bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of featured necroptosis-related genes and imbalanced immune infiltration in sepsis via machine learning
Authors: She Han , Tan Lei , Yang Ruibo , Zheng Jie , Wang Yi , Du Yuanlin , Peng Xiaoyong , Li Qinghui , Lu Haibin , Xiang Xinming , Hu Yi , Liu Liangming , Li Tao
Published: April 2023

Background: The precise diagnostic and prognostic biological markers were needed in immunotherapy for sepsis. Considering the role of necroptosis and immune cell infiltration in sepsis, differentially expressed necroptosis-related genes (DE-NRGs) were identified, and the relationship between DE-NRGs and the immune microenvironment in sepsis was analyzed.

Methods: Machine learning algorithms were applied for screening hub genes related to necroptosis in the training cohort. CIBERSORT algorithms were employed for immune infiltration landscape analysis. Then, the diagnostic value of these hub genes was verified by the receiver operating characteristic (ROC) curve and nomogram. In addition, consensus clustering was applied to divide the septic patients into different subgroups, and quantitative real-time PCR was used to detect the mRNA levels of the hub genes between septic patients (SP) (n = 30) and healthy controls (HC) (n = 15). Finally, a multivariate prediction model based on heart rate, temperature, white blood count and 4 hub genes was established.

Results: A total of 47 DE-NRGs were identified between SP and HC and 4 hub genes (BACH2, GATA3, LEF1, and BCL2) relevant to necroptosis were screened out via multiple machine learning algorithms. The high diagnostic value of these hub genes was validated by the ROC curve and Nomogram model. Besides, the immune scores, correlation analysis and immune cell infiltrations suggested an immunosuppressive microenvironment in sepsis. Septic patients were divided into 2 clusters based on the expressions of hub genes using consensus clustering, and the immune microenvironment landscapes and immune function between the 2 clusters were significantly different. The mRNA levels of the 4 hub genes significantly decreased in SP as compared with HC. The area under the curve (AUC) was better in the multivariate prediction model than in other indicators.

Conclusion: This study indicated that these necroptosis hub genes might have great potential in prognosis prediction and personalized immunotherapy for sepsis.
ProgClust: A progressive clustering method to identify cell populations
Authors: Li Han , Wang Ying , Lai Yongxuan , Zeng Feng , Yang Fan
Published: April 2023

Identifying different types of cells in scRNA-seq data is a critical task in single-cell data analysis. In this paper, we propose a method called ProgClust for the decomposition of cell populations and detection of rare cells. ProgClust represents the single-cell data with clustering trees where a progressive searching method is designed to select cell population-specific genes and cluster cells. The obtained trees reveal the structure of both abundant cell populations and rare cell populations. Additionally, it can automatically determine the number of clusters. Experimental results show that ProgClust outperforms the baseline method and is capable of accurately identifying both common and rare cells. Moreover, when applied to real unlabeled data, it reveals potential cell subpopulations which provides clues for further exploration. In summary, ProgClust shows potential in identifying subpopulations of complex single-cell data.
Integrating maternal depression care at primary private clinics in low-income settings in Pakistan: A secondary analysis
Authors: Owais Syeda Somyyah , Horner Ronnie D. , Khan Muhammad Amir , Kenison Kelli , Probst Janice C.
Published: April 2023

Introduction

The prevalence of depression among women in Pakistan ranges from 28% to 66%. There is a lack of structured mental healthcare provision at private primary care clinics in low-income urban settings in Pakistan. This study investigated the effectiveness and processes of a facility-based maternal depression intervention at private primary care clinics in low-income settings.

Materials and methods

A mixed-methods study was conducted using secondary data from the intervention. Mothers were assessed for depression using the Patient Health Questionnaire-9 (PHQ-9). A total of 1,957 mothers (1,037 and 920 in the intervention and control arms, respectively) were retrieved for outcome measurements after 1 year of being registered. This study estimated the effectiveness of the depression intervention through cluster adjusted differences in the change in PHQ-9 scores between the baseline and the endpoint measurements for the intervention and control arms. Implementation was evaluated through emerging themes and codes from the framework analysis of 18 in-depth interview transcriptions of intervention participants.

Results

Intervention mothers had a 3.06-point (95% CI: −3.46 to −2.67) reduction in their PHQ-9 score at the endpoint compared with their control counterparts. The process evaluation revealed that the integration of structured depression care was feasible at primary clinics in poor urban settings. It also revealed gaps in the public–private care linkage system and the need to improve referral systems.

Conclusions

Intervening for depression care at primary care clinics can be effective in reducing maternal depression. Clinic assistants can be trained to identify and deliver key depression counseling messages. The study invites policymakers to seize an opportunity to implement a monitoring mechanism toward standard mental health care.
The small molecule inhibitor BX-795 uncouples IL-2 production from inhibition of Th2 inflammation and induces CD4+ T cells resembling iTreg
Authors: Tauber Peter A. , Kratzer Bernhard , Schatzlmaier Philipp , Smole Ursula , Köhler Cordula , Rausch Lisa , Kranich Jan , Trapin Doris , Neunkirchner Alina , Zabel Maja , Jutz Sabrina , Steinberger Peter , Gadermaier Gabriele , Brocker Thomas , Stockinger Hannes , Derdak Sophia , Pickl Winfried F.
Published: April 2023

Background

Treg cells have been shown to be an important part of immune-homeostasis and IL-2 which is produced upon T cell receptor (TCR)-dependent activation of T lymphocytes has been demonstrated to critically participate in Treg development.

Objective

To evaluate small molecule inhibitors (SMI) for the identification of novel IL-2/Treg enhancing compounds.

Materials and methods

We used TCR-dependent and allergen-specific cytokine secretion of human and mouse T cells, next generation messenger ribonucleic acid sequencing (RNA-Seq) and two different models of allergic airway inflammation to examine lead SMI-compounds.

Results

We show here that the reported 3-phosphoinositide dependent kinase-1 (PDK1) SMI BX-795 increased IL-2 in culture supernatants of Jurkat E6-1 T cells, human peripheral blood mononuclear cells (hPBMC) and allergen-specific mouse T cells upon TCR-dependent and allergen-specific stimulation while concomitantly inhibiting Th2 cytokine secretion. RNA-Seq revealed that the presence of BX-795 during allergen-specific activation of T cells induces a bona fide Treg cell type highly similar to iTreg but lacking Foxp3 expression. When applied in mugwort pollen and house dust mite extract-based models of airway inflammation, BX-795 significantly inhibited Th2 inflammation including expression of Th2 signature transcription factors and cytokines and influx into the lungs of type 2-associated inflammatory cells such as eosinophils.

Conclusions

BX-795 potently uncouples IL-2 production from Th2 inflammation and induces Th-IL-2 cells, which highly resemble induced (i)Tregs. Thus, BX-795 may be a useful new compound for the treatment of allergic diseases.
Syphilis vaccine: challenges, controversies and opportunities
Authors: Ávila-Nieto Carlos , Pedreño-López Núria , Mitjà Oriol , Clotet Bonaventura , Blanco Julià , Carrillo Jorge
Published: April 2023

Syphilis is a sexually or vertically (mother to fetus) transmitted disease caused by the infection of Treponema pallidum subspecie pallidum (TPA). The incidence of syphilis has increased over the past years despite the fact that this bacterium is an obligate human pathogen, the infection route is well known, and the disease can be successfully treated with penicillin. As complementary measures to preventive campaigns and early treatment of infected individuals, development of a syphilis vaccine may be crucial for controlling disease spread and/or severity, particularly in countries where the effectiveness of the aforementioned measures is limited. In the last century, several vaccine prototypes have been tested in preclinical studies, mainly in rabbits. While none of them provided protection against infection, some prototypes prevented bacteria from disseminating to distal organs, attenuated lesion development, and accelerated their healing. In spite of these promising results, there is still some controversy regarding the identification of vaccine candidates and the characteristics of a syphilis-protective immune response. In this review, we describe what is known about TPA immune response, and the main mechanisms used by this pathogen to evade it. Moreover, we emphasize the importance of integrating this knowledge, in conjunction with the characterization of outer membrane proteins (OMPs), to expedite the development of a syphilis vaccine that can protect against TPA infection.
Immunotherapy resistance in non-small-cell lung cancer: From mechanism to clinical strategies
Authors: Zhou Suna , Yang Haihua
Published: April 2023

The high primary resistance incidence and unavoidable secondary resistance are the major clinical obstacle to lasting long-term benefits in Non-small-cell lung cancer (NSCLC) patients treated with immunotherapy. The mechanisms of immunotherapy resistance in NSCLC are complex, mainly involving tumor cells and tumor microenvironment (TME) infiltrating immune cells, including TAMs, B cells, NK cells, and T cells. The selection of clinical strategies for NSCLC progression after immunotherapy resistance should depend on the progressive mode. The progression pattern of NSCLC patients after immunotherapy resistance can be divided into oligo-progression and systemic/multiple progression, which should be considered for further treatment selection. In the future, it needs to explore how to optimize the combined therapy and explore strategies to reprogram infiltrating immune cells under various genetic backgrounds of tumor cells and timely reshape TME during antitumor treatments.
Modulation of NK cell activation by exogenous calcium from alginate dressings in vitro
Authors: Adib Yara , Boy Maxime , Serror Kevin , Dulphy Nicolas , des Courtils Céline , Duciel Laura , Boccara David , Mimoun Maurice , Samardzic Marina , Bagot Martine , Bensussan Armand , Michel Laurence
Published: April 2023

Natural Killer (NK) cells participate in the defense against infection by killing pathogens and infected cells and secreting immuno-modulatory cytokines. Defects in NK cell activity have been reported in obese, diabetic, and elderly patients that are at high risk of developing infected chronic wounds. Calcium alginate dressings are indicated for the debridement during the inflammatory phase of healing. Since calcium ions are major activators of NK cells, we hypothesized that these dressings could enhance NK functions, as investigated in vitro herein. Primary human blood NK cells were freshly-isolated from healthy volunteers and exposed to conditioned media (CM) from two alginate dressings, Algosteril® (ALG, pure Ca2+ alginate) and Biatain® Alginate (BIA, Ca2+ alginate with CMC), in comparison with an exogenous 3mM calcium solution. Our results demonstrated that exogenous calcium and ALG-CM, but not BIA-CM, induced NK cell activation and enhanced their capacity to kill their targets as a result of increased degranulation. NK cell stimulation by ALG depended on the influx of extracellular Ca2+via the SOCE Ca2+ permeable plasma membrane channels. ALG-CM also activated NK cell cytokine production of IFN-γ and TNF-α through a partly Ca2+-independent mechanism. This work highlights the non-equivalence between alginate dressings for NK cell stimulation and shows that the pure calcium alginate dressing Algosteril® enhances NK cell cytotoxic and immuno-modulatory activities. Altogether, these results underline a specific property of this medical device in innate defense that is key for the cutaneous wound healing process.
New insights into autophagy in inflammatory subtypes of asthma
Authors: Dong Hongna , Yang Wei , Li Wei , Zhu Simin , Zhu Ling , Gao Peng , Hao Yuqiu
Published: April 2023

Asthma is a heterogeneous airway disease characterized by airway inflammation and hyperresponsiveness. Autophagy is a self-degrading process that helps maintain cellular homeostasis. Dysregulation of autophagy is involved in the pathogenesis of many diseases. In the context of asthma, autophagy has been shown to be associated with inflammation, airway remodeling, and responsiveness to drug therapy. In-depth characterization of the role of autophagy in asthma can enhance the understanding of the pathogenesis, and provide a theoretical basis for the development of new biomarkers and targeted therapy for asthma. In this article, we focus on the relationship of autophagy and asthma, and discuss its implications for asthma pathogenesis and treatment.
Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury
Authors: Zhao Yue , Jin Hua , Lei Kawai , Bai Li-Ping , Pan Hudan , Wang Caiyan , Zhu Xiaoming , Tang Yanqing , Guo Zhengyang , Cai Jiye , Li Ting
Published: April 2023

Introdcution

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of COVID-19 mortality. However, drug delivery to lung tissues is impeded by endothelial cell barriers, limiting the efficacy of existing treatments. A prompt and aggressive treatment strategy is therefore necessary.

Methods

We assessed the ability of anti-CD31-ORI-NPs to penetrate endothelial cell barriers and specifically accumulate in lung tissues using an animal model. We also compared the efficacy of anti-CD31-ORI-NPs to that of free oridonin in ameliorating acute lung injury and evaluated the cytotoxicity of both treatments on endothelial cells.

Results

Compared to free ORI, the amount of anti-CD31-ORI-NPs accumulated in lung tissues increase at least three times. Accordingly, anti-CD31-ORI-NPs improve the efficacy three times on suppressing IL-6 and TNF-a secretion, ROS production, eventually ameliorating acute lung injury in animal model. Importantly, anti-CD31-ORI-NPs significantly decrease the cytotoxicity at least two times than free oridonin on endothelial cells.

Discussion

Our results from this study will not only offer a novel therapeutic strategy with high efficacy and low toxicity, but also provide the rational design of nanomaterials of a potential drug for acute lung injury therapy.
Effects of heat and hyposalinity on the gene expression in Acropora pruinosa larvae
Authors: Chui Apple Pui Yi , Wong Yue Him , Sun Jin , Chang Taison Ka Tai , Qiu Jian-Wen , Qian Pei-Yuan , Ang Put
Published: April 2023

Introduction

Climate change has resulted in elevated sea surface temperature as well as increased frequency of extreme weather events, e.g. cyclones and rainstorms, which could lead to reduced seawater salinity. While temperature effects on corals have been widely examined, the combined effects of both temperature and salinity on corals, especially their early stages, remain poorly known. This study aimed to examine how the larvae of Acropora pruinosa in a marginal coral habitat, Hong Kong, respond to high temperature (+5°C ambient, HT), low salinity (26 psu, LS), and the combined effects of both stressors (HTLS).

Methods

We recorded larval survival and settlement success under different experimental treatments, and used RNA-Seq technique to compare the gene expression patterns of these larvae to understand the underlying molecular mechanism of stress responses.

Results

Our results showed that the survivorship of coral larvae was not affected in all experimental treatments, with all larvae surviving through the 72-hour period of the experiment. Yet, larval settlement was compromised under all stress treatments. The settlement rates were 39.3%, 12%, and 0% for the elevated temperature, reduced salinity, and the combined treatment, respectively, which were all significantly lower than that under the control treatment (78%). We demonstrated that low salinity (LS) triggered responsive gene sets with functions in ATP production, protein translation, and receptor for neuroactive ligands. In addition, high temperature (HT) treatment also triggered MAPK and NF-kB signaling and apoptosis in these coral larvae. The combined stressor treatment (HTLS) acted synergistically, resulting in the up-regulation of intracellular transducers that could trigger the intrinsic apoptosis pathway. This may explain the total failure in larval settlement under HTLS that could further increase larval vulnerability in the natural environment.

Discussion

Our results provide new insights into the molecular responses of coral larvae and represent an essential first step in expanding ourunderstanding of the mechanisms of tolerance that may be exhibited by coral larvae exposed to multiple stressors.
Temporal patterns and causal drivers of aboveground plant biomass in a coastal wetland: Insights from time-series analyses
Authors: Biçe Kadir , Schalles John , Sheldon Joan E. , Alber Merryl , Meile Christof
Published: April 2023

Salt marshes play a crucial role in coastal biogeochemical cycles and provide unique ecosystem services. Salt marsh biomass, which can strongly influence such services, varies over time in response to hydrologic conditions and other environmental drivers. We used gap-filled monthly observations of Spartina alterniflora aboveground biomass derived from Landsat 5 and Landsat 8 satellite imagery from 1984-2018 to analyze temporal patterns in biomass in comparison to air temperature, precipitation, river discharge, nutrient input, sea level, and drought index for a southeastern US salt marsh. Wavelet analysis and ensemble empirical mode decomposition identified month to multi-year periodicities in both plant biomass and environmental drivers. Wavelet coherence detected cross-correlations between annual biomass cycles and precipitation, temperature, river discharge, nutrient concentrations (NOx and PO43–) and sea level. At longer periods we detected coherence between biomass and all variables except precipitation. Through empirical dynamic modeling we showed that temperature, river discharge, drought, sea level, and river nutrient concentrations were causally connected to salt marsh biomass and exceeded the confounding effect of seasonality. This study demonstrated the insights into biomass dynamics and causal connections that can be gained through the analysis of long-term data.
Metabarcoding the eukaryotic community of a threatened, iconic Mediterranean habitat: Posidonia oceanica seagrass meadows
Authors: Turon Xavier , Zarcero Jesús , Antich Adrià , Wangensteen Owen Simon , Ballesteros Enric , Cebrian Emma , Marco-Méndez Candela , Alcoverro Teresa
Published: April 2023

Against the accelerating pace of worldwide species extinction, reliable biodiversity assessments are critical, both as baselines and to track potential declines. DNA metabarcoding techniques allow for fast and comprehensive assessment of biodiversity in both terrestrial and marine habitats. However, these methods need to be adapted and standardised for each ecosystem in order to be effective. Seagrass meadows are among the most diverse marine habitats and are irreplaceable in terms of the ecosystem services they provide, yet metabarcoding has never been implemented for these systems. In this study, we developed and tested a protocol for metabarcoding the eukaryotic community of meadows of the iconic species, Posidonia oceanica L. (Delile). This seagrass is the main habitat-forming species in Mediterranean coastal waters and is known for its high diversity due to the structural complexity of its canopy and rhizome structures. This habitat is experiencing a range-wide retreat, and there is an urgent need for fast and efficient methods for its biomonitoring and detection of early changes. Our proposed method involves direct sampling of the community, collecting and processing the leaves and rhizome strata separately. To test the utility of the method in distinguishing between different meadow conditions, we sampled two distinct meadows that differ in their prevailing wind and surge conditions, and a nearby rocky reef for comparison. We then adapted a method and pipeline for COI metabarcoding using generalist primers that target the eukaryote diversity present. We detected a high diversity in the two meadows analysed (3,350 molecular operational taxonomic units, dominated by Metazoa and Archaeplastida) and a clear differentiation of the seagrass samples from those of the nearby rocky reefs. The leaves and rhizomes harboured clearly distinct assemblages, and differences were also detected between the two meadows sampled. This new tool has the potential to deliver big biodiversity data for seagrass habitats in a fast and efficient way, which is crucial for the implementation of protection and management measures for this key coastal habitat.
Commercial production of Florida pompano (Trachinotus carolinus) larvae at low salinity induces variable changes in whole-larvae microbial diversity, gene expression, and gill histopathology
Authors: Bradshaw David J. , Perricone Carlie S. , King Laura E. , Allmon Elizabeth B. , Sepúlveda Maria , Riche Marty , Wills Paul S. , Kirchhoff Nicole , Mejri Sahar
Published: April 2023

Introduction

Salinity presents economic and technical challenges in land-based recirculating aquaculture systems (RAS) in the U.S. warm water marine finfish aquaculture industry. Many studies have shown euryhaline fish reared at salinities closer to their iso-osmotic salinity can yield enhanced production performance as well as potential reduced costs to farms. However, there is potential for osmotic stress in fish larvae to negatively impact larvae microbiome and innate immune system. Florida pompano (Trachinotus carolinus) is a popular sportfish has been targeted for land-based RAS due to its impressive market value and euryhaline capacity. This study investigated the impacts of rearing Florida pompano larvae at salinities closer to their iso-osmotic salinity.

Materials and methods

Larvae were cultured at 10, 20, and 30 ppt in triplicates, and larvae samples were collected for histopathology, microbiome, and whole transcriptomics analysis every three days from hatching until the time of weaning (24 days post hatch [DPH]). Water samples were also taken for microbiome analysis on every other larval sampling day.

Discussion

These changes were driven more by metamorphosis, causing an increase in expression of antioxidant genes (cat, gss, gsto1, and scara3) than by the presence of potentially pathogenic genera, which failed to induce an immune response (low or unchanged expression of downstream elements of the NOD1 or TLR5 pathways). These findings provide baseline information on Florida pompano low salinity tolerance in larviculture during early developmental stages. In addition, we have shown minimal effects on the immune system at salinities as low as 10 ppt. This work has important implications for larval health management and can be used to refine and direct future research regarding improving commercial production of warm water marine species
Drivers of HIV self-testing among female sex workers: Findings from a multi-state study in Malaysia
Authors: Kim Rayne S. , Wickersham Jeffrey A. , Maviglia Francesca , Galka Jonathan M. , Azwa Iskandar , Gautam Kamal , Shrestha Roman
Published: April 2023

Background

Although research on HIV self-testing (HIVST) has rapidly increased, few studies have explored HIVST uptake in female sex workers (FSW), and none in Malaysia. Therefore, we endeavored to assess the willingness to use HIVST in this at-risk, vulnerable population.

Methods

A cross-sectional survey study was conducted among 113 HIV-negative Malaysian FSW in 2017. Participants were recruited using advertisements on social media, flyers, and direct referrals from community-based organizations. Data were collected using self-administered surveys. Multivariable logistic regression was used to identify correlates of willingness to use HIVST.

Results

Nearly a third of participants (30.1%) reported they would be willing to use HIVST. Multivariable analyses adjusting for Malay ethnicity, stable housing, living in Kuala Lumpur (KL), years in sex work, age of first sex work, childhood sexual assault, history of HIV testing, and previously in prison indicated that living in KL [adjusted odds ratio (aOR) = 5.214, p = 0.0137] was associated with a greater willingness to use HIVST. In contrast, having stable housing (aOR = 0.100, p = 0.0064) was negatively associated with willingness to use HIVST.

Conclusions

Our results indicate that HIVST may potentially enhance the uptake of HIV testing among FSWs living in an urban environment and experiencing unstable housing, but an overall willingness to use HIVST is low. These findings highlight the need for efforts to increase awareness of HIVST among FSWs and additional research on the effective implementation of HIVST for FSW.
Typical course of cystinuria leading to untypical complications in pregnancy: A case report and review of literature
Authors: Ivandic Ema , Maric Marjan , Elvedi-Gasparovic Vesna , Fistrek Prlic Margareta , Lamot Lovro , Jelakovic Bojan , Vukovic Brinar Ivana
Published: April 2023

Cystinuria is a rare genetic disorder inherited by an autosomal recessive pattern which affects the transmembrane transporter for the base amino acid cystine. It has a general prevalence of 1 in 7000 with demographic variations. Patients with cystinuria have excessive urinary excretion of cystine, which can lead to the formation of stones. Up to 70% of patients will develop chronic kidney disease that can progress even to end-stage renal disease. Symptoms usually start in the first two decades of life with a typical presentation consisting of flank pain and renal colic, usually accompanied by urinary tract infection and deterioration of kidney function. Men are typically affected twice as often as women and have a more severe clinical course. Diagnosis is made by spectrophotometric analysis of the stones that are collected after spontaneous expulsion or medical intervention. Genetic testing is not mandatory but is recommended in uncertain cases or as a part of genetic counseling. Treatment consists of diet modification, alkalization of urine, and thiol-based therapies if other measures fail to prevent stone formation. In pregnancy, cystinuria with the formation of cystine stones represents a therapeutic challenge and requires a multidisciplinary approach consisting of an uro-nephrology team and a gynecologist. We present the case of a 34-year-old woman with cystinuria on whom the diagnosis was made by analysis of the expulsed stone. While her previous pregnancies were without complications, her third pregnancy was accompanied by frequent urinary tract infections, acute worsening of kidney function, and urological interventions during pregnancy due to the formation of new stones. Despite the complicated course, the pregnancy was successfully carried to term with the delivery of a healthy female child.
Serotyping, a challenging approach for Toxoplasma gondii typing
Authors: Sousa Susana , Fernandes Maria , Correia da Costa José Manuel
Published: April 2023

Genotype analysis has revealed a high genetic diversity in strains of Toxoplasma gondii, isolated from a wide range of intermediate hosts and different geographic origins. Diversity is notably striking for parasites from wild hosts in South America, generally referred as non-archetypal genotypes. Those genotypes are implicated in the etiology of severe clinical disease, multivisceral toxoplasmosis, associated with high rate of mortality in immunocompetent individuals. Can we accept specific antibodies produced during T. gondii infection as biomarkers to identify infecting genotypes? Scientific evidence supports a positive response to this question; however, the genetic diversity of T. gondii genotypes organized into 16 haplogroups and collectively defined in 6 major clades, provides a reminder of the complexity and difficulty for the purpose. This review discusses serological approaches to genotyping T. gondii.
Usefulness of continuous glucose monitoring of blood glucose control in patients with diabetes undergoing hemodialysis: A pilot study
Authors: Lee Sua , Lee Soyoung , Kim Kyeong Min , Shin Jong Ho
Published: April 2023

Background

Blood glucose stability has recently been considered important in the treatment of diabetes. Both hypoglycemia and hyperglycemia can frequently occur in patients with diabetes undergoing hemodialysis. This study aimed to determine the usefulness of continuous glucose monitoring (CGM) for glycemic control and glycemic variability stabilization in patients with diabetes undergoing hemodialysis.

Materials and methods

Eighteen patients aged ≥18 years with type 1 or 2 diabetes and ≥3 months on hemodialysis at the Eulji Medical Center, Daejeon, Republic of Korea between November 2021 and May 2022 were included. Patients underwent 7 days CGM twice: the baseline study period (T0) and the follow-up study period (T1), at a 12 weeks interval. Physicians modified the treatment strategy according to the T0 results, and then patients conducted T1. As indicators of glycemic control, the mean glucose levels, glycated hemoglobin A1c (HbA1c), and time in range were measured. As indicators of glycemic variability, standard deviation (SD) and % coefficient variation (%CV) were measured.

Results

Data from 18 patients were analyzed. The mean glucose levels, HbA1c, SD, and %CV improved in T1 compared to T0 (P < 0.05). During T0, the mean glucose level was significantly lower on a day with hemodialysis than on a day without (P < 0.05), and SD and %CV were significantly higher on a day with hemodialysis than on a day without (P < 0.05). After the physicians modified the treatment according to the T0 results, there were no differences in the mean glucose levels, SD, and %CV between days with and without hemodialysis during T1.

Conclusion

Continuous glucose monitoring could be a promising tool for individualizing treatment strategies in patients with diabetes undergoing hemodialysis.
Molecular and microscopy detection of Pneumocystis jirovecii in hospitalized patients during the COVID-19 pandemic
Authors: Matouri Roya , Aboutalebian Shima , Nasri Elahe , Sadeghi Somayeh , Rostami Soodabeh , Fakhim Hamed , Ghafel Safiyeh , Hosseini Mahnaz , Mousavi Somayeh , Rouhi Faezeh , Pestechian Nader , Mirhendi Hossein
Published: April 2023

Introduction

Early detection of Pneumocystis jirovecii as an opportunistic pathogen that may endanger predisposed persons, including COVID-19 patients, may help to choose the optimal management.

Methods

In this study, 585, including 530 COVID-19 patients, with clinical and radiological evidence of respiratory diseases, were investigated for P. jirovecii screening. Clinical specimens were examined by direct microscopy and PCR, and randomly selected positive PCR products were confirmed through DNA sequence analysis.

Results

Thirty-one (5.3%) samples were positive in P. jirovecii-specific nested-PCR, while by direct microscopic tests, Pneumocystis was observed in 22 (3.76%) samples. Males (61.7%) and patients over 50 years old (75.6%) were more commonly affected than others, and malaise and fatigue (84%), and wheezing (75%) were the most common symptoms, followed by fever (40.48%) and dyspnea (39.51%). Among the Pneumocystis-positive patients, three cases had coinfection with Aspergillus fumigatus, A. flavus, and A. niger (each n = 1), as documented by direct microscopy, culture, and species identification by PCR-sequencing.

Conclusion

Pneumocystis pneumonia is still a diagnostic challenge; therefore, additional large-scale studies are needed to clarify the epidemiology of the disease in immunocompromised or COVID-19 patients.
“Long COVID-19” and viral “fibromyalgia-ness”: Suggesting a mechanistic role for fascial myofibroblasts (Nineveh, the shadow is in the fascia)
Authors: Plaut Shiloh
Published: April 2023

The coronavirus pandemic has led to a wave of chronic disease cases; “Long COVID-19” is recognized as a new medical entity and resembles “fibromyalgia” which, likewise, lacks a clear mechanism. Observational studies indicate that up to 30%–40% of convalescent COVID-19 patients develop chronic widespread pain and fatigue and fulfill the 2016 diagnostic criteria for “fibromyalgia.” A recent study suggested a theoretical neuro-biomechanical model (coined “Fascial Armoring”) to help explain the pathogenesis and cellular pathway of fibromyalgia, pointing toward mechanical abnormalities in connective tissue and fascia, driven by contractile myo/fibroblasts and altered extracellular matrix remodeling with downstream corresponding neurophysiological aberrations. This may help explain several of fibromyalgia’s manifestations such as pain, distribution of pain, trigger points/tender spots, hyperalgesia, chronic fatigue, cardiovascular abnormalities, metabolic abnormalities, autonomic abnormalities, small fiber neuropathy, various psychosomatic symptoms, lack of obvious inflammation, and silent imaging investigations. Pro-inflammatory and pro-fibrotic pathways provide input into this mechanism via stimulation of proto/myofibroblasts. In this hypothesis and theory paper the theoretical model of Fascial Armoring is presented to help explain the pathogenesis and manifestations of “long COVID-19” as a disease of immuno-rheumo-psycho-neurology. The model is also used to make testable experimental predictions on investigations and predict risk and relieving factors.
Genomic diversity and metabolic potential of marine Pseudomonadaceae
Authors: Girard Léa , Lood Cédric , De Mot René , van Noort Vera , Baudart Julia
Published: April 2023

Recent changes in the taxonomy of the Pseudomonadaceae family have led to the delineation of three new genera (Atopomonas, Halopseudomonas and Stutzerimonas). However, the genus Pseudomonas remains the most densely populated and displays a broad genetic diversity. Pseudomonas are able to produce a wide variety of secondary metabolites which drives important ecological functions and have a great impact in sustaining their lifestyles. While soilborne Pseudomonas are constantly examined, we currently lack studies aiming to explore the genetic diversity and metabolic potential of marine Pseudomonas spp. In this study, 23 Pseudomonas strains were co-isolated with Vibrio strains from three marine microalgal cultures and rpoD-based phylogeny allowed their assignment to the Pseudomonas oleovorans group (Pseudomonas chengduensis, Pseudomonas toyotomiensis and one new species). We combined whole genome sequencing on three selected strains with an inventory of marine Pseudomonas genomes to assess their phylogenetic assignations and explore their metabolic potential. Our results revealed that most strains are incorrectly assigned at the species level and half of them do not belong to the genus Pseudomonas but instead to the genera Halopseudomonas or Stutzerimonas. We highlight the presence of 26 new species (Halopseudomonas (n = 5), Stutzerimonas (n = 7) and Pseudomonas (n = 14)) and describe one new species, Pseudomonas chaetocerotis sp. nov. (type strain 536T = LMG 31766T = DSM 111343T). We used genome mining to identify numerous BGCs coding for the production of diverse known metabolites (i.e., osmoprotectants, photoprotectants, quorum sensing molecules, siderophores, cyclic lipopeptides) but also unknown metabolites (e.g., ARE, hybrid ARE-DAR, siderophores, orphan NRPS gene clusters) awaiting chemical characterization. Finally, this study underlines that marine environments host a huge diversity of Pseudomonadaceae that can drive the discovery of new secondary metabolites.
Linking between soil properties, bacterial communities, enzyme activities, and soil organic carbon mineralization under ecological restoration in an alpine degraded grassland
Authors: Shu Xiangyang , Hu Yufu , Liu Weijia , Xia Longlong , Zhang Yanyan , Zhou Wei , Liu Wanling , Zhang Yulin
Published: April 2023

Soil organic carbon (SOC) mineralization is affected by ecological restoration and plays an important role in the soil C cycle. However, the mechanism of ecological restoration on SOC mineralization remains unclear. Here, we collected soils from the degraded grassland that have undergone 14 years of ecological restoration by planting shrubs with Salix cupularis alone (SA) and, planting shrubs with Salix cupularis plus planting mixed grasses (SG), with the extremely degraded grassland underwent natural restoration as control (CK). We aimed to investigate the effect of ecological restoration on SOC mineralization at different soil depths, and to address the relative importance of biotic and abiotic drivers of SOC mineralization. Our results documented the statistically significant impacts of restoration mode and its interaction with soil depth on SOC mineralization. Compared with CK, the SA and SG increased the cumulative SOC mineralization but decreased C mineralization efficiency at the 0–20 and 20–40 cm soil depths. Random Forest analyses showed that soil depth, microbial biomass C (MBC), hot-water extractable organic C (HWEOC), and bacterial community composition were important indicators that predicted SOC mineralization. Structural equal modeling indicated that MBC, SOC, and C-cycling enzymes had positive effects on SOC mineralization. Bacterial community composition regulated SOC mineralization via controlling microbial biomass production and C-cycling enzyme activities. Overall, our study provides insights into soil biotic and abiotic factors in association with SOC mineralization, and contributes to understanding the effect and mechanism of ecological restoration on SOC mineralization in a degraded grassland in an alpine region.
Fecal microbiota transplantation from Suncus murinus, an obesity-resistant animal, to C57BL/6NCrSIc mice, and the antibiotic effects in the approach
Authors: Zhang Mingshou , Sasaki Hiraku , Yang Ting , Chen Juefei , Li Rujia , Yi Cheng , Li Jun , He Maozhang , Yi Shuang-Qin
Published: April 2023

Introduction

Important studies on the relationship of the intestinal microbial flora with obesity have uncovered profound changes in the composition of the gut microbiota in obese individuals. Animal studies successfully altered body phenotypes by fecal microbiota transplantation (FMT).

Methods

In this study, we analyzed the gut microbiome of Suncus murinus (S. murinus), a naturally obesity-resistant animal, and the changes of the gut flora of C57BL/6NCrSIc mice that received gut bacteria transplantation from S. murinus by 16S rRNA gene analysis method. And analyzed and discussed the possible impact of the use of antibiotics before transplantation on the outcome of transplantation.

Results

Our results showed no significant changes in body weight in the FMT group compared to the control (AB) group, but large fluctuations due to antibiotics. There was no change in blood lipid levels between groups before and after FMT. The gut microbiota of S. murinus were enriched in Firmicutes and Proteobacteria, while Bacteroidetes were not detected, and fewer OTUs were detected in the intestine gut in comparison to other mouse groups. Statistically significant differences in alpha diversity were observed between the FMT group and other groups. Furthermore, a beta diversity analysis indicated an apparent structural separation between the FMT group and other groups.

Conclusion

It was suggested that the gut flora of S. murinus was not well established in the gut trace of mice through FMT, and the administration of antibiotics before transplantation was an important factor affecting the overall composition of the gut flora. Although FMT of S. murinus failed to completely colonize the intestinal tract of the mice, it still had a certain effect on the establishment of the intestinal flora of the mice. The unpredictable effects of pre-transplantation antibiotics on the results of transplantation cannot be ignored.
A longitudinal study to examine the influence of farming practices and environmental factors on pathogen prevalence using structural equation modeling
Authors: Ferguson Martine , Hsu Chiun-Kang , Grim Christopher , Kauffman Michael , Jarvis Karen , Pettengill James B. , Babu Uma S. , Harrison Lisa M. , Li Baoguang , Hayford Alice , Balan Kannan V. , Freeman Josefina P. , Rajashekara Gireesh , Lipp Erin K. , Rozier Ralph Scott , Zimeri Anne Marie , Burall Laurel S.
Published: April 2023

The contamination of fresh produce with foodborne pathogens has been an on-going concern with outbreaks linked to these commodities. Evaluation of farm practices, such as use of manure, irrigation water source, and other factors that could influence pathogen prevalence in the farming environment could lead to improved mitigation strategies to reduce the potential for contamination events. Soil, water, manure, and compost were sampled from farms in Ohio and Georgia to identify the prevalence of Salmonella, Listeria monocytogenes (Lm), Campylobacter, and Shiga-toxin-producing Escherichia coli (STEC), as well as Arcobacter, an emerging human pathogen. This study investigated agricultural practices to determine which influenced pathogen prevalence, i.e., the percent positive samples. These efforts identified a low prevalence of Salmonella, STEC, and Campylobacter in soil and water (< 10%), preventing statistical modeling of these pathogens. However, Lm and Arcobacter were found in soil (13 and 7%, respectively), manure (49 and 32%, respectively), and water samples (18 and 39%, respectively) at a comparatively higher prevalence, suggesting different dynamics are involved in their survival in the farm environment. Lm and Arcobacter prevalence data, soil chemical characteristics, as well as farm practices and weather, were analyzed using structural equation modeling to identify which factors play a role, directly or indirectly, on the prevalence of these pathogens. These analyses identified an association between pathogen prevalence and weather, as well as biological soil amendments of animal origin. Increasing air temperature increased Arcobacter and decreased Lm. Lm prevalence was found to be inversely correlated with the use of surface water for irrigation, despite a high Lm prevalence in surface water suggesting other factors may play a role. Furthermore, Lm prevalence increased when the microbiome’s Simpson’s Diversity Index decreased, which occurred as soil fertility increased, leading to an indirect positive effect for soil fertility on Lm prevalence. These results suggest that pathogen, environment, and farm management practices, in addition to produce commodities, all need to be considered when developing mitigation strategies. The prevalence of Arcobacter and Lm versus the other pathogens suggests that multiple mitigation strategies may need to be employed to control these pathogens.
A methodology for the selection and characterization of riboflavin-overproducing Weissella cibaria strains after treatment with roseoflavin
Authors: Diez-Ozaeta Iñaki , Martín-Loarte Lucía , Mohedano Mari Luz , Tamame Mercedes , Ruiz-Masó José Ángel , del Solar Gloria , Dueñas María Teresa , López Paloma
Published: April 2023

Fermentative processes by lactic acid bacteria can produce metabolites of interest to the health and food industries. Two examples are the production of B-group vitamins, and of prebiotic and immunomodulatory dextran-type exopolysaccharides. In this study, three riboflavin- and dextran-producing Weissella cibaria strains (BAL3C-5, BAL3C-7 and BAL3C-22) were used to develop a new method for selection and isolation of spontaneous riboflavin-overproducing W. cibaria mutants. This method was based on the selection of strains resistant to roseoflavin. The DNA sequencing of the FMN riboswitch of bacterial cell populations treated with various roseoflavin concentrations, revealed the existence of at least 10 spontaneous and random point mutations at this location. Folding and analysis of the mutated FMN riboswitches with the RNA fold program predicted that these mutations could result in a deregulation of the rib operon expression. When the roseoflavin-treated cultures were plated on medium supporting dextran synthesis, the most promising mutants were identified by the yellow color of their mucous colonies, exhibiting a ropy phenotype. After their isolation and recovery in liquid medium, the evaluation of their riboflavin production revealed that the mutant strains synthesized a wide range of riboflavin levels (from 0.80 to 6.50 mg/L) above the wild-type level (0.15 mg/L). Thus, this was a reliable method to select spontaneous riboflavin-overproducing and dextran-producing strains of W. cibaria. This species has not yet been used as a starter or adjunct culture, but this study reinforces the potential that it has for the food and health industry for the production of functional foods or as a probiotic. Furthermore, analysis of the influence of FMN present in the growth medium, on rib mRNA and riboflavin levels, revealed which mutant strains produce riboflavin without flavin regulation. Moreover, the BAL3C-5 C120T mutant was identified as the highest riboflavin-overproducer. Determination of its chromosomal DNA sequence and that of BAL3C-5, revealed a total identity between the 2 strains except for the C120T mutation at the FMN riboswitch. To our knowledge, this work is the first demonstration that only a single alteration in the genome of a lactic acid bacteria is required for a riboflavin-overproducing phenotype.
Amphotericin B resistance correlates with increased fitness in vitro and in vivo in Leishmania (Mundinia) martiniquensis
Authors: Mano Chonlada , Kongkaew Aphisek , Tippawangkosol Pongsri , Somboon Pradya , Roytrakul Sittiruk , Pescher Pascale , Späth Gerald F. , Uthaipibull Chairat , Tantiworawit Adisak , Siriyasatien Padet , Jariyapan Narissara
Published: April 2023

Amphotericin B (AmpB) deoxycholate is the available first-line drug used to treat visceral leishmaniasis caused by Leishmania (Mundinia) martiniquensis, however, some cases of AmpB treatment failure have been reported in Thailand. Resistance to drugs is known to affect parasite fitness with a potential impact on parasite transmission but still little is known about the effect of resistance to drugs on L. martiniquensis. Here we aimed to gain insight into the fitness changes occurring after treatment failure or in vitro-induced resistance to AmpB. L. martiniquensis parasites isolated from a patient before (LSCM1) and after relapse (LSCM1-6) were compared for in vitro and in vivo fitness changes together with an in vitro induced AmpB-resistant parasite generated from LSCM1 parasites (AmpBRP2i). Results revealed increased metacyclogenesis of the AmpBPR2i and LSCM1-6 strains (AmpB-resistant strains) compared to the LSCM1 strain and increased fitness with respect to growth and infectivity. The LSCM1-6 and AmpBRP2i strains were present in mice for longer periods compared to the LSCM1 strain, but no clinical signs of the disease were observed. These results suggest that the AmpB-resistant parasites could be more efficiently transmitted to humans and maintained in asymptomatic hosts longer than the susceptible strain. The asymptomatic hosts therefore may represent “reservoirs” for the resistant parasites enhancing transmission. The results in this study advocate an urgent need to search and monitor for AmpB-resistant L. martiniquensis in patients with relapsing leishmaniasis and in asymptomatic patients, especially, in HIV/Leishmania coinfected patients.