bluuebunny/crossref_metadata_2025 huggingface dataset:
Perioperative Hemodynamic Optimization in Patients at Risk for Delirium – A Randomized-Controlled Trial
Authors: Fuest Kristina E. , Servatius Ariane , Ulm Bernhard , Schaller Stefan J. , Jungwirth Bettina , Blobner Manfred , Schmid Sebastian
Published: July 2022

Background

Post-operative delirium is common in elderly patients and associated with increased morbidity and mortality. We evaluated in this pilot study whether a perioperative goal-directed hemodynamic optimization algorithm improves cerebral oxygenation and can reduce the incidence of delirium.

Materials and Methods

Patients older than 70 years with high risk for post-operative delirium undergoing elective non-cardiac surgery were randomized to an intervention or control group. Patients in the intervention group received a perioperative hemodynamic optimization protocol based on uncalibrated pulse-contour analysis. Patients in the control group were managed according to usual standard of care. Incidence of delirium until day seven was assessed with confusion assessment method (CAM) and chart review. Cerebral oxygenation was measured with near-infrared spectroscopy.

Results

Delirium was present in 13 of 85 (15%) patients in the intervention group and 18 of 87 (21%) in the control group [risk difference −5.4%; 95% confidence interval, −16.8 to 6.1%; P = 0.47]. Intervention did not influence length of stay in hospital or in-hospital mortality. Amounts of fluids and vasopressors applied, mean arterial pressure, cardiac index, and near-infrared spectroscopy values were comparable between groups.

Conclusion

The hemodynamic algorithm applied in high-risk non-cardiac surgery patients did not change hemodynamic interventions, did not improve patient hemodynamics, and failed to increase cerebral oxygenation. An effect on the incidence of post-operative delirium could not be observed.

Clinical Trial Registration

[Clinicaltrials.gov], identifier [NCT01827501].
Case Report: Spontaneous Rupture of Hepatic Hemangioma
Authors: Pan Bing , Lyu Shao-Cheng , He Qiang
Published: July 2022

Background

Hepatic hemangioma (HH) is a congenital vasal malformation that seemed like the most probable benign liver neoplasm, composed of masses of blood vessels, which are anomalous in arrangement and size. In most cases, HH is asymptomatic, and patients have an excellent prognosis. According to research, the location and size of the mass are correlated with the symptoms and complications. Reports of spontaneous rupture of HH have been less reported in the literature. In this emergency condition, dynamic contrast-enhanced CT scanning, especially triple-phase computed tomography (CT) with delayed imaging, is preferred.

Case Presentation

Here, we presented two middle-aged female patients with spontaneous rupture of HH in our hospital. Following an accurate diagnosis of enhanced CT and emergency surgery, patients recovered well and were discharged from the hospital.

Conclusion

Appropriate imaging studies, especially enhanced CT, and emergency surgery are indispensable for patients with spontaneous rupture of HH. As a surgeon, we need to pay attention to the asymptomatic patient with HH.
Cyanobacteria as a Promising Alternative for Sustainable Environment: Synthesis of Biofuel and Biodegradable Plastics
Authors: Agarwal Preeti , Soni Renu , Kaur Pritam , Madan Akanksha , Mishra Reema , Pandey Jayati , Singh Shreya , Singh Garvita
Published: July 2022

With the aim to alleviate the increasing plastic burden and carbon footprint on Earth, the role of certain microbes that are capable of capturing and sequestering excess carbon dioxide (CO2) generated by various anthropogenic means was studied. Cyanobacteria, which are photosynthetic prokaryotes, are promising alternative for carbon sequestration as well as biofuel and bioplastic production because of their minimal growth requirements, higher efficiency of photosynthesis and growth rates, presence of considerable amounts of lipids in thylakoid membranes, and cosmopolitan nature. These microbes could prove beneficial to future generations in achieving sustainable environmental goals. Their role in the production of polyhydroxyalkanoates (PHAs) as a source of intracellular energy and carbon sink is being utilized for bioplastic production. PHAs have emerged as well-suited alternatives for conventional plastics and are a parallel competitor to petrochemical-based plastics. Although a lot of studies have been conducted where plants and crops are used as sources of energy and bioplastics, cyanobacteria have been reported to have a more efficient photosynthetic process strongly responsible for increased production with limited land input along with an acceptable cost. The biodiesel production from cyanobacteria is an unconventional choice for a sustainable future as it curtails toxic sulfur release and checks the addition of aromatic hydrocarbons having efficient oxygen content, with promising combustion potential, thus making them a better choice. Here, we aim at reporting the application of cyanobacteria for biofuel production and their competent biotechnological potential, along with achievements and constraints in its pathway toward commercial benefits. This review article also highlights the role of various cyanobacterial species that are a source of green and clean energy along with their high potential in the production of biodegradable plastics.
Synbiotic Effects of Fermented Rice on Human Health and Wellness: A Natural Beverage That Boosts Immunity
Authors: Fuloria Shivkanya , Mehta Jyoti , Talukdar Manash Pratim , Sekar Mahendran , Gan Siew Hua , Subramaniyan Vetriselvan , Rani Nur Najihah Izzati Mat , Begum M. Yasmin , Chidambaram Kumarappan , Nordin Rusli , Maziz Mohammad Nazmul Hasan , Sathasivam Kathiresan V. , Lum Pei Teng , Fuloria Neeraj Kumar
Published: July 2022

Fermented foods have been an important component of the human diet from the time immemorial. It contains a high amount of probiotics that have been associated to a wide range of health benefits, including improved digestion and immunity. This review focuses on the indigenously prepared prebiotic- and probiotic-containing functional fermented rice (namedXaj-pani) by the Ahom Community from Assam, in Northeast India, including all the beneficial and potential effects on human health. Literature was searched from scientific databases such as PubMed, ScienceDirect and Google Scholar. Glutinous rice (commonly known as bora rice of sali variety) is primarily employed to prepare beverages that are recovered through the filtration process. The beer is normally consumed during religious rites, festivals and ritual practices, as well as being used as a refreshing healthy drink. Traditionally, it is prepared by incorporating a variety of medicinal herbs into their starter culture (Xaj-pitha) inoculum which is rich in yeasts, molds and lactic acid bacteria (LAB) and then incorporated in alcoholic beverage fermentation. The Ahom communities routinely consume this traditionally prepared alcoholic drink with no understanding of its quality and shelf life. Additionally, a finally produced dried cake, known asvekur pithaact as a source ofSaccharomyces cerevisiaeand can be stored for future use. Despite the rampant use in this community, the relationship betweenXaj-pani’s consumption, immunological response, infectious and inflammatory processes remains unknown in the presence of factors unrelated or indirectly connected to immune function. Overall, this review provides the guidelines to promote the development of prebiotic- and probiotic-containing functional fermented rice that could significantly have an impact on the health of the consumers.
Developing Graphene Grids for Cryoelectron Microscopy
Authors: Fan Hongcheng , Sun Fei
Published: July 2022

Cryogenic electron microscopy (cryo-EM) single particle analysis has become one of the major techniques used to study high-resolution 3D structures of biological macromolecules. Specimens are generally prepared in a thin layer of vitrified ice using a holey carbon grid. However, the sample quality using this type of grid is not always ideal for high-resolution imaging even when the specimens in the test tube behave ideally. Various problems occur during a vitrification procedure, including poor/nonuniform distribution of particles, preferred orientation of particles, specimen denaturation/degradation, high background from thick ice, and beam-induced motion, which have become important bottlenecks in high-resolution structural studies using cryo-EM in many projects. In recent years, grids with support films made of graphene and its derivatives have been developed to efficiently solve these problems. Here, the various advantages of graphene grids over conventional holey carbon film grids, functionalization of graphene support films, production methods of graphene grids, and origins of pristine graphene contamination are reviewed and discussed.
Application of weighted co-expression network analysis and machine learning to identify the pathological mechanism of Alzheimer's disease
Authors: Chai Keping , Zhang Xiaolin , Chen Shufang , Gu Huaqian , Tang Huitao , Cao Panlong , Wang Gangqiang , Ye Weiping , Wan Feng , Liang Jiawei , Shen Daojiang
Published: July 2022

Aberrant deposits of neurofibrillary tangles (NFT), the main characteristic of Alzheimer's disease (AD), are highly related to cognitive impairment. However, the pathological mechanism of NFT formation is still unclear. This study explored differences in gene expression patterns in multiple brain regions [entorhinal, temporal, and frontal cortex (EC, TC, FC)] with distinct Braak stages (0- VI), and identified the hub genes via weighted gene co-expression network analysis (WGCNA) and machine learning. For WGCNA, consensus modules were detected and correlated with the single sample gene set enrichment analysis (ssGSEA) scores. Overlapping the differentially expressed genes (DEGs, Braak stages 0 vs. I-VI) with that in the interest module, metascape analysis, and Random Forest were conducted to explore the function of overlapping genes and obtain the most significant genes. We found that the three brain regions have high similarities in the gene expression pattern and that oxidative damage plays a vital role in NFT formation via machine learning. Through further filtering of genes from interested modules by Random Forest, we screened out key genes, such as LYN, LAPTM5, and IFI30. These key genes, including LYN, LAPTM5, and ARHGDIB, may play an important role in the development of AD through the inflammatory response pathway mediated by microglia.
Neurocognitive Impairment and Associated Factors Among Elderly in the Bahir Dar City Administration, Northwest Ethiopia
Authors: Fekadu Betelhem , Tareke Minale , Tadesse Meseret , Anbesaw Tamrat
Published: July 2022

Background

Neurocognitive impairment is a widely common problem in the elderly. It encompasses mild and major cognitive impairment, which will lead to disability and increase the risk of death. It also compromises the quality of life of the patient and poses a burden on the family and society as a whole. However, there is a paucity of information concerning neurocognitive impairment among the elderly in Ethiopia. This study aimed to assess the prevalence of neurocognitive impairment and associated factors among the elderly in Bahir Dar city, Ethiopia 2020.

Methods

A community-based cross-sectional study was conducted among 423 respondents using a simple random sampling technique from 1 June to 30 June 2020. Neurocognitive impairment was measured using the Mini-Mental State Exam adjusted cutoff point (presence or absence) by the level of education of the participants. Data were entered into EpiData version 4.62 and exported to SPSS version 23 for analysis: descriptive statistics were used for summarization and presentation and binary logistic regression for a measure of association between exposures and outcome variable.

Results

The prevalence of neurocognitive impairment was 42.1%. Factors such as having no spouse [AOR = 1.76, 95% confidence interval (CI): 1.08–2.86], having depression (AOR = 3.04, 95% CI: 1.80–5.14), lifetime alcohol use (AOR = 2.90, 95% CI: 1.19–7.07), and having low family support (AOR = 3.07, 95% CI: 1.35–6.96) and moderate family support (AOR = 1.83; 95% CI: 1.10–3.06) were significantly associated with neurocognitive impairment.

Conclusion and Recommendation

The prevalence of neurocognitive impairment was high in Bahir Dar city administration. Neurocognitive impairment has shown significant association with no spouse, depression, alcohol use, and low and moderate family social support. It is important to pay attention to old age with comorbid mental illness and also to strengthen social support systems to prevent and manage neurocognitive impairment.
MRI Markers of Small Vessel Disease and the APOE Allele in Cognitive Impairment
Authors: Shams Mana , Shams Sara , Martola Juha , Cavallin Lena , Granberg Tobias , Kaijser Magnus , Wintermark Max , Westman Eric , Aspelin Peter , Kristoffersen Wiberg Maria , Wahlund Lars-Olof
Published: July 2022

Objective

The apolipoprotein E (APOE) ε4 allele is the main genetic risk factor for dementia and Alzheimer's disease (AD), but the underlying mechanism for the increased risk is not well understood. Cerebral small vessel disease (SVD) is prevalent among patients with cognitive impairment and is thought to play an important role in the pathophysiology of dementia. We aimed to investigate the association between the APOE ε genotype and magnetic resonance imaging (MRI) markers of SVD in a memory clinic population.

Material and Methods

This is a cross-sectional study with a total of 520 patients undergoing dementia investigation, including an MRI brain scan and APOE genotyping in all patients enrolled, and cerebrospinal fluid (CSF) analysis for routine AD biomarkers in 399 patients. MR images were assessed for markers of SVD: cerebral microbleeds (CMBs), cortical superficial siderosis, intracerebral hemorrhage, white matter hyperintensities, lacunar infarcts, and enlarged perivascular spaces.

Results

Apolipoprotein E carriers with AD had a higher number of CMBs when looking at all brain regions and lobar brain regions (p < 0.001). A lower number of CMBs were seen in APOE ε2 (p < 0.05), ε3 and ε3/3 carriers (p < 0.001) when looking at all brain regions. A higher number of CMBs in deep and infratentorial regions were seen in APOE ε2 and ε3 (p < 0.05). In APOE ε4/4 carriers, CMBs, cortical superficial siderosis, white matter hyperintensities, and enlarged perivascular spaces were associated with lower levels of CSF amyloid β (Aβ) 42 in the whole cohort, and in individuals with AD and mild cognitive impairment (p < 0.05).

Conclusion

Apolipoprotein E ε4 is associated with MRI markers of SVD related to amyloid pathology, specifically CMBs and Aβ42 plaque formation in the brain, as reflected by decreased CSF Aβ42 levels, whereas APOE ε3 and ε2 are associated with the markers of hypertensive arteriopathy, as reflected by the association with CMBs in deep and infratentorial brain regions.
Environmental Enrichment Reverses Maternal Sleep Deprivation-Induced Anxiety-Like Behavior and Cognitive Impairment in CD-1 Mice
Authors: Zhang Yue-Ming , Cheng Yun-Zhou , Wang Ya-Tao , Wei Ru-Meng , Ge Yi-Jun , Kong Xiao-Yi , Li Xue-Yan
Published: July 2022

Preclinical studies have clearly indicated that offspring of mothers who suffered sleep deprivation during pregnancy exhibit anxiety, depression-like behaviors, and cognitive deficits. The cognitive impairment induced by maternal sleep deprivation (MSD) is currently poorly treated. Growing evidence indicates that an enriched environment (EE) improves cognition function in models of Alzheimer’s disease, schizophrenia, and lipopolysaccharide. However, the effects of EE on hippocampal-dependent learning and memory, as well as synaptic plasticity markers changes induced by MSD, are unclear. In the present study, pregnant CD-1 mice were randomly divided into a control group, MSD group, and MSD+EE group. Two different living environments, including standard environment and EE, were prepared. When male and female offspring were 2 months, the open field test and elevated plus maze were used to assess anxiety-like behavior, and the Morris water maze was used to evaluate hippocampal learning and memory. Western blotting and real-time fluorescence quantitative polymerase chain reaction were used to detect the expression of brain-derived neurotrophic factor and Synaptotagmin-1 in the hippocampus of offspring. The results revealed that MSD-induced offspring showed anxiety-like behaviors and cognitive impairment, while EE alleviated anxiety-like behavior and cognitive impairment in offspring of the MSD+EE group. The cognitive impairment induced by MSD was associated with a decreased brain-derived neurotrophic factor and an increased Synaptotagmin-1, while EE increased and decreased brain-derived neurotrophic factor and Synaptotagmin-1 in the hippocampus of mice from the MSD+EE group, respectively. Taken together, we can conclude that EE has beneficial effects on MSD-induced synaptic plasticity markers changes and can alleviate anxiety-like behaviors and cognitive impairment.
Replacement of Mouse Microglia With Human Induced Pluripotent Stem Cell (hiPSC)-Derived Microglia in Mouse Organotypic Slice Cultures
Authors: Ogaki Ari , Ikegaya Yuji , Koyama Ryuta
Published: July 2022

Microglia, the major immune cells in the brain, are reported to differ in gene expression patterns among species. Therefore, it would be preferable in some cases to use human microglia rather than mouse microglia in microglia-targeted disease research. In the past half a decade, researchers have developed in vivo transplantation methods in which human induced pluripotent stem cell-derived microglia (hiPSC-MG) are transplanted into a living mouse brain. However, in vivo transplantation methods are not necessarily accessible to all researchers due to the difficulty of obtaining the materials needed and the transplantation technique itself. In addition, for in vivo systems for microglia-targeted drug screening, it is difficult to control the pharmacokinetics, especially blood-brain barrier permeability. Therefore, in addition to existing in vivo transplantation systems, the development of an ex vivo transplantation system would help to further evaluate the properties of hiPSC-MG. In this study, we aimed to establish a method to efficiently transplant hiPSC-MG into cultured mouse hippocampal slices. We found that approximately 80% of the total microglia in a cultured slice were replaced by hiPSC-derived microglia when innate microglia were pharmacologically removed prior to transplantation. Furthermore, when neuronal death was induced by applying Kainic acid (KA) to slice cultures, transplanted hiPSC-MG changed their morphology and phagocytosed cell debris. Thus, this study provides a method to transplant hiPSC-MG into the mouse hippocampal slice cultures with a high replacement rate. Because the transplanted microglia survived and exerted phagocytic functions, this method will be useful for evaluating the properties of hiPSC-MG ex vivo.
Comparing the Conventional and Balloon-Guided Catheter-Assisted SWIM Technology for the Treatment of Acute Ischemic Stroke
Authors: Chen Zhengwen , Liu Yizhi , Li Bo , Yuan Chen , Hou Kaiwen , Chen Long , Li Peicheng
Published: July 2022

Objective

Acute ischemic stroke is common in elder patients. This study investigates whether using the balloon-guided catheter (BGC) would improve the effect of stent thrombectomy (Solitaire FR With Intracranial Support Catheter for Mechanical Thrombectomy, SWIM) for patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO).

Method

The data of 209 patients with AIS-LVO underwent SWIM were collected retrospectively from January 2017 to June 2021. These patients were divided into two groups based on whether they used of BGC or not. The propensity score matching (PSM) analysis was used to compare the differences in the first pass effect (FPE), successful recanalization, embolus escape rate, symptomatic intracranial hemorrhage (sICH), 90-day clinical favorable outcome, 90-day all-cause mortality, and complications in the patients treated with SWIM combined with balloon-guided catheter or conventional catheter.

Results

Among the 209 patients, 44 patients were treated with BGC and 165 patients were not. After matching, a total of 111 patients were included. The results showed that there was no statistical difference in FPE (35.1% in non-BGC group compared to 24.3% in BGC group, matched RR, 0.59; 95% CI, 0.24–1.44), successful recanalization (89.2 vs. 91.9%, matched RR, 1.37; 95%CI, 0.34–5.51), embolus escape (6.8 vs. 8.1%, matched RR, 1.22; 95%CI, 0.28–5.40), sICH (8.1 vs. 13.5%; matched RR, 1.77; 95%CI 0.50–6.24), 90-day clinical favorable outcome (48.7 vs. 54.1%, matched RR, 1.11; 95%CI 0.51–2.46), 90-day all-cause mortality (17.6 vs. 21.6%, matched RR, 1.29; 95%CI 0.48–3.47), and the incidence of complications (6.8 vs. 5.4%, matched RR, 0.79 95%CI 0.15–4.27). These results indicate that using SWIM as the first-line treatment for patients with AIS-LVO, there is no statistical significance in FPE, final successful recanalization, distal emboli, sICH, procedural time, 90-day favorable outcome, 90-day mortality, and complications with or without BGC.

Conclusion

Balloon-guided catheter does not affect the result of using SWIM as the first-line treatment for patients with AIS-LVO. Our results will guide daily practice, with the adoption of the use of a guided catheter without a balloon.
Detection of Abnormal Spontaneous Brain Activity Patterns in Patients With Orbital Fractures Using Fractional Amplitude of Low Frequency Fluctuation
Authors: Kang Min , Gao YuXuan , Zhang LiJuan , Liang RongBin , Li QiuYu , Shu HuiYe , Pan YiCong , Ying Ping , Xu SanHua , Yi Shao
Published: July 2022

Background

To date, no in-depth study has been conducted on the intrinsic pathological relationship between altered brain activity and related behavioral changes in patients with orbital fracture (OF).

Purpose

The present research aimed to explore the potential functional network cerebrum activities in patients with OF using resting state functional magnetic resonance imaging–fractional amplitude of low-frequency fluctuation (rsfMRI-fALFF). This technique can reveal dynamic functional changes in specific cerebrum areas.

Methods

Twenty patients with OF and 20 healthy controls (HCs) were included, closely matched in terms of gender, age, weight, and education level. To record spontaneous cerebral activity changes, the rsfMRI-fALFF tool was applied. Receiver operating characteristic (ROC) curves and Pearson's correlation analysis were used to analyze mean fALFF values in specific cerebrum regions and to explore changes of behavioral changes in patients with OF. The Hospital Depression and Anxiety scale was applied to reveal the relationship between emotional states and fALFF values of the right superior temporal gyrus in patients with OF.

Results

In comparison with HCs, significantly lower fALFF values were detected in the left anterior cingulate gyrus (LACG) and right superior temporal gyrus (RSTG) in patients with OF. ROC curve analysis showed excellent accuracy. The mean fALFF values of the RSTG negatively correlated with the depression score as well as the anxiety score.

Conclusion

The finding of abnormal spontaneous activities in cerebral regions may contribute to more comprehensive understanding of the potential neural network changes in patients with OF. The changes of fALFF value in patients with OF may help to gauge their emotional changes and clinical recovery levels.
From the New Diagnostic Criteria to COVID-19 Pandemic Passing Through the Placebo Effect. What Have We Learned in the Management of Pediatric Migrane Over the Past 5 Years?
Authors: Papetti Laura , Tarantino Samuela , Ursitti Fabiana , Moavero Romina , Proietti Martina Checchi , Sforza Giorgia , Monte Gabriele , Ferilli Michela Ada Noris , Balestri Martina , Vigevano Federico , Valeriani Massimiliano
Published: July 2022

In 2018, the Food and Drug Administration (FDA) approval of anti-calcitonin gene-related peptide (CGRP) therapies for the treatment of migraine represented a milestone for the management of the disease in adults. On the contrary, the novelties in the field of pediatric migraine are inserted in a different scenario and still concern: (1) diagnostic criteria of the international classification of headache disorders-3 (ICHD-3) that show numerous limits of applicability in the developmental age; (2) the release of the results of the Childhood and Adolescent Migraine Prevention (CHAMP) study that raised doubts about the usefulness of traditional drugs for the treatment of pediatric migraine; (3) the Coronavirus disease 2019 (COVID-19) pandemic has put the spotlight on the importance of managing the psychological factors associated with the disease. In this mini review we discuss the most relevant news in pediatric migraine over the last 5 years.
Beauty and Uncertainty as Transformative Factors: A Free Energy Principle Account of Aesthetic Diagnosis and Intervention in Gestalt Psychotherapy
Authors: Sarasso Pietro , Francesetti Gianni , Roubal Jan , Gecele Michela , Ronga Irene , Neppi-Modona Marco , Sacco Katiuscia
Published: July 2022

Drawing from field theory, Gestalt therapy conceives psychological suffering and psychotherapy as two intentional field phenomena, where unprocessed and chaotic experiences seek the opportunity to emerge and be assimilated through the contact between the patient and the therapist (i.e., the intentionality of contacting). This therapeutic approach is based on the therapist’s aesthetic experience of his/her embodied presence in the flow of the healing process because (1) the perception of beauty can provide the therapist with feedback on the assimilation of unprocessed experiences; (2) the therapist’s attentional focus on intrinsic aesthetic diagnostic criteria can facilitate the modification of rigid psychopathological fields by supporting the openness to novel experiences. The aim of the present manuscript is to review recent evidence from psychophysiology, neuroaesthetic research, and neurocomputational models of cognition, such as the free energy principle (FEP), which support the notion of the therapeutic potential of aesthetic sensibility in Gestalt psychotherapy. Drawing from neuroimaging data, psychophysiology and recent neurocognitive accounts of aesthetic perception, we propose a novel interpretation of the sense of beauty as a self-generated reward motivating us to assimilate an ever-greater spectrum of sensory and affective states in our predictive representation of ourselves and the world and supporting the intentionality of contact. Expecting beauty, in the psychotherapeutic encounter, can help therapists tolerate uncertainty avoiding impulsive behaviours and to stay tuned to the process of change.
Altered Temporal Dynamics of the Amplitude of Low-Frequency Fluctuations in Comitant Exotropia Patients
Authors: Chen Ri-Bo , Ye Shu-Yuan , Pei Chong-Gang , Zhong Yu-Lin
Published: July 2022

Purpose

Growing evidence reported that patients with comitant exotropia (CE) were accompanied by static cerebral neural activity changes. However, whether the dynamic time-varying of neural activity changes in patients with CE remains unknown.

Methods

A total of 36 patients with CE (25 men and 11 women) and 36 well-matched healthy controls are enrolled in the study. The dynamic amplitude of low-frequency fluctuation (dALFF) combined with the sliding window method was used to assess the dynamic neural activity changes in patients with CE.

Results

Compared with HCs, patients with CE had decreased dALFF values in the right superior parietal lobule (SPL) and right precuneus gyrus (PreCUN). Moreover, we found that the dALFF maps showed an accuracy of 48.61% and an area under the curve of.54 for distinguishing the patients with CE from HCs.

Conclusion

Our study demonstrated that patients with CE showed altered dynamic neural activity changes in the right SPL and right PreCUN, which might indicate the neuropathological mechanism of stereoscopic dysfunction in patients with CE.
Autism-Risk Gene necab2 Regulates Psychomotor and Social Behavior as a Neuronal Modulator of mGluR1 Signaling
Authors: Chen Zexu , Long Han , Guo Jianhua , Wang Yiran , He Kezhe , Tao Chenchen , Li Xiong , Jiang Keji , Guo Su , Pi Yan
Published: July 2022

Background

De novo deletion of the neuronal calcium-binding protein 2 (NECAB2) locus is associated with idiopathic autism spectrum disorders (ASDs). The in vivo function of NECAB2 in the brain remains largely elusive.

Methods

We investigated the morphological and behavioral profiles of both necab2 knock-out and overexpression zebrafish models. The expression pattern and molecular role of necab2 were probed through a combination of in vitro and in vivo assays.

Results

We show that Necab2 is a neuronal specific, cytoplasmic, and membrane-associated protein, abundantly expressed in the telencephalon, habenula, and cerebellum. Necab2 is distributed peri-synaptically in subsets of glutamatergic and GABAergic neurons. CRISPR/Cas9-generated necab2 knock-out zebrafish display normal morphology but exhibit a decrease in locomotor activity and thigmotaxis with impaired social interaction only in males. Conversely, necab2 overexpression yields behavioral phenotypes opposite to the loss-of-function. Proteomic profiling uncovers a role of Necab2 in modulating signal transduction of G-protein coupled receptors. Specifically, co-immunoprecipitation, immunofluorescence, and confocal live-cell imaging suggest a complex containing NECAB2 and the metabotropic glutamate receptor 1 (mGluR1). In vivo measurement of phosphatidylinositol 4,5-bisphosphate further substantiates that Necab2 promotes mGluR1 signaling.

Conclusions

Necab2 regulates psychomotor and social behavior via modulating a signaling cascade downstream of mGluR1.
Multi-mtDNA Variants May Be a Factor Contributing to Mitochondrial Function Variety in the Skin-Derived Fibroblasts of Leber's Hereditary Optic Neuropathy Patients
Authors: Yao Shun , Zhou Qingru , Yang Mingzhu , Li Ya , Jin Xiuxiu , Guo Qingge , Yang Lin , Qin Fangyuan , Lei Bo
Published: July 2022

Heterogeneity is a major feature of Leber's hereditary optic neuropathy (LHON) and has a significant impact on the manifestation and diagnosis of the disease. This study explored whether multiple variations in mitochondrial genes were associated with the heterogeneity, mainly phenotypic heterogeneity. Ophthalmic examinations were conducted in two probands with LHON with G11778A and multiple mitochondrial DNA gene (mtDNA) variants. Skin fibroblast cell lines were generated from patients and age- and sex-matched controls. ROS levels, mitochondrial membrane potential, cell energy respiration, and metabolic functions were measured. Flow cytometry and cell viability tests were performed to evaluate the cell apoptosis levels and fate. We found that cells with more mtDNA variants had higher ROS levels, lower mitochondrial membrane potential, and weaker respiratory function. Flow cytometry and cell viability testing showed that multiple mtDNA variants are associated with different levels of cell viability and apoptosis. In conclusion, we found that skin-derived fibroblast cells from G11778A LHON patients could be used as models for LHON research. Multi-mtDNA variants contribute to mitochondrial function variety, which may be associated with heterogeneity in patients with LHON.
Circadian Neuropeptide-Expressing Clock Neurons as Regulators of Long-Term Memory: Molecular and Cellular Perspectives
Authors: Inami Show , Sato Tomohito , Sakai Takaomi
Published: July 2022

The neuropeptide pigment-dispersing factor (Pdf) is critically involved in the regulation of circadian rhythms in various insects. The function of Pdf in circadian rhythms has been best studied in the fruitfly, i.e., Drosophila melanogaster. Drosophila Pdf is produced in a small subset of circadian clock neurons in the adult brain and functions as a circadian output signal. Recently, however, Pdf has been shown to play important roles not only in regulating circadian rhythms but also in innate and learned behaviors in Drosophila. In this mini-review, we will focus on the current findings that Pdf signaling and Pdf-producing neurons are essential for consolidating and maintaining long-term memory induced by the courtship conditioning in Drosophila and discuss the mechanisms of courtship memory processing through Pdf-producing neurons.
Integrating Dietary Impacts in Food Life Cycle Assessment
Authors: Jolliet Olivier
Published: July 2022

Food production and food consumption have been too long studied separately. This paper therefore reviews progresses in assessment methods and identifies how nutrition effects on human health and environmental impacts of the entire food production and consumption can and should be consistently and systematically assessed, on a life cycle-based and a health-based perspective. Main observations include: (a) The strong activity in the Life Cycle Assessment (LCA) of a large range of agriculture production, covering beyond carbon footprint the biodiversity and health impacts of land, water, fertilizers, and pesticide use. (b) The multi-functionality of all foods and the need to compare a wide range of possible alternative including comparing serving size, meal alternatives and diets. (c) The availability of epidemiological dietary risk factors expressed in DALYs, enabling the creation of an additional LCA nutritional impact category and providing much broader flexibility in the choice of the functional unit and the kind of valid comparison LCA can address. (d) The need to use Big Data and machine learning method to better understand interactions and propose healthy and sustainable food baskets. As illustrated by the fruit yogurt example, dietary impacts on human health often dominate the life cycle impacts on human health and it is strongly recommended to consider them in the life cycle inventory and impact assessment of all commodities and foods that will eventually be consumed.
Benefits of A2 Milk for Sports Nutrition, Health and Performance
Authors: Kaplan Merve , Baydemir Barış , Günar Bilgetekin Burak , Arslan Ayşenur , Duman Hatice , Karav Sercan
Published: July 2022

Bovine milk is one of the best pre-and pro-workout sources for athletes owing to its rich nutritional content. Even though bovine milk consumption significantly benefits athletes' health and performance, many athletes cannot consume bovine milk since they struggle with gastrointestinal problems caused after milk consumption. Especially, the consumption of regular milk, which contains A1 β-casein, is associated with a variety of diseases ranging from gastrointestinal discomfort to ischemic heart diseases. The main reason behind this is related to β-casomorphine 7 (BCM-7), which is derived from A1 β-casein during the digestion of A1 milk. A1 β-casein is formed as a result of a point mutation in the position of 67th in the amino acid sequence A2 β-casein by changing proline to histidine. Therefore, this mutated form of β-casein in regular milk cannot easily be digested by the human-associated digestion enzymes. A2 milk, which includes A2 β-casein instead of A1 β-casein, is the best substitute for regular milk with the same nutritional content. This natural form of milk positively affects the athlete's health as well as performance without causing any gastrointestinal discomfort or more serious problems which are seen in the consumption of regular milk. In this review, A2 milk and its potential health effects in comparison to diseases related to A1 milk consumption are discussed.
Smartphone-Based Ecological Momentary Assessment for the Measurement of the Performance Status and Health-Related Quality of Life in Cancer Patients Under Systemic Anticancer Therapies: Development and Acceptability of a Mobile App
Authors: Escudero-Vilaplana Vicente , Romero-Medrano Lorena , Villanueva-Bueno Cristina , Rodríguez de Diago Marta , Yánez-Montesdeoca Alberto , Collado-Borrell Roberto , Campaña-Montes Juan José , Marzal-Alfaro Belén , Revuelta-Herrero José Luis , Calles Antonio , Galera Mar , Álvarez Rosa , Herranz Ana , Sanjurjo María , Artés-Rodríguez Antonio
Published: July 2022

Background

We have defined a project to develop a mobile app that continually records smartphone parameters which may help define the Eastern Cooperative Oncology Group performance status (ECOG-PS) and the health-related quality of life (HRQoL), without interaction with patients or professionals. This project is divided into 3 phases. Here we describe phase 1. The objective of this phase was to develop the app and assess its usability concerning patient characteristics, acceptability, and satisfaction.

Methods

The app eB2-ECOG was developed and installed in the smartphone of cancer patients who will be followed for six months. Criteria inclusion were: age over 18-year-old; diagnosed with unresectable or metastatic lung cancer, gastrointestinal stromal tumor, sarcoma, or head and neck cancer; under systemic anticancer therapies; and possession of a Smartphone. The app will collect passive and active data from the patients while healthcare professionals will evaluate the ECOG-PS and HRQoL through conventional tools. Acceptability was assessed during the follow-up. Patients answered a satisfaction survey in the app between 3-6 months from their inclusion.

Results

The app developed provides a system for continuously collecting, merging, and processing data related to patient’s health and physical activity. It provides a transparent capture service based on all the available data of a patient. Currently, 106 patients have been recruited. A total of 36 patients were excluded, most of them (21/36) due to technological reasons. We assessed 69 patients (53 lung cancer, 8 gastrointestinal stromal tumors, 5 sarcomas, and 3 head and neck cancer). Concerning app satisfaction, 70.4% (20/27) of patients found the app intuitive and easy to use, and 51.9% (17/27) of them said that the app helped them to improve and handle their problems better. Overall, 17 out of 27 patients [62.9%] were satisfied with the app, and 14 of them [51.8%] would recommend the app to other patients.

Conclusions

We observed that the app’s acceptability and satisfaction were good, which is essential for the continuity of the project. In the subsequent phases, we will develop predictive models based on the collected information during this phase. We will validate the method and analyze the sensitivity of the automated results.
Development and Validation of a Clinical-Image Model for Quantitatively Distinguishing Uncertain Lipid-Poor Adrenal Adenomas From Nonadenomas
Authors: Pan Wenting , Zhang Huangqi , Jin Shengze , Li Xin , Yang Jiawen , Zhang Binhao , Dong Xue , Ma Ling , Ji Wenbin
Published: July 2022

Background

There remains a demand for a practical method of identifying lipid-poor adrenal lesions.

Purpose

To explore the predictive value of computed tomography (CT) features combined with demographic characteristics for lipid-poor adrenal adenomas and nonadenomas.

Materials and Methods

We retrospectively recruited patients with lipid-poor adrenal lesions between January 2015 and August 2021 from two independent institutions as follows: Institution 1 for the training set and the internal validation set and Institution 2 for the external validation set. Two radiologists reviewed CT images for the three sets. We performed a least absolute shrinkage and selection operator (LASSO) algorithm to select variables; subsequently, multivariate analysis was used to develop a generalized linear model. The probability threshold of the model was set to 0.5 in the external validation set. We calculated the sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) for the model and radiologists. The model was validated and tested in the internal validation and external validation sets; moreover, the accuracy between the model and both radiologists were compared using the McNemar test in the external validation set.

Results

In total, 253 patients (median age, 55 years [interquartile range, 47–64 years]; 135 men) with 121 lipid-poor adrenal adenomas and 132 nonadenomas were included in Institution 1, whereas another 55 patients were included in Institution 2. The multivariable analysis showed that age, male, lesion size, necrosis, unenhanced attenuation, and portal venous phase attenuation were independently associated with adrenal adenomas. The clinical-image model showed AUCs of 0.96 (95% confidence interval [CI]: 0.91, 0.98), 0.93 (95% CI: 0.84, 0.97), and 0.86 (95% CI: 0.74, 0.94) in the training set, internal validation set, and external validation set, respectively. In the external validation set, the model showed a significantly and non-significantly higher accuracy than reader 1 (84% vs. 65%, P = 0.031) and reader 2 (84% vs. 69%, P = 0.057), respectively.

Conclusions

Our clinical-image model displayed good utility in differentiating lipid-poor adrenal adenomas. Further, it showed better diagnostic ability than experienced radiologists in the external validation set.
Stable CDK12 Knock-Out Ovarian Cancer Cells Do Not Show Increased Sensitivity to Cisplatin and PARP Inhibitor Treatment
Authors: Chilà Rosaria , Chiappa Michela , Guffanti Federica , Panini Nicolò , Conconi Donatella , Rinaldi Andrea , Cascione Luciano , Bertoni Francesco , Fratelli Maddalena , Damia Giovanna
Published: July 2022

Cyclin-dependent kinase 12 (CDK12) is a serine/threonine kinase involved in the regulation of RNA polymerase II and in the transcription of a subset of genes involved in the DNA damage response. CDK12 is one of the most mutated genes in ovarian carcinoma. These mutations result in loss-of-function and can predict the responses to PARP1/2 inhibitor and platinum. To investigate the role of CDK12 in ovarian cancer, CRISPR/Cas9 technology was used to generate a stable CDK12 knockout (KO) clone in A2780 ovarian carcinoma cells. This is the first report on a CDK12 null cell line. The clone had slower cell growth and was less clonogenic than parental cells. These data were confirmed in vivo, where CDK12 KO transplanted cells had a much longer time lag and slightly slower growth rate than CDK12-expressing cells. The slower growth was associated with a higher basal level of apoptosis, but there were no differences in the basal level of autophagy and senescence. While cell cycle distribution was similar in parental and knockout cells, there was a doubling in DNA content, with an almost double modal number of chromosomes in the CDK12 KO clone which, however did not display any increase in γH2AX, a marker of DNA damage. We found partial down-regulation of the expression of DNA repair genes at the mRNA level and, among the down-regulated genes, an enrichment in the G2/M checkpoint genes. Although the biological features of CDK12 KO cells are compatible with the function of CDK12, contrary to some reports, we could not find any difference in the sensitivity to cisplatin and olaparib between wild-type and CDK12 KO cells.
Capsaicin: A Two-Decade Systematic Review of Global Research Output and Recent Advances Against Human Cancer
Authors: Adetunji Tomi Lois , Olawale Femi , Olisah Chijioke , Adetunji Ademola Emmanuel , Aremu Adeyemi Oladapo
Published: July 2022

Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is one of the most important natural products in the genus Capsicum. Due to its numerous biological effects, there has been extensive and increasing research interest in capsaicin, resulting in increased scientific publications in recent years. Therefore, an in-depth bibliometric analysis of published literature on capsaicin from 2001 to 2021 was performed to assess the global research status, thematic and emerging areas, and potential insights into future research. Furthermore, recent research advances of capsaicin and its combination therapy on human cancer as well as their potential mechanisms of action were described. In the last two decades, research outputs on capsaicin have increased by an estimated 18% per year and were dominated by research articles at 93% of the 3753 assessed literature. In addition, anti-cancer/pharmacokinetics, cytotoxicity, in vivo neurological and pain research studies were the keyword clusters generated and designated as thematic domains for capsaicin research. It was evident that the United States, China, and Japan accounted for about 42% of 3753 publications that met the inclusion criteria. Also, visibly dominant collaboration nodes and networks with most of the other identified countries were established. Assessment of the eligible literature revealed that the potential of capsaicin for mitigating cancer mainly entailed its chemo-preventive effects, which were often linked to its ability to exert multi-biological effects such as anti-mutagenic, antioxidant and anti-inflammatory activities. However, clinical studies were limited, which may be related to some of the inherent challenges associated with capsaicin in the limited clinical trials. This review presents a novel approach to visualizing information about capsaicin research and a comprehensive perspective on the therapeutic significance and applications of capsaicin in the treatment of human cancer.
Single-Cell Metabolomics in Hematopoiesis and Hematological Malignancies
Authors: Zuo Fengli , Yu Jing , He Xiujing
Published: July 2022

Aberrant metabolism contributes to tumor initiation, progression, metastasis, and drug resistance. Metabolic dysregulation has emerged as a hallmark of several hematologic malignancies. Decoding the molecular mechanism underlying metabolic rewiring in hematological malignancies would provide promising avenues for novel therapeutic interventions. Single-cell metabolic analysis can directly offer a meaningful readout of the cellular phenotype, allowing us to comprehensively dissect cellular states and access biological information unobtainable from bulk analysis. In this review, we first highlight the unique metabolic properties of hematologic malignancies and underscore potential metabolic vulnerabilities. We then emphasize the emerging single-cell metabolomics techniques, aiming to provide a guide to interrogating metabolism at single-cell resolution. Furthermore, we summarize recent studies demonstrating the power of single-cell metabolomics to uncover the roles of metabolic rewiring in tumor biology, cellular heterogeneity, immunometabolism, and therapeutic resistance. Meanwhile, we describe a practical view of the potential applications of single-cell metabolomics in hematopoiesis and hematological malignancies. Finally, we present the challenges and perspectives of single-cell metabolomics development.