bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon gamma‐mediated prevention of tumor progression in a mouse model of multiple myeloma
Authors: Kellermayer Zoltán , Tahri Sabrin , de Jong Madelon M. E. , Papazian Natalie , Fokkema Cathelijne , Stoetman Elodie C. G. , Hoogenboezem Remco , van Beek Gregory , Sanders Mathijs A. , Boon Louis , Den Hollander Chelsea , Broijl Annemiek , Sonneveld Pieter , Cupedo Tom 
Published: December 2024

AbstractMalignant plasma cells in multiple myeloma patients reside in the bone marrow and continuously interact with local immune cells. Progression and therapy response are influenced by this immune environment, highlighting the need for a detailed understanding of endogenous immune responses to malignant plasma cells. Here we used the 5TGM1 murine transfer model of multiple myeloma to dissect early immune responses to myeloma cells. We modeled stable and progressive disease by transferring 5TGM1 murine myeloma cells into C57Bl/6 mice and KaLwRij mice, respectively. We used flow cytometry and single‐cell and bulk transcriptomic analyses to characterize differential immune responses in stable and progressive disease. Transfer of 5TGM1 cells in C57Bl/6 mice led to stable disease with low tumor burden in a subset of animals. Stable disease was associated with sustained activation and expansion of NK cells, ILC1, and CD8+ T cells, a response that was lost upon disease progression. Single‐cell RNA‐sequencing of immune cells and bulk RNA sequencing of immune and mesenchymal stromal cells implicated the activation of interferon responses as a central immune pathway during stable disease. Experimentally, neutralization of IFNγ significantly increased myeloma development and progression in C57Bl/6 mice, testifying to the importance of this pathway in early disease control. In conclusion, we provide a framework for studying immune responses to multiple myeloma progression in immunocompetent and genetically modifiable mice and highlight the importance of bone marrow immunity in tumor control.
Impact of the peak period of coronavirus disease 2019 on 28‐day mortality, emergency department visits and length of hospital stay of emergency admissions: A single center retrospective observational study in Hong Kong
Authors: Li Rebecca Sin Tung , Law Alex K. K. , Graham Colin A. 
Published: December 2024

AbstractBackgroundDuring the fifth wave of COVID‐19, accident and emergency departments in Hong Kong experienced significant overcrowding yet there was limited evidence available regarding emergency services and patients' clinical outcomes. The aim of this study was to compare the 28‐day mortality, emergency department (ED) visits, and length of stay (LOS) between the peak period of COVID‐19 and a control period in 2019.MethodThis was a retrospective case‐control study comparing the peak period of COVID‐19 (7 Feb 2022 to 23 Apr 2022) with a control period (7 Feb 2019 to 23 Apr 2019). Patients' characteristics, ED visits, diagnoses, mortality, and LOS were compared.Results35,429 patients were included. The 28‐day in‐hospital mortality was significantly higher in the peak period of COVID‐19 with a risk ratio of 3.91 (95% CI: 3.38–4.53). There was a 36% reduction in ED visits during the peak period of COVID‐19 while there was a 53.7% increase in critical cases at triage. The average LOS of emergency admissions increased from 3.8 days (Median = 2.0; IQR = 1.0–3.0) in the control period to 5.1 days (Median = 2.0; IQR = 1.0–6.0) in the peak period of COVID‐19 especially in the subgroups of chronic kidney disease, influenza and pneumonia, diabetes, and mental disorders.ConclusionIncreased risk of all‐cause 28‐day in‐hospital deaths was observed during the peak period of COVID‐19 along with a reduction in overall ED visits and lengthened LOS.
Safety and Efficacy of Tinostamustine in a Subpopulation of Patients With Relapsed/Refractory Hodgkin Lymphoma From a Phase I Trial
Authors: Sureda Anna , Pinto Antonio , Ghesquières Hervé , Morschhauser Franck , Tournilhac Olivier , Mutsaers Pim , Zijlstra Josée M. , De Filippi Rosaria , Hilgier Kasia , Manamley Nick , Janik Tomas , Zinzani Pier Luigi 
Published: December 2024

ABSTRACTA significant unmet need remains for patients with Hodgkin lymphoma (HL) who fail to respond to first‐line treatment or experience an early relapse. Tinostamustine, a novel alkylating deacetylase inhibitor, inhibits tumor cell growth and slows disease progression in models of hematological malignancies and solid tumors. This was a Phase I, multicenter, open‐label, two‐stage trial investigating the safety and efficacy of tinostamustine in patients ≥ 18 years with relapsed/refractory (R/R) hematological malignancies, including HL. Stage 1 involved dose‐escalation to determine the maximum tolerated dose (MTD) of tinostamustine, optimal infusion time and recommended Phase II dose (RP2D). Stage 2 confirmed the safety and efficacy of the RP2D in expansion cohorts of selected R/R hematological malignancies. Ten patients with heavily pre‐treated HL entered dose‐escalation, with nine patients experiencing treatment‐emergent adverse events (TEAEs) considered to be related to study treatment—primarily hematological toxicities. MTD was 100 mg/m2 tinostamustine over 60 min and signals of efficacy were observed for patients with HL. In Stage 2, all 20 patients with HL experienced ≥ 1 TEAE, which were principally hematological or gastrointestinal. There were no tinostamustine‐related deaths in either stage of the study. Overall response rate in Stage 2 was 37% (2 complete responses, 5 partial responses; 95% confidence interval [CI]: 16%, 62%) and median progression‐free survival 3.8 months (95% CI: 2.2–9.4 months). Tinostamustine is a promising new therapeutic approach for the treatment of patients with R/R classical HL with limited options. This study demonstrates a predictable and manageable safety profile with signals of efficacy.Trial Registration: ClinicalTrials.gov identifier: NCT02576496
Obstetrical Outcomes in Women With a History of Bladder Augmentation
Authors: Susanna Porela‐Tiihonen , Riina Jernman , Seppo Taskinen 
Published: November 2024

ABSTRACTPurposeTo evaluate possible problems during pregnancy or delivery in women with pediatric bladder augmentation.MethodsEleven of 59 women, who had undergone bladder augmentation in our pediatric hospital during 1990–2019, had given birth in our hospital district afterwards and their obstetrical records were evaluated.ResultsMedian age at first delivery was 32 years (range 26–42). Six patients had myelomeningocele, two had bladder exstrophy and the remainder had VATER association, epispadias or traumatic paraplegia with vesicovaginal fistula. The patients had altogether 18 children (all singletons). Catheterizations were performed through continent stoma in six cases and through urethra in five cases. None of the patients needed an indwelling catheter before delivery. Antibiotic prophylaxis was initially in use during two pregnancies. Symptomatic urinary tract infections (UTIs) developed for five mothers in 11 pregnancies without prophylaxis and prophylaxis was continued after UTI in these cases. Three of the five mothers with UTI were treated with intravenous antibiotics due to pseudomonas infection (three infections) or pyelonephritis (one).Two patients with myelomeningocele delivered vaginally (one woman three times and one woman once). In the remaining 14 cases a cesarean section (CS) was performed (two urgent and one emergency CS). A urologist was present in seven CSs. Some difficulties accessing the uterus were reported in seven surgeries. There were 10‐term, three late‐preterm and one very preterm delivery. In four cases the information on gestational age was unavailable. Six newborns had respiratory problems, two had severe asphyxia. One newborn had myelomeningocele like her mother.ConclusionsRisk for UTIs during pregnancy is high in bladder augmentation patients, hence prophylactic antibiotics are justified. A multidisciplinary team should be involved in the planning of delivery. When indicated for obstetrical or urological reasons, an elective cesarean section with a urologist present may be the most rational option for many, although vaginal delivery is possible in selected patients.
Diagnosing and treating cellulitis in horses
Authors: Braid Helen 
Published: November 2024

Background: Cellulitis is a commonly observed condition in horses, which often requires an urgent or emergency veterinary visit. The condition often presents with acute‐onset diffuse limb swelling, heat, pitting oedema and pain on palpation of the affected limb. Lameness is variable but can be severe and the horse may display signs of extreme discomfort, alongside tachycardia, tachypnoea and pyrexia. Risk factors such as blunt trauma, recent wounds, recent surgery or recent injections have been identified, and studies suggest that cellulitis is more common in the hindlimbs than forelimbs.Aim of the article: This article provides an overview of the physiology of oedema formation and discusses the diagnosis and treatment options available for cases of cellulitis in horses.
Influence of super absorbent hydrophilic polymers on enhancing resources use efficiency and crop productivity in Vertisols
Authors: Pandey Umashanker , Rao Kondapally Venkata Ramana , Rajwade Yogesh Anand , Jat Dilip , Singh Ranjay Kumar 
Published: November 2024

AbstractWater scarcity is a significant challenge in agriculture, particularly in arid and semiarid regions. Superabsorbent polymers (SAPs), such as hydrogels, have emerged as effective tools for enhancing soil moisture retention and improving crop yield and water productivity in these environments. A two‐year field study was conducted to examine the impacts of hydrogel type and application depth on soil water distribution, water productivity and spinach growth. Two types of hydrogels, polymer‐based (Hydrogel‐1) and small organic molecule‐based (Hydrogel‐2), were applied at three depths—surface (D1), 5 cm (D2) and 10 cm (D3)—in a randomized block design. The results revealed that the water absorption capacity and water salinity of Hydrogel‐1 were negatively correlated, whereas those of Hydrogel‐2 were unaffected by salinity. Compared with that of the control, the soil moisture retention improved with deeper hydrogel application, with the Hydrogel‐1 treatment at 10 cm extending irrigation intervals by 2–4 days. Hydrogel application at greater depths significantly increased spinach growth metrics, including plant height, leaf count, leaf area, root length, SPAD value and yield, resulting in the highest yield (5.7 kg/m2) and water productivity (44.8 kg/m3). The study concludes that applying hydrogels at a depth of 10 cm is optimal for maximizing resource use efficiency and water productivity in spinach grown in vertisols.
Quantification of Empty Lacunae in Tissue Sections of Osteonecrosis of the Femoral Head Using YOLOv8 Artificial Intelligence Model
Authors: Shinohara Issei , Inui Atsuyuki , Murayama Masatoshi , Susuki Yosuke , Gao Qi , Chow Simon Kwoon‐Ho , Mifune Yutaka , Matsumoto Tomoyuki , Kuroda Ryosuke , Goodman Stuart B. 
Published: December 2024

ABSTRACTHistomorphometry is an important technique in the evaluation of non‐traumatic osteonecrosis of the femoral head (ONFH). Quantification of empty lacunae and pyknotic cells on histological images is the most reliable measure of ONFH pathology, yet it is time and manpower consuming. This study focused on the application of artificial intelligence (AI) technology to tissue image evaluation. The aim of this study is to establish an automated cell counting platform using YOLOv8 as an object detection model on ONFH tissue images and to evaluate and validate its accuracy. From 30 ONFH model rabbits, 270 tissue images were prepared; based on evaluations by three researchers, ground truth labels were created to classify each cell in the image into two classes (osteocytes and empty lacunae) or three classes (osteocytes, pyknotic cells, and empty lacunae). Two and three classes were then annotated on each image. Transfer learning based on annotated data (80% for training and 20% for validation) was performed using YOLOv8n and YOLOv8x with different parameters. To evaluate the detection accuracy of the training model, the mean average precision (mAP (50)) and precision‐recall curve were identified. In addition, the reliability of cell counting by YOLOv8 relative to manual cell counting was evaluated by linear regression analysis using five histological images unused in previous experiments. The mAP (50) for the detection of empty lacunae was 0.868 for the YOLOv8n and 0.883 for the YOLOv8x. The mAP (50) for the three classes was 0.735 for the YOLOv8n model and 0.750 for the YOLOv8x model. The quantification of empty lacunae by automated cell counting obtained in the learning was highly correlated with the manual counting data. The development of an AI‐applied automated cell counting platform will significantly reduce the time and effort of manual cell counting in histological analysis.
FOXD2‐AS1 Binding to MYC Activates EGLN3 to Affect the Malignant Progression of Clear Cell Renal Cell Carcinoma
Authors: Huang Zhigang , Liu Bin , Li Xiaoju , Jin Chenghua , Hu Quansen , Zhao Zhiwei , Wang Qian 
Published: December 2024

ABSTRACTLong noncoding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2‐AS1) show high expression in various cancers with elusive regulatory mechanisms. This study investigated the regulatory mechanism of FOXD2‐AS1 in clear cell renal cell carcinoma (ccRCC) and its influence on ccRCC cell functions, providing novel insights into ccRCC treatment and a theoretical basis for refining prognoses of ccRCC patients.Through differential analysis and survival analysis, differentially expressed lncRNAs (DElncRNAs) that were significantly linked with the prognosis of ccRCC were initially identified, and lncRNA‐transcription factor‐mRNA triplet was predicted via lncMAP database. RNA immunoprecipitation, chromatin immunoprecipitation, and dual‐luciferase reporter assays were applied to verify the targeted relationship between MYC, FOXD2‐AS1, and Egl‐9 family hypoxia‐inducible factor 3 (EGLN3). Cell functions in ccRCC were detected by a set of cell functional assays. Mice experiment was utilized for in vivo validation.We uncovered the elevated FOXD2‐AS1 and EGLN3 expression in ccRCC, as well as the promotion effect of FOXD2‐AS1 on ccRCC cells to proliferate, migrate, and invade via upregulating EGLN3 expression. Our results also suggested that the regulatory influence of FOXD2‐AS1 on EGLN3 was achieved by recruiting MYC to the EGLN3 promoter region. In vitro and in vivo assays both confirmed that the FOXD2‐AS1/MYC/EGLN3 axis could accelerate the progression of ccRCC.FOXD2‐AS1 activated EGLN3 to accelerate ccRCC cell functions via binding to the transcription factor MYC.
Comparison of localization and release of multivesicular bodies and secretory granules in islet cells: Dysregulation during type‐2 diabetes
Authors: Veerabhadraswamy Priyadarshini , Lata Kiran , Dey Sristi , Belekar Prajakta , Kothegala Lakshmi , Mangala Prasad Vidya , Gandasi Nikhil R. 
Published: November 2024

AbstractMultivesicular bodies (MVBs) are vesicles of endosomal origin containing intraluminal vesicles, which upon fusion with plasma membrane, secrete exosomes. They play a significant role in the physiology and pathology of type‐2 diabetes (T2D) due to disrupted intercellular communication. The role of MVBs and their influence on insulin secretory granules (ISGs) of β‐cells or their characterization is yet to be uncovered. In our study, we compared MVBs to largely well‐characterized ISGs in β‐cells. This study compares the density, localization, and exocytosis of CD63+ compartments (CD63+c) with NPY labelled ISGs (NISGs) in β‐cells. For this, tetraspanin CD63 was exploited to majorly label MVBs in β‐cells. These labels preserve the structural integrity of labelled compartments and mostly do not localize with other endo‐lysosomal compartments. This study showed that the β‐cells have a significantly higher density of NISGs than CD63+c. CD63+c and NISGs are spatially localized apart within β‐cells. The proteins that localize with CD63+c are different from the ones that localize with NISGs. Exocytosis of NISGs occurs at the periphery of the β‐cells and takes significantly less time when compared to the release of CD63+c, which is non‐peripheral and takes a longer duration. Mechanistically, the availability of CD63+c for exocytosis was assessed and found that an equilibrium is maintained between docking and undocking states at the plasma membrane. Although there are a high number of short‐term residing, visiting CD63+c at the plasma membrane, the availability of CD63+c for exocytosis is maintained due to docking and undocking states. Further, a significant reduction in the density of NISGs and CD63+c was observed in β‐cells isolated from T2D donors compared to healthy counterparts. Studying the effect of MVBs on insulin secretion in physiological and T2D conditions has huge potential. This study provides a strong basis to open new avenues for such future studies.
Effects of electric fields on the release and content of extracellular vesicles
Authors: Wang Yihua , Worrell Gregory A. , Wang Hai‐Long 
Published: November 2024

AbstractExtracellular vesicles (EVs) are small membrane‐bound structures that originate from various cell types and carry molecular cargos to influence the behaviour of recipient cells. The use of EVs as biomarkers for diagnosis and as delivery vehicles for treatment in a wide range of human disease is a rapidly growing field in research and clinical practice. We hypothesized that electric fields (EFs) could influence the release and content of EVs. To examine this hypothesis, we developed a specialized bioreactor enabling cells to thrive in a three‐dimensional setting, replicating in‐vivo conditions amidst programmable EF environments. We established a three‐step EV purification protocol to achieve high‐density production of EVs. We also performed mass spectrometry‐based proteomics analysis on EV‐carrying proteins and used high‐resolution nanoparticle flowcytometry for single‐vesicle analysis. Findings from this report suggest that electrical stimulation, employing physiologically relevant amplitudes typical in therapeutic deep brain stimulation, influences the release of EVs and their cargo content in a frequency‐dependent fashion. This conclusion could carry significant implications for both fundamental biological understanding and medical advancements. First, it raises an intriguing question about how the endogenous electrical activity of neuronal and other cellular assemblies influence the production and composition of EVs. Second, it reveals a novel underlying mechanism of how therapeutic electrical stimulations can modulate EVs and treat human brain disorders. Third, it provides a novel approach to utilize electrical stimulation for generating desired EV cargos in a programmable setting.
カテコラミン製剤のシリンジ交換方法が患者の血圧変動に与える影響：単施設後方視的研究(Influence of catecholamine syringe changeover method on patient’s blood pressure variability: a single–center retrospective study)
Authors: 宥太 新津 , 拓見 土田 , 隆太 佐藤 , 珠奈 新宅 , 幸一 岩佐 
Published: November 2024

要旨【目的】本邦ではカテコラミンシリンジ交換法に関するエビデンスが不十分であり，シリンジ交換法も施設や個人により異なる。本研究の目的は，ICU患者におけるカテコラミンシリンジ交換方法が血圧変動に及ぼす影響を明らかにすることである。【対象】2020年4月1日から2022年3月31日までに行ったカテコラミン製剤のシリンジ交換308回（患者数119名）を対象とし，並列交換群とクイック交換群を傾向スコアマッチングを用いて比較した。また，収縮期血圧が90mmHg以下の状態における交換に限定したサブグループ解析と，シリンジ交換時の血圧変動におけるリスク因子を調べるためのロジスティック回帰分析を行った。【結果】傾向スコアマッチングによる解析およびサブグループ解析において，シリンジ交換後15分までの収縮期/拡張期/平均血圧の変動係数や絶対値は両群で有意差がなかった。ロジスティック回帰分析では，年齢がシリンジ交換時の血圧変動に対する唯一の危険因子であり（オッズ比：1.018，95%信頼区間：1.001 – 1.036），シリンジ交換方法は血圧変動に寄与しなかった（オッズ比：1.186，95%信頼区間：0.672 – 2.092）。【結語】カテコラミン製剤のシリンジ交換において，並列交換法とクイック交換法の違いは血圧変動に影響しなかったが，年齢は血圧変動に対するリスク因子と考えられた。
COVID–19罹患後早期に発症したBickerstaff型脳幹脳炎の2症例(Bickerstaff brainstem encephalitis developed quickly after COVID–19 infection)
Authors: 大樹 森 , 貴大 山田 , 博 福間 , 彰太 中尾 , 哲也 松岡 
Published: November 2024

要旨Bickerstaff型脳幹脳炎（Bickerstaff brainstem encephalitis: BBE）は意識障害，眼球運動障害，運動失調を三主徴とし，先行感染を契機に発症する稀な自己免疫疾患である。我々はCOVID–19罹患後早期に発症したBBEを2例経験した。症例1；51歳，男性。発熱4日目に前医を受診しCOVID–19の診断で転院した。入院日より意識障害が遷延し眼球運動障害や運動失調を認めたためステロイド，免疫グロブリンを投与したところ意識状態は改善した。抗GQ1b抗体陽性でBBEと診断した。症例2；28歳，女性。発熱とショックのため搬送され，COVID–19，誤嚥性肺炎の診断で入院となった。意識障害，眼球運動障害，ジスキネジアを認めた。ステロイド，免疫グロブリンの投与と血漿交換を行い意識状態は改善した。頭部MRIで脳幹部錐体路の変性を認めBBEと診断した。2症例ともCOVID–19発症から1週間以内に中枢神経症状が出現しており，感染後早期からBBEを発症することが明らかとなった。COVID–19罹患後早期に中枢神経症状が出現した際は本疾患を想起する必要がある。
A Component of the Septation Initiation Network Complex, SepL, Participates in the Cellobiose‐Responsive Expression of Cellulolytic Enzyme Genes in Aspergillus aculeatus
Authors: Sawada Kazumi , Kikuya Saki , Shiga Yui , Kawaguchi Takashi , Tani Shuji 
Published: December 2024

ABSTRACTThe production of cellulolytic enzymes in Aspergillus aculeatus is regulated at transcriptional levels in response to inducers and various physiological signals. In this study, we identified that a component of the septation initiation network complex, SepL, a putative protein kinase, was involved in the expression of carbohydrate‐active enzyme (CAZyme) encoding genes. The deletion of sepL (ΔsepL) in A. aculeatus resulted in a deficiency in both septation and conidiation and sensitivity to Congo red. These phenotypes of ΔsepL are conserved in Aspergillus. In addition to the conserved function of SepL in Aspergillus, we found that SepL in A. aculeatus was necessary for the inducible expression of the CAZyme genes in response to cellobiose, whereas the inducible expression of these genes in response to 1,4‐β‐mannobiose was significantly reduced but not abolished. Combining the results of the present functional analysis of SepL with previous evidence that the expression of the CAZyme genes, which is responsive to both cellobiose and 1,4‐β‐mannobiose, is regulated by a transcription factor ManR in A. aculeatus, indicates that SepL in A. aculeatus is involved in the selective expression of the cellobiose‐responsive CAZyme genes under the control of ManR.
Multisocietal Consensus on the Use of Cytoreductive Surgery and HIPEC for the Treatment of Diffuse Malignant Peritoneal Mesothelioma: A GRADE Approach for Evidence Evaluation and Recommendation
Authors: Kusamura Shigeki , Cinquini Michela , Morris David , Piso Pompiliu , Kindler Hedy , Brandl Andreas , Levine Edward , Glehen Olivier , Kepenekian Vahan , Sgarbura Olivia , Sugarbaker Paul H. , Baratti Dario , Marcello Guaglio , Marcello Deraco 
Published: November 2024

ABSTRACTThe Peritoneal Surface Oncology Group International (PSOGI) previously issued a recommendation endorsing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for treating diffuse malignant peritoneal mesothelioma (DMPM). However, broader acceptance of this approach, particularly within some segments of medical oncology, remains limited. To address this, PSOGI initiated a multisociety consensus effort, involving multidisciplinary International Societies, to strengthen and expand the endorsement of CRS‐HIPEC for DMPM. Using the GRADE ADOLOPMENT approach, the expert panel systematically reviewed existing guidelines and evaluated the available evidence to reinforce the recommendation. The panel unanimously recommended CRS‐HIPEC for a carefully selected subset of DMPM patients, emphasizing that this approach offers the best potential for improved survival compared to systemic chemotherapy alone. Despite the very low certainty of evidence, a strong recommendation was issued, reflecting the panel's recognition of the life‐threatening feature of DMPM and the limited efficacy of systemic chemotherapy. This consensus also highlights the importance of centralized and expert‐driven care. The recommendation aligns with previous guidelines and underscores the critical need for broader acceptance of this treatment strategy in managing this rare and aggressive malignancy.