bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating mid-regional proadrenomedullin is a predictor of mortality in patients with COVID-19: a systematic review and meta-analysis
Authors: Wang Na , Liu Lushan , He Wei , Shang Na , Li Junyu , Qin Zhou , Du Xiaoxia 
Published: May 2023

Abstract
Background
Although there is increasing understanding of the changes in the laboratory parameters of Coronavirus disease 2019 (COVID-19), the correlation between circulating Mid-regional Proadrenomedullin (MR-proADM) and mortality of patients with COVID-19 is not fully understood. In this study, we conducted a systematic review and meta-analysis to evaluate the prognostic value of MR-proADM in patients with COVID-19.

Methods
The PubMed, Embase, Web of Science, Cochrane Library, Wanfang, SinoMed and Chinese National Knowledge Infrastructure (CNKI) databases were searched from 1 January 2020 to 20 March 2022 for relevant literature. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess quality bias, STATA was employed to pool the effect size by a random effects model, and potential publication bias and sensitivity analyses were performed.

Results
14 studies comprising 1822 patients with COVID-19 met the inclusion criteria, there were 1145 (62.8%) males and 677 (31.2%) females, and the mean age was 63.8 ± 16.1 years. The concentration of MR-proADM was compared between the survivors and non-survivors in 9 studies and the difference was significant (P < 0.01), I2 = 46%. The combined sensitivity was 0.86 [0.73–0.92], and the combined specificity was 0.78 [0.68–0.86]. We drew the summary receiver operating characteristic (SROC) curve and calculated the area under curve (AUC) = 0.90 [0.87–0.92]. An increase of 1 nmol/L of MR-proADM was independently associated with a more than threefold increase in mortality (odds ratio (OR) 3.03, 95% confidence interval (CI) 2.26–4.06, I2 = 0.0%, P = 0.633). The predictive value of MR-proADM for mortality was better than many other biomarkers.

Conclusion
MR-proADM had a very good predictive value for the poor prognosis of COVID-19 patients. Increased levels of MR-proADM were independently associated with mortality in COVID-19 patients and may allow a better risk stratification.
Whipple’s disease presenting as weight gain and constipation in a Chinese woman
Authors: Ye Haiyan , Hu Xiao , Tong Tommy Richard Sun-Wing , Chen Shuang , Li Tao , Xing Fanfan , Chan Jasper Fuk-Woo , Yuen Kwok-Yung , Chiu Kelvin Hei-Yeung 
Published: May 2023

Abstract
Background
Whipple’s disease is a chronic infection due to Tropheryma whipplei, commonly reported in the Caucasian but not in the Chinese population.

Case presentation
A 52-year-old female with good past health, was diagnosed with Whipple’s disease, presenting with constipation, unintentional weight gain, and fleeting polyarthralgia. Investigations prior to admission showed raised CA125 and computed tomography of the abdomen showed multiple retroperitoneal mesenteric lymphadenopathies. Extensive investigations performed on secondary causes of weight gain were unrevealing. Subsequent PET-CT scan revealed generalized lymphadenopathy involving the left deep cervical, supraclavicular, and retroperitoneal mesenteric area. Excisional biopsy of the left supraclavicular lymph node was performed, with histology showing infiltrations of Periodic acid-Schiff positive foamy macrophages. T. whipplei DNA was detected in her serum, saliva, stool, and lymph node by PCR targeting the 16S ribosomal RNA gene. She was started on intravenous ceftriaxone, and then stepped down to oral antibiotics for a total of 44 months. The recurrence of fever after 12 days of ceftriaxone raised the suspicion of Immune Reconstitution Inflammatory Syndrome (IRIS). Serial imaging showed a gradual reduction in the size of retroperitoneal lymphadenopathies. Literature review on Whipple’s disease in the Chinese population identified 13 reports of detectable T. whipplei DNA in clinical specimens. The majority of the cases were pneumonia, followed by culture-negative endocarditis, encephalitis, and skin and soft tissue infection. However, most patients with pneumonia were diagnosed based on next generation sequencing alone, with the resolution of pulmonary infiltrates without adequate duration of antibiotics, suggesting the possibility of colonization instead of infection. The recommendation of long-term doxycycline suppression after treatment may be supported by the slow response of retroperitoneal lymphadenopathies to antibiotics in our patient.

Conclusions
Unintentional weight gain and constipation could be atypical presentations of Whipple’s disease. It is a rare disease in the Chinese population despite the advancement of molecular techniques in the diagnosis of infections. A prolonged course of antibiotics may be required due to slow clinical response as documented by serial imaging in our case. The possibility of IRIS should be considered in patients with breakthrough fever during treatment of Whipple’s disease.
What data collection methods work best for COVID19 outbreak surveillance for people with end stage kidney disease? An observational cohort study using the UK Renal Registry
Authors: Santhakumaran Shalini , Savino Manuela , Benoy-Deeney Fran , Steenkamp Retha , Medcalf James , Nitsch Dorothea 
Published: May 2023

Abstract
Background
Patients on kidney replacement therapy (KRT) are vulnerable to severe illness from COVID-19. Timely, accurate surveillance is essential for planning and implementing infection control at local, regional and national levels. Our aim was to compare two methods of data collection for COVID-19 infections amongst KRT patients in England.

Methods
Adults receiving KRT in England were linked to two sources of data on positive COVID-19 tests recorded March-August 2020: (1) submissions from renal centres to the UK Renal Registry (UKRR) and (2) Public Health England (PHE) laboratory data. Patient characteristics, cumulative incidence by modality (in-centre haemodialysis (ICHD), home HD, peritoneal dialysis (PD) and transplant), and 28-day survival were compared between the two sources.

Results
2,783/54,795 patients (5.1%) had a positive test in the combined UKRR-PHE dataset. Of these 2,783, 87% had positive tests in both datasets. Capture was consistently high for PHE (> 95% across modalities) but varied for UKRR (ranging from ICHD 95% to transplant 78%, p < 0.0001). Patients captured only by PHE were more likely to be on transplant or home therapies (OR 3.5 95% CI [2.3–5.2] vs. ICHD) and to be infected in later months (OR 3.3 95%CI [2.4–4.6] for May-June, OR 6.5 95%CI [3.8–11.3] for July-August, vs. March-April), compared to patients in both datasets. Stratified by modality, patient characteristics and 28-day survival were similar between datasets.

Conclusions
For patients undergoing ICHD treatment the collection of data submitted directly by renal centres allows constant monitoring in real time. For other KRT modalities, using a national swab test dataset through frequent linkage may be the most effective method. Optimising central surveillance can improve patient care by informing interventions and assisting planning at local, regional and national levels.
Proteogenomic characterization of ferroptosis regulators reveals therapeutic potential in glioblastoma
Authors: Wang Xinzhuang , Zhang Hong , Zhang Mingchu , Zhang Xuezhi , Mao Wenbin , Gao Ming 
Published: May 2023

Abstract
Background
Ferroptosis is iron-dependent non-apoptotic cell death, that is characterized by the excessive accumulation of lipid peroxides. Ferroptosis-inducing therapy also shows promise in the treatment of cancers. However, ferroptosis-inducing therapy for glioblastoma multiforme (GBM) is still in the exploratory stage.

Methods
We identified the differentially expressed ferroptosis regulators using Mann–Whitney U test in the proteome data from Clinical Proteomic Tumor Analysis Consortium (CPTAC). We next analyzed the effect of mutation on protein abundance. A multivariate Cox model was constructed to identify the prognostic signature.

Results
In this study, we systemically portrayed the proteogenomic landscape of ferroptosis regulators in GBM. We observed that some mutation-specific ferroptosis regulators, such as down-regulated ACSL4 in EGFR-mutated patients and up-regulated FADS2 in IDH1-mutated patients, were linked to the inhibited ferroptosis activity in GBM. To interrogate the valuable treatment targets, we performed the survival analysis and identified five ferroptosis regulators (ACSL3, HSPB1, ELAVL1, IL33, and GPX4) as the prognostic biomarkers. We also validated their efficiency in external validation cohorts. Notably, we found overexpressed protein and phosphorylation abundances of HSPB1 were poor prognosis markers for overall survival of GBM to inhibit ferroptosis activity. Alternatively, HSPB1 showed a significant association with macrophage infiltration levels. Macrophage-secreted SPP1 could be a potential activator for HSPB1 in glioma cells. Finally, we recognized that ipatasertib, a novel pan-Akt inhibitor, could be a potential drug for suppressing HSPB1 phosphorylation, inducing ferroptosis of glioma cells.

Conclusion
In summary, our study characterized the proteogenomic landscape of ferroptosis regulators and identified that HSPB1 could be a candidate target for ferroptosis-inducing therapy strategy for GBM.
Diagnostic value of SHOX2, RASSF1A gene methylation combined with CEA level detection in malignant pleural effusion
Authors: Chen Shaosen , Huang Kunlun , Zou Lin , Chen Lu , Hu Peicun 
Published: May 2023

Abstract
Aim
To investigate the diagnostic value of combined detection of SHOX2 and RASSF1A gene methylation with carcinoembryonic antigen (CEA) level in diagnosing malignant pleural effusion.

Methods
Between March 2020 and December 2021, we enrolled 68 patients with pleural effusion admitted to the Department of Respiratory and critical care medicine of Foshan Second People's Hospital. The study group included 35 cases of malignant pleural effusion and 33 cases of benign pleural effusion. Methylation of the short homeobox 2 genes (SHOX2) and RAS-related region family 1A gene (RASSF1A) in pleural effusion samples were detected by real-time fluorescence quantitative PCR, and the level of carcinoembryonic antigen (CEA) in pleural effusion samples was detected by immune flow cytometry fluorescence quantitative chemiluminescence.

Results
SHOX2 or RASSF1A gene methylation was detected in 5 cases in the benign pleural effusion group and 25 patients in the malignant pleural effusion group. The positive rate of SHOX2 or RASSF1A gene methylation in the malignant pleural effusion group was significantly higher than in the benign pleural effusion group (71.4% vs. 15.2%, P < 0.01). Positive CEA (CEA > 5 ng/m) was detected in 1 case in the benign pleural effusion group and 26 patients in the malignant pleural effusion group. The CEA-positive rate in the malignant pleural effusion group was significantly higher than in the benign pleural effusion group (74.3% vs. 3%, P < 0.01). When SHOX2 and RASSF1A gene methylation was combined with CEA detection, 6 cases were positive in the benign pleural effusion group, and 31 patients were positive in the malignant pleural effusion group. The positive rate of combined detection in the malignant pleural effusion group was significantly higher than in the benign pleural effusion group (88.6% vs. 18.2%, P < 0.01). The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and Youden’s index of SHOX2, RASSF1A gene methylation combined with CEA in diagnosing malignant pleural effusion were 88.6%, 81.8%, 85.3%, 83.8%, 87.1% and 0.7 respectively.

Conclusion
The combined detection of SHOX2 and RASSF1A gene methylation with CEA level in pleural effusion has a high diagnostic value for malignant pleural effusion.
Nursing students’ learning strategies for e-learning during the Covid-19 pandemic in Iran: a qualitative study
Authors: Cheraghbeigi Nesa , Molavynejad Shahram , Rokhafroz Dariush , Elahi Nasrin , Rezaei Eisa 
Published: May 2023

Abstract
Background
In response to the emergency brought about by the Covid-19 pandemic, many universities around the world had to change their teaching methods from in-person classes to e-learning. The purpose of this study was to identify the learning strategies of nursing students in e-learning during the pandemic.

Methods
This study had a qualitative design and used content analysis approach to collect and analyze the data. Sixteen semi-structured interviews were conducted with 12 Iranian undergraduate nursing students who were selected using purposive sampling method.

Results
Most nursing students in this study generally used two different strategies for e-learning, namely self-centered learning strategies and collaborative learning strategies. Some students, on the other hand, adopted a passive approach in which they did not take any effective action to contribute to their learning.

Conclusion
In e-learning during the pandemic, students adopted different learning strategies. Therefore, designing teaching strategies tailored to the students’ strategies can promote their learning and academic achievement. Also, knowledge of these strategies helps policy makers and nursing educators to take necessary measures in order to optimize and facilitate student learning in an e-learning environment.
Secondary structure of the human mitochondrial genome affects formation of deletions
Authors: Shamanskiy Victor , Mikhailova Alina A. , Tretiakov Evgenii O. , Ushakova Kristina , Mikhailova Alina G. , Oreshkov Sergei , Knorre Dmitry A. , Ree Natalia , Overdevest Jonathan B. , Lukowski Samuel W. , Gostimskaya Irina , Yurov Valerian , Liou Chia-Wei , Lin Tsu-Kung , Kunz Wolfram S. , Reymond Alexandre , Mazunin Ilya , Bazykin Georgii A. , Fellay Jacques , Tanaka Masashi , Khrapko Konstantin , Gunbin Konstantin , Popadin Konstantin 
Published: May 2023

Abstract
Background
Aging in postmitotic tissues is associated with clonal expansion of somatic mitochondrial deletions, the origin of which is not well understood. Such deletions are often flanked by direct nucleotide repeats, but this alone does not fully explain their distribution. Here, we hypothesized that the close proximity of direct repeats on single-stranded mitochondrial DNA (mtDNA) might play a role in the formation of deletions.

Results
By analyzing human mtDNA deletions in the major arc of mtDNA, which is single-stranded during replication and is characterized by a high number of deletions, we found a non-uniform distribution with a “hot spot” where one deletion breakpoint occurred within the region of 6–9 kb and another within 13–16 kb of the mtDNA. This distribution was not explained by the presence of direct repeats, suggesting that other factors, such as the spatial proximity of these two regions, can be the cause. In silico analyses revealed that the single-stranded major arc may be organized as a large-scale hairpin-like loop with a center close to 11 kb and contacting regions between 6–9 kb and 13–16 kb, which would explain the high deletion activity in this contact zone. The direct repeats located within the contact zone, such as the well-known common repeat with a first arm at 8470–8482 bp (base pair) and a second arm at 13,447–13,459 bp, are three times more likely to cause deletions compared to direct repeats located outside of the contact zone. A comparison of age- and disease-associated deletions demonstrated that the contact zone plays a crucial role in explaining the age-associated deletions, emphasizing its importance in the rate of healthy aging.

Conclusions
Overall, we provide topological insights into the mechanism of age-associated deletion formation in human mtDNA, which could be used to predict somatic deletion burden and maximum lifespan in different human haplogroups and mammalian species.
Mild photothermal/radiation therapy potentiates ferroptosis effect for ablation of breast cancer via MRI/PA imaging guided all-in-one strategy
Authors: Zhang Zhe , Lo Hsuan , Zhao Xingyang , Li Wenya , Wu Ke , Zeng Fanchu , Li Shiying , Sun Hongzan 
Published: May 2023

Abstract
Background
Nanotheranostics advances anticancer management by providing therapeutic and diagnostic functions, that combine programmed cell death (PCD) initiation and imaging-guided treatment, thus increasing the efficacy of tumor ablation and efficiently fighting against cancer. However, mild photothermal/radiation therapy with imaging-guided precise mediating PCD in solid tumors, involving processes related to apoptosis and ferroptosis, enhanced the effect of breast cancer inhibition is not fully understood.

Results
Herein, targeted peptide conjugated gold nano cages, iRGD-PEG/AuNCs@FePt NPs ternary metallic nanoparticles (Au@FePt NPs) were designed to achieve photoacoustic imaging (PAI)/Magnetic resonance imaging (MRI) guided synergistic therapy. Tumor-targeting Au@FePt forms reactive oxygen species (ROS), initiated by X-ray-induced dynamic therapy (XDT) in collaboration with photothermal therapy (PTT), inducing ferroptosis-augmented apoptosis to realize effective antitumor therapeutics. The relatively high photothermal conversion ability of Au@FePt increases the temperature in the tumor region and hastens Fenton-like processes to achieve enhanced synergistic therapy. Especially, RNA sequencing found Au@FePt inducting the apoptosis pathway in the transcriptome profile.

Conclusion
Au@FePt combined XDT/PTT therapy activate apoptosis and ferroptosis related proteins in tumors to achieve breast cancer ablation in vitro and in vivo. PAI/MRI images demonstrated Au@FePt has real-time guidance for monitoring synergistic anti-cancer therapy effect. Therefore, we have provided a multifunctional nanotheranostics modality for tumor inhibition and cancer management with high efficacy and limited side effects.

Graphical Abstract
Assessment of health-related quality of life and health status in patients with treatment-resistant depression treated with esketamine nasal spray plus an oral antidepressant
Authors: Jamieson Carol , Popova Vanina , Daly Ella , Cooper Kimberly , Drevets Wayne C. , Rozjabek Heather M. , Singh Jaskaran 
Published: May 2023

Abstract
Background
Patients with treatment-resistant depression (TRD) report significant deficits in physical and mental health, as well as severely impaired health-related quality of life (HRQoL) and functioning. Esketamine effectively enhances the daily functioning in these patients while also improving their depressive symptoms. This study assessed HRQoL and health status of patients with TRD, who were treated with esketamine nasal spray and an oral antidepressant (ESK + AD) vs. placebo nasal spray and an AD (AD + PBO).

Methods
Data from TRANSFORM-2, a phase 3, randomized, double-blind, short-term flexibly dosed study, were analyzed. Patients (aged 18–64 years) with TRD were included. The outcome assessments included the European Quality of Life Group, Five Dimension, Five Level (EQ-5D-5L), EQ-Visual Analogue Scale (EQ-VAS), and Sheehan Disability Scale (SDS). The health status index (HSI) was calculated using EQ-5D-5L scores.

Results
The full analysis set included 223 patients (ESK + AD: 114; AD + PBO: 109; mean [SD] age: 45.7 [11.89]). At Day 28, a lower percentage of patients reported impairment in the ESK + AD vs. AD + PBO group in all five EQ-5D-5L dimensions: mobility (10.6% vs. 25.0%), self-care (13.5% vs. 32.0%), usual activities (51.9% vs. 72.0%), pain/discomfort (35.6% vs. 54.0%), and anxiety/depression (69.2% vs. 78.0%). The mean (SD) change from baseline in HSI at Day 28 was 0.310 (0.219) for ESK + AD and 0.235 (0.252) for AD + PBO, with a higher score reflecting better levels of health. The mean (SD) change from baseline in EQ-VAS score at Day 28 was greater in ESK + AD (31.1 [25.67]) vs. AD + PBO (22.1 [26.43]). The mean (SD) change in the SDS total score from baseline to Day 28 also favored ESK + AD (-13.6 [8.31]) vs. AD + PBO (-9.4 [8.43]).

Conclusions
Greater improvements in HRQoL and health status were observed among patients with TRD treated with ESK + AD vs. AD + PBO.

Trial registration
ClinicalTrials.gov Identifier: NCT02418585.
Contrast-enhanced ultrasound-guided sentinel lymph node biopsy in early-stage breast cancer: a prospective cohort study
Authors: Cui Qiuxia , Dai Li , Li Jialu , Shen Yang , Tao Huijiang , Zhou Xiaofeng , Xue Jialei 
Published: May 2023

Abstract
Objective
This study evaluated the identification efficiency of contrast-enhanced ultrasound (CEUS) for sentinel lymph nodes (SLN) to accurately represent the axillary node status in early-stage breast cancer.

Method
In total, 109 consecutive consenting patients with clinically node-negative and T1-2 breast cancer were included in this study. All patients received CEUS to identify SLN before surgery, and a guidewire was deployed to locate SLN in those who were successfully explored by CEUS. The patients underwent sentinel lymph node biopsy (SLNB), and the blue dye was used to trace SLN during the surgery. The decision to perform axillary lymph node dissection (ALND) depended on the intraoperative pathological identification of SLN by CEUS (CE-SLN). The concordance rate of pathological status between CE-SLN and dyed SLN was calculated.

Result
The CEUS detection rate was 96.3%; CE-SLN failed in 4 patients. Among the remaining 105 successful identifications, 18 were CE-SLN positive by intraoperative frozen section, and one with CE-SLN micrometastasis was diagnosed by paraffin section. No additional lymph node metastases were found in CE-SLN-negative patients. The concordance rate of pathological status between CE-SLN and dyed SLN was 100%.

Conclusion
CEUS can accurately represent the status of axillary lymph nodes in patients with clinically node-negative and small tumor burden breast cancer.

Graphical Abstract
PcTrim prevents early infection with white spot syndrome virus by inhibiting AP1-induced endocytosis
Authors: Cao Xiao-Tong , Wu Lian-Jie , Xu Feng-Lin , Li Xin-Cang , Lan Jiang-Feng 
Published: May 2023

AbstractViruses have evolved various strategies to achieve early infection by initiating transcription of their own early genes via host transcription factors, such as NF-κb, STAT, and AP1. How the host copes with this immune escape has been a topic of interest. Tripartite motif (TRIM) family proteins with RING-type domains have E3 ubiquitin ligase activity and are known as host restriction factors. Trim has been reported to be associated with phagocytosis and is also believed to be involved in the activation of autophagy. Preventing the virus from entering the host cell may be the most economical way for the host to resist virus infection. The role of TRIM in the early stage of virus infection in host cells remains to be further interpreted. In the current study, a crayfish TRIM with a RING-type domain, designated as PcTrim, was significantly upregulated under white spot syndrome virus (WSSV) infection in the red swamp crayfish (Procambarus clarkii). Recombinant PcTrim significantly inhibited WSSV replication in crayfish. RNAi targeting PcTrim or blocking PcTrim with an antibody promoted WSSV replication in crayfish. Pulldown and co-IP assays showed that PcTrim can interact with the virus protein VP26. PcTrim restricts the expression level of dynamin, which is involved in the regulation of phagocytosis, by inhibiting AP1 entry into the nucleus. AP1-RNAi effectively reduced the expression levels of dynamin and inhibited host cell endocytosis of WSSV in vivo. Our study demonstrated that PcTrim might reduce early WSSV infection by binding to VP26 and then inhibiting AP1 activation, resulting in reduced endocytosis of WSSV in crayfish hemocytes.