bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of cofactors in the regulation of microbial metabolism: A state of the art review
Authors: Sun Yang , Zhang Ting , Lu Bingqian , Li Xiangfei , Jiang Ling 
Published: April 2023

Cofactors are crucial chemicals that maintain cellular redox balance and drive the cell to do synthetic and catabolic reactions. They are involved in practically all enzymatic activities that occur in live cells. It has been a hot research topic in recent years to manage their concentrations and forms in microbial cells by using appropriate techniques to obtain more high-quality target products. In this review, we first summarize the physiological functions of common cofactors, and give a brief overview of common cofactors acetyl coenzyme A, NAD(P)H/NAD(P)+, and ATP/ADP; then we provide a detailed introduction of intracellular cofactor regeneration pathways, review the regulation of cofactor forms and concentrations by molecular biological means, and review the existing regulatory strategies of microbial cellular cofactors and their application progress, to maximize and rapidly direct the metabolic flux to target metabolites. Finally, we speculate on the future of cofactor engineering applications in cell factories.
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Prediction model for cognitive frailty in older adults: A systematic review and critical appraisal
Authors: Huang Jundan , Zeng Xianmei , Hu Mingyue , Ning Hongting , Wu Shuang , Peng Ruotong , Feng Hui 
Published: April 2023

BackgroundSeveral prediction models for cognitive frailty (CF) in older adults have been developed. However, the existing models have varied in predictors and performances, and the methodological quality still needs to be determined.ObjectivesWe aimed to summarize and critically appraise the reported multivariable prediction models in older adults with CF.MethodsPubMed, Embase, Cochrane Library, Web of Science, Scopus, PsycINFO, CINAHL, China National Knowledge Infrastructure, and Wanfang Databases were searched from the inception to March 1, 2022. Included models were descriptively summarized and critically appraised by the Prediction Model Risk of Bias Assessment Tool (PROBAST).ResultsA total of 1,535 articles were screened, of which seven were included in the review, describing the development of eight models. Most models were developed in China (n = 4, 50.0%). The most common predictors were age (n = 8, 100%) and depression (n = 4, 50.0%). Seven models reported discrimination by the C-index or area under the receiver operating curve (AUC) ranging from 0.71 to 0.97, and four models reported the calibration using the Hosmer–Lemeshow test and calibration plot. All models were rated as high risk of bias. Two models were validated externally.ConclusionThere are a few prediction models for CF. As a result of methodological shortcomings, incomplete presentation, and lack of external validation, the models’ usefulness still needs to be determined. In the future, models with better prediction performance and methodological quality should be developed and validated externally.Systematic review registrationwww.crd.york.ac.uk/prospero, identifier CRD42022323591.
Frequency of deep-seated cerebral microbleeds in patients with lobar hemorrhages and histopathological evidence for cerebral amyloid angiopathy
Authors: Huhndorf Monika , Röcken Christoph , Flüh Charlotte , Weiler Caroline , Kuhlenbäumer Gregor , Tegeler Nora , Schacht Hannes , Neumann Alexander , Margraf Nils G. , Jensen-Kondering Ulf 
Published: April 2023

BackgroundCerebral amyloid angiopathy (CAA) is a common disease and the most common cause of lobar hemorrhages in the elderly. Usually, deep-seated microhemorrhages preclude the diagnosis of CAA. In this study, we sought to estimate the frequency of deep-seated microbleeds on MRI in patients with lobar hemorrhages and histopathological evidence for cerebral amyloid angiopathy. In addition, we describe a cohort of patients with cortical and deep-seated microbleeds on MRI and a histopathological specimen available from lobar hematoma evacuation.MethodsRetrospective database search for histopathological specimens from lobar hematoma evacuation and review of imaging findings (CT and MRI) and patient charts was performed.ResultsBetween 1 January 2012 and 31 December 2020, 88 specimens from 88 patients were available. A total of 56 specimens were excluded (no brain tissue in the specimen n = 4, other diagnosis n = 8, no MRI n = 43, and no BOLD-based sequence n = 1). Of the remaining 32 patients, 25 patients (78%) did not harbor deep-seated lesions on MRI, of which 17 patients had histopathological features of CAA. A total of seven patients harbored deep-seated CMB. Of these seven patients, three (3/20, 15%) had histopathological features of CAA.ConclusionApproximately 15% of patients with histopathologically diagnosed CAA harbor deep-seated microbleeds. This finding may add to the discussion on how to identify patients with CAA and deep-seated CMB.
In vitro methods in autophagy research: Applications in neurodegenerative diseases and mood disorders
Authors: Sánchez-Vidaña Dalinda Isabel , Li Jingjing , Abokyi Samuel , Chan Jackie Ngai-Man , Ngai Shirley Pui-Ching , Lau Benson Wui-Man 
Published: April 2023

BackgroundAutophagy is a conserved physiological intracellular mechanism responsible for the degradation and recycling of cytoplasmic constituents (e.g., damaged organelles, and protein aggregates) to maintain cell homeostasis. Aberrant autophagy has been observed in neurodegenerative diseases, including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington’s Disease (HD), and recently aberrant autophagy has been associated with mood disorders, such as depression. Several in vitro methods have been developed to study the complex and tightly regulated mechanisms of autophagy. In vitro methods applied to autophagy research are used to identify molecular key players involved in dysfunctional autophagy and to screen autophagy regulators with therapeutic applications in neurological diseases and mood disorders. Therefore, the aims of this narrative review are (1) to compile information on the cell-based methods used in autophagy research, (2) to discuss their application, and (3) to create a catalog of traditional and novel in vitro methods applied in neurodegenerative diseases and depression.MethodsPubmed and Google Scholar were used to retrieve relevant in vitro studies on autophagy mechanisms in neurological diseases and depression using a combination of search terms per mechanism and disease (e.g., “macroautophagy” and “Alzheimer’s disease”). A total of 37 studies were included (14 in PD, 8 in AD, 5 in ALS, 5 in %, and 5 in depression).ResultsA repertoire of traditional and novel approaches and techniques was compiled and discussed. The methods used in autophagy research focused on the mechanisms of macroautophagy, microautophagy, and chaperone-mediated autophagy. The in vitro tools presented in this review can be applied to explore pathophysiological mechanisms at a molecular level and to screen for potential therapeutic agents and their mechanism of action, which can be of great importance to understanding disease biology and potential therapeutic options in the context of neurodegenerative disorders and depression.ConclusionThis is the first review to compile, discuss, and provide a catalog of traditional and novel in vitro models applied to neurodegenerative disorders and depression.
Impact of early enteral nutrition on ventilator associated pneumonia in intubated severe trauma patients: A propensity score-matched study
Authors: Wang Su , Zhao Xin , Wang Qian , Wu Yongran , Xu Jiaxin , Li Ruiting , Zhou Ting , Lv Zheng , Yang Jihong , Yang Le , Zou Xiaojing 
Published: April 2023

BackgroundEarly enteral nutrition (EN) is recommended for critically ill patients. However, the impact of early EN on intubated severe trauma patients remains unclear.MethodsSeverely traumatized adult patients who received invasive mechanical ventilation (MV) for more than 48 h during intensive care unit (ICU) stay at our institution between 2017 and 2022 were retrospectively included. Early EN was defined as EN initiation ≤48 h from ICU admission and late EN &gt;48 h. Propensity score matching (PSM) analysis was used to compare outcomes between the groups. The primary endpoint was the incidence of ventilator-associated pneumonia (VAP). Multivariable logistic regression analysis was performed to identify independent predictors of delayed EN.ResultsFor final analysis, 337 intubated severe trauma patients were available, including 204 (60.5%) in the early EN group and 133 (39.5%) in the late EN group. After PSM, early EN patients had a lower incidence of VAP (12.9 vs. 25.8%, p = 0.026) and a shorter length of hospital stay (21 vs. 24 days, p = 0.015) compared to late EN patients. There was no demonstrable difference in mortality between the two groups. Abdominal trauma, massive blood transfusion, and serum albumin were identified as independent risk factors for delayed EN.ConclusionEarly EN decreased the VAP rate and reduced the length of hospital stay in invasively ventilated patients with severe trauma. Abdominal injury, massive blood transfusion and low albumin were associated with delayed EN.
A single-arm phase II clinical trial of anlotinib combined with chemotherapy for the treatment of metastatic triple-negative breast cancer
Authors: Huang Jia-Yi , Xie Xiao-Feng , Chen Xue-Lian , Zhang Qiu-Yi , Chen Li-Ping , Bai Xue , Lan Xiao-Feng , Song Lin , Guo Jin-Feng , Du Cai-Wen 
Published: April 2023

BackgroundAnlotinib is a novel oral small-molecule tyrosine kinase inhibitor (TKI), which can inhibit angiogenesis. The purpose of this study was to evaluate the efficacy and safety of anlotinib combined with chemotherapy in patients with metastatic triple-negative breast cancer (TNBC).MethodsThis phase II clinical trial included 40 patients with metastatic TNBC who had previously received anthracycline and/or taxane treatment. All patients received anlotinib combined with chemotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR) and safety.ResultsDuring May 1, 2019 and April 30, 2022, there were 40 patients enrolled in this study. The median PFS and median OS were 8.8 months (95% confidence interval [CI] 6.5-11.1 months) and 19.0 months (95% CI, 12.1–25.9 months), respectively. The ORR, CBR and DCR were 40.0% (16/40), 85.0% (34/40) and 95.0% (38/40), respectively. Cox univariate and multivariate analyses demonstrated that having more than 3 metastatic sites (p = 0.001; p = 0.020) was an independent and meaningful unfavorable prognostic factor for PFS. 37.5% of patients had grade 3 to 4 treatment-related adverse events (TRAEs). The grade 3 to 4 TRAEs included neutropenia (22.5%), leukopenia (20.0%), secondary hypertension (10.0%), hand-foot syndrome (5.0%), vomiting (5.0%), proteinuria (5.0%) and thrombocytopenia (2.5%). None of the patients withdrew from the study or died due to TRAEs.ConclusionIn this single-arm study, the treatment of metastatic TNBC with anlotinib combined with chemotherapy showed certain efficacy, and its toxicity was acceptable.
Efficacy and safety of pembrolizumab versus sintilimab treatment in patients with advanced squamous lung cancer: A real-world study in China
Authors: Yang Wenyu , Li Tao , Bai Yibing , Long Yaping , Gao Ming , Wang Ting , Jing Fangfang , Zhang Fan , Tao Haitao , Ma Junxun , Wang Lijie , Hu Yi 
Published: April 2023

ImportanceBoth pembrolizumab and sintilimab have been approved by the Chinese State Drug Administration (NMPA) for the first-line treatment of patients with advanced squamous lung cancer. The differences of the two drugs in efficacy and safety are unclear.ObjectivesTo compare the real-world efficacy and safety of first-line treatments in patients with advanced squamous lung cancer.Materials and methodsThis was a retrospective review of patients with advanced squamous carcinoma who received sintilimab or pembrolizumab in combination with chemotherapy as first-line therapy between June 2018 and April 2022 in the Chinese PLA Hospital. The primary objective was to compare the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) between the two groups. Secondary objectives were to compare the disease control rate (DCR) and to analyze adverse events (AEs) between the two groups.ResultsA total of 164 patients were enrolled, including 63 patients (38.4%) in the sintilimab-combined chemotherapy group and 101 patients (61.6%) in the pembrolizumab-combined chemotherapy group. The ORR was 65.10% in the sintilimab group and 61.40% in the pembrolizumab group (P=0.634). The DCR was 92.10% and 92.10% in the sintilimab and pembrolizumab groups, respectively (P=0.991). The median PFS was 22.2 months for patients treated with sintilimab group compared with 16.5 months for patients treated with pembrolizumab group[hazard ratio (HR) = 0.743; 95% confidence interval (CI): 0.479-1.152; P = 0.599]. Patients treated with pembrolizumab did not achieve a median OS, and patients treated with sintilimab had a median OS of 30.7 months. In the sintilimab group, the incidence of all treatment-related adverse events (TRAEs) was 92.1% (58/63), and the incidence of grade 3-4 TRAEs of 42.9% (27/63). In the pembrolizumab group, the incidence of all TRAEs was 90.1% (91/101), and the incidence of grade 3-4 TRAEs was 37.6% (38/101).ConclusionIn the clinical treatment of Chinese patients with advanced squamous lung cancer, first-line treatment with sintilimab in combination with chemotherapy provided similar efficacy to pembrolizumab in combination with chemotherapy, and the treatment-related adverse effect profiles were comparable between the two groups, including similar rates of grade 3-4 and all adverse events.
Long-term health outcomes of allogeneic hematopoietic stem cell transplantation
Authors: Kelkar Amar H. , Antin Joseph H. , Shapiro Roman M. 
Published: April 2023

BackgroundFifty years of hematopoietic cell transplantation (HCT) has ushered in an exciting era of cellular therapy and has led to enormous progress in improving the outcomes of patients with both malignant and non-malignant hematologic disease. As the survival of transplanted patients has increased, so has the recognition of long-term complications related to this therapy.PurposeThe goal of this review is to highlight some of the most common long-term complications of HCT.Data sourcesTo this end, we have conducted a review of the published literature on the long-term complications of HCT encompassing the past 50 years.Study selectionWe have endeavored to include long-term complications reported in research articles, case series and case reports, reviews, and abstracts. We have focused primarily on adult allogeneic HCT, but have included some data from studies of pediatric allogeneic HCT as well. We have also prioritized the literature published in the last 15 years.Data extractionKey data supporting the onset and prevalence of the most common long-term complications was extracted.LimitationsWhile the list of long-term complications extracted and reported was comprehensive, it was not exhaustive.ConclusionsWe have endeavored to highlight some of the most common long-term complications of HCT, the recognition and management of which constitutes an important part of HCT survivorship care.
Relationship between serum phosphate and mortality in critically ill children receiving continuous renal replacement therapy
Authors: Zhou Xiong , He Jie , Zhu Desheng , Yao Zhenya , Peng Dan , Zhang Xinping 
Published: April 2023

PurposeWe aimed to explore the relationship between serum phosphate concentration and 90-day mortality in critically ill children receiving continuous renal replacement therapy (CRRT).MethodsData from the medical records of children aged &lt;13 years who received CRRT at the Pediatric Intensive Care Unit of Hunan Children's Hospital, China from January 2015 to June 2020 were retrospectively collected. Children were grouped into four categories according to the baseline phosphate concentration before CRRT and mean serum phosphate concentration during CRRT: &lt;0.81 mmol/L (hypophosphatemia), 0.81–1.19 mmol/L, 1.2–2.4 mmol/L (normal phosphate concentration), and &gt;2.4 mmol/L (hyperphosphatemia), with the normal phosphate group serving as the comparator group. The correlation of the serum phosphate concentration before and during CRRT with the 90-day mortality after CRRT initiation was analyzed using logistic regression.ResultsA total of 177 children were included in our study. The mean serum phosphate concentration before CRRT was 1.46 mmol/L (quartiles: 1.04, 2.20). The 90-day mortality rate was increased in children with a serum phosphate concentration &gt;2.4 mmol/L before CRRT (adjusted odds ratio [aOR] 3.74, 95% confidence interval [CI] 1.42–9.86, P = 0.008). The mean serum phosphate concentration during CRRT was 1.2 mmol/L (quartiles: 0.91, 1.49). The 90-day mortality rate was increased in children with a mean serum phosphate concentration &gt;2.4 mmol/L during CRRT (aOR 7.34, 95% CI 1.59–33.88, P = 0.011).ConclusionHyperphosphatemia before and during CRRT predicts a higher 90-day mortality rate.
Fetal and neonatal outcome in severe alloimmunization managed with intrauterine transfusion: 18-year experience in a tertiary referral hospital in China
Authors: Pan Wenxu , Wu Haiyan , Chen Junlin , Mo Xinyue , Wang Hongxin , Fang Qun , Li Yijuan , Huang Yuefang 
Published: April 2023

BackgroundHemolytic disease of the fetus and newborn (HDFN) due to red cell alloimmunization, is an important cause of fetal and neonatal morbidity and mortality. However, fetal and neonatal outcome of HDFN managed with intrauterine transfusion (IUT) in China are unknown. In addition, fetal and neonatal outcomes according to the type of maternal red cell alloantibodies involved and outcomes of hydrops fetalis are also unclear.ObjectivesThe objective of this study was to evaluate fetal and neonatal outcomes of severe red-cell alloimmunization treated by IUT, to compare the outcomes according to the type of antibody, and to investigate the perinatal and postnatal outcomes of hydrops fetalis due to red cell alloimmunization.MethodsA retrospective study of pregnancies affected by HDFN and managed with IUT at a tertiary care university hospital in China between January 2001 and December 2018 was performed. Fetal and neonatal outcomes were investigated, and comparison of outcomes depending on the type of antibody and comparison of outcome between hydrops fetalis and fetuses without hydrops were also conducted.Results244 IUTs were performed in 81 fetuses from 80 pregnancies. Anti-RhD was the major etiology of HDFN requiring IUT (71.6%). The fetal survival rate was 90.1%. The survival rate of the hydropic fetuses was significantly lower than those of the non hydropic fetuses (61.2% vs. 95.6%) (P = 0.002**). Compared with non hydropic fetuses, hydropic fetuses had significantly lower gestational age and lower hemoglobin level at first IUT. The neonatal survival rate was 98.6%. Exchange transfusions were required in 26% of the neonates. 30.1% of neonates had late anemia and required top-up transfusions, and hydropic fetuses required more late top-up transfusions than fetuses without hydrops. No significant difference in fetal and neonatal outcomes was found among the four subgroups stratified by the antibody involved.ConclusionOur study demonstrates that IUT is an effective and safe therapy for severe HDFN at our institution. Early detection and treatment of hydrops is critical for perinatal outcomes. Particular attention should be paid to late postnatal anemia in affected neonates and top-up transfusion is still commonly needed.
Mechanistic assessment and ablation of left ventricular assist device related ventricular tachycardia in patients with severe heart failure
Authors: Hohendanner Felix , Bock Matthias , Keznickl-Pulst Julian , Furundzija Vesna , Scholz Sebastian , Schöppenthau Doreen , Hrytsyna Yuriy , Falk Volkmar , Pieske Burkert , Hindricks Gerhard , Potapov Evgenij , Gerds-Li Jin-Hong 
Published: April 2023

Aims: Left-ventricular-assist-devices (lvad) are an established treatment for patients with severe heart failure with reduced ejection fraction (HF) and reduce mortality. However, HF patients have significant substrate for ventricular tachycardia (VT) and the lvad itself might be pro-arrhythmogenic. We investigated the mechanism of VT in lvad-patients in relation to the underlying etiology and provide in silico and ex-vivo data for ablation in these HF patients.Methods and Results: We retrospectively analyzed invasive electrophysiological (EP) studies of 17 patients with VT and lvad. The mechanism of VT was determined using electroanatomical, entrainment and activation time mapping. Ischemic cardiomyopathy was present in 70% of patients. VT originated from the lvad region in &gt;30%. 1/6 patients with VT originating from the lvad region had episodes before lvad implantation, while 7/11 patients with VT originating from other regions had episodes before implantation. Number and time of radiofrequency (RF)-ablation lesions were not different between VTs originating from the lvad or other regions. Long-term freedom from VT was 50% upon ablation in patients with VT originating from the lvad region and 64% if ablation was conducted in other regions. To potentially preemptively mitigate lvad related VT in patients undergoing lvad implantation, we obtained in silico derived data and performed ex-vivo experiments targeting ventricular myocardium. Of the tested settings, application of 25 W for 30 s was safe and associated with optimal lesion characteristics.Conclusion: A significant percentage of patients with lvad undergoing VT ablation exhibit arrhythmia originating in close vicinity to the device and recurrence rates are high. Based on in silico and ex-vivo data, we propose individualized RF-ablation in selected patients at risk for/with lvad related VT.