bluuebunny/crossref_metadata_2025 huggingface dataset:
Doing community-based research during dual public health emergencies (COVID and overdose)
Authors: Beck McGreevy Phoenix , Wood Shawn , Thomson Erica , Burmeister Charlene , Spence Heather , Pelletier Josh , Giesinger Willow , McDougall Jenny , McLeod Rebecca , Hutchison Abby , Lock Kurt , Norton Alexa , Barker Brittany , Urbanoski Karen , Slaunwhite Amanda , Nosyk Bohdan , Pauly Bernie
Published: September 2023

Meaningful engagement and partnerships with people who use drugs are essential to conducting research that is relevant and impactful in supporting desired outcomes of drug consumption as well as reducing drug-related harms of overdose and COVID-19. Community-based participatory research is a key strategy for engaging communities in research that directly affects their lives. While there are growing descriptions of community-based participatory research with people who use drugs and identification of key principles for conducting research, there is a gap in relation to models and frameworks to guide research partnerships with people who use drugs. The purpose of this paper is to provide a framework for research partnerships between people who use drugs and academic researchers, collaboratively developed and implemented as part of an evaluation of a provincial prescribed safer supply initiative introduced during dual public health emergencies (overdose and COVID-19) in British Columbia, Canada. The framework shifts from having researchers choose among multiple models (advisory, partnership and employment) to incorporating multiple roles within an overall community-based participatory research approach. Advocacy by and for drug users was identified as a key role and reason for engaging in research. Overall, both academic researchers and Peer Research Associates benefited within this collaborative partnerships approach. Each offered their expertise, creating opportunities for omni-directional learning and enhancing the research. The shift from fixed models to flexible roles allows for a range of involvement that accommodates varying time, energy and resources. Facilitators of involvement include development of trust and partnering with networks of people who use drugs, equitable pay, a graduate-level research assistant dedicated to ongoing orientation and communication, technical supports as well as fluidity in roles and opportunities. Key challenges included working in geographically dispersed locations, maintaining contact and connection over the course of the project and ensuring ongoing sustainable but flexible employment.
Prevalence of unmet health care need in older adults in 83 countries: measuring progressing towards universal health coverage in the context of global population ageing
Authors: Kowal Paul , Corso Barbara , Anindya Kanya , Andrade Flavia C. D. , Giang Thanh Long , Guitierrez Maria Teresa Calzada , Pothisiri Wiraporn , Quashie Nekehia T. , Reina Herney Alonso Rengifo , Rosenberg Megumi , Towers Andy , Vicerra Paolo Miguel Manalang , Minicuci Nadia , Ng Nawi , Byles Julie
Published: September 2023

Current measures for monitoring progress towards universal health coverage (UHC) do not adequately account for populations that do not have the same level of access to quality care services and/or financial protection to cover health expenses for when care is accessed. This gap in accounting for unmet health care needs may contribute to underutilization of needed services or widening inequalities. Asking people whether or not their needs for health care have been met, as part of a household survey, is a pragmatic way of capturing this information. This analysis examined responses to self-reported questions about unmet need asked as part of 17 health, social and economic surveys conducted between 2001 and 2019, representing 83 low-, middle- and high-income countries. Noting the large variation in questions and response categories, the results point to low levels (less than 2%) of unmet need reported in adults aged 60+ years in countries like Andorra, Qatar, Republic of Korea, Slovenia, Thailand and Viet Nam to rates of over 50% in Georgia, Haiti, Morocco, Rwanda, and Zimbabwe. While unique, these estimates are likely underestimates, and do not begin to address issues of poor quality of care as a barrier or contributing to unmet need in those who were able to access care. Monitoring progress towards UHC will need to incorporate estimates of unmet need if we are to reach universality and reduce health inequalities in older populations.
Arginine methylation of HSPA8 by PRMT9 inhibits ferroptosis to accelerate hepatitis B virus-associated hepatocellular carcinoma progression
Authors: Deng Wensheng , Ai Jiaoyu , Zhang Wanlin , Zhou Zhenyu , Li Muqi , Yan Likun , Zhang Lidong , Huang Zongjing , Wu Ziyi , Ai Junhua , Jiang Hai
Published: September 2023

Background

The hepatitis B virus X (HBx) protein is an established cause of hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). Whether arginine methylation regulates ferroptosis involved in HBx-induced HCC progression has not been reported. This study aimed to explore whether HBx-regulated protein arginine methyltransferase 9 (PRMT9) mediates the involvement of ferroptosis in the development of HCC.

Methods and results

HBx inhibited ferroptosis through promoting PRMT9 expression in HCC cells. PRMT9 suppressed ferroptosis to accelerate HCC progression in vivo. PRMT9 targeted HSPA8 and enhanced arginine methylation of HSPA8 at R76 and R100 to regulate ferroptosis in HCC. HSPA8 overexpression altered the transcriptome profile of HepG2 cells, in particular, ferroptosis and immune-related pathways were significantly enriched by differentially expressed genes, including CD44. HSPA8 overexpression up-regulated CD44 expression and knockdown of CD44 significantly reversed the inhibition of ferroptosis caused by PRMT9 overexpression.

Conclusions

In conclusion, HBx/PRMT9/HSPA8/CD44 axis is a vital signal pathway regulating ferroptosis in HCC cells. This study provides new opportunities and targets for the treatment of HBV-induced HCC.

Graphical Abstract
Targeting FGFRs by pemigatinib induces G1 phase cell cycle arrest, cellular stress and upregulation of tumor suppressor microRNAs
Authors: Pace Angelica , Scirocchi Fabio , Napoletano Chiara , Zizzari Ilaria Grazia , Po Agnese , Megiorni Francesca , Asquino Angela , Pontecorvi Paola , Rahimi Hassan , Marchese Cinzia , Ferretti Elisabetta , Nuti Marianna , Rughetti Aurelia
Published: September 2023

Background

Fibroblast growth factor receptor (FGFR) gene family alterations are found in several cancers, indicating their importance as potential therapeutic targets. The FGFR-tyrosine kinase inhibitor (TKI) pemigatinib has been introduced in the treatment of advanced cholangiocarcinoma and more recently for relapsed or refractory myeloid/lymphoid neoplasms with FGFR2 and FGFR1 rearrangements, respectively. Several clinical trials are currently investigating the possible combination of pemigatinib with immunotherapy.

In this study, we analyzed the biological and molecular effects of pemigatinib on different cancer cell models (lung, bladder, and gastric), which are currently objective of clinical trial investigations.

Methods

NCI-H1581 lung, KATO III gastric and RT-112 bladder cancer cell lines were evaluated for FGFR expression by qRT-PCR and Western blot. Cell lines were treated with Pem and then characterized for cell proliferation, apoptosis, production of intracellular reactive oxygen species (ROS), and induction of senescence. The expression of microRNAs with tumor suppressor functions was analyzed by qRT-PCR, while modulation of the proteins coded by their target genes was evaluated by Western blot and mRNA. Descriptive statistics was used to analyze the various data and student’s t test to compare the analysis of two groups.

Results

Pemigatinib exposure triggered distinct signaling pathways and reduced the proliferative ability of all cancer cells, inducing G1 phase cell cycle arrest and strong intracellular stress resulting in ROS production, senescence and apoptosis. Pemigatinib treatment also caused the upregulation of microRNAs (miR-133b, miR-139, miR-186, miR-195) with tumor suppressor functions, along with the downregulation of validated protein targets with oncogenic roles (c-Myc, c-MET, CDK6, EGFR).

Conclusions

These results contribute to clarifying the biological effects and molecular mechanisms mediated by the anti-FGFR TKI pemigatinib in distinct tumor settings and support its exploitation for combined therapies.
Neural precursor cell delivery induces acute post-ischemic cerebroprotection, but fails to promote long-term stroke recovery in hyperlipidemic mice due to mechanisms that include pro-inflammatory responses associated with brain hemorrhages
Authors: Yin Dongpei , Wang Chen , Qi Yachao , Wang Ya-Chao , Hagemann Nina , Mohamud Yusuf Ayan , Dzyubenko Egor , Kaltwasser Britta , Tertel Tobias , Giebel Bernd , Gunzer Matthias , Popa-Wagner Aurel , Doeppner Thorsten R. , Hermann Dirk M.
Published: September 2023

Background

The intravenous delivery of adult neural precursor cells (NPC) has shown promising results in enabling cerebroprotection, brain tissue remodeling, and neurological recovery in young, healthy stroke mice. However, the translation of cell-based therapies to clinical settings has encountered challenges. It remained unclear if adult NPCs could induce brain tissue remodeling and recovery in mice with hyperlipidemia, a prevalent vascular risk factor in stroke patients.

Methods

Male mice on a normal (regular) diet or on cholesterol-rich Western diet were exposed to 30 min intraluminal middle cerebral artery occlusion (MCAO). Vehicle or 106 NPCs were intravenously administered immediately after reperfusion, at 3 day and 7 day post-MCAO. Neurological recovery was evaluated using the Clark score, Rotarod and tight rope tests over up to 56 days. Histochemistry and light sheet microscopy were used to examine ischemic injury and brain tissue remodeling. Immunological responses in peripheral blood and brain were analyzed through flow cytometry.

Results

NPC administration reduced infarct volume, blood–brain barrier permeability and the brain infiltration of neutrophils, monocytes, T cells and NK cells in the acute stroke phase in both normolipidemic and hyperlipidemic mice, but increased brain hemorrhage formation and neutrophil, monocyte and CD4+ and CD8+ T cell counts and activation in the blood of hyperlipidemic mice. While neurological deficits in hyperlipidemic mice were reduced by NPCs at 3 day post-MCAO, NPCs did not improve neurological deficits at later timepoints. Besides, NPCs did not influence microglia/macrophage abundance and activation (assessed by morphology analysis), astroglial scar formation, microvascular length or branching point density (evaluated using light sheet microscopy), long-term neuronal survival or brain atrophy in hyperlipidemic mice.

Conclusions

Intravenously administered NPCs did not have persistent effects on post-ischemic neurological recovery and brain remodeling in hyperlipidemic mice. These findings highlight the necessity of rigorous investigations in vascular risk factor models to fully assess the long-term restorative effects of cell-based therapies. Without comprehensive studies in such models, the clinical potential of cell-based therapies cannot be definitely determined.
Feed plants, ethnoveterinary medicine, and biocultural values: insights on the Luchuan pig from Hakka communities in China
Authors: Liufu Yongqing , Zhou Jilong , Fu Qiongyao , Shao Min , Xie Yaozhang , Luo Binsheng
Published: September 2023

Background

The Luchuan pig is an indigenous breed from Luchuan County, China, with cultural and genetic significance. However, traditional knowledge and conservation status have not been systematically documented.

Methods

Using ethnobiological methods, we surveyed 72 Luchuan pig farmers in 7 townships during 2021–2023. Semi-structured interviews and participant observation were conducted to document traditional knowledge and management practices.

Results

The locals reported 51 plant species used as pig feed, with 30 wild species. Growth-stage-specific feeding and seasonal adjustment practices were documented. We recorded 62 ethnoveterinary plant uses, mainly for treating pigs' heat stress and skin conditions. Luchuan pigs play central roles in local Hakka customs, rituals, and cuisine. Additonally, the new ecological farming models minimize the environmental impacts to the local community. However, there are still some challenges remained for conserving and promoting Luchuan pigs.

Conclusions

The Luchuan Hakka people possess rich traditional knowledge and management experience in raising Luchuan pigs. Our study provides extensive documentation of traditional knowledge and recommends integrating cultural and genetic aspects for sustaining this biocultural heritage. Findings can inform initiatives supporting local breed conservation globally.
Causal associations of Sjögren’s syndrome with cancers: a two-sample Mendelian randomization study
Authors: Jia Yiwei , Yao Peizhuo , Li Jia , Wei Xinyu , Liu Xuanyu , Wu Huizi , Wang Weiwei , Feng Cong , Li Chaofan , Zhang Yu , Cai Yifan , Zhang Shuqun , Ma Xingcong
Published: September 2023

Background

Several observational studies have explored the associations between Sjögren’s syndrome (SS) and certain cancers. Nevertheless, the causal relationships remain unclear. Mendelian randomization (MR) method was used to investigate the causality between SS and different types of cancers.

Methods

We conducted the two-sample Mendelian randomization with the public genome-wide association studies (GWASs) summary statistics in European population to evaluate the causality between SS and nine types of cancers. The sample size varies from 1080 to 372,373. The inverse variance weighted (IVW) method was used to estimate the causal effects. A Bonferroni-corrected threshold of P < 0.0031 was considered significant, and P value between 0.0031 and 0.05 was considered to be suggestive of an association. Sensitivity analysis was performed to validate the causality. Moreover, additional analysis was used to assess the associations between SS and well-accepted risk factors of cancers.

Results

After correcting the heterogeneity and horizontal pleiotropy, the results indicated that patients with SS were significantly associated with an increased risk of lymphomas (odds ratio [OR] = 1.0010, 95% confidence interval [CI]: 1.0005–1.0015, P = 0.0002) and reduced risks of prostate cancer (OR = 0.9972, 95% CI: 0.9960–0.9985, P = 2.45 × 10−5) and endometrial cancer (OR = 0.9414, 95% CI: 0.9158–0.9676, P = 1.65 × 10−5). Suggestive associations were found in liver and bile duct cancer (OR = 0.9999, 95% CI: 0.9997–1.0000, P = 0.0291) and cancer of urinary tract (OR = 0.9996, 95% CI: 0.9992–1.0000, P = 0.0281). No causal effect of SS on other cancer types was detected. Additional MR analysis indicated that causal effects between SS and cancers were not mediated by the well-accepted risk factors of cancers. No evidence of the causal relationship was observed for cancers on SS.

Conclusions

SS had significant causal relationships with lymphomas, prostate cancer, and endometrial cancer, and suggestive evidence of association was found in liver and bile duct cancer and cancer of urinary tract, indicating that SS may play a vital role in the incidence of these malignancies.
Appendiceal mucocele as an exceptional cause of ileocecocolic intussusception in adults: a case report
Authors: Zabeirou Aliou , Efared Boubacar , James Didier Lassey , Younssa Hama , Adama Saidou , Moussa Younoussa , Rachid Sani
Published: September 2023

Background

Intussusception is a rare condition in adults, accounting for 5% of intestinal intussusception and being responsible for approximately 1% of all adult bowel obstructions. Neoplastic origin is the most common etiology of intestinal intussusception in adults, unlike pediatric intussusception, which is usually idiopathic. Intussusception due to the appendiceal mucocele is exceptional, and only a few cases have been reported in the medical literature.

Case presentation

We report the case of a 25-year-old black African male patient with no medical history. He presented to the emergency department for abdominal pain, nausea, and bilious vomiting. The abdominal examination revealed typical signs of acute bowel obstruction. Enhanced abdominopelvic computed tomography showed an invagination of the last ileal loop, cecum, and ascending colon into the lumen of the transverse colon, with a rounded image with hypodense content and some calcifications compatible with an appendiceal mucocele. An emergency exploratory laparoscopy was performed and confirmed the ileocecocolic intussusception. Right hemicolectomy and ileocolic anastomosis were performed. The patient recovery postoperatively was uneventful, and he was discharged 4 days later. Histological examination of the surgical specimen confirmed the diagnosis of mucinous cystadenoma.

Conclusion

The symptoms of bowel intussusception with the appendiceal mucocele as the lead point in adults are similar to any other bowel intussusception. Differential diagnosis is often carried out thanks to the injected abdominal computed tomography scan.
rMSIfragment: improving MALDI-MSI lipidomics through automated in-source fragment annotation
Authors: Baquer Gerard , Sementé Lluc , Ràfols Pere , Martín-Saiz Lucía , Bookmeyer Christoph , Fernández José A. , Correig Xavier , García-Altares María
Published: September 2023

Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) spatially resolves the chemical composition of tissues. Lipids are of particular interest, as they influence important biological processes in health and disease. However, the identification of lipids in MALDI-MSI remains a challenge due to the lack of chromatographic separation or untargeted tandem mass spectrometry. Recent studies have proposed the use of MALDI in-source fragmentation to infer structural information and aid identification. Here we present rMSIfragment, an open-source R package that exploits known adducts and fragmentation pathways to confidently annotate lipids in MALDI-MSI. The annotations are ranked using a novel score that demonstrates an area under the curve of 0.7 in ROC analyses using HPLC–MS and Target-Decoy validations. rMSIfragment applies to multiple MALDI-MSI sample types and experimental setups. Finally, we demonstrate that overlooking in-source fragments increases the number of incorrect annotations. Annotation workflows should consider in-source fragmentation tools such as rMSIfragment to increase annotation confidence and reduce the number of false positives.
A 14-year series of leaf phenological data collected for European beech (Fagus sylvatica L.) and silver fir (Abies alba Mill.) from their geographic range margins in south-eastern France
Authors: Jean Frederic , Davi Hendrik , Oddou-Muratorio Sylvie , Fady Bruno , Scotti Ivan , Scotti-Saintagne Caroline , Ruffault Julien , Journe Valentin , Clastre Philippe , Marloie Olivier , Brunetto William , Correard Marianne , Gilg Olivier , Pringarbe Mehdi , Rei Franck , Thevenet Jean , Turion Norbert , Pichot Christian
Published: September 2023

Key message

Phenology is of increasing interest to climate change science and adaptation ecology. Here, we provide bud development, leafing, and leaf senescence data, collected on 772 European beech and silver fir trees between 2006 and 2019 on Mont Ventoux, France. Dataset access is at https://doi.org/10.15454/TRFMZN. Associated metadata are available at https://metadata-afs.nancy.inra.fr/geonetwork/srv/fre/catalog.search#/metadata/a33c8375-9a90-4bc3-a0d7-19317160b68f.
Paedoksan ameliorates allergic disease through inhibition of the phosphorylation of STAT6 in DNCB-induced atopic dermatitis like mice
Authors: Lee Sang Heon , Oh Youngse , Bong Sim-Kyu , Lee Jin Woo , Park No-June , Kim Young-Joo , Park Hyun Bong , Kim Yong Kee , Kim Seung Hyun , Kim Su-Nam
Published: September 2023

Various allergic diseases such as atopic dermatitis (AD), allergic rhinitis, and asthma are considered incurable conditions that have yet to be fully conquered. Paedoksan (PDS), an herbal preparation consisting of 14 medicines, displays effective anti-inflammatory and anti-allergic properties, yet its underlying molecular mechanism is unknown. This study aims to uncover PDS’s mechanism for treating allergic diseases and suggest its therapeutic potential. Through a network pharmacological prediction, its impact on signal transducer and activator of transcription 6 (STAT6) regulation, a sub-mechanism of interleukin 4 (IL-4), a major inflammatory cytokine involved in degranulation and allergy, was investigated in RBL-2H3 cells and an atopic mouse model. PDS inhibits immunoglobulin E (IgE)-induced degranulation and STAT6 phosphorylation evoked by IL-4 in granulocytes. The downregulation of phospho-STAT6 and thymic stromal lymphopoietin (TSLP) by PDS was confirmed in 2,4-dinitrochlorobenzene (DNCB)-induced mouse skin. The results demonstrate that PDS exhibited remarkable effects on degranulation and STAT6 phosphorylation in RBL-2H3 cells, as well as in an atopic mouse model. Furthermore, the main active components from PDS based on chromatographic analysis showed good accordance with PDS’s effects on RBL-2H3 cells. In summary, these findings collectively suggest that PDS holds the potential to effectively suppress inflammatory and allergic reactions by obstructing the target IL-4 protein and its downstream effects, as elucidated through a network pharmacological analysis.
Chest computed tomography severity score is a reliable predictor of mortality in patients with chronic obstructive pulmonary disease co-infected with COVID-19
Authors: Alipour Khabir Yalda , Alipour Khabir Sevda , Anari Hassan , Mohammadzadeh Bahman , Hoseininia Saeed , Aslani Mohammad Reza
Published: September 2023

Background

Coronavirus disease 2019 (COVID-19) pandemic is considered a global health crisis. The data related to chronic obstructive pulmonary disease (COPD) patients with COVID-19 are incomplete, especially the findings of the chest computed tomography (CT). The aim of the current study was to investigate the severity of the disease of COVID-19 in patients with COPD based on CT severity score and to evaluate its predictive power in the mortality of patients.

Methods

In a retrospective study, demographic, clinical, and CT scan findings of COPD patients with COVID-19 were extracted from March 2020 to February 2022. CT severity score was determined based on the extent and nature of involvement of lungs in CT scan findings. By performing receiver operating characteristics (ROC) and Kaplan–Meier survival analysis were determined the disease severity and survival probability.

Results

The most frequent radiological findings in chest CT scan included ground glass opacities (89.3%), consolidations (51.8%), crazy-paving pattern (46.4%), and septal thickening (35.7%). The mean CT severity score of deceased patients (34.61 ± 18.73) was significantly higher than recovered patients (16.71 ± 14.01, p < 0.001). Based on the ROC and Kaplan–Meier survival curves, it was revealed that CT severity score was a valuable criteria in the diagnosis of mortality in COPD patients with COVID-19.

Conclusion

The findings of this study revealed that the CT severity scoring in COPD patients with COVID-19 was valuable in identifying poor prognosis, although further studies are needed.
Household environment and animal fecal contamination are critical modifiers of the gut microbiome and resistome in young children from rural Nicaragua
Authors: Mills Molly , Lee Seungjun , Piperata Barbara A. , Garabed Rebecca , Choi Boseung , Lee Jiyoung
Published: September 2023

Background

Early life plays a vital role in the development of the gut microbiome and subsequent health. While many factors that shape the gut microbiome have been described, including delivery mode, breastfeeding, and antibiotic use, the role of household environments is still unclear. Furthermore, the development of the gut antimicrobial resistome and its role in health and disease is not well characterized, particularly in settings with water insecurity and less sanitation infrastructure.

Results

This study investigated the gut microbiome and resistome of infants and young children (ages 4 days-6 years) in rural Nicaragua using Oxford Nanopore Technology’s MinION long-read sequencing. Differences in gut microbiome diversity and antibiotic resistance gene (ARG) abundance were examined for associations with host factors (age, sex, height for age z-score, weight for height z-score, delivery mode, breastfeeding habits) and household environmental factors (animals inside the home, coliforms in drinking water, enteric pathogens in household floors, fecal microbial source tracking markers in household floors). We identified anticipated associations of higher gut microbiome diversity with participant age and vaginal delivery. However, novel to this study were the significant, positive associations between ruminant and dog fecal contamination of household floors and gut microbiome diversity. We also identified greater abundance of potential pathogens in the gut microbiomes of participants with higher fecal contamination on their household floors. Path analysis revealed that water quality and household floor contamination independently and significantly influenced gut microbiome diversity when controlling for age. These gut microbiome contained diverse resistome, dominated by multidrug, tetracycline, macrolide/lincosamide/streptogramin, and beta-lactam resistance. We found that the abundance of ARGs in the gut decreased with age. The bacterial hosts of ARGs were mainly from the family Enterobacteriaceae, particularly Escherichia coli.

Conclusions

This study identified the role of household environmental contamination in the developing gut microbiome and resistome of young children and infants with a One Health perspective. We found significant relationships between host age, gut microbiome diversity, and the resistome. Understanding the impact of the household environment on the development of the resistome and microbiome in early life is essential to optimize the relationship between environmental exposure and human health.

Graphical Abstract
Identification of molecular signatures and pathways involved in Rett syndrome using a multi-omics approach
Authors: Pascual-Alonso Ainhoa , Xiol Clara , Smirnov Dmitrii , Kopajtich Robert , Prokisch Holger , Armstrong Judith
Published: September 2023

Background

Rett syndrome (RTT) is a neurodevelopmental disorder mainly caused by mutations in the methyl-CpG-binding protein 2 gene (MECP2). MeCP2 is a multi-functional protein involved in many cellular processes, but the mechanisms by which its dysfunction causes disease are not fully understood. The duplication of the MECP2 gene causes a distinct disorder called MECP2 duplication syndrome (MDS), highlighting the importance of tightly regulating its dosage for proper cellular function. Additionally, some patients with mutations in genes other than MECP2 exhibit phenotypic similarities with RTT, indicating that these genes may also play a role in similar cellular functions. The purpose of this study was to characterise the molecular alterations in patients with RTT in order to identify potential biomarkers or therapeutic targets for this disorder.

Methods

We used a combination of transcriptomics (RNAseq) and proteomics (TMT mass spectrometry) to characterise the expression patterns in fibroblast cell lines from 22 patients with RTT and detected mutation in MECP2, 15 patients with MDS, 12 patients with RTT-like phenotypes and 13 healthy controls. Transcriptomics and proteomics data were used to identify differentially expressed genes at both RNA and protein levels, which were further inspected via enrichment and upstream regulator analyses and compared to find shared features in patients with RTT.

Results

We identified molecular alterations in cellular functions and pathways that may contribute to the disease phenotype in patients with RTT, such as deregulated cytoskeletal components, vesicular transport elements, ribosomal subunits and mRNA processing machinery. We also compared RTT expression profiles with those of MDS seeking changes in opposite directions that could lead to the identification of MeCP2 direct targets. Some of the deregulated transcripts and proteins were consistently affected in patients with RTT-like phenotypes, revealing potentially relevant molecular processes in patients with overlapping traits and different genetic aetiology.

Conclusions

The integration of data in a multi-omics analysis has helped to interpret the molecular consequences of MECP2 dysfunction, contributing to the characterisation of the molecular landscape in patients with RTT. The comparison with MDS provides knowledge of MeCP2 direct targets, whilst the correlation with RTT-like phenotypes highlights processes potentially contributing to the pathomechanism leading these disorders.
Language-dependent cue weighting in distinctive feature: evidence from the perception of Mandarin high vowels by native English speakers
Authors: Zhu Wenhui , Lee Sun-Hee , Zhang Xinting
Published: September 2023

This study investigates the perception of the three Mandarin high vowels /i, u, y/ after dental, retroflex, and palatal fricatives and affricates (/s/-/ʦ/-/ʦʰ/; /ʂ/-/tʂ/-/tʂʰ/, and /ʨ/, /ʨʰ/, /ɕ/) by native English speakers. The results of the perceptual identification and categorization experiments show that among the three target vowels, the high front rounded vowel /y/ presents the greatest challenge for native English speakers. They have a significantly higher tendency to confuse /y/ with the Mandarin high-back rounded vowel /u/ compared to the Mandarin high-front unrounded vowel /i/, as they perceptually classified /y/ and /u/ into the same English vowel category /u/. The findings of the study suggest that native English speakers adopt a perceptual strategy that differs from that of native Japanese and Korean speakers, relying heavier on the feature of roundness as opposed to backness in perceiving the Mandarin /y/. This study contributes to the perceptual cue weighting field by examining the weighting of phonetic cues (i.e., distinctive features) in Mandarin high vowels by native English speakers. These results hold pedagogical significance as they highlight the importance of targeted perception training for learners of different language backgrounds to enhance both their recognition and reproduction of second language sounds.
Predicting volatility of bitcoin returns with ARCH, GARCH and EGARCH models
Authors: Yıldırım Hakan , Bekun Festus Victor
Published: September 2023

The ınvestment decisions of institutional and individual investors in financial markets are largely influenced by market uncertainty and volatility of the investment instruments. Thus, the prediction of the uncertainty and volatilities of the prices and returns of the investment instruments becomes imperative for successful investment. In this study we seek to identify the best fit model that can predict the volatility of return of Bitcoin, which is in high demand as an investment tool in recent times. Using the opening data of weekly Bitcoin prices for the period of 11.24.2013–03.22.2020, their logarithmic returns were calculated. The stationarity properties of the Bitcoin return series was tested by applying the ADF unit root test and the series were found to be stationary. After reaching the average equation model as ARMA (2.2), it was tested whether there was an ARCH effect in the ARMA (2,2) model. As a result of the applied ARCH-LM test, it is reached that the residuals of the average equation model selected have ARCH effect. Volatility of Bitcoin return series after detection of ARCH effect has been tried to predict with conditional variance models such as ARCH (1), ARCH (2), ARCH (3), GARCH (1,1), GARCH (1,2), GARCH (1,3), GARCH (2,1), GARCH (2,2), EGARCH (1,1) and EGARCH (1,2). While the obtained findings indicate that the best model is in the direction of GARCH (1,1) according to Akaike info criterion, it was found that GARCH (1,1) model does not have ARCH effect as a result of the applied ARCH-LM test. Thus, our empirical findings highlight an ample guide on appropriate modeling of price information in the Bitcoin market.
Prognostic Factors in High-Grade Osteosarcoma of theExtremities or Trunk: An Analysis of 1,702 Patients Treatedon Neoadjuvant Cooperative Osteosarcoma Study GroupProtocols
Authors: Bielack Stefan S. , Kempf-Bielack Beate , Delling Günter , Exner G. Ulrich , Flege Silke , Helmke Knut , Kotz Rainer , Salzer-Kuntschik Mechthild , Werner Matthias , Winkelmann Winfried , Zoubek Andreas , Jürgens Heribert , Winkler Kurt
Published: September 2023

PURPOSE: To define prognostic factors for response and long-term outcome for a wide spectrum of osteosarcomas, extending well beyond those of the typical young patient with seemingly localized extremity disease.

PATIENTS AND METHODS: A total of 1,702 consecutive newly diagnosed patients with high-grade osteosarcoma of the trunk or limbs registered into the neoadjuvant studies of the Cooperative Osteosarcoma Study Group before July 1998 were entered into an analysis of demographic, tumor-related, and treatment-related variables, response, and survival. The intended therapeutic strategy included preoperative and postoperative chemotherapy with multiple agents as well as surgery of all operable lesions.

RESULTS: Axial tumor site, male sex, and a long history of symptoms were associated with poor response to chemotherapy in univariate and multivariate analysis. Actuarial 10-year overall and event-free survival rates were 59.8% and 48.9%. Among the variables assessable at diagnosis, patient age (actuarial 10-year survival ≥ 40, 41.6%; < 40, 60.2%; P = .012), tumor site (axial, 29.2%; limb, 61.7%; P < .0001), and primary metastases (yes, 26.7%; no, 64.4%; P < .0001), and for extremity osteosarcomas, also size (≥ one third, 52.5%; < one third, 66.7%; P < .0001) and location within the limb (proximal, 49.3%; other, 63.9%; P < .0001), had significant influence on outcome. Two additional important prognostic factors were treatment related: response to chemotherapy (poor, 47.2%; good, 73.4%; P < .0001) and the extent of surgery (incomplete, 14.6%; macroscopically complete, 64.8%; P < .0001). All factors except age maintained their significance in multivariate testing, with surgical remission and histologic response emerging as the key prognostic factors.

CONCLUSION: Tumor site and size, primary metastases, response to chemotherapy, and surgical remission are of independent prognostic value in osteosarcoma.
Hyperbolic cones for casual diffeomorphisms
Authors: Rahimi Moghbeli S. , Molaei M. R.
Published: September 2023

This paper begins with introducing a new class of diffeomorphisms on pseudo-Riemannian manifolds which are called casual diffeomorphisms. We deduce a new pseudo-Riemannian metric via a casual diffeomorphism. We introduce a class of cones for a diffeomorphism, and we prove the existence of such cones for each p in a hyperbolic set of a casual diffeomorphism. As an example we find a hyperbolic casual diffeomorphism on a Schwarzschild pseudo-Riemannian manifold, and show that the whole manifold is a hyperbolic set for it.
Associations Between Fresh Gas Flow and Duration of Anesthetic on the Maximum Potential Benefit of Anesthetic Gas Capture in Operating Rooms and in Postanesthesia Care Units to Capture Waste Anesthetic Gas
Authors: Dexter Franklin , Epstein Richard H.
Published: September 2023

BACKGROUND:

Sevoflurane and desflurane are halogenated hydrocarbons with global warming potential. We examined the maximum potential benefit assuming 100% efficiency of waste gas capture technology used in operating rooms and recovery locations.

METHODS:

We performed computer simulations of adult patients using the default settings of the Gas Man software program, including the desflurane vaporizer setting of 9% and the sevoflurane vaporizer setting of 3.7%. We performed 21 simulations with desflurane and 21 simulations with sevoflurane, the count of 21 = 1 simulation with 0-hour maintenance + (1, 2, 3, 4, or 5 hours of maintenance) × (0.5, 1, 2, or 4 L per minute fresh gas flow during maintenance).

RESULTS:

(1) A completely efficient gas capture system could recover a substantive amount of agent even when the case is managed with low flows. All simulations had at least 22 mL agent recovered per case, considerably greater than the 12 mL that we considered the minimum volume of economic and environmental importance. (2) All 42 simulations had at least 73% recovery of the total agent administered, considerably greater than the median 52% recovery measured during an experimental study with one gas capture technology and desflurane. (3) The maximum percentage desflurane (or sevoflurane) that could be captured decreased substantively with progressively longer duration anesthetics for low-flow anesthetics but not for higher-flow anesthetics. However, for all 8 combinations of drug and liters per minute simulated, there was a substantively greater recovery in milliliters of agent for longer duration anesthetics. In other words, if gas capture could be near perfectly efficient, it would have greater utility per case for longer duration anesthetics. (4) Even using a 100% efficient gas capture process, at most 6 mL liquid desflurane or 3 mL sevoflurane per case would be exhaled during the patient’s stay in the postanesthesia care unit. Therefore, the volume of agent exhaled during the first 1 hour postoperatively is not a substantial amount from an environmental and economic perspective to warrant consideration of agent capture by having all these patients in the postanesthesia care unit, or equivalent locations, using the specialized anesthetic gas scavenging masks with access to the hospital scavenging system at each bed.

CONCLUSIONS:

Simulations with Gas Man show a strong rationale based on agent uptake and distribution for using volatile anesthetic agent capture in operating rooms if the technology can be highly efficient at volatile agent recovery.
Postanesthesia Care Unit Recovery Time According to Volatile Anesthetic Used in Clinical Practice
Authors: Sprung Juraj , Deljou Atousa , Warner David O. , Schroeder Darrell R. , Weingarten Toby N.
Published: September 2023

BACKGROUND:

Whether volatile anesthetic solubility affects postanesthesia recovery time in clinical practice is unclear. We investigated the association among 3 volatile agents and 2 clinically relevant outcomes—postanesthesia care unit (PACU) recovery time (time from PACU admission to fulfillment of discharge criteria) and oversedation (Richmond Agitation-Sedation Scale score ≤−3)—as a potential contributor to delaying PACU discharge. The volatile agents studied were isoflurane, desflurane, and sevoflurane. We hypothesized that increased solubility of the volatile agent (isoflurane versus desflurane or sevoflurane) would be associated with longer PACU recovery time and higher rates of oversedation.

METHODS:

This retrospective observational study included adults (≥18 years) who underwent surgical procedures under general anesthesia with a volatile agent and were admitted to the PACU from May 5, 2018, to December 31, 2020. The primary outcome was PACU recovery time, and the secondary outcome was oversedation. PACU recovery time was log-transformed and analyzed with linear regression. Oversedation was analyzed by using logistic regression. To account for potential confounding, inverse probability of treatment weighting (IPTW) was used. Pairwise comparisons of the 3 agents were performed, with P < .017 (Bonferroni-adjusted) considered significant.

RESULTS:

Of 47,847 patients included, 11,817 (24.7%) received isoflurane, 11,286 (23.6%) received desflurane, and 24,744 (51.7%) received sevoflurane. Sevoflurane had an estimated 4% shorter PACU recovery time (IPTW-adjusted median [interquartile range {IQR}], 61 [42–89] minutes) than isoflurane (64 [44–92] minutes) (ratio of geometric means [98.3% confidence interval {CI}], 0.96 [0.95–0.98]; P < .001). Differences in PACU recovery time between desflurane and the other agents were not significant. The IPTW-adjusted frequency of oversedation was 8.8% for desflurane, 12.2% for sevoflurane, and 16.7% for isoflurane; all pairwise comparisons were observed to be significant (odds ratio [98.3% CI], 0.70 [0.62–0.79] for desflurane versus sevoflurane, 0.48 [0.42–0.55] for desflurane vs isoflurane, and 0.69 [0.63–0.76] for sevoflurane versus isoflurane; all P < .001). Although oversedated patients had longer PACU recovery time, differences in the oversedation rate across agents did not result in meaningful differences in time to PACU recovery.

CONCLUSIONS:

In clinical practice, only small, clinically unimportant differences in PACU recovery time were observed between the volatile anesthetics. Although oversedation was associated with increased PACU recovery time, differences in the rate of oversedation among agents were insufficient to produce meaningful differences in overall PACU recovery time across the 3 volatile agents. Practical attempts to decrease PACU recovery time should address factors other than volatile agent selection.
The Women in Cardiothoracic Anesthesiology Special Interest Group: What Can the Lessons of One Anesthesiology Affinity Group Tell Us About How to Build Impactful Professional Communities?
Authors: Methangkool Emily , Faloye Abimbola , Kolarczyk Lavinia , Deshpande Seema , Belani Kiran , Trzcinka Agnieszka , Lewis Choy R. , Balimunkwe Rebecca Mutesi , Oakes Daryl
Published: September 2023

The Women In Cardiothoracic Anesthesiology (WICTA), a special interest group of the Society of Cardiovascular Anesthesiologists, has been highly successful in mobilizing WICTA, a historically underrepresented and marginalized group in the subspecialty, and in supporting real and meaningful change in the professional community. The experience of WICTA as a professional affinity group in impacting a professional organization to diversify, evolve, and become more responsive to a wider professional audience has important lessons for other professional organizations. This article discusses the recent history of affinity organizations in anesthesiology, the benefits they offer professional organizations, and the strategies that have been used to effectively motivate change in professional communities. These strategies include engaging a strong advisory board, identifying the need of constituents, creating additional opportunities for networking and membership, addressing gaps in professional development, and aligning goals with those of the larger national organization. WICTA is just one example of the potential opportunities that affinity groups offer to professional societies and organizations for expanding their reach, enhancing their impact on physicians in their target audience, and achieving organizational missions.
The Drosophila homolog of APP promotes Dscam expression to drive axon terminal growth, revealing interaction between Down syndrome genes
Authors: Pizzano Sarah , Sterne Gabriella R. , Veling Macy W. , Xu L. Amanda , Hergenreder Ty , Ye Bing
Published: September 2023

Down syndrome (DS) is caused by triplication of human chromosome 21 (HSA21). Although several HSA21 genes have been found to be responsible for aspects of DS, whether and how HSA21 genes interact with each other is poorly understood. DS patients and animal models present with a number of neurological changes, including aberrant connectivity and neuronal morphology. Previous studies have indicated that amyloid precursor protein (APP) and Down syndrome cell adhesion molecule (DSCAM) regulate neuronal morphology and contribute to neuronal aberrations in DS. Here, we report the functional interaction between the Drosophila homologs of these two genes, Amyloid precursor protein-like (Appl) and Dscam (Dscam1). We show that Appl requires Dscam to promote axon terminal growth in sensory neurons. Moreover, Appl increases Dscam protein expression post-transcriptionally. We further demonstrate that regulation of Dscam by Appl does not require the Appl intracellular domain or second extracellular domain. This study presents an example of functional interactions between HSA21 genes, providing insights into the pathogenesis of neuronal aberrations in DS.
Short tandem repeat profiling via next-generation sequencing for cell line authentication
Authors: Chen Yi-Hsien , Connelly Jon P. , Florian Colin , Cui Xiaoxia , Pruett-Miller Shondra M.
Published: September 2023

Cell lines are indispensable models for modern biomedical research. A large part of their usefulness derives from the ability of a cell line to proliferate over multiple passages (often indefinitely), allowing multiple experiments to be performed. However, over time, cell line identity and purity can be compromised by human errors. Cross-contamination from other cell lines and complete misidentification are both possible. Routine cell line authentication is a necessary preventive measure and has become a requirement for many funding applications and publications. Short tandem repeat (STR) profiling is the most common method for cell line authentication and is usually carried out using standard polymerase chain reaction-capillary electrophoresis analysis (STR-CE). Here, we evaluated next-generation sequencing (NGS)-based STR profiling of human and mouse cell lines at 18 and 15 loci, respectively, in a high-throughput format. Using the Python program STRight, we demonstrate that NGS-based analysis (STR-NGS) is superior to standard STR-CE in terms of the ability to report the sequence context of repeat motifs, sensitivity and flexible multiplexing capability. STR-NGS is thus a valuable alternative for cell line authentication.
Cdc42 couples septin recruitment to the axial landmark assembly via Axl2 in budding yeast
Authors: Kang Pil Jung , Mullner Rachel , Lian Kendra , Park Hay-Oak
Published: September 2023

Cell polarization generally occurs along a single axis that is directed by a spatial cue. Cells of the budding yeast Saccharomyces cerevisiae undergo polarized growth and oriented cell division in a spatial pattern by selecting a specific bud site. Haploid a or α cells bud in the axial pattern in response to a transient landmark that includes Bud3, Bud4, Axl1 and Axl2. Septins, a family of filament-forming GTP-binding proteins, are also involved in axial budding and are recruited to an incipient bud site, but the mechanism of recruitment remains unclear. Here, we show that Axl2 interacts with Bud3 and the Cdc42 GTPase in its GTP-bound state. Axl2 also interacts with Cdc10, a septin subunit, promoting efficient recruitment of septins near the cell division site. Furthermore, a cdc42 mutant defective in the axial budding pattern at a semi-permissive temperature had a reduced interaction with Axl2 and compromised septin recruitment in the G1 phase. We thus propose that active Cdc42 brings Axl2 to the Bud3–Bud4 complex and that Axl2 then interacts with Cdc10, linking septin recruitment to the axial landmark.