives for the clerkship are not defined, although the acquisition of different competencies is implicitly demanded. Therefore, an additional understanding of the clerkship students’ learning experience is needed. The goal of this study is to explore the student’s learning perspective and experiences in the clerkship.

Methods
Twelve guideline-based interviews were conducted with third year medical students. All participants completed their first clerkship. A qualitative content analysis was performed. The inductively identified categories were transferred into a quantitative questionnaire using a 5-point Likert-scale to explore their relevance in a validation cohort. The questionnaire was completed by 222 clinical students of the Otto-von-Guericke-Universität Magdeburg.

Results
The qualitative analysis led to 26 individual items assigned to 4 main categories that describe the clerkship experience: 1) “coping with insecurities”, 2) “the clerkship as a social arrangement”, 3) “the clerkship as a learning opportunity” and 4) “the clerkship as a teaching opportunity”. In the quantitative validation cohort, category one yielded a well-balanced result (median 3 = “neither agree nor disagree”; IQR 2–4), items addressed in categories 2–4 were generally supported by the students, predominantly selecting “strongly agree” or “agree” (Median 2; IQR 1–2 for each category). Students rated the role of the clinical team as especially important for their learning success and feared exclusion or negative reactions.

Conclusions
The medical clerkship provides an institutional, professional, and social framework, in which students are learning. Insecurities arose from curricular inconsistencies, a high dependency on the clinical team as well as the absence of specific learning objectives. Therefore, a better curricular integration regarding the semester structure and the learning objectives of the German clerkship is needed.
Using Normalisation Process Theory (NPT) to develop an intervention to improve referral and uptake rates for self-management education for patients with type 2 diabetes in UK primary care
Authors: Turner Jessica , Martin Graham , Hudson Nicky , Shaw Liz , Huddlestone Lisa , Weis Christina , Northern Alison , Schreder Sally , Davies Melanie , Eborall Helen 
Published: September 2022

Abstract
Background
Referral and uptake rates of structured self-management education (SSME) for Type 2 diabetes (T2DM) in the UK are variable and relatively low. Research has documented contributing factors at patient, practitioner and organisational levels. We report a project to develop an intervention to improve referral to and uptake of SSME, involving an integrative synthesis of existing datasets and stakeholder consultation and using Normalisation Process Theory (NPT) as a flexible framework to inform the development process.

Methods
A three-phase mixed-methods development process involved: (1) synthesis of existing evidence; (2) stakeholder consultation; and (3) intervention design. The first phase included a secondary analysis of data from existing studies of T2DM SSME programmes and a systematic review of the literature on application of NPT in primary care. Influences on referral and uptake of diabetes SSME were identified, along with insights into implementation processes, using NPT constructs to inform analysis. This gave rise to desirable attributes for an intervention to improve uptake of SSME. The second phase involved engaging with stakeholders to prioritise and then rank these attributes, and develop a list of associated resources needed for delivery. The third phase addressed intervention design. It involved translating the ranked attributes into essential components of a complex intervention, and then further refinement of components and associated resources.

Results
In phase 1, synthesised analysis of 64 transcripts and 23 articles generated a longlist of 46 attributes of an embedded SSME, mapped into four overarching domains: valued, integrated, permeable and effectively delivered. Stakeholder engagement in phase 2 progressed this to a priority ranked list of 11. In phase 3, four essential components attending to the prioritised attributes and forming the basis of the intervention were identified: 1) a clear marketing strategy for SSME; 2) a user friendly and effective referral pathway; 3) new/amended professional roles; and 4) a toolkit of resources.

Conclusions
NPT provides a flexible framework for synthesising evidence for the purpose of developing a complex intervention designed to increase and reduce variation in uptake to SSME programmes in primary care settings.
Key factors predicting suspected severe malaria case management and health outcomes: an operational study in the Democratic Republic of the Congo
Authors: Okitawutshu Jean , Signorell Aita , Kalenga Jean-Claude , Mukomena Eric , Delvento Giulia , Burri Christian , Mwaluke Fatou , Buj Valentina , Sangare Moulaye , Luketa Sylvie , Brunner Nina , Lee Tristan , Hetzel Manuel , Lengeler Christian , Tshefu Antoinette 
Published: September 2022

Abstract
Background
Evidence suggests that pre-referral Rectal Artesunate (RAS) can be a life-saving intervention for severe malaria in remote settings in Africa. Recognition of danger signs indicative of severe malaria is critical for prompt and appropriate case management.

Methods
This was an observational study conducted in three Health Zones of the Democratic Republic of the Congo to determine the distribution of dangers signs for severe malaria and assess their impact on RAS use, referral completion, injectable treatment and ACT provision, and health outcomes including death. An individual-level analysis was carried out, using multilevel-mixed effects logistic regression models. Severely ill febrile children < 5 years seeking care from community-based healthcare providers were recruited into a patient surveillance system based on the presence of key danger signs. Clinical and case management data were collected comprehensively over a 28 days period. Treatment seeking was elicited and health outcomes assessed during 28 days home visits.

Results
Overall, 66.4% of patients had iCCM general danger signs. Age of 2–5 years and iCCM general danger signs predicted RAS use (aOR = 2.77, 95% CI 2.04–3.77). RAS administration positively affected referral completion (aOR = 0.63, 95% CI 0.44–0.92). After RAS rollout, 161 children died (case fatality ratio: 7.1%, 95% CI 6.1–8.2). RAS improved the health status of the children on Day 28 (aOR = 0.64, 95% CI 0.45–0.92) and there was a non-significant trend that mortality was higher in children not receiving RAS (aOR = 1.50, 95% CI 0.86–2.60). Full severe malaria treatment at the RHF including injectable anti-malarial and a course of ACT was highly protective against death (aOR = 0.26, 95% CI 0.09–0.79).

Conclusions
The main findings point towards the fact that danger signs are reasonably well recognized by health provider at the primary care level, and that RAS could influence positively health outcomes of such severe disease episodes and death. Its effectiveness is hampered by the insufficient quality of care at RHF, especially the provision of a full course of ACT following parenteral treatment. These are simple but important findings that requires urgent action by the health system planners and implementers.
Co-expression IL-15 receptor alpha with IL-15 reduces toxicity via limiting IL-15 systemic exposure during CAR-T immunotherapy
Authors: Zhang Ying , Zhuang Qinghui , Wang Fang , Zhang Can , Xu Chang , Gu Aiqin , Zhong William H. , Hu Yi , Zhong Xiaosong 
Published: September 2022

Abstract
Background
Chimeric antigen receptor (CAR)-T cell therapy is a powerful adoptive immunotherapy against both B-cell malignancies and some types of solid tumors. Interleukin (IL) -15 is an important immune stimulator that may provide ideal long-term persistent CAR-T cells. However, higher base line or peak serum IL-15 levels are also related to severe toxicity, such as cytokine release syndrome (CRS), graft-versus-host disease (GVHD), and neurotoxicity.

Methods
We successfully constructed CD19 specific armored CAR-T cells overexpressing IL-I5 and IL-15 receptor alpha (IL-15Ra). In vitro cell differentiation and viability were monitored by flow cytometry, and an in vivo xenograft mouse models was used to evaluate the anti-tumor efficiency and liver damage of CAR-T cells.

Results
CAR-T cells overexpressing IL-15 alone demonstrated enhanced viability, retarded exhaustion in vitro and superior tumor-inhibitory effects in vivo. However, these tumor-free mice had lower survival rates, with serious liver injuries, as a possible result of toxicity. As expected, CAR-T cells overexpressing IL-15 combined with IL-15Ra had reduced CD132 expression and released fewer cytokines (IFNγ, IL-2 and IL-15) in vitro, as well as had the tendency to improve mouse survival via repressing the growth of tumor cells and keeping livers healthier compared to CAR-IL-15 T cells.

Conclusions
These results indicated the importance of IL-15 in enhancing T cells persistence and IL-15Ra in reducing the adverse effects of IL-15, with superior tumor retardation during CAR-T therapy. This study paves the way for the rapid exploitation of IL-15 in adoptive cell therapy in the future.
Ultrastructural characterization of dark microglia during aging in a mouse model of Alzheimer’s disease pathology and in human post-mortem brain samples
Authors: St-Pierre Marie-Kim , Carrier Micaël , González Ibáñez Fernando , Šimončičová Eva , Wallman Marie-Josée , Vallières Luc , Parent Martin , Tremblay Marie-Ève 
Published: September 2022

AbstractA diverse heterogeneity of microglial cells was previously described in Alzheimer’s disease (AD) pathology, including dark microglia, a state characterized by ultrastructural markers of cellular stress. To provide novel insights into the roles of dark microglia during aging in the context of AD pathology, we performed a quantitative density and ultrastructural analysis of these cells using high-throughput scanning electron microscopy in the ventral hippocampus CA1stratum lacunosum-moleculareof 20-month-old APP-PS1 vs C57BL/6J male mice. The density of dark microglia was significantly higher in APP-PS1 vs C57BL/6J mice, with these cells accounting for nearly half of all microglia observed near amyloid-beta (Aβ) plaques. This dark microglial state interacted more with dystrophic neurites compared to other APP-PS1 microglia and possessed glycogen granules, associated with a metabolic shift toward glycolysis, which provides the first ultrastructural evidence of their presence in microglia. Dark microglia were further observed in aging human post-mortem brain samples showing similar ultrastructural features as in mouse. Overall, our results provide a quantitative ultrastructural characterization of a microglial state associated with cellular stress (i.e., dark microglia) that is primarily restricted near Aβ plaques and dystrophic neurites. The presence of this microglial state in the aging human post-mortem brain is further revealed.
The reference ranges and characteristics of lymphocyte parameters and the correlation between lymphocyte parameters and routine health indicators in adults from China
Authors: Liu Wei , Xu Jie , Pu Qiyao , Lan Mingwei , Zhang Xiaolu , Gu Yufeng , Wang Ying , Zheng Fan , Qian Jingjing , Fan Chunxue , Sui Jun , Xu Yanli , Zhang Yongchen , Luo Jing , Lin Xiangyang , Shi Shaorui , Wang Liying , Sun Chengming , Zhou Maohua , Yue Baohong , Wang Feng 
Published: September 2022

AbstractBackgroundAssessment of immune function is of key importance in recognition of disease or healthy status, which still faces challenge in clinical practice. We conducted a 10-center study to investigate lymphocyte parameters including the number, phenotype and IFN-γ-producing ability, and routine laboratory indicators by using the standard method.ResultsAlthough the heterogeneity of lymphocyte parameters was widely found, we have established the normal ranges of these parameters by using pooled data which showed no significant difference among centers. Cluster analysis of 35 parameters found 3 interesting clusters which represented different immunological status. Cluster 1 (parameters: IFN-γ+CD4+T cell percentage and IFN-γ+CD8+T cell percentage) represented current lymphocyte function, which was associated with indicators such as body mass index and red blood cell; Cluster 2 (parameters: NK cell number and CD45RA+CD4+T cell percentage) represented potential of lymphocytes, which was associated with indicators such as albumin and high-density lipoprotein. Cluster 3 (parameters: HLA-DR+CD8+T cell percentage) represented inflammatory status, which was associated with indicators such as low-density lipoprotein, globulin and age. Correlation analysis found that nutritional indicator albumin is significantly positively correlated with lymphocyte potential. Triglyceride and body mass index were positively correlated with current lymphocyte function rather than lymphocyte potential. The loss of CD8+T cells was extremely pronounced with increasing age and was one of the most important factors to cause immunosenescence, which may be associated with increased glucose.ConclusionsWe have established the normal ranges of lymphocyte parameters in different areas. This study elucidates the key indicators used to reflect the current function or potential of lymphocytes, which may provide a valuable clue for how to keep immunity healthy.
Antimicrobial treatment improves tryptophan metabolism and mood of patients with small intestinal bacterial overgrowth
Authors: Chojnacki Cezary , Popławski Tomasz , Konrad Paulina , Fila Michał , Błasiak Janusz , Chojnacki Jan 
Published: September 2022

Abstract
Background
Optimal composition of intestinal bacteria is an essential condition for good health. Excessive growth of these bacteria can cause various ailments. The aim of this study was to assess the mental state and gastrointestinal complaints of patients with small intestinal bacterial overgrowth (SIBO) in relation to tryptophan metabolism and rifaximin treatment.

Methods
120 subjects, aged 23–61 years, were enrolled in the study, and divided into 3 groups, 40 individuals each: healthy subjects (Controls), patients with SIBO and chronic diarrhea (SIBO-D), and with chronic constipation (SIBO-C). The lactulose hydrogen breath test (LHBT) was performed to diagnose SIBO. The mental state of patients was assessed using the Hamilton Anxiety Rating Scale (HAM-A), and the Hamilton Depression Rating Scale (HAM-D). L-tryptophan (TRP) and its metabolites: 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), xanthurenic acid (XA) and quinolinic acid (QA) were measured in urine by liquid-chromatography-tandem mass spectrometry and related to creatinine level. Patients with SIBO were recommended to take rifaximin for 10 days at daily dose 1200 mg, and this cycle was repeated in subsequent two months.

Results
Mild and moderate anxiety, as well as mild depression were diagnosed in all SIBO patients. Changes in TRP metabolism were also observed in these patients. Specifically, an increase in the activity of the serotonin pathway of TRP metabolism in the group SIBO-D was observed. The SIBO-C patients showed an increase in the concentration of KYN, XA and QA. 5-HIAA/TRP and KYN/TRP ratios significantly decreased in group SIBO-D, and KYN and QA levels decreased in group SIBO-C after treatment with rifaximin. The levels of anxiety and depression decreased in both groups.

Conclusion
Rifaximin treatment of SIBO patients ameliorated their mood disorders and gastrointestinal aliments underlined by changes in tryptophan metabolism.
Trial registration Retrospectively registered (if applicable).