bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental DNA metabarcoding reveals spatial and seasonal patterns in the fish community in the Venice Lagoon
Authors: Cananzi Gabriele , Gregori Irene , Martino Francesco , Li Tianshi , Boscari Elisa , Camatti Elisa , Congiu Leonardo , Marino Ilaria Anna Maria , Pansera Marco , Schroeder Anna , Zane Lorenzo
Published: November 2022

Environmental DNA (eDNA) is an emerging tool for assessing biodiversity and understanding spatial and temporal community patterns and processes, directly from DNA sequencing of environmental samples such as air, water, and sediments. We applied eDNA methods to monitor bony fish communities, detecting as well locally allochthonous species, and to reveal seasonal patterns at two sites in the Venice Lagoon. We analyzed 17 water samples collected over 12 months at two ecologically distinct sites by using available primers for teleosts and High Throughput Illumina sequencing. We identified 1,289 amplicon sequence variants (ASVs) assigned to 62 fish taxa. Most of the species known to inhabit or to enter the Venice Lagoon were detected, with eDNA data reflecting differences in fish communities between the internal (freshwater associated) and the external (sea associated) part of the lagoon. Moreover, seasonal trends of migration have been portrayed, highlighting the most involved species and disclosing possible clashes between migration events and the temporary interruption of sea-lagoon connectivity due to MOSE (MOdulo Sperimentale Elettromeccanico). Of interest, the first-time detection of Oceanic puffer (Lagocephalus lagocephalus) DNA in the Venice Lagoon provides evidence of the further northward expansion of this species in the high Adriatic Sea. eDNA successfully profiled fish communities by season and habitat in the Venice Lagoon. Our results support routine application of eDNA to monitor potential ecological consequences of MOSE closures in this World Heritage site.
Bone fragility and sarcoidosis: An underestimated relationship
Authors: Caffarelli Carla , Cameli Paolo , Al Refaie Antonella , Giglio Elisa , Manzana Giulio , Mondillo Caterina , Noacco Yari , Olivieri Carmela , Bargagli Elena , Gonnelli Stefano
Published: November 2022

Introduction

Sarcoidosis is a chronic multisystem inflammatory disease which may affect any organ. Also bone can be involved both directly and indirectly. Data on BMD values and fragility fractures in sarcoidosis patients are few and heterogeneous. This study aimed to characterized the presence of fracture and the relative risk factors in patients with sarcoidosis.

Materials and methods

In this single center cross-sectional study we evaluated 252 sarcoidosis patients (54.7 ± 12.1 years) compared to sex-and age matched healthy controls. We measured BMD at lumbar spine, at femoral neck and at total hip. Moreover, the presence of fragility fractures was collected during osteoporosis visit and all radiological images were examined for the presence of any vertebral fracture according to Genant’s method’s. Lung function measurements, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, and diffusion capacity for carbon monoxide (DLCO) were assessed.

Results

Bone Mineral Density T-scores were lower in patients affected by sarcoidosis with respect to those obtained in healthy controls, but the difference was statistically significant only for BMD-LS (p < 0.01) and BMD-TH (p < 0.05). Moreover, BMD values at all skeletal sites were significantly associated with DLCO (%) (p < 0.05). The prevalence of fragility fracture was higher in patients with sarcoidosis than in healthy controls (30.6 vs. 12.3%). The patients with ≥3 vertebral fracture had lower values of FVC (%), FEV1 (%), and DLCO (%). Multiple regression analyses showed that BMI was positively associated with fragility fracture, while BMD-TH, DLCO(%) and therapy use was negatively associated.

Conclusions

Vertebral fractures represent a frequent complication in patients with sarcoidosis. Furthermore, the number of vertebral fractures was linked with a worsening in pulmonary functional tests. Therefore, the degree of severity of the sarcoidosis disease appears to be the main determinant of bone fragility.
Dietary supplementation for female infertility: Recent advances in the nutritional therapy for premature ovarian insufficiency
Authors: Han Qixin , Chen Zi-Jiang , Du Yanzhi
Published: November 2022

Premature ovarian insufficiency (POI) ranks top in the reproductive disorders that may impair multiple functioning systems, reduce the quality of life and ultimately deprive patients of their fertility among women. Symptoms can be partially alleviated by present hormone replacement therapy that cannot improve conception or decrease occurrence rates of systemic complication. Nutritional dietary supplements are attracting more and more attention because of their safety, bioavailability, and efficacy for well-being. Nutrients in the daily food are composed of carbohydrates, fat and lipoprotein, protein and polypeptide, vitamins, and vegetable or fruits containing phytoestrogens. These are functional nutrients due to the proliferative, anti-inflammatory, anti-oxidant, and mitochondria-protective potential during the course of menopause. Apart from dietary nutrients, microbe-related nutritional substances, including probiotics, prebiotics and the combination-synbiotics, display high potential as well in supporting estrous cycle, ovarian viability and modulating other vital reproductive functions. The present review will discuss dietary and microbial nutrients and their roles and applications in the living body based upon animal or human research, evaluate possible effect mechanisms from molecular, cellular and tissue levels, and provide insights into nutritional therapy for prolonging reproductive lifespan in female patients.
Capture Hi-C reveals the influence on dynamic three-dimensional chromosome organization perturbed by genetic variation or vanillin stress in Saccharomyces cerevisiae
Authors: Wang Xinning , Yang Bolun , Zhao Weiquan , Cao Wenyan , Shen Yu , Li Zailu , Bao Xiaoming
Published: November 2022

Studying the mechanisms of resistance to vanillin in microorganisms, which is derived from lignin and blocks a major pathway of DNA double-strand break repair in yeast, will benefit the design of robust cell factories that produce biofuels and chemicals using lignocellulosic materials. A high vanillin-tolerant Saccharomyces cerevisiae strain EMV-8 carrying site mutations compared to its parent strain NAN-27 was selected for the analyses. The dynamics of the chromatin structure of eukaryotic cells play a critical role in transcription and the regulation of gene expression and thus the phenotype. Consequently, Hi-C and transcriptome analyses were conducted in EMV-8 and NAN-27 in the log phase with or without vanillin stress to determine the effects of mutations and vanillin disturbance on the dynamics of three-dimensional chromosome organization and the influence of the organization on the transcriptome. The outcomes indicated that the chromosome interaction pattern disturbed by vanillin stress or genetic mutations in the log phase was similar to that in mouse cells. The short chromosomes contact the short chromosomes, and the long chromosomes contact the long chromosomes. In response to vanillin stress, the boundaries of the topologically associating domain (TAD) in the vanillin-tolerant strain EMV-8 were more stable than those in its parent strain NAN-27. The motifs of SFL1, STB3, and NHP6A/B were enriched at TAD boundaries in both EMV-8 and NAN-27 with or without vanillin, indicating that these four genes were probably related to TAD formation. The Indel mutation of YRR1, whose absence was confirmed to benefit vanillin tolerance in EMV-8, caused two new interaction sites that contained three genes, WTM2, PUP1, and ALE1, whose overexpression did not affect vanillin resistance in yeast. Overall, our results revealed that in the log phase, genetic mutations and vanillin disturbance have a negligible effect on three-dimensional chromosome organization, and the reformation or disappearance of TAD boundaries did not show an association with gene expression, which provides an example for studying yeast chromatin structure during stress tolerance using Hi-C technology.
Furanoids from the Gymnadenia conopsea (Orchidaceae) seed germination supporting fungus Ceratobasidium sp. (GS2)
Authors: Shi Lixin , Han Li , Zhao Zeyu , Li Qi , Wang Yanduo , Ding Gang , Xing Xiaoke
Published: November 2022

Five furanoids including a new analog (S)-1,4-di(furan-2-yl)-2-hydroxybutane-1,4-dione (1) together with four known ones, rhizosolaniol (2), 5-hydroxymethylfurfural (3), 2-furoic acid (4) and (2-furyl) oxoacetamide (5), were isolated from the fungal strain Ceratobasidium sp. (GS2) inducing seed germination of the endangered medicinal plant Gymnadenia conopsea of Orchidaceae. The structure of new furanoid 1 was determined mainly based on HR-ESI-MS and NMR spectral data. Modified Mosher’s reactions were used to establish the stereochemistry of the hydroxyl group in 1, which was not stable in Mosher’s reagents and transformed into four analogs 6–9. These degraded products (6–9) were elucidated based on UPLC-Q-TOF-MS/MS analysis, and compound 8 was further isolated from the degraded mixture and its structure was characterized through NMR experiments. Therefore, the absolute configuration of compound 1 was determined by electronic circular dichroism combined with quantum-chemical calculations adopting time-dependent density functional theory. Compounds (1–5), and 8 showed weak antioxidant activities, and compounds (2–4) displayed phytotoxicity on punctured detached green foxtail leaves. In addition, compounds 3 and 4 strongly showed inhibition activities on the seed germination of G. conopsea. This was the first chemical investigation of the symbiotic fungus of G. conopsea.
Mouse adaptation of H6 avian influenza viruses and their molecular characteristics
Authors: Wan Zhimin , Gong Jianxi , Sang Jianjun , Jiang Wenjie , Zhao Zhehong , Lian Mingjun , Tang Ting , Li Yafeng , Kan Qiuqi , Xie Quan , Li Tuofan , Shao Hongxia , Gao Wei , Qin Aijian , Ye Jianqiang
Published: November 2022

H6 avian influenza viruses (AIVs) not only continue to circulate in both domestic poultry and wild waterfowl, but also have occasionally caused spillovers infections in pigs and humans, posing a potential threat to public health. However, the molecular mechanism of H6 AIV adaptation to mammals remains largely unknown. In this study, two mouse-adapted (MA) H6 AIV strains, named as MA E-Teal/417 and MA GWF-Goose/740, were generated through blind passages in BALB/c mice. The two MA H6 strains replicated more efficiently and showed higher virulence than the corresponding wild type (WT) H6 strains in mice. Genome sequencing revealed that MA E-Teal/417 and MA GWF-Goose/740 carried six amino acid mutations (PB2-T224A/E627K, HA-G124R, NA-F167L/Y356H and M1-M92R), and four amino acid mutations (PB1-K577E, PA-T97I/D514E and HA-T276K), respectively, when compared to the corresponding WT virus. Receptor binding assay showed MA E-Teal/417 had stronger binding activity to α-2,3 SA than WT E-Teal/417. Moreover, the polymerase activity analysis found the RNP polymerase activity of both MA H6 viruses was significantly higher than that of the corresponding WT virus in 293T cells. All these demonstrate that H6 AIV can acquire limit amino acid substitutions to adapt to mammals and increase virulence, highlighting the significance of monitoring such mutations of H6 AIV in the field for alarming the potential of its cross-transmission and pathogenesis in mammals.
Transfer of Erwinia toletana and Erwinia iniecta to a novel genus Winslowiella gen. nov. as Winslowiella toletana comb. nov. and Winslowiella iniecta comb. nov. and description of Winslowiella arboricola sp. nov., isolated from bleeding cankers on broadleaf hosts
Authors: Brady Carrie , Kaur Sundeep , Crampton Bridget , Maddock Daniel , Arnold Dawn , Denman Sandra
Published: November 2022

Following a screening campaign of bleeding cankers of broadleaf hosts in Great Britain, numerous bacterial strains were isolated, identified by 16S rRNA and protein-coding gene sequencing and ultimately classified. During the course of the study, several Gram-negative, facultatively anaerobic strains were isolated from bleeding Platanus x acerifolia (London plane) and Tilia x europaea (common lime) cankers that could not be assigned to an existing species. Partial 16S rRNA gene sequencing placed these strains in the genus Erwinia, as a close phylogenetic relative of Erwinia toletana. In an effort to determine the taxonomic position of the strains, a polyphasic approach was followed including genotypic, genomic, phenotypic, and chemotaxonomic assays. Multilocus sequence analysis based on four protein-coding genes (gyrB, rpoB, infB, and atpD) confirmed the phylogenetic position of the strains as a novel taxon of subgroup 3 of the genus Erwinia, along with E. toletana and E. iniecta, and furthermore, provided support for their reclassification in a novel genus. Whole genome comparisons allowed the delimitation of the novel species and also supported the proposed transfer of subgroup 3 species to a novel genus in the Erwiniaeae. Phenotypically the novel species could be differentiated from E. toletana and E. iniecta, and the novel genus could be differentiated from the closely related genera Erwinia and Mixta. Therefore, we propose (1) the reclassification of E. toletana and E. iniecta in a novel genus, Winslowiella gen. nov., as Winslowiella toletana comb. nov. and Winslowiella iniecta comb. nov., with W. toletana comb. nov. as the type species (type strain A37T = CFBP 6631T = ATCC 700880T = CECT 5263T), and (2) classification of the novel strains as Winslowiella arboricola sp. nov. (type strain BAC 15a-03bT = LMG 32576T = NCPPB 4696T).
Microbial ecology of a shallow alkaline hydrothermal vent: Strýtan Hydrothermal Field, Eyjafördur, northern Iceland
Authors: Twing Katrina I. , Ward L. M. , Kane Zachary K. , Sanders Alexa , Price Roy Edward , Pendleton H. Lizethe , Giovannelli Donato , Brazelton William J. , McGlynn Shawn E.
Published: November 2022

Strýtan Hydrothermal Field (SHF) is a submarine system located in Eyjafördur in northern Iceland composed of two main vents: Big Strýtan and Arnarnesstrýtan. The vents are shallow, ranging from 16 to 70 m water depth, and vent high pH (up to 10.2), moderate temperature (Tmax ∼70°C), anoxic, fresh fluids elevated in dissolved silica, with slightly elevated concentrations of hydrogen and methane. In contrast to other alkaline hydrothermal vents, SHF is unique because it is hosted in basalt and therefore the high pH is not created by serpentinization. While previous studies have assessed the geology and geochemistry of this site, the microbial diversity of SHF has not been explored in detail. Here we present a microbial diversity survey of the actively venting fluids and chimneys from Big Strýtan and Arnarnesstrýtan, using 16S rRNA gene amplicon sequencing. Community members from the vent fluids are mostly aerobic heterotrophic bacteria; however, within the chimneys oxic, low oxygen, and anoxic habitats could be distinguished, where taxa putatively capable of acetogenesis, sulfur-cycling, and hydrogen metabolism were observed. Very few archaea were observed in the samples. The inhabitants of SHF are more similar to terrestrial hot spring samples than other marine sites. It has been hypothesized that life on Earth (and elsewhere in the solar system) could have originated in an alkaline hydrothermal system, however all other studied alkaline submarine hydrothermal systems to date are fueled by serpentinization. SHF adds to our understandings of hydrothermal vents in relationship to microbial diversity, evolution, and possibly the origin of life.
Probiotic assessment and antioxidant characterization of Lactobacillus plantarum GXL94 isolated from fermented chili
Authors: Zhou Yingjun , Gong Wenbing , Xu Chao , Zhu Zuohua , Peng Yuande , Xie Chunliang
Published: November 2022

Oxidative stress is caused by an imbalance between prooxidants and antioxidants, which is the cause of various chronic human diseases. Lactic acid bacteria (LAB) have been considered as an effective antioxidant to alleviate oxidative stress in the host. To obtain bacterium resources with good antioxidant properties, in the present study, 113 LAB strains were isolated from 24 spontaneously fermented chili samples and screened by tolerance to hydrogen peroxide (H2O2). Among them, Lactobacillus plantarum GXL94 showed the best antioxidant characteristics and the in vitro antioxidant activities of this strain was evaluated extensively. The results showed that L. plantarum GXL94 can tolerate hydrogen peroxide up to 22 mM, and it could normally grow in MRS with 5 mM H2O2. Its fermentate (fermented supernatant, intact cell and cell-free extract) also had strong reducing capacities and various free radical scavenging capacities. Meanwhile, eight antioxidant-related genes were found to up-regulate with varying degrees under H2O2 challenge. Furthermore, we evaluated the probiotic properties by using in vitro assessment. It was showed that GXL94 could maintain a high survival rate at pH 2.5% or 2% bile salt or 8.0% NaCl, live through simulated gastrointestinal tract (GIT) to colonizing the GIT of host, and also show higher abilities of auto-aggregation and hydrophobicity. Additionally, the usual antibiotic susceptible profile and non-hemolytic activity indicated the safety of the strain. In conclusion, this study demonstrated that L. plantarum GXL94 could be a potential probiotic candidate for producing functional foods with antioxidant properties.
Exogenous miRNAs from Moringa oleifera Lam. recover a dysregulated lipid metabolism
Authors: Roglia Valentina , Potestà Marina , Minchella Alessandra , Bruno Stefania Paola , Bernardini Roberta , Lettieri-Barbato Daniele , Iacovelli Federico , Gismondi Angelo , Aquilano Katia , Canini Antonella , Muleo Rosario , Colizzi Vittorio , Mattei Maurizio , Minutolo Antonella , Montesano Carla
Published: November 2022

A balanced diet is critical for human health, and edible plants play an important role in providing essential micronutrients as well as specific microRNAs (miRNAs) that can regulate human gene expression. Here we present the effects of Moringa oleifera (MO) miRNAs (mol-miRs) on lipid metabolism. Through in silico studies we identified the potential genes involved in lipid metabolism targeted by mol-miRs. To this end, we tested the efficacy of an aqueous extract of MO seeds (MOES), as suggested in traditional African ethnomedicine, or its purified miRNAs. The biological properties of MO preparations were investigated using a human derived hepatoma cell line (HepG2) as a model. MOES treatment decreased intracellular lipid accumulation and induced apoptosis in HepG2. In the same cell line, transfection with mol-miRs showed similar effects to MOES. Moreover, the effect of the mol-miR pool was investigated in a pre-obese mouse model, in which treatment with mol-miRs was able to prevent dysregulation of lipid metabolism.
Altered functional connectivity and topology structures in default mode network induced by inflammatory exposure in aged rat: A resting-state functional magnetic resonance imaging study
Authors: Liu Yang , Feng Huiru , Fu Huiqun , Wu Yan , Nie Binbin , Wang Tianlong
Published: November 2022

Inflammatory stress in anesthesia management and surgical process has been reported to induce long-term cognitive dysfunction in vulnerable aged brain, while few studies focused on the network mechanism. The default mode network (DMN) plays a significant role in spontaneous cognitive function. Changes in topology structure and functional connectivity (FC) of DMN in vulnerable aged brain following inflammatory stress-induced long-term cognitive dysfunction are rarely studied. Eighty-eight aged male rats received intraperitoneal injection of lipopolysaccharide (LPS) as treatment or equal amount of normal saline (NS) as control. Morris Water Maze (MWM) was performed to assess short- (<7 days) and long-term (>30 days) learning and spatial working memory. Enzyme-linked immunosorbent assay (ELISA) was used to measure systemic and hippocampus inflammatory cytokines. Real-time polymerase chain reaction (RT-PCR) was used to measure the changes in gene level. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to exam brain function prior to MWM on days 3, 7, and 31 after LPS exposure. Graph theory analysis was used to analyze FC and topology structures in aged rat DMN. Aged rats treated with LPS showed short- and long-term impairment in learning and spatial working memory in MWM test. Graph theory analysis showed temporary DMN intrinsic connectivity increased on day 3 followed with subsequent DMN intrinsic connectivity significantly altered on day 7 and day 31 in LPS-exposed rats as compared with controls. Short- and long-term alterations were observed in FC, while alterations in topology structures were only observed on day 3. Rats with inflammatory stress exposure may cause short- and long-term alterations in intrinsic connectivity in aged rat’s DMN while the changes in topology structures only lasted for 3 days. Inflammatory stress has prolonged effects on FC, but not topology structures in venerable aged brain.
Role of hippocampal circKcnk9 in visceral hypersensitivity and anxiety comorbidity of irritable bowel syndrome
Authors: Liu Yuan , Chen Zhong , Lin Wei , Zhou Yifei , Liu Zihan , Zhao Ruixia , Chen Yu , Wu Bin , Chen Aiqin , Lin Chun
Published: November 2022

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by recurrent visceral pain and altered bowel habits (diarrhea or constipation). However, the molecular and pathological mechanisms are poorly understood. This study found neonatal colorectal distension to induce visceral hypersensitivity and anxiety. The expression of hippocampal circKcnk9, a novel circRNA, was significantly increased in IBS-like rats. Interestingly, CA1 shcircKcnk9 treatment inhibited long-term potentiation (LTP) and alleviated visceral hypersensitivity and anxiety in IBS-like rats, whereas overexpression of CA1 circKcnk9 induced LTP, visceral hypersensitivity, and anxiety in controls. Several experiments indicated that increased CA1 circKcnk9 acted as a miR-124-3p sponge, which resulted in the inhibitory effect of miR-124-3p on gene silencing. There was a negative correlation between circKcnk9 and miR-124-3p expression. As expected, CA1 administration of agomiR-124-3p decreased CA1 LTP, visceral hypersensitivity, and anxiety in the IBS-like rats. In contrast, CA1 treatment with antagomiR-124-3p induced LTP, visceral hypersensitivity, and anxiety in the controls. Furthermore, bioinformatic analysis and experimental data showed that EZH2 is a circKcnk9/miR-124-3p target gene, and increased EZH2 expression was involved in visceral hypersensitivity and anxiety in IBS-like rats by enhancing hippocampal synaptic plasticity. In conclusion, early life stress induces increased expression of circKcnk9 in the CA1 of IBS-like rats. Increased circKcnk9 expression regulates synaptic transmission and enhances LTP, leading to visceral hypersensitivity and anxiety in IBS-like rats. The underlying circKcnk9 signaling pathway is miR124-3p/EZH2. Increased circKcnk9 reinforces its sponging of miR124-3p and strongly suppresses miR124-3p activity, resulting in increased expression of the target gene EZH2. This study provides a new epigenetic mechanism for visceral hypersensitivity and anxiety in IBS-like rats.
Dynamic control of eye-head gaze shifts by a spiking neural network model of the superior colliculus
Authors: Alizadeh Arezoo , Van Opstal A. John
Published: November 2022

Introduction

To reorient gaze (the eye’s direction in space) towards a target is an overdetermined problem, as infinitely many combinations of eye- and head movements can specify the same gaze-displacement vector. Yet, behavioral measurements show that the primate gaze-control system selects a specific contribution of eye- and head movements to the saccade, which depends on the initial eye-in-head orientation. Single-unit recordings in the primate superior colliculus (SC) during head-unrestrained gaze shifts have further suggested that cells may encode the instantaneous trajectory of a desired straight gaze path in a feedforward way by the total cumulative number of spikes in the neural population, and that the instantaneous gaze kinematics are thus determined by the neural firing rates. The recordings also indicated that the latter is modulated by the initial eye position. We recently proposed a conceptual model that accounts for many of the observed properties of eye-head gaze shifts and on the potential role of the SC in gaze control.

Methods

Here, we extend and test the model by incorporating a spiking neural network of the SC motor map, the output of which drives the eye-head motor control circuitry by linear cumulative summation of individual spike effects of each recruited SC neuron. We propose a simple neural mechanism on SC cells that explains the modulatory influence of feedback from an initial eye-in-head position signal on their spiking activity. The same signal also determines the onset delay of the head movement with respect to the eye. Moreover, the downstream eye- and head burst generators were taken to be linear, as our earlier work had indicated that much of the non-linear main-sequence kinematics of saccadic eye movements may be due to neural encoding at the collicular level, rather than at the brainstem.

Results and discussion

We investigate how the spiking activity of the SC population drives gaze to the intended target location within a dynamic local gaze-velocity feedback circuit that yields realistic eye- and head-movement kinematics and dynamic SC gaze-movement fields.
Management of anti-seizure medications in lactating women with epilepsy
Authors: Yan Rong , Tuo Jinmei , Tai Zhenzhen , Zhang Haiqing , Yang Juan , Yu Changyin , Xu Zucai
Published: November 2022

Epilepsy is a common neurological disease. At present, there are about 70 million epilepsy patients in the world, half of them are women, and 30–40% of women with epilepsy are of childbearing potential. Patients with epilepsy who are of childbearing potential face more challenges, such as seizures caused by hormonal fluctuations and the risk of adverse effects on the mother and baby from taking anti-seizure medications (ASMs). Breast milk is one of the best gifts that a mother can give her baby, and breastfeeding can bring more benefits to the baby. Compared with healthy people, people with epilepsy have more concerns about breastfeeding because they are worried that ASMs in their milk will affect the growth and development of the baby, and they are always faced with the dilemma of whether to breastfeed after childbirth. Regarding, whether women with epilepsy can breastfeed while taking ASMs, and whether breastfeeding will adversely affect the baby is still an important topic of concern for patients and doctors. This article reviews the existing research on breastfeeding-related issues in women with epilepsy to guide clinical practice, and improve the breastfeeding compliance of women with epilepsy.
Case report: Early-onset Parkinson's disease with initial spastic paraparesis and hyperreflexia caused by compound heterozygous PRKN-gene exon 2 and 4 deletions
Authors: Jensen Ida , Hendrich Corinna , Klietz Martin , Berding Georg , Höglinger Günter U. , Wegner Florian
Published: November 2022

Pathogenic variants in the Parkin-gene (PRKN) are among the most common genetic causes of early onset Parkinson's disease (EOPD). Patients with EOPD can present with atypical clinical features and misdiagnosis is frequent. Here, we report a clinical phenotype with atypical signs and symptoms of a 35-year-old male patient with EOPD caused by a compound heterozygous PRKN-gene deletion of exons 2 and 4. After the initial diagnosis of stiff person syndrome, the patient was admitted to our department for a second opinion after 8 years of untreated disease progression. The patient presented with prominent spastic paraparesis pronounced on the right side and hyperreflexia as well as Parkinsonism with rigidity predominantly affecting the upper limbs, bradykinesia, and resting tremor. In the diagnostic assessment, magnetic evoked potentials to the anterior tibial muscles showed a low amplitude on the right side, compatible with pyramidal tract disturbance. However, an MRI of the head and the spine did not show any pathologies or atrophy. A [123I] FP-CIT SPECT scan revealed profoundly and left-pronounced reduced striatal uptake suggesting a neurodegenerative Parkinson's syndrome. Even though an acute levodopa challenge did not show marked improvement of symptoms, the chronic levodopa challenge with up to 450 mg/day significantly reduced the rigidity and bradykinesia. Surprisingly, spastic paraparesis and hyperreflexia diminished under dopaminergic treatment. Finally, genetic analysis by next-generation sequencing via copy number variant analysis (CNV) and multiplex ligation-dependent probe amplification (MLPA) confirmed compound heterozygous deletions of exons 2 and 4 in the PRKN-gene. As presented in this case, the awareness of atypical clinical symptoms of EOPD is essential to prevent misdiagnosis in young patients.
Emotional and qualitative outcomes among patients with left and right hemisphere stroke
Authors: Stockbridge Melissa D. , Vitti Emilia , Faria Andreia V. , Hillis Argye E.
Published: November 2022

The differences in mental health outcomes of right and left hemisphere strokes are well studied; however, there is a long-standing controversy surrounding whether depression is associated with lateralization of stroke or not. In this investigation, we examined the effect of lesion location on post-stroke depression controlling for lesion size and hemiparesis in a longitudinal sample assessed at acute, subacute, and chronic timepoints. As a secondary aim, we further examined the effect of lesion location on self-reported difficulties across a wide array of domains. A series of 134 patients with left hemisphere strokes and 79 with right hemisphere strokes completed the Patient Health Questionnaire-9 and an inventory of post-stroke abilities at within acute, subacute, and chronic windows following stroke. When controlling for hemiparesis and overall lesion volume, we found no difference in depression between groups at any timepoint. Additional exploratory analyses provided a further look at differing challenges associated with depression in each group.
Functional and neuromuscular changes induced via a low-cost, muscle-computer interface for telerehabilitation: A feasibility study in chronic stroke
Authors: Marin-Pardo Octavio , Donnelly Miranda Rennie , Phanord Coralie S. , Wong Kira , Pan Jessica , Liew Sook-Lei
Published: November 2022

Stroke is a leading cause of adult disability in the United States. High doses of repeated task-specific practice have shown promising results in restoring upper limb function in chronic stroke. However, it is currently challenging to provide such doses in clinical practice. At-home telerehabilitation supervised by a clinician is a potential solution to provide higher-dose interventions. However, telerehabilitation systems developed for repeated task-specific practice typically require a minimum level of active movement. Therefore, severely impaired people necessitate alternative therapeutic approaches. Measurement and feedback of electrical muscle activityviaelectromyography (EMG) have been previously implemented in the presence of minimal or no volitional movement to improve motor performance in people with stroke. Specifically, muscle neurofeedback training to reduce unintended co-contractions of the impaired hand may be a targeted intervention to improve motor control in severely impaired populations. Here, we present the preliminary results of a low-cost, portable EMG biofeedback system (Tele-REINVENT) for supervised and unsupervised upper limb telerehabilitation after stroke. We aimed to explore the feasibility of providing higher doses of repeated task-specific practice during at-home training. Therefore, we recruited 5 participants (age = 44–73 years) with chronic, severe impairment due to stroke (Fugl-Meyer = 19–40/66). They completed a 6-week home-based training program that reinforced activity of the wrist extensor muscles while avoiding coactivation of flexor musclesviacomputer games. We used EMG signals to quantify the contribution of two antagonistic muscles and provide biofeedback of individuated activity, defined as a ratio of extensor and flexor activity during movement attempt. Our data suggest that 30 1-h sessions over 6 weeks of at-home training with our Tele-REINVENT system is feasible and may improve individuated muscle activity as well as scores on standard clinical assessments (e.g., Fugl-Meyer Assessment, Action Research Arm Test, active wrist range of motion) for some individuals. Furthermore, tests of neuromuscular control suggest modest changes in the synchronization of electroencephalography (EEG) and EMG signals within the beta band (12–30 Hz). Finally, all participants showed high adherence to the training protocol and reported enjoying using the system. These preliminary results suggest that using low-cost technology for home-based telerehabilitation after severe chronic stroke is feasible and may be effective in improving motor controlviafeedback of individuated muscle activity.
Naturalistic neuroscience and virtual reality
Authors: Thurley Kay
Published: November 2022

Virtual reality (VR) is one of the techniques that became particularly popular in neuroscience over the past few decades. VR experiments feature a closed-loop between sensory stimulation and behavior. Participants interact with the stimuli and not just passively perceive them. Several senses can be stimulated at once, large-scale environments can be simulated as well as social interactions. All of this makes VR experiences more natural than those in traditional lab paradigms. Compared to the situation in field research, a VR simulation is highly controllable and reproducible, as required of a laboratory technique used in the search for neural correlates of perception and behavior. VR is therefore considered a middle ground between ecological validity and experimental control. In this review, I explore the potential of VR in eliciting naturalistic perception and behavior in humans and non-human animals. In this context, I give an overview of recent virtual reality approaches used in neuroscientific research.
Women’s visibility at European Society for Clinical Nutrition and Metabolism congresses from 2011 to 2019: Is the floor yours?
Authors: Occhiali Emilie , Demailly Zoe , Clavier Thomas , Achamrah Najate
Published: November 2022

Purpose

Participating in international conferences is an essential way to promote scholarly work. We aimed to assess the trend of women’s visibility at the European Society for Clinical Nutrition and Metabolism (ESPEN) congress by describing the evolution of the proportion of women speakers between 2011 and 2019.

Materials and methods

This is a retrospective study including public data obtained from the 2011, 2015, and 2019 ESPEN congresses. The primary endpoint was the percentage of women speakers in major oral sessions (oral communications and specific conferences including prestigious lectures). The secondary endpoints were the proportion of women in other high-visibility positions (moderators, industry-led symposia interventions) and countries of origin.

Results

The proportion of women speakers in oral communications remained stable between 2011 and 2019 [43% (43/100) vs. 41% (46/111), respectively; p = 0.89]. The proportion of women moderators in oral communications sessions significantly increased between 2011 and 2019 [13% (6/45) vs. 41% (19/46), respectively; p = 0.004]. The percentage of women speakers and moderators in industry-led symposia significantly increased between 2011 and 2019 [11% (2/18) vs. 41% (11/27), p = 0.05; 0% (0/6) vs. 60% (6/10), p = 0.03, respectively]. The percentage of women moderators in educational sessions also remained stable during the period with a marked under-representation of women in 2015. During all three congresses, women from the host countries were over-represented as moderators compared to women from other countries.

Conclusion

The percentage of women speakers in oral communications remained stable in the last 8 years at ESPEN congresses, although women’s representation in other high-visibility positions has increased. As men remained over-represented, women should be more encouraged to promote their academic work in the field of clinical nutrition, particularly during this international congress.
Treatment beyond progression in non-small cell lung cancer: A systematic review and meta-analysis
Authors: Kuo Wei-Ke , Weng Ching-Fu , Lien Yin-Ju
Published: November 2022

Objectives

Treatment beyond progression (TBP) is defined as treatment continuing in spite of disease progression, according to the Response Evaluation Criteria In Solid Tumors. We performed a systematic review and meta-analysis to provide evidence for the effects of TBP on lung cancer survival.

Materials and methods

This study has been conducted following the PRISMA guidelines. A systematic review of PubMed, MEDLINE, Embase, and Cochrane Collaboration Central Register of Controlled Clinical Trials from the inception of each database to December 2021 was conducted. Two authors independently reviewed articles for inclusion and extract data from all the retrieved articles. Random-effects meta-analysis was performed using Comprehensive Meta-Analysis software, version 3 (Biostat, Englewood, NJ, USA). Hazard ratios (HRs) with the corresponding 95% confidence intervals (CI) were used for survival outcomes.

Results

We identified five (15.6%) prospective randomized trials and twenty-seven (84.4%) retrospective observational studies of a total of 9,631 patients for the meta-analysis. 3,941 patients (40.9%) were in a TBP group and 5,690 patients (59.1%) were in a non-TBP group. There is a statistically significant advantage for patients who received TBP compared with those who did not in post progression progression-free survival (ppPFS), post progression overall survival (ppOS), and overall survival (OS) from initiation of drugs (ppPFS: HR, 0.746; 95% CI, 0.644-0.865; P<0.001; ppOS: HR, 0.689; 95% CI, 0.596-0.797; P<0.001; OS from initiation of drugs: HR, 0.515; 95% CI, 0.387-0.685; P<0.001)

Conclusion

This study provides further evidence in support of TBP for NSCLC, however, these results require cautious interpretation. Large, randomized, controlled trials investigating the efficacy of TBP in lung cancer treatment are warranted.

Systemic Review Registration

https://www.crd.york.ac.uk/PROSPERO/ identifier CRD42021285147
Review of the endocrine organ–like tumor hypothesis of cancer cachexia in pancreatic ductal adenocarcinoma
Authors: Yu Ying-Chun , Ahmed Azaj , Lai Hsueh-Chou , Cheng Wei-Chung , Yang Juan-Chern , Chang Wei-Chun , Chen Lu-Min , Shan Yan-Shen , Ma Wen-Lung
Published: November 2022

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal types of solid tumors, associated with a high prevalence of cachexia (~80%). PDAC-derived cachexia (PDAC-CC) is a systemic disease involving the complex interplay between the tumor and multiple organs. The endocrine organ–like tumor (EOLT) hypothesis may explain the systemic crosstalk underlying the deleterious homeostatic shifts that occur in PDAC-CC. Several studies have reported a markedly heterogeneous collection of cachectic mediators, signaling mechanisms, and metabolic pathways, including exocrine pancreatic insufficiency, hormonal disturbance, pro-inflammatory cytokine storm, digestive and tumor-derived factors, and PDAC progression. The complexities of PDAC-CC necessitate a careful review of recent literature summarizing cachectic mediators, corresponding metabolic functions, and the collateral impacts on wasting organs. The EOLT hypothesis suggests that metabolites, genetic instability, and epigenetic changes (microRNAs) are involved in cachexia development. Both tumors and host tissues can secrete multiple cachectic factors (beyond only inflammatory mediators). Some regulatory molecules, metabolites, and microRNAs are tissue-specific, resulting in insufficient energy production to support tumor/cachexia development. Due to these complexities, changes in a single factor can trigger bi-directional feedback circuits that exacerbate PDAC and result in the development of irreversible cachexia. We provide an integrated review based on 267 papers and 20 clinical trials from PubMed and ClinicalTrials.gov database proposed under the EOLT hypothesis that may provide a fundamental understanding of cachexia development and response to current treatments.
Improved NGS-based detection of microsatellite instability using tumor-only data
Authors: Marques Ana Claudia , Ferraro-Peyret Carole , Michaud Frederic , Song Lin , Smith Ewan , Fabre Guillaume , Willig Adrian , Wong Melissa M. L. , Xing Xiaobin , Chong Chloe , Brayer Marion , Fenouil Tanguy , Hervieu Valérie , Bancel Brigitte , Devouassoux Mojgan , Balme Brigitte , Meyronet David , Menu Philippe , Lopez Jonathan , Xu Zhenyu
Published: November 2022

Microsatellite instability (MSI) is a molecular signature of mismatch repair deficiency (dMMR), a predictive marker of immune checkpoint inhibitor therapy response. Despite its recognized pan-cancer value, most methods only support detection of this signature in colorectal cancer. In addition to the tissue-specific differences that impact the sensitivity of MSI detection in other tissues, the performance of most methods is also affected by patient ethnicity, tumor content, and other sample-specific properties. These limitations are particularly important when only tumor samples are available and restrict the performance and adoption of MSI testing. Here we introduce MSIdetect, a novel solution for NGS-based MSI detection. MSIdetect models the impact of indel burden and tumor content on read coverage at a set of homopolymer regions that we found are minimally impacted by sample-specific factors. We validated MSIdetect in 139 Formalin-Fixed Paraffin-Embedded (FFPE) clinical samples from colorectal and endometrial cancer as well as other more challenging tumor types, such as glioma or sebaceous adenoma or carcinoma. Based on analysis of these samples, MSIdetect displays 100% specificity and 96.3% sensitivity. Limit of detection analysis supports that MSIdetect is sensitive even in samples with relatively low tumor content and limited microsatellite instability. Finally, the results obtained using MSIdetect in tumor-only data correlate well (R=0.988) with what is obtained using tumor-normal matched pairs, demonstrating that the solution addresses the challenges posed by MSI detection from tumor-only data. The accuracy of MSI detection by MSIdetect in different cancer types coupled with the flexibility afforded by NGS-based testing will support the adoption of MSI testing in the clinical setting and increase the number of patients identified that are likely to benefit from immune checkpoint inhibitor therapy.
Ginsenoside Rg1 interferes with the progression of diabetic osteoporosis by promoting type H angiogenesis modulating vasculogenic and osteogenic coupling
Authors: Chen Wenhui , Jin Xinyan , Wang Ting , Bai Rui , Shi Jun , Jiang Yunxia , Tan Simin , Wu Ruijie , Zeng Shiqi , Zheng Hongxiang , Jia Hongyang , Li Shuanglei
Published: November 2022

Ginsenoside Rg1 (Rg1) has been demonstrated to have antidiabetic and antiosteoporotic activities. The aim of this study was to investigate the protective effect of Rg1 against diabetic osteoporosis and the underlying mechanism. In vitro, we found that Rg1 increased the number of osteoprogenitors and alleviated high glucose (HG) induced apoptosis of osteoprogenitors by MTT assays and flow cytometry. qRT‒PCR and western blot analysis suggested that Rg1 can also promote the secretion of vascular endothelial growth factor (VEGF) by osteoprogenitors and promote the coupling of osteogenesis and angiogenesis. Rg1 can also promote the proliferation of human umbilical vein endothelial cells (HUVECs) cultured in high glucose, enhance the angiogenic ability of endothelial cells, and activate the Notch pathway to promote endothelial cells to secrete the osteogenesis-related factor Noggin to regulate osteogenesis, providing further feedback coupling of angiogenesis and osteogenesis. Therefore, we speculated that Rg1 may have similar effects on type H vessels. We used the Goto-Kakizaki (GK) rat model to perform immunofluorescence staining analysis on two markers of type H vessels, Endomucin (Emcn) and CD31, and the osteoblast-specific transcription factor Osterix, and found that Rg1 stimulates type H angiogenesis and bone formation. In vivo experiments also demonstrated that Rg1 promotes VEGF secretion, activates the Noggin/Notch pathway, increases the level of coupling between type H vessels and osteogenesis, and improves the bone structure of GK rats. All of these data reveal that Rg1 is a promising candidate drug for treating diabetic osteoporosis as a potentially bioactive molecule that promotes angiogenesis and osteointegration coupling.
Neoadjuvant targeted therapy for resectable EGFR-mutant non-small cell lung cancer: Current status and future considerations
Authors: Liu Wenliang , Ren Siying , Xiao Ying , Yang Lulu , Zeng Chao , Hu Yan
Published: November 2022

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) targeted therapy has become the standard of care for patients with EGFR-mutated metastatic non-small cell lung cancer (NSCLC) on the basis of improved prognosis and reduced toxicities compared with chemotherapy. In view of the therapeutic potential of EGFR-TKIs in EGFR-mutated advanced NSCLC, several scholars have explored the value of preoperative use of EGFR-TKIs in patients with EGFR-mutated resectable NSCLC. However, the field of neoadjuvant targeted therapy for EGFR-mutated resectable NSCLC is currently in its infancy. In this mini-review, we summarize the current evidence on neoadjuvant EGFR-TKIs targeted therapy for resectable EGFR-mutated NSCLC and focus on discussing potential clinical strategies of treating resectable EGFR-mutated patients by preoperative administration of EGFR-TKIs-based multimodality therapy.