bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bloodstream infections due to Carbapenem-Resistant Enterobacteriaceae in hematological patients: assessment of risk factors for mortality and treatment options
Authors: Zhang Lining , Zhen Sisi , Shen Yuyan , Zhang Tingting , Wang Jieru , Li Jia , Lin Qingsong , Xiao Zhijian , Zheng Yizhou , Jiang Erlie , Han Mingzhe , Wang Jianxiang , Feng Sizhou 
Published: May 2023

Abstract
Purpose
Bloodstream infection (BSI) caused by Carbapenem-Resistant Enterobacteriaceae (CRE) are associated with poor outcomes in hematological patients. The aim of this study was to identify risk factors for mortality and evaluate the value of epidemiological feature of carbapenemases in guiding antimicrobial treatment options.

Methods
Hematological patients with monomicrobial CRE BSI between January 2012 and April 2021 were included. The primary outcome was all-cause mortality 30 days after BSI onset.

Results
A total of 94 patients were documented in the study period. Escherichia coli was the most common Enterobacteriaceae, followed by Klebsiella pneumoniae. 66 CRE strains were tested for carbapenemase genes, and 81.8% (54/66) were positive, including NDM (36/54), KPC (16/54), IMP (1/54). Besides, one E. coli isolate was found to express both NDM and OXA-48-like genes. Overall, 28 patients received an antimicrobial treatment containing ceftazidime-avibactam (CAZ-AVI), of which 21 cases were combined with aztreonam. The remaining 66 patients were treated with other active antibiotics (OAAs). The 30-day mortality rate was 28.7% (27/94) for all patients, and was only 7.1% ((2/28) for patients treated with CAZ-AVI. In multivariate analysis, the presence of septic shock at BSI onset (OR 10.526, 95% CI 1.376–76.923) and pulmonary infection (OR 6.289, 95% CI 1.351–29.412) were independently risk factors for 30-day mortality. Comparing different antimicrobial regimens, CAZ-AVI showed a significant survive benefit than OAAs (OR 0.068, 95% CI 0.007–0.651).

Conclusion
CAZ-AVI-containing regimen is superior to OAAs for CRE BSI. As the predominance of blaNDM in our center, we recommend the combination with aztreonam when choose CAZ-AVI.
Evolocumab loaded Bio-Liposomes for efficient atherosclerosis therapy
Authors: Li Zhenxian , Zhu Haimei , Liu Hao , Liu Dayue , Liu Jianhe , Jiang Jiazheng , Zhang Yi , Qin Zhang , Xu Yijia , Peng Yuan , Liu Bin , Long Yun 
Published: May 2023

AbstractPCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within the plaque of ApoE−/− mice.
Integrating automated liquid handling in the separation workflow of extracellular vesicles enhances specificity and reproducibility
Authors: Van Dorpe Sofie , Lippens Lien , Boiy Robin , Pinheiro Cláudio , Vergauwen Glenn , Rappu Pekka , Miinalainen Ilkka , Tummers Philippe , Denys Hannelore , De Wever Olivier , Hendrix An 
Published: May 2023

Abstract
Background
Extracellular vesicles (EV) are extensively studied in human body fluids as potential biomarkers for numerous diseases. Major impediments of EV-based biomarker discovery include the specificity and reproducibility of EV sample preparation as well as intensive manual labor. We present an automated liquid handling workstation for the density-based separation of EV from human body fluids and compare its performance to manual handling by (in)experienced researchers.

Results
Automated versus manual density-based separation of trackable recombinant extracellular vesicles (rEV) spiked in PBS significantly reduces variability in rEV recovery as quantified by fluorescent nanoparticle tracking analysis and ELISA. To validate automated density-based EV separation from complex body fluids, including blood plasma and urine, we assess reproducibility, recovery, and specificity by mass spectrometry-based proteomics and transmission electron microscopy. Method reproducibility is the highest in the automated procedure independent of the matrix used. While retaining (in urine) or enhancing (in plasma) EV recovery compared to manual liquid handling, automation significantly reduces the presence of body fluid specific abundant proteins in EV preparations, including apolipoproteins in plasma and Tamm-Horsfall protein in urine.

Conclusions
In conclusion, automated liquid handling ensures cost-effective EV separation from human body fluids with high reproducibility, specificity, and reduced hands-on time with the potential to enable larger-scale biomarker studies.

Graphical Abstract
Small extracellular vesicle-mediated metabolic reprogramming: from tumors to pre-metastatic niche formation
Authors: Jiang Chuwen , Jiang Zhengting , Sha Gengyu , Wang Daorong , Tang Dong 
Published: May 2023

AbstractMetastasis, the spread of a tumor or cancer from the primary site of the body to a secondary site, is a multi-step process in cancer progression, accounting for various obstacles in cancer treatment and most cancer-related deaths. Metabolic reprogramming refers to adaptive metabolic changes that occur in cancer cells in the tumor microenvironment (TME) to enhance their survival ability and metastatic potential. Stromal cell metabolism also changes to stimulate tumor proliferation and metastasis. Metabolic adaptations of tumor and non-tumor cells exist not only in the TME but also in the pre-metastatic niche (PMN), a remote TME conducive for tumor metastasis. As a novel mediator in cell-to-cell communication, small extracellular vesicles (sEVs), which have a diameter of 30–150 nm, reprogram metabolism in stromal and cancer cells within the TME by transferring bioactive substances including proteins, mRNAs and miRNAs (microRNAs). sEVs can be delivered from the primary TME to PMN, affecting PMN formation in stroma rewriting, angiogenesis, immunological suppression and matrix cell metabolism by mediating metabolic reprogramming. Herein, we review the functions of sEVs in cancer cells and the TME, how sEVs facilitate PMN establishment to trigger metastasis via metabolic reprogramming, and the prospective applications of sEVs in tumor diagnosis and treatment.
Physiological and pathological consequences of exosomes at the blood–brain-barrier interface
Authors: Salimi Leila , Seyedaghamiri Fatemehsadat , Karimipour Mohammad , Mobarak Halimeh , Mardi Narges , Taghavi Maryam , Rahbarghazi Reza 
Published: May 2023

AbstractBlood–brain barrier (BBB) interface with multicellular structure controls strictly the entry of varied circulating macromolecules from the blood-facing surface into the brain parenchyma. Under several pathological conditions within the central nervous system, the integrity of the BBB interface is disrupted due to the abnormal crosstalk between the cellular constituents and the recruitment of inflammatory cells. Exosomes (Exos) are nano-sized extracellular vesicles with diverse therapeutic outcomes. These particles transfer a plethora of signaling molecules with the potential to modulate target cell behavior in a paracrine manner. Here, in the current review article, the therapeutic properties of Exos and their potential in the alleviation of compromised BBB structure were discussed.
Synergistic immunotherapy targeting cancer-associated anemia: prospects of a combination strategy
Authors: Yuan Ting , Jia Qingzhu , Zhu Bo , Chen Degao , Long Haixia 
Published: May 2023

AbstractCancer-associated anemia promotes tumor progression, leads to poor quality of life in patients with cancer, and even obstructs the efficacy of immune checkpoint inhibitors therapy. However, the precise mechanism for cancer-associated anemia remains unknown and the feasible strategy to target cancer-associated anemia synergizing immunotherapy needs to be clarified. Here, we review the possible mechanisms of cancer-induced anemia regarding decreased erythropoiesis and increased erythrocyte destruction, and cancer treatment-induced anemia. Moreover, we summarize the current paradigm for cancer-associated anemia treatment. Finally, we propose some prospective paradigms to slow down cancer-associated anemia and synergistic the efficacy of immunotherapy.
Aquaporin-4 IgG antibodies: predictors of positivity and their relationship with neuropsychiatric disorders and white matter lesions in Juvenile systemic lupus erythematosus
Authors: Shaaban Yasmeen , EL-Marsafawy Hala , El-Farahaty Reham M , El-Ziny Sherine , EL-Refaey Ahmed M 
Published: May 2023

Abstract
Background
This study aimed to describe the prevalence of the various clinical features and severity of juvenile systemic lupus erythematosus (jSLE) and to assess predictors of AQP4-Ab positivity in jSLE. In addition, we assessed the relationship of AQP4-Abs with neuropsychiatric disorders and white matter lesions in jSLE.

Method
For 90 patients with jSLE, demographic data, clinical manifestations, and treatments received were recorded, and all of the patients were underwent clinical examinations, including assessments for the neurological manifestations of jSLE and neuropsychiatric disorders; Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score evaluations; laboratory investigations, including serum AQP4-Ab assays; and 1.5 Tesla brain MRI. Echocardiography and renal biopsy were performed for the indicated patients.

Result
Fifty-six patients (62.2%) tested positive for AQP4-Abs. These patients were more likely to have higher disease activity scores (p < 0.001); discoid lesions (p = 0.039); neurological disorders (p = 0.001), mainly psychosis and seizures (p = 0.009 and p = 0.032, respectively); renal and cardiac involvement (p = 0.004 and p = 0.013, respectively); lower C3 levels (p = 0.006); white matter hyperintensities (p = 0.008); and white matter atrophy (p = 0.03) than patients who were negative for AQP4-Abs. Furthermore, AQP4-Ab-positive patients were more likely to have received cyclophosphamide (p = 0.028), antiepileptic drugs (p = 0.032) and plasma exchange therapy (p = 0.049).

Conclusion
jSLE patients with higher severity scores, neurological disorders, or white matter lesions could develop antibodies against AQP4. We recommend more studies for systematic screening of AQP4-Ab positivity in jSLE patients to confirm its relationship with neurological disorders.
Study on association of serum uric acid levels with bipolar disorder: systematic review and meta-analysis in Chinese patients
Authors: Chen Haihan , Sun Fengli , Jin Weidong 
Published: May 2023

AbstractBackgroundThe purine system represented by uric acid may be involved in the pathogenesis of bipolar disorder, This study intends to explore the association of serum uric acid levels with bipolar disorder in Chinese patients through meta-analysis.MethodsElectronic databases, including PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI), searching from inception to December 2022. Randomized Controlled Trials that reported serum uric acid levels and bipolar disorder were included. Two investigators independently extracted data and RevMan5.4 and Stata14.2 were used for statistical analyses.ResultsTwenty-eight studies with 4482 bipolar disorder, 1568 depression, 785 schizophrenia, and 2876 healthy control subjects were included in this meta-analysis. The results of the meta-analysis showed that serum uric acid levels in the bipolar disorder group were significantly higher than those in depression [SMD 0.53 (0.37, 0.70),p < 0.00001], schizophrenia [SMD 0.27 (0.05, 0.49),p = 0.02] and healthy control group [SMD 0.87 (0.67, 1.06),p < 0.00001]. Subgroup-analysis showed that in Chinese people with bipolar disorder, uric acid levels of the manic episode were higher than the depressed episode [SMD 0.31 (0.22, 0.41),p < 0.00001].ConclusionOur results indicated a strong association between serum uric acid levels and bipolar disorder in Chinese patients, but further studies about whether uric acid levels can be a biomarker for bipolar disorder still need to investigate.
Bearing the mark of pain: mystery in medicine
Authors: Celie Karel-Bart , Paris John J. 
Published: May 2023

AbstractDostoevsky wrote that love in action is a harsh and terrible thing compared to love in dreams. That reality is particularly evident in medicine, where there is an almost universal, involuntary participation of physicians and other healthcare workers in the suffering of their patients. This paper explores this phenomenon through the paradigm of ‘mystery’ as explained by the French existentialist philosopher Gabriel Marcel. A mystery is different from a problem in the sense that the former requires the active immersion of the person involved in order to be truly experienced. It is a ‘meta-problem’ that cannot be analyzed objectively and separately from the person that it affects, without changing the nature of the thing experienced. The authors contend that the human suffering encountered in medicine is one such phenomenon, and the paper draws on illustrations of this concept in art and literature. Awareness of the subtle but important difference between mystery and problem may help physicians better understand their personal entanglement with the suffering of patients.
Complex duodenal fistulae: a surgical nightmare
Authors: Leppäniemi Ari , Tolonen Matti , Mentula Panu 
Published: May 2023

Abstract
Introduction
A common feature of external duodenal fistulae is the devastating effect of the duodenal content rich in bile and pancreatic juice on nearby tissues with therapy-resistant local and systemic complications. This study analyzes the results of different management options with emphasis on successful fistula closure rates.

Methods
A retrospective single academic center study of adult patients treated for complex duodenal fistulas over a 17-year period with descriptive and univariate analyses was performed.

Results
Fifty patients were identified. First line treatment was surgical in 38 (76%) cases and consisted of resuture or resection with anastomosis combined with duodenal decompression and periduodenal drainage in 36 cases, rectus muscle patch, and surgical decompression with T-tube in one each. Fistula closure rate was 29/38 (76%). In 12 cases, the initial management was nonoperative with or without percutaneous drainage. The fistula was closed without surgery in 5/6 patients (1 patient died with persistent fistula). Among the remaining 6 patients eventually operated, fistula closure was achieved in 4 cases. There was no difference in successful fistula closure rates among initially operatively versus nonoperatively managed patients (29/38 vs. 9/12, p = 1.000). However, when considering eventually failed nonoperative management in 7/12 patients, there was a significant difference in the fistula closure rate (29/38 vs. 5/12, p = 0.036). The overall in-hospital mortality rate was 20/50 (40%).

Conclusions
Surgical closure combined with duodenal decompression in complex duodenal leaks offers the best chance of successful outcome. In selected cases, nonoperative management can be tried, accepting that some patients may require surgery later.
The PRESIDE (PhaRmacogEnomicS In DEpression) Trial: a double-blind randomised controlled trial of pharmacogenomic-informed prescribing of antidepressants on depression outcomes in patients with major depressive disorder in primary care
Authors: Saya Sibel , Chondros Patty , Abela Anastasia , Mihalopolous Cathrine , Chatterton Mary Lou , Gunn Jane , Chen Timothy F. , Polasek Thomas M. , Dettmann Elise , Brooks Rachel , King Michelle , Spencer Luke , Alphonse Pavithran , Milton Shakira , Ramsay Georgia , Siviour Zoe , Liew Jamie , Ly Philip , Thoenig Matthew , Seychell Raushaan , La Rocca Floriana , Hesson Luke B. , Mejias Nydia , Sivertsen Terri , Galea Melanie Anne , Bousman Chad , Emery Jon 
Published: May 2023

Abstract
Background
The evidence for the clinical utility of pharmacogenomic (PGx) testing is growing, and guidelines exist for the use of PGx testing to inform prescribing of 13 antidepressants. Although previous randomised controlled trials of PGx testing for antidepressant prescribing have shown an association with remission of depression in clinical psychiatric settings, few trials have focused on the primary care setting, where most antidepressant prescribing occurs.

Methods
The PRESIDE Trial is a stratified double-blinded randomised controlled superiority trial that aims to evaluate the impact of a PGx-informed antidepressant prescribing report (compared with standard prescribing using the Australian Therapeutic Guidelines) on depressive symptoms after 12 weeks, when delivered in primary care. Six hundred seventy-two patients aged 18–65 years of general practitioners (GPs) in Victoria with moderate to severe depressive symptoms, measured using the Patient Health Questionnaire-9 (PHQ-9), will be randomly allocated 1:1 to each arm using a computer-generated sequence. Participants and GPs will be blinded to the study arm. The primary outcome is a difference between arms in the change of depressive symptoms, measured using the PHQ-9 after 12 weeks. Secondary outcomes include a difference between the arms in change in PHQ-9 score at 4, 8 and 26 weeks, proportion in remission at 12 weeks, a change in side effect profile of antidepressant medications, adherence to antidepressant medications, change in quality of life and cost-effectiveness of the intervention.

Discussion
This trial will provide evidence as to whether PGx-informed antidepressant prescribing is clinically efficacious and cost-effective. It will inform national and international policy and guidelines about the use of PGx to select antidepressants for people with moderate to severe depressive symptoms presenting in primary care.

Trial registration
Australian and New Zealand Clinical Trial Registry ACTRN12621000181808. Registered on 22 February 2021.
Transcriptomic and metabolomic analyses revealed regulation mechanism of mixotrophic Cylindrotheca sp. glycerol utilization and biomass promotion
Authors: Wang Song , Zhou Xiyi , Wu Sha , Zhao Mengkai , Hu Zhangli 
Published: May 2023

Abstract
Background
Diatoms have been viewed as ideal cell factories for production of some high-value bioactive metabolites, such as fucoxanthin, but their applications are restrained by limited biomass yield. Mixotrophy, by using both CO2 and organic carbon source, is believed effective to crack the bottleneck of biomass accumulation and achieve a sustainable bioproduct supply.

Results
Glycerol, among tested carbon sources, was proved as the sole that could significantly promote growth of Cylindrotheca sp. with illumination, a so-called growth pattern, mixotrophy. Biomass and fucoxanthin yields of Cylindrotheca sp., grown in medium with glycerol (2 g L−1), was increased by 52% and 29%, respectively, as compared to the autotrophic culture (control) without compromise in photosynthetic performance. As Cylindrotheca sp. was unable to use glycerol without light, a time-series transcriptomic analysis was carried out to elucidate the light regulation on glycerol utilization. Among the genes participating in glycerol utilization, GPDH1, TIM1 and GAPDH1, showed the highest dependence on light. Their expressions decreased dramatically when the alga was transferred from light into darkness. Despite the reduced glycerol uptake in the dark, expressions of genes associating with pyrimidine metabolism and DNA replication were upregulated when Cylindrotheca sp. was cultured mixotrophically. Comparative transcriptomic and metabolomic analyses revealed amino acids and aminoacyl-tRNA metabolisms were enhanced at different timepoints of diurnal cycles in mixotrophic Cylindrotheca sp., as compared to the control.

Conclusions
Conclusively, this study not only provides an alternative for large-scale cultivation of Cylindrotheca, but also pinpoints the limiting enzymes subject to further metabolic manipulation. Most importantly, the novel insights in this study should aid to understand the mechanism of biomass promotion in mixotrophic Cylindrotheca sp.
Immune-related transcripts, microbiota and vector competence differ in dengue-2 virus-infected geographically distinct Aedes aegypti populations
Authors: Chen Tse-Yu , Bozic Jovana , Mathias Derrick , Smartt Chelsea T. 
Published: May 2023

Abstract
Background
Vector competence in Aedes aegypti is influenced by various factors. Crucial new control methods can be developed by recognizing which factors affect virus and mosquito interactions.

Methods
In the present study we used three geographically distinct Ae. aegypti populations and compared their susceptibility to infection by dengue virus serotype 2 (DENV-2). To identify any differences among the three mosquito populations, we evaluated expression levels of immune-related genes and assessed the presence of microbiota that might contribute to the uniqueness in their vector competence.

Results
Based on the results from the DENV-2 competence study, we categorized the three geographically distinct Ae. aegypti populations into a refractory population (Vilas do Atlântico), a susceptible population (Vero) and a susceptible but low transmission population (California). The immune-related transcripts were highly expressed in the California population but not in the refractory population. However, the Rel-1 gene was upregulated in the Vilas do Atlântico population following ingestion of a non-infectious blood meal, suggesting the gene’s involvement in non-viral responses, such as response to microbiota. Screening of the bacteria, fungi and flaviviruses revealed differences between populations, and any of these could be one of the factors that interfere with the vector competence.

Conclusions
The results reveal potential factors that might impact the virus and mosquito interaction, as well as influence the Ae. aegypti refractory phenotype.

Graphical Abstract