bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic Landscape of Early-Stage Prostate Adenocarcinoma in Mexican patients: An exploratory study
Authors: Cerrato-Izaguirre Dennis , González-Ruíz Jonathan , Diaz-Chavez José , Ramírez Andrea , Scavuzzo Anna , Jimenez Miguel A. , Cortés-González Carlo , Rubio Jairo A. , Pérez-Montiel María D. , García-Cuellar Claudia M. , Herrera Luis A. , Sánchez-Pérez Yesennia , Vaca-Paniagua Felipe , Barquet-Muñoz Salim , Cantu-de-Leon David , Bose Promita , Prada Diddier
Published: April 2024

Background
Health disparities have been highlighted among patient with prostate adenocarcinoma (PRAD) due to ethnicity. Mexican men present a more aggressive disease than other patients resulting in less favorable treatment outcome. We aimed to identify the mutational landscape which could help to reduce the health disparities among minority groups and generate the first genomics exploratory study of PRAD in Mexican patients.
Methods
Paraffin-embedded formalin-fixed tumoral tissue from 20 Mexican patients with early-stage PRAD treated at The Instituto Nacional de Cancerología, Mexico City from 2017–2019 were analyzed. Tumoral DNA was prepared for whole exome sequencing, the resulting files were mapped against h19 using BWA-MEM. Strelka2 and Lancet packages were used to identify single nucleotide variants (SNV) and insertions or deletions. FACETS was used to determine somatic copy number alterations (SCNA). Cancer Genome Interpreter web interface was used to determine the clinical relevance of variants.
Results
Patients were in an early clinical stage and had a mean age of 59.55 years (standard deviation [SD]: 7.1 years) with 90% of them having a Gleason Score of 7. Follow-up time was 48.50 months (SD: 32.77) with recurrences and progression in 30% and 15% of the patients, respectively. NUP98 (20%), CSMD3 (15%) and FAT1 (15%) were the genes most frequently affected by SNV; ARAF (75%) and ZNF419 (70%) were the most frequently affected by losses and gains SNCA’s. One quarter of the patients had mutations useful as biomarkers for the use of PARP inhibitors, they comprise mutations in BRCA, RAD54L and ATM. SBS05, DBS03 and ID08 were the most common mutational signatures present in this cohort. No associations with recurrence or progression were identified.
Conclusions
This study reveals the mutational landscape of early-stage prostate adenocarcinoma in men. Understanding mutational patterns and actionable mutations in early prostate cancer can inform personalized treatment approaches and reduce the underrepresentation in genomic cancer studies.
The Kampo formulae “Juzen-taiho-to (TJ-48), Boi-ogi-to (TJ-20), Keishi-bukuryo-gan (TJ-25),and Oren-gedoku-to (TJ-15)” inhibit the activation of hepatic stellate cells
Authors: Jiang Yaxuan , Li Hongyang , Ngo Quang Trung , Kawami Masashi , Kawahara Akihiro , Kanno Keishi , Ito Masanori , Ogawa-Ochiai Keiko
Published: April 2024

Aim
This study aimed to explore the effects of TJ-48 (juzen-taiho-to), TJ-20 (boi-ogi-to), TJ-25 (keishi-bukuryo-gan), and TJ-15 (oren-gedoku-to) on hepatic stellate cell (HSC) activation, as well as the impact of different concentrations of Kampo formulae on metabolic dysfunction-associated steatohepatitis (MASH) liver fibrosis by analyzing the changes in the expression levels of alpha smooth muscle actin (α-SMA) and collagen type I alpha 1 chain (COL1A1) gene.
Methods
Different concentrations (0, 100, 500, 1000 µg/mL) of Kampo formulae were added to HSC-LX2 cells and cultured for 48 h. Real-time PCR and western blotting were used to detect α-SMA and COL1A1 mRNA and protein expression.
Results
Increasing TJ-48 concentrations caused the α-SMA and COL1A1 mRNA and protein expression to decrease sequentially, with a significant decrease in α-SMA mRNA levels at 500 and 1000 µg/mL TJ-48. Further, increasing TJ-20 concentrations resulted in a linear decrease in α-SMA mRNA expression. Similarly, adding TJ-25 led to a sequential decrease in α-SMA and COL1A1 mRNA and protein expression, with a significant drop in α-SMA mRNA and protein expression at 500 and 1000 µg/mL TJ-25. Likewise, the addition of TJ-15 caused a steady decline in α-SMA mRNA and protein levels, with a significant decrease in α-SMA mRNA and COL1A1 mRNA and protein levels at 1000 µg/mL TJ-15.
Conclusion
Our findings indicated that TJ-48, TJ-20, TJ-25, and TJ-15 significantly inhibited the activation of hepatic stellate cells and prevented the development of liver fibrosis. Future in vivo and clinical studies are warranted on this topic.
Influence of Exfoliated G-c3n4 on the Mechanical Properties of Structural Mortars
Authors: Fernandes Izabella Katia Maciel , Costa Bianca da Silva Lima Miconi , Reis Leonardo Mayer , de Oliveira Raquel Kenya Ferreira Gonçalves , Calixto José Marcio Fonseca , Ladeira Luiz Orlando , de Souza Tarcizo da Cruz Costa , Houmard Manuel
Published: April 2024

This study intends to develop a new mortar material with improving microstructural properties through the addition of nanomaterials in its composition. Among the nanomaterials with interesting features, graphitic carbon nitride (g-C3N4) stands out for having a graphene-like carbon-based structure, in addition to exhibiting high chemical/thermal stability, and excellent electronic and optical properties. The present study evaluated the influence of exfoliated g-C3N4 addition, with 0.25%, 0.50%, and 1.00% by weight of anhydrous cement, on the physical and mechanical properties of structural mortars. The microstructure of the exfoliated g-C3N4 was characterized by transmission electron microscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy. Regarding the characterization of the mortars, the physical and mechanical properties were evaluated by flow table test, porosity and density measurements, SEM microscopy, and flexural and compressive strength tests. When the dosage of g-C3N4 nanosheets was 1.0% by weight of cement, the compressive and flexural tensile strengths at 28 days increased by 16% and 18%, respectively. At the same time, the addition of the nanomaterials also seems to have reduced the workability and slightly increased the total porosity. When compared with regular cement mortar, despite negatively affecting the compaction of the structure, it reveals that the exfoliated g-C3N4 addition could act as a reinforcing agent, improving the engineering performance of the cement composites making possible the production of lighter and stronger structures.
Increased frequency of CHD1 deletions in prostate cancers of African American men is associated with rapid disease progression without inducing homologous recombination deficiency
Authors: Szallasi Zoltan , Diossy Miklos , Tisza Viktoria , Li Hua , Sahgal Pranshu , Zhou Jia , Sztupinszki Zsofia , Young Denise , Nuosome Darryl , Kuo Claire , Jiang Jiji , Chen Yongmei , Ebner Reinhard , Sesterhenn Isabell , Moncur Joel , Chesnut Gregory , Petrovics Gyorgy , T.Klus Gregory , Valcz Gábor , Nuzzo Pier , Ribli Dezso , Börcsök Judit , Prósz Aurél , Krzystanek Marcin , Ried Thomas , Szüts Dávid , Rizwan Kinza , Kaochar Salma , Pathania Shailja , D'Andrea Alan , Csabai István , Srivast Shib , Freedman Matthew , Dobi Albert , Spisak Sandor
Published: April 2024

We analyzed genomic data derived from the prostate cancer of African and European American men in order to identify differences that may contribute to racial disparity of outcome and that could also define novel therapeutic strategies. In addition to analyzing patient derived next generation sequencing data, we performed FISH based confirmatory studies of Chromodomain helicase DNA-binding protein 1 (CHD1) loss on prostate cancer tissue microarrays. We created CRISPR edited, CHD1 deficient prostate cancer cell lines for genomic, drug sensitivity and functional homologous recombination (HR) activity analysis. We found that subclonal deletion of CHD1 is nearly three times as frequent in prostate tumors of African American men than in men of European ancestry and it associates with rapid disease progression. We further showed that CHD1 deletion is not associated with homologous recombination deficiency associated mutational signatures in prostate cancer. In prostate cancer cell line models CHD1 deletion did not induce HR deficiency as detected by RAD51 foci formation assay or mutational signatures, which was consistent with the moderate increase of olaparib sensitivity. CHD1 deficient prostate cancer cells, however, showed higher sensitivity to talazoparib. CHD1 loss may contribute to worse outcome of prostate cancer in African American men. A deeper understanding of the interaction between CHD1 loss and PARP inhibitor sensitivity will be needed to determine the optimal use of targeted agents such as talazoparib in the context of castration resistant prostate cancer.
Subjective Performance Assessment Protocol for Visual Explanations-based Face Verification Explainability
Authors: Bousnina Naima , Ascenso João , Correia Paulo Lobato , Pereira Fernando
Published: April 2024

The integration of Face Verification (FV) systems into multiple critical moments of daily life has become increasingly prevalent, raising concerns regarding the transparency and reliability of these systems. Consequently, there is a growing need for FV explainability tools to provide insights into the behavior of these systems. FV explainability tools that generate visual explanations, e.g., saliency maps, heatmaps, contour-based visualization maps, and face segmentation maps show promise in enhancing FV transparency by highlighting the contributions of different face regions to the FV decision-making process. However, evaluating the performance of such explainability tools remains challenging due to the lack of standardized assessment metrics and protocols. In this context, this paper proposes a subjective performance assessment protocol for evaluating the explainability performance of visual explanation-based FV explainability tools through pairwise comparisons of their explanation outputs. The proposed protocol encompasses a set of key specifications designed to efficiently collect the subjects’ preferences and estimate explainability performance scores, facilitating the relative assessment of the explainability tools. This protocol aims to address the current gap in evaluating the effectiveness of visual explanation-based FV explainability tools, providing a structured approach for assessing their performance and comparing with alternative tools. The proposed protocol is exercised and validated through an experiment conducted using two distinct heatmap-based FV explainability tools, notably FV-RISE and CorrRISE, taken as examples of visual explanation-based explainability tools, considering the various types of FV decisions, i.e., True Acceptance (TA), False Acceptance (FA), True Rejection (TR), and False Rejection (FR). A group of subjects with variety in age, gender, and ethnicity was tasked to express their preferences regarding the heatmap-based explanations generated by the two selected explainability tools. The subject preferences were collected and statistically processed to derive quantifiable scores, expressing the relative explainability performance of the assessed tools. The experimental results revealed that both assessed explainability tools exhibit comparable explainability performance for FA, TR, and FR decisions with CorrRISE performing slightly better than FV-RISE for TA decisions.
Optimal use of urban rooftops can synergize food and energy production objectives
Authors: Hu Yuanchao , Yang Rui , Xu Chao , Zhang Haoran , Wang Zhen , Pradhan Prajal , Lian Xihong , Jiao Limin , Bai Xuemei , Cui Shenghui , Zhu Yong-Guan
Published: April 2024

Urban rooftop agriculture (RA) and photovoltaics (RPV) offer sustainable solutions for energy-food systems in cities but compete for limited rooftop space. We explore the potential benefits (provisioning, economic, and environmental) and allocation strategy of RA and RPV across 13 million buildings in 124 Chinese cities, considering building height, age, function, rooftop type and occupation, and regional productivity. We found that RA yields superior economic benefits, while RPV excels in cradle-to-grave greenhouse gas emission reduction benefits. Prioritizing either RA or RPV compromises 70–100% of the above benefits brought by the other. An optimized allocation to maximize the overall benefits would retain >55% of their potential, meeting 14% (mean, 0.5–99% across cities) of urban vegetable needs and 5% (0.5–27% across cities) of the electricity needs. Such a scenario requires allocating 54% (varied 4–99% across cities) of the flat rooftop area to RA, and all remaining rooftops to RPV. Together, the productivity from rooftop RA and RPV are equivalent to 2.3×103 km2 of cropland and 86 Mt of coal, contribute 1.5% of the national GDP and reduce 1.6% of national greenhouse gas emissions (account for 0.1–33% of city levels), requiring considerable water (up to 18% of urban residential water use) and material demand (e.g., totalling 9 kt silver). By elucidating the benefits and resource costs of rooftop utilization, our findings can support synergetic decision-making to meet multiple sustainability goals in diverse cities.
Cryptographic Parameters Enhancement Using Pulsar Orbital Optimization
Authors: Hwaitat Ahmad K. Al , fakhouri hussam , Tahoun Samir M. Abu , ishtaiwi abdelraouf
Published: April 2024

In ophthalmic diagnostics, achieving precise segmentation of retinal blood vessels is a critical yet challenging task, primarily due to the complex nature of retinal images. The intricacies of these images often hinder the accuracy and efficiency of segmentation processes. To overcome these challenges, we introduce the Cognitive DL Retinal Blood Vessel Segmentation (CoDLRBVS), a novel hybrid model that synergistically combines the deep learning capabilities of the U-Net Architecture with a suite of advanced image processing techniques. This model uniquely integrates a preprocessing phase using a Matched Filter (MF) for feature enhancement and a post-processing phase employing Morphological Techniques (MT) for refining the segmentation output. Also, the model incorporates Multi-Scale Line Detection and Scale Space methods to enhance its segmentation capabilities. Hence, CoDLRBVS leverages the strengths of these combined approaches within the cognitive computing framework, endowing the system with human-like adaptability and reasoning. This strategic integration enables the model to emphasize blood vessels, accurately segment effectively, and proficiently detect vessels of varying sizes. CoDLRBVS achieves a notable mean accuracy of 96.7%, precision of 96.9%, sensitivity of 99.3%, and specificity of 80.4% across all of the studied datasets, including DRIVE, STARE, HRF, Retinal Blood Vessel and Chase-DB1. CoDLRBVS has been compared with different models, and the resulting metrics surpass the compared models and establish a new benchmark in retinal vessel segmentation. The success of CoDLRBVS underscores its significant potential in advancing medical image processing, particularly in the realm of retinal blood vessel segmentation.
‘Not taking medications and taking medication, it was the same thing:’ Perspectives of antiretroviral therapy among people hospitalised with advanced HIV disease
Authors: Loveday Marian , Hlangu Sindisiwe , Manickchund Pariva , Govender Thiloshini , Furin Jennifer
Published: April 2024

Background
Despite HIV's evolution to a chronic disease, the burden of advanced HIV disease (AHD) remains high among PLHIV on ART, due in part to treatment interruptions. TB is the most common cause of hospital admission and death in PLHIV. As little is known about the experiences of patients hospitalised with AHD, this study sought to discern patterns and forces driving hospitalisation with AHD which could inform strategies to reduce HIV-related morbidity and mortality.
Methods
We conducted a qualitative study with patients hospitalised with AHD who had a history of poor adherence. Thematic analysis based in grounded theory was used in conjunction with the Patient Health Engagement model to analyse interview transcripts.
Results
20 individuals participated in the research process. The most distinct pattern to emerge was the repeated periods of engagement versus disengagement with HIV services. This was driven by physical well-being, together with a denial of HIV and a lack of understanding of the insidious nature of HIV progression in the absence of signs and symptoms. Life circumstances or competing life priorities were another force which drove disengagement from the health services. Health system factors which contributed to disengagement or delayed re-engagement included the inflexibility of HIV services, together with the unhelpfulness and rudeness of clinic staff.
Conclusions
Current practices fail to address the challenges to lifelong ART. A bold strategy to involve people living with advanced HIV as active members of the health care team (i.e. ‘PLHIV as Partners’), could contribute to ensuring health care decisions are compatible with their lives and reduce periods of disengagement from HIV services.
Quantum Hall effect in a CVD-grown oxide
Authors: Zheliuk Oleksandr , Kreminska Yuliia , Fu Qundong , Pizzirani Davide , Ammerlaan Andrew , Wang Ying , Hameed Sardar , Wan Puhua , Peng Xiaoli , Wiedmann Steffen , Liu Zheng , Ye Jianting , Zeitler Uli
Published: April 2024

Two-dimensional electron systems (2DES) are promising for investigating correlated quantum phenomena. In particular, 2D oxides provide a platform that can host various quantum phases such as quantized Hall effect, superconductivity, or magnetism. The realization of such quantum phases in 2D oxides heavily relies on dedicated heterostructure growths. Here we show the integer quantum Hall effect achieved in chemical vapor deposition grown Bi2O2Se - a representative member of a more accessible oxide family. A single or few sub-band 2DES can be prepared in thin films of Bi2O2Se, where the film thickness acts as the sole design parameter and the sub-band occupation is determined by the electric field effect. This new oxide platform exhibits characteristic advantages in structural flexibility due to its layered nature, making it suitable for scalable growth. The unique small mass distinguishes Bi2O2Se from other high-mobility oxides, providing a new platform for exploring quantum Hall physics in 2D oxides.
The antipsychotic agent sulpiride microinjected into the ventral pallidum restores positive symptom-like habituation disturbance in MAM-E17 schizophrenia model rats
Authors: Péczely László , Dusa Daniella , Lénárd László , Ollmann Tamás , Kertes Erika , Gálosi Rita , Berta Beáta , Szabó Ádám , László Kristóf , Zagoracz Olga , Karádi Zoltán , Kállai Veronika
Published: April 2024

The malfunction of subcortical D2-like dopamine receptors (D2Rs) can lead to positive symptoms of schizophrenia and the analogue increased locomotor activity in schizophrenia model MAM-E17 rats. The ventral pallidum (VP) is a limbic structure containing D2Rs. The D2R antagonist sulpiride is a widespread antipsychotic drug, which can alleviate positive symptoms in human patients. However, it is still not known how sulpiride can influence positive symptoms via the VP D2Rs.
We hypothesize that the sulpiride microinjected into the VP can normalize hyperactivity of MAM-E17 rats. In addition, recently, we have shown that the sulpirid microinjected into the VP induces place preference in neurotypical rats. Thus, we aim to test whether intra-VP sulpiride can have a rewarding effect in MAM-E17 rats as well.
Therefore, open field-based conditioned place preference (CPP) test was applied in neurotypical and MAM-E17 schizophrenia model rats to test their locomotor activity and the potential locomotor-reducing and rewarding effect of sulpiride. Sulpiride was microinjected bilaterally in three different doses into the VP, controls received only vehicle.
Results of present experiments demonstrate that the increased locomotor activity of the MAM-E17 rats is in fact caused by habituation disturbance. Accordingly, larger doses of sulpiride in the VP reduce the positive symptom-analogue habituation disturbance of the MAM-E17 animals. Furthermore, we show that the largest dose of sulpiride administered into the VP induces CPP in neurotypical, but not in MAM-E17 animals.
These findings reveal that the VP D2Rs play an important role in the formation of the positive symptom-like habituation disturbance of MAM-E17 rats.
Feline cardiomyopathy-driven thrombogenesis: imaging and computational fluid dynamics for the study of left atrial morphology and haemodynamics
Authors: Pons Maria Isabel , Olivares Andy L. , Mill Jordi , Matos Jose Novo , Garcia-Canadilla Patricia , Cerrada Inma , Guy Anna , Morales Xabier , Hutchinson J. Ciaran , Simcock Ian C. , Arthurs Owen J. , Cook Andrew C. , Fuentes Virginia Luis , Camara Oscar
Published: April 2024

The intricate relationship between atrial fibrillation (AF), blood flow disturbances, and thrombus emergence is well-established in humans. Thrombi primarily form in the left atrial appendage (LAA), but the specific role of LAA morphology in this process remains unclear. Felines, despite rarely experiencing AF, present a valuable model for studying human heart diseases. Cats exhibit a high incidence of cardiomyopathies, often accompanied by significant left atrial dilation and thrombus formation. This unique aspect prompts research into LAA morphology and function in thrombus development. Our study, using advanced image processing and fluid simulations on 24 cat hearts ranging from normal to cardiomyopathic subjects, aims to discern distinctions in left atrium (LA) and LAA morphologies, blood flow patterns, and their relation to thrombus formation. Significantly different variables in distinguishing groups include heart weight, LAA volume, LA volume, ostium area, ostium area-to-heart weight ratio, centreline length, and velocity at the ostium. Fluid simulations revealed lower LAA blood flow velocities and increased thrombotic risk in cases with thrombi. This study enhances our understanding of LAA structure and function, offering insights into thrombus formation mechanisms with potential implications for managing thrombosis risk in patients.
Removal of benzo[a]pyrene by a highly degradable microbial community immobilized by modified wheat straw biochar
Authors: Chen Xiaoxiao , Meng Rong , Geng Meihui , Zhou Jiahui , Pu Yuewu
Published: April 2024

Benzo[a]pyrene, a high-molecular-weight polycyclic aromatic hydrocarbon, is a prevalent organic pollutant. In this study, a microbial community with high efficiency of BaP degradation was enriched in oil-contaminated soil, and the microbial community was immobilized using modified wheat straw biochar. The highest removal efficiency of 5–20 mg/L BaP was 75.18% in 12 days. Through 16SrRNA sequencing, Pseudomonas, Stenotrophomonas and Bacillus were found to be the dominant bacteria in the community. Additionally, metagenomic annotation revealed the gene function and metabolic pathway of the microbial community during BaP degradation.
Enhanced Security Hash Function Leveraging Chaotic Coupling Coefficient in Cross-Coupled Map Lattice
Authors: Li Yuxuan
Published: April 2024

The recent surge in interest within the scientific community towards spatiotemporal chaos underscores its potential for bolstering secure communications and cryptographic mechanisms. This research presents a cutting-edge methodology to amplify the spatiotemporal chaos exhibited by conventional cross-coupled image lattices through the adoption of chaotic coupling coefficients. By innovatively adjusting the structure of these lattices to incorporate chaotic coupling coefficients, we markedly enhance their chaotic dynamics across temporal and spatial dimensions. This advancement facilitates the creation of a secure hash function characterized by substantial security enhancements. Rigorous experimental validation attests to the security, highlighting the chaotic coupling coefficients' pivotal role in augmenting the hash function's defenses against various attacks. This investigation not only introduces a revolutionary alteration to the framework of cross-coupled image lattices but also unveils a pragmatic secure hash function application, demonstrating the significant potential of chaotic systems in the sphere of cryptography. Our findings suggest that integrating chaotic coupling coefficients into cross-coupled image lattices represents a fertile ground for crafting sophisticated cryptographic instruments, thereby paving new pathways in the realm of secure digital communications.
Probabilistic hazard assessment for pyroclastic density currents at Tungurahua volcano, Ecuador
Authors: Aravena Alvaro , Tadini Alessandro , Bevilacqua Andrea , Samaniego Pablo , Bernard Benjamin , Hidalgo Silvana , Pennec Jean-Luc Le , Martínez Pablo , García Johnny , Roche Olivier
Published: April 2024

We assess the volcanic hazard derived from pyroclastic density currents (PDCs) at Tungurahua volcano, Ecuador, using a probabilistic approach based on the analysis of calibrated numerical simulations. We address the expected variability of explosive eruptions at Tungurahua volcano by adopting a scenario-based strategy, where we consider three cases: small magnitude violent Strombolian to Vulcanian eruption (VEI 2), intermediate magnitude sub-Plinian eruption (VEI 3), and large magnitude sub-Plinian to Plinian eruption (VEI 4–5). PDCs are modeled using the branching energy cone model and the branching box model, considering reproducible calibration procedures based on the geological record of Tungurahua volcano. The use of different calibration procedures and reference PDC deposits allows us to define uncertainty ranges for the inundation probability of each scenario. Numerical results indicate that PDCs at Tungurahua volcano propagate preferentially toward W and NW, where a series of catchment ravines can be recognized. Two additional valleys of channelization are observed in the N and NE flanks of the volcano, which may affect the city of Baños. The mean inundation probability calculated for Baños is small (6 ± 3%) for PDCs similar to those emplaced during the VEI 2 eruptions of July 2006, February 2008, May 2010, July 2013, February 2014 and February 2016, and on the order of 13 ± 4% for a PDC similar to that produced during the sub-Plinian phase of the August 2006 eruption (VEI 3). The highest energy scenario (VEI 4–5), for which we present and implement a novel calibration procedure based on a few control points, produces inundation areas that nearly always include inhabited centers such as Baños, Puela and Cotaló, among others. This calibration method is well suited for eruptive scenarios that lack detailed field information, and could be replicated for poorly-known active volcanoes around the world.
Protocol for combined N-of-1 trials to assess cerebellar neurostimulation for movement disorders in children and young adults with dyskinetic cerebral palsy
Authors: Luciano Marta San , Oehrn Carina R , Wang Sarah S , Tolmie John S , Wiltshire Allisun , Graff Rebecca E , Zhu Jennifer , Starr Philip A
Published: April 2024

Background: Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders.
Methods: Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS.
Discussion: Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies.
Trial registration: ClinicalTrials.gov NCT06122675, first registered November 7, 2023.
Dual pathway inhibition with faricimab for previously treated neovascular age-related macular degeneration and diabetic macular oedema: Guidance from a UK panel of retina specialists
Authors: Downey Louise , Sivaprasad Sobha , Chhabra Ramandeep , Bailey Clare , Chakrabarti Soma , Elsherbiny Samer , patel Jignesh , Silvestri Giuliana , Watson Sarah-Lucie , Williams Gwyn , Parker Antony , Khokhar Saima , Lotery Andrew
Published: April 2024

Background/objectives Some eyes with neovascular age-related macular degeneration (nAMD) and centre-involving diabetic macular oedema (DMO) fail to respond sufficiently or lose response over time to standard of care intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. This paper explores clinical scenarios for switching to dual action angiopoietin-2/VEGF-A inhibitor faricimab (Vabysmo, Roche Products Limited) in previously anti-VEGF-treated patients.
Methods A national steering group meeting of UK retina specialists was held in London on 27 October 2023. Clinician practice and experience were reviewed together with pivotal clinical trial data and early findings from real-world settings. Roche Products Limited facilitated and funded the meeting.
Results While there is no standardised protocol for identifying suboptimal response, the authors review relevant clinical biomarkers of disease activity used in routine clinical practice to determine patient response and guide treatment decisions. Common reasons identified for considering a change of treatment were lack of efficacy demonstrated by suboptimal anatomic or visual improvement and insufficient durability of response. The panel outline strategies for switching to faricimab among eligible patients with a prior anti-VEGF treatment history, with initial monthly loading doses or maintaining the previous treatment interval before attempting to extend, that may be integrated into current treat-and-extend clinical pathways for treating patients with nAMD and DMO. General considerations for switching between treatments are also reviewed.
Conclusion Clinicians may consider a treatment switch to faricimab in nAMD and DMO patients who have suboptimal disease control or insufficient durability of response on initial anti-VEGF therapy.
Strategies for Fidelity Monitoring a Solution-Focused Brief Intervention in a Randomized Clinical Trial
Authors: Cooper Zach , Johnson Leslie
Published: April 2024

Background: Integrated Care (IC) models that include behavioral health providers to enhance patient care have increased, but the current mechanisms to analyze the efficacy and fidelity of behavioral interventions within IC models are limited.
Method:A mixed methods concurrent process evaluation was utilized within the context of a randomized clinical trial to assess intervention fidelity for a Solution Focused Brief Therapy (SFBT) intervention implemented within an IC model. Data was collected through 1) participant surveys, 2) self-report surveys with the interventionist, and 3) data from patient charts. Descriptive statistics in addition to repeated measures ANOVA were utilized to acquire quantitative data. Qualitative data was acquired through content analyses and data triangulation was used to present findings.
Results: The average SFBT intervention was 24.6 minutes with a range of 15-30 minutes. Of the 34 participants in the intervention group, 33 completed all 3 SFBT sessions. The majority of visits were weekly follow-ups (53.9%), followed by biweekly follow-ups (28.2%), and the remaining 3-week follow-ups (5.1%). The interventionist utilized session templates, and a self-report checklist to monitor intervention integrity. A SFBT scale was utilized to analyze the uptake of SFBT skills and there was a significant difference between those in the SFBT group and the treatment-as-usual group (F [1, 64] = 22.7, p<.001): mean difference, 15.1 [95% CI, 11.2- 18.9].
Conclusion: Our study examined fidelity efficiently and comprehensively and provides a foundation for studies interested in fidelity monitoring of SFBT interventions as well as behavioral interventions within IC models.
Trial Registration: The study was pre-registered at ClinicalTrials.gov Identifier: NCT05838222 on 01/05/2023.
Lung Quantitative Ultrasound to Stage and Monitor Interstitial Lung Diseases
Authors: Dashti Azadeh , Roshankhah Roshan , Lye Theresa , Blackwell John , Montgomery Stephanie , Egan Thomas , Mamou Jonathan , Muller Marie
Published: April 2024

Chronic interstitial lung diseases (ILDs) require frequent point-of-care monitoring. X-ray-based methods lack resolution and are ionizing. Chest computerized tomographic (CT) scans are expensive and provide more radiation. Conventional ultrasound can detect severe lung damage via vertical artifacts (B-lines). However, this information is not quantitative, and the appearance of B-lines is operator- and system-dependent. Here we demonstrate novel ultrasound-based biomarkers to assess severity of ILDs. Lung alveoli scatter ultrasound waves, leading to a complex acoustic signature, which is affected by changes in alveolar density due to ILDs. We exploit ultrasound scattering in the lung and combine Quantitative Ultrasound (QUS) parameters, to develop ultrasound-based biomarkers that significantly correlate to the severity of pulmonary fibrosis and edema in rodent lungs. These innovative QUS biomarkers will be very significant for monitoring severity of chronic ILDs and response to treatment, especially in this new era of miniaturized and highly portable ultrasound devices.
Factors associated with quality of Postnatal Care in Kenya: An analysis of the 2022 Kenya demographic and health survey
Authors: Nuwabaine Lilian , Namulema Angella , Sserwanja Quraish , Kawuki Joseph , Amperiize Mathius , Amwiine Earnest , Nakate Mary Grace , Asiimwe John Baptist
Published: April 2024

Despite the relevance of the postnatal period (PNC) to the survival of the mother and the newborn, there is limited research exploring the quality of postnatal care received by the mothers during this period. Therefore, this study aimed to determine the prevalence and factors associated with the quality of PNC, using the 2022 Kenya Demographic and Health Survey (KDHS).
Methods
In this study, secondary data from the KDHS of 2022 were analyzed, comprising 11,863 women, aged 15 to 49 years. The quality of PNC was indicated as receiving all components of postnatal care in the first two days after childbirth. Multivariable logistic regression was conducted to determine the factors associated with the quality of PNC, using SPSS, version 20.
Results
Out of the 11,863 women, 39% (95% CI: 37.0-40.9) had received all components of postnatal care in the first two days after childbirth. Additionally, older women aged 35- 49 years (AOR 1.88, 95%CI: 1.07-3.29), those who made decisions to seek health care jointly (AOR 1.48, 95%CI: 1.18-1.85), those who owned a telephone (AOR 1.36, 95%CI: 1.05-1.76), women who received quality antenatal care (AOR 4.62, 95%CI: 3.69-5.76), older women aged 30-34 years at the time of their first childbirth (AOR 2.25, 95%CI: 1.11-4.55), those who gave birth through cesarean section birth (AOR 1.93, 95%CI: 1.49-2.49), gave birth at public health facilities (AOR 1.69, 95%CI: 1.01-2.82) and those who received quality intrapartum care (AOR 1.87, 95%CI: 1.43-2.43) were more likely to receive quality postnatal care. On the other hand, women from other provinces of Kenya i.e. Western (AOR 0.51, 95%CI: 0.33-0.80), and Rift Valley (AOR 0.57, 95%CI: 0.39-0.81), those who gave birth to female children (AOR 0.75, 95%CI: 0.61-0.91) and those who reported to have not been respected at all times during their hospital stay (AOR 0.49, 95%CI: 0.29-0.82) were less likely to receive quality postnatal care.
Conclusion
The proportion of mothers receiving quality postnatal care was found to be low. The study also highlights the need to continue encouraging mothers to attend numerous ANC visits. Moreover, emphasis should be placed on providing quality ANC, intrapartum care, and respectful maternity care by health workers. Targeted interventions to increase access to quality PNC may need to focus on young mothers, mothers living in certain regions of Kenya, and those giving birth to female babies, most especially at private facilities, and through vaginal birth.
Tetanus Infection in an 11-Year-Old Male with Full Infant Vaccination History: A Rare Case Report
Authors: Akello Fridah , Achen Sharon , Najjuma Flavia , Musiime Victor
Published: April 2024

Background
Tetanus is a potentially life-threatening neurologic disorder caused by the toxin-producing bacterium Clostridium tetani. Primary prevention is achieved through vaccination, typically administered during infancy, however, breakthrough cases of tetanus in fully immunized individuals, especially in pediatric populations have been noted posing unique challenges for diagnosis and management. Uganda currently does not provide the World Health Organisation (WHO) recommended 3 dose Tetanus Toxoid (TT) booster at ages 12–23 months, 4–7 years and 9–15 years. This case report focuses on an unusual instance of an 11-year-old male who, despite having received complete vaccinations in infancy, manifested with symptoms consistent with tetanus.
Case presentation
An 11-year-old male Muganda was referred to Mulago National Referral Hospital's Acute Care Unit from a peripheral health facility with worsening backache, trismus, difficulty swallowing, and heightened sensitivity to touch and noise. On admission, he presented with severe pain, an arched back, and frequent muscle spasms indicative of tetanus, despite a history of complete vaccination during infancy. The patient received intravenous metronidazole, alternate diazepam, and chlorpromazine, leading to a steady improvement in symptoms after which he was discharged on day 29.
Conclusion
This case underscores the critical necessity of remaining vigilant for tetanus, even in individuals with a documented history of full immunization at infancy. Additionally, this scenario highlights the pressing need for reviews of vaccination policies in regions where WHO-recommended booster doses are not currently integrated into routine immunization schedules. Emphasizing adherence to these booster doses is paramount to enhancing tetanus immunity throughout childhood and adolescence.
Histopathologic patterns of skin cancer and associated factors in Jimma University Medical Center, Jimma, South West Ethiopia: Retrospective study
Authors: Yeshiwas Birtukan Ewunetu , Kedir Abdo , Zewdu Yohannes
Published: April 2024

Background
Skin cancer is a major global public health problem and the incidence has been increasing at an alarming rate worldwide. However, the data about the pattern in sub-Saharan Africa are limited. This study aims to determine histopathologic patterns of skin cancer and associated factors in patients with skin cancer.
Method and materials
A retrospective cross-sectional study was done with a review of 207 biopsies that were histologically diagnosed as skin cancer at the Jimma University Medical Center (JUMC) between August 2018 and August 2022. Data was analyzed by SPSS version 26 and descriptive and analytic studies were done. For all statistical significance tests, p < 0.05 and AOR with 95% CI were used. Logistic regression with multivariate analysis was done to identify independent predictor factors and determine the association between variables.
Results
The majority of skin cancer occurred in the 7th decade 49 (23.7%)) with a mean age of 50 ± 16.1 with slight female predominance 109 (52.7%). The commonest site for skin cancer was lower extremity 113 (54.6%) and ulceration 162 (78.3%) was the most common presenting symptom. Squamous cell carcinoma (SCC) 98 (47.3%) was the commonest skin cancer followed by cutaneous melanoma (CM) 50 (24.2%). Basal cell carcinoma (BCC) 13 (6.3%) was 5th skin cancer. Using the lower extremity as a reference group, head and neck skin cancer cases had an AOR of 6.03 being involved by Non-melanoma skin cancer (NMSC) (CI: 2.23–16.31, P = 0.000) and trunk skin cancer cases had AOR of 9.204 (CI: 1.16- 73, p = 0.036) being involved by NMSC.
Conclusion
NMSC was 3 times more common than MSC. The most common type of skin cancer is SCC followed by CM but BCC is a rare skin cancer. In contrast to Western and Asian countries, the lower extremity was the most common site for skin cancer which indicates differences in predisposing factors in different areas. Overall, the Lower extremity was the most common site of involvement. There is a statistically significant association between anatomic site and incidence of NMSC which warrants further study.
Origin and diversification of Aquilaria (Thymelaeaceae): inferences from a phylogenetic study based on matK sequences
Authors: Xie Zhaoqi , Fan Siqing , Xu Junyu , Xiao Haijing , Yang Jiaxin , Guo Min , Cheng Chunsong
Published: April 2024

In the realm of Aquilaria classification and grading, a persistent market uncertainty persists, questioning whether the basis should be geographical distribution or biological origin. In this study, our goal is to shed light on the origin and diversification of the Aquilaria genera. We collected and analyzed a total of 320 specimens belonging to 25 species within the Aquilaria genera. Noteworthy findings include observed leaf similarities among three distinct species—A. yunnanensis, A. sinensis, and A. beccariana. Further results emphasize the effectiveness of matK molecular markers in differentiating Aquilaria species, leveraging 8 stable polymorphic loci. The integration of matK and trnL-trnF not only validates this efficacy but also streamlines the systematic categorization of 34 agarwood products. Delving into the evolutionary status and genetic background of Aquilaria, this study employs molecular clock analyses, revealing four distinct pedigrees: the Chinese pedigree 1 and 2, the Indonesian pedigree, and the Indochina pedigree, aligning with A. sinensis, A. malaccensis, and A. cumingiana, respectively. Notably, we identified A. sinensis and A. malacca as part of the youngest branch of Aquilaria evolution, with A. hirta emerging as the oldest member dating back to 6.78 million years ago. Furthermore, the research challenges previous assumptions by reevaluating G. walla, placing it at 5.75 million years ago, and suggesting its incorporation within the Aquilaria genus rather than considering it as an early divergent species.
Study on Microbial Diversity of Clothing in Maternal and Infant Population
Authors: Yuan Shai , Yang Xiao , Zhao Zhenyao , Yao Su , Pang Lingling , Kang Jiali
Published: April 2024

With the improvement of Chinese people's living standards, the maintenance of infants and young children is becoming more and more sophisticated. Coupled with the impact of the COVID-19 epidemic in the past few years, mother-to-child families have paid unprecedented attention and expectations to household appliances with sterilization and disinfection functions. In addition to washing machines as household clothing care equipment, clothing care machines with further sterilization, drying, and disinfection functions for infant and young children's clothing are gradually entering households, especially in southern China during the rainy season. In order to thoroughly solve the problem of sterilization of clothing from the source, the distribution of microbial contamination of clothing should be fully investigated. At present, there are few systematic studies on microbial community structure in clothing in China. Therefore, the purpose of this study is to analyze the microbial community structure in Chinese maternal and infant household clothing and explore the key factors affecting the microbial community structure of clothing. A plate culture method and a high-throughput sequencing technology are utilized to comprehensively analyze the community structure of the microorganism in the clothes of the mother and infant. The Chao and Shannon index were used as indicators to explore the key factors affecting the microbial community structure of clothing by one-way analysis of variance. In this study, 149 strains of microorganisms were isolated from 24 clothing samples of mothers and infants, including 102 strains of bacteria, covering 16 genera. The bacteria with higher isolation frequency and wider distribution were Staphylococcus and Micrococcus, Moraxella; 47 strains of fungi covering 24 genera were isolated and the fungi with higher isolation frequency and wider distribution were Cladosporium, Alteraria, Rhodotorula. At present, the sterilization technology of clothing care machine has not been fully investigated in combination with the distribution of clothing microorganisms. Based on the specific distribution of microorganisms in clothing and the types of microorganisms contained, clothing care machines can provide more targeted sterilization treatment for clothing. This study will help to thoroughly address the sterilization and disinfection of microorganisms in clothing from the source.
P2X7-receptor binding in new-onset and secondary progressive MS – a [11C]SMW139 PET study
Authors: Lehto Jussi , Aarnio Richard , Tuisku Jouni , Sucksdorff Marcus , Koivumäki Esa Mikko , Nylund Marjo , Helin Semi , Rajander Johan , Danon Jonathan , Gilchrist Jayson , Kassiou Michael , Oikonen Vesa , Airas Laura
Published: April 2024

Background
PET imaging of activated microglia has improved our understanding of the pathology behind disability progression in MS, and pro-inflammatory microglia at ‘smoldering’ lesion rims have been implicated as drivers of disability progression. The P2X7R is upregulated in the cellular membranes of activated microglia. A single-tissue dual-input model was applied to quantify P2X7R binding in the normal appearing white matter, perilesional areas and thalamus among progressive MS patients, healthy controls and newly diagnosed relapsing MS patients.
Results
Overall, tracer uptake in the MS brain was not significantly higher compared to HCs. In the 3 mm perilesional rim of all T1 lesions, tracer binding was higher among relapsing patients compared to progressive patients. Tracer binding was higher in males compared to females. Disease duration correlated with tracer binding in the normal appearing white matter. Age correlated negatively with tracer binding in the perilesional rims.
Conclusions
Binding estimates obtained with the dual-input model were consistent with the expected distribution of P2X7Rs in the MS brain. According to our study, [11C]SMW139-binding may capture a glial cell phenotype significant in early development of chronic active lesions in relapsing stages of MS. Only tentative evidence for the applicability of [11C]SMW139 to detect MS-related diffuse smoldering inflammation was obtained.