bluuebunny/crossref_metadata_2025_split huggingface dataset:
Susceptibility to Adrenal Crisis Is Associated With Differences in Cortisol Excretion in Patients With Secondary Adrenal Insufficiency
Authors: Vulto Annet , van Faassen Martijn , Kerstens Michiel N. , van Beek André P. 
Published: April 2022

ObjectiveTo compare cortisol pharmacokinetics and pharmacodynamics mapped through several glucocorticoid sensitive pathways in patients on hydrocortisone substitution with or without an adrenal crisis.DesignA post-hoc analysis of a previously conducted randomized controlled trial in patients with secondary adrenal insufficiency examining the effects of 2 weight-adjusted hydrocortisone doses.MethodsComparisons were primarily made on a hydrocortisone dose of 0.2-0.3 mg/kg/day for plasma cortisol and cortisone, 24-hour urinary steroid profile, the glucocorticoid sensitive tryptophan-kynurenine pathway, the renin-angiotensin-aldosterone system and aspects of quality of life. Variables of interest were also analyzed on the hydrocortisone dose of 0.4-0.6 mg/kg/day.ResultsOut of 52 patients, 9 (17%) experienced at least one adrenal crisis (AC+ group) and 43 did not develop an adrenal crisis (AC- group) during an observation period of 10 years. 24-hour urinary excretion of cortisol and cortisone were lower in the AC+ group (0.05 [IQR 0.03; 0.05] vs. 0.09 [0.05; 0.12] µmol/24h, P=0.01and 0.13 [0.10; 0.23] vs. 0.24 [0.19; 0.38] µmol/24h, P=0.04, respectively). No differences in pharmacokinetics of cortisol were observed. Kynurenine concentrations were higher in the AC+ group (2.64 [2.43; 3.28] vs. 2.23 [1.82; 2.38] µmol/L, P=0.03) as was general fatigue (Z-scores 1.02 [-0.11; 1.42] vs. -0.16 [- 0.80; 0.28], P=0.04). On the higher hydrocortisone dose urinary excretion of cortisol and cortisone was still significantly lower between the AC- and AC + group. The differences in glucocorticoid sensitive variables disappeared.ConclusionPatients susceptible to an adrenal crisis demonstrated differences in cortisol and cortisone excretion as well as in pharmacodynamics when compared to patients who did not experience an adrenal crisis, suggesting a biological predisposition in certain patients for the development of an adrenal crisis.
Body Mass Index Has a Nonlinear Association With Postoperative 30-Day Mortality in Patients Undergoing Craniotomy for Tumors in Men: An Analysis of Data From the ACS NSQIP Database
Authors: Liu Yufei , Hu Haofei , Han Yong , Li Lunzou , Li Zongyang , Zhang Liwei , Luo Zhu , Huang Guodong , Lan Zhan 
Published: April 2022

BackgroundThe association between body mass index (BMI) and mortality is controversial. Thus, the purpose of our research was to survey the association between BMI and postoperative 30-day mortality in brain tumor patients undergoing craniotomy.MethodsThis study analyzed data collected in a multicenter, cross-sectional study that consecutively and nonselectively collected data from a total of 18,642 patients undergoing craniotomy for tumors in the ACS NSQIP from 2012 to 2015. We constructed three linear and non-linear binomial logistic models (the inflection point was set at 18.5) to evaluate the association between BMI and postoperative 30-day mortality, respectively. We also conducted subgroup analyses. Additionally, we compared non-linear models with vs. without interaction with sex.ResultsA total of 17,713 patients were included in this analysis. Of these, 47.38% were male. The postoperative 30-day mortality of the included cases was 2.39% (423/17,713), and the mean BMI was 28.41 ± 6.05 kg/m2. The linear logistic models suggested that after adjusting for the covariates, BMI was not associated with postoperative 30-day mortality (OR=0.999; 95% CI: 0.981, 1.017). The non-linear binomial logistic models suggested a nonlinear relationship between BMI and postoperative 30-day mortality. When BMI was &lt; 18.5, we observed a stronger negative association between them after adjusting for covariates; the OR and 95% CI were 0.719, 0.576-0.896. When BMI was &gt; 18.5, the relationship between them was not significant. We also found that a one-unit decrease in BMI for male patients with BMI &lt; 18.5 kg/m2 was related to a 34.6% increase in the risk of postoperative 30-day mortality (OR=0.654, 95% CI (0.472, 0.907). There was no significant association between them in male patients with BMI &gt; 18.5 kg/m2 or female patients.ConclusionsThis study demonstrates a non-linear relationship between BMI and the risk of postoperative death. Preoperative underweight (BMI &lt; 18.5 kg/m2) would increase the risk of postoperative death in male patients (&gt; 18 years old) undergoing craniotomy for brain tumors. Appropriate nutritional management prior to craniotomy for brain tumors may reduce the risk of postoperative 30-day mortality in underweight men.
Prediction of Fertilization Disorders in the In Vitro Fertilization/Intracytoplasmic Sperm Injection: A Retrospective Study of 106,728 Treatment Cycles
Authors: Tian Tian , Chen Lixue , Yang Rui , Long Xiaoyu , Li Qin , Hao Yongxiu , Kong Fei , Li Rong , Wang Yuanyuan , Qiao Jie 
Published: April 2022

PurposeThis study aimed to develop a risk prediction of fertilization disorders during the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).MethodsA retrospective study was performed with 106,728 fresh embryo IVF/ICSI cycles from 2009 to 2019. Basic characteristics of patients, clinical treatment data, and laboratory parameters were involved. The associations between the selected variables and risks for low fertilization rate (LFR) and total fertilization failure (TFF) were investigated. Ordinal logistic regression and the receiver operating characteristic curves (ROCs) were used to construct and evaluate the prediction models.ResultsA total of 97,181 controls, 4,343 LFR and 5,204 TFF cases were involved in this study. The model based on clinical characteristics (the ages of the couples, women’s BMI, types of infertility, ART failure history, the diminished ovarian reserve, sperm quality, insemination method, and the number of oocytes retrieved) had an AUC of 0.743 for TFF. The laboratory model showed that primary infertility, ART failure history, minimal-stimulation cycle/natural cycle, numbers of oocyte retrieved &lt; 5, IVF, and Anti-Mullerian hormone (AMH) level &lt; 1.1ng/ml are predictors of TFF, with an AUC of 0.742.ConclusionWe established a clinical and a laboratory prediction model for LFR/TFF. Both of the models showed relatively high AUCs.
Single-Cell Transcriptome Analysis Reveals Inter-Tumor Heterogeneity in Bilateral Papillary Thyroid Carcinoma
Authors: Wang Tiantian , Shi Jinyuan , Li Luchuan , Zhou Xiaoming , Zhang Hui , Zhang Xiaofang , Wang Yong , Liu Lian , Sheng Lei 
Published: April 2022

BackgroundThe tumor microenvironment (TME) plays a pivotal role in cancer progression in papillary thyroid carcinoma (PTC), yet the composition and the phenotype of cells within the TME in bilateral PTC are poorly understood.MethodsWe performed unbiased transcriptome-wide single-cell RNA sequencing (scRNA-seq) analysis on 29,561 cells from 3 pairs of bilateral PTC and 1 non-tumor thyroid sample. The results of the analysis were validated by a large-scale bulk transcriptomic dataset deposited in The Cancer Genome Atlas (TCGA) database.ResultsOur integrative analysis of thyroid follicular cells revealed 42 signaling pathways enriched in malignant follicular cells, including cytokine–cytokine receptor interaction, PI3K/Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and tumor necrosis factor (TNF) signaling pathway. A 6-gene signature (CXCL3, CXCL1, IL1A, CCL5, TNFRSF12A, and IL18) in the cytokine–cytokine receptor interaction pathway was constructed to predict the prognosis of patients with PTC, with high risk scores being associated with decreased overall survival [hazard ratio (HR) = 3.863, 95% CI = 2.233−6.682, p &lt; 0.001]. Gene set variation analysis (GSVA) indicated that the pathways enriched in bilateral PTC were significantly different, indicating great heterogeneity in bilateral PTC, even with the same BRAF V600E mutation. Comprehensive analysis of T cells revealed that the proportion of CD8+ tissue-resident memory T cells expressing IFNG decreased in tumor samples with advanced N stage. Within the myeloid compartment, the ratio of suppressive M2-like to pro-inflammatory M1-like macrophages increased with advanced disease stage, which was confirmed in the bulk dataset using transcriptomic profiles. In addition, we also identified numerous biologically critical interactions among myeloid cells, T cells, and follicular cells, which were related to T-cell recruitment, M2-like macrophage polarization, malignant follicular cell progression, and T-cell inhibitory signaling.ConclusionOur integrative analyses revealed great inter-tumor heterogeneity within the TME in bilateral PTC, which will offer assistance for precise diagnosis and treatment.
Seasonal Dynamics and Predilection Sites of Ticks (Acari: Ixodidae) Feeding on Cows in the Western Parts of the Djurdjura, Algeria
Authors: Bedouhene Amina , Kelanemer Rabah , Medrouh Bachir , Kernif Tahar , Saidi Fairouz , Tail Ghania , Ziam Hocine 
Published: April 2022

The present study aimed to determine the phenology and predilection sites of ticks infesting cattle in the western region of Djurdjura (North Algeria) from November 2018 and October 2020. Nineteen cattle farms located in thirteen localities within four provinces were visited monthly for two years. Among the 289 examined cattle, 64.36 ± 2.81% (n=189) were infested by ticks. Of the 10,243 collected ticks, the most abundant tick species was Rhipicephalus bursa (31.57 ± 0.46%), followed by R. annulatus (31.26 ± 0.45%), Hyalomma marginatum (10.67 ± 0.30%), H. lusitanicum (7.02 ± 0.25%), H. excavatum (5.52±%0.22), H. scupense (4.27 ± 0.19%) and H. impeltatum (3.32 ± 0.17%). Ticks of the Hyalomma species were present throughout the year but in a limited number during the winter. H. scupense and H. impletatum showed similar activity from March to October and peaked in April and July, respectively (P&lt;0.001). H. lusitanicum and H. excavatum were active from April to November and both peaked in September and October respectively. Rhipicephalus bursa was collected from April to August and R. annulatus from July to October. R. turanicus was active between April and June. Hyalomma genus had an affinity of attachment for the inguinal region (P&lt;0.001). All parasitic stages of R. annulatus had an affinity for the necks (P&lt;0.001). Nymphs of R. bursa prefer the neck (P&lt;0.001), the adults attach to the perennial and inguinal regions (P&lt;0.001). R. turanicus attach to the ears (P&lt;0.001). As far as we know, this is the first study on the phenology and predilection sites of cattle ticks in the west region of Djurdjura in Algeria.
SLC7A11, a Potential Therapeutic Target Through Induced Ferroptosis in Colon Adenocarcinoma
Authors: Cheng Xin , Wang Yadong , Liu Liangchao , Lv Chenggang , Liu Can , Xu Jingyun 
Published: April 2022

Background: Ferroptosis induced by SLC7A11 has an important translational value in the treatment of cancers. However, the mechanism of SLC7A11 in the pathogenesis of colon adenocarcinoma (COAD) is rarely studied in detail.Methods: SLC7A11 expression was explored with The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases, and Western blot assay. The correlation of SLC7A11 expression with the abundance of infiltrating immune cells was evaluated via the TIMER database. The relation of SLC7A11 expression with immune cell markers was investigated via Gene Expression Profiling Interactive Analysis (GEPIA). The co-expression genes of SLC7A11 were screened by R packages, and the PPI was constructed via the STRING database. SLC7A11 and co-expressed gene modulators were selected by NetworkAnalyst and DSigDB database. The correlations between SLC7A11 and cancer immune characteristics were analyzed via the TIMER and TISIDB databases.Results: SLC7A11 is overexpressed in most tumors, including COAD. The expression level of SLC7A11 has a significant correlation with the infiltration levels of CD8+ T cells, neutrophils, and dendritic cells in COAD. The infiltrated lymphocyte markers of Th1 cell such as TBX21, IL12RB2, IL27RA, STAT1, and IFN-γ were strongly correlated with SLC7A11 expression. Five hub genes co-expressed with SLC7A11 that induce ferroptosis were identified, and mir-335-5p, RELA, and securinine have regulatory effects on it. SLC7A11 was negatively correlated with the expression of chemokines and chemokine receptors, such as CCL17, CCL19, CCL22, CCL23, CXCL14, CCR10, CX3CR1, and CXCR3, in COAD.Conclusion: SLC7A11 may play a role in induced ferroptosis and regulating tumor immunity, which can be considered as potential therapeutic targets in COAD.
ENTT/ENTTR: A Family of Improved Emerging NVM-Based Trojan Triggers and Resets
Authors: Nagarajan Karthikeyan , Khan Mohammad Nasim Imtiaz , Ghosh Swaroop 
Published: April 2022

Hardware Trojans in Integrated Circuits (ICs), that are inserted as hostile modifications in the design phase and/or the fabrication phase, are a security threat since the semiconductor manufacturing process is increasingly becoming globalized. These Trojans are devised to stay hidden during standard structural and functional testing procedures and only activate under pre-determined rare conditions (e.g., after a large number of clock cycles or the assertion of an improbable net). Once triggered, they can deliver malicious payloads (e.g., denial-of-service and information leakage attacks). Current literature identifies a collection of logic Trojans (both trigger circuits and payloads), but minimal research exists on memory Trojans despite their high feasibility. Emerging Non-Volatile Memories (NVMs), such as Resistive RAM (RRAM), have special properties such as non-volatility and gradual drift in bitcell resistance under a pulsing voltage input that make them prime targets to deploy hardware Trojans. In this paper, we present two delay-based and two voltage-based Trojan triggers using emerging NVM (ENTT) by utilizing RRAM’s resistance drift under a pulsing voltage input. Simulations show that ENTTs can be triggered by reading/writing to a specific memory address N times (N could be 2,500–3,500 or a different value for each ENTT design). Since the RRAM is non-volatile, address accesses can be intermittent and therefore stay undetected from system-level techniques that can identify continuous hammering as a possible security threat. We also present three reset techniques to de-activate the triggers. The resulting static/dynamic power overhead and maximum area overhead incurred by the proposed ENTTs are 104.24 μW/0.426 μW and 9.15 μm2, respectively in PTM 65 nm technology. ENTTs are effective against contemporary Trojan detection techniques and system level protocols. We also propose countermeasures to detect ENTT during the test phase and/or prevent fault-injection attacks during deployment.
A Comparison Study of Impulsiveness, Cognitive Function, and P300 Components Between Gamma-Hydroxybutyrate and Heroin-Addicted Patients: Preliminary Findings
Authors: Zeng Tingting , Li Shida , Wu Li , Feng Zuxing , Fan Xinxin , Yuan Jing , Wang Xin , Meng Junyu , Ma Huan , Zeng Guanyong , Kang Chuanyuan , Yang Jianzhong 
Published: April 2022

PurposeThe aim of this study was to investigate and compare impulsiveness, negative emotion, cognitive function, and P300 components among gamma-hydroxybutyrate (GHB)-addicted patients, heroin-dependent patients, and methadone maintenance treatment (MMT) subjects.MethodsA total of 48 men including 17 GHB addicts, 16 heroin addicts, 15 MMT subjects, and 15 male mentally healthy controls (HC) were recruited. All subjects were evaluated for symptoms of depression, anxiety, impulsiveness, and cognitive function through the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder 7-item (GAD-7), the Barratt Impulsiveness Scale version II (BIS-II), the Beijing version of the Montreal Cognitive Assessment (BJ-MoCA), the behavioral test (response time), and event-related potential P300 detection.Results(1) The mean scores of BIS-II in the GHB addiction group, heroin dependence group, and MMT group were significantly higher than those of the HC group (F = 30.339, P = 0.000). (2) The total scores of BJ-MOCA in GHB addiction group was the worst among the four groups, followed by heroin addiction, MMT group and HC group (F = 27.880, P = 0.000). (3) The response time in the GHB addiction group was the longest among the four groups, followed by the heroin addiction, MMT, and HC groups (F = 150.499, P = 0.000). (4) The amplitude and latency of P300 in GHB addiction subjects were significantly lower and longer than those of the MMT group and the HC group. (5) For the three types of addiction, the P300 amplitudes at Fz, Cz, Pz, T5, and T6 were negatively correlated with the scores of GAD-7, PHQ-9, and BIS-II; the P300 latencies were positively correlated with the response time and negatively correlated with the scores of the BJ-MoCA.ConclusionPeople with an addiction were likely to have increased impulsiveness. The cognitive function of the GHB and heroin-addicted subjects, including the heroin detoxification and the MMT groups, was severely impaired, especially for the GHB-addicted patients. The impairment manifested as abnormalities of BJ-MoCA, response time, and P300 components.
Deep Learning for Prediction of Progression and Recurrence in Nonfunctioning Pituitary Macroadenomas: Combination of Clinical and MRI Features
Authors: Chen Yan-Jen , Hsieh Hsun-Ping , Hung Kuo-Chuan , Shih Yun-Ju , Lim Sher-Wei , Kuo Yu-Ting , Chen Jeon-Hor , Ko Ching-Chung 
Published: April 2022

ObjectivesA subset of non-functioning pituitary macroadenomas (NFMAs) may exhibit early progression/recurrence (P/R) after tumor resection. The purpose of this study was to apply deep learning (DL) algorithms for prediction of P/R in NFMAs.MethodsFrom June 2009 to December 2019, 78 patients diagnosed with pathologically confirmed NFMAs, and who had undergone complete preoperative MRI and postoperative MRI follow-up for more than one year, were included. DL classifiers including multi-layer perceptron (MLP) and convolutional neural network (CNN) were used to build predictive models. Categorical and continuous clinical data were fed into the MLP model, and images of preoperative MRI (T2WI and contrast enhanced T1WI) were analyzed by the CNN model. MLP, CNN and multimodal CNN-MLP architectures were performed to predict P/R in NFMAs.ResultsForty-two (42/78, 53.8%) patients exhibited P/R after surgery. The median follow-up time was 42 months, and the median time to P/R was 25 months. As compared with CNN using MRI (accuracy 83%, precision 87%, and AUC 0.84) or MLP using clinical data (accuracy 73%, precision 73%, and AUC 0.73) alone, the multimodal CNN-MLP model using both clinical and MRI features showed the best performance for prediction of P/R in NFMAs, with accuracy 83%, precision 90%, and AUC 0.85.ConclusionsDL architecture incorporating clinical and MRI features performs well to predict P/R in NFMAs. Pending more studies to support the findings, the results of this study may provide valuable information for NFMAs treatment planning.
The Landscape of Immunotherapy Resistance in NSCLC
Authors: Frisone Daniele , Friedlaender Alex , Addeo Alfredo , Tsantoulis Petros 
Published: April 2022

Lung cancer is the leading cause of cancer mortality worldwide. Immunotherapy has demonstrated clinically significant benefit for non-small-cell lung cancer, but innate (primary) or acquired resistance remains a challenge. Criteria for a uniform clinical definition of acquired resistance have been recently proposed in order to harmonize the design of future clinical trials. Several mechanisms of resistance are now well-described, including the lack of tumor antigens, defective antigen presentation, modulation of critical cellular pathways, epigenetic changes, and changes in the tumor microenvironment. Host-related factors, such as the microbiome and the state of immunity, have also been examined. New compounds and treatment strategies are being developed to target these mechanisms with the goal of maximizing the benefit derived from immunotherapy. Here we review the definitions of resistance to immunotherapy, examine its underlying mechanisms and potential corresponding treatment strategies. We focus on recently published clinical trials and trials that are expected to deliver results soon. Finally, we gather insights from recent preclinical discoveries that may translate to clinical application in the future.
Synthetic MRI for Radiotherapy Planning for Brain and Prostate Cancers: Phantom Validation and Patient Evaluation
Authors: Gouel Pierrick , Hapdey Sebastien , Dumouchel Arthur , Gardin Isabelle , Torfeh Eva , Hinault Pauline , Vera Pierre , Thureau Sebastien , Gensanne David 
Published: April 2022

PurposeWe aimed to evaluate the accuracy of T1 and T2 mappings derived from a multispectral pulse sequence (magnetic resonance image compilation, MAGiC®) on 1.5-T MRI and with conventional sequences [gradient echo with variable flip angle (GRE-VFA) and multi-echo spin echo (ME-SE)] compared to the reference values for the purpose of radiotherapy treatment planning.MethodsThe accuracy of T1 and T2 measurements was evaluated with 2 coils [head and neck unit (HNU) and BODY coils] on phantoms using descriptive statistics and Bland–Altman analysis. The reproducibility and repeatability of T1 and T2 measurements were performed on 15 sessions with the HNU coil. The T1 and T2 synthetic sequences obtained by both methods were evaluated according to quality assurance (QA) requirements for radiotherapy. T1 and T2in vivo measurements of the brain or prostate tissues of two groups of five subjects were also compared.ResultsThe phantom results showed good agreement (mean bias, 8.4%) between the two measurement methods for T1 values between 490 and 2,385 ms and T2 values between 25 and 400 ms. MAGiC® gave discordant results for T1 values below 220 ms (bias with the reference values, from 38% to 1,620%). T2 measurements were accurately estimated below 400 ms (mean bias, 8.5%) by both methods. The QA assessments are in agreement with the recommendations of imaging for contouring purposes for radiotherapy planning. On patient data of the brain and prostate, the measurements of T1 and T2 by the two quantitative MRI (qMRI) methods were comparable (max difference, &lt;7%).ConclusionThis study shows that the accuracy, reproducibility, and repeatability of the multispectral pulse sequence (MAGiC®) were compatible with its use for radiotherapy treatment planning in a range of values corresponding to soft tissues. Even validated for brain imaging, MAGiC® could potentially be used for prostate qMRI.