bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of Abdominal Magnetic Resonance Imaging in Patients With Residual Concentrated Enteric Contrast After Fluoroscopic Abdominal Examination
Authors: Dane Bari , Hindman Nicole
Published: September 2021

Objective

This study aimed to evaluate the image quality, image artifacts, radiologist confidence, and ability to provide definitive diagnosis for all patients with magnetic resonance imaging (MRI) performed after an abdominal fluoroscopic examination and to determine the utility of MRI in this setting.

Methods

Thirty-one MRI examinations performed a median of 2 days after fluoroscopic bowel evaluation (barium, n = 13; iodine, n = 18), 20 within 3 days of MRI, were retrospectively reviewed. The image quality, artifact emanating from bowel, inhomogeneity artifact, radiologist confidence, ability to render a definitive diagnosis, and identification of emergent or important findings for all MRI examinations were assessed. These same features were evaluated on 5 computed tomographies performed after fluoroscopy (before the MRI) in the same cohort.

Results

All 31 MRI examinations performed after fluoroscopic studies with concentrated barium or iodine solutions were diagnostic for answering the clinical question according to radiologist and report review, regardless of magnet strength and type of fluoroscopic contrast ingested. Magnetic resonance imaging after fluoroscopy had excellent overall image quality (mean score, 4.74/5), minimal to no artifact emanating from bowel (mean, 4.63/5), minimal inhomogeneity artifact (mean, 4.38/5), and excellent diagnostic confidence (mean, 4.98/5). No additional imaging was necessary for diagnosis after MRI. Computed tomography after fluoroscopy had lower overall image quality, more image artifacts, and lower diagnostic confidence (P < 0.05).

Conclusions

Magnetic resonance imaging is a useful tool for evaluating patients with retained concentrated enteric contrast from recent fluoroscopic examinations. In the absence of contraindication, MRI should be considered in the evaluation of urgent clinical problems in patients who recently underwent a fluoroscopic bowel evaluation.
Evaluation of Background Parenchymal Enhancement and Histogram-Based Diffusion-Weighted Image in Determining the Molecular Subtype of Breast Cancer
Authors: You Chao , Zhang Yunyan , Chen Yanqiong , Hu Xiaoxin , Hu Danting , Wu Jiong , Gu Yajia , Peng Weijun
Published: September 2021

Rationale and Objectives

This study aimed to evaluate the value of background parenchymal enhancement (BPE) and diffusion-weighted image (DWI) histogram features in differentiating among different molecular subtypes of breast cancers and investigate the relationship between BPE and DWI features.

Materials and Methods

We prospectively enrolled 142 patients with breast cancer between January and November 2018. All patients underwent breast magnetic resonance imaging before core needle biopsy. The quantitative BPE from dynamic enhanced images and the first-order histogram features extracted from DWI were analyzed. Univariate analysis of variance was used to compare differences in DWI histogram features and BPE characteristics among different molecular subtypes. Spearman test was used to compare the correlation between these imaging indexes.

Results

A total of 142 patients had 142 lesions, including 17 cases of triple-negative breast cancer, 12 cases of luminal A type breast cancer, 39 cases of luminal B type breast cancer, and 74 cases of human epidermal growth factor receptor 2–positive breast cancer. The apparent diffusion coefficient (ADC) 95th percentile, ADC kurtosis, and BPE were significantly different among 4 subtype groups (P < 0.05), especially between the triple-negative subtype and any other subtype (P < 0.05 in pairwise comparisons). There was a weak but significant correlation between BPE and kurtosis of ADC (r = −0.176, P = 0.036).

Conclusions

Diffusion-weighted image histogram features (95th percentile ADC value and kurtosis value of ADC) and BPE features were different in the 4 molecular subtypes of breast cancer, especially in the triple-negative breast cancer subtype. Background parenchymal enhancement was negatively correlated with the kurtosis value of ADC.
Psychosocial Experiences in Children With Congenital Melanocytic Nevus on the Face and Their Parents Throughout the Tissue Expansion Treatment
Authors: Zhang Chang , Wu Lehao , Zhao Sichun , Wang Qianwen , Li Tao , Wang Jiaqi
Published: September 2021

Large congenial melanocytic nevus (LCMN) on the head and face can have negative psychological effects on children and possibly also parents. Patients and their families experience prolonged periods of stress during tissue expansion treatment. The purpose of this study was to evaluate the psychological impact of LCMN on children and parents and explore their fluctuations of psychological status during treatment. Psychosocial status was evaluated in 30 children with LCMN on the head and face and a control group of 56 sex- and age-matched children using the Child Behavior Checklist and the inventory of Subjective Life Quality for Child and Adolescents. The parents of both groups were also evaluated using the Symptom Checklist-90, the Hospital Anxiety and Depression Scale, and the Perceived Stress Scale. Psychological assessments were performed before expander implantation, before lesion resection, and after operation. Results indicated that children with LCMN were more prone to social problems, withdrawal, and aggressive behavior. Furthermore, their psychological problems increased after entering to school. Parents of children with LCMN had high levels of emotional problems and stress. Continuous expansion resulted in the psychosocial status of both children and parents to reach the worst levels during the period before lesion resection. Six months after surgery, most of these psychosocial effects reduced to levels lower than before surgery. Additionally, we identified several risk factors, namely sex, number of operations, being in education, employment status of mother, and family pressures. Large congenial melanocytic nevus on head and face have considerable psychological impact on children and their parents throughout the tissue expansion treatment. This study demonstrates the need for appropriate psychological screening and interventions.
Anatomical Relationship Between the Lingual Nerve and Submandibular Duct
Authors: Iwai Toshinori , Sugiyama Satomi , Oguri Senri , Mitsudo Kenji
Published: September 2021

The purpose of this study was to investigate the anatomical relationship between the lingual nerve and submandibular duct. This study included 1403 patients with submandibular or sublingual gland diseases who underwent intraoral removal of submandibular gland sialoliths, submandibular glands, or sublingual glands. Of all patients, 33 patients underwent bilateral surgeries. All surgeries were performed a single surgeon, and the anatomical relationship between the lingual nerve and submandibular duct was always identified intraoperatively and recorded in the operation recorded. The anatomical relationship was investigated based on the intraoperative findings. The lingual nerve which crosses above the submandibular duct was detected in 8 of 1436 sides (0.6%). There were 4 in the right sides and 4 in the left sides. The lingual nerve below the submandibular gland was seen in 99.4%. Although the lingual nerve crosses above the submandibular duct with a rarer incidence, surgeons should beware of injuring the lingual nerve during intraoral salivary gland surgery.
Chemical Sterilization of Lipoplasty Cannula and Nontuberculous Mycobacteria Disinfection: An Experimental Study
Authors: Lee Yun-Hwan , Kim Hyung-Kyu , Kim Min-Sook , You Hi-Jin , Kim Deok-Woo , Lee Tae-Yul
Published: September 2021

Background:

Nontuberculous mycobacteria are commonly found pathogens; however, skin and soft tissue infections due to nontuberculous mycobacteria are often associated with surgical procedures, particularly after lipoplasty. Although nontuberculous mycobacteria are resistant to some chemical disinfectants, glutaraldehyde, peracetic acid, povidone iodine, alcohol, and chlorine are still used for the sterilization of medical instruments. This study investigated the efficacy of various disinfectants in a fatty environment with adipose and a bloody environment without adipose. In addition, this study was also used to identify the most effective disinfectant against nontuberculous mycobacteria.

Methods:

Three nontuberculous mycobacteria (Mycobacterium avium, M. abscessus, and M. fortuitum), pathogens frequently found in skin and soft tissue infections, were used. Seven chemical disinfectants were tested in both fatty and bloody environments. The disinfectants used were considered to have a sterilization effect when the log10 reduction factor exceeded 5.

Results:

Most disinfectants had some sterilizing effects against nontuberculous mycobacteria; however, glutaraldehyde was the most effective against all 3. Chlorhexidine and povidone iodine also displayed sterilizing effects. Of the disinfectants tested, only alkyldiaminoethylglycine hydrochloride showed a diminished effect with statistical significance, specifically against M. fortuitum in a fatty environment, whereas it had effective results in a bloody environment.

Conclusions:

Glutaraldehyde showed the greatest sterilizing effect on nontuberculous mycobacteria with a log10 reduction factor >5 in both fatty and bloody environments. However, some chemical disinfectants did not show sufficient sterilizing effects in a fatty environment and, therefore, should be used with caution for the sterilization of nontuberculous mycobacteria.

Level of Evidence:

Level II
Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection
Authors: Clotet-Freixas Sergi , Kotlyar Max , McEvoy Caitriona M. , Pastrello Chiara , Rodríguez-Ramírez Sonia , Farkona Sofia , Cardinal Heloise , Dieudé Mélanie , Hébert Marie-Josée , Li Yanhong , Famure Olusegun , Chen Peixuen , Kim S. Joseph , Chan Emilie , Jurisica Igor , John Rohan , Chruscinski Andrzej , Konvalinka Ana
Published: September 2021

Background.

Antibody-mediated rejection (AMR) causes more than 50% of late kidney graft losses. In addition to anti-human leukocyte antigen (HLA) donor-specific antibodies, antibodies against non-HLA antigens are also linked to AMR. Identifying key non-HLA antibodies will improve our understanding of AMR.

Methods.

We analyzed non-HLA antibodies in sera from 80 kidney transplant patients with AMR, mixed rejection, acute cellular rejection (ACR), or acute tubular necrosis. IgM and IgG antibodies against 134 non-HLA antigens were measured in serum samples collected pretransplant or at the time of diagnosis.

Results.

Fifteen non-HLA antibodies were significantly increased (P < 0.05) in AMR and mixed rejection compared with ACR or acute tubular necrosis pretransplant, and 7 at diagnosis. AMR and mixed cases showed significantly increased pretransplant levels of IgG anti-Ro/Sjögren syndrome-antigen A (SS-A) and anti-major centromere autoantigen (CENP)-B, compared with ACR. Together with IgM anti-CENP-B and anti-La/SS-B, these antibodies were significantly increased in AMR/mixed rejection at diagnosis. Increased IgG anti-Ro/SS-A, IgG anti-CENP-B, and IgM anti-La/SS-B were associated with the presence of microvascular lesions and class-II donor-specific antibodies (P < 0.05). Significant increases in IgG anti-Ro/SS-A and IgM anti-CENP-B antibodies in AMR/mixed rejection compared with ACR were reproduced in an external cohort of 60 kidney transplant patients.

Conclusions.

This is the first study implicating autoantibodies anti-Ro/SS-A and anti-CENP-B in AMR. These antibodies may participate in the crosstalk between autoimmunity and alloimmunity in kidney AMR.
Phocaeicola faecicola sp. nov., isolated from porcine faeces
Authors: Choi Ji Young , Choi Seung-Hyeon , Park Jam-Eon , Kim Ji-Sun , Lee Jiyoung , Lee Mi-Kyung , Lee Jung-Sook , Lee Ju Huck , Jung Hyunjung , Hur Tai-Young , Kim Hyeun Bum , Lee Ju-Hoon , Kim Jae-Kyung , Kang Se Won , Park Seung-Hwan
Published: September 2021

An obligately anaerobic, non-motile, Gram-negative and rod-shaped strain (AGMB03916T) was isolated from faeces of a 2-week-old piglet raised at the National Institute of Animal Science in Wanju, Republic of Korea. Growth of strain AGMB03916T occurred at 30–45 °C (optimum, 37 °C), at pH 6–9 (optimum, pH 8) and in the presence of 0.5–1.0 % (w/v) NaCl. Based on the results of 16S rRNA gene sequence analyses, strain AGMB03916T was closely related to two validly published species of the genus

Phocaeicola

,

Phocaeicola plebeius

and

Phocaeicola coprocola

. The 16S rRNA gene sequence similarity of strain AGMB03916T compared to

P. plebeius

M12T (=KCTC 5793T) and

P. coprocola

M16T (=KCTC 5443T) were 96.3 and 95.0 %, respectively. The genomic DNA G+C content of strain AGMB03916T was 46.4 mol%. The average nucleotide identity values between strain AGMB03916T and the reference strains were 74.9–78.5 %. Cells were able to utilize d-glucose, lactose, sucrose, maltose, salicin, aesculin hydrolysis, cellobiose and raffinose. The major end product of metabolism was acetate. The major cellular fatty acids (>10 %) of the isolate were iso-C15 : 0, anteiso-C15 : 0, C16 : 0, C16 : 0 3-OH and summed feature 11 (iso-C17 : 0 3-OH and/or C18 : 2 DMA). On the basis of the genotypic, biochemical, chemotaxonomic, phenotypic and phylogenetic data, strain AGMB03916T represents a novel species of the genus

Phocaeicola

, for which the name Phocaeicola faecicola sp. nov. is proposed. The type strain is AGMB03916T (=KCTC 25014T=GDMCC 1.2574T).
Absence of SARS-CoV-2 in the air and on the surfaces within the school environment
Authors: Thakar Amit , Dutkiewicz Shawn , Hoffman Timothy , Joyce Paul , Shah Vishal
Published: September 2021

To the best of our knowledge to date there are no scientific studies specifically investigating whether the SARS-CoV-2 virus is present in the air or on the various surfaces in the school environment. The aim of this study was to determine if SARS-CoV-2 is present on various high touch surfaces and in the air across the elementary, middle and high schools in the Chester County of Pennsylvania, USA. One hundred and fifty surface swab samples and 45 air samples were analysed for the presence of the virus. All the samples tested were negative for the presence of SARS-CoV-2. The results indicate that the spread of the virus through contact and through air in the school buildings across the USA is highly unlikely.
Correlates of COVID-19 vaccine acceptance, hesitancy and refusal among employees of a safety net California county health system with an early and aggressive vaccination program: Results from a cross-sectional survey
Authors: Gatto Nicole M. , Lee Jerusha E. , Massai Donatella , Zamarripa Susanna , Sasaninia Bijan , Khurana Dhruv , Michaels Kelsey , Freund Deborah , Nightingale Judi , Firek Anthony ,   for the Riverside University Health System (RUHS) Comparative Effectiveness and Clinical Outcomes Research Center (CECORC)-Claremont Graduate University (CGU) COVID-19 Research Group
Published: September 2021

Information on vaccine acceptance among healthcare workers is needed as health professionals provide front line care to COVID-19 patients. We developed and implemented an anonymous internet-based cross-sectional survey with direct solicitation among employees of a safety net health system. Items queried demographic and health-related characteristics, experience with and knowledge of COVID-19, and determinants of decisions to vaccinate. COVID-19 vaccine acceptance groups (acceptors, hesitant, refusers) were defined; an adapted version of the WHO vaccine hesitancy scale was included. The survey demonstrated good reliability (Cronbach’s alpha = 0.92 for vaccine hesitancy scale; 0.93 for determinants). General linear and logistic regression methods examined factors which were univariately associated with vaccine hesitancy and vaccine acceptance, respectively. Multivariable models were constructed with stepwise model-building procedures. Race/ethnicity, marital status, job classification, immunocompromised status, flu vaccination and childhood vaccination opinions independently predicted hesitancy scale scores. Gender, education, job classification and BMI independently predicted acceptance, hesitancy and refusal groups. Among hesitant employees, uncertainty was reflected in reports of motivating factors influencing their indecision. Despite a strong employee-support environment and job protection, respondents reported physical and mental health effects. Appreciation of varied reasons for refusing vaccination should lead to culturally sensitive interventions to increase vaccination rates in healthcare workers.
Why do fungicide mixtures delay the evolution of resistance? An experimental evolutionary approach
Authors: Ballu Agathe , Dérédec Anne , Walker Anne-Sophie , Carpentier Florence
Published: September 2021

Pesticide resistance poses a critical threat to agriculture, human health and biodiversity. Mixtures of fungicides are recommended and widely used in resistance management strategies. However, the components of the efficiency of such mixtures remain unclear. We performed an experimental evolution study on the fungal pathogen Z. tritici, to determine how mixtures managed resistance. We compared the effect of the continuous use of single active ingredients to that of mixtures, at the minimal dose providing full control of the disease, which we refer to as the “efficient” dose. We found that the performance of efficient-dose mixtures against an initially susceptible population depended strongly on the components of the mixture. Such mixtures were either as durable as the best mixture component used alone, or worse than all components used alone. Moreover, efficient-dose mixture regimes probably select for generalist resistance profiles as a result of the combination of selection pressures exerted by the various components and their lower doses. Our results indicate that mixtures should not be considered a universal strategy. Experimental evaluations of specificities for the pathogens targeted, their interactions with fungicides and the interactions between fungicides are crucial for the design of sustainable resistance management strategies.
A novel B.1.1.523 SARS-CoV-2 variant that combines many spike mutations linked to immune evasion with current variants of concern
Authors: van der Veer Brian M.J.W. , Dingemans Jozef , van Alphen Lieke B. , Hoebe Christian J.P.A. , Savelkoul Paul H.M.
Published: September 2021

In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic several variants have emerged that are linked to increased transmissibility and immune evasion. These variants are recognized as variants of concern (VOC). In this study, we describe a B.1.1.523 variant that shares many spike mutations with current VOC. Receptor-binding domain mutations E484K and S494P were observed but also a deletion (position 156-158) in the N-terminal antigenic supersite that is similar to the delta-variant. These mutations are linked to immune evasion in VOC that could lead to less effective vaccines. This variant has been reported in various different countries and continents despite the dominance of B.1.1.7 (alpha) and B.1.617.2 (delta) variant. Furthermore, the B.1.1.523 pangolin lineage as a whole is recognized as a variant under monitoring since 14th of July 2021.
Long Term Physical, Mental and Social Health Effects of COVID-19 in the Pediatric Population: A Scoping Review
Authors: Borel Madeline , Xie Luyu , Mihalcea Adrian , Kahn Jeffrey , Messiah Sarah E.
Published: September 2021

Background

The majority of COVID-19 symptom presentations in adults and children appear to run their course within a couple of weeks. However, a subgroup of adults has started to emerge with effects lasting several months or more after initial infection. However, little is known about long term physical, mental and social health effects of COVID-19 in the pediatric population. The purpose of this review was to determine these impacts well into the second year of the pandemic.

Methods

A search was conducted using PUBMED, Web of Science, Science Direct, and COCHRANE between 11/1/2019 and 9/1/2021. Search inclusion criteria were as follows: (1) COVID-19 illness and symptoms in children; (2) SARS-COv2 in children; (3) English language; and (4) human studies only.

Results

The few studies that have documented long-term physical symptoms in children show that fatigue, difficulty in concentrating (brain fog), sleep disturbances, and sensory problems are the most reported outcomes. Most studies examining the impact of COVID-19 in pediatric populations have focused on initial clinical presentation, and symptoms, which are similar to those in adult populations. Additionally, COVID-19 has had a moderate impact on children and adolescents’ social environment, which may exacerbate current and future physiological, psychological, behavioral, and academic outcomes.

Conclusions

There are limited studies reporting long physical symptoms of COVID-19 in the pediatric population. However, pediatric COVID-19 cases are underreported due to low rates of testing and symptomatic infection, which calls for more longitudinal studies. Children who have experienced COVID-19 illness should be monitored for long physiological, psychological, behavioral, and academic outcomes.
Gene networks under circadian control exhibit diurnal organization in primate organs
Authors: Li Jie , Nie Pengxing , Turck Christoph W. , Wang Guang-Zhong
Published: September 2021

Mammalian organs are individually controlled by autonomous circadian clocks. At the molecular level, this process is defined by the cyclical co-expression of both core transcription factors and off-target genes across time. While interactions between these molecular clocks are likely necessary for proper homeostasis, these features remain undefined. Here, we utilize integrative analysis of a baboon diurnal transcriptome atlas to characterize the properties of gene networks under circadian control. We found that 53.4% (8,120) of baboon genes are rhythmically expressed body-wide. In addition, >30% of gene-gene interactions exhibit periodic co-expression patterns, with core circadian genes more cyclically co-expressed than others. Moreover, two basic network modes were observed at the systems level: daytime and nighttime mode. Daytime networks were enriched for genes involved in metabolism, while nighttime networks were enriched for genes associated with growth and cellular signaling. A substantial number of diseases only form significant disease modules at either daytime or nighttime. In addition, we found that 216 of 313 genes encoding products that interact with SARS-CoV-2 are rhythmically expressed throughout the body. Importantly, more than 80% of SARS-CoV-2 related genes enriched modules are rhythmically expressed, and have significant network proximities with circadian regulators. Our data suggest that synchronization amongst circadian gene networks is necessary for proper homeostatic functions and circadian regulators have close interactions with SARS-CoV-2 infection.
The synaptic basis of activity-dependent eye-specific competition
Authors: Zhang Chenghang , Speer Colenso M.
Published: September 2021

Binocular vision requires proper developmental wiring of eye-specific inputs to the brain. Axons from the two eyes initially overlap in the dorsal lateral geniculate nucleus and undergo activity-dependent competition to segregate into target domains. The synaptic basis of such refinement is unknown. Here we used volumetric super-resolution imaging to measure the nanoscale molecular reorganization of developing retinogeniculate eye-specific synapses in the mouse brain. The outcome of binocular synaptic competition was determined by the relative eye-specific maturation of presynaptic vesicle content. Genetic disruption of spontaneous retinal activity prevented subsynaptic vesicle pool maturation, recruitment of vesicles to the active zone, synaptic development and eye-specific competition. These results reveal an activity-dependent presynaptic basis for axonal refinement in the mammalian visual system.

One-Sentence Summary

Spontaneous activity regulates the nanoscale remodeling of presynaptic terminals underlying eye-specific synaptogenesis and competition.
Naturalistic viewing conditions can increase task engagement and aesthetic preference but have only minimal impact on EEG Quality
Authors: Welke Dominik , Vessel Edward A.
Published: September 2021

Abstract

Free gaze and moving images are typically avoided in EEG experiments due to the expected generation of artifacts and noise. Yet for a growing number of research questions, loosening these rigorous restrictions would be beneficial. Among these is research on visual aesthetic experiences, which often involve open-ended exploration of highly variable stimuli. Here we systematically compare the effect of conservative vs. more liberal experimental settings on various measures of behavior, brain activity and physiology in an aesthetic rating task. Our primary aim was to assess EEG signal quality. 43 participants either maintained fixation or were allowed to gaze freely, and viewed either static images or dynamic (video) stimuli consisting of dance performances or nature scenes. A passive auditory background task (auditory steady-state response; ASSR) was added as a proxy measure for overall EEG recording quality. We recorded EEG, ECG and eyetracking data, and participants rated their aesthetic preference and state of boredom on each trial. Whereas both behavioral ratings and gaze behavior were affected by task and stimulus manipulations, EEG SNR was barely affected and generally robust across all conditions, despite only minimal preprocessing and no trial rejection. In particular, we show that using video stimuli does not necessarily result in lower EEG quality and can, on the contrary, significantly reduce eye movements while increasing both the participants’ aesthetic response and general task engagement. We see these as encouraging results indicating that – at least in the lab – more liberal experimental conditions can be adopted without significant loss of signal quality.

Highlights

We assess trade-offs between EEG quality and behavior for common task constraints

Investigated constraints: fixation task vs. free gaze, and video vs. static stimuli

Measures: EEG quality, aesthetic preference, task engagement, gaze and heart rate

Video stimuli reduce eye movements, increase engagement and do not affect EEG SNR

Fixation task only slightly increases SNR and does not influence ratings
Identification of potential proteins and microRNAs in Multiple Sclerosis and Huntington’s diseases using in silico methods
Authors: Maiti Tarasankar , Chakraborty Souvik
Published: September 2021

Neurogenerative diseases like multiple sclerosis, Huntington’s disease are the major roadblocks in the way towards a healthy brain. Neurodegenerative diseases like multiple sclerosis and Huntington’s disease are affected by several factors such as environmental, immunological, genetics, and the worse scenario we can think of is that they are on the rise worldwide. Degenerative diseases specifically target a limited group of neurons at first resulting in the loss of specific functions associated with the specific part of the brain. The early diagnosis of these neurodegenerative diseases is important so that treatments can start from the early stages of these diseases. In this study, we have established a link between Multiple sclerosis and Huntington’s disease, and also we were able to establish the possible microRNAs that were connected to the expression of genes associated with these two diseases. In this present study, we analyzed the microarray datasets obtained from Gene Expression Omnibus and we identified 266 differentially expressed genes tried to identify using in silico methods the Hub genes involved in Multiple sclerosis and Huntington’s disease. After identifying the genes and proteins we tried to identify the microRNAs that are interacting with the Hub genes. In our study, we identified that the protein network has PTPRC, CXCL8, RBM25 proteins that have maximum connectivity. The top Hub genes are then subjected to a database that contains information concerning the microRNAs that are interacting with the Hub proteins as well as with each other. According to our study, the hsa-mir-155-5p has one of the highest degrees in the microRNA network. Our study will be useful in the future for the development of new drug targets for these neurodegenerative diseases.
Efference information flow during skill acquisition mediate its interaction with medical simulation technology
Authors: Kamat Anil , Makled Basiel , Norfleet Jack , Schwaitzberg Steven D. , Intes Xavier , De Suvranu , Dutta Anirban
Published: September 2021

Despite substantial progress towards establishing virtual reality (VR) simulators as a replacement for physical ones for skill training, its effect on the brain network during skill acquisition has not been well addressed. In this study, we employed portable optical neuroimaging technology and Granger causality approach to uncover the impact of the two medical simulation technologies on the directed functional brain network of the subjects with two different skill levels. The mobile brain-behavior relantionship was evaluated using functional near-infrared spectroscopy (fNIRS) while right-handed subjects performed well-established fundamentals of laparoscopic surgery (FLS) pattern cutting task. A multiple regression path analysis found that the cognitive-action information flow from the right prefrontal cortex to the supplementary motor area statistically significantly predicted the FLS task performance. Here, the skill level (expert vs novice) affected the cognitive-action information flow from the right prefrontal cortex and the efference copy information flow from the left primary motor cortex via supplementary motor area as hub to the cognitive-perception at the left prefrontal cortex, i.e., the action-preception link. The simulation technology (physical vs VR simulator) affected solely the cognitive-action information flow from the right prefrontal cortex to the left primary motor cortex; however, the interaction between the medical simulation technology) and the skill level affected the efference information flow from the left primary motor cortex to the right prefrontal cortex and from the supplementary motor area to the left prefrontal cortex. These discriminative findings are crucial since our VR simulator had face and construct validity. Therefore, our study highlighted the importance of efference information flow within the framework of the perception-action cycle when comparing medical simulation technology for visuomotor skill acquisition.
The therapeutic and diagnostic potential of amyloid β oligomers (AβOs) selective antibodies to treat Alzheimer’s disease
Authors: Viola Kirsten L. , Bicca Maira A. , Bebenek Adrian M. , Kranz Daniel L. , Nandwana Vikas , Waters Emily A. , Haney Chad R. , Lee Maxwell , Gupta Abhay , Brahmbhatt Zach , Huang Weijian , Chang Ting-Tung , Peck Anderson , Valdez Clarissa , Dravid Vinayak P. , Klein William L.
Published: September 2021

Improvements have been made in the diagnosis of Alzheimer’s disease (AD), manifesting mostly in the development of in vivo imaging methods that allow for the detection of pathological changes in AD by MRI and PET scans. Many of these imaging methods, however, use agents that probe amyloid fibrils and plaques - species that do not correlate well with disease progression and are not present at the earliest stages of the disease. Amyloid β oligomers (AβOs), rather, are now widely accepted as the Aβ species most germane to AD onset and progression. Here we report evidence further supporting the role of AβOs as pathological instigators of AD and introduce promising anti-AβO diagnostic probes capable of distinguishing the 5xFAD mouse model from wild type mice by PET and MRI. In a developmental study, Aβ oligomers in 5xFAD mice were found to appear at 3 months of age, just prior to the onset of memory dysfunction, and spread as memory worsened. The increase of AβOs is prominent in the subiculum and correlates with concomitant development of reactive astrocytosis. The impact of these AβOs on memory is in harmony with findings that intraventricular injection of synthetic AβOs into wild type mice induced hippocampal dependent memory dysfunction within 24 hours. Compelling support for the conclusion that endogenous AβOs cause memory loss was found in experiments showing that intranasal inoculation of AβO-selective antibodies into 5xFAD mice completely restored memory function, measured 30-40 days post-inoculation. These antibodies, which were modified to give MRI and PET imaging probes, were able to distinguish 5xFAD mice from wild type littermates. These results provide strong support for the role of AβOs in instigating memory loss and salient AD neuropathology, and they demonstrate that AβO selective antibodies have potential both for therapeutics and for diagnostics.
RNA polymerase II dynamics and mRNA stability feedback scale mRNA in proportion to cell size
Authors: Swaffer Matthew P. , Marinov Georgi K. , Zheng Huan , Tsui Crystal Yee , Jones Andrew W. , Greenwood Jessica , Kundaje Anshul , Greenleaf William J. , Reyes-Lamothe Rodrigo , Skotheim Jan M.
Published: September 2021

A fundamental feature of cellular growth is that protein and RNA amounts scale with cell size so that concentrations remain constant. A key component to this is that global transcription rates increase in larger cells, but the underlying mechanism has remained unknown. Here, we identify RNAPII as the major limiting factor increasing transcription with cell size in budding yeast as transcription is highly sensitive to the dosage of RNAPII but not to other components of the general transcriptional machinery. Our experiments support a dynamic equilibrium model where global transcription at a given size is set by the mass-action recruitment kinetics of unengaged nucleoplasmic RNAPII, and DNA content. This drives a sub-linear increase in transcription with size, which is precisely compensated for by a decrease in mRNA decay rates as cells enlarge. Thus, limiting RNAPII and feedback on mRNA stability work in concert to ensure mRNA concentration homeostasis in growing cells.
Mechanistic Insights into the Effects of Key Mutations on SARS-CoV-2 RBD-ACE2 Binding
Authors: Aggarwal Abhishek , Naskar Supriyo , Maroli Nikhil , Gorai Biswajit , Dixit Narendra M. , Maiti Prabal K.
Published: September 2021

Some recent SARS-CoV-2 variants appear to have increased transmissibility than the original strain. An underlying mechanism could be the improved ability of the variants to bind receptors on target cells and infect them. In this study, we provide atomic-level insight into the binding of the receptor binding domain (RBD) of the wild-type SARS-CoV-2 spike protein and its single (N501Y), double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants to the human ACE2 receptor. Using extensive all-atom molecular dynamics simulations and advanced free energy calculations, we estimate the associated binding affinities and binding hotspots. We observe significant secondary structural changes in the RBD of the mutants, which lead to different binding affinities. We find higher binding affinities of the double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants than the wild type and the N501Y variant, which could contribute to the higher transmissibility of recent variants containing these mutations.
Comparison of two injectable anaesthetic protocols in Egyptian fruit bats(Rousettus aegyptiacus)undergoing gonadectomy
Authors: Amari Martina , Brioschi Federica A. , Rabbogliatti Vanessa , Di Cesare Federica , Pecile Alessandro , Giordano Alessia , Moretti Pierangelo , Magnone William , Bonato Francesco , Ravasio Giuliano
Published: September 2021

Egyptian fruit bats are experimental animals of increasing interest because they have been identified as a natural reservoir for several emerging zoonotic viruses. For this reason, bats could undergo different experimental procedures that require sedation or anaesthesia. Our aim was to compare the effects of two balanced anaesthetic protocols on sedation, cardiopulmonary variables and recovery in bats undergoing gonadectomy. Twenty bats were randomized into two groups; patients in group DK received intramuscular injection of dexmedetomidine (40 μg kg-1) and ketamine (7 mg kg-1), whereas those in group DBM were anaesthetized with intramuscular dexmedetomidine (40 μg kg-1), butorphanol (0.3 mg kg-1) and midazolam (0.3 mg kg-1). Time of induction, cardiopulmonary parameters and anaesthetic depth were measured. If anaesthesia plan was considered inadequate, fraction of inspired isoflurane was titrate-to-effect to achieve immobility. At the end of the surgery venous blood gas analysis was performed and intramuscular atipamezole (200 μg kg-1) or atipamezole (200 μg kg-1) and flumazenil (0.03 mg kg-1) was administered for timed and scored recovery phase. A significantly higher heart rate and peripheral oxygen saturation were recorded in DBM group (p= 0.001;p= 0.003 respectively), while respiratory rate was significantly lower than DK group (p= 0.001). All bats required isoflurane supplementation during surgery with no significant difference. No differences were observed in rectal temperature, induction and recovery times. Sodium and chlorine where significantly higher in DBM group (p= 0.001;p= 0.002 respectively). Recovery scores in group DK were significantly better than in group DBM (p= 0.034). Both protocols induced anaesthesia in Egyptian fruit bats with comparable sedative and cardiorespiratory effect. These drug combinations may be useful for minor procedures in bats, and they could be associated with inhalation anaesthesia in determining and maintaining a surgical anaesthetic plan.
Distinct ground state and activated state modes of firing in forebrain neurons
Authors: Levenstein Daniel , Gornet Jonathan , Huszár Roman , Girardeau Gabrielle , Grosmark Andres , Peyrache Adrien , Senzai Yuta , Watson Brendon O. , Mizuseki Kenji , Rinzel John , Buzsáki György
Published: September 2021

Neuronal firing patterns have significant spatiotemporal variability with no agreed upon theoretical framework. Using a combined experimental and modeling approach, we found that spike interval statistics can be described by discrete modes of activity. Of these, a “ground state” (GS) mode of low-rate spiking is universal among forebrain excitatory neurons and characterized by irregular spiking at neuron-specific rates. In contrast, “activated state” (AS) modes consist of spiking at characteristic timescales and regularity that are specific to neuron populations in a given region and brain state. The majority of spiking is contributed by GS mode, while neurons can transiently switch to AS spiking in response to stimuli or in coordination with population activity patterns. We hypothesize that GS spiking serves to maintain a persistent backbone of neuronal activity while AS modes support communication functions.
Slow-oscillatory tACS does not modulate human motor cortical response to repeated plasticity paradigms
Authors: Bradley Claire , Elliott Jessica , Dudley Samuel , Kieseker Genevieve A. , Mattingley Jason B. , Sale Martin V.
Published: September 2021

Previous history of activity and learning modulates synaptic plasticity and can lead to saturation of synaptic connections. According to the synaptic homeostasis hypothesis, neural oscillations during slow-wave sleep play an important role in restoring plasticity within a functional range. However, it is not known whether slow-wave oscillations – without the concomitant requirement of sleep – play a causal role in human synaptic homeostasis. Here, slow-oscillatory transcranial alternating current stimulation (tACS, 1Hz, 1mA, 18 minutes) was interleaved between two plasticity-inducing interventions: motor learning, and a paradigm known to induce long-term-potentiation-like plasticity in human motor cortex (paired associative stimulation; PAS). The hypothesis tested was that slow-oscillatory tACS would abolish the expected interference between motor learning and PAS, and facilitate plasticity from successive interventions. Thirty-six participants received sham and active fronto-motor tACS in two separate sessions, along with electroencephalography (EEG) recordings. A further 38 participants received tACS through a control (posterior midline) montage. Using neuro-navigated transcranial magnetic stimulation (TMS) over the left motor cortex, motor evoked potentials (MEPs) were recorded throughout the session. Bayesian statistics were used to quantify evidence for or against the hypothesis of an effect of each intervention on MEP amplitude. As expected, there was converging evidence that motor training increased MEPs. Importantly, we found moderate evidence against an effect of active tACS in restoring PAS plasticity, and no evidence of lasting entrainment of slow-oscillations in the EEG. This suggests that, under the conditions tested here, slow-oscillatory tACS does not modulate synaptic homeostasis in the motor system of awake humans.
PCDH7 Promotes Cell Migration by Regulating Myosin Activity
Authors: Qureshi Mohammad Haroon , Bayraktar Halil , Cinko M. Talha , Akkaya Cansu , Kamacioglu Altug , Uretmen-Kagiali Z. Cansu , Bozluolcay Erdem , Ozlu Nurhan
Published: September 2021

Cell migration requires spatiotemporally coordinated activities of multicomponent structures including the actomyosin cortex, plasma membrane, adhesion complexes and the polarity proteins. How they function together to drive this complex dynamic process remains an outstanding question. Here, we show that a member of the protocadherin family, PCDH7 displays a polarized localization in migratory cells with a dynamic enrichment at the leading and rear edges. Perturbation of PCDH7 interferes with the migration of nontransformed retinal pigment epithelial cells and the invasion of cancer cells. The overexpression of PCDH7 enhances the migration capability of cortical neurons in vivo. PCDH7 interacts with the myosin phosphatase subunits MYPT1 and PP1cβ. Ectopic expression of PCDH7 enhances the MYPT1 inhibitory phosphorylation levels and the phosphorylation of the myosin regulatory light chain and ERM at the polarized cortex. The chemical inhibition of phosphatase activity recovers migration phenotypes of PCDH7 knockout cells. We propose that PCDH7 regulates phosphorylation thus the activity of myosin and ERM at the polarized cortex through its interaction with myosin phosphatase. Collectively, our study suggests a new component for the spatial coordination of the plasma membrane and the cortex during cell migration.
Hippocampal representations switch from errors to predictions during acquisition of predictive associations
Authors: Aitken Fraser , Kok Peter
Published: September 2021

We constantly exploit the statistical regularities in our environment to help guide our perception. The hippocampus has been suggested to play a pivotal role in both learning environmental statistics, as well as exploiting them to generate perceptual predictions. However, it is unclear how the hippocampus balances encoding new predictive associations with the retrieval of existing ones. Here, we present the results of two high resolution human fMRI studies (N=24 for both experiments) directly investigating this. Participants were exposed to auditory cues that predicted the identity of an upcoming visual shape (with 75% validity). Using multivoxel decoding analysis, we found that the hippocampus initially preferentially represented unexpected shapes (i.e., those that violated the cue regularities), but later switched to representing the cue-predicted shape regardless of which was actually presented. These findings demonstrate that the hippocampus in involved both acquiring and exploiting predictive associations, and switches between these modes depending on whether learning is ongoing or complete.
Understanding distortions of inorganic substructures in chloridobismuthates(III)
Authors: Bujak Maciej
Published: September 2021

The molar ratio variations of organic and inorganic reactants of chloridobismuthates(III) with N,N-dimethylethane-1,2-diammonium, [(CH3)2NH(CH2)2NH3]2+, and N,N,N′,N′-tetramethylguanidinium, [NH2C{N(CH3)2}2]+, cations lead to the formation of four different products, namely, tris(N,N-dimethylethane-1,2-diammonium) bis[hexachloridobismuthate(III)], [(CH3)2NH(CH2)2NH3]3[BiCl6]2 (1), catena-poly[N,N-dimethylethane-1,2-diammonium [[tetrachloridobismuthate(III)]-μ-chlorido]], {[(CH3)2NH(CH2)2NH3][BiCl5]}
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(2), tris(N,N,N′,N′-tetramethylguanidinium) tri-μ-chlorido-bis[trichloridobismuthate(III)], [NH2C{N(CH3)2}2]3[Bi2Cl9] (3), and catena-poly[N,N,N′,N′-tetramethylguanidinium [[dichloridobismuthate(III)]-di-μ-chlorido]], {[NH2C{N(CH3)2}2][BiCl4]}
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(4). The hybrid crystals 1–4, containing relatively large but different organic cations, are composed of four distinct anionic substructures. They are built up from isolated [BiCl6]3− octahedra in 1, from face-sharing bioctahedral [Bi2Cl9]3− units in 3, from polymeric corner-sharing {[BiCl5]2−}
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chains in 2 and from edge-sharing {[BiCl4]−}
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chains in 4. The distortions shown by the single [BiCl6]3− polyhedra in 1–4 are associated with intrinsic interactions within the anionic substructures and the organic...inorganic substructures interactions, namely, N/C—H...Cl hydrogen bonds. The first factor is the stronger, which is evident in comparison of the experimentally determined geometrical and calculated distortion parameters for the isolated octahedron in 1 to the more complex inorganic substructures in 2–4. The formation of N—H...Cl hydrogen bonds, in terms of their number and strength, is favoured for 1 and 3 containing relatively easily accessed hydrogen-bond acceptors of isolated [BiCl6]3− and [Bi2Cl9]3− units. The studies of the deviations from regularity of the [BiCl6]3− octahedra within inorganic substructures were supported by a survey of the Cambridge Structural Database, which confirmed the role played by different factors in the variations in geometry of the inorganic anions.
A general model for the crystal structure of orthorhombic martensite in Ti alloys
Authors: Demakov Sergey , Kylosova Iana , Stepanov Stepan , Bönisch Matthias
Published: September 2021

The present work develops a novel unified approach to describe the crystal structure of orthorhombic martensite (α′′) in Ti alloys independent of chemical composition. By employing a straightforward yet highly instructive solid sphere model for the basic tetrahedral structural unit the crystal structures involved in the β ↔ α′′/α′ martensitic transformation are categorized into several intermediate configurations. Importantly, a new metric is introduced, δ, which unambiguously characterizes the atomic positions inside the orthorhombic unit cell depending on unit-cell geometry. Furthermore, the exclusive use of relative quantities to describe unit-cell geometry and atom positions renders the approach developed herein independent of alloy content. In this way, shortcomings of commonly suggested structural metrics for α′′ are eliminated. Subsequently, the novel methodology is applied to analyse and compare the crystal structure of α′′ across a broad range of Ti alloys based on experimentally measured unit-cell parameters. From this analysis it emerges that a large fraction of structural configurations along the b.c.c.–Cmcm–h.c.p. transformation path is not observed in quenched alloys. The threshold between the not-observed and the remaining well observed configurations is identified with an ideal Cmcm crystal structure, relative to which the experimentally found α′′ is compressed along its c axis.