bluuebunny/crossref_metadata_2025 huggingface dataset:
Reaction Time Sensitivity to Spectrotemporal Modulations of Sound
Authors: Veugen Lidwien C. E. , van Opstal A. John , van Wanrooij Marc M.
Published: September 2022

We tested whether sensitivity to acoustic spectrotemporal modulations can be observed from reaction times for normal-hearing and impaired-hearing conditions. In a manual reaction-time task, normal-hearing listeners had to detect the onset of a ripple (with density between 0–8 cycles/octave and a fixed modulation depth of 50%), that moved up or down the log-frequency axis at constant velocity (between 0–64 Hz), in an otherwise-unmodulated broadband white-noise. Spectral and temporal modulations elicited band-pass filtered sensitivity characteristics, with fastest detection rates around 1 cycle/oct and 32 Hz for normal-hearing conditions. These results closely resemble data from other studies that typically used the modulation-depth threshold as a sensitivity criterion. To simulate hearing-impairment, stimuli were processed with a 6-channel cochlear-implant vocoder, and a hearing-aid simulation that introduced separate spectral smearing and low-pass filtering. Reaction times were always much slower compared to normal hearing, especially for the highest spectral densities. Binaural performance was predicted well by the benchmark race model of binaural independence, which models statistical facilitation of independent monaural channels. For the impaired-hearing simulations this implied a “best-of-both-worlds” principle in which the listeners relied on the hearing-aid ear to detect spectral modulations, and on the cochlear-implant ear for temporal-modulation detection. Although singular-value decomposition indicated that the joint spectrotemporal sensitivity matrix could be largely reconstructed from independent temporal and spectral sensitivity functions, in line with time-spectrum separability, a substantial inseparable spectral-temporal interaction was present in all hearing conditions. These results suggest that the reaction-time task yields a valid and effective objective measure of acoustic spectrotemporal-modulation sensitivity.
The Associations Between Patients’ Characteristics and the Quality of Life Among Acute Coronary Syndrome Patients in Jordan: A Cross-Sectional Study
Authors: Aljabery Mohannad A. , Rajeh Saifan Ahmad , Alrimawi Intima , Alzoubi Ahmad Mahmoud , Atout Maha
Published: September 2022

Introduction

Acute coronary syndrome (ACS) is one of the most significant leading causes of death and disability in the world. The quality of life (QoL) score is used to evaluate the impact of ACS treatments on the patients’ physical, emotional, and social functioning. It is considered a significant indicator of the progress of the patients’ health status and is useful in predicting patients’ needs for continuing, modifying, or changing their treatment plans.

Objective

To identify the associations between patients’ characteristics and the QoL among ACS patients in Jordan.

Methods

A descriptive cross-sectional study was conducted using a convenience sample of 372 participants with ACS from six referral hospitals in Jordan.

Results

Jordanian patients with higher educational level and exercise had significant and positive association with QoL (β = 0.257, p < .001), (β = 0.191, p < .001), respectively. Also, patients who reported having dyslipidaemia and having unstable angina (UA) had lower score of QoL (β = −0.165, p < .001), (β = −0.149, p < .001), respectively. Finally, gender and working status did not significantly appear to have an association with the total QoL.

Conclusions

This study sheds light on the importance of increasing the level of patients’ awareness about their illness by educating them about it and encouraging them to engage in physical activity programs.
Reflecting Race and Status: The Dynamics of Material Hardship and How People Are Perceived
Authors: Sosina Victoria E. , Saperstein Aliya
Published: September 2022

In most stratification research, race is treated as a static and one-dimensional individual characteristic, though a growing literature indicates dynamic and multidimensional measures better represent experiences of racial categorization and inequality. The authors leverage such measures to explore the relationship between material hardship and racial reflected appraisals, or how people report being perceived by others. Results from the New York City Longitudinal Survey of Wellbeing are consistent with a bidirectional relationship: first, people who reported being seen as Black or Hispanic were significantly more likely to experience later material hardship, net of both racial self-identification and earlier hardship; second, people with hardship experience were significantly more likely to report been perceived as Hispanic and significantly less likely to report being perceived as White, no matter how they self-identified. These findings underscore the dynamics of racial categorization and highlight the utility of including reflected race measures in studies of inequality.
Case report: Anti-PLA2R positive membranous nephropathy associated with atezolizumab
Authors: Oleas Diana , Saurina Ana
Published: September 2022

Background:

Immunotherapy has transformed cancer treatment in advanced malignancies. Increased survival compared with the standard of care has made immunotherapy a fundamental component of oncotherapeutics. Immune checkpoint inhibitors (ICI) trigger a stimulus to kill cancer cells. Immune-related adverse events (irAEs), derived from its potent stimulus, affect diverse organs. Acute interstitial nephritis (AIN) is the most frequent kidney irAE. Glomerulopathies, although rare, constitute a more challenging diagnosis and treatment.

Case presentation:

A 72-year-old man with lung adenocarcinoma treated with Bevacizumab and Atezolizumab. During treatment, he developed nephrotic syndrome. A diagnosis of a phospholipase A2 receptor positive primary membranous nephropathy associated with atezolizumab was made. After failing to respond to steroid therapy, treatment with rituximab was the preferred option. Eight months after being treated with rituximab and 10 months after atezolizumab was stopped, the patient maintained preserved renal function and negativization of anti-PLA2R was achieved. Proteinuria declined to half of its initial value 5 months following anti-PLA2R negativization.

Conclusion:

Monitoring proteinuria as well as declining kidney function in patients being treated with ICI is a valuable measure to determine an indication for a timely kidney biopsy and treatment.
Knitted Denim Fabrics: Fabrication Process and Fibrous Influence on Several Properties of the Fabric
Authors: Hoque Md. Saiful , Shahid Md. Imranul , Parvez Abdullah Al , Hossain Md. Jakir , Sheen Sheenrina Miyan
Published: September 2022

Denim-like knitted fabrics are getting popular for their several favorable properties, such as flexibility, comfort, and ease of manufacturing. This study aimed to manufacture knitted denim fabrics made from various blend ratios of cotton, polyester, and spandex fibers. Seven fabrics with a fiber blend ratio ranging from 95% cotton/5% spandex to 30% cotton/65% polyester/5% spandex were developed using a weft circular knitting machine. First, the twill effect of the knitted denim fabric was brought by following a cross terry knitting structure to produce each fabric sample of this study. After that, the fabric performance was analyzed by characterizations, such as areal density, pilling and abrasion resistance, dimensional stability, stretch, and recovery, tear strength, bursting strength, air permeability, vertical wicking, liquid absorbency capacity, and different colorfastness tests. The results showed that different cotton, polyester, and spandex fiber compositions did not significantly affect knitted denim fabrics’ weight per unit area, abrasion resistance, and different color fastness properties. However, the elongation and vertical wicking test data showed that the knitted denim fabrics with a higher cotton fiber ratio were better. However, the results from shrinkage, spirality, pilling, recovery, strength, air permeability, and liquid absorbency capacity tests revealed the benefits of having a higher polyester fiber ratio in the cotton/polyester/spandex blended knitted denim fabrics. One-way analysis of the variance test was also performed on the generated data of this study and reported in the respective section of the article.
Alterations in metabolic flux in migraine and the translational relevance
Authors: Grech Olivia , Sassani Matilde , Terwindt Gisela , Lavery Gareth G. , Mollan Susan P. , Sinclair Alexandra J.
Published: September 2022

Background

Migraine is a highly prevalent disorder with significant economical and personal burden. Despite the development of effective therapeutics, the causes which precipitate migraine attacks remain elusive. Clinical studies have highlighted altered metabolic flux and mitochondrial function in patients. In vivo animal experiments can allude to the metabolic mechanisms which may underlie migraine susceptibility. Understanding the translational relevance of these studies are important to identifying triggers, biomarkers and therapeutic targets in migraine.

Main body

Functional imaging studies have suggested that migraineurs feature metabolic syndrome, exhibiting hallmark features including upregulated oxidative phosphorylation yet depleted available free energy. Glucose hypometabolism is also evident in migraine patients and can lead to altered neuronal hyperexcitability such as the incidence of cortical spreading depression (CSD). The association between obesity and increased risk, frequency and worse prognosis of migraine also highlights lipid dysregulation in migraine pathology. Calcitonin gene related peptide (CGRP) has demonstrated an important role in sensitisation and nociception in headache, however its role in metabolic regulation in connection with migraine has not been thoroughly explored. Whether impaired metabolic function leads to increased release of peptides such as CGRP or excessive nociception leads to altered flux is yet unknown.

Conclusion

Migraine susceptibility may be underpinned by impaired metabolism resulting in depleted energy stores and altered neuronal function. This review discusses both clinical and in vivo studies which provide evidence of altered metabolic flux which contribute toward pathophysiology. It also reviews the translational relevance of animal studies in identifying targets of biomarker or therapeutic development.
Synaptic alterations in visual cortex reshape contrast-dependent gamma oscillations and inhibition-excitation ratio in a genetic mouse model of migraine
Authors: Meneghetti Nicolò , Cerri Chiara , Vannini Eleonora , Tantillo Elena , Tottene Angelita , Pietrobon Daniela , Caleo Matteo , Mazzoni Alberto
Published: September 2022

Background

Migraine affects a significant fraction of the world population, yet its etiology is not completely understood. In vitro results highlighted thalamocortical and intra-cortical glutamatergic synaptic gain-of-function associated with a monogenic form of migraine (familial-hemiplegic-migraine-type-1: FHM1). However, how these alterations reverberate on cortical activity remains unclear. As altered responsivity to visual stimuli and abnormal processing of visual sensory information are common hallmarks of migraine, herein we investigated the effects of FHM1-driven synaptic alterations in the visual cortex of awake mice.

Methods

We recorded extracellular field potentials from the primary visual cortex (V1) of head-fixed awake FHM1 knock-in (n = 12) and wild type (n = 12) mice in response to square-wave gratings with different visual contrasts. Additionally, we reproduced in silico the obtained experimental results with a novel spiking neurons network model of mouse V1, by implementing in the model both the synaptic alterations characterizing the FHM1 genetic mouse model adopted.

Results

FHM1 mice displayed similar amplitude but slower temporal evolution of visual evoked potentials. Visual contrast stimuli induced a lower increase of multi-unit activity in FHM1 mice, while the amount of information content about contrast level remained, however, similar to WT.

Spectral analysis of the local field potentials revealed an increase in the β/low γ range of WT mice following the abrupt reversal of contrast gratings. Such frequency range transitioned to the high γ range in FHM1 mice. Despite this change in the encoding channel, these oscillations preserved the amount of information conveyed about visual contrast. The computational model showed how these network effects may arise from a combination of changes in thalamocortical and intra-cortical synaptic transmission, with the former inducing a lower cortical activity and the latter inducing the higher frequencies ɣ oscillations.

Conclusions

Contrast-driven ɣ modulation in V1 activity occurs at a much higher frequency in FHM1. This is likely to play a role in the altered processing of visual information. Computational studies suggest that this shift is specifically due to enhanced cortical excitatory transmission. Our network model can help to shed light on the relationship between cellular and network levels of migraine neural alterations.

Graphical Abstract
Choroidal sarcoid granuloma: a case report and review of the literature
Authors: Hage Dany G. , Wahab Charbel H. , Kheir Wajiha J.
Published: September 2022

Background

Choroidal sarcoid granulomas are often diagnosed in patients without a prior history of sarcoidosis. They are often mistaken for choroidal metastasis, choroidal nevi, amelanotic choroidal melanomas, and uveal lymphomas; however, are easily treatable when accurately identified.

Observations

We searched PubMed, Medline, and Scopus for English-Language case reports published before September 2021. Additionally, we presented a case of a 45-year-old woman with a right-sided amelanotic choroidal mass whose diagnosis was delayed by a COVID-19 infection. Of the 26 cases reported in the literature, 46% were female, 38% were African American, and 19% had bilateral involvement. There was a mean age of 42.15 years and a mean follow-up period of 27 months. The most common complaint was of a progressive, painless blurring of vision, and only five patients had been previously diagnosed with sarcoidosis. The choroidal granulomas were typically described as yellow lesions, single or multiple, found temporal to or at the macula. Most patients were administered steroids, with 69% receiving them systemically, 5% topically, and 8% locally with a triamcinolone injection. All patients reported symptomatic improvement at their final follow-up with resolution of the mass in 65% of patients and improved visual acuity in 76%.

Conclusion

Primary testing including fundoscopy, fluorescein angiography, fundus autofluorescence, A/B-scan, and OCT are useful for diagnosis, differentiation from other choroidal lesions, and monitoring treatment response. Steroids are a mainstay of treatment for sarcoidosis and are effective at treating choroidal granulomas. Therefore, early recognition and diagnosis of choroidal granulomas is imperative as treatment can be curative and sight-sparing.
Small molecule modulation of microbiota: a systems pharmacology perspective
Authors: Liu Qiao , Lee Bohyun , Xie Lei
Published: September 2022

Background

Microbes are associated with many human diseases and influence drug efficacy. Small-molecule drugs may revolutionize biomedicine by fine-tuning the microbiota on the basis of individual patient microbiome signatures. However, emerging endeavors in small-molecule microbiome drug discovery continue to follow a conventional “one-drug-one-target-one-disease” process. A systematic pharmacology approach that would suppress multiple interacting pathogenic species in the microbiome, could offer an attractive alternative solution.

Results

We construct a disease-centric signed microbe–microbe interaction network using curated microbe metabolite information and their effects on host. We develop a Signed Random Walk with Restart algorithm for the accurate prediction of effect of microbes on human health and diseases. With a survey on the druggable and evolutionary space of microbe proteins, we find that 8–10% of them can be targeted by existing drugs or drug-like chemicals and that 25% of them have homologs to human proteins. We demonstrate that drugs for diabetes can be the lead compounds for development of microbiota-targeted therapeutics. We further show that the potential drug targets that specifically exist in pathogenic microbes are periplasmic and cellular outer membrane proteins.

Conclusion

The systematic studies of the polypharmacological landscape of the microbiome network may open a new avenue for the small-molecule drug discovery of the microbiome. We believe that the application of systematic method on the polypharmacological investigation could lead to the discovery of novel drug therapies.
Effects of growth hormone/estrogen/androgen on COVID-19-type proinflammatory responses in normal human lung epithelial BEAS-2B cells
Authors: Zhu Zemin , Zhao Zhijian , Chen Xun , Chu Zhou , He Yi , Tan Yingzheng , Zhou Juan , Tang Caixi
Published: September 2022

Background

COVID-19 is a disease caused by SARS-CoV-2, which can cause mild to serious infections in humans. We aimed to explore the effect of growth hormone (GH)/estrogen/androgen in normal human lung epithelial BEAS-2B cells on COVID-19-type proinflammatory responses.

Methods

A BEAS-2B COVID-19-like proinflammatory cell model was constructed. After that, the cells were treated with GH, 17β-estradiol (E2), and testosterone (Tes) for 24 h. CCK-8 assays were utilized to evaluate cell viability. The mRNA expression of ACE2, AGTR1, TMRRSS2, and ISG15 and the protein expression of ACE2, AGTR1, TMRRSS2, and ISG15 were measured by qRT‒PCR and Western blotting, respectively. ELISAs were performed to determine IL-6, MCP-1, MDA and SOD expression. Flow cytometry was used to measure ROS levels. Finally, MAPK/NF-κB pathway-related factor expression was evaluated.

Results

The COVID-19-type proinflammatory model was successfully constructed, and 1000 ng/mL RBD treatment for 24 h was selected as the condition for the model group for subsequent experiments. After RBD treatment, cell viability decreased, the mRNA expression of ACE2, AGTR1, TMRRSS2, and ISG15 and the protein expression of ACE2, AGTR1, TMRRSS2, and ISG15 increased, IL-6, MCP-1, MDA and ROS levels increased, and MDA levels decreased. The mRNA levels of MAPK14 and RELA increased, but the protein levels did not change significantly. In addition, phospho-MAPK14 and phospho-RELA protein levels were also increased. Among the tested molecules, E2 had the most pronounced effect, followed by GH, while Tes showed the opposite effect.

Conclusion

GH/E2 alleviated inflammation in a COVID-19-type proinflammatory model, but Tes showed the opposite effect.
Comparative transcriptomic analysis revealed dynamic changes of distinct classes of genes during development of the Manila clam (Ruditapes philippinarum)
Authors: Zhang Yanming , Nie Hongtao , Yin Zhihui , Yan Xiwu
Published: September 2022

Background

The Manila clam Ruditapesphilippinarum is one of the most economically important marine shellfish. However, the molecular mechanisms of early development in Manila clams are largely unknown. In this study, we collected samples from 13 stages of early development in Manila clam and compared the mRNA expression pattern between samples by RNA-seq techniques.

Results

We applied RNA-seq technology to 13 embryonic and larval stages of the Manila clam to identify critical genes and pathways involved in their development and biological characteristics. Important genes associated with different morphologies during the early fertilized egg, cell division, cell differentiation, hatching, and metamorphosis stages were identified. We detected the highest number of differentially expressed genes in the comparison of the pediveliger and single pipe juvenile stages, which is a time when biological characteristics greatly change during metamorphosis. Gene Ontology (GO) enrichment analysis showed that expression levels of microtubule protein-related molecules and Rho genes were upregulated and that GO terms such as ribosome, translation, and organelle were enriched in the early development stages of the Manila clam. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the foxo, wnt, and transforming growth factor-beta pathways were significantly enriched during early development. These results provide insights into the molecular mechanisms at work during different periods of early development of Manila clams.

Conclusion

These transcriptomic data provide clues to the molecular mechanisms underlying the development of Manila clam larvae. These results will help to improve Manila clam reproduction and development.
Comparative transcriptome analysis reveals different defence responses during the early stage of wounding stress in Chi-Nan germplasm and ordinary Aquilaria sinensis
Authors: Lv Feifei , Yang Yun , Sun Peiwen , Zhang Yan , Liu Peiwei , Fan Xiaohong , Xu Yanhong , Wei Jianhe
Published: September 2022

Background

Agarwood is a valuable Chinese medicinal herb and spice that is produced from wounded Aquilaria spp., is widely used in Southeast Asia and is highly traded on the market. The lack of highly responsive Aquilaria lines has seriously restricted agarwood yield and the development of its industry. In this article, a comparative transcriptome analysis was carried out between ordinary A. sinensis and Chi-Nan germplasm, which is a kind of A. sinensis tree with high agarwood-producing capacity in response to wounding stress, to elucidate the molecular mechanism underlying wounding stress in different A. sinensis germplasm resources and to help identify and breed high agarwood-producing strains.

Results

A total of 2427 and 1153 differentially expressed genes (DEGs) were detected in wounded ordinary A. sinensis and Chi-Nan germplasm compared with the control groups, respectively. KEGG enrichment analysis revealed that genes participating in starch metabolism, secondary metabolism and plant hormone signal transduction might play major roles in the early regulation of wound stress. 86 DEGs related to oxygen metabolism, JA pathway and sesquiterpene biosynthesis were identified. The majority of the expression of these genes was differentially induced between two germplasm resources under wounding stress. 13 candidate genes related to defence and sesquiterpene biosynthesis were obtained by WGCNA. Furthermore, the expression pattern of genes were verified by qRT-PCR. The candidate genes expression levels were higher in Chi-Nan germplasm than that in ordinary A. sinensis during early stage of wounding stress, which may play important roles in regulating high agarwood-producing capacity in Chi-Nan germplasm.

Conclusions

Compared with A. sinensis, Chi-Nan germplasm invoked different biological processes in response to wounding stress. The genes related to defence signals and sesquiterepene biosynthesis pathway were induced to expression differentially between two germplasm resources. A total of 13 candidate genes were identified, which may correlate with high agarwood-producting capacity in Chi-Nan germplasm during the early stage of wounding stress. These genes will contribute to the development of functional molecular markers and the rapid breeding highly of responsive Aquilaria lines.
De novo transcriptome assembly, gene annotation, and EST-SSR marker development of an important medicinal and edible crop, Amomum tsaoko (Zingiberaceae)
Authors: Ma Mengli , Meng Hengling , Lei En , Wang Tiantao , Zhang Wei , Lu Bingyue
Published: September 2022

Background

Amomum tsaokois a medicinal and food dual-use crop that belongs to the Zingiberaceae family. However, the lack of transcriptomic and genomic information has limited the understanding of the genetic basis of this species. Here, we performed transcriptome sequencing of samples from differentA. tsaokotissues, and identified and characterized the expressed sequence tag-simple sequence repeat (EST-SSR) markers.

Results

A total of 58,278,226 high-quality clean reads were obtained and de novo assembled to generate 146,911 unigenes with an N50 length of 2002 bp. A total of 128,174 unigenes were successfully annotated by searching seven protein databases, and 496 unigenes were identified as annotated as putative terpenoid biosynthesis-related genes. Furthermore, a total of 55,590 EST-SSR loci were detected, and 42,333 primer pairs were successfully designed. We randomly selected 80 primer pairs to validate their polymorphism inA. tsaoko; 18 of these primer pairs produced distinct, clear, and reproducible polymorphisms. A total of 98 bands and 96 polymorphic bands were amplified by 18 pairs of EST-SSR primers for the 72A. tsaokoaccessions. The Shannon's information index (I) ranged from 0.477 (AM208) to 1.701 (AM242) with an average of 1.183, and the polymorphism information content (PIC) ranged from 0.223 (AM208) to 0.779 (AM247) with an average of 0.580, indicating that these markers had a high level of polymorphism. Analysis of molecular variance (AMOVA) indicated relatively low genetic differentiation among the sixA. tsaokopopulations. Cross-species amplification showed that 14 of the 18 EST-SSR primer pairs have transferability between 11 Zingiberaceae species.

Conclusions

Our study is the first to provide transcriptome data of this important medicinal and edible crop, and these newly developed EST-SSR markers are a very efficient tool for germplasm evaluation, genetic diversity, and molecular marker-assisted selection inA. tsaoko.
Characteristics and comparison between e-scooters and bicycle-related trauma: a multicentre cross-sectional analysis of data from a road collision registry
Authors: Benhamed Axel , Gossiome Amaury , Ndiaye Amina , Tazarourte Karim
Published: September 2022

Background

Urban mobility has drastically evolved over the last decade and micromobility rapidly became an expanding segment of contemporary daily transportation routines. E-scooter riders and bicyclists may share similar trauma characteristics, but this has been little explored. The objective was to describe and compare the characteristics of e-scooter and bicycle-related trauma.

Methods

We conducted a cross-sectional analysis of data from the Rhône road collision registry (January 1, 2019 to December 31, 2019). We included all e-scooter or bicycle riders injured in traffic collisions during the study period; there were no exclusion criterion.

Results

A total of 2,779 patients were included; 825 (29.7%) were e-scooter riders and 1,954 (70.3%) were bicyclists. E-scooter riders were younger (median [IQR]: 24 [20–32] vs 29 [20–45] years, p < 0.001) and less frequently male (64.2% vs 73.4%, p < 0.001). Most e-scooter and bicycle road collisions were consequent to a fall or loss of vehicle control (74.2% vs 67.7%, p < 0.001). E-scooter riders were less frequently wearing a helmet at the time of the road collision (6.1% vs 30.7%, p < 0.001) and had more frequently head (24.2% vs 19.9%, p = 0.01) and face (30.6 vs 20.5%, p < 0.001) injuries compared to bicyclists. The median injury severity score was 2 [1–4] in both groups with no significant difference (p = 0.77).

Conclusions

E-scooter and bicycle-related trauma patients were mainly young males with minor injuries and most of them sustained a road collision with no third-party. However, they suffered from different injury patterns; e-scooter riders suffered more frequently face and head injuries than bicycle riders, which may be at least partly the consequence of less frequent helmet use among e-scooter riders compared to bicyclists. Hence the two groups of users should not be considered as a single trauma entity. This issue should be promptly addressed to bring down the incidence of preventable injuries and avoid healthcare costs.
Item response theory and differential test functioning analysis of the HBSC-Symptom-Checklist across 46 countries
Authors: Heinz Andreas , Sischka Philipp E. , Catunda Carolina , Cosma Alina , García-Moya Irene , Lyyra Nelli , Kaman Anne , Ravens-Sieberer Ulrike , Pickett William
Published: September 2022

Background

The Symptom Checklist (SCL) developed by the Health Behaviour in School-aged Children (HBSC) study is a non-clinical measure of psychosomatic complaints (e.g., headache and feeling low) that has been used in numerous studies. Several studies have investigated the psychometric characteristics of this scale; however, some psychometric properties remain unclear, among them especially a) dimensionality, b) adequacy of the Graded Response Model (GRM), and c) measurement invariance across countries.

Methods

Data from 229,906 adolescents aged 11, 13 and 15 from 46 countries that participated in the 2018 HBSC survey were analyzed. Adolescents were selected using representative sampling and surveyed by questionnaire in the classroom. Dimensionality was investigated using exploratory graph analysis. In addition, we investigated whether the GRM provided an adequate description of the data. Reliability over the latent variable continuum and differential test functioning across countries were also examined.

Results

Exploratory graph analyses showed that SCL can be considered as one-dimensional in 16 countries. However, a comparison of the unidimensional with a post-hoc bifactor GRM showed that deviation from a hypothesized one-dimensional structure was negligible in most countries. Multigroup invariance analyses supported configural and metric invariance, but not scalar invariance across 32 countries. Alignment analysis showed non-invariance especially for the items irritability, feeling nervous/bad temper and feeling low.

Conclusion

HBSC-SCL appears to represent a consistent and reliable unidimensional instrument across most countries. This bodes well for population health analyses that rely on this scale as an early indicator of mental health status.
Circulating miR-181a as a novel potential plasma biomarker for multimorbidity burden in the older population
Authors: Iannone Francesca , Crocco Paolina , Dato Serena , Passarino Giuseppe , Rose Giuseppina
Published: September 2022

Background

Chronic low-level inflammation is thought to play a role in many age-related diseases and to contribute to multimorbidity and to the disability related to this condition. In this framework, inflamma-miRs, an important subset of miRNA able to regulate inflammation molecules, appear to be key players. This study aimed to evaluate plasma levels of the inflamma-miR-181a in relation to age, parameters of health status (clinical, physical, and cognitive) and indices of multimorbidity in a cohort of 244 subjects aged 65- 97.

Methods

MiR-181a was isolated from plasma according to standardized procedures and its expression levels measured by qPCR. Correlation tests and multivariate regression analyses were applied on gender-stratified groups.

Results

MiR-181a levels resulted increased in old men, and significantly correlated with worsened blood parameters of inflammation (such as low levels of albumin and bilirubin and high lymphocyte content), particularly in females. Furthermore, we found miR-181a positively correlated with the overall multimorbidity burden, measured by CIRS Comorbidity Score, in both genders.

Conclusions

These data support a role of miR-181a in age-related chronic inflammation and in the development of multimorbidity in older adults and indicate that the routes by which this miRNA influence health status are likely to be gender specific. Based on our results, we suggest that miR-181a is a promising biomarker of health status of the older population.
Assessment of genotypes, endosymbionts and clinical characteristics of Acanthamoeba recovered from ocular infection
Authors: Rayamajhee Binod , Sharma Savitri , Willcox Mark , Henriquez Fiona L. , Rajagopal Raksheeth Nathan , Shrestha Gauri Shankar , Subedi Dinesh , Bagga Bhupesh , Carnt Nicole
Published: September 2022

Introduction

Acanthamoeba is an emerging pathogen, infamous for its resilience against antiprotozoal compounds, disinfectants and harsh environments. It is known to cause keratitis, a sight-threatening, painful and difficult to treat corneal infection which is often reported among contact lens wearers and patients with ocular trauma. Acanthamoeba comprises over 24 species and currently 23 genotypes (T1-T23) have been identified.

Aims

This retrospective study was designed to examine the Acanthamoeba species and genotypes recovered from patients with Acanthamoeba keratitis (AK), determine the presence of endosymbionts in ocular isolates of Acanthamoeba and review the clinical presentations.

Methodology

Thirteen culture-confirmed AK patients treated in a tertiary eye care facility in Hyderabad, India from February to October 2020 were included in this study. The clinical manifestations, medications and visual outcomes of all patients were obtained from medical records. The Acanthamoeba isolates were identified by sequencing the ribosomal nuclear subunit (rns) gene. Acanthamoeba isolates were assessed for the presence of bacterial or fungal endosymbionts using molecular assays, PCR and fluorescence in situ hybridization (FISH).

Results

The mean age of the patients was 33 years (SD ± 17.4; 95% CI 22.5 to 43.5 years). Six (46.2%) cases had AK associated risk factors; four patients had ocular trauma and two were contact lens wearers. A. culbertsoni (6/13, 46.2%) was the most common species, followed by A. polyphaga and A. triangularis. Most of the isolates (12/13) belonged to genotype T4 and one was a T12; three sub-clusters T4A, T4B, and T4F were identified within the T4 genotype. There was no significant association between Acanthamoeba types and clinical outcomes. Eight (61.5%) isolates harboured intracellular bacteria and one contained Malassezia restricta. The presence of intracellular microbes was associated with a higher proportion of stromal infiltrates (88.9%, 8/9), epithelial defect (55.6%, 5/9) and hypopyon (55.6%, 5/9) compared to 50% (2/4), 25% (1/4) and 25% (1/4) AK cases without intracellular microbes, respectively.

Conclusions

Genotype T4 was the predominant isolate in southern India. This is the second report of T12 genotype identified from AK patient in India, which is rarely reported worldwide. The majority of the Acanthamoeba clinical isolates in this study harboured intracellular microbes, which may impact clinical characteristics of AK.
Hemorrhagic fever with renal syndrome caused by destruction of residential area of rodent in a construction site: epidemiological investigation
Authors: Wei Xiao , Meng Biao , Peng Hong , Li Yan , Liu Min , Si Hairui , Wu Rui , Chen Hailong , Bai Ying , Li Yan , Feng Qunling , Wang Changjun , Zhao Xiangna
Published: September 2022

Background

An outbreak of hemorrhagic fever with renal syndrome (HFRS), caused by a Hantavirus, affected nine adult males in the southwest area of Xi’an in November 2020 was analyzed in this study.

Methods

Clinical and epidemiological data of HFRS patients in this outbreak were retrospectively analyzed. The whole genome of a hantavirus named 201120HV03xa (hv03xa for short) isolated from Apodemus agrarius captured in the construction site was sequenced and analyzed. In addition, nine HFRS patients were monitored for the IgG antibody against the HV N protein at 6 and 12 months, respectively.

Results

In this study, inhalation of aerosolized excreta and contaminated food may be the main source of infection. Genome analysis and phylogenetic analysis showed that hv03xa is a reassortment strain of HTNV, having an S segment related to A16 of HTN 4, an M segment related to Q37 and Q10 of HTN 4, and an L segment related to prototype strain 76–118 of HTN 7. Potential recombination was detected in the S segment of hv03xa strain. The anti-HV-IgG level of all the patients persist for at least one year after infection.

Conclusions

This report documented an HFRS outbreak in Xi’an, China, which provided the basic data for epidemiological surveillance of endemic HTNV infection and facilitated to predict disease risk and implement prevention measures.
Three-dimensional nuclear telomere architecture and differential expression of aurora kinase genes in chronic myeloid leukemia to measure cell transformation
Authors: de Oliveira Fábio Morato , Jamur Valderez Ravaglio , Merfort Lismeri Wuicik , Pozzo Aline Rangel , Mai Sabine
Published: September 2022

Background

Telomere dysfunction results in aneuploidy, and ongoing chromosomal abnormalities. The three-dimensional (3D) nuclear organization of telomeres allows for a distinction between normal and tumor cells. On the other hand, aurora kinase genes (AURKAandAURKB) play an important role regulating the cell cycle. A correlation between overexpression of aurora kinase genes and clinical aggressiveness has been demonstrated in different types of neoplasias. To better understand cellular and molecular mechanisms of CML evolution, it was examined telomere dysfunction (alterations in the 3D nuclear telomere architecture), and the expression levels ofAURKAandAURKBgenes in two clinical distinct subgroups of CML samples, from the same patient.

Methods

Eighteen CML patients, in total, 36 bone marrow samples (18 patients,chronicvs.accelerated/blast phase) were eligible for 3D telomeric investigations. Quantitative 3D imaging, cytologic diagnosis and cytogenetic determination of additional chromosomal abnormalities were assessed according to standard protocols.

Results

Using TeloView software, two CML subgroups were defined based on their 3D telomeric profiles, reflecting the different stages of the disease (chronicvs.accelerated/blast phase). Statistical analyses showed significant differences between the CML subgroups (p < 0.001). We also found thatAURKAandAURKBmRNA were expressed at significantly higher levels in both CML subgroups, when compared with healthy donors. Our findings suggest that the evolution of CML progresses from a low to a high level of telomere dysfunction, that is, from an early stage to a more aggressive stage, followed by disease transformation, as demonstrated by telomere, additional chromosomal abnormalities, and gene expression profile dynamics.

Conclusions

Thus, we demonstrated that 3D telomere organization, in accordance with the genomic instability observed in CML samples were able to distinguish subgroup CML patients. Classifying CML patients based on these characteristics might represent an important strategy to define better therapeutic strategies.
Identifying individuals with undiagnosed post-traumatic stress disorder in a large United States civilian population – a machine learning approach
Authors: Gagnon-Sanschagrin Patrick , Schein Jeff , Urganus Annette , Serra Elizabeth , Liang Yawen , Musingarimi Primrose , Cloutier Martin , Guérin Annie , Davis Lori L.
Published: September 2022

Background

The proportion of patients with post-traumatic stress disorder (PTSD) that remain undiagnosed may be substantial. Without an accurate diagnosis, these patients may lack PTSD-targeted treatments and experience adverse health outcomes. This study used a machine learning approach to identify and describe civilian patients likely to have undiagnosed PTSD in the US commercial population.

Methods

The IBM® MarketScan® Commercial Subset (10/01/2015–12/31/2018) was used. A random forest machine learning model was developed and trained to differentiate between patients with and without PTSD using non–trauma-based features. The model was applied to patients for whom PTSD status could not be confirmed to identify individuals likely and unlikely to have undiagnosed PTSD. Patient characteristics, symptoms and complications potentially related to PTSD, treatments received, healthcare costs, and healthcare resource utilization were described separately for patients with PTSD (Actual Positive PTSD cohort), patients likely to have PTSD (Likely PTSD cohort), and patients without PTSD (Without PTSD cohort).

Results

A total of 44,342 patients were classified in the Actual Positive PTSD cohort, 5683 in the Likely PTSD cohort, and 2,074,471 in the Without PTSD cohort. While several symptoms/comorbidities were similar between the Actual Positive and Likely PTSD cohorts, others, including depression and anxiety disorders, suicidal thoughts/actions, and substance use, were more common in the Likely PTSD cohort, suggesting that certain symptoms may be exacerbated among those without a formal diagnosis. Mean per-patient-per-6-month healthcare costs were similar between the Actual Positive and Likely PTSD cohorts ($11,156 and $11,723) and were higher than those of the Without PTSD cohort ($3616); however, cost drivers differed between cohorts, with the Likely PTSD cohort experiencing more inpatient admissions and less outpatient visits than the Actual Positive PTSD cohort.

Conclusions

These findings suggest that the lack of a PTSD diagnosis and targeted management of PTSD may result in a greater burden among undiagnosed patients and highlights the need for increased awareness of PTSD in clinical practice and among the civilian population.
The impact of human resources for health on the health outcomes of Chinese people
Authors: Cheng Jingjing , Kuang Xianming , Zeng Linghuang
Published: September 2022

Human resources for health (HRH) is a cornerstone in the medical system. This paper combined data envelopment analysis (DEA) with Tobit regression analysis to evaluate the efficiency of health care services in China over the years between 2007 and 2019. Efficiency was first estimated by using DEA with the choice of inputs and outputs being specific to health care services and residents’ health status. Malmquist index model was selected for estimating the changes in total factor productivity of provinces and exploring whether their performance had improved over the years. Tobit regression model was then employed in which the efficiency score obtained from the DEA computations used as the dependent variable, and HRH was chosen as the independent variables. The results showed that all kinds of health personnel had a significantly positive impact on the efficiency, and more importantly, pharmacists played a critical role in affecting both the provincial and national efficiency. Therefore, the health sector should pay more attention to optimizing allocation of HRH and focusing on professional training of clinical pharmacists.
LncRNA Airn maintains LSEC differentiation to alleviate liver fibrosis via the KLF2-eNOS-sGC pathway
Authors: Chen Ting , Shi Zhemin , Zhao Yanmian , Meng Xiaoxiang , Zhao Sicong , Zheng Lina , Han Xiaohui , Hu Zhimei , Yao Qingbin , Lin Huajiang , Du Xiaoxiao , Zhang Kun , Han Tao , Hong Wei
Published: September 2022

Background

Long noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases. The dysregulation of liver sinusoidal endothelial cell (LSEC) phenotype is a critical early event in the fibrotic process. However, the biological function of lncRNAs in LSEC still remains unclear.

Methods

The expression level of lncRNA Airn was evaluated in both human fibrotic livers and serums, as well as mouse fibrotic livers. Gain- and loss-of-function experiments were performed to detect the effect of Airn on LSEC differentiation and hepatic stellate cell (HSC) activation in liver fibrosis. Furthermore, RIP, RNA pull-down-immunoblotting, and ChIP experiments were performed to explore the underlying mechanisms of Airn.

Results

We have identified Airn was significantly upregulated in liver tissues and LSEC of carbon tetrachloride (CCl4)-induced liver fibrosis mouse model. Moreover, the expression of AIRN in fibrotic human liver tissues and serums was remarkably increased compared with healthy controls. In vivo studies showed that Airn deficiency aggravated CCl4- and bile duct ligation (BDL)-induced liver fibrosis, while Airn over-expression by AAV8 alleviated CCl4-induced liver fibrosis. Furthermore, we revealed that Airn maintained LSEC differentiation in vivo and in vitro. Additionally, Airn inhibited HSC activation indirectly by regulating LSEC differentiation and promoted hepatocyte (HC) proliferation by increasing paracrine secretion of Wnt2a and HGF from LSEC. Mechanistically, Airn interacted with EZH2 to maintain LSEC differentiation through KLF2-eNOS-sGC pathway, thereby maintaining HSC quiescence and promoting HC proliferation.

Conclusions

Our work identified that Airn is beneficial to liver fibrosis by maintaining LSEC differentiation and might be a serum biomarker for liver fibrogenesis.
Clinical and genetic analyses of patients with lateralized overgrowth
Authors: Kim Yoon-Myung , Lee Yena , Choi Yunha , Choi In Hee , Heo Sun Hee , Choi Jung Min , Do Hyo-Sang , Jang Ja-Hyun , Yum Mi-Sun , Yoo Han-Wook , Lee Beom Hee
Published: September 2022

Background

The genetic features and treatment strategies of lateralized overgrowth have been elusive. We performed this study to analyze the genetic characteristics and treatment results of propranolol- or alpelisib-treated patients with lateralized overgrowth.

Methods

Fifteen patients with lateralized overgrowth were involved. Clinical characteristics and whole-body magnetic resonance imaging (WB-MRI) findings were evaluated. Targeted exome sequencing with a gene panel of affected tissue and peripheral white blood cells was performed. Propranolol was administered and treatment results were evaluated. The PIK3CA inhibitor alpelisib was prescribed via a managed access program.

Results

The identified mutations were PIK3CA (n = 7), KRAS (n = 2), PTEN (n = 1), MAP2K3 (n = 1), GNAQ (n = 1), TBC1D4 (n = 1), and TEK (n = 1). Propranolol was prescribed in 12 patients, and 7 experienced mild improvement of symptoms. Alpelisib was prescribed in two patients with a PIK3CA mutation, and the reduction of proliferated masses after 1 year of treatment was proved by WB-MRI.

Conclusions

Targeted exome sequencing identified various genetic features of lateralized overgrowth. Propranolol could be applied as an adjuvant therapy for reducing vascular symptoms, but a PIK3CA inhibitor would be the primary therapeutic strategy for PIK3CA-related overgrowth syndrome.
Enhancing therapeutic anti-cancer responses by combining immune checkpoint and tyrosine kinase inhibition
Authors: Daly Roger J. , Scott Andrew M. , Klein Oliver , Ernst Matthias
Published: September 2022

Over the past decade, immune checkpoint inhibitor (ICI) therapy has been established as the standard of care for many types of cancer, but the strategies employed have continued to evolve. Recently, much clinical focus has been on combining targeted therapies with ICI for the purpose of manipulating the immune setpoint. The latter concept describes the equilibrium between factors that promote and those that suppress anti-cancer immunity. Besides tumor mutational load and other cancer cell-intrinsic determinants, the immune setpoint is also governed by the cells of the tumor microenvironment and how they are coerced by cancer cells to support the survival and growth of the tumor. These regulatory mechanisms provide therapeutic opportunities to intervene and reduce immune suppression via application of small molecule inhibitors and antibody-based therapies against (receptor) tyrosine kinases and thereby improve the response to ICIs. This article reviews how tyrosine kinase signaling in the tumor microenvironment can promote immune suppression and highlights how therapeutic strategies directed against specific tyrosine kinases can be used to lower the immune setpoint and elicit more effective anti-tumor immunity.