bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome characterization and taxonomy of Actinomyces acetigenes sp. nov., and Actinomyces stomatis sp. nov., previously isolated from the human oral cavity
Authors: Tian Xuechen , Teo Wee Fei Aaron , Wee Wei Yee , Yang Yixin , Ahmed Halah , Jakubovics Nicholas S. , Choo Siew Woh , Tan Geok Yuan Annie
Published: December 2023

Background

Actinomyces strains are commonly found as part of the normal microflora on human tissue surfaces, including the oropharynx, gastrointestinal tract, and female genital tract. Understanding the diversity and characterization of Actinomyces species is crucial for human health, as they play an important role in dental plaque formation and biofilm-related infections. Two Actinomyces strains ATCC 49340 T and ATCC 51655 T have been utilized in various studies, but their accurate species classification and description remain unresolved.

Results

To investigate the genomic properties and taxonomic status of these strains, we employed both 16S rRNA Sanger sequencing and whole-genome sequencing using the Illumina HiSeq X Ten platform with PE151 (paired-end) sequencing. Our analyses revealed that the draft genome of Actinomyces acetigenes ATCC 49340 T was 3.27 Mbp with a 68.0% GC content, and Actinomyces stomatis ATCC 51655 T has a genome size of 3.08 Mbp with a 68.1% GC content. Multi-locus (atpA, rpoB, pgi, metG, gltA, gyrA, and core genome SNPs) sequence analysis supported the phylogenetic placement of strains ATCC 51655 T and ATCC 49340 T as independent lineages. Digital DNA-DNA hybridization (dDDH), average nucleotide identity (ANI), and average amino acid identity (AAI) analyses indicated that both strains represented novel Actinomyces species, with values below the threshold for species demarcation (70% dDDH, 95% ANI and AAI). Pangenome analysis identified 5,731 gene clusters with strains ATCC 49340 T and ATCC 51655 T possessing 1,515 and 1,518 unique gene clusters, respectively. Additionally, genomic islands (GIs) prediction uncovered 24 putative GIs in strain ATCC 49340 T and 16 in strain ATCC 51655 T, contributing to their genetic diversity and potential adaptive capabilities. Pathogenicity analysis highlighted the potential human pathogenicity risk associated with both strains, with several virulence-associated factors identified. CRISPR-Cas analysis exposed the presence of CRISPR and Cas genes in both strains, indicating these strains might evolve a robust defense mechanism against them.

Conclusion

This study supports the classification of strains ATCC 49340 T and ATCC 51655 T as novel species within the Actinomyces, in which the name Actinomyces acetigenes sp. nov. (type strain ATCC 49340 T = VPI D163E-3 T = CCUG 34286 T = CCUG 35339 T) and Actinomyces stomatis sp. nov. (type strain ATCC 51655 T = PK606T = CCUG 33930 T) are proposed.
Genome-wide identification, structural homology analysis, and evolutionary diversification of the phospholipase D gene family in the venom gland of three scorpion species
Authors: Baradaran Masoumeh , Salabi Fatemeh
Published: December 2023

Background

Venom phospholipase D (PLDs), dermonecrotic toxins like, are the major molecules in the crude venom of scorpions, which are mainly responsible for lethality and dermonecrotic lesions during scorpion envenoming. The purpose of this study was fivefold: First, to identify transcripts coding for venom PLDs by transcriptomic analysis of the venom glands from Androctonus crassicauda, Hottentotta saulcyi, and Hemiscorpius lepturus; second, to classify them by sequence similarity to known PLDs and motif extraction method; third, to characterize scorpion PLDs; fourth to structural homology analysis with known dermonecrotic toxins; and fifth to investigate phylogenetic relationships of the PLD proteins.

Results

We found that the venom gland of scorpions encodes two PLD isoforms: PLD1 ScoTox-beta and PLD2 ScoTox-alpha I. Two highly conserved regions shared by all PLD1s beta are GAN and HPCDC (HX2PCDC), and the most important conserved regions shared by all PLD2s alpha are two copies of the HKDG (HxKx4Dx6G) motif. We found that PLD1 beta is a 31–43 kDa acidic protein containing signal sequences, and PLD2 alpha is a 128 kDa basic protein without known signal sequences. The gene structures of PLD1 beta and PLD2 alpha contain 6 and 21 exons, respectively. Significant structural homology and similarities were found between the modeled PLD1 ScoTox-beta and the crystal structure of dermonecrotic toxins from Loxosceles intermedia.

Conclusions

This is the first report on identifying PLDs from A. crassicauda and H. saulcyi venom glands. Our work provides valuable insights into the diversity of scorpion PLD genes and could be helpful in future studies on recombinant antivenoms production.
Genome-wide identification of resistance genes and cellular analysis of key gene knockout strain under 5-hydroxymethylfurfural stress in Saccharomyces cerevisiae
Authors: Li Qian , Feng Peng , Tang Hao , Lu Fujia , Mou Borui , Zhao Lan , Li Nan , Yang Yaojun , Fu Chun , Long Wencong , Xiao Ximeng , Li Chaohao , Wu Wei , Wang Gang , Liu Beidong , Tang Tianle , Ma Menggen , Wang Hanyu
Published: December 2023

In bioethanol production, the main by-product, 5-hydroxymethylfurfural (HMF), significantly hinders microbial fermentation. Therefore, it is crucial to explore genes related to HMF tolerance in Saccharomyces cerevisiae for enhancing the tolerance of ethanol fermentation strains. A comprehensive analysis was conducted using genome-wide deletion library scanning and SGAtools, resulting in the identification of 294 genes associated with HMF tolerance in S. cerevisiae. Further KEGG and GO enrichment analysis revealed the involvement of genes OCA1 and SIW14 in the protein phosphorylation pathway, underscoring their role in HMF tolerance. Spot test validation and subcellular structure observation demonstrated that, following a 3-h treatment with 60 mM HMF, the SIW14 gene knockout strain exhibited a 12.68% increase in cells with abnormal endoplasmic reticulum (ER) and a 22.41% increase in the accumulation of reactive oxygen species compared to the BY4741 strain. These findings indicate that the SIW14 gene contributes to the protection of the ER structure within the cell and facilitates the clearance of reactive oxygen species, thereby confirming its significance as a key gene for HMF tolerance in S. cerevisiae.
Targeted elimination of Vancomycin resistance gene vanA by CRISPR-Cas9 system
Authors: Tao Shuan , Hu Chunwei , Fang Yewei , Zhang He , Xu Yao , Zheng Lin , Chen Luyan , Liang Wei
Published: December 2023

Objective

The purpose of this study is to reduce the spread of the vanA gene by curing the vanA-harboring plasmid of vancomycin-resistant using the CRISPR-Cas9 system.

Methods

Two specific spacer sequence (sgRNAs) specific was designed to target the vanA gene and cloned into plasmid CRISPR-Cas9. The role of the CRISPR-Cas system in the plasmid elimination of drug-resistance genes was verified by chemically transformation and conjugation delivery methods. Moreover, the elimination efficiency in strains was evaluated by plate counting, PCR, and quantitative real-time PCR (qPCR). Susceptibility testing was performed by broth microdilution assay and by Etest strips (bioMérieux, France) to detect changes in bacterial drug resistance phenotype after drug resistance plasmid clearance.

Results

In the study, we constructed a specific prokaryotic CRISPR-Cas9 system plasmid targeting cleavage of the vanA gene. PCR and qPCR results indicated that recombinant pCas9-sgRNA plasmid can efficiently clear vanA-harboring plasmids. There was no significant correlation between sgRNA lengths and curing efficiency. In addition, the drug susceptibility test results showed that the bacterial resistance to vancomycin was significantly reduced after the vanA-containing drug-resistant plasmid was specifically cleaved by the CRISPR-Cas system. The CRISPR-Cas9 system can block the horizontal transfer of the conjugated plasmid pUC19-vanA.

Conclusion

In conclusion, our study demonstrated that CRISPR-Cas9 achieved plasmid clearance and reduced antimicrobial resistance. The CRISPR-Cas9 system could block the horizontal transfer of plasmid carrying vanA. This strategy provided a great potential to counteract the ever-worsening spread of the vanA gene among bacterial pathogens and laid the foundation for subsequent research using the CRISPR-Cas9 system as adjuvant antibiotic therapy.
Transcriptional insights of citrus defense response against Diaporthe citri
Authors: Li Pudong , Xiao Xiaoe , Wang Jingrui , Niu Fan , Huang Jiangnan , Xie Bianyue , Ye Lu , Zhang Chaofan , Wang Dengliang , Wu Qun , Zheng Xueliang , Gai Yunpeng , Li Hongye , Jiao Chen
Published: December 2023

Citrus melanose, caused by Diaporthe citri, is one of the most important and widespread fungal diseases of citrus. Previous studies demonstrated that the citrus host was able to trigger the defense response to restrict the spread of D. citri. However, the molecular mechanism underlying this defense response has yet to be elucidated. Here, we used RNA-Seq to explore the gene expression pattern at the early (3 days post infection, dpi) and late (14 dpi) infection stages of citrus leaves in response to D. citri infection, and outlined the differences in transcriptional regulation associated with defense responses. The functional enrichment analysis indicated that the plant cell wall biogenesis was significantly induced at the early infection stage, while the callose deposition response was more active at the late infection stage. CYP83B1 genes of the cytochrome P450 family were extensively induced in the callus deposition-mediated defense response. Remarkably, the gene encoding pectin methylesterase showed the highest upregulation and was only found to be differentially expressed at the late infection stage. Genes involved in the synthesis and regulation of phytoalexin coumarin were effectively activated. F6’H1 and S8H, encoding key enzymes in the biosynthesis of coumarins and their derivatives, were more strongly expressed at the late infection stage than at the early infection stage. Collectively, our study profiled the response pattern of citrus leaves against D. citri infection and provided the transcriptional evidence to support the defense mechanism.
The relationship between sleep status and activity of daily living: based on China Hainan centenarians cohort study
Authors: Yang Shanshan , Wang Shengshu , Liu Guangdong , Li Rongrong , Li Xuehang , Chen Shimin , Zhao Yali , Liu Miao , Liu Yunxi , He Yao
Published: December 2023

Objective

This study, based on the China Hainan Centenarians Cohort Study (CHCCS), aims to comprehensively describe the characteristic of daytime, night and total sleep duration, sleep quality and different sleep mode of Hainan centenarians and their associations with activity of daily living (ADL) functions.

Method

The baseline data of CHCCS was used. ADL function was evaluated the Bathel index, sleep quality was evaluated by Pittsburgh sleep quality index (PSQI), sleep status including daytime, night and total sleep duration as well as sleep quality and sleep mode. Multivariate logistic regression model was used to explore the association between sleep status and ADL disability and ADL moderate & severe disability.

Results

A total of 994 centenarians were included in this study with the age range 100–116 years old. Compared with the centenarians who sleep 6–9 h at night and < 2 h in the daytime, the adjusted OR between sleep > 9 h at night and sleep ≥ 2 h in the daytime and ADL disability was 2.93 (95% CI: 1.02–8.44), and adjusted OR of ADL moderate & severe disability was 2.75 (95% CI: 1.56–4.83). Compared with centenarians who sleep for 7–9 h and have good sleep quality, centenarians who sleep for > 9 h and have poor sleep quality have an increased risk of ADL moderate & severe disability (OR = 3.72, 95% CI: 1.54–9.00).

Conclusion

Relation between sleep duration and ADL disability was more significant compared with sleep quality in Hainan centenarians. Poor sleep quality can aggravate the relationship between sleep duration and ADL moderate & severe disability.
De novo normotensive scleroderma renal crisis six years after living-donor renal transplantation in a patient with overlapping systemic sclerosis/systemic lupus erythematosus syndrome: a case report
Authors: Sanada Hajime , Hara Satoshi , Horita Makoto , Kawahara Hiroyuki , Yoshida Misaki , Takahashi Yoshinori , Tsuge Shunsuke , Zoshima Takeshi , Nishioka Ryo , Ito Kiyoaki , Mizushima Ichiro , Matsushita Takashi , Kawano Mitsuhiro
Published: December 2023

Background

Scleroderma renal crisis (SRC) is a critical kidney involvement of systemic sclerosis (SSc), often resulting in end-stage renal disease. Although the recurrence of SRC in the allograft has been reported, the development of de novo SRC after kidney transplantation has not been reported. Furthermore, normotensive SRC, which rarely occurs, makes prompt diagnosis more challenging. This fact should be recognized widely among nephrologists.

Case presentation

We report a 37-year-old Japanese man with overlapping SSc/systemic lupus erythematous syndrome who developed normotensive SRC in the transplanted kidney shortly after glucocorticoid escalation. Six years prior to admission, he underwent an ABO-compatible living donor kidney transplantation because of lupus nephritis. He was admitted to our hospital for gradually worsening kidney dysfunction. A kidney biopsy showed idiopathic granulomatous interstitial nephritis and high-dose prednisolone was prescribed. Although renal function improved tentatively, it deteriorated again a week later. A secondary kidney biopsy revealed acute thrombotic microangiopathy, leading to the diagnosis of normotensive SRC because all other causes were excluded, and blood pressure was within normal range. Adding an angiotensin-converting enzyme inhibitor and tapering glucocorticoid slowed the speed of deterioration of his kidney function, but he finally required hemodialysis induction.

Conclusions

SRC can newly develop even in the transplanted kidney, especially when high-dose glucocorticoid is administered. Normotensive SRC makes the diagnosis challenging, so nephrologists should carefully monitor patients with SSc and transplanted kidneys to treat SRC promptly.
Prevalence and determinants of adequate postnatal care in Ethiopia: evidence from 2019 Ethiopia mini demographic and health survey
Authors: Ashemo Mubarek Yesse , Shiferaw Desalegn , Biru Bayise , Feyisa Bikila Regassa
Published: December 2023

Background

The postpartum period is critical for both the mother's and newborn child's health and survival. Rising morbidity and mortality are usually the consequence of absence of adequate, suitable, or timely care during that time period. There is lack of information on the adequacy of postnatal care in Ethiopia and this study was aimed to investigate adequacy of postnatal care and its determinants in the study area.

Methods

In this study, we used a cross-sectional dataset from the 2019 Ethiopia Mini Demographic and Health Survey. A multistage stratified clustered design applied and survey weights were used to take into account the complicated sample design. A multilevel mixed effects logistic regression was fitted on 3772 women who were nested within 305 clusters. The fixed effect models were fitted and expressed as adjusted odds ratios with 95% confidence intervals, while intra-class correlation coefficients, median odds ratio, and proportional change in variance explained measures of variation. As model fitness criteria, the deviance information criterion and the Akaike information criterion were used.

Results

This study found that only 563(16.14%, 95% CI: 16.05–16.24) women had adequate post natal care. Age of between 25–35 years old (AOR = 1.55, 95%CI = 1.04–2.31), secondary level of education (AOR = 2.23, 95%CI = 1.43–3.45), Having parity of between two and four had (AOR = 0.62, 95%CI = 0.42 0.93), having ANC follow up four and above (AOR = 1.74, 95%CI = 1.31–2.33), being residents of Oromia region (AOR = 0.10, 95CI = 0.02- 0.43) were strong predictors of adequate postnatal care.

Conclusion

The study found that prevalence of adequate PNC in Ethiopia was significantly low. To increase postnatal care adequacy, it was recommended to reinforce existing policies and strategies such as increasing number of antenatal care follow up, and scheduling mothers based on the national postnatal care follow-up protocol.
A practical prognostic peripheral blood-based risk model for the evaluation of the likelihood of a response and survival of metastatic cancer patients treated with immune checkpoint inhibitors
Authors: Tiainen Satu , Nurmela Veera , Selander Tuomas , Turunen Patrik , Pasonen-Seppänen Sanna , Kettunen Tiia , Kuittinen Outi , Auvinen Päivi , Rönkä Aino
Published: December 2023

Background

Less than half of unselected metastatic cancer patients benefit from the immune checkpoint inhibitor (ICI) therapy. Systemic cancer-related inflammation may influence the efficacy of ICIs and thus, systemic inflammatory markers could have prognostic and/or predictive potential in ICI therapy. Here, we aimed to identify a combination of inflammation-related laboratory parameters to establish a practical prognostic risk model for the pretreatment evaluation of a response and survival of ICI-treated patients with different types of metastatic cancers.

Methods

The study-cohort consisted of a real-world patient population receiving ICIs for metastatic cancers of different origins (n = 158). Laboratory parameters determined before the initiation of the ICI treatment were retrospectively collected. Six inflammation-related parameters i.e., elevated values of neutrophils, platelets, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and lactate dehydrogenase (LDH), and the presence of anemia, were each scored with one point, giving 0–6 risk points for each patient. The patients with information of all these six parameters (n = 109) were then stratified into low-risk (0–3 points) and high-risk (4–6 points) groups. The overall response rate (ORR), overall survival (OS), and progression-free survival (PFS) according to the risk scores were determined.

Results

The risk model was strongly associated with the outcome of the patients. The ORR to ICI treatment in the high-risk group was 30.3% in comparison to 53.9% in the low-risk group (p = 0.023). The medians for OS were 10.0 months and 27.3 months, respectively (p < 0.001), and the corresponding medians for PFS were 3.9 months and 6.3 months (p = 0.002). The risk group remained as a significant prognostic factor for both OS (HR 3.04, 95% CI 1.64–5.64, p < 0.001) and PFS (HR 1.79, 95% CI 1.04–3.06, p = 0.035) in the Cox multivariate analyses.

Conclusions

We propose a readily feasible, practical risk model consisted of six inflammation-related laboratory parameters as a tool for outcome prediction in metastatic cancer patients treated with ICIs. The risk model was strongly associated with the outcome of the patients in terms of all the evaluated indicators i.e., ORR, OS and PFS. Yet, further studies are needed to validate the risk model.
Composition and diversity analysis of the TCR CDR3 repertoire in patients with idiopathic orbital inflammation using high-throughput sequencing
Authors: Fang Yenan , Shen Bingyan , Dai Qin , Xie Qiqi , Li Xinyu , Wu Wencan , Wang Min
Published: December 2023

Background

Idiopathic orbital inflammation (IOI) is a nonspecific orbital inflammatory disease with the third highest prevalence among orbital diseases, and its pathogenesis is associated with T-cell-mediated immune responses. This study aimed to investigate the differences in T-cell receptor (TCR) expression between IOI patients and healthy subjects by high-throughput sequencing and to characterize TCR expression in patients with IOI and with respect to glucocorticoid response.

Methods

A total of 19 subjects were enrolled in this study and were divided into the idiopathic orbital inflammation group (IOI group, n = 13) and the healthy control group (HC group, n = 6), and within the IOI group were further divided into the glucocorticoid therapy sensitive group (IOI(EF) group, n = 6) and the glucocorticoid therapy ineffective group (IOI(IN) group, n = 7) based on the degree of effectiveness to glucocorticoid therapy. High-throughput TCR sequencing was performed on peripheral blood mononuclear cells of IOI patients and healthy control individuals using 5’ RACE technology combined with Unique Identifier (UID) digital tag correction technology. The TCR CDR3 region diversity, sharing patterns, and differential sequences between the IOI and HC groups, and between the IOI(EF) and IOI(IN) groups were analyzed.

Results

It was found that the diversity of TCR CDR3 in the IOI group was significantly lower than that in the HC group, and the frequency of V gene use was significantly different between groups. The diversity of TCR CDR3 in patients in the IOI(EF) group was significantly lower than that in patients in the IOI(IN) group, and the frequency of V and J gene use was significantly different between the IOI(EF) group and the IOI(IN) group. Additionally, we found 133 nucleotide sequences shared in all IOI samples and screened two sequences with higher expression from them.

Conclusions

Our results suggested that abnormal clonal expansion of specific T-cells exists in IOI patients and that TCR diversity may had an impact on the prognosis of glucocorticoid-treated IOI. This study may contribute to a better understanding of the immune status of IOI and provide new insights for T-cell -associated IOI pathogenesis, diagnosis and treatment prediction.
Association between the MCP-1 -2518 A > G (rs1024611) polymorphism and susceptibility to type 2 diabetes mellitus and diabetic nephropathy: a meta-analysis
Authors: Chang Wei-wei , Zhang Liu , Wen Li-ying , Tao Yu-jing , Xiong Jia-jie , Tong Xin , Jin Yue-long , Su Hong
Published: December 2023

Background

Studies evaluating the association between monocyte chemoattractant protein-1 (MCP-1) -2518 A > G (rs1024611) polymorphism and type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) are contradictory. The present study aims to provide a comprehensive assessment and more reliable estimation of the relationship between the MCP-1 rs1024611 polymorphism and T2DM and DN risk.

Methods

Eligible articles were retrieved from the PubMed, Web of Science, EMBASE, Cochrane, and China National Knowledge Infrastructure databases. The effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained to calculate the summary effect size. Heterogeneity was analyzed by subgroup analysis and meta-regression. Publication bias was tested using funnel plots and Egger’s test.

Results

In total, sixteen studies were included. Thirteen studies involving 2,363 patients with T2DM and 4,650 healthy controls found no significant association between the MCP-1 rs1024611 polymorphism and T2DM in the overall population. Ethnicity stratification found an association between the GG + GA genotype and decreased T2DM risk in Caucasians (OR = 0.79, 95% CI: 0.66–0.93,P = 0.006;PQ= 0.372). No significant risks were found in the Asian population for any genetic models. Seven studies found an association between the GG + GA genotype and DN risk in the Asian population (OR = 1.37, 95% CI: 1.11–1.71,P = 0.004,PQ= 0.222). No significant risks were found in the Caucasian population with any genetic models. There were no statistically significant differences in genotype distribution between patients with T2DM and DN in Asians or Caucasians. Meta-regression revealed that genotyping method was a major driver of heterogeneity in five genetic models (GG + GA vs. AA:P = 0.032; GG vs. GA + AA:P = 0.028; GG vs. AA:P = 0.035; GG vs. GA:P = 0.041; G vs. A:P = 0.041).

Conclusion

The MCP-1 rs1024611 polymorphism is associated with susceptibility to T2DM in Caucasians and DN in Asians. Larger, well-designed cohort studies are needed in the future to verify this association.
Guidance provided by pharmacists to customers regarding to destination of unused household medications: disposal of household medications
Authors: Michelin Aparecida de Fatima , Bonifácio Neuza Alves , Nagata Walter Bertequini , da Silva Valéria Maria Savoya , Gobbo Laura Emilia Michelin , Bresciani Katia Denise Saraiva
Published: December 2023

Background

Discarding pharmaceuticals in the garbage or into the sewage system are still the most common methods in many countries. This study aims to investigate the guidance provided by pharmacists to customers on the disposal of unused and expired household medications in São Paulo State, Brazil.

Method

The study population consisted of 630 pharmacists from the State of São Paulo, who work in community pharmacies. They answered an online questionnaire with questions composed in three blocks: demographic, work, and academic information on the pharmacist; guidance about the disposal of household medications; and knowledge regarding the reverse logistics of these medications. An invitation to participate in the questionnaire was made via WhatsApp, individually and collectively. Inferential statistics were performed using the chi-square test and were considered significant when p < 0.05%.

Results

Among the participating pharmacists, the majority were women under 60 years old,56 (8.89%) stated that they never orient the customer regarding the disposal of unused and expired household medications, while 574 (91,12%) indicated that they almost provide guidance. The frequency with which they provided guidance was influenced by the number of years since graduation (p = 0.0047), the time they had worked in pharmacies and drugstores (p = 0.0007), and whether or not they had a graduate degree (p = 0.0181). Regarding the disposal of medications, among the 643 responses provided by the pharmacists,516 (80.25%) indicated that they oriented customers to return them to a pharmacy.

Conclusion

A small number of pharmacists always orient customers on the proper disposal that should be followed for unused and expired household medications, prioritizing their return to a pharmacy. In general, these pharmacists have longer periods of work experience and higher academic qualifications. Thus, it is important to increase knowledge through professional training and further education programs.
Classification of lung pathologies in neonates using dual-tree complex wavelet transform
Authors: Aujla Sagarjit , Mohamed Adel , Tan Ryan , Magtibay Karl , Tan Randy , Gao Lei , Khan Naimul , Umapathy Karthikeyan
Published: December 2023

Introduction

Undiagnosed and untreated lung pathologies are among the leading causes of neonatal deaths in developing countries. Lung Ultrasound (LUS) has been widely accepted as a diagnostic tool for neonatal lung pathologies due to its affordability, portability, and safety. However, healthcare institutions in developing countries lack well-trained clinicians to interpret LUS images, which limits the use of LUS, especially in remote areas. An automated point-of-care tool that could screen and capture LUS morphologies associated with neonatal lung pathologies could aid in rapid and accurate diagnosis.

Methods

We propose a framework for classifying the six most common neonatal lung pathologies using spatially localized line and texture patterns extracted via 2D dual-tree complex wavelet transform (DTCWT). We acquired 1550 LUS images from 42 neonates with varying numbers of lung pathologies. Furthermore, we balanced our data set to avoid bias towards a pathology class.

Results

Using DTCWT and clinical features as inputs to a linear discriminant analysis (LDA), our approach achieved a per-image cross-validated classification accuracy of 74.39% for the imbalanced data set. Our classification accuracy improved to 92.78% after balancing our data set. Moreover, our proposed framework achieved a maximum per-subject cross-validated classification accuracy of 64.97% with an imbalanced data set while using a balanced data set improves its classification accuracy up to 81.53%.

Conclusion

Our work could aid in automating the diagnosis of lung pathologies among neonates using LUS. Rapid and accurate diagnosis of lung pathologies could help to decrease neonatal deaths in healthcare institutions that lack well-trained clinicians, especially in developing countries.
Mildly elevated serum bilirubin and its correlations with lipid levels among male patients undergoing health checkups
Authors: Bai Xin , Qiao Jing , Zhang Hong
Published: December 2023

Background

Bilirubin’s ability to lower lipid levels was confirmed by several studies, but those studies mainly focused on total bilirubin (TBil). The present study aimed to elucidate the correlations of the two subtypes of bilirubin with lipid levels.

Methods

A total of 1732 male patients undergoing health checkups were categorized into three groups according to the levels of direct bilirubin (DBil) and indirect bilirubin (IBil). The differences in medical characteristics among the three groups were analysed.

Results

Subjects in the elevated DBil group had the lowest serum alanine aminotransferase (ALT), total cholesterol (TC), blood urea nitrogen (BUN), γ-glutamyl transpeptidase (γ-GT), fasting blood glucose (FBG), haemoglobin (HGB), and triglyceride (TG) levels in contrast to the other groups (P < 0.01), while subjects in the elevated IBil group had the highest ALT, γ-GT, BUN, serum creatinine (SCR), HGB, TC, and TG levels among the three groups (P < 0.01). DBil levels exhibited a significant negative correlation with TC (r = -0.777, P < 0.01) and TG (r = -0.397, P < 0.01) levels, while IBil levels exhibited a significant positive correlation with TC (r = 0.790, P < 0.01) and TG (r = 0.302, P < 0.01) levels. The frequencies of abnormal TC, TG, HGB and BUN levels were the lowest in the elevated DBil group, while the levels of these four variables were the highest in the elevated IBil group. Mildly elevated DBil levels were related to lower TG (OR = 0.112, 95% CI = 0.027–0.458) and TC (OR = 0.097, 95% CI = 0.013–0.700), and mildly elevated IBil levels were connected with increased TC (OR = 3.436, 95% CI = 2.398–4.924) and TG (OR = 1.636, 95% CI = 1.163–2.303). DBil was an independent protective factor against increased TC (OR = 0.702, 95% CI = 0.602–0.817, P < 0.01) and TG (OR = 0.632, 95% CI = 0.541–0.739, P < 0.01) levels, and IBil was an independent risk factors for increased TC (OR = 1.251, 95% CI = 1.176–1.331, P < 0.01).

Conclusions

DBil was an independent protective factor against high TC and TG levels. IBil was an independent risk factors for elevated TC levels. The prognostic value of IBil levels warrants further attention.
The effect of restrictive versus liberal selection criteria on survival in ECPR: a retrospective analysis of a multi-regional dataset
Authors: Diehl Arne , Read Andrew C. , Southwood Timothy , Buscher Hergen , Dennis Mark , Nanjayya Vinodh Bhagyalakshmi , Burrell Aidan J. C.
Published: December 2023

Background

Extracorporeal cardiopulmonary resuscitation (ECPR) is an established rescue therapy for both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). However, there remains significant heterogeneity in populations and outcomes across different studies. The primary aim of this study was to compare commonly used selection criteria and their effect on survival and utilisation in an Australian ECPR cohort.

Methods

We performed a retrospective, observational study of three established ECPR centres in Australia, including cases from 1 January 2013 to 31 December 2020 to establish the baseline cohort. We applied five commonly used ECPR selection criteria, ranging from restrictive to liberal.

Results

The baseline cohort included 199 ECPR cases: 95 OHCA and 104 IHCA patients. Survival to hospital discharge was 20% for OHCA and 41.4% for IHCA. For OHCA patients, strictly applying the most restrictive criteria would have resulted in the highest survival rate 7/16 (43.8%) compared to the most liberal criteria 16/73 (21.9%). However, only 16/95 (16.8%) in our cohort strictly met the most restrictive criteria versus 73/95 (76.8%) with the most liberal criteria. Similarly, in IHCA, the most restrictive criteria would have resulted in a higher survival rate in eligible patients 10/15 (66.7%) compared to 27/59 (45.8%) with the most liberal criteria. With all criteria a large portion of survivors in IHCA would not have been eligible for ECMO if strictly applying criteria, 33/43 (77%) with restrictive and 16/43 (37%) with the most liberal criteria.

Conclusions

Adherence to different selection criteria impacts both the ECPR survival rate and the total number of survivors. Commonly used selection criteria may be unsuitable to select IHCA ECPR patients.
The MeSH heading “Call Center” is due for an update: why we recommend the more precise heading “Emergency Medical Communication Center”
Authors: Harring Astrid K. V. , Blinkenberg Jesper , Brattebø Guttorm , Hjortdahl Magnus , Idland Siri , Iversen Emil , Leonardsen Ann-Chatrin. L. , Zakariassen Erik , Jørgensen Trine M.
Published: December 2023

Call centers can be found in various industries. However as a Medical Subject Heading (MeSH) the term “Call centers” does not reflect the critical purpose of handling emergency calls. We recommend “emergency medical communication center(s)”, as this provides clarity and precision regarding the primary function and purpose of the center.
Hypoglycemia in patients with type 2 diabetes mellitus during hospitalization: associated factors and prognostic value
Authors: González-Vidal Tomás , Rivas-Otero Diego , Gutiérrez-Hurtado Alba , Alonso Felgueroso Carlos , Martínez Tamés Gema , Lambert Carmen , Delgado-Álvarez Elías , Menéndez Torre Edelmiro
Published: December 2023

Background

The risk factors for hypoglycemia during hospital admission and its consequences in patients with diabetes are not entirely known. The present study aimed to investigate the risk factors for hypoglycemia, as well as the potential implications of hypoglycemia in patients with type 2 diabetes mellitus admitted to the hospital.

Methods

This retrospective cohort study included 324 patients (214 [66.0%] men; median age 70 years, range 34–95 years) with type 2 diabetes admitted to a university hospital who were consulted the Endocrinology Department for glycemic control during a 12-month period. We investigated the potential role of demographic factors, metabolic factors, therapy, and comorbidities on the development of in-hospital hypoglycemia. We explored the prognostic value of hypoglycemia on mortality (both in-hospital and in the long-term), hospital readmission in the following year, and metabolic control (HbA1c value) after discharge (median follow-up, 886 days; range 19–1255 days).

Results

Hypoglycemia occurred in 154 (47.5%) patients during their hospitalization and was associated with advanced age, previous insulin therapy, higher Charlson Comorbidity Index, lower body mass index and lower baseline HbA1c values. Hypoglycemia was associated with greater in-hospital and long-term mortality, longer hospital stays, higher readmission rates, and poorer metabolic control after discharge. These negative consequences of hypoglycemia were more frequent in patients with severe (≤ 55 mg/dL) hypoglycemia and in patients who had hypoglycemia during a greater percentage of hospitalization days.

Conclusions

Hypoglycemia during hospital admission is a marker of a poor prognosis in patients with type 2 diabetes.
Effects of combined aerobic exercise and diet on cardiometabolic health in patients with obesity and type 2 diabetes: a systematic review and meta-analysis
Authors: Al-Mhanna Sameer Badri , Rocha-Rodriguesc Sílvia , Mohamed Mahaneem , Batrakoulis Alexios , Aldhahi Monira I. , Afolabi Hafeez Abiola , Yagin Fatma Hilal , Alhussain Maha H. , Gülü Mehmet , Abubakar Bishir Daku , Ghazali Wan Syaheedah Wan , Alghannam Abdullah F. , Badicu Georgian
Published: December 2023

Background

Lifestyle modifications involving diet and exercise are recommended for patients diagnosed with obesity and type 2 diabetes mellitus (T2DM). The purpose of this review was to systematically evaluate the effects of combined aerobic exercise and diet (AEDT) on various cardiometabolic health-related indicators among individuals with obesity and T2DM.

Methodology

A comprehensive search of the PubMed/Medline, Web of Science, Scopus, Science Direct, Cochrane, and Google Scholar databases was conducted for this meta-analysis. The Cochrane risk of bias tool was used to evaluate eligible studies, and the GRADE tool was used to rate the certainty of evidence. A random-effects model for continuous variables was used, and the results were presented as mean differences or standardised mean differences with 95% confidence intervals.

Results

A total of 16,129 studies were retrieved; 20 studies were included, and data were extracted from 1,192 participants. The findings revealed significant improvements in body mass index, body weight, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, fasting blood glucose, fasting plasma insulin, glycated hemoglobin, leptin, interleukin-6, C-reactive protein, and adiponectin (p < 0.05) compared to the standard treatment (ST) group. No significant differences were observed between the AEDT and ST groups in fat mass, hip circumference, waist-to-hip ratio, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and tumor necrosis factor-alpha. The present findings are based on low- to moderate-quality evidence.

Conclusions

AEDT may be a critical behavior for holistic cardiometabolic health-related benefits as a contemporary anti-obesity medication due to its significant positive impact on patients with obesity and T2DM. Nevertheless, further robust evidence is necessary to determine whether AEDT is an effective intervention for lowering cardiovascular and metabolic risk factors among individuals with obesity and T2DM.
Replenishing NAD+ content reduces aspects of striated muscle disease in a dog model of Duchenne muscular dystrophy
Authors: Cardoso Déborah , Barthélémy Inès , Blot Stéphane , Muchir Antoine
Published: December 2023

Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in DMD gene and loss of the protein dystrophin, which ultimately leads to myofiber membrane fragility and necrosis, with eventual muscle atrophy and contractures. Affected boys typically die in their second or third decade due to either respiratory failure or cardiomyopathy. Among the developed therapeutic strategies for DMD, gene therapy approaches partially restore micro-dystrophin or quasi-dystrophin expression. However, despite extensive attempts to develop definitive therapies for DMD, the standard of care remains corticosteroid, which has only palliative benefits. Animal models have played a key role in studies of DMD pathogenesis and treatment development. The golden retriever muscular dystrophy (GRMD) dog displays a phenotype aligning with the progressive course of DMD. Therefore, canine studies may translate better to humans. Recent studies suggested that nicotinamide adenine dinucleotide (NAD+) cellular content could be a critical determinant for striated muscle function. We showed here that NAD+ content was decreased in the striated muscles of GRMD, leading to an alteration of one of NAD+ co-substrate enzymes, PARP-1. Moreover, we showed that boosting NAD+ content using nicotinamide (NAM), a natural NAD+ precursor, modestly reduces aspects of striated muscle disease. Collectively, our results provide mechanistic insights into DMD.
Design thinking teams and team innovation performance
Authors: Heldal Frode
Published: December 2023

Design thinking (DT) is hailed as a cornerstone of innovation. It is based on teamwork, yet we know little about how the DT team operates and collaborates. In this study, we investigate 51 Norwegian master’s student teams as they work on an innovation project using DT. We seek especially to understand how they communicate and collaborate while working with DT tools, with special attention to divergent and convergent thinking. Using a mixed methods approach, we analyze the teams´ behaviors and developments in these. Findings suggest that the highest performing groups use the DT method with greater discipline than the other groups. To achieve this, they employ more authority-based behaviors and fewer supportive behaviors than the other groups. This disciplined approach to DT as a process and the use of tools, such as brainstorming, are in turn associated with convergent and divergent thinking. The main conclusions are that a disciplined approach using DT as a team tool, enables team reflexivity and psychological safety. This enhances innovative performance.
Inhibiting tau-induced elevated nSMase2 activity and ceramides is therapeutic in an Alzheimer’s disease mouse model
Authors: Tallon Carolyn , Bell Benjamin J. , Malvankar Medhinee M. , Deme Pragney , Nogueras-Ortiz Carlos , Eren Erden , Thomas Ajit G. , Hollinger Kristen R. , Pal Arindom , Mustapic Maja , Huang Meixiang , Coleman Kaleem , Joe Tawnjerae R. , Rais Rana , Haughey Norman J. , Kapogiannis Dimitrios , Slusher Barbara S.
Published: December 2023

Background

Cognitive decline in Alzheimer’s disease (AD) is associated with hyperphosphorylated tau (pTau) propagation between neurons along synaptically connected networks, in part via extracellular vesicles (EVs). EV biogenesis is triggered by ceramide enrichment at the plasma membrane from neutral sphingomyelinase2 (nSMase2)-mediated cleavage of sphingomyelin. We report, for the first time, that human tau expression elevates brain ceramides and nSMase2 activity.

Methods

To determine the therapeutic benefit of inhibiting this elevation, we evaluated PDDC, the first potent, selective, orally bioavailable, and brain-penetrable nSMase2 inhibitor in the transgenic PS19 AD mouse model. Additionally, we directly evaluated the effect of PDDC on tau propagation in a mouse model where an adeno-associated virus (AAV) encoding P301L/S320F double mutant human tau was stereotaxically-injected unilaterally into the hippocampus. The contralateral transfer of the double mutant human tau to the dentate gyrus was monitored. We examined ceramide levels, histopathological changes, and pTau content within EVs isolated from the mouse plasma.

Results

Similar to human AD, the PS19 mice exhibited increased brain ceramide levels and nSMase2 activity; both were completely normalized by PDDC treatment. The PS19 mice also exhibited elevated tau immunostaining, thinning of hippocampal neuronal cell layers, increased mossy fiber synaptophysin immunostaining, and glial activation, all of which were pathologic features of human AD. PDDC treatment reduced these changes. The plasma of PDDC-treated PS19 mice had reduced levels of neuronal- and microglial-derived EVs, the former carrying lower pTau levels, compared to untreated mice. In the tau propagation model, PDDC normalized the tau-induced increase in brain ceramides and significantly reduced the amount of tau propagation to the contralateral side.

Conclusions

PDDC is a first-in-class therapeutic candidate that normalizes elevated brain ceramides and nSMase2 activity, leading to the slowing of tau spread in AD mice.
Intensive care unit mortality and cost-effectiveness associated with intensivist staffing: a Japanese nationwide observational study
Authors: Ikumi Saori , Shiga Takuya , Ueda Takuya , Takaya Eichi , Iwasaki Yudai , Kaiho Yu , Tarasawa Kunio , Fushimi Kiyohide , Ito Yukiko , Fujimori Kenji , Yamauchi Masanori
Published: December 2023

Background

Japan has four types of intensive care units (ICUs) that are divided into two categories according to the management fee charged per day: ICU management fees 1 and 2 (ICU1/2) (equivalent to high-intensity staffing) and 3 and 4 (ICU3/4) (equivalent to low-intensity staffing). Although ICU1/2 charges a higher rate than ICU3/4, no cost-effectiveness analysis has been performed for ICU1/2. This study evaluated the clinical outcomes and cost-effectiveness of ICU1/2 compared with those of ICU3/4.

Methods

This retrospective observational study used a nationwide Japanese administrative database to identify patients admitted to ICUs between April 2020 and March 2021 and divided them into the ICU1/2 and ICU3/4 groups. The ICU mortality rates and in-hospital mortality rates were determined, and the incremental cost-effectiveness ratio (ICER) (Japanese Yen (JPY)/QALY), defined as the difference between quality-adjusted life year (QALY) and medical costs, was compared between ICU1/2 and ICU3/4. Data analysis was performed using the Chi-squared test; an ICER of < 5 million JPY/QALY was considered cost-effective.

Results

The ICU1/2 group (n = 71,412; 60.7%) had lower ICU mortality rates (ICU 1/2: 2.6% vs. ICU 3/4: 4.3%, p < 0.001) and lower in-hospital mortality rates (ICU 1/2: 6.1% vs. ICU 3/4: 8.9%, p < 0.001) than the ICU3/4 group (n = 46,330; 39.3%). The average cost per patient of ICU1/2 and ICU3/4 was 2,249,270 ± 1,955,953 JPY and 1,682,546 ± 1,588,928 JPY, respectively, with a difference of 566,724. The ICER was 718,659 JPY/QALY, which was below the cost-effectiveness threshold.

Conclusions

ICU1/2 is associated with lower ICU patient mortality than ICU3/4. Treatments under ICU1/2 are more cost-effective than those under ICU3/4, with an ICER of < 5 million JPY/QALY.
Case-mix adjustments for patient reported experience and outcome measures in primary care: an empirical approach to identify patient characteristics as case-mix adjusters based on a secondary analysis of an international survey among patients and their general practitioners in 34 countries
Authors: Groenewegen Peter P. , Spreeuwenberg Peter , Leyland Alastair H. , de Boer Dolf , Boerma Wienke
Published: December 2023

Background

Case-mix adjustment of patient reported experiences (PREMs) and outcomes (PROMs) of care are meant to enable fair comparison between units (e.g. care providers or countries) and to show where improvement is possible. It is important to distinguish between fair comparison and improvement potential, as case-mix adjustment may mask improvement potential. Case-mix adjustment takes into account the effect of patient characteristics that are related to the PREMs and PROMs studied, but are outside the sphere of influence of the units being compared. We developed an approach to assess which patient characteristics would qualify as case-mix adjusters, using data from an international primary care study.

Results

We used multilevel analysis, with patients nested in general practices nested in countries. Case-mix adjustment is indicated under the following conditions: there is a main effect of the potential case-mix adjuster on the PREM/PROM; this effect does not vary between units; and the distribution of the potential case-mix adjuster differs between units. Random slope models were used to assess whether the impact of a potential case-mix adjuster varied between units. To assess whether a slope variance is big enough to decide that case-mix adjustment is not indicated, we compared the variances in the categories of a potential case-mix adjuster. Significance of the slope variance is not enough, because small variances may be significantly different from zero when numbers are large. We therefore need an additional criterion to consider a slope variance as important. Borrowing from the idea of a minimum clinically important difference (MCID) we proposed a difference between the variances of 0.25*variance (equivalent to a medium effect size). We applied this approach to data from the QUALICOPC (Quality and costs of primary care in Europe) study.

Conclusions

Our approach provides guidance to decide whether or not patient characteristics should be considered as case-mix adjusters. The criterion of a difference between variances of 0.25*variance works well for continuous PREMs and PROMs, but seems to be too strict for binary PREMs and PROMs. Without additional information, it is not possible to decide whether important slope variation is the result of either differences in performance between general practices or countries, or cultural differences.