bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistical analysis of high-dimensional biomedical data: a gentle introduction to analytical goals, common approaches and challenges
Authors: Rahnenführer Jörg , De Bin Riccardo , Benner Axel , Ambrogi Federico , Lusa Lara , Boulesteix Anne-Laure , Migliavacca Eugenia , Binder Harald , Michiels Stefan , Sauerbrei Willi , McShane Lisa ,   for topic group “High-dimensional data” (TG9) of the STRATOS initiative
Published: May 2023

AbstractBackgroundIn high-dimensional data (HDD) settings, the number of variables associated with each observation is very large. Prominent examples of HDD in biomedical research include omics data with a large number of variables such as many measurements across the genome, proteome, or metabolome, as well as electronic health records data that have large numbers of variables recorded for each patient. The statistical analysis of such data requires knowledge and experience, sometimes of complex methods adapted to the respective research questions.MethodsAdvances in statistical methodology and machine learning methods offer new opportunities for innovative analyses of HDD, but at the same time require a deeper understanding of some fundamental statistical concepts. Topic group TG9 “High-dimensional data” of the STRATOS (STRengthening Analytical Thinking for Observational Studies) initiative provides guidance for the analysis of observational studies, addressing particular statistical challenges and opportunities for the analysis of studies involving HDD. In this overview, we discuss key aspects of HDD analysis to provide a gentle introduction for non-statisticians and for classically trained statisticians with little experience specific to HDD.ResultsThe paper is organized with respect to subtopics that are most relevant for the analysis of HDD, in particular initial data analysis, exploratory data analysis, multiple testing, and prediction. For each subtopic, main analytical goals in HDD settings are outlined. For each of these goals, basic explanations for some commonly used analysis methods are provided. Situations are identified where traditional statistical methods cannot, or should not, be used in the HDD setting, or where adequate analytic tools are still lacking. Many key references are provided.ConclusionsThis review aims to provide a solid statistical foundation for researchers, including statisticians and non-statisticians, who are new to research with HDD or simply want to better evaluate and understand the results of HDD analyses.
Construction of a CCL20-centered circadian-signature based prognostic model in cervical cancer
Authors: Yu Yuchong , Liu Yao , Li Yuhong , Yang Xiaoming , Han Mi , Fan Qiong 
Published: May 2023

Abstract
Background
Rather low vaccination rates for Human papillomavirus (HPV) and pre-existing cervical cancer patients with limited therapeutic strategies ask for more precise prognostic model development. On the other side, the clinical significance of circadian clock signatures in cervical cancer lacks investigation.

Methods
Subtypes classification based upon eight circadian clock core genes were implemented in TCGA-CESC through k-means clustering methods. Afterwards, KEGG, GO and GSEA analysis were conducted upon differentially expressed genes (DEGs) between high and low-risk groups, and tumor microenvironment (TME) investigation by CIBERSORT and ESTIMATE. Furthermore, a prognostic model was developed by cox and lasso regression methods, and verified in GSE44001 by time-dependent receiver-operating characteristic curve (ROC) analysis. Lastly, FISH and IHC were used for validation of CCL20 expression in patients’ specimens and U14 subcutaneous tumor models were built for TME composition.

Results
We successfully classified cervical patients into high-risk and low-risk groups based upon circadian-oscillation-signatures. Afterwards, we built a prognostic risk model composed of GJB2, CCL20 and KRT24 with excellent predictive value on patients’ overall survival (OS). We then proposed metabolism unbalance, especially for glycolysis, and immune related pathways to be major enriched signatures between the high-risk and low-risk groups. Then, we proposed an ‘immune-desert’-like suppressive myeloid cells infiltration pattern in high-risk group TME and verified its resistance to immunotherapies. Finally, CCL20 was proved positively correlated with real-world patients’ stages and induced significant less CD8+ T cells and more M2 macrophages infiltration in mouse model.

Conclusions
We unraveled a prognostic risk model based upon circadian oscillation and verified its solidity. Specifically, we unveiled distinct TME immune signatures in high-risk groups.
Knowledge, attitudes, and practices of mothers regarding childhood malaria in southeastern Gabon
Authors: Lendongo Wombo Judicaël Boris , Mbani Mpega Ntigui Chérone Nancy , Oyegue-Liabagui Lydie Sandrine , Ibinga Euloge , Maghendji-Nzondo Sydney , Mounioko Franck , Ontoua Steede Seinnat , Okouga Alain Prince , Lekana-Douki Jean Bernard , Ngoungou Edgard Brice 
Published: May 2023

Abstract
Background
In Gabon, children under 5 years of age and pregnant women are the populations who are most at risk of malaria. Despite the presence of accessible health facilities, the community-based management of childhood fever remains a very common practice in Gabon, which may have serious consequences on child health. As such, the objective of this descriptive cross-sectional survey is to assess the mothers’ perception and knowledge of malaria and its severity.

Methods
Different households were selected using the simple random sampling method.

Results
A total of 146 mothers from different households were interviewed in the city of Franceville, in southern Gabon. Among the households interviewed, 75.3% had a low monthly income (below the minimum monthly income of $272.73). Among the respondents, 98.6% of mothers had heard of malaria and 55.5% had heard of severe malaria. Regarding preventive measures, 83.6% of mothers used an insecticide-treated net as a means of protection. Self-medication was practiced by 68.5% of women (100/146).

Discussion
The use of health facilities was motivated by better care, the decision of the head of the family, but above all by the severity of the disease. Women identified fever as the main symptom of malaria, which could be beneficial for a quicker and more efficient management of the disease in children. Malaria educational campaigns should also increase awareness of severe forms of malaria and its manifestations. This study shows that Gabonese mothers react quickly when their children have fever. However, several external factors lead them to practice self-medication as a first resort. In this survey population, the practice of self-medication did not depend on social status, marital status, level of education, on the young age or inexperience of mothers (p > 0.05).

Conclusions
The data revealed that mothers may underestimate severe malaria and delay medical care by self-medicating, which can have detrimental effects for children and hinder the regression of the disease.
Necrotising pneumonia caused by Curvularia hawaiiensis (syn. Bipolaris hawaiiensis) and Mycobacterium tuberculosis coinfection in a patient with ascariasis: a case report and review
Authors: Aguirre Cristina , Acosta-España Jaime David , Patajalo-Villata Sheila Jissela , Rodriguez-Morales Alfonso J. 
Published: May 2023

Abstract
Introduction
Curvularia hawaiiensis (formerly Bipolaris hawaiiensis) is a plant pathogen often isolated from soil and vegetative material. However, only a few cases of opportunistic invasive infections in humans have been described.

Case
A 16-year-old female patient without comorbidities was admitted to the emergency department because of fever and chest pain. We described the first coinfection of Curvularia hawaiiensis and Mycobacterium tuberculosis necrotising pneumonia.

Discussion
Multiple infections can alter immune responses. However, immunosuppression is the most critical risk factor for infection with species of the genus Curvularia. Therefore, it is crucial to carefully examine patients with tuberculosis, as they may rarely be coinfected with unusual fungi.
Posterior paramedian approach combined with a novel inverted V-shaped surgical access for intraspinal schwannomas: a retrospective case series study
Authors: Zhai Pengfei , Wu Haiyang , Tong Linjian , Wang Yulin , Sun Zhiming 
Published: May 2023

Abstract
Objective
To explore the efficacy and safety of the posterior paramedian approach combined with a novel inverted V-shaped surgical access for the treatment of intraspinal schwannomas.

Methods
This study retrospectively reviewed consecutive patients who underwent surgical resection of the intraspinal schwannomas via the inverted V-shaped approach at our center between January 2016 and May 2021. Changes between the preoperative and postoperative visual analog scale (VAS) scores and neurological function Japan Orthopaedic Association (JOA) scores were assessed. Secondary outcomes such as success rate of tumor resection, operation time, blood loss, spinal stability, and disruption degree of intervertebral joints. Postoperative complications were also investigated.

Results
Of these 36 consecutive patients, there were 6 cases in the cervical spine, 2 cases at the cervical-thoracic junction, 11 cases in the thoracic spine, 4 cases at the thoracic-lumbar junction and 13 cases in the lumbar spine. The average operation time was 99 min, and the average blood loss was 95.4 mL. The tumor removal rate was 100%. Postoperative CT re-examination showed that the spinous processes were intact in all cases, the facet joint surfaces were intact in 32 cases. At the time of last follow-up, the median JOA score was 25 (9–27), which was significantly improved compared to the preoperative median JOA score of 15 (10–22) (P < 0.01). The overall excellent and good rate were 88.9 %. The median VAS score at post-surgery was 0 (0–2), which was significantly improved compared to the preoperative median VAS score of 4 (2–8) (P < 0.01). As for complications, there were no cases of cerebrospinal fluid leakage or spinal instability. Three patients who had a postoperative fever finally recovered after lumbar cistern drainage.

Conclusion
The inverted V-shaped surgical access via the posterior paramedian approach is an effective and safe method for the treatment of intraspinal schwannomas.
Multivariate analysis and model building for classifying patients in the peroxisomal disorders X-linked adrenoleukodystrophy and Zellweger syndrome in Chinese pediatric patients
Authors: Zhu Zhixing , Genchev Georgi Z. , Wang Yanmin , Ji Wei , Zhang Xiaofen , Lu Hui , Sriswasdi Sira , Tian Guoli 
Published: May 2023

AbstractBackgroundThe peroxisome is a ubiquitous single membrane-enclosed organelle with an important metabolic role. Peroxisomal disorders represent a class of medical conditions caused by deficiencies in peroxisome function and are segmented into enzyme-and-transporter defects (defects in single peroxisomal proteins) and peroxisome biogenesis disorders (defects in the peroxin proteins, critical for normal peroxisome assembly and biogenesis). In this study, we employed multivariate supervised and non-supervised statistical methods and utilized mass spectrometry data of neurological patients, peroxisomal disorder patients (X-linked adrenoleukodystrophy and Zellweger syndrome), and healthy controls to analyze the role of common metabolites in peroxisomal disorders, to develop and refine a classification models of X-linked adrenoleukodystrophy and Zellweger syndrome, and to explore analytes with utility in rapid screening and diagnostics.ResultsT-SNE, PCA, and (sparse) PLS-DA, operated on mass spectrometry data of patients and healthy controls were utilized in this study. The performance of exploratory PLS-DA models was assessed to determine a suitable number of latent components and variables to retain for sparse PLS-DA models. Reduced-features (sparse) PLS-DA models achieved excellent classification performance of X-linked adrenoleukodystrophy and Zellweger syndrome patients.ConclusionsOur study demonstrated metabolic differences between healthy controls, neurological patients, and peroxisomal disorder (X-linked adrenoleukodystrophy and Zellweger syndrome) patients, refined classification models and showed the potential utility of hexacosanoylcarnitine (C26:0-carnitine) as a screening analyte for Chinese patients in the context of a multivariate discriminant model predictive of peroxisomal disorders.
A wide spectrum of phenotype of deficiency of deaminase 2 (DADA2): a systematic literature review
Authors: Maccora Ilaria , Maniscalco Valerio , Campani Silvia , Carrera Simona , Abbati Giulia , Marrani Edoardo , Mastrolia Maria Vincenza , Simonini Gabriele 
Published: May 2023

Abstract
Introduction
Deficiency of adenosine deaminase 2 (DADA2) is a rare monogenic autoinflammatory disease, whose clinical phenotype was expanded since the first cases, originally described as mimicker of polyarteritis nodosa, with immunodeficiency and early-onset stroke.

Methods
A systematic review according to PRISMA approach, including all articles published before the 31st of August 2021 in Pubmed and EMBASE database was performed.

Results
The search identified 90 publications describing 378 unique patients (55.8% male). To date 95unique mutations have been reported. The mean age at disease onset was 92.15 months (range 0–720 months), 32 (8.5%) showed an onset of the first signs/symptoms after 18 years old and 96 (25.4%) after 10 years old. The most frequent clinical characteristics described were cutaneous (67.9%), haematological manifestations (56.3%), recurrent fever (51.3%), neurological as stroke and polyneuropathy (51%), immunological abnormalities (42.3%), arthralgia/arthritis (35.4%), splenomegaly (30.6%), abdominal involvement (29.8%), hepatomegaly (23.5%), recurrent infections (18.5%), myalgia (17.9%), kidney involvement (17.7%) etc. Patients with skin manifestations were older than the others (101.1 months SD ± 116.5, vs. 75.3 SD ± 88.2, p 0.041), while those with a haematological involvement (64.1 months SD ± 75.6 vs. 133.1 SD ± 133.1, p < 0.001) and immunological involvement (73.03 months SD ± 96.9 vs. 103.2 SD ± 112.9, p 0.05) are younger than the others. We observed different correlations among the different clinical manifestations. The use of anti-TNFα and hematopoietic cell stems transplantation (HCST) has improved the current history of the disease.

Conclusion
Due to this highly variable phenotype and age of presentation, patients with DADA2 may present to several type of specialists. Given the important morbidity and mortality, early diagnosis and treatment are mandatory.
Phenome-wide analyses identify an association between the parent-of-origin effects dependent methylome and the rate of aging in humans
Authors: Gao Chenhao , Amador Carmen , Walker Rosie M. , Campbell Archie , Madden Rebecca A. , Adams Mark J. , Bai Xiaomeng , Liu Ying , Li Miaoxin , Hayward Caroline , Porteous David J. , Shen Xueyi , Evans Kathryn L. , Haley Chris S. , McIntosh Andrew M. , Navarro Pau , Zeng Yanni 
Published: May 2023

Abstract
Background
The variation in the rate at which humans age may be rooted in early events acting through the genomic regions that are influenced by such events and subsequently are related to health phenotypes in later life. The parent-of-origin-effect (POE)-regulated methylome includes regions enriched for genetically controlled imprinting effects (the typical type of POE) and regions influenced by environmental effects associated with parents (the atypical POE). This part of the methylome is heavily influenced by early events, making it a potential route connecting early exposures, the epigenome, and aging. We aim to test the association of POE-CpGs with early and later exposures and subsequently with health-related phenotypes and adult aging.

Results
We perform a phenome-wide association analysis for the POE-influenced methylome using GS:SFHS (Ndiscovery = 5087, Nreplication = 4450). We identify and replicate 92 POE-CpG-phenotype associations. Most of the associations are contributed by the POE-CpGs belonging to the atypical class where the most strongly enriched associations are with aging (DNAmTL acceleration), intelligence, and parental (maternal) smoking exposure phenotypes. A proportion of the atypical POE-CpGs form co-methylation networks (modules) which are associated with these phenotypes, with one of the aging-associated modules displaying increased within-module methylation connectivity with age. The atypical POE-CpGs also display high levels of methylation heterogeneity, fast information loss with age, and a strong correlation with CpGs contained within epigenetic clocks.

Conclusions
These results identify the association between the atypical POE-influenced methylome and aging and provide new evidence for the “early development of origin” hypothesis for aging in humans.
Peripheral precocious puberty in Li–Fraumeni syndrome: a case report and literature review of pure androgen-secreting adrenocortical tumors
Authors: Ryckx Sofie , De Schepper Jean , Giron Philippe , Maes Ken , Vaeyens Freya , Wilgenhof Kaat , Lefesvre Pierre , Ernst Caroline , Vanderlinden Kim , Klink Daniel , Hes Frederik , Vanbesien Jesse , Gies Inge , Staels Willem 
Published: May 2023

Abstract
Introduction
Pure androgen-secreting adrenocortical tumors are a rare but important cause of peripheral precocious puberty.

Case presentation
Here, we report a pure androgen-secreting adrenocortical tumor in a 2.5-year-old boy presenting with penile enlargement, pubic hair, frequent erections, and rapid linear growth. We confirmed the diagnosis through laboratory tests, medical imaging, and histology. Furthermore, genetic testing detected a pathogenic germline variant in the TP53 gene, molecularly confirming underlying Li–Fraumeni syndrome.

Discussion
Only 15 well-documented cases of pure androgen-secreting adrenocortical tumors have been reported so far. No clinical or imaging signs were identified to differentiate adenomas from carcinomas, and no other cases of Li–Fraumeni syndrome were diagnosed in the four patients that underwent genetic testing. However, diagnosing Li–Fraumeni syndrome is important as it implies a need for intensive tumor surveillance and avoidance of ionizing radiation.

Conclusion
In this article, we emphasize the need to screen for TP53 gene variants in children with androgen-producing adrenal adenomas and report an association with arterial hypertension.
Studies in differentiating psoriasis from other dermatoses using small data set and transfer learning
Authors: Nieniewski Mariusz , Chmielewski Leszek J. , Patrzyk Sebastian , Woźniacka Anna 
Published: May 2023

AbstractPsoriasis is a common skin disorder that should be differentiated from other dermatoses if an effective treatment has to be applied. Regions of Interests, or scans for short, of diseased skin are processed by the VGG16 (or VGG19) deep convolutional neural network operating as a feature extractor. 1280 features related to a given scan are passed to the Support Vector Machine (SVM) classifier using Radial Basis Functions (RBF) kernels. The main quality of the described setup is a very small number of 75 psoriasis patients and 75 non-psoriasis patients used in the teaching and testing sets taken together. For each patient, a variable number of clinical images are taken. Then, the scans of size $$256 \times 256$$

256
×
256

pixels are cropped from these images. There are 1988 scans of psoriasis patients and 1582 of non-psoriasis patients. The other quality of the described setup is the use of transfer learning for carrying over the neural network’s weights from non-medical domain (ImageNet) to clinical images of dermatoses. The next quality is that the input images are obtained with smart phone cameras without any special arrangements or equipment, so there is a great variability in working conditions, which hampers discriminative power of the classifier. The primary classification is carried out on individual scans, and then, majority voting is executed among the scans pertaining to an individual patient. The obtained recall (sensitivity) is 85.33%, and the precision is 82.58%. The 95% confidence interval for the accuracy of 80.08% is [77.14, 83.04]%. These numbers indicate that the described system can be useful for remote diagnosing of psoriasis, particularly in areas where access to dermatological personnel is limited.
Learning a crowd-powered perceptual distance metric for facial blendshapes
Authors: Cipiloglu Yildiz Zeynep 
Published: May 2023

AbstractIt is known that purely geometric distance metrics cannot reflect the human perception of facial expressions. A novel perceptually based distance metric designed for 3D facial blendshape models is proposed in this paper. To develop this metric, comparative evaluations of facial expressions were collected from a crowdsourcing experiment. Then, the weights of a distance metric, based on descriptive features of the models, were optimized to match the results with crowdsourced data, through a metric learning process. The method incorporates perceptual properties such as curvature and visual saliency. A formal analysis of the results proves the high correlation between the metric output and human perception. The effectiveness and success of the proposed metric were also compared to other distance alternatives. The proposed metric will enable intelligent processing of 3D facial blendshapes data in several ways. It will be possible to generate perceptually valid clustering and visualization of 3D facial blendshapes. It will help reduce storage and computational requirements by removing redundant expressions that are perceptually identical from the overall dataset. It can also be used to assist novice animators while creating plausible and expressive facial animations.
Metastatic clear-cell renal cell carcinoma: a frequent NOTCH1 mutation predictive of response to anti-NOTCH1 CB-103 treatment
Authors: Bui Thi Oanh , Angeli Eurydice , El Bouchtaoui Morad , Gapihan Guillaume , Dao Van Tu , Paris Justine , Leboeuf Christophe , Soussan Michael , Villarese Patrick , Ziol Marianne , Van Glabeke Emmanuel , Le Thi Huong , Feugeas Jean-Paul , Janin Anne , Bousquet Guilhem 
Published: May 2023

Abstract
Background
Clear-cell renal cell carcinomas (ccRCCs) are malignant tumors with high metastatic potential and resistance to treatments occurs almost constantly. Compared to primary tumors, there are still limited genomic data that has been obtained from metastatic samples.

Methods
We aimed to characterize metastatic ccRCC by way of whole-genome analyses of metastatic formalin-fixed samples, using OncoScan® technology. We identified a frequent, unexpected pL1575P NOTCH1 mutation which we set out to characterize for translational purposes. We thus implemented patient-derived xenografts from metastatic samples of human ccRCC to explore its clinical significance.

Results
We showed that pL1575P NOTCH1 mutation was an activating mutation, leading to the expression of NOTCH1-intracellular domain-active fragments in both cancer cells and tumor endothelial cells, suggesting a trans-differentiation of cancer cells into tumor micro-vessels. We demonstrated that this mutation could be used as a predictive biomarker of response to CB-103, a specific NOTCH1-intracellular domain inhibitor. One striking result was the considerable anti-angiogenic effect, coherent with the presence of NOTCH1 mutation in tumor micro-vessels.

Conclusions
We identified a frequent, unexpected pL1575P_c4724T_C NOTCH1 mutation as a new biomarker for ccRCC metastases, predictive of response to the CB103 NOTCH1-intracellular domain inhibitor.