bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients’ experience of accessing hepatitis C treatment through the Myanmar national hepatitis C treatment program: a qualitative evaluation
Authors: Draper Bridget , Yee Win Lei , Bowring Anna , Naing Win , Kyi Khin Pyone , Htay Hla , Howell Jessica , Hellard Margaret , Pedrana Alisa 
Published: January 2024

Abstract
Background
Globally, 56.8 million people are living with hepatitis C and over three-quarters of those reside in low and middle-income countries (LMICs). Barriers and enablers to hepatitis C care among people who inject drugs in high-income countries are well documented. However, there is scant literature describing the patient experience in LMICs. Understanding the barriers and enablers to care from the patient perspective is important to inform service refinements to improve accessibility and acceptability of hepatitis C care.

Methods
We conducted a qualitative evaluation of the patient experience of accessing the national hepatitis C program at eight hospital sites in Myanmar. Semi-structured interviews were conducted with four to five participants per site. Interview data were analysed thematically, with deductive codes from Levesque et al.’s (2013) Framework on patient-centred access to healthcare.

Results
Across the eight sites, 38 participants who had completed treatment were interviewed. Barriers to accessing care were mostly related to attending for care and included travel time and costs, multiple appointments, and wait times. Some participants described how they did not receive adequate information on hepatitis C, particularly its transmission routes, and on the level of cirrhosis of their liver and what they were required to do after treatment (i.e. reduce alcohol consumption, liver cirrhosis monitoring). Many participants commented that they had few or no opportunities to ask questions. Provision of treatment at no cost was essential to accessibility, and gratitude for free treatment led to high acceptability of care, even when accessing care was inconvenient.

Conclusions
These findings highlight the importance of streamlining and decentralising health services, adequate human resourcing and training, and affordable treatment in maximising the accessibility and acceptability of hepatitis C care in LMICs. Findings from this work will inform future service delivery refinements for national program and other decentralised programs to improve accessibility and acceptability of hepatitis C care in Myanmar.
Barriers and facilitators in developing patient versions of clinical practice guidelines - qualitative interviews on experiences of international guideline producers
Authors: Meyer Nora , Hauprich Julia , Breuing Jessica , Hellbrecht Irma , Wahlen Sarah , Könsgen Nadja , Bühn Stefanie , Becker Monika , Blödt Susanne , Carl Günther , Follmann Markus , Frenz Stefanie , Langer Thomas , Nothacker Monika , Schaefer Corinna , Pieper Dawid 
Published: January 2024

Abstract
Background
Several guideline organizations produce patient versions of clinical practice guidelines (PVGs) which translate recommendations into simple language. A former study of our working group revealed that few guideline organizations publish their methods used to develop PVGs. Clear definitions of PVGs do not prevail and their purposes often remain unclear. We aimed to explore experts’ perspectives on developing, disseminating and implementing PVGs to discuss and incorporate these experiences when consenting on methodological guidance and further improving PVGs.

Methods
We conducted 17 semi-structured telephone interviews with international experts working with PVGs from September 2021 through January 2022. We conducted the interviews in English or German, they were recorded and transcribed verbatim. We utilized Mayring’s qualitative content analysis with MAXQDA software to analyze the data.

Results
In two interviews two participants were interviewed at the same time. This resulted in a total of 19 participants from 16 different organizations and eight different countries participated. Most were female (16/19) and their experience in working with PVGs ranged from 1 to 20 years. All follow methodological standards when developing PVGs, but the extent of these standards and their public accessibility differs. Aims and target groups of PVGs vary between organizations. Facilitators for developing PVGs are working with a multidisciplinary team, financial resources, consultation processes and a high-quality underlying CPG. Facilitators for disseminating and implementing PVGs are using various strategies. Barriers, on the other hand, are the lack of these factors. All participants mentioned patient involvement as a key aspect in PVG development.

Conclusion
The steps in the PVG development process are largely similar across the countries. Focus is placed on the involvement of patients in the development process, although the extent of participation varies. The experts collectively attribute great importance to PVGs overall, but in order to constantly adapt to medical progress and changing conditions, the focus in the future may be more on formats like living guidelines. Although there are different views on the mandatory development of PVGs, there is a consistent call for more transparency regarding the methodology used for PVGs.
Construction of an ER stress-related prognostic signature for predicting prognosis and screening the effective anti-tumor drug in osteosarcoma
Authors: Chen Weidong , Liao Yan , Sun Pengxiao , Tu Jian , Zou Yutong , Fang Ji , Chen Ziyun , Li Hongbo , Chen Junkai , Peng Yuzhong , Wen Lili , Xie Xianbiao 
Published: January 2024

Abstract
Background
Osteosarcoma is the most common malignant primary bone tumor in infants and adolescents. The lack of understanding of the molecular mechanisms underlying osteosarcoma progression and metastasis has contributed to a plateau in the development of current therapies. Endoplasmic reticulum (ER) stress has emerged as a significant contributor to the malignant progression of tumors, but its potential regulatory mechanisms in osteosarcoma progression remain unknown.

Methods
In this study, we collected RNA sequencing and clinical data of osteosarcoma from The TCGA, GSE21257, and GSE33382 cohorts. Differentially expressed analysis and the least absolute shrinkage and selection operator regression analysis were conducted to identify prognostic genes and construct an ER stress-related prognostic signature (ERSRPS). Survival analysis and time dependent ROC analysis were performed to evaluate the predictive performance of the constructed prognostic signature. The “ESTIMATE” package and ssGSEA algorithm were utilized to evaluate the differences in immune cells infiltration between the groups. Cell-based assays, including CCK-8, colony formation, and transwell assays and co-culture system were performed to assess the effects of the target gene and small molecular drug in osteosarcoma. Animal models were employed to assess the anti-osteosarcoma effects of small molecular drug.

Results
Five genes (BLC2, MAGEA3, MAP3K5, STC2, TXNDC12) were identified to construct an ERSRPS. The ER stress-related gene Stanniocalcin 2 (STC2) was identified as a risk gene in this signature. Additionally, STC2 knockdown significantly inhibited osteosarcoma cell proliferation, migration, and invasion. Furthermore, the ER stress-related gene STC2 was found to downregulate the expression of MHC-I molecules in osteosarcoma cells, and mediate immune responses through influencing the infiltration and modulating the function of CD8+ T cells. Patients categorized by risk scores showed distinct immune status, and immunotherapy response. ISOX was subsequently identified and validated as an effective anti-osteosarcoma drug through a combination of CMap database screening and in vitro and in vivo experiments.

Conclusion
The ERSRPS may guide personalized treatment decisions for osteosarcoma, and ISOX holds promise for repurposing in osteosarcoma treatment.
On mental pain and suicide risk in modern psychiatry
Authors: Pompili Maurizio 
Published: January 2024

AbstractFacing suicide risk is probably the most difficult task for clinicians when dealing with patients in crisis. It requires professional, intellectual, and emotional efforts. Suicide risk assessment can sometimes be distressing for clinicians, and such a state may favour the avoidance of an in-depth exploration of suicidal thoughts and behaviour. Patients often feel subjected to interpersonal assessments with little opportunity to explore their perspectives. The "One size fits all" approach tends to create distance and paradoxically contributes to an increase in the risk of suicide. Traditional clinical factors may be of limited value if a shared understanding of the patient’s suicide risk is missed. To understand the suicidal mind, it is necessary to take the point of view of the subject in crisis. In this essay, the “operational model of mental pain as a main ingredient of suicide” provided by Edwin Shneidman is overviewed with the aim of a better empathic understanding of patients’ sufferance. With a phenomenological approach, the suicidal crisis appears as a complex, pervasive state rather than as a symptom of a mental disorder, as the new paradigm also suggests. In this regard, the "mentalistic" aspects of suicide propose a broader insight into the suicidal scenario far beyond the diagnosis of psychiatric disorders. In this article, the perspective of individuals who deem their mental pain to be intolerable is described to make sense of their ambivalence between the wish to die and the wish to live that can prevail if relief is provided.
North Korea’s COVID-19 policy dilemma: epidemic prevention conflicting with trade
Authors: Park Byungjin , Cho Joonmo 
Published: January 2024

Abstract
Background
Amidst the COVID-19 pandemic, striking a delicate balance between sustaining economic activity and safeguarding public health has become a crucial concern. The border closures for COVID-19 prevention have further intensified concerns for North Korea, which conducts over 90% of its trade with China and Russia, countries sharing its borders.

Methods
This study aims to scrutinize North Korea’s response to these competing imperatives by examining the impact of border closures on the country’s trade dynamics with China and Russia. This study employed the difference-in-difference (DID) method to analyze transformations in North Korea’s economic activity before and after the border closures, utilizing trade data and nighttime satellite imagery captured in 2019 and 2020.

Results
The results reveal that North Korea actively reoriented its trade priorities towards Russia and accorded precedence to its epidemic prevention system over its economy during the pandemic. A noticeable increase in imports of food and pharmaceuticals was observed, indicating a significant rise in the inflow of these essential commodities.

Conclusion
The findings of this study suggest that during the early stages of the COVID-19 pandemic, North Korea placed significant policy emphasis on preserving public health. However, due to economic hardships and food shortages, if the pandemic persists in the long term, it indicates the possibility of partial or complete lifting of border closures to mitigate these challenges.
Quercetin inhibits caspase-1-dependent macrophage pyroptosis in experimental folic acid nephropathy
Authors: Gao Xianli , Guo Caiyun , Li Wenjun , Deng Yingdong , Ning Wenjun , Xie Jiaqi , Zhan Xiaoying , Fan Youling , Chen Hongtao , Huang Zengping , Zhou Jun 
Published: January 2024

Abstract
Background
The role of pyroptosis in kidney disease is limited and incomplete. Quercetin, a flavonoid compound present in a variety of fruits, vegetables, and plants, has shown antioxidant and anti-inflammatory properties. This study was designed to validate the importance of pyroptosis in an experimental model of folic acid nephropathy and to explore the effect of quercetin in protecting against pyroptosis.

Methods
Gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were used to establish the correlation between pyroptosis and folic acid nephropathy. Immune cell infiltration, network pharmacology and single-cell RNA sequencing analysis were utilized to ascertain the specific target of quercetin in relation to pyroptosis. Finally, quercetin’s role was verified in vivo and in vitro.

Results
The GSEA analysis revealed a significant correlation between pyroptosis and folic acid nephropathy (NES = 1.764, P = 0.004). The hub genes identified through WGCNA were closely associated with inflammation. Molecular docking demonstrated a strong binding affinity between quercetin and caspase-1, a protein known to be involved in macrophage function, as confirmed by immune cell infiltration and single-cell analysis. Quercetin demonstrated a significant amelioration of kidney injury and reduction in macrophage infiltration in the animal model. Furthermore, quercetin exhibited a significant inhibition of caspase-1 expression, subsequently leading to the inhibition of pro-inflammatory cytokines expression, such as IL-1β, IL-18, TNF-α, and IL-6. The inhibitory effect of quercetin on macrophage pyroptosis was also confirmed in RAW264.7 cells.

Conclusion
This study contributes substantial evidence to support the significant role of pyroptosis in the development of folic acid nephropathy, and highlights the ability of quercetin to downregulate caspase-1 in macrophages as a protective mechanism against pyroptosis.
Imposter or knight in shining armor? Pelvic circumferential compression devices (PCCD) for severe pelvic injuries in patients with multiple trauma: a trauma-registry analysis
Authors: Trentzsch H. , Lefering R. , Schweigkofler U. ,   the TraumaRegister DGU
Published: January 2024

Abstract
Background
Pelvic Circumferential Compression Devices (PCCD) are standard in hemorrhage-control of unstable pelvic ring fractures (UPF). Controversial data on their usefulness exists. Aim of the study was to investigate whether prehospital application of PCCD can reduce mortality and transfusion requirements in UPF.

Methods
Retrospective cohort study. From 2016 until 2021, 63,371 adult severely injured patients were included into TraumaRegister DGU® of the German Trauma Society (TR-DGU). We analyzed PCCD use over time and compared patients with multiple trauma patients and UPF, who received prehospital PCCD to those who did not (noPCCD). Groups were adjusted for risk of prehospital PCCD application by propensity score matching. Primary endpoints were hospital mortality, standardized mortality rate (SMR) and transfusion requirements.

Results
Overall UPF incidence was 9% (N = 5880) and PCCD use increased over time (7.5% to 20.4%). Of all cases with UPF, 40.2% received PCCD and of all cases with PCCD application, 61% had no pelvic injury at all. PCCD patients were more severely injured and had higher rates of shock or transfusion. 24-h.-mortality and hospital mortality were higher with PCCD (10.9% vs. 9.3%; p = 0.033; 17.9% vs. 16.1%, p = 0.070). Hospital mortality with PCCD was 1% lower than predicted. SMR was in favor of PCCD but failed statistical significance (0.95 vs. 1.04, p = 0.101). 1,860 propensity score matched pairs were analyzed: NoPCCD-patients received more often catecholamines (19.6% vs. 18.5%, p = 0.043) but required less surgical pelvic stabilization in the emergency room (28.6% vs. 36.8%, p < 0.001). There was no difference in mortality or transfusion requirements.

Conclusion
We observed PCCD overuse in general and underuse in UPF. Prehospital PCCD appears to be more a marker of injury severity and less triggered by presence of UPF. We found no salutary effect on survival or transfusion requirements. Inappropriate indication and technical flaw may have biased our results. TR-DGU does not contain data on these aspects. Further studies are necessary. Modular add-on questioners to the registry could offer one possible solution to overcome this limitation. We are concerned that PCCD use may be unfairly discredited by misinterpretation of the available evidence and strongly vote for a prospective trial.
Improved modeling of RNA-binding protein motifs in an interpretable neural model of RNA splicing
Authors: Gupta Kavi , Yang Chenxi , McCue Kayla , Bastani Osbert , Sharp Phillip A. , Burge Christopher B. , Solar-Lezama Armando 
Published: January 2024

AbstractSequence-specific RNA-binding proteins (RBPs) play central roles in splicing decisions. Here, we describe a modular splicing architecture that leverages in vitro-derived RNA affinity models for 79 human RBPs and the annotated human genome to produce improved models of RBP binding and activity. Binding and activity are modeled by separate Motif and Aggregator components that can be mixed and matched, enforcing sparsity to improve interpretability. Training a new Adjusted Motif (AM) architecture on the splicing task not only yields better splicing predictions but also improves prediction of RBP-binding sites in vivo and of splicing activity, assessed using independent data.
Strongyloides stercoralis genotyping in a human population in southwestern Iran
Authors: Beiromvand Molouk , Ashiri Alireza , de Ree Veroni , Harbecke Dorothee , Rödelsperger Christian , Streit Adrian , Rafiei Abdollah 
Published: January 2024

Abstract
Background
Strongyloidiasis is a neglected tropical disease (NTD) that is caused mainly by Strongyloides stercoralis, with an estimated 600 million people infected worldwide, and in fewer cases by Strongyloides fuelleborni fuelleborni and Strongyloides fuelleborni kellyi. A number of studies have been conducted on the genetic diversity of S. stercoralis in East and Southeast Asia; however, there is very limited corresponding information from West Asian countries, including Iran.

Methods
For Strongyloides worms collected from patients in southwestern Iran, the hypervariable regions I (HVR-I) and IV (HVR-IV) of the nuclear 18S ribosomal DNA (rDNA) locus (SSU) and a fragment of the subunit 1 mitochondrial cytochrome c oxidase gene (cox-1) were sequenced. For a subset of the worms, whole-genome sequencing data were generated.

Results
The cox-1 sequences of 136 worms isolated from 23 patients indicated that all isolates were S. stercoralis. Among the cox-1 sequences, 33 polymorphic sites and 13 haplotypes were found. The phylogenetic analysis demonstrated that some sequences clustered fairly closely with sequences from humans and dogs from other parts of the world, while others formed a separate, Iran-specific group. Among 64 S. stercoralis analyzed, we found three of the previously described SSU HVR-I haplotypes, with haplotype II being the most frequent haplotype. In contrast to Southeast Asia, where S. stercoralis heterozygous for different haplotypes at the HVR-I locus are rare, we found 20 worms to be heterozygous for two different HVR-I haplotypes, 18 of which fell into the Iran-specific cox-1 cluster. SSU-heterozygous worms also showed elevated heterozygosity at the whole-genome level.

Conclusions
We conclude that the S. stercoralis population from the Khuzestan province shares much of the genetic diversity with the population in Southeast Asia, but there is an indication of additional genetic input. There appears to be some population structure with different subpopulations, which however do interbreed at least occasionally.

Graphical Abstract
The causal relationship between immune cells and ankylosing spondylitis: a bidirectional Mendelian randomization study
Authors: Fei Yuchang , Yu Huan , Wu Yulun , Gong Shanshan 
Published: January 2024

Abstract
Background
Ankylosing spondylitis (AS) is one of several disorders known as seronegative spinal arthritis (SpA), the origin of which is unknown. Existing epidemiological data show that inflammatory and immunological factors are important in the development of AS. Previous research on the connection between immunological inflammation and AS, however, has shown inconclusive results.

Methods
To evaluate the causal association between immunological characteristics and AS, a bidirectional, two-sample Mendelian randomization (MR) approach was performed in this study. We investigated the causal connection between 731 immunological feature characteristic cells and AS risk using large, publically available genome-wide association studies.

Results
After FDR correction, two immunophenotypes were found to be significantly associated with AS risk: CD14 − CD16 + monocyte (OR, 0.669; 95% CI, 0.544 ~ 0.823; P = 1.46 × 10−4; PFDR = 0.043), CD33dim HLA DR + CD11b + (OR, 0.589; 95% CI = 0.446 ~ 0.780; P = 2.12 × 10−4; PFDR = 0.043). AS had statistically significant effects on six immune traits: CD8 on HLA DR + CD8 + T cell (OR, 1.029; 95% CI, 1.015 ~ 1.043; P = 4.46 × 10−5; PFDR = 0.014), IgD on IgD + CD24 + B cell (OR, 0.973; 95% CI, 0.960 ~ 0.987; P = 1.2 × 10−4; PFDR = 0.021), IgD on IgD + CD38 − unswitched memory B cell (OR, 0.962; 95% CI, 0.945 ~ 0.980; P = 3.02 × 10−5; PFDR = 0.014), CD8 + natural killer T %lymphocyte (OR, 0.973; 95% CI, 0.959 ~ 0.987; P = 1.92 × 10−4; PFDR = 0.021), CD8 + natural killer T %T cell (OR, 0.973; 95% CI, 0.959 ~ 0.987; P = 1.65 × 10−4; PFDR = 0.021).

Conclusion
Our findings extend genetic research into the intimate link between immune cells and AS, which can help guide future clinical and basic research.
Pancreatic cancer acquires resistance to MAPK pathway inhibition by clonal expansion and adaptive DNA hypermethylation
Authors: Godfrey Laura K. , Forster Jan , Liffers Sven-Thorsten , Schröder Christopher , Köster Johannes , Henschel Leonie , Ludwig Kerstin U. , Lähnemann David , Trajkovic-Arsic Marija , Behrens Diana , Scarpa Aldo , Lawlor Rita T. , Witzke Kathrin E. , Sitek Barbara , Johnsen Steven A. , Rahmann Sven , Horsthemke Bernhard , Zeschnigk Michael , Siveke Jens T. 
Published: January 2024

AbstractBackgroundPancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis. It is marked by extraordinary resistance to conventional therapies including chemotherapy and radiation, as well as to essentially all targeted therapies evaluated so far. More than 90% of PDAC cases harbor an activatingKRASmutation. As the most commonKRASvariants in PDAC remain undruggable so far, it seemed promising to inhibit a downstream target in the MAPK pathway such as MEK1/2, but up to now preclinical and clinical evaluation of MEK inhibitors (MEKi) failed due to inherent and acquired resistance mechanisms. To gain insights into molecular changes during the formation of resistance to oncogenic MAPK pathway inhibition, we utilized short-term passaged primary tumor cells from ten PDACs of genetically engineered mice. We followed gain and loss of resistance upon MEKiexposure and withdrawal by longitudinal integrative analysis of whole genome sequencing, whole genome bisulfite sequencing, RNA-sequencing and mass spectrometry data.ResultsWe found that resistant cell populations under increasing MEKitreatment evolved by the expansion of a single clone but were not a direct consequence of known resistance-conferring mutations. Rather, resistant cells showed adaptive DNA hypermethylation of 209 and hypomethylation of 8 genomic sites, most of which overlap with regulatory elements known to be active in murine PDAC cells. Both DNA methylation changes and MEKiresistance were transient and reversible upon drug withdrawal. Furthermore, MEKiresistance could be reversed by DNA methyltransferase inhibition with remarkable sensitivity exclusively in the resistant cells.ConclusionOverall, the concept of acquired therapy resistance as a result of the expansion of a single cell clone with epigenetic plasticity sheds light on genetic, epigenetic and phenotypic patterns during evolvement of treatment resistance in a tumor with high adaptive capabilities and provides potential for reversion through epigenetic targeting.