bluuebunny/crossref_metadata_2025 huggingface dataset:
Simple low-cost construction and calibration of accurate pneumotachographs for monitoring mechanical ventilation in low-resource settings
Authors: Farré Ramon , Rodríguez-Lázaro Miguel A. , Gozal David , Trias Gerard , Solana Gorka , Navajas Daniel , Otero Jorge
Published: August 2022

Assessing tidal volume during mechanical ventilation is critical to improving gas exchange while avoiding ventilator-induced lung injury. Conventional flow and volume measurements are usually carried out by built-in pneumotachographs in the ventilator or by stand-alone flowmeters. Such flow/volume measurement devices are expensive and thus usually unaffordable in low-resource settings. Here, we aimed to design and test low-cost and technically-simple calibration and assembly pneumotachographs. The proposed pneumotachographs are made by manual perforation of a plate with a domestic drill. Their pressure-volume relationship is characterized by a quadratic equation with parameters that can be tailored by the number and diameter of the perforations. We show that the calibration parameters of the pneumotachographs can be measured through two maneuvers with a conventional resuscitation bag and by assessing the maneuver volumes with a cheap and straightforward water displacement setting. We assessed the performance of the simplified low-cost pneumotachographs to measure flow/volume during mechanical ventilation as carried out under typical conditions in low-resource settings, i.e., lacking gold standard expensive devices. Under realistic mechanical ventilation settings (pressure- and volume-control; 200–600 mL), inspiratory tidal volume was accurately measured (errors of 2.1% on average and <4% in the worst case). In conclusion, a simple, low-cost procedure facilitates the construction of affordable and accurate pneumotachographs for monitoring mechanical ventilation in low- and middle-income countries.
Adherence to weekly anal self-examination among men who have sex with men for detection of anal syphilis
Authors: Aung Ei T. , Fairley Christopher K. , Ong Jason J. , Phillips Tiffany P. , Tran Julien , Chen Marcus Y. , Maddaford Kate , Chow Eric P. F.
Published: August 2022

Background

Men who have sex with men (MSM) practicing exclusively receptive anal sex are more likely to present with secondary than primary syphilis, implying primary anorectal lesions may be missed. If men could detect anorectal lesions by regular anal self-examination, the duration of infectiousness could be reduced. This study aimed to examine adherence to weekly anal self-examination.

Method

We conducted a longitudinal feasibility study examining the adherence to weekly anal self-examinations among MSM attending a sexual health clinic in Melbourne, Australia between December 2020 and June 2021. Adherence to weekly anal self-examinations over 12 weeks was assessed from a logbook and 4-weekly surveys. Participants who identified abnormalities in their anus were recommended to seek medical review.

Results

Of the 30 men who completed the study, anal self-examination was performed at least weekly for 308 of 360 person-weeks (86% of the weeks, 95% CI: 82–89). The mean adherence was 3.6 (95% CI: 3.3–3.9) examinations per 4-weeks per person in Weeks 1–4, 3.5 (95% CI: 3.1–3.8) in Weeks 5–8 and 3.3 (95% CI: 2.9–3.7) in Weeks 9–12 (Ptrend = 0.06). Six men (20%, 6/30) were seen for medical review after they identified abnormalities, whilst eight men (27%, 8/30) reported abnormalities, but did not seek medical review. No participants were diagnosed with syphilis during the study period.

Conclusion

We conclude that men adhered well to weekly anal self-examination. Therefore, it is feasible to trial this as a routine practice among MSM. Future studies should investigate possible reductions in adherence over time and ways to increase medical review for abnormalities that men find.
Case report: A case of corneal epithelial injury associated with Pthiriasis palpebrarum
Authors: Wang Da-Hu , Liu Xin-Quan
Published: August 2022

Significance

Phthiriasis palpebrarum is an uncommon infection due to Phthirus pubis inoculating the eyelashes and surrounding tissues of the eye. Because of its rarity, it may be misdiagnosed as blepharitis or conjunctivitis clinically.

Purpose

This report described a rare case of corneal epithelial injury associated with Phthiriasis palpebrarum.

Case report

A 59-year-old woman presented with 1 month history of repeated episodes of itching and irritation symptoms in both eyes. A slit-lamp examination was performed, which revealed mild conjunctival hyperemia and corneal epithelial defects in both eyes. On closer examination, crab-like lice, nits, and red pinpoint excretions were seen on her eyelashes and eyelids bilaterally. Corneal fluorescein staining in both eyes was observed, and tear film break-up time (BUT) in each eye was 2 s. Numerous lice were also found attached to the scalp hair. Therefore, a clinical diagnosis of corneal epithelial injury associated with Pthiriasis palpebrarum was made. For treatment, eyelashes with nits and/or lice were removed mechanically with a fine tweezers. Then, 0.01% Hypochlorous Acid eye wash was used to clean the eyelid margin twice daily. Also, she was prescribed a combination of Vitamin A Palmitate eye gel three times a day and Tobradex® eye ointment once daily. Meanwhile, the patient was provided with suggestions on how to improve personal hygiene and environmental hygiene, including cutting of the scalp hair and the application of 0.01% permethrin rinse. One week later, no evidence of lice and nits of the eyelashes and scalp hair was found, and the patient's symptoms and signs also improved significantly.

Conclusion

This rare case suggested that the eyelashes of patients presenting with itching and irritation symptoms should be carefully examined with a slit-lamp. Besides removal of the parasites, attention should be paid to the treatment of corneal epithelial injury associated with Pthiriasis palpebrarum.
Rapid progression of marginal zone B-cell lymphoma after COVID-19 vaccination (BNT162b2): A case report
Authors: Sekizawa Akinori , Hashimoto Kenichi , Kobayashi Shinichi , Kozono Sawako , Kobayashi Takahiro , Kawamura Yusuke , Kimata Motohiro , Fujita Naoya , Ono Yosuke , Obuchi Yasuhiro , Tanaka Yuji
Published: August 2022

B-cell lymphomas are neoplastic diseases occasionally associated with chronic inflammation. mRNA vaccines for coronavirus disease 2019 (COVID-19) induce inflammatory responses, which often lead to fever and lymphadenopathies indistinguishable from lymphomas. Although both lymphadenopathies and lymphomas can be influential, the correlation between them is unclear. Herein, we present the first case of marginal zone B-cell lymphoma following mRNA COVID-19 vaccination. An 80-year-old Japanese woman presented with a right temporal mass that appeared the morning after she was administered her first mRNA COVID-19 vaccination (BNT162b2). The mass gradually decreased in size but persisted over 6 weeks after her first vaccination (3 weeks after her second vaccination). At her first visit to our hospital, ultrasound revealed the size of the mass to be 28.5 × 5.7 mm, and computed tomography revealed multiple lymphadenopathies in the right parotid, submandibular, jugular, and supraclavicular regions. Initially, we suspected head-and-neck benign lymphadenopathy as a side effect of vaccination. Nine weeks later, the number of swollen submandibular and parotid glands increased, and the lymph nodes further enlarged. Finally, the right temporal mass was diagnosed as marginal zone B-cell lymphoma based on immunohistochemical and flow cytometry findings of biopsy specimens. Our findings suggest that although 4–6 weeks of observation for lymph node inflammation after the second vaccination is recommended, malignancy should also be considered in the differential diagnosis of lymphadenopathy following vaccination.
Case report: Bilateral central serous chorioretinopathy-like abnormalities in a man with pulmonary arterial hypertension
Authors: Zhou Xinrong , Zhang Jingxiang , Gu Limin , Zhou Hao , Zhang Jingfa
Published: August 2022

Background

Pulmonary arterial hypertension (PAH) leads to progressive increases in pulmonary vascular resistance, right heart failure, and death if left untreated. Ocular complications secondary to PAH were less reported. In this study, we reported a case of bilateral visual loss and metamorphopsia in a patient with PAH, who developed central serous chorioretinopathy (CSCR)-like abnormalities and optic disc atrophy.

Case summary

A 45-year-old man presented with decreasing central vision and metamorphopsia in both eyes. He had a history of PAH and 6-year history of low-dose oral sildenafil treatment. Slit-lamp examination revealed prominent dilated and tortuous episcleral and conjunctival vessels. Ultrawide-field color picture showed retinal pigment epithelial mottling and atrophy in ring-like configurations. Ultrawide-field autofluorescence showed multiple irregular hyper-autofluorescence with a constellation-like pattern surrounding the optic nerve head and macular region. Optical coherence tomography angiography (OCTA) b-scan demonstrated CSCR-like changes. Swept-source optical coherence tomography (SS-OCT) analysis showed optic nerve atrophy with enlarged cup/disc ratio in right eye, which was confirmed with perimetry. Fluorescein angiography (FA) showed marked leakage of macula and optic nerve head with time, cystoid macular edema, early blocking with late staining of the flecks as shown in the backgrounds of infrared and autofluorescence, and mild leakage in peripheral retina. Indocyanine green angiography (ICGA) showed dilation, tortuosity and congestion of all vortex veins without obvious leakage.

Conclusion

Undertreated PAH may cause the congestion of the choroid and induce CSCR-like abnormalities.
Mobile Tigecycline Resistance: An Emerging Health Catastrophe Requiring Urgent One Health Global Intervention
Authors: Anyanwu Madubuike Umunna , Nwobi Obichukwu Chisom , Okpala Charles Odilichukwu R. , Ezeonu Ifeoma M.
Published: August 2022

Mobile tigecycline resistance (MTR) threatens the clinical efficacy of the salvage antibiotic, tigecycline (TIG) used in treating deadly infections in humans caused by superbugs (multidrug-, extensively drug-, and pandrug-resistant bacteria), including carbapenem- and colistin-resistant bacteria. Currently, non-mobiletet(X) and mobile plasmid-mediated transmissibletet(X) and resistance-nodulation-division (RND) efflux pumptmexCD-toprJgenes, conferring high-level TIG (HLT) resistance have been detected in humans, animals, and environmental ecosystems. Given the increasing rate of development and spread of plasmid-mediated resistance against the two last-resort antibiotics, colistin (COL) and TIG, there is a need to alert the global community on the emergence and spread of plasmid-mediated HLT resistance and the need for nations, especially developing countries, to increase their antimicrobial stewardship. Justifiably, MTR spread projects One Health ramifications and portends a monumental threat to global public and animal health, which could lead to outrageous health and economic impact due to limited options for therapy. To delve more into this very important subject matter, this current work will discuss why MTR is an emerging health catastrophe requiring urgent One Health global intervention, which has been constructed as follows: (a) antimicrobial activity of TIG; (b) mechanism of TIG resistance; (c) distribution, reservoirs, and traits of MTR gene-harboring isolates; (d) causes of MTR development; (e) possible MTR gene transfer mode and One Health implication; and (f) MTR spread and mitigating strategies.
Indigenous oil-degrading bacteria more efficient in soil bioremediation than microbial consortium and active even in super oil-saturated soils
Authors: Ali Nedaa , Khanafer Majida , Al-Awadhi Husain
Published: August 2022

A microbial consortium of the hydrocarbonoclastic bacterial species, comprising Actinotalea ferrariae, Arthrobacter ginsengisoli, Dietzia cinnamea, Dietzia papillomatosis, and Pseudomonas songnenensis, isolated from oil-saturated desert soil did not consume more oil in batch cultures than the individual species with the maximum oil consumption. In oil-polluted desert soil microcosms, the rate of oil removal in the soil samples bioaugmented with the microbial consortium was similar to the rate of oil removal in the unbioaugmented ones through a 6-month bioremediation experiment. Although the composition of hydrocarbonoclastic bacterial communities in the unbioaugmented and bioaugmented soil samples was different, the predominant bacterial species during most of the months were the same. Toward the end of the bioremediation experiment, Ar. ginsengisoli prevailed in both soil samples, suggesting its important role in oil removal. Self-cleaning proceeded in desert soil samples artificially polluted with 1, 10, 20, and 30% of crude oil and incubated at 30 °C for 6 months. Oil was removed effectively at rates reaching 73.6 and 69.3% in the soils polluted with 1 and 10% oil concentrations, respectively, and reached 50% in desert soils polluted with 20 and 30% oil concentrations. The bacterial numbers increased in all soil samples from hundreds of thousands per gram of soil samples at time zero to millions and tens of millions per gram of soil samples after 6 months. It was concluded that bioaugmenting oil-polluted soil samples with microbial consortium of hydrocarbonoclastic bacterial species with high oil removal potential did not drastically enhance oil bioremediation and that even in super oil-saturated soils, indigenous oil-degrading bacteria will prevail and effectively contribute to oil removal from the surrounding environment.
Metatranscriptome sequencing identifies Escherichia are major contributors to pathogenic functions and biofilm formation in diabetes related foot osteomyelitis
Authors: Radzieta Michael , Malone Matthew , Ahmad Mehtab , Dickson Hugh G. , Schwarzer Saskia , Jensen Slade O. , Lavery Lawrence A.
Published: August 2022

Osteomyelitis in the feet of persons with diabetes is clinically challenging and is associated with high rates of amputation. In this study RNA-sequencing was employed to explore microbial metatranscriptomes with a view to understand the relative activity and functions of the pathogen/s responsible for diabetes foot osteomyelitis (DFO). We obtained 25 intraoperative bone specimens from persons with confirmed DFO, observing that Escherichia spp. (7%), Streptomyces spp. (7%), Staphylococcus spp. (6%), Klebsiella spp. (5%) and Proteus spp. (5%) are the most active taxa on average. Data was then subset to examine functions associated with pathogenesis (virulence and toxins), biofilm formation and antimicrobial/multi-drug resistance. Analysis revealed Escherichia spp. are the most active taxa relative to pathogenic functions with K06218 (mRNA interferase relE), K03699 (membrane damaging toxin tlyC) and K03980 (putative peptidoglycan lipid II flippase murJ), K01114 (membrane damaging toxin plc) and K19168 (toxin cptA) being the most prevalent pathogenic associated transcripts. The most abundant transcripts associated with biofilm pathways included components of the biofilm EPS matrix including glycogen synthesis, cellulose synthesis, colonic acid synthesis and flagella synthesis. We further observed enrichment of a key enzyme involved in the biosynthesis of L-rhamnose (K01710 -dTDP-glucose 4,6-dehydratase rfbB, rmlB, rffG) which was present in all but four patients with DFO.
Changes in the fermentation products, taxonomic and functional profiles of microbiota during high-moisture sweet sorghum silage fermentation
Authors: Zhao Jie , Yin Xue-Jing , Wang Si-Ran , Li Jun-Feng , Dong Zhi-Hao , Shao Tao
Published: August 2022

The purpose of this study was to evaluate the fermentation quality, microbial community, and functional shifts of sweet sorghum during ensiling. The high-moisture sweet sorghum (SS) was naturally ensiled for 1, 3, 7, 15, 30, and 60 days. After 60 days of ensiling, sweet sorghum silage (SSS) showed homolactic fermentation with absent butyric acid, low pH value, acceptable concentrations of propionic acid, ethanol, and ammonia nitrogen and high lactic acid concentration. Acinetobacter, Sphingomonas, and Pseudomonas were the advantage genera in SS. While, Lactococcus, Weissella, and Pediococcus were dominant in 3-day SSS and subsequently replaced by Lactobacillus in 60-day SSS. Spearman’s correlation heatmap showed that Pediococcus and Leuconostoc were negatively related to the pH value of SSS. There were great differences in the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional profiles of SS and SSS. Ensiling process downregulated the metabolism of amino acid, energy, cofactors, and vitamins, but upregulated the metabolism of nucleotides and carbohydrates. Overall, next-generation sequencing in conjunction with KEGG functional prediction revealed the distinct differences in the initial and late phases of ensiling in terms of both community succession and functional shifts. The knowledge regarding bacterial community dynamics and functional shifts of SS during ensiling is important for understanding the fermentation mechanism and may contribute to the production of high-quality sweet sorghum silage.
ATP1A3 mutation in rapid-onset dystonia parkinsonism: New data and genotype-phenotype correlation analysis
Authors: Yu Lihua , Peng Guoping , Yuan Yuan , Tang Min , Liu Ping , Liu Xiaoyan , Ni Jie , Li Yi , Ji Caihong , Fan Ziqi , Zhu Wenli , Luo Benyan , Ke Qing
Published: August 2022

Background

Rapid-onset dystonia parkinsonism (RDP) is a rare disease caused by ATP1A3 mutation with considerable clinical heterogeneity. Increased knowledge of RDP could be beneficial in its early diagnosis and treatment.

Objective

This study aimed to summarize the gene mutation spectrum of ATP1A3 associated with RDP, and to explore the correlation of ATP1A3 variants with RDP clinical phenotypes.

Methods

In this study, we reported two RDP patients from a family with a novel inherited ATP1A3 variant. Then, we reviewed and analyzed the available literature in English focused on ATP1A3-causative RDP. A total of 35 articles covering 15 families (59 patients) and 36 sporadic RDP cases were included in our analysis.

Results

The variant A813V (2438C>T) in ATP1A3 found in our cases was a novel mutant. Delays in diagnosis were common, with a mean delay time of 14 years. ATP1A3 had distinct RDP-related mutation hotspots, which consisted of exon8, 14, 17, and 18, and the most frequently occurring variants were T613M and I578S. Approximately 74.5% of patients have specific triggers before disease onset, and 82.1% of RDPs have stable symptoms within 1 month. The incidence rates of dystonia and bradykinesia are 100 and 88.1%, respectively. The onset site varied and exhibited a rostrocaudal gradient distribution pattern in 45% of patients with RDP. Approximately 63.6% of patients had mild improvement after receiving comprehensive interventions, especially in gait disturbance amelioration.

Conclusion

In patients with acute and unexplained dystonia or bradykinesia, gene screening on ATP1A3 should be timely performed. When a diagnosis has been made, treatments that may be effective are to be attempted. Our study would be helpful for the early diagnosis and treatment of ATP1T3-related RDP.
The Structural Basis of Long-Term Potentiation in Hippocampal Synapses, Revealed by Electron Microscopy Imaging of Lanthanum-Induced Synaptic Vesicle Recycling
Authors: Heuser John E.
Published: August 2022

Hippocampal neurons in dissociated cell cultures were exposed to the trivalent cation lanthanum for short periods (15–30 min) and prepared for electron microscopy (EM), to evaluate the stimulatory effects of this cation on synaptic ultrastructure. Not only were characteristic ultrastructural changes of exaggerated synaptic vesicle turnover seen within the presynapses of these cultures—including synaptic vesicle depletion and proliferation of vesicle-recycling structures—but the overall architecture of a large proportion of the synapses in the cultures was dramatically altered, due to large postsynaptic “bulges” or herniations into the presynapses. Moreover, in most cases, these postsynaptic herniations or protrusions produced by lanthanum were seen by EM to distort or break or “perforate” the so-called postsynaptic densities (PSDs) that harbor receptors and recognition molecules essential for synaptic function. These dramatic EM observations lead us to postulate that such PSD breakages or “perforations” could very possibly create essential substrates or “tags” for synaptic growth, simply by creating fragmented free edges around the PSDs, into which new receptors and recognition molecules could be recruited more easily, and thus, they could represent the physical substrate for the important synaptic growth process known as “long-term potentiation” (LTP). All of this was created simply in hippocampal dissociated cell cultures, and simply by pushing synaptic vesicle recycling way beyond its normal limits with the trivalent cation lanthanum, but we argued in this report that such fundamental changes in synaptic architecture—given that they can occur at all—could also occur at the extremes of normal neuronal activity, which are presumed to lead to learning and memory.
Genetic association of apolipoprotein E genotype with EEG alpha rhythm slowing and functional brain network alterations during normal aging
Authors: Ponomareva Natalya V. , Andreeva Tatiana V. , Protasova Maria , Konovalov Rodion N. , Krotenkova Marina V. , Kolesnikova Ekaterina P. , Malina Daria D. , Kanavets Elena V. , Mitrofanov Andrey A. , Fokin Vitaly F. , Illarioshkin Sergey N. , Rogaev Evgeny I.
Published: August 2022

The ε4 allele of the apolipoprotein E (APOE4+) genotype is a major genetic risk factor for Alzheimer’s disease (AD), but the mechanisms underlying its influence remain incompletely understood. The study aimed to investigate the possible effect of the APOE genotype on spontaneous electroencephalogram (EEG) alpha characteristics, resting-state functional MRI (fMRI) connectivity (rsFC) in large brain networks and the interrelation of alpha rhythm and rsFC characteristics in non-demented adults during aging. We examined the EEG alpha subband’s relative power, individual alpha peak frequency (IAPF), and fMRI rsFC in non-demented volunteers (age range 26–79 years) stratified by the APOE genotype. The presence of the APOE4+ genotype was associated with lower IAPF and lower relative power of the 11–13 Hz alpha subbands. The age related decrease in EEG IAPF was more pronounced in the APOE4+ carriers than in the APOE4+ non-carriers (APOE4-). The APOE4+ carriers had a stronger fMRI positive rsFC of the interhemispheric regions of the frontoparietal, lateral visual and salience networks than the APOE4– individuals. In contrast, the negative rsFC in the network between the left hippocampus and the right posterior parietal cortex was reduced in the APOE4+ carriers compared to the non-carriers. Alpha rhythm slowing was associated with the dysfunction of hippocampal networks. Our results show that in adults without dementia APOE4+ genotype is associated with alpha rhythm slowing and that this slowing is age-dependent. Our data suggest predominant alterations of inhibitory processes in large-scale brain network of non-demented APOE4+ carriers. Moreover, dysfunction of large-scale hippocampal network can influence APOE-related alpha rhythm vulnerability.
Efficient graph convolutional networks for seizure prediction using scalp EEG
Authors: Jia Manhua , Liu Wenjian , Duan Junwei , Chen Long , Chen C. L. Philip , Wang Qun , Zhou Zhiguo
Published: August 2022

Epilepsy is a chronic brain disease that causes persistent and severe damage to the physical and mental health of patients. Daily effective prediction of epileptic seizures is crucial for epilepsy patients especially those with refractory epilepsy. At present, a large number of deep learning algorithms such as Convolutional Neural Networks and Recurrent Neural Networks have been used to predict epileptic seizures and have obtained better performance than traditional machine learning methods. However, these methods usually transform the Electroencephalogram (EEG) signal into a Euclidean grid structure. The conversion suffers from loss of adjacent spatial information, which results in deep learning models requiring more storage and computational consumption in the process of information fusion after information extraction. This study proposes a general Graph Convolutional Networks (GCN) model architecture for predicting seizures to solve the problem of oversized seizure prediction models based on exploring the graph structure of EEG signals. As a graph classification task, the network architecture includes graph convolution layers that extract node features with one-hop neighbors, pooling layers that summarize abstract node features; and fully connected layers that implement classification, resulting in superior prediction performance and smaller network size. The experiment shows that the model has an average sensitivity of 96.51%, an average AUC of 0.92, and a model size of 15.5 k on 18 patients in the CHB-MIT scalp EEG dataset. Compared with traditional deep learning methods, which require a large number of parameters and computational effort and are demanding in terms of storage space and energy consumption, this method is more suitable for implementation on compact, low-power wearable devices as a standard process for building a generic low-consumption graph network model on similar biomedical signals. Furthermore, the edge features of graphs can be used to make a preliminary determination of locations and types of discharge, making it more clinically interpretable.
Dietary pattern characterized by a balanced diet rich in high-quality protein intake is associated with mild initial clinical manifestations in tuberculosis
Authors: Li Xiaona , Zhong Zhaoyi , Liu Yufeng , Gong Guifang , Zhang Yangting , Wang Yukang , Liu Chunchun , Wang Qiuzhen
Published: August 2022

Background

The relationship between a single food or nutrient and pulmonary tuberculosis (TB) has been explored in many studies; however, the relationship between dietary patterns and TB is still lacking.

Objective

Our study aims to investigate the association between dietary patterns and the initial clinical manifestations in patients with TB.

Materials and methods

A cross-sectional study including 1,661 patients with active TB was conducted in Qingdao, China, from 2011 to 2019. A semiquantitative food frequency questionnaire was used to collect dietary data. Dietary patterns were determined by principal component factor analysis. Initial clinical manifestations were assessed using a combination of the patient self-reported clinical symptoms and the admission results indicated by the TB score. The associations between dietary patterns and TB scores in patients with TB were examined by the logistics regression model.

Results

The analysis identified four dietary patterns: meat-fruit-seafood pattern; dairy-egg pattern; beans and their products-whole grain pattern; and refined grain-vegetable pattern. In a multiple-adjusted model, higher adherence to the meat-fruit-seafood pattern showed a protective effect on the TB score (OR 0.53, 95% CI 0.39, 0.84, P for trend = 0.010) and the association was stronger in patients older than 45 years (OR 0.32, 95% CI 0.16, 0.64, P for trend < 0.001). The higher adherence to beans and their products-whole grain pattern was a protective factor for TB score (OR 0.57, 95% CI 0.37, 0.87, P for trend = 0.025), and the association was also observed in patients with concurrent TB and diabetes mellitus (DM) with a more significant effect (OR 0.33, 95% CI 0.14, 0.80, P for trend = 0.025). No significant association was found between dairy-egg pattern and refined grain–vegetable dietary pattern with TB score.

Conclusion

Dietary patterns characterized by a balanced diet rich in high-quality protein, sufficient energy, as well as marine n-3 PUFA, phytochemicals, B vitamins, and fiber are associated with mild initial clinical manifestations, and the association is stronger in patients older than 45 years and those with concurrent TB and DM.
Identification of a novel FGFR2-KIAA1217 fusion in esophageal gastrointestinal stromal tumours: A case report
Authors: Luo Yuehao , Wu Ying , Chang Xiaona , Huang Bo , Luo Danju , Zhang Jiwei , Zhang Peng , Shi Heshui , Fan Jun , Nie Xiu
Published: August 2022

Background

Gastrointestinal stromal tumours (GISTs) rarely arise in the esophagus. The clinical course and treatment options for esophageal GISTs are poorly understood because of their rarity. In general, the mutation spectrum of esophageal GISTs resembles that of gastric GISTs. Wild-type (WT) GISTs lacking KIT and PDGFRA gene mutations occasionally occur in adults; primary esophageal GISTs are commonly WT.

Case presentation

Herein, we report the case of a 41-year-old female patient who presented with a 1-week history of anterior upper chest pain. Chest computed tomography revealed a 3.7 cm × 2.8 cm × 6.7 cm soft tissue mass in the right posterior mediastinum adjacent to the esophagus. The patient underwent thoracoscopic mediastinal tumor resection and was subsequently diagnosed with an esophageal GIST. Neither KIT nor PDGFRA mutations were detected by Sanger sequencing; however, next-generation sequencing (NGS) identified an FGFR2-KIAA1217 gene fusion in the tumor tissue. No relapse was observed in this patient during the 8-month treatment-free follow-up period.

Conclusion

To the best of our knowledge, this report is the first to describe an FGFR2-KIAA1217 fusion in a patient with a quadruple WT esophageal GIST. When WT KIT/PDGFRA GISTS are suspected, intensive genetic analysis is recommended, and obtaining a better molecular characterization of these tumours might reveal novel therapeutic avenues.
Digital quantitative tissue image analysis of hypoxia in resected pancreatic ductal adenocarcinomas
Authors: Siddiqui Iram , Bilkey Jade , McKee Trevor D. , Serra Stefano , Pintilie Melania , Do Trevor , Xu Jing , Tsao Ming-Sound , Gallinger Steve , Hill Richard P. , Hedley David W. , Dhani Neesha C.
Published: August 2022

Background

Tumor hypoxia is theorized to contribute to the aggressive biology of pancreatic ductal adenocarcinoma (PDAC). We previously reported that hypoxia correlated with rapid tumor growth and metastasis in patient-derived xenografts. Anticipating a prognostic relevance of hypoxia in patient tumors, we developed protocols for automated semi-quantitative image analysis to provide an objective, observer-independent measure of hypoxia. We further validated this method which can reproducibly estimate pimonidazole-detectable hypoxia in a high-through put manner.

Methods

We studied the performance of three automated image analysis platforms in scoring pimonidazole-detectable hypoxia in resected PDAC (n = 10) in a cohort of patients enrolled in PIMO-PANC. Multiple stained tumor sections were analyzed on three independent image-analysis platforms, Aperio Genie (AG), Definiens Tissue Studio (TS), and Definiens Developer (DD), which comprised of a customized rule set.

Results

The output from Aperio Genie (AG) had good concordance with manual scoring, but the workflow was resource-intensive and not suited for high-throughput analysis. TS analysis had high levels of variability related to misclassification of cells class, while the customized rule set of DD had a high level of reliability with an intraclass coefficient of more than 85%.

Discussion

This work demonstrates the feasibility of developing a robust, high-performance pipeline for an automated, quantitative scoring of pimonidazole-detectable hypoxia in patient tumors.
The CURB65 score predicted 180-day mortality of non-small cell lung carcinoma patients with immune checkpoint inhibitor-associated pneumonitis: A pilot retrospective analysis
Authors: Lan Fen , Fan Bo , Wang Lihua , Xia Lixia , Zhang Ting , Li Wen , Mao Yanxiong
Published: August 2022

Introduction

The immune checkpoint inhibitor-associated pneumonitis (CIP) is a particularly worrisome and potentially lethal form of immune-related adverse events. An objective and evidence-based assessment tool for evaluating the severity of CIP is in urgent need. CURB65 (consciousness, urea nitrogen, respiratory rate, blood pressure, and age) is a potential candidate to meet the need.

Methods

A retrospective study was conducted to explore preliminarily if CURB65 could predict the mortality in non-small cell lung carcinoma (NSCLC) patients with CIP.

Results

A total number of 28 NSCLC patients with CIP were included in the current study and classified into low-CURB65 group (n = 21) and high-CURB65 group (n = 7). Mortality after onset of CIP was consistently higher in the high-CURB65 group than in the low-CURB65 group (30-day: 57.1% vs. 0; 90-day: 71.4% vs. 4.76%; 180-day:71.4% vs. 14.29%). Two patients (9.5%) in the low-CURB65 group had severe CIP, and more than half of patients in the high-CURB65 group had severe CIP (p = 0.0008). The patients in the high-CURB65 group received more aggressive treatment. Both groups showed a predominant organizing pneumonia-like pattern on CT scan. CURB65 was moderately correlated with the American Society of Clinical Oncology (ASCO) grade of CIP, with a Pearson correlation coefficient R of 0.524.

Conclusion

CURB65 accurately stratified the risk of mortality in NSCLC patients with CIP. CURB65 might complement the ASCO grade in the assessment and prediction of mortality in these populations.
The role of Vitamin D3 in ocular fibrosis and its therapeutic potential for the glaucomatous trabecular meshwork
Authors: Morelli-Batters Alexander , Lamont Hannah C. , Elghobashy Mirna , Masood Imran , Hill Lisa J.
Published: August 2022

Glaucoma is the leading cause of irreversible blindness globally. The most prevalent subtype, Primary Open Angle Glaucoma (POAG), is characterized by increased intraocular pressure (IOP), damage to the optic nerve head and irreversible visual loss. IOP increases aqueous humor (AqH) outflow is reduced through the trabecular meshwork (TM) and Schlemm’s canal (SC). Increased outflow resistance is partly due to TM/SC dysregulation, including loss of normal trabecular meshwork cell (TMC) function, following increased levels of oxidative stress within TMC, dysregulated extracellular matrix (ECM) deposition and remodeling alongside alterations in TMC phenotype and apoptosis. Current widely available POAG treatments do not target the aberrant expression of ECM in the TM directly. As a result, most drug treatments can fail as the underlying pathological process continues unabated. Rho-kinase inhibitors have demonstrated the benefit of restoring TM/SC function, however there is a clear need to develop further treatment strategies that can target the underlying cellular processes which become dysregulated within the TMC during POAG pathogenesis. Vitamin D is suggested to be beneficial in alleviating the symptoms of fibrosis and inflammation in soft tissues. It has important functions in many major organ systems, including regulation of calcium, phosphate and parathyroid hormone. Evidence suggests that Vitamin D3 modulates ECM turnover through the conventional TGFβ-SMAD signaling, which is associated with the development of POAG. The link between Vitamin D3, inflammation and fibrosis within ocular tissues will be discussed and the potential roles of Vitamin D3 in the management of POAG patients will be explored within this review.
Pediatric uveitis: Role of the pediatrician
Authors: Shivpuri Abhay , Turtsevich Inga , Solebo Ameenat Lola , Compeyrot-Lacassagne Sandrine
Published: August 2022

The challenges of childhood uveitis lie in the varied spectrum of its clinical presentation, the often asymptomatic nature of disease, and the evolving nature of the phenotype alongside normal physiological development. These issues can lead to delayed diagnosis which can cause significant morbidity and severe visual impairment. The most common ocular complications include cataracts, band keratopathy, glaucoma, and macular oedema, and the various associated systemic disorders can also result in extra-ophthalmic morbidity. Pediatricians have an important role to play. Their awareness of the various presentations and etiologies of uveitis in children afford the opportunity of prompt diagnosis before complications arise. Juvenile Idiopathic Arthritis (JIA) is one of the most common associated disorders seen in childhood uveitis, but there is a need to recognize other causes. In this review, different causes of uveitis are explored, including infections, autoimmune and autoinflammatory disease. As treatment is often informed by etiology, pediatricians can ensure early ophthalmological referral for children with inflammatory disease at risk of uveitis and can support management decisions for children with uveitis and possible underling multi-system inflammatory disease, thus reducing the risk of the development of irreversible sequelae.
Thermal servo-controlled systems in the management of VLBW infants at birth: A systematic review
Authors: Ercolino Orietta , Baccin Erica , Alfier Fiorenza , Villani Paolo Ernesto , Trevisanuto Daniele , Cavallin Francesco
Published: August 2022

Background

Thermal management of the newborn at birth remains an actual challenge. This systematic review aimed to summarize current evidence on the use of thermal servo-controlled systems during stabilization of preterm and VLBW infants immediately at birth.

Methods

A comprehensive search was conducted including MEDLINE/Pubmed, EMBASE, SCOPUS, clinicaltrials.gov, and the Cochrane Database through December 2021. PRISMA guidelines were followed. Risk of bias was appraised using Cochrane RoB2 and Risk Of Bias In Non-Randomized Studies of Interventions (ROBIN-I) tools, and certainty of evidence using GRADE framework.

Results

One randomized controlled trial and one observational study were included. Some aspects precluded the feasibility of a meaningful meta-analysis; hence, a qualitative review was conducted. Risk of bias was low in the trial and serious in the observational study. In the trial, the servo-controlled system did not affect normothermia (36.5–37.5°C) but was associated with increased mild hypothermia (from 22.2 to 32.9%). In the observational study, normothermia (36–38°C) increased after the introduction of the servo-controlled system and the extension to larger VLBW infants.

Conclusion

Overall, this review found very limited information on the use of thermal servo-controlled systems during stabilization of preterm and VLBW infants immediately at birth. Further research is needed to investigate the opportunity of including such approach in the neonatal thermal management in delivery room.

Registration

PROSPERO (CRD42022309323).
Monogenic developmental and epileptic encephalopathies of infancy and childhood, a population cohort from Norway
Authors: Stenshorne Ida , Syvertsen Marte , Ramm-Pettersen Anette , Henning Susanne , Weatherup Elisabeth , Bjørnstad Alf , Brüggemann Natalia , Spetalen Torstein , Selmer Kaja K. , Koht Jeanette
Published: August 2022

Introduction

Developmental and epileptic encephalopathies (DEE) is a group of epilepsies where the epileptic activity, seizures and the underlying neurobiology contributes to cognitive and behavioral impairments. Uncovering the causes of DEE is important in order to develop guidelines for treatment and follow-up. The aim of the present study was to describe the clinical picture and to identify genetic causes in a patient cohort with DEE without known etiology, from a Norwegian regional hospital.

Methods

Systematic searches of medical records were performed at Drammen Hospital, Vestre Viken Health Trust, to identify patients with epilepsy in the period 1999–2018. Medical records were reviewed to identify patients with DEE of unknown cause. In 2018, patients were also recruited consecutively from treating physicians. All patients underwent thorough clinical evaluation and updated genetic diagnostic analyses.

Results

Fifty-five of 2,225 patients with epilepsy had DEE of unknown etiology. Disease-causing genetic variants were found in 15/33 (45%) included patients. Three had potentially treatable metabolic disorders (SLC2A1, COQ4 and SLC6A8). Developmental comorbidity was higher in the group with a genetic diagnosis, compared to those who remained undiagnosed. Five novel variants in known genes were found, and the patient phenotypes are described.

Conclusion

The results from this study illustrate the importance of performing updated genetic investigations and/or analyses in patients with DEE of unknown etiology. A genetic cause was identified in 45% of the patients, and three of these patients had potentially treatable conditions where available targeted therapy may improve patient outcome.
A review for discovering bioactive minor saponins and biotransformative metabolites in Panax quinquefolius L.
Authors: Yang Zhiyou , Deng Jiahang , Liu Mingxin , He Chuantong , Feng Xinyue , Liu Shucheng , Wei Shuai
Published: August 2022

Panax quinquefolius L. has attracted extensive attention worldwide because of its prominent pharmacological properties on type 2 diabetes, cancers, central nervous system, and cardiovascular diseases. Ginsenosides are active phytochemicals of P. quinquefolius, which can be classified as propanaxdiol (PPD)-type, propanaxtriol (PPT)-type, oleanane-type, and ocotillol-type oligo-glycosides depending on the skeleton of aglycone. Recently, advanced analytical and isolated methods including ultra-performance liquid chromatography tandem with mass detector, preparative high-performance liquid chromatography, and high speed counter-current chromatography have been used to isolate and identify minor components in P. quinquefolius, which accelerates the clarification of the material basis. However, the poor bioavailability and undetermined bio-metabolism of most saponins have greatly hindered both the development of medicines and the identification of their real active constituents. Thus, it is essential to consider the bio-metabolism of constituents before and after absorption. In this review, we described the structures of minor ginsenosides in P. quinquefolius, including naturally occurring protype compounds and their in vivo metabolites. The preclinical and clinical pharmacological studies of the ginsenosides in the past few years were also summarized. The review will promote the reacquaint of minor saponins on the growing appreciation of their biological role in P. quinquefolius.
Silver-Nanoparticle- and Silver-Nitrate-Induced Antioxidant Disbalance, Molecular Damage, and Histochemical Change on the Land Slug (Lehmannia nyctelia) Using Multibiomarkers
Authors: Bakr Zeinab , Said Shimaa Mohamed , Mohammad Wafaa A. , Aboulnasr Gehad N. , Elshimy Naser A.
Published: August 2022

It is known that silver nanoparticles (Ag NPs) and AgNO3 have harmful effects on the surrounding organisms, which may cause damage to these organisms. Therefore, the aim of this study is to detect damage caused by Ag NPs and silver nitrate to land slugs (Lehmannia nyctelia). In this study, the slugs were exposed to various concentrations of Ag NPs and AgNO3 for 15 days. The biochemical, antioxidant, lipid peroxidation (LPO), DNA fragmentation, and histopathological endpoints were assessed after 15 days of exposure to different concentrations of Ag NPs (0.04, 0.08, 0.4, and 0.8 g/L) and silver nitrate (0.04, 0.08, 0.4, and 0.8 g/L). The results show a significant decrease in total protein, total carbohydrate, superoxide dismutase, and GST and a significant increase in total lipid, LPO, and DNA fragmentation after exposure to Ag NPs and AgNO3 for 15 days compared with the control group. Histopathiological alterations were observed in the digestive glands which were indicated by histochemical staining. We concluded that exposure to AgNO3 and Ag NPs caused oxidative stress, genetic damage and alterations in the profile of muscle proteins and histological structure in L. nyctelia.
Environmentally driven transcriptomic and metabolic changes leading to color differences in “Golden Reinders” apples
Authors: Fernández-Cancelo Pablo , Iglesias-Sanchez Ariadna , Torres-Montilla Salvador , Ribas-Agustí Albert , Teixidó Neus , Rodriguez-Concepcion Manuel , Giné-Bordonaba Jordi
Published: August 2022

Apple is characterized by its high adaptation to diverse growing environments. However, little is still known about how different environments can regulate at the metabolic or molecular level specific apple quality traits such as the yellow fruit peel color. In this study, changes in carotenoids and chlorophylls, antioxidants as well as differences in the transcriptome were investigated by comparing the peel of “Golden Reinders” apples grown at different valley and mountain orchards. Mountain environment favored the development of yellow color, which was not caused by an enhanced accumulation of carotenoids but rather by a decrease in the chlorophyll content. The yellow phenotype was also associated to higher expression of genes related to chloroplast functions and oxidative stress. Time-course analysis over the last stages of apple development and ripening, in fruit from both locations, further revealed that the environment differentially modulated isoprenoids and phenylpropanoid metabolism and pointed out a key role for H2O2 in triggering apple peel degreening. Overall, the results presented herein provide new insights into how different environmental conditions regulate pigment and antioxidant metabolism in apple leading to noticeable differences in the apple peel color.
Seed position in spikelet as a contributing factor to the success of the winter annual invasive grass Aegilops tauschii
Authors: Wang AiBo , Baskin Carol C. , Baskin Jerry M. , Ding Jianqing
Published: August 2022

Seed position – dependent effects on seed dormancy/germination are well documented at the inflorescence/infructescence level, but less is known about seeds at different positions within a dispersal unit. For the invasive winter annual grassAegilops tauschii,we quantified morphology, mass and dormancy/germination of seeds from basal (1), middle (2), and distal (3) positions in two spikelet types (Left and Right). We also investigated seedling emergence, survival, plant size and seed production of plants from seeds in different spikelet positions of two spikelet types under different soil nutrient and water conditions. We found that these seed, seedling and plant traits performed as mirror images between the Left and Right spikelet types. The middle seed was significantly the longest and had the maximum mass, while the basal seed was the shortest and had medium mass. Middle seeds had the highest increase in mass during imbibition and the highest germination percentages and rates, while basal seeds had the lowest. Seedling emergence and survival, plant size and seed production for each position of seeds were highest in the added fertilizer combined with regular watering treatment and lowest in the no fertilizer combined with natural moisture, while height of plants derived from the middle and the distal seeds was significantly higher than that of plants derived from the basal seeds under all soil nutrient and water conditions. Seedling survival, number of tillers per plant and seed production per plant from the middle and distal seeds were significantly lower than those from basal seeds under all soil nutrient and water treatments. The considerable variation in seedling emergence and survival, plant size and seed production between seeds in different positions in the spikelet results in much flexibility in all stages of the life cycle, thereby likely contributing to the invasiveness ofA. tauschii.