bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteinuria in hospitalised internal medicine adult patients
Authors: Shimoni Zvi , Froom Paul , Benbassat Jochanan 
Published: September 2021

AbstractRationaleDipstick proteinuria may be a sign of a renal disorder, false-positive or associated with acute disease, and consequently, transient in hospitalised patients.ObjectiveTo assess (a) the prevalence of proteinuria in hospitalised patients; (b) its association with estimated glomerular filtration rate (eGFR), findings known to cause false-positive test results and indicators of acute disease and (c) the need for follow-up after discharge.Setting and participantsAll patients who had a dipstick urinalysis on admission to medical wards of a 400-bed regional hospital in 2018–2019.Outcome variableProteinuria.Independent variables(a) Other findings on dipstick urinalysis; (b) patients' age, gender, presence of urinary catheter and eGFR and (c) white blood cell count (WBC) and fever.ResultsOf 22 329 patients, 6609 (29.6%) had urinalysis. Of those, 2973 patients (45.0%) had proteinuria of ≥+1 (≥0.30 g/L). The variables independently associated with proteinuria were other dipstick findings known to cause false-positive test results, elevated WBC, fever on presentation, presence of a urethral catheter and a low eGFR. eGFR alone was a poor predictor of proteinuria (c-stat 0.62); however, addition of the remaining independent variables to the model significantly improved its predictive ability (c-stat 0.80).ConclusionsDipstick proteinuria is common in hospitalised patients. Although weakly associated with eGFR, proteinuria is mainly associated with confounding factors that may result in false-positive test results. The need for follow-up of proteinuria after discharge has questionable clinical utility and its high frequency would entail a considerable cost.
Epinephrine (adrenaline) compared to selective beta-2-agonist in adults or children with acute asthma: a systematic review and meta-analysis
Authors: Baggott Christina , Hardy Jo Katherine , Sparks Jenny , Sabbagh Doñah , Beasley Richard , Weatherall Mark , Fingleton James 
Published: September 2021

BackgroundInternational asthma guidelines recommend against epinephrine (adrenaline) administration in acute asthma unless associated with anaphylaxis or angio-oedema. However, administration of intramuscular epinephrine in addition to nebulised selective β2-agonist is recommended for acute severe or life-threatening asthma in many prehospital guidelines. We conducted a systematic review to determine the efficacy of epinephrine in comparison to selective β2-agonist in acute asthma.MethodsWe included peer-reviewed publications of randomised controlled trials (RCTs) that enrolled children or adults in any healthcare setting and compared epinephrine by any route to selective β2-agonist by any route for an acute asthma exacerbation. The primary outcome was treatment failure, including hospitalisation, need for intubation or death.ResultsThirty-eight of 1140 studies were included. Overall quality of evidence was low. Seventeen studies contributed data on 1299 participants to the meta-analysis. There was significant statistical heterogeneity, I2=56%. The pooled Peto’s OR for treatment failure with epinephrine versus selective β2-agonist was 0.99 (0.75 to 1.32), p=0.95. There was strong evidence that recruitment age group was associated with different estimates of the odds of treatment failure; with studies recruiting adults-only having lower odds of treatment failure with epinephrine. It was not possible to determine whether epinephrine in addition to selective β2-agonist improved outcomes.ConclusionThe low-quality evidence available suggests that epinephrine and selective β2-agonists have similar efficacy in acute asthma. There is a need for high-quality double-blind RCTs to determine whether addition of intramuscular epinephrine to inhaled or nebulised selective β2-agonist improves outcome.PROSPERO registration numberCRD42017079472.
Sox2 Is an Oncogenic Driver of Small-Cell Lung Cancer and Promotes the Classic Neuroendocrine Subtype
Authors: Voigt Ellen , Wallenburg Madeline , Wollenzien Hannah , Thompson Ethan , Kumar Kirtana , Feiner Joshua , McNally Moira , Friesen Hunter , Mukherjee Malini , Afeworki Yohannes , Kareta Michael S. 
Published: September 2021

Abstract

Although many cancer prognoses have improved in the past 50 years due to advancements in treatments, there has been little improvement in therapies for small-cell lung cancer (SCLC). One promising avenue to improve treatment for SCLC is to understand its underlying genetic alterations that drive its formation, growth, and cellular heterogeneity. RB1 loss is one key driver of SCLC, and RB1 loss has been associated with an increase in pluripotency factors such as SOX2. SOX2 is highly expressed and amplified in SCLC and has been associated with SCLC growth. Using a genetically engineered mouse model, we have shown that Sox2 is required for efficient SCLC formation. Furthermore, genome-scale binding assays have indicated that SOX2 can regulate key SCLC pathways such as NEUROD1 and MYC. These data suggest that SOX2 can be associated with the switch of SCLC from an ASCL1 subtype to a NEUROD1 subtype. Understanding this genetic switch is key to understanding such processes as SCLC progression, cellular heterogeneity, and treatment resistance.

Implications:
Understanding the molecular mechanisms of SCLC initiation and development are key to opening new potential therapeutic options for this devastating disease.
MYC Hyperactivates Wnt Signaling in APC/CTNNB1-Mutated Colorectal Cancer Cells through miR-92a–Dependent Repression of DKK3
Authors: Sehgal Priyanka , Lanauze Claudia , Wang Xin , Hayer Katharina E. , Torres-Diz Manuel , Leu N. Adrian , Sela Yogev , Stanger Ben Z. , Lengner Christopher J. , Thomas-Tikhonenko Andrei 
Published: September 2021

Abstract

Activation of Wnt signaling is among the earliest events in colon cancer development. It is achieved either via activating mutations in the CTNNB1 gene encoding β-catenin, the key transcription factor in the Wnt pathway, or most commonly by inactivating mutations affecting APC, a major β-catenin binding partner and negative regulator. However, our analysis of recent Pan Cancer Atlas data revealed that CTNNB1 mutations significantly co-occur with those affecting Wnt receptor complex components (e.g., Frizzled and LRP6), underscoring the importance of additional regulatory events even in the presence of common APC/CTNNB1 mutations. In our effort to identify non-mutational hyperactivating events, we determined that KRAS-transformed murine colonocytes overexpressing direct β-catenin target MYC show significant upregulation of the Wnt signaling pathway and reduced expression of Dickkopf 3 (DKK3), a reported ligand for Wnt co-receptors. We demonstrate that MYC suppresses DKK3 transcription through one of miR-17-92 cluster miRNAs, miR-92a. We further examined the role of DKK3 by overexpression and knockdown and discovered that DKK3 suppresses Wnt signaling in Apc-null murine colonic organoids and human colon cancer cells despite the presence of downstream activating mutations in the Wnt pathway. Conversely, MYC overexpression in the same cell lines resulted in hyperactive Wnt signaling, acquisition of epithelial-to-mesenchymal transition markers, and enhanced migration/invasion in vitro and metastasis in a syngeneic orthotopic mouse colon cancer model.

Implications:
Our results suggest that the MYC→miR-92a-|DKK3 axis hyperactivates Wnt signaling, forming a feed-forward oncogenic loop.
Dietary Neu5Ac Intervention Protects Against Atherosclerosis Associated With Human-Like Neu5Gc Loss—Brief Report
Authors: Kawanishi Kunio , Coker Joanna K. , Grunddal Kaare V. , Dhar Chirag , Hsiao Jason , Zengler Karsten , Varki Nissi , Varki Ajit , Gordts Philip L.S.M. 
Published: September 2021

Objective:

Species-specific pseudogenization of the
CMAH
gene during human evolution eliminated common mammalian sialic acid
N
-glycolylneuraminic acid (Neu5Gc) biosynthesis from its precursor
N
-acetylneuraminic acid (Neu5Ac). With metabolic nonhuman Neu5Gc incorporation into endothelia from red meat, the major dietary source, anti-Neu5Gc antibodies appeared. Human-like
Ldlr
−/−
Cmah
−/−
mice on a high-fat diet supplemented with a Neu5Gc-enriched mucin, to mimic human red meat consumption, suffered increased atherosclerosis if human-like anti-Neu5Gc antibodies were elicited.

Approach and Results:

We now ask whether interventional Neu5Ac feeding attenuates metabolically incorporated Neu5Gc-mediated inflammatory acceleration of atherogenesis in this
Cmah
−/−
Ldlr
−/−
model system. Switching to a Neu5Gc-free high-fat diet or adding a 5-fold excess of Collocalia mucoid-derived Neu5Ac in high-fat diet protects against accelerated atherosclerosis. Switching completely from a Neu5Gc-rich to a Neu5Ac-rich diet further reduces severity. Remarkably, feeding Neu5Ac-enriched high-fat diet alone has a substantial intrinsic protective effect against atherosclerosis in
Ldlr
−/−
mice even in the absence of dietary Neu5Gc but only in the human-like
Cmah
-null background.

Conclusions:
Interventional Neu5Ac feeding can mitigate or prevent the red meat/Neu5Gc-mediated increased risk for atherosclerosis, and has an intrinsic protective effect, even in the absence of Neu5Gc feeding. These findings suggest that similar interventions should be tried in humans and that Neu5Ac-enriched diets alone should also be investigated further.

Graphic Abstract:
A graphic abstract is available for this article.
Yellow Wine Polyphenolic Compound Protects Against Doxorubicin-Induced Cardiotoxicity by Modulating the Composition and Metabolic Function of the Gut Microbiota
Authors: Lin Hui , Meng Liping , Sun Zhenzhu , Sun Shiming , Huang Xingxiao , Lin Na , Zhang Jie , Lu Wenqiang , Yang Qi , Chi Jufang , Guo Hangyuan 
Published: September 2021

Background:
Dietary polyphenols help to prevent cardiovascular diseases, and interactions between polyphenols and gut microbiota are known to exist. In this study, we speculated that gut microbiota-mediated metabolite regulation might contribute to the anticardiotoxic effects of yellow wine polyphenolic compound (YWPC) in doxorubicin (DOX)-treated rats.

Methods:
16S-rDNA sequencing was performed to analyze the effects of YWPC on the gut microbiota in DOX-treated rats (n=6). Antibiotics were used to investigate the contribution of the altered microbiome to the role of YWPC (n=6). Plasma metabolomics were also analyzed by untargeted gas chromatography-mass spectrometry systems.

Results:

YWPC ameliorated DOX-mediated cardiotoxicity, as evidenced by increased cardiac and mitochondrial function and reduced levels of inflammation and myocardial apoptosis (
P
<0.05 for all). The low abundance of
Escherichia
–
Shigella
,
Dubosiella
, and
Allobaculum
, along with enrichment of
Muribaculaceae_unclassified
,
Ralstonia
, and
Rikenellaceae_RC9_gut_group
in the gut, suggested that YWPC ameliorated DOX-induced microbial dysbiosis. YWPC also influenced the levels of metabolites altered by DOX, resulting in lower arachidonic acid and linoleic acid metabolism and higher tryptophan metabolite levels (
P
<0.05 for all). Correlational studies indicated that YWPC alleviated DOX-induced inflammation and mitochondrial dysfunction by modulating the gut microbial community and its associated metabolites. Antibiotic treatment exacerbated cardiotoxicity in DOX-treated rats, and its effect on the gut microbiota partly abolished the anticardiotoxic effects of YWPC, suggesting that the microbiota is required for the cardioprotective role of YWPC.

Conclusions:
YWPC protected against DOX-induced cardiotoxicity in a gut microbiota–dependent manner. This supports the use of dietary polyphenols as a therapeutic approach for the treatment of cardiovascular diseases via microbiota regulation.
Clinical Heart Failure Among Patients With and Without Severe Mental Illness and the Association With Long-Term Outcomes
Authors: Polcwiartek Christoffer , Loewenstein Daniel , Friedman Daniel J. , Johansson Karin G. , Graff Claus , Sørensen Peter L. , Nielsen René E. , Kragholm Kristian , Torp-Pedersen Christian , Søgaard Peter , Jensen Svend E. , Jackson Kevin P. , Atwater Brett D. 
Published: September 2021

Background:
Patients with severe mental illness (SMI) including schizophrenia, bipolar disorder, and severe depression have earlier onset of cardiovascular risk factors, predisposing to worse future heart failure (HF) compared with the general population. We investigated associations between the presence/absence of SMI and long-term HF outcomes.

Methods:
We identified patients with HF with and without SMI in the Duke University Health System from 2002 to 2017. Using multivariable Cox regression, we examined the primary outcome of all-cause mortality. Secondary outcomes included rates of implantable cardioverter defibrillator use, cardiac resynchronization therapy, left ventricular assist device implantation, and heart transplantation.

Results:

We included 20 906 patients with HF (SMI, n=898; non-SMI, n=20 008). Patients with SMI presented clinically 7 years earlier than those without SMI. We observed an interaction between SMI and sex on all-cause mortality (
P
=0.002). Excess mortality was observed among men with SMI compared with men without SMI (hazard ratio, 1.36 [95% CI, 1.17–1.59]). No association was observed among women with and without SMI (hazard ratio, 0.97 [95% CI, 0.84–1.12]). Rates of implantable cardioverter defibrillator use, cardiac resynchronization therapy, left ventricular assist device implantation, and heart transplantation were similar between patients with and without SMI (6.1% versus 7.9%,
P
=0.095). Patients with SMI receiving these procedures for HF experienced poorer prognosis than those without SMI (hazard ratio, 2.12 [95% CI, 1.08–4.15]).

Conclusions:
SMI was associated with adverse HF outcome among men and not women. Despite equal access to procedures for HF between patients with and without SMI, those with SMI experienced excess postprocedural mortality. Our data highlight concurrent sex- and mental health-related disparities in HF prognosis, suggesting that patients with SMI, especially men, merit closer follow-up.
Stress, Dyadic Coping, and Relationship Instability During the COVID-19 Pandemic
Authors: Ogan Matthew A. , Monk J. Kale , Kanter Jeremy B. , Proulx Christine M. 
Published: September 2021

How romantic partners respond to stress has important implications for the well-being of their relationship. In this study, we examined the effects of three types of stress on relationship instability and evaluated individuals’ perceptions of their partner’s dyadic coping as a mediator in a sample of 117 different-gender couples ( N = 234) across 6 months of the COVID-19 pandemic. We found that perceived stress, but not economic pressure or pandemic concerns, was associated with increases in relationship instability for both men and women. For women but not men, perceived stress was negatively associated with dyadic coping, and dyadic coping was related to lower relationship instability. Although direct effects were present for most of the variables of interest, dyadic coping did not mediate the associations between stress and relationship instability for either partner. These findings underscore the direct paths between stress, adaptive responses, and relationship instability, building upon past theorizing and research on stress and dyadic coping.
Enhancement of the GluN2B subunit of glutamatergic NMDA receptors in rat brain areas after cocaine abstinence
Authors: Smaga Irena , Wydra Karolina , Suder Agata , Sanak Marek , Caffino Lucia , Fumagalli Fabio , Filip Małgorzata 
Published: September 2021

Background: Cocaine use disorder is associated with compulsive drug-seeking and drug-taking, whereas relapse may be induced by several factors, including stress, drug-related places, people, and cues. Recent observations strongly support the involvement of the N-methyl-D-aspartate (NMDA) receptors in cocaine use disorders and abstinence, whereas withdrawal in different environments may affect the intensification of relapse. Methods: The aim of this study was to examine the GluN2B subunit expression and its association with the postsynaptic density protein 95 (PSD95) in several brain structures in rats with a history of cocaine self-administration and housed either in an enriched environment or in an isolated condition. Furthermore, a selective antagonist of the GluN2B subunit—CP 101,606 (10 and 20 mg/kg) administered during exposure to cocaine or a drug-associated conditional stimulus (a cue) was used to evaluate seeking behavior in rats. Results: In rats previously self-administering cocaine, we observed an increase in the GluN2B expression in the total homogenate from the dorsal hippocampus under both enriched environment and isolation. Cocaine abstinence under isolation conditions increased the GluN2B and GluN2B/PSD95 complex levels in the PSD fraction of the prelimbic cortex in rats previously self-administering cocaine. Administration of CP 101,606 attenuated cue-induced cocaine-seeking behavior only in isolation-housed rats. Conclusion: In summary, in this study we showed region-specific changes in both the expression of GluN2B subunit and NMDA receptor trafficking during cocaine abstinence under different housing conditions. Furthermore, we showed that the pharmacological blockade of the GluN2B subunit may be useful in attenuating cocaine-seeking behavior.
Evaluation of circulating tumor cells in colorectal cancer using flow cytometry
Authors: Mușină Ana-Maria , Zlei Mihaela , Mentel Mihaela , Scripcariu Dragoș-Viorel , Ștefan Mădălina , Aniţei Maria-Gabriela , Filip Bogdan , Radu Iulian , Gavrilescu Mihaela-Mădălina , Panuţa Andrian , Buna-Arvinte Mihaela , Cordun Cristiana-Ioana , Predescu Dragoș-Valentin , Scripcariu Viorel , Huţanu Ionuţ 
Published: September 2021

Objective We aimed to evaluate the prognostic value of circulating tumor cells (CTCs) and the impact of intraoperative tumor manipulation on CTCs in colorectal cancer (CRC) patients. Methods We performed a prospective study on 40 patients with CRC stages I to IV who received curative surgery using the no-touch technique. Flow cytometry was used to identify CTCs in peripheral blood samples (4 mL/sample) collected at two surgical moments: skin incision (T1) and after surgical resection (T2). A threshold of ≥4 CTCs/4 mL blood was established for considering patients CTC positive. Results In the univariate analysis, CTC evaluation at T2 was correlated with female sex, vascular invasion, tumor localization in the colon and metastatic lymph nodes. In the multivariate analysis, only female sex and colon cancer maintained statistical significance. At a medium follow-up of 15 months (1–25 months), the mortality rate was 10% (n = 4), with no significant differences between the overall survival of T1 or T2 CTC-positive and CTC-negative patients. Conclusions Flow cytometry is a feasible CTC identification technique in CRC, and although surgical manipulation has no influence on CTC numbers, CTCs may serve as a prognostic and predictive factor.
Anastomotic leakage and postoperative mortality in patients after esophageal cancer resection
Authors: Su Quanguan , Yin Chenxi , Liao Wei , Yang Haoxian , Ouyang Liying , Yang Rong , Ma Gang 
Published: September 2021

Objective Esophagectomy is a high-risk surgical procedure with significant postoperative morbidity and mortality. This study aimed to investigate the risk factors of cervical anastomotic leakage and postoperative mortality. Methods In this retrospective, observational study, we recruited 1010 patients with esophageal cancer. Cox regression analysis was performed to identify factors affecting anastomotic leakage and postoperative mortality. After propensity score matching, the Kaplan–Meier curve was used to evaluate the effect of leakage on postoperative mortality. Results The number of patients with cervical anastomotic leakage, in-hospital mortality, 30-day postoperative mortality, and 60-day postoperative mortality was 194 (19.2%), 13 (1.3%), 12 (1.2%), and 16 (1.6%), respectively. The total length of hospital stay and hospital stay postoperatively were 29.7 ± 21.1 and 21.3 ± 20.3 days, respectively. Diabetes, stage IV, and an upper thoracic tumor were significant risk factors for leakage. Leakage and diabetes were significant risk factors for postoperative mortality. After propensity score matching, leakage also significantly affected postoperative mortality. Conclusions Patients with tumors in the upper thoracic segment of the esophagus may be more prone to developing anastomotic leakage compared with those with tumors in the middle or lower thoracic segment. Anastomotic leakage may prolong the length of hospital stay and increase postoperative mortality.
Relationship between non-alcoholic fatty liver disease and cardiac arrhythmia: a systematic review and meta-analysis
Authors: Gong Hang , Liu Xianli , Cheng Fang 
Published: September 2021

Objective We performed a meta-analysis to create a quantitative estimate of the association between non-alcoholic fatty liver disease (NAFLD) and the risk of cardiac arrhythmia (including atrial fibrillation (AF), prolonged QT interval, premature atrial/ventricular contraction [PAC/PVC] and heart block). Methods A literature review was conducted using PubMed, Embase, Web of Science and the Cochrane Library database to identify observational studies of the link between NAFLD and cardiac arrhythmia. Effect sizes were expressed as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs). The method of analysis of AF was also analysed separately, according to the effect estimate (OR or HR). Results Nineteen studies of 7,012,960 individuals were included. NAFLD was independently associated with higher risks of AF (OR 1.71, 95% CI: 1.14–2.57; HR 1.12, 95% CI: 1.11–1.13), prolonged QT interval (OR 2.86, 95% CI: 1.64–4.99), PAC/PVC (OR 2.53, 95% CI: 1.70–3.78) and heart block (OR 2.65, 95% CI: 1.88–3.72). The heterogeneity of the data with respect to AF and prolonged QT was moderate on sensitivity analysis. Conclusions We found a significantly higher risk of cardiac arrhythmia in patients with NAFLD, but the observational design of the studies does not permit conclusions regarding causality.
A predictive web-based nomogram for the early death of patients with lung adenocarcinoma and bone metastasis: a population-based study
Authors: Li Zhehong , Wei Junqiang , Cao Haiying , Song Mingze , Zhang Yafang , Jin Yu 
Published: September 2021

Objective To identify risk factors and develop predictive web-based nomograms for the early death of patients with bone metastasis of lung adenocarcinoma (LUAD). Methods Patients in the Surveillance, Epidemiology, and End Results database diagnosed with bone metastasis of LUAD between 2010 and 2016 were included and randomly divided into training and validation sets. Early death-related risk factors (survival time ≤7 months) were evaluated by logistic regression. Two predictive nomograms were established and validated by calibration curves, receiver operating characteristic curves, and decision curve analysis. Results A total of 9189 patients (56.59%) died from all causes within 7 months of being diagnosed, including 8585 patients (56.67%) who died from cancer-specific causes. Age >65 years, sex (men), T stage (T3 and T4), N stage (N2 and N3), brain metastasis, and liver metastasis were risk factors for all-cause and cancer-specific early death. The area under the curves of the nomograms for all-cause and cancer-specific early death prediction were 0.754 and 0.753 (training set) and 0.747 and 0.754 (validation set), respectively. Further analysis showed that the two nomograms performed well. Conclusions Our two web-based nomograms for all-cause and cancer-specific early death provide valuable tools for predicting early death in these patients.