bluuebunny/crossref_metadata_2025 huggingface dataset:
The Face Module Emerged in a Deep Convolutional Neural Network Selectively Deprived of Face Experience
Authors: Xu Shan , Zhang Yiyuan , Zhen Zonglei , Liu Jia
Published: May 2021

Can we recognize faces with zero experience on faces? This question is critical because it examines the role of experiences in the formation of domain-specific modules in the brain. Investigation with humans and non-human animals on this issue cannot easily dissociate the effect of the visual experience from that of the hardwired domain-specificity. Therefore, the present study built a model of selective deprivation of the experience on faces with a representative deep convolutional neural network, AlexNet, by removing all images containing faces from its training stimuli. This model did not show significant deficits in face categorization and discrimination, and face-selective modules automatically emerged. However, the deprivation reduced the domain-specificity of the face module. In sum, our study provides empirical evidence on the role of nature vs. nurture in developing the domain-specific modules that domain-specificity may evolve from non-specific experience without genetic predisposition, and is further fine-tuned by domain-specific experience.
Patient-Tailored, Home-Based Non-invasive Brain Stimulation for Memory Deficits in Dementia Due to Alzheimer's Disease
Authors: Bréchet Lucie , Yu Wanting , Biagi Maria Chiara , Ruffini Giulio , Gagnon Margaret , Manor Brad , Pascual-Leone Alvaro
Published: May 2021

Alzheimer's disease (AD) is an irreversible, progressive brain disorder that can cause dementia (Alzheimer's disease-related dementia, ADRD) with growing cognitive disability and vast physical, emotional, and financial pressures not only on the patients but also on caregivers and families. Loss of memory is an early and very debilitating symptom in AD patients and a relevant predictor of disease progression. Data from rodents, as well as human studies, suggest that dysregulation of specific brain oscillations, particularly in the hippocampus, is linked to memory deficits. Animal and human studies demonstrate that non-invasive brain stimulation (NIBS) in the form of transcranial alternating current stimulation (tACS) allows to reliably and safely interact with ongoing oscillatory patterns in the brain in specific frequencies. We developed a protocol for patient-tailored home-based tACS with an instruction program to train a caregiver to deliver daily sessions of tACS that can be remotely monitored by the study team. We provide a discussion of the neurobiological rationale to modulate oscillations and a description of the study protocol. Data of two patients with ADRD who have completed this protocol illustrate the feasibility of the approach and provide pilot evidence on the safety of the remotely-monitored, caregiver-administered, home-based tACS intervention. These findings encourage the pursuit of a large, adequately powered, randomized controlled trial of home-based tACS for memory dysfunction in ADRD.
Patients With Becker Muscular Dystrophy Have Severe Paraspinal Muscle Involvement
Authors: Sheikh Aisha M. , Rudolf Karen , de Stricker Borch Josefine , Khawajazada Tahmina , Witting Nanna , Vissing John
Published: May 2021

Introduction: Paraspinal muscles are important for gross motor functions. Impairment of these muscles can lead to poor postural control and ambulation difficulty. Little knowledge exists about the involvement of paraspinal muscles in Becker muscular dystrophy.

Objective: In this cross-sectional study, we investigated the involvement of paraspinal muscles with quantitative trunk strength measure and quantitative muscle MRI.

Methods and Materials: Eighteen patients with Becker muscular dystrophy underwent trunk, hip, and thigh strength assessment using a Biodex dynamometer and an MRI Dixon scan. Fourteen age- and body mass index-matched healthy men were included for comparison.

Results: Muscle fat fraction (FF) of the paraspinal muscles (multifidus and erector spinae) was higher in participants with Becker muscular dystrophy vs. healthy controls at all three examined spinal levels (C6, Th12, and L4/L5) (p < 0.05). There was a strong and inverse correlation between paraspinal muscle FF and trunk extension strength (ρ = −0.829, p < 0.001), gluteus maximus FF and hip extension strength (ρ = −0.701, p = 0.005), FF of the knee extensor muscles (quadriceps and sartorius) and knee extension strength (ρ = −0.842, p < 0.001), and FF of the knee flexor muscles (hamstring muscles) and knee flexion strength (ρ = −0.864, p < 0.001). Fat fraction of the paraspinal muscles also correlated with muscle FF of the thigh muscles and lower leg muscles.

Conclusion: In conclusion, patients with Becker muscular dystrophy demonstrate severe paraspinal muscular involvement indicated by low back extension strength and high levels of fat replacement, which parallel involvement of lower limb muscles. Assessment of paraspinal muscle strength and fat replacement may serve as a possible biomarker for both the clinical management and further study of the disease.
Behavioral and Histopathological Impairments Caused by Topical Exposure of the Rat Brain to Mild-Impulse Laser-Induced Shock Waves: Impulse Dependency
Authors: Jitsu Motoyuki , Niwa Katsuki , Suzuki Go , Obara Takeyuki , Iwama Yukiko , Hagisawa Kohsuke , Takahashi Yukihiro , Matsushita Yoshitaro , Takeuchi Satoru , Nawashiro Hiroshi , Sato Shunichi , Kawauchi Satoko
Published: May 2021

Although an enormous number of animal studies on blast-induced traumatic brain injury (bTBI) have been conducted, there still remain many uncertain issues in its neuropathology and mechanisms. This is partially due to the complex and hence difficult experimental environment settings, e.g., to minimize the effects of blast winds (tertiary mechanism) and to separate the effects of brain exposure and torso exposure. Since a laser-induced shock wave (LISW) is free from dynamic pressure and its energy is spatially well confined, the effects of pure shock wave exposure (primary mechanism) solely on the brain can be examined by using an LISW. In this study, we applied a set of four LISWs in the impulse range of 15–71 Pa·s to the rat brain through the intact scalp and skull; the interval between each exposure was ~5 s. For the rats, we conducted locomotor activity, elevated plus maze and forced swimming tests. Axonal injury in the brain was also examined by histological analysis using Bodian silver staining. Only the rats with exposure at higher impulses of 54 and 71 Pa·s showed significantly lower spontaneous movements at 1 and 2 days post-exposure by the locomotor activity test, but after 3 days post-exposure, they had recovered. At 7 days post-exposure, however, these rats (54 and 71 Pa·s) showed significantly higher levels of anxiety-related and depression-like behaviors by the elevated plus maze test and forced swimming test, respectively. To the best of the authors' knowledge, there have been few studies in which a rat model showed both anxiety-related and depression-like behaviors caused by blast or shock wave exposure. At that time point (7 days post-exposure), histological analysis showed significant decreases in axonal density in the cingulum bundle and corpus callosum in impulse-dependent manners; axons in the cingulum bundle were found to be more affected by a shock wave. Correlation analysis showed a statistically significant correlation between the depression like-behavior and axonal density reduction in the cingulum bundle. The results demonstrated the dependence of behavior deficits and axonal injury on the shock wave impulse loaded on the brain.
Insular Connectivity Is Associated With Self-Appraisal of Cognitive Function After a Concussion
Authors: Churchill Nathan W. , Hutchison Michael G. , Graham Simon J. , Schweizer Tom A.
Published: May 2021

Concussion is associated with acute cognitive impairments, with declines in processing speed and reaction time being common. In the clinical setting, these issues are identified via symptom assessments and neurocognitive test (NCT) batteries. Practice guidelines recommend integrating both symptoms and NCTs into clinical decision-making, but correlations between these measures are often poor. This suggests that many patients experience difficulties in the self-appraisal of cognitive issues. It is presently unclear what neural mechanisms give rise to appraisal mismatch after a concussion. One promising target is the insula, which regulates aspects of cognition, particularly interoception and self-monitoring. The present study tested the hypothesis that appraisal mismatch is due to altered functional connectivity of the insula to frontal and midline structures, with hypo-connectivity leading to under-reporting of cognitive issues and hyper-connectivity leading to over-reporting. Data were collected from 59 acutely concussed individuals and 136 normative controls, including symptom assessments, NCTs and magnetic resonance imaging (MRI) data. Analysis of resting-state functional MRI supported the hypothesis, identifying insular networks that were associated with appraisal mismatch in concussed athletes that included frontal, sensorimotor, and cingulate connections. Subsequent analysis of diffusion tensor imaging also determined that symptom over-reporting was associated with reduced fractional anisotropy and increased mean diffusivity of posterior white matter. These findings provide new insights into the mechanisms of cognitive appraisal mismatch after a concussion. They are of particular interest given the central role of symptom assessments in the diagnosis and clinical management of concussion.
Ranking the Predictive Power of Clinical and Biological Features Associated With Disease Progression in Huntington's Disease
Authors: Ghazaleh Naghmeh , Houghton Richard , Palermo Giuseppe , Schobel Scott A. , Wijeratne Peter A. , Long Jeffrey D.
Published: May 2021

Huntington's disease (HD) is characterised by a triad of cognitive, behavioural, and motor symptoms which lead to functional decline and loss of independence. With potential disease-modifying therapies in development, there is interest in accurately measuring HD progression and characterising prognostic variables to improve efficiency of clinical trials. Using the large, prospective Enroll-HD cohort, we investigated the relative contribution and ranking of potential prognostic variables in patients with manifest HD. A random forest regression model was trained to predict change of clinical outcomes based on the variables, which were ranked based on their contribution to the prediction. The highest-ranked variables included novel predictors of progression—being accompanied at clinical visit, cognitive impairment, age at diagnosis and tetrabenazine or antipsychotics use—in addition to established predictors, cytosine adenine guanine (CAG) repeat length and CAG-age product. The novel prognostic variables improved the ability of the model to predict clinical outcomes and may be candidates for statistical control in HD clinical studies.
The Effect of Focal Damage to the Right Medial Posterior Cerebellum on Word and Sentence Comprehension and Production
Authors: Geva Sharon , Schneider Letitia M. , Roberts Sophie , Green David W. , Price Cathy J.
Published: May 2021

Functional imaging studies of neurologically intact adults have demonstrated that the right posterior cerebellum is activated during verb generation, semantic processing, sentence processing, and verbal fluency. Studies of patients with cerebellar damage converge to show that the cerebellum supports sentence processing and verbal fluency. However, to date there are no patient studies that investigated the specific importance of the right posterior cerebellum in language processing, because: (i) case studies presented patients with lesions affecting the anterior cerebellum (with or without damage to the posterior cerebellum), and (ii) group studies combined patients with lesions to different cerebellar regions, without specifically reporting the effects of right posterior cerebellar damage. Here we investigated whether damage to the right posterior cerebellum is critical for sentence processing and verbal fluency in four patients with focal stroke damage to different parts of the right posterior cerebellum (all involving Crus II, and lobules VII and VIII). We examined detailed lesion location by going beyond common anatomical definitions of cerebellar anatomy (i.e., according to lobules or vascular territory), and employed a recently proposed functional parcellation of the cerebellum. All four patients experienced language difficulties that persisted for at least a month after stroke but three performed in the normal range within a year. In contrast, one patient with more damage to lobule IX than the other patients had profound long-lasting impairments in the comprehension and repetition of sentences, and the production of spoken sentences during picture description. Spoken and written word comprehension and visual recognition memory were also impaired, however, verbal fluency was within the normal range, together with object naming, visual perception and verbal short-term memory. This is the first study to show that focal damage to the right posterior cerebellum leads to language difficulties after stroke; and that processing impairments persisted in the case with most damage to lobule IX. We discuss these results in relation to current theories of cerebellar contribution to language processing. Overall, our study highlights the need for longitudinal studies of language function in patients with focal damage to different cerebellar regions, with functional imaging to understand the mechanisms that support recovery.
Feature Counting Is Impaired When Shifting Attention Between the Eyes in Adults With Amblyopia
Authors: Hou Chuan , Acevedo Munares Gabriela
Published: May 2021

Background

Feature counting requires rapid shifts of attention in the visual field and reflects higher-level cortical functions. This process is drastically impaired in the amblyopic eye of strabismic amblyopes. In this study, we hypothesized that feature counting performance in anisometropic and strabismic amblyopes is further impaired when shifts in attention is required between the eyes.

Materials and Methods

Through a mirror stereoscope, highly visible Gabor patches were presented to the same eye within a block or randomly presented to the left eye or to the right eye with an equal probability within a block. The task was to report the number of Gabors (3 to 9) as accurately as possible. Counting performance was compared between the amblyopes and the normal-vision observers and between the viewing conditions (shifting attention between the eyes versus maintaining attention in the same eye).

Results

When attention was maintained in the same eye, the amblyopic eye of both anisometropic and strabismic groups undercounted the number of Gabors, but achieved near-perfect performance with their fellow eye, compared to normal-vision observers. In contrast, when shifting attention randomly to the left or to the right eye, the amblyopic eye further undercounted the number of Gabors. Undercounting was also found in the fellow eye of strabismic amblyopes, but was not in the fellow eye of anisometropic amblyopes. Performance in normal-vision observers did not differ between shifting attention between the eyes and maintaining attention in the same eye.

Conclusion

Our data showed that the amblyopic eye of both anisometropic and strabismic amblyopes further undercounted features when shifting attention between the eyes, compared to when maintaining attention in the same eye. This suggests that the ability to quickly redirect attention, particularly under interocular suppression, is impaired in amblyopia. The fellow eye of strabismic amblyopes also undercounted features when shifting attention between the eyes. However, such fellow eye abnormality was not found in anisometropic amblyopes, suggesting that different patterns of visual deficits are associated with amblyopia of different etiologies. The inability to count multiple features accurately reflects dysfunctions of high-level cortices in the amblyopic brain.
Combining Electrostimulation With Fiber Tracking to Stratify the Inferior Fronto-Occipital Fasciculus
Authors: Roux Alexandre , Lemaitre Anne-Laure , Deverdun Jeremy , Ng Sam , Duffau Hugues , Herbet Guillaume
Published: May 2021

The inferior fronto-occipital fasciculus (IFOF) is one of the longest association fiber tracts of the brain. According to the most recent anatomical studies, it may be formed by several layers, suggesting a role in multiple cognitive functions. However, to date, no attempt has been made to dissociate the functional contribution of the IFOF subpathways. In this study, real-time, cortico-subcortical mapping with direct electrostimulation was performed in 111 patients operated on in wide-awake surgery for a right low-grade glioma. Patients performed two behavioral tasks during stimulation, tapping, respectively, mentalizing and visual semantic cognition—two functions supposed to be partly mediated by the IFOF. Responsive white matter sites were first subjected to a clustering analysis to assess potential topological differences in network organization. Then they were used as seeds to generate streamline tractograms based on the HC1021 diffusion dataset (template-based approach). The tractograms obtained for each function were overlapped and contrasted to determine whether some fiber pathways were more frequently involved in one or the other function. The obtained results not only provided strong evidence for a role of the right IFOF in both functions, but also revealed that the tract is dissociable into two functional strata according to a ventral (semantic) and dorsal (mentalizing) compartmentalization. Besides, they showed a high degree of anatomo-functionnal variability across patients in the functional implication of the IFOF, possibly related to symmetrical/hemispheric differences in network organization. Collectively, these findings support the view that the right IFOF is a functionally multi-layered structure, with nevertheless interindividual variations.
Safety Evaluation of Yeasts With Probiotic Potential
Authors: Fernández-Pacheco Pilar , Ramos Monge Inés María , Fernández-González Mónica , Poveda Colado Justa María , Arévalo-Villena María
Published: May 2021

This work has evaluated the safety aspects of 20 yeast strains, isolated from food environments, selected in previous works due to their probiotic potential. Among the different strains, there are Saccharomyces and non-Saccharomyces yeasts. Before safety evaluation, differentiation of Saccharomyces cerevisiae strains was done by PCR amplification of inter-δ region with pairs of primers δ2-12 and δ12-21, which showed that they were all different from each other and also had different profiles to Saccharomyces boulardii (the only commercial probiotic yeast). The non-Saccharomyces ones were already known. The evaluation tests carried out were antibiotic and antifungal resistance, production of biogenic amines, deconjugation activity of bile salts, and different enzymatic activities: coagulase, deoxyribonuclease, hemolysin, proteolytic, and phospholipase. None of the studied strains demonstrated coagulase, hemolytic or DNase capacity (clear virulence factors), although all of them showed protease activity, some showed phospholipase activity, and half of the yeasts were capable of conjugating bile salts. Regarding antimicrobial compounds, all were resistant to antibiotics but showed sensitivity to the antimycotics used. Nevertheless, only one strain of Hanseniaspora osmophila was excluded for use in the food industry, due to its high production of tyramine.
Performance of Bioelectrical Impedance and Anthropometric Predictive Equations for Estimation of Muscle Mass in Chronic Kidney Disease Patients
Authors: Bellafronte Natália Tomborelli , Vega-Piris Lorena , Cuadrado Guillermina Barril , Chiarello Paula Garcia
Published: May 2021

Background: Patients with chronic kidney disease (CKD) are vulnerable to loss of muscle mass due to several metabolic alterations derived from the uremic syndrome. Reference methods for body composition evaluation are usually unfeasible in clinical settings.

Aims: To evaluate the accuracy of predictive equations based on bioelectrical impedance analyses (BIA) and anthropometry parameters for estimating fat free mass (FFM) and appendicular FFM (AFFM), compared to dual energy X-ray absorptiometry (DXA), in CKD patients.

Methods: We performed a longitudinal study with patients in non-dialysis-dependent, hemodialysis, peritoneal dialysis and kidney transplant treatment. FFM and AFFM were evaluated by DXA, BIA (Sergi, Kyle, Janssen and MacDonald equations) and anthropometry (Hume, Lee, Tian, and Noori equations). Low muscle mass was diagnosed by DXA analysis. Intra-class correlation coefficient (ICC), Bland-Altman graphic and multiple regression analysis were used to evaluate equation accuracy, linear regression analysis to evaluate bias, and ROC curve analysis and kappa for reproducibility.

Results: In total sample and in each CKD group, the predictive equation with the best accuracy was AFFMSergi (men, n = 137: ICC = 0.91, 95% CI = 0.79–0.96, bias = 1.11 kg; women, n = 129: ICC = 0.94, 95% CI = 0.92–0.96, bias = −0.28 kg). AFFMSergi also presented the best performance for low muscle mass diagnosis (men, kappa = 0.68, AUC = 0.83; women, kappa = 0.65, AUC = 0.85). Bias between AFFMSergi and AFFMDXA was mainly affected by total body water and fat mass. None of the predictive equations was able to accurately predict changes in AFFM and FFM, with all ICC lower than 0.5.

Conclusion: The predictive equation with the best performance to asses muscle mass in CKD patients was AFFMSergi, including evaluation of low muscle mass diagnosis. However, assessment of changes in body composition was biased, mainly due to variations in fluid status together with adiposity, limiting its applicability for longitudinal evaluations.
Establishment of a Prognostic Model for Hepatocellular Carcinoma Based on Endoplasmic Reticulum Stress-Related Gene Analysis
Authors: Liu Peng , Wei Jinhong , Mao Feiyu , Xin Zechang , Duan Heng , Du Yan , Wang Xiaodong , Li Zhennan , Qian Jianjun , Yao Jie
Published: May 2021

Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide and its incidence continues to increase year by year. Endoplasmic reticulum stress (ERS) caused by protein misfolding within the secretory pathway in cells and has an extensive and deep impact on cancer cell progression and survival. Growing evidence suggests that the genes related to ERS are closely associated with the occurrence and progression of HCC. This study aimed to identify an ERS-related signature for the prospective evaluation of prognosis in HCC patients. RNA sequencing data and clinical data of patients from HCC patients were obtained from The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC). Using data from TCGA as a training cohort (n=424) and data from ICGC as an independent external testing cohort (n=243), ERS-related genes were extracted to identify three common pathways IRE1, PEKR, and ATF6 using the GSEA database. Through univariate and multivariate Cox regression analysis, 5 gene signals in the training cohort were found to be related to ERS and closely correlated with the prognosis in patients of HCC. A novel 5-gene signature (including HDGF, EIF2S1, SRPRB, PPP2R5B and DDX11) was created and had power as a prognostic biomarker. The prognosis of patients with high-risk HCC was worse than that of patients with low-risk HCC. Multivariate Cox regression analysis confirmed that the signature was an independent prognostic biomarker for HCC. The results were further validated in an independent external testing cohort (ICGC). Also, GSEA indicated a series of significantly enriched oncological signatures and different metabolic processes that may enable a better understanding of the potential molecular mechanism mediating the progression of HCC. The 5-gene biomarker has a high potential for clinical applications in the risk stratification and overall survival prediction of HCC patients. In addition, the abnormal expression of these genes may be affected by copy number variation, methylation variation, and post-transcriptional regulation. Together, this study indicated that the genes may have potential as prognostic biomarkers in HCC and may provide new evidence supporting targeted therapies in HCC.
Primary Intracranial Leiomyosarcoma Secondary to Glioblastoma: Case Report and Literature Review
Authors: Zhao Liyan , Jiang Yining , Wang Yubo , Bai Yang , Sun Ying , Li Yunqian
Published: May 2021

Background

Leiomyosarcoma is a highly malignant soft-tissue sarcoma with a poor prognosis. In recent years, treatment for leiomyosarcoma has not shown much progress. Primary intracranial leiomyosarcoma (PILMS) is a much rarer type of neoplasm, which occurs more frequently in immunocompromised patients. PILMS cases reported in the literature are scarce and treatment strategy and prognosis are still under debate. In this study, a case of PILMS secondary to the total resection of giant cell glioblastoma is reported.

Case Description

A 38-year-old male was hospitalized with a three-month history of a temporal opisthotic bump. His medical history included a total resection of a tumor located in the right temporal lobe performed 4 years earlier. Pathological examination led to a diagnosis of giant cell glioblastoma, and the patient underwent postoperative chemotherapy with temozolomide for 6 weeks plus simultaneous radiotherapy with 63.66 Gary. Four years later, during regular follow-up, a preoperative MRI brain scan resulted in a well-defined signal pointing out two nodule-like features located at the right temporal lobe and subcutaneous soft tissue, respectively, and near the area where the previous giant cell glioblastoma was located. The mass was completely removed by a transtemporal approach and postoperative pathology revealed that the mass was a leiomyosarcoma. The patient underwent postoperative radiotherapy and no recurrence occurred until now.

Conclusions

To date, research on soft-tissue sarcoma, especially PILMS, has not made much progress, and a limited number of studies have provided few details on the management of PILMS. The treatment of choice for PILMS is aggressive multimodal treatment based on total tumor resection and radiotherapy. Moreover, systemic treatment with chemotherapy and targeted therapy, such as olaratumab, as well as further research still needs to be performed as many questions are left unanswered. To our knowledge, this is the first report on a case of PILMS secondary to glioblastoma, which might serve as a potential reference for clinicians and clinical studies.
High Expression of ACE2 and TMPRSS2 at the Resection Margin Makes Lung Cancer Survivors Susceptible to SARS-CoV-2 With Unfavorable Prognosis
Authors: Wang Qianqian , Li Liangyu , Qu Tianyu , Li Jie , Wu Lingxiang , Li Kening , Wang Ziyu , Zhu Mengyan , Huang Bin , Wu Wei , Wu Min , Ding Rong , Zhang Zhihong , Wang Qianghu , Xia Xinyi , Li Pengping , Zhang Zhi , Guo Renhua
Published: May 2021

Background

Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide. Systematic analysis of lung cancer survivors at molecular and clinical levels is warranted to understand the disease course and clinical characteristics.

Methods

A single-center, retrospective cohort study was conducted in 65 patients with COVID-19 from Wuhan Huoshenshan Hospital, of which 13 patients were diagnosed with lung cancer. The study was conducted from February 4 to April 11, 2020.

Results

During the course of treatment, lung cancer survivors infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) had shorter median time from symptom onset to hospitalization (P = 0.016) and longer clinical symptom remission time (P = 0.020) than non-cancer individuals. No differences were observed among indicators such as time from symptom onset to hospitalization and symptom remission time between medium-term and short-term survivors. The expression of ACE2 (P = 0.013) and TMPRSS2 (P <0.001) was elevated in lung cancer survivors as compared with that in non-cancer individuals.

Conclusions

ACE2 and TMPRSS2 levels were higher at resection margins of lung cancer survivors than those in normal tissues of non-cancerous individuals and may serve as factors responsible for the high susceptibility to COVID-19 among lung cancer survivors. Lung cancer patients diagnosed with COVID-19, including medium-term survivors, have worse outcomes than the general population.
A Clinical Analysis of Pharyngeal Bronchogenic Cysts in the Pharynx of Children
Authors: Xu Ying , Han Fugen , Seng Dongjie , Jiang Lan , Wang Shengcai , Ni Xin , Zhang Jie
Published: May 2021

Objective: This study was designed to summarize the clinical characteristics, diagnosis and treatment of pharyngeal bronchogenic cysts in children to help in making the correct diagnosis and developing an appropriate treatment plan.

Methods: The clinical data of 13 children with bronchogenic cysts in the pharynx, who were treated in otolaryngology head and neck surgery department between September 2013 and July 2019, were analyzed retrospectively. The clinical characteristics were evaluated, and the related factors for diagnosis and treatment were analyzed. Clinical characteristics and imaging features of three cases whose lesions located in the nasopharyngeal, oropharynx, and laryngopharyngeal were demonstrated.

Results: All 13 children were male, the youngest being 4 days old, the oldest 6 years and 6 months, and the median age being 1 year and 4 months. Eight patients were diagnosed during a physical examination, and five patients visited the doctor with different degrees of upper airway obstruction. The mass was located in the nasopharynx in one patient, in the oropharynx in eight patients, and in the laryngopharynx in the other four patients. Computed tomography (CT) scanning, which is helpful for a topical diagnosis, showed a dense homogeneous mass. Electronic nasopharyngoscopy showed cystic masses of different sizes in the pharynx. All the children underwent cyst resection under general anesthesia, and the postoperative pathology result was a bronchogenic cyst. One child was lost to follow-up, but the remaining 12 children were followed up for between 6 months and 6 years, during which no recurrence of a cyst was found.

Conclusion: Bronchogenic cysts are a rare cyst of the head and neck, and the most common site of the cyst is the oropharynx. The impact on airway obstruction depends on the location and size of the cyst. CT scanning is of great significance for diagnosis. Surgical treatment should be carried out as soon as possible after diagnosis, as surgery is the most effective way to treat bronchogenic cysts. Follow-ups should be carried out regularly to prevent cyst recurrence.
Endourology Methods in Pediatric Population for Kidney Stones Located in Lower Calyx: FlexURS vs. Micro PCNL (MicroPERC®)
Authors: Halinski Adam , Steyaert Henri , Wojciech Magdalena , Sobolewski Bartłomiej , Haliński Andrzej
Published: May 2021

Kidney stone disease in children is always a therapeutic challenge. It is a multifactorial condition and it should be approached, diagnosed and treated as such. One of the biggest challenges is kidney stones located in the lower renal calyx. There are currently three main surgical techniques to treat this condition: ESWL—Extracorporeal Shock Wave Lithotripsy, RIRS—Retrograde IntraRenal Surgery, and PCNL—PerCutaneous Nephro-Lithotripsy. In pediatric population, the most frequently used method is ESWL, and in the event of failure, endoscopic procedures are the second-best choice. In this article, a sample of 53 children admitted to a tertiary medical center was examined. Thirty-eight of those children underwent flexible URS, while the remaining 15—micro PCNL. The average size of the deposit in the former group was 12.2 mm, against 13.5 mm in the latter. The full Stone Free Rate (SFR) was achieved in RIRS at 84.21 and 86.7% in percutaneous nephrolithotripsy. Flexible ureterorenoscopy and MicroPERC are two comparably effective methods for treating lower calyx stones of any size. However, according to our data, flexible ureterorenoscopy carries a lower risk of complications and inpatient care (with the mean of 3 days). The learning curve for these procedures in pediatric urology is long and relies on a limited number of patients. The number of pediatric patients qualifying for these procedures is restricted also due to the high efficacy of extracorporeal shock wave lithotripsy in pediatric population. Radiation exposure is an important factor in every endoscopy procedure and should never exceed the limits set in the ALARA protocol. ESWL remains to this day the treatment of choice for stone disease in children and can be performed under ultrasound control. For many parents, it is a first-choice treatment preference for their child due to its greater apparent safety, although data on this remains insufficient. Prospective, randomized, multicenter trials are definitely needed.
Diagnostic Accuracy of Plasma Ghrelin Concentrations in Pediatric Sepsis-Associated Acute Respiratory Distress Syndrome: A Single-Center Cohort Study
Authors: Yuan Xiu , Li Shaojun , Zhou Liang , Tang Tian , Cheng Yuwei , Ao Xiaoxiao , Tan Liping
Published: May 2021

Background: Ghrelin is the endogenous ligand of growth hormone secretagogue receptor 1a, which plays a role in regulating immunity and inflammation. The aim of this study is to assess the diagnostic value of plasma ghrelin in sepsis-associated pediatric acute respiratory distress syndrome (PARDS).

Methods: We recruited patients who were admitted to the pediatric ICU (PICU) of the Children's Hospital of Chongqing Medical University between January 2019 and January 2020 and met the diagnostic criteria for sepsis. Data on clinical variables, laboratory indicators, plasma ghrelin concentrations, and inflammatory factors were collected and evaluated, and patients were followed up for 28 days. The area under the receiver-operating characteristic curves (AUROC) were determined using logistic regression to calculate and test cut-off values for ghrelin as a diagnostic indicator of sepsis-associated PARDS. The log-rank test was used to compare survival according to ghrelin levels.

Main results: Sixty-six PICU patients (30 with ARDS and 36 without ARDS) who met the diagnostic criteria of sepsis were recruited. The ghrelin level was significantly higher in the ARDS group than in the non-ARDS group. The AUROC of ghrelin was 0.708 (95% confidence interval: 0.584–0.833) and the positivity cutoff value was 445 pg/mL. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of plasma ghrelin for the diagnosis of PARDS-associated sepsis were 86.7, 50.0, 59.1, 81.8, 1.734, and 0.266%, respectively. The survival rate of sepsis patients were significantly improved when the ghrelin level was >445 pg/mL.

Conclusions: Ghrelin plasma levels were higher in sepsis-associated PARDS, and accompanied by increased levels of inflammatory factors. High ghrelin levels are a positive predictor of ICU survival in sepsis patients. Yet, there is no evidence to prove that elevated ghrelin is a promising diagnostic indicator of sepsis-associated PARDS.

Trial registration: Clinicaltrials, ChiCTR1900023254. Registered 1 December 2018 - Retrospectively registered, http://www.clinicaltrials.gov/ChiCTR1900023254.
Effects of Pharmacist-Led Clinical Pathway/Order Sets on Cancer Patients: A Systematic Review
Authors: Tan Zhiyuan , Yu Zhiheng , Chen Ken , Liu Wei , Zhao Rongsheng
Published: May 2021

Background: Pharmacist-led clinical pathways/order sets (PLCOs) were first applied for designated diseases and surgical operations, such as cancer. They were not used in pharmacotherapy until recently. After screening a large number of publications, we found that PLCOs were rarely accessible.

Objective: To evaluate the effects and the changes of relevant medical outcomes of PLCOs.

Methods: Articles from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and China Biology Medicine disc (CBM) were systematically retrieved. Clinical research comparing cancer patients’ clinical effects with or without clinical pathway/order sets was performed. Two reviewers performed quality assessment, and the data were abstracted independently. A narrative synthesis of the extracted data was performed due to heterogeneity.

Results: Nine studies were identified, including six uncontrolled before–after studies and three case-series studies. The scopes of PLCOs of included research can be divided into two types, one focusing on chemotherapy agents and the other on the managements of chemotherapy-induced complications. The PLCOs shortened hospital length of stay, decreased initial antibiotic time intervals in patients with febrile neutropenia, reduced medication error incidence, and increased physicians’ adherence rate to clinical pathway/order sets. Moreover, three articles included economic effects showing positive savings on medication costs through PLCOs.

Conclusion: PLCOs can have beneficial effects on medication effectiveness, safety, and economic outcomes. Nevertheless, clinical pathway/order sets need to be further optimized and expanded to other clinical areas.
Estrogenic Plants: to Prevent Neurodegeneration and Memory Loss and Other Symptoms in Women After Menopause
Authors: Echeverria Valentina , Echeverria Florencia , Barreto George E. , Echeverría Javier , Mendoza Cristhian
Published: May 2021

In mammals, sexual hormones such as estrogens play an essential role in maintaining brain homeostasis and function. Estrogen deficit in the brain induces many undesirable symptoms such as learning and memory impairment, sleep and mood disorders, hot flushes, and fatigue. These symptoms are frequent in women who reached menopausal age or have had ovariectomy and in men and women subjected to anti-estrogen therapy. Hormone replacement therapy alleviates menopause symptoms; however, it can increase cardiovascular and cancer diseases. In the search for therapeutic alternatives, medicinal plants and specific synthetic and natural molecules with estrogenic effects have attracted widespread attention between the public and the scientific community. Various plants have been used for centuries to alleviate menstrual and menopause symptoms, such as Cranberry, Ginger, Hops, Milk Thistle, Red clover, Salvia officinalis, Soy, Black cohosh, Turnera diffusa, Ushuva, and Vitex. This review aims to highlight current evidence about estrogenic medicinal plants and their pharmacological effects on cognitive deficits induced by estrogen deficiency during menopause and aging.
Unconjugated Bilirubin Attenuates DSS-Induced Colitis Potentially via Enhancement of Bilirubin Reabsorption
Authors: Zhao Chong , Huang Hongli , Pan Qiuhua , Huang Wenqi , Peng Wu , Xu Haoming , Feng Zhiqiang , Du Yanlei , Nie Yuqiang , Zhou Yongjian
Published: May 2021

Studies increasingly show that ulcerative colitis (UC) is a consequence of an imbalance between oxidative stress and antioxidant capacity. Bilirubin exerts an anti-inflammatory effect by scavenging reactive oxygen species (ROS), although the exact mechanism is not completely understood. The aim of this study was to determine the role of serum bilirubin in UC using patient data and a mouse model of dextran sodium sulfate (DSS)-induced colitis. We found that low levels of serum bilirubin correlated to a higher risk of UC in a retrospective case-control population. Pre-treatment with exogenous unconjugated bilirubin (UCB) significantly enhanced colonic bilirubin absorption in mice, and attenuated the DSS-induced body weight loss, colon shortening and histopathological damage. Mechanistically, bilirubin prevented the infiltration of inflammatory cells, and decreased the levels of myeloperoxidase and pro-inflammatory cytokines in the serum and colon. Moreover, bilirubin inhibited ROS and malondialdehyde production, scavenged superoxide anions (O2·−) from the colon and enhanced the total antioxidant capacity. In conclusion, exogenous UCB attenuated DSS-induced colitis by directly scavenging O2·− and enhancing bilirubin reabsorption in the colon via enterohepatic cycling.
Characterization of B- and T-Cell Compartment and B-Cell Related Factors Belonging to the TNF/TNFR Superfamily in Patients With Clinically Active Systemic Lupus Erythematosus: Baseline BAFF Serum Levels Are the Strongest Predictor of Response to Belimumab after Twelve Months of Therapy
Authors: Piantoni Silvia , Regola Francesca , Masneri Stefania , Merletti Michele , Lowin Torsten , Airò Paolo , Tincani Angela , Franceschini Franco , Andreoli Laura , Pongratz Georg
Published: May 2021

Background:Patients with systemic lupus erythematosus (SLE) show increased serum levels of tumor necrosis factor (TNF)/TNF receptor (R) superfamily member, e.g. BAFF (B lymphocyte stimulator). Belimumab, a monoclonal antibody against soluble BAFF, is used for treatment of SLE. Although B cells are the main target, a BAFF-dependent T-cell activation pathway also plays a role. High levels of anti-DNA antibodies and low complement at baseline are known predictors of response to Belimumab.

Objectives:To explore the association of circulating lymphocytes and serum levels of B- cell related TNF/TNFR superfamily members with response to Belimumab in SLE patients.

Methods:Twenty-one SLE patients received Belimumab. Clinical evaluation and laboratory tests were performed at baseline, at 6 and 12 months. TNF super-family members (BAFF, APRIL, sBCMA, sCD40L, sTACI, TWEAK) were tested by high-sensitivity ELISA in all patients, and lymphocyte immunophenotyping was performed by flow cytometry in ten subjects. SLE-disease activity was assessed by SLEDAI-2K score. Linear regression modeling was used to investigate parameters influencing SLEDAI-2K and anti-dsDNA antibody titers over time and for predictive models.

Results:Clinical improvement was observed in all patients. A global reduction of circulating B cells, especially naïve, was detected, without variation in the T-cell compartment. All TNF family members decreased, whereas APRIL remained constant. The increase in serum levels of C3 (p= 0.0004) and sTACI (p= 0.0285) was associated with a decrease of SLEDAI-2K. The increase of C4 (p= 0.027) and sBCMA (p= 0.0015) and the increase of CD8+T cells (p= 0.0160) were associated with a decrease, whereas an increase of sCD40L in serum (p= 0.0018) and increased number of CD4+T cells (p= 0.0029) were associated with an increase, in anti-dsDNA antibody titers, respectively. Using stepwise forward inclusion, the minimal model to predict SLEDAI-2K response at 12 months included BAFF (p= 3.0e− 07) and SLEDAI-2K (p= 7.0e− 04) at baseline. Baseline APRIL levels also showed an association, although the overall model fit was weaker.

Conclusion:In our real-life cohort, baseline serum levels of BAFF were the best predictor of response to Belimumab, confirming post-hoc results of the BLISS study and suggesting the utility of this particular biomarker for the identification of patients who are more likely to respond.
Brief Review of the Results Regarding the Possible Underlying Mechanisms Driving the Neutrinoless Double Beta Decay
Authors: Neacsu Andrei , Sevestrean Vasile Alin , Stoica Sabin
Published: May 2021

Since the experimental discovery of neutrino oscillations, the search for the neutrinoless double beta (0νββ) decay has intensified greatly, as this particular decay mode, if experimentally discovered, could offer a testing ground for Beyond Standard Model (BSM) theories related to the yet hidden fundamental properties of neutrinos and the possibility of violating of some fundamental symmetries. In this work we make a brief review of the nuclear matrix elements and phase space factors calculations performed mainly by our group. Next, using these calculations and the most recent experimental half-life limits, we revise the constraints on the BSM parameters violating the lepton number corresponding to four mechanisms that could contribute to 0νββ decay. Finally, using the values obtained for the BSM parameters from one of the most sensitive double-beta decay experiments, we provide a comparison with the sensitivities of other experiments.
Effects of Tissue Flossing on the Healthy and Impaired Musculoskeletal System: A Scoping Review
Authors: Konrad Andreas , Močnik Richard , Nakamura Masatoshi
Published: May 2021

There is a belief that tissue flossing can improve the range of motion or performance, speed up recovery, and decrease the pain caused by various diseases or injuries. As a result, many therapists, patients, and athletes are now using this technique. Consequently, in the last 5 years, a number of studies have addressed these assumptions. The purpose of this scoping review is to introduce the application of a floss band and to summarize the existing evidence for the effect of floss band treatment on the range of motion, performance, recovery, and pain (due to disease or injuries). A further goal is to suggest what needs to be addressed in future studies. The online search was performed in PubMed, Scopus, and Web of Science databases. Any studies dealing with the effects of a floss band treatment on the range of motion, performance, recovery, or pain parameters in any population (e.g., patients, athletes) were included in this review. Twenty-four studies met the inclusion criteria, with a total of 513 participants. The included studies revealed that there is evidence that a single floss band treatment is able to increase the range of motion of the related joint and can positively affect jumping and strength performance. However, these findings show only small to moderate effect sizes. Although not yet clearly understood, a possible mechanism for such changes in the range of motion or performance is likely due to changed neuromuscular function, rather than changed mechanical properties, of the muscle (e.g., stiffness). All in all, there is a need to conduct long-term studies about the effects of flossing treatment on the range of motion and performance (e.g., strength or jumping parameters) and its related mechanism (e.g., pain tolerance). There is weak evidence that flossing can be of value for pain relief in the treatment of certain diseases and for speeding up recovery after exercise. Moreover, there is weak evidence that flossing might have a superior conditioning (warm-up) effect compared to stretching when the goal is to improve the range of motion or certain aspects of muscle strength, while no such superior effect has been reported when compared to foam rolling.