bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroprotective effect of Dl-3-n-butylphthalide against ischemia–reperfusion injury is mediated by ferroptosis regulation via the SLC7A11/GSH/GPX4 pathway and the attenuation of blood–brain barrier disruption
Authors: Xu Shuangli , Li Xuewei , Li Yutian , Li Xiangling , Lv E. , Zhang Xiaojun , Shi Youkui , Wang Yanqiang
Published: February 2023

Background

Stroke is one of the most severe diseases worldwide, resulting in physical and mental problems. Dl-3-n-butylphthalide, a compound derived from celery seed, has been approved for treating ischemic stroke in China. No study has evaluated how Dl-3-n-butylphthalide affects the ferroptosis SLC7A11/GSH/GPX4 signal pathway and blood–brain barrier (BBB) PDGFRβ/PI3K/Akt signal pathways in the rat middle cerebral artery occlusion/reperfusion (MCAO/R) model of ischemic stroke.

Methods

Sprague–Dawley rats were used to develop the MCAO/R model. Our study used three incremental doses (10, 20, and 30) of Dl-3-n-butylphthalide injected intraperitoneally 24 h after MCAO/R surgery. The neuroprotective effect and success of the model were evaluated using the neurofunction score, brain water content determination, and triphenyl-tetrazolium chloride-determined infarction area changes. Pathological changes in the brain tissue and the degree of apoptosis were examined by hematoxylin and eosin, Nissl, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. In addition, pathway proteins and RNA expression levels were studied to verify the effects of Dl-3-n-butyphthalide on both pathways. At the same time, commercial kits were used to detect glutathione, reactive oxygen species, and malondialdehyde, to detect oxidative stress in brain tissues.

Results

The middle dose of Dl-3-n-butylphthalide not only improved MCAO-induced brain dysfunction and alleviated pathological damage, brain inflammatory response, oxidative stress, and apoptosis but also protected against ferroptosis and reduced BBB damage. These changes resulted in improved neurological function in the cerebral cortex.

Conclusion

We speculate that Dl-3-n-butylphthalide has a neuroprotective effect on focal cerebral ischemia/reperfusion, which may be mediated through ferroptosis-dependent SLC7A11/GSH/GPX4 signal pathway and PDGFRβ/PI3/Akt signal pathway.
Real world validation of activity recognition algorithm and development of novel behavioral biomarkers of falls in aged control and movement disorder patients
Authors: Nouriani Ali , Jonason Alec , Sabal Luke T. , Hanson Jacob T. , Jean James N. , Lisko Thomas , Reid Emma , Moua Yeng , Rozeboom Shane , Neverman Kaiser , Stowe Casey , Rajamani Rajesh , McGovern Robert A.
Published: February 2023

The use of wearable sensors in movement disorder patients such as Parkinson’s disease (PD) and normal pressure hydrocephalus (NPH) is becoming more widespread, but most studies are limited to characterizing general aspects of mobility using smartphones. There is a need to accurately identify specific activities at home in order to properly evaluate gait and balance at home, where most falls occur. We developed an activity recognition algorithm to classify multiple daily living activities including high fall risk activities such as sit to stand transfers, turns and near-falls using data from 5 inertial sensors placed on the chest, upper-legs and lower-legs of the subjects. The algorithm is then verified with ground truth by collecting video footage of our patients wearing the sensors at home. Our activity recognition algorithm showed >95% sensitivity in detection of activities. Extracted features from our home monitoring system showed significantly better correlation (~69%) with prospectively measured fall frequency of our subjects compared to the standard clinical tests (~30%) or other quantitative gait metrics used in past studies when attempting to predict future falls over 1 year of prospective follow-up. Although detecting near-falls at home is difficult, our proposed model suggests that near-fall frequency is the most predictive criterion in fall detection through correlation analysis and fitting regression models.
A simultaneous EEG-fMRI study of thalamic load-dependent working memory delay period activity
Authors: Gomes Bernard A. , Plaska Chelsea Reichert , Ortega Jefferson , Ellmore Timothy M.
Published: February 2023

Introduction

Working memory (WM) is an essential component of executive functions which depend on maintaining task-related information online for brief periods in both the presence and absence of interfering stimuli. Active maintenance occurs during the WM delay period, the time between stimulus encoding and subsequent retrieval. Previous studies have extensively documented prefrontal and posterior parietal cortex activity during the WM delay period, but the role of subcortical structures including the thalamus remains to be fully elucidated, especially in humans.

Methods

Using a simultaneous electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) approach, we investigated the role of the thalamus during the WM delay period in a modified Sternberg paradigm following low and high memory load encoding of naturalistic scenes. During the delay, participants passively viewed scrambled scenes containing similar color and spatial frequency to serve as a perceptual baseline. Individual source estimation was weighted by the location of the thalamic fMRI signal relative to the WM delay period onset.

Results

The effects memory load on maintenance were observed bilaterally in thalamus with higher EEG source amplitudes in the low compared to high load condition occurring 160–390 ms after the onset of the delay period.

Conclusion

The main finding that thalamic activation was elevated during the low compared to high condition despite similar duration of perceptual input and upcoming motor requirements suggests a capacity-limited role for sensory filtering of the thalamus during consolidation of stimuli into WM, where the highest activity occurs when fewer stimuli need to be maintained in the presence of interfering perceptual stimuli during the delay. The results are discussed in the context of theories regarding the role of the thalamus in sensory gating during working memory.
The diagnostic value of quantitative parameters on dual-layer detector-based spectral CT in identifying ischaemic stroke
Authors: Huang Jian , Chen Jinghua , Wang Ximing , Hao Ling , Zhang Jinfeng , Zhang Xiaohui , Sheng Zhihong , Liu Kefu
Published: February 2023

Objective

To investigate the diagnostic value of quantitative parameters of spectral computed tomography (CT) in ischaemic stroke areas.

Methods

The medical records of 57 patients with acute ischaemic stroke (AIS) who underwent plain computed tomography (CT) head scans, CT angiography (CTA), and CT perfusion (CTP) were retrospectively reviewed. The ischaemic areas (including the core infarct area and penumbra) and non-ischaemic areas in each patient were quantitatively analyzed using F-STROKE software. Two independent readers measured the corresponding values of the spectroscopic quantitative parameters (effective atomic number [Zeff value], iodine density value, and iodine–no-water value) in the ischaemic area and contralateral normal area alone. The differences in spectroscopic quantitative parameters between the two groups were compared, and their diagnostic efficacy was obtained.

Results

The Zeff, iodine–no-water value, and iodine density value of the ischaemic area all showed significant lower than those of non-ischaemic tissue (P < 0.001). For differentiating the ischaemic area from non-ischaemic tissue, the area under the curve (AUC) of the Zeff value reached 0.869 (cut-off value: 7.385; sensitivity: 93.0%; specificity: 70.2%), the AUC of the iodine density value reached 0.932 (cut-off value: 0.235; sensitivity: 91.2%; specificity: 82.5%), and the AUC of the iodine–no-water value reached 0.922 (cut-off value: 0.205; sensitivity: 96.5%; specificity: 78.9%).

Conclusion

The study showed the spectral CT would be a potential novel rapid method for identifying AIS. The spectral CT quantitative parameters (Zeff, iodine density values, and iodine–no-water values) can effectively differentiate the ischaemic area from non-ischaemic tissue in stroke patients.
Spontaneous nystagmus with an upbeat component: Central or peripheral vestibular disorders?
Authors: Ling Xia , Wu Yue-Xia , Feng Yu-Fei , Zhao Tong-Tong , Zhao Gui-Ping , Kim Ji-Soo , Yang Xu , Wang Zhao-Xia
Published: February 2023

Objective

To determine the topical diagnosis and etiologies of spontaneous nystagmus (SN) with an upbeat component.

Methods

We retrospectively recruited 43 patients with SN with an upbeat component at a university hospital in China from 2020 to 2022. SN with an upbeat component was divided into pure upbeat nystagmus (UBN), SN with a predominant upbeat component, and SN with a non-predominant upbeat component. We analyzed their clinical and neurotologic findings and the final diagnosis.

Results

Fourteen (32.6%) of them showed pure UBN, while 29 (67.4%) exhibited SN mixed with an upbeat component, mixed upbeat-horizontal in 15, mixed upbeat-horizontal-torsional in 13, and upbeat-torsional in the remaining one. Pure UBN and SN with a predominant upbeat component were more common in central than in peripheral vestibular disorders [16 (80.0%) vs. 0 (0%), Chi-Square test, p < 0.001]. Central vestibular disorders were diagnosed in 20 (46.5%) patients, peripheral in 14 (32.6%), and undetermined in nine (20.9%) patients. The underlying causes mainly included acute unilateral peripheral vestibulopathy (n = 11), posterior circulation infarction (n = 9), benign recurrent vertigo (n = 4), vestibular migraine (VM, n = 3), and VM of childhood (n = 2).

Conclusion

SN with an upbeat component can be seen in both central and peripheral vestibular disorders. Pure UBN was a characteristic sign of central vestibular dysfunction. Central vestibular disorders should be highly suspected when patients show pure UBN or SN with a predominant upbeat component.
Wernicke's encephalopathy after acute pancreatitis with upper gastrointestinal obstruction: A case report and literature review
Authors: Wang Zongding , Zhang Lei , Deng Xingzhen , Peng Zili , Liang Shaoyong
Published: February 2023

A 42-year-old female was admitted with upper abdominal pain. Imaging studies and laboratory tests were performed to consider acute lipogenic pancreatitis. After symptomatic treatment, her abdominal pain was significantly relieved. However, the patient was accompanied by upper gastrointestinal obstruction, which was gradually relieved after long-term fasting, gastrointestinal decompression, and fluid rehydration. The patient developed dizziness and ataxia, which worsened. Cranial magnetic resonance imaging (MRI) indicated patchy abnormal signal shadows in the bilateral thalami and dorsal brainstem and suggested metabolic encephalopathy. Wernicke's encephalopathy (WE) was the initial diagnosis of suspicion, adequate vitamin B1 was immediately replenished until the complete resolution of symptoms, and the patient made a rapid and dramatic recovery.
Muscle fiber conduction velocity in situ revisited: A new approach to an ancient technique
Authors: Kouyoumdjian João Aris , Graca Carla Renata
Published: February 2023

The aim of this study was to measure the muscle fiber conduction velocity (MFCV) in situ in the tibialis anterior muscle in healthy subjects. A total of 36 subjects matched for age and sex were studied. The MFCV was measured with a concentric needle by intramuscular monopolar needle electrical activation at a distance of 50 mm. The mean consecutive difference (MCD) of <5 μs was obtained after a median of 62 muscle fiber action potentials (MFAPs), confirming a direct muscle fiber activation. The measuring latency was at the median point of ascending depolarizing line of the MFAP. The calculated MFCV from 784 MFAPs was 4.10 ± 0.66 m/s, 3.99 ± 0.57 for female subjects (95%, 2.85 to 5.13), and 4.20 ± 0.73 for male subjects (95%, 2.74 to 5.67). The MFCV was 5.22% faster in male subjects. The calculated fast-to-slow MFCV ratio (F/S ratio) was 1.47 for female subjects (95%, 1.27 to 2.54) and 1.67 for male subjects (95%, 1.31 to 3.74). Aging significantly increased the F/S ratio. As the MFCVs mainly depend on the muscle diameter, their assessment is a quick and helpful tool for estimating it. Its variability by the F/S ratio is also a powerful tool in the follow-up of some neuromuscular disorders.
Effects of synbiotics supplementation on anthropometric and lipid profile parameters: Finding from an umbrella meta-analysis
Authors: Musazadeh Vali , Mohammadi Anilou Maryam , Vajdi Mahdi , Karimi Arash , Sedgh Ahrabi Sana , Dehghan Parvin
Published: February 2023

Introduction

Several systematic reviews and meta-analyses have been carried out to assess the impact of synbiotics on lipid profiles and anthropometric parameters. In this regard, an umbrella meta-analysis was performed to provide a more accurate view of the overall impacts of synbiotic supplementation on lipid profile and anthropometric parameters.

Methods

Databases such as PubMed, Scopus, Embase, Web of Science, and Google Scholar were searched for this study from inception to January 2022. A random-effects model was applied to evaluate the effects of synbiotic supplementation on lipid profile and anthropometric parameters. The methodological quality of eligible articles was evaluated using the AMSTAR2 questionnaire. The GRADE approach was used to evaluate the overall certainty of the evidence in the meta-analyses.

Results

Meta-analyses of 17 studies revealed significant decreases in body mass index (BMI) (ES: −0.13 kg/m2; 95% CI: −0.19, −0.06, p < 0.001, I2 = 0.0%, p = 0.870), BW (ES: −1.30 kg; 95% CI: −2.19, −0.41, p = 0.004, I2 = 88.9%, p < 0.001), waist circumference (WC) (ES: −1.80 cm; 95% CI: −3.26, −0.34, p = 0.016, I2 = 94.1%, p < 0.001), low-density lipoprotein cholesterol (LDL-C) (ES: −2.81 mg/dl; 95% CI: −3.90, −1.72, p < 0.001, I2 = 95.1%, p < 0.001), total cholesterol (TC) (ES = −2.24 mg/dl; 95% CI: −3.18, −1.30, p < 0.001, I2 = 94.5%, p < 0.001), and triglyceride (TG) (ES: −0.43 mg/dl; 95% CI: −0.79, −0.07, p = 0.019, I2 = 78.0%, p < 0.001) but not high-density lipoprotein cholesterol (HDL-C) (ES: 0.23 mg/dl; 95% CI: −0.11, 0.56, p = 0.193, I2 = 45.2%, p = 0.051) following synbiotic supplementation.

Discussion

The present umbrella meta-analysis suggests synbiotic supplementation can slightly improve lipid profile and anthropometric indices and might be a therapeutic option for obesity and its related disorders.

Systematic review registration

www.crd.york.ac.uk/prospero, identifier CRD42022304376.
Ferroptosis-based drug delivery system as a new therapeutic opportunity for brain tumors
Authors: Yao Yansheng , Ji Peng , Chen Hao , Ge Jianwen , Xu Yajing , Wang Peng , Xu Li , Yan Zhirong
Published: February 2023

The brain tumor is a kind of malignant tumor with brutal treatment, high recurrence rate, and poor prognosis, and the incidence and death rate is increasing yearly. Surgery is often used to remove the primary tumor, supplemented by radiotherapy and chemotherapy, which have highly toxic side effects. Therefore, there is an urgent need to explore new strategies, methods, and technologies that can genuinely improve the treatment of brain tumors. Ferroptosis differs from traditional apoptosis’s morphological and biochemical characteristics, and ferroptosis possesses its unique characteristics and mechanisms, opening up a new field of ferroptosis treatment for cancer. It has been found that there is a close relationship between ferroptosis and brain tumors, and a novel nano-drug delivery system based on ferroptosis has been used for the ferroptosis treatment of brain tumors with remarkable effects. This review firstly analyzes the characteristics of ferroptosis, summarizes the mechanism of its occurrence and some factors that can be involved in the regulation of ferroptosis, introduces the potential link between ferroptosis and brain tumors, and clarifies the feasibility of ferroptosis in the treatment of brain tumors. It then presents the ferroptosis nano drug delivery systems developed under different metabolic pathways for ferroptosis treatment of brain tumors. Finally, it summarizes the current problems and solutions of ferroptosis nano drugs for brain tumor treatment, aiming to provide a reference for developing ferroptosis nano drugs against brain tumors.
Circulating immune index predicting the prognosis of patients with hepatocellular carcinoma treated with lenvatinib and immunotherapy
Authors: Guo De-Zhen , Zhang Shi-Yu , Dong San-Yuan , Yan Jia-Yan , Wang Yu-Peng , Cao Ya , Rao Sheng-Xiang , Fan Jia , Yang Xin-Rong , Huang Ao , Zhou Jian
Published: February 2023

Background

Immune checkpoint inhibitor (ICI)-based combination therapy has opened a new avenue for the treatment of multiple malignancies including hepatocellular carcinoma (HCC). However, considering the unsatisfactory efficacy, biomarkers are urgently needed to identify the patients most likely to benefit from ICI-based combination therapy.

Methods

A total of 194 patients undergoing ICI-based combination therapy for unresectable HCC were retrospectively enrolled and divided into a training cohort (n = 129) and a validation cohort (n = 65) randomly. A novel circulating immune index (CII) defined as the ratio of white blood cell count (×109/L) to lymphocyte proportion (%) was constructed and its prognostic value was determined and validated.

Results

Patients with CII ≤ 43.1 reported prolonged overall survival (OS) compared to those with CII > 43.1 (median OS: 24.7 vs 15.1 months; 6-, 12-, 18-month OS: 94.2%, 76.7%, 66.1% vs 86.4%, 68.2%, 22.8%, P = 0.019), and CII was identified as an independent prognostic factor for OS (hazard ratio, 2.24; 95% confidence interval, 1.17-4.31; P = 0.015). These results were subsequently verified in the validation cohort. Additionally, patients with low CII levels had improved best radiological tumor response (complete response, partial response, stable disease, progressive disease: 3%, 36%, 50%, 11% vs 0%, 27%, 46%, 27%; P = 0.037) and disease control rate (89% vs 73%; P = 0.031) in the pooled cohort and better pathologic response (pathologic complete response, major pathologic response, partial pathologic response, no pathologic response: 20%, 44%, 28%, 8% vs 0%, 0%, 40%, 60%; P = 0.005) in the neoadjuvant cohort. Detection of lymphocyte subsets revealed that an elevated proportion of CD4+ T cells was related to better OS, while the proportion of CD8+ T cells was not.

Conclusions

We constructed a novel circulating immune biomarker that was capable of predicting OS and therapeutic efficacy for HCC patients undergoing ICI and lenvatinib combination therapy.
Integrating copy number data of 64 iAMP21 BCP-ALL patients narrows the common region of amplification to 1.57 Mb
Authors: Hormann Femke M. , Hoogkamer Alex Q. , Boeree Aurélie , Sonneveld Edwin , Escherich Gabriele , den Boer Monique L. , Boer Judith M.
Published: February 2023

Background and purpose

Intrachromosomal amplification of chromosome 21 (iAMP21) is a rare subtype of B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). It is unknown how iAMP21 contributes to leukaemia. The currently known commonly amplified region is 5.1 Mb.

Methods

We aimed to narrow down the common region of amplification by using high resolution techniques. Array comparative genomic hybridization (aCGH) was used to determine copy number aberrations, Affymetrix U133 Plus2 expression arrays were used to determine gene expression. Genome-wide expression correlations were evaluated using Globaltest.

Results

We narrowed down the common region of amplification by combining copy number data from 12 iAMP21 cases with 52 cases from literature. The combined common region of amplification was 1.57 Mb, located from 36.07 to 37.64 Mb (GRCh38). This region is located telomeric from, but not including, RUNX1, which is the locus commonly used to diagnose iAMP21. This narrow region, which falls inside the Down Syndrome critical region, includes 13 genes of which the expression of eight genes was significantly upregulated compared with 143 non-iAMP21 B-other cases. Among these, transcriptional repressor RIPPLY3 (also known as DSCR6) was the highest overexpressed gene (fold change = 4.2, FDR < 0.001) and most strongly correlated (R = 0.58) with iAMP21-related genome-wide expression changes.

Discussion

The more precise definition of the common region of amplification could be beneficial in the diagnosis of iAMP21 based on copy number analysis from DNA sequencing or arrays as well as stimulate functional research into the role of the included genes in iAMP21 biology.
Association of circulating tumor cells and IMP3 expression with metastasis of osteosarcoma
Authors: Dai Shuangwu , Shao Xinxin , Wei Qingzhu , Du Shaohua , Hou Changhe , Li Haomiao , Jin Dadi
Published: February 2023

Background

Circulating tumor cells (CTCs) have been identified as a prognostic biomarker of tumors such as breast cancer and nasopharyngeal carcinoma, because they are obtained through a simple and noninvasive blood draw or liquid biopsy, but its clinical significance in osteosarcoma is still unclear. In this study, we analyzed the relationship between CTCs and clinicopathological features and discussed whether CTCs could be used as a biomarker for metastasis in osteosarcoma.

Methods

We enrolled 50 osteosarcoma patients with Enneking Stage IIB and Stage III and detected CTCs in 5 ml of peripheral blood samples collected from patients using the Canpatrol® CTC detection platform. Subsequently, multiplex RNA in situ hybridization (RNA-ISH) based on various molecular markers was performed to identify and classify CTCs. The relationships between clinical pathological features and CTC counts, subtypes (epithelial type, E type; hybrid epithelial/mesenchymal type, H type; mesenchymal type, M type), and insulin-like growth factor mRNA-binding protein 3 (IMP3) expression in CTCs were analyzed.

Results

CTCs were detected in 86% (43/50) of the osteosarcoma patients. The CTC counts, especially the total CTCs and H-type CTCs, signifcantly differed between Enneking Stage IIB and Stage III patients (P < 0.05). No significant differences were observed between the CTC count or type and other clinicopathological features (P > 0.05). There were significant differences in the expression of IMP3 in different types of CTCs, and the IMP3 positive rates in E/H/M type CTCs were 38.4, 65.6, and 62.0%, respectively (P < 0.001). Receiver operating characteristic (ROC) curve analysis showed that IMP3-positive CTC count had the best performance for diagnostic metastasis, with the largest area under the curve of 0.873 and cutoff value of four cells/5ml blood (sensitivity = 87.5%; specificity = 82.4%). Serial CTC monitoring in one patient suggested that total CTCs and H-type CTCs were associated with disease progression.

Conclusion

This study demonstrates that the CTCs, especially the IMP3-positive CTCs and H/M-type CTCs, are related to the metastasis of osteosarcoma.
Case report: Complete and durable response to larotrectinib (TRK inhibitor) in an infant diagnosed with angiosarcoma harbouring a KHDRBS1-NTRK3 fusion gene
Authors: Cervi Catherine , Sápi Zoltán , Bedics Gábor , Zajta Erik , Hegyi Lajos , Pápay Judit , Dezső Katalin , Varga Edit , Mudra Katalin , Bödör Csaba , Csóka Monika
Published: February 2023

Significant improvements in the survival rates of paediatric cancer have been achieved over the past decade owing to recent advances in therapeutic and diagnostic strategies. However, disease progression and relapse remain a major challenge for the clinical management of paediatric angiosarcoma. Comprehensive genomic profiling of these rare tumours using high-throughput sequencing technologies may improve patient stratification and identify actionable biomarkers for therapeutic intervention. Here, we describe the clinical, histopathological, immunohistochemical and molecular profile of a novel and precision medicine-informed case where a KHDRBS1-NTRK3 fusion determined by next-generation sequencing-based comprehensive genomic profiling led to complete and sustained remission (clinical and radiological response) in an otherwise incurable disease. Our patient represents the first paediatric angiosarcoma harbouring a targetable NTRK3 fusion in the literature and demonstrates the first example of targeting this alteration in angiosarcoma using larotrectinib, an NTRK inhibitor. Clinical and radiological remission was achieved in under two months of therapy, and the patient is currently in complete remission, 4 month after stopping larotrectinib therapy, which was given over 17 months with only mild side effects reported. Therefore, this remarkable case exemplifies the true essence of precision-based care by incorporating conventional pathology with the why, when, and how to test for rare oncogenic drivers and agnostic biomarkers in paediatric angiosarcoma.
A feasibility study of pre-sleep audio and visual alpha brain entrainment for people with chronic pain and sleep disturbance
Authors: Halpin Stephen J. , Casson Alexander J. , Tang Nicole K. Y. , Jones Anthony K. P. , O’Connor Rory J. , Sivan Manoj
Published: February 2023

Introduction

Chronic pain and sleep disturbance are bi-directionally related. Cortical electrical activity in the alpha frequency band can be enhanced with sensory stimulation via the phenomenon of entrainment, and may reduce pain perception. A smartphone based programme which delivers 10 Hz stimulation through flickering light or binaural beats was developed for use at night, pre-sleep, with the aim of improving night time pain and sleep and thereby subsequent pain and related daytime symptoms. The aim of this study was to assess the feasibility and give an indication of effect of this programme for individuals with chronic pain and sleep disturbance.

Materials and methods

In a non-controlled feasibility study participants used audio or visual alpha entrainment for 30 min pre-sleep each night for 4 weeks, following a 1 week baseline period. The study was pre-registered at ClinicalTrials.gov with the ID NCT04176861.

Results

28 participants (79% female, mean age 45 years) completed the study with high levels of data completeness (86%) and intervention adherence (92%). Daily sleep diaries showed an increase compared to baseline in total sleep time of 29 min (p = 0.0033), reduction in sleep onset latency of 13 min (p = 0.0043), and increase in sleep efficiency of 4.7% (p = 0.0009). Daily 0–10 numerical rating scale of average pain at night improved by 0.5 points compared to baseline (p = 0.027). Standardised questionnaires showed significant within-participant improvements in sleep quality (change in median Global PSQI from 16 to 12.5), pain interference (change in median BPI Pain Interference from 7.5 to 6.8), fatigue (change in median MFI total score from 82.5 to 77), and depression and anxiety (change in median HADS depression score from 12 to 10.5 and anxiety from 13.5 to 11).

Discussion

Pre-sleep use of a smartphone programme for alpha entrainment by audio or visual stimulation was feasible for individuals with chronic pain and sleep disturbance. The effect on symptoms requires further exploration in controlled studies.
Right ventricular electromechanical dyssynchrony in adults with repaired Tetralogy of Fallot
Authors: Bowen Daniel , Kauling Martijn , Loff Barreto Bernardo , McGhie Jackie , Cuypers Judith , Szili-Torok Tamas , Roos-Hesselink Jolien , van den Bosch Annemien
Published: February 2023

Background and purpose

Electromechanical dyssynchrony, manifested by right bundle branch block and regional wall mechanical dysfunction, contributes to inefficient RV function in repaired Tetralogy of Fallot (ToF). This study aims to evaluate the synchronicity of multiple RV walls using two-dimensional multi-plane echocardiography (2D-MPE) in order to augment current understanding of the mechanisms behind RV dyssynchrony.

Methods

Sixty-nine adult ToF patients [aged 33 (23–45) years; 61% male] and twenty-five matched healthy controls underwent deformational analysis of the RV lateral, anterior, inferior and septal walls following 2D-MPE acquisitions. RV synchronicity was assessed by the intra-RV deformation delay between each basal RV wall and mid-septal segment in addition to mechanical dispersion calculated across four, six and eight segments (MD).

Results

All RV wall-septum delays plus MD-4 and MD-6 indices were significantly greater in ToF patients compared to healthy controls (p < 0.001–0.03). In ToF patients, the lateral and anterior RV walls were last to reach peak deformation and anterior wall longitudinal strain was lower (p = 0.001). Post systolic shortening of at least one RV wall segment was identified in 19 (28%) ToF patients. Despite similar ECG characteristics, lateral and anterior wall-septum delays were significantly longer in patients with greater degrees of dyssynchrony (73 [37–108]ms vs. 37 [0–63]ms, p = 0.006; 91 [52-116]ms vs. 41 [1–69]ms, p = 0.013), although RV ejection fraction (RVEF) was not significantly lower. MD-4 and MD-8 indices displayed moderate negative associations with RVEF, strengthened by inclusion of lateral wall longitudinal strain (r = 0.64/0.65; p ≤0.01).

Conclusion

RV dyssynchrony in ToF is characterised by electromechanical delays between the lateral, anterior and septal walls, with anterior wall dysfunction likely associated with surgical repair of the RV outflow tract. Prospectively, 2D-MPE may have an emerging role evaluating RV mechanical response to electrical resynchronisation therapy
Protective effect of antihypertensive drugs on the risk of Parkinson’s disease lacks causal evidence from mendelian randomization
Authors: Jiang Zheng , Gu Xiao-Jing , Su Wei-Ming , Duan Qing-Qing , Ren Yan-Lin , Li Ju-Rong , Chi Li-Yi , Wang Yi , Cao Bei , Chen Yong-Ping
Published: February 2023

Background: Evidence from observational studies concerning the causal role of blood pressure (BP) and antihypertensive medications (AHM) on Parkinson’s disease (PD) remains inconclusive. A two-sample Mendelian randomization (MR) study was performed to evaluate the unconfounded association of genetic proxies for BP and first-line AHMs with PD.

Methods: Instrumental variables (IV) from the genome-wide association study (GWAS) for BP traits were used to proxy systolic BP (SBP), diastolic BP, and pulse pressure. SBP-associated variants either located within encoding regions or associated with the expression of AHM targets were selected and then scaled to proxy therapeutic inhibition of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, and thiazides. Positive control analyses on coronary heart disease (CHD) and stroke were conducted to validate the IV selection. Summary data from GWAS for PD risk and PD age at onset (AAO) were used as outcomes.

Results: In positive control analyses, genetically determined BP traits and AHMs closely mimicked the observed causal effect on CHD and stroke, confirming the validity of IV selection methodology. In primary analyses, although genetic proxies identified by “encoding region-based method” for β-blockers were suggestively associated with a delayed PD AAO (Beta: 0.115; 95% CI: 0.021, 0.208; p = 1.63E-2; per 10-mmHg lower), sensitivity analyses failed to support this association. Additionally, MR analyses found little evidence that genetically predicted BP traits, overall AHM, or other AHMs affected PD risk or AAO.

Conclusion: Our data suggest that BP and commonly prescribed AHMs may not have a prominent role in PD etiology.
Insights into bone morphogenetic proteins in cardiovascular diseases
Authors: Ye Di , Liu Yinghui , Pan Heng , Feng Yongqi , Lu Xiyi , Gan Liren , Wan Jun , Ye Jing
Published: February 2023

Bone morphogenetic proteins (BMPs) are secretory proteins belonging to the transforming growth factor-β (TGF-β) superfamily. These proteins play important roles in embryogenesis, bone morphogenesis, blood vessel remodeling and the development of various organs. In recent years, as research has progressed, BMPs have been found to be closely related to cardiovascular diseases, especially atherosclerosis, vascular calcification, cardiac remodeling, pulmonary arterial hypertension (PAH) and hereditary hemorrhagic telangiectasia (HHT). In this review, we summarized the potential roles and related mechanisms of the BMP family in the cardiovascular system and focused on atherosclerosis and PAH.
Hypoglycemic medicines in the treatment of Alzheimer’s disease: Pathophysiological links between AD and glucose metabolism
Authors: Wang Yixuan , Hu Hao , Liu Xinyu , Guo Xiangyu
Published: February 2023

Alzheimer’s Disease (AD) is a global chronic disease in adults with beta-amyloid (Aβ) deposits and hyperphosphorylated tau protein as the pathologic characteristics. Although the exact etiology of AD is still not fully elucidated, aberrant metabolism including insulin signaling and mitochondria dysfunction plays an important role in the development of AD. Binding to insulin receptor substrates, insulin can transport through the blood-brain barrier (BBB), thus mediating insulin signaling pathways to regulate physiological functions. Impaired insulin signaling pathways, including PI3K/Akt/GSK3β and MAPK pathways, could cause damage to the brain in the pathogenesis of AD. Mitochondrial dysfunction and overexpression of TXNIP could also be causative links between AD and DM. Some antidiabetic medicines may have benefits in the treatment of AD. Metformin can be beneficial for cognition improvement in AD patients, although results from clinical trials were inconsistent. Exendin-4 may affect AD in animal models but there is a lack of clinical trials. Liraglutide and dulaglutide could also benefit AD patients in adequate clinical studies but not semaglutide. Dipeptidyl peptidase IV inhibitors (DPP4is) such as saxagliptin, vildagliptin, linagliptin, and sitagliptin could boost cognitive function in animal models. And SGLT2 inhibitors such as empagliflozin and dapagliflozin were also considerably protective against new-onset dementia in T2DM patients. Insulin therapy is a promising therapy but some studies indicated that it may increase the risk of AD. Herbal medicines are helpful for cognitive function and neuroprotection in the brain. For example, polyphenols, alkaloids, glycosides, and flavonoids have protective benefits in cognition function and glucose metabolism. Focusing on glucose metabolism, we summarized the pharmacological mechanism of hypoglycemic drugs and herbal medicines. New treatment approaches including antidiabetic synthesized drugs and herbal medicines would be provided to patients with AD. More clinical trials are needed to produce definite evidence for the effectiveness of hypoglycemic medications.
Pure vibrational state energies and statistical-mechanical models for the reparameterized scarf oscillator
Authors: Eyube E. S. , Notani P. P. , Nyam G. G. , Jabil Y. Y. , Izam M. M.
Published: February 2023

In this work, the reparameterized Scarf II oscillator was employed to describe the internal vibration of diatomic systems. Analytical equations for bound state pure vibrational energies and canonical partition function were obtained. The equations were used to derive statistical-mechanical models for the prediction of molar entropy, enthalpy, Gibbs free energy and constant pressure (isobaric) heat capacity of gaseous substances. The obtained model equations were used to generate numerical data on bound state energy eigenvalues and, to investigate the thermodynamic properties of the ground states chloroborane (BCl), bromine fluoride (BrF), and bromine chloride (BrCl) molecules. With the aid of the expression for molar entropy of the system, average absolute deviations obtained for the molecules are 0.1878%, 0.1267%, and 0.0586% from experimental data. The isobaric heat capacity model yields average absolute deviation of 2.1608%, 1.8601%, and 1.9805%. The results obtained are in good agreement with available literature data on gaseous molecule. The work could be applicable in the fields of molecular physics, chemical physics, solid-state physics and chemical engineering.
The NAC transcription factors play core roles in flowering and ripening fundamental to fruit yield and quality
Authors: Liu Jianfeng , Qiao Yuyuan , Li Cui , Hou Bingzhu
Published: February 2023

Fruits are derived from flowers and play an important role in human food, nutrition, and health. In general, flowers determine the crop yield, and ripening affects the fruit quality. Although transcription factors (TFs) only account for a small part of plant transcriptomes, they control the global gene expression and regulation. The plant-specific NAC (NAM, ATAF, and CUC) TFs constitute a large family evolving concurrently with the transition of both aquatic-to-terrestrial plants and vegetative-to-reproductive growth. Thus, NACs play an important role in fruit yield and quality by determining shoot apical meristem (SAM) inflorescence and controlling ripening. The present review focuses on the various properties of NACs together with their function and regulation in flower formation and fruit ripening. Hitherto, we have a better understanding of the molecular mechanisms of NACs in ripening through abscisic acid (ABA) and ethylene (ETH), but how NACs regulate the expression of the inflorescence formation-related genes is largely unknown. In the future, we should focus on the analysis of NAC redundancy and identify the pivotal regulators of flowering and ripening. NACs are potentially vital manipulation targets for improving fruit quantity and quality.
Responses of sorghum to cold stress: A review focused on molecular breeding
Authors: Vera Hernández Pedro Fernando , Mendoza Onofre Leopoldo Ernesto , Rosas Cárdenas Flor de Fátima
Published: February 2023

Climate change has led to the search for strategies to acclimatize plants to various abiotic stressors to ensure the production and quality of crops of commercial interest. Sorghum is the fifth most important cereal crop, providing several uses including human food, animal feed, bioenergy, or industrial applications. The crop has an excellent adaptation potential to different types of abiotic stresses, such as drought, high salinity, and high temperatures. However, it is susceptible to low temperatures compared with other monocotyledonous species. Here, we have reviewed and discussed some of the research results and advances that focused on the physiological, metabolic, and molecular mechanisms that determine sorghum cold tolerance to improve our understanding of the nature of such trait. Questions and opportunities for a comprehensive approach to clarify sorghum cold tolerance or susceptibility are also discussed.
The history of olive cultivation in the southern Levant
Authors: Barazani Oz , Dag Arnon , Dunseth Zachary
Published: February 2023

The olive tree (Olea europaeaL. subsp.europaeavar.europaea) is one of the most important crops across the Mediterranean, particularly the southern Levant. Its regional economic importance dates at least to the Early Bronze Age (~3600 BCE) and its cultivation contributed significantly to the culture and heritage of ancient civilizations in the region. In the southern Levant, pollen, pits and wood remains of wild olives (O. europaeasubsp.europaeavar.sylvestris) has been found in Middle Pleistocene sediments dating to approximately 780 kya, and are present in numerous palynological sequences throughout the Pleistocene and into the Holocene. Archeological evidence indicates the olive oil production from at least the Pottery Neolithic to Chalcolithic transition (~7600-7000 BP), and clear evidence for cultivation by, 7000 BP. It is hypothesized that olive cultivation began through the selection of local genotypes of the wild var.sylvestris. Local populations of naturally growing trees today have thus been considered wild relatives of the olive. However, millennia of cultivation raises questions about whether genuine populations of var. sylvestris remain in the region. Ancient olive landraces might thus represent an ancient genetic stock closer to the ancestor gene pool. This review summarizes the evidence supporting the theory that olives were first cultivated in the southern Levant and reviews our genetic work characterizing local ancient cultivars. The significance and importance of old cultivars and wild populations are discussed, given the immediate need to adapt agricultural practices and crops to environmental degradation and global climate change.
Impact of genome duplications in drought tolerance and distribution of the diploid-tetraploid Jasione maritima
Authors: Castro Helena , Dias Maria Celeste , Castro Mariana , Loureiro João , Castro Sílvia
Published: February 2023

Polyploidy has important ecological effects, including ploidy-mediated effects on morphology, breeding system and ecological tolerances. However, there is still little comprehensive research available to test its adaptive significance and its role in driving distributional patterns. This work aimed to assess the contribution of genome duplications to ecological divergence using an experimental approach with the diploid-tetraploid Jasione maritima polyploid complex. We explored if individuals with different ploidy differ in their tolerance to water deficit and if this may contribute to explaining the distribution patterns along a latitudinal gradient in the northwest Iberian Peninsula. For that, we used three cytogenetic entities: diploids and established tetraploids collected in natural populations along a latitudinal gradient, and neotetraploids synthesized from diploid populations after treatments with colchicine. Thirty plants from each of the nine populations were grown under controlled conditions with half randomly assigned to the water deficit treatment, and half used as control. We determined experimental plants’ response by measuring fitness-related parameters, such as above and belowground biomass, plant water status, photosynthetic efficiency and pigments, membrane stability, antioxidant capacity and sugars content. Our data shows that biomass, chlorophyll content, photochemical quenching (qP) and non-photochemical quenching (NPQ) in neotetraploids and established tetraploids were significantly higher than in diploids and that these differences could be attributed to genome duplications. In response to the water deficit, diploids seem to use a strategy of avoidance, whereas tetraploids seem to employ the strategy of tolerance to overcome water deficit stress, which appears equally efficient. Additionally, we did not observe a response pattern along the latitudinal gradient of the distributional range of the J. maritima complex. The results indicate that the response to water deficit is population dependent. Further studies are necessary to understand the role of ploidy in explaining the distribution patterns of the J. maritima complex.
Quality of life in parents of autistic children: A transcultural perspective
Authors: Eapen Valsamma , Karlov Lisa , John James Rufus , Beneytez Carmen , Grimes Poppy Z. , Kang Ying Qi , Mardare Ileana , Minca Dana Galieta , Voicu Laura , Malek Khasnur Abd , Ramkumar Aishworiya , Stefanik Krisztina , Gyori Miklos , Volgyesi-Molnar Marta
Published: February 2023

Introduction

The concepts of health, illness, and disability as well as the perceptions of autism and quality of life (QoL) vary greatly across cultures and across time. This study sought to explore the interplay of culture on QoL and impact on parents caring for autistic children.

Methods

We used a transcultural dataset from seven countries (Australia, Hungary, Malaysia, Romania, Singapore, Spain, and the United Kingdom) with participating parents/carers reporting on the Quality of Life in Autism (QoLA) questionnaire. The QoLA questionnaire is a validated measure of QoL for parents of autistic children, with Part A subscale measuring parental QoL and part B subscale assessing the parental impact of the child’s autism spectrum disorder (ASD) symptoms or features. We used the Quade’s ranked analysis of covariance to determine significant differences between the countries in relation to QoLA Part A and Part B scores while adjusting for baseline differences using covariates such as parents’ gender, child’s age, and gender. Additionally, a post-hoc analysis with Bonferroni correction was also conducted to examine multiple pairwise comparisons.

Results and conclusion

We found that while the effect of features of ASD (Part B subscale) stayed strongly comparable between cultures, the self-reported parental QoL was most likely determined by different aspects of culture in different countries. It is concluded that while the ASD symptoms or features appear to affect parents in the same way across different countries, the parental QoL may be a culturally informed construct.
Multiple teams, multiple projects, multiple groups at the intersection of (multiple) research fields: A bibliometric study
Authors: Meslec Nicoleta , Curseu Petru Lucian , Fodor Oana C. , Batistič Saša , Kenda Renata
Published: February 2023

Multi-teaming is a concept studied across a variety of disciplines. While using a bibliometric approach on 255 research papers extracted from Web of Science, we aimed to depict the architecture of the multi-teaming concept across academic disciplines and time. Results of citation, co-citation and bibliographic coupling analyses identified four major fields looking at the concept of multi-teaming. The fields emerged over time from fragmentation to integration and acknowledging similarities. We identify gaps and propose (multi)-disciplinary research ideas that can benefit the field of multi-teaming.
Human perception and machine vision reveal rich latent structure in human figure drawings
Authors: Jensen Clint A. , Sumanthiran Dillanie , Kirkorian Heather L. , Travers Brittany G. , Rosengren Karl S. , Rogers Timothy T.
Published: February 2023

For over a hundred years, children’s drawings have been used to assess children’s intellectual, emotional, and physical development, characterizing children on the basis of intuitively derived checklists to identify the presence or absence of features within children’s drawings. The current study investigates whether contemporary data science tools, including deep neural network models of vision and crowd-based similarity ratings, can reveal latent structure in human figure drawings beyond that captured by checklists, and whether such structure can aid in understanding aspects of the child’s cognitive, perceptual, and motor competencies. We introduce three new metrics derived from innovations in machine vision and crowd-sourcing of human judgments and show that they capture a wealth of information about the participant beyond that expressed by standard measures, including age, gender, motor abilities, personal/social behaviors, and communicative skills. Machine-and human-derived metrics captured somewhat different aspects of structure across drawings, and each were independently useful for predicting some participant characteristics. For example, machine embeddings seemed sensitive to the magnitude of the drawing on the page and stroke density, while human-derived embeddings appeared sensitive to the overall shape and parts of a drawing. Both metrics, however, independently explained variation on some outcome measures. Machine embeddings explained more variation than human embeddings on all subscales of the Ages and Stages Questionnaire (a parent report of developmental milestones) and on measures of grip and pinch strength, while each metric accounted for unique variance in models predicting the participant’s gender. This research thus suggests that children’s drawings may provide a richer basis for characterizing aspects of cognitive, behavioral, and motor development than previously thought.