bluuebunny/crossref_metadata_2025 huggingface dataset:
Ancient Channel-Mouth Bifurcation Angles on Earth and Mars
Authors: Mahon Robert , Hughes Cory , Chen Hehe , Shaw John
Published: October 2024

Channel mouth bifurcation angles on modern river deltas are remarkably consistent with a theoretical prediction of 72°. However, the persistence of this angle through channel evolution and preservation into the stratigraphic record remains untested. Ancient channel mouth bifurcations were measured using stratal slices from 3D seismic volumes as well as outcropping delta deposits in Mars orbital imagery. We find that channel mouth bifurcations interpreted from terrestrial strata exhibit a mean angle of 71.9° ± 3.8° (95% confidence interval), consistent with modern deltas as well as theoretical and numerical predictions. Angles from martian strata preserved as inverted topography exhibit a mean angle of 80.1° ± 4.8°. A larger angle on Mars may be biased by measurements on eroding outcrops, or possibly the signature of altered sediment transport processes on Mars. Expanding channel network analysis into the stratigraphic archive for the first time provides a new mechanism interpreting paleohydraulics on Earth and Mars.
Recurrent Large Spinal Hemangioendothelioma: A Rare Case Report
Authors: Chung Suhmi , Jung Nuri Hyun , Choi Sang-Ji , Kim Choonghyo
Published: October 2024

Epithelioid hemangioendothelioma (EHE) is a rare benign vascular tumor, affecting fewer than one in a million individuals. Spinal EHE is exceptionally rare. This case report presents a case of recurrent spinal EHE, focusing on its clinical manifestation and providing a brief overview of its genetic characteristics. Seven years prior, a patient underwent subtotal resection of a lumbar and retroperitoneal EHE. Due to severe intraoperative bleeding, part of the lumbar spine mass was left unresected and subsequently treated with a moderate dose of radiation therapy. More recently, the patient presented with bilateral lower extremity weakness and urinary incontinence. Imaging studies revealed metastases in the thoracic and sacral bones, along with regrowth in the anterior portion of the previously treated spinal EHE. The patient underwent a series of operations to address both the regrowth and metastases, followed by intensity-modulated radiation therapy to target the remaining tumor tissue while minimizing damage to surrounding structures. Although EHE is generally considered benign, this indolent tumor has a tendency for persistent regrowth and metastasis. This case highlights the importance of radical resection and the potential role of higher radiation doses in preventing recurrence. Molecular testing may aid in achieving an accurate diagnosis and guiding effective treatment strategies.
Identification of therapeutic targets for chronic kidney disease through Mendelian randomization analysis of druggable genes
Authors: Liang Run-Sen , Su Jin-Qi , Wu Xiang-Qi , Wang Qi , Cai Yong-Mei , Su Hong-Yong , Tang Ji-Xin , Yao Cui-Wei
Published: October 2024

BACKGROUND
Chronic Kidney Disease (CKD) is a multifaceted and gradually advancing condition characterized by a complex pathogenesis. The current therapeutic options for CKD remain limited in efficacy. Consequently, the identification and exploration of novel drug targets for CKD are of paramount importance.
METHODS
We identified cis-expression quantitative trait loci (cis-eQTLs) with potential as drug targets from the eQTLGen Consortium database to serve as the exposure. For the outcome, we utilized a genome-wide association study (GWAS) of chronic kidney disease (CKD) from the FinnGen database, which comprised a case group of 11,265 individuals and a control group of 436,208 individuals. MR analysis was employed to investigate druggable genes closely associated with CKD. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to elucidate the functional roles of these significant genes. Finally, a colocalization analysis was conducted to determine the likelihood that a cis-eQTL for a druggable gene and CKD share a causal variant.
RESULTS
The expression of 12 genes was found to be significantly associated with CKD risk, with a false discovery rate (FDR) of less than 0.05. GO and KEGG enrichment analyses indicated that these genes are primarily involved in the regulation of MAP kinase activity, regulation of protein serine/threonine kinase activity, Gap junction, Platelet activation and Oxytocin signaling pathway. The colocalization analysis results suggested that CKD and the TUBB gene may share a causal variant, with a posterior probability (PP.H4) exceeding 80% (TUBB: 97.27%).
CONCLUSION
Compelling statistical evidence indicates that TUBB represents the most promising pharmacological target for the treatment of CKD. This study not only identifies potential therapeutic targets but also offers valuable insights for future drug development in the context of CKD.
A changing hepatitis B virus genetic diversity pattern in North-western Tanzania: Is it a concern for Tanzania?
Authors: Mlewa Mathias , Henerico Shimba , Nyawale Helmut A. , Mangowi Ivon , Shangali Aminiel Robert , Manisha Anselmo Mathias , Kisanga Felix , Kidenya Benson R. , Jaka Hyasinta , Kilonzo Semvua B. , Groendahl Britta , Koliopoulos Philipp , Stephan Gehring , Ntinginya Nyanda Elias , Mirambo Mariam M. , Mshana Stephen E.
Published: October 2024

Background
Frequent evaluation and understanding of the genetic diversity of the HBV virus in different affected global settings is essential towards the elimination of infection by 2030. In this regard, HBV genetic diversity evaluation is scarcely done in Tanzania, imposing a crucial knowledge gap. We serologically and genetically characterized the HBV from 21 chronically HBV-infected patients attending Bugando Medical Centre to determine the HBV genetic diversity.
Methods
This cross-sectional study was conducted on the selected 21 plasma samples with high HBV-deoxyribonucleic acid (DNA) levels of > 300,000IU/mL. DNA extraction was done using Qiagen DNA Blood Mini Kit (Qiagen, Hilden, Germany). The Partial amplification of HBV DNA, sequencing and analysis was done at Institute of Virology, Giessen Germany.
Results
The mean age of 21 HBV chronically infected patients was 41 ± 11 years with HBV-DNA median of 979 [185.5–8457.5] IU/mL. Majority (85.7%, 18/21) were males from Mwanza. The genotypes detected were HBV/A; 76.2% (16/21), all being A1, followed by HBV/D; 19% (4/21), all being D4 and lastly HBV/G, 4.8% (1/21). The HBV/A1 serotypes were Adw2; 81.3% (13/16), followed by Ayw2; 12.5% (2/16) and all 4 HBV/D4 genotypes were serotype Ayw2. Overall, 19% (4/21) of the patients had HBV escape mutations (T123V, Y134N, P120T and T123A). The HBV/A identified in this study were distributed randomly among other HBV/As from all regions of Tanzania reported previous. On the other hand, HBV/D identified in this study were distributed among HBV/Ds from the North-western Tanzania identified previously. However, most of the HBV/As and all of the HBV/Ds identified in this study did not mix-up with HBV/As and HBV/Ds from other parts of the world.
Conclusion
HBV/A (HBV/A1) is predominant over time in North-western Tanzania. Most HBV/A1 and all HBV/D are unique to Tanzania as had been previously reported. However, the molecular epidemiology of HBV in this region is changing with occurrence of HBV/G as a new genotype and increasing HBV escape mutations which are mostly not due to drug pressure selection. The observation of HBV escape mutations threatening the future efficacy of serologic diagnostic tests and HBV vaccination in Tanzania underscoring the continuous monitoring of these mutants.
Archived natural DNA samplers reveal four decades of biodiversity change across the tree of life
Authors: Krehenwinkel Henrik , Junk Isabelle , Hans Julian , Perez-Lamarque Benoît , Weber Sven , Stothut Manuel , Gold Elisabeth , Schubert Caroline , Schumacher Alice , Schmitt Nina , Melcher Anja , Paulus Martin , Klein Roland , Teubner Diana , Koschorreck Jan , Kennedy Susan , Morlon Helene
Published: October 2024

Detecting the imprints of global environmental change on biological communities is a paramount task for ecological research1,2,3,4. But due to a lack of standardized long-term biomonitoring data, community assembly in the Anthropocene remains poorly understood5,6,7. Novel sources of data for analyzing biodiversity change across time and space are urgently needed8,9. By metabarcoding highly standardized biota samples from a long-term pollution monitoring archive in Germany, we here analyze four decades of community diversity for tens of thousands of species across the tree of life. The samples – tree leaves, marine macroalgae, and marine and limnic mussels – represent natural community DNA samplers10,11, preserving a taxonomically diverse imprint of their associated biodiversity at the time of collection9,12. We find no evidence for localized diversity declines1, but a strong, gradual compositional turnover as a universal pattern of temporal biodiversity change in Germany’s terrestrial and aquatic ecosystems5,13,14. This turnover results in biotic homogenization in terrestrial ecosystems, indicative of country-wide diversity decline. Our work uncovers a massive cryptic biodiversity loss across ecosystems, resulting from out-of-equilibrium ecological dynamics. This highlights the immense promise of alternative sample sources to provide standardized time series data of biodiversity change in the Anthropocene.
Hybrid approaches enhance hydrological model usability for local streamflow prediction
Authors: Pechlivanidis Ilias , Du Yiheng
Published: October 2024

Hydrological models are essential for predicting water flux dynamics, including extremes, and managing water resources, yet traditional process-based large-scale models often struggle with accuracy and process understanding due to their inability to represent complex, non-linear hydrometeorological processes, limiting their effectiveness in local conditions. Here we explore hybrid methods combining process-based modelling and statistical or machine learning post-processors to improve streamflow predictive accuracy, including extremes, across Europe’s hydro-climatic gradient. We investigate various post-processing methods, such as random forest, long short-term memory model, quantile mapping and generalised linear model, demonstrating significant improvements in model performance, particularly in terms of reducing total volume errors and increasing robustness across diverse climatic and geographic conditions. We further show that hydrologic similarity is one of the key drivers that control the hybrid approach’s improvements, together with other basin characteristics, such as mean precipitation and mean temperature. Our results also reveal spatial complementarity among the post-processing methods, with no absolute superiority identified from a single method, pointing towards multi-model averaging approaches for the future evolution of hybrid hydrological modelling.
Clinicoradiologic Differences between Orbital Schwannoma and Cavernous Venous Malformation: A Retrospective Comparative Case Series
Authors: Yap Ulysses Joseph , Chung Sae Rom , Lee Jeong Hyun , Sa Ho-Seok
Published: October 2024

OBJECTIVE
To compare the clinical and radiological characteristics, and surgical outcomes of orbital schwannoma and cavernous venous malformation (CVM).
MATERIALS AND METHODS
We retrospectively compared 13 and 26 patients with biopsy-proven orbital schwannoma and CVM, respectively, analyzing clinical features, magnetic resonance imaging (MRI) and computed tomography (CT) features (including dynamic contrast enhancement [DCE] imaging, apparent diffusion coefficient [ADC] and CT values), surgery type, and outcomes.
RESULTS
In both the schwannoma (mean age, 45 ± 16.7 years; 53.8% females) and CVM (mean age, 50.2 ± 8.6 years; 61.5% females) groups, gradual proptosis was the most common symptom (53,8% and 46.2%; mean measurements of 3.0 ± 1.97 mm and 2.5 ± 1.64 mm, respectively. Both groups had a common intraconal location (61.5 and 53.8%; mean sizes of 21.0 ± 7 mm and 20 ± 5 mm, respectively). On MRI, schwannomas were significantly more heterogeneous than CVM (p = 0.044). Tail sign and target sign were seen in 46.2% of schwannomas (p < 0.001), and linear T2 hypointensity was present in 57.7% of CVM (p = 0.008). DCE-MRI revealed diffuse early enhancement for schwannomas and nodular early enhancement for CVMs (p < 0.001). Schwannomas displayed higher ADC value without statistical significance (1.64 ± 0.56 x 10− 3 mm2/s vs. 1.26 ± 0.21 x 10− 3 mm2/s; p = 0.078), but significantly lower median CT value (40 HU vs. 56 HU; p = 0.001) than CVM. Majority underwent en bloc surgical excision without capsule violation (schwannoma, 76.9%; CVM, 100%). Schwannoma patients more frequently required lateral bony marginotomy compared to CVMs (23.1% vs. 7.7%). 23.1% of schwannoma patients underwent subtotal resection to avoid complications, with no recurrence observed during a 4.3 ± 3.4-year follow-up.
CONCLUSION
MRI aids in pre-operatively diagnosing orbital schwannoma and CVM. Schwannomas exhibit heterogeneous T2WI appearance, diffuse early-phase enhancement, and tail/target signs. Conversely, CVMs display homogenous T2WI signal, linear T2 hypointensity, and nodular early-phase enhancement. Additionally, schwannomas showed lower value on CT. For schwannomas, physicians should not risk vision loss or strabismus for total excision in anatomically challenging cases, as the risk of recurrence after subtotal resection is rare.
All Irradiance-Applicable, Perovskite Solar Cells-Powered Flexible Self-Sustaining Sensor Nodes for Wireless Internet-of-Things
Authors: Shi Yantao , Han Wenqi , Nie Ruicheng , Yin Bing , Zhang Jie , Qiu Sen , Wei Jiazhen , Pei Mingzhu , Qin Yuan , Wang Wen , Zhang Xiangyang , Cheng Jiashuo , Liu Lida
Published: October 2024

Currently, there are 17 billion IoT nodes, mostly powered by cables or batteries, leading to high maintenance costs and increased risk of data loss during power outages. Despite various energy harvesting technologies, the widespread deployment of self-sustaining IoT nodes is limited due to the lack of stable, continuous energy sources and limited power efficiency. We introduce an all-irradiance, 24-hour self-sustaining flexible node (SSN) with a perovskite solar cell module (FPSM) for steady power. The FPSM achieves over 30.54% power conversion efficiency (PCE) indoors, providing power in various lighting. The SSN, equipped with temperature and humidity sensors, uses a low-power Zigbee module for wireless data transfer. The FPSM-SSN reliably conducts 24-hour environmental monitoring indoors and achieves comprehensive three-dimensional data collection across "indoor-outdoor-aerial" environments. Additionally, it can also intelligently control household appliances based on temperature changes. The FPSM-SSN's robust self-sustaining capabilities demonstrate significant potential for IoT applications.
Findings from computed tomography examinations of Viking skulls
Authors: Bertilsson Carolina , Borg Eva , Vretemark Maria , Lund Henrik
Published: October 2024

Introduction Computed tomography images can provide information about anatomical structures and pathological processes in ancient skulls. A previous study on the teeth and jaws of 171 individuals in a late Swedish Viking-age population, dating around the 10th − 12th century made clinical examinations that included intraoral radiographs. To gain more information about these unique remains, this study examined a subset of this population with computed tomography.Materials and method The skulls of 15 Viking-era individuals were examined with computed tomography. Two dental specialists in maxillofacial radiology and one general dentist examined the images together, performing the diagnostics.Results Findings included signs of pathological conditions of the teeth; of the alveolar, auricular, mandibular, and maxillary bone; and of the sinuses and temporomandibular joints. These findings indicated the presence of dental caries, periodontal disease, periapical destructions with and without communication to the maxillary sinus or the oral cavity, infection-induced periosteal bone deposition, remodelling of the caput mandibulae, infection located to the ramus mandibulae, and sinusitis.Conclusion Computed tomography investigation of skeletal remains from an early Christian community in the Viking era in Sweden found that the population suffered from numerous orofacial pathologies, including dental disease, sinusitis, otitis, and various infections. As an investigation method of skeletal remains, computed tomography imagery was able to identify pathologies that might be difficult to find through clinical examination.
Photocatalytic degradation of free cholesterol using UV light: Kinetics and clinical studies, in vitro
Authors: Taha Ali Amajad , Al-Garawi Zahraa
Published: October 2024

Cholesterol, a steroid compound, is a waxy molecule that is found in approximately all types of cells in the human body. A higher concentration of cholesterol in the blood is associated with cardiovascular disease, which causes atherosclerosis. Lowering cholesterol is the most frequently prescribed target for reducing morbidity and mortality related to heart disease. Here, the photocatalytic degradation of diluted serum from atherosclerosis patients (1:5, potassium phosphate buffer, pH 6.5: serum) over 48 hr was investigated, in vitro, by a UV-light-based catalyst (370 nm, 220 V, 56 W). The resulting species were characterized using an ultraviolet spectrophotometer and HPLC. The results showed that the maximum degradation of cholesterol (350 mg/dl) was 19.7%. The kinetics of degradation followed the pseudo first order and kinetic model with a constant rate (k) of (4.7x10-3 min-1). The degradation was successfully confirmed by the formation of free fatty acids, for which the acid content was equal to 6.1 after degradation compared to its negligible value before degradation. On the other hand, the enzymatic degradation percentage of cholesterol (405 mg/dL) was also studied, and the results indicated 50% degradation after ~ one hour. Therefore, this study demonstrated that ultraviolet absorption can offer a feasible direction for the quantitative degradation of high concentrations of cholesterol. Photocatalysis is an alternative method for removing cholesterol from serum samples.
Unusual radiographic appearance of Fecalith leading to acute abdomen in a patient consuming Iron: A Case Report
Authors: Pathak Niharika , Thapa Megha , Sah Sushil , Pandey Prakash , Joshi Padam Raj
Published: October 2024

Background: Fecalith is common clinical condition, delay in diagnosis and management can lead to life threatening complications.
Case Presentation: We are reporting the case of an 18 years old lady which have unusual radiographic appearance of fecalith which was diagnosed in rural emergency setting and managed with simple conservative approach.
Conclusion: Fecalith can present with acute abdomen and confusing radiographic picture. It can lead to life-threatening bowel complications but can be managed conservatively with early diagnosis.
The Efficacy of Different Acupuncture Methods in Patients with Disorders of Consciousness Based on Electroencephalography: an autocontrol trial
Authors: Cao Ziyuan , Zhang Hao , Fu Guan , Huang Binbin , Li Hongwei , Li Wei
Published: October 2024

Objective
This study aimed to investigate the effects of Xingnao Kaiqiao (XNKQ) needling method and the Xingnao Kaiqiao needling method combined with Shixuan and Yongquan points (XNKQSY needling method) on brain function in patients with different levels of consciousness.
Methods
Thirty-three patients with disorders of consciousness (DOCs) were divided into minimally conscious state (MCS) (n=16) and unresponsive wakefulness syndrome (UWS) (n=17) groups according to their Coma Recovery Scale-Revised (CRS-R) scores. The patients in both groups were treated using XNKQ and XNKQSY needling methods. XNKQ needling method was administered on day 1, whereas the techniques in XNKQSY needling method were administered at the same time on next day. The MMN and CRS-R scores were measured before acupuncture treatment (T0), after single treatment with XNKQ needling method (T1), and after single treatment with XNKQSY needling method (T2). The electroencephalography (EEG) data were acquired using a 64-channel wireless EEG amplifier.
Results
(1) MCS group: The patients with MCS showed a significant increase in MMN amplitude after the application of XNKQ needling method (T1) compared with pre-treatment (T0) (0.84 [0.67, 1.05)] vs 1.21 [0.96, 1.92], respectively, p=0.001). Although increased MNN amplitude was observed after the application of XNKQSY needling method (T2), the difference was not statistically significant (0.84 [0.67, 1.05] vs 1.05 [0.72, 1.53], respectively, p=0.867).
(2) UWS group: Compared with pre-treatment (T0), the patients with UWS showed significant increases in MMN amplitude after the application of both XNKQ needling methods (T1) (0.34 [0.26, 0.59] vs 0.72 [0.55, 1.22], respectively, p=0.049) and XNKQSY needling method (T2) (0.34 [0.26, 0.59] vs 1.15 [0.93, 1.87], respectively, p<0.001), with a more significant increase for XNKQSY needling method (0.72 [0.55, 1.22] vs 1.15 [0.93, 1.87], p=0.049).
Conclusion
As measured by MMN, Xingnao Kaiqiao needling method appears to be more suitable for patients with MCS, whereas Xingnao Kaiqiao needling method combined with Shixuan and Yongquan points may be more suitable for those with UWS. MMN can be used as an auxiliary evaluation tool during acupuncture treatment. There may be a delay in behavioural changes in patients with DOCs compared to changes in brain function during the assessment of consciousness.
Heterogeneity in Kawasaki disease patients with coronary artery abnormalities investigated by data-driven cluster analysis
Authors: Sunaga Yuto , Hasebe Yohei , Kikuchi Natsumi , Yoshizawa Masashi , Kono Yosuke , Katsumata Nobuyuki , Inukai Takeshi
Published: October 2024

Purpose: To investigate possible heterogeneity in Kawasaki disease (KD) cases that developed coronary artery abnormality (CAA) in the acute phase and to assess associated clinical characteristics.
Methods: We performed a cluster analysis in 103 KD cases that developed CAA (maximum Z score for any coronary arteries > 2.5) within 30 days after disease onset among 726 consecutive KD cases. The hierarchical cluster analysis was performed based on 20 continuous variables derived from 33 continuous variables before initial treatment.
Results: 101 out of 103 cases with CAA in the acute phase were clustered into 4 subgroups. Cluster 1 (22 cases, 21.8%) was a younger group characterized by leukocytosis and elevated serum triglyceride levels, together with frequent coronary artery dilation before treatment and good initial treatment responses. Cluster 2 (32 cases, 31.7%) was a younger group characterized by anemia and lower serum total cholesterol levels, together with average initial treatment responses. Cluster 3 (30 cases, 29.7%) was an older group lacking distinct features, together with frequent coronary artery dilation before treatment. Cluster 4 (17 cases, 16.8%) was an older group characterized by elevated levels of serum aspartate aminotransferase, alanine aminotransferase, and total bilirubin and decreased serum sodium levels, together with poor initial treatment response and the lowest incidence of coronary artery dilatation before treatment.
Conclusion: Our cluster analysis identified four subgroups with distinct features suggesting different　backgrounds for CAA development. Consideration of possible heterogeneity might be helpful for better understanding of the pathophysiology and better treatment strategies in KD cases.
Dysplasia of cortical capillaries as the origin of Alzheimer’s disease: experimental evidence from APP/PS1
Authors: Xie Yirong , Pi Shurong , Zhong Jingyi , Lu Yao , Liu Jieyi , Li Xin , Jiang Jun , Li Hongya , Su Heng , Zhao Zhiqiang , Wei Qing , Chen Fubin , Lu Lingeng , He Yun
Published: October 2024

To investigate the time course changes of key pathological features of Alzheimer’s disease (AD) and relationship between vascular damage, neuro-inflammation and Aβ in AD model. VEGFR2 expression, vascular number and Aβ levels in cortex and cerebrospinal fluid, cortical and serum inflammatory factor levels, and autonomic activity/memory were analyzed in APP/PS1 mice from 1 to 12-month-old. Transcriptomic analysis of cortical capillaries in one-month-old mice and pathway analysis were performed. Validation of cortical transcriptome data in AD patients from GEO database. Soluble Aβ1−42 oligomers were treated with mouse brain vascular pericytes and endothelial cells. APP/PS1 mice had decreased cortical capillary VEGFR2 expression and vascular dysplasia at 1-month-old, increased endothelial cell apoptosis and decreased capillary density at 3-month-old, increased cortical Aβ1−42 deposition and neuron apoptosis at 6-month-old. APP/PS1 mice showed decreased autonomic activity and increased memory loss at 9-month-old. Cortical capillary transcriptome profiling indicated that a significant energy metabolism deficit was observed at 1-month-old. Increased mRNA expression of vascular-related genes in elderly surviving AD patients. 0.1µM soluble Aβ1−42 oligomers promote angiogenesis, whereas 10µM inhibit it. Cortical capillary dysplasia is a primary contributor to the onset of AD. The accumulation of Aβ in the brain exacerbates vascular hypoplasia by damaging blood vessels, and the interplay between these factors accelerates the progression of AD. Improving vascular functions and energy metabolisms may have potential in delaying or preventing AD.
Faricimab Efficacy in Type 1 Macular Neovascularization: AI-Assisted Quantification of Pigment Epithelium Detachment (PED) Volume Reduction Over 12 Months in Naïve and Switch Eyes
Authors: Cattaneo Jennifer , Forte Paolo , Forte Giovanni , Eandi Chiara M.
Published: October 2024

Background: This study evaluates the efficacy of intravitreal Faricimab in reducing pigment epithelium detachment (PED) and fluid volumes in both treatment-naïve eyes and eyes unresponsive to anti-VEGF mono-therapies, all diagnosed with type 1 macular neovascularization (T1 MNV) over a period of 12-month.
Methods: A retrospective, single-center cohort study was conducted at the Jules Gonin Eye Hospital, Lausanne, Switzerland. Clinical records of treatment-naïve and non-responder switch patients presenting T1 MNV secondary to neovascular age-related macular degeneration (nAMD) from September 2022 to March 2023 were reviewed. Patients received a loading dose of three monthly Faricimab injections followed by a treat-and-extend (T&E) regimen. Multimodal imaging, including structural OCT and AI-assisted analysis, was used to quantify PED volumes and related fluid biomarkers at baseline, 3-month, 6-month, and 12-month follow-up. Statistical analyses included linear mixed models to evaluate differences and trends in intraretinal (IRF), subretinal fluid (SRF) and PED volumes.
Results: 65 eyes of 65 patients were enrolled (female: 70.7%; mean age =80.7yrs, SD=6.9yrs). 80% had received anti-VEGF treatment (Switch group) and 20% were treatment-Naïve at baseline. At 12-months, intravitreal treatments were more frequent in the Switch group (mean number=8.3 vs. 6.0; p=0.009). No cases of intraocular inflammation were observed. Significant reduction in SRF and IRF volumes were noted in both groups. A significant reduction in PED volume was observed over the follow-up period in both groups (mean slope = -206 nL, 95%CL = -273/-138; p-value<0.001).
Conclusions: Intravitreal Faricimab significantly reduced PED volumes in both treatment-Naïve and non-responder Switch patients over 12 months. The study highlights Faricimab's potential as an effective treatment option for T1 MNV in nAMD, offering significant improvements in PED volume and related fluid biomarkers.
A Systematic Identification of RBPs Driving Aberrant Splicing in Cancer
Authors: Lobato-Fernández César , Gimeno Marian , Martín Ane San , Anorbe Ana , Rubio Angel , Ferrer-Bonsoms Juan A.
Published: October 2024

Background: Alternative Splicing (AS) is a post-transcriptional process that allows a single RNA to produce different mRNA variants and, in some cases, multiple proteins. Various processes, many yet to be discovered, regulate AS. This study focuses on regulation by RNA-binding proteins (RBPs), which are not only crucial for splicing regulation but also linked to cancer prognosis and are emerging as therapeutic targets for cancer treatment. CLIP-seq experiments help identify where RBPs bind on nascent transcripts, potentially revealing changes in splicing status that suggest causal relationships. Selecting specific RBPs for CLIP-seq experiments is often driven by a priori hypotheses.
Results: We developed an algorithm to detect RBPs likely related to splicing changes between conditions by integrating several CLIP-seq databases and a differential splicing detection algorithm. This work refines a previous study by improving splicing event prediction, testing different enrichment statistics, and performing additional validation experiments. The new method provides more accurate predictions and is included in the Bioconductor package EventPointer. We tested the algorithm in four experiments involving knockdowns of seven different RBPs. The algorithm accurately assessed the statistical significance of these RBPs using only splicing alterations. Additionally, we applied the algorithm to study sixteen cancer types from The Cancer Genome Atlas (TCGA). We identified relationships between RBPs and various cancer types, including alterations in CREBBP and MBNL2 in adenocarcinomas of the lung, liver, prostate, rectum, stomach, and colon. Some of these findings are validated in the literature, while others are novel.
Conclusions: The developed algorithm enhances the ability to predict and understand RBP-related splicing changes, offering more accurate predictions and novel insights into cancer-related splicing alterations. This work highlights the potential of RBPs as therapeutic targets and contributes to the broader understanding of their roles in cancer biology.
Dimensions of Quadriceps Tendon Autograft Are Variable Based on Patient Age and Graft Type: A Systematic Review
Authors: Glassman Isaac , Singh Harasees , Sritha Praveen , Abdel-Khalik Hassaan , Meena Amit , Hoshino Yuichi , de SA Darren
Published: October 2024

Purpose
The purpose of this study is to compile graft dimensions reported in quadriceps tendon anterior cruciate ligament reconstruction surgical papers.
Methods
A systematic literature search was conducted in accordance with PRISMA and R-AMSTAR guidelines. PubMed, EMBASE, MEDLINE, and Web of Science were searched from inception to June 18, 2024. All studies were searched and screened in duplicate; Cohen’s kappa was calculated at each stage. Quality assessment was conducted using MINORs for non-randomized studies and Cochrane’s RoB 2.0 for randomized studies. Descriptive statistics are presented.
Results
Thirty-one studies featuring 2,756 knees were included. Twenty-one papers used quadriceps tendon autograft with bone block (B-QT) and 10 used all-soft tissue quadriceps tendon autograft (S-QT). Included patients had a weighted mean age of 24.2 years and a range of 7–58 years. Of the papers featuring an adult population (average age ≥ 18 years), mean B-QT total graft length was 72.5mm (range: 50-90mm), bone block length was 18.5mm (range: 15-20mm), width was 9.9mm (range: 7-12mm), and diameter was 6.5mm (range: 5-9mm). For S-QT grafts in the adult population, the mean graft length was 78.8mm (range: 60-100mm), width was 10.6mm (range: 9-12mm), and diameter was 8.4mm (range: 5-10mm). In studies featuring a pediatric population (average age ≤ 18 years), the mean B-QT total graft length was 70.0mm (range: 60-80mm), bone block length was 16.7mm (range: 15-20mm), width was 9.7mm (range: 9-10mm), and diameter was 9mm (range: 8-10mm). For S-QT grafts in the pediatric population, the mean graft length was 64.2mm (range: 50-80mm), width was 10.0mm (range: 9-11mm), and diameter was 7.8mm (range: 5-10mm).
Conclusions
This review highlights the variability in graft dimensions for QT ACL-R grafts based on patient age and graft type. The paucity of consistent reporting of graft dimensions highlights the need for standardized reporting to promote the comparability of studies using QT ACL-R.
Level of evidence Level IV
Spontaneous Atlas Fracture in a Patient with Pycnodysostosis and Mandibular Osteomyelitis: A Case Report
Authors: Pablo Crespo Reinoso , Karina Ana
Published: October 2024

Pycnodysostosis is a rare autosomal recessive syndrome with an incidence of 1 in 1.7 million, caused by mutations in the CTSK gene, located on chromosome 1q21. We present a case of pycnodysostosis in a 30-year-old male patient who developed osteomyelitis of the jaw and an unusual fracture of the atlas, representing the first description of this complication. Patients with Pycnodysostosis, besides osteomyelitis, may seek maxillofacial attention for bone distraction assessment or orthognathic surgery. Therefore, we emphasize the importance of a thorough cervical assessment before any intervention.
Concurrent EGFR L858R and K860I mutations: PCR-negative but NGS-positive alterations that respond to EGFR inhibitors in non-small cell lung cancer
Authors: Shi Huiyang , Li Weihua , Guo Lei , Ying Jianming , Hu Xingsheng
Published: October 2024

Introduction: Clinical routine amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and next generation sequencing (NGS) are able to identify sensitizing EGFR mutations of non-small cell lung cancer (NSCLC) patients. Nevertheless, the detection and treatment response of NSCLC patients with concurrent L858R and uncommon EGFRexon 21 mutations remain unclear.
Methods: Concurrent NGS and ARMS-PCR were performed to identify EGFR mutations in 5033 NSCLC cases.
Results: Totally, EGFRL858R mutations were identified in 1024 (20.3%) cases, among which 54 concurrent L858R and uncommon EGFR exon 21 mutations were identified by NGS but not ARMS-PCR. The most common concurrent pathogenic mutations in EGFR exon 21 were V834L, K860I and L833V. Of those, 23 patients received EGFR-TKIs as the first-line treatment with median progression-free survival (PFS) of 16.7 months (95% CI: 12.8–20.7 months) and objective response rate (ORR) of 38.9% (95% CI: 9.1% – 46.9%). Interestingly, concurrent L858R and K860I mutations were observed in 10 cases by NGS, while ARMS-PCR showed completely negative results in EGFR mutations. Of those, three patients received EGFR-TKIs as the first-line treatment, with median PFS of 11.0 months and ORR of 100.0%. Furthermore, three patients with concurrent L858R and K860I mutations identified by NGS received adjuvant targeted therapy after surgery with median disease free survival of 10.0 months.
Conclusion: NSCLC patients with concurrentEGFR L858R and K860I mutations are able to benefit from EGFR-TKIs, which can be detected by NGS but not by ARMS-PCR.
Rapid and modular workflows for same-day sequencing-based detection of bloodstream infections and antimicrobial resistance determinants
Authors: Sajib Mohammad Saiful Islam , Oravcova Katarina , Brunker Kirstyn , Everest Paul , Fuentes Manuel , Wilson Catherine , Murphy Michael E. , Forde Taya
Published: October 2024

Background
Bloodstream infections (BSI) are a major global health concern, and existing diagnostic methods are too slow to guide targeted antibiotic therapy for critically ill patients, risking poor clinical outcomes. Rapid metagenomic-sequencing (mNGS) can facilitate swift pathogen and antimicrobial resistance (AMR) detection, but identification is challenged by significant host versus bacterial DNA in blood. To accelerate microbiological diagnosis, we developed M-15, a rapid and modular mNGS-based host DNA depletion workflow, validated with suspected BSI blood-culture samples and rapid culture-enriched spiked blood.
Methods
To assess chemical host DNA depletion (CHDD) efficiency, M-15 was benchmarked with five commercial/published protocols. Later, M-15 was combined with rapid mNGS with/without adaptive sampling (AS) and tested on clinical blood-culture samples (n = 33) from suspected BSI cases identified on BACT/ALERT VIRTUO (30 flagged positive, three remained negative). To determine whether it is possible to utilise M-15 mNGS prior to blood-culture flagging positive, a rapid enrichment method was tested starting with 1–10 colony forming units of the top 15 bacterial species causing BSI spiked into BACTEC medium enriched with 10 mL sheep blood.
Results
All six chemical depletion protocols reduced host DNA by 2.5x100 to 4.1x106-fold, with the in-house M-15 protocol performing best, while adaptive sampling depleted host > 5-fold. With BACT/ALERT specimens, M-15 mNGS accurately identified 3/3 negative, 28/28 mono-bacterial, and 2/4 multi-bacterial species. With rapid culture-enrichment and M-15 mNGS, < 18% DNA was classified as host and all bacterial species tested (n = 10) were correctly identified. M-15 mNGS accurately predicted phenotypic AMR/susceptibility for 90.3% (232/257) of drug/bacteria combinations from BACT/ALERT positive samples.
Conclusions
This study demonstrates that M-15 mNGS can facilitate species and AMR gene detection within 5–7 hours of BACT/ALERT positivity. Including 8-hour culture enrichment, microbiological and AMR confirmation is possible within 13–15 hours of sample collection. Thus, the M-15 mNGS workflow has the potential to improve patient outcomes in BSI.
Assessment of a Risk-Based Stratified Management Strategy for Cervical Cancer Screening in Central China: A Real-World Study across Diverse Populations of 223,533 Opportunistic and 43,102 Health Check-up Participants Over a Decade
Authors: Wu Qihui , Yan Junxia , Li Peiyao , Zhang Fan , Zhang Yu
Published: October 2024

Background: The evolving landscape of cervical cancer screening emphasizes risk-based stratification for effective management. This study aims to assess the applicability of a risk-based cervical cancer screening and management strategy in opportunistic screening populations at outpatient clinics and regular health check-up populations in central China.
Methods: The study validated the screening management strategy recommended by the 2019 ASCCP guidelines for 1-year and 3-year follow-up intervals in opportunistic screening and health check-up populations. Data were collected from a large tertiary hospital in central China, including 223,533 outpatient records from April 2012 to April 2022 and 43,102 health check-up records from April 2017 to April 2022. High-risk human papillomavirus (hrHPV) infection rates, cytology results, and subsequent high-grade cervical intraepithelial neoplasia (CIN3+) incidences were evaluated across different age groups. Follow-up data were examined to discern the effectiveness of risk-based management.
Results: The study revealed significant prevalence of hrHPV infection, with overall positivity rates of 18.17% in opportunistic screening and 13.22% in health check-up populations. Among screened individuals, the prevalence of CIN3+ exhibited age-related differences. Specifically, among individuals meeting the follow-up criteria, only the 25-65 years old group in the 1-year follow-up cohort had CIN3+ detection, with a prevalence of 0.47% in the outpatient population and 0.09% in the health check-up population.
Conclusions: The CIN3+ detection rates align with expectations, supporting the applicability of the ASCCP approach in varied screening settings. This study provides valuable insights into the real-world implementation of risk-based cervical cancer screening, contributing to the ongoing paradigm shift towards risk-based stratification. It underscores the importance of continuous efforts to refine screening protocols on a global scale.
The Mediation Effect of Cotinine Between Depression, Inflammation, and Mortality: A National Cohort Study
Authors: Liu Yang , Wang Linbin , Xiu Jia , Zhao Jing , Voon Valerie
Published: October 2024

Background
Depression is a major mental health issue that affects millions globally. Inflammation is linked to depression, and smoking is prevalent among depressed individuals. Serum cotinine, a nicotine metabolite, may mediate the effects of smoking on inflammation and mortality in depression. This study aims to explore the mediating role of cotinine between depression, inflammation, and all-cause mortality.
Methods
This study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2005 and 2014. A total of 24,937 participants were included after excluding individuals with missing data on depressive symptoms, serum cotinine concentration, and mortality outcomes. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), and serum cotinine levels were measured by isotope-dilution HPLC-APCI MS/MS. Multivariable logistic regression was used to assess the association between depression and cotinine. Mediation analysis was conducted to evaluate the mediating role of cotinine in the relationship between depression and WBC count, as well as between WBC count and mortality. Cox proportional hazards models were employed to determine the associations between cotinine, WBC count, and all-cause mortality.
Results
The analysis showed that individuals with depression had significantly higher serum cotinine levels (95.615 ng/mL vs. 53.546 ng/mL, P < 0.001) and WBC counts (7.665 vs. 7.203, P < 0.001) compared to those without depression. Multivariable logistic regression revealed that serum cotinine was positively associated with depression (OR = 1.002, 95% CI: 1.002–1.002, P < 0.001). Mediation analysis indicated that cotinine significantly mediated the association between depression and WBC count, accounting for 37.01% of the total effect after adjusting for confounders. Higher cotinine levels were also associated with increased all-cause mortality (HR = 1.889, 95% CI: 1.691–2.111, P < 0.001). Furthermore, cotinine mediated the relationship between WBC count and mortality, contributing to 27.39% of the total effect after adjustment.
Conclusion
This study highlights cotinine's role as a dual mediator in the relationships between depression, inflammation, and all-cause mortality. These findings underscore the need for targeted interventions, including smoking cessation and inflammation management, to improve health outcomes in individuals with depression.
Associations Between Lipid Traits and Breast Cancer Risk: A Mendelian Randomization Study in African Women
Authors: Ansah¹ Emmanuel Owusu , Kyei¹ Foster , Opoku Caleb Frimpong , Danquah¹ Andrews , Fosu Kwadwo , Agyenim⁵ Emmanuel Boateng , Agyirifo Daniel Sakyi
Published: October 2024

Backgrounds
Blood lipids are associated with breast cancer. An increasing number of reports have attempted to explore the genetic connection between blood lipids and the risk of developing breast cancer. However, observational studies can be affected by confounding factors and reverse causation, which can compromise the reliability of the findings.
Methods We used univariate and multivariable two-sample mendelian randomization to explore the causal association between blood lipids and breast cancer. Summary-level data for lipid traits were obtained from the Africa Wits-INDEPTH partnership for Genomic Research (AWI-Gen) (N = 10,603, 58.5% of women). For breast cancer, we leveraged summary statistics from the most comprehensive Genome-wide Association Studies (GWAS) on breast cancer consisting of 18,034 cases and 22,104 controls of women of African ancestry.
Results Our analysis suggests that genetically predicted triglycerides had a potential protective effect on breast carcinoma (OR = 0.73, 95% CI = 0.56, 0.95, FDR = 0.001). We found no evidence that genetically elevated levels of TC, HDL, and LDL may be associated with the risk of breast cancer TC (OR = 1.04; 95% CI, 0.93, 1.18; FDR = 0.029); HDL (OR = 1.29, 95% CI = 0.93, 1.79, FDR = 0.008); LDL (OR = 1.04, 95% CI = 0.90, 1.20, FDR = 0.036). Multivariate mendelian randomization analysis, which adjusted for the effects of TG, TC, LDL, and HDL, attenuated the observation of TG and breast cancer and also found no relationship between TC, HDL, LDL, and breast cancers. Furthermore, there was no evidence for a causal association between lipid traits and breast cancer subtypes. Our findings were robust in several sensitivity analyses.
Conclusions This study provides strong evidence that circulating TG may be associated with a decreased risk of breast cancer, while TC, LDL and HDL may not be related to the risk of breast cancer among African women. Our findings align with both observational and MR studies conducted in European populations. However, in contrast to our results, some studies suggest that TG, LDL, and HDL may increase breast cancer risk in Europeans, indicating potential ethnic differences in the lipid profiles of breast cancer patients.
Mind the gap between the tip of the plate and the tibial stem of the revision knee prosthesis – a survey with orthopaedic trauma surgeons
Authors: Caravellos Renato , Nery Filipe , de Souza Nicolle Barreto , Labronici Pedro , Freitas Anderson , Giordano Vincenzo
Published: October 2024

Purpose
In the herein study, we assessed the preferences among experienced orthopaedic surgeons regarding plate size and location when treating a distal tibia fracture in a patient with a revision stem of a total knee prosthesis. We aimed to determine how the stem size of the tibial component of the prosthesis influenced the choices of locking plates.
Methods
An online-based survey was sent to 35 members of the Brazilian Orthopaedic Trauma Association, consisting of eight multiple-choice questions addressing aspects of the management of lower limb injuries, including two scenarios of fractures of the distal tibia in the presence of a revision stem of a total knee prosthesis. Four large fragment locking plate lengths were used, ranging from 8 to 14 holes, whereas two different stem lengths were used, a 50-mm tibial stem and an 80-mm tibial stem. This gave to the participants 4 possibilities for each experimental situation. Descriptive and inferential analysis of the answers were performed, with a p-value of .05.
Results
For the 50-mm tibial stem, 48.6% of the surgeons chose the 8-hole plate, while 51.4% chose longer plates (10, 12 or 14-hole) (p > .05). In the presence of an 80-mm stem, the majority (57.1%) of the respondents opted for the 8-hole plate, with 42.9% choosing longer plates (p > .05). The choice for longer plates was more common among more experienced surgeons in treating tibia fractures (> 15 cases a year), and this was statistically significant (88.9% for the 50-mm tibial stem; p = 0.022) and (93.3% for the 80-mm stem; p = 0.014).
Conclusion
The presence and size of a revision tibial stem in a total knee prosthesis influence the choice of plate length for the fixation of a distal tibia fracture, and there is controversy among orthopaedic surgeons regarding the best construction for the tested scenarios. More experienced surgeons prefer longer plates, and this is statistically significant.