bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospect of genetic disorders in Saudi Arabia
Authors: Alqahtani Amerh S. , Alotibi Raniah S. , Aloraini Taghrid , Almsned Fahad , Alassali Yara , Alfares Ahmed , Alhaddad Bader , Al Eissa Mariam M.
Published: September 2023

Introduction: Rare diseases (RDs) create a massive burden for governments and families because sufferers of these diseases are required to undergo long-term treatment or rehabilitation to maintain a normal life. In Saudi Arabia (SA), the prevalence of RDs is high as a result of cultural and socio-economic factors. This study, however, aims to shed light on the genetic component of the prevalence of RDs in SA.

Methodology: A retrospective study was conducted between September 2020 and December 2021 at King Saud Medical City, a tertiary hospital of the Ministry of Health (MOH), SA. A total of 1080 individuals with 544 potentially relevant variants were included. The index was 738, and the samples were tested in a commercialized laboratory using different molecular techniques, including next-generation sequencing.

Result: A total of 867 molecular genetics tests were conducted on 738 probands. These tests included 610 exome sequencing (ES) tests, four genome sequencing (GS) tests, 82 molecular panels, 106 single nucleotide polymorphism (SNP) array, four methylation studies, 58 single-gene studies and three mitochondrial genome sequencing tests. The diagnostic yield among molecular genetics studies was 41.8% in ES, 24% in panels, 12% in SNP array and 24% in single gene studies. The majority of the identified potential variants (68%) were single nucleotide variants (SNV). Other ascertained variants included frameshift (11%), deletion (10%), duplication (5%), splicing (9%), in-frame deletion (3%) and indels (1%). The rate of positive consanguinity was 56%, and the autosomal recessive accounted for 54%. We found a significant correlation between the ES detection rate and positive consanguinity. We illustrated the presence of rare treatable conditions in DNAJC12, SLC19A3, and ALDH7A1, and the presence of the founder effect variant in SKIC2. Neurodevelopmental disorders were the main phenotype for which genetics studies were required (35.7%).

Conclusion: This is the sixth-largest local study reporting next-generation sequencing. The results indicate the influence of consanguineous marriages on genetic disease and the burden it causes for the Kingdom of SA. This study highlights the need to enrich our society’s knowledge of genetic disorders. We recommend utilising ES as a first-tier test to establish genetic diagnosis in a highly consanguineous population.
TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype and is associated with increased survival in cancer patients with high tumor macrophage content
Authors: Gunalp Sinem , Helvaci Derya Goksu , Oner Aysenur , Bursalı Ahmet , Conforte Alessandra , Güner Hüseyin , Karakülah Gökhan , Szegezdi Eva , Sag Duygu
Published: September 2023

Background

TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can either induce cell death or activate survival pathways after binding to death receptors (DRs) DR4 or DR5. TRAIL is investigated as a therapeutic agent in clinical trials due to its selective toxicity to transformed cells. Macrophages can be polarized into pro-inflammatory/tumor-fighting M1 macrophages or anti-inflammatory/tumor-supportive M2 macrophages and an imbalance between M1 and M2 macrophages can promote diseases. Therefore, identifying modulators that regulate macrophage polarization is important to design effective macrophage-targeted immunotherapies. The impact of TRAIL on macrophage polarization is not known.

Methods

Primary human monocyte-derived macrophages were pre-treated with either TRAIL or with DR4 or DR5-specific ligands and then polarized into M1, M2a, or M2c phenotypes in vitro. The expression of M1 and M2 markers in macrophage subtypes was analyzed by RNA sequencing, qPCR, ELISA, and flow cytometry. Furthermore, the cytotoxicity of the macrophages against U937 AML tumor targets was assessed by flow cytometry. TCGA datasets were also analyzed to correlate TRAIL with M1/M2 markers, and the overall survival of cancer patients.

Results

TRAIL increased the expression of M1 markers at both mRNA and protein levels while decreasing the expression of M2 markers at the mRNA level in human macrophages. TRAIL also shifted M2 macrophages towards an M1 phenotype. Our data showed that both DR4 and DR5 death receptors play a role in macrophage polarization. Furthermore, TRAIL enhanced the cytotoxicity of macrophages against the AML cancer cells in vitro. Finally, TRAIL expression was positively correlated with increased expression of M1 markers in the tumors from ovarian and sarcoma cancer patients and longer overall survival in cases with high, but not low, tumor macrophage content.

Conclusions

TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype via both DR4 and DR5. Our study defines TRAIL as a new regulator of macrophage polarization and suggests that targeting DRs can enhance the anti-tumorigenic response of macrophages in the tumor microenvironment by increasing M1 polarization.
Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease
Authors: Dai Zhi-Cheng , Chen Jin-Xia , Zou Rong , Liang Xuan-Bing , Tang Ji-Xin , Yao Cui-Wei
Published: September 2023

Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages. However, recent findings from the DAPA-CKD and EMPA-KIDNEY studies have revealed equally beneficial cardiorenal effects of SGLT-2 inhibitors in individuals at stage G4 DKD, although the underlying mechanism behind this phenomenon remains unclear. In this comprehensive analysis, we provide a systematic review of the mechanisms and functioning of SGLT-2 inhibitors, potential renal protection mechanisms, and the therapeutic efficacy and safety of SGLT-2 inhibitors in kidney diseases, with a particular focus on stage G4 DKD. Gaining a deeper understanding of the renal protective effect of SGLT-2 inhibitors and their underlying mechanisms is highly significance for the successful utilization of these inhibitors in the treatment of diverse kidney disorders.
The interplay between neoantigens and immune cells in sarcomas treated with checkpoint inhibition
Authors: Anzar Irantzu , Malone Brandon , Samarakoon Pubudu , Vardaxis Ioannis , Simovski Boris , Fontenelle Hugues , Meza-Zepeda Leonardo A. , Stratford Richard , Keung Emily Z. , Burgess Melissa , Tawbi Hussein A. , Myklebost Ola , Clancy Trevor
Published: September 2023

Introduction

Sarcomas are comprised of diverse bone and connective tissue tumors with few effective therapeutic options for locally advanced unresectable and/or metastatic disease. Recent advances in immunotherapy, in particular immune checkpoint inhibition (ICI), have shown promising outcomes in several cancer indications. Unfortunately, ICI therapy has provided only modest clinical responses and seems moderately effective in a subset of the diverse subtypes.

Methods

To explore the immune parameters governing ICI therapy resistance or immune escape, we performed whole exome sequencing (WES) on tumors and their matched normal blood, in addition to RNA-seq from tumors of 31 sarcoma patients treated with pembrolizumab. We used advanced computational methods to investigate key immune properties, such as neoantigens and immune cell composition in the tumor microenvironment (TME).

Results

A multifactorial analysis suggested that expression of high quality neoantigens in the context of specific immune cells in the TME are key prognostic markers of progression-free survival (PFS). The presence of several types of immune cells, including T cells, B cells and macrophages, in the TME were associated with improved PFS. Importantly, we also found the presence of both CD8+ T cells and neoantigens together was associated with improved survival compared to the presence of CD8+ T cells or neoantigens alone. Interestingly, this trend was not identified with the combined presence of CD8+ T cells and TMB; suggesting that a combined CD8+ T cell and neoantigen effect on PFS was important.

Discussion

The outcome of this study may inform future trials that may lead to improved outcomes for sarcoma patients treated with ICI.
Non-classical HLA-E restricted CMV 15-mer peptides are recognized by adaptive NK cells and induce memory responses
Authors: Martín Almazán Nerea , Sala Benedetta Maria , Sandalova Tatyana , Sun Yizhe , Resink Tom , Cichocki Frank , Söderberg-Nauclér Cecilia , Miller Jeffrey S. , Achour Adnane , Sarhan Dhifaf
Published: September 2023

Introduction

Human cytomegalovirus (HCMV) reactivation causes complications in immunocompromised patients after hematopoietic stem cell transplantation (HSCT), significantly increasing morbidity and mortality. Adaptive Natural Killer (aNK) cells undergo a persistent reconfiguration in response to HCMV reactivation; however, the exact role of aNK cell memory in HCMV surveillance remains elusive.

Methods

We employed mass spectrometry and computational prediction approaches to identify HLA-E-restricted HCMV peptides that can elucidate aNK cell responses. We also used the K562 cell line transfected with HLA-E0*0103 for specific peptide binding and blocking assays. Subsequently, NK cells were cocultured with dendritic cells (DCs) loaded with each of the identified peptides to examine aNK and conventional (c)NK cell responses.

Results

Here, we discovered three unconventional HLA-E-restricted 15-mer peptides (SEVENVSVNVHNPTG, TSGSDSDEELVTTER, and DSDEELVTTERKTPR) derived from the HCMV pp65-protein that elicit aNK cell memory responses restricted to HCMV. aNK cells displayed memory responses towards HMCV-infected cells and HCMV-seropositive individuals when primed by DCs loaded with each of these peptides and predicted 9-mer versions. Blocking the interaction between HLA-E and the activation NKG2C receptor but not the inhibitory NKG2A receptor abolished these specific recall responses. Interestingly, compared to the HLA-E complex with the leader peptide VMAPRTLIL, HLA-E complexes formed with each of the three identified peptides significantly changed the surface electrostatic potential to highly negative. Furthermore, these peptides do not comprise the classical HLA-E-restriction motifs.

Discussion

These findings suggest a differential binding to NKG2C compared to HLA-E complexes with classical leader peptides that may result in the specific activation of aNK cells. We then designed six nonameric peptides based on the three discovered peptides that could elicit aNK cell memory responses to HCMV necessary for therapeutic inventions. The results provide novel insights into HLA-E-mediated signaling networks that mediate aNK cell recall responses and maximize their reactivity.
Widespread and dynamic expression of granzyme C by skin-resident antiviral T cells
Authors: Lujan Ramon A. , Pei Luxin , Shannon John P. , Dábilla Nathânia , Dolan Patrick T. , Hickman Heather D.
Published: September 2023

After recognition of cognate antigen (Ag), effector CD8+ T cells secrete serine proteases called granzymes in conjunction with perforin, allowing granzymes to enter and kill target cells. While the roles for some granzymes during antiviral immune responses are well characterized, the function of others, such as granzyme C and its human ortholog granzyme H, is still unclear. Granzyme C is constitutively expressed by mature, cytolytic innate lymphoid 1 cells (ILC1s). Whether other antiviral effector cells also produce granzyme C and whether it is continually expressed or responsive to the environment is unknown. To explore this, we analyzed granzyme C expression in different murine skin-resident antiviral lymphocytes. At steady-state, dendritic epidermal T cells (DETCs) expressed granzyme C while dermal γδ T cells did not. CD8+ tissue-resident memory T cells (TRM) generated in response to cutaneous viral infection with the poxvirus vaccinia virus (VACV) also expressed granzyme C. Both DETCs and virus-specific CD8+ TRM upregulated granzyme C upon local VACV infection. Continual Ag exposure was not required for maintained TRM expression of granzyme C, although re-encounter with cognate Ag boosted expression. Additionally, IL-15 treatment increased granzyme C expression in both DETCs and TRM. Together, our data demonstrate that granzyme C is widely expressed by antiviral T cells in the skin and that expression is responsive to both environmental stimuli and TCR engagement. These data suggest that granzyme C may have functions other than killing in tissue-resident lymphocytes.
A comprehensive pan-cancer analysis of CDH5 in immunological response
Authors: Li Yuantao , Wu Qikai , Lv Jiancheng , Gu Junwei
Published: September 2023

Background

Cadherin 5 (CDH5) functions critically in maintaining cell adhesion and integrity of endothelial and vascular cells. The expression of CDH5 is abnormal in tumor cells, which may have great potential to serve as a new immune checkpoint. The current pan-cancer analysis was performed to better understand the role of CDH5 in tumor.

Methods

The clinical significance and immunological function of CDH5 in pan-cancers were comprehensively analyzed based on the correlations between CDH5 and clinicopathologic features, prognosis values, tumor mutation burden (TMB), microsatellite instability (MSI), immune cells infiltration and immune response genes using 33 datasets from The Cancer Genome Atlas (TCGA). We further confirmed the expression of CDH5 in bladder cancer (BCa) tissues and cell lines. The CD8+ T cells were screened from peripheral blood of healthy controls and activated. BCa cell-CD8+ T cell co-culture assay and ELISA assay were carried out to verify the immunological function of CDH5.

Results

The expression of CDH5 was down-regulated in 8 types of tumors including in BCa but up-regulated in 4 types of tumors. CDH5 was significantly correlated with tumor stage in 6 types of tumors. In addition, CDH5 was positively or negatively correlated with tumor prognosis. Furthermore, CDH5 was closely associated with TMB in 15 types of tumors and with MSI in 9 types of tumors. KEGG-GSEA and Hallmarks-GSEA analyses results indicated that CDH5 was positively related to immune response in most tumor types. In many tumors, CDH5 showed a positive correlation with immune cell infiltration. Enrichment analyses demonstrated that CDH5 was significantly related to the expression of many immunomodulators and chemokines. Further experiments showed that CDH5 was low-expressed in BCa tissues and cell lines in comparison to adjacent normal tissues and normal urothelial cell line, but it was positively associated with a better prognosis of BCa patients. The results of in vitro co-culture assay and ELISA assay demonstrated that CDH5 could promote the function of CD8+ T cells in TME of BCa.

Conclusion

In summary, CDH5 was positively associated with a favorable prognosis and effective immune response in tumors, showing a great potential to serve as a novel tumor biomarker and immune checkpoint.
Immune monitoring of SARS-CoV-2-specific T cell and B cell responses in patients with multiple sclerosis treated with ocrelizumab
Authors: Groß-Albenhausen Elina , Weier Alicia , Velten Markus , Heider Thorsten , Chunder Rittika , Kuerten Stefanie
Published: September 2023

Introduction

Since the development of the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there has been significant interest in determining the effectiveness of SARS-CoV-2 vaccines in patients under immunomodulatory or immunosuppressive therapies. The aim of this study was to evaluate the impact of ocrelizumab, a monoclonal anti-CD20 antibody, on SARS-CoV-2-specific T cell and B cell responses in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods

To this end, peripheral blood mononuclear cells (PBMCs) were isolated from n = 23 patients with RRMS. Of these patients, n = 17 were tested before (time point t0) and one month after (time point t1) their first dose of ocrelizumab. In addition, we studied n = 9 RRMS patients that got infected with SARS-CoV-2 over the course of ocrelizumab therapy (time point t2). PBMCs were also isolated from n = 19 age- and gender-matched healthy controls (HCs) after vaccination or infection with SARS-CoV-2, respectively. Interferon-γ (IFN-γ)/interleukin-2 (IL-2) and granzyme B (GzB)/perforin (PFN) double-color enzyme-linked immunospot (ELISPOT) assays or single-color ELISPOT assays were performed to measure SARS-CoV-2 antigen-specific T cell and B cell responses. Anti-viral antibody titers were quantified in the serum by chemiluminescence immunoassay.

Results

Our data indicate a significant difference in the SARS-CoV-2 specific IFN-γ (P = 0.0119) and PFN (P = 0.0005) secreting T cell compartment in the MS cohort at t0 compared to HCs. Following the first dose of ocrelizumab treatment, a significant decrease in the number of SARS-CoV-2 spike protein-specific B cells was observed (P = 0.0012). Infection with SARS-CoV-2 in MS patients under ocrelizumab therapy did not significantly alter their existing immune response against the virus. Kaplan-Meier survival analysis suggested that the spike S1 protein-specific immunoglobulin (Ig)G response might be a key parameter for predicting the probability of (re)infection with SARS-CoV-2.

Discussion

Our results call for a critical discussion regarding appropriate vaccination intervals and potential biomarkers for the prediction of (re)infection with SARS-CoV-2 in patients with MS receiving ocrelizumab.

Unique identifier

DRKS00029110; URL: http://apps.who.int/trialsearch/.
Modulation of intestinal IL-37 expression and its impact on the epithelial innate immune response and barrier integrity
Authors: Kröhn Laura , Azabdaftari Aline , Heuberger Julian , Hudert Christian , Zilbauer Matthias , Breiderhoff Tilman , Bufler Philip
Published: September 2023

Background and Aims

Intestinal epithelial cells separate the luminal flora from lamina propria immune cells and regulate innate immune responses in the gut. An imbalance of the mucosal immune response and disrupted intestinal barrier integrity contribute to the evolution of inflammatory bowel diseases. Interleukin (IL)-37 has broad anti- inflammatory activity and is expressed by the human intestinal epithelium. Mice ectopically expressing human IL-37 show reduced epithelial damage and inflammation after DSS-induced colitis. Here, we investigated the impact of IL-37 on the innate immune response and tight junction protein expression of mouse intestinal organoids and the modulation of IL37 expression in human intestinal organoids.

Methods

Murine intestinal organoids were generated from IL-37tg and wildtype mice. Human ileal organoids were generated from healthy young donors.

Results

Expression of transgene IL-37 or recombinant IL-37 protein did not significantly reduce overall proinflammatory cytokine mRNA expression in murine intestinal organoids. However, higher IL37 expression correlated with a reduced proinflammatory cytokine response in murine colonic organoids. IL37 mRNA expression in human ileal organoids was modulated by proinflammatory cytokines showing an increased expression upon TNF-α-stimulation and decreased expression upon IFN-gamma stimulation. Transgene IL-37 expression did not rescue TNF-α-induced changes in morphology as well as ZO-1, occludin, claudin-2, and E-cadherin expression patterns of murine jejunal organoids.

Conclusions

We speculate that the anti-inflammatory activity of IL-37 in the intestine is mainly mediated by lamina propria immune cells protecting intestinal epithelial integrity.
Etiologic characteristics revealed by mNGS-mediated ultra-early and early microbiological identification in airway secretions from lung transplant recipients
Authors: Zhang Xiaoqin , Tang Xuemei , Yi Xiaoli , Lei Yu , Lu Sen , Li Tianlong , Yue Ruiming , Pan Lingai , Feng Gang , Huang Xiaobo , Wang Yiping , Cheng Deyun
Published: September 2023

Background

Post-operative etiological studies are critical for infection prevention in lung transplant recipients within the first year. In this study, mNGS combined with microbial culture was applied to reveal the etiological characteristics within one week (ultra-early) and one month (early) in lung transplant recipients, and the epidemiology of infection occurred within one month.

Methods

In 38 lung transplant recipients, deep airway secretions were collected through bronchofiberscope within two hours after the operation and were subjected to microbial identification by mNGS and microbial culture. The etiologic characteristics of lung transplant recipients were explored. Within one month, the infection status of recipients was monitored. The microbial species detected by mNGS were compared with the etiological agents causing infection within one month.

Results

The detection rate of mNGS in the 38 airway secretions specimens was significantly higher than that of the microbial culture (P<0.0001). MNGS identified 143 kinds of pathogenic microorganisms; bacterial pathogens account for more than half (72.73%), with gram-positive and -negative bacteria occupying large proportions. Fungi such as Candida are also frequently detected. 5 (50%) microbial species identified by microbial culture had multiple drug resistance (MDR). Within one month, 26 (68.42%) recipients got infected (with a median time of 9 days), among which 10 (38.46%) cases were infected within one week. In the infected recipients, causative agents were detected in advance by mNGS in 9 (34.62%) cases, and most of them (6, 66.67%) were infected within one week (ultra-early). In the infection that occurred after one week, the consistency between mNGS results and the etiological agents was decreased.

Conclusion

Based on the mNGS-reported pathogens in airway secretions samples collected within two hours, the initial empirical anti-infection regimes covering the bacteria and fungi are reasonable. The existence of bacteria with MDR forecasts the high risk of infection within 48 hours after transplant, reminding us of the necessity to adjust the antimicrobial strategy. The predictive role of mNGS performed within two hours in etiological agents is time-limited, suggesting continuous pathogenic identification is needed after lung transplant.
Effects of climate change and variability on large pelagic fish in the Northwest Atlantic Ocean: implications for improving climate resilient management for pelagic longline fisheries
Authors: Dell’Apa Andrea , Boenish Robert , Fujita Rod , Kleisner Kristin
Published: September 2023

Climate change influences marine environmental conditions and is projected to increase future environmental variability. In the North Atlantic, such changes will affect the behavior and spatiotemporal distributions of large pelagic fish species (i.e., tunas, billfishes, and sharks). Generally, studies on these species have focused on specific climate-induced changes in abiotic factors separately (e.g., water temperature) and on the projection of shifts in species abundance and distribution based on these changes. In this review, we consider the latest research on spatiotemporal effects of climate-induced environmental changes to HMS’ life history, ecology, physiology, distribution, and habitat selection, and describe how the complex interplay between climate-induced changes in biotic and abiotic factors, including fishing, drives changes in species productivity and distribution in the Northwest Atlantic. This information is used to provide a baseline for investigating implications for management of pelagic longline fisheries and to identify knowledge gaps in this region. Warmer, less oxygenated waters may result in higher post-release mortality in bycatch species. Changes in climate variability will likely continue to alter the dynamics of oceanographic processes regulating species behavior and distribution, as well as fishery dynamics, creating challenges for fishery management. Stock assessments need to account for climate-induced changes in species abundance through the integration of species-specific responses to climate variability. Climate-induced changes will likely result in misalignment between current spatial and temporal management measures and the spatiotemporal distribution of these species. Finally, changes in species interactions with fisheries will require focused research to develop best practices for adaptive fisheries management and species recovery.
Effects of marine seismic surveys on free-ranging fauna: a systematic literature review
Authors: Affatati Alice , Camerlenghi Angelo
Published: September 2023

Among anthropogenic activities, marine seismic surveys are a fundamental tool for oil and gas explorations, geophysical research, environmental hazard, and risk analysis. This resulting noise may affect a range of species, eliciting masking, behavioral responses, and changes in acoustic repertoires. There is an urgency to understand in depth the potential effects of seismic surveys on marine ecosystems since the information available is still scarce. Using Scopus® and Web of Science™ 2023 Clarivate bibliographic databases, we systematically reviewed the scientific literature addressing seismic surveys’ effects on free-ranging marine fauna. The first selection of articles matching selected keywords yielded 680 articles from Scopus and 320 from Web of Science. Screening for research articles written in English investigating marine fauna in its natural environment and performing a quality assessment process resulted in selecting 31 articles since 2001. We found a trend of increasing research efforts in this field with a decrease after 2020 and a broad spectrum of journals that hosted the publications (31 papers published in 12 journals). Although several taxa are investigated, most studies focused on effects on marine mammals. There is a lack of research on diverse animal taxa, and no research papers compare the effects on different taxa along the food chain. Behavioral and physiological effects are the most found by authors in the field. However, observed behavioral changes cannot always be uniquely attributed to the exposure to seismic surveys, as many authors report the influence of other variables (e.g., environmental conditions) during the observations.
Evaluation of medication errors in nursing during the COVID-19 pandemic and their relationship with shift work at teaching hospitals: a cross-sectional study in Iran
Authors: Gilavand Abdolreza , Jafarian Negar , Zarea Kourosh
Published: September 2023

Introduction

Medication errors in nursing negatively affect the quality of the provided health-treatment services and society’s mentality about the health system, threatening the patient’s life. Therefore, this study evaluates medication errors in nursing during the COVID-19 pandemic and their relationship with shift work at teaching hospitals.

Materials and methods

All the nurses working at teaching hospitals affiliated with Ahvaz Jundishapur University of Medical Sciences (southwest of Iran) comprised the statistical population of this research (260 participants). Data were collected using three questionnaires: a demographic characteristics questionnaire, a medication error questionnaire, and the standard Circadian Type Inventory (CTI) for a normal physiological cycle.

Results

At least one medication error was observed in 83.1% of nurses during their work span. A medication error was found in 36.2% of nurses during the COVID-19 pandemic (over the past year). Most medication errors (65.8%) occurred during the night shift. A significant relationship was detected between medication errors and shift work. Medicating one patient’s drug to another (28.84%) and giving the wrong dose of drugs (27.69) were the most common types of medication errors. The utmost medication error was reported in emergency wards. The fear of reporting (with an average of 33.06) was the most important reason for not reporting medication errors (p < 0.01).

Discussion and conclusion

Most nurses experienced a history of medication errors, which were increased by shift work and the COVID-19 pandemic. Necessary plans are recommended to reduce the fatigue and anxiety of nurses and prevent their burnout, particularly in critical situations. Efforts to identify risky areas, setting up reporting systems and error reduction strategies can help to develop preventive medicine. On the other hand, since the quality of people’s lives is considered the standard of countries’ superiority, by clarifying medical errors, a higher level of health, satisfaction and safety of patients will be provided.
Association between alkaline phosphatase/albumin ratio and the prognosis in patients with chronic kidney disease stages 1–4: results from a C-STRIDE prospective cohort study
Authors: Xue Xue , Li Jia-Xuan , Wang Jin-Wei , Lin La-Mei , Cheng Hong , Deng Dan-Fang , Xu Wen-Cheng , Zhao Yu , Zou Xin-Rong , Yuan Jun , Zhang Lu-Xia , Zhao Ming-Hui , Wang Xiao-Qin
Published: September 2023

Background

The alkaline phosphatase-to-albumin ratio (APAR) has been demonstrated to be a promising non-invasive biomarker for predicting prognosis in certain diseases. However, the relationship between APAR and prognosis in non-dialysis chronic kidney disease (CKD) patients remains unclear. This study aims to identify the association between APAR and prognosis among CKD stages 1–4 in China.

Methods

Patients with CKD stages 1–4 were consecutively recruited from 39 clinical centers in China from 2011 to 2016. New occurrences of end-stage kidney disease (ESKD), major adverse cardiovascular and cerebrovascular events, and all-cause deaths were the outcome events of this study. Subdistribution hazard competing risk and Cox proportional hazards regression models were adopted.

Results

A total of 2,180 participants with baseline APAR values were included in the analysis. In the primary adjusted analyses, higher APAR level [per 1-standard deviation (SD) increase in natural logarithm transformed (ln-transformed) APAR] was associated with 33.5% higher risk for all-cause deaths [adjusted hazard ratio (HR) 1.335, 95% confidence interval (CI) 1.068–1.670]. In addition, there was evidence for effect modification of the association between APAR and ESKD by baseline estimated glomerular filtration rate (eGFR) (P interaction < 0.001). A higher APAR level (per 1-SD increase in ln-transformed APAR) was associated with a greater risk of ESKD among participants with eGFR ≥ 60 ml/min/1.73 m2 (adjusted SHR 1.880, 95% CI 1.260–2.810) but not in eGFR < 60 ml/min/1.73 m2.

Conclusion

Higher APAR levels in patients with CKD stages 1–4 seemed to be associated with an increased risk of all-cause death. Thus, APAR appears to be used in risk assessment for all-cause death among patients with CKD stages 1–4.
Therapies for people hospitalized with COVID-19 and alignment with national clinical guidelines in a large hospital, Almaty, Kazakhstan, 2020–2021
Authors: Gazezova Saya , Nabirova Dilyara , Detmar Ariana , Smagul Manar , Kasabekova Lena , Zikriyarova Sanam , Horth Roberta
Published: September 2023

Background

Clinical practice guidelines were continually changing during the COVID-19 pandemic to reflect the best available evidence for a novel virus. In Kazakhstan, the national clinical guidelines for COVID-19 patient care were regularly modified and it was not known if and to what extent these guidelines were being followed in practice.

Methods

We conducted a sub-analysis of data collected from an observational study among people hospitalized with COVID-19 in a large infectious disease hospital in Almaty in four cross-sections of increased COVID-19 incidence: T1 (1 June–30 August 2020); T2 (1 October–31 December 2020); T3 (1 April–31 May 2021); and T4 (1 July–26 October 2021). Modifications to the national COVID-19 treatment guidelines were identified and clinical data were abstracted from electronic medical records. We assessed frequency of antibiotic, glucocorticoid, anticoagulant, and antiviral administered in each period and determined if these aligned with national clinical guidelines. We used multivariable logistic regression to compare practices across periods.

Results

Six modifications were made to national COVID-19 treatment guidelines during this study. Of 1,146 people hospitalized with COVID-19, 14% were in T1, 14% in T2, 22% in T3, and 50% in T4. Anticoagulant treatment was administered to 87% (range: 56%–95%), antibiotic treatment to 60% (range: 58%–64%), glucocorticoid to 55% (range: 43%–64%) and antiviral therapy 15% (range: 7%–22%). Majority of treatments were not aligned with national guidelines, including 98% of anticoagulant use, 95% of antibiotic use, 56% of glucocorticoid use, and 56% of antiviral use. There were no significant changes in practice following changes in guidelines for antibiotic use (64% in T1 to 58% in T2, p = 0.30). There was significant increase in use of anticoagulant (84% in T2 vs. 95% in T3, p < 0.01), glucocorticoid (43% in T2 vs. 64% in T3, p < 0.01), and antiviral treatment (7% in T3 vs. 15% in T4, p < 0.01) after guidelines updates.

Conclusion

The majority of treatments administered to people hospitalized with COVID-19 in four periods of high incidence in Almaty were not aligned with updated clinical guidelines. Antibiotic misuse was markedly high throughout. Increased awareness and training on clinical practice guidelines as updates are released may help improve adoption of evidence-based practices.
Israeli pediatricians’ confidence level in diagnosing and treating children with skin disorders: a cross-sectional questionnaire pilot study
Authors: Andre Nicolas , Muallem Liezl , Yahav Lior , Golan-Tripto Inbal , Shmuel Atar Ben , Horev Amir
Published: September 2023

Background

Pediatricians daily see large numbers of patients with skin disorders. However, they encounter limited guidance as a result of a marked deficiency in pediatric dermatologists. Hence, reevaluation of training opportunities during pediatric residency has become essential. Our aim was to evaluate the confidence level of pediatric residents and specialists in diagnosing and treating skin disorders in children and to determine career and training-related characteristics that influence it.

Methods

Conducted as a cross-sectional study, we administered a questionnaire to 171 pediatricians across Israel. We assessed respondents’ self-efficacy about their ability to diagnose and treat skin disorders and collected data regarding their previous dermatology training and preferred training methods.

Results

77.8% of respondents reported below or average self-efficacy scores in diagnosing and managing children with skin disorders. Older age (>40 years old; OR = 5.51, p = 0.019), treating a higher number of patients with skin disorders (OR = 2.96, p = 0.032), and having any training in dermatology, either during medical school or residency (OR = 7.16, p = 0.031, OR = 11.14, p = 0.003 respectively), were all significant parameters involved in pediatricians reporting high self-efficacy in skin disorder management.

Conclusion

Most pediatric residents and pediatricians have average or below-average confidence in managing pediatric skin disorders. We suggest incorporating dermatology rotations during pediatric residency to improve young pediatricians’ self-efficacy in managing skin disorders and ultimately help pediatricians provide better care for patients presenting with dermatological conditions. These findings can ultimately help refine a pilot program in dermatology that might be implemented during pediatric residency.
Effects of different types of vegetation cover on soil microorganisms and humus characteristics of soda-saline land in the Songnen Plain
Authors: Guo Liangliang , Tóth Tibor , Yang Fan , Wang Zhichun
Published: September 2023

Introduction

In the soda-saline grasslands of the Songnen Plain, Jilin Province, China, the prohibition of grazing has led to significant changes in plant communities and soil properties. However, the intricate interplay between soil physical and chemical attributes, the soil microbial community, and their combined influence on soil humus composition remains poorly understood.

Methods

Our study aimed to evaluate the impact of natural vegetation restoration on soil properties, microbial community diversity, and composition in the soda-saline soil region of the Songnen Plain. We conducted assessments of soil physical and chemical properties, analyzed community diversity, and composition at a soil depth range of 0–20 cm. The study covered soils with dominant soda-saline vegetation species, including Suaeda glauca Bunge, Puccinellia chinampoensis Ohwi, Chloris virgata Swarta, Phragmites australis (Clay.), Leymus chinensis (Trin.), and Tzvelev. We compared these vegetated soils to bare land devoid of any plants.

Results

We found that soil organic content (SOC) in vegetation restoration areas was higher than in bare land, with SOC content varying between 3.64 and 11.15 g/kg in different vegetated areas. Notably, soil pH emerged as a pivotal factor, explaining 11.4% and 12.2% of the variance in soil bacteria and fungi, respectively. There were correlations between SOC content and the relative abundance of specific microbial groups, with Acidobacteria and Mortierella showing a positive correlation, while Actinobacteria, Gemmatimonadetes, and Ascomycota exhibited significant negative correlations with SOC.

Discussion

The disparities in SOC composition and content among the soda-saline vegetation types were primarily attributed to variations in pH. Consequently, reducing soil pH is identified as a critical step in the process of vegetation restoration in soda-saline land. Prohibiting grazing has the potential to increase soda-saline SOC content and enhance microbial diversity, with Leymus chinensis and Phragmites australis showing particularly promising results in terms of higher SOC carbon content and microbial diversity.
Exploring the mechanisms of endophytic bacteria for suppressing early blight disease in tomato (Solanum lycopersicum L.)
Authors: Sallam Nashwa M. A. , AbdElfatah Heba-Alla S. , Khalil Bagy Hadeel M. M. , Elfarash Ameer , Abo-Elyousr Kamal A. M. , Sikora Edward J. , Sallam Ahmed
Published: September 2023

Controlling early blight of tomatoes using endophytic bacteria is an eco-friendly and sustainable approach to manage this common fungal disease caused by Alternaria solani, Alternaria alternata, and Curvularia lunata. Endophytic bacteria are microorganisms that live inside plant tissues without causing harm and can help protect the host plant from pathogens. In this work, twenty endophytic bacterial isolates from tomato healthy plants were tested against pathogenic fungal isolates that caused early blight disease in vitro. Out of the 20 tested isolates, three (B4, B7, and B17) were considered effective isolates against the growth of fungal pathogens. The three isolates were recognized as Enterobacter cloacae HS-6 (B4), Pseudomonas gessardii HS-5 (B 7), and Pseudomonas mediterranea HS-4 (B17) using 16s-rDNA sequencing. Different concentrations of bacterial cultural diltrates at 20, 40, and 60% were tested for their antagonistic effects on the development of pathogenic fungi in vitro. The lowest dry weights of pathogenic isolates in all bacterial culture filtrates were discovered at 60%. In all culture filtrates, phenolic compounds showed the largest peak area. Under greenhouse conditions, the least disease severity of tomato early blight was found for E. cloacae and its culture filtrate compared to other treatments. Real-time PCR was used to examine the expression pattern of the defense response gene β-1.3 glucanase gene in infected tomato plants with pathogenic fungi (control) as well as its relations with efficient biocontrol agent (E. cloacae). The expression of the gene increased substantially and significantly after three days from the inoculation-infected plants with C. lunata and E. cloacae while it reached the maximum after five days from the inoculation with A. alternata, A. solani and E. cloacae. Our study concluded that the endophytic bacterial isolate E. cloacae can be considered a promising biocontrol agent for preventing tomato early blight.
Antibacterial activities of coumarin-3-carboxylic acid against Acidovorax citrulli
Authors: Zhu Fa-Di , Fu Xin , Ye Huo-Chun , Ding Hai-Xin , Gu Liu-Shuang , Zhang Jing , Guo Yong-Xia , Feng Gang
Published: September 2023

Coumarin-3-carboxylic acid (3-CCA), previously screened from natural coumarins, was found to possess strong antibacterial activity against Acidovorax citrulli (Ac). In order to further evaluate the activity of this compound against plant bacterial pathogens and explore its potential value as a bactericidal lead compound, the activity of 3-CCA against 14 plant pathogenic bacteria in vitro and in vivo was tested. Results showed that 3-CCA exhibited strong in vitro activities against Ac, Ralstonia solanacearum, Xanthomonas axonopodis pv. manihotis, X. oryzae pv. oryzae, and Dickeya zeae with EC50 values ranging from 26.64 μg/mL to 40.73 μg/mL. Pot experiment results showed that 3-CCA had powerful protective and curative effects against Ac. In addition, the protective efficiency of 3-CCA was almost equivalent to that of thiodiazole copper at the same concentration. The results of SEM and TEM observation and conductivity tests showed that 3-CCA disrupted the integrity of the cell membrane and inhibited polar flagella growth. Furthermore, 3-CCA resulted in reductions in motility and extracellular exopolysaccharide (EPS) production of Ac while inhibiting the biofilm formation of Ac. These findings indicate that 3-CCA could be a promising natural lead compound against plant bacterial pathogens to explore novel antibacterial agents.
REPercussions: how geminiviruses recruit host factors for replication
Authors: Shakir Sara , Mubin Muhammad , Nahid Nazia , Serfraz Saad , Qureshi Muhammad Amir , Lee Taek-Kyun , Liaqat Iram , Lee Sukchan , Nawaz-ul-Rehman Muhammad Shah
Published: September 2023

Circular single-stranded DNA viruses of the family Geminiviridae encode replication-associated protein (Rep), which is a multifunctional protein involved in virus DNA replication, transcription of virus genes, and suppression of host defense responses. Geminivirus genomes are replicated through the interaction between virus Rep and several host proteins. The Rep also interacts with itself and the virus replication enhancer protein (REn), which is another essential component of the geminivirus replicase complex that interacts with host DNA polymerases α and δ. Recent studies revealed the structural and functional complexities of geminivirus Rep, which is believed to have evolved from plasmids containing a signature domain (HUH) for single-stranded DNA binding with nuclease activity. The Rep coding sequence encompasses the entire coding sequence for AC4, which is intricately embedded within it, and performs several overlapping functions like Rep, supporting virus infection. This review investigated the structural and functional diversity of the geminivirus Rep.
Lactobacillus plantarum surface-displayed FomA (Fusobacterium nucleatum) protein generally stimulates protective immune responses in mice
Authors: Zhang Xiaoyu , Xiao Huijie , Zhang Huaiyu , Jiang Yang
Published: September 2023

A significant correlation is observed between Fusobacterium nucleatum (F. nucleatum) and the evolution of inflammatory bowel disease (IBD). Particularly, FomA, a critical pathogenic element of F. nucleatum, inflicts substantial detriment to human intestinal health. Our research focused on the development of recombinant Lactobacillus plantarum that expresses FomA protein, demonstrating its potential in protecting mice from severe IBD induced by F. nucleatum. To commence, two recombinant strains, namely L. plantarum NC8-pSIP409-pgsA'-FomA and NC8-pSIP409-FnBPA-pgsA'-FomA, were successfully developed. Validation of the results was achieved through flow cytometry, ELISA, and MTT assays. It was observed that recombinant L. plantarum instigated mouse-specific humoral immunity and elicited mucosal and T cell-mediated immune responses. Significantly, it amplified the immune reaction of B cells and CD4+T cells, facilitated the secretion of cytokines such as IgA, IL4, and IL10, and induced lymphocyte proliferation in response to FomA protein stimulation. Finally, we discovered that administering recombinant L. plantarum could protect mice from severe IBD triggered by F. nucleatum, subsequently reducing pathological alterations and inflammatory responses. These empirical findings further the study of an innovative oral recombinant Lactobacillus vaccine.
Rhodobacteraceae dominate the core microbiome of the sea star Odontaster validus (Koehler, 1906) in two opposite geographical sectors of the Antarctic Ocean
Authors: Buschi Emanuela , Dell’Anno Antonio , Tangherlini Michael , Stefanni Sergio , Lo Martire Marco , Núñez-Pons Laura , Avila Conxita , Corinaldesi Cinzia
Published: September 2023

Microbiota plays essential roles in the health, physiology, and in adaptation of marine multi-cellular organisms to their environment. In Antarctica, marine organisms have a wide range of unique physiological functions and adaptive strategies, useful for coping with extremely cold conditions. However, the role of microbiota associated with Antarctic organisms in such adaptive strategies is underexplored. In the present study, we investigated the diversity and putative functions of the microbiome of the sea star Odontaster validus, one of the main keystone species of the Antarctic benthic ecosystems. We compared the whole-body bacterial microbiome of sea stars from different sites of the Antarctic Peninsula and Ross Sea, two areas located in two opposite geographical sectors of the Antarctic continent. The taxonomic composition of O. validus microbiomes changed both between and within the two Antarctic sectors, suggesting that environmental and biological factors acting both at large and local scales may influence microbiome diversity. Despite this, one bacterial family (Rhodobacteraceae) was shared among all sea star individuals from the two geographical sectors, representing up to 95% of the microbial core, and suggesting a key functional role of this taxon in holobiont metabolism and well-being. In addition, the genus Roseobacter belonging to this family was also present in the surrounding sediment, implying a potential horizontal acquisition of dominant bacterial core taxa via host-selection processes from the environment.