bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of Dialysate Bolus-Based Absolute Blood Volume Estimation in Maintenance Hemodialysis Patients
Authors: Krenn Simon , Schmiedecker Michael , Schneditz Daniel , Hödlmoser Sebastian , Mayer Christopher C. , Wassertheurer Siegfried , Omic Haris , Schernhammer Eva , Wabel Peter , Hecking Manfred
Published: February 2022

Background

Absolute blood volume (ABV) is a critical component of fluid status, which may inform target weight prescriptions and hemodynamic vulnerability of dialysis patients. Here, we utilized the changes in relative blood volume (RBV), monitored by ultrasound (BVM) upon intradialytic 240 mL dialysate fluid bolus-infusion 1 h after hemodialysis start, to calculate the session-specific ABV. With the main goal of assessing clinical feasibility, our sub-aims were to (i) standardize the BVM-data read-out; (ii) determine optimal time-points for ABV-calculation, “before-” and “after-bolus”; (iii) assess ABV-variation.

Methods

We used high-level programming language and basic descriptive statistics in a retrospective study of routinely measured BVM-data from 274 hemodialysis sessions in 98 patients.

Results

Regarding (i) and (ii), we automatized the processing of RBV-data, and determined an algorithm to select the adequate RBV-data points for ABV-calculations. Regarding (iii), we found in 144 BVM-curves from 75 patients, that the average ABV ± standard deviation was 5.2 ± 1.5 L and that among those 51 patients who still had ≥2 valid estimates, the average intra-patient standard deviation in ABV was 0.8 L. Twenty-seven of these patients had an average intra-patient standard deviation in ABV <0.5 L.

Conclusions

We demonstrate feasibility of ABV-calculation by an automated algorithm after dialysate bolus-administration, based on the BVM-curve. Based on our results from this simple “abridged” calculation approach with routine clinical measurements, we encourage the use of multi-compartment modeling and comparison with reference methods of ABV-determination. Hopes are high that clinicians will be able to use ABV to inform target weight prescription, improving hemodynamic stability.
Orthokeratology Lens Wear for 2 Years in Children Did Not Alter Tear Film Lipid Thickness by Non-Invasive Interferometry
Authors: Yu Haozhe , Yuan Yifei , Wu Wenyu , Zeng Weizhen , Tong Louis , Zhang Yu , Feng Yun
Published: February 2022

Purpose

Previous studies suggest that overnight orthokeratology (OOK) may be detrimental to tear function. We aimed to investigate the effect of OOK on lipid layer thickness (LLT), blink pattern, and meibomian gland and elucidate the relationship of these variables.

Methods

Thirty-seven participants who wore OOK lenses every night for at least 2 years and twenty-four healthy non-contact lens wearers (controls) were enrolled in this retrospective study. LipiView interferometry, blink pattern analysis, the ocular surface status, and morphology and function of the meibomian gland were determined.

Results

The OOK group and healthy controls had similar LLT, blink patterns, ocular surface status, and the function of the meibomian gland. OOK participants demonstrated higher meiboscore in the lower eyelids (p < 0.05) but not in the upper eyelids. Within the OOK group, LLT was significantly impacted by the partial blink rate (p < 0.05) and the total score of the upper meibomian gland (p = 0.10).

Conclusions

Wearing OOK for 2 or more years increased lower eyelid meibomian gland dropout but did not have a reduction of LLT.
Cost-Sensitive Uncertainty Hypergraph Learning for Identification of Lymph Node Involvement With CT Imaging
Authors: Ma Qianli , Yan Jielong , Zhang Jun , Yu Qiduo , Zhao Yue , Liang Chaoyang , Di Donglin
Published: February 2022

Lung adenocarcinoma (LUAD) is the most common type of lung cancer. Accurate identification of lymph node (LN) involvement in patients with LUAD is crucial for prognosis and making decisions of the treatment strategy. CT imaging has been used as a tool to identify lymph node involvement. To tackle the shortage of high-quality data and improve the sensitivity of diagnosis, we propose a Cost-Sensitive Uncertainty Hypergraph Learning (CSUHL) model to identify the lymph node based on the CT images. We design a step named “Multi-Uncertainty Measurement” to measure the epistemic and the aleatoric uncertainty, respectively. Given the two types of attentional uncertainty weights, we further propose a cost-sensitive hypergraph learning to boost the sensitivity of diagnosing, targeting task-driven optimization of the clinical scenarios. Extensive qualitative and quantitative experiments on the real clinical dataset demonstrate our method is capable of accurately identifying the lymph node and outperforming state-of-the-art methods across the board.
Cervicovaginal Microbiota Predicts Neisseria gonorrhoeae Clinical Presentation
Authors: Lovett Angela , Seña Arlene C. , Macintyre Andrew N. , Sempowski Gregory D. , Duncan Joseph A. , Waltmann Andreea
Published: February 2022

Neisseria gonorrhoeae infection of the female lower genital tract can present with a spectrum of phenotypes ranging from asymptomatic carriage to symptomatic cervical inflammation, or cervicitis. The factors that contribute to the development of asymptomatic or symptomatic infections are largely uncharacterized. We conducted a pilot study to assess differences in the cervicovaginal microbial community of patients presenting with symptomatic vs. asymptomatic N. gonorrhoeae infections to a sexually transmitted infections (STI) clinic. DNA was isolated from cervicovaginal swab specimens from women who tested positive for N. gonorrhoeae infection using a clinical diagnostic nucleic acid amplification test. We performed deep sequencing of 16S ribosomal RNA gene amplicons, followed by microbiome analyses with QIIME, and species-specific real-time PCR to assess the composition of microbial communities cohabitating the lower genital tract with the infecting N. gonorrhoeae. Specimens collected from asymptomatic individuals with N. gonorrhoeae infection and no co-infection with Chlamydia trachomatis and/or Trichomonas vaginalis carried Lactobacillus-dominant microbial communities more frequently than symptomatic patients without co-infection. When compared to asymptomatic individuals, symptomatic women had microbial communities characterized by more diverse and heterogenous bacterial taxa, typically associated with bacterial vaginosis (BV) [Prevotella, Sneathia, Mycoplasma hominis, and Bacterial Vaginosis-Associated Bacterium-1 (BVAB1)/“Candidatus Lachnocurva vaginae”]. Both symptomatic and asymptomatic N. gonorrhoeae patients with additional STI co-infection displayed a BV-like microbial community. These findings suggest that Lactobacillus-dominant vaginal microbial community may protect individuals from developing symptoms during lower genital tract infection with N. gonorrhoeae.
Multi-Omics Analysis Reveals the Dynamic Changes of RNA N6-Methyladenosine in Pear (Pyrus bretschneideri) Defense Responses to Erwinia amylovora Pathogen Infection
Authors: Han Chenyang , Zhang Feng , Qiao Xin , Zhao Yancun , Qiao Qinhai , Huang Xiaosan , Zhang Shaoling
Published: February 2022

N6-methylated adenine (m6A) is the most prevalent modification of mRNA methylation and can regulate many biological processes in plants, such as mRNA processing, development, and stress response. Some studies have increased our understanding of its various roles in model plants in recent years. Nevertheless, the distribution of m6A and the impact of m6A on the regulation of plant defense responses against pathogen inoculation are virtually unknown in pear. In this study, MeRIP-seq and RNA-seq data from healthy and inoculated plants were analyzed to assess the changes in the transcript levels and posttranscriptional modification of pear in response to the fire blight pathogen Erwinia amylovora. Following the analysis of 97,261 m6A peaks, we found that m6A preferred to modify duplicate genes rather than singleton genes and that m6A-methylated genes underwent stronger purifying selection. A total of 2,935 specific m6A sites were detected at the transcriptome level after inoculation, which may increase defense-related transcript abundance to enhance pear resistance. In addition, 1,850 transcripts were detected only in the mock-inoculated groups. The hypomethylated transcripts were mainly related to transcriptional regulation and various biological processes, such as chloroplast organization and sucrose biosynthetic processes. In addition, we found that the extent of m6A methylation was significantly positively correlated with the transcript level, suggesting a regulatory role for m6A in the plant response.
Alteration of Porcine Intestinal Microbiota in Response to Dietary Manno-Oligosaccharide Supplementation
Authors: Yu En , Chen Daiwen , Yu Bing , Huang Zhiqing , Mao Xiangbing , Zheng Ping , Luo Yuheng , Yin Heng , Yu Jie , Luo Junqiu , Yan Hui , He Jun
Published: February 2022

Manno-oligosaccharide (MOS) is a prebiotic derived from natural plants or yeasts. Here, we explored the response of intestinal microbiota and epithelial functions after ingestion of MOS in a porcine model. Sixteen pigs were randomly assigned into two treatments and fed with basal or MOS-containing (0.3% MOS) diet for 21 days. Results showed that MOS supplementation increased the cecal acetate content and ileal 16S rRNA gene copies (p < 0.05). Importantly, MOS decreased the abundance of phylum Proteobacteria in cecal digesta (p < 0.05). Moreover, MOS elevated the expression level of SCL5A8 and GPR109A but decreased the expression levels of HDAC1 and TNF-α in the ileal and cecal mucosa (p < 0.05). MOS upregulated the expression levels of tight-junction protein (ZO-1, claudin-1, and occludin) and IGF-1 in the ileum and cecum (p < 0.05). This study presents the alteration of intestinal microbiota composition and intestinal barrier function after MOS administration, and facilitates our understanding of the mechanisms behind the dietary MOS-modulated intestinal microbiota and health.
Characterization of Metronidazole-Resistant Giardia intestinalis Lines by Comparative Transcriptomics and Proteomics
Authors: Krakovka Sascha , Ribacke Ulf , Miyamoto Yukiko , Eckmann Lars , Svärd Staffan
Published: February 2022

Metronidazole (MTZ) is a clinically important antimicrobial agent that is active against both bacterial and protozoan organisms. MTZ has been used extensively for more than 60 years and until now resistance has been rare. However, a recent and dramatic increase in the number of MTZ resistant bacteria and protozoa is of great concern since there are few alternative drugs with a similarly broad activity spectrum. To identify key factors and mechanisms underlying MTZ resistance, we utilized the protozoan parasite Giardia intestinalis, which is commonly treated with MTZ. We characterized two in vitro selected, metronidazole resistant parasite lines, as well as one revertant, by analyzing fitness aspects associated with increased drug resistance and transcriptomes and proteomes. We also conducted a meta-analysis using already existing data from additional resistant G. intestinalis isolates. The combined data suggest that in vitro generated MTZ resistance has a substantial fitness cost to the parasite, which may partly explain why resistance is not widespread despite decades of heavy use. Mechanistically, MTZ resistance in Giardia is multifactorial and associated with complex changes, yet a core set of pathways involving oxidoreductases, oxidative stress responses and DNA repair proteins, is central to MTZ resistance in both bacteria and protozoa.
Structural and Functional Analysis of Nonheme Iron Enzymes BCMO-1 and BCMO-2 from Caenorhabditis elegans
Authors: Pan Weimin , Zhou Yong-Ling , Wang Jian , Dai Huai-En , Wang Xiao , Liu Lin
Published: February 2022

Carotenoid metabolism is critical for diverse physiological processes. The nematode Caenorhabditis elegans has two genes that are annotated as β-carotene 15,15′-monooxygenase (BCMO) and are 17 centimorgan apart on chromosome II, but the function of BCMO-1 and BCMO-2 remains uncharacterized. Sequence homology indicates that the two enzymes belong to the carotenoid cleavage dioxygenase family that share a seven-bladed β-propeller fold with a nonheme iron center. Here we determined crystal structures of BCMO-1 and BCMO-2 at resolutions of 1.8 and 1.9 Å, respectively. Structural analysis reveals that BCMO-1 and BCMO-2 are strikingly similar to each other. We also characterized their β-carotene cleavage activity, but the results suggest that they may not act as β-carotene 15,15′-oxygenases.
The Frontal and Cerebellar Metabolism Related to Cognitive Dysfunction in Multiple System Atrophy
Authors: Shen Cong , Chen Qi-Si , Zuo Chuan-Tao , Liu Feng-Tao , Wang Jian
Published: February 2022

Background

Cognitive dysfunctions have been reported in multiple system atrophy (MSA). However the underlying mechanisms remain to be elucidated. This study aimed to explore the possible cerebral metabolism associated with domain-specific cognitive performances in MSA.

Methods

A total of 84 patients were diagnosed as probable or possible MSA, comprised of 27 patients as MSA with predominant parkinsonism (MSA-P) and 57 patients as MSA with predominant cerebellar ataxia (MSA-C). The comprehensive neuropsychological tests and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging were performed. Z-score was calculated to non-dimensionalize and unify indicators of different tests in the domains of executive function, attention, language, memory, and visuospatial function. Correlations between specific Z-score and cerebral 18F-FDG uptake were analyzed using statistical parametric mapping. The cognition-related metabolic differences between patients with MSA-P and MSA-C were analyzed using the post-hoc test.

Results

Z-scores of the domains including attention, executive function, and language correlated positively with the metabolism in the superior/inferior frontal gyrus and cerebellum, but negatively with that in the insula and fusiform gyrus (p < 0.001). No significant differences in neuropsychological performances and frontal metabolism were found between patients with MSA-P and MSA-C. Only lower metabolism in the cerebellum was observed in MSA-C.

Conclusion

Metabolic changes in the frontal lobe and cerebellum may participate in the cognitive impairments of patients with MSA. Nevertheless, cognitive and corresponding metabolic differences between the two subtypes of MSA still need more exploration.
Friend of the Devil: Negative Social Influences Driving Substance Use Disorders
Authors: Pomrenze Matthew B. , Paliarin Franciely , Maiya Rajani
Published: February 2022

Substance use disorders in humans have significant social influences, both positive and negative. While prosocial behaviors promote group cooperation and are naturally rewarding, distressing social encounters, such as aggression exhibited by a conspecific, are aversive and can enhance the sensitivity to rewarding substances, promote the acquisition of drug-taking, and reinstate drug-seeking. On the other hand, withdrawal and prolonged abstinence from drugs of abuse can promote social avoidance and suppress social motivation, accentuating drug cravings and facilitating relapse. Understanding how complex social states and experiences modulate drug-seeking behaviors as well as the underlying circuit dynamics, such as those interacting with mesolimbic reward systems, will greatly facilitate progress on understanding triggers of drug use, drug relapse and the chronicity of substance use disorders. Here we discuss some of the common circuit mechanisms underlying social and addictive behaviors that may underlie their antagonistic functions. We also highlight key neurochemicals involved in social influences over addiction that are frequently identified in comorbid psychiatric conditions. Finally, we integrate these data with recent findings on (±)3,4-methylenedioxymethamphetamine (MDMA) that suggest functional segregation and convergence of social and reward circuits that may be relevant to substance use disorder treatment through the competitive nature of these two types of reward. More studies focused on the relationship between social behavior and addictive behavior we hope will spur the development of treatment strategies aimed at breaking vicious addiction cycles.
Characteristic Variation of Electromechanical Delay After the Botulinum Toxin Injection in Spastic Biceps Brachii Muscles
Authors: Chandra Sourav , Afsharipour Babak , Rymer William Z. , Suresh Nina L.
Published: February 2022

The objective of this study was to characterize the effects of intramuscular botulinum toxin (BT) injections on the electromechanical delay (EMD) in spastic human biceps muscles. The EMD is calculated as the time lag between the muscle activation onset, as recorded from the surface electromyogram (sEMG), and the onset of recorded force. In a cohort of chronic stroke survivors, we compared the computed EMD derived from the spastic (injected) biceps brachii with that from the contralateral muscle. Eight participants were tested before and up to 3 months after a BT injection. At each session, participants followed an isometric trapezoidal force trajectory at 50 and 30%, respectively, of the tested maximum voluntary contraction (MVC). Joint force and sEMG signals were recorded as well. The number of zero crossings (ZC) of the sEMG during the steady-state portion of the task was also computed. The EMD post-BT was found to increase by 64 ± 10% (at 50% MVC) and 93 ± 18% (at 30% MVC) when compared to pre-BT values, while the number of sEMG-ZC, the mean MVC values, and the force-EMD slope exhibited striking reductions. These parameters, calculated on the contralateral side, remained relatively constant across sessions, with the EMD significantly lower and the MVC values much higher. We discuss potential contributing factors to an increase in EMD values on the affected side, both pre- and post-BT. The observed co-variation across sessions of the increased EMD values with the decreased ZC estimates, a surrogate of motor outflow, and, potentially, more compliant muscle fascicles suggests that the altered motor unit (MU) behavior contributes, at least in part, to the delayed force production.
Case Report: Diffuse Cerebral Microbleeds in Cerebral Autosomal Recessive Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
Authors: Wen Lan , Yuan Jichao , Li Shuang , Zhao Jieyi , Li Congjun , Li Jiafei , Han Yuanyuan , Wang Chaohua , Li Guangjian
Published: February 2022

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary cerebral small vascular disease caused by a homozygous mutation in the high-temperature requirement A serine peptidase 1 (HTRA1) gene. Cerebral microbleeds (CMBs) are increasingly being recognized as neuroimaging findings occurring with cerebrovascular disease and have different etiologies. Mild to moderate CMBs are not unusual in CARASIL, and they are observed to affect cortical and subcortical structures; in contrast, diffuse CMBs, especially in the cerebellum, are rare. In this case, we report a novel mutation of HTRA1 in a 43-year-old woman whose imaging indicated multiple CMBs in all lobes, brain stem, and cerebellum. The amount and location of CMBs vary in CARASIL cases, and the potential cause is not fully understood. This study revealed that specific imaging findings of this patient may be related to a new genetic mutation.
Long-Term Follow-Up of the Auditory Threshold After a Fully Implantable Middle Ear Implant
Authors: Monini Simonetta , Filippi Chiara , Salerno Gerardo , Barbara Maurizio
Published: February 2022

A fully implantable active middle ear device has been proposed and indicated for the rehabilitation of bilateral moderate or moderate-to-severe sensorineural hearing loss, assuming it would overcome the disadvantages of a conventional hearing aid. The indications have further been extended to severe or severe-to-profound forms of hearing loss in the case of an expected limited or null efficacy of hearing aids. While the literature has highlighted several positive aspects of the device, including a better quality of life related to its invisibility, the improvement of auditory and perceptual functions has not been controlled for throughout a long period of follow-up. The present study aimed to verify the behavior of the auditory threshold, especially the bone conduction (BC) component, in the implanted ear in a group of implantees affected by initial bilateral symmetric hearing loss of different severity grades. The BC threshold was assessed preoperatively at activation and at the last follow-up (ranging from 4 to 12 years) in the implanted ear, and preoperatively and at the last follow-up in the contralateral ear, to monitor eventual deteriorated values in both ears over time. The pure tone average (PTA; 250–4,000 Hz), speech reception threshold (SRT) and the maximum word recognition score as a percentage (% WRS) and in dB HL were measured in the implanted ear to verify the efficacy of the device after the first fitting at device activation. A significant worsening of the BC threshold with respect to the baseline threshold was noticed during further follow-up. When comparing the implanted ear with the contralateral ear, a significant worsening of the bone PTA was assessed in the former with respect to the contralateral ear. Despite the worsened hearing found in the implanted ears, the beneficial gains in PTA and speech audiometry observed at the first activation remained constant at the follow-up, thus showing an extension of the efficacy of this device in aiding those with up to the most severe forms of sensorineural hearing loss.
Case Report: Moving Tumor-Like Foci Behind Refractory Epilepsy-Cerebral Sparganosis Successfully Treated by Surgery After Failure of Praziquantel Treatment
Authors: Chen Yusi , Chen Xu , Kang Huicong
Published: February 2022

Cerebral sparganosis is clinically non-specific and easily misdiagnosed, exposing patients to the risk of severe brain damage and neurological dysfunction caused by actively migrating larvae. Diagnostic biomarkers from typical cases can help to establish an early diagnosis and proper treatment. We present a 25-year-old woman who suffered from 9 years of refractory epilepsy and was misdiagnosed with glioma and subjected to surgery. The postoperative pathology confirmed granuloma, and the tumor-like foci reappeared 3 months later. Along with the “tunnel sign” on MRI, cerebral sparganosis was suspected and confirmed by positive serum and cerebrospinal fluid antibodies against Spirometra mansoni. The patient visited us after a failure of four cycles of praziquantel treatment, recurrent seizures and hemiplegia with basal ganglia foci. Craniotomy was not carried out until the larva moved to the superficial lobe on follow-up MRIs, and pathology revealed sparganosis granuloma. The patient became seizure-free and recovered myodynamia but had long-lasting cognitive dysfunction due to severe brain damage. This case indicated the importance of tunnel signs and moving tumor-like foci on MRI as diagnostic clues of cerebral sparganosis. An early diagnosis is vitally important to avoid severe neural dysfunction by the long-living and moving larvae. Surgical removal of the larva is a critical remedy for cases failed by praziquantel treatment.
Dynamics of Oddball Sound Processing: Trial-by-Trial Modeling of ECoG Signals
Authors: Lecaignard Françoise , Bertrand Raphaëlle , Brunner Peter , Caclin Anne , Schalk Gerwin , Mattout Jérémie
Published: February 2022

Recent computational models of perception conceptualize auditory oddball responses as signatures of a (Bayesian) learning process, in line with the influential view of the mismatch negativity (MMN) as a prediction error signal. Novel MMN experimental paradigms have put an emphasis on neurophysiological effects of manipulating regularity and predictability in sound sequences. This raises the question of the contextual adaptation of the learning process itself, which on the computational side speaks to the mechanisms of gain-modulated (or precision-weighted) prediction error. In this study using electrocorticographic (ECoG) signals, we manipulated the predictability of oddball sound sequences with two objectives: (i) Uncovering the computational process underlying trial-by-trial variations of the cortical responses. The fluctuations between trials, generally ignored by approaches based on averaged evoked responses, should reflect the learning involved. We used a general linear model (GLM) and Bayesian Model Reduction (BMR) to assess the respective contributions of experimental manipulations and learning mechanisms under probabilistic assumptions. (ii) To validate and expand on previous findings regarding the effect of changes in predictability using simultaneous EEG-MEG recordings. Our trial-by-trial analysis revealed only a few stimulus-responsive sensors but the measured effects appear to be consistent over subjects in both time and space. In time, they occur at the typical latency of the MMN (between 100 and 250 ms post-stimulus). In space, we found a dissociation between time-independent effects in more anterior temporal locations and time-dependent (learning) effects in more posterior locations. However, we could not observe any clear and reliable effect of our manipulation of predictability modulation onto the above learning process. Overall, these findings clearly demonstrate the potential of trial-to-trial modeling to unravel perceptual learning processes and their neurophysiological counterparts.
Speech Recognition and Listening Effort in Cochlear Implant Recipients and Normal-Hearing Listeners
Authors: Abdel-Latif Khaled H. A. , Meister Hartmut
Published: February 2022

The outcome of cochlear implantation is typically assessed by speech recognition tests in quiet and in noise. Many cochlear implant recipients reveal satisfactory speech recognition especially in quiet situations. However, since cochlear implants provide only limited spectro-temporal cues the effort associated with understanding speech might be increased. In this respect, measures of listening effort could give important extra information regarding the outcome of cochlear implantation. In order to shed light on this topic and to gain knowledge for clinical applications we compared speech recognition and listening effort in cochlear implants (CI) recipients and age-matched normal-hearing listeners while considering potential influential factors, such as cognitive abilities. Importantly, we estimated speech recognition functions for both listener groups and compared listening effort at similar performance level. Therefore, a subjective listening effort test (adaptive scaling, “ACALES”) as well as an objective test (dual-task paradigm) were applied and compared. Regarding speech recognition CI users needed about 4 dB better signal-to-noise ratio to reach the same performance level of 50% as NH listeners and even 5 dB better SNR to reach 80% speech recognition revealing shallower psychometric functions in the CI listeners. However, when targeting a fixed speech intelligibility of 50 and 80%, respectively, CI users and normal hearing listeners did not differ significantly in terms of listening effort. This applied for both the subjective and the objective estimation. Outcome for subjective and objective listening effort was not correlated with each other nor with age or cognitive abilities of the listeners. This study did not give evidence that CI users and NH listeners differ in terms of listening effort – at least when the same performance level is considered. In contrast, both listener groups showed large inter-individual differences in effort determined with the subjective scaling and the objective dual-task. Potential clinical implications of how to assess listening effort as an outcome measure for hearing rehabilitation are discussed.
Hierarchical Synchronization Estimation of Low- and High-Order Functional Connectivity Based on Sub-Network Division for the Diagnosis of Autism Spectrum Disorder
Authors: Zhao Feng , Han Zhongwei , Cheng Dapeng , Mao Ning , Chen Xiaobo , Li Yuan , Fan Deming , Liu Peiqiang
Published: February 2022

Functional connectivity network (FCN) calculated by resting-state functional magnetic resonance imaging (rs-fMRI) plays an increasingly important role in the exploration of neurologic and mental diseases. Among the presented researches, the method of constructing FCN based on Matrix Variate Normal Distribution (MVND) theory provides a novel perspective, which can capture both low- and high-order correlations simultaneously with a clear mathematical interpretability. However, when fitting MVND model, the dimension of the parameters (i.e., population mean and population covariance) to be estimated is too high, but the number of samples is relatively quite small, which is insufficient to achieve accurate fitting. To address the issue, we divide the brain network into several sub-networks, and then the MVND based FCN construction algorithm is implemented in each sub-network, thus the spatial dimension of MVND is reduced and more accurate estimates of low- and high-order FCNs is obtained. Furthermore, for making up the functional connectivity which is lost because of the sub-network division, the rs-fMRI mean series of all sub-networks are calculated, and the low- and high-order FCN across sub-networks are estimated with the MVND based FCN construction method. In order to prove the superiority and effectiveness of this method, we design and conduct classification experiments on ASD patients and normal controls. The experimental results show that the classification accuracy of “hierarchical sub-network method” is greatly improved, and the sub-network found most related to ASD in our experiment is consistent with other related medical researches.
Detecting Small Vessel Pathology in Cocaine Use Disorder
Authors: Öchsner Marco , Mak Elijah , Ersche Karen D.
Published: February 2022

Background

Cocaine use is associated with an increased risk of cerebrovascular accidents. Small vessel pathology has been linked to the risk of stroke in cocaine users, but can be challenging to detect on conventional magnetic resonance (MR) scans. Fluid-attenuated inversion recovery (FLAIR) scans permit better resolution of small vessel lesions.

Objectives

FLAIR scans are currently only acquired based on the subjective judgement of abnormalities on MR scans at face value. We sought to evaluate this practice and the added value of FLAIR scans for patients with cocaine use disorder (CUD), by comparing microbleeds detected by MR and FLAIR scans. We hypothesised that microbleeds are more pronounced in CUD patients, particularly so in participants who had been selected for a FLAIR scan by radiographers.

Methods

Sixty-four patients with CUD and 60 control participants underwent a brain scan. The MR of 20 CUD patients and 16 control participants showed indicators of cerebral infarction at face value and were followed up by a FLAIR scan. We determined the volume of microbleeds in both MR and FLAIR scans and examined associations with various risk factors.

Results

While MR lesion volumes were significantly increased in CUD patients, no significant differences in lesion volume were found in the subgroup of individuals who received a FLAIR.

Conclusion

The current practice of subjectively evaluating MR scans as a basis for the follow-up FLAIR scans to detect vascular pathology may miss vulnerable individuals. Hence, FLAIR scans should be included as a routine part of research studies.
Single-Cell RNA Sequencing Characterizes the Molecular Heterogeneity of the Larval Zebrafish Optic Tectum
Authors: Martin Annalie , Babbitt Anne , Pickens Allison G. , Pickett Brett E. , Hill Jonathon T. , Suli Arminda
Published: February 2022

The optic tectum (OT) is a multilaminated midbrain structure that acts as the primary retinorecipient in the zebrafish brain. Homologous to the mammalian superior colliculus, the OT is responsible for the reception and integration of stimuli, followed by elicitation of salient behavioral responses. While the OT has been the focus of functional experiments for decades, less is known concerning specific cell types, microcircuitry, and their individual functions within the OT. Recent efforts have contributed substantially to the knowledge of tectal cell types; however, a comprehensive cell catalog is incomplete. Here we contribute to this growing effort by applying single-cell RNA Sequencing (scRNA-seq) to characterize the transcriptomic profiles of tectal cells labeled by the transgenic enhancer trap line y304Et(cfos:Gal4;UAS:Kaede). We sequenced 13,320 cells, a 4X cellular coverage, and identified 25 putative OT cell populations. Within those cells, we identified several mature and developing neuronal populations, as well as non-neuronal cell types including oligodendrocytes and microglia. Although most mature neurons demonstrate GABAergic activity, several glutamatergic populations are present, as well as one glycinergic population. We also conducted Gene Ontology analysis to identify enriched biological processes, and computed RNA velocity to infer current and future transcriptional cell states. Finally, we conducted in situ hybridization to validate our bioinformatic analyses and spatially map select clusters. In conclusion, the larval zebrafish OT is a complex structure containing at least 25 transcriptionally distinct cell populations. To our knowledge, this is the first time scRNA-seq has been applied to explore the OT alone and in depth.
The Mechanotransduction Channel and Organic Cation Transporter Are Critical for Cisplatin Ototoxicity in Murine Hair Cells
Authors: Li Jinan , Liu Chang , Kaefer Samuel , Youssef Mariam , Zhao Bo
Published: February 2022

Cisplatin is one of the most widely used chemotherapeutic drugs across the world. However, the serious ototoxic effects, leading to permanent hair cell death and hearing loss, significantly limit the utility of cisplatin. In zebrafish, the functional mechanotransduction channel is required for cisplatin ototoxicity. However, it is still unclear the extent to which the mechanotransduction channel is involved in cisplatin uptake and ototoxicity in mammalian hair cells. Herein, we show that genetically disrupting mechanotransduction in mouse partially protects hair cells from cisplatin-induced hair cell death. Using a fluorescent-dye conjugated cisplatin, we monitored cisplatin uptake in cochlear explants and found that functional mechanotransduction is required for the uptake of cisplatin in murine hair cells. In addition, cimetidine, an inhibitor of the organic cation transporter, also partially protects hair cells from cisplatin ototoxicity. Notably, the otoprotective effects of cimetidine do not require mechanotransduction. These findings suggest that both the mechanotransduction channel and the organic cation transporter are critical for cisplatin ototoxicity in murine hair cells.
Extraction of Squalene From Tea Leaves (Camellia sinensis) and Its Variations With Leaf Maturity and Tea Cultivar
Authors: Sheng Yue Yue , Xiang Jing , Wang Kai Rong , Li Ze Yu , Li Kai , Lu Jian Liang , Ye Jian Hui , Liang Yue Rong , Zheng Xin Qiang
Published: February 2022

Squalene is a precursor of steroids with diverse bioactivities. Tea was previously found to contain squalene, but its variation between tea cultivars remains unknown. In this study, tea leaf squalene sample preparation was optimized and the squalene variation among 30 tea cultivars was investigated. It shows that squalene in the unsaponified tea leaf extracts was well separated on gas chromatography profile. Saponification led to a partial loss of squalene in tea leaf extract and so it is not an essential step for preparing squalene samples from tea leaves. The tea leaf squalene content increased with the maturity of tea leaf and the old leaves grown in the previous year had the highest level of squalene among the tested samples. The squalene levels in the old leaves of the 30 tested cultivars differentiated greatly, ranging from 0.289 to 3.682 mg/g, in which cultivar “Pingyun” had the highest level of squalene. The old tea leaves and pruned littering, which are not used in tea production, are an alternative source for natural squalene extraction.
Pine (Pinus massoniana Lamb.) Needle Extract Supplementation Improves Performance, Egg Quality, Serum Parameters, and the Gut Microbiome in Laying Hens
Authors: Guo Yanxin , Huang Shimeng , Zhao Lihong , Zhang Jianyun , Ji Cheng , Ma Qiugang
Published: February 2022

The effects of Masson pine (Pinus massoniana Lamb.) needle extract (PNE) on gastrointestinal disorders and oxidative stress have been widely investigated using experimental models; however, the functions and mechanisms of these effects in chicken models remain unknown. We investigated the effects of Masson PNE supplementation on performance, egg quality, serum parameters, and the gut microbiome in laying hens. A total of 60 healthy 50-week-old Peking Pink laying hens with similar body conditions and egg production were randomly divided into the control (CON) (0 mg/kg PNE), PNE100 (100 mg/kg PNE), PNE200 (200 mg/kg PNE), and PNE400 (400 mg/kg PNE) groups, with fifteen replicates per treatment and one hen per replicate. Compared with the CON group, egg mass, feed conversion ratios, and yolk weight were significantly increased (p < 0.01) in the PNE100 group. Dietary supplementation of 100 mg/kg PNE increased the serum total protein, albumin, and glucose concentrations (p < 0.01) and decreased the alanine aminotransferase activity (p < 0.05) compared with those of the CONs. Hens in the PNE100 group had reduced serum malondialdehyde levels (p < 0.05) and increased catalase, superoxide dismutase, and glutathione peroxidase activities (p < 0.01) compared with those of the CON group. Serum proinflammatory cytokine concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α were lower (p < 0.01) and the IL-10 level was higher (p < 0.01) in the PNE100 group than in the CON group. Serum immunoglobulin (Ig)A, IgG, and IgM concentrations were increased in the PNE100 group (p < 0.01). The relative abundance of Bacteroidetes was increased, while the relative abundances of Firmicutes and Proteobacteria were decreased in the PNE100 group. The relative abundances of Vibrio, Shewanella, and Lactobacillus were decreased, while the relative abundances of unclassified_o_Bacteroidales, Rikenellaceae_RC9_gut_group, unclassified_f_Rikenellaceae, and Butyricicoccaceae were increased in the PNE100 group compared with those of the CON group. PNE supplementation at 100 mg/kg improved the diversity and structure of the gut microbial composition, production performance, egg quality, and serum parameters of laying hens. The laying hens in this study had good production performance when supplemented with 100 mg/kg PNE.
The Role of the SOX9/lncRNA ANXA2P2/miR-361-3p/SOX9 Regulatory Loop in Cervical Cancer Cell Growth and Resistance to Cisplatin
Authors: He Shasha , Feng Yeqian , Zou Wen , Wang Jingjing , Li Guiyuan , Xiong Wei , Xie Yangchun , Ma Jin-an , Liu Xianling
Published: February 2022

Cervical cancer is a highly prevalent female malignancy. Presently, cisplatin (DDP) is a first-line agent for cervical cancer chemotherapy. However, its curative effect is limited because of chemo-resistance. It has been previously reported that SOX9 targeted and activated oncogenic genes, enhancing cervical cancer cell resistance to DDP. The effects of the SOX9/lncRNA ANXA2P2/miR-361-3p/SOX9 regulatory loop on cervical cancer cell growth and resistance to DDP have been demonstrated. miR-361-3p expression was decreased in DDP-resistant cervical cancer cells and tissues. Moreover, miR-361-3p overexpression inhibited the growth of resistant cervical cancer cells and the resistance to DDP, whereas miR-361-3p inhibition exerted opposite effects. miR-361-3p inhibited SOX9 expression through binding; the effects of miR-361-3p inhibition were partially reversed by SOX9 knockdown. LncRNA ANXA2P2 expression was elevated in DDP-resistant cervical cancer cells and tissues. LncRNA ANXA2P2 inhibited miR-361-3p expression by binding, thereby upregulating SOX9. LncRNA ANXA2P2 knockdown inhibited DDP-resistant cervical cancer cell growth and resistance to DDP, whereas the effects of lncRNA ANXA2P2 knockdown were partially reversed by miR-361-3p inhibition. SOX9 expression was elevated in DDP-resistant cervical cancer cells and tissues, and SOX9 activated lncRNA ANXA2P2 transcription by binding. Collectively, SOX9, lncRNA ANXA2P2, and miR-361-3p form a regulatory loop, modulating DDP-resistant cervical cancer cell growth and response to DDP treatment.
Image Analysis of Circulating Tumor Cells and Leukocytes Predicts Survival and Metastatic Pattern in Breast Cancer Patients
Authors: Da Col Giacomo , Del Ben Fabio , Bulfoni Michela , Turetta Matteo , Gerratana Lorenzo , Bertozzi Serena , Beltrami Antonio Paolo , Cesselli Daniela
Published: February 2022

Background

The purpose of the present work was to test whether quantitative image analysis of circulating cells can provide useful clinical information targeting bone metastasis (BM) and overall survival (OS >30 months) in metastatic breast cancer (MBC).

Methods

Starting from cell images of epithelial circulating tumor cells (eCTC) and leukocytes (CD45pos) obtained with DEPArray, we identified the most significant features and applied single-variable and multi-variable methods, screening all combinations of four machine-learning approaches (Naïve Bayes, Logistic regression, Decision Trees, Random Forest).

Results

Best predictive features were circularity (OS) and diameter (BM), in both eCTC and CD45pos. Median difference in OS was 15 vs. 43 (months), p = 0.03 for eCTC and 19 vs. 36, p = 0.16 for CD45pos. Prediction for BM showed low accuracy (64%, 53%) but strong positive predictive value PPV (79%, 91%) for eCTC and CD45, respectively. Best machine learning model was Naïve Bayes, showing 46 vs 11 (months), p <0.0001 for eCTC; 12.5 vs. 45, p = 0.0004 for CD45pos and 11 vs. 45, p = 0.0003 for eCTC + CD45pos. BM prediction reached 91% accuracy with eCTC, 84% with CD45pos and 91% with combined model.

Conclusions

Quantitative image analysis and machine learning models were effective methods to predict survival and metastatic pattern, with both eCTC and CD45pos containing significant and complementary information.
Tertiary Lymphoid Structures and Chemokine Landscape in Virus-Positive and Virus-Negative Merkel Cell Carcinoma
Authors: Nakamura Motoki , Magara Tetsuya , Kano Shinji , Matsubara Akihiro , Kato Hiroshi , Morita Akimichi
Published: February 2022

Tertiary lymphoid structures (TLSs) are used as biomarkers in many cancers for predicting the prognosis and assessing the response to immunotherapy. In Merkel cell carcinoma (MCC), TLSs have only been examined in MCPyV-positive cases. Here, we examined the prognostic value of the presence or absence of TLSs in 61 patients with MCC, including MCPyV-positive and MCPyV-negative cases. TLS-positive samples had a significantly better prognosis than TLS-negative samples. MCPyV-positive samples had a good prognosis with or without TLSs, and MCPyV-negative/TLS-positive samples had a similarly good prognosis as MCPyV-positive samples. Only MCPyV-negative/TLS-negative samples had a significantly poor prognosis. All cases with spontaneous regression were MCPyV-positive/TLS-positive. We also performed a comprehensive analysis of the chemokines associated with TLS formation using next-generation sequencing (NGS). The RNA sequencing results revealed 5 chemokine genes,CCL5,CCR2,CCR7,CXCL9, andCXCL13, with significantly high expression in TLS-positive samples compared with TLS-negative samples in both MCPyV-positive and MCPyV-negative samples. Only 2 chemokine genes,CXCL10andCX3CR1, had significantly different expression levels in the presence or absence of MCPyV infection in TLS-negative samples. Patients with high CXCL13 or CCL5 expression have a significantly better prognosis than those with low expression. In conclusion, the presence of TLSs can be a potential prognostic marker even in cohorts that include MCPyV-negative cases. Chemokine profiles may help us understand the tumor microenvironment in patients with MCPyV-positive or MCPyV-negative MCC and may be a useful prognostic marker in their own right.
The Effectiveness of Traditional Chinese Medicine Combined With Surgery to Treat Granulomatous Mastitis: A Propensity-Matched Analysis
Authors: Sawuer Reziya , Wu Chunyu , Sun Zhenping , Liu Sheng
Published: February 2022

Purpose

The etiology and pathology of granulomatous mastitis (GLM) are still unknown. Expert consensus on the treatment of GLM has not been developed. The objective of this study is to study the effectiveness of traditional Chinese medicine (TCM) combined with surgery in treating GLM.

Materials and Methods

A retrospective cohort study was implemented at Longhua Hospital of Shanghai University of Traditional Chinese Medicine in China between September 2019 and August 2021. Female patients were included according to the propensity-score matching (PSM) method and balanced according to age and BMI. Patients with GLM diagnosed by pathology and a course of disease ≥ 6 months were included in this trial. Patients were divided into the TCM alone group or TCM + surgery group.

Results

In total, 168 female patients were assessed and 102 patients were included in the study after PSM (51 in the TCM group and 51 in the TCM + surgery group). The average age of the patients was 32 years (21-47 years). There was no significant baseline characteristics difference between two groups after PSM. The suppuration rate in the TCM + surgery group was less than that in the TCM group (64.7% vs. 83.35%, P < 0.05), and the TCM + surgery group had a higher 9-month cure rate than the TCM group (86.3% vs. 52.9%, P < 0.05). The full course of disease in the TCM + surgery group was shorter than that in the TCM group (253.9 ± 117.3 days vs. 332.5 ± 111.6 days, P < 0.05).

Conclusions

TCM combined with surgery can improve the cure rate and shorten the full course of GLM treatment, indicating surgery should be integrated in the clinical management of GLM.
Infectious Complications in Paediatric Haematopoetic Cell Transplantation for Acute Lymphoblastic Leukemia: Current Status
Authors: Zajac-Spychala Olga , Kampmeier Stefanie , Lehrnbecher Thomas , Groll Andreas H.
Published: February 2022

Haematopoietic stem cell transplantation (HSCT) in paediatric patients with acute lymphoblastic leukaemia (ALL) is associated with a variety of infectious complications which result in significant morbidity and mortality. These patients are profoundly immunocompromised, and immune reconstitution after HSCT generally occurs in astrictly defined order. During the early phase after HSCT until engraftment, patients are at risk of infections due to presence of neutropenia and mucosal damage, with Gramme-positive and Gramme-negative bacteria and fungi being the predominant pathogens. After neutrophil recovery, the profound impairment of cell-mediated immunity and use of glucocorticosteroids for control of graft-vs.-host disease (GvHD) increases the risk of invasive mould infection and infection or reactivation of various viruses, such as cytomegalovirus, varicella zoster virus, Epstein-Barr virus and human adenovirus. In the late phase, characterised by impaired cellular and humoral immunity, particularly in conjunction with chronic GvHD, invasive infections with encapsulated bacterial infections are observed in addition to fungal and viral infections. HSCT also causes a loss of pretransplant naturally acquired and vaccine-acquired immunity; therefore, complete reimmunization is necessary to maintain long-term health in these patients. During the last two decades, major advances have been made in our understanding of and in the control of infectious complications associated with HSCT. In this article, we review current recommendations for the diagnosis, prophylaxis and treatment of infectious complications following HSCT for ALL in childhood.