bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Mn coordination compounds be good candidates for medical applications?
Authors: Kozieł Sandra , Wojtala Daria , Szmitka Magdalena , Sawka Jacek , Komarnicka Urszula K.
Published: January 2024

Metal centres provide unique foci for varied biological modes of action that often but not exclusively involve redox or metal-ligand reactions. Metal complexes offer alternative and flexible coordination geometries, electron and proton transfer sites, inner and outer sphere reactivities, sites for redox-active, hemi-labile, and non-innocent ligands, and a variety of potentially controllable properties for exploitation in a therapeutic or biological context. The discovery of the first anticancer, the metal-based compound cisplatin in 1965 by Barnett Rosenberg was a historical outstanding breakthrough and led to a new area of metal-drug discovery. Some metal-based compounds have FDA approval for clinical use, while some undergo clinical trials for various medical therapies. This mini-review focuses on recent progress on Mn-based complexes with potential anticancer, antibacterial, and antifungal activities.
The host mannose-6-phosphate pathway and viral infection
Authors: Liu Qincheng , Wang Weiqi , Xu Liwei , Zhang Qisheng , Wang Hongna
Published: January 2024

Viruses, despite their simple structural composition, engage in intricate and complex interactions with their hosts due to their parasitic nature. A notable demonstration of viral behavior lies in their exploitation of lysosomes, specialized organelles responsible for the breakdown of biomolecules and clearance of foreign substances, to bolster their own replication. The man-nose-6-phosphate (M6P) pathway, crucial for facilitating the proper transport of hydrolases into lysosomes and promoting lysosome maturation, is frequently exploited for viral manipulation in support of replication. Recently, the discovery of lysosomal enzyme trafficking factor (LYSET) as a pivotal regulator within the lysosomal M6P pathway has introduced a fresh perspective on the intricate interplay between viral entry and host factors. This groundbreaking revelation illuminates unexplored dimensions of these interactions. In this review, we endeavor to provide a thorough overview of the M6P pathway and its intricate interplay with viral factors during infection. By consolidating the current understanding in this field, our objective is to establish a valuable reference for the development of antiviral drugs that selectively target the M6P pathway.
Climate smart agriculture? Adaptation strategies of traditional agriculture to climate change in sub-Saharan Africa
Authors: Okoronkwo David John , Ozioko Remigius Ikechukwu , Ugwoke Rachael Ujunwa , Nwagbo Uzoh Victor , Nwobodo Cynthia , Ugwu Chidiebere Happiness , Okoro Gozie Godswill , Mbah Esther C.
Published: January 2024

Introduction

Sub-Saharan Africa faces increasingly unpredictable and extreme weather patterns due to climate change, posing significant threats to food security and rural livelihoods. Traditional agriculture, deeply rooted in the region's history and culture, is particularly vulnerable to these changes. This study investigates the adaptation strategies of traditional agricultural farmers to climate change using southeast Nigeria as a microcosm of the broader challenges facing sub-Saharan Africa.

Methods

Multistage sampling procedure was used to select 75 farmer group leaders in the study region. Cross-sectional data were collected through semi-structured interview schedules and focus group discussions. Data were analyzed using descriptive statistics and principal component analysis using Varimax rotated matrix.

Results

Findings showed that farmers rely on face-to-face discussions with neighbors (76.0%), fellow farmers (66.7%), and radio (54.7%) as their primary sources of information on climate change. Results showed that traditional adaptation practices such as use of organic manure (x¯ = 3.89), traditional organic composting (x¯ = 3.80), afforestation (x¯ = 3.71), agroforestry (x¯ = 3.61) were the topmost traditional agricultural practices use to cushion the effect of climate change. Conserving the overall soil health, soil moisture retention, reducing CO2 emissions and maintaining crop productivity were the major reasons for using the traditional approaches. Climate-induced drought and high cost of accessing weather information (x¯ = 1.93), and inadequate funding (x¯ = 1.92), among others were the key constraints to adaptation.

Discussion

Results showed that farmers prioritize agronomic manipulation and integrated research approaches as key strategies to adapting traditional agriculture to climate anomalies. Although farmers used their indigenous practices, continuous learning and improvement through capacity-building workshops and progress monitoring are essential for effective climate change adaptation. Policymakers should invest in promoting indigenous knowledge, provide access to credit for climate-resilient infrastructure, promote climate-smart agricultural practices and foster collaborative research as the cornerstone for sustainable rural development.
A diabetic patient increased premature ventricular contractions after using liraglutide: a case report
Authors: Huang Lilan , Yu He , Fang Ying
Published: January 2024

The common adverse reactions of liraglutide are hypoglycemia and gastrointestinal reactions. This case reports a patient with type 2 diabetes mellitus who had an increase in ventricular premature beats after using liraglutide and a decrease in ventricular premature beats after stopping liraglutide, suggesting that clinicians should rule out the possibility of drug-related adverse reactions when using liraglutide in the treatment of diabetes mellitus complicated with coronary heart disease and arrhythmia.
Release of delta-9-tetrahydrocannabinol from polyvinyl alcohol hydrogels and its safe interaction with human skin fibroblasts
Authors: Cui Shujun , Zhang Ze , Rodrigue Denis , Béland François , Rouabhia Mahmoud
Published: January 2024

This study aimed to design a THC-rich hydrogel to deliver cannabis derivatives topically. We developed hydrogels using polyvinyl alcohol (PVA) mixed with propylene glycol (PG), vegetable glycerin (VG), or both to facilitate the dissolution of delta-9-tetrahydrocannabinol (THC). The hydrogels showed a brown color, confirming the presence of the cannabinoid. They exhibit a porous structure and better mechanical properties than PVA alone. Indeed, the hydrogel containing PG, VG, or both showed elastic deformation behaviors with lower water content. FTIR analysis demonstrated the presence of THC with two specific peaks at 1,575 and 1,619 cm−1, confirming the presence of THC in the hydrogels. Human dermal fibroblast cultures onto the surface of all hydrogels confirmed the safety of the THC-rich hydrogel as the cell adhesion was comparable to the control (no THC). Furthermore, cells adhering to the hydrogels could proliferate, showing increased cell viability at 48 and 72 h, with a higher proliferation obtained with the THC-rich PVA-PG-VG hydrogels. Such cell behavior could be due to the release of the THC in the culture medium, as demonstrated by ultra-high performance liquid chromatography (UPLC), showing the presence of THC in the culture medium, ranging from 203 to 290 μg after 24 h of incubation of the hydrogels containing PG and VG or both. In comparison, the released THC from the PVA hydrogel was higher, reaching 852 μg. It is interesting to note that the THC release at 24, 48, and 72 h was slower with the hydrogels containing PG, VG, and both, compared to PVA alone. Overall, the present study has designed safe THC-rich PVA-PG-VG hydrogels as a functional delivery system for the topical use of cannabinoids to control tissue diseases, such as inflammation.
Obesity- and lipid-related indices as a predictor of type 2 diabetes in a national cohort study
Authors: Wang Ying , Zhang Xiaoyun , Li Yuqing , Gui Jiaofeng , Mei Yujin , Yang Xue , Liu Haiyang , Guo Lei-lei , Li Jinlong , Lei Yunxiao , Li Xiaoping , Sun Lu , Yang Liu , Yuan Ting , Wang Congzhi , Zhang Dongmei , Li Jing , Liu Mingming , Hua Ying , Zhang Lin
Published: January 2024

Objective

Type 2 diabetes mellitus (T2DM) remains a major and widespread public health concern throughout the world. The prevalence of T2DM in the elderly has risen to the top of the list of public health concerns. In this study, obesity- and lipid-related indices were used to predict T2DM in middle-aged and elderly Chinese adults.

Methods

The data came from the China Health and Retirement Longitudinal Study (CHARLS), including 7902 middle-aged and elderly participants aged 45 years or above. The study assessed the association of obesity- and lipid-related indices and T2DM by measuring 13 indicators, including body mass index (BMI), waist circumference(WC), waist-height ratio (WHtR), conicity index(CI), visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), a body shape index (ABSI), body roundness index (BRI), triglyceride glucose index (TyG-index) and its correlation index (TyG-BMI, TyG-WC, TyG-WHtR). The association of 13 obesity- and lipid-related indices with T2DM was investigated by binary logistic regression. Additionally, the predictive anthropometric index was evaluated, and the ideal cut-off value was established using the receiver operating characteristic (ROC) curve analysis and area under the curve (AUC).

Results

The study included 7902 participants, of whom 3638(46.04) and 4264(53.96) were male and female. The prevalence of T2DM in mid-aged and old adults in China was 9.02% in males and 9.15% in females. All the above 13 indicators show a modest predictive power (AUC>0.5), which was significant for predicting T2DM in adults (middle-aged and elderly people) in China (P<0.05). The results revealed that TyG-WHtR [AUC =0.600, 95%CI: 0.566–0.634] in males and in females [AUC =0.664, 95%CI: 0.636–0.691] was the best predictor of T2DM (P<0.05).

Conclusion

Most obesity- and lipid-related indices have important value in predicting T2DM. Our results can provide measures for the early identification of T2DM in mid-aged and elderly Chinese to reduce the prevalence of T2DM and improve health.
Deep response to a combination of mTOR inhibitor temsirolimus and dual immunotherapy of nivolumab/ipilimumab in poorly differentiated thyroid carcinoma with PTEN mutation: a case report and literature review
Authors: Oh Youjin , Park Joo Hee , Djunadi Trie Arni , Shah Zunairah , Chung Liam Il-Young , Chae Young Kwang
Published: January 2024

Treating advanced thyroid cancer presents challenges due to its resistance to various treatment modalities, thereby limiting therapeutic options. To our knowledge, this study is the first to report the efficacy of temsirolimus in conjunction with dual immunotherapy of nivolumab/ipilimumab to treat heavily treated advanced PDTC. A 50-year-old female initially presented with a rapidly enlarging mass on her right neck. Subsequent diagnosis revealed poorly differentiated thyroid carcinoma, leading to a total thyroidectomy followed by post-operative radioablation therapy. After four years, an examination for persistent cough revealed a recurrence of the disease within multiple mediastinal nodes. Genetic analysis of blood samples uncovered somatic mutations in the tumor, specifically involving PTEN and TP53. The disease progressed despite palliative radiation, lenvatinib, and nivolumab/ipilimumab therapy. Consequently, temsirolimus, functioning as an mTOR inhibitor, was introduced as an adjunct to the nivolumab/ipilimumab regimen. This combination approach yielded remarkable clinical improvement and disease control for a duration of approximately six months. Temsirolimus likely suppressed the aberrantly activated PI3K/AKT/mTOR signaling pathway, facilitated by the PTEN genetic alteration, thus engendering an effective treatment response. This synergy between targeted agents and immunotherapy presents a promising therapeutic strategy for advanced PDTC patients with limited treatment alternatives. In previous clinical trials, mTOR inhibitors have demonstrated the ability to maintain stable disease (SD) in 65% to 74% for advanced thyroid cancer patients, including those with PDTC. When combined with other targeted therapies, the observed SD or partial response rates range from 80% to 97%. Many of these trials primarily involved differentiated thyroid carcinoma, with diverse genetic mutations. Thyroid cancer patients with alterations in the PI3K/mTOR/Akt appeared to benefit most from mTOR inhibitors. However, no clear association between the efficacy of mTOR inhibitors and specific histologies or genetic mutations has been established. Future studies are warranted to elucidate these associations.
The use of race terms in epigenetics research: considerations moving forward
Authors: King Dillon E. , Lalwani Pooja D. , Mercado Gilberto Padilla , Dolan Emma L. , Frierson Johnna M. , Meyer Joel N. , Murphy Susan K.
Published: January 2024

The field of environmental epigenetics is uniquely suited to investigate biologic mechanisms that have the potential to link stressors to health disparities. However, it is common practice in basic epigenetic research to treat race as a covariable in large data analyses in a way that can perpetuate harmful biases without providing any biologic insight. In this article, we i) propose that epigenetic researchers open a dialogue about how and why race is employed in study designs and think critically about how this might perpetuate harmful biases; ii) call for interdisciplinary conversation and collaboration between epigeneticists and social scientists to promote the collection of more detailed social metrics, particularly institutional and structural metrics such as levels of discrimination that could improve our understanding of individual health outcomes; iii) encourage the development of standards and practices that promote full transparency about data collection methods, particularly with regard to race; and iv) encourage the field of epigenetics to continue to investigate how social structures contribute to biological health disparities, with a particular focus on the influence that structural racism may have in driving these health disparities.
Gut microbiota and sepsis and sepsis-related death: a Mendelian randomization investigation
Authors: Shang Weifeng , Zhang Sheng , Qian Hang , Huang Sisi , Li Hui , Liu Jiao , Chen Dechang
Published: January 2024

Background

It is unclear what the causal relationship is between the gut microbiota and sepsis. Therefore, we employed Mendelian randomization (MR) to determine whether a causal link exists between the two.

Methods

This study used publicly available genome-wide association studies (GWAS) summary data of gut microbiota, sepsis, sepsis (critical care), and sepsis (28-day death in critical care) to perform a two-sample MR analysis. To ensure the robustness of the results, we also conducted a sensitivity analysis.

Results

For sepsis susceptibility, inverse variance weighted (IVW) estimates revealed that Victivallales (OR = 0.86, 95% CI, 0.78–0.94, p = 0.0017) was protective against sepsis, while Lentisphaerae (OR = 0.89, 95% CI, 0.80–0.99), Gammaproteobacteria (OR = 1.37, 95% CI, 1.08–1.73), Clostridiaceae1 (OR = 1.21, 95% CI, 1.04–1.40), RuminococcaceaeUCG011 (OR = 1.10, 95% CI, 1.01–1.20), Dialister (OR = 0.85, 95% CI, 0.74–0.97), and Coprococcus2 (OR = 0.81, 95% CI, 0.69–0.94) presented a suggestive association with the development of sepsis (all p < 0.05). For sepsis (critical care), IVW estimates indicated that Lentisphaerae (OR = 0.70, 95% CI, 0.53–0.93), Victivallales (OR = 0.67, 95% CI, 0.50–0.91), Anaerostipes (OR = 0.49, 95% CI, 0.31–0.76), LachnospiraceaeUCG004 (OR = 0.51, 95% CI, 0.34–0.77), and Coprococcus1 (OR = 0.66, 95% CI, 0.44–0.99) showed a suggestive negative correlation with sepsis (critical care) (all p < 0.05). For sepsis (28-day death in critical care), IVW estimates suggested that four bacterial taxa had a normally significant negative correlation with the risk of sepsis-related death, including Victivallales (OR = 0.54, 95% CI, 0.30–0.95), Coprococcus2 (OR = 0.34, 95% CI, 0.14–0.83), Ruminiclostridium6 (OR = 0.43, 95% CI, 0.22–0.83), and Coprococcus1 (OR = 0.45, 95% CI, 0.21–0.97), while two bacterial taxa were normally significantly positively linked to the risk of sepsis-related death, namely, Mollicutes (OR = 2.03, 95% CI, 1.01–4.08) and Bacteroidales (OR = 2.65, 95% CI, 1.18–5.96) (all p < 0.05). The robustness of the above correlations was verified by additional sensitivity analyses.

Conclusion

This MR research found that several gut microbiota taxa were causally linked to the risk of sepsis, sepsis in critical care, and sepsis-related 28-day mortality in critical care.
Exploring the causal relationship between inflammatory cytokines and immunoinflammatory dermatoses: a Mendelian randomization study
Authors: Li Jiaxuan , Lu Yining , Zhao Xuelian
Published: January 2024

Objectives

Previous studies have shown that the onset and progression of several immunoinflammatory dermatoses are closely related to specific immune-inflammatory responses. To further assess the causal relationship between 41 inflammatory cytokines and immunoinflammatory dermatoses, we used a Mendelian randomization method.

Methods

Mendelian two-sample randomization utilized inflammatory cytokines from a GWAS abstract containing 8,293 healthy participants as well as psoriasis (4,510 cases and 212,242 controls), atopic dermatitis (7,024 cases and 198,740 controls), and vitiligo (131 cases and 207,482 controls). The causal relationship between exposure and outcome was explored primarily using inverse variance weighting. In addition, multiple sensitivity analyses, including MR-Egger, weighted median, simple model, weighted model, and MR-PRESSO, were simultaneously applied to enhance the final results.

Results

The results showed that in clinical practice, IL-4 and IL-1RA were suggestive indicators of atopic dermatitis risk (OR = 0.878, 95% CI = 0.78–0.99, p = 0.036; OR = 0.902, 95% CI = 0.82–1.00, p = 0.045). SCGF-b was a suggestive indicator of psoriasis risk (OR = 1.095, 95% CI = 1.01–1.18, p = 0.023). IL-4 is a suggestive indicator of vitiligo risk (OR = 2.948, 95% CI = 1.28–6.79, p = 0.011).

Conclusion

Our findings suggest that circulating inflammatory cytokines may play a crucial role in the pathogenesis of chronic skin inflammation. IL-4 and IL-1RA may have inhibitory roles in the risk of developing atopic dermatitis, while SCGF-b may have a promoting role in the risk of developing psoriasis. Furthermore, IL-4 may contribute to the risk of developing vitiligo. These results provide insights into further understanding the mechanisms of chronic skin inflammation and offer new targets and strategies for the prevention and treatment of related diseases.
Dynamics of Whole Transcriptome Analysis (WTA) and Surface markers expression (AbSeq) in Immune Cells of COVID-19 Patients and Recovered captured through Single Cell Genomics
Authors: Soni Jyoti , Chattopadhyay Partha , Mehta Priyanka , Mohite Ramakant , Tardalkar Kishore , Joshi Meghnad , Pandey Rajesh
Published: January 2024

Introduction

Single-cell multi-omics studies, such as multidimensional transcriptomics (whole transcriptomic analysis, WTA), and surface marker analysis (antibody sequencing, AbSeq), have turned out to be valuable techniques that offer inaccessible possibilities for single-cell profiling of mRNA, lncRNA, and proteins.

Methods

We used this technique to understand the dynamics of mRNA and protein-level differences in healthy, COVID-19-infected and recovered individuals using peripheral blood mononuclear cells (PBMCs). Our results demonstrate that compared to mRNA expression, protein abundance is a better indicator of the disease state.

Results

We demonstrate that compared to mRNA expression, protein abundance is a better indicator of the disease state. We observed high levels of cell identity and regulatory markers, CD3E, CD4, CD8A, CD5, CD7, GITR, and KLRB1 in healthy individuals, whereas markers related to cell activation, CD38, CD28, CD69, CD62L, CD14, and CD16 elevated in the SARS-CoV-2 infected patients at both WTA and AbSeq levels. Curiously, in recovered individuals, there was a high expression of cytokine and chemokine receptors (CCR5, CCR7, CCR4, CXCR3, and PTGRD2). We also observed variations in the expression of markers within cell populations under different states.

Discussion

Furthermore, our study emphasizes the significance of employing an oligo-based method (AbSeq) that can help in diagnosis, prognosis, and protection from disease/s by identifying cell surface markers that are unique to different cell types or states. It also allows simultaneous study of a vast array of markers, surpassing the constraints of techniques like FACS to query the vast repertoire of proteins.
New findings in prognostic factor assessment for adenocarcinoma of transverse colon: a comparison study between competing-risk and COX regression analysis
Authors: Su Hongbo , Xie Shuping , Wang Shanshan , Huang Liying , Lyu Jun , Pan Yunlong
Published: January 2024

Purpose

Competing-risk analysis was used to accurately assess prognostic factors for cancer-specific death in patients with adenocarcinoma of transverse colon (ATC), and the results were compared with those from a conventional Cox regression analysis.

Materials and Methods

Patients diagnosed with ATC between 2000 and 2019 were selected from the Surveillance, Epidemiology, and End Results database. The crude mortality rates of patients with ATC were calculated and their differences were tested using the Gray’s test, respectively. In performing multivariate analysis, the Cox regression model and the subdistribution hazard function (SD) in competing risk analysis were utilized, respectively.

Results

This study included 21,477 eligible patients. The SD model indicated that age, etc. are actual independent prognostic factors. In contrast to previous recognition, the results of the Cox regression showed false-positives for sex and Carcinoembryonic antigen, and underestimated point-estimates in the stage and American Joint Committee on Cancer stage due to competing events. A detailed comparison of treatment revealed that the larger surgical scopes were prognostic risk factors compared with the smaller scope of local tumor excision, partial colectomy, or segmental resection. Patients treated with external proton beam radiotherapy had an increased risk compared with those with no radiotherapy and internal radiotherapy.

Conclusions

After comparing the results of the two methods and mitigating the significant bias introduced by Cox regression, we found independent factors that really affect the prognosis of ATC. On the other hand, in terms of ATC, a larger surgical scope and external proton beam radiotherapy may not improve the long-term survival of patients. Therefore, when faced with ATC patients, these differences should be noted and treated differently from common colorectal cancer patients. Thus, clinicians are able to give more targeted treatment plans and prognostic assessments.
Automated wound care by employing a reliable U-Net architecture combined with ResNet feature encoders for monitoring chronic wounds
Authors: Alabdulhafith Maali , Ba Mahel Abduljabbar S. , Samee Nagwan Abdel , Mahmoud Noha F. , Talaat Rawan , Muthanna Mohammed Saleh Ali , Nassef Tamer M.
Published: January 2024

Quality of life is greatly affected by chronic wounds. It requires more intensive care than acute wounds. Schedule follow-up appointments with their doctor to track healing. Good wound treatment promotes healing and fewer problems. Wound care requires precise and reliable wound measurement to optimize patient treatment and outcomes according to evidence-based best practices. Images are used to objectively assess wound state by quantifying key healing parameters. Nevertheless, the robust segmentation of wound images is complex because of the high diversity of wound types and imaging conditions. This study proposes and evaluates a novel hybrid model developed for wound segmentation in medical images. The model combines advanced deep learning techniques with traditional image processing methods to improve the accuracy and reliability of wound segmentation. The main objective is to overcome the limitations of existing segmentation methods (UNet) by leveraging the combined advantages of both paradigms. In our investigation, we introduced a hybrid model architecture, wherein a ResNet34 is utilized as the encoder, and a UNet is employed as the decoder. The combination of ResNet34’s deep representation learning and UNet’s efficient feature extraction yields notable benefits. The architectural design successfully integrated high-level and low-level features, enabling the generation of segmentation maps with high precision and accuracy. Following the implementation of our model to the actual data, we were able to determine the following values for the Intersection over Union (IOU), Dice score, and accuracy: 0.973, 0.986, and 0.9736, respectively. According to the achieved results, the proposed method is more precise and accurate than the current state-of-the-art.
Evaluating early lymphocyte-to-monocyte ratio as a predictive biomarker for delirium in older adult patients with sepsis: insights from a retrospective cohort analysis
Authors: Shi Xiaopeng , Yang Lei , Bai Weimin , Jing Lijuan , Qin Lijie
Published: January 2024

Background

This study aims to explore the value of the Lymphocyte-to-Monocyte Ratio (LMR) in predicting delirium among older adult patients with sepsis.

Methods

Retrospective data were obtained from the MIMIC-IV database in accordance with the STROBE guidelines. Patients aged 65 and above, meeting the Sepsis 3.0 criteria, were selected for this study. Delirium was assessed using the Confusion Assessment Method for the ICU (CAM-ICU). Demographic information, comorbid conditions, severity of illness scores, vital sign measurements, and laboratory test results were meticulously extracted. The prognostic utility of the Lymphocyte-to-Monocyte Ratio (LMR) in predicting delirium was assessed through logistic regression models, which were carefully adjusted for potential confounding factors.

Results

In the studied cohort of 32,971 sepsis patients, 2,327 were identified as meeting the inclusion criteria. The incidence of delirium within this subgroup was observed to be 55%. A univariate analysis revealed a statistically significant inverse correlation between the Lymphocyte-to-Monocyte Ratio (LMR) and the risk of delirium (p < 0.001). Subsequent multivariate analysis, which accounted for comorbidities and illness severity scores, substantiated the role of LMR as a significant predictive marker. An optimized model, achieving the lowest Akaike Information Criterion (AIC), incorporated 17 variables and continued to demonstrate LMR as a significant prognostic factor (p < 0.01). Analysis of the Receiver Operating Characteristic (ROC) curve indicated a significant enhancement in the Area Under the Curve (AUC) upon the inclusion of LMR (p = 0.035).

Conclusion

The Lymphocyte-to-Monocyte Ratio (LMR) serves as a significant, independent prognostic indicator for the occurrence of delirium in older adult patients with sepsis. Integrating LMR into existing predictive models markedly improves the identification of patients at elevated risk, thereby informing and potentially guiding early intervention strategies.
Higher diagnostic value of metagenomic next-generation sequencing in acute infection than chronic infection: a multicenter retrospective study
Authors: Yao Anjie , Wang Jiale , Xu Qintao , Shah Binay Kumar , Sun Kai , Hu Feng , Wang Changhui , Xie Shuanshuan
Published: January 2024

Background

The aim of this study is to compare the diagnostic value of metagenomic next-generation sequencing (mNGS) vs. conventional culture methods (CM) in chronic infection and acute infection.

Methods

We retrospectively analyzed the bronchoalveolar lavage fluid (BALF) of 88 patients with acute infection and 105 patients with chronic infection admitted to three hospitals from 2017 to 2022.

Results

The results showed that the sensitivity and specificity of mNGS were higher than those of CM. The number of patients who changed the antibiotic treatment in the mNGS positive group was larger than that of patients in the mNGS negative group in both the acute infection group (60.5 vs. 28.0%, P = 0.0022) and chronic infection group (46.2 vs. 22.6%, P = 0.01112). High levels of temperature (OR: 2.02, 95% CI: 1.18–3.70, P: 0.015), C-reactive protein (CRP) (OR: 15, 95% CI: 2.74–280.69, P: 0.011), neutrophil count (OR: 3.09, 95% CI: 1.19–8.43, P: 0.023), and low levels of lymphocyte count (OR: 3.43, 95% CI:1.26–10.21, P: 0.020) may lead to positive mNGS results in the acute infection group while no significant factor was identified to predict positive results in the chronic infection group.

Conclusion

mNGS could provide useful guidance on antibiotic strategies in infectious diseases and may be more valuable for the diagnosis and treatment of acute infection vs. chronic infection.
CyanoCyc cyanobacterial web portal
Authors: Moore Lisa R. , Caspi Ron , Campbell Douglas A. , Casey John R. , Crevecoeur Sophie , Lea-Smith David J. , Long Bin , Omar Naaman M. , Paley Suzanne M. , Schmelling Nicolas M. , Torrado Alejandro , Zehr Jonathan P. , Karp Peter D.
Published: January 2024

CyanoCyc is a web portal that integrates an exceptionally rich database collection of information about cyanobacterial genomes with an extensive suite of bioinformatics tools. It was developed to address the needs of the cyanobacterial research and biotechnology communities. The 277 annotated cyanobacterial genomes currently in CyanoCyc are supplemented with computational inferences including predicted metabolic pathways, operons, protein complexes, and orthologs; and with data imported from external databases, such as protein features and Gene Ontology (GO) terms imported from UniProt. Five of the genome databases have undergone manual curation with input from more than a dozen cyanobacteria experts to correct errors and integrate information from more than 1,765 published articles. CyanoCyc has bioinformatics tools that encompass genome, metabolic pathway and regulatory informatics; omics data analysis; and comparative analyses, including visualizations of multiple genomes aligned at orthologous genes, and comparisons of metabolic networks for multiple organisms. CyanoCyc is a high-quality, reliable knowledgebase that accelerates scientists’ work by enabling users to quickly find accurate information using its powerful set of search tools, to understand gene function through expert mini-reviews with citations, to acquire information quickly using its interactive visualization tools, and to inform better decision-making for fundamental and applied research.
Rapid detection of mexX in Pseudomonas aeruginosa based on CRISPR-Cas13a coupled with recombinase polymerase amplification
Authors: Zhu Xiao-Xuan , Wang Ying-Si , Li Su-Juan , Peng Ru-Qun , Wen Xia , Peng Hong , Shi Qing-Shan , Zhou Gang , Xie Xiao-Bao , Wang Jie
Published: January 2024

The principal pathogen responsible for chronic urinary tract infections, immunocompromised hosts, and cystic fibrosis patients is Pseudomonas aeruginosa, which is difficult to eradicate. Due to the extensive use of antibiotics, multidrug-resistant P. aeruginosa has evolved, complicating clinical therapy. Therefore, a rapid and efficient approach for detecting P. aeruginosa strains and their resistance genes is necessary for early clinical diagnosis and appropriate treatment. This study combines recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats-association protein 13a (CRISPR-Cas13a) to establish a one-tube and two-step reaction systems for detecting the mexX gene in P. aeruginosa. The test times for one-tube and two-step RPA-Cas13a methods were 5 and 40 min (including a 30 min RPA amplification reaction), respectively. Both methods outperform Quantitative Real-time Polymerase Chain Reactions (qRT-PCR) and traditional PCR. The limit of detection (LoD) of P. aeruginosa genome in one-tube and two-step RPA-Cas13a is 10 aM and 1 aM, respectively. Meanwhile, the designed primers have a high specificity for P. aeruginosa mexX gene. These two methods were also verified with actual samples isolated from industrial settings and demonstrated great accuracy. Furthermore, the results of the two-step RPA-Cas13a assay could also be visualized using a commercial lateral flow dipstick with a LoD of 10 fM, which is a useful adjunt to the gold-standard qRT-PCR assay in field detection. Taken together, the procedure developed in this study using RPA and CRISPR-Cas13a provides a simple and fast way for detecting resistance genes.
Effects of increasing drip irrigation at different maize growth stages on soil microorganisms
Authors: Wang Lei , Wang Xiaojuan , Wang Tianle
Published: January 2024

Introduction

To investigate the effects of different drip irrigation periods on soil microbial communities and functions.

Methods

Increasing drip irrigation amount at the seedling (S), jointing (J), bell (B), tasseling (T) and grain filling (G) stages of maize were studied using no increase in irrigation amount as control (CK). Principal component analysis was conducted to comprehensively evaluate soil microbial quality following the different drip irrigation treatments. In addition, the characteristics of the community structure and the potential functional composition of soil bacteria and fungi were comparatively analyzed by combining amplicon sequencing and functional prediction methods.

Results

The results indicated that MBNT15 was the most important genus for the classification of soil bacterial samples, Saitozyma was the most important genus for the classification of soil fungal samples, and fungi were more important than bacteria for the classification of soil microbial samples. Compared with fungal communities, bacterial communities exhibited high levels of functional diversity. The proportion of metabolism was the highest in the prediction of bacterial primary functions, and carbohydrate metabolism and amino acid metabolism were important functions in the prediction of bacterial secondary functions. BugBase phenotype prediction results showed that soil bacteria under B treatment had a higher number of aerobic bacteria and greater resistance to disease and stress. The J treatment had the highest number of bacteria with biofilm forms, and the J, S, and G treatments contained more potentially pathogenic bacteria but fewer stress-tolerant bacteria compared with the CK treatment. The number of Saprotroph was the largest and the number of Symbiotroph was the least. The relative abundances of Saprotroph, Pathotroph and Symbiotroph were 68.60%~74.33%, 15.76%~20.60% and 9.16%~11.13%, respectively.

Discussion

The findings provide a reference for conserving water resources, improving maize yield, and predicting soil microbial metabolic potential and function by reflecting the richness of the soil microbial community structure in maize fields.
Aerobic granular sludge for complex heavy metal-containing wastewater treatment: characterization, performance, and mechanisms analysis
Authors: Liu Chong , Shen Yao , Li Yuguang , Huang Fengguang , Wang Shuo , Li Ji
Published: January 2024

Complex heavy metal (HM)-containing wastewater discharges pose substantial risks to global water ecosystems and human health. Aerobic granular sludge (AGS) has attracted increased attention as an efficient and low-cost adsorbent in HM-containing wastewater treatment. Therefore, this study systematically evaluates the effect of Cu(II), Ni(II), and Cr(III) addition on the characteristics, performance and mechanism of AGS in complex HM-containing wastewater treatment process by means of fourier transform infrared spectroscopy, inductively coupled plasma spectrocopcy, confocal laser scanning microscopy, extracellular polymeric substances (EPS) fractions detection and scanning electron microscope-energy dispersive X-ray. The results showed that AGS efficiently eliminated Cu(II), Ni(II), and Cr(III) by the orchestrated mechanisms of ion exchange, three-layer EPS adsorption [soluble microbial products EPS (SMP-EPS), loosely bound EPS (LB-EPS), tightly bound EPS (TB-EPS)], and inner-sphere adsorption; notably, almost 100% of Ni(II) was removed. Three-layer EPS adsorption was the dominant mechanism through which the HM were removed, followed by ion exchange and inner-sphere adsorption. SMP-EPS and TB-EPS were identified as the key EPS fractions for adsorbing Cr(III) and Cu(II), respectively, while Ni(II) was adsorbed evenly on SMP-EPS, TB-EPS, and LB-EPS. Moreover, the rates at which the complex HM penetrated into the granule interior and their affinity for EPS followed the order Cu(II) > Ni(II) > Cr(III). Ultimately, addition of complex HM stimulated microorganisms to excrete massive phosphodiesterases (PDEs), leading to a pronounced decrease in cyclic diguanylate (c-di-GMP) levels, which subsequently suppressed EPS secretion due to the direct linkage between c-di-GMP and EPS. This study unveils the adaptability and removal mechanism of AGS in the treatment of complex HM-containing wastewater, which is expected to provide novel insights for addressing the challenges posed by intricate real wastewater scenarios.
Assessing the impact of novel risk loci on Alzheimer’s and Parkinson’s diseases in a Chinese Han cohort
Authors: Yan Huimin , Liu Minglei , Gao Yuan , Yuan Yanpeng , Liu Xiaojing , Wang Yangyang , Li Lanjun , Wang Qingzhi , Wang Yanlin , Shi Changhe , Xu Yuming , Yang Jing
Published: January 2024

Background

Overwhelming evidence points to that genetic factors contributing to the development of Alzheimer’s disease (AD) and Parkinson’s disease (PD). Genome-Wide Association Study (GWAS) has come a long way in the last decade. So far, a large number of GWAS studies have been published on neurological diseases and many other diseases, providing us with a wealth of genetic information and unique biological insights.

Methods

Genomic DNA was extracted from both patients’ and controls’ peripheral blood samples utilizing the Blood Genome Extraction Kit. Single nucleotide polymorphisms (SNPs) were genotyped employing the enhanced multiple ligase detection reaction (iMLDR) technology.

Results

A case-control study was conducted, involving 211 AD patients, 508 PD patients (including 117 with dementia), and 412 healthy individuals. Age and sex stratification analysis revealed that rs871269/TNIP1 was associated with LOAD (p = 0.035), and rs5011436/TMEM106B was associated with AD in males (p = 0.044) in the genotype model. In the allele model, rs871269/TNIP1 was found to be associated with PD in the Chinese Han population (p = 0.0035, OR 0.741, 95% CI 0.559-0.983), and rs708382/GRN was identified as a risk factor for Parkinson’s disease dementia (PDD) in the Chinese Han population (p = 0.004, odds ratio (OR) 0.354, 95% confidence interval (CI) 0.171-0.733). However, no significant associations with AD or PD were observed for the remaining four loci (rs113020870/AGRN, rs6891966/HAVCR2, rs2452170/NTN5, rs1761461/LILRB2) in terms of allele or genotype frequencies.

Conclusion

This study identifies rs871269/TNIP1 as a potential risk factor for both LOAD and PD, rs708382/GRN as a risk factor for PDD, and rs5011436/TMEM106B as associated with AD in males when stratified by age.
Prevalence, cognitive characteristics, and influencing factors of amnestic mild cognitive impairment among older adults residing in an urban community in Chengdu, China
Authors: Rao Shan , Cai Yan , Zhong Zhujun , Gou Tianyuan , Wang Yangyang , Liao Shiyi , Qiu Peiyuan , Kuang Weihong
Published: January 2024

Objective

Dementia is a significant public health concern, and mild cognitive impairment (MCI) serves as a transitional stage between normal aging and dementia. Among the various types of MCI, amnestic MCI (aMCI) has been identified as having a higher likelihood of progressing to Alzheimer’s dimension. However, limited research has been conducted on the prevalence of aMCI in China. Therefore, the objective of this study is to investigate the prevalence of aMCI, examine its cognitive characteristics, and identify associated risk factors.

Methods

In this cross-sectional study, we investigated a sample of 368 older adults aged 60 years and above in the urban communities of Chengdu, China. The participants underwent a battery of neuropsychological assessments, including the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating (CDR), Auditory Verbal Learning Test (AVLT), Wechsler’s Logical Memory Task (LMT), Boston Naming Test (BNT) and Trail Making Test Part A (TMT-A). Social information was collected by standard questionnaire. Multiple logistic regression analysis was utilized to screen for the risk and protective factors of aMCI.

Results

The data analysis included 309 subjects with normal cognitive function and 59 with aMCI, resulting in a prevalence of 16.0% for aMCI. The average age of participants was 69.06 ± 7.30 years, with 56.0% being females. After controlling for age, gender and education, the Spearman partial correlation coefficient between various cognitive assessments and aMCI ranged from −0.52 for the long-term delayed recall scores in AVLT to 0.19 for the time-usage scores in TMT-A. The results indicated that all cognitive domains, except for naming scores (after semantic cue of BNT) and error quantity (in TMT-A), showed statistically significant associations with aMCI. Furthermore, the multiple logistic regression analysis revealed that older age (OR = 1.044, 95%CI: 1.002~1.087), lower educational level, and diabetes (OR = 2.450, 95%CI: 1.246~4.818) were risk factors of aMCI.

Conclusion

This study found a high prevalence of aMCI among older adults in Chengdu, China. Individuals with aMCI exhibited lower cognitive function in memory, language, and executive domains, with long-term delayed recall showing the strongest association. Clinicians should prioritize individuals with verbal learning and memory difficulties, especially long-term delayed recall, in clinical practice.
Clinical value of serum complement component 1q levels in the prognostic analysis of aneurysmal subarachnoid hemorrhage: a prospective cohort study
Authors: Wang Linjie , Zhou Haotian , Zheng Wenhao , Wang Heng , Wang Zheng , Dong Xiaoqiao , Du Quan
Published: January 2024

Objective

To analyze the relationship between serum complement component 1q (C1q) levels and functional prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH), and to reveal its clinical value.

Methods

In this prospective cohort study, we collected clinical data of aSAH patients admitted to the Department of Neurosurgery, Hangzhou First People’s Hospital from January 2020 to October 2022. Parameters such as serum C1q levels, Hunt-Hess grade, modified Fisher grade, and the modified Rankin scale (mRS) at 3 months were included for evaluation. Patients were grouped based on the occurrence of delayed cerebral ischemia (DCI). Spearman rank correlation test and Kruskal-Wallis rank sum test were used to analyze the correlation between serum C1q levels, disease severity, and prognosis. Potential risk factors affecting prognosis and the occurrence of DCI were screened through Independent sample t-test or Mann–Whitney U test. Variables with significant differences (p < 0.05) were incorporated into a logistic regression model to identify independent risk factors affecting prognosis and DCI occurrence. Serum C1q levels were plotted as a ROC curve for predicting prognosis and DCI, and the area under the curve was calculated.

Results

A total of 107 aSAH patients were analyzed. Serum C1q levels positively correlated with Hunt-Hess grade, modified Fisher grade and mRS (all p < 0.001). Significant differences were observed in C1q levels among different Hunt-Hess grade, mFisher grade and mRS (all p < 0.001). Notably, higher serum C1q levels were seen in the poor prognosis group and DCI group, and correlated with worse prognosis (OR = 36.927, 95%CI 2.003–680.711, p = 0.015), and an increased risk for DCI (OR = 17.334, 95%CI 1.161–258.859, p = 0.039). ROC analysis revealed the significant discriminative power of serum C1q levels for poor prognosis (AUC 0.781; 95%CI 0.673–0.888; p < 0.001) and DCI occurrence (AUC 0.763; 95%CI 0.637–0.888; p < 0.001). Higher C1q levels independently predicted a poor prognosis and DCI with equivalent predictive abilities to Hunt-Hess grade and modified Fisher grade (both p < 0.05).

Conclusion

High levels of C1q in the blood is an independent risk factor for poor prognosis and the development of DCI in patients with aSAH. This can more objectively and accurately predict functional outcomes and the incidence of DCI. C1q may have a significant role in the mechanism behind DCI after aSAH.
A systematic-search-and-review of registered pharmacological therapies investigated to improve neuro-recovery after a stroke
Authors: Lee Tsong-Hai , Uchiyama Shinichiro , Kusuma Yohanna , Chiu Hou Chang , Navarro Jose C. , Tan Kay Sin , Pandian Jeyaraj , Guo Liang , Wong Yoko , Venketasubramanian Narayanaswamy ,   for the Asian Stroke Advisory Panel
Published: January 2024

Background

Stroke burden is largely due to long-term impairments requiring prolonged care with loss of productivity. We aimed to identify and assess studies of different registered pharmacological therapies as treatments to improve post-stroke impairments and/or disabilities.

Methods

We performed a systematic-search-and-review of treatments that have been investigated as recovery-enhancing or recovery-promoting therapies in adult patients with stroke. The treatment must have received registration or market authorization in any country regardless of primary indication. Outcomes included in the review were neurological impairments and functional/disability assessments. “The best available studies” based on study design, study size, and/or date of publication were selected and graded for level of evidence (LOE) by consensus.

Results

Our systematic search yielded 7,801 citations, and we reviewed 665 full-text papers. Fifty-eight publications were selected as “the best studies” across 25 pharmacological classes: 31 on ischemic stroke, 21 on ischemic or hemorrhagic stroke, 4 on intracerebral hemorrhage, and 2 on subarachnoid hemorrhage (SAH). Twenty-six were systematic reviews/meta-analyses, 29 were randomized clinical trials (RCTs), and three were cohort studies. Only nimodipine for SAH had LOE A of benefit (systematic review and network meta-analysis). Many studies, some of which showed treatment effects, were assessed as LOE C-LD, mainly due to small sample sizes or poor quality. Seven interventions had LOE B-R (systematic review/meta-analysis or RCT) of treatment effects.

Conclusion

Only one commercially available treatment has LOE A for routine use in stroke. Further studies of putative neuroprotective drugs as adjunctive treatment to revascularization procedures and more confirmatory trials on recovery-promoting therapies will enhance the certainty of their benefit. The decision on their use must be guided by the clinical profile, neurological impairments, and target outcomes based on the available evidence.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=376973, PROSPERO, CRD42022376973.