bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term effects of the COVID-19 pandemic on five mental and psychological disorders: in terms of the number of disease visits, drug consumption, and scale scores
Authors: Zhu Han-Yu , Guo Yi-Mo , Pan Zhi-Ming , Wang Yan , Zhang Meng-Li , Zhu Ru-Huang , Li Zhang-Ping , Wang Zhen
Published: September 2023

Background

COVID-19 caused mild to severe infections in humans. The long-term epidemic environment harms people’s mental health. To explore the impact of the epidemic on people’s mental and psychological conditions, we surveyed in Wenzhou.

Methods

We collected the data of people who visited the First Affiliated Hospital of Wenzhou Medical University for five types of mental and psychological diseases from January 2018 to December 2021. Then, taking December 2019 as the cut-off point, the 48-month data were divided into the pre-epidemic group and the dur-epidemic group. Based on the above data, statistical analysis was done.

Results

From 2018 to 2021, the number of initial diagnoses, the number of disease visits, and drug consumption for these five types of mental and psychological diseases were all on the rise. Compared with the number of disease visits for all disorders in both psychiatry and neurology departments, it was found that the growth rate of these five diseases was higher than the growth rate of all disorders. We found that the number of disease visits, drug consumption, and scale scores after the COVID-19 outbreak were significantly different from those before the outbreak (P < 0.05). And the number of disease visits positively correlated with drug consumption (P < 0.0001, r = 0.9503), which verified the stability of the data.

Conclusion

The epidemic environment has had a long-term and negative impact on people’s mental and psychological conditions. Therefore, whether or not the epidemic is receding, we still need to be concerned about the impact of COVID-19 on mental and psychological health.
Dietary niacin intake in relation to depression among adults: a population-based study
Authors: Tian Sheng , Wu Lanxiang , Zheng Heqing , Zhong Xianhui , Liu Mingxu , Yu Xinping , Wu Wei
Published: September 2023

Background

Previous studies have shown that an antioxidant diet is a protective factor against depression. However, the association between niacin, an important antioxidant consumed from the diet, and depression has received little attention. Therefore, we explored the association between niacin intake and depression through a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016.

Methods

Depression was measured using the Patient Health Questionnaire (PHQ-9, score ≥ 10). Niacin intake was assessed through 24-h dietary recall interviews. The relationship of niacin intake with depression among adults in US was assessed by using a weighted multiple logistic regression model with subgroup analysis. Non-linear associations were explored using restricted cubic spline models. And we used a two-piece-wise logistic regression model with smoothing to explore the threshold for association between them.

Results

A total of 16,098 adults were included in this study. Compared with individuals with lowest niacin intake Q1 (≤ 15.96 mg/day), the adjusted OR values for dietary niacin intake and depression in Q2 (15.97–22.86 mg/day), Q3 (22.87–32.28 mg/day) and Q4 (≥ 32.29 mg/day), were 0.92 (95% CI: 0.70–1.20), 0.76 (95% CI: 0.56–0.99,) and 0.68 (95% CI: 0.48–0.98), respectively. The results were not modified by sex, by age and by BMI. Furthermore, the relationship between dietary niacin intake and depression exhibited a U-shaped curve (nonlinear, p < 0.001). And depression risk was lowest when dietary consumption of niacin was around 36 mg/day.

Conclusions

In present study, moderate niacin intake, but not high intake, was associated with lower odds of depression suggesting a U-shaped association.
Effect of poly (lactic-co-glycolic acid) polymer nanoparticles loaded with vancomycin against Staphylococcus aureus biofilm
Authors: Nouruzi Ellahe , Hosseini Seyed Mostafa , Asghari Babak , Mahjoub Reza , Zare Ehsan Nazarzadeh , Shahbazi Mohammad-Ali , Kalhori Fereshte , Arabestani Mohammad Reza
Published: September 2023

Staphylococcus aureus is a unique challenge for the healthcare system because it can form biofilms, is resistant to the host's immune system, and is resistant to numerous antimicrobial therapies. The aim of this study was to investigate the effect of poly (lactic-co-glycolic acid) (PLGA) polymer nanoparticles loaded with vancomycin and conjugated with lysostaphin (PLGA-VAN-LYS) on inhibiting S. aureus biofilm formation. Nano drug carriers were produced using the double emulsion evaporation process. we examined the physicochemical characteristics of the nanoparticles, including particle size, polydispersity index (PDI), zeta potential, drug loading (DL), entrapment efficiency (EE), Lysostaphin conjugation efficiency (LCE), and shape. The effect of the nano drug carriers on S. aureus strains was evaluated by determining the minimum inhibitory concentration (MIC), conducting biofilm formation inhibition studies, and performing agar well diffusion tests. The average size, PDI, zeta potential, DL, EE, and LCE of PLGA-VAN-LYS were 320.5 ± 35 nm, 0.270 ± 0.012, -19.5 ± 1.3 mV, 16.75 ± 2.5%, 94.62 ± 2.6%, and 37% respectively. Both the agar well diffusion and MIC tests did not show a distinction between vancomycin and the nano drug carriers after 72 h. However, the results of the biofilm analysis demonstrated that the nano drug carrier had a stronger inhibitory effect on biofilm formation compared to the free drug. The use of this technology for treating hospital infections caused by the Staphylococcus bacteria may have favorable effects on staphylococcal infections, considering the efficacy of the nano medicine carrier developed in this study.
Expanding the genetic toolbox for Cutaneotrichosporon oleaginosus employing newly identified promoters and a novel antibiotic resistance marker
Authors: Stellner Nikolaus I. , Rerop Zora S. , Mehlmer Norbert , Masri Mahmoud , Ringel Marion , Brück Thomas B.
Published: September 2023

Background

Cutaneotrichosporon oleaginosus is an oleaginous yeast that can produce up to 80% lipid per dry weight. Its high capacity for the biosynthesis of single cell oil makes it highly interesting for the production of engineered lipids or oleochemicals for industrial applications. However, the genetic toolbox for metabolic engineering of this non-conventional yeast has not yet been systematically expanded. Only three long endogenous promoter sequences have been used for heterologous gene expression, further three dominant and one auxotrophic marker have been established.

Results

In this study, the structure of putative endogenous promoter sequences was analyzed based on more than 280 highly expressed genes. The identified motifs of regulatory elements and translational initiation sites were used to annotate the four endogenous putative promoter sequences D9FADp, UBIp, PPIp, and 60Sp. The promoter sequences were tested in a construct regulating the known dominant marker hygromycin B phosphotransferase. The four newly described promoters and the previously established GAPDHp successfully initiated expression of the resistance gene and PPIp was selected for further marker development. The geneticin G418 resistance (aminoglycoside 3’-phosphotransferase, APH) and the nourseothricin resistance gene N-acetyl transferase (NAT) were tested for applicability in C. oleaginosus. Both markers showed high transformation efficiency, positive rate, and were compatible for combined use in a successive and simultaneous manner.

Conclusions

The implementation of four endogenous promoters and one novel dominant resistance markers for C. oleaginosus opens up new opportunities for genetic engineering and strain development. In combination with recently developed methods for targeted genomic integration, the established toolbox allows a wide spectrum of new strategies for genetic and metabolic engineering of the industrially highly relevant yeast.
The Neonatal-Perinatal Medicine fellowship application webinar series: a novel approach to helping applicants succeed
Authors: Bartlett Michelle J. , Ribar Ellen , Zheng Yingying , Amiri Sasha , Dyess Nicolle Fernández , Lucke Ashley M. , French Heather
Published: September 2023

Background

In 2022, 13,586 candidates applied to subspecialty fellowships. Formal resources to inform candidates on subspecialty-specific fellowship application are limited. Candidates rely on residency application experience, informal advice, and online research for navigating the application process. Thus, a need exists for formal subspecialty-specific fellowship application guidance. The American Academy of Pediatrics Organization of Neonatal-Perinatal Medicine Training Program Directors (ONTPD) and Trainees and Early Career Neonatologists (TECaN) created a webinar-based curriculum to help educate trainees about the application process and recruit diverse fellowship applicants.

Methods

In 2022, ONTPD and TECaN co-hosted and implemented a four-part national webinar series focused on different aspects of the Neonatal-Perinatal Medicine (NPM) fellowship application and interview processes. Webinars were advertised through list-servs and social media, conducted in two time zones, and recorded for asynchronous viewing. Registration, demographic data, and questions for webinar panelists were collected via electronic survey. Program evaluation data was collected after each webinar and following the fellowship match.

Results

In the 2022 appointment year, 310 candidates participated in the NPM fellowship match and 250 individuals registered for the webinar series. A quarter (26%) of registrants identified as underrepresented in medicine. Most registrants reported minimal or no knowledge of the fellowship application (64%, 158/248) and interview (81%, 201/248) processes. The majority of registrants (70%, 173/248) were planning on applying to fellowship in 2022, and 91% of post-webinar respondents (43/47) felt the webinars were moderately or extremely helpful, a finding that was sustained beyond the match (37/42). Almost all respondents rated the quality of the webinars as good or higher and were likely or very likely to recommend them to peers (39/42). There was considerable variability amongst respondents in the number of fellowship programs applied to, interviewed at, and ranked, and factors influencing rank list.

Conclusion

We describe a virtual curriculum to prepare trainees for the NPM fellowship application and interview process. This webinar series provides needed education to fellowship candidates, bridges the gap between candidate knowledge and program director expectations, is generalizable to other specialties, and can be replicated with minimal resources.
How to prepare nursing students for mental health clinical engagement: a qualitative study
Authors: Shaygan Maryam , Jaberi Azita , Hosseini Fahimeh Alsadat , Fereidooni Moghadam Malek
Published: September 2023

Background

Since clinical experience is challenging, identifying the factors influencing the learning process and acquiring clinical competence in mental departments is essential. Limited studies have investigated students’ concerns regarding attending this clinical setting and how they are mentally and academically prepared.

Aim/question

Explaining the various aspects of nursing students' preparation to attend the mental clinical environment.

Methods

This qualitative study was conducted on bachelorette nursing students and college professors using in-depth, semi-structured interviews. Inductive content analysis was used for data analysis, and Lincoln and Guba’s criteria were used for the rigor of the data.

Results

The participants’ viewpoints regarding how to prepare nursing students to enter mental clinical settings can be summarized in 4 categories: “understanding the students’ concerns” “understanding the students’ expectations” “the necessity of the students’ mental preparation” and “preparing the scientific materials needed to attend in a mental ward”.

Conclusion

Nursing students have fears and worries about entering mental departments and have expectations of themselves and their instructors. To help students deal with these concerns, psychological and educational preparations should be provided, among which the role of new educational technologies can be mentioned.
Application effect of head-mounted mixed reality device combined with 3D printing model in neurosurgery ventricular and hematoma puncture training
Authors: Peng Yilong , Xie Zhengyuan , Chen Shaoai , Wu Yi , Dong Jiajun , Li Jinhong , He Jinlang , Chen Xiaolei , Gao Hongzhi
Published: September 2023

Background

The purpose of this study was to explore the applicability of application effect of head-mounted mixed reality (MR) equipment combined with a three-dimensional (3D) printed model in neurosurgical ventricular and haematoma puncture training.

Methods

Digital Imaging and Communications in Medicine (DICOM) format image data of two patients with common neurosurgical diseases (hydrocephalus and basal ganglia haemorrhage) were imported into 3D Slicer software for 3D reconstruction, saved, and printed using 3D printing to produce a 1:1-sized head model with real person characteristics. The required model (brain ventricle, haematoma, puncture path, etc.) was constructed and imported into the head-mounted MR device, HoloLens, and a risk-free, visual, and repeatable system was designed for the training of junior physicians. A total of 16 junior physicians who studied under this specialty from September 2020 to March 2022 were selected as the research participants, and the applicability of the equipment and model during training was evaluated with assessment score sheets and questionnaires after training.

Results

According to results of the assessment and questionnaire, the doctors trained by this system are more familiar with the localization of the lateral anterior ventricle horn puncture and the common endoscopic surgery for basal ganglia haemorrhage, as well as more confident in the mastery of these two operations than the traditional training methods.

Conclusions

The use of head-mounted MR equipment combined with 3D printing models can provide an ideal platform for the operation training of young doctors. Through holographic images created from the combination of virtual and real images, operators can be better immersed in the operation process and deepen their understanding of the operation and related anatomical structures. The 3D printed model can be repeatedly reproduced so that doctors can master the technology, learn from mistakes, better achieve the purpose of teaching and training, and improve the effect of training.
The Infomóvel—An information system for managing HIV/AIDS patients in rural areas of Mozambique
Authors: Karajeanes E. , Bila D. , Luis M. , Tovela M. , Anjos C. , Ramanlal N. , Vaz P. , Lapão L. V.
Published: September 2023

Background

Mobile health is gradually revolutionizing the way medical care is delivered worldwide. In Mozambique, a country with a high human immunodeficiency virus prevalence, where antiretroviral treatment coverage is 77% accompanied by a 67% of retention rate, the use of mobile health technology may boost the antiretroviral treatment, by delivering care beyond health facilities and reaching underrepresented groups. Leveraging new technologies is crucial to reach the 95–95-95 United Nations target by 2030. The design, development, implementation, and evaluation of a mobile health platform called Infomóvel were covered in this article. Its intended use involves collaboration with community health workers and aims to increase human immunodeficiency virus patient access, adherence, and retention to care.

Methods

Using the Design Science Research Methodology, Infomóvel was created, as well as this publication. The explanation of various actions includes everything from problem description to observational study and goal-following for a solution, which results in the design and development of a platform proposal. Before the utility assessment of Infomóvel was conducted to make adjustments, a demonstration phase was conducted in one region of Mozambique.

Results

The initial subjects of the Infomóvel flowchart and physical process design were patients receiving antiretroviral medication who were enrolled in the patients tracking system and who had consented to home visits. The case manager examines the file before importing it into the Infomóvel database stored on a cloud server using the website www.commcarehq.org. The case manager application synchronises with the Infomóvel server database, enabling the import of latest data and access to the lists of new patients and community health workers. The community health worker uses his phone to access his application, which allows him to record the geographic coordinates and sort the list of patients by priority and type of visit.

Conclusion

Results from Infomóvel add to the growing body of data showing that mobile health techniques are beneficial for managing stable individuals with chronic conditions in Mozambique. These approaches can be scaled up and better utilised. However, additional studies should be conducted to quantify the resources needed to implement on a larger scale.
Nurse anesthetists’ perceptions of heat conservation measures in connection with surgery – a phenomenographic study
Authors: Gustafsson Ingrid L. , Elmqvist Carina , Fridlund Bengt , Schildmeijer Kristina , Rask Mikael
Published: September 2023

Background

To minimize the risk of perioperative hypothermia, it is recommended that healthcare professionals be familiar with heat conservation measures and use passive and active warming methods, in line with international guidelines. However, there is a low level of adherence perioperatively to the use of heat conservation measures. To understand why, there is a need to capture the nurse anesthetists’ perspective. The aim is to describe nurse anesthetists’ perceptions of heat conservation measures in connection with surgery.

Methods

An inductive descriptive design with a phenomenographic approach was chosen. A total of 19 nurse anesthetists participated and were interviewed. Data were analyzed according to Larsson and Holmström’s phenomenographic seven-step model.

Results

Six ways of understanding the phenomenon heat conservation measures in connection with surgery were found: the preventive, the useable, the untenable, the caring, the adaptive, and the routine care approach. These approaches were related to each other in a flexible way, allowing for several to co-exist at the same time, depending on the situation.

Conclusions

Nurse anesthetists want to prevent the patients’ heat loss and maintain normothermia, regardless of the type of surgery. This willingness, motivation, and intention enable the use of heat conservation measures. However, there are perceptions that have an impact, such as doubts and uncertainty, access, time and financial constraints, preconditions, routines or habits, and lack of availability of education/training. These barriers will require support from an organizational level to promote lifelong education and guidelines. As well as offer education at the nurse anesthetists’ program.
Scale up of anaesthesia services in underserved rural Tanzania
Authors: Kweyamba E. , Nyamtema AS , LeBlanc JC , Shayo A. , George RB , Scott H. , Kilume O. , Bulemela J. , Abel Z. , Mtey G.
Published: September 2023

Background

Because of critical shortage of physician anaesthesiologists, the government of Tanzania adopted a task shifting strategy for provision of anaesthesia services. This paper describes the results of an operational study designed to increase the number of anaesthesia providers for emergency obstetric surgeries in order to reduce maternal and perinatal mortality in underserved rural Tanzania.

Methods

In 2016 a before-after cohort study was conducted in seven health centres in rural Tanzania. Five health centres received an intervention and two were selected to track secular trends (control group). Ten associate clinicians, i.e. assistant medical officers, clinical officers, and nurse midwives, from five health centres were trained in anaesthesia skills for emergency obstetric surgeries for three months followed by quarterly supportive supervision, mentoring and teleconsultation to reinforce skills. Primary and secondary outcome measures included Caesarean delivery (CD) rate, quality and safety of anaesthesia, and uptake of the educational program for anaesthesia.

Results

Out of the 2,179 CDs performed in the intervention facilities from 2016 to 2019, two women died from complications of anaesthesia. The risk of death from anaesthetic complications was 0.9 per 1000 CD (95% CI 0.1–3.3. The risk of death was not established in the control group because of inadequate documentation and records keeping. The proportion of CD performed under spinal anaesthesia in intervention facilities doubled from 28% (60/214 with 95% CI 22–35) at baseline (July 2014 – June 2016) to 57% (558/971 with 95% CI of 54–61) in year three (July 2018 - June 2019), while in the control group increased by only 40% from 19% (92/475 with 95% CI of 16–23) at baseline and 27% (68/251 with 95% CI of 22–33) in year three. In 2020I, this educational training program was then adopted by the government with minor content changes and increasing duration of training to six months.

Conclusions

This three month educational training program for associate clinicians in anaesthesia, complemented by supportive supervision, can increase the CD rate to one that fills the “unmet need” and the proportion of operations performed under spinal anaesthesia, the gold standard technique for CD. The program can be used to meet the urgent demand for anaesthesia services in other underserved areas in Africa.
Optimizing inpatient bed management in a rural community-based hospital: a quality improvement initiative
Authors: Bartlett Brian N. , Vanhoudt Nadine N. , Wang Hanyin , Anderson Ashley A. , Juliar Danielle L. , Bartelt Jennifer M. , Lanz April D. , Bhandari Pawan , Anil Gokhan
Published: September 2023

Background

Appropriate use of available inpatient beds is an ongoing challenge for US hospitals. Historical capacity goals of 80% to 85% may no longer serve the intended purpose of maximizing the resources of space, staff, and equipment. Numerous variables affect the input, throughput, and output of a hospital. Some of these variables include patient demand, regulatory requirements, coordination of patient flow between various systems, coordination of processes such as bed management and patient transfers, and the diversity of departments (both inpatient and outpatient) in an organization.

Methods

Mayo Clinic Health System in the Southwest Minnesota region of the US, a community-based hospital system primarily serving patients in rural southwestern Minnesota and part of Iowa, consists of 2 postacute care and 3 critical access hospitals. Our inpatient bed usage rates had exceeded 85%, and patient transfers from the region to other hospitals in the state (including Mayo Clinic in Rochester, Minnesota) had increased. To address these quality gaps, we used a blend of Agile project management methodology, rapid Plan-Do-Study-Act cycles, and a proactive approach to patient placement in the medical-surgical units as a quality improvement initiative.

Results

During 2 trial periods of the initiative, the main hub hospital (Mayo Clinic Health System hospital in Mankato) and other hospitals in the region increased inpatient bed usage while reducing total out-of-region transfers.

Conclusion

Our novel approach to proactively managing bed capacity in the hospital allowed the region’s only tertiary medical center to increase capacity for more complex and acute cases by optimizing the use of historically underused partner hospital beds.
Developing diagnostic tools for canine periodontitis: combining molecular techniques and machine learning models
Authors: Ruparell Avika , Gibbs Matthew , Colyer Alison , Wallis Corrin , Harris Stephen , Holcombe Lucy J.
Published: September 2023

Background

Dental plaque microbes play a key role in the development of periodontal disease. Numerous high-throughput sequencing studies have generated understanding of the bacterial species associated with both canine periodontal health and disease. Opportunities therefore exist to utilise these bacterial biomarkers to improve disease diagnosis in conscious-based veterinary oral health checks. Here, we demonstrate that molecular techniques, specifically quantitative polymerase chain reaction (qPCR) can be utilised for the detection of microbial biomarkers associated with canine periodontal health and disease.

Results

Over 40 qPCR assays targeting single microbial species associated with canine periodontal health, gingivitis and early periodontitis were developed and validated. These were used to quantify levels of the respective taxa in canine subgingival plaque samples collected across periodontal health (PD0), gingivitis (PD1) and early periodontitis (PD2). When qPCR outputs were compared to the corresponding high-throughput sequencing data there were strong correlations, including a periodontal health associated taxa,Capnocytophagasp. COT-339 (rs=0.805), and two periodontal disease associated taxa, Peptostreptococcaceae XI [G-4] sp. COT-019 (rs=0.902) and Clostridiales sp. COT-028 (rs=0.802). The best performing models, from five machine learning approaches applied to the qPCR data for these taxa, estimated 85.7% sensitivity and 27.5% specificity forCapnocytophagasp. COT-339, 74.3% sensitivity and 67.5% specificity for Peptostreptococcaceae XI [G-4] sp. COT-019, and 60.0% sensitivity and 80.0% specificity for Clostridiales sp. COT-028.

Conclusions

A qPCR-based approach is an accurate, sensitive, and cost-effective method for detection of microbial biomarkers associated with periodontal health and disease. Taken together, the correlation between qPCR and high-throughput sequencing outputs, and early accuracy insights, indicate the strategy offers a prospective route to the development of diagnostic tools for canine periodontal disease.
Disparities in spatially variable gene calling highlight the need for benchmarking spatial transcriptomics methods
Authors: Charitakis Natalie , Salim Agus , Piers Adam T. , Watt Kevin I. , Porrello Enzo R. , Elliott David A. , Ramialison Mirana
Published: September 2023

Identifying spatially variable genes (SVGs) is a key step in the analysis of spatially resolved transcriptomics data. SVGs provide biological insights by defining transcriptomic differences within tissues, which was previously unachievable using RNA-sequencing technologies. However, the increasing number of published tools designed to define SVG sets currently lack benchmarking methods to accurately assess performance. This study compares results of 6 purpose-built packages for SVG identification across 9 public and 5 simulated datasets and highlights discrepancies between results. Additional tools for generation of simulated data and development of benchmarking methods are required to improve methods for identifying SVGs.
Structural variation and introgression from wild populations in East Asian cattle genomes confer adaptation to local environment
Authors: Xia Xiaoting , Zhang Fengwei , Li Shuang , Luo Xiaoyu , Peng Lixin , Dong Zheng , Pausch Hubert , Leonard Alexander S. , Crysnanto Danang , Wang Shikang , Tong Bin , Lenstra Johannes A. , Han Jianlin , Li Fuyong , Xu Tieshan , Gu Lihong , Jin Liangliang , Dang Ruihua , Huang Yongzhen , Lan Xianyong , Ren Gang , Wang Yu , Gao Yuanpeng , Ma Zhijie , Cheng Haijian , Ma Yun , Chen Hong , Pang Weijun , Lei Chuzhao , Chen Ningbo
Published: September 2023

Background

Structural variations (SVs) in individual genomes are major determinants of complex traits, including adaptability to environmental variables. The Mongolian and Hainan cattle breeds in East Asia are of taurine and indicine origins that have evolved to adapt to cold and hot environments, respectively. However, few studies have investigated SVs in East Asian cattle genomes and their roles in environmental adaptation, and little is known about adaptively introgressed SVs in East Asian cattle.

Results

In this study, we examine the roles of SVs in the climate adaptation of these two cattle lineages by generating highly contiguous chromosome-scale genome assemblies. Comparison of the two assemblies along with 18 Mongolian and Hainan cattle genomes obtained by long-read sequencing data provides a catalog of 123,898 nonredundant SVs. Several SVs detected from long reads are in exons of genes associated with epidermal differentiation, skin barrier, and bovine tuberculosis resistance. Functional investigations show that a 108-bp exonic insertion in SPN may affect the uptake of Mycobacterium tuberculosis by macrophages, which might contribute to the low susceptibility of Hainan cattle to bovine tuberculosis. Genotyping of 373 whole genomes from 39 breeds identifies 2610 SVs that are differentiated along a “north–south” gradient in China and overlap with 862 related genes that are enriched in pathways related to environmental adaptation. We identify 1457 Chinese indicine-stratified SVs that possibly originate from banteng and are frequent in Chinese indicine cattle.

Conclusions

Our findings highlight the unique contribution of SVs in East Asian cattle to environmental adaptation and disease resistance.
The anesthetic efficacy of ultrasound-guided lumbar plexus combined with quadratus lumborum block with Shamrock approach in total hip arthroplasty: study protocol for a randomized controlled trial
Authors: Wang Xiaofeng , Zhang Hui , Chen Yongzhu , Xie Zhenwei , Chen Moxi , Chen Yonglin , Zhang Junfeng
Published: September 2023

Introduction

The lumbar plexus originates from multiple segments of the spinal cord. Both single-level lumbar plexus block (LPB) and transmuscular quadratus lumborum block (TQLB) are commonly used to provide analgesia for the patients undergoing total hip arthroplasty (THA). However, neither of them can completely cover the lumbar plexus. Multiple-level LPB is also not recommended since this expert technique involves more potential risks. To achieve a better anesthetic effect and avoid risks, we propose to combine ultrasound-guided LPB with TQLB with Shamrock approach. We aim to assess the anesthetic efficacy of this combination technique and expect it will be an ideal alternative for conventional LPBs in THA.

Methods and analysis

In this prospective randomized controlled trial, 84 patients schedule for THA will be enrolled. The patients will be randomly assigned at a 1:1:1 ratio to receive LPB at L3 level (P group), T12 paravertebral block combined with LPB at L3 and L4 levels (TP group), or LPB combined with TQLB at L3 level (PQ group). Each method will be evaluated in terms of the successful rate of sensory blockade, postoperative pain, performance time of block, requirement for intraoperative sufentanil, cumulative doses of intraoperative vasoactive medications, and adverse events.

Ethics and dissemination

The study protocol has been approved by the institutional review board (IRB) at Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, China (No.2020–031). The results will be disseminated in a peer-reviewed journal and the ClinicalTrials.gov registry.

Trial registration

ClinicalTrials.gov, NCT04266236. Registered on 10 February 2020. ClinicalTrials.gov PRS: Record Summary NCT04266236.
Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human
Authors: Niskanen Julia E. , Ohlsson Åsa , Ljungvall Ingrid , Drögemüller Michaela , Ernst Robert F. , Dooijes Dennis , van Deutekom Hanneke W. M. , van Tintelen J. Peter , Snijders Blok Christian J. B. , van Vugt Marion , van Setten Jessica , Asselbergs Folkert W. , Petrič Aleksandra Domanjko , Salonen Milla , Hundi Sruthi , Hörtenhuber Matthias ,   DoGA consortium, Daub Carsten , Araujo César L. , Quintero Ileana B. , Kyöstilä Kaisa , Kaukonen Maria , Arumilli Meharji , Sarviaho Riika , Puurunen Jenni , Sulkama Sini , Karjalainen Sini , Sukura Antti , Syrjä Pernilla , Airas Niina , Pekkarinen Henna , Kareinen Ilona , Javela Hanna-Maaria , Knuuttila Anna , Nordgren Heli , Hagner Karoliina , Pääkkönen Tarja , Iivanainen Antti , Krjutskov Kaarel , Ezer Sini , Saarinen Auli , Katayama Shintaro , Yoshihara Masahito , Mukarram Abdul Kadir , Aljelaify Rasha Fahad , Ross Fiona , Raman Amitha , Stevens Irene , Gusev Oleg , Bannasch Danika , Schoenebeck Jeffrey J. , Kere Juha , Pyle W. Glen , Donner Jonas , Postma Alex V. , Leeb Tosso , Andersson Göran , Hytönen Marjo K. , Häggström Jens , Wiberg Maria , Friederich Jana , Eberhard Jenny , Harakalova Magdalena , van Steenbeek Frank G. , Wess Gerhard , Lohi Hannes
Published: September 2023

Background

Dilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis.

Methods

We performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts.

Results

Our results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes.

Conclusions

Collectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies.
Intra-articular delivery of an indoleamine 2,3-dioxygenase galectin-3 fusion protein for osteoarthritis treatment in male Lewis rats
Authors: Partain Brittany D. , Bracho-Sanchez Evelyn , Farhadi Shaheen A. , Yarmola Elena G. , Keselowsky Benjamin G. , Hudalla Gregory A. , Allen Kyle D.
Published: September 2023

Objective

Osteoarthritis (OA) is driven by low-grade inflammation, and controlling local inflammation may offer symptomatic relief. Here, we developed an indoleamine 2,3-dioxygenase and galectin-3 fusion protein (IDO-Gal3), where IDO increases the production of local anti-inflammatory metabolites and Gal3 binds carbohydrates to extend IDO’s joint residence time. In this study, we evaluated IDO-Gal3’s ability to alter OA-associated inflammation and pain-related behaviors in a rat model of established knee OA.

Methods

Joint residence was first evaluated with an analog Gal3 fusion protein (NanoLuc™ and Gal3, NL-Gal3) that produces luminescence from furimazine. OA was induced in male Lewis rats via a medial collateral ligament and medial meniscus transection (MCLT + MMT). At 8 weeks, NL or NL-Gal3 were injected intra-articularly (n = 8 per group), and bioluminescence was tracked for 4 weeks. Next, IDO-Gal3s’s ability to modulate OA pain and inflammation was assessed. Again, OA was induced via MCLT + MMT in male Lewis rats, with IDO-Gal3 or saline injected into OA-affected knees at 8 weeks post-surgery (n = 7 per group). Gait and tactile sensitivity were then assessed weekly. At 12 weeks, intra-articular levels of IL6, CCL2, and CTXII were assessed.

Results

The Gal3 fusion increased joint residence in OA and contralateral knees (p < 0.0001). In OA-affected animals, both saline and IDO-Gal3 improved tactile sensitivity (p = 0.008), but IDO-Gal3 also increased walking velocities (p ≤ 0.033) and improved vertical ground reaction forces (p ≤ 0.04). Finally, IDO-Gal3 decreased intra-articular IL6 levels within the OA-affected joint (p = 0.0025).

Conclusion

Intra-articular IDO-Gal3 delivery provided long-term modulation of joint inflammation and pain-related behaviors in rats with established OA.
Pan cancer characterization of genes whose expression has been associated with LINE-1 antisense promoter activity
Authors: Xu Baohong , Li Xueer , Zhang Shaoqi , Lian Meina , Huang Wenbin , Zhang Yin , Wang Yudong , Huang Zhiquan
Published: September 2023

Background

Long interspersed nuclear element-1 (LINE-1 or L1) comprises 17% of the human genome. As the only autonomous and active retrotransposons, L1 may take part in cancer initiation and progression in some ways. The studies of L1 in cancer mainly focus on the impact of L1 insertion into the new genome locus. The L1 5´ untranslated region (UTR) also contains antisense promoter (ASP) activity, generating L1-gene chimeric transcripts to a neighbor exon. Some of these ASP-associated genes have been reported to be overexpressed in cancer and promote cancer cell growth. However, little is known about overall expression patterns and the roles of L1 ASP-associated genes in human cancers.

Results

L1 ASP-associated genes were frequently dysregulated in cancer and associated with the cell cycle, the PI3K/AKT pathway, and the GTPase signaling pathway. The expression of L1 ASP-associated genes was correlated with tumor patient prognosis. Hub L1 ASP-associated genes CENPU and MCM2 showed a correlation with immune infiltration, clinical T stage, and cancer stemness in pan-cancer. Knockdown of L1 ASP-associated gene LINC00491 resulted in a significant decrease in tumor growth and migration ability.

Conclusions

The expression of L1 ASP-associated genes is significantly dysregulated at the pan-cancer level, which is closely related to the tumor microenvironment, progression, and patient prognosis. Hub genes CENPU and MCM2 are expected to be new tumor diagnostic markers and therapeutic targets.
TLR8 escapes X chromosome inactivation in human monocytes and CD4+ T cells
Authors: Youness Ali , Cenac Claire , Faz-López Berenice , Grunenwald Solange , Barrat Franck J. , Chaumeil Julie , Mejía José Enrique , Guéry Jean-Charles
Published: September 2023

Background

Human endosomal Toll-like receptors TLR7 and TLR8 recognize self and non-self RNA ligands, and are important mediators of innate immunity and autoimmune pathogenesis. TLR7 and TLR8 are, respectively, encoded by adjacent X-linked genes. We previously established that TLR7 evades X chromosome inactivation (XCI) in female immune cells. Whether TLR8 also evades XCI, however, has not yet been explored.

Method

In the current study, we used RNA fluorescence in situ hybridization (RNA FISH) to directly visualize, on a single-cell basis, primary transcripts of TLR7 and TLR8 relative to X chromosome territories in CD14+ monocytes and CD4+ T lymphocytes from women, Klinefelter syndrome (KS) men, and euploid men. To assign X chromosome territories in cells lacking robust expression of a XIST compartment, we designed probes specific for X-linked genes that do not escape XCI and therefore robustly label the active X chromosome. We also assessed whether XCI escape of TLR8 was associated with sexual dimorphism in TLR8 protein expression by western blot and flow cytometry.

Results

Using RNA FISH, we show that TLR8, like TLR7, evades XCI in immune cells, and that cells harboring simultaneously TLR7 and TLR8 transcript foci are more frequent in women and KS men than in euploid men, resulting in a sevenfold difference in frequency. This transcriptional bias was again observable when comparing the single X of XY males with the active X of cells from females or KS males. Interestingly, TLR8 protein expression was significantly higher in female mononuclear blood cells, including all monocyte subsets, than in male cells.

Conclusions

TLR8, mirroring TLR7, escapes XCI in human monocytes and CD4+ T cells. Co-dependent transcription from the active X chromosome and escape from XCI could both contribute to higher TLR8 protein abundance in female cells, which may have implications for the response to viruses and bacteria, and the risk of developing inflammatory and autoimmune diseases.
Evolving prion-like tau conformers differentially alter postsynaptic proteins in neurons inoculated with distinct isolates of Alzheimer’s disease tau
Authors: Hromadkova Lenka , Kim Chae , Haldiman Tracy , Peng Lihua , Zhu Xiongwei , Cohen Mark , de Silva Rohan , Safar Jiri G.
Published: September 2023

Objectives

Although accumulation of misfolded tau species has been shown to predict cognitive decline in patients with Alzheimer’s disease (AD) and other tauopathies but with the remarkable diversity of clinical manifestations, neuropathology profiles, and time courses of disease progression remaining unexplained by current genetic data. We considered the diversity of misfolded tau conformers present in individual AD cases as an underlying driver of the phenotypic variations of AD and progressive loss of synapses.

Methods

To model the mechanism of tau propagation and synaptic toxicity of distinct tau conformers, we inoculated wild-type primary mouse neurons with structurally characterized Sarkosyl-insoluble tau isolates from the frontal cortex of six AD cases and monitored the impact for fourteen days. We analyzed the accumulation rate, tau isoform ratio, and conformational characteristics of de novo-induced tau aggregates with conformationally sensitive immunoassays, and the dynamics of synapse formation, maintenance, and their loss using a panel of pre-and post-synaptic markers.

Results

At the same concentrations of tau, the different AD tau isolates induced accumulation of misfolded predominantly 4-repeat tau aggregates at different rates in mature neurons, and demonstrated distinct conformational characteristics corresponding to the original AD brain tau. The time-course of the formation of misfolded tau aggregates and colocalization correlated with significant loss of synapses in tau-inoculated cell cultures and the reduction of synaptic connections implicated the disruption of postsynaptic compartment as an early event.

Conclusions

The data obtained with mature neurons expressing physiological levels and adult isoforms of tau protein demonstrate markedly different time courses of endogenous tau misfolding and differential patterns of post-synaptic alterations. These and previous biophysical data argue for an ensemble of various misfolded tau aggregates in individual AD brains and template propagation of their homologous conformations in neurons with different rates and primarily postsynaptic interactors. Modeling tau aggregation in mature differentiated neurons provides a platform for investigating divergent molecular mechanisms of tau strain propagation and for identifying common structural features of misfolded tau and critical interactors for new therapeutic targets and approaches in AD.
Standardized approach for extubation during extracorporeal membrane oxygenation in severe acute respiratory distress syndrome: a prospective observational study
Authors: Roncon-Albuquerque Roberto , Gaião Sérgio , Vasques-Nóvoa Francisco , Basílio Carla , Ferreira Ana Rita , Touceda-Bravo Alberto , Pimentel Rodrigo , Vaz Ana , Silva Sofia , Castro Guiomar , Veiga Tiago , Martins Hélio , Dias Francisco , Pereira Catarina , Marto Gonçalo , Coimbra Isabel , Chico-Carballas Juan Ignacio , Figueiredo Paulo , Paiva José Artur
Published: September 2023

Background

Extubation during extracorporeal oxygenation (ECMO) in severe acute respiratory distress syndrome (ARDS) has not been well studied. Despite the potential benefits of this strategy, weaning from ECMO before liberation from invasive mechanical ventilation remains the most frequent approach. Our aim was to evaluate the safety and feasibility of a standardized approach for extubation during ECMO in patients with severe ARDS.

Results

We conducted a prospective observational study to assess the safety and feasibility of a standardized approach for extubation during ECMO in severe ARDS among 254 adult patients across 4 intensive care units (ICU) from 2 tertiary ECMO centers over 6 years. This consisted of a daily assessment of clinical and gas exchange criteria based on an Extracorporeal Life Support Organization guideline, with extubation during ECMO after validation by a dedicated intensive care medicine specialist. Fifty-four (21%) patients were extubated during ECMO, 167 (66%) did not reach the clinical criteria, and in 33 (13%) patients, gas exchange precluded extubation during ECMO. At ECMO initiation, there were fewer extrapulmonary organ dysfunctions (lower SOFA score [OR, 0.88; 95% CI, 0.79–0.98; P = .02] with similar PaO2/FiO2) when compared with patients not extubated during ECMO. Extubation during ECMO associated with shorter duration of invasive mechanical ventilation (7 (4–18) vs. 32 (18–54) days; P < .01) and of ECMO (12 (7–25) vs. 19 (10–41) days; P = .01). This was accompanied by a lower incidence of hemorrhagic shock (2 vs. 11%; P = .05), but more cannula-associated deep vein thrombosis (49 vs. 31%; P = .02) and failed extubation (20 vs. 6%; P < .01). There were no increased major adverse events. Extubation during ECMO is associated with a lower risk of all-cause death, independently of measured confounding (adjusted logistic regression OR 0.23; 95% confidence interval 0.08–0.69, P = .008).

Conclusions

A standardized approach was safe and feasible allowing extubation during ECMO in 21% of patients with severe ARDS, selecting patients who will have a shorter duration of invasive mechanical ventilation, ECMO course, and ICU stay, as well as fewer infectious complications, and high hospital survival.
Approximation by multivariate Baskakov–Durrmeyer operators in Orlicz spaces
Authors: Han Ling-Xiong , Bai Yu-Mei , Qi Feng
Published: September 2023

Employing some properties of multivariate Baskakov–Durrmeyer operators and utilizing modified K-functional and a decomposition technique, the authors obtain the direct theorem and weak type inverse theorem in the Orlicz spaces.
Discrepancies between media portrayals and actual demographics of eating disorders in TV and film: implications of representation
Authors: Bassett Lucy , Ewart Maya
Published: September 2023

Background

Media has a reputation for painting a narrow, simplistic, sensationalized portrait of eating disorders. There is little analysis of how film and TV portray eating disorders nor the implications of this representation. This study fills that gap by comparing demographics of US film and TV characters since the 1980s to actual population demographics of people with eating disorders.

Methods

We compiled a dataset of TV and movie characters with eating disorders and categorized characters’ gender, age, race/ethnicity, and sexual orientation. We narrowed the dataset to include only US media depictions to facilitate comparisons with empirical prevalence, resulting in a total of 66 characters over the period 1981 to 2022. We then compared the demographic characteristics of our sample to national statistics on eating disorder prevalence.

Results

US media depictions of eating disorders overrepresented characters who were heterosexual (75.56%), White (84.85%), women (89.39%), and under age 30 (84.85%). This does not accurately reflect the populations experiencing eating disorders in the US.

Conclusions

Eating disorders have an image problem. TV and movies inaccurately portray them as primarily affecting heterosexual, White, women under age 30. Misrepresentation could fuel existing stigmas that inhibit individuals with eating disorders from seeking and receiving treatment. It could also perpetuate stereotypes that fuel misperceptions of the disease by medical providers, families, and policymakers. We recommend more accurate representation in the media to better reflect current demographics and increase awareness of the range of people who can experience eating disorders.