bluuebunny/crossref_metadata_2025 huggingface dataset:
BRCA1 Promoter Hypermethylation in Malignant Breast Tumors and in the Histologically Normal Adjacent Tissues to the Tumors: Exploring Its Potential as a Biomarker and Its Clinical Significance in a Translational Approach
Authors: Oubaddou Yassire , Oukabli Mohamed , Fenniche Salma , Elktaibi Abderrahim , Elochi Mohamed Reda , Al Bouzidi Abderrahmane , Qmichou Zineb , Dakka Nadia , Diorio Caroline , Richter Antje , Bakri Youssef , Ameziane El Hassani Rabii
Published: August 2023

The hypermethylation status of the promoter region of the breast cancer 1 (BRCA1), a well-known tumor suppressor gene, has been extensively investigated in the last two decades as a potential biomarker for breast cancer. In this retrospective study, we investigated the prevalence of BRCA1 promoter methylation in 84 human breast tissues, and we correlated this epigenetic silencing with the clinical and histopathological parameters of breast cancer. We used methylation-specific PCR (MSP) to analyze BRCA1 promoter hypermethylation in 48 malignant breast tumors (MBTs), 15 normal adjacent tissues (NATs), and 21 benign breast lesions (BBLs). The results showed that BRCA1 promoter hypermethylation was higher in MBTs (20/48; 41.67%) and NATs (7/15; 46.67%) compared to BBLs (4/21; 19.05%). The high percentage of BRCA1 hypermethylation in the histologically normal adjacent tissues to the tumors (NATs) suggests the involvement of this epigenetic silencing as a potential biomarker of the early genomic instability in NATs surrounding the tumors. The detection of BRCA1 promoter hypermethylation in BBLs reinforces this suggestion, knowing that a non-negligible rate of benign breast lesions was reported to evolve into cancer. Moreover, our results indicated that the BRCA1 promoter hypermethylated group of MBTs exhibited higher rates of aggressive features, as indicated by the SBR III grade (14/19; 73.68%), elevated Ki67 levels (13/16; 81.25%), and Her2 receptor overexpression (5/20; 25%). Finally, we observed a concordance (60%) in BRCA1 promoter hypermethylation status between malignant breast tumors and their paired histologically normal adjacent tissues. This study highlights the role of BRCA1 promoter hypermethylation as a potential useful biomarker of aggressiveness in MBTs and as an early marker of genomic instability in both histological NATs and BBLs.
Epigenetic Modulations for Prevention of Infectious Diseases in Shrimp Aquaculture
Authors: Wikumpriya Gunasekara Chathura , Prabhatha Madhuranga Walawedurage Srinith , Lee Jiye , Kim Chan-Hee
Published: August 2023

Aquaculture assumes a pivotal role in meeting the escalating global food demand, and shrimp farming, in particular, holds a significant role in the global economy and food security, providing a rich source of nutrients for human consumption. Nonetheless, the industry faces formidable challenges, primarily attributed to disease outbreaks and the diminishing efficacy of conventional disease management approaches, such as antibiotic usage. Consequently, there is an urgent imperative to explore alternative strategies to ensure the sustainability of the industry. In this context, the field of epigenetics emerges as a promising avenue for combating infectious diseases in shrimp aquaculture. Epigenetic modulations entail chemical alterations in DNA and proteins, orchestrating gene expression patterns without modifying the underlying DNA sequence through DNA methylation, histone modifications, and non-coding RNA molecules. Utilizing epigenetic mechanisms presents an opportunity to enhance immune gene expression and bolster disease resistance in shrimp, thereby contributing to disease management strategies and optimizing shrimp health and productivity. Additionally, the concept of epigenetic inheritability in marine animals holds immense potential for the future of the shrimp farming industry. To this end, this comprehensive review thoroughly explores the dynamics of epigenetic modulations in shrimp aquaculture, with a particular emphasis on its pivotal role in disease management. It conveys the significance of harnessing advantageous epigenetic changes to ensure the long-term viability of shrimp farming while deliberating on the potential consequences of these interventions. Overall, this appraisal highlights the promising trajectory of epigenetic applications, propelling the field toward strengthening sustainability in shrimp aquaculture.
Genetic Modifiers of Mendelian Monogenic Collagen IV Nephropathies in Humans and Mice
Authors: Deltas Constantinos , Papagregoriou Gregory , Louka Stavroula F. , Malatras Apostolos , Flinter Frances , Gale Daniel P. , Gear Susie , Gross Oliver , Hoefele Julia , Lennon Rachel , Miner Jeffrey H. , Renieri Alessandra , Savige Judy , Turner A. Neil
Published: August 2023

Familial hematuria is a clinical sign of a genetically heterogeneous group of conditions, accompanied by broad inter- and intrafamilial variable expressivity. The most frequent condition is caused by pathogenic (or likely pathogenic) variants in the collagen-IV genes, COL4A3/A4/A5. Pathogenic variants in COL4A5 are responsible for the severe X-linked glomerulopathy, Alport syndrome (AS), while homozygous or compound heterozygous variants in the COL4A3 or the COL4A4 gene cause autosomal recessive AS. AS usually leads to progressive kidney failure before the age of 40-years when left untreated. People who inherit heterozygous COL4A3/A4 variants are at-risk of a slowly progressive form of the disease, starting with microscopic hematuria in early childhood, developing Alport spectrum nephropathy. Sometimes, they are diagnosed with benign familial hematuria, and sometimes with autosomal dominant AS. At diagnosis, they often show thin basement membrane nephropathy, reflecting the uniform thin glomerular basement membrane lesion, inherited as an autosomal dominant condition. On a long follow-up, most patients will retain normal or mildly affected kidney function, while a substantial proportion will develop chronic kidney disease (CKD), even kidney failure at an average age of 55-years. A question that remains unanswered is how to distinguish those patients with AS or with heterozygous COL4A3/A4 variants who will manifest a more aggressive kidney function decline, requiring prompt medical intervention. The hypothesis that a subgroup of patients coinherit additional genetic modifiers that exacerbate their clinical course has been investigated by several researchers. Here, we review all publications that describe the potential role of candidate genetic modifiers in patients and include a summary of studies in AS mouse models.
Identification and Analysis of Sex-Biased MicroRNAs in Human Diseases
Authors: Zhong Bitao , Cui Chunmei , Cui Qinghua
Published: August 2023

It is well known that significant differences exist between males and females in both physiology and disease. Thus, it is important to identify and analyze sex-biased miRNAs. However, previous studies investigating sex differences in miRNA expression have predominantly focused on healthy individuals or restricted their analysis to a single disease. Therefore, it is necessary to comprehensively identify and analyze the sex-biased miRNAs in diseases. For this purpose, in this study, we first identified the miRNAs showing sex-biased expression between males and females in diseases based on a number of miRNA expression datasets. Then, we performed a bioinformatics analysis for these sex-biased miRNAs. Notably, our findings revealed that women exhibit a greater number of conserved miRNAs that are highly expressed compared to men, and these miRNAs are implicated in a broader spectrum of diseases. Additionally, we explored the enriched transcription factors, functions, and diseases associated with these sex-biased miRNAs using the miRNA set enrichment analysis tool TAM 2.0. The insights gained from this study could carry implications for endeavors such as precision medicine and possibly pave the way for more targeted and tailored approaches to disease management.
Genome-Wide Identification of GSTs Gene Family and Functional Analysis of BraGSTF2 of Winter Rapeseed (Brassica rapa L.) under Cold Stress
Authors: Niu Zaoxia , Liu Lijun , Yue Jinli , Wu Junyan , Wang Wangtian , Pu Yuanyuan , Ma Li , Fang Yan , Sun Wancang
Published: August 2023

The largest gene families in plants were found to be Glutathione transferases (GSTs), which played significant roles in regulating plant growth, development, and stress response. Within the GSTs gene family, members were found to play a crucial role in the low-temperature response process of plants. A comprehensive study identified a total of 70 BraGSTs genes. Cluster analysis results demonstrated that the BraGSTs in Brassica rapa (B. rapa) could be categorized into eight sub-families and were unevenly distributed across ten chromosomes. The 39 BraGSTs genes were found to be organized into 15 tandem gene clusters, with the promoters containing multiple cis-elements associated with low-temperature response. Cold stress was observed to stimulate the expression of 15 genes, with the BraGSTF2 gene exhibiting the highest level of expression, suggesting its significant involvement in winter B. rapa’s response to low-temperature stress. Subcellular localization analysis of the BraGSTF2 protein indicated its potential expression in both the cell membrane and nucleus. The analysis of stress resistance in BraGSTF2 transgenic Arabidopsis thaliana lines demonstrated that the over-expression of this gene resulted in significantly elevated levels of SOD, POD activity, and SP content compared to the wild type following exposure to low temperatures. These levels reached their peak after 24 h of treatment. Conversely, the MDA content was lower in the transgenic plants compared to the wild-type (WT) Arabidopsis (Arabidopsis thaliana L.). Additionally, the survival rate of BraGSTF2 transgenic Arabidopsis was higher than that of the WT Arabidopsis thaliana, suggesting that the BraGSTF2 gene may play a crucial role in enhancing the cold stress tolerance of winter B. rapa. This study lays a foundation for further research on the role of the BraGSTs gene in the molecular regulation of cold resistance in winter B. rapa.
Whole-Exome Sequencing Reveals High Mutational Concordance between Primary and Matched Recurrent Triple-Negative Breast Cancers
Authors: Kaur Jaspreet , Chandrashekar Darshan S. , Varga Zsuzsanna , Sobottka Bettina , Janssen Emiel , Gandhi Khanjan , Kowalski Jeanne , Kiraz Umay , Varambally Sooryanarayana , Aneja Ritu
Published: August 2023

Purpose: Triple-negative breast cancer (TNBC) is a molecularly complex and heterogeneous breast cancer subtype with distinct biological features and clinical behavior. Although TNBC is associated with an increased risk of metastasis and recurrence, the molecular mechanisms underlying TNBC metastasis remain unclear. We performed whole-exome sequencing (WES) analysis of primary TNBC and paired recurrent tumors to investigate the genetic profile of TNBC. Methods: Genomic DNA extracted from 35 formalin-fixed paraffin-embedded tissue samples from 26 TNBC patients was subjected to WES. Of these, 15 were primary tumors that did not have recurrence, and 11 were primary tumors that had recurrence (nine paired primary and recurrent tumors). Tumors were analyzed for single-nucleotide variants and insertions/deletions. Results: The tumor mutational burden (TMB) was 7.6 variants/megabase in primary tumors that recurred (n = 9); 8.2 variants/megabase in corresponding recurrent tumors (n = 9); and 7.3 variants/megabase in primary tumors that did not recur (n = 15). MUC3A was the most frequently mutated gene in all groups. Mutations in MAP3K1 and MUC16 were more common in our dataset. No alterations in PI3KCA were detected in our dataset. Conclusions: We found similar mutational profiles between primary and paired recurrent tumors, suggesting that genomic features may be retained during local recurrence.
A Systematic Review on Deep Structured Learning for COVID-19 Screening Using Chest CT from 2020 to 2022
Authors: Santosh KC , GhoshRoy Debasmita , Nakarmi Suprim
Published: August 2023

The emergence of the COVID-19 pandemic in Wuhan in 2019 led to the discovery of a novel coronavirus. The World Health Organization (WHO) designated it as a global pandemic on 11 March 2020 due to its rapid and widespread transmission. Its impact has had profound implications, particularly in the realm of public health. Extensive scientific endeavors have been directed towards devising effective treatment strategies and vaccines. Within the healthcare and medical imaging domain, the application of artificial intelligence (AI) has brought significant advantages. This study delves into peer-reviewed research articles spanning the years 2020 to 2022, focusing on AI-driven methodologies for the analysis and screening of COVID-19 through chest CT scan data. We assess the efficacy of deep learning algorithms in facilitating decision making processes. Our exploration encompasses various facets, including data collection, systematic contributions, emerging techniques, and encountered challenges. However, the comparison of outcomes between 2020 and 2022 proves intricate due to shifts in dataset magnitudes over time. The initiatives aimed at developing AI-powered tools for the detection, localization, and segmentation of COVID-19 cases are primarily centered on educational and training contexts. We deliberate on their merits and constraints, particularly in the context of necessitating cross-population train/test models. Our analysis encompassed a review of 231 research publications, bolstered by a meta-analysis employing search keywords (COVID-19 OR Coronavirus) AND chest CT AND (deep learning OR artificial intelligence OR medical imaging) on both the PubMed Central Repository and Web of Science platforms.
Sleep Quality and Fatigue during Exam Periods in University Students: Prevalence and Associated Factors
Authors: Bouloukaki Izolde , Tsiligianni Ioanna , Stathakis Giorgos , Fanaridis Michail , Koloi Athina , Bakiri Ekaterini , Moudatsaki Maria , Pouladaki Eleptheria , Schiza Sophia
Published: August 2023

The aim of our study was to assess university students’ sleep quality and fatigue before and during the academic exam period and identify potential associated factors. A Web-based survey was completed by 940 students of 20 different Tertiary Institutions including demographics, sleep habits, exercise, caffeine, tobacco, alcohol use, subjective sleep quality (Pittsburgh Sleep Quality Index—PSQI), and fatigue (Fatigue severity scale—FSS) at the beginning of the semester and during the examination period. During the exam period, PSQI (8.9 vs. 6.1, p < 0.001) and FSS scores (36.9 vs. 32.7, p < 0.001) were significantly elevated compared to the pre-exam period. An increase in the PSQI score was associated with age (β = 0.111, p = 0.011), presence of chronic disease (β = 0.914, p = 0.006), and depressive symptoms (β = 0.459, p = 0.001). An increase in the FSS score was associated with female gender (β = 1.658, p < 0.001), age, (β = 0.198, p = 0.010), increase in smoking (β = 1.7, p = 0.029), coffee/energy drinks consumption (β = 1.988, p < 0.001), decreased levels of physical exercise (β = 1.660, p < 0.001), and depressive symptoms (β = 2.526, p < 0.001). In conclusion, our findings indicate that exam periods have a negative impact on the sleep quality and fatigue levels of university students. Potential factors were identified that could contribute to the formulation of strategies for improved sleep quality and wellness.
A Case of Axillary Web Syndrome Caused by Venous Blood Sampling
Authors: Kitajima Hironori , Ichiseki Toru , Kaneuji Ayumi , Kawahara Norio
Published: August 2023

Axillary web syndrome (AWS) occurs after breast cancer surgery, sentinel lymph node dissection, or sentinel lymph node biopsy. Here, cord-like structures from the axilla to the forearm limit the range of motion of the shoulder joint and cause pain. Although the etiology is unknown, AWS has been attributed to the blockage of normal lymphatic flow. Here, we report a novel case of AWS after venous blood sampling in a patient. A healthy, 31-year-old male patient experienced pain with a limited range of motion of the shoulder joint the day after venous blood was collected from the left upper extremity for a medical checkup, and he presented to an orthopedic outpatient clinic on the day. Palpation of the axillary region disclosed a cord-like structure in the axillary region of the shoulder joint during abduction, and the patient was diagnosed with AWS. The cord-like structure was noted to be a hypoechogenic luminal structure on ultrasound (US) examination of the axilla, extending from the axilla to below the ulnar cutaneous vein from which the blood was drawn. In patients with pain and a limited range of motion of the shoulder joint, only the shoulder joint is examined during an orthopedic examination. It is important to obtain appropriate physical findings for possible AWS.
Re-Thinking Visitor Experience with Ancient Manuscripts via the Holographic Showcase: The Case of the Codex4D Project and Its First Public Results from a Mixed-Method Evaluation In Situ
Authors: Schettino Patrizia , Pietroni Eva , d’Annibale Enzo
Published: August 2023

Ancient manuscripts are precious and fragile objects, preserved in libraries, museums, and archives. Some of them are masterpieces, made with several materials and insights, but generally they are not accessible to wide communities of users. The purpose of this study is to present the preliminary results of the Codex4D project: a holographic showcase, conceived for museums, presenting the first 4D model of an ancient manuscript to the public at the Science Festival in Genoa in 2022. The manuscript, preserved in the Angelica Library in Rome, has been represented in a multidimensional digital model, documenting both its visible and invisible aspects, on the surface and in the stratigraphic layers. We analysed the visitor experience: informal learning, the meaning-making process, interactions between visitors, and gesture-based interaction with the showcase. The methodology used for evaluation is based on four different qualitative methods (grounded theory, narrative inquiry, case study, and digital ethnography). We collected notes from observation, narratives from interviews, and answers from structured interviews. The main findings are patterns of the visitors’ experiences with a digital interactive 4D model of an ancient manuscript, supported by storytelling, and a list of design issues and possible improvements for the next version of the Codex4D holographic showcase.
A Systematic Review and Meta-Analysis of the Effects of Race in the Criminal Justice System with Respect to Forensic Science Decision Making: Implications for Forensic Anthropology
Authors: Yim An-Di , Passalacqua Nicholas V.
Published: August 2023

Instances of racial disparities are well documented in the United States’ criminal justice system. This study reviewed the literature and conducted quantitative analyses on the role of race in forensic decision making among practitioners and other stakeholders in the criminal justice system. We hypothesized that Black, Indigenous, and People of Color (BIPOC) individuals will be significantly more likely to be associated with adverse outcomes than White individuals. A search strategy was developed and registered before the study commenced. Quantitative data were extracted from eligible studies to estimate the pooled effect size (odds ratio) for the effects of race. A final sample of 11 data sources (published study or dataset) was identified. Decision making by all stakeholders in the criminal justice system, including forensic practitioners, case investigators, and juries were evaluated in these studies. Two datasets evaluated the decision-making process involving forensic psychology or psychiatry, three focused on forensic evidence, four on forensic pathology, one involved forensic anthropology cases, and one involved clinical forensic medicine cases. The pooled odds ratio was estimated to be 1.10 (95% confidence interval: 0.67–1.81), indicating a trivial or negligible effect of race (i.e., BIPOC individuals were no more likely to be associated with adverse outcomes given the current evidence). Importantly, the results of this study do not indicate that bias or disparity related to race does not exist in forensic decision making in the criminal justice system. More research into systemic bias in forensic decision making, especially in relation to race, is needed. Forensic anthropologists are uniquely positioned to study and address racial disparities in the criminal justice system involving forensic science because of its interdisciplinary and multidisciplinary nature. This study highlights the need for further research and advocates for forensic anthropologists to be more involved in the study of the science and the impacts of forensic science rather than focusing on methodological advancement.
Young Adult Cancer Care Partners: A Theoretical Description of an Emerging Population with Unique Needs
Authors: Warner Echo L. , Hebdon Megan , Tay Djin L. , Smith Keely , Welling Anna , Xu Jiayun
Published: August 2023

As the U.S. population’s demographics shift, young U.S. adults are increasingly engaged in informal caregiving for aging generations. Yet, there is little research on the unique experiences and needs of young adults who take on caregiving roles for adult cancer patients. Herein we demonstrate through a theoretical description that young adult cancer care partners deserve distinct recognition in the cancer control continuum given the psychological, physical, financial, and social features unique to their cancer experience.
IFC-CityGML Data Integration for 3D Property Valuation
Authors: El Yamani Siham , Hajji Rafika , Billen Roland
Published: August 2023

The accurate assessment of proper value in complex and increasingly high-rise urban environments is a significant challenge. Previous research has identified property value as a composite of indoor elements, such as volume and height, and 3D simulations of the outdoor environment, including variables such as view, noise, and pollution. These simulations have been preliminary performed in taxation context; however, there has been no work addressing the simulation of property valuation. In this paper, we propose an IFC-CityGML data integration approach for property valuation and develop a workflow based on IFC-CityGML 3.0 to simulate and model 3D property variables at the Level of Information Need. We evaluate this approach by testing it for two indoor variables, indoor daylight and property unit cost. Our proposed approach aims to improve the accuracy of property valuation by integrating data from indoor and outdoor environments and providing a standardized and efficient workflow for property valuation modeling using IFC and CityGML. Our approach represents a solid base for future works toward a 3D property valuation extension.
Modeling Long and Short Term User Preferences by Leveraging Multi-Dimensional Auxiliary Information for Next POI Recommendation
Authors: Li Zheng , Huang Xueyuan , Gong Liupeng , Yuan Ke , Liu Chun
Published: August 2023

Next Point-of-Interest (POI) recommendation has shown great value for both users and providers in location-based services. Existing methods mainly rely on partial information in users’ check-in sequences, and are brittle to users with few interactions. Moreover, they ignore the impact of multi-dimensional auxiliary information such as user check-in frequency, POI category on user preferences modeling and the impact of dynamic changes in user preferences over different time periods on recommendation performance. To address the above limitations, we propose a novel method for next POI recommendation by modeling long and short term user preferences with multi-dimensional auxiliary information. In particular, the proposed model includes a static LSTM module to capture users’ multi-dimensional long term static preferences and a dynamic meta-learning module to capture users’ multi-dimensional dynamic preferences. Furthermore, we incorporate a POI category filter into our model to comprehensively simulate users’ preferences. Experimental results on two real-world datasets demonstrate that our model outperforms the state-of-the-art baseline methods in two commonly used evaluation metrics.
CRISPR-Cas9 Library Screening Identifies Novel Molecular Vulnerabilities in KMT2A-Rearranged Acute Lymphoblastic Leukemia
Authors: Schneider Pauline , Wander Priscilla , Arentsen-Peters Susan T. C. J. M. , Vrenken Kirsten S. , Rockx-Brouwer Dedeke , Adriaanse Fabienne R. S. , Hoeve Veerle , Paassen Irene , Drost Jarno , Pieters Rob , Stam Ronald W.
Published: August 2023

In acute lymphoblastic leukemia (ALL), chromosomal translocations involving the KMT2A gene represent highly unfavorable prognostic factors and most commonly occur in patients less than 1 year of age. Rearrangements of the KMT2A gene drive epigenetic changes that lead to aberrant gene expression profiles that strongly favor leukemia development. Apart from this genetic lesion, the mutational landscape of KMT2A-rearranged ALL is remarkably silent, providing limited insights for the development of targeted therapy. Consequently, identifying potential therapeutic targets often relies on differential gene expression, yet the inhibition of these genes has rarely translated into successful therapeutic strategies. Therefore, we performed CRISPR-Cas9 knock-out screens to search for genetic dependencies in KMT2A-rearranged ALL. We utilized small-guide RNA libraries directed against the entire human epigenome and kinome in various KMT2A-rearranged ALL, as well as wild-type KMT2A ALL cell line models. This screening approach led to the discovery of the epigenetic regulators ARID4B and MBD3, as well as the receptor kinase BMPR2 as novel molecular vulnerabilities and attractive therapeutic targets in KMT2A-rearranged ALL.
A Machine Learning Python-Based Search Engine Optimization Audit Software
Authors: Roumeliotis Konstantinos I. , Tselikas Nikolaos D.
Published: August 2023

In the present-day digital landscape, websites have increasingly relied on digital marketing practices, notably search engine optimization (SEO), as a vital component in promoting sustainable growth. The traffic a website receives directly determines its development and success. As such, website owners frequently engage the services of SEO experts to enhance their website’s visibility and increase traffic. These specialists employ premium SEO audit tools that crawl the website’s source code to identify structural changes necessary to comply with specific ranking criteria, commonly called SEO factors. Working collaboratively with developers, SEO specialists implement technical changes to the source code and await the results. The cost of purchasing premium SEO audit tools or hiring an SEO specialist typically ranges in the thousands of dollars per year. Against this backdrop, this research endeavors to provide an open-source Python-based Machine Learning SEO software tool to the general public, catering to the needs of both website owners and SEO specialists. The tool analyzes the top-ranking websites for a given search term, assessing their on-page and off-page SEO strategies, and provides recommendations to enhance a website’s performance to surpass its competition. The tool yields remarkable results, boosting average daily organic traffic from 10 to 143 visitors.
Developmental Indicators of Chrysomya nigripes Aubertin under Different Constant Temperature Conditions and an Application Case for Estimating the PMImin
Authors: Guo Yi , Hu Gengwang , Li Liangliang , Liao Mingqing , Wang Jiangfeng , Wang Yu , Tao Luyang
Published: August 2023

Chrysomya nigripes Aubertin, 1932, is a Calliphoridae species that colonize the carcass after the bloat phase and remains for long periods. Some early sarcosaprophagous insects complete one generation of development and are no longer associated with the corpse and surrounding environment, while C. nigripes larvae and pupae remain, providing a basis for the estimation of the minimum postmortem interval (PMImin) for highly decomposed or skeletonized carcasses. However, data on the growth and development of this species are not yet complete. As a result, we studied the developmental patterns of C. nigripes at eight constant temperatures ranging from 16–37 °C and constructed various developmental models, including the isomorphen diagram, isomegalen diagram, linear thermal summation model, nonlinear thermodynamic Optim SSI model, and logistic regression model. Chrysomya nigripes could not complete the entire developmental process at 16 °C, although it could be completed at other temperatures. The mean developmental times (±SD) of C. nigripes from egg to adult at 19 °C, 22 °C, 25 °C, 28 °C, 31 °C, 34 °C, and 37 °C were 644.9 ± 36.8 h, 422.9 ± 20.1 h, 323.1 ± 13.9 h, 246.6 ± 11.2 h, 202.5 ± 1.8 h, 191.5 ± 3.8 h, and 191.8 ± 2.0 h, respectively. The thermal summation constant (K) and lower critical thermal threshold (TL) derived from the linear thermal summation models were 4083.00 ± 293.39 degree hours and 12.52 ± 0.83 °C, respectively. In addition, TL, intrinsic optimum temperature (TΦ), and upper critical thermal threshold (TH) estimated by the optimized nonlinear thermodynamic Optim SSI model were 15.76 °C, 24.88 °C, and 38.15 °C, respectively. This study provides more comprehensive developmental data of C. nigripes for PMImin estimation.
Trends in Medical and Device Therapies Following Incident Heart Failure in Denmark during 1996–2019: A Nationwide Register-Based Follow-Up Study
Authors: Ettrup-Christensen Asbjørn , Butt Jawad H. , Andersen Mikkel Porsborg , Sessa Maurizio , Polcwiartek Christoffer , Fosbøl Emil L. , Rørth Rasmus , Kristensen Søren L. , Torp-Pedersen Christian , Køber Lars , Schou Morten , Tayal Bhupendar , Søgaard Peter , Kragholm Kristian
Published: August 2023

Introduction: Data on temporal trends in guideline-based medical and device therapies in real-world chronic heart failure (HF) patients are lacking. Methods: Register-based nationwide follow-ups of temporal trends in characteristics, guideline-recommended therapies, one-year all-cause mortality, and HF rehospitalizations in incident HF patients in Denmark during 1996–2019. Results: Among 291,720 incident HF patients, the age at the onset of HF was stable over time. While initially fairly equal, the sex distribution markedly changed over time with more incidents occurring in men overall. Hypertension and diabetes increased significantly over time, while other comorbidities remained stable. Between 1996 and 2019, significant increases in angiotensin-converting enzyme inhibitor and angiotensin II-receptor blocker (ACEi/ARB) therapy (38.2% to 69.9%), beta-blocker therapy (15.5% to 70.6%), and mineralocorticoid receptor antagonist (MRA) therapy (11.8% to 34.5%) were seen. Angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) were introduced in the middle of the past decade, with minor increases but overall low uses: ARNI (2015: 0.1% vs. 2019: 3.9%) and SGLT2i (2012: <0.1% vs. 2019: 3.9%). Between 1999 and 2019, implantable cardioverter-defibrillator (ICD) use increased significantly: 0.1% to 3–4%. Cardiac resynchronization therapy (CRT) use similarly increased between 2000 and 2019: 0.2% to 2.3%. Between 1996 and 2019, one-year all-cause mortality decreased significantly: 34.6% to 20.9%, as did HF rehospitalizations (6% to 1.3%). Conclusions: Among 291,720 incident HF patients in Denmark during 1996–2019, significant increases in the use of ACEi/ARB, beta-blockers, MRAs, and devices were seen, with concurrent significant decreases in the one-year all-cause mortality and HF rehospitalization rates. The use of CRT, ARNI, and SGLT2i remained low, and MRAs were relatively underutilized, thereby representing future targets to potentially further improve HF prognoses.
The Role of Back Muscle Dysfunctions in Chronic Low Back Pain: State-of-the-Art and Clinical Implications
Authors: Matheve Thomas , Hodges Paul , Danneels Lieven
Published: August 2023

Changes in back muscle function and structure are highly prevalent in patients with chronic low back pain (CLBP). Since large heterogeneity in clinical presentation and back muscle dysfunctions exists within this population, the potential role of back muscle dysfunctions in the persistence of low back pain differs between individuals. Consequently, interventions should be tailored to the individual patient and be based on a thorough clinical examination taking into account the multidimensional nature of CLBP. Considering the complexity of this process, we will provide a state-of-the-art update on back muscle dysfunctions in patients with CLBP and their implications for treatment. To this end, we will first give an overview of (1) dysfunctions in back muscle structure and function, (2) the potential of exercise therapy to address these dysfunctions, and (3) the relationship between changes in back muscle dysfunctions and clinical parameters. In a second part, we will describe a framework for an individualised approach for back muscle training in patients with CLBP.
Tissue RNA Sequencing Reveals Novel Biomarkers Associated with Postoperative Keloid Recurrence
Authors: Tang Yanqiu , Ren Kehui , Yin Xufeng , Yang Yunning , Fang Fang , Zhou Bingrong , Bu Wenbo
Published: August 2023

Keloids can be resected through surgery, but they may still recur. The purpose of this study was to explore the biomarkers to predict the postoperative recurrence of keloids. Patients who underwent surgical treatment and postoperative superficial X-ray radiation between January 2019 and December 2020 were recruited with clinical data and keloid samples for RNA-seq. By screening differentially expressed genes (DEGs) between postoperative recurrent and non-recurrent sample groups and constructing a co-expression network via the weighted gene co-expression network analysis (WGCNA), an immunity-related module was chosen for subsequent analysis. By constructing a DEG co-expression network and using the Molecular Complex Detection (MCODE) algorithm, five hub genes were identified in the key module. Receiver Operating Characteristic (ROC) curve analysis showed that the area under the curve (AUC) for the five combined hub genes was 0.776. The result of qRT-PCR showed that CHI3L1, IL1RN, MMP7, TNFAIP3, and TNFAIP6 were upregulated in the recurrent group with statistical significance (p < 0.05). Immune infiltration analysis showed that mast cells, macrophages, and T cells were the major components of the keloid immune microenvironment. This study provides potential biomarkers for predicting keloid recurrence and offers insights into genetic targets for recurrence prevention.
Triage of Critically Ill Patients: Characteristics and Outcomes of Patients Refused as Too Well for Intensive Care
Authors: Sridharan Govind , Fleury Yvan , Hergafi Leila , Doll Sébastien , Ksouri Hatem
Published: August 2023

Background: The appropriate selection of patients for the intensive care unit (ICU) is a concern in acute care settings. However, the description of patients deemed too well for the ICU has been rarely reported. Methods: We conducted a single-centre retrospective observational study of all patients either deemed “too well” for or admitted to the ICU during one year. Refused patients were screened for unexpected events within 7 days, defined as either ICU admission without another indication, or death without treatment limitations. Patients’ characteristics and organisational factors were analysed according to refusal status, outcome and delay in ICU admission. Results: Among 2219 enrolled patients, the refusal rate was 10.4%. Refusal was associated with diagnostic groups, treatment limitations, patients’ location on a ward, night time and ICU occupancy. Unexpected events occurred in 16 (6.9%) refused patients. A worse outcome was associated with time spent in hospital before refusal, patients’ location on a ward, SOFA score and physician’s expertise. Delayed ICU admissions were associated with ICU and hospital length of stay. Conclusions: ICU triage selected safely most patients who would have probably not benefited from the ICU. We identified individual and organisational factors associated with ICU refusal, subsequent ICU admission or death.
Peripheral Nerve Blockade in Total Hip Arthroplasty: A Retrospective Study with Propensity Score Matching
Authors: Kwon Hyuck Min , Lee Tae Sung , Park Heon Jung , Lee Bora , Choi Yong Seon , Park Kwan Kyu
Published: August 2023

The effect of peripheral nerve block (PNB) according to leg lengthening following total hip arthroplasty (THA) has not been studied yet. The purpose of this study was to investigate the effect of PNB according to the change in leg length after THA. From January 2016 to August 2021, 353 patients who underwent unilateral THA for osteonecrosis of the femoral head or osteoarthritis of the hip joint were retrospectively reviewed. The patients were divided into two groups for comparison: 217 patients who controlled postoperative pain using only intravenous venous patient-controlled analgesia (IV PCA) (PCA group) and 136 patients who controlled postoperative pain using PNB and IV PCA (PCA + PNB group). We further divided the patients into two groups (leg lengthening after surgery < 10 mm and >10 mm) and compared them. After propensity score matching, the PCA and PCA + PNB groups, with 134 patients each, were compared and analyzed. The pain intensity at rest was significantly lower in the PCA + PNB group compared with that in the PCA group at postoperative 6, 24, and 48 h (p = 0.0001, 0.0009, and <0.0001, respectively). In the subgroup analysis, for patients whose limb lengthening was less than 10 mm after THA, the pain intensity at rest was significantly lower in the PCA + PNB group compared with that in the PCA group at postoperative 24 and 48 h (p = 0.0165 and 0.0015, respectively). However, in patients whose limb lengthening was more than 10 mm after THA, there was no significant difference between the pain intensity at activity and rest in the two groups at postoperative 6, 24, and 48 h (p > 0.05). PNB did not show superiority in terms of pain reduction in patients whose limb lengthening was more than 10 mm after THA. Further investigations on methods for reducing pain in patients whose leg length is increased by more than 10 mm are needed.
Prevalence and Factors Associated with Atrial Fibrillation in Patients with Transient Ischemic Attack or Ischemic Stroke in Northern Vietnam
Authors: Phong Phan Dinh , Tung Bui Nguyen , Hung Pham Manh , Quang Nguyen Ngoc , Hoai Nguyen Thi Thu , Dung Nguyen Viet , Nguyen Thanh N. , Phuong Dao Viet , Ton Mai Duy
Published: August 2023

Background: The prevalence and risk factors of atrial fibrillation (AF) in patients with transient ischemic attack (TIA) or ischemic stroke in Northern Vietnam are not well understood. This study aimed to estimate the prevalence and identify factors associated with AF in this population. Methods: A cross-sectional study was conducted on 2038 consecutive patients with TIA or ischemic stroke admitted to Bach Mai Hospital. AF was diagnosed using an electrocardiogram or Holter monitor. Logistic regression analyses were performed to determine the association between AF and risk factors. Results: Among the patients, 18.1% (95% CI: 16.46 to 19.85) had AF. Older age, renal dysfunction, valvular heart disease (VHD), and low ejection fraction were significantly associated with AF. Advanced age (per 10 years) (adjusted OR, aOR 1.39; 95% CI, 1.23 to 1.57), estimated glomerular filtration ratio decrease (per 10 mL/min/1.73 m2) (aOR 1.12; 95% CI, 1.06 to 1.17), VHD (aOR 9.59; 95% CI, 7.10 to 12.95), and low ejection fraction (<50%) (aOR 2.61; 95% CI, 1.62 to 4.21) had notable odds ratios for AF. Conclusions: Atrial fibrillation is prevalent among patients with TIA or ischemic stroke in Northern Vietnam, surpassing rates in other Southeast Asian countries. Age, renal dysfunction, VHD, and low ejection fraction were significant risk factors for AF in this population.
Tolerability and Safety of Sublingual Immunotherapy in Patients with Tree Pollen Allergy in Daily Practice—An Open, Prospective, Non-Interventional Study
Authors: Owenier Christoph , Barnowski Cornelia , Leineweber Margret , Yu Donghui , Verhagen Marjan , Distler Andreas
Published: August 2023

To investigate the tolerability and safety of two sublingual tree pollen extracts approved in 2018, a non-interventional study (NIS) was performed. This NIS was an 8-month observational study conducted at 84 sites throughout Germany. Study participants received either a sublingual liquid allergen extract of birch pollen (SBPE) or a liquid allergen extract consisting of a mixture of birch, hazel, and alder tree pollen (STPE). Data from 432 patients were analyzed for the occurrence of adverse events and patient compliance. At least one local reaction occurred in 69 (22.2%) patients, whereas systemic reactions were only observed in 27 (6.3%) patients. STPE-treated patients developed systemic reactions more frequently than SBPE-treated patients (SBPE: 9 (4.3%) vs. STPE: 18 (8.0%)). Only one patient developed a systemic grade III reaction. Severe systemic grade IV reactions were not observed. A total of 348 (98.6%) of the patients who completed all visits were satisfied or very satisfied with the sublingual immunotherapy (SLIT), and 322 (71%) patients completed all visits. Both investigated products were well tolerated by the patients and demonstrated a good safety profile. AEs were observed less frequently than in the preceding clinical phase III trial, and no new safety concerns were identified.
Exploring Adaptive Cycling Interventions for Young People with Disability: An Online Survey of Providers in Australia
Authors: Carey John , Toovey Rachel , Spittle Alicia , Imms Christine , Shields Nora
Published: August 2023

Adapted cycles offer young people with disability a fun way to participate in over-ground cycling, but little is known about current practices to train and sustain cycling in this group. This study aimed to describe interventions used to introduce adaptive cycling to young people with disability and explore barriers and facilitators to adapted cycle use. A cross-sectional online survey was distributed among Australian allied health, education and recreation providers through targeted advertizing and snowball methods. Data were analysed using mixed methods and reporting was guided by the CHERRIES and CROSS checklists. There were 107 respondents with n = 90 (84.1%) who fully completed the survey. Respondents worked with riders who had cerebral palsy, neurodevelopmental disabilities and movement impairments. Adaptive cycling interventions were customized according to a rider’s goals, needs and resourcing. The training of cycling skills included “an eclectic mix” of experiential learning, individual goals, task-specific training and holistic practice models. Diverse factors impacted cycling participation, with opportunities reliant on access to a supportive environment, including a suitable adapted cycle. This study found that providers viewed adaptive cycling as a therapeutic or active leisure experience within protected traffic-free environments. Strategies to extend adaptive cycling opportunities into the community are required.
Non-Pharmacological Stroke Prevention in Atrial Fibrillation
Authors: Anduaga Iñigo , Affronti Alessandro , Cepas-Guillén Pedro , Alcocer Jorge , Flores-Umanzor Eduardo , Regueiro Ander , Brugaletta Salvatore , Quintana Eduard , Sanchis Laura , Sabaté Manel , Freixa Xavier
Published: August 2023

Atrial fibrillation (AF) is the most common arrhythmia worldwide. It is associated with increased mortality and morbidity, especially due to the increased risk of ischemic stroke and systemic embolism in these patients. For this reason, thromboembolism prevention is the cornerstone of managing AF, and oral anticoagulation is nowadays the first-line treatment. However, since most thrombi form in the left atrial appendage and anticoagulant therapy may have side effects and be contraindicated in some patients, surgical and percutaneous left atrial appendage occlusion (LAAO) have emerged as a non-pharmacological alternative. This review summarizes all existing evidence on surgical and percutaneous LAAO.
Quantification of Myocardial Contraction Fraction with Three-Dimensional Automated, Machine-Learning-Based Left-Heart-Chamber Metrics: Diagnostic Utility in Hypertrophic Phenotypes and Normal Ejection Fraction
Authors: Barbieri Andrea , Imberti Jacopo F. , Bartolomei Mario , Bonini Niccolò , Laus Vera , Torlai Triglia Laura , Chiusolo Simona , Stuani Marco , Mari Chiara , Muto Federico , Righelli Ilaria , Gerra Luigi , Malaguti Mattia , Mei Davide A. , Vitolo Marco , Boriani Giuseppe
Published: August 2023

Aims: The differentiation of left ventricular (LV) hypertrophic phenotypes is challenging in patients with normal ejection fraction (EF). The myocardial contraction fraction (MCF) is a simple dimensionless index useful for specifically identifying cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) when calculated by cardiac magnetic resonance. The purpose of this study was to evaluate the value of MCF measured by three-dimensional automated, machine-learning-based LV chamber metrics (dynamic heart model [DHM]) for the discrimination of different forms of hypertrophic phenotypes. Methods and Results: We analyzed the DHM LV metrics of patients with CA (n = 10), hypertrophic cardiomyopathy (HCM, n = 36), isolated hypertension (IH, n = 87), and 54 healthy controls. MCF was calculated by dividing LV stroke volume by LV myocardial volume. Compared with controls (median 61.95%, interquartile range 55.43–67.79%), mean values for MCF were significantly reduced in HCM—48.55% (43.46–54.86% p < 0.001)—and CA—40.92% (36.68–46.84% p < 0.002)—but not in IH—59.35% (53.22–64.93% p < 0.7). MCF showed a weak correlation with EF in the overall cohort (R2 = 0.136) and the four study subgroups (healthy adults, R2 = 0.039 IH, R2 = 0.089; HCM, R2 = 0.225; CA, R2 = 0.102). ROC analyses showed that MCF could differentiate between healthy adults and HCM (sensitivity 75.9%, specificity 77.8%, AUC 0.814) and between healthy adults and CA (sensitivity 87.0%, specificity 100%, AUC 0.959). The best cut-off values were 55.3% and 52.8%. Conclusions: The easily derived quantification of MCF by DHM can refine our echocardiographic discrimination capacity in patients with hypertrophic phenotype and normal EF. It should be added to the diagnostic workup of these patients.
Full Digital Workflow for Mandibular Ameloblastoma Management: Showcase for Technical Description
Authors: Abbate Vincenzo , Togo Giulia , Committeri Umberto , Zarone Fernando , Sammartino Gilberto , Valletta Alessandra , Elefante Andrea , Califano Luigi , Dell’Aversana Orabona Giovanni
Published: August 2023

This is a showcase for technical description of a full digital workflow aimed to reconstruct and prosthetically rehabilitate the mandible after surgical resection. The surgery was performed following a computer-aided design and computer-aided manufacturing (CAD-CAM) guided workflow, using 3D reconstruction of the mandible and the fibula. After 2 years, when the ossification of the flap was reached and verified by a computed tomography (CT) scan, surgery was performed using a two-step implant rehabilitation, with successful outcomes.