bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular vesicles derived from immortalized human natural killer cell line NK3.3 as a novel therapeutic for multiple myeloma
Authors: Matchett Emily C. , Kornbluth Jacki 
Published: September 2023

IntroductionOver the last decade, there have been many advancements in the therapeutic treatment of multiple myeloma (MM), including the use of natural killer (NK) cells. However, despite promising results from clinical trials, there are concerns over the use of NK cell-based therapy. Cells often undergo growth arrest, limiting their experimental utility; donor cells are extremely heterogeneous, resulting in content variability; and patients receiving allogeneic cells are at risk for graft-versus-host disease and/or cytokine release syndrome. Extracellular vesicles (EVs) have emerged as a new natural therapeutic tool. EVs are known to carry cargo derived from the parent cell from which they originate. NK cells play an important role in the innate immune system, targeting and killing tumor cells. This has led many researchers to isolate EVs from NK cells for their cytotoxic potential.MethodsIn this study, we isolated EVs from the NK cell line, NK3.3, which was derived from the peripheral blood of a healthy donor. Currently, it is the only normal human NK cell line reported with all the functional characteristics of healthy NK cells. To address the issue of growth arrest, we immortalized NK3.3 cells with lentivirus encoding the catalytic subunit of human telomerase htert (NK3.3-LTV). EVs from these cells were isolated using a modified polyethylene glycol (PEG)-acetate precipitation protocol to simplify processing and increase EV yield.Results and conclusionsWe demonstrated that NK3.3-LTV EVs target both sensitive and drug-resistant MM cell lines as well as primary patient MM cells in vitro, decreasing proliferation and inducing apoptotic cell death as well as or better than EVs from non-immortalized cells with no toxicity towards normal cells. This study is the first step towards developing an immunotherapeutic product designed to treat patients with relapsed/refractory MM.
Real-world outcomes of immunotherapy-based neoadjuvant therapy in resectable non-small cell lung cancer
Authors: Shen Jie , Gu Linping , Qi Yuwen , Yao Yaxian , Lu Shun , Chen Zhiwei 
Published: September 2023

ObjectivesRecent clinical studies have demonstrated that immunotherapy-based neoadjuvant therapy have promising effectiveness for patients with resectable non-small cell lung cancer (NSCLC) in terms of pathologic response. Therefore, we performed this study to investigate whether immunotherapy-based neoadjuvant therapy is effective and safe for patients with resectable NSCLC.Materials and methodsThis open-label observational two-arm clinical study was performed at Shanghai Chest Hospital in China with patients who had resectable NSCLC and received two to three cycles of immunotherapy-based neoadjuvant therapy or neoadjuvant chemotherapy alone, followed by surgical resection. The primary endpoint was a major pathologic response (MPR). The secondary endpoints include a complete pathological response (pCR), a radiologic response to neoadjuvant therapy (TRR), event-free survival (EFS), and overall survival (OS).ResultsA total of 51 patients was included in this clinical study, of which 31 patients received immunotherapy-based neoadjuvant therapy and 20 patients received neoadjuvant chemotherapy alone. The percentage of patients achieving a major pathologic response was 41.9% with immunotherapy-based neoadjuvant therapy and 15.0% (95% CI, 0.008 to 0.468; P = 0.043) with neoadjuvant chemotherapy alone. The percentage of patients with pathologic complete response was 19.4% in the immunotherapy-based group and 5% (95% CI, -0.069 to 0.318; P = 0.223) in the chemotherapy group. The radiographic response rate was 71% after immunotherapy-based neoadjuvant therapy and 60% (95% CI, -0.143 to 0.359; P = 0.417) after neoadjuvant chemotherapy. At a median follow-up of 28 months, the median EFS and OS endpoints were not reached.ConclusionsNeoadjuvant immunotherapy offers a considerable advantage over chemotherapy alone for resectable NSCLC in terms of the major pathologic response. Moreover, it did not enhance the risk of adverse events or hinder surgical resection.
Effects of duration of long-acting GnRH agonist downregulation on assisted reproductive technology outcomes in patients with adenomyosis: a retrospective cohort study
Authors: Li Yexing , Ge Li , Yang Xiaohe , Cui Linlin , Chen Zi-Jiang 
Published: September 2023

ObjectivesTo elucidate the relationship between long-acting GnRH agonist (GnRHa) downregulation and assisted reproductive technology (ART) outcomes and identify the optimal duration of downregulation in patients with adenomyosis.DesignRetrospective cohort study.ParticipantsThe study was designed to evaluate ART outcomes in adenomyosis patients with and without GnRHa downregulation between January 2016 and December 2020. A total of 374 patients with adenomyosis (621 cycles) were included with 281 cycles in downregulation group versus 340 cycles in non-downregulation group. After 1:1 propensity score matching (PSM), a sample size of 272 cycles in each group was matched. The matched downregulation group was further divided into 1-month (147 cycles), 2-months (72 cycles), and ≥3 months downregulation (53 cycles) subgroups. Stratification analysis was conducted on pregnancy outcomes in 239 fresh embryo transfer (ET) cycles and 305 frozen embryo transfer (FET) cycles.ResultsThe downregulation group had larger mean diameter of initial uterus and higher proportion of severer dysmenorrhea compared to non-downregulation group. The pregnancy-related parameters in GnRHa downregulation group were similar to those in non-downregulation group, except for higher late miscarriage rate (MR) (13.4% vs. 3.1%, P = 0.003). The subgroup comparisons in fresh ET cycles indicated that implantation rate (75.0% vs. 39.2%, P = 0.002), biochemical pregnancy rate (91.7% vs. 56.0%, P = 0.036) and clinical pregnancy rate (83.3% vs. 47.0%, P = 0.016) could be improved by prolonged GnRHa downregulation (≥3 months), whereas late MR was difficult to be reversed (30.0% vs. 3.2%, P = 0.017). In FET cycles, higher MR (53.6% vs. 29.9%, P = 0.029; 58.8% vs. 29.9%, P = 0.026) and lower live birth rate (18.8% vs. 34.1%, P = 0.023; 17.1% vs. 34.1%, P = 0.037) were observed in the 1-month and ≥3 months downregulation group, while no differences were found in the 2-months downregulation group compared to the non-downregulation group.ConclusionIn patients with severer adenomyosis, long-acting GnRHa downregulation might be correlated with improved ART outcomes. In fresh ET cycles, prolonged downregulation (≥3 months) might be beneficial to improve live birth rate, which needed to be verified by further study with larger sample. In FET cycles, the optimal duration of downregulation was not certain and still needed further exploration.
Dynamic changes of rumen bacteria and their fermentative ability in high-producing dairy cows during the late perinatal period
Authors: Mao Yongxia , Wang Feifei , Kong Weiyi , Wang Ruiling , Liu Xin , Ding Hui , Ma Yun , Guo Yansheng 
Published: September 2023

BackgroundHigh-producing dairy cows face varying degrees of metabolic stress and challenges during the late perinatal period, resulting in ruminal bacteria abundance and their fermentative ability occurring as a series of changes. However, the dynamic changes are still not clear.Aims/methodsTen healthy, high-producing Holstein dairy cows with similar body conditions and the same parity were selected, and ruminal fluid from the dairy cows at postpartum 0, 7, 14, and 21 d was collected before morning feeding. 16S rRNA high-throughput sequencing, GC-MS/MS targeted metabolomics, and UPLC-MS/MS untargeted metabolomics were applied in the study to investigate the dynamic changes within 21 d postpartum.ResultsThe results displayed that the structures of ruminal bacteria were significantly altered from 0 to 7 d postpartum (R = 0.486, P = 0.002), reflecting the significantly declining abundances of Euryarchaeota and Chloroflexi phyla and Christensenellaceae, Methanobrevibacter, and Flexilinea genera (P &lt; 0.05) and the obviously ascending abundances of Ruminococcaceae, Moryella, Pseudobutyrivibrio, and Prevotellaceae genera at 7 d postpartum (P &lt; 0.05). The structures of ruminal bacteria also varied significantly from 7 to 14 d postpartum (R = 0.125, P = 0.022), reflecting the reducing abundances of Christensenellaceae, Ruminococcaceae, and Moryella genera (P &lt; 0.05), and the elevating abundances of Sharpea and Olsenella genera at 14 d postpartum (P &lt; 0.05). The metabolic profiles of ruminal SCFAs were obviously varied from 0 to 7 d postpartum, resulting in higher levels of propionic acid, butyric acid, and valeric acid at 7 d postpartum (P &lt; 0.05); the metabolic profiles of other ruminal metabolites were significantly shifted from 0 to 7 d postpartum, with 27 significantly elevated metabolites and 35 apparently reduced metabolites (P &lt; 0.05). The correlation analysis indicated that propionic acid was positively correlated with Prevotellaceae and Ruminococcaceae (P &lt; 0.05), negatively correlated with Methanobrevibacter (P &lt; 0.01); butyric acid was positively associated with Prevotellaceae, Ruminococcaceae, and Pseudobutyrivibrio (P &lt; 0.05), negatively associated with Christensenellaceae (P &lt; 0.01); valeric acid was positively linked with Prevotellaceae and Ruminococcaceae (P &lt; 0.05); pyridoxal was positively correlated with Flexilinea and Methanobrevibacter (P &lt; 0.05) and negatively correlated with Ruminococcaceae (P &lt; 0.01); tyramine was negatively linked with Ruminococcaceae (P &lt; 0.01).ConclusionThe findings contribute to the decision of nutritional management and prevention of metabolic diseases in high-producing dairy cows during the late perinatal period.
Endoscopic transorbital resection of the temporal lobe: anatomic qualitative and quantitative study
Authors: De Rosa Andrea , Mosteiro Alejandra , Guizzardi Giulia , Roldán Pedro , Torales Jorge , Matas Fassi Jessica , Cavallo Luigi Maria , Solari Domenico , Prats-Galino Alberto , Di Somma Alberto , Enseñat Joaquim 
Published: September 2023

ObjectiveStarting from an anatomic study describing the possibility of reaching the temporal region through an endoscopic transorbital approach, many clinical reports have now demonstrated the applicability of this strategy when dealing with intra-axial lesions. The study aimed to provide both a qualitative anatomic description of the temporal region, as seen through a transorbital perspective, and a quantitative analysis of the amount of temporal lobe resection achievable via this route.Material and methodsA total of four cadaveric heads (eight sides) were dissected at the Laboratory of Surgical Neuroanatomy (LSNA) of the University of Barcelona, Spain. A stepwise description of the resection of the temporal lobe through a transorbital perspective is provided. Qualitative anatomical descriptions and quantitative analysis of the amount of the resection were evaluated by means of pre- and post-dissection CT and MRI scans, and three-dimensional reconstructions were made by means of BrainLab®Software.ResultsThe transorbital route gives easy access to the temporal region, without the need for extensive bone removal. The resection of the temporal lobe proceeded in a subpial fashion, mimicking what happens in a surgical scenario. According to our quantitative analysis, the mean volume removed was 51.26%, with the most superior and lateral portion of the temporal lobe being the most difficult to reach.ConclusionThis anatomic study provides qualitative and quantitative details about the resection of the temporal lobe via an endoscopic transorbital approach. Our results showed that the resection of more than half of the temporal lobe is possible through this surgical corridor. While the anterior, inferior, and mesial portions of the temporal lobe were easily accessible, the most superior and lateral segment was more difficult to reach and resect. Our study serves as an integration to the current anatomic knowledge and clinical practice knowledge highlighting and also as a starting point for further anatomic studies addressing more selected segments of the temporal lobe, i.e., the mesial temporal region.
Hypometabolic patterns of focal cortical dysplasia in PET-MRI co-registration imaging: a retrospective evaluation in a series of 83 patients
Authors: Wang Xiu , Hu Wenhan , Shao Xiaoqiu , Zheng Zhong , Ai Lin , Sang Lin , Zhang Chao , Zhang Jian-guo , Zhang Kai 
Published: September 2023

ObjectiveTo characterize the PET-MRI co-registration of hypometabolic patterns in focal cortical dysplasia (FCD) types I and II and provide some suggestions in presurgical evaluation of epilepsy surgery.MethodsWe retrospectively analyzed PET-MRI co-registration imaging data from a cohort of 83 epilepsy patients with histologically confirmed FCD types I and II. Hypometabolic patterns were classified into 4 types: bottom of sulcus hypometabolism (BOSH), single island of sulcus hypometabolism (SIOS), single gyrus or sulcus hypometabolism (SGOS), and multiple gyri and sulci hypometabolism (MGOS).ResultsMost of cases that were overlooked by conventional MRI and PET evaluation but positive in PET-MRI co-registration were focalized lesions in dorsolateral frontal lobe (9/15) and FCD type IIa was the most prevalent pathological type (11/15). The FCD histological types (p = 0.027) and locations (p &lt; 0.001) were independent predictors of PET-MRI co-registration hypometabolic patterns. Focalized hypometabolic patterns (BOSH, SIOS, SGOS) were primarily observed in the frontal lobe (33/39) and FCD type II (43/62) and extensive pattern (MGOS) in temporal lobe (18/20) and FCD type I (16/21; p &lt; 0.005).ConclusionPET-MRI co-registration enhanced the detection of FCD type IIa compared with conventional MRI and PET reading. The hypometabolic patterns of FCD type I and temporal lobe FCD were more extensive than those of FCD type II and frontal lobe FCD, respectively. The predilection of focalized hypometabolic patterns in frontal lobe FCD suggested that subtle lesions should be checked carefully in patients with suspected frontal lobe epilepsy.
The efficacy and safety of different systemic combination therapies on advanced hepatocellular carcinoma: a systematic review and meta-analysis
Authors: Li Ping , Hu Ming , Liu Mei , Ren Xiangyu , Liu Donghong , Liu Jiluo , Yin Jianhua , Tan Xiaojie , Cao Guangwen 
Published: September 2023

Background and aimsSystemic combinations have recently brought significant therapeutic benefits for advanced hepatocellular carcinoma (aHCC). To design the most effective combination regimens, a systematic review (PROSPERO ID: CRD42022321949) was conducted to evaluate the efficacy and safety of systemic combinations on aHCC.MethodsWe retrieved all the studies from PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and China National Knowledge Infrastructure (CNKI) using the Medical Subject Headings (MeSH) terms until December 21, 2022. The effect indicators (hazard ratio [HR], relative risk [RR], and median) were pooled by a fixed- or random-effects model. A subgroup analysis was conducted according to types and specific therapies.ResultsIn total, 88 eligible studies were selected from 7249 potential records. Each kind of combination treatment (chemotherapy plus chemotherapy, targeted plus immune checkpoint inhibitor (ICI) therapy, targeted plus chemotherapy, and targeted plus targeted therapy) had a better objective response rate (ORR) in patients with aHCC, compared to the monotherapy mostly with sorafenib (RR: 1.57 [1.44–1.71]; I2 = 30%). Of those, targeted plus ICI therapy showed better therapeutic efficiency in overall survival (median: 15.02 [12.67–17.38]), progression-free survival (median: 7.08 [6.42–7.74]), and ORR (RR: 1.81 [1.55–2.13]), compared to the monotherapy. Specifically, Atezo plus Beva showed all those benefits. Our pooled result showed all the combinations had increased ≥3 Grade treatment-related adverse events (TrAEs), with an RR of 1.25 [95% CI: 1.15–1.36], compared to the monotherapy.ConclusionThe systemic combinations, especially targeted plus ICI therapy, including Atezo plus Beva, significantly improve clinical outcomes but increase side effects in patients with aHCC. Future trials should concentrate on improvement in therapeutic efficiency and reduction of toxicity of targeted plus ICI therapy.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022321949.
Ustekinumab trough levels in children with Crohn’s disease refractory to anti-tumor necrosis factor agents: a prospective case series of off-label use
Authors: Bouhuys Marleen , Mian Paola , van Rheenen Patrick F. 
Published: September 2023

Background: Ustekinumab is used off-label in pediatric Crohn’s disease refractory to anti-tumor necrosis factor. Data on optimal dosing, target trough levels, and potential benefit of therapeutic drug monitoring in children treated with ustekinumab are limited.Materials and Methods: We describe a series of six adolescents who consented to be treated with ustekinumab. We measured their trough levels, C-reactive protein, and fecal calprotectin before every administration.Results: Standard adult dosing was effective to achieve biochemical remission (fecal calprotectin &lt; 250 mg/kg) in one patient and clinical remission (resolution of symptoms) in another. The other four patients failed to respond on standard dosing and underwent intravenous re-induction and interval shortening to increase ustekinumab trough levels. This resulted in biochemical remission in one patient and clinical remission in another, suggesting an exposure–response relationship. The remaining two patients had no therapeutic benefit, and ustekinumab was discontinued.Conclusion: In this report, we show that ustekinumab can induce remission in pediatric patients with anti-tumor necrosis factor refractory Crohn’s disease. It is worth escalating the dose before abandoning the drug as ineffective. Prospective studies in children are needed to determine long-term efficacy of ustekinumab, usefulness of therapeutic drug monitoring strategies, and, if applicable, optimal target trough levels.
Analysis of drug resistance in pulmonary tuberculosis patients with positive sputum tuberculosis culture in Northeast China
Authors: Sichen Li , Rui Wang , Yue Yang , Xin Liu , Youbin Cui , Ze Tang , Hongfei Cai 
Published: September 2023

Objective: The objective of this study is to determine the drug resistance status of pulmonary tuberculosis patients in Jilin Province.Methods: A retrospective survey was conducted on 395 sputum culture TB-positive patients admitted to the tuberculosis hospital in Jilin Province in 2019. Sputum samples were cultured in acidic Roche medium. Drug sensitivity testing was conducted using the proportional method. Sensitivity was reported if the percentage of drug resistance was less than 1%, and resistance was reported if the percentage was ≥1%. Statistical analysis was performed using SPSS 22.0.Results: 395 tuberculosis patients with positive sputum tuberculosis culture were included in the study, with 102 being initially treated and 293 being retreated. The study population consisted of 283 males and 112 females. Sex, age, nationality, occupation, marital status, diabetes comorbidity, initial treatment, normal health status, BCG vaccine vaccination, smoking, and alcohol consumption were considered as factors that may affect the rate of multidrug resistance. And only the history of treatment (initial treatment) was associated with multidrug resistance (p = 0.032). This indicates that retreatment is the most significant risk factor for the occurrence of multidrug resistance in tuberculosis. The multidrug resistance rate in retreated patients is 3.764 times higher than that in initially treated patients.Conclusion: The prevalence of multidrug-resistant is higher in retreated patients compared to initially treated patients in the study population. Multidrug resistance is only associated with the treatment history (initial retreatment) and not with other factors.
Dense attention network identifies EEG abnormalities during working memory performance of patients with schizophrenia
Authors: Perellón-Alfonso Ruben , Oblak Aleš , Kuclar Matija , Škrlj Blaž , Pileckyte Indre , Škodlar Borut , Pregelj Peter , Abellaneda-Pérez Kilian , Bartrés-Faz David , Repovš Grega , Bon Jurij 
Published: September 2023

IntroductionPatients with schizophrenia typically exhibit deficits in working memory (WM) associated with abnormalities in brain activity. Alterations in the encoding, maintenance and retrieval phases of sequential WM tasks are well established. However, due to the heterogeneity of symptoms and complexity of its neurophysiological underpinnings, differential diagnosis remains a challenge. We conducted an electroencephalographic (EEG) study during a visual WM task in fifteen schizophrenia patients and fifteen healthy controls. We hypothesized that EEG abnormalities during the task could be identified, and patients successfully classified by an interpretable machine learning algorithm.MethodsWe tested a custom dense attention network (DAN) machine learning model to discriminate patients from control subjects and compared its performance with simpler and more commonly used machine learning models. Additionally, we analyzed behavioral performance, event-related EEG potentials, and time-frequency representations of the evoked responses to further characterize abnormalities in patients during WM.ResultsThe DAN model was significantly accurate in discriminating patients from healthy controls, ACC = 0.69, SD = 0.05. There were no significant differences between groups, conditions, or their interaction in behavioral performance or event-related potentials. However, patients showed significantly lower alpha suppression in the task preparation, memory encoding, maintenance, and retrieval phases F(1,28) = 5.93, p = 0.022, η2 = 0.149. Further analysis revealed that the two highest peaks in the attention value vector of the DAN model overlapped in time with the preparation and memory retrieval phases, as well as with two of the four significant time-frequency ROIs.DiscussionThese results highlight the potential utility of interpretable machine learning algorithms as an aid in diagnosis of schizophrenia and other psychiatric disorders presenting oscillatory abnormalities.