bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD56brightcytokine-induced memory-like NK cells and NK-cell engagers synergize against non-small cell lung cancer cancer-stem cells
Authors: Guevara Lopez Maria L , Gebo Ann , Parodi Monica , Persano Stefano , Maus-Conn Josephine , Mingari Maria Cristina , Loiacono Fabrizio , Orecchia Paola , Sivori Simona , Cantoni Claudia , Gentili Marco , Facchinetti Federica , Ferracini Riccardo , Vallera Daniel A , Felices Martin , Bertolini Giulia , Pravetoni Marco , Roz Luca , Vitale Massimo 
Published: February 2025

BackgroundDue to their enhanced responsiveness and persistence, cytokine-induced memory-like (CIML)-natural killer (NK) cells have emerged as new immunotherapeutic tools against malignancies. However, their effects on tumor-cell spread and metastases in solid tumors remain poorly investigated. Moreover, a clear identification of the most effective CIML-NK subsets, especially in controlling cancer stem cells (CSC), is still lacking.MethodsWe performed combined phenotypical and functional analyses of CIML-NK cell subsets, either selected by flow-cytometry gating, or generated from sorted CD56bright/CD56dimNK cells.By co-culture experiments, we analyzed the effect of CIML-NK cells on non-small cell lung cancer (NSCLC) cell spheroids, or patient-derived xenografts (PDX), assessing changes in their CSC content, tumorigenicity, and/or tumor disseminating capability in vivo. CIML-NK cells were also infused in PDX-bearing mice to validate their effect on the CSC dissemination from the PDX to the lungs.Finally, we generated and functionally analyzed CIML-NK cells from patients with stages I/III NSCLC (n=6).ResultsWe show that CIML-NK cells exert antitumor activity mostly through their CD56brightcell subset, which greatly expands during CIML differentiation. Compared with NK cells conventionally activated with interleukin-2, CIML-NK cells express lower levels of check-point receptors, TIGIT and TIM3, and higher effector functions against NSCLC cells from PDX, and against in vitro-generated tumor spheroids. Remarkably, CIML-NK cells also significantly reduce the CSC-containing CD133+cell subpopulation within spheroids and PDX, and limit tumor cell tumorigenicity and ability to disseminate CSCs from primary tumors to distant sites. Sorting experiments on CIML or tumor cell subsets reveal that CD56brightcells drive most of this anti-CSC activity, and suggest that such functional advantage could be related to increased expression of LFA-1 and ICAM-1 on CD56brightcells and CSCs, respectively. We also show that the tri-specific killer cell engager (TriKE) 1615133 significantly enhances CIML-NK cell activity against CSCs. Finally, we demonstrate that CIML-NK cells, capable of killing autologous tumor cells and responding to the 1615133 TriKE, could be induced from patients with NSCLC.ConclusionsOur study discloses for the first time the therapeutic potential of CIML-NK cells in controlling CSCs and metastatic spread, highlighting the role of the CD56brightsubset expansion and 1615133 TriKE for optimizing CIML-NK-based therapies against metastatic tumors.
Arteriovenous malformation from a patient with JP-HHT harbours two second-hit somatic DNA alterations inSMAD4
Authors: DeBose-Scarlett Evon , Ressler Andrew K , Friday Cassi , Prickett Kara K , Roberts James W , Gossage James R , Marchuk Douglas A 
Published: February 2025

BackgroundHereditary haemorrhagic telangiectasia (HHT) is an inherited disorder of vascular malformations. It is caused by inherited loss-of-function mutations in one of three genes,ENG,ACVRL1orSMAD4. We recently showed that HHT-associated vascular malformations from liver, lung, brain and skin develop via a two-hit genetic mechanism resulting from biallelic loss-of-function mutations in eitherENGorACVRL1. Second-hit somatic mutations inSMAD4have not been reported in HHT-associated vascular malformations. Here, we investigate a large, aggressively growing craniofacial arteriovenous malformation (AVM) from an individual with juvenile polyposis-HHT caused by a germline mutation inSMAD4.MethodsWe sequenced DNA from the AVM using a targeted gene sequencing panel to at least 1000X to identify somatic mutations that might contribute to the development of the AVM. We analysed whole genome SNP genotyping data using the algorithm Mosaic Chromosomal Alterations (MoChA) to identify somatic loss of heterozygosity.ResultsWe confirmed the germline mutation inSMAD4(c.1610A>T, p.Asp537Val) and identified a second-hit somatic mutation also inSMAD4(c.350dup, p.Tyr117*) that occurred intransrelative to the germline mutation. We also identified somatic loss of heterozygosity on the q arm of chromosome 18, includingSMAD4. Additionally, we confirmed that the loss of heterozygosity causes loss of the wild-type allele. Thus, we identified two independent somatic alterations inSMAD4causing biallelic loss ofSMAD4function in the AVM tissue.ConclusionWe identified biallelic loss of function ofSMAD4in a craniofacial AVM, evidence thatSMAD4also follows the two-hit mutation mechanism of HHT-associated vascular malformation pathogenesis.
Smoking-attributable neurological health loss: age-specific burden and health disparities
Authors: Zhao Yingjie , Fei Lu 
Published: February 2025

BackgroundSmoking is a significant risk factor for neurological disorders, yet its global impact on these conditions remains underexplored.MethodsUsing Global Burden of Diseases 2021 data, we analysed trends in age-standardised disability-adjusted life-years (DALYs) and deaths attributable to smoking from 1990 to 2021 for three neurological disorders: stroke, Alzheimer’s disease and other dementias, and Multiple Sclerosis. Socioeconomic disparities were assessed using the lope index of inequality and the relative concentration index. Bayesian age-period-cohort models were employed to forecast smoking-attributable burden through 2050.ResultsBetween 1990 and 2021, annual smoking-attributable DALYs and death rates slightly declined by −1.93% and −1.92%, respectively, but absolute numbers continued to rise, from 26.10 million to 30.18 million DALYs and from 0.93 million to 1.15 million deaths. Older adults (aged 60 and above) experienced the greatest burden, contributing 58.15% of DALYs and 75.57% of deaths in 2021. Smoking-attributable stroke was increasingly concentrated in low sociodemographic index regions, whereas disparities in dementias and multiple sclerosis were more pronounced in socioeconomically advantaged regions, particularly for multiple sclerosis.ConclusionsThis study identified an age-specific burden and widening disparities for neurological disorders attributable to smoking, with older adults disproportionately experiencing an escalating impact. Targeted prevention and equitable healthcare access tailored for older adults are critical to mitigating smoking-attributable neurological health loss.
Time trends of variability in disease activity in systemic lupus erythematosus
Authors: Li Ning , Hoi Alberta , Luo Shue-Fen , Wu Yeong-Jian Jan , Louthrenoo Worawit , Golder Vera , Sockalingam Sargunan , Cho Jiacai , Lateef Aisha , O’Neill Sean , Lau Chak Sing , Hamijoyo Laniyati , Nikpour Mandana , Oon Shereen , Hao Yanjie , Chan Madelynn , Li Zhanguo , Navarra Sandra , Zamora Leonid , Katsumata Yasuhiro , Harigai Masayoshi , Goldblatt Fiona , Bae Sang-Cheol , Zhang Zhuoli , Takeuchi Tsutomu , Kikuchi Jun , Ng Kristine , Tugnet Nicola , Tanaka Yoshiya , Ohkubo Naoaki , Chen Yi-Hsing , Basnayake B M D B , Law Annie , Kumar Sunil , Tee Cherica , Tee Michael Lucas , Choi Jiyoon , Kandane-Rathnayake Rangi , Morand Eric 
Published: February 2025

ObjectiveDisease activity both between and within patients with SLE is highly variable, yet factors driving this variability remain unclear. This study aimed to identify predictors of variability in SLE disease activity over time.MethodsWe analysed data from 2930 patients with SLE across 13 countries, collected over 38 754 clinic visits between 2013 and 2020. Clinic visit records were converted to panel data with 1-year intervals. The time-adjusted mean disease activity, termedAMS, was calculated. The yearly change inAMS, denoted asΔAMSt, was regressed ontoAMSt−1and other potential predictors using random-effects models. Some variables were split into a person-mean component to assess between-patient differences and a demeaned component to assess within-patient variability.ResultsOverall, variability in SLE disease activity exhibited stabilisation over time. A significant inverse relationship emerged between a patient’s disease activity in a given year and variability in disease activity in the subsequent year: a 1-point increase in person-mean disease activity was associated with a 0.27-point decrease (95% CI −0.29 to –0.26, p<0.001) in subsequent variability. Additionally, a 1-point increase in within-patient disease activity variability was associated with a 0.56-point decrease (95% CI −0.57 to –0.55, p<0.001) in the subsequent year. Furthermore, each 1-point increase in the annual average time-adjusted mean Physician Global Assessment was associated with a 0.08-point decrease (90% CI −0.13 to –0.03, p=0.002) in disease activity variability for the following year. Prednisolone dose and the duration of activity in specific organ systems exhibited negative and positive associations, respectively, with disease activity variability in the subsequent year. Patients from less affluent countries displayed greater disease activity variability compared with those from wealthier nations.ConclusionDisease activity tends to be less variable among patients with higher or more variable disease activity in the previous year. Within-patient variability in disease activity has a stronger impact on subsequent fluctuations than differences between individual patients.
Analysis of complications of minimally invasive approaches for symptomatic lumbar spinal stenosis
Authors: Mekhail Nagy , Costandi Shrif , Botros Mina , Mukhdomi Junaid , Yassa Peter , Mukhdomi Taif 
Published: February 2025

IntroductionCurrent treatment modalities of lumbar spinal stenosis range from conservative medical management and physical therapy to open surgical decompression. Minimally invasive lumbar decompression (MILD) and Superion interspinous spacers (SISS) Vertiflex offer the promise of effective pain relief with shorter recovery time and lesser potential complications compared with open surgical decompression procedures and general anesthesia. Despite their increasing utilization, their complication profile is not well established in the literature.MethodsWe searched the FDA’s Manufacturer and User facility Device Experience (MAUDE) database for all entries on MILD product code ‘HRX’ and SISS product code ‘NQO’. MAUDE database was queried from 2010 to 2021. Duplicate entries were removed, and complications were classified based on the event descriptions.ResultsFor the MILD procedure, a total of 10 entries were found in the MAUDE database. Among these, 8 were classified as surgical complications and 2 were device related. On the other hand, a total of 919 reports were found in the MAUDE database for Vertiflex, with 385 medical device reports were included in the analysis. Device-related were the most reported complication, accounting for 189 cases.ConclusionAs with any new intervention, we must proceed with caution and evaluate the procedure performance over time. Such data should aid physicians to make informed decisions before choosing either technique for their patients. The findings from this study provide insight into the complication profile associated with both MILD and Vertiflex procedures, highlighting the need for continued evaluation and careful consideration in clinical decision-making.
Exploring Early Prediction of CKD Using InfNet Segmentation with Cross Domain-Based Few Shot Learning
Authors: Stella A. , Kumari P. Vasanthi 
Published: February 2025

Chronic kidney disease (CKD) is a life-threatening condition which is hard to identify early, as there are no symptoms. It is possible to prevent or minimize the evolution of this chronic condition before it reaches an end stage, where dialysis or surgical intervention is the only way to save the patient’s life. Early detection and adequate therapy can increase the risk of this occurring. The majority of supervised techniques employ labeled datasets to build in-domain predictions of CKD. However, the results are typically poor when a classifier is used to categorize an image of CKD in a different domain after it has been trained on labeled images for that domain. However, a machine learning technique known as “cross-domain few-shot learning” involves training a model to generalize information from one domain to another using only a small number of samples from the target domain. So, a novel hybrid classifier with few shot learning is proposed to improve the cross-domain CKD prediction performance. The kidney’s CT images were collected and preprocessed using ENSNet annotation, autoencoder denoising, green fire blue filter and image restoration. The pre-data were provided for the segmentation process using supervised InfNet segmentation, which segments an exact region of CKD. The segmented regions were fed to an input of the classification process. A few shot learning-based hybrid classifiers were developed to predict CKD in the cross-domain. In a few shot learning, more samples were collected for the training phase, and fewer samples were used for the classifier’s testing. Based on the few shot learning, the proposed CKD model was tested and diagnosed with the input samples at appropriate conditions. The designed proposed model offers 97.9% accuracy, 96.4% precision, 96.4% recall and 98.6% negative predictive value. In addition, observed values of the proposed model were contrasted with some other approaches for validating the process. The proposed few-shot learning-based hybrid classifier is an effective choice for more precise cross-domain CKD prediction at low processing time.
Prevalence of Pulmonary Tuberculosis and Rifampicin Resistance Among Patients Attending Adama Hospital Medical College
Authors: Kumbi Hawi , Abate Alegntaw , Kedir Abdela , Chala Tesfaye , Gemechu Milkesa , Garedew Alemayehu , Ali Musa 
Published: February 2025

Background: Tuberculosis (TB) is among the leading causes of morbidity and mortality in resource‐limited countries. The burden of TB varies from country to country, depending on the country’s condition and the effort made to prevent its transmission. The magnitude of pulmonary TB and drug resistance in eastern Ethiopia is mainly unknown due to limited information.Objective: This study aimed to determine the prevalence of pulmonary TB and rifampicin‐resistant Mycobacterium tuberculosis and factors associated with pulmonary TB.Methods: A hospital‐based prospective cross‐sectional study was conducted among 424 presumptive TB patients who attended Adama Hospital Medical College from January 10, 2023, to November 10, 2023. Sputum (gastric lavage for children) was collected and diagnosed using the Ziehl–Neelsen (ZN) staining method and GeneXpert. A structured questionnaire was used to collect sociodemographic and clinical data. SPSS Version 20 computer software was used for data analysis. A variable with a p value less than 0.05 was considered statistically significant.Results: The prevalence of the ZN staining method and GeneXpert‐confirmed TB was 160 (37.7%), 95% CI: 33–42.7 and 189 (44.6%), 95% CI: 39.8–49.5, respectively. Of the study participants, nine (2.1%) were infected with rifampicin‐resistant M. tuberculosis. Out of the 189 confirmed TB cases, 4.7% were infected with rifampicin‐resistant gene‐positive M. tuberculosis. Gender—male (AOR = 1.47 [0.95–2.26], p = 0.081), history of contact with TB patient (AOR = 7.19 [2.55–20.25], p < 0.001), previously treated TB patients (AOR = 3.11 [1.49–6.50], p = 0.003), and smoking cigarette (AOR = 14.8 [1.88–117], p = 0.010) were significantly associated with GeneXpert‐confirmed pulmonary TB.Conclusion: The prevalence of pulmonary TB was high, with a moderate proportion of rifampicin‐resistant gene‐carrying M. tuberculosis in the study area. Being male, having a history of contact with TB patients, having a history of infection with TB, and smoking cigarettes were significant predictors of pulmonary TB.
ІННОВАЦІЙНІ ТЕХНОЛОГІЇ У ХІРУРГІЧНОМУ ЛІКУВАННІ ОКЛЮЗІЙНО-СТЕНОТИЧНИХ УРАЖЕНЬ АРТЕРІЙ ІНФРАРЕНАЛЬНОГО ВІДДІЛУ АОРТИ
Authors: ШАПРИНСЬКИЙ В. В. 
Published: February 2025

Мета роботи: підвищити ефективність хірургічного лікування оклюзійно-стенотичних уражень магістральних артерій інфраренального відділу аорти у хворих на атеросклероз шляхом диференційованого підходу до використання інноваційних технологій відкритих, ендоваскулярних та гібридних оперативних втручань.
Матеріали і методи. У дослідження увійшло 420 хворих з оклюзійно-стенотичними ураженнями магістральних артерій інфраренального відділу аорти. Пацієнтів поділили на підгрупи за сегментами атеросклеротичного ураження: аорто-здухвинний – 20 (4,76 %), здухвинно-стегновий – 45 (10,72 %), стегново-підколінний – 166 (39,52 %), підколінно-гомілковий – 124 (29,53 %), гомілково-стопний – 65 (15,47 %). Залежно від характеру, оперативного втручання роподілили на: відкриті – 98 (23,33 %), ендоваскулярні – 243 (57,86 %), гібридні – 79 (18,81 %).
Результати. Аналіз ранніх результатів оперативних втручань показав вірогідне зменшення тривалості лікування пацієнтів у стаціонарі з (5,2±0,7) до (1,3±0,6) ліжко-дня, а також повторної госпіталізації у термінах до 12 місяців на 12,5 %, зниження кількості післяопераційних ускладнень із 10,5 до 4,9 %, повторних операцій – з 9,72 до 3,06 %, ампутацій – із 5,4 до 1,84 % і летальності – з 3,89 до 1,84 %. У віддаленому післяопераційному періоді (до 5 років) вдалось підвищити ефективність лікування пацієнтів з оклюзійно-стенотичними ураженнями магістральних артерій (ОСУМА), про що свідчить зменшення кількості післяопераційних ускладнень із 7,87 до 4,39 %, повторних операцій – з 7,87 до 4,39 %, ампутацій – із 3,63 до 2,19 % і летальності – з 3,03 до 1,09 %.
Висновки. Застосування інноваційних технологій при відкритих, ендоваскулярних та гібридних оперативних втручаннях із впровадженням алгоритму лікування на основі індивідуальних анатомічних і гемодинамічних особливостей, удосконалення методів оперативних втручань, застосування 2D-перфузії при оцінці периферійного кровотоку, використання імплантатів, оброблених сироваткою реципієнта перед імплантацією, та ультразвукове дослідження супроводу під час оперативних втручань дали можливість покращити результати лікування пацієнтів з оклюзійно-стенотичними ураженнями магістральних артерій інфраренального відділу аорти.
The Double-Derivative Text
Authors: Zuckier Shlomo 
Published: February 2025

Abstract
A brief Damascus Document passage, CD 2:14–18, utilizes two authoritative corpora simultaneously. This study demonstrates through a close textual analysis that the passage is rewriting or reusing both Proverbs 7:24–27 and 1QS 1:3–9 of Serekh ha-Yahad. It goes on to consider the particular methodological advantages and complications that such a phenomenon offers for understanding rewriting in the Qumran context.
From Pandas to Corals: Assessing the Animal Welfare Impacts of Assisted Reproduction Technologies
Authors: Sims Toni , Franks Becca , Ryan Erin , Sebo Jeff 
Published: February 2025

Abstract
While assisted reproduction is potentially beneficial for wild animals, it also raises significant ethical concerns. In this paper, we consider the welfare effects of assisted reproduction for individual wild animals, considering corals and pandas as case studies. Many (if not all) wild animals are welfare subjects who deserve moral consideration. We emphasize that human interventions in wild animals’ lives, even when made with good intentions, can often have unintended and undermining consequences.
Flame-retardant functionalized boron nitride for epoxy resin with excellent flame retardancy and enhanced thermal conductivity
Authors: Yang Yongze , Lin Liming , Wang Zhengzhou 
Published: February 2025

A flame-retardant functionalized boron nitride (BN@DT) was prepared through the modification of boron nitride (BN) by a reaction product (DT) among 9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO), 4-aminobenzoic acid, and p-phthalaldehyde, and the effect of BN@DT on flame retardancy, thermal conductivity and mechanical properties of epoxy resin (EP) was investigated. The EP composite with 15 wt% BN@DT (EP/15BN@DT) achieves the UL-94 V-0 rating and a limiting oxygen index of 40%. The peak heat release rate, total heat release and total smoke production of EP/15BN@DT are reduced by 36.3%, 31.9% and 38.9%, respectively compared with the ones of pure EP. The thermal conductivity of EP/15BN@DT increases by 148% in comparison with that of pure EP. Moreover, the tensile and impact strengths of EP/15BN@DT are higher than the ones of the EP composite containing 15 wt% unmodified BN. This work provides a promising method for the preparation of the thermally conductive EP composites with excellent flame retardancy.
Prevalence and outcomes of mild stroke patients undergoing reperfusion therapy: A meta-analysis and SAFE recommendations for optimal management
Authors: Rajeswaran Pathmesh , Huasen Bella B. , Stanwell Peter , Killingsworth Murray C. , Bhaskar Sonu M. M. 
Published: February 2025

Background Mild acute ischemic stroke (AIS), characterized by a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less, can lead to significant long-term disabilities. Reperfusion therapies like intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) are commonly used in AIS, but their efficacy and safety in mild stroke cases remain unclear. Objectives This meta-analysis aims to clarify the prevalence of mild AIS and evaluate the outcomes of reperfusion therapy, specifically IVT and EVT, in terms of functional recovery, mortality, stroke recurrence, and adverse events such as symptomatic intracerebral hemorrhage (sICH), intracerebral hemorrhage (ICH), and early neurological deterioration (END). Design A meta-analysis was conducted following PRISMA guidelines to combine and assess the results of independent studies examining the use of reperfusion therapies in patients with mild AIS. Data Sources and Methods A systematic search of PubMed, Embase, and Cochrane databases was performed. Studies assessing mild AIS prevalence and the outcomes of reperfusion therapy were included. Random effects modelling was applied to evaluate associations between reperfusion therapy and clinical outcomes at 90 days. Results Fifty-six studies, including 474 778 patients, were analyzed. The pooled prevalence of mild stroke was 54% among all AIS cases, 29% in IVT-treated patients, and 9% in EVT-treated patients. Reperfusion therapy was associated with significantly increased odds of sICH (OR 2.92), ICH (OR 2.20), and END (OR 2.37). However, no significant association was found with excellent functional outcomes (OR 0.93), good functional outcomes (OR 0.91), mortality (OR 1.14), or stroke recurrence (OR 0.93) at 90 days. Variations were observed between different reperfusion subgroups. Conclusion Mild AIS is prevalent, and reperfusion therapy in these cases is linked to higher rates of adverse events without a clear benefit in functional outcomes or mortality. These findings support the need for selective reperfusion therapy in mild stroke patients. The proposed SAFE framework—Selective use of IVT, Assessment of individual factors, Focus on EVT for large vessel occlusion (LVO), and Establishment of region-specific guidelines—may help guide clinical decisions. Further research should refine patient selection criteria and explore adjunctive therapies.