bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights Into Patients’ Perceptions of Health-Related Social Needs and the Role of the Adult Primary Care Clinic
Authors: Meltzer Kerry K. , Rhodes Corinne M. , Morgan Anna U. , Lautenbach Gillian L. , Shea Judy A. , Balasta Marguerite A.
Published: June 2023

Introduction/Objectives:

While it is well established that unmet healthrelated social needs (HRSN) adversely affect health outcomes, there has been limited evaluation in adult primary care of patients’ perceptions of how these needs impact their health and the role of the primary care provider (PCP). The objective of this study is to identify patients’ perceptions of HRSN and how PCPs could help address them. Secondary objectives include exploring the impact of goal setting and a 1-time cash transfer (CT).

Methods:

This qualitative study used semi-structured baseline and follow-up interviews with patients in internal medicine clinics. Adult primary care patients were included if they screened positive as having 1 of 3 HRSN: financial resource strain, transportation needs, or food insecurity. All participants completed an initial interview about their HRSN and health, and were asked to set a 6-month health goal. At enrollment, participants were randomized to receive a $500 CT or a $50 participation reward. At 6-months, patients were interviewed again to investigate progress toward meeting their health goals, [when applicable] how the CT helped, and their beliefs about the role of PCPs in addressing HRSN.

Results:

We completed 30 initial and 25 follow-up interviews. Participants identified their HRSN, however most did not readily connect identified needs to health. Although participants were receptive to HRSN screening, they did not feel it was their PCP’s responsibility to address these needs. Verbal goal-setting appeared to be a useful tool, and while the CTs were appreciated, patients often found them inadequate to address HRSN.

Conclusions:

Given the importance of identifying the social conditions that shape patients’ health, providers, and health systems have an opportunity to re-evaluate their role in helping patients address these barriers. Future studies could examine the effect of more frequent disbursement of CTs over time.
Investigating the Relationships Between University Students’ Epistemological Beliefs and Learning Approaches: A Path Analysis Study
Authors: Yağan Saadet Aylin , Parlar Hanifi
Published: June 2023

The purpose of this study was to investigate the relationships between epistemological beliefs and learning approaches of university students. The mediator effect of gender was also tested. A theoretical model was created, and considering the literature personality types’ effects on learning approaches were kept under control. A total of 244 university students studying in 26 different departments of a university in Turkey participated in the study. Data collection tools were Epistemological Beliefs Scale (attaining knowledge, nurture vs. nature, absolute and single reality, and epistemic confliction), Learning Approaches Scale (deep approach and surface approach), and Personality Types Scale (type A and type B personality). It was hypothesized that sophisticated epistemological beliefs positively predict deep approach and naive epistemological beliefs positively predict surface approach. In addition, it is predicted that the model will differ for males and females. Path analysis method was used to test the models. Results showed that in attaining knowledge and epistemic confliction dimensions sophisticated epistemological beliefs positively predict deep approach. In absolute and single reality, nurture versus nature, and epistemic confliction dimensions naive epistemological beliefs positively predict surface approach. The moderator effect of gender was not significant in the overall model. The results of the research indicate that epistemological beliefs and learning approaches are interrelated structures.
Interlimb Asymmetry in Knee Extension Moment During Double-Leg Squatting Is Associated With Persistent Quadriceps Weakness After ACL Reconstruction
Authors: Ishida Tomoya , Samukawa Mina , Koshino Yuta , Ino Takumi , Kasahara Satoshi , Tohyama Harukazu
Published: June 2023

Background:

Although double-leg squatting is less dynamic and places less demand on the quadriceps compared with landing tasks, the relationship between double-leg squatting biomechanics and persistent quadriceps weakness after anterior cruciate ligament reconstruction (ACLR) is unknown.

Purpose:

To clarify the relationships between asymmetries in quadriceps strength and lower limb biomechanics during double-leg squatting >1 year after ACLR.

Study Design:

Controlled laboratory study.

Methods:

A total of 26 participants (5.5 ± 3.8 years after ACLR) were enrolled. The limb symmetry index (LSI) of isokinetic quadriceps strength was used to divide participants into the high-quadriceps (HQ) group (LSI ≥90%; n = 18) and the low-quadriceps (LQ) group (LSI <90%; n = 8). The knee, hip, and ankle extension moment (relative to body weight and support moment [sum of knee, hip, and ankle moments]) and vertical ground-reaction force during double-leg squatting were analyzed using 3-dimensional motion analysis. The association of quadriceps strength and biomechanical variables was tested using 2-way analysis of variance and univariate regression analysis.

Results:

A significant group-by-limb interaction was found for the peak knee extension moment and the ratios of knee and hip extension moment to support moment ( P < .001, P = .015 and P < .001, respectively). The LQ group showed a significantly smaller peak knee extension moment and knee to support moment ratio but a larger hip to support moment ratio in the involved limb than in the uninvolved limb (95% CIs: knee extension moment, −0.273 to −0.088 N·m/kg; knee to support moment ratio, −10.7% to −2.2%; hip to support moment ratio, 3.2% to 8.5%). No interlimb difference was found for the HQ group. The LSI of quadriceps strength was significantly associated with the LSI of peak knee extension moment ( R 2 = 0.183), knee to support moment ratio ( R 2 = 0.256), and hip to support moment ratio ( R 2 = 0.233). The mean maximum isokinetic quadriceps strength and peak knee extension moment during squatting on the involved limb of the LQ group were 2.40 ± 0.39 and 0.90 ± 0.16 N·m/kg, respectively.

Conclusion:

Asymmetrical biomechanics during double-leg squatting was associated with persistent quadriceps weakness after ACLR. The LQ group had reduced knee extensor moment on the involved side during squatting despite loading at approximately half the maximum strength.

Clinical Relevance:

Quadriceps strengthening exercises, together with interventions to improve neuromuscular control, may reduce asymmetrical biomechanics during double-leg squatting.
Visualizing the Decline in Cultural Participation in Europe Post-crisis
Authors: Lizardo Omar
Published: June 2023

Whether cultural practices change gradually—at the timescale of generations—or can be lastingly affected by short-term exogenous shocks is a question that continues to inspire much debate in the social sciences. Previous work shows that trends in cultural participation, if they exist, tend to be slow and gradual, responding to cohort changes and impervious to period-specific events. Here I use data from the two Eurobarometer surveys fielded just before (2007) and in the immediate aftermath (2013) of the Great Recession-related eurozone crisis to visualize the impact of a once-in-a-generation period-specific shock for the four national cases most deeply affected: Portugal, Spain, Italy, and Greece. In all cases, with the possible exception of Spain, we can observe steep increases in rates of nonparticipation, impacting particularly the less educated, except for Greece, for which we can see general negative impacts of the crisis on participation across all levels of education. Overall, the results depicted in this visualization suggest that cultural participation practices can be affected by large exogenous shocks at timescales below gradual cohort change.
Socioeconomic Disparities in Patients Receiving Intravitreal Injections for Age-Related Macular Degeneration Amid the COVID-19 Pandemic
Authors: Nguyen Anh H. , Davoudi Samaneh , Dong Kaylin , Bains Ashank , Ness Steven , Subramanian Manju L. , Siegel Nicole H. , Chen Xuejing
Published: June 2023

Purpose: To determine the effects of socioeconomic factors on visit adherence and the resultant visual outcomes for patients receiving intravitreal injections for neovascular age-related macular degeneration during the COVID-19 pandemic. Methods: In this retrospective case-control study, medical records were reviewed to collect appointment attendance, age, sex, self-reported race/ethnicity, primary language, marital status, insurance, distance from clinic, and Area Deprivation Index (ADI), a measure of socioeconomic disadvantage. Multivariate regression models were created to determine differences in socioeconomic factors between individuals who attended (show group) and those who did not attend (no-show group) appointments. Results: The study enrolled 126 patients in the show group and 115 in the no-show group. On univariate analysis, nonadherence was significantly higher in non-White patients than in White patients ( P = .04), urban sites than in suburban sites ( P = 1.7 × 10−4), and non-English-speaking patients than in English-speaking patients ( P = 4.0 × 10−3). The associations remained significant in multivariate analysis for non-English-speaking patients ( P = .03) and urban-site patients ( P = .01) after adjusting for age, sex, self-reported race/ethnicity, primary language, marital status, insurance, distance from clinic, site of visit, and ADI. At 6 months and 1 year, a 1-, 2-, and 3-line vision loss was significantly higher in the no-show group than in the show group on univariate and multivariate analysis after adjusting for age, sex, race, lens status, and presence of glaucoma and diabetic retinopathy. Conclusions: Non-English-speaking patients and urban-based patients were less likely to present for intravitreal injection appointments during the initial peak of the COVID-19 pandemic. This disparity translated to worse vision outcomes at 6 months and 1 year.
Arthroscopic Transtibial Repair of Acute Traumatic Posterior Medial Meniscus Root Tear
Authors: Nammour Michael A. , James Michael , Arner Justin W. , Bradley James P.
Published: June 2023

Background:

The posteromedial meniscal root is a critical structure in maintaining balanced tibiofemoral contact stresses and joint stability. Studies have shown that posterior root tears are biomechanically equivalent to total meniscectomy and can lead to the rapid development of osteoarthritis. Our presentation focuses on the less common, acute, traumatic posteromedial meniscal root avulsion, although our technique is also applicable to the more common degenerative posteromedial meniscal root tears.

Indications:

Surgical indications include acute tears, as well as chronic or degenerative tears in patients without advanced osteoarthritis. Absolute surgical contraindications include subchondral bone collapse, substantial concurrent meniscal pathology, malalignment of >5°, and advanced knee osteoarthritis.

Technique Description:

Once the tear is identified, the bone at the root insertion is prepared with a meniscal rasp. Two looped sutures are passed through the meniscal root in a cinch-type fashion using a knee scorpion. A tunnel is drilled at the root insertion using a specialized meniscal root repair guide. Approximately, 10 mm of bone are drilled in a retrograde fashion with a flip cutter deployed to 7 mm to decorticate the bone and enhance healing. The drill is then removed and a rubber tube with a retrieval suture is advanced through the drill guide into the joint. The loop suture is retrieved through the anteromedial portal and the repair sutures are passed through the retrieval loop. Under arthroscopic visualization, the root is then reduced to its anatomic insertion and the sutures secured to the tibia using a knotless suture anchor placed 1 cm distal to the transtibial tunnel.

Results:

Several recent studies have shown that meniscal root repair decreases rapid knee degeneration as gauged by meniscal extrusion, progression of Kellgren-Lawrence grade and rate of conversion to total knee arthroplasty (TKA).

Discussion/Conclusion:

Posteromedial meniscal root tears are increasingly being recognized as a distinct meniscal pathology that can lead to rapid arthritis if left unrepaired. Arthroscopic repair techniques continue to improve allowing orthopedic surgeons to more readily address this significant, but treatable pathology.

Patient Consent Disclosure Statement:

The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Fostering Trust in Music Classrooms: A Review of the Literature
Authors: Hendricks Karin S. , Dansereau Diana R. , Bauman-Field Betty , Freeze Cheryl M.
Published: June 2023

This article is a systematic review of literature related to collective and relational trust in general school settings, with applications to music education. We focused on trauma-sensitive approaches and emerging pedagogies of trust and considered how they interact with theoretical facets of relational trust (vulnerability, confidence, honesty, openness, reliability, benevolence, and competence) in music learning settings. Trauma-sensitive approaches to trust include (a) using consistent rules and routines, (b) creating engaging lessons that are fun and enjoyable, and (c) praising students honestly and authentically. Pedagogies of trust involve (a) promoting collaboration and consistency, (b) open communication and authentic listening, (c) commitment and persistence to shared goals, and (d) the teacher’s willingness to be vulnerable, take musical risks, and continue learning along with students. More research is needed to understand processes of trust involving racial trauma as well as generational differences in how trust is viewed, developed, and/or received.
Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial
Authors: Stolz Daiana , Papakonstantinou Eleni , Pascarella Maria , Jahn Kathleen , Siebeneichler Aline , Darie Andrei M. , Herrmann Matthias J. , Strobel Werner , Salina Anna , Grize Leticia , Savic Prince Spasenija , Tamm Michael
Published: June 2023

Background

Although inhaled corticosteroids (ICS) are highly effective in asthma, they provide significant, but modest, clinical benefit in COPD. Here, we tested the hypothesis that high bronchial airway smooth muscle cell (ASMC) area in COPD is associated with ICS responsiveness.

Methods

In this investigator-initiated and -driven, double-blind, randomised, placebo-controlled trial (HISTORIC), 190 COPD patients, Global Initiative for Chronic Obstructive Lung Disease stage B–D, underwent bronchoscopy with endobronchial biopsy. Patients were divided into groups A and B, with high ASMC area (HASMC: >20% of the bronchial tissue area) and low ASMC area (LASMC: ≤20% of the bronchial tissue area), respectively, and followed a run-in period of 6 weeks on open-label triple inhaled therapy with aclidinium (ACL)/formoterol (FOR)/budesonide (BUD) (400/12/400 μg twice daily). Subsequently, patients were randomised to receive either ACL/FOR/BUD or ACL/FOR/placebo and followed for 12 months. The primary end-point of the study was the difference in post-bronchodilator forced expiratory volume in 1 s (FEV1) over 12 months between patients with LASMC and HASMC receiving or not receiving ICS.

Results

In patients with LASMC, ACL/FOR/BUD did not significantly improve FEV1over 12 months, as compared to ACL/FOR/placebo (p=0.675). However, in patients with HASMC, ACL/FOR/BUD significantly improved FEV1, as compared to ACL/FOR/placebo (p=0.020). Over 12 months, the difference of FEV1change between the ACL/FOR/BUD group and the ACL/FOR/placebo group was 50.6 mL·year−1within the group of patients with LASMC and 183.0 mL·year−1within the group of patients with HASMC.

Conclusion

COPD patients with ΗASMC respond better to ICS than patients with LASMC, suggesting that this type of histological analysis may predict ICS responsiveness in COPD patients receiving triple therapy.
Quantifying COPD as a risk factor for cardiac disease in a primary prevention cohort
Authors: Maclagan Laura C. , Croxford Ruth , Chu Anna , Sin Don D. , Udell Jacob A. , Lee Douglas S. , Austin Peter C. , Gershon Andrea S.
Published: June 2023

Background

Despite COPD being a risk factor for cardiovascular disease (CVD) and knowing that risk stratification for CVD primary prevention is important, little is known about the real-world risk of CVD among people with COPD with no history of CVD. This knowledge would inform CVD management for people with COPD. The current study aimed to examine the risk of major adverse cardiovascular events (MACE) (including acute myocardial infarction, stroke or cardiovascular death) in a large, complete real-world population with COPD without previous CVD.

Methods

We conducted a retrospective population cohort study using health administrative, medication, laboratory, electronic medical record and other data from Ontario, Canada. People without a history of CVD with and without physician-diagnosed COPD were followed between 2008 and 2016, and cardiac risk factors and comorbidities compared. Sequential cause-specific hazard models adjusting for these factors determined the risk of MACE in people with COPD.

Results

Among ∼5.8 million individuals in Ontario aged ≥40 years without CVD, 152 125 had COPD. After adjustment for cardiovascular risk factors, comorbidities and other variables, the rate of MACE was 25% higher in persons with COPD compared with those without COPD (hazard ratio 1.25, 95% CI 1.23–1.27).

Conclusions

In a large real-world population without CVD, people with physician-diagnosed COPD were 25% more likely to have a major CVD event, after adjustment for CVD risk and other factors. This rate is comparable to the rate in people with diabetes and calls for more aggressive CVD primary prevention in the COPD population.
Shared genetic architecture of blood eosinophil counts and asthma in UK Biobank
Authors: Li Boyang , Wang Yuxuan , Wang Zixiao , Li Xinyue , Kay Shannon , Chupp Geoffrey L. , Zhao Hongyu , Gomez Jose L.
Published: June 2023

Rationale

Asthma is a complex, heterogeneous disease strongly associated with type 2 inflammation, and blood eosinophil counts guide therapeutic interventions in moderate and severe asthma. Eosinophils are leukocytes involved in type 2 immune responses. Despite these critical associations between asthma and blood eosinophil counts, the shared genetic architecture of these two traits remains unknown. The objective of the present study was to characterise the genetic architecture of blood eosinophil counts and asthma in the UK Biobank.

Methods

We performed genome-wide association studies (GWAS) of doctor-diagnosed asthma, blood eosinophil, neutrophil, lymphocyte and monocyte counts in the UK Biobank. Genetic correlation analysis was performed on GWAS results and validated in the Trans-National Asthma Genetic Consortium (TAGC) study of asthma.

Results

GWAS of doctor-diagnosed asthma and blood eosinophil counts in the UK Biobank identified 585 and 3429 significant variants, respectively.STAT6, a transcription factor involved in interleukin-4 signalling, was a key shared pathway between asthma and blood eosinophil counts. Genetic correlation analysis demonstrated a positive correlation between doctor-diagnosed asthma and blood eosinophil counts (r=0.38±0.10, correlation±se;p=4.7×10−11). As a validation of this association, we found a similar correlation between TAGC and blood eosinophil counts in the UK Biobank (0.37±0.08, correlation±se;p=1.2×10−6)

Conclusions

These findings define the shared genetic architecture between blood eosinophil counts and asthma risk in subjects of European ancestry and point to a genetic link to theSTAT6signalling pathway in these two traits.
Impulse oscillometry indices in relation to respiratory symptoms and spirometry in the Swedish Cardiopulmonary Bioimage Study
Authors: Qvarnström Björn , Engström Gunnar , Frantz Sophia , Zhou Xingwu , Zaigham Suneela , Sundström Johan , Janson Christer , Wollmer Per , Malinovschi Andrei
Published: June 2023

Background

Impulse oscillometry (IOS) is sensitive in detecting lung function impairment. In small studies, impaired IOS relates better to respiratory symptoms than spirometry. We studied how IOS related to spirometry and respiratory symptoms in a large population of individuals (n=10 360) in a cross-sectional analysis.

Methods

Normal values for IOS and spirometry were defined in healthy, never-smoking individuals, aged 50–64 years, from the Swedish CArdioPulmonary bioImage Study (n=3664 for IOS and 3608 for spirometry). For IOS, abnormal values for resistance at 5 Hz (R5) and at 20 Hz and area of reactance were defined using the 95th percentile. Abnormal reactance at 5 Hz for IOS and abnormal conventional spirometry indices (forced expiratory volume in 1 s (FEV1), forced and slow vital capacity and their ratios) were defined using the 5th percentile.

Results

Abnormal IOS parameters were found in 16% of individuals and were associated with increased odds ratios for nearly all respiratory symptoms when adjusted for age, gender and smoking. In individuals with normal spirometry, abnormal IOS resistance was related to cough and dyspnoea, while abnormal reactance was related to wheeze. In these individuals, the combination of abnormalR5with abnormal reactance resulted in approximately two-fold higher likelihood for having cough, chronic bronchitis and dyspnoea, even when further adjusting for FEV1, expressed as % predicted.

Conclusions

Abnormal IOS is related to increased respiratory burden in middle-aged individuals with normal spirometry, especially when resistance and reactance parameters are combined. The different relationships between respiratory symptoms and reactance and resistance warrant further research.
Inhibition of glutamatergic trigeminal nucleus caudalis- vestibular nucleus projection neurons attenuates vestibular dysfunction in the chronic-NTG model of migraine
Authors: Zhang Yun , Zhang Yixin , Wang Yanyun , Zhang Xiaoyan , Qin Guangcheng , Zhang Dunke , Chen Lixue , Zhou Jiying
Published: June 2023

Background

Prior clinical studies suggest a shared mechanism between vestibular symptoms and migraine headache. However, the specific neuroanatomical substrate connecting vestibular symptoms with migraine remains to be largely unknown. Thus, the aim of this study was to further investigate the mechanisms that whether and how trigeminovestibular neurons produce effects on neuronal activation in vestibular nucleus (VN).

Methods

A chronic-NTG rat model was established by recurrent intermittent administration of nitroglycerin (NTG). Pain- and vestibular-related behaviors were assessed. To selectively inhibit the glutamatergic neurons and trigeminal nucleus caudalis (TNC) to VN projection neurons, the AAVs encoding engineered Gi-coupled hM4D receptor were administered in the TNC or VN area.

Results

We identify a glutamatergic projection from TNC to VN that mediates vestibular dysfunction in a chronic-NTG rat model. Inhibition of the GlutamateTNC neurons alleviates vestibular dysfunction in the chronic-NTG rat. Calcitonin gene-related peptide (CGRP)-expressing neurons in the VN received glutamatergic projections from TNC neurons. Silencing the glutamatergic TNC-VN projection neurons attenuates vestibular dysfunction in the chronic-NTG rat.

Conclusions

Together, we reveal a modulatory role of glutamatergic TNC-VN projection neurons in vestibular dysfunction of migraine.

Graphical Abstract
Genetic dissection of 26 meat cut, meat quality and carcass traits in four pig populations
Authors: Xie Lei , Qin Jiangtao , Yao Tianxiong , Tang Xi , Cui Dengshuai , Chen Liqing , Rao Lin , Xiao Shijun , Zhang Zhiyan , Huang Lusheng
Published: June 2023

Background

Currently, meat cut traits are integrated in pig breeding objectives to gain extra profit. However, little is known about the heritability of meat cut proportions (MCP) and their correlations with other traits. The aims of this study were to assess the heritability and genetic correlation of MCP with carcass and meat quality traits using single nucleotide polymorphism chips and conduct a genome-wide association study (GWAS) to identify candidate genes for MCP.

Results

Seventeen MCP, 12 carcass, and seven meat quality traits were measured in 2012 pigs from four populations (Landrace; Yorkshire; Landrace and Yorkshire hybrid pigs; Duroc, and Landrace and Yorkshire hybrid pigs). Estimates of the heritability for MCP ranged from 0.10 to 0.55, with most estimates being moderate to high and highly consistent across populations. In the combined population, the heritability estimates for the proportions of scapula bone, loin, back fat, leg bones, and boneless picnic shoulder were 0.44 ± 0.04, 0.36 ± 0.04, 0.44 ± 0.04, 0.38 ± 0.04, and 0.39 ± 0.04, respectively. Proportion of middle cuts was genetically significantly positively correlated with intramuscular fat content and backfat depth. Proportion of ribs was genetically positively correlated with carcass oblique length and straight length (0.35 ± 0.08 to 0.45 ± 0.07) and negatively correlated with backfat depth (− 0.26 ± 0.10 to − 0.45 ± 0.10). However, weak or nonsignificant genetic correlations were observed between most MCP, indicating their independence. Twenty-eight quantitative trait loci (QTL) for MCP were detected by GWAS, and 24 new candidate genes related to MCP were identified, which are involved with growth, height, and skeletal development. Most importantly, we found that the development of the bones in different parts of the body may be regulated by different genes, among which HMGA1 may be the strongest candidate gene affecting forelimb bone development. Moreover, as previously shown, VRTN is a causal gene affecting vertebra number, and BMP2 may be the strongest candidate gene affecting hindlimb bone development.

Conclusions

Our results indicate that breeding programs for MCP have the potential to enhance carcass composition by increasing the proportion of expensive cuts and decreasing the proportion of inexpensive cuts. Since MCP are post-slaughter traits, the QTL and candidate genes related to these traits can be used for marker-assisted and genomic selection.
An insight into the functional genomics and species classification of Eudiplozoon nipponicum (Monogenea, Diplozoidae), a haematophagous parasite of the common carp Cyprinus carpio
Authors: Vorel Jiří , Kmentová Nikol , Hahn Christoph , Bureš Petr , Kašný Martin
Published: June 2023

Background

Monogenea (Platyhelminthes, Neodermata) are the most species-rich class within the Neodermata superclass of primarily fish parasites. Despite their economic and ecological importance, monogenean research tends to focus on their morphological, phylogenetic, and population characteristics, while comprehensive omics analyses aimed at describing functionally important molecules are few and far between. We present a molecular characterisation of monogenean representative Eudiplozoon nipponicum, an obligate haematophagous parasite infecting the gills of the common carp. We report its nuclear and mitochondrial genomes, present a functional annotation of protein molecules relevant to the molecular and biochemical aspect of physiological processes involved in interactions with the fish hosts, and re-examinate the taxonomic position of Eudiplozoon species within the Diplozoidae family.

Results

We have generated 50.81 Gbp of raw sequencing data (Illumina and Oxford Nanopore reads), bioinformatically processed, and de novo assembled them into a genome draft 0.94 Gbp long, consisting of 21,044 contigs (N50 = 87 kbp). The final assembly represents 57% of the estimated total genome size (~ 1.64 Gbp), whereby repetitive and low-complexity regions account for ~ 64% of the assembled length. In total, 36,626 predicted genes encode 33,031 proteins and homology-based annotation of protein-coding genes (PCGs) and proteins characterises 14,785 (44.76%) molecules. We have detected significant representation of functional proteins and known molecular functions. The numbers of peptidases and inhibitors (579 proteins), characterised GO terms (16,016 unique assigned GO terms), and identified KEGG Orthology (4,315 proteins) acting in 378 KEGG pathways demonstrate the variety of mechanisms by which the parasite interacts with hosts on a macromolecular level (immunomodulation, feeding, and development). Comparison between the newly assembled E. nipponicum mitochondrial genome (length of 17,038 bp) and other diplozoid monogeneans confirms the existence of two distinct Eudiplozoon species infecting different fish hosts: Cyprinus carpio and Carassius spp.

Conclusions

Although the amount of sequencing data and characterised molecules of monogenean parasites has recently increased, a better insight into their molecular biology is needed. The E. nipponicum nuclear genome presented here, currently the largest described genome of any monogenean parasite, represents a milestone in the study of monogeneans and their molecules but further omics research is needed to understand these parasites’ biological nature.
Optimizing tumor-associated antigen-stimulated autologous dendritic cell and cytokine-induced killer cell coculture to enhance cytotoxicity for cancer immunotherapy in manufacturing
Authors: Lee Yi-Yen , Luo Shao-Ciao , Lee Chung-Hsin , Tang Chien-Lun , Shen Chiung-Chyi , Cheng Wen-Yu , Yang Yi-Chin , Yang Meng-Yin , Yen Chun-Ming
Published: June 2023

Background

Dendritic Cell Cytokine-induced killer cell (DC-CIK) coculture treatment in cancer immunotherapy has been shown to be effective. However, the cost of DC- CIK therapy is prohibitive for many patients, and the lack of standard manufacturing processes and treatment strategies are major limitations. Our study used tumor lysate as a tumor-associated antigen source and DCs and CIK cells in coculture. We developed an efficient method to obtain autologous DCs- and CIK cells from peripheral blood. We used flow cytometry to assess DC activation and the cytometric bead array assay to quantify cytokines secreted by CIK cells.

Results

We evaluated the antitumor activity of DC- CIK coculture in vitro with the K562 cell line. We demonstrated that a manufacturing process employing frozen immature DCs can yield the lowest loss with the highest economic benefits. DC-CIK coculture can effectively upgrade CIK cells’ immunological specificity to tumors in the presence of tumor-associated antigens.

Conclusion

In vitro experiments revealed that when the DC- CIK cell ratio was 1: 20 in the coculture, CIK cells secreted the highest number of cytokines on the 14th day and the antitumor immune effect showed the highest potency. CIK cells’ cytotoxicity to K562 cells was highest when the CIK: K562 cell ratio was 25: 1. We developed an efficient manufacturing process for DC- CIK coculture, while also establishing the optimal DC- CIK cell ratio for immunological activity and the best cytotoxic CIK: K562 cell ratio.
Study of bacterial respiratory infections and antimicrobial susceptibility profile among antibiotics naive outpatients visiting Meru teaching and referral hospital, Meru County, Kenya in 2018
Authors: Miriti Dinah Muthoni , Muthini John Maingi , Nyamache Anthony Kebira
Published: June 2023

Objective

Respiratory tract infections cause significant morbidity and mortality globally and are the most common infectious diseases in humans. This study aims at assessing the presence of bacterial respiratory infections, number of people infected and antimicrobial susceptibility profile among antibiotic naïve outpatients presenting with respiratory tract infections in Meru Teaching and Referral Hospital.

Methods

The study was conducted in Meru Teaching and Referral Hospital, Meru County from April 2017 to August 2018. Upper respiratory infections were characterized by acute infection of nasal cavity, pharynx and larynx while lower respiratory infections were characterized by chest pains, prolonged cough, productive sputum, difficulty in breathing, fever and weight loss. A total of 384 sputum and throat samples were collected aseptically from patients who were clinically suspected to have respiratory infections and cultured in blood agar, MacConkey agar and chocolate agar. Bacterial isolates were identified by colonial morphology, Gram stain and confirmed by biochemical tests. Antimicrobial susceptibility profile was determined using agar disc diffusion method.

Results

Respiratory bacterial pathogens were isolated in 45.6% of the samples. The prevalence of the bacteria species isolated were as followsPseudomonasspecies (36.6%),Klebsiellaspecies (20.6%),Staphylococcus aureus(16.6%),Streptococcus pyogenes(13.7%),Streptococcus pneumoniae (10.3%) and mixed isolates (2.3%). Amoxicillin and ampicillin recorded the highest resistance rate. Most of the isolates displayed high level of resistance to more than two antibiotics. Although multidrug resistance is reported in the study, gentamicin, amikacin and cefuroxime are recommended as the antibiotics of choice against bacterial isolates obtained.

Conclusion

Bacterial respiratory infections were prevalent in the study area and the isolates obtained showed resistance to commonly used antibiotics such as amoxicillin, ampicillin, ciprofloxacin piperacillin ciprofloxacin, ceftazidime, piperacillin-tazobactam and cephalexin. Therefore need for a continuous surveillance of antimicrobial resistance in management of respiratory infections in the study area.
Genome skimming as an efficient tool for authenticating commercial products of the pharmaceutically important Paris yunnanensis (Melanthiaceae)
Authors: Zhou Nian , Tang Lilei , Xie Pingxuan , Miao Ke , Yang Chengjin , Liu Haiyang , Ji Yunheng
Published: June 2023

Background

Paris yunnanensis (Melanthiaceae) is a traditional Chinese medicinal plant of significant pharmaceutical importance. Due to previous taxonomic confusion, a congeneric species, Paris liiana, has been mistaken for P. yunnanensis and cultivated on a large scale, leading to the mixing of commercial products (i.e., seedlings and processed rhizomes) of P. yunnanensis with those of P. liiana. This may have adverse effects on quality control in the standardization of P. yunnanensis productions. As the lack of PCR amplifiable genomic DNA within processed rhizomes is an intractable obstacle to the authentication of P. yunnanensis products using PCR-based diagnostic tools, this study aimed to develop a PCR-free method to authenticate commercial P. yunnanensis products, by applying genome skimming to generate complete plastomes and nrDNA arrays for use as the molecular tags.

Results

Based on a dense intraspecies sampling of P. liiana and P. yunnanensis, the robustness of the proposed authentication systems was evaluated by phylogenetic inferences and experimental authentication of commercial seedling and processed rhizome samples. The results indicate that the genetic criteria of both complete plastomes and nrDNA arrays were consistent with the species boundaries to achieve accurate discrimination of P. yunnanensis and P. liinna. Owing to its desirable accuracy and sensitivity, genome skimming can serve as an effective and sensitive tool for monitoring and controlling the trade of P. yunnanensis products.

Conclusion

This study provides a new way to solve the long-standing problem of the molecular authentication of processed plant products due to the lack of PCR amplifiable genomic DNA. The proposed authentication system will support quality control in the standardization of P. yunnanensis products in cultivation and drug production. This study also provides molecular evidence to clarify the long-standing taxonomic confusion regarding the species delimitation of P. yunnanensis, which will contribute to the rational exploration and conservation of the species.
Transfemoral transcatheter aortic valve replacement for pure native aortic regurgitation: one-year outcomes of a single-center study
Authors: Zheng Hua-Jie , Cheng Yong-Bo , Yan Chao-Jun , Lin De-Qing , Yu San-Jiu , Li Jun , He Ping , Cheng Wei
Published: June 2023

Background

Evidence about safety and efficacy of transcatheter aortic valve replacement (TAVR) with the Venus A-Valve system (Venus Medtech, Hangzhou, China) remains limited for patients with pure native aortic regurgitation (PNAR).

Objectives

The single-center study sought to report the one-year clinical outcomes of the Venus A-Valve in the treatment of PNAR.

Methods

This study was a retrospective analysis of prospectively collected data. Data was from all consecutive patients who had PNAR and underwent TAVR with the Venus A-Valve system at our center from July 2020 and June 2021. Procedural and clinical outcomes up to one year were analyzed using Valve Academic Research Consortium-2 criteria.

Results

A total of 45 consecutive patients with PNAR underwent transfemoral TAVR with the Venus A-Valve system. The Mean age was 73.5 ± 5.5 years and 26.7% were female. All the TAVR procedures were performed via transfemoral access. Implantations were successful in 44 cases (97.8%). Only one patient was converted to surgical aortic valve replacement. No patient died intraoperatively. No second valve was implanted. In-hospital mortality rate was 2.3%. The one-year all-cause mortality rate was 4.7% without cardiovascular related death. No patient had moderate or severe paravalvular leakage during follow-up. At one year, the mean pressure gradient was 8.8 ± 0.9 mmHg, and left ventricular ejection fraction increased to 61.5 ± 3.6%.

Conclusions

This single-center study demonstrated the safety and efficacy of transfemoral TAVR with the Venus A-Valve in the treatment of patients with PNAR.
Increase in power by obtaining 10 or more controls per case when type-1 error is small in large-scale association studies
Authors: Katki Hormuzd A. , Berndt Sonja I. , Machiela Mitchell J. , Stewart Douglas R. , Garcia-Closas Montserrat , Kim Jung , Shi Jianxin , Yu Kai , Rothman Nathaniel
Published: June 2023

Background

The rule of thumb that there is little gain in statistical power by obtaining more than 4 controls per case, is based on type-1 error α = 0.05. However, association studies that evaluate thousands or millions of associations use smaller α and may have access to plentiful controls. We investigate power gains, and reductions in p-values, when increasing well beyond 4 controls per case, for small α.

Methods

We calculate the power, the median expected p-value, and the minimum detectable odds-ratio (OR), as a function of the number of controls/case, as α decreases.

Results

As α decreases, at each ratio of controls per case, the increase in power is larger than for α = 0.05. For α between 10–6 and 10–9 (typical for thousands or millions of associations), increasing from 4 controls per case to 10–50 controls per case increases power. For example, a study with power = 0.2 (α = 5 × 10–8) with 1 control/case has power = 0.65 with 4 controls/case, but with 10 controls/case has power = 0.78, and with 50 controls/case has power = 0.84. For situations where obtaining more than 4 controls per case provides small increases in power beyond 0.9 (at small α), the expected p-value can decrease by orders-of-magnitude below α. Increasing from 1 to 4 controls/case reduces the minimum detectable OR toward the null by 20.9%, and from 4 to 50 controls/case reduces by an additional 9.7%, a result which applies regardless of α and hence also applies to “regular” α = 0.05 epidemiology.

Conclusions

At small α, versus 4 controls/case, recruiting 10 or more controls/cases can increase power, reduce the expected p-value by 1–2 orders of magnitude, and meaningfully reduce the minimum detectable OR. These benefits of increasing the controls/case ratio increase as the number of cases increases, although the amount of benefit depends on exposure frequencies and true OR. Provided that controls are comparable to cases, our findings suggest greater sharing of comparable controls in large-scale association studies.
Lower end of treatment HBsAg and HBcrAg were associated with HBsAg loss after nucleos(t)ide analog cessation
Authors: Xie Yandi , Li Minghui , Ou Xiaojuan , Zheng Sujun , Gao Yinjie , Xu Xiaoyuan , Yang Ying , Ma Anlin , Li Jia , Nan Yuemin , Zheng Huanwei , Liu Juan , Wei Lai , Feng Bo
Published: June 2023

Background

Since hepatitis B surface antigen (HBsAg) loss is rarely achieved with nucleos(t)ide analog (NA) treatment, most patients require life-long NA treatment. Previous studies have shown that some patients remain virologically responsive even after NA cessation. However, there is still controversy surrounding whether NA discontinuation increases the HBsAg loss rate. Therefore, this study aimed to assess the cumulative rate of HBsAg loss and identify the predictors of HBsAg loss after NA discontinuation.

Methods

This multicenter prospective study included HBV e antigen (HBeAg)-positive patients without cirrhosis from 12 hospitals in China who met the inclusion criteria. The enrolled patients stopped NA and were followed up with clinical and laboratory assessments every 3 months for 24 months after NA cessation or until clinical relapse (CR) occurred.

Results

Overall, 158 patients were classified into two groups. Group A included patients with HBsAg positivity at NA cessation (n = 139), and Group B included patients with HBsAg negativity at NA cessation (n = 19). In Group A, the 12-month and 24-month cumulative rates of HBsAg loss were4.3%and 9.4%, respectively. End of treatment (EOT) HBsAg (hazard ratio (HR) = 0.152, P < 0.001) and EOT hepatitis B core-related antigen (HBcrAg) (HR = 0.257, P = 0.001) were associated with HBsAg loss. The areas under the receiver operating characteristic curves for EOT HBsAg and HBcrAg levels were 0.952 (P < 0.001) and 0.765 (P < 0.001), respectively. Patients with EOT HBsAg ≤ 135 IU/mL (59.2% vs. 1.3%, P < 0.001) or HBcrAg ≤ 3.6 logU/mL (17% vs. 5.4%, P = 0.027) had a higher 24-month cumulative HBsAg loss rate. In Group B, none of the patients experienced virological relapse after NA cessation. Only 1 (5.3%) patient had HBsAg reversion.

Conclusions

EOT HBsAg ≤ 135 IU/mL or HBcrAg ≤ 3.6 logU/mL can be used to identify patients with a higher likelihood of HBsAg loss after NA cessation. Patients with HBsAg negativity after NA cessation have favorable clinical outcomes, and HBsAg loss was durable in most cases.
Microperimetric evaluation for different methods of epiretinal membrane surgery
Authors: Nam Seung Wan , Byun Zeeyoon , Ham Don-Il , Kong Mingui
Published: June 2023

Purpose

To investigate the anatomic and functional outcomes using microperimetry for the surgical methods for idiopathic epiretinal membranes (ERM).

Methods

This retrospective study included 41 eyes from 41 patients. All patients underwent combined epiretinal membrane and cataract surgery. Best-corrected visual acuity (BCVA), optical coherence tomography, and microperimetry were performed before and 6 months and 1 year after surgery. The patients were divided into 3 groups; “ERM removal only without indocyanine green (ICG) staining”, “ERM and internal limiting membrane (ILM) removal without ICG staining”, and “ERM and ILM removal with ICG staining”.

Results

Preoperatively, the ages, BCVAs, central macular thickness (CMT), and mean retinal sensitivities of central 6° (MRSs) of the groups were not significantly different (p > 0.05). Postoperatively, the MRSs of the “ERM removal only without ICG staining” and “ERM and ILM removal without ICG staining” groups were not significantly different (p > 0.05). The MRSs of the “ERM and ILM removal without ICG staining” and “ERM and ILM removal with ICG staining” groups were not significantly different (p > 0.05). However, the MRSs of the “ERM and ILM removal with ICG staining” group significantly reduced than “ERM removal only without ICG staining” group (p < 0.05).

Conclusion

This retrospective study found reduced retinal sensitivity in ERM and ILM removal with ICG staining group compared to ERM removal only without ICG staining. Further studies with larger sample sizes are required.
Childhood tuberous sclerosis complex in southern Sweden: a paradigm shift in diagnosis and treatment
Authors: Pearsson Kevin , Björk Werner Josefin , Lundgren Johan , Gränse Lotta , Karlsson Emma , Källén Kristina , Eklund Erik A. , Bekassy Zivile
Published: June 2023

Aim

To investigate the complete clinical spectrum of individuals with paediatric tuberous sclerosis complex in southern Sweden and explore changes over time.

Methods

In this retrospective observational study, 52 individuals aged up to 18 years at the study start were followed-up at regional hospitals and centres for habilitation from 2000 to 2020.

Results

Cardiac rhabdomyoma was detected prenatally/neonatally in 69.2% of the subjects born during the latest ten years of the study period. Epilepsy was diagnosed in 82.7% of subjects, and 10 (19%) were treated with everolimus, mainly (80%) for a neurological indication. Renal cysts were detected in 53%, angiomyolipomas in 47%, astrocytic hamartomas in 28% of the individuals. There was a paucity of standardized follow-up of cardiac, renal, and ophthalmological manifestations and no structured transition to adult care.

Conclusion

Our in-depth analysis shows a clear shift towards an earlier diagnosis of tuberous sclerosis complex in the latter part of the study period, where more than 60% of cases showed evidence of this condition already in utero due to the presence of a cardiac rhabdomyoma. This allows for preventive treatment of epilepsy with vigabatrin and early intervention with everolimus for potential mitigation of other symptoms of tuberous sclerosis complex.