bluuebunny/crossref_metadata_2025_split huggingface dataset:
M-type pyruvate kinase 2 (PKM2) tetramerization alleviates the progression of right ventricle failure by regulating oxidative stress and mitochondrial dynamics
Authors: Guo Lizhe , Wang Lu , Qin Gang , Zhang Junjie , Peng Jin , Li Longyan , Chen Xiang , Wang Dandan , Qiu Jian , Wang E. 
Published: December 2023

Abstract
Background
Right ventricle failure (RVF) is a progressive heart disease that has yet to be fully understood at the molecular level. Elevated M-type pyruvate kinase 2 (PKM2) tetramerization alleviates heart failure, but detailed molecular mechanisms remain unclear.

Objective
We observed changes in PKM2 tetramerization levels during the progression of right heart failure and in vitro cardiomyocyte hypertrophy and explored the causal relationship between altered PKM2 tetramerization and the imbalance of redox homeostasis in cardiomyocytes, as well as its underlying mechanisms. Ultimately, our goal was to propose rational intervention strategies for the treatment of RVF.

Method
We established RVF in Sprague Dawley (SD) rats by intraperitoneal injection of monocrotaline (MCT). The pulmonary artery pressure and right heart function of rats were assessed using transthoracic echocardiography combined with right heart catheterization. TEPP-46 was used both in vivo and in vitro to promote PKM2 tetramerization.

Results
We observed that oxidative stress and mitochondrial disorganization were associated with increased apoptosis in the right ventricular tissue of RVF rats. Quantitative proteomics revealed that PKM2 was upregulated during RVF and negatively correlated with the cardiac function. Facilitating PKM2 tetramerization promoted mitochondrial network formation and alleviated oxidative stress and apoptosis during cardiomyocyte hypertrophy. Moreover, enhancing PKM2 tetramer formation improved cardiac mitochondrial morphology, mitigated oxidative stress and alleviated heart failure.

Conclusion
Disruption of PKM2 tetramerization contributed to RVF by inducing mitochondrial fragmentation, accumulating ROS, and finally promoted the progression of cardiomyocyte apoptosis. Facilitating PKM2 tetramerization holds potential as a promising therapeutic approach for RVF.
Clinical features of acute attacks, chronic symptoms, and long-term complications among patients with acute hepatic porphyria in Japan: a real-world claims database study
Authors: Horie Yutaka , Yasuoka Yuka , Adachi Tomohide 
Published: December 2023

Abstract
Background
Acute hepatic porphyria (AHP) is a family of rare genetic diseases, including acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and delta-aminolevulinic acid dehydratase-deficient porphyria. The objective of this retrospective cohort study was to provide information on the clinical features of AHP in Japan—including acute attacks, chronic symptoms, and long-term complications.

Methods
Patients with AHP between April 2008 and June 2020 were selected from Japan’s Medical Data Vision claims database. Patients with AHP were matched 1:10, by sex and age, to patients without AHP. The outcomes were evaluated overall, for patients age ≥ 55 years, and for the matched population.

Results
A total of 391 patients with AHP were included from the Japanese Medical Data Vision database. During the observation period (April 2008–June 2020), 18.2% (71/391) of patients experienced 1 acute attack and 10.5% (41/391) experienced ≥ 2 attacks. Chronic symptoms with rates ~ 10% or higher in the AHP population compared with the matched population included neurotic, stress-related, and somatoform disorders (21.7% vs. 6.7% [15.0% difference]); sleep disorders (23.0% vs. 9.9% [13.1% difference]); other and unspecified abdominal pain (13.6% vs. 3.7% [9.9% difference]); and nausea and vomiting, excluding chemotherapy-induced emesis (17.9% vs. 8.1% [9.8% difference]). Long-term complications with higher incidence rates in the AHP population compared with the matched population included fibrosis and cirrhosis of liver (15.9% vs. 3.0% [12.9% difference]), polyneuropathies and other disorders of the peripheral nervous system (20.5% vs. 7.9% [12.6% difference]), liver cancer (16.9% vs. 4.7% [12.2% difference]), renal failure (16.4% vs. 4.3% [12.1% difference]), and hypertension (26.1% vs. 18.8% [7.3% difference]). Among AHP patients age ≥ 55 years, the most common long-term complications were hypertension, kidney failure, and liver cancer.

Conclusions
In Japan, patients with AHP experience a high clinical burden in terms of acute attacks, chronic symptoms, and long-term complications. The clinical burden related to chronic symptoms and long-term complications was substantially higher in Japanese patients with AHP compared with a matched population without AHP. Recognizing these signs and symptoms of AHP may aid physicians in making an earlier diagnosis, which may help patients avoid attack triggers, implement disease management, and reduce lifetime disease burden.
Association of preoperative retinal microcirculation and perioperative outcomes in patients undergoing congenital cardiac surgery
Authors: Li Cong , Zhu Zhuoting , Yuan Haiyun , Hu Yijun , Xue Yunlian , Zhong Pingting , Huang Manqing , Ren Yun , Kuang Yu , Zeng Xiaomin , Yu Honghua , Yang Xiaohong 
Published: December 2023

Abstract
Background
Microcirculatory dysfunction is associated with increased morbidity and mortality in cardiac surgery patients. This study aimed to investigate the association between preoperative retinal microcirculation evaluated using optical coherence tomography angiography (OCTA) and perioperative outcomes in patients with congenital heart disease (CHD).

Methods
This prospective, observational study was performed from May 2017 to January 2021. OCTA was used to automatically quantify the vessel density (VD) of the superficial capillary plexus, deep capillary plexus (DCP), and radial peripapillary capillary (RPC) preoperatively. The primary outcome was excessive postoperative bleeding, defined as bleeding volume > 75th percentile for 24-hour postoperative chest tube output. The secondary outcome was composite adverse outcomes, including one or more operative mortalities, early postoperative complications, and prolonged length of stay. The association between retinal VD and outcomes was assessed using Poisson regression.

Results
In total, 173 CHD patients who underwent cardiac surgery were included (mean age, 26 years). Among them, 43 (24.9%) and 46 (26.6%) developed excessive postoperative bleeding and composite adverse outcomes, respectively. A lower VD of DCP (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.08–1.43; P = 0.003) was independently associated with excessive postoperative bleeding, and a lower VD of RPC (OR, 1.97; 95% CI, 1.08–3.57; P = 0.027), and DCP (OR, 2.17; 95% CI, 1.08–4.37; P = 0.029) were independently associated with the postoperative composite adverse outcomes.

Conclusion
Preoperative retinal hypoperfusion was independently associated with an increased risk of perioperative adverse outcomes in patients with CHD, suggesting that retinal microcirculation evaluation could provide valuable information about the outcomes of cardiac surgery, thereby aiding physicians in tailoring individualized treatment.
Participatory approaches and methods in gender equality and gender-based violence research with refugees and internally displaced populations: a scoping review
Authors: Lokot Michelle , Hartman Erin , Hashmi Iram 
Published: December 2023

AbstractUsing participatory approaches or methods are often positioned as a strategy to tackle power hierarchies in research. Despite momentum on decolonising aid, humanitarian actors have struggled to describe what ‘participation’ of refugees and internally displaced persons (IDPs) means in practice. Efforts to promote refugee and IDP participation can be tokenistic. However, it is not clear if and how these critiques apply to gender-based violence (GBV) and gender equality—topics that often innately include power analysis and seek to tackle inequalities. This scoping review sought to explore how refugee and IDP participation is conceptualised within research on GBV and gender equality. We found that participatory methods and approaches are not always clearly described. We suggest that future research should articulate more clearly what constitutes participation, consider incorporating feminist research methods which have been used outside humanitarian settings, take more intentional steps to engage refugees and IDPs, ensure compensation for their participation, and include more explicit reflection and strategies to address power imbalances.
Pediatric glioma histone H3.3 K27M/G34R mutations drive abnormalities in PML nuclear bodies
Authors: Voon Hsiao P. J. , Hii Linda , Garvie Andrew , Udugama Maheshi , Krug Brian , Russo Caterina , Chüeh Anderly C. , Daly Roger J. , Morey Alison , Bell Toby D. M. , Turner Stephen J. , Rosenbluh Joseph , Daniel Paul , Firestein Ron , Mann Jeffrey R. , Collas Philippe , Jabado Nada , Wong Lee H. 
Published: December 2023

Abstract
Background
Point mutations in histone variant H3.3 (H3.3K27M, H3.3G34R) and the H3.3-specific ATRX/DAXX chaperone complex are frequent events in pediatric gliomas. These H3.3 point mutations affect many chromatin modifications but the exact oncogenic mechanisms are currently unclear. Histone H3.3 is known to localize to nuclear compartments known as promyelocytic leukemia (PML) nuclear bodies, which are frequently mutated and confirmed as oncogenic drivers in acute promyelocytic leukemia.

Results
We find that the pediatric glioma-associated H3.3 point mutations disrupt the formation of PML nuclear bodies and this prevents differentiation down glial lineages. Similar to leukemias driven by PML mutations, H3.3-mutated glioma cells are sensitive to drugs that target PML bodies. We also find that point mutations in IDH1/2—which are common events in adult gliomas and myeloid leukemias—also disrupt the formation of PML bodies.

Conclusions
We identify PML as a contributor to oncogenesis in a subset of gliomas and show that targeting PML bodies is effective in treating these H3.3-mutated pediatric gliomas.
DNA methylation modulated genetic variant effect on gene transcriptional regulation
Authors: Zeng Yong , Jain Rahi , Lam Magnus , Ahmed Musaddeque , Guo Haiyang , Xu Wenjie , Zhong Yuan , Wei Gong-Hong , Xu Wei , He Housheng Hansen 
Published: December 2023

Abstract
Background
Expression quantitative trait locus (eQTL) analysis has emerged as an important tool in elucidating the link between genetic variants and gene expression, thereby bridging the gap between risk SNPs and associated diseases. We recently identified and validated a specific case where the methylation of a CpG site influences the relationship between the genetic variant and gene expression.

Results
Here, to systematically evaluate this regulatory mechanism, we develop an extended eQTL mapping method, termed DNA methylation modulated eQTL (memo-eQTL). Applying this memo-eQTL mapping method to 128 normal prostate samples enables identification of 1063 memo-eQTLs, the majority of which are not recognized as conventional eQTLs in the same cohort. We observe that the methylation of the memo-eQTL CpG sites can either enhance or insulate the interaction between SNP and gene expression by altering CTCF-based chromatin 3D structure.

Conclusions
This study demonstrates the prevalence of memo-eQTLs paving the way to identify novel causal genes for traits or diseases associated with genetic variations.
Ukumela impilo randomised trial: preliminary findings of height-adjustable sit-to-stand workstations on health outcomes of South African office workers
Authors: Phaswana Merling , Gradidge Philippe Jean-Luc 
Published: December 2023

Abstract
Background
The prevalence of sedentary behaviour has concurrently risen with multiple cardiometabolic risk markers independent of physical activity levels. Office-based workers accumulate the highest levels of sitting time during occupational times. This study aims to investigate the short-term effects of using height-adjustable sit-to-stand workstations on cardiometabolic risk markers of office-based workers in South Africa.

Results
Sixty-two office-based workers were randomized into intervention (n = 44), and the control group (n = 18). Small improvements were observed in BMI, blood pressure, and cholesterol levels in this cohort.

Conclusion
This preliminary investigation confirms that short-term height-adjustable sit-stand interventions are effective in reducing workplace sitting time and selected health outcomes. South Africa has been attributed with the highest burden of obesity in Sub-Saharan Africa, as a result, there is a need to implement long-term workplace intervention to reverse these implications.

Trial registration
Pan African Clinical Trial Registry, PACTR201911656014962 on the 12th of November 2019.
Elevation of cancer antigen 15-3 owing to oncocytic renal neoplasm in a patient without evidence of breast cancer recurrence on follow-up: a case report
Authors: Cockey Samuel G. , Xu Hongzhi , Al-Jumayli Mohammed 
Published: December 2023

Abstract
Background
Cancer antigen 15-3 is a protein that clinicians commonly measure to monitor outcomes and response to treatment in patients with breast cancer. However, cancer antigen 15-3 can also be elevated in other, benign and malignant conditions.

Case presentation
A 73-year-old White woman with history of breast cancer presented to her primary care physician with right hip pain, and laboratory testing revealed elevated cancer antigen 15-3. Further workup with radiographic imaging revealed a large mass in her right kidney. The renal mass was subsequently removed, and the cancer antigen 15-3 level returned to normal.

Conclusions
Elevation of cancer antigen 15-3 owing to causes other than breast cancer recurrence can be a potential diagnostic pitfall during a patient’s follow-up. It is important for clinicians to be aware of the limitations of cancer markers and to utilize a combination of diagnostic tests for patient evaluation.
Homozygous missense variant F12 (Gly506Asp) associated with severe factor XII deficiency: a case report
Authors: Aljabry Mansour , Algazlan Aljoud , Alsubaie Nouf , Dher Shatha Bin , Aljabri Hassan Semar , Alotaibi Ghazi S. 
Published: December 2023

Abstract
Background
Factor XII deficiency can be related to either homozygous or compound heterozygous pathogenic variants in the F12 gene. The disease is commonly known as Hageman trait and is inherited in both autosomal recessive or dominant patterns. Clinically, factor XII deficiency is not associated with bleeding but conversely has been linked to thrombotic events, recurrent pregnancy loss, and hereditary angioedema. Molecular data of F12 deficiency are scarce and have revealed varying results between cases. However, most of the reported variants are missense mutations, gross deletions, or small insertion. Factor XII deficiency has been reported in the Saudi population in several studies, either as isolated case reports or included within the studies of rare bleeding factors deficiency. However, molecular data are lacking as no case report of genetic studies related to factor XII deficiency has been published in our local population, to the best of our knowledge.

Case report
Herein we describe a homozygous missense variant involving exon 12 within F12 gene (5:176,830,269 G>A; p.Gly506Asp) in a 36-year-old Saudi multiparous female referred from the surgical clinic with significantly high activated partial thromboplastin time during preoperative assessment for sleeve gastrectomy. The patient had no history of bleeding episodes during the previous deliveries nor any tooth extractions. She had single event of spontaneous abortion during the 15th week of gestation without any bleeding complication. There was no history of thrombosis or skin manifestations, and she was not taking any medicines. There was no family history of bleeding or thrombosis. Family history revealed consanguinity as the parents are first-degree cousins. Physical examination was unremarkable. Upon investigation, the prolonged activated partial thromboplastin time was fully corrected by a 1:1 mixing study with normal pool plasma while lupus anticoagulant tests were negative. Factor assays and von Willebrand factor tests are all within normal ranges except for factor XII, which was severely deficient. A homozygous missense variant involving exon 12 within F12 gene (5:176,830,269 G>A; p.Gly506Asp) was identified.

Conclusion
F12 (5:176,830,269 G>A; p.Gly506Asp) variant is likely to be a pathogenic variant among homozygous factor XII-deficient patients. Genetic counseling and management of the patients and families should be based on clinical evaluation.
Confronting urethrorrhagia after Otis urethrotomy: a case report
Authors: Mete Uttam Kumar , Deshpande Rohit Sanjay 
Published: December 2023

Abstract
Background
Otis urethrotomy can sometimes lead to troublesome bleeding after seemingly uneventful procedures. This case report highlights one such case which went unnoticed initially; the bleeding was erroneously ascribed to the prostate, thereby falsely indicting the “decoy” prostate.

Case presentation
A 78-year-old Asian gentleman was referred to our hospital with complaint of intractable bleeding after undergoing laser enucleation of prostate at another institute, wherein he further underwent unsuccessful bilateral angioembolization of pudendal arteries. On endoscopy (for hemostasis), we found a spurting vessel in the navicular fossa, which was effectively controlled.

Conclusions
This case report highlights the importance of performing prompt endoscopy in case of uncontrolled bleeding after prostate endoscopic surgery.
BioBLP: a modular framework for learning on multimodal biomedical knowledge graphs
Authors: Daza Daniel , Alivanistos Dimitrios , Mitra Payal , Pijnenburg Thom , Cochez Michael , Groth Paul 
Published: December 2023

Abstract
Background
Knowledge graphs (KGs) are an important tool for representing complex relationships between entities in the biomedical domain. Several methods have been proposed for learning embeddings that can be used to predict new links in such graphs. Some methods ignore valuable attribute data associated with entities in biomedical KGs, such as protein sequences, or molecular graphs. Other works incorporate such data, but assume that entities can be represented with the same data modality. This is not always the case for biomedical KGs, where entities exhibit heterogeneous modalities that are central to their representation in the subject domain.

Objective
We aim to understand how to incorporate multimodal data into biomedical KG embeddings, and analyze the resulting performance in comparison with traditional methods. We propose a modular framework for learning embeddings in KGs with entity attributes, that allows encoding attribute data of different modalities while also supporting entities with missing attributes. We additionally propose an efficient pretraining strategy for reducing the required training runtime. We train models using a biomedical KG containing approximately 2 million triples, and evaluate the performance of the resulting entity embeddings on the tasks of link prediction, and drug-protein interaction prediction, comparing against methods that do not take attribute data into account.

Results
In the standard link prediction evaluation, the proposed method results in competitive, yet lower performance than baselines that do not use attribute data. When evaluated in the task of drug-protein interaction prediction, the method compares favorably with the baselines. Further analyses show that incorporating attribute data does outperform baselines over entities below a certain node degree, comprising approximately 75% of the diseases in the graph. We also observe that optimizing attribute encoders is a challenging task that increases optimization costs. Our proposed pretraining strategy yields significantly higher performance while reducing the required training runtime.

Conclusion
BioBLP allows to investigate different ways of incorporating multimodal biomedical data for learning representations in KGs. With a particular implementation, we find that incorporating attribute data does not consistently outperform baselines, but improvements are obtained on a comparatively large subset of entities below a specific node-degree. Our results indicate a potential for improved performance in scientific discovery tasks where understudied areas of the KG would benefit from link prediction methods.
Exploring the surface epitope and nuclear localization analysis of porcine circovirus type 3 capsid protein
Authors: Chang Chia-Chun , Wu Ching-Ying , Ciou Jhao-Guan , Wu Ching-Wei , Wang Yi-Chen , Chang Hui-Wen , Chien Maw-Sheng , Huang Chienjin 
Published: December 2023

AbstractPorcine circovirus 3 (PCV3) is a newly emerging virus associated with porcine dermatitis and nephropathy syndrome (PDNS) and reproductive disorders, impacting global pig populations. Porcine circoviruses contain two major open reading frames (ORFs), and the ORF2 encodes the viral capsid protein (Cap). Cap is the most antigenic structural protein and an ideal candidate for the development of vaccines and diagnostic reagents. This study generated a monoclonal antibody (MAb) specific to PCV3 Cap, MAb CCC160, for diagnosis and pathogenesis studies of this novel virus. The MAb specifically recognized PCV3-infected swine lymph node tissue in an immunohistochemical analysis confirming its clinical diagnostic potential. In addition, a novel linear B-cell epitope recognized by MAb CCC160 was identified at the amino acid region 120–134 of Cap. Nuclear localization analysis of PCV3 Cap revealed a potential nuclear localization signal (NLS) in the middle region (aa 131–143) in addition to the dominant N-terminal NLS that is already known. A cell viability assay further demonstrated that the cytotoxicity of PCV3 Cap is correlated with its nuclear localization, indicating a crucial role of Cap in the pathogenic mechanism of PCV3. A full-length construct of PCV3 Cap was successfully expressed using a baculovirus expression system and purified recombinant proteins self-assembled into virus-like particles (VLPs). The protein constitution of the VLPs was confirmed by MAb CCC160 recognition, indicating the correct conformation and specificity of VLP and exhibiting the linear epitope aa 120–134 on the VLP surface. These results provide insights for developing diagnostic tools and potential VLP vaccines for PCV3, revealing its pathogenesis and antigenic properties.