bluuebunny/crossref_metadata_2025 huggingface dataset:
Dermatopathology and the Diagnosis of Fungal Infections
Authors: Howell S. A.
Published: June 2023

Diagnosis of superficial/cutaneous fungal infections from skin, hair and nail samples is generally achieved using microscopy and culture in a microbiology laboratory, however, any presentation that is unusual or subcutaneous is sampled by taking a biopsy. Using histological techniques a tissue biopsy enables a pathologist to perform a full examination of the skin structure, detect any inflammatory processes or the presence of an infectious agent or foreign body. Histopathological examination can give a presumptive diagnosis while a culture result is pending, and may provide valuable diagnostic information if culture fails. This review demonstrates how histopathology contributes to the diagnosis of fungal infections from the superficial to the life threatening.
High-resolution ultrasound tendon-to-bone distances in partial and complete finger flexor A2 pulley ruptures simulated in human cadaver dissection: toward understanding imaging of partial pulley ruptures
Authors: Iruretagoiena Xeber , Schöffl Volker , Balius Ramón , Blasi Marc , Dávila Fernando , Sala Xavier , Sancho Igor , De La Fuente Javier
Published: June 2023

Introduction: The A2 pulley tear is the most common injury in rock climbing. Whereas complete A2 pulley ruptures have been extensively researched, studies focused on partial A2 pulley ruptures are lacking. A2 pulleys rupture distally to proximally. High-resolution ultrasound imaging is considered the gold-standard tool for diagnosis and the most relevant ultrasound measurement is the tendon-to-bone distance (TBD), which increases when the pulley ruptures. The purpose of this study was to establish tendon-to-bone distance values for different sizes of partial A2 pulley ruptures and compare these values with those of complete ruptures.

Material and methods: The sample consisted of 30 in vitro fingers randomly assigned to 5 groups: G1, no simulated tear (control); G2, simulated 5 mm tear (low-grade partial rupture); G3, simulated 10 mm tear (medium-grade partial rupture); G4, simulated 15 mm tear (high-grade partial rupture); and G5, simulated 20 mm or equivalent tear (complete rupture). A highly experienced sonographer blinded to the randomization process and dissections examined all fingers.

Results: The tendon-to-bone distance measurements (medians and interquartile ranges) were as follows: G1, 0.95 mm (0.77–1.33); G2, 2.11 mm (1.78–2.33); G3, 2.28 mm (1.95–2.42); G4, 3.06 mm (2.79–3.28); and G5, 3.66 mm (3.55–4.76). Significant differences were found between non-torn pulleys and simulated partial and complete pulley ruptures.

Discussion: In contrast, and inconsistent with other findings, no significant differences were found among the different partial rupture groups. In conclusion, the longer the partial pulley rupture, the higher the tendon-to-bone distance value. The literature is inconsistent regarding the tendon-to-bone distance threshold to diagnose a partial A2 pulley rupture. The minimum tendon-to-bone distance value for a partial rupture was 1.6 mm, and tendon-to-bone distance values above 3 mm suggest a high-grade partial pulley rupture (15 mm incision) or a complete pulley rupture.
Characterization of cuproptosis in gastric cancer and relationship with clinical and drug reactions
Authors: Chen Guoming , Luo Dongqiang , Qi Xiangjun , Li Danyun , Zheng Jiyuan , Luo Yang , Zhang Cheng , Ren Qing , Lu Yuanjun , Chan Yau-Tuen , Chen Bonan , Wu Junyu , Wang Ning , Feng Yibin
Published: June 2023

Gastric cancer (GC) is the fifth most common cancer worldwide. Cuproptosis is associated with cell growth and death as well as tumorigenesis. Aiming to lucubrate the potential influence of CRGs in gastric cancer, we acquired datasets of gastric cancer patients from TCGA and GEO. The identification of molecular subtypes with CRGs expression was achieved through unsupervised learning-cluster analysis. To evaluate the application value of subtypes, the K-M survival analysis was conducted to evaluate the clinical prognostic characteristics. Subsequently, we performed Gene Set Variation Analysis (GSVA) and utilized ssGSEA to quantify the extent of immune infiltration. Further, the K-M survival analysis was used to identify the prognosis-related CRGs. Next, signature genes of diagnostic predictive value were screened using the least absolute shrinkage and selection operator (LASSO) algorithm from the expression matrix for TCGA, as well as the signature gene-related subtype was clustered by the “ConsensusClusterPlus” package. Finally, the immunological and drug sensitivity assessments of the signature gene-related subtypes were conducted. A total of 173 CRGs were identified, most of the CRGs undergo copy number variation in gastric cancer. Under different patient subtypes, immune cell levels differed significantly, and the subtype exhibiting high expression of the CRGs had a better prognosis. Furthermore, we selected 34 CRGs that were highly correlated with the prognosis of gastric cancer. By constructing a multivariate Cox proportional-hazards model and a hazard scoring system, we were able to categorize patients into high- and low-risk groups based on their hazard score. K-M analysis demonstrated a significant survival disadvantage in the high-risk group. Based on Lasso regression analysis, we screened 16 signature genes, a multivariate logistic regression model [cutoff: 0.149 (0.000, 0.974), AUC:0.987] and a prognosis network diagram was constructed and their prediction efficiency for gastric cancer prognostic diagnosis was well validated. According to the signature genes, the patients were separated to two signature subtypes. We found that patients with higher CRGs expression and better prognosis had lower levels of immune infiltration. Finally, according to the results of drug susceptibility analysis, docetaxel, 5-Fluorouracil, gemcitabin, and paclitaxel were found to be more sensitive to gastric cancer.
Unlocking the potential of approved drugs for the allosteric inhibition of tropomyosin-receptor kinase A using molecular docking and molecular dynamics studies
Authors: Mukhtar Rua M. , Abdelmoniem Nihal , Elrufaie Hisham A. , Edris Alaa , Ghaboosh Hiba , Mahgoub Mohanad A. , Garelnabi Elrashied A. E. , Osman Wadah , Sherif Asmaa E. , Ashour Ahmed , Ghazawi Kholoud F. , Samman Waad A. , Alhaddad Aisha A. , Bafail Rawan , Ibrahim Sabrin R. M. , Mohamed Gamal A. , Alzain Abdulrahim A.
Published: June 2023

Tropomyosin-receptor kinase A (TrkA) is the primary isoform among the tropomyosin-receptor kinases that have been associated with human cancer development, contributing to approximately 7.4% of all cancer cases. TrkA represents an attractive target for cancer treatment; however, currently available TrkA inhibitors face limitations in terms of resistance development and potential toxicity. Hence, the objective of this study was to identify new allosteric-approved inhibitors of TrkA that can overcome these challenges and be employed in cancer therapy. To achieve this goal, a screening of 9,923 drugs from the ChEMBL database was conducted to assess their repurposing potential using molecular docking. The top 49 drug candidates, exhibiting the highest docking scores (−11.569 to −7.962 kcal/mol), underwent MM-GBSA calculations to evaluate their binding energies. Delanzomib and tibalosin, the top two drugs with docking scores of −10.643 and −10.184 kcal/mol, respectively, along with MM-GBSA dG bind values of −67.96 and −50.54 kcal/mol, were subjected to 200 ns molecular dynamic simulations, confirming their stable interactions with TrkA. Based on these findings, we recommend further experimental evaluation of delanzomib and tibalosin to determine their potential as allosteric inhibitors of TrkA. These drugs have the potential to provide more effective and less toxic therapeutic alternatives. The approach employed in this study, which involves repurposing drugs through molecular docking and molecular dynamics, serves as a valuable tool for identifying novel drug candidates with distinct therapeutic uses. This methodology can contribute to reducing the attrition rate and expediting the process of drug discovery.
Higher-order G-quadruplexes in promoters are untapped drug targets
Authors: Monsen Robert C.
Published: June 2023

G-quadruplexes (G4s) are four-stranded nucleic acid secondary structures that form within guanine-rich regions of chromatin. G4 motifs are abundant in the genome, with a sizable proportion (∼40%) existing within gene promoter regions. G4s are proven epigenetic features that decorate the promoter landscape as binding centers for transcription factors. Stabilizing or disrupting promoter G4s can directly influence adjacent gene transcription, making G4s attractive as indirect drug targets for hard-to-target proteins, particularly in cancer. However, no G4 ligands have progressed through clinical trials, mostly owing to off targeting effects. A major hurdle in G4 drug discovery is the lack of distinctiveness of the small monomeric G4 structures currently used as receptors. This mini review describes and contrasts monomeric and higher-order G-quadruplex structure and function and provides a rationale for switching focus to the higher-order forms as selective molecular targets. The human telomerase reverse transcriptase (hTERT) core promoter G-quadruplex is then used as a case study that highlights the potential for higher-order G4s as selective indirect inhibitors of hard-to-target proteins in cancer.
Integration of Functional Imaging, Cytometry, and Unbiased Proteomics Reveals New Features of Endothelial-to-Mesenchymal Transition in Ischemic Mitral Valve Regurgitation in Human Patients
Authors: Lupieri Adrien , Nagata Yasufumi , Passos Livia S. A. , Beker-Greene Dakota , Kirkwood Katherine A. , Wylie-Sears Jill , Alvandi Zahra , Higashi Hideyuki , Hung Judy W. , Singh Sasha A. , Bischoff Joyce , Levine Robert A. , Aikawa Elena
Published: June 2023

Background: Following myocardial infarction, mitral regurgitation (MR) is a common complication. Previous animal studies demonstrated the association of endothelial-to-mesenchymal transition (EndMT) with mitral valve (MV) remodeling. Nevertheless, little is known about how MV tissue responds to ischemic heart changes in humans.

Methods: MVs were obtained by the Cardiothoracic Surgical Trials Network from 17 patients with ischemic mitral regurgitation (IMR). Echo-doppler imaging assessed MV function at time of resection. Cryosections of MVs were analyzed using a multi-faceted histology and immunofluorescence examination of cell populations. MVs were further analyzed using unbiased label-free proteomics. Echo-Doppler imaging, histo-cytometry measures and proteomic analysis were then integrated.

Results: MVs from patients with greater MR exhibited proteomic changes associated with proteolysis-, inflammatory- and oxidative stress-related processes compared to MVs with less MR. Cryosections of MVs from patients with IMR displayed activated valvular interstitial cells (aVICs) and double positive CD31+ αSMA+ cells, a hallmark of EndMT. Univariable and multivariable association with echocardiography measures revealed a positive correlation of MR severity with both cellular and geometric changes (e.g., aVICs, EndMT, leaflet thickness, leaflet tenting). Finally, proteomic changes associated with EndMT showed gene-ontology enrichment in vesicle-, inflammatory- and oxidative stress-related processes. This discovery approach indicated new candidate proteins associated with EndMT regulation in IMR.

Conclusion: We describe an atypical cellular composition and distinctive proteome of human MVs from patients with IMR, which highlighted new candidate proteins implicated in EndMT-related processes, associated with maladaptive MV fibrotic remodeling.
Barriers, facilitators and motivators of electronic community health information system use among health workers in Ethiopia
Authors: Bogale Tariku Nigatu , Teklehaimanot Selamawit Meressa , Fufa Debela Tilahun , Enyew Daniel Berhanie , Nigusse Bedada Abebe , Dufera Kebebew Segni , Nigusie Weldeab Adane , Wolde Daka Dawit , Willems Herman Jozef , Bekele Tadesse Alemu
Published: June 2023

Background

The electronic community health information system (eCHIS) has been implemented in Ethiopia to support health services delivered by community health workers. Despite the many benefits of digitizing community health information systems, the implementation of the eCHIS is challenged by many barriers resulting in low uptake. This study assessed the barriers, facilitators, and motivators of eCHIS use among health workers with focus on health extension workers (HEWs) in Ethiopia.

Methods

Phenomenological approach was used to assess the barriers, facilitators and motivators of eCHIS use in Amhara, Harari, Oromia, Sidama, South West Ethiopia and Southern Nation Nationalities and People's regions of Ethiopia. Data were collected from 15–29 May 2022. A total of 54 face-to-face in-depth interviews were conducted among HEWs, HEW supervisors, health information technicians and managers. The interviews were audiotaped using Open Data Kit, transcribed verbatim and translated into English. OpenCode 4.03 software was used for coding and categorizing the data. Thematic analysis was used to analyze the data.

Results

The HEWs and other eCHIS users reported lack of infrastructure and resources; poor quality of training, follow-up, and supervision; parallel recording using the manual and electronic system; and HEWs' workload as barriers hindering eCHIS use. Data quality, retrievability, and traceability; tablet portability; encouragement from supervisors; and positive image in the community resulting from HEWs using tablets in their routine activities were the main facilitators of eCHIS use.

Conclusion

The study identified various barriers that adversely affect the use of eCHIS. An integrated and coordinated approach to eCHIS implementation that encompasses removing the barriers, and reinforcing facilitators is required.
Fetal genome predicted birth weight and polycystic ovary syndrome in later life: a Mendelian randomization study
Authors: Liu Dong , Gan Yuexin , Zhang Yue , Cui Linlin , Tao Tao , Zhang Jun , Zhao Jian
Published: June 2023

Associations between lower birth weight and higher polycystic ovary syndrome (PCOS) risk have been reported in previous observational studies, however, the causal relationship is still unknown. Based on decomposed fetal and maternal genetic effects on birth weight (n  =  406,063), we conducted a two-sample Mendelian randomization (MR) analysis to assess potential causal relationships between fetal genome predicted birth weight and PCOS risk using a large-scale genome-wide association study (GWAS) including 4,138 PCOS cases and 20,129 controls. To further eliminate the maternally transmitted or non-transmitted effects on fetal growth, we performed a secondary MR analysis by utilizing genetic instruments after excluding maternally transmitted or non-transmitted variants, which were identified in another birth weight GWAS (n = 63,365 parent-offspring trios from Icelandic birth register). Linkage disequilibrium score regression (LDSR) analysis was conducted to estimate the genetic correlation. We found little evidence to support a causal effect of fetal genome determined birth weight on the risk of developing PCOS (primary MR analysis, OR: 0.86, 95% CI: 0.52 to 1.43; secondary MR analysis, OR: 0.86, 95% CI: 0.54 to 1.39). In addition, a marginally significant genetic correlation (rg = -0.14, se = 0.07) between birth weight and PCOS was revealed via LDSR analysis. Our findings indicated that observed associations between birth weight and future PCOS risk are more likely to be attributable to genetic pleiotropy driven by the fetal genome rather than a causal mechanism.
Machine learning immune-related gene based on KLRB1 model for predicting the prognosis and immune cell infiltration of breast cancer
Authors: Huang Guo , Xiao Shuhui , Jiang Zhan , Zhou Xue , Chen Li , Long Lin , Zhang Sheng , Xu Ke , Chen Juan , Jiang Bin
Published: June 2023

Objective

Breast cancer is a prevalent malignancy that predominantly affects women. The development and progression of this disease are strongly influenced by the tumor microenvironment and immune infiltration. Therefore, investigating immune-related genes associated with breast cancer prognosis is a crucial approach to enhance the diagnosis and treatment of breast cancer.

Methods

We analyzed data from the TCGA database to determine the proportion of invasive immune cells, immune components, and matrix components in breast cancer patients. Using this data, we constructed a risk prediction model to predict breast cancer prognosis and evaluated the correlation between KLRB1 expression and clinicopathological features and immune invasion. Additionally, we investigated the role of KLRB1 in breast cancer using various experimental techniques including real-time quantitative PCR, MTT assays, Transwell assays, Wound healing assays, EdU assays, and flow cytometry.

Results

The functional enrichment analysis of immune and stromal components in breast cancer revealed that T cell activation, differentiation, and regulation, as well as lymphocyte differentiation and regulation, play critical roles in determining the status of the tumor microenvironment. These DEGs are therefore considered key factors affecting TME status. Additionally, immune-related gene risk models were constructed and found to be effective predictors of breast cancer prognosis. Further analysis through KM survival analysis and univariate and multivariate Cox regression analysis demonstrated that KLRB1 is an independent prognostic factor for breast cancer. KLRB1 is closely associated with immunoinfiltrating cells. Finally, in vitro experiments confirmed that overexpression of KLRB1 inhibits breast cancer cell proliferation, migration, invasion, and DNA replication ability. KLRB1 was also found to inhibit the proliferation of breast cancer cells by blocking cell division in the G1/M phase.

Conclusion

KLRB1 may be a potential prognostic marker and therapeutic target associated with the microenzymic environment of breast cancer tumors, providing a new direction for breast cancer treatment.
Major contributing factors to the lower level of connection to the existing sewer network in Addis Ababa: the case of the Kality catchment
Authors: Ali Mohammed , Robele Sirak
Published: June 2023

Many households in Addis Ababa have not been connected to a sewer network, even when it passes by their homes. This study was designed to investigate major factors that have contributed to the lower level of connection to the existing sewer network in the Kality catchment of Addis Ababa. A household survey was conducted via questionnaire to identify the reasons hindering customers from connecting to sewers. The main factors identified were lack of awareness, connection fee, topography, customers’ preference for onsite sanitation over sewers, customers’ unwillingness to reinstate fences or pavements in their compound, and the unreliability of the water utility service. The survey results were analyzed with a binary logistic regression model using SPSS software. Except for topography (p-value 0.792) and connection fee (p-value 0.446), the other four independent variables had significant p values of less than 0.05, which implied a good model. Customers’ preference for onsite sanitations over sewers, followed by the unreliability of the water utility service and customers’ unwillingness to reinstate fences or pavements in their compounds were found to be the factors that most contribute to the lower level of user interest in sewer connection. However, a lack of awareness and information was also crucial in determining the rate of connection to sewers in the Kality catchment of Addis Ababa. The study also revealed that there was a gap in legislation and its enforcement: there was neither a regulator nor regulations for monitoring wastewater management, including mandatory sewer connection in the city.
The impact of NKG2A and NKG2D receptors and HLA-E and MICA ligands polymorphisms on post-transplant complications after paediatric allogeneic HSCT: a single-centre experience
Authors: Siemaszko Jagoda , Ussowicz Marek , Rybka Blanka , Ryczan-Krawczyk Renata , Kałwak Krzysztof , Bogunia-Kubik Katarzyna
Published: June 2023

Introduction: Natural Killer cells are the first subpopulation of lymphocytes that reconstitute after allogeneic haematopoietic stem cell transplantation (HSCT). Their activity is regulated by various receptor-ligand interactions, including stimulation of the activating NKG2D receptor by the MICA molecule, and inhibitory NKG2A receptor interacting with the HLA-E. In this study the research effort focused on the effect of selected NKG2A and NKG2D receptors and their ligands (HLA-E and MICA molecules) polymorphisms that may affect the pathomechanisms of post-transplant complications after HSCT in children.

Methods: One hundred donor-recipient pairs from a single paediatric transplantation centre were investigated. Altogether six single nucleotide substitutions (NKG2A rs7301582; NKG2D rs1049174, rs1154831; HLA-E rs1264457; MICA rs1051792, rs1063635) were genotyped, and the influence of polymorphisms was analysed on acute and chronic graft-versus-host disease (GvHD), cytomegalovirus (CMV) infection incidence, disease relapse and survival.

Results: The distribution of the evaluated polymorphisms did not differ between patients and their donors. The results showed a significant influence of HLA-E rs1264457 polymorphism in patients’ HLA-E*01:01 allele, which was associated with increased risk of CMV infection (p = 0.050), especially in children positive for CMV IgG before transplantation (p = 0.001). Furthermore, the effect of HLA-E*01:01 allele on CMV infections was more evident in children above the age of 7 years (p = 0.031). Strong tendencies (0.05 < p < 0.10) towards association with the risk of acute GvHD were also observed for the NKG2A or MICA polymorphisms of the recipients. In addition, NKG2D rs1154831 AA and MICA rs1063635 GG might play a protective role as they were not present in any recipient who died after transplantation.

Conclusion: In summary, there is emerging evidence that genotyping results of NKG2 receptors and their ligands, may have prognostic value for the outcome of paediatric allogeneic HSCT, but more extensive studies performed on larger groups of donors and transplant recipients are required to confirm these observations.
Co-expression of Foxp3 and Helios facilitates the identification of human T regulatory cells in health and disease
Authors: Morina Lyra , Jones Madalyn E. , Oguz Cihan , Kaplan Mariana J. , Gangaplara Arunakumar , Fitzhugh Courtney D. , Kanakry Christopher G. , Shevach Ethan M. , Buszko Maja
Published: June 2023

Foxp3 is regarded as the major transcription factor for T regulatory (Treg) cells and expression of Foxp3 is used to identify and quantitate Treg cells in mouse models. However, several studies have demonstrated that human CD4+ T conventional (Tconv) cells activated in vitro by T cell receptor (TCR) stimulation can express Foxp3. This observation has raised doubt as to the suitability of Foxp3 as a Treg marker in man. Helios, a member of the Ikaros gene family, has been shown to be expressed by 80-90% of human Foxp3+ Treg cells and can potentially serve as a marker of human Treg. Here, we confirm that Foxp3 expression is readily upregulated by Tconv upon TCR stimulation in vitro, while Helios expression is not altered. More importantly, we show that Foxp3 expression is not elevated by stimulation of hTconv in a humanized mouse model of graft versus host disease (GVHD) and in patients with a wide variety of acute and chronic inflammatory diseases including sickle cell disease, acute and chronic GVHD, systemic lupus erythematosus, as well as critical COVID-19. In all patients studied, an excellent correlation was observed between the percentage of CD4+ T cells expressing Foxp3 and the percentage expressing Helios. Taken together, these studies demonstrate that Foxp3 is not induced upon Tconv cell activation in vivo and that Foxp3 expression alone can be used to quantitate Treg cells in humans. Nevertheless, the combined use of Foxp3 and Helios expression provides a more reliable approach for the characterization of Treg in humans.
Integrated single-cell and bulk characterization of cuproptosis key regulator PDHB and association with tumor microenvironment infiltration in clear cell renal cell carcinoma
Authors: Wu Jiajin , Wang Songbo , Liu Yiyang , Zhang Tongtong , Wang Xiaoyi , Miao Chenkui
Published: June 2023

Background

Renal clear cell carcinoma (ccRCC) is one of the most prevalent cancers worldwide. Accumulating evidence revealed that copper-induced cell death played a vital role in various tumors. However, the underlying mechanism of cuproptosis with molecular heterogeneity and tumor microenvironment (TME) in ccRCC remains to be elucidated. The present study aimed to discover the biological function of cuproptosis regulators with the potential to guide clinical therapy.

Methods

Using Single-cell RNA-seq, bulk transcriptome and other multi-omics datasets, we identify essential cuproptosis-related hub gene PDHB for further study. The dysregulation of PDHB in ccRCC was characterized, together with survival outcomes, pathway enrichment and immune infiltration among tumor microenvironments. The functional significance and clinical association of PDHB was validated with loss of function experiments and surgical removal specimens.

Results

PDHB mRNA and protein expression level was significantly downregulated in ccRCC tissues compared with normal and paired normal tissues. Clinicopathological parameters and tissue microarray (TMA) indicated that PDHB was identified as a prognostic factor for survival outcomes among ccRCC patients. Additionally, low PDHB was negatively correlated with Treg cells, indicating an immunosuppressive microenvironment. Mechanistically, knockdown PDHB appeared to promote the RCC cells proliferation, migration, and invasion potentials. Subsequent studies showed that copper-induced cell death activation could overcome sunitinib resistance in RCC cells.

Conclusion

This research illustrated a cuproptosis-related hub gene PDHB which could serve as a potential prognostic marker and provide therapeutic benefits for clinical treatment of ccRCC patients.
The components of tumor microenvironment as biomarker for immunotherapy in metastatic renal cell carcinoma
Authors: Su Jiaming , Zhou Lu , Zhang Zhe , Xiao Xue , Qin Yanning , Zhou Xiaoying , Huang Tingting
Published: June 2023

Substantial improvement in prognosis among metastatic renal cell carcinoma (mRCC) patients has been achieved, owing to the rapid development and utilization of immunotherapy. In particular, immune checkpoint inhibitors (ICIs) have been considered the backbone of systemic therapy for patients with mRCC alongside multi-targeted tyrosine kinase inhibitors (TKIs) in the latest clinical practice guidelines. However, controversies and challenges in optimal individualized treatment regarding immunotherapy remains still About 2/3 of the patients presented non-response or acquired resistance to ICIs. Besides, immune-related toxicities, namely immune-related adverse events, are still elusive and life-threatening. Thus, reliable biomarkers to predict immunotherapeutic outcomes for mRCC patients are needed urgently. Tumor microenvironment (TME), consisting of immune cells, vasculature, signaling molecules, and extracellular matrix and regulates tumor immune surveillance and immunological evasion through complex interplay, plays a critical role in tumor immune escape and consequently manipulates the efficacy of immunotherapy. Various studied have identified the different TME components are significantly associated with the outcome of mRCC patients receiving immunotherapy, making them potential valuable biomarkers in therapeutic guidance. The present review aims to summarize the latest evidence on the associations between the components of TME including immune cells, cytokines and extracellular matrix, and the therapeutic responses among mRCC patients with ICI-based treatment. We further discuss the feasibility and limitation of these components as biomarkers.
Human immunodeficiency virus and antiretroviral therapy-mediated immune cell metabolic dysregulation in children born to HIV-infected women: potential clinical implications
Authors: Mataramvura Hope , Bunders Madeleine J. , Duri Kerina
Published: June 2023

Commencing lifelong antiretroviral therapy (ART) immediately following HIV diagnosis (Option B+) has dramatically improved the health of HIV-infected women and their children, with the majority being of HIV-exposed children born uninfected (HEU). This success has led to an increasing population of HIV-infected women receiving ART during pregnancy and children exposed to ART in utero. Nonetheless, a small proportion of children are still infected with HIV (HEI) each year. HEI children suffer from reduced immunocompetence and host-defence, due to CD4+ T lymphocyte depletion, but also dysregulation of other immune cells including CD8+ T lymphocytes, natural killer (NK) cells, macrophages including B lymphocytes. Furthermore, although HEU children are uninfected, altered immune responses are observed and associated with increased vulnerability to infections. The mechanisms underlying immune dysregulation in HEU children remain poorly described. Building on early studies, emerging data suggests that HIV/ART exposure early in life affects cell metabolic function of HEU children. Prenatal HIV/ART exposure has been associated with dysregulation of mitochondria, including impaired DNA polymerase activity. Furthermore, dysregulation of oxidative phosphorylation (OXPHOS) causes a decreased generation of adenosine triphosphate (ATP) and increased production of reactive oxygen species (ROS), resulting in oxidative stress. These altered metabolic processes can affect immune cell viability and immune responses. Recent studies have indicated that immune-metabolic dysregulation may contribute to HIV-associated pathogenesis and clinical observations associated with HIV and ART exposure in HEU/HEI children. Given the critical role metabolic processes in immune cell functioning, immune-metabolic dysregulation in HEU and HEI children may have implications in effective host-defence responses against pathogens, as well as efficacy of standard ART regimens and future novel HIV cure approaches in HEI children. At the same time, targeting metabolic pathways of immune cells may provide safer and novel approaches for HIV cure strategies. Here, we review the current literature investigating immune-metabolic dysregulation in paediatric HIV pathogenesis.
Identification of Key Genes and Pathways in Persistent Hyperplastic Primary Vitreous of the Eye Using Bioinformatic Analysis
Authors: Thomas Derin M. , Kannabiran Chitra , Balasubramanian D.
Published: June 2023

Graphical Abstract

Schematic diagram for evaluating and identifying the key genes, molecular pathways, predicted drug targets of PHPV.
Monocyte at diagnosis as a prognosis biomarker in tuberculosis patients with anemia
Authors: Luo Mengxing , Zou Xin , Zeng Qibing , Wu Yaxing , Yang Hua , Qin Lianhua , Zheng Ruijuan , Yu Fangyou , Hu Yang , Liu Zhonghua
Published: June 2023

Background

Anemia leads to a lower cure rate and poor prognosis in tuberculosis patients. Effective predictors for the prognosis of tuberculosis with anemia (A-TB) are urgently needed. Monocyte has been proven to be a prognostic biomarker of many lung diseases. Whether monocyte that the predominant innate immune cell as early defense against tuberculosis can predict A-TB is not known.

Methods

Data for A-TB patients with initial treatment in Shanghai Pulmonary Hospital were retrospectively collected and analyzed. Logistics regression analysis was used to study the correlation between peripheral blood cells and treatment outcomes. The receiver operating characteristic (ROC) curve was used to determine the cut-off value. We estimated a 12-month prognosis using Kaplan–Meier techniques. The Cox proportional hazards model was used for the univariate and multivariate analyses to analyze the predictors of poor prognosis of A-TB.

Results

Of 181 patients analyzed, 94 were cured and 87 non-cured. Logistic regression analysis identified monocyte as an independent immune-related risk factor for the prognosis of A-TB (OR: 7.881, 95% CI: 1.675–37.075, P = 0.009). The ROC curve analysis proved that the most discriminative cut-off value of monocyte was 0.535 × 10^9/L. K–M analysis demonstrated that the cumulative cure rates of A-TB were significantly higher in A-TB with monocyte < 0.535 × 10^9/L (69.62%) than that in those with monocyte ≥ 0.535 × 10^9/L (38.24%) (Log-rank, χ2 = 16.530, P < 0.0001). On univariate and multivariable analysis, monocyte was an independent predictor of poor prognosis in A-TB. Similarly, monocyte was also an independent predictor of poor pulmonary cavity closure in A-TB (HR: 3.614, 95% CI: 1.335–9.787, P = 0.011).

Conclusion

In A-TB patients, elevated monocyte was associated with poor prognosis and poor cavity pulmonary closure. Monocyte may provide a simple and inexpensive prognostic biomarker in A-TB.
Sex and age differences in chronic postoperative pain among patients undergoing thoracic surgery: a retrospective cohort study
Authors: Zhao Ying , Liu Xin-Min , Zhang Lu-Yao , Li Bing , Wang Ruo-Han , Yuan Qin-Yue , Wang Shi-Chao , Zhu Hai-Peng , Zhi Hui , Zhang Jia-Qiang , Zhang Wei
Published: June 2023

Background

The effect of sex and age on chronic post-thoracic surgical pain (CPTP) at rest and with activity remains unclear. The main purpose of this study was to investigate the relationship between the incidence of chronic postoperative pain (at rest and with activity) and sex/age differences.

Methods

This was a single-center retrospective study that included adult patients who had undergone elective thoracic surgery. Patients were divided into two groups based on sex. Demographic and perioperative data were collected, including age, sex, education level, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) physical status, and medical history (hypertension, diabetes mellitus). Chronic postoperative pain data were collected by telephone follow-up.

Results

Among the 3,159 patients enrolled, 1,762 were male, and 1,397 were female. After creating a matched-pairs cohort, 1,856 patients were analyzed. The incidence of CPTP at rest was 14.9% among males and 17.8% among females (p = 0.090). The incidence of CPTP with activity was 28.4% among males and 35.0% among females (p = 0.002). We analyzed three different models after propensity matching to validate the stability of the prediction model between sex and CPTP, and female sex was a significant predictor of CPTP with activity 3 months after surgery. Further analysis showed that females in the 45-55-year-old age group were more prone to develop CPTP.

Conclusion

Females have a higher incidence of chronic postoperative pain with activity after thoracic surgery. Females in the 45-55-year-old age group are more prone to develop CPTP than females in other age groups.
Brazilian Semi-Arid Mangroves-Associated Microbiome as Pools of Richness and Complexity in a Changing World
Authors: Tavares Tallita Cruz Lopes , Bezerra Walderly Melgaço , Normando Leonardo Ribeiro Oliveira , Rosado Alexandre Soares , Melo Vânia Maria Maciel
Published: June 2023

Mangrove microbiomes play an essential role in the fate of mangroves in our changing planet, but the factors regulating the biogeographical distribution of mangrove microbial communities remain essentially vague. This paper contributes to our understanding of mangrove microbiomes distributed along three biogeographical provinces and ecoregions, covering the exuberant mangroves of Amazonia ecoregion (North Brazil Shelf) as well as mangroves located in the southern limit of distribution (Southeastern ecoregion, Warm Temperate Southwestern Atlantic) and mangroves localized on the drier semi-arid coast (Northeastern ecoregion, Tropical Southwestern Atlantic), two important ecotones where poleward and landward shifts, respectively, are expected to occur related to climate change. This study compared the microbiomes associated with the conspicuous red mangrove (Rhizophora mangle) root soils encompassing soil properties, latitudinal factors, and amplicon sequence variants of 105 samples. We demonstrated that, although the northern and southern sites are over 4,000 km apart, and despite R. mangle genetic divergences between north and south populations, their microbiomes resemble each other more than the northern and northeastern neighbors. In addition, the northeastern semi-arid microbiomes were more diverse and displayed a higher level of complexity than the northern and southern ones. This finding may reflect the endurance of the northeast microbial communities tailored to deal with the stressful conditions of semi-aridity and may play a role in the resistance and growing landward expansion observed in such mangroves. Minimum temperature, precipitation, organic carbon, and potential evapotranspiration were the main microbiota variation drivers and should be considered in mangrove conservation and recovery strategies in the Anthropocene. In the face of changes in climate, land cover, biodiversity, and chemical composition, the richness and complexity harbored by semi-arid mangrove microbiomes may hold the key to mangrove adaptability in our changing planet.
Landscape characteristics shape surface soil microbiomes in the Chihuahuan Desert
Authors: Hansen Frederick A. , James Darren K. , Anderson John P. , Meredith Christy S. , Dominguez Andrew J. , Pombubpa Nuttapon , Stajich Jason E. , Romero-Olivares Adriana L. , Salley Shawn W. , Pietrasiak Nicole
Published: June 2023

Introduction

Soil microbial communities, including biological soil crust microbiomes, play key roles in water, carbon and nitrogen cycling, biological weathering, and other nutrient releasing processes of desert ecosystems. However, our knowledge of microbial distribution patterns and ecological drivers is still poor, especially so for the Chihuahuan Desert.

Methods

This project investigated the effects of trampling disturbance on surface soil microbiomes, explored community composition and structure, and related patterns to abiotic and biotic landscape characteristics within the Chihuahuan Desert biome. Composite soil samples were collected in disturbed and undisturbed areas of 15 long-term ecological research plots in the Jornada Basin, New Mexico. Microbial diversity of cross-domain microbial groups (total Bacteria, Cyanobacteria, Archaea, and Fungi) was obtained via DNA amplicon metabarcode sequencing. Sequence data were related to landscape characteristics including vegetation type, landforms, ecological site and state as well as soil properties including gravel content, soil texture, pH, and electrical conductivity.

Results

Filamentous Cyanobacteria dominated the photoautotrophic community while Proteobacteria and Actinobacteria dominated among the heterotrophic bacteria. Thaumarchaeota were the most abundant Archaea and drought adapted taxa in Dothideomycetes and Agaricomycetes were most abundant fungi in the soil surface microbiomes. Apart from richness within Archaea (p = 0.0124), disturbed samples did not differ from undisturbed samples with respect to alpha diversity and community composition (p ≥ 0.05), possibly due to a lack of frequent or impactful disturbance. Vegetation type and landform showed differences in richness of Bacteria, Archaea, and Cyanobacteria but not in Fungi. Richness lacked strong relationships with soil variables. Landscape features including parent material, vegetation type, landform type, and ecological sites and states, exhibited stronger influence on relative abundances and microbial community composition than on alpha diversity, especially for Cyanobacteria and Fungi. Soil texture, moisture, pH, electrical conductivity, lichen cover, and perennial plant biomass correlated strongly with microbial community gradients detected in NMDS ordinations.

Discussion

Our study provides first comprehensive insights into the relationships between landscape characteristics, associated soil properties, and cross-domain soil microbiomes in the Chihuahuan Desert. Our findings will inform land management and restoration efforts and aid in the understanding of processes such as desertification and state transitioning, which represent urgent ecological and economical challenges in drylands around the world.
Phenotypic and genetic features of a novel clinically isolated rough morphotype Candida auris
Authors: Tian Sufei , Bing Jian , Chu Yunzhuo , Li Hailong , Wang Qihui , Cheng Shitong , Chen Jingjing , Shang Hong
Published: June 2023

Introduction

Candida auris is a newly emerging pathogenic fungus of global concern and has been defined by the World Health Organization (WHO) as a member of the critical group of the most health-threatening fungi.

Methods

This study reveals and reports for the first time that a rough morphotype C. auris strain causes urinary tract infections in non-intensive care unit (ICU) inpatients. Furthermore, the morphology, the scanning electronmicroscopy (SEM), Whole-genome resequencing and RNA sequencing of C. auris possessing rough morphotype colonies compared to their smooth morphotype counterparts.

Results

The newly identified phenotypic variation of C. auris appears round, convex, dry, and burr-like with a rough texture. SEM shows that rough type C. auris has a rough and uneven colony surface with radial wrinkles and irregular spore arrangement. Cells of the rough morphotype C. auris naturally aggregate into clusters with tight connections in the liquid, and it seems that the cell division is incomplete. A genome-wide analysis of the rough type C. auris confirmed its genetic association with the smooth type of C. auris prevalent in China (Shenyang) two years ago; however, single nucleotide polymorphism (SNP) mutations of five genes (ACE2, IFF6, RER2, UTP20, and CaO19.5847) were identified more recently. RNA-seq revealed IFF2/HYR3, DAL5, PSA31, and SIT1 were notably up-regulated, while multiple cell wall-associated genes (ALS1, MNN1, PUL1, DSE1, SCW11, PGA38, RBE1, FGR41, BGLI, GIT3, CEP3, and SAP2) were consistently down-regulated in rough morphotype C. auris.

Discussion

The rough phenotypic variation of C. auris is likely to be related to the structural and functional changes in cell wall proteins. This novel rough morphotype C. auris will provide a basis for further studies concerning the evolutionary characteristics of C. auris.
Multi-omic analysis of glycolytic signatures: exploring the predictive significance of heterogeneity and stemness in immunotherapy response and outcomes in hepatocellular carcinoma
Authors: Zhang Shiyu , Pei Yangting , Zhu Feng
Published: June 2023

Background: Hepatocellular carcinoma (HCC) is a global health challenge with complex pathophysiology, characterized by high mortality rates and poor early detection due to significant tumor heterogeneity. Stemness significantly contributes to the heterogeneity of HCC tumors, and glycolysis is crucial for maintaining stemness. However, the predictive significance of glycolysis-related metabolic genes (GMGs) in HCC remains unknown. Therefore, this study aimed to identify critical GMGs and establish a reliable model for HCC prognosis.

Methods: GMGs associated with prognosis were identified by evaluating genes with notable expression changes between HCC and normal tissues retrieved from the MsigDB database. Prognostic gene characteristics were established using univariate and multivariate Cox regression studies for prognosis prediction and risk stratification. The “CIBERSORT” and “pRRophetic” R packages were respectively used to evaluate the immunological environment and predict treatment response in HCC subtypes. The HCC stemness score was obtained using the OCLR technique. The precision of drug sensitivity prediction was evaluated using CCK-8 experiments performed on HCC cells. The miagration and invasion ability of HCC cell lines with different riskscores were assessed using Transwell and wound healing assays.

Results: The risk model based on 10 gene characteristics showed high prediction accuracy as indicated by the receiver operating characteristic (ROC) curves. Moreover, the two GMG-related subgroups showed considerable variation in the risk of HCC with respect to tumor stemness, immune landscape, and prognostic stratification. The in vitro validation of the model’s ability to predict medication response further demonstrated its reliability.

Conclusion: Our study highlights the importance of stemness variability and inter-individual variation in determining the HCC risk landscape. The risk model we developed provides HCC patients with a novel method for precision medicine that enables clinical doctors to customize treatment plans based on unique patient characteristics. Our findings have significant implications for tailored immunotherapy and chemotherapy methods, and may pave the way for more personalized and effective treatment strategies for HCC.
Continuation of immunosuppression vs. immunosuppression weaning in potential repeat kidney transplant candidates: a care management perspective
Authors: Hickey Michelle J. , Singh Gurbir , Lum Erik L.
Published: June 2023

Management of immunosuppression in patients with a failing or failed kidney transplant requires a complete assessment of their clinical condition. One of the major considerations in determining immunosuppression is whether or not such an individual is considered a candidate for re-transplantation. Withdrawal of immunosuppression in a re-transplant candidate can result in allosensitization and markedly reduce the chances of a repeat transplant. In this review, we summarize the effects of immunosuppression reduction on HLA sensitization, discuss the impacts of allosensitization in these patients, and explore reduction protocols and future directions. Risks of chronic immunosuppression, medical management of the failing allograft, and the effect of nephrectomy are covered elsewhere in this issue.
A comprehensive review of stroke-related signaling pathways and treatment in western medicine and traditional Chinese medicine
Authors: Chen Binhao , Jin Weifeng
Published: June 2023

This review provides insight into the complex network of signaling pathways and mechanisms involved in stroke pathophysiology. It summarizes the historical progress of stroke-related signaling pathways, identifying potential interactions between them and emphasizing that stroke is a complex network disease. Of particular interest are the Hippo signaling pathway and ferroptosis signaling pathway, which remain understudied areas of research, and are therefore a focus of the review. The involvement of multiple signaling pathways, including Sonic Hedgehog (SHH), nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE), hypoxia-inducible factor-1α (HIF-1α), PI3K/AKT, JAK/STAT, and AMPK in pathophysiological mechanisms such as oxidative stress and apoptosis, highlights the complexity of stroke. The review also delves into the details of traditional Chinese medicine (TCM) therapies such as Rehmanniae and Astragalus, providing an analysis of the recent status of western medicine in the treatment of stroke and the advantages and disadvantages of TCM and western medicine in stroke treatment. The review proposes that since stroke is a network disease, TCM has the potential and advantages of a multi-target and multi-pathway mechanism of action in the treatment of stroke. Therefore, it is suggested that future research should explore more treasures of TCM and develop new therapies from the perspective of stroke as a network disease.