bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the mechanism of immediate analgesic effect of 1-time tuina intervention in minor chronic constriction injury rats using RNA-seq
Authors: Wang Hourong , Liu Zhifeng , Yu Tianyuan , Zhang Yingqi , Xu Yajing , Jiao Yi , Guan Qian , Liu Di
Published: October 2022

Previous studies have proved and investigated the mechanism of the analgesic effect of tuina treatment on neuropathic pain. The purpose of this study was to analyze changes in gene expression in the dorsal root ganglia (DRG) and spinal dorsal horn (SDH) after 1-time tuina intervention to investigate the immediate analgesic mechanism by tuina. An improvement in nociceptive behavior in minor chronic constriction injury (CCI) rats after 1-time tuina was observed. 1-time tuina was more effective in the amelioration of thermal hyperalgesia, but no changes were found in the ultrastructure of DRG and SDH. Sixty-five differentially expressed genes (DEGs) modulated by tuina were detected in the DRG and 123 DEGs were detected in the SDH. Potential immediate analgesic mechanisms of tuina were analyzed by the Kyoto Encyclopedia of Genes and Genomes. DEGs were enriched in 75 pathways in DRG, and 107 pathways in SDH. The immediate analgesic mechanism of tuina is related to the calcium signaling pathway, thermogenesis, and regulation of lipolysis in adipocytes.
Vibrotactile enhancement in hand rehabilitation has a reinforcing effect on sensorimotor brain activities
Authors: Du Qiang , Luo Jingjing , Cheng Qiying , Wang Youhao , Guo Shijie
Published: October 2022

Objective

Stroke patients often suffer from hand dysfunction or loss of tactile perception, which in turn interferes with hand rehabilitation. Tactile-enhanced multi-sensory feedback rehabilitation is an approach worth considering, but its effectiveness has not been well studied. By using functional near-infrared spectroscopy (fNIRS) to analyze the causal activity patterns in the sensorimotor cortex, the present study aims to investigate the cortical hemodynamic effects of hand rehabilitation training when tactile stimulation is applied, and to provide a basis for rehabilitation program development.

Methods

A vibrotactile enhanced pneumatically actuated hand rehabilitation device was tested on the less-preferred hand of 14 healthy right-handed subjects. The training tasks consisted of move hand and observe video (MO), move hand and vibration stimulation (MV), move hand, observe video, and vibration stimulation (MOV), and a contrast resting task. Region of interest (ROI), a laterality index (LI), and causal brain network analysis methods were used to explore the brain’s cortical blood flow response to a multi-sensory feedback rehabilitation task from multiple perspectives.

Results

(1) A more pronounced contralateral activation in the right-brain region occurred under the MOV stimulation. Rehabilitation tasks containing vibrotactile enhancement (MV and MOV) had significantly more oxyhemoglobin than the MO task at 5 s after the task starts, indicating faster contralateral activation in sensorimotor brain regions. (2) Five significant lateralized channel connections were generated under the MV and MOV tasks (p < 0.05), one significant lateralized channel connection was generated by the MO task, and the Rest were not, showing that MV and MOV caused stronger lateralization activation. (3) We investigated all thresholds of granger causality (GC) resulting in consistent relative numbers of effect connections. MV elicited stronger causal interactions between the left and right cerebral hemispheres, and at the GC threshold of 0.4, there were 13 causal network connection pairs for MV, 7 for MO, and 9 for MOV.

Conclusion

Vibrotactile cutaneous stimulation as a tactile enhancement can produce a stronger stimulation of the brain’s sensorimotor brain areas, promoting the establishment of neural pathways, and causing a richer effect between the left and right cerebral hemispheres. The combination of kinesthetic, vibrotactile, and visual stimulation can achieve a more prominent training efficiency from the perspective of functional cerebral hemodynamics.
Relationship between obesity-related parameters and chronic kidney disease in middle-aged and elderly populations in Taiwan: A community-based study
Authors: Chen I-Ju , Hsu Le-Tien , Lin Ting-Wei , Chen Jau-Yuan
Published: October 2022

Globally, obesity is a major health problem and can markedly increase the risk of various diseases, including type 2 diabetes mellitus, hypertension (HTN), dyslipidemia, and chronic kidney disease (CKD). The association of obesity-related parameters, such as lipid parameters and their ratio, with CKD in clinical settings is not well understood. This study aimed to investigate the association of obesity-related parameters with CKD in the middle-aged and elderly population in Taiwan. This cross-sectional, community-based study recruited 400 participants (141 males and 259 females) aged 50 years or over from a community health promotion project at the Linkou Chang Gung Memorial Hospital (Guishan District, Taoyuan City) in 2014. Each participant completed a questionnaire including personal information and medical history during a face-to-face interview. Laboratory data were obtained from blood and urine sampling. The data were analyzed using t-test, chi-square test, Pearson's correlation test, multivariate logistic regression, and receiver operating characteristic (ROC) analysis. A total of 81 participants were identified as having CKD [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 or urine albumin/creatinine ratio ≥30 mg/g], and their mean triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio was 3.37 ± 2.72. The mean TG/HDL-C ratio of the 319 participants without CKD was 2.35 ± 1.66. After adjusting for age, TG/HDL-C was significantly positively correlated with blood pressure, body mass index, waist circumference, and fasting plasma glucose but not low-density lipoprotein cholesterol. There was a negative correlation between TG/HDL-C and eGFR. Multiple logistic regression model analysis showed that TG/HDL-C was still significantly associated with CKD (OR: 1.17, 95% CI: 1.01–1.36, p = 0.04) after adjusting for multiple covariates. The cut-off point of TG/HDL-C as a predictor of CKD was 2.54 with an area under the ROC curve of 0.61 (95% CI: 0.53–0.68). There was a significant positive correlation between TG/HDL-C and several cardiovascular disease risk factors, including obesity indices. The TG/HDL-C ratio was significantly associated with the risk of CKD and demonstrated predictive ability for CKD in the middle-aged and elderly population. Further studies on its application in clinical settings are warranted.
Weissella cibaria riboflavin-overproducing and dextran-producing strains useful for the development of functional bread
Authors: Hernández-Alcántara Annel M. , Chiva Rosana , Mohedano María Luz , Russo Pasquale , Ruiz-Masó José Ángel , del Solar Gloria , Spano Giuseppe , Tamame Mercedes , López Paloma
Published: October 2022

This work describes a method for deriving riboflavin overproducing strains of Weissella cibaria by exposing three strains (BAL3C-5, BAL3C-7, and BAL3C-22) isolated from dough to increasing concentrations of roseoflavin. By this procedure, we selected one mutant overproducing strain from each parental strain (BAL3C-5 B2, BAL3C-7 B2, and BAL3C-22 B2, respectively). Quantification of dextran and riboflavin produced by the parental and mutant strains in a defined medium lacking riboflavin and polysaccharides confirmed that riboflavin was only overproduced by the mutant strains, whereas dextran production was similar in both mutant and parental strains. The molecular basis of the riboflavin overproduction by the mutants was determined by nucleotide sequencing of their rib operons, which encode the enzymes of the riboflavin biosynthetic pathway. We detected a unique mutation in each of the overproducing strains. These mutations, which map in the sensor domain (aptamer) of a regulatory element (the so-called FMN riboswitch) present in the 5’ untranslated region of the rib operon mRNA, appear to be responsible for the riboflavin-overproducing phenotype of the BAL3C-5 B2, BAL3C-7 B2, and BAL3C-22 B2 mutant strains. Furthermore, the molecular basis of dextran production by the six W. cibaria strains has been characterized by (i) the sequencing of their dsr genes encoding dextransucrases, which synthesize dextran using sucrose as substrate, and (ii) the detection of active Dsr proteins by zymograms. Finally, the parental and mutant strains were analyzed for in situ production of riboflavin and dextran during experimental bread making. The results indicate that the mutant strains were able to produce experimental wheat breads biofortified with both riboflavin and dextran and, therefore, may be useful for the manufacture of functional commercial breads.
Case report: Novel junctional sarcoplasmic reticulum protein 1 intergenic region–anaplastic lymphoma kinase fusion in a patient with lung adenocarcinoma responds to alectinib
Authors: Xue Feng , Xu Shengyuan , Jiang Cailing , Kang Mafei , Usman Muhammad , Zhu Lin
Published: October 2022

Novel anaplastic lymphoma kinase (ALK) fusions are still being discovered in non-small cell lung cancer (NSCLC). Most patients with ALK+ NSCLC respond favorably to ALK tyrosine kinase inhibitors. In this case report, we identified a novel nonreciprocal ALK fusion, namely, junctional sarcoplasmic reticulum protein 1 (JSRP1) intergenic region–ALK fusion (Jintergenic: A20) via next-generation sequencing in a female patient initially diagnosed with stage IV B lung adenocarcinoma. Further examination of biopsy specimen and analysis of clinical samples by a multidisciplinary team confirmed the diagnosis of ALK+ NSCLC. At the 2- and 4-months follow-up after receiving alectinib, the patient responded rapidly, implying that alectinib had a remarkable therapeutic effect. We identified a novel JSRP1 intergenic region–ALK fusion as a carcinogenic mutation that responds to alectinib, thereby expanding the spectrum of ALK fusion partners in ALK + NSCLC. This study may help clinicians detect oncogenic mutations and provide timely treatment to patients with ALK+ NSCLC.
Comparison of complications and long-term survival after minimally invasive esophagectomy versus open esophagectomy in patients with esophageal cancer and chronic obstructive pulmonary disease
Authors: Rong Yu , Hao Yanbing , Xue Jun , Li Xiaoyuan , Li Qian , Wang Li , Li Tian
Published: October 2022

Objective

To compare the complications and long-term survival of esophageal cancer patients with chronic obstructive pulmonary disease (COPD) after minimally invasive esophagectomy (MIE) versus open esophagectomy (OE) using propensity score matching (PSM).

Methods

Esophageal cancer patients who underwent esophagectomy at the Thoracic Surgery Department of the First Affiliated Hospital of Hebei North University from January 2010 to December 2018 were retrospectively enrolled. The incidence of postoperative complications and prognosis of the MIE (n = 132) and OE (n = 138) groups were compared. To reduce bias, 1:1 PSM was adopted for the analysis.

Results

The median disease-free survival (DFS) of the MIE and OE groups were 24 months and 26 months, respectively, and neither group reached median survival. There was no significant difference between the two groups in terms of 3-year DFS and overall survival (OS). The stratification of the patients on the basis of the percentage of estimated forced expiratory volume in the first second (%FEV1) did not result in significant differences in the survival rates. A total of 42 patients (50%) in the MIE group and 55 patients (65.48%) in the OE group experienced complications, and the difference was statistically significant (OR=0.527, 95% CI: 0.283–0.981, P=0.042). The incidence of acute COPD exacerbation (OR=0.213, 95% OR, CI: 0.068–0.666, P=0.004) and pulmonary atelectasis requiring bronchoscopic aspiration (OR=0.232, 95% OR, CI: 0.082–0.659, P=0.004) were significantly higher in the OE versus the MIE group. In addition, the distribution of the various grades of complications also differed significantly between the two groups (P=0.016). While the incidence of minor complications (≤Grade II) was similar in both groups (P=0.503), that of severe complications (≥Grade III) was markedly higher in the OE group (P=0.002) and the Grade-IIIa complications were predominant (P=0.001). The severity of complications was correlated with the postoperative duration of hospital stay in both groups (r=0.187, P=0.015). No significant difference was observed in the incidence of minor complications (≤Grade II) between the two groups following stratification on the basis of %FEV1, whereas severe complications were more frequent in the OE group among patients with %FEV1 between 60% and 70% (P=0.001<0.05).

Conclusion

There was no significant difference in the postoperative DFS and OS of esophageal cancer patients with COPD after undergoing MIE or OE. However, MIE significantly reduced the incidence of severe postoperative complications among patients with %FEV1 between 60% and 70%.
Knowledge-based planning for multi-isocenter VMAT total marrow irradiation
Authors: Ahn Kang-Hyun , Rondelli Damiano , Koshy Matthew , Partouche Julien A. , Hasan Yasmin , Liu Hongtao , Yenice Kamil , Aydogan Bulent
Published: October 2022

Purpose

Total marrow irradiation (TMI) involves optimization of extremely large target volumes and requires extensive clinical experience and time for both treatment planning and delivery. Although volumetric modulated arc therapy (VMAT) achieves substantial reduction in treatment delivery time, planning process still presents a challenge due to use of multiple isocenters and multiple overlapping arcs. We developed and evaluated a knowledge-based planning (KBP) model for VMAT-TMI to address these clinical challenges.

Methods

Fifty-one patients previously treated in our clinic were selected for the model training, while 22 patients from another clinic were used as a test set. All plans used a 3-isocenter to cover sub-target volumes of head and neck (HN), chest, and pelvis. Chest plan was performed first and then used as the base dose for both the HN and pelvis plans to reduce hot spots around the field junctions. This resulted in a wide range of dose-volume histograms (DVH). To address this, plans without the base-dose plan were optimized and added to the library to train the model.

Results

KBP achieved our clinical goals (95% of PTV receives 100% of Rx) in a single day, which used to take 4-6 days of effort without KBP. Statistically significant reductions with KBP were observed in the mean dose values to brain, lungs, oral cavity and lenses. KBP substantially improved 105% dose spillage (14.1% ± 2.4% vs 31.8% ± 3.8%), conformity index (1.51 ± 0.06 vs 1.81 ± 0.12) and homogeneity index (1.25 ± 0.02 vs 1.33 ± 0.03).

Conclusions

KBP improved dosimetric performance with uniform quality. It reduced dependence on planner experience and achieved a factor of 5 reduction in planning time to produce quality plans to allow its wide-spread clinical implementation.
Clinical characteristics and gene mutation profiles of chronic obstructive pulmonary disease in non-small cell lung cancer
Authors: Yuan Lin , Guo Ting , Hu Chengping , Yang Wei , Tang Xiaoli , Cheng Hao , Xiang Yang , Qu Xiangping , Liu Huijun , Qin Xiaoqun , Qin Ling , Liu Chi
Published: October 2022

Purpose

The coexistence of chronic obstructive pulmonary disease (COPD) often leads to a worse prognosis in patients with non-small cell lung cancer (NSCLC). Meanwhile, approaches targeting specific genetic alterations have been shown to significantly improve the diagnosis and treatment outcomes of patients with NSCLC. Herein, we sought to evaluate the impact of COPD on the clinical manifestations and gene mutation profiles of NSCLC patients with both circulating tumor (ctDNA) and tumor DNA (tDNA).

Materials and methods

The influence of COPD on clinical features was observed in 285 NSCLC cohorts suffering from NSCLC alone, NSCLC coexisting with COPD, or NSCLC coexisting with prodromal changes in COPD (with emphysema, bullae, or chronic bronchitis). The gene mutation profiles of specific 168 NSCLC-related genes were further analyzed in the NSCLC sub-cohorts with formalin-fixed and paraffin-embedded tumor DNA (FFPE tDNA) samples and plasma circulating tumor DNA (PLA ctDNA) samples. Moreover, mutation concordance was assessed in tDNA and paired ctDNA of 110 NSCLC patients.

Results

Relative to patients with NSCLC alone, patients with NSCLC coexisting with COPD and prodromal changes presented with worse lung functions, more clinical symptoms, signs and comorbidities, and inconsistent gene mutation profiles. In addition, patients in the latter two groups exhibited a higher average frequency of gene mutation. Lastly, mutation concordance between tDNA and ctDNA samples was significantly reduced in NSCLC patients coexisting with COPD.

Conclusions

Collectively, our findings revealed that coexistence of COPD leads to worse clinical manifestations and altered gene mutation profiles in patients with NSCLC. Additionally, for NSCLC patients with COPD, the use of ctDNA instead of tDNA may not be the most efficient approach to identifying gene mutations.
Pathologic light chain amyloidosis oligomer detection in urinary extracellular vesicles as a diagnostic tool for response and progression of disease
Authors: Cooper Shawna A. , Dick Christopher J. , Misra Pinaki , Leung Nelson , Schinstock Carrie A. , Ramirez-Alvarado Marina
Published: October 2022

Light Chain (AL) Amyloidosis is a plasma cell dyscrasia producing amyloidogenic light chains (LC) that misfold and form amyloid deposits that cause damage in vital organs, primarily the heart and kidneys. Urinary extracellular vesicles (uEVs) are nanoparticles produced by renal epithelial cells throughout the nephron. We previously showed that uEVs from active renal AL amyloidosis patients contain LC oligomers that are large (>250kDa), resistant to heat and chemical denaturation, but of low abundance. Renal dysfunction in AL amyloidosis results in high urine protein, compounding technical challenges to use uEVs as analytical tools. In this study, we assess the use of uEVs as analytical diagnostic tools for response and disease progression in AL amyloidosis. Our results suggest that uEV protein concentration, urine volume, and particle concentrations are not directly correlated. Multiple strategies for overcoming non-specific antibody binding in uEV samples were validated in our study. We demonstrated that the sensitivity for pre-clinical testing is improved with a urine sample requirement algorithm that we developed. The findings of our study will provide a pathway toward development of critically needed tools for patient management. Sensitive detection of LC oligomers from a non-invasive urine sample rather than an invasive renal biopsy will reduce patient burden and healthcare costs. The ability to detect LC oligomers in patients with renal progression, despite positive hematologic response; will allow clinicians to confidently treat, but not overtreat, patients at risk of ongoing significant renal injury.
A novel association of pyroptosis-related gene signature with the prognosis of hepatocellular carcinoma
Authors: Li Yuyao , Li Yue , Zhang Xuemei , Duan Xiangjuan , Feng Hai , Yu Zhuo , Gao Yueqiu
Published: October 2022

Background

Hepatocellular carcinoma (HCC) is one of the global leading lethal tumors. Pyroptosis has recently been defined as an inflammatory programmed cell death, which is closely linked to cancer progression. However, the significance of pyroptosis-related genes (PRGs) in the prognosis of HCC remains elusive.

Methods

RNA sequencing (RNA-seq) data of HCC cases and their corresponding clinical information were collected from the Cancer Genome Atlas (TCGA) database, and differential PRGs were explored. The prognostic PRGs were analyzed with univariate COX regression and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to build a prognostic model in the TCGA training cohort. The predictive model was further validated in the TCGA test cohort and ICGC validation cohort. Differential gene function and associated pathway analysis were performed by Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG). Single-sample gene set enrichment analysis (ssGSEA) was used to identify distinct immune cell infiltration. The mRNA and protein expression of prognostic PRGs was examined by quantitative RT-qPCR and immunohistochemistry.

Results

We identified 46 PRGs that were differentially expressed between normal and HCC tissues in a TCGA cohort, and HCC patients could be well categorized into two clusters associated with distinct survival rates based on expression levels of the PRGs. A three-PRG prognostic model comprising CHMP4A, HMGB1 and PLK1 was constructed in the training cohort, and HCC patients could be classified into the high- and low-risk subgroups based on the median risk score. High-risk patients exhibited shorter overall survival (OS) than low-risk ones, which was validated in the test cohort and ICGC validation cohort. The risk score of this model was confirmed as an independent prognostic factor to predict OS of HCC patients. GO, KEGG and ssGSEA demonstrated the differential immune cell infiltrations were associated with the risk scores. The higher expression of CHMP4A, HMGB1 and PLK1 were validated in HCC compared to normal in vivo and in vitro.

Conclusion

The three-PRG signature (CHMP4A, HMGB1, and PLK1) could act as an independent factor to predict the prognosis of HCC patients, which would shed light upon a potent therapeutic strategy for HCC treatment.
Brain temperature monitoring in newborn infants: Current methodologies and prospects
Authors: Verma Vinita , Lange Frederic , Bainbridge Alan , Harvey-Jones Kelly , Robertson Nicola J. , Tachtsidis Ilias , Mitra Subhabrata
Published: October 2022

Brain tissue temperature is a dynamic balance between heat generation from metabolism, passive loss of energy to the environment, and thermoregulatory processes such as perfusion. Perinatal brain injuries, particularly neonatal encephalopathy, and seizures, have a significant impact on the metabolic and haemodynamic state of the developing brain, and thereby likely induce changes in brain temperature. In healthy newborn brains, brain temperature is higher than the core temperature. Magnetic resonance spectroscopy (MRS) has been used as a viable, non-invasive tool to measure temperature in the newborn brain with a reported accuracy of up to 0.2 degrees Celcius and a precision of 0.3 degrees Celcius. This measurement is based on the separation of chemical shifts between the temperature-sensitive water peaks and temperature-insensitive singlet metabolite peaks. MRS thermometry requires transport to an MRI scanner and a lengthy single-point measurement. Optical monitoring, using near infrared spectroscopy (NIRS), offers an alternative which overcomes this limitation in its ability to monitor newborn brain tissue temperature continuously at the cot side in real-time. Near infrared spectroscopy uses linear temperature-dependent changes in water absorption spectra in the near infrared range to estimate the tissue temperature. This review focuses on the currently available methodologies and their viability for accurate measurement, the potential benefits of monitoring newborn brain temperature in the neonatal intensive care unit, and the important challenges that still need to be addressed.
Clinical efficacy of avatrombopag and recombinant human thrombopoietin in the treatment of chronic liver disease-associated severe thrombocytopenia: A real-world study
Authors: Wang Yong-Shuai , Wang Wei , Zhang Sai , Zhang Shen-Yu , Shen Ai-Zong , Wang Wei , Song Hua-Chuan , Yao Huan-Zhang , Song Rui-Peng , Meng Fan-Zheng , Li Lei , Nashan Bjoern , Wang Ji-Zhou , Liu Lian-Xin
Published: October 2022

Purpose: To investigate the clinical efficacy of avatrombopag, an oral thrombopoietin receptor agonist, versus subcutaneous recombinant human thrombopoietin (rh-TPO) in the treatment of severe thrombocytopenia (TCP) associated with chronic liver disease (CLD).

Methods: Clinical data of 250 patients with severe TCP associated with CLD were collected in a single hospital from January 2019 to January 2022. The main parameters measured were the therapeutic response rate, changes in platelets (PLTs), and adverse events. Propensity score matching (PSM) was used to avoid possible selection bias.

Results: After PSM, a total of 154 patients were enrolled in the study: 77 in the avatrombopag group and 77 in the rh-TPO group. There was no statistically significant difference between the two groups in the effect of increasing the PLT count (Waldχ2 = 1.659, p = 0.198; Waldχ2 = 0.220, p = 0.639). In addition, no interaction between time and different medications was found (Waldχ2 = 0.540, p = 0.910; Waldχ2 = 1.273, p = 0.736). Interestingly, in the subgroup analysis, both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A (88.89% vs. 63.41%, p =0.003; 81.33% vs. 61.76%, p = 0.043). Fewer patients reported dizziness in the avatrombopag group than in the rh-TPO group both before and after PSM (7.8% vs. 25.0%; 7.8% vs. 24.7%, p < 0.05).

Conclusion: Both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A and showed a lower incidence of dizziness in all patients.
Design and evaluation of rufinamide nanocrystals loaded thermoresponsive nasal in situ gelling system for improved drug distribution to brain
Authors: Dalvi Avantika , Ravi Punna Rao , Uppuluri Chandra Teja
Published: October 2022

Rufinamide (Rufi) is an antiepileptic drug used to manage Lennox-Gastaut Syndrome and partial seizures. The oral bioavailability of Rufi is less due to its poor solubility and low dissolution rate in the gastrointestinal fluids. This results in less amount of drug reaching the brain following the oral administration of drug. Oral formulations of Rufi are prescribed at a high dose and dosing frequency to increase its distribution to the brain. A Rufi loaded thermoresponsive nasal in situ gel which showed significantly high brain concentrations compared to aqueous suspension of Rufi administered through nasal route was developed by our research group and published. In the current work, we have formulated nanocrystals of Rufi and suspended them in a xyloglucan based thermoresponsive gel to improve the nose-to-brain distribution. The particle size, polydispersity index, and yield (%) of the optimized Rufi nanocrystals were 261.2 ± 2.1 nm, 0.28 ± 0.08, and 89.6 ± 2.0 respectively. The narrow PDI indicates that the manufacturing process is reproducible and reliable. Higher % yield suggested that the method of preparation is efficient. The sol-to-gel transition of in situ gel loaded with Rufi nanocrystals was at 32°C which suggested that the formulation transforms into gel at nasal epithelial temperatures. The nasal pharmacokinetic studies showed that Rufi nanocrystals loaded in situ gel produced higher concentration of the drug in brain (higher brain Cmax) and maintained the drug concentrations for longer duration (higher mean residence time) compared to aqueous suspension of Rufi nanocrystals as well aqueous suspension of Rufi and Rufi loaded in situ gel, reported previously. Nanometric size of the Rufi nanocrystals combined with the in situ gelling properties helped the optimized formulation achieve higher brain distribution and also sustain the drug concentrations in brain for longer duration compared to any of the formulations studied by our research group.
NLRP3 neuroinflammatory factors may be involved in atopic dermatitis mental disorders: an animal study
Authors: Yuan Huimin , Sun Yan , Zhang Shujing , Feng Jing , Tian Zijiao , Liu Jingang , Wang Hang , Gao Yushan , Tang Yang , Zheng Fengjie
Published: October 2022

Background: Numerous clinical studies have shown that atopic dermatitis (AD) is often associated with mental disorders. This could contribute to the overall burden of atopic dermatitis. However, the underlying mechanism of mental health symptoms in AD has not been fully elucidated.

Methods: An AD mouse was induced by 2,4-dinitrofluorobenzene (DNFB), which was repeatedly applied to the back skin of the BALB/C mice to establish an atopic dermatitis mental disorder model. The role of neuroinflammation in the pathogenesis of atopic dermatitis mental disorders was then explored.

Results: After the stimulation of DNFB for 35 days, the skin lesions, the HE staining of skin lesions, and the behavioral experiments (including elevated plus maze assay and tail suspension test) suggested that the AD mental disorder mouse model was successfully replicated. The expression of neuroinflammatory factors in the hippocampus was then investigated through Western blotting. The results showed a significant increase in the protein expression of NLRP3, caspase-1, and IL-1β.

Conclusion: Mental disorders in AD might be related to the neuroinflammatory response in the hippocampus. An alternative yet essential approach to promoting AD recovery could be through reducing neuroinflammation and improving mental disorders.
Dexmedetomidine postconditioning provides renal protection in patients undergoing laparoscopic partial nephrectomy: A randomized controlled trial
Authors: Jiang Lingling , Zhang Tao , Zhang Yang , Yu Dexin , Zhang Ye
Published: October 2022

Background: For localized disease, partial nephrectomy of small tumors continues to be the gold-standard treatment. However, temporary clamping is routinely performed during this process to control renal blood flow, which can cause renal ischemic/reperfusion injury. We evaluated whether dexmedetomidine postconditioning (DPOC) can reduce renal ischemic/reperfusion injury for patients receiving laparoscopic partial nephrectomy (LPN).

Methods: This randomized double-blind controlled trial included 77 patients who were scheduled for LPN at our hospital. Patients were randomly allocated to the DPOC or control group. DPOC was performed via intravenous administration of dexmedetomidine at 0.6 μg kg−1 for 10 min immediately after unclamping the renal artery. In the control group, saline was administered in place of dexmedetomidine under the same protocol. All participants underwent a 6-month follow-up. The primary outcome were the values of 99mTc-DTPA-GFR in the affected kidney at one and 6 months post-LPN.

Result: The GFR values in the DPOC group (35.65 ± 4.89 ml min−1.1.73 m−2) were significantly higher than those the control group (33.10 ± 5.41 ml min−1.1.73 m−2; p = 0.022) at 1 month after LPN. There was no statistically significant difference in GFR value between the two groups at 6 months after LPN.

Conclusion: DPOC provides therapeutic benefits to LPN patients, at least on a short-term basis, by alleviating renal ischemic/reperfusion injury.

Clinical Trial Registration: Chinese Clinical Trial Registry, identifier [ChiCTR-TRC-14004766].
A study on vague-valued hesitant fuzzy graph with application
Authors: Rao Yongsheng , Chen Ruxian , Kosari Saeed , Talebi A. A. , Mojahedfar Masome
Published: October 2022

The hesitant fuzzy graph (HFG) is one of the most powerful tools to find the strongest influential person in a network. Many problems of practical interest can be modeled and solved by using HFG algorithms. HFGs, belonging to the FG family, have good capabilities when faced with problems that cannot be expressed by FGs. The vague-valued hesitant fuzzy graph (VVHFG) is the generalization of the HFG. A VVHFG is a powerful and useful tool to find the influential person in various parts, such as meetings, conferences, and every group discussion. In this study, we introduce a new concept of the VVHFG. Our purpose is to develop a notion of the VVHFG and also to present some basic definitions, notations, remarks, and proofs related to VVHFGs. We propose a numerical method to find the most dominating person using our proposed work. Finally, an application of the VVHFG in decision-making has been introduced.
Interfacial quality to control tunnelling magnetoresistance
Authors: Hirohata Atsufumi , Elphick Kelvin , Lloyd David C. , Mizukami Shigemi
Published: October 2022

Theoretically, coherent tunnelling through an MgO barrier can achieve over 1,000% magnetoresistance at room temperature. To date, this has not been demonstrated experimentally. In this article, we have categorised magnetic tunnel junctions into four groups and have investigated possible causes of the reduction in their magnetoresistance by correlating their interfacial atomic structures and spin-polarised electron transport. We have concluded that the spin fluctuation induced by dislocations and disordering at a ferromagnet/barrier interface reduced the corresponding magnetoresistance.
Defining the pressures of a fluid in a nanoporous, heterogeneous medium
Authors: Galteland Olav , Rauter Michael T. , Varughese Kevin K. , Bedeaux Dick , Kjelstrup Signe
Published: October 2022

We describe the thermodynamic state of a single-phase fluid confined to a porous medium with Hill’s thermodynamics of small systems, also known as nanothermodynamics. This way of defining small system thermodynamics, with a separate set of control variables, may be useful for the study of transport in non-deformable porous media, where presently no consensus exists on pressure computations. For a confined fluid, we observe that there are two pressures, the integral and the differential pressures. We use molecular simulations to investigate and confirm the nanothermodynamic relations for a representative elementary volume (REV). For a model system of a single-phase fluid in a face-centered cubic lattice of solid spheres of varying porosity, we calculate the fluid density, fluid-solid surface tension, replica energy, integral pressure, entropy, and internal energy.
Assigning quantum labels and improving accuracy for the ro-vibrational eigenstates of H3+ calculated using ScalIT
Authors: Sarka János , Poirier Bill
Published: October 2022

In a recent article [AIP Adv. 11, 045033 (2021)], we carried out exact quantum dynamical calculations and computed ro-vibrational energy levels and wave functions for the H3+ molecular ion up to the dissociation threshold (at J = 46) using a recently developed potential energy surface (PES) [Mol. Phys. 117, 1663 (2019)]—arguably, the most accurate to date —together with the ScalIT suite of parallel codes. In this work, we further improved the convergence accuracy and range of our ScalIT calculations for all J values up to J = 20 to a few 10–5 cm−1 (or better). In addition, we performed an ab initio assignment of the ro-vibrational energy levels, providing vibrational ‘v1, v2, |l|’ and rotational ‘J, G, U, K’ quantum labels for more than 2,200 ro-vibrational states, including every single 0 ≤ J ≤ 20 state up to and above the barrier to linearity at 10,000 cm−1. The main underlying motivation of our work is to provide a list of reliably labeled, spectroscopically accurate energy levels in a format that can be used in spectroscopic line lists, which are based on both experimental and theoretical levels. Such line lists are of huge importance in various astrochemical and astrophysical contexts.
A deep 96-well plate RBC storage platform for high-throughput screening of novel storage solutions
Authors: Nikulina Maria , Nemkov Travis , D'Alessandro Angelo , Gaccione Peter , Yoshida Tatsuro
Published: October 2022

Background: Red blood cell (RBC) storage solutions, also known as additive solutions (ASs), first developed in the 1970s, enable extended storage of RBCs. Unfortunately, the advancements in this field have been limited, due to labor intensive and time-consuming serial in vitro and in vivo testing, coupled with very high commercialization hurdles. This study examines the utility of deep 96-well plates for preliminary screenings of novel ASs through comparison of RBC storage with the standard PVC bags in terms of hemolysis and ATP levels, under both normoxic (N) and hypoxic/hypocapnic (H) storage conditions. The necessity for the presence of DEHP, normally provided by PVC bags, is also examined.

Materials and methods: A pool of 2 ABO compatible RBC units was split between a bag and a plate. Each plate well contained either 1, 2 or 0 PVC strips cut from standard storage bags to supply DEHP. The H bags and plates were processed in an anaerobic glovebox and stored in O2 barrier bags. Hemolysis and ATP were measured bi-weekly using standard methods.

Results: Final ATP and hemolysis values for the plate-stored RBCs were comparable to the typical values observed for 6-week storage of leukoreduced AS-3 RBCs in PVC bags under both N and H conditions. Hemolysis was below FDA and EU benchmarks of 1% and 0.8%, respectively, and excluding DEHP from plates during storage, resulted in an inconsequential increase when compared to bag samples.

Discussion: In combination with high-throughput metabolomics workflow, this platform provides a highly efficient preliminary screening platform to accelerate the initial testing and consequent development of novel RBC ASs.
CT-based lung motion differences in patients with usual interstitial pneumonia and nonspecific interstitial pneumonia
Authors: Choi Jiwoong , Chae Kum Ju , Jin Gong Yong , Lin Ching-Long , Laroia Archana T. , Hoffman Eric A. , Lee Chang Hyun
Published: October 2022

We applied quantitative CT image matching to assess the degree of motion in the idiopathic ILD such as usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). Twenty-one normal subjects and 42 idiopathic ILD (31 UIP and 11 NSIP) patients were retrospectively included. Inspiratory and expiratory CT images, reviewed by two experienced radiologists, were used to compute displacement vectors at local lung regions matched by image registration. Normalized three-dimensional and two-dimensional (dorsal-basal) displacements were computed at a sub-acinar scale. Displacements, volume changes, and tissue fractions in the whole lung and the lobes were compared between normal, UIP, and NSIP subjects. The dorsal-basal displacement in lower lobes was smaller in UIP patients than in NSIP or normal subjects (p = 0.03, p = 0.04). UIP and NSIP were not differentiated by volume changes in the whole lung or upper and lower lobes (p = 0.53, p = 0.12, p = 0.97), whereas the lower lobe air volume change was smaller in both UIP and NSIP than normal subjects (p = 0.02, p = 0.001). Regional expiratory tissue fractions and displacements showed positive correlations in normal and UIP subjects but not in NSIP subjects. In summary, lung motionography quantified by image registration-based lower lobe dorsal-basal displacement may be used to assess the degree of motion, reflecting limited motion due to fibrosis in the ILD such as UIP and NSIP.
Acute ethanol-induced liver injury is prevented by betaine administration
Authors: Arumugam Madan Kumar , Chava Srinivas , Perumal Sathish Kumar , Paal Matthew C. , Rasineni Karuna , Ganesan Murali , Donohue Terrence M. , Osna Natalia A. , Kharbanda Kusum K.
Published: October 2022

Binge drinking is the most common form of excessive alcohol use. Repeated episodes of binge drinking cause multiple organ injuries, including liver damage. We previously demonstrated that chronic ethanol administration causes a decline in the intrahepatic ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). This decline causes impairments in essential methylation reactions that result in alcohol-induced fatty liver (steatosis) and other features of alcohol-associated liver disease (ALD). Co-treatment with betaine during chronic ethanol feeding, normalizes hepatocellular SAM:SAH ratio and alleviates many features of liver damage including steatosis. Here, we sought to examine whether betaine treatment similarly protects against liver injury in an alcohol binge-drinking model. We hypothesized that ethanol binge with prior or simultaneous betaine administration would prevent or attenuate acute alcohol-induced liver damage. Male C57Bl/6 mice were gavaged twice, 12 h apart, with either 6 g ethanol/kg BW or with an equal volume/kg BW of 0.9% NaCl. Two separate groups of mice (n = 5/group) were gavaged with 4 g betaine/kg BW, either 2 h before or simultaneously with the ethanol or saline gavages. All mice were sacrificed 8 h after the last gavage and serum and liver parameters were quantified. Ethanol binges caused a 50% decrease in hepatic SAM:SAH ratio and a >3-fold rise in liver triglycerides (p ≤ 0.05). These latter changes were accompanied by elevated serum AST and ALT activities and blood alcohol concentrations (BAC) that were ∼three-times higher than the legal limit of intoxication in humans. Mice that were treated with betaine 2 h before or simultaneously with the ethanol binges exhibited similar BAC as in mice given ethanol-alone. Both betaine treatments significantly elevated hepatic SAM levels thereby normalizing the SAM:SAH ratio and attenuating hepatic steatosis and other injury parameters, compared with mice given ethanol alone. Simultaneous betaine co-administration with ethanol was more effective in preventing or attenuating liver injury than betaine given before ethanol gavage. Our findings confirm the potential therapeutic value of betaine administration in preventing liver injury after binge drinking in an animal model.
ECG based assessment of circadian variation in AV-nodal conduction during AF—Influence of rate control drugs
Authors: Karlsson Mattias , Wallman Mikael , Platonov Pyotr G. , Ulimoen Sara R. , Sandberg Frida
Published: October 2022

The heart rate during atrial fibrillation (AF) is highly dependent on the conduction properties of the atrioventricular (AV) node. These properties can be affected using β-blockers or calcium channel blockers, mainly chosen empirically. Characterization of individual AV-nodal conduction could assist in personalized treatment selection during AF. Individual AV nodal refractory periods and conduction delays were characterized based on 24-hour ambulatory ECGs from 60 patients with permanent AF. This was done by estimating model parameters from a previously created mathematical network model of the AV node using a problem-specific genetic algorithm. Based on the estimated model parameters, the circadian variation and its drug-dependent difference between treatment with two β-blockers and two calcium channel blockers were quantified on a population level by means of cosinor analysis using a linear mixed-effect approach. The mixed-effects analysis indicated increased refractoriness relative to baseline for all drugs. An additional decrease in circadian variation for parameters representing conduction delay was observed for the β-blockers. This indicates that the two drug types have quantifiable differences in their effects on AV-nodal conduction properties. These differences could be important in treatment outcome, and thus quantifying them could assist in treatment selection.
Polycystin-2 (TRPP2) regulates primary cilium length in LLC-PK1 renal epithelial cells
Authors: Scarinci Noelia , Perez Paula L. , Cantiello Horacio F. , Cantero María del Rocío
Published: October 2022

Polycystin-2 (PC2, TRPP2) is a Ca2+ permeable nonselective cation channel whose dysfunction generates autosomal dominant polycystic kidney disease (ADPKD). PC2 is present in different cell locations, including the primary cilium of renal epithelial cells. However, little is known as to whether PC2 contributes to the primary cilium structure. Here, we explored the effect(s) of external Ca2+, PC2 channel blockers, and PKD2 gene silencing on the length of primary cilia in wild-type LLC-PK1 renal epithelial cells. Confluent cell monolayers were fixed and immuno-labeled with an anti-acetylated α-tubulin antibody to identify primary cilia and measure their length. Although primary cilia length measurements did not follow a Normal distribution, the data were normalized by Box-Cox transformation rendering statistical differences under all experimental conditions. Cells exposed to high external Ca2+ (6.2 mM) decreased a 13.5% (p < 0.001) primary cilia length as compared to controls (1.2 mM Ca2+). In contrast, the PC2 inhibitors amiloride (200 μM) and LiCl (10 mM), both increased primary ciliary length by 33.2% (p < 0.001), and 17.4% (p < 0.001), respectively. PKD2 gene silencing by siRNA elicited a statistically significant, 10.3% (p < 0.001) increase in primary cilia length compared to their respective scrambled RNA transfected cells. The data indicate that conditions that regulate PC2 function or gene expression modify the length of primary cilia in renal epithelial cells. Blocking of PC2 mitigates the effects of elevated external Ca2+ concentration on primary cilia length. Proper regulation of PC2 function in the primary cilium may be essential in the onset of mechanisms that trigger cyst formation in ADPKD.
Nitrogen fertilization coupled with foliar application of iron and molybdenum improves shade tolerance of soybean under maize-soybean intercropping
Authors: Nasar Jamal , Wang Gui Yang , Zhou Feng Jue , Gitari Harun , Zhou Xun Bo , Tabl Karim M. , Hasan Mohamed E. , Ali Habib , Waqas Muhammad Mohsin , Ali Izhar , Jahan Mohammad Shah
Published: October 2022

Maize-soybean intercropping is practiced worldwide because of some of the anticipated advantages such as high crop yield and better utilization of resources (i.e., water, light, nutrients and land). However, the shade of the maize crop has a detrimental effect on the growth and yield of soybean under the maize-soybean intercropping system. Hence, this experiment was conducted to improve the shade tolerance of such soybean crops with optimal nitrogen (N) fertilization combined with foliar application of iron (Fe) and molybdenum (Mo). The treatments comprised five (5) maize-soybean intercropping practices: without fertilizer application (F0), with N fertilizer application (F1), with N fertilizer combined with foliar application of Fe (F2), with N fertilizer coupled with foliar application of Mo (F3) and with N fertilizer combined with foliar application of Fe and Mo (F4). The findings of this study showed that maize-soybean intercropping under F4 treatment had significantly (p< 0.05) increased growth indices such as leaf area (cm2), plant height (cm), stem diameter (mm), stem strength (g pot-1), and internode length (cm) and yield indices (i.e., No of pods plant-1, grain yield (g plant-1), 100-grain weight (g), and biomass dry matter (g plant-1)) of the soybean crop. Moreover, intercropping under F4 treatment enhanced the chlorophyll SPAD values by 26% and photosynthetic activities such as Pn by 30%, gs by 28%, and Tr by 28% of the soybean crops, but reduced its CO2 by 11%. Furthermore, maize-soybean intercropping under F4 treatment showed improved efficiency of leaf chlorophyll florescence parameters of soybean crops such as Fv/Fm (26%), qp (17%), ϕPSII (20%), and ETR (17%), but reduced NPQ (12%). In addition, the rubisco activity and soluble protein content of the soybean crop increased by 18% in maize-soybean intercropping under F4 treatment. Thus, this suggested that intercropping under optimal N fertilization combined with foliar application of Fe and Mo can improve the shade tolerance of soybean crops by regulating their chlorophyll content, photosynthetic activities, and the associated enzymes, thereby enhancing their yield and yield traits.