bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of transcript isoforms in 19 chicken tissues by Oxford Nanopore long-read sequencing
Authors: Guan Dailu , Halstead Michelle M. , Islas-Trejo Alma D. , Goszczynski Daniel E. , Cheng Hans H. , Ross Pablo J. , Zhou Huaijun
Published: September 2022

To identify and annotate transcript isoforms in the chicken genome, we generated Nanopore long-read sequencing data from 68 samples that encompassed 19 diverse tissues collected from experimental adult male and female White Leghorn chickens. More than 23.8 million reads with mean read length of 790 bases and average quality of 18.2 were generated. The annotation and subsequent filtering resulted in the identification of 55,382 transcripts at 40,547 loci with mean length of 1,700 bases. We predicted 30,967 coding transcripts at 19,461 loci, and 16,495 lncRNA transcripts at 15,512 loci. Compared to existing reference annotations, we found ∼52% of annotated transcripts could be partially or fully matched while ∼47% were novel. Seventy percent of novel transcripts were potentially transcribed from lncRNA loci. Based on our annotation, we quantified transcript expression across tissues and found two brain tissues (i.e., cerebellum and cortex) expressed the highest number of transcripts and loci. Furthermore, ∼22% of the transcripts displayed tissue specificity with the reproductive tissues (i.e., testis and ovary) exhibiting the most tissue-specific transcripts. Despite our wide sampling, ∼20% of Ensembl reference loci were not detected. This suggests that deeper sequencing and additional samples that include different breeds, cell types, developmental stages, and physiological conditions, are needed to fully annotate the chicken genome. The application of Nanopore sequencing in this study demonstrates the usefulness of long-read data in discovering additional novel loci (e.g., lncRNA loci) and resolving complex transcripts (e.g., the longest transcript for the TTN locus).
Remote sensing of suspended sediment in high turbid estuary from sentinel-3A/OLCI: A case study of Hangzhou Bay
Authors: Yu Zhifeng , Wang Jingwen , Li Yuan , Shum CK , Wang Ben , He Xianqiang , Xu Huiyan , Xu Yuzhuang , Zhou Bin
Published: September 2022

The suspended sediment in water infers water quality, and directly reflects optical properties such as water transparency, turbidity, and water color. Thus, these physical properties provide a viable basis to rigorously retrieve for suspended sediment concentration (SSC) using satellite remote sensing water color measurements in estuaries. The contemporary Ocean and Land Color Instrument (OLCI) on Sentinel-3A, provides more waveband options for remote sensing of water color and an opportunity for retrieval of suspended sediment in estuarine coast. Yet, accurate retrieval of SSC in high turbid waters from OLCI is still challenging due primarily to the high uncertainty of atmospheric correction. Here, we use OLCI images to measure water quality in Hangzhou Bay, and construct a retrieval model of SSC, and cross-validated using Geostationary Ocean Color Imager (GOCI) data. The study shows that: (1) the atmospheric correction algorithm based on ultraviolet wavelengths (UV-AC) can achieve better results for both OLCI and GOCI data, and the overall correction accuracy for OLCI is higher than that for GOCI data; (2) the multi-band index model constructed by using Rrs(Oa16)/Rrs(Oa5) of OLCI data has higher retrieval accuracy and model stability, with R2 is 0.96, MRE is 17.52%, and RMSE is 69.10 mg/L; (3) the spatial distribution of SSC in the study area is complex, mainly showing that the SCC in the top of the bay is larger than the mouth of the bay, and the south shore is larger than the north shore; (4) whe distribution of SSC obtained from retrieving OLCI and GOCI data in general is consistent, with the OLCI SSC estimates with higher accuracy than GOCI data, and the numerical difference between the two retrieval results is more obvious in the ocean with high SSC; and (5) with appropriate atmospheric corrections and retrieval models, OLCI data can be used to estimate improved SSC observables in Hangzhou Bay. We conclude that the SSC retrieval models proposed here provide a good reference method for retrieval of water color observable in Hangzhou Bay coastal estuary.
Light and freshwater discharge drive the biogeochemistry and microbial ecology in a sub-Arctic fjord over the Polar night
Authors: Vonnahme T. R. , Klausen L. , Bank R. M. , Michellod D. , Lavik G. , Dietrich U. , Gradinger R.
Published: September 2022

The polar night has recently received increased attention as a surprisingly active biological season. Yet, polar night microbial ecology is a vastly understudied field. To identify the physical and biogeochemical parameters driving microbial activity over the dark season, we studied a sub-Arctic fjord system in northern Norway from autumn to early spring with detailed monthly sampling. We focused on the impact of mixing, terrestrial organic matter input and light on microbial ecosystem dynamics. Our study highlights strong differences in the key drivers between spring, autumn, and winter. The spring bloom started in March in a fully mixed water column, opposing the traditional critical depth hypothesis. Incident solar radiation was the key driver maximum Chlorophyll was reached in April. The onset of the autumn phytoplankton bloom was controlled by vertical mixing, causing nutrient upwelling and dilution of zooplankton grazers, which had their highest biomass during this time. According to the dilution-recoupling hypothesis grazer dilution reduced grazing stress and allowed the fall bloom formation. Mixing at that time was initiated by strong winds and reduced stratification as a consequence of freezing temperatures and lower freshwater runoff. During the light-limited polar night, the primary production was extremely low but bacteria continued growing on decaying algae, their exudates and also allochthonous organic matter. A melting event in January could have increased input of organic matter from land, supporting a mid-winter bacterial bloom. In conclusion, polar night biogeochemistry and microbial ecology was not only driven by light availability, but strongly affected by variability in reshwater discharge and allochthonous carbon input. With climate change freshwater discharge will increase in the Arctic, which will likely increase importance of the dynamics described in this study.
Southern Ocean ice charts at the Argentine Naval Hydrographic Service and their impact on safety of navigation
Authors: Scardilli Alvaro S. , Salvó Constanza S. , Saez Ludmila Gomez
Published: September 2022

Antarctica is a largely inhospitable and inaccessible continent that plays a key role in regulating the climate through ocean currents, winds, icebergs drift, and sea-ice concentration and thickness. The study area of ​​this work corresponds to the Weddell Sea, Bellingshausen Sea and the South Atlantic Ocean. These areas are relevant because of supply operations to Antarctic stations and scientific and tourist activities. The Antarctic Peninsula is the most visited region of the continent for tourist and research vessels and requires special efforts in the development and dissemination of updated ice information for Safety of Navigation. For this purpose, it is critical to have information that discriminates the origin of the ice from land and open water, sea-ice concentration, and stage of development. The high recurrence of cloud cover over the Antarctic Peninsula during the summer hinders the operational use of visible/infra red satellite imagery, therefore access to Synthetic Aperture Radar (SAR) sensors is considered to be a high priority. Between 2018 and 2020, with the launch of the SAOCOM (Satélite Argentino de Observación Con Microondas) constellation, Argentina has evidenced an increase in the availability of SAR images for sea-ice operations. This paper presents the current state of routine production of operational ice charts at the Argentine Naval Hydrographic Service for mariners in the vicinity of the Antarctic Peninsula and South Atlantic Ocean and discuss future developments in place to prepare for expected increases in marine traffic in these areas.
Parametermeasurement of aircraft-radiated noise from a single acoustic sensor node in three-dimensional space
Authors: Yu Shuwen , Xiao Lei , Sun Weitao
Published: September 2022

A line spectrum presents the form of a narrow-band time-varying signal due to Doppler effect when the single hydrophone node observes flight-radiated noise. The modulation law of the time-varying signal contains a large number of feature information of moving targets, which can be used for detection and classification. This paper studies the possibility of using instantaneous frequency measurements from the hydrophone node to improve the precision of the flight parameter estimates when the source spectrum contains a harmonic line of constant frequency. First of all, we build up and analyze the underwater sound field excited by the aircraft using the ray theory model; then the Doppler shift in the two isospeed media, which is caused by the aircraft, is established; finally, a robust time–frequency transform describes the time–frequency distribution of the received signal, and a geometric approach solves the flying parameters.
Postoperative complications of combined phacoemulsification and pars plana vitrectomy in diabetic retinopathy patients
Authors: Gershoni Assaf , Barayev Edward , Jbara Doha , Hadayer Amir , Axer-Siegel Ruth , Dotan Assaf , Gal-Or Orly , Tuuminen Raimo , Ehrlich Rita
Published: September 2022

Purpose

To compare intra- and postoperative complications in combined phacoemulsification and pars plana vitrectomy surgeries performed in patients with non-proliferative diabetic retinopathy (NPDR) vs. proliferative diabetic retinopathy (PDR).

Methods

Retrospective, case series of patients with diabetic retinopathy who underwent combined phacovitrectomy surgery between 2008 and 2017. We compared intraoperative complications including posterior capsular rupture and retinal tear, and postoperative complications including corneal edema, macular edema (ME), epiretinal membrane (ERM), neovascular glaucoma and persistent inflammation.

Results

A total of 104 eyes of 104 patients were included in this study. Twenty-four eyes (23.1%) were categorized as NPDR and 80 eyes (76.9%) as PDR. The most common indications for surgery in the NPDR group were ERM (67%) and rhegmatogenous retinal detachment (12.5%), while in the PDR group, indications were vitreous hemorrhage (56%) and tractional retinal detachment (19%). The most common intraoperative complication was retinal tear (8% in NPDR and 19% in PDR, p = 0.195) and postoperative complication was ME (29% in NPDR and 26% in PDR, p = 0.778). There were no statistically significant differences in intra- and postoperative complication rates between the NPDR and PDR groups, even after adjusting for confounders; patient age at surgery and indication for surgery.

Conclusion

After combined phacovitrectomy in NPDR and PDR patients, new-onset ME was found in about a quarter of eyes in both groups. Intraoperative anti-VEGF or steroid administration, and intense postoperative anti-inflammatory medication and follow-up should be regarded after phacovitrectomy regardless of the DR level.
Factors associated with low prevalence of Fuchs' uveitis syndrome in Japan
Authors: Yoneda Yu , Usui Yoshihiko , Tanaka Rie , Hase Keitaro , Namba Kenichi , Kamoi Koju , Takase Hiroshi , Takeuchi Masaki , Matsumiya Wataru , Kusuhara Sentaro , Takeda Atsunobu , Yawata Nobuyo , Yanai Ryoji , Hiyama Tomona , Harada Yosuke , Hashida Noriyasu , Maruyama Kazuichi , Nakai Kei , Taguchi Ryo , Kaburaki Toshikatsu , Mizuki Nobuhisa , Goto Hiroshi , Fujino Yujiro , Takeuchi Masaru
Published: September 2022

Aim

To investigate the causes of low prevalence of Fuchs' uveitis syndrome (FUS) in Japan.

Methods

Medical records of 160 patients diagnosed with FUS at 14 uveitis specialty facilities in Japan were reviewed retrospectively.

Results

In 160 FUS patients, mean follow-up period before referral to our uveitis facilities was 31.6 ± 50.9 months. The most common reason for referral was idiopathic uveitis (61.9%), followed by cataract (25.0%), high intraocular pressure (IOP) including glaucoma (16.3%), and FUS (14.4%). Unilateral involvement was 96.9%. The most frequent ocular finding of FUS was anterior inflammation (91.9%), followed by stellate-shaped keratic precipitates (88.1%), cataract/pseudophakia (88.1%), diffuse iris atrophy (84.4%), vitreous opacity (62.5%), heterochromia (53.1%) and high IOP including glaucoma (36.3%). As treatments of these ocular findings, cataract surgery was performed in 52.5%, glaucoma surgery in 10.6%, and vitrectomy in 13.8%. Mean logMAR VA was 0.28 ± 0.59 at the initial visit, and decreased significantly to 0.04 ± 0.32 at the last visit. Proportions of FUS patients with BCVA <0.1 and 0.1 to <0.5 decreased, while that of ≥0.5 increased at the last visit compared with the initial visit.

Conclusions

Ocular findings of FUS in Japanese FUS patients were consistent with the characteristic features. The low prevalence of FUS in Japan may be a result of being overlooked and misdiagnosed as mild idiopathic uveitis, cataract, and/or glaucoma.
Integrated metagenomics and targeted-metabolomics analysis of the effects of phenylalanine on loperamide-induced constipation in rats
Authors: Yang Chuanli , Bai Xinshu , Hu Tianjiao , Xue Xin , Su Xiaohu , Zhang Xuan , Wu Teng , Zhang Mingxia , Shen Xiaobing , Dong Xiushan
Published: September 2022

Functional constipation is a common functional gastrointestinal disease. In our previous study, we found that the gut microbiota structure was disordered and the level of phenylalanine (Phe) in serum was decreased in constipated women. We conducted the present study to elucidate the role of Phe in remodeling the composition of gut microbiota and the relationship between gut microbiota and serum metabolites. Here, we demonstrated that Phe treatment significantly enhanced intestinal motility, suppressed inflammatory responses, and prevented intestinal barrier damage in rats with loperamide (Lop)-induced constipation. By metagenomic sequencing, the disbalanced gut microbial profile was analyzed in constipated rats. Phe treatment reversed changes in the abundance of several gut bacteria at the phylum, genus, and species levels. Further, we observed distinct metabolic patterns in constipated rats through targeted metabolomics and identified constipation-related gut microbial species linked to changes in circulating neurotransmitter metabolites. The abundances of species s_Lactobacillus murinus, s_Enterococcus italicus, s_Lactobacillus animalis, s_Lactobacillus apodemi, s_Enterococcus faecalis, and s_Lactobacillus backii were positively correlated with L-asparagine, L-Glutamic acid, Putrescine, and Spermidine levels. The abundances of s_Lactobacillus johnsonii and s_Butyricimonas virosa were negatively correlated with L-asparagine, L-Glutamic acid, Putrescine, and Spermidine levels. Taken together, our findings suggest that Phe can ameliorate the development of Lop-induced constipation in rats by remodeling the gut microbial community structure and changing metabolite levels.
Molecular docking study of various Enterovirus—A71 3C protease proteins and their potential inhibitors
Authors: Le Tran Thao Vy , Do Phuc-Chau
Published: September 2022

Hand, foot, and mouth disease (HFMD) is a common infection that primarily affects children in preschool and kindergarten; however, there is yet no vaccination or therapy available. Despite the fact that current research is only focused on numerous strains of Enterovirus—A71 (EV-A71) 3C protease (3Cpro), these investigations are entirely separate and unrelated. Antiviral agents must therefore be tested on several EV strains or mutations. In total, 21 previously reported inhibitors were evaluated for inhibitory effects on eight EV-A71 3Cpro, including wild-type and mutant proteins in this study, and another 29 powerful candidates with inhibitory effects on EV-A71 were investigated using the molecular docking approach. This method is to determine the broad-spectrum of the antiviral agents on a range of strains or mutants because the virus frequently has mutations. Even though Rupintrivir is reported to pass phase I clinical trial, 4-iminooxazolidin-2-one moiety (FIOMC) was shown to have a broader anti-3Cpro spectrum than Rupintrivir. Meanwhile, Hesperidin possessed a better 3Cpro inhibitory capability than FIOMC. Thus, it could be considered the most promising candidate for inhibiting various strains of EV-A71 3Cpro proteins in the newly anti-EV compounds group. Furthermore, the mutation at E71A has the most significant impact on the docking results of all ligands evaluated. Future in vitro experiments on Hesperidin’s ability to inhibit 3Cpro activity should be conducted to compare with FIOMC’s in vitro results and validate the current in silico work.
A metabolism-associated gene signature for prognosis prediction of hepatocellular carcinoma
Authors: Tian Yilin , Lu Jing , Qiao Yongxia
Published: September 2022

Hepatocellular carcinoma (HCC), the most frequently occurring type of cancer, is strongly associated with metabolic disorders. In this study, we aimed to characterize the metabolic features of HCC and normal tissue adjacent to the tumor (NAT). By using samples from The Cancer Genome Atlas (TCGA) liver cancer cohort and comparing 85 well-defined metabolic pathways obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG), 70 and 7 pathways were found to be significantly downregulated and upregulated, respectively, in HCC, revealing that tumor tissue lacks the ability to maintain normal metabolic levels. Through unsupervised hierarchical clustering of metabolic pathways, we found that metabolic heterogeneity correlated with prognosis in HCC samples. Thus, using the least absolute shrinkage and selection operator (LASSO) and filtering independent prognostic genes by the Cox proportional hazards model, a six-gene-based metabolic score model was constructed to enable HCC classification. This model showed that high expression of LDHA and CHAC2 was associated with an unfavorable prognosis but that high ADPGK, GOT2, MTHFS, and FTCD expression was associated with a favorable prognosis. Patients with higher metabolic scores had poor prognoses (p value = 2.19e-11, hazard ratio = 3.767, 95% CI = 2.555–5.555). By associating the score level with clinical features and genomic alterations, it was found that NAT had the lowest metabolic score and HCC with tumor stage III/IV the highest. qRT‒PCR results for HCC patients also revealed that tumor samples had higher score levels than NAT. Regarding genetic alterations, patients with higher metabolic scores had more TP53 gene mutations than those with lower metabolic scores (p value = 8.383e-05). Validation of this metabolic score model was performed using another two independent HCC cohorts from the Gene Expression Omnibus (GEO) repository and other TCGA datasets and achieved good performance, suggesting that this model may be used as a reliable tool for predicting the prognosis of HCC patients.
Assessing spatial learning and memory in mice: Classic radial maze versus a new animal-friendly automated radial maze allowing free access and not requiring food deprivation
Authors: Kohler Joel , Mei Jie , Banneke Stefanie , Winter York , Endres Matthias , Emmrich Julius Valentin
Published: September 2022

The radial arm maze (RAM) is a common behavioral test to quantify spatial learning and memory in rodents. Prior attempts to refine the standard experimental setup have been insufficient. Previously, we demonstrated the feasibility of a fully automated, voluntary, and stress-free eight-arm RAM not requiring food or water deprivation. Here, we compared this newly developed refined RAM to a classic manual experimental setup using 24 female 10–12 weeks old C57BL/6J mice. We used a lipopolysaccharide (LPS)-induced model of systemic inflammation to examine long-term cognitive impairment for up to 13 weeks following LPS injection. Both mazes demonstrated robust spatial learning performance during the working memory paradigm. The refined RAM detected spatial learning and memory deficits among LPS-treated mice in the working memory paradigm, whereas the classic RAM detected spatial learning and memory deficits only in the combined working/reference memory paradigm. In addition, the refined RAM allowed for quantification of an animal’s overall exploratory behavior and day/night activity pattern. While our study highlights important aspects of refinement of the new setup, our comparison of methods suggests that both RAMs have their respective merits depending on experimental requirements.
Reliability of TMS measurements using conventional hand-hold method with different numbers of stimuli for tibialis anterior muscle in healthy adults
Authors: Su Bin , Jia Yanbing , Zhang Li , Li Duo , Shen Qianqian , Wang Chun , Chen Yating , Gao Fanglan , Wei Jing , Huang Guilan , Liu Hao , Wang Lin
Published: September 2022

Objective: The objective of this study was to determine the reliability of corticomotor excitability measurements using the conventional hand-hold transcranial magnetic stimulation (TMS) method for the tibialis anterior (TA) muscle in healthy adults and the number of stimuli required for reliable assessment.

Methods: Forty healthy adults participated in three repeated sessions of corticomotor excitability assessment in terms of resting motor threshold (rMT), slope of recruitment curve (RC), peak motor evoked potential amplitude (pMEP), and MEP latency using conventional TMS method. The first two sessions were conducted with a rest interval of 1 h, and the last session was conducted 7–10 days afterward. With the exception of rMT, the other three outcomes measure elicited with the block of first 3–10 stimuli were analyzed respectively. The within-day (session 1 vs. 2) and between-day (session 1 vs. 3) reliability for all four outcome measures were assessed using intraclass correlation coefficient (ICC), standard error of measurement, and minimum detectable difference at 95% confidence interval.

Results: Good to excellent within-day and between-day reliability was found for TMS-induced outcome measures examined using 10 stimuli (ICC ≥ 0.823), except in pMEP, which showed between-day reliability at moderate level (ICC = 0.730). The number of three stimuli was adequate to achieve minimum acceptable within-day reliability for all TMS-induced parameters and between-day reliability for MEP latency. With regard to between-day reliability of RC slope and pMEP, at least seven and nine stimuli were recommended respectively.

Conclusion: Our findings indicated the high reliability of corticomotor excitability measurement by TMS with adequate number of stimuli for the TA muscle in healthy adults. This result should be interpreted with caveats for the specific methodological choices, equipment setting, and the characteristics of the sample in the current study.

Clinical Trial Registration:http://www.chictr.org.cn, identifier ChiCTR2100045141.
Balance control impairments in Fabry disease
Authors: Peultier-Celli Laetitia , Jaussaud Roland , Kaminsky Pierre , Deibener-Kaminsky Joëlle , Feillet François , Perrin Philippe
Published: September 2022

Background

Fabry disease (FD) is a rare inherited lysosomal storage disorder caused by the deficiency of the enzyme alpha-galactosidase A. This deficiency leads to an accumulation of glycosphingolipids leading to progressive and multisystemic disease, including renal, cardiac, and neurological damages. FD may also have neuro-otological and visual impairments, which can generate postural control alterations, inner ear, and vision being involved in this function. This study aimed to evaluate the impact of FD on postural control.

Methods

In total, fourteen adult patients (8 men/6 women, mean age = 37.6 ± 11.4 years) and two children (mean age = 11 years) with FD and 19 healthy adults (12 men/7 women, mean age = 36.5 ± 16.9 years) and two healthy children (mean age = 10.5 years) took part in this study. Postural control was evaluated by a sensory organization test combining three visual situations (eyes open, eyes closed, and sway referenced visual surround motion) with two platform situations (stable platform and sway referenced platform motion), aiming to calculate a composite equilibrium score (CES), a high score being representative of good postural control. Somatosensory (RSOM), visual (RVIS), and vestibular (RVEST) contributions to postural control were calculated, a low score reflecting a poor use of the indicated sensory input.

Results

The CES was lower in adult patients with FD compared with the healthy subjects (p < 0.001). RVIS (p = 0.001) and RVEST (p = 0.003) were lower in patients with FD compared with the control group, whereas no difference in RSOM was observed.

Conclusion

Inner ear and visual pathologies associated with the central nervous system impairments are factors of postural control impairments. Physical activities, which can also be rehabilitative, by maintaining or increasing the weight of proprioception, may help diminish dependency on altered sensorial inputs.
A precise language network revealed by the independent component-based lesion mapping in post-stroke aphasia
Authors: Ren Weijing , Jia Chunying , Zhou Ying , Zhao Jingdu , Wang Bo , Yu Weiyong , Li Shiyi , Hu Yiru , Zhang Hao
Published: September 2022

Brain lesion mapping studies have provided the strongest evidence regarding the neural basis of cognition. However, it remained a problem to identify symptom-specific brain networks accounting for observed clinical and neuroanatomical heterogeneity. Independent component analysis (ICA) is a statistical method that decomposes mixed signals into multiple independent components. We aimed to solve this issue by proposing an independent component-based lesion mapping (ICLM) method to identify the language network in patients with moderate to severe post-stroke aphasia. Lesions were first extracted from 49 patients with post-stroke aphasia as masks applied to fMRI data in a cohort of healthy participants to calculate the functional connectivity (FC) within the masks and non-mask brain voxels. ICA was further performed on a reformatted FC matrix to extract multiple independent networks. Specifically, we found that one of the lesion-related independent components (ICs) highly resembled classical language networks. Moreover, the damaged level within the language-related lesioned network is strongly associated with language deficits, including aphasia quotient, naming, and auditory comprehension scores. In comparison, none of the other two traditional lesion mapping methods found any regions responsible for language dysfunction. The language-related lesioned network extracted with the ICLM method showed high specificity in detecting aphasia symptoms compared with the performance of resting ICs and classical language networks. In total, we detected a precise language network in patients with aphasia and proved its efficiency in the relationship with language symptoms. In general, our ICLM could successfully identify multiple lesion-related networks from complicated brain diseases, and be used as an effective tool to study brain-behavior relationships and provide potential biomarkers of particular clinical behavioral deficits.
Comparison of visual requirements and regulations for obtaining a driving license in different European countries and some open questions on their adequacy
Authors: Kobal Nina , Hawlina Marko
Published: September 2022

We reviewed the current state of knowledge regarding visual function and its suitability as part of medical examinations for driving licenses. We focused only on Group 1 drivers. According to previous studies, visual acuity, which is the most common test, is weakly associated with a higher risk of road accidents, with a greater role of visual field. The inclusion of the visual field test in medical examinations is therefore important, but the actual limit value is still unclear and further research in specific situations is needed. Color vision impairment was not found a threat to traffic safety. Contrast sensitivity decreases with age and is affected by abnormal eye conditions. Resulting glare can lead to an increased risk of traffic accidents during night driving in the elderly and others with conditions that impair contrast sensitivity. However, the universal cut-off limits have not been established either. The current European Union (EU) regulations therefore reflect minimum common denominator across the member states which may not entirely translate to optimal driving safety. Due to these open questions, standardized testing in simulators or on polygons that simulate real life conditions would be needed to better determine safe limits of visual function in different conditions. As there is a need to have better standardization across Europe regarding the requirements and rules regarding driving licenses in European countries, we first analyzed existing rules and compared them with each other, also in terms of deviations from the EU directive itself. We reviewed the literature in this field and prepared proposals for a more optimal regulation of the rules in the future. Particular attention is paid to the new method of examining the visual field that was created to respect the European directive. The paper can serve as a basis of information for research teams to design further protocols, as it gathers research findings to date on the importance and impact of various visual functions on driving safety, as well as a starting point for a debate on revising existing rules for obtaining and maintaining licenses, as it compares the current regulations in European countries and differences between them.
Electrophysiological indices of pain expectation abnormalities in fibromyalgia patients
Authors: Barjola Paloma , Peláez Irene , Ferrera David , González-Gutiérrez José Luis , Velasco Lilian , Peñacoba-Puente Cecilia , López-López Almudena , Fernandes-Magalhaes Roberto , Mercado Francisco
Published: September 2022

Fibromyalgia is a chronic pain syndrome characterized by dysfunctional processing of nociceptive stimulation. Neuroimaging studies have pointed out that pain-related network functioning seems to be altered in these patients. It is thought that this clinical symptomatology may be maintained or even strengthened because of an enhanced expectancy for painful stimuli or its forthcoming appearance. However, neural electrophysiological correlates associated with such attentional mechanisms have been scarcely explored. In the current study, expectancy processes of upcoming laser stimulation (painful and non-painful) and its further processing were explored by event-related potentials (ERPs). Nineteen fibromyalgia patients and twenty healthy control volunteers took part in the experiment. Behavioral measures (reaction times and subjective pain perception) were also collected. We manipulated the pain/no pain expectancy through an S1–S2 paradigm (cue-target). S1 (image: triangle or square) predicted the S2 appearance (laser stimulation: warmth or pinprick sensation). Laser stimuli were delivered using a CO2 laser device. Temporal and spatial principal component analyses were employed to define and quantify the ERP component reliability. Statistical analyses revealed the existence of an abnormal pattern of pain expectancy in patients with fibromyalgia. Specifically, our results showed attenuated amplitudes at posterior lCNV component in anticipation of painful stimulation that was not found in healthy participants. In contrast, although larger P2 amplitudes to painful compared to innocuous events were shown, patients did not show any amplitude change in this laser-evoked response as a function of pain predictive cues (as occurred in the healthy control group). Additionally, analyses of the subjective perception of pain and reaction time indicated that laser stimuli preceded by pain cues were rated as more painful than those signaling non-pain expectancy and were associated with faster responses. Differences between groups were not found. The present findings suggest the presence of dysfunction in pain expectation mechanisms in fibromyalgia that eventually may make it difficult for patients to correctly interpret signs that prevent pain symptoms. Furthermore, the abnormal pattern in pain expectancy displayed by fibromyalgia patients could result in ineffective pain coping strategies. Understanding the neural correlates of pain processing and its modulatory factors is crucial to identify treatments for chronic pain syndromes.
Low frequency repetitive transcranial magnetic stimulation to the right dorsolateral prefrontal cortex engages thalamus, striatum, and the default mode network
Authors: Caparelli Elisabeth de Castro , Abulseoud Osama A. , Gu Hong , Zhai Tianye , Schleyer Brooke , Yang Yihong
Published: September 2022

The positive treatment outcomes of low frequency (LF) repetitive transcranial magnetic stimulation (rTMS) when applied over the right dorsolateral prefrontal cortex (DLPFC) in treatment-refractory depression has been verified. However, the mechanism of action behind these results have not been well-explored. In this work we used simultaneous functional magnetic resonance imaging (fMRI) during TMS to explore the effect of LF rTMS on brain activity when applied to the right [RDLPFC1 (MNI: 50, 30, 36)] and left DLPFC sites [LDLPFC1 (MNI: -50, 30, 36), LDLPFC2 (MNI: -41, 16, 54)]. Seventeen healthy adult volunteers participated in this study. To identify brain areas affected by rTMS, an independent component analysis and a general linear model were used. Our results showed an important laterality effect when contrasting rTMS over the left and right sites. Specifically, LF rTMS increased brain activity at the striatum, thalamus, and areas of the default mode network when applied to the right, but not to the contralateral left DLPFC. In contrast, no site differences were observed when evaluating the effect of LF rTMS over the two left sites. These findings demonstrate that LF rTMS to the right DLPFC was able to stimulate the cortico-striato-thalamo-cortical pathway, which is dysregulated in patients with major depressive disorder; therefore, possibly providing some neurobiological justification for the successful outcomes found thus far for LF rTMS in the treatment of depression.
Study on the drunkenness of Chinese Baijiu with representative flavor based on behavioral characteristics
Authors: Guo Xuefeng , Cheng Yuxin , Huang Yongguang
Published: September 2022

The essential role of drunkenness on the healthy development of Chinese Baijiu was studied in this research. This study revealed the effects of Baijiu on the behaviors of mice and evaluated the degree of drunkenness of soy sauce-, strong-, light-, and light and soy sauce-flavored Baijiu. The parameters obtained from the open field test were transformed into the behavioral drunkenness index by mathematical statistical analysis and the drunkenness-associated key compounds of Baijiu were analyzed. The results showed that strong- and light-flavored Baijiu presented higher levels of drunkenness and sobriety than soy sauce-flavored Baijiu. Interestingly, light and soy sauce-flavored Baijiu showed low drunkenness but a high sobriety degree. Specifically, the degree of drunkenness was positively correlated with fusel alcohol and aldehydes but negatively correlated with esters and acids. This study will enrich references for Baijiu behavior studies and lay a foundation for the research and development of healthy Baijiu.
A functional role for Serum Amyloid A in the molecular regulation of autophagy in breast cancer
Authors: du Plessis Manisha , Davis Tanja Andrea , Olivier Daniel Wilhelm , de Villiers Willem Johan Simon , Engelbrecht Anna-Mart
Published: September 2022

It has been established that the acute phase protein, Serum amyloid A (SAA), which is usually synthesized by the liver, is also synthesized by cancer cells and cancer-associated cells in the tumor microenvironment. SAA also activates modulators of autophagy, such as the PI3K/Akt and MAPK signaling pathways. However, the role of SAA in autophagy in breast cancer still remains to be elucidated. The aim of this study was to investigate the role of SAA in the regulation of signaling pathways and autophagy in in vitro and in vivo models of breast cancer. The MDA-MB-231 and MCF7 cell lines were transiently transfected to overexpress SAA1. A tumor-bearing SAA1/2 knockout mouse model was also utilized in this study. SAA1 overexpression activated ERK signaling in the MDA-MB-231 cells, downregulated the PI3K pathway protein, PKB/Akt, in the MCF7 cell line, while SAA1/2 knockout also inhibited Akt. Furthermore, SAA1 overexpression in vitro downregulated autophagy, while the expression of SQSTM1/p62 was increased in the MCF7 cells, and SAA1/2 knockout induced autophagy in vivo. SAA overexpression in the MDA-MB-231 and MCF7 cells resulted in an increase in cell viability and increased the expression of the proliferation marker, MCM2, in the MCF7 cells. Furthermore, knockout of SAA1/2 resulted in an altered inflammatory profile, evident in the decrease of plasma IL-1β, IL-6 and IL-10, while increasing the plasma levels of MCP-1 and TNF-α. Lastly, SAA1/2 knockout promoted resistance to apoptosis and necrosis through the regulation of autophagy. SAA thus regulates autophagy in breast cancer cells to promote tumorigenesis.
ITGB5 promotes innate radiation resistance in pancreatic adenocarcinoma by promoting DNA damage repair and the MEK/ERK signaling pathway
Authors: Wen Xin , Chen Si , Chen Xueting , Qiu Hui , Wang Wei , Zhang Nie , Liu Wanming , Wang Tingting , Ding Xin , Zhang Longzhen
Published: September 2022

Pancreatic adenocarcinoma (PAAD) is one of the most aggressive digestive system tumors in the world, with a low early diagnosis rate and a high mortality. Integrin beta 5 (ITGB5) is demonstrated to be a potent tumor promoter in several carcinomas. However, it is unknown whether ITGB5 participates in the occurrence and development of PAAD. In this study, we confirmed a high expression of ITGB5 in PAAD and its role in promoting invasiveness and transitivity in PAAD. Besides, the knockdown of ITGB5 increased cell sensitivity to radiation by promoting DNA damage repair and the MEK/ERK signaling pathway. Collectively, these results show that ITGB5 plays an essential role in pancreatic cancer growth and survival.
Palestinian Patients with Cancer at King Hussein Cancer Center
Authors: Mansour Razan , Amarin Justin Z. , Al-Ani Abdallah , Al-Hussaini Maysa , Mansour Asem
Published: September 2022

Background

The Palestinian Ministry of Health (MoH) routinely refers Palestinian patients with cancer to King Hussein Cancer Center (KHCC), the largest cancer center in the Middle East.

Aims

We aimed to describe the characteristics of Palestinian patients with cancer.

Methods

We performed a retrospective chart review of all Palestinian patients with cancer who were treated at KHCC during 2018 and 2019, of which demographic and clinical characteristics were presented.

Results

We initially started with 521 cases, out of which 41 (7.9%) cases were excluded due to misdiagnosis as malignant on pathology review. We included 480 patients with a confirmed diagnosed of cancer. Most patients were adults (88.8%) with a mean age of 50.0 ± 15.0 years ranging from 19 to 87 years. The most common cancer sites in adult men, who comprised 46.9% of the cohort were the hematolymphoid system (23.5%), followed by the digestive system (17.5%), and lung and pleura (11.5%). In women (53.1%), the most common cancer sites were the breast (46.0%), followed by the digestive system (15.0%), and the hematolymphoid system (10.2%). Children and adolescents accounted for 11.3% of the total cases, among which the hematolymphoid system was the most common cancer site (50%), followed by the brain (14.8%). About 36.0% of all patients presented with advanced-stage disease (i.e., distant metastasis).

Conclusion

The most common cancer sites in our cohort are generally similar to data from the Palestinian territories. Many patients presented with advanced-stage disease, which signals the need for awareness campaigns and screening programs. Benign tumors are misdiagnosed in many patients as cancer. The limited resources and facilities including human resources remain important challenges to the proper and timely diagnosis and management of cancer among Palestinians living in the Palestinian Territories.
COMMD4 is a novel prognostic biomarker and relates to potential drug resistance mechanism in glioma
Authors: Liu Zongheng , Peng Long , Sun Yidan , Lu Zhichao , Wu Bing , Wang Weichen , Zhang Xiaomei , Hao Haiyan , Gong Peipei
Published: September 2022

Background: Glioma as the most frequently discovered tumor affecting the brain shows significant morbidity and fatality rates with unfavorable prognosis. There is an urgent need to find novel therapeutic targets to overcome the low chemotherapeutic efficacy of glioma. This research examined whether the copper-metabolism-domain protein, COMMD4, had predictive and therapeutic significance in glioma.

Methods: Using the freely accessible CGGA (The Chinese Glioma Atlas) and TCGA (The Cancer Genome Atlas) databases, we examined the function of COMMD4 in GBM and LGG. CIBERSORT and TIMER were utilized to assess the associations between COMMD4 and immune cells. The Gene Set Enrichment Analysis (GSEA) was employed to examine the functional data. Furthermore, the link between COMMD4 expression and predicted treatment response was evaluated via CellMiner Cross-Database. Meanwhile, qRT-PCR was conducted to examine COMMD4 expression in human glioma. Finally, Migration and invasion of glioma cells (U-87, U-251) were assessed using transwell assays. R was used to analyze the statistical data.

Results: According to our findings, COMMD4 expression level was higher in patients having grade-dependent glioma who also showed an unfavorable prognosis. Furthermore, qRT-PCR confirmed the high expression of COMMD4 in glioma tissues and cells. Additionally, using integrated correlation analysis, we acquired significant prognostic findings between isocitrate dehydrogenase 1(IDH1) and COMMD4. Meanwhile, a link between COMMD4 and many tumor-infiltrating immune cells was observed. GSEA and drug response analysis revealed the potential mechanism of COMMD4 in drug resistance of glioma.

Conclusion: The current findings validated COMMD4 as a novel biological marker, which might offer insights into the possible drug resistance mechanisms and the impact of the immune microenvironment on glioma. COMMD4 might be used to predict glioma prognosis.
Indirect effect of alpha-1-antitrypsin on endotoxin-induced IL-1β secretion from human PBMCs
Authors: Janciauskiene Sabina , Tumpara Srinu , Schebb Nils Helge , Buettner Falk F. R. , Mainka Malwina , Sivaraman Kokilavani , Immenschuh Stephan , Grau Veronika , Welte Tobias , Olejnicka Beata
Published: September 2022

Human alpha-1-antitrypsin (AAT) encoded by theSERPINA1gene, is an acute phase glycoprotein that regulates inflammatory responsesviaboth protease inhibitory and non-inhibitory activities. We previously reported that AAT controls ATP-induced IL-1β release from human mononuclear cells by stimulating the release of small bioactive molecules. In the current study, we aimed to elucidate the identity of these putative effectors released from human PBMCs in response to AAT, which may inhibit the LPS-induced release of IL-1β. We pre-incubated human PBMCs alone or with different preparations of AAT (4 mg/ml) for 30 min at 37°C, 5% CO2, and collected cell supernatants filtered through centrifugal filters (cutoff 3 kDa) to eliminate AAT and other high molecular weight substances. Supernatants passed through the filters were used to culture PBMCs isolated from the autologous or a heterologous donors with or without adding LPS (1 μg/ml) for 6 h. Unexpectedly, supernatants from PBMCs pre-incubated with AAT (Zemaira®), but not with other AAT preparations tested or with oxidized AAT (Zemaira®), lowered the LPS-induced release of IL-1β by about 25%–60% without affectingIL1BmRNA. The reversed-phase liquid chromatography coupled with mass spectrometry did not confirm the hypothesis that small pro-resolving lipid mediators released from PBMCs after exposure to AAT (Zemaira®) are responsible for lowering the LPS-induced IL-1β release. Distinctively from other AAT preparations, AAT (Zemaira®) and supernatants from PBMCs pre-treated with this protein contained high levels of total thiols. In line, mass spectrometry analysis revealed that AAT (Zemaira®) protein contains freer Cys232 than AAT (Prolastin®). Our data show that a free Cys232 in AAT is required for controlling LPS-induced IL-1β release from human PBMCs. Further studies characterizing AAT preparations used to treat patients with inherited AAT deficiency remains of clinical importance.
City network mining in china’s yangtze river economic belt based on “two-way time distance” modified gravity model and social network analysis
Authors: Chai Duo , Du Jiaze , Yu Zongqi , Zhang Dong
Published: September 2022

In order to improve the city network mining method, the inter-cities’ connection strength, structure and density, and distribution patterns of city network in the Yangtze River Economic Belt of China have been empirically analyzed through the combined application of SNA method, “Dual-direction time distance” modified gravity model and ArcGIS geographic visualization method. The results show that the modified gravity model can better reveal the interaction differences between cities and reflect the current and potential economic, population and resource relations among cities. The city network density of this area has positively close relationship with the regional economic development level. The average value of degree centrality in the basin is high, but the difference between cities is obvious. The “agglomeration effect” of the central cities is significant, and the urban connections have an obvious cluster structure, showing an “M” shaped spatial distribution along the Yangtze River; The inner interaction strength of city network subgroups is high, but the connection between subgroups is low. The law of “downstream > midstream > upstream” also appears on the closeness centrality and betweenness centrality. In the future, it is essential to improve the integration and multi-level connections of urban agglomeration in the river basin and form a development pattern of “downstream driving - midstream transition - upstream connection”; strengthen the functions and connections of central and subcentral cities.