bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural Effusion
Authors: Li Xinying , Wu Guannan , Chen Cen , Zhao Yuan , Zhu Suhua , Song Xincui , Yin Jie , Lv Tangfeng , Song Yong 
Published: December 2021

BackgroundMalignant tumors accompanied with malignant pleural effusion (MPE) often indicate poor prognosis. The therapeutic effect and mechanism of intrapleural injection of anti-programmed cell death protein 1 (PD1) on MPE need to be explored.MethodsA preclinical MPE mouse model and a small clinical study were used to evaluate the effect of intrapleural injection of anti-PD1 antibody. The role of immune cells was observedviaflow cytometry, RNA-sequencing, quantitative PCR, western blot, immunohistochemistry, and other experimental methods.ResultsIntrathoracic injection of anti-PD1 monoclonal antibody (mAb) has significantly prolonged the survival time of mice (P = 0.0098) and reduced the amount of effusion (P = 0.003) and the number of cancer nodules (P = 0.0043). Local CD8+ T cells participated in intrapleural administration of anti-PD1 mAb. The proportion of CD69+, IFN-γ+, and granzyme B+ CD8+ T cells in the pleural cavity was increased, and the expression of TNF-α and IL-1β in MPE also developed significantly after injection. Local injection promoted activation of the CCL20/CCR6 pathway in the tumor microenvironment and further elevated the expression of several molecules related to lymphocyte activation. Clinically, the control rate of intrathoracic injection of sintilimab (a human anti-PD1 mAb) for 10 weeks in NSCLC patients with MPE was 66.7%. Local injection improved the activity and function of patients’ local cytotoxic T cells (CTLs).ConclusionsIntrapleural injection of anti-PD1 mAb could control malignant pleural effusion and the growth of cancer, which may be achieved by enhancing local CTL activity and cytotoxicity.
Impact of Comorbidities on Beneficial Effect of Lactated Ringers vs. Saline in Sepsis Patients
Authors: Tseng Chien-Hua , Chen Tzu-Tao , Chan Ming-Cheng , Chen Kuan-Yuan , Wu Sheng-Ming , Shih Ming-Chieh , Tu Yu-Kang 
Published: December 2021

Background: Lactated Ringers reduced mortality more than saline in sepsis patients but increased mortality more than saline in traumatic brain injury patients.Method: This prospective cohort study was conducted in a medical intensive care unit (ICU) in central Taiwan. We applied standard sepsis evaluation protocol and identified heart, lung, liver, kidney, and endocrine comorbidities. We also evaluated resuscitation response with central venous pressure, central venous oxygen saturation, and serum lactate level simultaneously. Propensity-score matching and Cox regression were used to estimate mortality. The competing risk model compared the lengths of hospital stays with the subdistribution hazard ratio (SHR).Results: Overall, 938 patients were included in the analysis. The lactated Ringers group had a lower mortality rate (adjusted hazard ratio, 0.59; 95% CI 0.43-0.81) and shorter lengths of hospital stay (SHR, 1.39; 95% C.I. 1.15-1.67) than the saline group; the differences were greater in patients with chronic pulmonary disease and small and non-significant in those with chronic kidney disease, moderate to severe liver disease and cerebral vascular disease. The resuscitation efficacy was the same between fluid types, but serum lactate levels were significantly higher in the lactated Ringers group than in the saline group (0.12 mg/dl/h; 95% C.I.: 0.03, 0.21), especially in chronic liver disease patients. Compared to the saline group, the lactated Ringers group achieved target glucose level earlier in both diabetes and non-diabetes patients.Conclusion: Lactate Ringer's solution provides greater benefits to patients with chronic pulmonary disease than to those with chronic kidney disease, or with moderate to severe liver disease. Comorbidities are important in choosing resuscitation fluid types.
The Effect of Dexmedetomidine as a Sedative Agent for Mechanically Ventilated Patients With Sepsis: A Systematic Review and Meta-Analysis
Authors: Wang Caimu , Chen Qijiang , Wang Ping , Jin Weisheng , Zhong Chao , Ge Zisheng , Xu Kangmin 
Published: December 2021

Purpose: Dexmedetomidine has been shown to improve clinical outcomes in critically ill patients. However, its effect on septic patients remains controversial. Therefore, the purpose of this meta-analysis was to assess the effect of dexmedetomidine as a sedative agent for mechanically ventilated patients with sepsis.Methods: We searched PubMed, Embase, Scopus, and Cochrane Library from inception through May 2021 for randomized controlled trials that enrolled mechanically ventilated, adult septic patients comparing dexmedetomidine with other sedatives or placebo.Results: A total of nine studies involving 1,134 patients were included in our meta-analysis. The overall mortality (RR 0.97, 95%CI 0.82 to 1.13, P = 0.67, I2 = 25%), length of intensive care unit stay (MD −1.12, 95%CI −2.89 to 0.64, P = 0.21, I2 = 71%), incidence of delirium (RR 0.95, 95%CI 0.72 to 1.25, P = 0.70, I2 = 0%), and delirium free days (MD 1.76, 95%CI –0.94 to 4.47, P = 0.20, I2 = 80%) were not significantly different between dexmedetomidine and other sedative agents. Alternatively, the use of dexmedetomidine was associated with a significant reduction in the duration of mechanical ventilation (MD –0.53, 95%CI −0.85 to −0.21, P = 0.001, I2 = 0%) and inflammatory response (TNF-α: MD −5.27, 95%CI −7.99 to −2.54, P&lt;0.001, I2 = 0%; IL-1β: MD −1.25, 95%CI −1.91 to –0.59, P&lt;0.001, I2 = 0%).Conclusions: For patients with sepsis, the use of dexmedetomidine as compared with other sedative agents does not affect all-cause mortality, length of intensive care unit stay, the incidence of delirium, and delirium-free days. But the dexmedetomidine was associated with the reduced duration of mechanical ventilation and inflammatory response.
Cellular ATP Levels Determine the Stability of a Nucleotide Kinase
Authors: Brylski Oliver , Shrestha Puja , Gnutt Patricia , Gnutt David , Mueller Jonathan Wolf , Ebbinghaus Simon 
Published: December 2021

The energy currency of the cell ATP, is used by kinases to drive key cellular processes. However, the connection of cellular ATP abundance and protein stability is still under investigation. Using Fast Relaxation Imaging paired with alanine scanning and ATP depletion experiments, we study the nucleotide kinase (APSK) domain of 3′-phosphoadenosine-5′-phosphosulfate (PAPS) synthase, a marginally stable protein. Here, we show that the in-cell stability of the APSK is determined by ligand binding and directly connected to cellular ATP levels. The observed protein stability change for different ligand-bound states or under ATP-depleted conditions ranges from ΔGf0 = -10.7 to +13.8 kJ/mol, which is remarkable since it exceeds changes measured previously, for example upon osmotic pressure, cellular stress or differentiation. The results have implications for protein stability during the catalytic cycle of APS kinase and suggest that the cellular ATP level functions as a global regulator of kinase activity.
Basilar Artery Dolichosis Increases the Risk of Long–Term Recurrence in Patients With Pontine Infarction: A Prospective Cohort Study
Authors: Cao Shugang , Zhu Xiaoxia , Wu Qian , Ni Xiaoxing , He Jun , Cui Ping , Ge Tingting , Wang Jian , Xu Wen'an , Xia Mingwu 
Published: December 2021

Background and Purpose: Patients with basilar artery (BA) dolichosis are at high risk of acute pontine infarction (API), but the association between BA dolichosis and long–term stroke recurrence has received little attention. We aimed to identify the effect of BA dolichosis on the risk of long–term brainstem infarction recurrence in patients with API.Methods: In this prospective cohort study, we enrolled 113 patients with API admitted to our department. BA dolichosis was diagnosed by a BA curve length &gt;29.5 mm or bending length (BL) &gt;10 mm on magnetic resonance angiography. The primary outcome was the occurrence of diffusion–weighted imaging (DWI)–confirmed brainstem infarction. The Cox proportional hazard model was used to detect possible predictors of brainstem infarction recurrence.Results: Among 113 patients with API, 39 (34.5%) patients had BA dolichosis, and DWI–confirmed brainstem infarction recurred in 15 (13.3%) patients with a mean follow–up time of 31.2 months; the estimated 5–year incidence of brainstem infarction recurrence was 23.1% in patients with BA dolichosis, which was significantly higher than the incidence of 8.1% in patients without BA dolichosis. Cox proportional hazard analysis showed that age ≥65 years (hazard ratio (HR) = 3.341, 95% confidence interval (CI): 1.079–10.348, P = 0.036) and BA dolichosis (HR = 3.048, 95% CI: 1.069–8.693, P = 0.037) were significantly associated with a higher risk of brainstem infarction recurrence. In a subgroup analysis stratified by age, the patients aged ≥65 years with BA dolichosis had a higher risk of brainstem infarction recurrence (HR = 7.319, 95% CI: 1.525–35.123, P = 0.013).Conclusions: This study indicates that BA dolichosis may increase the risk of long–term brainstem infarction recurrence in patients with API, especially in elderly patients, and therefore warrants more attention in clinical practice.
Altered Resting State Functional Activity of Brain Regions in Neovascular Glaucoma: A Resting-State Functional Magnetic Resonance Imaging Study
Authors: Yu Chao , Li Chu-Qi , Ge Qian-Min , Shu Hui-Ye , Liao Xu-Lin , Pan Yi-Cong , Wu Jie-Li , Su Ting , Zhang Li-Juan , Liang Rong-Bin , Shao Yi , Zeng Er-Ming 
Published: December 2021

Background: Neovascular glaucoma (NVG) is a serious eye disease that causes irreversible damage to the eye. It can significantly increase intraocular pressure and cause severe pain, as well as abnormal activity in the cortical and pre-cortical visual systems. However, there are few studies in this area. This trial assessed the altered regional brain activity in patients with NVG using the percentage of fluctuation amplitude (PerAF) method.Methods: Resting-state functional MRI (rs-fMRI) scans were conducted in 18 individuals with NVG and 18 healthy controls (HCs), matched for education level, gender, and age. The PerAF method was applied to assess brain activity. Mean PerAF values of brain regions in NVG and HCs were compared using receiver operating characteristic (ROC) curves.Results: Lower PerAF values were found in the NVG group than in controls in the right anterior cingulate and paracingulate gyri (ACG.R), right superior occipital gyrus (SOG.R) and left superior frontal gyrus (orbital part) (ORBsup.L) (p &lt; 0.001). In contrast, PerAF value was higher in NVG patients than in controls in the left inferior temporal gyrus (ITG.L) (p &lt; 0.001). The hospital anxiety and depression scale (HADS) and visual analog score (VAS) were significantly and positively correlated with PerAF in ITG.L (r = 0.9331, p &lt; 0.0001; and r = 0.7816, p = 0.0001, respectively).Conclusion: Abnormal activity in the patient’s brain regions further confirms that the NVG affects the entire brain, not just the visual pathways and posterior retinal mechanisms (including the hypothalamic lateral geniculate nucleus and the primary visual cortex). This strengthens our understanding of the NVG and provides potential diagnostic and therapeutic support for patients who are difficult to diagnose and treat early.
Association Between Fish Consumption and Muscle Mass and Function in Middle-Age and Older Adults
Authors: Alhussain Maha H. , ALshammari Moodi Mathel 
Published: December 2021

Background: Sarcopenia, the age-related loss of skeletal muscle mass and function, represents a crucial risk factor for disability and mortality. Increasing intake of some nutrients, particularly protein and omega-3 fatty acids seems to be a promising strategy to augment muscle mass and function.Objective: The purpose of this study was to assess the beneficial effects of fish consumption on muscle mass and function among middle-age and older adults.Methods: Twenty-two adults aged 50–85 years participated in this study. Participants were asked to consume 150–170-g of fish for lunch twice a week for a 10-week period. During that period, participants were asked to maintain their normal diet and physical activity. Outcome measures included anthropometry, muscle mass, and muscle function. All these measures were assessed at baseline, week 5, and week 10. Repeated-measures analysis of variance was used to analyze statistical significance.Results: Consuming fish twice a week for 10 weeks significantly increased the skeletal muscle mass and appendicular lean mass divided by height squared (ALM/h2) (p &lt; 0.01). Handgrip strength and gait speed &lt;0.8 m/s were also improved (p &lt; 0.01) at week 10 compared with that at baseline.Discussion: Consuming fish seems to improve muscle mass and function and may slow sarcopenia progression in middle-age and older adults.
Prevalence of Vitamin D Deficiency and Associated Factors in Critically Ill Patients: A Multicenter Observational Study
Authors: Chen Kuo-Wei , Chen Chung-Wei , Yuan Kuo-Ching , Wang I-Ting , Hung Fang-Ming , Wang An-Yi , Wang Yin-Chin , Kuo Yu-Ting , Lin Yi-Che , Shih Ming-Chieh , Kung Yu-Chung , Ruan Sheng-Yuan , Chiu Ching-Tang , Chao Anne , Han Yin-Yi , Kuo Li-Kuo , Yeh Yu-Chang 
Published: December 2021

Background: Vitamin D deficiency is common in the general population worldwide, and the prevalence and severity of vitamin D deficiency increase in critically ill patients. The prevalence of vitamin D deficiency in a community-based cohort in Northern Taiwan was 22.4%. This multicenter cohort study investigated the prevalence of vitamin D deficiency and associated factors in critically ill patients in Northern Taiwan.Methods: Critically ill patients were enrolled and divided into five groups according to their length of stay at intensive care units (ICUs) during enrolment as follows: group 1, &lt;2 days with expected short ICU stay; group 2, &lt;2 days with expected long ICU stay; group 3, 3-7 days; group 4, 8-14 days; and group 5, 15-28 days. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25(OH)D) level &lt; 20 ng/ml, and severe vitamin D deficiency was defined as a 25(OH)D level &lt; 12 ng/ml. The primary analysis was the prevalence of vitamin D deficiency. The exploratory analyses were serial follow-up vitamin D levels in group 2, associated factors for vitamin D deficiency, and the effect of vitamin D deficiency on clinical outcomes in critically ill patients.Results: The prevalence of vitamin D deficiency was 59% [95% confidence interval (CI) 55-62%], and the prevalence of severe vitamin D deficiency was 18% (95% CI 15-21%). The median vitamin D level for all enrolled critically ill patients was 18.3 (13.7-23.9) ng/ml. In group 2, the median vitamin D levels were &lt;20 ng/ml during the serial follow-up. According to the multivariable analysis, young age, female gender, low albumin level, high parathyroid hormone (PTH) level, and high sequential organ failure assessment (SOFA) score were significantly associated risk factors for vitamin D deficiency. Patients with vitamin D deficiency had longer ventilator use duration and length of ICU stay. However, the 28- and 90-day mortality rate were not associated with vitamin D deficiency.Conclusions: This study demonstrated that the prevalence of vitamin D deficiency is high in critically ill patients. Age, gender, albumin level, PTH level, and SOFA score were significantly associated with vitamin D deficiency in these patients.
A Nomogram for Predicting Brain Metastasis in IIIA-N2 Non-Small Cell Lung Cancer After Complete Resection: A Competing Risk Analysis
Authors: Sun Shuang , Men Yu , Kang Jingjing , Sun Xin , Yuan Meng , Yang Xu , Bao Yongxing , Wang Jianyang , Deng Lei , Wang Wenqing , Zhai Yirui , Liu Wenyang , Zhang Tao , Wang Xin , Bi Nan , Lv Jima , Liang Jun , Feng Qinfu , Chen Dongfu , Xiao Zefen , Zhou Zongmei , Wang Luhua , Hui Zhouguang 
Published: December 2021

BackgroundBrain metastasis (BM) is one of the most common failure patterns of pIIIA-N2 non-small cell lung cancer (NSCLC) after complete resection. Prophylactic cranial irradiation (PCI) can improve intracranial control but not overall survival. Thus, it is particularly important to identify the risk factors that are associated with BM and subsequently provide instructions for selecting patients who will optimally benefit from PCI.Methods and MaterialsBetween 2011 and 2014, patients with pIIIA-N2 NSCLC who underwent complete resection in our institution were reviewed and enrolled in the study. Clinical characteristics, pathological parameters, treatment mode, BM time, and overall survival were analyzed. A nomogram was built based on the corresponding parameters by Fine and Gray’s competing risk analysis to predict the 1-, 3-, and 5-year probabilities of BM. Receiver operating characteristic curves and calibration curves were chosen for validation. A statistically significant difference was set as P &lt;0.05.ResultsA total of 517 patients were enrolled in our retrospective study. The median follow-up time for surviving patients was 53.2 months (range, 0.50–123.17 months). The median age was 57 (range, 25–80) years. Of the 517 patients, 122 (23.6%) had squamous cell carcinoma, 391 (75.6%) received adjuvant chemotherapy, and 144 (27.3%) received post-operative radiotherapy. The 1-, 3-, and 5-year survival rates were 94.0, 72.9, and 66.0%, respectively. The 1-, 3-, and 5-year BM rates were 5.4, 15.7, and 22.2%, respectively. According to the univariate analysis, female, non-smokers, patients with non-squamous cell carcinoma, bronchial invasion, perineural invasion, and patients who received adjuvant chemotherapy were more likely to develop BM. In a multivariate analysis, non-squamous cell carcinoma (subdistribution hazard ratios, SHR: 3.968; 95% confidence interval, CI: 1.743–9.040; P = 0.0010), bronchial invasion (SHR: 2.039, 95% CI: 1.325–3.139; P = 0.0012), perineural invasion (SHR: 2.514, 95% CI: 1.058–5.976; P = 0.0370), and adjuvant chemotherapy (SHR: 2.821, 95% CI: 1.424–5.589; P = 0.0030) were independent risk factors for BM. A nomogram model was established based on the final multivariable analysis result. The area under the curve was 0.767 (95% CI, 0.758–0.777).ConclusionsFor patients with IIIA-N2 NSCLC after complete resection, a nomogram was established based on clinicopathological factors and treatment patterns for predicting the BM. Based on this nomogram, patients with a high risk of BM who may benefit from PCI can be screened.
Bacillus thuringiensis and Chlorantraniliprole Trigger the Expression of Detoxification-Related Genes in the Larval Midgut of Plutella xylostella
Authors: Shabbir Muhammad Zeeshan , Yang Xiangbing , Batool Raufa , Yin Fei , Kendra Paul E. , Li Zhen-Yu 
Published: December 2021

Background: Diamondback moth (DBM), Plutella xylostella (L.), has developed resistance to many insecticides. The molecular mechanism of DBM resistance to Bt-G033A combined with chlorantraniliprole (CL) remains undefined.Methods: In this study, field-resistant strains of Plutella xylostella to three pesticides, namely, Bacillus thuringiensis (Bt) toxin (Bt-G033A), CL, and a mixture of Bt + CL, were selected to evaluate the resistance level. Additionally, transcriptomic profiles of a susceptible (SS-DBM), field-resistant (FOH-DBM), Bt-resistant (Bt-DBM), CL-resistant (CL-DBM), and Bt + CL-resistant (BtC-DBM) strains were performed by comparative analysis to identify genes responsible for detoxification.Results: The Bt-G033A was the most toxic chemical to all the DBM strains among the three insecticides. The comparative analysis identified 25,518 differentially expressed genes (DEGs) between pairs/combinations of strains. DEGs were enriched in pathways related to metabolic and catalytic activity and ABC transporter in resistant strains. In total, 17 metabolic resistance-related candidate genes were identified in resistance to Bt-G033A, CL, and Bt + CL by co-expression network analysis. Within candidate genes, the majority was upregulated in key genes including cytochrome P450, glutathione S-transferase (GST), carboxylesterase, and acetylcholinesterase in CL- and BtC-resistant strains. Furthermore, aminopeptidase N (APN), alkaline phosphatase (ALP), cadherin, trypsin, and ABC transporter genes were eminent as Bt-resistance-related genes. Expression patterns of key genes by the quantitative real-time PCR (qRT-PCR) proved the credibility of transcriptome data and suggest their association in the detoxification process.Conclusion: To date, this study is the most comprehensive research presenting functional transcriptome analysis of DBM using Bt-G033A and CL combined insecticidal activity.
Decreased Medial Prefrontal Cortex Glutamate Levels in Perimenopausal Women
Authors: Yap Sidney , Luki Jessica , Hanstock Christopher C. , Seres Peter , Shandro Tami , Hanstock Sarah E. C. , Lirette Alynna , Zhao Huaying (Helen) , Aitchison Katherine J. , Le Melledo Jean-Michel 
Published: December 2021

Objective: There is an increased risk of experiencing depression during perimenopause (PM), a period of rapidly changing female hormone concentrations. Women at particular risk of developing major depression (MD) during PM are those with history of mood sensitivity to female hormone fluctuations i.e., women with a history of premenstrual dysphoric disorder (PMDD) and/or post-partum depression (PPD). Depressive symptomology has been associated with fluctuations of glutamate (Glu) levels in the medial prefrontal cortex (MPFC) in MD patients as well as PMDD and PPD patients. The objective of the study was to compare MPFC Glu levels in healthy perimenopausal and reproductive-aged (RD) women.Methods: Medial prefrontal cortex Glu levels in healthy perimenopausal (n = 15) and healthy RD women (n = 16) were compared via Magnetic Resonance Spectroscopy (MRS) scan using a 3 Tesla (T) magnet. Absence of depressive symptomology and psychiatric comorbidity was confirmed via semi-structured interview. Participants were scanned during the early follicular phase (FP) of the menstrual cycle (MC).Results: Mean MPFC Glu concentrations were decreased in the PM group compared to RD group (PM mean = 0.57 ± 0.03, RD mean = 0.63 ± 0.06, t = −3.84, df = 23.97, p = 0.001).Conclusion: Perimenopause is associated with decreases in MPFC Glu levels. This decrease may be contributing to the increased risk of experiencing depression during PM. Further research should assess MPFC Glu levels in perimenopausal women suffering from MD.