bluuebunny/crossref_metadata_2025 huggingface dataset:
Aberrant resting-state brain activity in Huntington's disease: A voxel-based meta-analysis
Authors: Zhang Sirui , Lin Junyu , Cheng Yangfan , Hou Yanbin , Shang Huifang
Published: March 2023

Introduction

Functional neuroimaging could provide abundant information of underling pathophysiological mechanisms of the clinical triad including motor, cognitive and psychiatric impairment in Huntington's Disease (HD).

Methods

We performed a voxel-based meta-analysis using anisotropic effect size-signed differential mapping (AES-SDM) method.

Results

6 studies (78 symptomatic HD, 102 premanifest HD and 131 healthy controls) were included in total. Altered resting-state brain activity was primarily detected in the bilateral medial part of superior frontal gyrus, bilateral anterior cingulate/paracingulate gyrus, left insula, left striatum, right cortico-spinal projections area, right inferior temporal gyrus area, right thalamus, right cerebellum and right gyrus rectus area. Premanifest and symptomatic HD patients showed different alterative pattern in the subgroup analyses.

Discussion

The robust and consistent abnormalities in the specific brain regions identified in the current study could help to understand the pathophysiology of HD and explore reliable neuroimaging biomarkers for monitoring disease progression, or even predicting the onset of premanifest HD patients.
Application of intraoperative infrared thermography in bypass surgery for adult moyamoya syndrome: A preliminary study
Authors: Lin Jinghui , Wu Yiwen , Deng Xinpeng , Zhou Shengjun , Liu Yuchun , Zhang Junjun , Zeng Yiyong , Li Xianru , Gao Xiang , Xu Bin , Zhou Chenhui
Published: March 2023

Background and objectives

Cerebral revascularization surgery is the mainstay of treatment for moyamoya syndrome (MMS) today, and intraoperative determination of the patency of the revascularized vessel is a critical factor in the success of the procedure. Currently, major imaging modalities include intraoperative indocyanine green (ICG) videoangiography (ICG-VA), digital subtraction angiography (DSA), and vascular ultrasound Doppler. Infrared thermography is a modern imaging modality with non-contact devices for the acquisition and analysis of thermal data. We aimed to investigate the feasibility and advantages of infrared thermography in determining anastomotic patency during MMS surgery.

Methods

Indocyanine green videoangiography and infrared thermography were performed simultaneously in 21 patients with MMS who underwent bypass surgery. The detection result of vessel patency was compared, and the feasibility and advantages of infrared thermography were assessed.

Results

The patency of the anastomosis was accurately determined in 21 patients using either ICG angiography or infrared thermography. In 20 patients, the results of infrared thermography showed that the vascular anastomosis was unobstructed, and there was an agreement with the subsequent results of ICG-VA. In one patient, we suspected inadequate patency after testing the anastomosis with infrared thermography, and the results of ICG-VA evaluation of the anastomosis confirmed that there was indeed an anastomotic obstruction.

Conclusion

Compared with ICG-VA, infrared thermography might offer an alternative non-invasive, contrast-free option in assessing anastomosis patency compared with ICG-VA, and it is likely to become more widely used in the clinic in the near future.
Increased NOX2 expression in astrocytes leads to eNOS uncoupling through dihydrofolate reductase in endothelial cells after subarachnoid hemorrhage
Authors: Miao Shu-Hao , Gao Sheng-Qing , Li Hui-Xin , Zhuang Yun-Song , Wang Xue , Li Tao , Gao Chao-Chao , Han Yan-Ling , Qiu Jia-Yin , Zhou Meng-Liang
Published: March 2023

Introduction

Endothelial nitric oxide synthase (eNOS) uncoupling plays a significant role in acute vasoconstriction during early brain injury (EBI) after subarachnoid hemorrhage (SAH). Astrocytes in the neurovascular unit extend their foot processes around endothelia. In our study, we tested the hypothesis that increased nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression in astrocytes after SAH leads to eNOS uncoupling.

Methods

We utilized laser speckle contrast imaging for monitoring cortical blood flow changes in mice, nitric oxide (NO) kits to measure the level of NO, and a co-culture system to study the effect of astrocytes on endothelial cells. Moreover, the protein levels were assessed by Western blot and immunofluorescence staining. We used CCK-8 to measure the viability of astrocytes and endothelial cells, and we used the H2O2 kit to measure the H2O2 released from astrocytes. We used GSK2795039 as an inhibitor of NOX2, whereas lentivirus and adeno-associated virus were used for dihydrofolate reductase (DHFR) knockdown in vivo and in vitro.

Results

The expression of NOX2 and the release of H2O2 in astrocytes are increased, which was accompanied by a decrease in endothelial DHFR 12 h after SAH. Moreover, the eNOS monomer/dimer ratio increased, leading to a decrease in NO and acute cerebral ischemia. All of the above were significantly alleviated after the administration of GSK2795039. However, after knocking down DHFR both in vivo and in vitro, the protective effect of GSK2795039 was greatly reversed.

Discussion

The increased level of NOX2 in astrocytes contributes to decreased DHFR in endothelial cells, thus aggravating eNOS uncoupling, which is an essential mechanism underlying acute vasoconstriction after SAH.
Investigating the impact of visual perspective in a motor imagery-based brain-robot interaction: A pilot study with healthy participants
Authors: Farabbi Andrea , Figueiredo Patricia , Ghiringhelli Fabiola , Mainardi Luca , Sanches Joao Miguel , Moreno Plinio , Santos-Victor Jose , Vourvopoulos Athanasios
Published: March 2023

Introduction

Motor Imagery (MI)-based Brain Computer Interfaces (BCI) have raised gained attention for their use in rehabilitation therapies since they allow controlling an external device by using brain activity, in this way promoting brain plasticity mechanisms that could lead to motor recovery. Specifically, rehabilitation robotics can provide precision and consistency for movement exercises, while embodied robotics could provide sensory feedback that can help patients improve their motor skills and coordination. However, it is still not clear whether different types of visual feedback may affect the elicited brain response and hence the effectiveness of MI-BCI for rehabilitation.

Methods

In this paper, we compare two visual feedback strategies based on controlling the movement of robotic arms through a MI-BCI system: 1) first-person perspective, with visual information that the user receives when they view the robot arms from their own perspective; and 2) third-person perspective, whereby the subjects observe the robot from an external perspective. We studied 10 healthy subjects over three consecutive sessions. The electroencephalographic (EEG) signals were recorded and evaluated in terms of the power of the sensorimotor rhythms, as well as their lateralization, and spatial distribution.

Results

Our results show that both feedback perspectives can elicit motor-related brain responses, but without any significant differences between them. Moreover, the evoked responses remained consistent across all sessions, showing no significant differences between the first and the last session.

Discussion

Overall, these results suggest that the type of perspective may not influence the brain responses during a MI- BCI task based on a robotic feedback, although, due to the limited sample size, more evidence is required. Finally, this study resulted into the production of 180 labeled MI EEG datasets, publicly available for research purposes.
Dietary intake and serum concentrations of vitamin A and vitamin E and pre-eclampsia risk in Chinese pregnant women: A matched case-control study
Authors: Liu Yanhua , Ma Shunping , Huang Xuemin , Bo Yacong , Fu Wenjun , Cao Yuan , Duan Dandan , Dou Weifeng , Zeng Fangfang , Wang Xinyi , Gong Meiyuan , Zhang Xueyang , Lyu Quanjun , Zhao Xianlan
Published: March 2023

Background

Many studies have suggested that the serum concentrations of vitamin A (VA) and vitamin E (VE) influence preeclampsia (PE) risk in pregnant women. However, few studies have assessed whether dietary intake and serum concentrations of VA and VE are correlated with PE risk.

Methods

A 1:1 matched case-control study was conducted to explore the association between the dietary intake and serum concentrations of VA and VE and the risk of PE in pregnant Chinese women. A total of 440 pregnant women with PE and 440 control pregnant women were included in the study. Dietary information was obtained using a 78-item semi-quantitative food frequency questionnaire. Serum concentrations of VA and VE were measured by liquid chromatography-tandem mass spectrometry.

Results

Compared with the lowest quartile, the multivariate-adjusted odds ratios [95% confidence interval (CI)] of the highest quartiles were 0.62 (95% CI: 0.40-0.96, P trend = 0.02) for VA, 0.51 (95% CI: 0.33–0.80, P trend =0.002) for β-carotene, and 0.70 (95% CI: 0.45–1.08, P trend = 0.029) for retinol. Additionally, for serum VA and VE concentrations, the multivariate-adjusted odds ratios (95% CI) were 2.75 (95% CI: 1.24–6.13, P trend = 0.002) and 11.97 (95% CI: 4.01–35.77, P trend < 0.001), respectively. No significant association was seen between VE intake and PE risk.

Conclusions

Dietary VA intake was negatively correlated with PE risk, and serum VA and VE concentrations were positively correlated with PE risk among pregnant Chinese women.
Affordability of Canada's Food Guide: Current challenges amid COVID-19, War in Ukraine, and other world events
Authors: Taylor Stacey , Charlebois Sylvain , Music Janet
Published: March 2023

Since the 2019 Canada Food Guide was released, there have been concerns raised over the cost of food, with an emphasis on the affordability of nutritious food. In this study, we evaluate the affordability of the 2019 Canada Food Guide in relation to the previous edition from 2007. As a result of the pandemic and other significant world events, many are feeling financial stress as prices in many areas of life rise, including housing, gas, and food. Our results show that it is more cost-effective, on average, for children and teens to follow the 2019 Canada Food Guide, but more expensive for adults, when compared to the 2007 edition.
Dietary supplementation with jasmine flower residue improves meat quality and flavor of goat
Authors: Wang Jinxing , Lu Renhong , Li Yehong , Lu Junzhi , Liang Qiong , Zheng Zihua , Huang Heng , Deng Fuchang , Huang Huali , Jiang Huimin , Hu Junjie , Feng Ming , Xiao Peng , Yang Xiaogan , Liang Xingwei , Zeng Jun
Published: March 2023

Jasmine flower residue (JFR) is a by-product retained in the production process of jasmine tea and can be used as an unconventional feed due to its rich nutrient value. This study aimed to evaluate the effects of the addition of JFR to the diet of goats on their meat quality and flavor. Twenty-four castrated Nubian male goats were randomly divided into two groups and fed a mixed diet containing 10% JFR (JFR, n = 12) or a conventional diet (CON, n = 12) for 45 days. Meat quality and flavor were measured at the end of the treatment. The addition of JFR to the diet could reduce the shear force of the longissimus dorsi muscle, as well as, the cross-sectional area and diameter of muscle fibers, indicating that the addition of JFR improved meat quality. JFR also increased the content of glutamic acid and ω-3 polyunsaturated fatty acid (C18:3n3 and C20:5N3) and reduced the content of C24:1 and saturated fatty acid (C20:0 and C22:0). In addition, the use of JFR increased the content of acetaldehyde and hexanal in the meat. Furthermore, JFR introduced new volatile components in the meat. The umami, saltiness, and richness of the meat also improved. In conclusion, the addition of jasmine flower residue to the diet can improve the meat quality and flavor of goat.
Dysregulation of systemic soluble immune checkpoints in early breast cancer is attenuated following administration of neoadjuvant chemotherapy and is associated with recovery of CD27, CD28, CD40, CD80, ICOS and GITR and substantially increased levels of PD-L1, LAG-3 and TIM-3
Authors: Rapoport Bernardo L. , Steel Helen C. , Benn Carol A. , Nayler Simon , Smit Teresa , Heyman Liezl , Theron Annette J. , Hlatshwayo Nomsa , Kwofie Luyanda L.I. , Meyer Pieter W.A. , Anderson Ronald
Published: March 2023

Neoadjuvant chemotherapy (NAC) may alter the immune landscape of patients with early breast cancer (BC), potentially setting the scene for more effective implementation of checkpoint-targeted immunotherapy. This issue has been investigated in the current study in which alterations in the plasma concentrations of 16 soluble co-stimulatory and co-inhibitory, immune checkpoints were measured sequentially in a cohort of newly diagnosed, early BC patients (n=72), pre-treatment, post-NAC and post-surgery using a Multiplex® bead array platform. Relative to a group of healthy control subjects (n=45), the median pre-treatment levels of five co-stimulatory (CD27, CD40, GITRL, ICOS, GITR) and three co-inhibitory (TIM-3, CTLA-4, PD-L1) soluble checkpoints were significantly lower in the BC patients vs. controls (p<0.021-p<0.0001; and p<0.008-p<0.00001, respectively). Following NAC, the plasma levels of six soluble co-stimulatory checkpoints (CD28, CD40, ICOS, CD27, CD80, GITR), all involved in activation of CD8+ cytotoxic T cells, were significantly increased (p<0.04-p<0.00001), comparable with control values and remained at these levels post-surgery. Of the soluble co-inhibitory checkpoints, three (LAG-3, PD-L1, TIM-3) increased significantly post-NAC, reaching levels significantly greater than those of the control group. PD-1 remained unchanged, while BTLA and CTLA-4 decreased significantly (p<0.03 and p<0.00001, respectively). Normalization of soluble co-stimulatory immune checkpoints is seemingly indicative of reversal of systemic immune dysregulation following administration of NAC in early BC, while recovery of immune homeostasis may explain the increased levels of several negative checkpoint proteins, albeit with the exceptions of CTLA-4 and PD-1. Although a pathological complete response (pCR) was documented in 61% of patients (mostly triple-negative BC), surprisingly, none of the soluble immune checkpoints correlated with the pCR, either pre-treatment or post-NAC. Nevertheless, in the case of the co-stimulatory ICMs, these novel findings are indicative of the immune-restorative potential of NAC in early BC, while in the case of the co-inhibitory ICMs, elevated levels of soluble PD-L1, LAG-3 and TIM-3 post-NAC underscore the augmentative immunotherapeutic promise of targeting these molecules, either individually or in combination, as a strategy, which may contribute to the improved management of early BC.
Exploring a ferroptosis and oxidative stress-based prognostic model for clear cell renal cell carcinoma
Authors: Lin Dongxu , Hu Bintao , Zhu Shiqing , Wu Yue
Published: March 2023

Background

Ferroptosis is a newly defined cell death process triggered by increased iron load and tremendous lipid reactive oxygen species (ROS). Oxidative stress-related ferroptosis is of great important to the occurrence and progression of clear cell renal cell carcinoma (ccRCC), which is particularly susceptibility to ferroptosis agonist. Therefore, exploring the molecular features of ferroptosis and oxidative stress might guide the clinical treatment and prognosis prediction for ccRCC patients.

Methods

The differentially expressed ferroptosis and oxidative stress-associated genes (FPTOSs) between normal renal and ccRCC tissues were identified based on The Cancer Genome Atlas (TCGA) database, and those with prognostic significances were applied to develop a prognostic model and a risk scoring system (FPTOS_score). The clinical parameter, miRNA regulation, tumor mutation burden (TMB), immune cell infiltration, immunotherapy response, and drug susceptibility between two FPTOS-based risk stratifications were determined.

Results

We have identified 5 prognosis-associated FPTOSs (ACADSB, CDCA3, CHAC1, MYCN, and TFAP2A), and developed a reliable FPTOS_socre system to distinguish patients into low- and high-risk groups. The findings implied that patients from the high-risk group performed poor prognoses, even after stratified analysis of various clinical parameters. A total of 30 miRNA-FPTOS regulatory pairs were recognized to identify the possible molecular mechanisms. Meanwhile, patients from the high-risk group exhibited higher TMB levels than those from the low-risk groups, and the predominant mutated driver genes were VHL, PBRM1 and TTN in both groups. The main infiltrating immune cells of high- and low-risk groups were CD8+ T cells and resting mast cells, respectively, and patients from the high-risk groups showed preferable drug responsiveness to anti-PD-1 immunotherapy. Eventually, potential sensitive drugs (cisplatin, BI-D1870, and docetaxel) and their enrichment pathways were identified to guide the treatment of ccRCC patients with high-risk.

Conclusion

Our study comprehensively analyzed the expression profiles of FPTOSs and constructed a scoring system with considerable prognostic value, which would supply novel insights into the personalized treatment strategies and prognostic evaluation of ccRCC patient.
A macropinocytosis-related gene signature predicts the prognosis and immune microenvironment in hepatocellular carcinoma
Authors: Ding Xinjiang , Yao Tao , Liu Xi , Fan Zhongwen , Liu Yuanxing
Published: March 2023

Background

Available treatments for hepatocellular carcinoma (HCC), a common human malignancy with a low survival rate, remain unsatisfactory. Macropinocytosis (MPC), a type of endocytosis that involves the non-specific uptake of dissolved molecules, has been shown to contribute to HCC pathology; however, its biological mechanism remains unknown.

Methods

The current study identified 27 macropinocytosis-related genes (MRGs) from 71 candidate genes using bioinformatics. The R software was used to create a prognostic signature model by filtering standardized mRNA expression data from HCC patients and using various methods to verify the reliability of the model and indicate immune activity.

Results

The prognostic signature was constructed using seven MPC-related differentially expressed genes, GSK3B, AXIN1, RAC1, KEAP1, EHD1, GRB2, and SNX5, through LASSO Cox regression. The risk score was acquired from the expression of these genes and their corresponding coefficients. HCC patients in the discovery and validation cohorts were stratified, and the survival of low-risk score patients was improved in both cohorts. Time-dependent ROC analysis indicated that the model’s prediction reliability was the highest in the short term. Subsequent immunologic analysis, including KEGG, located the immune action pathway of the differentially expressed genes in the direction of the cancer pathway, etc. Immune infiltration and immune checkpoint tests provided valuable guidance for future follow-up experiments.

Conclusion

A risk model with MRGs was constructed to effectively predict HCC patient prognoses and suggest changes in the immune microenvironment during the disease process. The findings should benefit the development of a prognostic stratification and treatment strategy for HCC.
Effectiveness of neoadjuvant immunochemotherapy compared to neoadjuvant chemotherapy in non-small cell lung cancer patients: Real-world data of a retrospective, dual-center study
Authors: Fei Kailun , Guo Gang , Wang Jie , Wang Zhijie , Wang Yan , Hao Xuezhi , Zhong Jia , Guo Qinxiang , Guo Wei , Su Wenzhong , Zan Likun , Xu Jiaxi , Tan Fengwei , Zhuang Xiaofei , Duan Jianchun
Published: March 2023

Background

Studying the application of neoadjuvant immunochemotherapy (NICT) in the real world and evaluating its effectiveness and safety in comparison with neoadjuvant chemotherapy (NCT) are critically important.

Methods

This study included the II-IIIB stage non-small cell lung cancer (NSCLC) patients receiving NCT with or without PD-1 inhibitors and undergoing surgery after neoadjuvant treatments between January 2019 to August 2022. The clinical characteristics and treatment outcomes were retrospectively reviewed and analyzed.

Results

A total of 66 patients receiving NICT and 101 patients receiving NCT were included in this study. As compared to NCT, NICT showed similar safety while not increasing the surgical difficulty. The ORR in the NICT and NCT groups was 74.2% and 53.5%, respectively, P = 0.009. A total of 44 patients (66.7%) in the NICT group and 21 patients (20.8%) in the NCT group showed major pathology response (MPR) (P <0.001). The pathology complete response (pCR) rate was also significantly higher in NICT group than that in NCT group (45.5% vs. 10.9%, P <0.001). After Propensity Score Matching (PSM), 42 pairs of patients were included in the analysis. The results showed no significant difference in the ORR between the two groups (52.3% vs. 43.2%, P = 0.118), and the proportions of MPR (76.2%) and pCR (50.0%) in NICT group were significantly higher than those of MPR (11.9%) and pCR (4.7%) in the NCT group (P <0.001). The patients with driver mutations might also benefit from NICT.

Conclusions

As compared to NCT, the NICT could significantly increase the proportions of patients with pCR and MPR without increasing the operation-related bleeding and operation time.
Association between intraoperative dexmedetomidine and all-cause mortality and recurrence after laparoscopic resection of colorectal cancer: Follow-up analysis of a previous randomized controlled trial
Authors: Hu Jingping , Gong Chulian , Xiao Xue , Chen Liubing , Zhang Yihan , Li Xiaoyue , Li Yanting , Zang Xiangyang , Huang Pinjie , Zhou Shaoli , Chen Chaojin
Published: March 2023

Background

Dexmedetomidine (DEX) has been widely applied in the anesthesia and sedation of patients with oncological diseases. However, the potential effect of DEX on tumor metastasis remains contradictory. This study follows up on patients who received intraoperative DEX during laparoscopic resection of colorectal cancer as part of a previous clinical trial, examining their outcomes 5 years later.

Methods

Between June 2015 and December 2015, 60 patients undergoing laparoscopic colorectal resection were randomly assigned to the DEX and control groups. The DEX group received an initial loading dose of 1μ/kg before surgery, followed by a continuous infusion of 0.3μg/kg/h during the operation and the Control group received an equivalent volume of saline. A 5-year follow-up analysis was conducted to evaluate the overall survival, disease-free survival, and tumor recurrence.

Results

The follow-up analysis included 55 of the 60 patients. The DEX group included 28 patients, while the control group included 27 patients. Baseline characteristics were comparable between the two groups, except for vascular and/or neural invasion of the tumor in the DEX group (9/28 vs. 0/27, p = 0.002). We did not observe a statistically significant benefit but rather a trend toward an increase in overall survival and disease-free survival in the DEX group, 1-year overall survival (96.4% vs. 88.9%, p = 0.282), 2-year overall survival (89.3% vs. 74.1%, p = 0.144), 3-year overall survival (89.3% vs. 70.4%, p = 0.08), and 5-year overall survival (78.6% vs. 59.3%, p = 0.121). The total rates of mortality and recurrence between the two groups were comparable (8/28 vs. 11/27, p = 0.343).

Conclusion

Administration of DEX during laparoscopic resection of colorectal cancer had a nonsignificant trend toward improved overall survival and disease-free survival.

Clinical Trial Registration

http://www.chictr.org.cn/, identifier ChiCTRIOR-15006518.
Clinical thought-based software for diagnosing developmental dysplasia of the hip on pediatric pelvic radiographs
Authors: Sha Jia , Huang Luyu , Chen Yaopeng , Fan Zongzhi , Lin Jincong , Yang Qinghai , Li Yi , Yan Yabo
Published: March 2023

Background

The common methods of radiographic diagnosis of developmental dysplasia of the hip (DDH) include measuring hip parameters and quantifying the degree of hip dislocation. However, clinical thought-based analysis of hip parameters may be a more effective way to achieve expert-like diagnoses of DDH. This study aims to develop a diagnostic strategy-based software for pediatric DDH and validate its clinical feasibility.

Methods

In total, 543 anteroposterior pelvic radiographs were retrospectively collected from January 2017 to December 2021. Two independent clinicians measured four diagnostic indices to compare the diagnoses made by the software and conventional manual method. The diagnostic accuracy was evaluated using the receiver operator characteristic (ROC) curves and confusion matrix, and the consistency of parametric measurements was assessed using Bland-Altman plots.

Results

In 543 cases (1,086 hips), the area under the curve, accuracy, sensitivity, and specificity of the software for diagnosing DDH were 0.988–0.994, 99.08%–99.72%, 98.07%–100.00%, and 99.59%, respectively. Compared with the expert panel, the Bland-Altman 95% limits of agreement for the acetabular index, as determined by the software, were −2.09°–2.91° (junior orthopedist) and −1.98°–2.72° (intermediate orthopedist). As for the lateral center-edge angle, the 95% limits were −3.68°–5.28° (junior orthopedist) and −2.94°–4.59° (intermediate orthopedist).

Conclusions

The software can provide expert-like analysis of pelvic radiographs and obtain the radiographic diagnosis of pediatric DDH with great consistency and efficiency. Its initial success lays the groundwork for developing a full-intelligent comprehensive diagnostic system of DDH.
The therapeutic potential of glucagon-like peptide-1 for persons with addictions based on findings from preclinical and clinical studies
Authors: Jerlhag Elisabet
Published: March 2023

Although the multifaceted mechanisms underlying alcohol use disorder (AUD) have been partially defined, the neurobiological complexity of this disorder is yet to be unraveled. One of the systems that have gained attention in recent times is the gut–brain axis. Although numerous peptides participate in this axis, glucagon-like peptide-1 (GLP-1) plays a central role. GLP-1 is a crucial anorexigenic peptide, with potent abilities to reduce food intake and body weight. The physiological complexity of GLP-1 entails glucose homeostasis, gastrointestinal motility, and the release of insulin and glucagon. As reviewed in this study, acute or repeated treatment with GLP-1 receptor (GLP-1R) agonists decreases alcohol consumption in rodents. Moreover, the abilities of alcohol to promote hyperlocomotion, dopamine release in the nucleus accumbens, and reward in the conditioned place preference paradigm are all suppressed by GLP-1R ligands. Moreover, activation of GLP-1R suppresses the motivation to consume alcohol, alcohol-seeking behaviors, and relapse drinking in male rodents. Similarly, abstinence symptoms experienced during alcohol withdrawal are attenuated by activation of the GLP-1 pathway. On a similar note, the activation of GLP-1 receptors within areas of the brain that are processing reward modulates these alcohol-related responses. Another area that is crucial for this ability is the nucleus of the solitary tract, which is where GLP-1 is produced and from which GLP-1-containing neurons project to areas of reward. These findings may have clinical relevance as AUD is associated with polymorphisms in GLP-1-related genes. Although a GLP-1R agonist does not alter alcohol intake in AUD patients, it reduces this consumption in a sub-population of obese AUD individuals. Given the uncertainty of this outcome, additional clinical studies of obese AUD patients should explore the effects of the GLP-1R agonists on alcohol intake and body weight. Furthermore, GLP-1 receptors modulate the behavioral and neurochemical responses to addictive drugs. Taken together, these preclinical and clinical findings imply that the GLP-1 pathway plays a role in the complex mechanisms regulating alcohol and drug consumption patterns, unveiling a novel aspect of addiction medicine.
Association of diabetes, hypertension, and their combination with basal symptoms and treatment responses in overactive bladder patients
Authors: Müderrisoglu A. Elif , Sakul Ayse A. , Murgas Sandra , de la Rosette Jean J. M. C. H. , Michel Martin C.
Published: March 2023

Introduction: Pelvic hypoperfusion caused by atherosclerosis has been proposed as a cause of lower urinary tract dysfunction including overactive bladder syndrome (OAB). Limited data indicate that OAB patients with concomitant diabetes or hypertension, known risk factors of atherosclerosis, may exhibit greater baseline OAB symptoms and slightly smaller therapeutic responses to treatment, but the impact of a combined presence of diabetes and hypertension has not been reported. Therefore, we have explored whether the combined presence of both comorbidities is associated with greater baseline OAB symptoms than that of either comorbidity alone. Secondary questions were exploration of the impact of either comorbidity on baseline symptoms, and of the impact of either comorbidity alone and their combination on therapeutic responses.

Methods: Data from two non-interventional studies applying treatment with propiverine ER 30 or 45 mg/d for 12 weeks were analyzed.

Results: Number of urgency episodes in the combination group was greater than with each comorbidity alone. The impact of comorbidities on baseline intensity of incontinence, frequency or nocturia or Patient Perception of Bladder Condition was less consistent or absent. Either comorbidity alone was associated with a smaller % improvement of symptoms, and their combination had a greater effect than either alone. However, all attenuations associated with comorbidity were small relative to the overall improvement.

Conclusions: We conclude that comorbidities of diabetes and hypertension have detectable effects on OAB symptoms and treatment responses, but the small magnitude of these alterations does not justify changing existing paradigms for the clinical management of OAB.
Unravelling the role of obesity and lipids during tumor progression
Authors: Zhao Junzhe , Lee Keene , Toh Han Chong , Lam Kong Peng , Neo Shi Yong
Published: March 2023

The dysregulation of the biochemical pathways in cancer promotes oncogenic transformations and metastatic potential. Recent studies have shed light on how obesity and altered lipid metabolism could be the driving force for tumor progression. Here, in this review, we focus on liver cancer and discuss how obesity and lipid-driven metabolic reprogramming affect tumor, immune, and stroma cells in the tumor microenvironment and, in turn, how alterations in these cells synergize to influence and contribute to tumor growth and dissemination. With increasing evidence on how obesity exacerbates inflammation and immune tolerance, we also touch upon the impact of obesity and altered lipid metabolism on tumor immune escape.
Role of transporters in regulating mammalian intracellular inorganic phosphate
Authors: Jennings Michael L.
Published: March 2023

This review summarizes the current understanding of the role of plasma membrane transporters in regulating intracellular inorganic phosphate ([Pi]In) in mammals. Pi influx is mediated by SLC34 and SLC20 Na+-Pi cotransporters. In non-epithelial cells other than erythrocytes, Pi influx via SLC20 transporters PiT1 and/or PiT2 is balanced by efflux through XPR1 (xenotropic and polytropic retrovirus receptor 1). Two new pathways for mammalian Pi transport regulation have been described recently: 1) in the presence of adequate Pi, cells continuously internalize and degrade PiT1. Pi starvation causes recycling of PiT1 from early endosomes to the plasma membrane and thereby increases the capacity for Pi influx; and 2) binding of inositol pyrophosphate InsP8 to the SPX domain of XPR1 increases Pi efflux. InsP8 is degraded by a phosphatase that is strongly inhibited by Pi. Therefore, an increase in [Pi]In decreases InsP8 degradation, increases InsP8 binding to SPX, and increases Pi efflux, completing a feedback loop for [Pi]In homeostasis. Published data on [Pi]In by magnetic resonance spectroscopy indicate that the steady state [Pi]In of skeletal muscle, heart, and brain is normally in the range of 1–5 mM, but it is not yet known whether PiT1 recycling or XPR1 activation by InsP8 contributes to Pi homeostasis in these organs. Data on [Pi]In in cultured cells are variable and suggest that some cells can regulate [Pi] better than others, following a change in [Pi]Ex. More measurements of [Pi]In, influx, and efflux are needed to determine how closely, and how rapidly, mammalian [Pi]In is regulated during either hyper- or hypophosphatemia.
Computer-aided quantitative ultrasound algorithm of acromiohumeral distance among individuals with spinal cord injury
Authors: Lin Yen-Sheng , Kim Hyungtaek , Seitz Amee L. , Tsai Tsung-Yuan , Jain Nitin
Published: March 2023

Background: Shoulder ultrasound is a well-established point-of-care diagnostic modality in orthopaedic and sports medicine. Despite offering measurements of high-quality morphology, this methodology has faced several challenges, including variability in ultrasound systems, operator dependency, and lack of reliable and objective quantitative measures to track disease progression and responses to therapeutic interventions. Computer-aided quantitative ultrasound algorithm (CAQUSA) is an emerging novelty that automates the detection of normal and abnormal structures. Although CAQUSA has been shown to improve detections and diagnoses of soft tissue lesions, the proof-of-concept of utilizing CAQUSA to measure subacromial space width and its encroachment to the rotator cuff tendon have not been tested to assist in clinical decision-making for subacromial pain syndrome.

Objective: This study aimed to develop a CAQUSA that measured the acromiohumeral distance (AHD) and test the algorithm’s reliability and agreement with manual measurements in wheelchair users with spinal cord injury (SCI).

Methods: 116 ultrasound video clips recorded from 10 manual wheelchair users with SCI were evaluated manually by an experienced examiner with expertise in AHD examination and by the CAQUSA, which was developed for bone segmentation with probability mapping. The reliability and agreement of the diagnostic performance between the examiner and the CAQUSA were calculated and compared in both groups of AHD measurements.

Results: The CAQUSA achieved a satisfactory agreement between computer-aided (11.95 ± 2.29 mm) and manual (11.33 ± 2.48 mm) measurements. The intraclass correlation coefficient between the two measures was excellent (ICC = 0.95). The sensitivity was 0.2 mm, with 95% true positives and 5% false positives at the fixed threshold of CAQUSA.

Conclusion: AHD measurements made by the clinical observer were similar to that of the CAQUSA for assessing the clinical metrics related to subacromial pain syndrome. However, the CAQUSA showed greater reliability in its unclear or misleading image analysis. Based on the findings of this proof-of-concept study, the CAQUSA has promise for clinical utilization and interchangeability to minimize examiner-dependent errors and potentially reduce the cost of care.
Enabling unstructured-mesh computation on massively tiled AI processors: An example of accelerating in silico cardiac simulation
Authors: Burchard Luk , Hustad Kristian Gregorius , Langguth Johannes , Cai Xing
Published: March 2023

A new trend in processor architecture design is the packaging of thousands of small processor cores into a single device, where there is no device-level shared memory but each core has its own local memory. Thus, both the work and data of an application code need to be carefully distributed among the small cores, also termed as tiles. In this paper, we investigate how numerical computations that involve unstructured meshes can be efficiently parallelized and executed on a massively tiled architecture. Graphcore IPUs are chosen as the target hardware platform, to which we port an existing monodomain solver that simulates cardiac electrophysiology over realistic 3D irregular heart geometries. There are two computational kernels in this simulator, where a 3D diffusion equation is discretized over an unstructured mesh and numerically approximated by repeatedly executing sparse matrix-vector multiplications (SpMVs), whereas an individual system of ordinary differential equations (ODEs) is explicitly integrated per mesh cell. We demonstrate how a new style of programming that uses Poplar/C++ can be used to port these commonly encountered computational tasks to Graphcore IPUs. In particular, we describe a per-tile data structure that is adapted to facilitate the inter-tile data exchange needed for parallelizing the SpMVs. We also study the achievable performance of the ODE solver that heavily depends on special mathematical functions, as well as their accuracy on Graphcore IPUs. Moreover, topics related to using multiple IPUs and performance analysis are addressed. In addition to demonstrating an impressive level of performance that can be achieved by IPUs for monodomain simulation, we also provide a discussion on the generic theme of parallelizing and executing unstructured-mesh multiphysics computations on massively tiled hardware.
Distinct microRNA and protein profiles of extracellular vesicles secreted from myotubes from morbidly obese donors with type 2 diabetes in response to electrical pulse stimulation
Authors: Aas Vigdis , Øvstebø Reidun , Brusletto Berit Sletbakk , Aspelin Trude , Trøseid Anne-Marie Siebke , Qureshi Saba , Eid Desima Shitandi Otundo , Olstad Ole Kristoffer , Nyman Tuula A. , Haug Kari Bente Foss
Published: March 2023

Lifestyle disorders like obesity, type 2 diabetes (T2D), and cardiovascular diseases can be prevented and treated by regular physical activity. During exercise, skeletal muscles release signaling factors that communicate with other organs and mediate beneficial effects of exercise. These factors include myokines, metabolites, and extracellular vesicles (EVs). In the present study, we have examined how electrical pulse stimulation (EPS) of myotubes, a model of exercise, affects the cargo of released EVs. Chronic low frequency EPS was applied for 24 h to human myotubes isolated and differentiated from biopsy samples from six morbidly obese females with T2D, and EVs, both exosomes and microvesicles (MV), were isolated from cell media 24 h thereafter. Size and concentration of EV subtypes were characterized by nanoparticle tracking analysis, surface markers were examined by flow cytometry and Western blotting, and morphology was confirmed by transmission electron microscopy. Protein content was assessed by high-resolution proteomic analysis (LC-MS/MS), non-coding RNA was quantified by Affymetrix microarray, and selected microRNAs (miRs) validated by real time RT-qPCR. The size and concentration of exosomes and MV were unaffected by EPS. Of the 400 miRs identified in the EVs, EPS significantly changed the level of 15 exosome miRs, of which miR-1233-5p showed the highest fold change. The miR pattern of MV was unaffected by EPS. Totally, about 1000 proteins were identified in exosomes and 2000 in MV. EPS changed the content of 73 proteins in exosomes, 97 in MVs, and of these four were changed in both exosomes and MV (GANAB, HSPA9, CNDP2, and ATP5B). By matching the EPS-changed miRs and proteins in exosomes, 31 targets were identified, and among these several promising signaling factors. Of particular interest were CNDP2, an enzyme that generates the appetite regulatory metabolite Lac-Phe, and miR-4433b-3p, which targets CNDP2. Several of the regulated miRs, such as miR-92b-5p, miR-320b, and miR-1233-5p might also mediate interesting signaling functions. In conclusion, we have used a combined transcriptome-proteome approach to describe how EPS affected the cargo of EVs derived from myotubes from morbidly obese patients with T2D, and revealed several new factors, both miRs and proteins, that might act as exercise factors.
Effects of a myostatin mutation in Japanese quail (Coturnix japonica) on the physicochemical and histochemical characteristics of the pectoralis major muscle
Authors: Kim Dong-Hwan , Lee Boin , Lee Joonbum , Bohrer Benjamin M. , Choi Young Min , Lee Kichoon
Published: March 2023

The aim of this study was to compare the carcass, meat quality, and histochemical characteristics of pectoralis major (PM) muscle between wild type (WT) and myostatin (Mstn) homozygous mutant (HO) quail lines. The HO quail line exhibited significantly heavier body weight (HO vs. WT, 115.7 g vs. 106.2 g, approximately 110%) and PM muscle weight (HO vs. WT, 18.0 g vs. 15.2 g, approximately 120%) compared to the WT (p < 0.001). However, the two groups had similar traits (pH, redness, yellowness, and drip loss) for meat quality, although slightly higher lightness and cooking loss were observed in the mutant quail (103% and 141%, respectively, p < 0.05). For histochemical traits of PM muscle, Mstn mutant quail exhibited lower type IIA and higher type IIB percentage in the deep region than WT quail (p < 0.05), indicating a fiber conversion from the type IIA to IIB. However, the two quail lines had comparable histochemical traits in the superficial region (p > 0.05). These data suggest that Mstn mutation greatly increases muscle mass without significantly affecting meat quality.
Ankyrin-B is lipid-modified by S-palmitoylation to promote dendritic membrane scaffolding of voltage-gated sodium channel NaV1.2 in neurons
Authors: Gupta Julie P. , Jenkins Paul M.
Published: March 2023

Neuronal ankyrin-B is an intracellular scaffolding protein that plays multiple roles in the axon. By contrast, relatively little is known about the function of ankyrin-B in dendrites, where ankyrin-B is also localized in mature neurons. Recently, we showed that ankyrin-B acts as a scaffold for the voltage-gated sodium channel, NaV1.2, in dendrites of neocortical pyramidal neurons. How ankyrin-B is itself targeted to the dendritic membrane is not well understood. Here, we report that ankyrin-B is lipid-modified by S-palmitoylation to promote dendritic localization of NaV1.2. We identify the palmitoyl acyl transferase zDHHC17 as a key mediator of ankyrin-B palmitoylation in heterologous cells and in neurons. Additionally, we find that zDHHC17 regulates ankyrin-B protein levels independently of its S-acylation function through a conserved binding mechanism between the ANK repeat domain of zDHHC17 and the zDHHC ankyrin-repeat binding motif of ankyrin-B. We subsequently identify five cysteines in the N-terminal ankyrin repeat domain of ankyrin-B that are necessary for ankyrin-B palmitoylation. Mutation of these five cysteines to alanines not only abolishes ankyrin-B palmitoylation, but also prevents ankyrin-B from scaffolding NaV1.2 at dendritic membranes of neurons due to ankyrin-B’s inability to localize properly at dendrites. Thus, we show palmitoylation is critical for localization and function of ankyrin-B at dendrites. Strikingly, loss of ankyrin-B palmitoylation does not affect ankyrin-B-mediated axonal cargo transport of synaptic vesicle synaptotagmin-1 in neurons. This is the first demonstration of S-palmitoylation of ankyrin-B as an underlying mechanism required for ankyrin-B localization and function in scaffolding NaV1.2 at dendrites.
Characterizing conflict and congruence of molecular evolution across organellar genome sequences for phylogenetics in land plants
Authors: Tyszka Alexa S. , Bretz Eric C. , Robertson Holly M. , Woodcock-Girard Miles D. , Ramanauskas Karolis , Larson Drew A. , Stull Gregory W. , Walker Joseph F.
Published: March 2023

Chloroplasts and mitochondria each contain their own genomes, which have historically been and continue to be important sources of information for inferring the phylogenetic relationships among land plants. The organelles are predominantly inherited from the same parent, and therefore should exhibit phylogenetic concordance. In this study, we examine the mitochondrion and chloroplast genomes of 226 land plants to infer the degree of similarity between the organelles’ evolutionary histories. Our results show largely concordant topologies are inferred between the organelles, aside from four well-supported conflicting relationships that warrant further investigation. Despite broad patterns of topological concordance, our findings suggest that the chloroplast and mitochondrial genomes evolved with significant differences in molecular evolution. The differences result in the genes from the chloroplast and the mitochondrion preferentially clustering with other genes from their respective organelles by a program that automates selection of evolutionary model partitions for sequence alignments. Further investigation showed that changes in compositional heterogeneity are not always uniform across divergences in the land plant tree of life. These results indicate that although the chloroplast and mitochondrial genomes have coexisted for over 1 billion years, phylogenetically, they are still evolving sufficiently independently to warrant separate models of evolution. As genome sequencing becomes more accessible, research into these organelles’ evolution will continue revealing insight into the ancient cellular events that shaped not only their history, but the history of plants as a whole.
Using machine learning for crop yield prediction in the past or the future
Authors: Morales Alejandro , Villalobos Francisco J.
Published: March 2023

The use of ML in agronomy has been increasing exponentially since the start of the century, including data-driven predictions of crop yields from farm-level information on soil, climate and management. However, little is known about the effect of data partitioning schemes on the actual performance of the models, in special when they are built for yield forecast. In this study, we explore the effect of the choice of predictive algorithm, amount of data, and data partitioning strategies on predictive performance, using synthetic datasets from biophysical crop models. We simulated sunflower and wheat data using OilcropSun and Ceres-Wheat from DSSAT for the period 2001-2020 in 5 areas of Spain. Simulations were performed in farms differing in soil depth and management. The data set of farm simulated yields was analyzed with different algorithms (regularized linear models, random forest, artificial neural networks) as a function of seasonal weather, management, and soil. The analysis was performed with Keras for neural networks and R packages for all other algorithms. Data partitioning for training and testing was performed with ordered data (i.e., older data for training, newest data for testing) in order to compare the different algorithms in their ability to predict yields in the future by extrapolating from past data. The Random Forest algorithm had a better performance (Root Mean Square Error 35-38%) than artificial neural networks (37-141%) and regularized linear models (64-65%) and was easier to execute. However, even the best models showed a limited advantage over the predictions of a sensible baseline (average yield of the farm in the training set) which showed RMSE of 42%. Errors in seasonal weather forecasting were not taken into account, so real-world performance is expected to be even closer to the baseline. Application of AI algorithms for yield prediction should always include a comparison with the best guess to evaluate if the additional cost of data required for the model compensates for the increase in predictive power. Random partitioning of data for training and validation should be avoided in models for yield forecasting. Crop models validated for the region and cultivars of interest may be used before actual data collection to establish the potential advantage as illustrated in this study.