bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of Cardiac Fibrosis in and Beyond Cells
Authors: Fan Dong , Kassiri Zamaneh
Published: October 2021

The extracellular matrix (ECM) plays important roles in maintaining physiological structure and functions of various tissues and organs. Cardiac fibrosis is the excess deposition of ECM, including both fibrillar (collagens I and III) and non-fibrillar proteins. Characteristics of fibrosis can vary depending on the pathology, with focal fibrosis occurring following myocardial infarction (MI), and diffuse interstitial and perivascular fibrosis mainly in non-ischemic heart diseases. Compliance of the fibrotic tissue is significantly lower than the normal myocardium, and this can compromise the diastolic, as well as systolic dysfunction. Therefore, strategies to combat cardiac fibrosis have been investigated. Upon injury or inflammation, activated cardiac fibroblasts (myofibroblasts) produce more ECM proteins and cause fibrosis. The activation could be inhibited or the myofibroblasts could be ablated by targeting their specific expressed proteins. Modulation of tissue inhibitors of metalloproteinases (TIMPs) and moderate exercise can also suppress cardiac fibrosis. More recently, sex differences in cardiac fibrosis have come to light with differential fibrotic response in heart diseases as well as in fibroblast functions in vitro. This mini-review discusses recent progress in cardiac fibroblasts, TIMPs, sex differences and exercise in modulation of cardiac fibrosis.
Prospective Evaluation of the Association Between Arthritis and Cognitive Functions in Middle-Aged and Elderly Chinese
Authors: Liu Wenyu , Yang Xue , Jin Xingzhong , Xiu Peng , Wen Ying , Wu Nianwei , Zhao Jian , Zhou Dong , Pan Xiong-Fei
Published: October 2021

Background: Assessing the relation between arthritis and cognitive impairment could expand the understanding of health consequences of arthritis. The aim was to prospectively examine the association between arthritis and cognitive functions among middle-aged and elderly Chinese.

Methods: Our analyses were based on data from the nationwide China Health and Retirement Longitudinal Study (2011–2016). Arthritis was ascertained by self-reported doctor diagnosis during the baseline survey. Cognitive functions were evaluated in three domains including episodic memory, mental status, and global cognition. Linear mixed models were employed to assess the association between baseline arthritis and cognition functions.

Results: Of 7,529 Chinese adults, 49.79% were men, and mean age was 57.53 years. During a follow-up of 4 years, participants with baseline arthritis showed lower scores of episodic memory [β = −0.08; 95% confidence interval (CI): −0.14, −0.03], mental status (β = −0.14; 95% CI: −0.22, −0.05), and global cognition (β = −0.22; 95% CI: −0.34, −0.11), compared to those without arthritis. In addition, participants with arthritis showed increased rates of decline in mental status and global cognition by 0.04 (95% CI: 0.01, 0.08) and 0.05 (95% CI: 0.01, 0.09) units per year, respectively.

Conclusion: Arthritis was associated with subsequent risk of poorer cognitive functions and slightly faster declines in cognitive functions among Chinese middle-aged and elderly adults. Our findings should be confirmed in future large prospective studies in Chinese and other populations.
Neuromechanical Biomarkers for Robotic Neurorehabilitation
Authors: Garro Florencia , Chiappalone Michela , Buccelli Stefano , De Michieli Lorenzo , Semprini Marianna
Published: October 2021

One of the current challenges for translational rehabilitation research is to develop the strategies to deliver accurate evaluation, prediction, patient selection, and decision-making in the clinical practice. In this regard, the robot-assisted interventions have gained popularity as they can provide the objective and quantifiable assessment of the motor performance by taking the kinematics parameters into the account. Neurophysiological parameters have also been proposed for this purpose due to the novel advances in the non-invasive signal processing techniques. In addition, other parameters linked to the motor learning and brain plasticity occurring during the rehabilitation have been explored, looking for a more holistic rehabilitation approach. However, the majority of the research done in this area is still exploratory. These parameters have shown the capability to become the “biomarkers” that are defined as the quantifiable indicators of the physiological/pathological processes and the responses to the therapeutical interventions. In this view, they could be finally used for enhancing the robot-assisted treatments. While the research on the biomarkers has been growing in the last years, there is a current need for a better comprehension and quantification of the neuromechanical processes involved in the rehabilitation. In particular, there is a lack of operationalization of the potential neuromechanical biomarkers into the clinical algorithms. In this scenario, a new framework called the “Rehabilomics” has been proposed to account for the rehabilitation research that exploits the biomarkers in its design. This study provides an overview of the state-of-the-art of the biomarkers related to the robotic neurorehabilitation, focusing on the translational studies, and underlying the need to create the comprehensive approaches that have the potential to take the research on the biomarkers into the clinical practice. We then summarize some promising biomarkers that are being under investigation in the current literature and provide some examples of their current and/or potential applications in the neurorehabilitation. Finally, we outline the main challenges and future directions in the field, briefly discussing their potential evolution and prospective.
State-Dependent Effective Connectivity in Resting-State fMRI
Authors: Park Hae-Jeong , Eo Jinseok , Pae Chongwon , Son Junho , Park Sung Min , Kang Jiyoung
Published: October 2021

The human brain at rest exhibits intrinsic dynamics transitioning among the multiple metastable states of the inter-regional functional connectivity. Accordingly, the demand for exploring the state-specific functional connectivity increases for a deeper understanding of mental diseases. Functional connectivity, however, lacks information about the directed causal influences among the brain regions, called effective connectivity. This study presents the dynamic causal modeling (DCM) framework to explore the state-dependent effective connectivity using spectral DCM for the resting-state functional MRI (rsfMRI). We established the sequence of brain states using the hidden Markov model with the multivariate autoregressive coefficients of rsfMRI, summarizing the functional connectivity. We decomposed the state-dependent effective connectivity using a parametric empirical Bayes scheme that models the effective connectivity of consecutive windows with the time course of the discrete states as regressors. We showed the plausibility of the state-dependent effective connectivity analysis in a simulation setting. To test the clinical applicability, we applied the proposed method to characterize the state- and subtype-dependent effective connectivity of the default mode network in children with combined-type attention deficit hyperactivity disorder (ADHD-C) compared with age-matched, typically developed children (TDC). All 88 children were subtyped according to the occupation times (i.e., dwell times) of the three dominant functional connectivity states, independently of clinical diagnosis. The state-dependent effective connectivity differences between ADHD-C and TDC according to the subtypes and those between the subtypes of ADHD-C were expressed mainly in self-inhibition, magnifying the importance of excitation inhibition balance in the subtyping. These findings provide a clear motivation for decomposing the state-dependent dynamic effective connectivity and state-dependent analysis of the directed coupling in exploring mental diseases.
Circuit Contributions to Sensory-Driven Glutamatergic Drive of Olfactory Bulb Mitral and Tufted Cells During Odorant Inhalation
Authors: Moran Andrew K. , Eiting Thomas P. , Wachowiak Matt
Published: October 2021

In the mammalian olfactory bulb (OB), mitral/tufted (MT) cells respond to odorant inhalation with diverse temporal patterns that are thought to encode odor information. Much of this diversity is already apparent at the level of glutamatergic input to MT cells, which receive direct, monosynaptic excitatory input from olfactory sensory neurons (OSNs) as well as a multisynaptic excitatory drive via glutamatergic interneurons. Both pathways are also subject to modulation by inhibitory circuits in the glomerular layer of the OB. To understand the role of direct OSN input vs. postsynaptic OB circuit mechanisms in shaping diverse dynamics of glutamatergic drive to MT cells, we imaged glutamate signaling onto MT cell dendrites in anesthetized mice while blocking multisynaptic excitatory drive with ionotropic glutamate receptor antagonists and blocking presynaptic modulation of glutamate release from OSNs with GABAB receptor antagonists. GABAB receptor blockade increased the magnitude of inhalation-linked glutamate transients onto MT cell apical dendrites without altering their inhalation-linked dynamics, confirming that presynaptic inhibition impacts the gain of OSN inputs to the OB. Surprisingly, blockade of multisynaptic excitation only modestly impacted glutamatergic input to MT cells, causing a slight reduction in the amplitude of inhalation-linked glutamate transients in response to low odorant concentrations and no change in the dynamics of each transient. The postsynaptic blockade also modestly impacted glutamate dynamics over a slower timescale, mainly by reducing adaptation of the glutamate response across multiple inhalations of odorant. These results suggest that direct glutamatergic input from OSNs provides the bulk of excitatory drive to MT cells, and that diversity in the dynamics of this input may be a primary determinant of the temporal diversity in MT cell responses that underlies odor representations at this stage.
Dynamical Conventional Neural Network Channel Pruning by Genetic Wavelet Channel Search for Image Classification
Authors: Chen Lin , Gong Saijun , Shi Xiaoyu , Shang Mingsheng
Published: October 2021

Neural network pruning is critical to alleviating the high computational cost of deep neural networks on resource-limited devices. Conventional network pruning methods compress the network based on the hand-crafted rules with a pre-defined pruning ratio (PR), which fails to consider the variety of channels among different layers, thus, resulting in a sub-optimal pruned model. To alleviate this issue, this study proposes a genetic wavelet channel search (GWCS) based pruning framework, where the pruning process is modeled as a multi-stage genetic optimization procedure. Its main ideas are 2-fold: (1) it encodes all the channels of the pertained network and divide them into multiple searching spaces according to the different functional convolutional layers from concrete to abstract. (2) it develops a wavelet channel aggregation based fitness function to explore the most representative and discriminative channels at each layer and prune the network dynamically. In the experiments, the proposed GWCS is evaluated on CIFAR-10, CIFAR-100, and ImageNet datasets with two kinds of popular deep convolutional neural networks (CNNs) (ResNet and VGGNet). The results demonstrate that GNAS outperforms state-of-the-art pruning algorithms in both accuracy and compression rate. Notably, GNAS reduces more than 73.1% FLOPs by pruning ResNet-32 with even 0.79% accuracy improvement on CIFAR-100.
Tele-Neurorehabilitation During the COVID-19 Pandemic: Implications for Practice in Low- and Middle-Income Countries
Authors: Srivastava Abhishek , Swaminathan Aishwarya , Chockalingam Manigandan , Srinivasan Murali K. , Surya Nirmal , Ray Partha , Hegde Prasanna S. , Akkunje Preetie Shetty , Kamble Sanjivani , Chitnis Sonal , Kamalakannan Sureshkumar , Ganvir Suvarna , Shah Urvashi ,   The Indian Federation of Neurorehabilitation (IFNR) Research Task Force
Published: October 2021

The importance of neurorehabilitation services for people with disabilities is getting well-recognized in low- and middle-income countries (LMICs) recently. However, accessibility to the same has remained the most significant challenge, in these contexts. This is especially because of the non-availability of trained specialists and the availability of neurorehabilitation centers only in urban cities owned predominantly by private healthcare organizations. In the current COVID-19 pandemic, the members of the Task Force for research at the Indian Federation of Neurorehabilitation (IFNR) reviewed the context for tele-neurorehabilitation (TNR) and have provided the contemporary implications for practicing TNR during COVID-19 for people with neurological disabilities (PWNDs) in LMICs. Neurorehabilitation is a science that is driven by rigorous research-based evidence. The current pandemic implies the need for systematically developed TNR interventions that is evaluated for its feasibility and acceptability and that is informed by available evidence from LMICs. Given the lack of organized systems in place for the provision of neurorehabilitation services in general, there needs to be sufficient budgetary allocations and a sector-wide approach to developing policies and systems for the provision of TNR services for PWNDs. The pandemic situation provides an opportunity to optimize the technological innovations in health and scale up these innovations to meet the growing burden of neurological disability in LMICs. Thus, this immense opportunity must be tapped to build capacity for safe and effective TNR services provision for PWNDs in these settings.
Reorganization of Brain Functional Connectivity Network and Vision Restoration Following Combined tACS-tDCS Treatment After Occipital Stroke
Authors: Xu Jiahua , Wu Zheng , Nürnberger Andreas , Sabel Bernhard A.
Published: October 2021

Objective: Non-invasive brain stimulation (NIBS) is already known to improve visual field functions in patients with optic nerve damage and partially restores the organization of brain functional connectivity networks (FCNs). However, because little is known if NIBS is effective also following brain damage, we now studied the correlation between visual field recovery and FCN reorganization in patients with stroke of the central visual pathway.

Method: In a controlled, exploratory trial, 24 patients with hemianopia were randomly assigned to one of three brain stimulation groups: transcranial direct current stimulation (tDCS)/transcranial alternating current stimulation (tACS) (ACDC); sham tDCS/tACS (AC); sham tDCS/sham tACS (Sham), which were compared to age-matched controls (n = 24). Resting-state electroencephalogram (EEG) was collected at baseline, after 10 days stimulation and at 2 months follow-up. EEG recordings were analyzed for FCN measures using graph theory parameters, and FCN small worldness of the network and long pairwise coherence parameter alterations were then correlated with visual field performance.

Result: ACDC enhanced alpha-band FCN strength in the superior occipital lobe of the lesioned hemisphere at follow-up. A negative correlation (r = −0.80) was found between the intact visual field size and characteristic path length (CPL) after ACDC with a trend of decreased alpha-band centrality of the intact middle occipital cortex. ACDC also significantly decreased delta band coherence between the lesion and the intact occipital lobe, and coherence was enhanced between occipital and temporal lobe of the intact hemisphere in the low beta band. Responders showed significantly higher strength in the low alpha band at follow-up in the intact lingual and calcarine cortex and in the superior occipital region of the lesioned hemisphere.

Conclusion: While ACDC decreases delta band coherence between intact and damaged occipital brain areas indicating inhibition of low-frequency neural oscillations, ACDC increases FCN connectivity between the occipital and temporal lobe in the intact hemisphere. When taken together with the lower global clustering coefficient in responders, these findings suggest that FCN reorganization (here induced by NIBS) is adaptive in stroke. It leads to greater efficiency of neural processing, where the FCN requires fewer connections for visual processing.
Neurophysiological Examinations as Adjunctive Tool to Imaging Techniques in Spontaneous Intracerebral Hemorrhage: IRONHEART Study
Authors: Fekete Klára , Tóth Judit , Horváth László , Márton Sándor , Héja Máté , Csiba László , Árokszállási Tamás , Bagoly Zsuzsa , Sulina Dóra , Fekete István
Published: October 2021

Introduction: Intracerebral hemorrhage (ICH) is a devastating disease, which may lead to severe disability or even death. Although many factors may influence the outcome, neurophysiological examinations might also play a role in its course. Our aim was to examine whether the findings of electroencephalography (EEG) and transcranial magnetic stimulation (TMS) can predict the prognosis of these patients.

Methods: Between June 1 2017 and June 15 2021, 116 consecutive patients with ICH were enrolled prospectively in our observational study. Clinical examinations and non-Contrast computed tomography (NCCT) scan were done on admission for ICH; follow-up NCCT scans were taken at 14 ± 2 days and at 3 months ± 7 days after stroke onset. EEG and TMS examinations were also carried out.

Results: Of the patients in the study, 65.5% were male, and the mean age of the study population was 70 years. Most patients had a history of hypertension, 50.8% of whom had been untreated. In almost 20% of the cases, excessive hypertension was measured on admission, accompanied with >10 mmol/L blood glucose level, whereas their Glasgow Coma Scale was 12 on average. Presence of blood in the ventricles or subarachnoid space and high blood and perihematomal volumes meant poor prognosis. Pathological EEG was prognostic of a worse outcome. With TMS examination at 14 days, it might be possible to estimate outcome in a univariate model and the absence, or reduction of the amplitude of the motor evoked potentials was associated with poor prognosis.

Conclusion: Together with the clinical symptoms, the volume of bleeding, perihematomal edema (or their combined volume), and neurophysiological examinations like EEG and TMS play an important role in the neurological outcome of patients with ICH. This might affect the patients' rehabilitation plans in the future, since with the help of the examinations the subset of patients with potential for recovery could be identified.
Studying Synaptically Evoked Cortical Responses ex vivo With Combination of a Single Neuron Recording (Whole-Cell) and Population Voltage Imaging (Genetically Encoded Voltage Indicator)
Authors: Jang Jinyoung , Zhu Mei Hong , Jogdand Aditi H. , Antic Srdjan D.
Published: October 2021

In a typical electrophysiology experiment, synaptic stimulus is delivered in a cortical layer (1–6) and neuronal responses are recorded intracellularly in individual neurons. We recreated this standard electrophysiological paradigm in brain slices of mice expressing genetically encoded voltage indicators (GEVIs). This allowed us to monitor membrane voltages in the target pyramidal neurons (whole-cell), and population voltages in the surrounding neuropil (optical imaging), simultaneously. Pyramidal neurons have complex dendritic trees that span multiple cortical layers. GEVI imaging revealed areas of the brain slice that experienced the strongest depolarization on a specific synaptic stimulus (location and intensity), thus identifying cortical layers that contribute the most afferent activity to the recorded somatic voltage waveform. By combining whole-cell with GEVI imaging, we obtained a crude distribution of activated synaptic afferents in respect to the dendritic tree of a pyramidal cell. Synaptically evoked voltage waves propagating through the cortical neuropil (dendrites and axons) were not static but rather they changed on a millisecond scale. Voltage imaging can identify areas of brain slices in which the neuropil was in a sustained depolarization (plateau), long after the stimulus onset. Upon a barrage of synaptic inputs, a cortical pyramidal neuron experiences: (a) weak temporal summation of evoked voltage transients (EPSPs); and (b) afterhyperpolarization (intracellular recording), which are not represented in the GEVI population imaging signal (optical signal). To explain these findings [(a) and (b)], we used four voltage indicators (ArcLightD, chi-VSFP, Archon1, and di-4-ANEPPS) with different optical sensitivity, optical response speed, labeling strategy, and a target neuron type. All four imaging methods were used in an identical experimental paradigm: layer 1 (L1) synaptic stimulation, to allow direct comparisons. The population voltage signal showed paired-pulse facilitation, caused in part by additional recruitment of new neurons and dendrites. “Synaptic stimulation” delivered in L1 depolarizes almost an entire cortical column to some degree.
An Overview of Registered Clinical Trials on Glucosinolates and Human Health: The Current Situation
Authors: Marino Mirko , Martini Daniela , Venturi Samuele , Tucci Massimiliano , Porrini Marisa , Riso Patrizia , Del Bo' Cristian
Published: October 2021

Epidemiological studies suggest a potential role of glucosinolates (GSLs) and isothiocyanates on human health. However, evidence from intervention studies, due to heterogeneity in features of study design, duration, participants, food or food components administered, and outcomes analyzed, is still insufficient. The current review aims to provide an overview of the trials on GSLs and GSL-rich foods registered over the last 20 years with the intention to summarize the main topics and results, but also the existing gaps that still need to be covered. Studies were collected by using ClinicalTrials.gov and the International Standard Randomized Controlled Trial Number (ISRCTN) registry. A total of 87 registered trials were identified with which most of them were performed by using extracts or pure compounds (n = 60) while few were conducted with GSL-rich foods (n = 27). In detail, sulforaphane was the most investigated compound, while broccoli was the most frequent food tested in the trials. The majority of the studies assessed the health effects of GSLs focusing on outcomes related to cancer and cognitive function, even if the current findings are not univocal. Emerging topics also included the study of GSLs and gut microbiota interaction and impact on skin health. Further attention was also drawn to the bioavailability of GSLs and/or derivatives from foods, extracts, and single compounds by also considering the contribution of the different genetic polymorphisms. In conclusion, although considerable efforts have been made to study GSLs and GSL-rich foods, further studies are necessary to provide evidence-based research and to corroborate the findings obtained. The interindividual response due to genetic polymorphisms should be further investigated in order to explore the contribution to the overall beneficial effect.
Assessment of Food Supplement Consumption in Polish Population of Adults
Authors: Stoś Katarzyna , Woźniak Agnieszka , Rychlik Ewa , Ziółkowska Izabela , Głowala Aneta , Ołtarzewski Maciej
Published: October 2021

Introduction: In recent years, there has been a great interest in food supplements. However the use of food supplements can be associated with the risk of excessive intake of vitamins or minerals which may have adverse health effects.

Objective: Assessment of food supplement consumption in the adult population in Poland.

Materials and Methods: The study was conducted on 1,831 adults (913 men, 918 women) from which 178 (59 men, 119 women) food supplement users were selected. The consumption of food supplements were assessed by the 24-h recall repeated two times and the food propensity questionnaire (FPQ).

Results: 10% of the subjects consumed food supplements during the 12 months prior to the study (6% of men, 13% of women) and among users 68% (79% of men and 88% of women) in the day before the survey. Most respondents (44%) used vitamin supplements during the year. More men than women (27 vs. 11%, p = 0.0059) used mineral supplements while more women than men used vitamin and mineral supplements (31 vs. 8%, p = 0.0008). The most frequently supplemented vitamins were: B6 (58%), C (53%), and D (47%) and minerals were: magnesium (43%), zinc (34%), and iron (29%). More women than men supplemented vitamin B6 (71 vs. 40%, p = 0.0012), vitamin D (54 vs. 36%, p = 0.0061) and magnesium (49 vs. 34%, p = 0.0075). Intake of riboflavin, pantothenic acid and manganese were higher in the group of men (respectively: 3.3 mg ± 6.0 vs. 1.4 mg ± 0.3, p = 0.0329; 9.4 mg ± 5.6 vs. 6.1 mg ± 2.0, p = 0.0357; 2.2 mg ± 0.9 vs. 1.3 mg ± 0.6, p = 0.0080) but intake of vitamin D was higher in the group of women (15.7 μg ± 20.4 vs. 33.1 μg ± 26.4, p = 0.0085). In many cases, the intake of vitamins and minerals from food supplements covered the Dietary Reference Values for these nutrients in 100%. In some persons the intake of biotin, vitamin B12, C, B6, riboflavin, niacin was higher than the reference values several dozen times. The intake of vitamins and minerals exceed UL in a few cases relating to vitamin B6 and magnesium.

Conclusions: A minority of adults in Poland used food supplements. However, those products were a significant source of vitamins and minerals. Intake of vitamins and minerals from food supplements should be monitored.
College Students' Perception of Snacks Sold in Vending Machines in the US: A Mixed-Methods Study
Authors: Mengarelli Cristiana Assumpção , Kirchoff Christie , Palacios Cristina
Published: October 2021

Introduction: Food in vending machines in US colleges contain limited nutritious foods available for purchase, which could affect the food choices made by students leading to poor diet quality. Interventions to improve college foodscapes usually follow a top-down approach and fail to affect dietary behavioral changes ultimately. This research aims to uncover what students want and ways to achieve change.

Methods: The mixed-methods approach included peer-led qualitative focus group discussions and a brief quantitative questionnaire on satisfaction from foods available in vending machines. A convenience sample of 20 students (15 females) was recruited from a Hispanic serving institution for this study.

Results: Vending machines were perceived as convenient, plentiful, and unhealthy. Students expressed dissatisfaction with both the variety and nutritional quality of snacks in vending machines. Suggestions for improvement included more fresh items (fruits and vegetables) and refrigerated items with higher protein content (low-fat yogurt, hummus, and peanut butter). To implement these improvements, participants discussed the cost and feasibility of perishable items. Increasing awareness and partnering strategies were proposed to mediate potential cost and buy-in obstacles as was elevating the appeal of healthy vending machines with technological enhancements that draw customers in and educate.

Conclusion and Implication for Practice: This group of college students was eager for positive changes in foods sold in vending machines and understand the major difficulties. The suggested changes may help this and other colleges develop policies to regulate the foods in vending machines to promote overall health and help prevent chronic diseases in the future.
Can Ketogenic Diet Improve Alzheimer's Disease? Association With Anxiety, Depression, and Glutamate System
Authors: de la Rubia Ortí Jose Enrique , Fernández David , Platero Félix , García-Pardo María Pilar
Published: October 2021

Background: Alzheimer's disease is the most common neurodegenerative disorder in our society, mainly characterized by loss of cognitive function. However, other symptoms such as anxiety and depression have been described in patients. The process is mediated by alterations in the synaptic and extrasynaptic activity of the neurotransmitter glutamate, which are linked to a hypometabolism of glucose as the main source of brain energy. In that respect, Ketogenic diet (KD) has been proposed as a non-pharmacological treatment serving as an alternative energy source to the neurons increasing the fat percentage and reducing the carbohydrates percentage, showing promising results to improve the cognitive symptoms associated with different neurodegenerative disorders, including AD. However, the association of this type of diet with emotional symptoms and the modulation of glutamate neurotransmission systems after this dietary reduction of carbohydrates are unknown.

Objective: The aim of this short review is to provide update studies and discuss about the relationship between KD, anxiety, depression, and glutamate activity in AD patients.

Discussion: The main results suggest that the KD is an alternative energy source for neurons in AD with positive consequences for the brain at different levels such as epigenetic, metabolic and signaling, and that the substitution of carbohydrates for fats is also associated with emotional symptoms and glutamate activity in AD.
Laparoscopic Pancreaticoduodenectomy Versus Conventional Open Approach for Patients With Pancreatic Duct Adenocarcinoma: An Up-to-Date Systematic Review and Meta-Analysis
Authors: Feng Qingbo , Liao Wenwei , Xin Zechang , Jin Hongyu , Du Jinpeng , Cai Yunshi , Liao Mingheng , Yuan Kefei , Zeng Yong
Published: October 2021

Background

To compare perioperative and oncological outcomes of pancreatic duct adenocarcinoma (PDAC) after laparoscopic versus open pancreaticoduodenectomy (LPD vs. OPD), we performed a meta-analysis of currently available propensity score matching studies and large-scale retrospective cohorts to compare the safety and overall effect of LPD to OPD for patients with PDAC.

Methods

A meta-analysis was registered at PROSPERO and the registration number is CRD42021250395. PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched based on a defined search strategy to identify eligible studies before March 2021. Data on operative times, blood loss, 30-day mortality, reoperation, length of hospital stay (LOS), overall morbidity, Clavien–Dindo ≥3 complications, postoperative pancreatic fistula (POPF), blood transfusion, delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and oncologic outcomes (R0 resection, lymph node dissection, overall survival, and long-term survival) were subjected to meta-analysis.

Results

Overall, we identified 10 retrospective studies enrolling a total of 11,535 patients (1,514 and 10,021 patients underwent LPD and OPD, respectively). The present meta-analysis showed that there were no significant differences in overall survival time, 1-year survival, 2-year survival, 30-day mortality, Clavien-Dindo ≥3 complications, POPF, DGE, PPH, and lymph node dissection between the LPD and OPD groups. Nevertheless, compared with the OPD group, LPD resulted in significantly higher rate of R0 resection (OR: 1.22; 95% CI 1.06–1.40; p = 0.005), longer operative time (WMD: 60.01 min; 95% CI 23.23–96.79; p = 0.001), lower Clavien–Dindo grade ≥III rate (p = 0.02), less blood loss (WMD: −96.49 ml; 95% CI −165.14 to −27.83; p = 0.006), lower overall morbidity rate (OR: 0.65; 95% CI 0.50 to 0.85; p = 0.002), shorter LOS (MD = −2.73; 95% CI −4.44 to −1.03; p = 0.002), higher 4-year survival time (p = 0.04), 5-year survival time (p = 0.001), and earlier time to starting adjuvant chemotherapy after surgery (OR: −10.86; 95% CI −19.42 to −2.30; p = 0.01).

Conclusions

LPD is a safe and feasible alternative to OPD for patients with PDAC, and compared with OPD, LPD seemed to provide a similar OS.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/#recordDetails.
Case Report: The JAK-Inhibitor Ruxolitinib Use in Aicardi-Goutieres Syndrome Due to ADAR1 Mutation
Authors: Cattalini Marco , Galli Jessica , Zunica Fiammetta , Ferraro Rosalba Monica , Carpanelli Marialuisa , Orcesi Simona , Palumbo Giovanni , Pinelli Lorenzo , Giliani Silvia , Fazzi Elisa , Badolato Raffaele
Published: October 2021

Type I Interferonopathies comprise inherited inflammatory diseases associated with perturbation of the type I IFN response. Use of Janus kinase (JAK) inhibitors has been recently reported as possible tools for treating some of those rare diseases. We describe herein the clinical picture and treatment response to the JAK-inhibitor ruxolitinib in a 5-year-old girl affected by Aicardi-Goutières Syndrome type 6 (AGS6) due to ADAR1 mutation. The girl's interferon score (IS) was compared with that of her older brother, suffering from the same disorder, who was not treated. We observed a limited, but distinct neurological improvement (Gross Motor Function and Griffiths Mental Development Scales). Analysis of IS values of the two siblings during the treatment showed several changes, especially related to infections; the IS values of the child treated with ruxolitinib were consistently lower than those measured in her brother. Based on these observations we suggest that the use of ruxolitinib in children with the same condition might be effective in inhibiting type I interferon response and that starting this therapy at early age in children with AGS could mitigate the detrimental effects of type I interferon hyperproduction.
Persisting Motor Function Problems in School-Aged Survivors of Congenital Diaphragmatic Hernia
Authors: de Munck Sophie , van der Cammen-van Zijp Monique H. M. , Zanen-van den Adel Tabitha P. L. , Wijnen René M. H. , Cochius-den Otter Suzan C. M. , van Haren Neeltje E. M. , Gischler Saskia J. , van Rosmalen Joost , IJsselstijn Hanneke
Published: October 2021

Background and Objectives: Children born with congenital diaphragmatic hernia (CDH) and treated with extracorporeal membrane oxygenation (ECMO), are at risk for motor function impairment during childhood. We hypothesized that all children born with CDH are at risk for persistent motor function impairment, irrespective of ECMO-treatment. We longitudinally assessed these children's motor function.

Methods: Children with CDH with and without ECMO-treatment, born 1999–2007, who joined our structural prospective follow-up program were assessed with the Movement Assessment Battery for Children (M-ABC) at 5, 8, 12 years. Z-scores were used in a general linear model for longitudinal analysis.

Results: We included 55 children, of whom 25 had been treated with ECMO. Forty-three (78%) were evaluated at three ages. Estimated mean (95% CI) z-scores from the general linear model were −0.67 (−0.96 to −0.39) at 5 years of age, −0.35 (−0.65 to −0.05) at 8 years, and −0.46 (−0.76 to −0.17) at 12 years. The 5- and 8-years scores differed significantly (p = 0.02). Motor development was significantly below the norm in non-ECMO treated patients at five years; −0.44 (−0.83 to −0.05), and at all ages in the ECMO-treated-patients: −0.90 (−1.32 to −0.49), −0.45 (−0.90 to −0.02) and −0.75 (−1.2 to −0.34) at 5, 8, and 12 years, respectively. Length of hospital stay was negatively associated with estimated total z-score M-ABC (p = 0.004 multivariate analysis).

Conclusion: School-age children born with CDH are at risk for motor function impairment, which persists in those who received ECMO-treatment. Especially for them long-term follow up is recommended.
lncRNA OR3A4 Promotes the Proliferation and Metastasis of Ovarian Cancer Through KLF6 Pathway
Authors: Guo Fangfang , Du Jianan , Liu Lingling , Gou Yawei , Zhang Mingming , Sun Wei , Yu Hongmei , Fu Xueqi
Published: October 2021

Aim: Ovarian cancer is a collaborative malignant tumor of the female reproductive system in clinical research. Some clinical studies have shown that OR3A4, which is a cancer-causing lncRNA, plays a major role in promoting the occurrence and development of a variety of tumors. And we also expressed the view that it expressed in ovarian tissue. However, the function of OR3A4 in ovarian cancer remains unclear.

Methods and Results: To further verify the function of lncRNA OR3A4 in ovarian cancer, we established the xenograft model in the zebra fish. In this study, cells transformed with OR3A4 shRNA plasmids were transplanted into the zebra fish, and the cell proliferation and migration ability were significantly reduced compared to the empty vector. While knocking out OR3A4, we further downregulated its expression by siRNA of KLF6. Our study found that the knocked out OR3A4 resulted in a decrease in cell proliferation and migration level, which can be found in the downregulated expression of KLF6. We also verify the relationship between OR3A4 and circulating tumor cells in the zebra fish xenograft model, the results indicate that lncRNA OR3A4 may be involved in the resistance of ovarian cancer to complain.

Conclusion: lncRNA OR3A4 promotes the proliferation and metastasis of ovarian cancer through the KLF6 pathway.
Interelement Decoupling Strategies at UHF MRI
Authors: Zivkovic Irena
Published: October 2021

Moving to the ultrahigh field magnetic resonance imaging (UHF MRI) brought many benefits such as potentially higher signal-to-noise ratio, contrast-to-noise ratio, and improved spectral resolution. The UHF MRI regime also introduced some challenges which could prevent full exploitation of mentioned advantages. A higher static magnetic field means increase in Larmor frequency, which further implies the shorter wavelength in a tissue. The shorter wavelength causes interferences of the RF signal and inhomogeneous excitation, which can be partially resolved by the introduction of the multichannel coil arrays. The biggest problem in UHF multichannel densely populated arrays is the existence of the interelement coupling, which should be minimized as much as possible. This article presents the nonconventional, recently developed decoupling techniques used in UHF MRI.
Acute Exposure to Normobaric Hypoxia Impairs Balance Performance in Sub-elite but Not Elite Basketball Players
Authors: Pojskić Haris , Hanstock Helen G. , Tang Tsz-Hin , Rodríguez-Zamora Lara
Published: October 2021

Although high and simulated altitude training has become an increasingly popular training method, no study has investigated the influence of acute hypoxic exposure on balance in team-sport athletes. Therefore, the purpose of this study was to investigate whether acute exposure to normobaric hypoxia is detrimental to balance performance in highly-trained basketball players. Nine elite and nine sub-elite male basketball players participated in a randomized, single-blinded, cross-over study. Subjects performed repeated trials of a single-leg balance test (SLBT) in an altitude chamber in normoxia (NOR; approximately sea level) with FiO2 20.9% and PiO2 ranging from 146.7 to 150.4 mmHg and in normobaric hypoxia (HYP; ~3,800 m above sea level) with FiO2 13.0% and PiO2 ranging from 90.9 to 94.6 mmHg. The SLBT was performed three times: 15 min after entering the environmental chamber in NOR or HYP, then two times more interspersed by 3-min rest. Peripheral oxygen saturation (SpO2) and heart rate (HR) were recorded at four time points: after the initial 15-min rest inside the chamber and immediately after each SLBT. Across the cohort, the balance performance was 7.1% better during NOR than HYP (P < 0.01, ηp2 = 0.58). However, the performance of the elite group was not impaired by HYP, whereas the sub-elite group performed worse in the HYP condition on both legs (DL: P = 0.02, d = 1.23; NDL: P = 0.01, d = 1.43). SpO2 was lower in HYP than NOR (P < 0.001, ηp2 = 0.99) with a significant decline over time during HYP. HR was higher in HYP than NOR (P = 0.04, ηp2 = 0.25) with a significant increase over time. Acute exposure to normobaric hypoxia detrimentally affected the balance performance in sub-elite but not elite basketball players.
From Millimeters to Micrometers; Re-introducing Myocytes in Models of Cardiac Electrophysiology
Authors: Jæger Karoline Horgmo , Edwards Andrew G. , Giles Wayne R. , Tveito Aslak
Published: October 2021

Computational modeling has contributed significantly to present understanding of cardiac electrophysiology including cardiac conduction, excitation-contraction coupling, and the effects and side-effects of drugs. However, the accuracy ofin silicoanalysis of electrochemical wave dynamics in cardiac tissue is limited by the homogenization procedure (spatial averaging) intrinsic to standard continuum models of conduction. Averaged models cannot resolve the intricate dynamics in the vicinity of individual cardiomyocytes simply because the myocytes are not present in these models. Here we demonstrate how recently developed mathematical models based on representing every myocyte can significantly increase the accuracy, and thus the utility of modeling electrophysiological function and dysfunction in collections of coupled cardiomyocytes. The present gold standard of numerical simulation for cardiac electrophysiology is based on the bidomain model. In the bidomain model, the extracellular (E) space, the cell membrane (M) and the intracellular (I) space are all assumed to be present everywhere in the tissue. Consequently, it is impossible to study biophysical processes taking place close to individual myocytes. The bidomain model represents the tissue by averaging over several hundred myocytes and this inherently limits the accuracy of the model. In our alternative approach both E, M, and I are represented in the model which is therefore referred to as the EMI model. The EMI model approach allows for detailed analysis of the biophysical processes going on in functionally important spaces very close to individual myocytes, although at the cost of significantly increased CPU-requirements.
Osteopathy and Mental Health: An Embodied, Predictive, and Interoceptive Framework
Authors: Bohlen Lucas , Shaw Robert , Cerritelli Francesco , Esteves Jorge E.
Published: October 2021

Globally, mental and musculoskeletal disorders present with high prevalence, disease burden, and comorbidity. In order to improve the quality of care for patients with persistent physical and comorbid mental health conditions, person-centered care approaches addressing psychosocial factors are currently advocated. Central to successful person-centered care is a multidisciplinary collaboration between mental health and musculoskeletal specialists underpinned by a robust therapeutic alliance. Such a collaborative approach might be found in osteopathy, which is typically utilized to treat patients with musculoskeletal disorders but may arguably also benefit mental health outcomes. However, research and practice exploring the reputed effect of osteopathy on patients with mental health problems lack a robust framework. In this hypothesis and theory article, we build upon research from embodied cognition, predictive coding, interoception, and osteopathy to propose an embodied, predictive and interoceptive framework that underpins osteopathic person-centered care for individuals with persistent physical and comorbid mental health problems. Based on the premise that, for example, chronic pain and comorbid depression are underlined by overly precise predictions or imprecise sensory information, we hypothesize that osteopathic treatment may generate strong interoceptive prediction errors that update the generative model underpinning the experience of pain and depression. Thus, physical and mental symptoms may be reduced through active and perceptual inference. We discuss how these theoretical perspectives can inform future research into osteopathy and mental health to reduce the burden of comorbid psychological factors in patients with persistent physical symptoms and support person-centered multidisciplinary care in mental health.
Sexuality in Ultra-High Risk for Psychosis and First-Episode Psychosis. A Systematic Review of Literature
Authors: Ciocca Giacomo , Jannini Tommaso B. , Ribolsi Michele , Rossi Rodolfo , Niolu Cinzia , Siracusano Alberto , Jannini Emmanuele A. , Di Lorenzo Giorgio
Published: October 2021

A considerable body of literature reports that individuals with psychotic disorders often suffer from sexual dysfunctions (SDs), with these representing a major unmet need. Long-term antipsychotic drug treatment may be the main cause for SDs in psychotic patients, through a plethora of different mechanisms, including prolactin dyscrasia, histamine-mediated sedation, and serotonin-induced sexual demotivation. However, a few pieces of evidence treat sexuality in patients at risk or the onset of psychosis. For this purpose, we systematically reviewed literature of the last 10 years in order to investigate sexuality in ultra-high risk (UHR) for psychosis and first-episode psychosis (FEP). We included in our review 34 articles fitting our research criteria on SDs in UHR and FEP. Evidence of SDs in the transition from UHR to FEP emerges through the selected studies. In FEP, sexuality is affected by the severity of the psychotic symptoms and, in some cases, by the iatrogenic effects of psychopharmacological treatment. Further experimental and clinical studies should systematically investigate the role of sexual functioning in the transition from UHR to FEP and, consequently, clarify whether or not SDs could be considered a possible marker for the onset of psychosis in at-risk populations. Moreover, psychiatrists and clinical psychologists should take into consideration the role of sexual life in young people with prodromal mental symptoms or at the onset of psychosis. Focusing on a thorough sexual evaluation might be a major challenge that could break down barriers of mental health promotion among young people with schizophrenia-spectrum disorders and therefore achieve better clinical outcomes.
MEWAR: Development of a Cross-Platform Mobile Application and Web Dashboard System for Real-Time Mosquito Surveillance in Northeast Brazil
Authors: Aldosery Aisha , Musah Anwar , Birjovanu Georgiana , Moreno Giselle , Boscor Andrei , Dutra Livia , Santos George , Nunes Vania , Oliveira Rossandra , Ambrizzi Tercio , Massoni Tiago , dos Santos Wellington Pinheiro , Kostkova Patty
Published: October 2021

Mosquito surveillance is a crucial process for understanding the population dynamics of mosquitoes, as well as implementing interventional programs for controlling and preventing the spread of mosquito-borne diseases. Environmental surveillance agents who performing routine entomological surveys at properties in areas where mosquito-borne diseases are endemic play a critical role in vector surveillance by searching and destroying mosquito hotspots as well as collate information on locations with increased infestation. Currently, the process of recording information on paper-based forms is time-consuming and painstaking due to manual effort. The introduction of mobile surveillance applications will therefore improve the process of data collection, timely reporting, and field worker performance. Digital-based surveillance is critical in reporting real-time data; indeed, the real-time capture of data with phones could be used for predictive analytical models to predict mosquito population dynamics, enabling early warning detection of hotspots and thus alerting fieldworker agents into immediate action. This paper describes the development of a cross-platform digital system for improving mosquito surveillance in Brazil. It comprises of two components: a dashboard for managers and a mobile application for health agents. The former enables managers to assign properties to health workers who then survey them for mosquitoes and to monitor the progress of inspection visits in real-time. The latter, which is primarily designed as a data collection tool, enables the environmental surveillance agents to act on their assigned tasks of recording the details of the properties at inspections by filling out digital forms built into the mobile application, as well as details relating to mosquito infestation. The system presented in this paper was co-developed with significant input with environmental agents in two Brazilian cities where it is currently being piloted.