bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clustering care pathways of people with alcohol dependence using a data linkage of routine data in Bremen, Germany
Authors: Möckl Justin , Manthey Jakob , Murawski Monika , Lindemann Christina , Schulte Bernd , Reimer Jens , Pogarell Oliver , Kraus Ludwig 
Published: May 2024

AbstractBackgroundAlthough many individuals with alcohol dependence (AD) are recognized in the German healthcare system, only a few utilize addiction-specific treatment services. Those who enter treatment are not well characterized regarding their prospective pathways through the highly fragmented German healthcare system. This paper aims to (1) identify typical care pathways of patients with AD and their adherence to treatment guidelines and (2) explore the characteristics of these patients using routine data from different healthcare sectors.MethodsWe linked routinely collected register data of individuals with a documented alcohol-related diagnosis in the federal state of Bremen, Germany, in 2016/2017 and their addiction-specific health care: two statutory health insurance funds (outpatient pharmacotherapy for relapse prevention and inpatient episodes due to AD with and without qualified withdrawal treatment (QWT)), the German Pension Insurance (rehabilitation treatment) and a group of communal hospitals (outpatient addiction care). Individual care pathways of five different daily states of utilized addiction-specific treatment following an index inpatient admission due to AD were analyzed using state sequence analysis and cluster analysis. The follow-up time was 307 days (10 months). Individuals of the clustered pathways were compared concerning current treatment recommendations (1: QWT followed by postacute treatment; 2: time between QWT and rehabilitation). Patients’ characteristics not considered during the cluster analysis (sex, age, nationality, comorbidity, and outpatient addiction care) were then compared using a multinomial logistic regression.ResultsThe analysis of 518 individual sequences resulted in the identification of four pathway clusters differing in their utilization of acute and postacute treatment. Most did not utilize subsequent addiction-specific treatment after their index inpatient episode (n = 276) or had several inpatient episodes or QWT without postacute treatment (n = 205). Two small clusters contained pathways either starting rehabilitation (n = 26) or pharmacotherapy after the index episode (n = 11). Overall, only 9.3% utilized postacute treatment as recommended.ConclusionsA concern besides the generally low utilization of addiction-specific treatment is the implementation of postacute treatments for individuals after QWT.
Chronic endometritis and the endometrial microbiota: implications for reproductive success in patients with recurrent implantation failure
Authors: Zhang Hong , Zou Heng , Zhang Chanyu , Zhang Shen 
Published: May 2024

Abstract
Background
Chronic endometritis (CE) is associated with poor reproductive outcomes, yet the role of endometrial microbiota in patients with recurrent implantation failure (RIF) and CE remains unclear. This study aims to characterize endometrial microbiota in RIF patients with CE and assess its implications for reproductive outcomes.

Methods
In this prospective study, we enrolled RIF patients both with and without CE. Endometrial and cervical samples were collected for 16 S rRNA gene sequencing. Microbiota composition was compared between groups using diversity indices, phylum, and genus-level analysis. Canonical correlation analysis (CCA) and Spearman’s correlation coefficients were used to assess relationships between CE, reproductive outcomes, and microbiota. Predictive functional profiling was performed to evaluate metabolic pathways associated with CE.

Results
Endometrial microbiota in CE patients exhibited greater diversity and evenness compared to non-CE patients. Principal coordinates analysis (PCoA) revealed distinct clustering between CE and non-CE groups. Linear discriminant analysis (LDA) identified Proteobacteria, Aminicenantales, and Chloroflexaceae as characteristic of CE, while Lactobacillus, Acinetobacter, Herbaspirillum, Ralstonia, Shewanela, and Micrococcaceae were associated with non-CE. CCA demonstrated associations between CE, adverse reproductive outcomes, and specific bacterial taxa. Microbial metabolic pathways significantly differed between CE and non-CE groups, with enrichment in pathways related to cofactors, vitamins, secondary metabolites, and the immune system in CE patients.

Conclusion
RIF patients with CE exhibit distinct endometrial microbiota compositions associated with adverse reproductive outcomes. The increased microbial diversity and altered metabolic pathways in CE suggest a potential correlation with reproductive outcomes, although further studies are necessary to elucidate the causal relationship between microbiota alterations and fertility. Modulating the endometrial microbiome may represent a novel therapeutic strategy to improve IVF outcomes in patients with CE.
Molecular classification and biomarkers of outcome with immunotherapy in extensive-stage small-cell lung cancer: analyses of the CASPIAN phase 3 study
Authors: Xie Mingchao , Vuko Miljenka , Rodriguez-Canales Jaime , Zimmermann Johannes , Schick Markus , O’Brien Cathy , Paz-Ares Luis , Goldman Jonathan W. , Garassino Marina Chiara , Gay Carl M. , Heymach John V. , Jiang Haiyi , Barrett J. Carl , Stewart Ross A. , Lai Zhongwu , Byers Lauren A. , Rudin Charles M. , Shrestha Yashaswi 
Published: May 2024

Abstract
Background
We explored potential predictive biomarkers of immunotherapy response in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with durvalumab (D) + tremelimumab (T) + etoposide-platinum (EP), D + EP, or EP in the randomized phase 3 CASPIAN trial.

Methods
805 treatment-naïve patients with ES-SCLC were randomized (1:1:1) to receive D + T + EP, D + EP, or EP. The primary endpoint was overall survival (OS). Patients were required to provide an archived tumor tissue block (or ≥ 15 newly cut unstained slides) at screening, if these samples existed. After assessment for programmed cell death ligand-1 expression and tissue tumor mutational burden, residual tissue was used for additional molecular profiling including by RNA sequencing and immunohistochemistry.

Results
In 182 patients with transcriptional molecular subtyping, OS with D ± T + EP was numerically highest in the SCLC-inflamed subtype (n = 10, median 24.0 months). Patients derived benefit from immunotherapy across subtypes; thus, additional biomarkers were investigated. OS benefit with D ± T + EP versus EP was greater with high versus low CD8A expression/CD8 cell density by immunohistochemistry, but with no additional benefit with D + T + EP versus D + EP. OS benefit with D + T + EP versus D + EP was associated with high expression of CD4 (median 25.9 vs. 11.4 months) and antigen-presenting and processing machinery (25.9 vs. 14.6 months) and MHC I and II (23.6 vs. 17.3 months) gene signatures, and with higher MHC I expression by immunohistochemistry.

Conclusions
These findings demonstrate the tumor microenvironment is important in mediating better outcomes with D ± T + EP in ES-SCLC, with canonical immune markers associated with hypothesized immunotherapy mechanisms of action defining patient subsets that respond to D ± T.

Trial registration
ClinicalTrials.gov, NCT03043872.
Understanding adverse childhood experiences and the call for trauma-informed healthcare system in Turkey: a review
Authors: Yildiz Nadire Gülçin , Aydin Halide Z. , Aydin Kemal , Yildiz Hatice , Sambo Grace , Mwamulima Bwanalori , Zonda Joe Maganga , Phiri Doreen , Phiri Yohane Vincent Abero 
Published: May 2024

AbstractOver the past four decades, research has underscored the significance of approaching and preventing trauma from a systemic standpoint. Trauma-informed care (TIC) methodologies offer a structure for healthcare practices, striving to convert organizations into trauma-informed systems that employ trauma-specific interventions. This review employs epidemiological and household data from Turkey to underscore the importance of integrating trauma-informed care as a means of prevention and intervention. Through a desk review, the study examines the role of adverse childhood experiences (ACEs), delving into their origin from family dynamics, migration, violence, exposure to violence, juvenile delinquency, and child maltreatment. The research highlights innovative healthcare approaches that leverage data to address complex patient health issues while considering mental health needs. In contemporary times, healthcare organizations acknowledge the value of a data-driven approach to make informed clinical decisions, enhance treatment procedures, and improve overall healthcare outcomes. The reviewed research and empirical data furnish proof of the importance of effective and efficient treatment methods that prioritize trauma prevention and treatment, integrating the role of ACEs. This paper seeks to contribute to discussions on transforming the healthcare system to meet the healthcare needs of Turkish households, all the while taking into account the evolving sociopolitical factors that shape Turkey's population characteristics.
Explore the practice and barriers of collaborative health policy and system research-priority setting exercise in Ethiopia
Authors: Tilahun Binyam , Amare Getasew , Endehabtu Berhanu Fikadie , Atnafu Asmamaw , Derseh Lemma , Gurmu Kassu Ketema , Delllie Endalkachew , Nigusie Adane 
Published: May 2024

Abstract
Introduction
Collaboration is gaining prominence in the priority setting of Health Policy And System Research (HPSR). However, its practice and challenges are not well explored in Ethiopia. Understanding the practice and barriers of collaborative Health Policy and System Research will help design approaches and platforms for setting inclusive and participatory policy and system-level health research topics. This paper explores the practice and barriers of collaborative HPSR-priority setting exercise in Ethiopia.

Methods
This study investigates the practice and barriers of collaborative health policy and system research priority-setting exercises in Ethiopia. Utilizing a mixed-methods approach, we conducted Key Informant Interviews (KIIs) and an online self-administered survey with open-ended questionnaires to capture diverse perspectives from stakeholders involved in the research priority-setting process. Through conventional content analysis, we identified key contents related to current practices, challenges, and opportunities for enhancing collaboration in health policy and system research prioritization.

Results
Our findings reveal a complex landscape characterized by varying levels of stakeholder engagement, institutional capacity constraints, and competing priorities within the health research ecosystem. Despite notable efforts to foster collaboration, stakeholders identified persistent challenges such as limited resources, institutional fragmentation, and inadequate coordination mechanisms as barriers to effective priority-setting processes. The implications of our research extend beyond academic discourse, with direct relevance to health policy and system research practice in Ethiopia. By shedding light on the dynamics of collaborative priority-setting exercises, our findings offer valuable insights for policymakers, researchers, and practitioners seeking to enhance the effectiveness and inclusivity of health research prioritization processes. Addressing the identified barriers and leveraging existing strengths in the research ecosystem can contribute to more evidence-informed health policies and programs, ultimately improving health outcomes for Ethiopian populations.

Conclusions
Most institutions do not apply health policy and system research-priority setting to conduct informed decision-making. The barriers explored were weak integration, lack of knowledge, system, and platforms for the priority setting of Health Policy and System Resreach. So, it is recommended to build skills of different actors in the Health Policy and System Research-priority setting exercise and design a system and platform to integrate different stakeholders for collaborative research topics priority setting.
CircDCAF8 promotes the progression of hepatocellular carcinoma through miR-217/NAP1L1 Axis, and induces angiogenesis and regorafenib resistance via exosome-mediated transfer
Authors: Gong Jiahao , Han Guoyong , Chen Zhiqiang , Zhang Yinqi , Xu Bin , Xu Chao , Gao Wen , Wu Jindao 
Published: May 2024

Abstract
Background
Circular RNAs (circRNAs), which are a new type of single-stranded circular RNA, have significant involvement in progression of many diseases, including tumors. Currently, multiple circRNAs have been identified in hepatocellular carcinoma (HCC). Our study aims to investigate the function and mechanism of circDCAF8 in HCC.

Methods
The expression of circDCAF8 (hsa_circ_0014879) in HCC and para-carcinoma tissue samples was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The biological function of circDCAF8 in HCC was confirmed by experiments conducted both in vitro and in vivo. And the relationship between circDCAF8, miR-217 and NAP1L1 was predicted by database and verified using qRT-PCR, RNA-binding protein immunoprecipitation (RIP) and dual-luciferase reporter assays. Exosomes isolated from HCC cells were utilized to assess the connection of exosomal circDCAF8 with HCC angiogenesis and regorafenib resistance.

Results
CircDCAF8 is upregulated in HCC tissues and cell lines, and is linked to an unfavourable prognosis for HCC patients. Functionally, circDCAF8 was proved to facilitate proliferation, migration, invasion and Epithelial-Mesenchymal Transformation (EMT) in HCC cells. Animal examinations also validated the tumor-promoting characteristics of circDCAF8 on HCC. Besides, exosomal circDCAF8 promoted angiogenesis in HUVECs. Mechanistically, circDCAF8 interacted with miR-217 and NAP1L1 was a downstream protein of miR-217. CircDCAF8 promoted NAP1L1 expression by sponging miR-217. In addition, exosomes may transfer circDCAF8 from regorafenib-resistant HCC cells to sensitive cells, where it would confer a resistant phenotype.

Conclusion
CircDCAF8 facilitates HCC proliferation and metastasis via the miR-217/NAP1L1 axis. Meanwhile, circDCAF8 can promote angiogenesis and drive resistance to regorafenib, making it a viable therapeutic target for HCC patients.
BIBR1532 combined with radiotherapy induces ferroptosis in NSCLC cells and activates cGAS-STING pathway to promote anti-tumor immunity
Authors: Bao Yawei , Pan Zhipeng , Zhao Luqi , Qiu Jieping , Cheng Jingjing , Liu Lei , Qian Dong 
Published: May 2024

Abstract
Background
Telomerase, by safeguarding damaged telomeres and bolstering DNA damage repair, has the capacity to heighten the radioresistance of tumour cells. Thus, in turn, can compromise the efficacy of radiotherapy (RT) and radioimmunotherapy. Our previous studies have revealed that the highly selective telomerase inhibitor, BIBR1532, possesses the potential to enhance the radiosensitivity of Non-small cell lung cancer (NSCLC). In this study, we delve further into the impact of BIBR1532 on the immune activation induced by RT and elucidate the underlying mechanisms.

Methods
Biological information analyses, immunofluorescence assays, western blot assays, flow cytometry analysis were conducted to elucidate the functions of the combination of BIBR1532 with radiotherapy in NSCLC. Intracellular levels of lipid peroxides, glutathione, malondialdehyde, and Fe2+ were measured as indicators of ferroptosis status. Both in vitro and in vivo studies were conducted to examine the antitumor effects.

Results
Our findings indicate that the confluence of BIBR1532 with RT significantly augments the activation of the cGAS-STING pathway in both in vivo and in vitro settings, thereby fostering an effective anti-tumoral immune response. The effects can be ascribed to two key processes. Firstly, ionizing radiation, in precipitating DNA double-strand breaks (DSBs), prompts the release of tumour-derived double-stranded DNA (dsDNA) into the cytoplasm. Subsequently, BIBR1532 amplifies the activation of antigen-presenting cells by dsDNA post-RT and instigates the cGAS-STING pathway. Secondly, BIBR1532 enhances the ferroptosis response in NSCLC following RT, thereby promoting unrestrained lipid peroxidation and elevated levels of reactive oxygen species (ROS) within tumour cells. This ultimately leads to mitochondrial stress and the release of endogenous mitochondrial DNA (mtDNA) into the cytoplasm, thus facilitating the activation of the STING pathway and the induction of a type I interferon (IFN)-linked adaptive immune response.

Conclusion
This study underscores the potential of BIBR1532 as an efficacious and safe radiosensitizer and radioimmunotherapy synergist, providing robust preclinical research evidence for the treatment of NSCLC.
Neuromodulation of inhibitory control using phase-lagged transcranial alternating current stimulation
Authors: Kim Yukyung , Lee Je-Hyeop , Park Je-Choon , Kwon Jeongwook , Kim Hyoungkyu , Seo Jeehye , Min Byoung-Kyong 
Published: May 2024

Abstract
Background
Transcranial alternating current stimulation (tACS) is a prominent non-invasive brain stimulation method for modulating neural oscillations and enhancing human cognitive function. This study aimed to investigate the effects of individualized theta tACS delivered in-phase and out-of-phase between the dorsal anterior cingulate cortex (dACC) and left dorsolateral prefrontal cortex (lDLPFC) during inhibitory control performance.

Methods
The participants engaged in a Stroop task with phase-lagged theta tACS over individually optimized high-density electrode montages targeting the dACC and lDLPFC. We analyzed task performance, event-related potentials, and prestimulus electroencephalographic theta and alpha power.

Results
We observed significantly reduced reaction times following out-of-phase tACS, accompanied by reduced frontocentral N1 and N2 amplitudes, enhanced parieto-occipital P1 amplitudes, and pronounced frontocentral late sustained potentials. Out-of-phase stimulation also resulted in significantly higher prestimulus frontocentral theta and alpha activity.

Conclusions
These findings suggest that out-of-phase theta tACS potently modulates top-down inhibitory control, supporting the feasibility of phase-lagged tACS to enhance inhibitory control performance.
High-throughput color determination of red raspberry puree and correlation of color parameters with total anthocyanins
Authors: Baldassi Claudia , Lee Clover , Dossett Michael , Castellarin Simone D. 
Published: May 2024

Abstract
Background
Red raspberry fruit color is a key driver of consumer preference and a major target of breeding programs worldwide. Screening for fruit color typically involves the determination of anthocyanin content and/or the assessment of color through a colorimeter. However, both procedures are time-consuming when the analyses involve hundreds or thousands of samples. The objectives of this study were to develop a high-throughput method for red raspberry puree color measurement and to test the correlations between color parameters and total anthocyanin content. Color coordinates were collected with a colorimeter on 126 puree samples contained in Petri dishes and with the Tomato Analyzer Color Test (TACT) module to assess the same samples prepared in Petri dishes and in 96-well plates. An additional 425 samples were analyzed using only 96-well plates. Total anthocyanins were extracted from all 551 samples.

Results
Regression models for L*, a*, b* measured with the colorimeter and TACT using Petri dishes were all significant (p < 0.001), but very consistent only for L* (R2 = 0.94). Significant (p < 0.001) and very consistent regressions (R2 = 0.94 for L* and b*, R2 = 0.93 for a*) were obtained for color parameters measured with TACT using Petri dishes and TACT using plates. Of the color parameters measured with the colorimeter, only L*, a*/b*, and hue significantly correlated with total anthocyanins (p < 0.05), but, except for L* (R = − 0.79), the correlations were weak (R = − 0.23 for a*/b* and R = 0.22 for hue). Conversely, all correlations with total anthocyanins and color parameters measured with TACT were significant (p < 0.001) and moderately strong (e.g., R = − 0.69 for L* and R = 0.55 for a*/b*). These values were indicative of darker colors as total anthocyanin content increased.

Conclusions
While the colorimeter and TACT-based methods were not fully interchangeable, TACT better captured color differences among raspberry genotypes than the colorimeter. The correlations between color parameters measured with TACT and total anthocyanins were not strong enough to develop prediction models, yet the use of TACT with 96-well plates instead of Petri dishes would enable the high-throughput measurement of red raspberry puree color.
School refusal behavior in children and adolescents: a five-year narrative review of clinical significance and psychopathological profiles
Authors: Di Vincenzo Cristina , Pontillo Maria , Bellantoni Domenica , Di Luzio Michelangelo , Lala Maria Rosaria , Villa Marianna , Demaria Francesco , Vicari Stefano 
Published: May 2024

AbstractThe aim of the study was to explore the clinical significance of school refusal behavior, its negative impact on psychological well-being of children and adolescents and its relationship with the most common psychopathological conditions during childhood and adolescence (e.g. neurodevelopmental disorders, psychiatric disorders). School refusal behavior refers to a distressing condition experienced by children and adolescents that compromise regular school attendance and determine negative consequences on mental health and adaptive functioning. A narrative review of the literature published between January 2019 and March 2023 was conducted. Ten studies (n = 10) were included from a literature search of the electronic databases PubMed, CINAHL, PsycInfo, MedLine, and Cochrane Library. The results indicate that school refusal is highly present in neurodevelopmental disorders such as autism and attention-deficit/hyperactivity disorder due to the presence of behavioral problems and deficits in communication skills. As for psychiatric disorders, school refusal appears to be highly common in anxiety disorders, depressive disorders, and somatic symptoms. We also found that school refusal behavior may be associated with various emotional and behavioral conditions that act as risk factors. Especially, but are not limited to, it may be associated with a diminished self-concept, exposure to cyberbullying, specific affective profiles and excessive technology usage. Our results indicate that school refusal is a condition with many clinical facets. It can be attributed to both vulnerability factors, both temperamental and relational, and to various psychopathological conditions that differ significantly from each other, such as neurodevelopmental disorders and psychiatric disorders. Recognizing these aspects can improve the implementation of patient-tailored therapeutic interventions that are consequently more likely to produce effective outcomes. The therapeutic intervention should facilitate the recognition of cognitive biases regarding school as a threatening environment, while regulating negative emotions associated with school attendance. Additionally, therapeutic intervention programs linked to social skill training and problem-solving training, conducted directly within the school setting, can enhance children’s abilities to cope with academic performance and social relationships, ultimately preventing school refusal.