bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical application of metagenomic next-generation sequencing in sepsis of immunocompromised patients
Authors: Li Xingxing , Liang Shunda , Zhang Dan , He Miao , Zhang Hong 
Published: April 2023

BackgroundMetagenomic next-generation sequencing (mNGS) was commonly applied given its ability to identify and type all infections without depending upon culture and to retrieve all DNA with unbiasedness. In this study, we strive to compare outcomes of mNGS with conventional culture methods in adults with sepsis, investigate the differences between the immunocompromised and control group, and assess the clinical effects of mNGS.MethodsIn our study, 308 adult sepsis patients were included. We used both mNGS and conventional culture methods to analyze diagnostic results, pathogens, and sample types. The correlation between some laboratory tests and the frequency of pathogens by groups was also analyzed. Furthermore, the clinical impacts of mNGS were estimated.Results308 samples were assigned to an immunocompromised group (92/308,29.9%) and a control group (216/308,70.1%). There was the sensitivity of mNGS considered greater than that of the culture method in all samples (88.0% vs 26.3%; P &lt;​ 0.001), in the immunocompromised group (91.3% vs 26.1%; P &lt;​ 0.001), and the control group (86.6% vs 26.4%; P &lt;​ 0.001), particularly in all sample types of blood (P &lt;​ 0.001), BALF (P &lt;​ 0.001), CSF (P &lt;​ 0.001), sputum (P &lt;​ 0.001) and ascitic fluid (P = 0.008). When examining the mNGS results between groups, Pneumocystis jirovecii (P &lt; 0.001), Mucoraceae (P = 0.014), and Klebsiella (P = 0.045) all showed significant differences. On the whole, mNGS detected more pathogens than culture methods (111 vs 25), found 89 organisms that were continuously overlooked in entire samples by culture methods, and showed a favorable positive clinical effect in 76.3% (235 of 308) of patients. In 185 (60.1%) patients, mNGS prompted a modification in the course of management, which included antibiotic de-escalation in 61(19.8%) patients.ConclusionsThe research discovered that mNGS was more sensitive than the culture method, particularly in samples of blood, BALF, CSF, sputum, and ascitic fluid. When examining the mNGS results, Pneumocystis jirovecii and Mucoraceae were the pathogens seen more commonly in immunocompromised patients with sepsis, which required more attention from clinicians. There was a substantial benefit of mNGS in enhancing the diagnosis of sepsis and advancing patient treatment.
The impact of digital healthcare on vulnerable pregnant women: A review of the use of the MyCare app in the maternity department at a central London tertiary unit
Authors: Pierce Poppy , Whitten Melissa , Hillman Sara 
Published: April 2023

IntroductionDigitalisation offers innovative solutions within maternity services; however, vulnerable groups risk being overlooked. University College London Hospital's (UCLH) successful implementation of a digital maternity app, MyCare, gives women access to test results, information about appointments, and enables communication with healthcare professionals (HCPs). Yet, little is known about access and engagement among vulnerable pregnant women.MethodologyResearch was conducted over a 3-month period (April–June 2022) in the Maternity Department at UCLH, UK. MyCare datasets were analysed, and anonymised surveys completed by vulnerable pregnant women and HCPs.ResultsLower rates of utilisation and engagement with MyCare were seen in vulnerable pregnant women especially among refugee/asylum seekers, those with mental health issues, and those facing domestic violence. Non-users were also more likely to be individuals from ethnic minority backgrounds, with a lower average social-deprivation-index decile, whose first language was not English, and with a significant history of non-attendance to appointments. Patient and HCP surveys highlighted various barriers to MyCare engagement, including a lack of motivation, limited language options, low e-literacy levels, and complex app interfaces.ConclusionThe use of a single digital tool, without a formulated pathway to identify and assist those not accessing or engaging with it, risks unequal care provision which may exacerbate health inequalities. This research advances the idea that digital exclusion is not necessarily a matter of access to technology, but an issue of a lack of engagement with these tools. Therefore, vulnerable women and HCPs must be integral to the implementation of digital strategies, to ensure no one is left behind.
Demethyleneberberine alleviated the inflammatory response by targeting MD-2 to inhibit the TLR4 signaling
Authors: Zhao Yaxing , Liu Peng , Luan Haofan , Jiang Hua , Xu Yingmei , Zhang Yuanqiang , Zhang Yubin , Li Ruiyan 
Published: April 2023

IntroductionThe colitis induced by trinitrobenzenesulfonic acid (TNBS) is a chronic and systemic inflammatory disease that leads to intestinal barrier dysfunction and autoimmunedisorders. However, the existing treatments of colitis are associated with poor outcomes, and the current strategies remain deep and long-time remission and the prevention of complications. Recently, demethyleneberberine (DMB) has been reported to be a potential candidate for the treatment of inflammatory response that relied on multiple pharmacological activities, including anti-oxidation and antiinflammation. However, the target and potential mechanism of DMB in inflammatory response have not been fully elucidated.MethodsThis study employed a TNBS-induced colitis model and acute sepsis mice to screen and identify the potential targets and molecular mechanisms of DMB in vitro and in vivo. The purity and structure of DMB were quantitatively analyzed by high-performance liquid chromatography (HPLC), mass spectrometry (MS), Hydrogen nuclear magnetic resonance spectroscopy (1H-NMR), and infrared spectroscopy (IR), respectively. The rats were induced by a rubber hose inserted approximately 8 cm through their anus to be injected with TNBS. Acute sepsis was induced by injection with LPS via the tail vein for 60 h. These animals with inflammation were orally administrated with DMB, berberine (BBR), or curcumin (Curc), respectively. The eukaryotic and prokaryotic expression system of myeloid differentiation protein-2 (MD-2) and its mutants were used to evaluate the target of DMB in inflammatory response.ReslutsDMB had two free phenolic hydroxyl groups, and the purity exceeded 99% in HPLC. DMB alleviated colitis and suppressed the activation of TLR4 signaling in TNBS-induced colitis rats and LPS-induced RAW264.7 cells. DMB significantly blocked TLR4 signaling in both an MyD88-dependent and an MyD88-independent manner by embedding into the hydrophobic pocket of the MD-2 protein with non-covalent bonding to phenylalanine at position 76 in a pi–pi T-shaped interaction. DMB rescued mice from sepsis shock induced by LPS through targeting the TLR4–MD-2 complex.ConclusionTaken together, DMB is a promising inhibitor of the MD-2 protein to suppress the hyperactivated TLR4 signaling in inflammatory response.
Radiation upregulates macrophage TREM-1 expression to exacerbate injury in mice
Authors: Yamaga Satoshi , Murao Atsushi , Ma Gaifeng , Brenner Max , Aziz Monowar , Wang Ping 
Published: April 2023

IntroductionExposure to high-dose ionizing radiation causes tissue injury, infections and even death due to immune dysfunction. The triggering receptor expressed on myeloid cells-1 (TREM-1) has been demonstrated to critically amplify and dysregulate immune responses. However, the role of TREM-1 in radiation injury remains unknown. Extracellular cold-inducible RNA-binding protein (eCIRP), a new damage-associated molecular pattern, is released from activated or stressed cells during inflammation. We hypothesized that ionizing radiation upregulates TREM-1 expression via eCIRP release to worsen survivalMethodsRAW264.7 cells and peritoneal macrophages collected from C57BL/6 wild-type (WT) mice were exposed to 5- and 10-Gray (Gy) radiation. C57BL/6 WT and CIRP-/- mice underwent 10-Gy total body irradiation (TBI). TREM-1 expression on RAW264.7 cells and peritoneal macrophages in vitro and in vivo were evaluated by flow cytometry. eCIRP levels in cell culture supernatants and in peritoneal lavage isolated from irradiated mice were evaluated by Western blotting. We also evaluated 30-day survival in C57BL/6 WT, CIRP-/- and TREM-1-/- mice after 6.5-Gy TBI.ResultsThe surface protein and mRNA levels of TREM-1 in RAW264.7 cells were significantly increased at 24 h after 5- and 10-Gy radiation exposure. TREM-1 expression on peritoneal macrophages was significantly increased after radiation exposure in vitro and in vivo. eCIRP levels were significantly increased after radiation exposure in cell culture supernatants of peritoneal macrophages in vitro and in peritoneal lavage in vivo. Moreover, CIRP-/- mice exhibited increased survival after 6.5-Gy TBI compared to WT mice. Interestingly, TREM-1 expression on peritoneal macrophages in CIRP-/- mice was significantly decreased compared to that in WT mice at 24 h after 10-Gy TBI. Furthermore, 30-day survival in TREM-1-/- mice was significantly increased to 64% compared to 20% in WT mice after 6.5-Gy TBI.ConclusionOur data indicate that ionizing radiation increases TREM-1 expression in macrophages via the release of eCIRP, and TREM-1 contributes to worse survival after total body irradiation. Thus, targeting TREM-1 could have the potential to be developed as a novel medical countermeasure for radiation injury.
High density lipoprotein-cholesterol is inversely associated with blood eosinophil counts among asthmatic adults in the USA: NHANES 2011-2018
Authors: Wen Jun , Zhuang Rongjuan , He Chunyan , Giri Mohan , Guo Shuliang 
Published: April 2023

BackgroundA growing number of research strongly suggest that metabolic syndrome and dyslipidemia contribute to the establishment of a pro-inflammatory state in asthma, according to accumulating data. However, the majority of recent research has focused on the association between lipids and asthma in children and adolescents, with contradictory findings. Consequently, we analyzed the relationship between serum lipid and blood eosinophil counts using data from the NHANES in the USA.MethodsAfter screening the individuals from the 2011 to 2018 NHANES survey, a total of 2,544 out of 39156 participants were eligible for our study. The potential association was discussed using the linear regression model, XGBoost algorithm model, generalized additive model, and two-piecewise linear regression model. In addition, we ran stratified analysis to identify specific demographics.ResultsAfter adjusting for covariates, the result indicated that blood eosinophil counts decreased by 45.68 (-68.56, -22.79)/uL for each additional unit of HDL-C (mmol/L). But serum LDL-C, total cholesterol or triglyceride was not correlated with blood eosinophil counts. Furthermore, we used machine learning of the XGBoost model to determine LDL-C, age, BMI, triglyceride, and HDL-C were the five most critical variables in the blood eosinophil counts. The generalized additive model and two-piecewise linear regression model were used to further identify linear relationship between the serum HDL-C and blood eosinophil counts.ConclusionsOur study elucidated a negative and linear correlation between serum HDL-C and blood eosinophil counts among American asthmatic adults, suggesting that serum HDL-C levels might be associated with the immunological condition of asthmatic adults. There was no correlation between serum LDL-C, total cholesterol, or triglyceride levels and blood eosinophil counts.
Hippo dictates signaling for cellular homeostasis and immune defense in Crassostrea hongkongensis hemocytes
Authors: Mao Fan , Zheng Xiaoying , Wong Nai-Kei , Yi Wenjie , Song Jingchen , Fu Shiwei , Xiang Zhiming , Xiao Shu , Bao Yongbo , Yu Ziniu , Zhang Yang 
Published: April 2023

IntroductionThe Hippo signaling pathway is an evolutionarily conserved signaling cascade that plays a crucial role in regulating cell proliferation, differentiation, and apoptosis. It has been shown to be a key regulator of cell fate and cellular homeostasis in various immune processes. Despite its well-established functions in vertebrate immunity, its roles in marine invertebrate immunity remain poorly understood. Therefore, our present work provides fresh mechanistic insights into how the Hippo pathway orchestrates hemocytic functions in Crassostrea hongkongensis, with implications for studies on its major forms and modifications in animal evolution.MethodThe complete set of Hippo pathway genes, including SAV1, MOB1, LATS, YAP/TAZ, TEAD, and MST, were identified from the C. hongkongensis genome. Quantitative PCR assays were conducted to examine the mRNA expression levels of these genes in different tissues and the levels of these genes in hemocytes before and after bacterial challenges. The study also examined the crosstalk between the Hippo pathway and other immune pathways, such as the AP-1 and p53-dependent p21 signaling cascades. RNA interference was used to knock down MST and TEAD, and MST is a core orchestrator of non-canonical Hippo signaling, to investigate its impact on phagocytosis and bacterial clearance in hemocytes.ResultThe results demonstrated that members of the Hippo pathway were highly expressed in hemocytes, with their expression levels significantly increasing following bacterial challenges. Crosstalk between the Hippo pathway and other immune pathways triggered hemocytic apoptosis, which functioned similarly to the canonical Mst-Lats-Yap signaling pathway in Drosophila and mammals. Knocking down MST resulted in increased phagocytosis and boosted the efficiency of bacterial clearance in hemocytes, presumably due to mobilized antioxidant transcription by Nrf for maintaining immune homeostasis.DiscussionThis study provides novel insights into the regulatory mechanisms underlying the Hippo pathway in immune responses of C. hongkongensis hemocytes. The study highlights the importance of the Hippo pathway in maintaining immune homeostasis and orchestrating hemocytic functions in oysters. Moreover, this study demonstrates the divergence of the Hippo pathway's roles in marine invertebrate immunity from mammalian observations, indicating the need for further comparative studies across species. These findings have significant implications for future research aimed at elucidating the evolutionary trajectory and functional diversity of the Hippo signaling pathway in animal evolution.
Skin cancer in solid organ transplant recipients: still an open problem
Authors: Granata Simona , Tessari Gianpaolo , Stallone Giovanni , Zaza Gianluigi 
Published: April 2023

In the last two decades, the optimization of organ preservation and surgical techniques, and the personalized immunosuppression have reduced the rate of acute rejections and early post-transplant complications. However, long-term graft survival rates have not improved over time, and evidence suggest a role of chronic calcineurin inhibitor toxicity in this failure. Solid organ transplant recipients may develop chronic dysfunction/damage and several comorbidities, including post-transplant malignancies. Skin cancers, mostly non-melanoma skin cancers (squamous cell carcinoma and basal cell carcinoma), are the most common malignancies in Caucasian solid organ transplant recipients. Several factors, together with immunosuppression, may contribute to the susceptibility for skin cancers which, although often treatable, could be associated with a much higher mortality rate than in the general population. The rapid identification and treatment (including reduction of immunosuppression and early surgical treatments) have an important role to avoid an aggressive behavior of these malignancies. Organ transplant recipients with a history of skin cancer should be followed closely for developing new and metastatic lesions. Additionally, patient education on the daily use of sun-protective measures and the recognition of the early signs (self-diagnosis) of coetaneous malignancies are useful preventive measures. Finally, clinicians should make themselves aware of the problem and build, in every clinical follow-up center, collaborative network involving transplant clinicians, dermatologists and surgeons who should work together to easily identify and rapidly treat these complications.In this review, we discuss the current literature regarding the epidemiology, risk factors, diagnosis, preventive strategies and treatments of skin cancer in organ transplantation.
The SMC-like RecN protein is at the crossroads of several genotoxic stress responses in Escherichia coli
Authors: Camus Adrien , Espinosa Elena , Zapater Baras Pénélope , Singh Parul , Quenech’Du Nicole , Vickridge Elise , Modesti Mauro , Barre François Xavier , Espéli Olivier 
Published: April 2023

IntroductionDNA damage repair (DDR) is an essential process for living organisms and contributes to genome maintenance and evolution. DDR involves different pathways including Homologous recombination (HR), Nucleotide Excision Repair (NER) and Base excision repair (BER) for example. The activity of each pathway is revealed with particular drug inducing lesions, but the repair of most DNA lesions depends on concomitant or subsequent action of the multiple pathways.MethodsIn the present study, we used two genotoxic antibiotics, mitomycin C (MMC) and Bleomycin (BLM), to decipher the interplays between these different pathways in E. coli. We combined genomic methods (TIS and Hi-SC2) and imaging assays with genetic dissections.ResultsWe demonstrate that only a small set of DDR proteins are common to the repair of the lesions induced by these two drugs. Among them, RecN, an SMC-like protein, plays an important role by controlling sister chromatids dynamics and genome morphology at different steps of the repair processes. We further demonstrate that RecN influence on sister chromatids dynamics is not equivalent during the processing of the lesions induced by the two drugs. We observed that RecN activity and stability requires a pre-processing of the MMC-induced lesions by the NER but not for BLM-induced lesions.DiscussionThose results show that RecN plays a major role in rescuing toxic intermediates generated by the BER pathway in addition to its well-known importance to the repair of double strand breaks by HR.
Plasticity in parental behavior and vasopressin: responses to co-parenting, pup age, and an acute stressor are experience-dependent
Authors: Hiura Lisa C. , Lazaro Vanessa A. , Ophir Alexander G. 
Published: April 2023

IntroductionThe impact of variation in parental caregiving has lasting implications for the development of offspring. However, the ways in which parents impact each other in the context of caregiving is comparatively less understood, but can account for much of the variation observed in the postnatal environment. Prairie voles (Microtus ochrogaster) demonstrate a range of postnatal social groups, including pups raised by biparental pairs and by their mothers alone. In addition to the challenges of providing parental care, prairie vole parents often experience acute natural stressors (e.g., predation, foraging demands, and thermoregulation) that could alter the way co-parents interact.MethodsWe investigated how variation in the experience of raising offspring impacts parental behavior and neurobiology by administering an acute handling stressor on prairie vole families of single mothers and biparental parents over the course of offspring postnatal development.ResultsMothers and fathers exhibited robust behavioral plasticity in response to the age of their pups, but in sex-dependent ways. Pup-directed care from mothers did not vary as a function of their partner’s presence, but did covary with the number of hypothalamic vasopressin neurons in experience-dependent ways. The relationship between vasopressin neuron numbers and fathers’ behaviors was also contingent upon the stress handling manipulation, suggesting that brain-behavior associations exhibit stress-induced plasticity.ConclusionThese results demonstrate that the behavioral and neuroendocrine profiles of adults are sensitive to distinct and interacting experiences as a parent, and extend our knowledge of the neural mechanisms that may facilitate parental behavioral plasticity.
Small-angle neutron scattering study of neutron-irradiated and post-irradiation annealed VVER-1000 reactor pressure vessel weld material
Authors: Ulbricht A. , Dykas J. , Chekhonin P. , Altstadt E. , Bergner F. 
Published: April 2023

Post-irradiation annealing of neutron-irradiated reactor pressure vessel steels is a matter of both technical and scientific interest. Small-angle neutron scattering (SANS), while being sensitive to nm-sized irradiation-induced solute-atom clusters, provides macroscopically representative and statistically reliable measures of cluster volume fraction, number density and size. In the present study, SANS was applied to uncover the size distribution of clusters in as-irradiated samples of a VVER-1000 weld and their gradual dissolution as function of the post-irradiation annealing temperature. The same samples were used to measure Vickers hardness. The results are consistent with Mn-Ni-Si-rich clusters of less than 2 nm radius to be the dominant source of both scattering and hardening. Annealing gave rise to small but significant partial recovery at 350°C and almost complete recovery at 475°C. The dispersed-barrier hardening model was applied to bridge the gap between the characteristics of nano-features and macro-hardness.
CONUT score is associated with short-term prognosis in patients with severe acute pancreatitis: a propensity score matching cohort study
Authors: Shi Lvyuan , Li Ping , Wang Lietao , Wan Dingyuan , Wang Daojin , Yan Xin , He Min , Zhang Zhongwei 
Published: April 2023

BackgroundThe Controlling Nutritional Status (CONUT) score was designed to assess the immune-nutritional status in patients. This study aimed to investigate the role of the CONUT score in the short-term prognosis of severe acute pancreatitis.MethodsThis was a retrospective cohort study. 488 patients with severe acute pancreatitis at the Department of Critical Care Medicine of the West China Hospital of Sichuan University (Chengdu, China) were enrolled in the study. Baseline data were collected from the West China Hospital of Sichuan University database. The primary outcome during follow-up was all-cause mortality. The secondary outcomes were 28 day mortality, renal insufficiency, length of stay (LOS) in the ICU, and length of stay (LOS) in the hospital. Patients were divided into two groups based on a median CONUT score of 7, and baseline differences between the two groups were eliminated by propensity matching. Univariate Cox regression analyses were performed to estimate the association between CONUT score and outcomes. The Kaplan–Meier method was used to estimate the survival rate of patients.ResultsCONUT score was an independent predictor of all-cause mortality (hazard ratio [HR]:2.093; 95%CI: 1.342–3.263; p &lt; 0.001) and 28 day mortality (hazard ratio [HR]:1.813; 95%CI: 1.135–2.896; p &lt; 0.013). CONUT score was not statistically significant in predicting the incidence of renal insufficiency. The high CONUT group had significantly higher all-cause mortality (p &lt; 0.001), and 28 day mortality (p &lt; 0.011) than the low CONUT group.ConclusionThe CONUT score is an independent predictor of short-term prognosis in patients with severe acute pancreatitis, and timely nutritional support is required to reduce mortality in patients with severe acute pancreatitis.