bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognition is entangled with metabolism: relevance for resting-state EEG-fMRI
Authors: Jacob Michael , Ford Judith , Deacon Terrence
Published: April 2023

The brain is a living organ with distinct metabolic constraints. However, these constraints are typically considered as secondary or supportive of information processing which is primarily performed by neurons. The default operational definition of neural information processing is that (1) it is ultimately encoded as a change in individual neuronal firing rate as this correlates with the presentation of a peripheral stimulus, motor action or cognitive task. Two additional assumptions are associated with this default interpretation: (2) that the incessant background firing activity against which changes in activity are measured plays no role in assigning significance to the extrinsically evoked change in neural firing, and (3) that the metabolic energy that sustains this background activity and which correlates with differences in neuronal firing rate is merely a response to an evoked change in neuronal activity. These assumptions underlie the design, implementation, and interpretation of neuroimaging studies, particularly fMRI, which relies on changes in blood oxygen as an indirect measure of neural activity. In this article we reconsider all three of these assumptions in light of recent evidence. We suggest that by combining EEG with fMRI, new experimental work can reconcile emerging controversies in neurovascular coupling and the significance of ongoing, background activity during resting-state paradigms. A new conceptual framework for neuroimaging paradigms is developed to investigate how ongoing neural activity is “entangled” with metabolism. That is, in addition to being recruited to support locally evoked neuronal activity (the traditional hemodynamic response), changes in metabolic support may be independently “invoked” by non-local brain regions, yielding flexible neurovascular coupling dynamics that inform the cognitive context. This framework demonstrates how multimodal neuroimaging is necessary to probe the neurometabolic foundations of cognition, with implications for the study of neuropsychiatric disorders.
Steady electrocorticogram characteristics predict specific stress-induced behavioral phenotypes
Authors: Desnouveaux Laura , Poly Betty , Edmond Mathilde , Aphezberro Cathy , Coulon David , Boutet Francis , Le Coz Christine , Fargeau Francisca , Linard Cyril , Caillol Pierre , Duffaud Anaïs M. , Servonnet Aurélie , Ferhani Ouamar , Trousselard Marion , Taudon Nicolas , Canini Frédéric , Claverie Damien
Published: April 2023

Introduction

Depending on the individual, exposure to an intense stressor may, or may not, lead to a stress-induced pathology. Predicting the physiopathological evolution in an individual is therefore an important challenge, at least for prevention. In this context, we developed an ethological model of simulated predator exposure in rats: we call this the multisensorial stress model (MSS). We hypothesized that: (i) MSS exposure can induce stress-induced phenotypes, and (ii) an electrocorticogram (ECoG) recorded before stress exposure can predict phenotypes observed after stress.

Methods

Forty-five Sprague Dawley rats were equipped with ECoG telemetry and divided into two groups. The Stress group (n = 23) was exposed to an MSS that combined synthetic fox feces odor deposited on filter paper, synthetic blood odor, and 22 kHz rodent distress calls; the Sham group (n = 22) was not exposed to any sensorial stimulus. Fifteen days after initial exposure, the two groups were re-exposed to a context that included a filter paper soaked with water as a traumatic object (TO) reminder. During this re-exposure, freezing behavior and avoidance of the filter paper were measured.

Results

Three behaviors were observed in the Stress group: 39% developed a fear memory phenotype (freezing, avoidance, and hyperreactivity); 26% developed avoidance and anhedonia; and 35% made a full recovery. We also identified pre-stress ECoG biomarkers that accurately predicted cluster membership. Decreased chronic 24 h frontal Low θ relative power was associated with resilience; increased frontal Low θ relative power was associated with fear memory; and decreased parietal β2 frequency was associated with the avoidant-anhedonic phenotype.

Discussion

These predictive biomarkers open the way to preventive medicine for stress-induced diseases.
Amyloid-beta aggregation implicates multiple pathways in Alzheimer’s disease: Understanding the mechanisms
Authors: Iliyasu Musa O. , Musa Sunday A. , Oladele Sunday B. , Iliya Abdullahi I.
Published: April 2023

Alzheimer’s disease (AD) is a progressive neurodegenerative condition characterized by tau pathology and accumulations of neurofibrillary tangles (NFTs) along with amyloid-beta (Aβ). It has been associated with neuronal damage, synaptic dysfunction, and cognitive deficits. The current review explained the molecular mechanisms behind the implications of Aβ aggregation in ADviamultiple events. Beta (β) and gamma (γ) secretases hydrolyzed amyloid precursor protein (APP) to produce Aβ, which then clumps together to form Aβ fibrils. The fibrils increase oxidative stress, inflammatory cascade, and caspase activation to cause hyperphosphorylation of tau protein into neurofibrillary tangles (NFTs), which ultimately lead to neuronal damage. Acetylcholine (Ach) degradation is accelerated by upstream regulation of the acetylcholinesterase (AChE) enzyme, which leads to a deficiency in neurotransmitters and cognitive impairment. There are presently no efficient or disease-modifying medications for AD. It is necessary to advance AD research to suggest novel compounds for treatment and prevention. Prospectively, it might be reasonable to conduct clinical trials with unclean medicines that have a range of effects, including anti-amyloid and anti-tau, neurotransmitter modulation, anti-neuroinflammatory, neuroprotective, and cognitive enhancement.
Evidence for a protective effect of the loss of α4-containing nicotinic acetylcholine receptors on Aβ-related neuropathology in Tg2576 mice
Authors: Vilella Antonietta , Romoli Benedetto , Bodria Martina , Pons Stéphanie , Maskos Uwe , Zoli Michele
Published: April 2023

Introduction

Loss of cholinergic neurons as well as α4β2* (* = containing) nicotinic acetylcholine receptors (nAChRs) is a prominent feature of Alzheimer’s disease (AD). Specifically, amyloid β (Aβ), the principal pathogenic factor of AD, is a high affinity ligand for nAChRs. Yet, the pathophysiological role of nAChRs in AD is not well established.

Methods

In the present study, we have investigated the effects of the loss of α4* nAChRs on the histological alterations of the Tg2576 mouse model of AD (APPswe) crossing hemizygous APPswe mice with mice carrying the genetic inactivation of α4 nAChR subunit (α4KO).

Results

A global decrease in Aβ plaque load was observed in the forebrain of APPswe/α4KO mice in comparison with APPswe mice, that was particularly marked in neocortex of 15 month-old mice. At the same age, several alterations in synaptophysin immunoreactivity were observed in cortico-hippocampal regions of APPswe mice that were partially counteracted by α4KO. The analysis of the immunoreactivity of specific astroglia (glial fibrillary acidic protein, GFAP) and microglia (ionized calcium-binding adapter molecule, Iba1) markers showed an increase in the number as well as in the area occupied by these cells in APPswe mice that were partially counteracted by α4KO.

Conclusion

Overall, the present histological study points to a detrimental role of α4* nAChRs that may be specific for Aβ-related neuropathology.
Alterations of peripheral cytokines, BDNF, and surface-based morphometry indices in T2DM patients without cognitive impairment
Authors: Lyu Wenjiao , Chen Yuna , Zhao Kui , Tan Xin , Wu Ye , Qiu Shijun
Published: April 2023

Purpose

This study aimed to investigate potential biological mechanisms underlying cognitive function alterations in Type 2 diabetes mellitus (T2DM) patients by integrating cortical morphology with peripheral cytokine levels and brain-derived neurotrophic factor (BDNF) levels, and to offer potential insights for the early detection of T2DM-related cognitive impairment.

Methods

This study included 16 T2DM patients with a Montreal Cognitive Assessment (MoCA) score of at least 26 points, as well as 16 healthy controls with normal cognitive function. The participants also completed the digit span test and digit symbol substitution test. Participants’ serum levels of Interleukin 4 (IL-4), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and BDNF were also examined. Each subject underwent a high-resolution 3T structural brain MRI scan. Based on the aparc. a2009s atlas, we calculated the cortical thickness, sulcus depth, gyrification index, and fractal dimension for each participant using surface-based morphometry (SBM). Correlation analysis between cognitive measures, serum levels of cytokines and BDNF, and SBM indices were further performed.

Results

The levels of IL-4 and BDNF showed significant group differences. In the T2DM group, the sulcus depth exhibited a significant decrease in the left transverse frontopolar gyri and sulci, as well as in the right pole-occipital; the fractal dimension showed a significant increase in the right posterior-dorsal part of the cingulate gyrus; and the gyrification index significantly increased in the left inferior part of the precentral sulcus and right triangular part of the inferior frontal gyrus. Correlation analysis revealed a significant positive correlation between IL-10 levels and the sulcus depth of left transverse frontopolar gyri and sulci; a significant positive correlation between the sulcus depth of the right pole-occipital and the digit span test-forward scores, and a significant negative correlation between the gyrification index of the left inferior part of the precentral sulcus and the digit span test-backward scores among T2DM participants.

Conclusion

T2DM patients without cognitive impairment displayed reductions in IL 4 and BDNF levels, as well as significant alterations in their SBM indices, indicating that prior to the emergence of cognitive impairment, the SBM indices, peripheral cytokines, and BDNF may have altered in T2DM patients. IL-10 may lessen inflammation-related brain edema and preserve sulcus depth in T2DM patients through its anti-inflammatory activity.
Vertebrobasilar artery cooling infusion in acute ischemic stroke for posterior circulation following thrombectomy: Rationale, design and protocol for a prospective randomized controlled trial
Authors: Cheng Zhe , Ding Yuchuan , Rajah Gary B. , Gao Jie , Li Fenghai , Ma Linlin , Geng Xiaokun
Published: April 2023

Background

Although endovascular mechanical thrombectomy demonstrates clinical efficacy in posterior circulation acute ischemic stroke (AIS), only one third of these patients attain functional independence with a third of patients’ expiring despite vascular recanalization. Neuroprotection strategies, such as therapeutic hypothermia (TH) have been considered a promising adjunctive treatment in AIS. We propose the following rationale, design and protocol for a prospective randomized controlled trial (RCT) aimed to determine whether Vertebrobasilar Artery Cooling Infusion (VACI) improves functional outcomes in posterior circulation AIS patients post mechanical thrombectomy.

Methods

Subjects in the study will be assigned randomly to either the cooling infusion or the control group in a 1:1 ratio (n = 40). Patients allocated to the cooling infusion group will receive 300 ml cool saline at 4C through the catheter (30 ml/min) into vertebral artery after thrombectomy. The control group will receive the same volume of 37C saline. All patients enrolled will receive standard care according to current guidelines for stroke management. The primary outcome is symptomatic intracranial hemorrhage (ICH), whereas the secondary outcomes include functional outcome score, infarction volume, mortality, ICH, fatal ICH, cerebral vasospasm, coagulation abnormality, pneumonia and urinary infection.

Discussions

This study will determine the preliminary safety, feasibility, and neuroprotective benefits of VACI in posterior circulation AIS patients with reperfusion therapy. The results of this study may provide evidence for VACI as a new therapy in posterior circulation AIS.

Clinical Trial Registration:

www.chictr.org.cn, ChiCTR2200065806, registered on November 15, 2022.
Preoperative prediction of sonic hedgehog and group 4 molecular subtypes of pediatric medulloblastoma based on radiomics of multiparametric MRI combined with clinical parameters
Authors: Wang Yuanlin , Wang Longlun , Qin Bin , Hu Xihong , Xiao Wenjiao , Tong Zanyong , Li Shuang , Jing Yang , Li Lusheng , Zhang Yuting
Published: April 2023

Purpose

To construct a machine learning model based on radiomics of multiparametric magnetic resonance imaging (MRI) combined with clinical parameters for predicting Sonic Hedgehog (SHH) and Group 4 (G4) molecular subtypes of pediatric medulloblastoma (MB).

Methods

The preoperative MRI images and clinical data of 95 patients with MB were retrospectively analyzed, including 47 cases of SHH subtype and 48 cases of G4 subtype. Radiomic features were extracted from T1-weighted imaging (T1), contrast-enhanced T1 weighted imaging (T1c), T2-weighted imaging (T2), T2 fluid-attenuated inversion recovery imaging (T2FLAIR), and apparent diffusion coefficient (ADC) maps, using variance thresholding, SelectKBest, and Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithms. The optimal features were filtered using LASSO regression, and a logistic regression (LR) algorithm was used to build a machine learning model. The receiver operator characteristic (ROC) curve was plotted to evaluate the prediction accuracy, and verified by its calibration, decision and nomogram. The Delong test was used to compare the differences between different models.

Results

A total of 17 optimal features, with non-redundancy and high correlation, were selected from 7,045 radiomics features, and used to build an LR model. The model showed a classification accuracy with an under the curve (AUC) of 0.960 (95% CI: 0.871−1.000) in the training cohort and 0.751 (95% CI: 0.587−0.915) in the testing cohort, respectively. The location of the tumor, pathological type, and hydrocephalus status of the two subtypes of patients differed significantly (p < 0.05). When combining radiomics features and clinical parameters to construct the combined prediction model, the AUC improved to 0.965 (95% CI: 0.898−1.000) in the training cohort and 0.849 (95% CI: 0.695−1.000) in the testing cohort, respectively. There was a significant difference in the prediction accuracy, as measured by AUC, between the testing cohorts of the two prediction models, which was confirmed by Delong’s test (p = 0.0144). Decision curves and nomogram further validate that the combined model can achieve net benefits in clinical work.

Conclusion

The combined prediction model, constructed based on radiomics of multiparametric MRI and clinical parameters can potentially provide a non-invasive clinical approach to predict SHH and G4 molecular subtypes of MB preoperatively.
Association of plant-based diets with adropin, atherogenic index of plasma, and metabolic syndrome and its components: A cross-sectional study on adults
Authors: Shahdadian Farnaz , Saneei Parvane , Lotfi Keyhan , Feizi Awat , Askari Gholamreza , Safavi Sayyed Morteza
Published: April 2023

Background

Little is known about the association of plant-based diet indices with metabolic syndrome (MetS) and its novel predictive biomarkers, including the atherogenic index of plasma (AIP) and adropin. We aimed to investigate the association of plant-based diets with adropin, atherogenic index of plasma, and MetS and its components in adults.

Methods

The present population-based cross-sectional study was conducted on a representative sample of adults aged 20–60 years in Isfahan, Iran. Dietary intake was obtained through a validated 168-item semi-quantitative food frequency questionnaire (FFQ). Peripheral blood was obtained after an overnight fast of at least 12 h from each participant. MetS was identified based on the Joint Interim Statement (JIS). AIP was calculated as a logarithmically transformed ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-c), and serum levels of adropin were measured by an ELISA kit.

Results

A total of 28.7% of subjects had MetS. No significant association was found between the overall plant-based diet index (PDI) and the healthful plant-based diet index (hPDI) with MetS. However, a non-linear association was observed between hPDI and MetS. Subjects in the third quartile of the unhealthful plant-based diet index (uPDI) had higher odds of MetS compared to the first quartile (OR: 2.39; 95% CI: 1.01, 5.66). The highest quartile of PDI (OR: 0.46; 95% CI: 0.21, 0.97) and the third quartile of hPDI (OR: 0.40; 95% CI: 0.18, 0.89) were associated with decreased odds of having high-risk AIP compared to the first quartile, after adjusting for potential confounders. No linear association was found between quartiles of plant-based diet indices and serum levels of adropin.

Conclusion

Plant-based diet index (PDI) and hPDI were not associated with the prevalence of MetS in adults, while moderate adherence to uPDI increased the prevalence of MetS. In addition, high adherence to PDI and moderate adherence to hPDI were associated with decreased odds of high-risk AIP. No significant association was found between plant-based diet indices and serum adropin levels. To confirm these findings, further studies with prospective designs are warranted.
Trends in elevated waist-to-height ratio and waist circumference in U.S. adults and their associations with cardiometabolic diseases and cancer, 1999–2018
Authors: Yang Bo , Yang Jingli , Wong Martin Ming-him , Rana Juwel , Yang Qinghua , Chan Vicky , Khan Moyukh Shabon , Yang Aimin , Lo Kenneth
Published: April 2023

Introduction

Although waist-to-height ratio (WHtR) has established association with cardiometabolic disease, the trend of changes in elevated WHtR among general population have not been examined adequately.

Methods

This study examined the prevalence of elevated WHtR and waist circumference (WC) and their trends over time using Joinpoint regression models among adults who participated in the United States National Health and Nutrition Examination Survey (U.S. NHANES) 1999–2018. We performed weighted logistic regression to identify the association between central obesity subtypes and the prevalence of comorbidities, including diabetes, chronic kidney disease, hypertension, cardiovascular disease, and cancer.

Results

The prevalence of elevated WHtR has increased from 74.8% in 1999–2000 to 82.7% in 2017–2018 while elevated WC also increased from 46.9% in 1999–2000 to 60.3% in 2017–2018. Men, older adults, former smokers, and people with lower education levels were more likely to have elevated WHtR. A total of 25.5% of American adults had normal WC but elevated WHtR, and they had a significantly higher chance of suffering from diabetes (odds ratio [OR] = 2.06 [1.66, 2.55]), hypertension (OR = 1.75 [1.58, 1.93]) and CVD (OR = 1.32 [1.11, 1.57]).

Discussion

In conclusion, the burden of elevated WHtR and WC have been increasing among U.S. adults throughout the years, and the changes have been more significant across most subgroups. It is also notable that approximately a quarter of the population had normal WC but elevated WHtR, which had increased likelihood of having cardiometabolic diseases, especially diabetes. Future clinical practices should pay more attention to this subgroup of the population with overlooked health risks.
Ultrasound improves the physicochemical and foam properties of whey protein microgel
Authors: Wang Zhaoxin , Zhao Haibo , Tao Haiteng , Yu Bin , Cui Bo , Wang Yan
Published: April 2023

Whey protein microgel (WPM) is an emerging multifunctional protein particle and methods to improve its functional properties are continuously being explored. We developed a method to prepare WPM by heat-induced self-assembly under different ultrasound power (160, 320, 480, and 640 W/cm2) and characterized the particle size, surface hydrophobicity, disulfide bond, viscosity, and foam properties of WPM. Ultrasound increased the particle size of WPM-160 W to 31 μm. However, the increase in ultrasound power gradually reduced the average particle size of samples. The intrinsic fluorescence spectrum showed that ultrasound unfolded the structure of whey protein and exposed more hydrophobic groups, which increased the surface hydrophobicity of WPM. In addition, infrared spectroscopy suggested ultrasound decreased the α-helix content of WPM, implying an increase in the flexibility of protein molecules. The disulfide bond of WPM was broken by ultrasound, and the content of the-SH group increased correspondingly. The rheology indicated that the apparent viscosity decreased with the increase of ultrasonic power. Compared with the control, the ultrasonicated WPM displayed higher foam ability. Ultrasound improved the foam stability of WPM-160 W but destroyed the foam stability of other samples. These results suggest that proper ultrasound treatment can improve the physicochemical and foam properties of WPM.
Association of a novel nutritional index with stroke in Chinese population with hypertension: Insight from the China H-type hypertension registry study
Authors: Shi Yumeng , Wang Xingjiu , Yu Chao , Zhou Wei , Wang Tao , Zhu Lingjuan , Bao Huihui , Cheng Xiaoshu
Published: April 2023

Objective

The abbreviated TCB index (TCBI) is a novel indicator of nutritional status, calculated by multiplying the serum values of triglycerides (TG), total serum cholesterol (TC), and body weight. The research on the relationship between this index and stroke is limited. We aimed to investigate the association between TCBI and stroke in Chinese hypertensive patients.

Methods and results

A total of 13,358 adults with hypertension from the China H-type Hypertension Registry Study were enrolled. The TCBI was calculated as TG (mg/dL) * TC (mg/dL) * body weight (kg)/1,000. The primary outcome was an incidence of stroke. Multivariable adjusted models revealed an inverse association between TCBI and the prevalence of stroke. In the fully adjusted model, the results showed that the prevalence of stroke decreased by 13% (OR, 0.87; 95% CI, 0.78–0.98, p = 0.018) per SD increment of LgTCBI. When TCBI was assessed as a categorical variable, compared with those in group Q4 (TCBI ≥ 2,399), the participants in group Q3 (TCBI ≥ 1,476 and <2,399), group Q2 (TCBI ≥ 920 and <1,476), and group Q1 (TCBI < 920) had increases in stroke prevalence of 42% (OR, 1.42; 95% CI, 1.13–1.80; p-value = 0.003), 38% (OR, 1.38; 95% CI, 1.07–1.80; p-value = 0.014), and 68% (OR, 1.68; 95% CI, 1.24–2.27; p-value = 0.001), respectively. Subgroup analysis showed an interaction between age and TCBI and stroke (age < 60 years OR, 0.69; 95% CI, 0.58–0.83; vs. age ≥ 60 years OR, 0.95; 95% CI, 0.84–1.07; P for interaction = 0.001).

Conclusion

We found an independent negative association between TCBI and the prevalence of stroke, especially in hypertensive patients aged < 60 years.
Nanomaterial Technology and Triple Negative Breast Cancer
Authors: Hou Kai , Ning Zeng , Chen Hongbo , Wu Yiping
Published: April 2023

Triple negative breast cancer (TNBC) is a malignant breast cancer subtype that is prone to progression, with high associated metastasis and five-year mortality rates and an overall poor prognosis. Chemotherapy is usually administered to treat TNBC without additional targeted therapies. Novel nanomaterials have a variety of excellent physical and chemical properties and biological functions (including targeting specificity), and contrast agents and drug delivery vectors based on nanotechnology are progressing towards a more accurate and targeted direction. This review discusses the mechanisms of action and prospects for the use of nanotechnology in the treatment of TNBC, thus providing potential new strategies for the diagnosis and treatment of TNBC.
Paradoxical activation of chronic lymphocytic leukemia cells by ruxolitinib in vitro and in vivo
Authors: Spaner David E. , Luo Tina YuXuan , Wang Guizhi , Schreiber Gideon , Harari Daniel , Shi Yonghong
Published: April 2023

Introduction

Chronic lymphocytic leukemia (CLL) is characterized by an aberrant cytokine network that can support tumor growth by triggering janus kinase (JAK)/STAT pathways. Targeting cytokine-signaling should then be a rational therapeutic strategy but the JAK inhibitor ruxolitinib failed to control and seemingly accelerated the disease in clinical trials.

Methods

The effect of ruxolitinib on primary human CLL cells was studied in vitro and in vivo.

Results

Ruxolitinib increased phosphorylation of IRAK4, an important toll-like receptor (TLR)- signaling intermediate, in circulating CLL cells in vitro. It also enhanced p38 and NFKB1 phosphorylation while lowering STAT3 phosphorylation in CLL cells activated with TLR-7/8 agonists and IL-2. Among the cytokines made by activated CLL cells, high levels of IL-10 contributed strongly to STAT3 phosphorylation and inhibited TLR7 activity. Ruxolitinib limited TLR-mediated IL10 transcription and markedly reduced IL-10 production in vitro. It also decreased blood levels of IL-10 while increasing TNFα along with phospho-p38 expression and gene sets associated with TLR-activation in CLL cells in vivo. The bruton's tyrosine kinase inhibitor ibrutinib decreased IL-10 production in vitro but, in contrast to ruxolitinib, blocked initial IL10 transcription induced by TLR-signaling in vitro, decreased TNFα production, and deactivates CLL cells in vivo.

Discussion

These findings suggest the possible benefits of inhibiting growth factors with JAK inhibitors in CLL are outweighed by negative effects on potential tumor suppressors such as IL-10 that allow unrestrained activation of NFκB by drivers such as TLRs. Specific inhibition of growth-promoting cytokines with blocking antibodies or infusing suppressive cytokines like IL-10 might be better strategies to manipulate cytokines in CLL.
Case report: Malignant melanoma of the lower limb with gastric metastasis
Authors: Hu Qiang , Zhou Fengru , Sun Yuanshui
Published: April 2023

Introduction

Malignant melanoma with gastric metastasis is extremely rare. We report a case of gastric metastasis caused by malignant melanoma of the lower limb.

Case presentation

A 60-year-old woman was hospitalized for left plantar pain. The patient found a black maculopapular eruption on the left sole of her left foot, which caused pain when pressed, and the pain was aggravated by walking, so she went to our hospital for treatment. On the second day of admission, the lesion of the left foot was removed under local anesthesia, and the removed tissue was sent for pathological examination. Combined with immunohistochemistry, it was consistent with malignant melanoma. During hospitalization, the patient developed abdominal pain and asked for gastroscopy. Gastroscopy revealed two 0.5 cm × 0.6 cm spots that can be seen arising from the stomach mucosa which were slightly swollen, slightly black in the center, and without erosion, and no abnormality was found in the other parts. At the same time, a biopsy was taken under a gastroscope and pathology suggests malignant melanoma. The patient could not undergo subsequent treatment due to cost. The patient was followed up until February 2022 and was within the survival period.

Conclusion

Malignant melanoma gastric metastasis is extremely rare. When a patient has a previous history of melanoma surgery, this needs to be considered when gastrointestinal symptoms are present, and regular endoscopic screening is recommended. Early surgical treatment and postoperative chemotherapy or combined targeted therapy may improve the prognosis of patients.
Characterization of pain-, anxiety-, and cognition-related behaviors in the complete Freund's adjuvant model of chronic inflammatory pain in Wistar–Kyoto rats
Authors: Ferdousi Mehnaz I. , Calcagno Patricia , Sanchez Connie , Smith Karen L. , Kelly John P. , Roche Michelle , Finn David P.
Published: April 2023

Introduction

Chronic pain is often associated with comorbid anxiety and cognitive dysfunction, negatively affecting therapeutic outcomes. The influence of genetic background on such interactions is poorly understood. The stress-hyperresponsive Wistar–Kyoto (WKY) rat strain, which models aspects of anxiety and depression, displays enhanced sensitivity to noxious stimuli and impaired cognitive function, compared with Sprague–Dawley (SD) counterparts. However, pain- and anxiety-related behaviors and cognitive impairment following induction of a persistent inflammatory state have not been investigated simultaneously in the WKY rats. Here we compared the effects of complete Freund's adjuvant (CFA)-induced persistent inflammation on pain-, negative affect- and cognition-related behaviors in WKY vs. SD rats.

Methods

Male WKY and SD rats received intra-plantar injection of CFA or needle insertion (control) and, over the subsequent 4 weeks, underwent behavioral tests to assess mechanical and heat hypersensitivity, the aversive component of pain, and anxiety- and cognition-related behaviors.

Results

The CFA-injected WKY rats exhibited greater mechanical but similar heat hypersensitivity compared to SD counterparts. Neither strain displayed CFA-induced pain avoidance or anxiety-related behavior. No CFA-induced impairment was observed in social interaction or spatial memory in WKY or SD rats in the three-chamber sociability and T-maze tests, respectively, although strain differences were apparent. Reduced novel object exploration time was observed in CFA-injected SD, but not WKY, rats. However, CFA injection did not affect object recognition memory in either strain.

Conclusions

These data indicate exacerbated baseline and CFA-induced mechanical hypersensitivity, and impairments in novel object exploration, and social and spatial memory in WKY vs. SD rats.
A qualitative study to explore the acceptability and feasibility of implementing person-focused evidence-based pain education concepts in pre-registration physiotherapy training
Authors: Thompson Kate , Milligan James , Briggs Michelle , Deane Janet A. , Johnson Mark I.
Published: April 2023

Objectives

The purpose of this study was to engage with physiotherapy clinicians, academics, physiotherapy students and patients to explore the acceptability, feasibility, and practical considerations of implementing person-focused evidence-based pain education concepts, identified from our previous research, in pre-registration physiotherapy training.

Design

This qualitative study took a person-focused approach to ground pain education in the perspectives and experiences of people who deliver and use it. Data was collected via focus groups and in-depth semi-structured interviews. Data was analysed using the seven stage Framework approach.

Setting

Focus groups and interviews were conducted either face to face, via video conferencing or via telephone. This depended on geographical location, participant preference, and towards the end of data collection the limitations on in-person contact due to the Covid-19 pandemic.

Participants

UK based physiotherapy clinicians, physiotherapy students, academics and patients living with pain were purposively sampled and invited to take part.

Results

Five focus groups and six semi-structured interviews were conducted with twenty-nine participants. Four key dimensions evolved from the dataset that encapsulate concepts underpinning the acceptability and feasibility of implementing pain education in pre-registration physiotherapy training. These are (1) make pain education authentic to reflect diverse, real patient scenarios, (2) demonstrate the value that pain education adds, (3) be creative by engaging students with content that requires active participation, (4) openly discuss the challenges and embrace scope of practice.

Conclusions

These key dimensions shift the focus of pain education towards practically engaging content that reflects people experiencing pain from diverse sociocultural backgrounds. This study highlights the need for creativity in curriculum design and the importance of preparing graduates for the challenges that they will face in clinical practice.
Maternal and fetal factors influencing fetal fraction: A retrospective analysis of 153,306 pregnant women undergoing noninvasive prenatal screening
Authors: Deng Cechuan , Liu Jianlong , Liu Sha , Liu Hongqian , Bai Ting , Jing Xiaosha , Xia Tianyu , Liu Yunyun , Cheng Jing , Wei Xiang , Xing Lingling , Luo Yuan , Zhou Quanfang , Zhu Qian , Liu Shanling
Published: April 2023

Background

Genetic factors are important causes of birth defects. Noninvasive prenatal screening (NIPS) is widely used for prenatal screening of trisomy 21, trisomy 18, and trisomy 13, which are the three most common fetal aneuploidies. Fetal fraction refers to the proportion of cell-free fetal DNA in maternal plasma, which can influence the accuracy of NIPS. Elucidating the factors that influence fetal fraction can provide guidance for the interpretation of NIPS results and genetic counseling. However, there is currently no broad consensus on the known factors that influence fetal fraction.

Objective

The study aimed to explore the maternal and fetal factors influencing fetal fraction.

Methods

A total of 153,306 singleton pregnant women who underwent NIPS were included. Data on gestational age; maternal age; body mass index (BMI); z-scores for chromosomes 21, 18, and 13; and fetal fraction in NIPS were collected from the study population, and the relationships between fetal fraction and these factors were examined. The relationship between fetal fraction and different fetal trisomy types was also analyzed.

Results

The results showed that the median gestational age, maternal age, and BMI of the pregnant women were 18 (16, 20) weeks, 29 (25, 32) years, and 22.19 (20.40, 24.24) kg/m2, respectively. The median fetal fraction was 11.62 (8.96, 14.7)%. Fetal fraction increased with gestational age and decreased with maternal age and BMI (P < 0.001). Fetal fraction of fetuses with trisomies 21, 18, and 13 was similar to that of the NIPS-negative group. The z-scores of pregnant women with trisomy 21 and 18 fetuses were positively correlated with fetal fraction, but not with that of the trisomy 13 cases.

Conclusions

The factors that influence fetal fraction need to be taken into consideration before NIPS for quality control and after NIPS for result interpretation.
Opioids Regulate the Immune System: Focusing on Macrophages and Their Organelles
Authors: Wen Shaohua , Jiang Yuan , Liang Shuang , Cheng Zhigang , Zhu Xiaoyan , Guo Qulian
Published: April 2023

Opioids are the most widely used analgesics and therefore have often been the focus of pharmacological research. Macrophages are the most plastic cells in the hematopoietic system. They show great functional diversity in various organism tissues and are an important consideration for the study of phagocytosis, cellular immunity, and molecular immunology. The expression of opioid receptors in macrophages indicates that opioid drugs act on macrophages and regulate their functions. This article reviewed the collection of research on effects of opioids on macrophage function. Studies show that opioids, both endogenous and exogenous, can affect the function of macrophages, effecting their proliferation, chemotaxis, transport, phagocytosis, expression of cytokines and chemokine receptors, synthesis and secretion of cytokines, polarization, and apoptosis. Many of these effects are closely associated with mitochondrial function and functions of other organelles in macrophages. Therefore, in depth research into effects of opioids on macrophage organelles may lead to some interesting new discoveries. In view of the important role of macrophages in HIV infection and tumor progression, this review also discusses effects of opioids on macrophages in these two pathological conditions.
Boost of cosmetic active ingredient penetration triggered and controlled by the delivery of kHz plasma jet on human skin explants
Authors: Vijayarangan Vinodini , Dozias Sébastien , Heusèle Catherine , Jeanneton Olivier , Nizard Carine , Pichon Chantal , Pouvesle Jean Michel , Stancampiano Augusto , Robert Eric
Published: April 2023

This work reports on the demonstration of the penetration of cosmetic active ingredients (caffeine and hyaluronic acid) in human skin explants following safe and controlled plasma jet exposure. First, temperature increase and immunohistochemistry in the stratum corneum and epidermis were characterized to check the safe delivery of plasma jets and to select two operation regimes at 1 and 20 kHz. Plasma exposure for tens of seconds is shown to induce transient modulations of skin pH, transepidermal water loss, and skin wettability, revealing a reversible skin barrier function modulation. Then, it is demonstrated that plasma exposure significantly accelerates the penetration of active ingredients. The tuning of the plasma jet pulse repetition rate allows controlling the penetration kinetics. Such ex vivo results agree with previous in vitro experiments also exhibiting a transient permeabilization time window. A preliminary demonstration of human skin wettability modulation with a low-power, user-friendly dielectric barrier discharge setup is documented, opening perspectives for plasma-based home cosmetic care device development. To the best of our knowledge, this work is one of the first demonstrations of safe and controlled plasma-assisted active ingredients’ skin penetration in the context of cosmetic applications.
Effects of internal cooling on physical performance, physiological and perceptional parameters when exercising in the heat: A systematic review with meta-analyses
Authors: Heydenreich Juliane , Koehler Karsten , Braun Hans , Grosshauser Mareike , Heseker Helmut , Koenig Daniel , Lampen Alfonso , Mosler Stephanie , Niess Andreas , Schek Alexandra , Carlsohn Anja
Published: April 2023

Background: An elevated core temperature (Tcore) increases the risk of performance impairments and heat-related illness. Internal cooling (IC) has the potential to lower Tcore when exercising in the heat. The aim of the review was to systematically analyze the effects of IC on performance, physiological, and perceptional parameters.

Methods: A systematic literature search was performed in the PubMed database on 17 December 2021. Intervention studies were included assessing the effects of IC on performance, physiological, or perceptional outcomes. Data extraction and quality assessment were conducted for the included literature. The standardized mean differences (SMD) and 95% Confidence Intervals (CI) were calculated using the inverse-variance method and a random-effects model.

Results: 47 intervention studies involving 486 active subjects (13.7% female; mean age 20–42 years) were included in the meta-analysis. IC resulted in significant positive effects on time to exhaustion [SMD (95% CI) 0.40 (0.13; 0.67), p < 0.01]. IC significantly reduced Tcore [−0.19 (22120.34; −0.05), p < 0.05], sweat rate [−0.20 (−0.34; −0.06), p < 0.01], thermal sensation [−0.17 (−0.33; −0.01), p < 0.05], whereas no effects were found on skin temperature, blood lactate, and thermal comfort (p > 0.05). IC resulted in a borderline significant reduction in time trial performance [0.31 (−0.60; −0.02), p = 0.06], heart rate [−0.13 (−0.27; 0.01), p = 0.06], rate of perceived exertion [−0.16 (−0.31; −0.00), p = 0.05] and borderline increased mean power output [0.22 (0.00; 0.44), p = 0.05].

Discussion: IC has the potential to affect endurance performance and selected physiological and perceptional parameters positively. However, its effectiveness depends on the method used and the time point of administration. Future research should confirm the laboratory-based results in the field setting and involve non-endurance activities and female athletes.

Systematic review registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022336623.
ECT9 condensates with ECT1 and regulates plant immunity
Authors: Wang Hui , Niu Ruixia , Zhou Yulu , Tang Zhijuan , Xu Guoyong , Zhou Guilong
Published: April 2023

Mounting an efficient defense against pathogens requires RNA binding proteins (RBPs) to regulate immune mRNAs transcription, splicing, export, translation, storage, and degradation. RBPs often have multiple family members, raising the question of how they coordinate to carry out diverse cellular functions. In this study, we demonstrate that EVOLUTIONARILY CONSERVED C-TERMINAL REGION 9 (ECT9), a member of the YTH protein family in Arabidopsis, can condensate with its homolog ECT1 to control immune responses. Among the 13 YTH family members screened, only ECT9 can form condensates that decrease after salicylic acid (SA) treatment. While ECT1 alone cannot form condensates, it can be recruited to ECT9 condensates in vivo and in vitro. Notably, the ect1/9 double mutant, but not the single mutant, exhibits heightened immune responses to the avirulent pathogen. Our findings suggest that co-condensation is a mechanism by which RBP family members confer redundant functions.
Non-rhizobial nodule endophytes improve nodulation, change root exudation pattern and promote the growth of lentil, for prospective application in fallow soil
Authors: Debnath Sourav , Chakraborty Subhradeep , Langthasa Mrinalini , Choure Kamlesh , Agnihotri Vivek , Srivastava Arpit , Rai Piyush Kant , Tilwari Anita , Maheshwari D. K. , Pandey Piyush
Published: April 2023

Non-rhizobial endophytes (NREs) are active colonizers inhabiting the root nodules. Though their active role in the lentil agroecosystem is not well defined, here we observed that these NREs might promote the growth of lentils, modulate rhizospheric community structure and could be used as promising organisms for optimal use of rice fallow soil. NREs from root nodules of lentils were isolated and examined for plant growth-promoting traits, exopolysaccharide (EPS) and biofilm production, root metabolites, and the presence of nifH and nifK elements. The greenhouse experiment with the chosen NREs, i.e., Serratia plymuthica 33GS and Serratia sp. R6 significantly increased the germination rate, vigour index, development of nodules (in non-sterile soil) and fresh weight of nodules (33GS 94%, R6 61% growth) and length of the shoot (33GS 86%, R6 51.16%) as well as chlorophyll levels when compared to the uninoculated control. Scanning Electron Microscopy (SEM) revealed that both isolates could successfully colonize the roots and elicit root hair growth. The inoculation of the NREs resulted in specific changes in root exudation patterns. The plants with 33GS and R6 treatment significantly stimulated the exudation of triterpenes, fatty acids, and their methyl esters in comparison to the uninoculated plants, altering the rhizospheric microbial community structure. Proteobacteria dominated the rhizospheric microbiota in all the treatments. Treatment with 33GS or R6 also enhanced the relative abundance of other favourable microbes, including Rhizobium, Mesorhizobium, and Bradyrhizobium. The correlation network analysis of relative abundances resulted in numerous bacterial taxa, which were in cooperation with each other, having a possible role in plant growth promotion. The results indicate the significant role of NREs as plant growth promoters, which also includes their role in root exudation patterns, enhancement of soil nutrient status and modulation of rhizospheric microbiota, suggesting their prospects in sustainable, and bio-based agriculture.
Executive functions in daily living skills: A study in adults with autism spectrum disorder
Authors: Yon-Hernández Jo A. , Canal-Bedia Ricardo , Wojcik Dominika Z. , García-García Laura , Fernández-Álvarez Clara , Palacio-Duque Stefanny , Franco-Martín Manuel A.
Published: April 2023

Introduction

Adults with autism and adults with schizophrenia show difficulties in adaptive skills, especially those related to daily functioning. Some studies suggest that adaptive skills are associated with deficits in executive functions (EF), while others indicate that intelligence quotient (IQ) might also play a role. Literature suggests that autistic symptoms further affect adaptive skills. The interest of the current study, therefore, was to explore to what extent IQ, EFs as well as core autistic symptoms predict adaptive skills.

Methods

To do this, 25 controls, 24 adults with autism, and 12 with schizophrenia were assessed on IQ (Wechsler Adult Intelligence Scale), and executive functioning. The EF was measured with neuropsychological tasks (inhibition, updating, and task switching) and with the Dysexecutive-Spanish Questionnaire (DEX-Sp) which assessed everyday life EF problems. Core ASD symptoms were measured using the Autism Diagnostic Observation Schedule, the Autism Spectrum Quotient-Short version (AQ-S), and the Repetitive Behavior Questionnaire – 3 (RBQ-3).

Results

The results indicated EF difficulties in both, autism and schizophrenia. The IQ explained a high percentage of the variance found in adaptive skills, but only in the autism group. We can conclude, therefore, that high IQ is associated with low adaptive skills levels and EFs affect adaptive functioning in people with autism; however, this does not explain the difficulties in adaptive functioning in the schizophrenia group. Core features of autism assessed with self-report questionnaires (but not the ADOS-2) predicted low scores on the adaptive skills, only in the autism group.

Discussion

Both EF measures predicted adaptive skills scores in autism, but not in schizophrenia. Our results suggest that different factors affect the adaptive functioning in each disorder. For instance, the EFs should be a central focus for improvement, especially for individuals with autism.