bluuebunny/crossref_metadata_2025_split huggingface dataset:
Before the Party Hijacks: The Limited Role of Party Cues in Appraisal of Low-Salience Policies—Experimental Evidence
Authors: Treger Clareta 
Published: February 2023

AbstractWhat shapes Americans’ policy preferences: partisanship or policy content? While previous studies have addressed this question, many of them focused on high-salience policies. This raises an identification challenge because the content of such policies contains party cues. The current study employs a diverse set of low-salience policies to discern the unique effects of party cues and policy content, before the issues are “hijacked” by the parties. These policies are embedded in an original conjoint experiment administered among a national US sample. The design enables me to assess the effects of policy content and partisan sponsorship orthogonally. Contrary to previous studies, I find that respondents are attentive to policy content on low-salience issues, and it influences their policy preferences similarly or even more than party cues, across policy domains. Moreover, the support patterns and levels of Democrats and Republicans for many low-salience policies are similar. Party cues, by contrast, polarize partisans’ preferences across domains.
Facilitating discharge planning: the Risk Assessment of Complex Discharge Index
Authors: Bert Fabrizio , Cugudda Eleonora , Lo Moro Giuseppina , Devardo Carolina , Citino Elena , Faenzi Cristina , Scarmozzino Antonio , Siliquini Roberta 
Published: February 2023

Abstract

Background
Untimely social interventions prolong hospitalizations, suggesting discharge planning should begin early. This study aimed to create a tool to identify, already in Emergency department, patients at risk of complex discharge for social reasons.

Methods
We developed the Risk Assessment of Complex Discharge Index (RACDI). In Emergency department, we administered RACDI to patients destined to hospitalization. We calculated sensitivity and specificity of RACDI in identifying patients who need a social intervention. RACDI was compared with simplified BRASS. A multivariable logistic regression explored social intervention predictors (P-value &lt; 0.05).

Results
RACDI was administered to 296 patients. There were significant associations between classes of risk defined by RACDI or by simplified BRASS and social intervention. The sensitivity of RACDI and simplified BRASS was, respectively, 0.59 and 0.43; the specificity 0.81 and 0.83. Chances of social intervention were higher for patients at high risk with RACDI (adjOR:3.13, 95% CI: 1.23–8.00, P = 0.017).

Conclusions
The reduced items and mostly dichotomous answers made RACDI a tool easy to be used in daily practice. RACDI helps in classifying patients needing discharge planning for social care and is a starting point to standardize the evaluation of social context early in hospitalization. Further work is needed to overcome limitations and assess additional outcomes.
Hinterlands, City Formation and Growth: Evidence from the U.S. Westward Expansion
Authors: Nagy Dávid Krisztián 
Published: February 2023

Abstract
I study how geography shaped city formation and aggregate development in the U.S. prior to the Civil War. To guide my analysis, I present a conjecture that cities’ farm hinterlands fostered both city development and aggregate growth: the hinterland hypothesis. The hinterland hypothesis has rich implications on how various elements of U.S. geography—railroads, changes in U.S. political borders, and international trade—affected city formation and U.S. growth. To evaluate the hinterland hypothesis and its implications, I assemble a novel historical dataset on population, trading routes, and agricultural productivity at a high spatial resolution. I combine the data with a dynamic quantitative model of economic geography that yields the hinterland hypothesis as a prediction. I find evidence for the hinterland hypothesis by showing that the model can replicate the key patterns of U.S. urbanization and city formation. Finally, I conduct a series of counterfactuals in the model to quantify the effect of geography on cities and growth, guided by the implications of the hinterland hypothesis. Results indicate that railroads were responsible for 1.8% of urban population in 1860 and for 25% of real GDP growth between 1830 and 1860. The effect of international trade was similar in magnitude, while the effect of political border changes was small during the period.
Investigating the effect of myricetin against arsenic-induced cardiac toxicity in rats
Authors: Aminzadeh Azadeh , Darijani Mohammad Hossein , Bashiri Hamideh 
Published: February 2023

AbstractArsenic intoxication is a serious health hazard worldwide. Its toxicity is associated with several disorders and health problems in humans. Recent studies revealed that myricetin has various biological effects, including anti-oxidation. The aim of this study is to investigate the protective effect of myricetin against arsenic-induced cardiotoxicity in rats. Rats were randomized to one of the following groups: control, myricetin (2 mg/kg), arsenic (5 mg/kg), myricetin (1 mg/kg) + arsenic, and myricetin (2 mg/kg) + arsenic. Myricetin was given intraperitoneally 30 min before arsenic administration (5 mg/kg for 10 days). After treatments, the activity of lactate dehydrogenase (LDH) and the levels of aspartate aminotransferase (AST), creatine kinase myocardial band (CK-MB), lipid peroxidation (LPO), total antioxidant capacity (TAC), and total thiol molecules (TTM) were determined in serum samples and cardiac tissues. Also, histological changes in cardiac tissue were evaluated. Myricetin pretreatment inhibited arsenic-induced increase in LDH, AST, CK-MB, and LPO levels. Pretreatment with myricetin also enhanced the decreased TAC and TTM levels. In addition, myricetin improved histopathological alterations in arsenic-treated rats. In conclusion, the results of the present study demonstrated that treatment with myricetin prevented arsenic-induced cardiac toxicity at least in part by decreasing oxidative stress and restoring the antioxidant system.
Upregulation of sphingosine kinase 1 in response to doxorubicin generates an angiogenic response via stabilization of Snail
Authors: Bonica Joseph , Clarke Christopher J. , Obeid Lina M. , Luberto Chiara , Hannun Yusuf A. 
Published: February 2023

AbstractSphingosine kinase 1 (SK1) converts the pro‐death lipid sphingosine to the pro‐survival sphingosine‐1‐phosphate (S1P) and is upregulated in several cancers. DNA damaging agents, such as the chemotherapeutic doxorubicin (Dox), have been shown to degrade SK1 protein in cancer cells, a process dependent on wild‐type p53. As mutations in p53 are very common across several types of cancer, we evaluated the effects of Dox on SK1 in p53 mutant cancer cells. In the p53 mutant breast cancer cell line MDA‐MB‐231, we show that Dox treatment significantly increases SK1 protein and S1P. Using MDA‐MB‐231 cells with CRISPR‐mediated knockout of SK1 or the selective SK1 inhibitor PF‐543, we implicated SK1 in both Dox‐induced migration and in a newly uncovered proangiogenic program induced by Dox. Mechanistically, inhibition of SK1 suppressed the induction of the cytokine BMP4 and of the EMT transcription factor Snail in response to Dox. Interestingly, induction of BMP4 by SK1 increased Snail levels following Dox treatment by stabilizing Snail protein. Furthermore, we found that SK1 was required for Dox‐induced p38 MAP kinase phosphorylation and that active p38 MAPK in turn upregulated BMP4 and Snail, positioning p38 downstream of SK1 and upstream of BMP4/Snail. Modulating production of S1P by inhibition of de novo sphingolipid synthesis or knockdown of the S1P‐degrading enzyme S1P lyase identified S1P as the sphingolipid activator of p38 in this model. This work establishes a novel angiogenic pathway in response to a commonly utilized chemotherapeutic and highlights the potential of SK1 as a secondary drug target for patients with p53 mutant cancer.
Echinacoside from Cistanche tubulosa ameliorates alcohol‐induced liver injury and oxidative stress by targeting Nrf2
Authors: Ding Yuhao , Zhang Yuan , Wang Zhonghao , Zeng Fanle , Zhen Qianzhen , Zhao Huizi , Li Jun , Ma Taotao , Huang Cheng 
Published: February 2023

AbstractCistanche tubulosa (Schrenk) Wight, named Guan hua Rou Cong‐Rong in Chinese, is a traditional plant with liver, kidney, and intestine protective effects. Echinacoside (ECH) is its active constituent and has been found to have various biological effects, including antioxidative stress and anti‐inflammatory effects. Liver injury caused by acetaminophen or CCL4 has been proven to benefit from ECH; however, the effects of ECH against alcoholic liver disease (ALD) remain unclear. This study was used to estimate the effect of echinacoside on nuclear factor erythroid 2‐related factor 2 (Nrf2), which ameliorates ALD by inhibiting oxidative stress and cell apoptosis through affecting Nrf2.A mouse model of ALD was established with ethanol using hematoxylin and eosin (HE) staining, oiled staining, and biochemical indices. Alpha Mouse Liver 12 (AML‐12) cells were induced with ethanol in vitro and analyzed using western blotting, flow cytometry, and biochemical assays. In the animal model of ALD, ECH dramatically reduced liver damage, as proven by the downregulation of aspartate aminotransferase (AST) and HE staining. In vitro, ECH distinctly reduced the damage caused by ethanol through the decreased expression of cleaved caspase‐3 measured by western blotting. ECH significantly increased the activity of Nrf2 in vivo and in vitro. Nrf2 knockout may diminish the influence of ECH on ALD. Meanwhile, ECH also increased the expression of haem oxygenase‐1 (HO‐1) and glutamate‐cysteine ligase catalytic subunit (GCLC), while it inhibited levels of oxidative stress and cell apoptosis. Our findings suggest that ECH protects against ethanol‐induced liver injuries by alleviating oxidative stress and cell apoptosis by increasing the activity of Nrf2. Therefore, ECH is promising for the treatment of ALD.
Human umbilical cord mesenchymal stem cells‐derived exosomal circDLGAP4 promotes angiogenesis after cerebral ischemia–reperfusion injury by regulating miR‐320/KLF5 axis
Authors: Feng Jie , He Wei , Xia Jian , Huang Qing , Yang Jie , Gu Wen‐Ping , Zhang Ning , Liu Yun‐Hai 
Published: February 2023

AbstractAccumulating evidence suggests that human umbilical cord mesenchymal stem cell‐derived exosomes (hUC‐MSCs‐Exos) are a promising therapeutic strategy for cerebral ischemia–reperfusion injury (CIRI). However, the underlying mechanism remains unclear. hUC‐MSCs‐Exos were identified by electron microscopy, NTA, and Western blotting. In the hypoxia/reoxygenation (H/R) cell model, human brain microvascular endothelial cells (HBMECs) were cocultured with hUC‐MSCs‐Exos. Then, cell viability, migration, apoptosis, and tube formation were measured by MTT, flow cytometry, transwell, and tube formation assays. RT‐qPCR and Western blotting were used to detect the changes in RNA and protein. RNA pull‐down and dual luciferase reporter assays confirmed the relationship between circDLGAP4, miR‐320, and KLF5. Ischemia–reperfusion (I/R) rat model was established for in vivo experiments. hUC‐MSCs‐Exos increased the expression levels of circDLGAP4 and KLF5 but decreased miR‐320 in H/R‐treated HBMECs by transferring exosomal circDLGAP4. Knockdown of circDLGAP4 in hUC‐MSCs‐Exos reversed the promoting effects of hUC‐MSCs‐Exos on cell viability, migration, and tube formation in H/R‐treated HBMECs in vitro and also abolished the protective effects of hUC‐MSCs‐Exos on cerebrovascular injury in I/R rats. Mechanistically, exosomal circDLGAP4 negatively regulated miR‐320 in HBMECs, which directly bound to KLF5. In addition, the downregulation of miR‐320 could reverse the regulatory effect of exosomal shcircDLGAL5 in H/R‐treated HBMECs by upregulating KLF5. hUC‐MSCs‐Exos‐derived circDLGAP4 reduced cerebrovascular injury by regulating miR‐320/KLF5 signaling. These results provide a stem cell‐based approach to treat CIRI.
DNAJB8 facilitates autophagic‐lysosomal degradation of viral Vif protein and restricts HIV‐1 virion infectivity by rescuing APOBEC3G expression in host cells
Authors: Chand Kailash , Barman Muneesh Kumar , Ghosh Payel , Mitra Debashis 
Published: February 2023

AbstractHSP40/DNAJ family of proteins is the most diverse chaperone family, comprising about 49 isoforms in humans. Several reports have demonstrated the functional role of a few of these isoforms in the pathogenesis of various viruses, including HIV‐1. Our earlier study has shown that several isoforms of HSP40 get significantly modulated at the mRNA level during HIV‐1 infection in T cells. To explore the biological role of these significantly modulated isoforms, we analyzed their effect on HIV‐1 gene expression and virus production using knockdown and overexpression studies. Among these isoforms, DNAJA3, DNAJB1, DNAJB7, DNAJC4, DNAJC5B, DNAJC5G, DNAJC6, DNAJC22, and DNAJC30 seem to positively regulate virus replication, whereas DNAJB3, DNAJB6, DNAJB8, and DNAJC5 negatively regulate virus replication. Further investigation on the infectivity of the progeny virion demonstrated that only DNAJB8 negatively regulates the progeny virion infectivity. It was further identified that DNAJB8 protein is involved in the downregulation of Vif protein, required for the infectivity of HIV‐1 virions. DNAJB8 seems to direct Vif protein for autophagic‐lysosomal degradation, leading to rescue of the cellular restriction factor APOBEC3G from Vif‐mediated proteasomal degradation, resulting in enhanced packaging of APOBEC3G in budding virions and release of less infective progeny virion particles. Finally, our results also indicate that during the early stage of HIV‐1 infection, enhanced expression of DNAJB8 promotes the production of less infective progeny virions, but at the later stage or at the peak of infection, reduced expression of DNJAB8 protein allows the HIV‐1 to replicate and produce more infective progeny virion particles.
The Power of One Word to Paint a Halo or a Horn: Demonstrating the Halo Effect in Learner Handover and Subsequent Evaluation
Authors: Seehusen Dean A. , Kleinheksel A.J. , Huang Hannah , Harrison Zachary , Ledford Christy J.W. 
Published: February 2023

Purpose
Learner evaluation based upon direct observation is a cornerstone of modern competency-based medical education. Learner handover has become a widely accepted practice. Cognitive attribution bias is a potential threat to the validity of learner evaluation following learner handover.

Method
In this 2 x 2 (learner handover: halos/horns x learner gender: man/woman) factorial, nonequivalent comparison group experimental design, registered attendees at a national medical education conference watched 1 of 2 videos (depicting a woman learner or man learner) of simulated learner–patient encounters. Data were collected on April 30 and May 1, 2022. Participants received learner handover conditioning before watching the video. The conditioning was randomized to suggest the learner they were about to watch was either “above-average” (halos) or “below-average” (horns). Following the video, participants completed an evaluation form.

Results
Participants rated the learner in a video encounter preceded by a horns statement significantly lower than the learner in a video encounter preceded by a halo statement, F (1,65) = 10.15, P < .01, η2
= .14, horns meanadj = 12.49 (CI 11.34, 13.63), halo meanadj = 15.10 (CI 13.93, 16.28). This represented a scoring difference of 2.61 points on a 30-point scale. More years of teaching experience was negatively associated with the score, F (1,65) = 13.44, P < .001, η2
= .17.

Conclusions
Learner conditioning differing by a single word, labeling a learner as either “above-average” or “below-average” resulted in a large difference in scoring by medical educators.
Association Between Hypocholesterolemia and Mortality in Critically Ill Patients With Sepsis: A Systematic Review and Meta-Analysis
Authors: Hofmaenner Daniel A. , Arina Pietro , Kleyman Anna , Black Lauren Page , Salomao Reinaldo , Tanaka Sébastien , Guirgis Faheem W. , Arulkumaran Nishkantha , Singer Mervyn 
Published: February 2023

OBJECTIVE:
To ascertain the association between cholesterol and triglyceride levels on ICU admission and mortality in patients with sepsis.

DATA SOURCES:
Systematic review and meta-analysis of published studies on PubMed and Embase.

STUDY SELECTION:
All observational studies reporting ICU admission cholesterol and triglyceride levels in critically ill patients with sepsis were included. Authors were contacted for further data.

DATA EXTRACTION:
Eighteen observational studies were identified, including 1,283 patients with a crude overall mortality of 33.3%. Data were assessed using Revman (Version 5.1, Cochrane Collaboration, Oxford, United Kingdom) and presented as mean difference (MD) with 95% CIs, p values, and I

2
values.

DATA SYNTHESIS:
Admission levels of total cholesterol (17 studies, 1,204 patients; MD = 0.52 mmol/L [0.27–0.77 mmol/L]; p < 0.001; I

2
= 91%), high-density lipoprotein (HDL)-cholesterol (14 studies, 991 patients; MD = 0.08 mmol/L [0.01–0.15 mmol/L]; p = 0.02; I

2
= 61%), and low-density lipoprotein (LDL)-cholesterol (15 studies, 1,017 patients; MD = 0.18 mmol/L [0.04–0.32 mmol/L]; p = 0.01; I

2
= 71%) were significantly lower in eventual nonsurvivors compared with survivors. No association was seen between admission triglyceride levels and mortality (15 studies, 1,070 patients; MD = 0.00 mmol/L [–0.16 to 0.15 mmol/L]; p = –0.95; I

2
= 79%).

CONCLUSIONS:
Mortality was associated with lower levels of total cholesterol, HDL-cholesterol, and LDL-cholesterol, but not triglyceride levels, in patients admitted to ICU with sepsis. The impact of cholesterol replacement on patient outcomes in sepsis, particularly in at-risk groups, merits investigation.
Immunogenicity and reactogenicity of heterologous immunization schedules with COVID-19 vaccines: a systematic review and network meta-analysis
Authors: Li Pei , Wang Weiwei , Tao Yiming , Tan Xiaoyu , Li Yujing , Mao Yinjun , Gao Le , Feng Lei , Zhan Siyan , Sun Feng 
Published: February 2023

Abstract

Background:
Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules.

Methods:
Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model.

Results:
In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53–24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06–1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16–2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25–2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36–14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08–3.91). No significant difference in the risk for SAEs was found in any comparisons.

Conclusions:
Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted.

Registration:
No.CRD42021278149
HIV and chronic lung disease
Authors: Leung Janice M. 
Published: February 2023

Purpose of review
As people living with human immunodeficiency virus (HIV, PLWH) age, aging-related comorbidities have come into focus as major challenges to their overall health. In this review, an in-depth overview of the two most commonly encountered chronic lung diseases in PLWH, chronic obstructive pulmonary disease (COPD) and lung cancer, is provided.

Recent findings
The risk for both COPD and lung cancer remains significantly higher in PLWH compared to the HIV-uninfected population, although fortunately rates of lung cancer appear to be declining over the last two decades. Outcomes for PLWH with these conditions, though, continue to be poor with worse survival rates in comparison to the general population. PLWH still face major barriers in accessing care for these conditions, including a higher likelihood of being underdiagnosed with COPD and a lower likelihood of being referred for lung cancer screening or treatment. A lack of evidence for optimal treatment strategies for both COPD and lung cancer still hampers the care of PLWH with these conditions.

Summary
COPD and lung cancer represent substantial burdens of disease in PLWH. Improved access to standard-of-care screening and treatment and greater investigation into therapeutic responses specifically in this population are recommended.
Do sleep disturbances contribute to comorbidities in HIV?
Authors: Kunisaki Ken M. 
Published: February 2023

Purpose of review
To highlight recent publications about sleep disorders and sleep health in adult persons with HIV (PWH), with a focus on how sleep relates to comorbidities in PWH.

Recent findings
Sleep disorders are more common in PWH than in seronegative controls, especially insomnia, with four different recent studies estimating insomnia prevalence in PWH at 21–35%. Sleep apnea prevalence estimates in PWH have varied widely. Most studies suggest PWH do not have higher sleep apnea prevalence compared with controls, though definitions of sleep apnea may affect these analyses. Comorbidities recently associated with sleep in PWH include myocardial infraction (insomnia), depressive symptoms (insomnia and restless legs syndrome), and pain (insomnia). Cognition associations with sleep were inconsistent and may depend on data collection and analytic methods. Sleep health dimensions are uncommonly reported, but PWH appear to report worse sleep health dimensions and these demonstrated mixed associations with cognition and depressive symptoms in recent studies.

Summary
Sleep disorders and poor sleep health are common in PWH and are related to comorbidities. More data from longitudinal studies and clinical trials are needed. Clinical trials of insomnia interventions in PWH are especially warranted.