bluuebunny/crossref_metadata_2025_split huggingface dataset:
Administration of granulocyte-macrophage colony-stimulating factor enhanced chimeric antigen receptor T-cell expansion and cellular immunity recovery without inducing cytokine release syndrome
Authors: Jiang Ying , Feng Dan , Wang Chun , Zhang Yanlei , Zhao Chuxian , Li Su , Qin Youwen , Chang Alex H. , Zhu Jun 
Published: November 2022

BackgroundNeutropenia and cytokine release syndrome (CRS) are two major toxicities of chimeric antigen receptor (CAR)-T cell therapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an ideal candidate treatment for neutropenia except for its potential aggravation of CRS. We hypothesized that the optimal timing of supplemental with GM-CSF in a shortage of host immunity and CAR T-cell was chosen as avoidance of CRS. In the study we evaluated the safety and efficacy of GM-CSF intervention post-CAR T-cell therapy while circulating CAR T-cell declined.Materials and methodsNine patients received GM-CSF therapy who displayed moderate neutropenia with absolute neutrophil counts (ANC) &lt; 1,500 cells/mm3 with concomitant declination of circulating CAR T-cell.ResultsThe median duration of GM-CSF intervention was 15 days (4–30). CAR T-cell expansion was observed in peripheral blood (PB) of seven patients (7/9). The median baseline and peak CAR T cells count in PB of the seven patients with CAR T-cell expansion were 0.85 × 106/L (0–50.9) and 6.06 × 106/L (1.43–112.55). And the peaks of CAR T-cell levels in PB appeared in day 7 (2–11) following the initiation of GM-CSF administration with increases of 2.84 × 106/L (0.38–61.65). Also, increased white blood cells in PB were observed in all patients. The median onset and duration time of WBC recovery were 9 (1–14) and 17 (3–53) days. Moreover, the increment of WBC, neutrophil, lymphocyte and CD3-CD16 + CD56 + natural killer cell in PB was observed. In addition, no CRS or fatal infection occurred during GM-CSF treatment.ConclusionThis study provides evidence for the clinical feasibility of combining CAR T-cell therapy with the GM-CSF to treat neutropenia patients with concomitant declination of circulating CAR T-cell.
Antimicrobial resistance and genomic characterization of Salmonella enterica serovar Senftenberg isolates in production animals from the United States
Authors: Srednik Mariela E. , Morningstar-Shaw Brenda R. , Hicks Jessica A. , Mackie Tonya A. , Schlater Linda K. 
Published: November 2022

In the USA, Salmonella enterica subspecies enterica serovar Senftenberg is among the top five serovars isolated from food and the top 11 serovars isolated from clinically ill animals. Human infections are associated with exposure to farm environments or contaminated food. The objective of this study was to characterize S. Senftenberg isolates from production animals by analyzing phenotypic antimicrobial resistance profiles, genomic features and phylogeny.Salmonella Senftenberg isolates (n = 94) from 20 US states were selected from NVSL submissions (2014–2017), tested against 14 antimicrobial drugs, and resistance phenotypes determined. Resistance genotypes were determined using whole genome sequencing analysis with AMRFinder and the NCBI and ResFinder databases with ABRicate. Plasmids were detected using PlasmidFinder. Integrons were detected using IntFinder and manual alignment with reference genes. Multilocus-sequence-typing (MLST) was determined using ABRicate with PubMLST database, and phylogeny was determined using vSNP.Among 94 isolates, 60.6% were resistant to at least one antimicrobial and 39.4% showed multidrug resistance. The most prevalent resistance findings were for streptomycin (44.7%), tetracycline (42.6%), ampicillin (36.2%) and sulfisoxazole (32.9%). The most commonly found antimicrobial resistance genes were aac(6′)-Iaa (100%), aph(3″)-Ib and aph(6)-Id (29.8%) for aminoglycosides, followed by blaTEM-1 (26.6%) for penicillins, sul1 (25.5%) and sul2 (23.4%) for sulfonamides and tetA (23.4%) for tetracyclines. Quinolone-resistant isolates presented mutations in gyrA and/or parC genes. Class 1 integrons were found in 37 isolates. Thirty-six plasmid types were identified among 77.7% of the isolates. Phylogenetic analysis identified two distinct lineages of S. Senftenberg that correlated with the MLST results. Isolates were classified into two distinct sequence types (ST): ST14 (97.9%) and ST 185 (2.1%). The diversity of this serotype suggests multiple introductions into animal populations from outside sources.This study provided antimicrobial susceptibility and genomic characteristics of S. Senftenberg clinical isolates from production animals in the USA during 2014 to 2017. This study will serve as a base for future studies focused on the phenotypic and molecular antimicrobial characterization of S. Senftenberg isolates in animals. Monitoring of antimicrobial resistance to detect emergence of multidrug-resistant strains is critical.
Moderating effect of cognitive reserve on brain integrity and cognitive performance
Authors: Nelson Monica E. , Veal Britney M. , Andel Ross , Martinkova Julie , Veverova Katerina , Horakova Hana , Nedelska Zuzana , Laczó Jan , Vyhnalek Martin , Hort Jakub 
Published: November 2022

BackgroundDementia syndrome is one of the most devastating conditions in older adults. As treatments to stop neurodegeneration become available, accurate and timely diagnosis will increase in importance. One issue is that cognitive performance sometimes does not match the corresponding level of neuropathology, affecting diagnostic accuracy. Cognitive reserve (CR), which can preserve cognitive function despite underlying neuropathology, explains at least some variability in cognitive performance. We examined the influence of CR proxies (education and occupational position) on the relationship between hippocampal or total gray matter volume and cognition.MethodsWe used data from the Czech Brain Aging Study. Participants were clinically confirmed to be without dementia (n = 457, including subjective cognitive decline and amnestic mild cognitive impairment) or with dementia syndrome (n = 113).ResultsFor participants without dementia, higher education magnified the associations between (a) hippocampal volume and executive control (b = 0.09, p = 0.033), (b) total gray matter volume and language (b = 0.12, p &lt; 0.001), and (c) total gray matter volume and memory (b = 0.08, p = 0.018). Similarly, higher occupational position magnified the association between total gray matter volume and (a) attention/working memory (b = 0.09, p = 0.009), (b) language (b = 0.13, p = 0.002), and (c) memory (b = 0.10, p = 0.013). For participants with dementia, the associations between hippocampal (b = –0.26, p = 0.024) and total gray matter (b = –0.28, p = 0.024) volume and visuospatial skills decreased in magnitude with higher education.ConclusionWe found that the association between brain volume and cognitive performance varies based on CR, with greater CR related to a stronger link between brain volume and cognition before, and a weaker link after, dementia diagnosis.
Molar loss further exacerbates 2-VO-induced cognitive impairment associated with the activation of p38MAPK/NFκB pathway
Authors: Lu Yunping , Pang Qian , Wu Qianqian , Luo Bin , Tang Xiaofei , Jiang Qingsong 
Published: November 2022

BackgroundVascular dementia is characterized by reduced cognitive function due to chronic cerebral hypoperfusion and has become a significant public health challenge as the global population ages. Recent studies suggested that molar loss, a common problem among the elderly, may trigger the development of cognitive decline. Our previous study found that the molar loss affected cognitive dysfunction, and the astrocytes in the hippocampus of chronic cerebral ischemia rats were affected, but the underlying mechanism is unclear.MethodsIn this study, we established the animal model of molar loss with 2-VO rats and the Morris water maze was used to test the cognitive ability of rats in each group. The damage to neurons was observed via Nissl staining, and neuronal apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in the hippocampus of the rats. Quantitative Real-Time PCR and immunohistochemistry and histology (IHC) were used to detect the expression of p38MAPK, NFκB, caspase 3, and iNOS in the hippocampus. The astrocytes were detected by IHC and Immunofluorescence analysis for GFAP. After 2-VO MO surgery, rats were administered DMSO or p38MAPK inhibitor (SB203580) by intrathecal injection.ResultsThe Morris water maze test showed that the molar loss aggravated spatial memory learning ability with chronic cerebral ischemia decreased in the rats. The neuronal damage and more apoptotic cells were observed in the hippocampus of 2-VO rats. After the molar loss, the mRNA and protein expression of iNOS, p38MAPK, NFκB, and caspase 3 were further upregulated in 2-VO rats. Molar loss upregulated GFAP expression, and the p38MAPK-positive cells were labeled with the astrocyte marker GFAP. SB203580 reduced cognitive impairment and apoptosis of hippocampal neurons in 2-VO rats following the molar loss.ConclusionMolar loss can aggravate cognitive impairment in 2-VO rats to a certain extent. The mechanism of molar loss exacerbating the cognitive decline in 2-VO rats may be associated with the activation of the p38MAPK-NFκB-caspase 3 signaling pathway, which induces neuronal apoptosis.
PCDH19-related epilepsy in mosaic males: The phenotypic implication of genotype and variant allele frequency
Authors: Chen Yi , Yang Xiaoxu , Chen Jiaoyang , Yang Xiaoling , Yang Ying , Liu Aijie , Zhang Xiaoli , Wu Wenjuan , Sun Dan , Yang Zhixian , Jiang Yuwu , Zhang Yuehua 
Published: November 2022

ObjectiveTo analyze the genotypes and phenotypes of mosaic male patients with PCDH19-related epilepsy (PCDH19-RE) and explore the correlation between genotype, variant allele frequency (VAF), and phenotypic severity.MethodsClinical data and peripheral blood samples of 11 male mosaic patients were collected and analyzed in our study. The VAF of the PCDH19 gene from peripheral blood was quantified using amplicon-based deep sequencing. Additional 20 mosaic male patients with PCDH19-RE were collected from the published literature, with 10 patients whose VAFs of the PCDH19 gene were available for analytic purposes.ResultsIn our cohort of 11 patients, 10 variants were identified, and four were novel. The VAF of the PCDH19 gene from peripheral blood ranged from 27 to 90%. The median seizure onset age was 6 months (range: 4–9 months). Clinical manifestations included cluster seizures (100%), fever sensitivity (73%), focal seizures (91%), developmental delay/intellectual disability (DD/ID, 82%), and autistic features (45%). Thirty-one mosaic male patients collected from our cohort and the literature developed seizures mostly (87%) within one year of age. Variant types included missense variants (42%), truncating variants (52%), splice variants (3%), and whole PCDH19 deletion (3%). Among 21 patients with a definite VAF from our cohort and the literature, nine had a low VAF ( ≤ 50%) and 12 had a high VAF (&gt; 50%). Seventy-five percent of variants from the high VAF group were missense, whereas 89% of those from the low VAF group were truncations. The median seizure onset age was 6 months in the low VAF group and 9 months in the high VAF group (p = 0.018). Forty-four percent (4/9) of patients from the low VAF group achieved seizure-free for ≥1 year, whereas none of the 12 patients from the high VAF group did (p = 0.021). DD/ID was present in 83% (10/12) of the high VAF group and 56% (5/9) of the low VAF group (p = 0.331).ConclusionThe predominant variant types were truncating and missense variants. Missense variants tended to have higher VAFs. Patients with a high VAF were more likely to have a more severe epileptic phenotype. Our findings shed light on the phenotypic implications of VAF in mosaic males with PCDH19-RE.
Analysis of postoperative effects of different semicircular canal surgical technique in patients with labyrinthine fistulas
Authors: Meng Wei , Cai Mingjing , Gao Yanhui , Ji Hongbo , Sun Chuan , Li Guangfei , Wei Yanyan , Chen Yan , Ni Hui , Yan Min , He Shuangba 
Published: November 2022

ObjectiveDifferent semicircular canal surgery techniques have been used to treat patients with labyrinthine fistulas caused by middle ear cholesteatoma. This study evaluated postoperative hearing and vestibular function after various semicircular canal surgeries.Materials and methodsIn group 1, from January 2008 to December 2014, 29 patients with middle ear cholesteatoma complicated by labyrinthine fistulas were treated with surgery involving covering the fistulas with simple fascia. In group 2, from January 2015 to October 2021, 36 patients with middle ear cholesteatoma complicated by labyrinthine fistulas were included. Cholesteatomas on the surface of type I labyrinthine fistulas were cleaned using the “under water technique” and capped with a “sandwich” composed of fascia, bone meal, and fascia. Cholesteatomas on the surface of type II and III fistulas were cleaned using the “under water technique,” and the labyrinthine fistula was plugged with a “pie” composed of fascia, bone meal, and fascia, and then covered with bone wax.ResultsSome patients with labyrinthine fistulas in group 1 exhibited symptoms of vertigo after surgery. In group 2 Patients with type II labyrinthine fistulas experienced short-term vertigo after semicircular canal occlusion, but no cases of vertigo were reported during long-term follow-up. “sandwich.” In patients with type II labyrinthine fistulas, the semicircular canal occlusion influenced postoperative hearing improvement. However, postoperative patient hearing was still superior to preoperative hearing.ConclusionThe surface of type I labyrinthine fistulas should be capped by a “sandwich” composed of fascia, bone meal, and fascia. Type II and III labyrinthine fistulas should be plugged with a “pie” composed of fascia, bone meal, and fascia, covered with bone wax.
Comparison of dural puncture and dural incision in deep brain stimulation surgery: A simple but worthwhile technique modification
Authors: Fan Shiying , Zhang Quan , Meng Fangang , Fang Huaying , Yang Guang , Shi Zhongjie , Liu Huanguang , Zhang Hua , Yang Anchao , Zhang Jianguo , Shi Lin 
Published: November 2022

BackgroundThe accuracy of the deep brain stimulation (DBS) electrode placement is influenced by a myriad of factors, among which pneumocephalus and loss of cerebrospinal fluid that occurs with dural opening during the surgery are considered most important. This study aimed to describe an effective method for decreasing pneumocephalus by comparing its clinical efficacy between the two different methods of opening the dura.Materials and methodsWe retrospectively compared two different methods of opening the dura in 108 patients who underwent bilateral DBS surgery in our center. The dural incision group comprised 125 hemispheres (58 bilateral and 9 unilateral) and the dural puncture group comprised 91 (41 bilateral and 9 unilateral). The volume of intracranial air, dural opening time, intraoperative microelectrode recordings (MERs), postoperative electrode displacement, clinical efficacy, and complications were examined. Spearman correlation analysis was employed to identify factors associated with the volume of intracranial air and postoperative electrode displacement.ResultsThe volume of intracranial air was significantly lower (0.35 cm3 vs. 5.90 cm3) and dural opening time was significantly shorter (11s vs. 35s) in the dural puncture group. The volume of intracranial air positively correlated with dural opening time. During surgery, the sensorimotor area was longer (2.47 ± 1.36 mm vs. 1.92 ± 1.42 mm) and MERs were more stable (81.82% vs. 47.73%) in the dural puncture group. Length of the sensorimotor area correlated negatively with the volume of intracranial air. As intracranial air was absorbed after surgery, significant anterior, lateral, and ventral electrode displacement occurred; the differences between the two groups were significant (total electrode displacement, 1.0mm vs. 1.4mm). Electrode displacement correlated positively with the volume of intracranial air. Clinical efficacy was better in the dural puncture group than the dural incision group (52.37% ± 16.18% vs. 43.93% ± 24.50%), although the difference was not significant.ConclusionOur data support the hypothesis that opening the dura via puncture rather than incision when performing DBS surgery reduces pneumocephalus, shortens dural opening time, enables longer sensorimotor area and more stable MERs, minimizes postoperative electrode displacement, and may permit a better clinical efficacy.
Salvage external beam radiotherapy after HIFU failure in localized prostate cancer: A single institution experience
Authors: Di Lalla Vanessa , Elakshar Sara , Anidjar Maurice , Tolba Marwan , Hassan Toufic , Bahoric Boris , McPherson Victor , Probst Stephan , Niazi Tamim 
Published: November 2022

Purpose/objectivesHigh-intensity focused ultrasound (HIFU) remains investigational as primary treatment for localized prostate cancer but is sometimes offered to select patients. At HIFU failure, data guiding salvage treatment is limited to small retrospective series with short follow-up. We evaluated our institutional experience using salvage radiation therapy (SRT) after HIFU failure.Materials/methodsWe conducted a retrospective analysis of patients with local failure post-HIFU who received salvage image-guided external beam radiation therapy (EBRT) delivered via intensity-modulated radiotherapy (IMRT). Our primary endpoint was biochemical failure-free survival (bFFS) defined as prostate-specific antigen (PSA) nadir + 2 ng/mL. Secondary endpoints included metastasis-free survival (MFS) and overall survival (OS). Endpoints were evaluated using Kaplan-Meier analysis.ResultsFrom 2013 to 2018, 12 out of 96 patients treated with primary HIFU received SRT via conventional or moderate hypofractionation. Median time from HIFU to SRT was 13.5 months. Seven patients had stage migration to high-risk disease at the time of SRT. Mean PSA prior to SRT was 8.2ug/L and mean nadir post-SRT was 1.2ug/L. Acute International Prostate Symptom Score (IPSS) as well as International Index of Erectile Dysfunction (IIEF) scores were similar to baseline (p = 0.5 and 0.1, respectively). Late toxicities were comparable to those reported after primary EBRT for localized prostate cancer. At a median follow-up of 46 months, the OS was 100%. The 5-year bFFS and MFS were both 83.3%.ConclusionsTo our knowledge, we report one of the largest series on contemporary SRT post HIFU failure. We show that SRT is feasible, effective and carries no additional acute or delayed toxicity.
Optimizing the spectrum of high power narrow linewidth fiber amplifier through the same complex degree of coherence
Authors: Lai Wenchang , Ma Pengfei , Song Jiaxin , Ren Shuai , Liu Wei , Zhou Pu 
Published: November 2022

The spectra of narrow linewidth fiber amplifiers are closely related to both the stimulated Brillouin scattering (SBS) threshold in power scaling process and the combining efficiency in coherent beam combining (CBC) system. In this manuscript, the SBS thresholds of fiber amplifier with different spectral distributions (Gaussian, sinc2 and rectangular) have been compared under the same spectral complex degree of coherence (CDC), which could promise the same combining efficiency in CBC system. A SBS dynamic model is established to analyze the SBS process in fiber amplifier and a comparing experiment is also performed by measuring the SBS thresholds of different spectra that have the same CDC set to be 0.96. The FWHM linewidths of Gaussian, sinc2 and rectangular spectra are adjusted to be 1.1 GHz, 0.5 GHz and 1.06 GHz, respectively. The corresponding SBS thresholds are measured to be 108 W, 77 W, and 135 W. By contrast, the rectangular spectra could have most excellent capacity on improving SBS threshold in fiber amplifier under the same combining efficiency in CBC system. Overall, it could provide a feasible method on spectra designing in high power narrow linewidth fiber amplifiers used in CBC system.
Could cardiac autonomic modulation be an objective method to identify hypobaric hypoxia symptoms at 25.000ft among Brazilian military airmen?
Authors: Honorato Fernando Sousa , Deus Lysleine Alves de , Reis Andrea Lucena , Neves Rodrigo Vanerson Passos , Corrêa Hugo de Luca , Medeiros Ana Paola Brasil , Haberland Débora Fernanda , Medeiros Radamés Maciel Vitor , Prestes Jonato , Ferreira Carlos Ernesto Santos , Rosa Thiago Santos 
Published: November 2022

Hypobaric hypoxia during a flight can cause accidents, resulting in deaths. Heart rate variability may be more sensitive than self-reported hypoxia symptoms to the effects of HH. The level of physical fitness can contribute to efficient cardiac autonomic modulation. However, no studies have examined the association between fitness, heart rate variability, and the time of onset of hypobaric hypoxia symptoms. To analyze the influence of hypobaric hypoxia on cardiac autonomic function at the time of onset of the first symptoms and its association with physical fitness. Male airmen trained and belonging to the staff of the Brazilian Air Force (n = 23; 30 ± 6.7 years) participated in a flight simulation in a 25.000 ft hypobaric chamber. Heart rate variability was recorded with a Polar® cardiac monitor. Data were analyzed in the time-domain method using Kubios software. We evaluated pulse oximetry with the Mindray PM-60 oximeter. Physical fitness assessment test results were collected from the archive. At moments rest vs. hypoxia revealed a decrease in heart rate variability indices iRR and RMSSD (p &lt; 0.001). The individual analysis of hypoxia-rest variation showed that 100% of the airmen had a negative delta for both iRR and RMSSD indices. The time of onset of hypoxia symptoms was not associated with body composition, physical fitness, oxygen saturation, and HRV indices. Also, we suggest that cardiac autonomic modulation seems to be more sensitive to the effects of hypobaric hypoxia at 25.000 ft than the self-reported subjective perception of symptoms. Further devices that alert to a hypoxic condition during a flight should consider heart rate variability allowing more time and security to reestablish control of the flight.