bluuebunny/crossref_metadata_2025 huggingface dataset:
Inference of genomic landscapes using ordered Hidden Markov Models with emission densities (oHMMed)
Authors: Vogl Claus , Karapetiants Mariia , Yıldırım Burçin , Kjartansdóttir Hrönn , Kosiol Carolin , Bergman Juraj , Majka Michal , Mikula Lynette Caitlin
Published: April 2024

Background

Genomes are inherently inhomogeneous, with features such as base composition, recombination, gene density, and gene expression varying along chromosomes. Evolutionary, biological, and biomedical analyses aim to quantify this variation, account for it during inference procedures, and ultimately determine the causal processes behind it. Since sequential observations along chromosomes are not independent, it is unsurprising that autocorrelation patterns have been observed e.g., in human base composition. In this article, we develop a class of Hidden Markov Models (HMMs) called oHMMed (ordered HMM with emission densities, the corresponding R package of the same name is available on CRAN): They identify the number of comparably homogeneous regions within autocorrelated observed sequences. These are modelled as discrete hidden states; the observed data points are realisations of continuous probability distributions with state-specific means that enable ordering of these distributions. The observed sequence is labelled according to the hidden states, permitting only neighbouring states that are also neighbours within the ordering of their associated distributions. The parameters that characterise these state-specific distributions are inferred.

Results

We apply our oHMMed algorithms to the proportion of G and C bases (modelled as a mixture of normal distributions) and the number of genes (modelled as a mixture of poisson-gamma distributions) in windows along the human, mouse, and fruit fly genomes. This results in a partitioning of the genomes into regions by statistically distinguishable averages of these features, and in a characterisation of their continuous patterns of variation. In regard to the genomic G and C proportion, this latter result distinguishes oHMMed from segmentation algorithms based in isochore or compositional domain theory. We further use oHMMed to conduct a detailed analysis of variation of chromatin accessibility (ATAC-seq) and epigenetic markers H3K27ac and H3K27me3 (modelled as a mixture of poisson-gamma distributions) along the human chromosome 1 and their correlations.

Conclusions

Our algorithms provide a biologically assumption free approach to characterising genomic landscapes shaped by continuous, autocorrelated patterns of variation. Despite this, the resulting genome segmentation enables extraction of compositionally distinct regions for further downstream analyses.
MetageNN: a memory-efficient neural network taxonomic classifier robust to sequencing errors and missing genomes
Authors: Peres da Silva Rafael , Suphavilai Chayaporn , Nagarajan Niranjan
Published: April 2024

Background

With the rapid increase in throughput of long-read sequencing technologies, recent studies have explored their potential for taxonomic classification by using alignment-based approaches to reduce the impact of higher sequencing error rates. While alignment-based methods are generally slower, k-mer-based taxonomic classifiers can overcome this limitation, potentially at the expense of lower sensitivity for strains and species that are not in the database.

Results

We present MetageNN, a memory-efficient long-read taxonomic classifier that is robust to sequencing errors and missing genomes. MetageNN is a neural network model that uses short k-mer profiles of sequences to reduce the impact of distribution shifts on error-prone long reads. Benchmarking MetageNN against other machine learning approaches for taxonomic classification (GeNet) showed substantial improvements with long-read data (20% improvement in F1 score). By utilizing nanopore sequencing data, MetageNN exhibits improved sensitivity in situations where the reference database is incomplete. It surpasses the alignment-based MetaMaps and MEGAN-LR, as well as the k-mer-based Kraken2 tools, with improvements of 100%, 36%, and 23% respectively at the read-level analysis. Notably, at the community level, MetageNN consistently demonstrated higher sensitivities than the previously mentioned tools. Furthermore, MetageNN requires < 1/4th of the database storage used by Kraken2, MEGAN-LR and MMseqs2 and is > 7× faster than MetaMaps and GeNet and > 2× faster than MEGAN-LR and MMseqs2.

Conclusion

This proof of concept work demonstrates the utility of machine-learning-based methods for taxonomic classification using long reads. MetageNN can be used on sequences not classified by conventional methods and offers an alternative approach for memory-efficient classifiers that can be optimized further.
Development of a smartphone screening test for preclinical Alzheimer’s disease and validation across the dementia continuum
Authors: Alty Jane , Goldberg Lynette R. , Roccati Eddy , Lawler Katherine , Bai Quan , Huang Guan , Bindoff Aidan D , Li Renjie , Wang Xinyi , St George Rebecca J. , Rudd Kaylee , Bartlett Larissa , Collins Jessica M. , Aiyede Mimieveshiofuo , Fernando Nadeeshani , Bhagwat Anju , Giffard Julia , Salmon Katharine , McDonald Scott , King Anna E. , Vickers James C.
Published: April 2024

Background

Dementia prevalence is predicted to triple to 152 million globally by 2050. Alzheimer’s disease (AD) constitutes 70% of cases. There is an urgent need to identify individuals with preclinical AD, a 10–20-year period of progressive brain pathology without noticeable cognitive symptoms, for targeted risk reduction. Current tests of AD pathology are either too invasive, specialised or expensive for population-level assessments. Cognitive tests are normal in preclinical AD. Emerging evidence demonstrates that movement analysis is sensitive to AD across the disease continuum, including preclinical AD. Our new smartphone test, TapTalk, combines analysis of hand and speech-like movements to detect AD risk. This study aims to [1] determine which combinations of hand-speech movement data most accurately predict preclinical AD [2], determine usability, reliability, and validity of TapTalk in cognitively asymptomatic older adults and [3], prospectively validate TapTalk in older adults who have cognitive symptoms against cognitive tests and clinical diagnoses of Mild Cognitive Impairment and AD dementia.

Methods

Aim 1will be addressed in a cross-sectional study of at least 500 cognitively asymptomatic older adults who will complete computerised tests comprising measures of hand motor control (finger tapping) and oro-motor control (syllabic diadochokinesis). So far, 1382 adults, mean (SD) age 66.20 (7.65) years, range 50–92 (72.07% female) have been recruited. Motor measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 to develop an algorithm that classifies preclinical AD risk.Aim 2comprises three sub-studies in cognitively asymptomatic adults: (i) a cross-sectional study of 30–40 adults to determine the validity of data collection from different types of smartphones, (ii) a prospective cohort study of 50–100 adults ≥ 50 years old to determine usability and test-retest reliability, and (iii) a prospective cohort study of ~1,000 adults ≥ 50 years old to validate against cognitive measures.Aim 3will be addressed in a cross-sectional study of ~200 participants with cognitive symptoms to validate TapTalk against Montreal Cognitive Assessment and interdisciplinary consensus diagnosis.

Discussion

This study will establish the precision of TapTalk to identify preclinical AD and estimate risk of cognitive decline. If accurate, this innovative smartphone app will enable low-cost, accessible screening of individuals for AD risk. This will have wide applications in public health initiatives and clinical trials.

Trial registration

ClinicalTrials.gov identifier: NCT06114914, 29 October 2023. Retrospectively registered.
Essential components of an educational program for implementing skin-to-skin contact for preterm infants in intensive care units: an integrative literature review
Authors: Denge Takalani T. , Bam Nokwanda Edith , Lubbe Welma , Rakhudu Annah
Published: April 2024

Background

Globally, prematurity is the primary factor behind the mortality of children under the age of 5 years, resulting in approximately 1 million children dying annually. The World Health Organization (WHO) recommends Skin-to-Skin Contact (SSC) as part of routine care for preterm infants. Evidence shows that SSC reduces mortality, possibly by improving thermoregulation, facilitating the earlier initiation of breastfeeding and reducing the risk of nosocomial infection. An educational program for implementing SSC has been demonstrated to enhance the knowledge and practice of parents and nurses in intensive care units. This study, the first of its kind in the North West Province (NWP), aims to identify the essential components of an educational program for implementing SSC for premature infants in intensive care units.

Objective

This paper presents an integrative literature review that critically synthesizes research-based literature on essential components of an educational program for implementing SSC for preterm infants in intensive care units.

Methods

A comprehensive search of electronic databases, such as CINAHL, MEDLINE, PsycINFO, ProQuest and Health Source: Nursing/Academic Edition and Health Source-Consumer Edition, was conducted using different keywords and references lists from the bibliography.

Results

Twelve articles relevant to this review were identified, read and synthesized to answer the research question. Three essential components emerged from the findings of this review, namely (1) the necessity of policy and role players for implementing SSC, (2) the availability of education and training, and (3) counseling and support for parents of preterm infants.

Conclusions

The outcomes of this study have the potential to facilitate the implementation and expansion of SSC in intensive care units. This could aid program implementers, policymakers, and researchers to implement and scale up this important tool in intensive care units.
Efficacy of salvage surgery versus re-irradiation for isolated regional lymph node recurrence in patients with nasopharyngeal carcinoma
Authors: Chen Yuebing , Huang Yiping , Chen Xiaoqiang , Chen Zhiwei , Peng Xiane , Lin Shaojun , Lin Cheng , Zong Jingfeng
Published: April 2024

Background

To compare the clinical characteristics and prognoses of patients with isolated regional lymph node recurrent nasopharyngeal carcinoma (irrNPC) who underwent surgery or re-irradiation treatment.

Methods

We retrospectively reviewed 124 irrNPC patients who underwent initial radiotherapy between January 2010 and December 2020. The staging of regional lymph node recurrence was as follows: 75.8% for rN1, 14.5% for rN2, and 9.7% for rN3. Fifty-five patients underwent regional lymph node surgery (Surgery group), and sixty-nine patients received salvage radiotherapy with or without chemotherapy (Re-irradiation group). The survival rate was compared using Kaplan‒Meier analysis and evaluated by the log-rank test. Cox proportional hazard models were used to analyze prognostic factors.

Results

The median follow-up time was 70 months, the 5-year overall survival (OS) was 74%, and the median survival time was 60.8 months. There were no significant differences in 5-year OS (75.6% vs. 72.4%, P = 0.973), regional recurrence-free survival (RRFS, 62.7% vs. 71.1%, P = 0.330) or distant metastasis-free survival (DMFS, 4.2% vs.78.7%, P = 0.677) between the Surgery group and Re-irradiation group. Multivariate analysis revealed age at recurrence, radiologic extra-nodal extension (rENE) status, and recurrent lymph node (rN) classification as independent prognostic factors for OS. The rENE status was an independent prognostic factor for DMFS. Subgroup analysis of the Surgery group revealed that the rN3 classification was an adverse prognostic factor for OS. Age at recurrence ≥ 50 years, GTV-N dose, and induction chemotherapy were found to be independent prognostic factors for OS, RRFS, and DMFS, respectively, in the Re-irradiation group.

Conclusions

For NPC patients with isolated regional lymph node recurrence after initial radiotherapy, those who underwent surgery had survival prognosis similar to those who underwent re-radiotherapy with or without chemotherapy. A prospective study is needed to validate these findings.
Efficacy and adverse reactions of peripheral add multifocal soft contact lenses in childhood myopia: a meta-analysis
Authors: Song Desheng , Qiu Wen , Jiang Ting , Chen Zhijun , Chen Juan
Published: April 2024

Objectives

This study aims to compare the efficacy of peripheral add multifocal soft contact lenses (SCLs) (excluding bifocal SCLs) with single vision contact lenses or spectacles in controlling myopia progression.

Method

A comprehensive literature search was conducted in the Pubmed, EMBASE, Web of Science, and Cochrane Library databases until October 2023. The literature was thoroughly screened based on predetermined eligibility criteria. Pooled odds ratios (ORs) were calculated for dichotomous data and weighted mean differences (WMD) for continuous data.

Results

A total of 11 articles comprising 787 participants were included in this meta-analysis. Our pooled results demonstrated that the peripheral add multifocal SCLs groups exhibited significantly reduced refraction progression (MD = 0.20; 95%CI, 0.14 ∼ 0.27;P<0.001) and less axial length elongation (MD=-0.08; 95%CI, -0.09∼-0.08;P<0.001) compared to the control group. There was no significant difference in high-contrast logMAR distance visual acuity between the two groups (MD = 0.01; 95%CI, -0.00 ∼ 0.02;P = 0.19). However, the group using single-vision lenses had better low-contrast logMAR distance visual acuity compared to those using peripheral add multifocal SCLs (MD = 0.06; 95%CI, 0.02 ∼ 0.10;P = 0.004). Data synthesis using a random-effects model indicated an incidence of contact lens-related adverse events of 0.065 (95%CI, 0.048 ∼ 0.083).

Conclusions

The present meta-analysis signifies that peripheral defocus modifying contact lenses are effective in slowing down the progression of myopia and reducing axial elongation.
Comparative efficacy and safety of all kinds of intraocular lenses in presbyopia-correcting cataract surgery: a systematic review and meta-analysis
Authors: Li Jinyu , Sun Bin , Zhang Yuexin , Hao Yansong , Wang Ze , Liu Chengjiang , Jiang Shanhao
Published: April 2024

Purpose

To assess the efficacy and safety of various intraocular lenses (IOLs), including standard monofocal, bifocal, trifocal, extended depth of focus (EDOF), and enhanced monofocal IOLs, post-cataract surgery through a network meta-analysis.

Methods

A systematic search of PubMed, Cochrane Library, and Web of Science was conducted to identify relevant studies from the past 5 years. Parameters such as binocular visual acuities, spectacle independence, contrast sensitivity (CS), and optical quality were used to evaluate efficacy and safety. Data from the selected studies were analyzed using Review Manager 5.4 and STATA 17.0 software.

Results

Twenty-eight Randomized Controlled Trials (RCTs) comprising 2465 subjects were included. Trifocal IOLs exhibited superior uncorrected near visual acuity (UNVA) compared to monofocal IOLs (MD: -0.35; 95% CI: -0.48, -0.22). Both trifocal (AcrySof IQ PanOptix IOLs group MD: -0.13; 95% CI: -0.21, -0.06) and EDOF IOLs (MD: -0.13; 95% CI: -0.17, -0.09) showed better uncorrected intermediate visual acuity (UIVA) than monofocal IOLs. Trifocal IOLs ranked highest in spectacle independence at various distances (AT LISAtri 839MP group: SUCRA 97.5% for distance, 80.7% for intermediate; AcrySof IQ PanOptix group: SUCRA 83.0% for near).

Conclusions

For cataract patients who want to treat presbyopia, trifocal IOLs demonstrated better visual acuity and spectacle independence at near distances. Different types of trifocal IOL characteristics differ. EDOF and enhanced monofocal IOLs have improved visual quality at intermediate distances.Therefore, It is very important to select the appropriate IOLs based on the lens characteristics and patient needs.
Unexplained recurrent high fever observed in a depressed adolescent
Authors: Guo Xunyi , Li Yuning , Bai Lu , Lin Feng , Chen Jing , Zou Tao
Published: April 2024

Background

Depressive episodes in adolescents are often accompanied by various physical symptoms, but few studies have explored the association between depression and fever, This case study is the first to report the relationship between unexplained recurrent high fever and depression.

Case presentation

H is a 15 year old adolescent female currently in junior year. 2 + months ago, H gradually felt depressed after a class change. Around the time, the patient suddenly developed chills with no obvious trigger and fever. H was treated with anti-infective and anti-viral treatments all of which did not show significant improvement. No significant abnormality was seen in any of the related examinations. Considering that the patient’s anxiety, depression and somatic symptoms were obvious during the course of the disease, she was given venlafaxine hydrochloride extended-release capsule 75 mg/d; tandospirone citrate capsule 10 mg Bid; alprazolam tablets 0.4 mg qn to improve mood and sleep; supplemented with transcranial repetitive magnetic stimulation therapy 2 times/d; visible light therapy 1 time/d and psychological counseling once. Over the 6 days of treatment, the patient’s body temperature gradually returned to the normal range and her mood improved significantly.

Conclusion

Depression should be considered a potential cause of unexplained recurrent fevers in adolescents, even when the temperature is significantly outside the normal range.
The association between psychological distress, abusive experiences, and help-seeking among people with intimate partner violence
Authors: Zhang Bohan , Wong Arkers , Constantino Rose E. , Hui Vivian
Published: April 2024

Background

Intimate partner violence (IPV) is a serious public health problem associated with countless adverse physical and mental health outcomes. It places an enormous economic and public health burden on communities. The aim of this study was to examine the associations between psychological states (such as depression or hopeless) and help-seeking experiences of IPV survivors after experiencing IPV, based on the Allegheny County Health Survey (ACHS).

Methods

Data from 2015 to 2016 Allegheny County Health Survey with N = 8,012 adults were analyzed. The 6-item version of the Kessler Psychological Stress Scale, located in Module 11 of the ACHS questionnaire, was used to measure psychological stress in participants. Module 12 of the ACHS questionnaire collected information on participants’ experiences of intimate partner violence and help-seeking in the past 12 months. Descriptive statistical analysis, Pearson’s chi-square or two sample independent t-tests statistical analysis, and multivariate binary logistic regression models were used to analyze the relationship between IPV experience and psychological distress.

Results

A total of 212 of the 8,012 participants had IPV experience, with age, marital status, education, income, and race significantly different from those without IPV experience. The psychological stress of participants feeling hopeless (OR = 2.02, 95% CI = 1.37–2.99), restless or fidgety (OR = 1.83, 95% CI = 1.27–2.65), perceiving everything was an effort (OR = 1.55, 95% CI = 1.08–2.22) and worthless (OR = 1.49, 95% CI = 1.01–2.20) was associated with the IPV experience. Help-seeking behaviors of IPV survivors were associated with psychological distress, such as hopelessness (OR = 6.71, 95% CI = 1.38–32.60).

Conclusions

This study explored the association between IPV experience, help-seeking and psychological distress, and the need to expand community support. It is necessary to implement targeted interventions, enhance training of professionals, and promote the identification of early IPV cases as well as collaboration between healthcare and social support departments to reduce the occurrence of IPV or psychological distress following IPV.
Expression patterns of mechanosensitive ion channel PIEZOs in irreversible pulpitis
Authors: Yang Wenying , Lin Lu , Hu Shucheng , Jiang Bin , Yang Ruhan , Yu Weijun , Tang Jiaqi , Zhao Dan , Gu Yuting , Jin Min , Li Jin , Lu Eryi
Published: April 2024

Background

Mechanosensitive ion channel PIEZOs have been widely reported to involve inflammation and pain. This study aimed to clarify expression patterns of PIEZOs and their potential relations to irreversible pulpitis.

Materials and methods

Normal pulp tissues (n = 29) from patients with impacted third molars and inflamed pulp tissues (n = 23) from patients with irreversible pulpitis were collected. Pain levels were assessed using a numerical rating scale. PIEZO expressions were measured using real-time PCR and then confirmed using GEO datasets GSE77459, immunoblot, and immunohistochemistry staining. Correlations of PIEZO mRNA expression with inflammatory markers, pain markers, or clinical pain levels were evaluated using Spearman’s correlation analysis. Univariate analysis was conducted to analyze PIEZO expressions based on pain description and clinical examinations of cold test, percussion, palpation, and bite test.

Results

Compared with normal pulp tissues, mRNA expression levels of PIEZO1 were significantly increased in inflamed pulp tissues, while PIEZO2 was significantly decreased, which was further confirmed in GSE77459 and on a protein and histological level. The positive correlation of the mRNA expression levels between PIEZO1 and inflammatory markers, as well as between PIEZO2 and pain markers, was verified. PIEZO2 expression was also positively correlated with pain levels. Besides, irreversible pulpitis patients who reported continuous pain and who detected a positive response to cold stimulus exhibited a higher expression level of PIEZO2 in the inflamed pulp tissues. By contrast, patients reporting pain duration of more than one week showed a higher expression level of PIEZO1.

Conclusions

This study demonstrated the upregulation of PIEZO1 and the downregulation of PIEZO2 in irreversible pulpitis and revealed the potential relation of PIEZO1 and PIEZO2 to inflammation and pain. These findings suggested that PIEZOs might play critical roles in the progression of irreversible pulpitis and paved the way for further investigations aimed at novel therapies of irreversible pulpitis by targeting PIEZOs.
Optimizing cardiovascular disease mortality prediction: a super learner approach in the tehran lipid and glucose study
Authors: Darabi Parvaneh , Gharibzadeh Safoora , Khalili Davood , Bagherpour-Kalo Mehrdad , Janani Leila
Published: April 2024

Background & aim

Cardiovascular disease (CVD) is the most important cause of death in the world and has a potential impact on health care costs, this study aimed to evaluate the performance of machine learning survival models and determine the optimum model for predicting CVD-related mortality.

Method

In this study, the research population was all participants in Tehran Lipid and Glucose Study (TLGS) aged over 30 years. We used the Gradient Boosting model (GBM), Support Vector Machine (SVM), Super Learner (SL), and Cox proportional hazard (Cox-PH) models to predict the CVD-related mortality using 26 features. The dataset was randomly divided into training (80%) and testing (20%). To evaluate the performance of the methods, we used the Brier Score (BS), Prediction Error (PE), Concordance Index (C-index), and time-dependent Area Under the Curve (TD-AUC) criteria. Four different clinical models were also performed to improve the performance of the methods.

Results

Out of 9258 participants with a mean age of (SD; range) 43.74 (15.51; 20–91), 56.60% were female. The CVD death proportion was 2.5% (228 participants). The death proportion was significantly higher in men (67.98% M, 32.02% F). Based on predefined selection criteria, the SL method has the best performance in predicting CVD-related mortality (TD-AUC > 93.50%). Among the machine learning (ML) methods, The SVM has the worst performance (TD-AUC = 90.13%). According to the relative effect, age, fasting blood sugar, systolic blood pressure, smoking, taking aspirin, diastolic blood pressure, Type 2 diabetes mellitus, hip circumference, body mss index (BMI), and triglyceride were identified as the most influential variables in predicting CVD-related mortality.

Conclusion

According to the results of our study, compared to the Cox-PH model, Machine Learning models showed promising and sometimes better performance in predicting CVD-related mortality. This finding is based on the analysis of a large and diverse urban population from Tehran, Iran.
The mediating role of learning motivation in the relationship among perceived stress and emotional regulation among Saudi nursing students in clinical practice
Authors: Albagawi Bander Saad , Alsalamah Yasir S. , Nashwan Abdulqadir J. , Rawili Rakan Mansuor AL , Babkair Lisa A. , Alkharji Sara A. , Alslamah Thamer , Fawaz Mirna
Published: April 2024

Background

Nursing students often face high levels of stress due to demanding responsibilities during clinical placement. Emotional regulation, the ability to manage and regulate one’s emotions effectively, is crucial for nursing students in dealing with stress and maintaining their overall well-being. Additionally, learning motivation plays a vital role in students’ engagement and academic success. The current investigation aimed at studying the link that exists among stress, learning motivation, and emotional regulation among Saudi undergraduate nursing students. The study also aimed at investigating the sequential mediating effects that motivation might perform in this association.

Methods

A quantitative cross-sectional methodology was used in the present research, which recruited 367 Saudi undergraduate nursing students.

Results

The results of the ANOVA showed that the level of perceived stress was linearly and negatively correlated with emotional regulation and motivation. Upon conducting structural equation modeling, significant direct and indirect effect pathways were identified between perceived stress, emotional regulation, and motivation, while only indirect pathways were identified between perceived stress and emotional regulation.

Conclusions

This study provides evidence of the mediating role of learning motivation in the relationship between perceived stress and emotional regulation among Saudi nursing students. The results highlight the negative impact of stress on emotional regulation and learning motivation and emphasize the importance of addressing motivational factors in interventions aimed at enhancing emotional regulation among nursing students.
Polystyrene nanoplastic and engine oil synergistically intensify toxicity in Nile tilapia, Oreochromis niloticus
Authors: Sayed Alaa El-Din H. , Emeish Walaa F. A. , Bakry Karima A. , Al-Amgad Zeinab , Lee Jae-Seong , Mansour Salwa
Published: April 2024

Polystyrene nanoplastic (PS-NPs) and Engine oil (EO) pose multiple ecotoxic effects with increasing threat to fish ecosystems. The current study investigated the toxicity of 15 days exposure to PS-NPs and / or EO to explore their combined synergistic effects on Nile tilapia, Oreochromis niloticus (O. niloticus). Hematobiochemical parameters, proinflammatory cytokines, and oxidative stress biomarkers as well as histological alterations were evaluated. The experimental design contained 120 acclimated Nile tilapia distributed into four groups, control, PS-NPs (5 mg/L), EO (1%) and their combination (PS-NPs + EO). After 15-days of exposure, blood and tissue samples were collected from all fish experimental groups. Results indicated that Nile tilapia exposed to PS-NPs and / or EO revealed a significant decrease in almost all the measured hematological parameters in comparison to the control, whereas WBCs and lymphocyte counts were significantly increased in the combined group only. Results clarified that the combined PS-NPs + EO group showed the maximum decrease in RBCs, Hb, MCH and MCHC, and showed the maximum significant rise in interleukin-1β (IL-1β), and interleukin-6 (IL-6) in comparison to all other exposed groups. Meanwhile, total antioxidant capacity (TAC) showed a significant (p < 0.05) decline only in the combination group, whereas reduced glutathione (GSH) showed a significant decline in all exposed groups in comparison to the control. Both malondialdehyde (MDA) and aspartate aminotransferase (AST) showed a significant elevation only in the combination group. Uric acid showed the maximum elevation in the combination group than all other groups, whereas creatinine showed significant elevation in the EO and combination group when compared to the control. Furthermore, the present experiment proved that exposure to these toxicants either individually or in combination is accompanied by pronounced histomorpholgical damage characterized by severe necrosis and hemorrhage of the vital organs of Nile tilapia, additionally extensively inflammatory conditions with leucocytes infiltration. We concluded that combination exposure to both PS-NPs and EO caused severe anemia, extreme inflammatory response, oxidative stress, and lipid peroxidation effects, thus they can synergize with each other to intensify toxicity in fish.
Novel likely pathogenic variant in the EYA1 gene causing Branchio oto renal syndrome and the exploration of pathogenic mechanisms
Authors: Zhang Hui , Gao Jian , Wang Hanjun , Liu Mengli , Lu Shuangshuang , Xu Hongen , Tang Wenxue , Zheng Guoxi
Published: April 2024

Objective

Branchio-oto-renal syndrome (BOR, OMIM#113,650) is a rare autosomal dominant disorder that presents with a variety of symptoms, including hearing loss (sensorineural, conductive, or mixed), structural abnormalities affecting the outer, middle, and inner ear, branchial fistulas or cysts, as well as renal abnormalities.This study aims to identify the pathogenic variants by performing genetic testing on a family with Branchio-oto-renal /Branchio-otic (BO, OMIM#602,588) syndrome using whole-exome sequencing, and to explore possible pathogenic mechanisms.

Methods

The family spans 4 generations and consists of 9 individuals, including 4 affected by the BOR/BO syndrome. Phenotypic information, including ear malformation and branchial cleft, was collected from family members. Audiological, temporal bone imaging, and renal ultrasound examinations were also performed. Whole-exome sequencing was conducted to identify candidate pathogenic variants and explore the underlying molecular etiology of BOR/BO syndrome by minigene experiments.

Results

Intra-familial variability was observed in the clinical phenotypes of BOR/BO syndrome in this family. The severity and nature of hearing loss varied in family members, with mixed or sensorineural hearing loss. The proband, in particular, had profound sensorineural hearing loss on the left and moderate conductive hearing loss on the right. Additionally, the proband exhibited developmental delay, and her mother experienced renal failure during pregnancy and terminated the pregnancy prematurely. Genetic testing revealed a novel heterozygous variant NM_000503.6: c.639 + 3 A > C in the EYA1 gene in affected family members. In vitro minigene experiments demonstrated its effect on splicing. According to the American College of Medical Genetics (ACMG) guidelines, this variant was classified as likely pathogenic.

Conclusion

This study highlights the phenotypic heterogeneity within the same family, reports the occurrence of renal failure and adverse pregnancy outcomes in a female patient at reproductive age with BOR syndrome, and enriches the mutational spectrum of pathogenic variants in the EYA1 gene.
Identification and analysis of MSC-Exo-derived LncRNAs related to the regulation of EMT in hypospadias
Authors: Chang Mengmeng , Gao Hongjie , Li Yingying , Ding Chen , Lu Zhiyi , Li Ding , Huang Fan , Chen Jiawei , Sun Fengyin
Published: April 2024

Objective

This study aims to screen the differentially expressed long non-coding RNAs (DELncRNAs) related to the regulation of epithelial-mesenchymal transition (EMT) in hypospadias in mesenchymal stem cell-derived exosomes (MSC-Exons) and explore the potential mechanism of these lncRNAs for the EMT in hypospadias.

Methods

In this study, the microarray data related to MSC-Exos and hypospadias were downloaded from Gene Expression Omnibus (GEO). Besides, the lncRNAs highly expressed in MSC-Exos and the differentially expressed mRNAs and lncRNAs in children with hypospadias were screened, respectively. In addition, the lncRNAs enriched in MSC-Exos and differentially expressed lncRNAs in hypospadias were intersected to obtain the final DElncRNAs. Moreover, the co-expression interaction pairs of differentially expressed lncRNAs and mRNAs were analyzed to construct a Competing Endogenous RNA (ceRNA) network. Finally, the candidate lncRNAs in exosomes were subjected to in vitro cell function verification.

Results

In this study, a total of 4 lncRNAs were obtained from the microarray data analysis. Further, a ceRNA regulatory network of MSC-Exo-derived lncRNAs related to the regulation of EMT in hypospadias was constructed, including 4 lncRNAs, 2 mRNAs, and 6 miRNAs. The cell function verification results indicated that the exosomes secreted by MSCs may transport HLA complex group 18 (HCG18) into target cells, which promoted the proliferation, migration, and EMT of these cells.

Conclusion

MSC-Exo-derived lncRNA HCG18 can enter target cells, and it may be involved in the regulation of EMT in hypospadias through the ceRNA network.
Human genetic associations of the airway microbiome in chronic obstructive pulmonary disease
Authors: Gao Jingyuan , Yang Yuqiong , Xiang Xiaopeng , Zheng Huimin , Yi Xinzhu , Wang Fengyan , Liang Zhenyu , Chen Dandan , Shi Weijuan , Wang Lingwei , Wu Di , Feng Shengchuan , Huang Qiaoyun , Li Xueping , Shu Wensheng , Chen Rongchang , Zhong Nanshan , Wang Zhang
Published: April 2024

Little is known about the relationships between human genetics and the airway microbiome. Deeply sequenced airway metagenomics, by simultaneously characterizing the microbiome and host genetics, provide a unique opportunity to assess the microbiome-host genetic associations. Here we performed a co-profiling of microbiome and host genetics with the identification of over 5 million single nucleotide polymorphisms (SNPs) through deep metagenomic sequencing in sputum of 99 chronic obstructive pulmonary disease (COPD) and 36 healthy individuals. Host genetic variation was the most significant factor associated with the microbiome except for geography and disease status, with its top 5 principal components accounting for 12.11% of the microbiome variability. Within COPD individuals, 113 SNPs mapped to candidate genes reported as genetically associated with COPD exhibited associations with 29 microbial species and 48 functional modules (P < 1 × 10−5), where Streptococcus salivarius exhibits the strongest association to SNP rs6917641 in TBC1D32 (P = 9.54 × 10−8). Integration of concurrent host transcriptomic data identified correlations between the expression of host genes and their genetically-linked microbiome features, including NUDT1, MAD1L1 and Veillonella parvula, TTLL9 and Stenotrophomonas maltophilia, and LTA4H and Haemophilus influenzae. Mendelian randomization analyses revealed a potential causal link between PARK7 expression and microbial type III secretion system, and a genetically-mediated association between COPD and increased relative abundance of airway Streptococcus intermedius. These results suggest a previously underappreciated role of host genetics in shaping the airway microbiome and provide fresh hypotheses for genetic-based host-microbiome interactions in COPD.
Comprehensive analysis of m6A modification in immune infiltration, metabolism and drug resistance in hepatocellular carcinoma
Authors: Shi Yunxing , Li Kai , Yuan Yichuan , Wang Chenwei , Yang Zhiwen , Zuo Dinglan , Niu Yi , Qiu Jiliang , Li Binkui , Yuan Yunfei , He Wei
Published: April 2024

N6-methyladenosine (m6A) is important in regulating mRNA stability, splicing, and translation, and it also contributes to tumor development. However, there is still limited understanding of the comprehensive effects of m6A modification patterns on the tumor immune microenvironment, metabolism, and drug resistance in hepatocellular carcinoma (HCC). In this study, we utilized unsupervised clustering based on the expression of 23 m6A regulators to identify m6A clusters. We identified differential m6A modification patterns and characterized m6A-gene-cluster A, which exhibited poorer survival rates, a higher abundance of Treg cells, and increased expression of TGFβ in the tumor microenvironment (TME). Additionally, m6A-gene-cluster A demonstrated higher levels of glycolysis activity, cholesterol metabolism, and fatty acid biosynthesis. We also found that the m6A score was associated with prognosis and drug resistance. Patients with a low m6A score experienced worse prognoses, which were linked to an abundance of Treg cells, upregulation of TGFβ, and increased metabolic activity. HCC patients with a higher m6A score showed improved prognosis following sorafenib treatment and immunotherapy. In conclusion, we reveals the association between m6A modification patterns and the tumor immune microenvironment, metabolism, and drug resistance in HCC. Furthermore, the m6A score holds potential as a predictive factor for the efficacy of targeted therapy and immunotherapy in HCC.
Significance of PSCA as a novel prognostic marker and therapeutic target for cancer
Authors: Nayerpour Dizaj Tina , Doustmihan Abolfazl , Sadeghzadeh Oskouei Behnaz , Akbari Morteza , Jaymand Mehdi , Mazloomi MirAhmad , Jahanban-Esfahlan Rana
Published: April 2024

One of the contributing factors in the diagnosis and treatment of most cancers is the identification of their surface antigens. Cancer tissues or cells have their specific antigens. Some antigens that are present in many cancers elicit different functions. One of these antigens is the prostate stem cell antigen (PSCA) antigen, which was first identified in the prostate. PSCA is a cell surface protein that has different functions in different tissues. It can play an inhibitory role in cell proliferation as well as a tumor-inducing role. PSCA has several genetic variants involved in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship with clinical features can provide more information on diagnosis and treatment of patients with cancers. Most studies on the PSCA have focused on prostate cancer. While it is also expressed in other cancers, little attention has been paid to its role as a valuable diagnostic, prognostic, and therapeutic tool in other cancers. PSCA has several genetic variants that seem to play a significant role in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship and variants with clinical features can be beneficial in concomitant cancer therapy and diagnosis, as theranostic tools. In this study, we will review the alteration of the PSCA expression and its polymorphisms and evaluate its clinical and theranostics significance in various cancers.
Efficacy and safety of bispecific antibodies vs. immune checkpoint blockade combination therapy in cancer: a real-world comparison
Authors: Cheng Linyan , Chen Lujun , Shi Yuan , Gu Weiying , Ding Weidong , Zheng Xiao , Liu Yan , Jiang Jingting , Zheng Zhuojun
Published: April 2024

Emerging tumor immunotherapy methods encompass bispecific antibodies (BSABs), immune checkpoint inhibitors (ICIs), and adoptive cell immunotherapy. BSABs belong to the antibody family that can specifically recognize two different antigens or epitopes on the same antigen. These antibodies demonstrate superior clinical efficacy than monoclonal antibodies, indicating their role as a promising tumor immunotherapy option. Immune checkpoints are also important in tumor immunotherapy. Programmed cell death protein-1 (PD-1) is a widely acknowledged immune checkpoint target with effective anti-tumor activity. PD-1 inhibitors have demonstrated notable therapeutic efficacy in treating hematological and solid tumors; however, more than 50% of patients undergoing this treatment exhibit a poor response. However, ICI-based combination therapies (ICI combination therapies) have been demonstrated to synergistically increase anti-tumor effects and immune response rates. In this review, we compare the clinical efficacy and side effects of BSABs and ICI combination therapies in real-world tumor immunotherapy, aiming to provide evidence-based approaches for clinical research and personalized tumor diagnosis and treatment.
Approaches to locum physician recruitment and retention: a systematic review
Authors: Ferreira Nathan , McKenna Odessa , Lamb Iain R. , Campbell Alanna , DeMiglio Lily , Orrantia Eliseo
Published: April 2024

A robust workforce of locum tenens (LT) physicians is imperative for health service stability. A systematic review was conducted to synthesize current evidence on the strategies used to facilitate the recruitment and retention of LT physicians. English articles up to October 2023 across five databases were sourced. Original studies focusing on recruitment and retention of LT’s were included. An inductive content analysis was performed to identify strategies used to facilitate LT recruitment and retention. A separate grey literature review was conducted from June–July 2023. 12 studies were retained. Over half (58%) of studies were conducted in North America. Main strategies for facilitating LT recruitment and retention included financial incentives (83%), education and career factors (67%), personal facilitators (67%), clinical support and mentorship (33%), and familial considerations (25%). Identified subthemes were desire for flexible contracts (58%), increased income (33%), practice scouting (33%), and transitional employment needs (33%). Most (67%) studies reported deterrents to locum work, with professional isolation (42%) as the primary deterrent-related subtheme. Grey literature suggested national physician licensure could enhance license portability, thereby increasing the mobility of physicians across regions. Organizations employ five main LT recruitment facilitators and operationalize these in a variety of ways. Though these may be incumbent on local resources, the effectiveness of these approaches has not been evaluated. Consequently, future research should assess LT the efficacy of recruitment and retention facilitators. Notably, the majority of identified LT deterrents may be mitigated by modifying contextual factors such as improved onboarding practices.
KLF5 promotes the ossification process of ligamentum flavum by transcriptionally activating CX43
Authors: Guo Hubing , Yang Lingxia , Liu Jin , Chen Liqi , Huang Yufeng , Li Jinsong
Published: April 2024

Background

Ossification of ligamentum flavum (OLF) is a prevalent degenerative spinal disease, typically causing severe neurological dysfunction. Kruppel-like factor 5 (KLF5) plays an essential role in the regulation of skeletal development. However, the mechanism KLF5 plays in OLF remains unclear, necessitating further investigative studies.

Methods

qRT-PCR, immunofluorescent staining and western blot were used to measure the expression of KLF5. Alkaline Phosphatase (ALP) staining, Alizarin red staining (ARS), and the expression of Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN) were used to evaluate the osteogenic differentiation. Luciferase activity assay and ChIP-PCR were performed to investigate the molecular mechanisms.

Results

KLF5 was significantly upregulated in OLF fibroblasts in contrast to normal ligamentum flavum (LF) fibroblasts. Silencing KLF5 diminished osteogenic markers and mineralized nodules, while its overexpression had the opposite effect, confirming KLF5’s role in promoting ossification. Moreover, KLF5 promotes the ossification of LF by activating the transcription of Connexin 43 (CX43), and overexpressing CX43 could reverse the suppressive impact of KLF5 knockdown on OLF fibroblasts’ osteogenesis.

Conclusion

KLF5 promotes the OLF by transcriptionally activating CX43. This finding contributes significantly to our understanding of OLF and may provide new therapeutic targets.
Exosomes derived from M2 macrophages prevent steroid-induced osteonecrosis of the femoral head by modulating inflammation, promoting bone formation and inhibiting bone resorption
Authors: Yuan Na , Zhang Weiying , Yang Weizhou , Ji Wenchen , Li Jia
Published: April 2024

Inflammatory reactions are involved in the development of steroid-induced osteonecrosis of the femoral head(ONFH). Studies have explored the therapeutic efficacy of inhibiting inflammatory reactions in steroid-induced ONFH and revealed that inhibiting inflammation may be a new strategy for preventing the development of steroid-induced ONFH. Exosomes derived from M2 macrophages(M2-Exos) display anti-inflammatory properties. This study aimed to examine the preventive effect of M2-Exos on early-stage steroid-induced ONFH and explore the underlying mechanisms involved. In vitro, we explored the effect of M2-Exos on the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells(BMMSCs). In vivo, we investigated the role of M2-Exos on inflammation, osteoclastogenesis, osteogenesis and angiogenesis in an early-stage rat model of steroid-induced ONFH. We found that M2-Exos promoted the proliferation and osteogenic differentiation of BMMSCs. Additionally, M2-Exos effectively attenuated the osteonecrotic changes, inhibited the expression of proinflammatory mediators, promoted osteogenesis and angiogenesis, reduced osteoclastogenesis, and regulated the polarization of M1/M2 macrophages in steroid-induced ONFH. Taken together, our data suggest that M2-Exos are effective at preventing steroid-induced ONFH. These findings may be helpful for providing a potential strategy to prevent the development of steroid-induced ONFH.
A middle lobe sparing sleeve resection versus bilobectomy for right lower central non-small cell lung cancer: a retrospective propensity score matched cohort study
Authors: Wang Jiongjie , Guo Jichao , Shi Haizhan , Chen Xiangru , He Wenxin , Li Zhixin
Published: April 2024

Objectives

The right lower sleeve lobectomy is a rarely performed major lung resection.This study aims to evaluate the safety and effectiveness of this procedure by comparing to right lower bilobectomy in non-small cell lung cancer patients.

Methods

We retrospectively reviewed a prospective database of non-small cell lung cancer patients who underwent right lower sleeve lobectomy (group S) or right lower bilobectomy (group B) from January 2014 to January 2020 in Shanghai Pulmonary Hospital. Propensity score matching method was applied to balance confounders between the two groups, resulting in 41 matched pairs.The analysis was performed to compare perioperative outcomes, long-term survival, and postoperative pulmonary volume between the two groups.

Results

No significant differences in the characteristics were observed between the two matched groups.Major postoperative complications developed in 31.7% of the patients in group B and 12.1% of the patients in group S (P = 0.032).Intervention rate for surgical residual cavity in group B is significantly higher than those patients in group S(21.9%vs7.3%,p = 0.037).The postoperative right lateral and overall lung volume in group S were both significantly larger than that in group B (P = 0.026,P = 0.001,respectively).

Conclusions

Compared to bi-lobectomy, a middle lobe sparing sleeve resection obtains a less prevalence of major complications, smaller postoperative residual air space and similar long-term survival for selected central right lower NSCLC patients.