bluuebunny/crossref_metadata_2025_split huggingface dataset:
First Do No Harm? Modeling Risks and Benefits of Challenge Trials for Hepatitis C Vaccine Development
Authors: Bilinski Alyssa , Slimovitch Rachel , Mendlowitz Andrew , Feld Jordan J , Salomon Joshua A 
Published: August 2023

Abstract

Background
In 2019, about 58 million individuals were chronically infected with hepatitis C virus. Some experts have proposed challenge trials for hepatitis C virus vaccine development.

Methods
We modeled incremental infections averted through a challenge approach, under varying assumptions regarding trial duration, number of candidates, and vaccine uptake. We computed the benefit-risk ratio of incremental benefits to risks for challenge versus traditional approaches. We also benchmarked against monetary costs of achieving incremental benefits through treatment.

Results
Our base case assumes 3 vaccine candidates, each with an 11% chance of success, corresponding to a 30% probability of successfully developing a vaccine. Given this probability, and assuming a 5-year difference in duration between challenge and traditional trials, a challenge approach would avert an expected 185 000 incremental infections with 20% steady-state uptake compared to a traditional approach and 832 000 with 90% uptake (quality-adjusted life-year benefit-risk ratio, 72 000 & 323 000). It would cost at least $92 million and $416 million, respectively, to obtain equivalent benefits through treatment. BRRs vary considerably across scenarios, depending on input assumptions.

Conclusions
Benefits of a challenge approach increase with more vaccine candidates, faster challenge trials, and greater uptake.
The diagnostic performance of quantitative flow ratio and perfusion imaging in patients with prior coronary artery disease
Authors: van Diemen Pepijn A , de Winter Ruben W , Schumacher Stefan P , Everaars Henk , Bom Michiel J , Jukema Ruurt A , Somsen Yvemarie B , Raijmakers Pieter G , Kooistra Rolf A , Timmer Janny , Maaniitty Teemu , Robbers Lourens F , von Bartheld Martin B , Demirkiran Ahmet , van Rossum Albert C , Reiber Johan H , Knuuti Juhani , Underwood S Richard , Nagel Eike , Knaapen Paul , Driessen Roel S , Danad Ibrahim 
Published: August 2023

Abstract

Aims
In chronic coronary syndrome (CCS) patients with documented coronary artery disease (CAD), ischaemia detection by myocardial perfusion imaging (MPI) and an invasive approach are viable diagnostic strategies. We compared the diagnostic performance of quantitative flow ratio (QFR) with single-photon emission computed tomography (SPECT), positron emission tomography (PET), and cardiac magnetic resonance imaging (CMR) in patients with prior CAD [previous percutaneous coronary intervention (PCI) and/or myocardial infarction (MI)].

Methods and results
This PACIFIC-2 sub-study evaluated 189 CCS patients with prior CAD for inclusion. Patients underwent SPECT, PET, and CMR followed by invasive coronary angiography with fractional flow reserve (FFR) measurements of all major coronary arteries (N = 567), except for vessels with a sub-total or chronic total occlusion. Quantitative flow ratio computation was attempted in 488 (86%) vessels with measured FFR available (FFR ≤0.80 defined haemodynamically significant CAD). Quantitative flow ratio analysis was successful in 334 (68%) vessels among 166 patients and demonstrated a higher accuracy (84%) and sensitivity (72%) compared with SPECT (66%, P &lt; 0.001 and 46%, P = 0.001), PET (65%, P &lt; 0.001 and 58%, P = 0.032), and CMR (72%, P &lt; 0.001 and 33%, P &lt; 0.001). The specificity of QFR (87%) was similar to that of CMR (83%, P = 0.123) but higher than that of SPECT (71%, P &lt; 0.001) and PET (67%, P &lt; 0.001). Lastly, QFR exhibited a higher area under the receiver operating characteristic curve (0.89) than SPECT (0.57, P &lt; 0.001), PET (0.66, P &lt; 0.001), and CMR (0.60, P &lt; 0.001).

Conclusion
QFR correlated better with FFR in patients with prior CAD than MPI, as reflected in the higher diagnostic performance measures for detecting FFR-defined, vessel-specific, significant CAD.
Insufficient information size and potentially false results in orthodontic meta-analyses using trial sequential analysis
Authors: Mheissen Samer , Aldandan Mays , Khan Haris 
Published: August 2023

Abstract

Background
Meta-analysis (MA) is a common mathematical method used in systematic reviews (SRs) to gather data from different studies. MA may result in overestimation or underestimation of the effect due to systematic and random errors. Trial sequential analysis (TSA) has been used to overcome the limitations of conventional MA. The objective of this study was to re-evaluate the findings of orthodontic MAs using TSA to investigate the conclusiveness of the effect and to estimate the required information size (IS).

Methods
Orthodontic SRs with MA published between 1 January 2013 and 31 December 2022 in the leading orthodontic journals were sourced. Data from arm-level MAs were extracted and re-entered in TSA software.

Results
A total of 180 papers were assessed against the inclusion criteria. Finally, 50 SRs with MAs were included. TSA found that almost half of the MAs with significant results demonstrated firm evidence of effect. While 38% of the significant MAs confirmed potentially spurious evidence of effect. In contrast, only one MA with insignificant findings showed a lack of effect. Furthermore, a larger number of patients were needed when the evidence of the effect was absent.

Conclusions
TSA revealed that many orthodontic MAs have potentially false-positive results and have insufficient IS.
The Operational Codes of Pacific Island Countries’ Leaders: Beliefs about the World amidst Climate Change
Authors: Kesgin Barış 
Published: August 2023

Abstract
Small island states such as Tuvalu face major risks due to anthropogenic climate change and rise in sea levels. Whereas these microstates face an existential crisis, there is scant interest in understanding how their leaders view the world. This paper takes a political leadership approach and explores the belief systems of Pacific Island countries (PICs). Drawing from the United Nations plenary addresses of the PICs’ leaders, it uses the operational code construct to assess their general and climate change-specific beliefs. Given their small state status in world politics and imminent threats to the viability of their communities, how do the PICs view the world and specifically the global politics of climate change? The findings suggest the PICs leaders have a more hostile view concerning climate change, with few exceptions they believe the PICs have less control over climate change matters, and again, with few exceptions, the PICs have less cooperative strategies in the global politics of climate change. This paper captures a preliminary account of beliefs about climate change, presents an empirical foundation to trace these in the Pacific Island states, and suggests venues for future research.
Ebola Virus Infection Induces HCAR2 Expression Leading to Cell Death
Authors: Kuroda Makoto , Halfmann Peter J , Kawaoka Yoshihiro 
Published: August 2023

Abstract
Ebola virus (EBOV) induces cell death not only in infected permissive cells but also in nonpermissive, bystander cells by employing different mechanisms. Hydroxycarboxylic acid receptor 2 (HCAR2) has been reported to be involved in apoptotic cell death. We previously reported an increase in the expression of HCAR2-specific mRNA in EBOV-infected individuals with fatal outcomes. Here, we report that infection with an EBOV lacking the VP30 gene (EBOVΔVP30) results in the upregulation of HCAR2 mRNA expression in human hepatocyte Huh7.0 cells stably expressing VP30. Transient overexpression of HCAR2 reduced the viability of Huh7.0 cells and human embryonic kidney cells. Phosphatidylserine externalization and cell membrane permeabilization by HCAR2 overexpression was also observed. Interestingly, coexpression of HCAR2 with EBOV VP40 further reduced cell viability in transfected cells compared to HCAR2 coexpression with other viral proteins. Our data suggest that HCAR2 may contribute to EBOV-induced cell death.
High-level ceftazidime/avibactam resistance inEscherichia coliconferred by the novel plasmid-mediated β-lactamase CMY-185 variant
Authors: Shropshire William C , Endres Bradley T , Borjan Jovan , Aitken Samuel L , Bachman William C , McElheny Christi L , Wu Chin-Ting , Egge Stephanie L , Khan Ayesha , Miller William R , Bhatti Micah M , Saharasbhojane Pranoti , Kawai Akito , Shields Ryan K , Shelburne Samuel A , Doi Yohei 
Published: August 2023

AbstractObjectivesTo characterize a blaCMY variant associated with ceftazidime/avibactam resistance from a serially collected Escherichia coli isolate.MethodsA patient with an intra-abdominal infection due to recurrent E. coli was treated with ceftazidime/avibactam. On Day 48 of ceftazidime/avibactam therapy, E. coli with a ceftazidime/avibactam MIC of &gt;256 mg/L was identified from abdominal drainage. Illumina and Oxford Nanopore Technologies WGS was performed on serial isolates to identify potential resistance mechanisms. Site-directed mutants of CMY β-lactamase were constructed to identify amino acid residues responsible for ceftazidime/avibactam resistance.ResultsWGS revealed that all three isolates were E. coli ST410. The ceftazidime/avibactam-resistant strain uniquely acquired a novel CMY β-lactamase gene, herein called blaCMY-185, harboured on an IncI-γ/K1 conjugative plasmid. The CMY-185 enzyme possessed four amino acid substitutions relative to CMY-2, including A114E, Q120K, V211S and N346Y, and conferred high-level ceftazidime/avibactam resistance with an MIC of 32 mg/L. Single CMY-2 mutants did not confer reduced ceftazidime/avibactam susceptibility. However, double and triple mutants containing N346Y previously associated with ceftazidime/avibactam resistance in other AmpC enzymes, conferred ceftazidime/avibactam MICs ranging between 4 and 32 mg/L as well as reduced susceptibility to the newly developed cephalosporin, cefiderocol. Molecular modelling suggested that the N346Y substitution confers the reduction of avibactam inhibition due to steric hindrance between the side chain of Y346 and the sulphate group of avibactam.ConclusionsWe identified ceftazidime/avibactam resistance in E. coli associated with a novel CMY variant. Unlike other AmpC enzymes, CMY-185 appears to require an additional substitution on top of N346Y to confer ceftazidime/avibactam resistance.
Propolis prevents vascular endothelial dysfunction by attenuating inflammation and oxidative damage in the chronic unpredictable stress model of depression in rats
Authors: Celebi Gulsen , Gocmez Semil Selcen , Ozer Cuneyt , Duruksu Gokhan , Yazır Yusufhan , Utkan Tijen 
Published: August 2023

Abstract

Objectives
Chronic stress may lead to depression and vascular endothelial dysfunction. We aimed to evaluate the effects of propolis on vascular functions and the possible mechanisms of its vascular effects in the rat model of chronic unpredictable mild stress (CUMS)-induced depression.

Methods
Male Wistar rats were divided into control, stress (exposure to CUMS), control+propolis and stress+propolis groups (n = 8/each group). CUMS model was induced by exposing rats to various mild stressors daily for 5 weeks. The extract of propolis (100 mg/kg/day) was administered orally to propolis-treated groups for 5 weeks. The depression-like behaviours were assessed with the forced swimming test (FST). Chronic stress resulted in increased immobility response in FST and elevated serum corticosterone levels. Thoracic endothelial functions and expressions of endothelial nitric oxide synthase (eNOS), tumor necrosis factor-alpha (TNFα), interleukin-1beta (IL-1β), Heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) level were assessed.

Key findings
Compared to control group, stress group exhibited a significant decrease in endothelium-dependent relaxations, and eNOS, SOD and HO-1 expressions, whereas a significant increase in the thoracic expressions of TNFα and IL-1β. Propolis ameliorated depression-like behaviours, vascular endothelial dysfunctions and alterations of protein expressions.

Conclusion
Propolis exerted antidepressant-like and vasculoprotective effects in CUMS-induced depression in rats. Chronic propolis treatment may have a protective effect on CUMS-induced vascular endothelial dysfunction by its anti-inflammatory and antioxidant effects.
YouTube’s recommendation algorithm is left-leaning in the United States
Authors: Ibrahim Hazem , AlDahoul Nouar , Lee Sangjin , Rahwan Talal , Zaki Yasir 
Published: August 2023

Abstract
With over two billion monthly active users, YouTube currently shapes the landscape of online political video consumption, with 25% of adults in the United States regularly consuming political content via the platform. Considering that nearly three-quarters of the videos watched on YouTube are delivered via its recommendation algorithm, the propensity of this algorithm to create echo chambers and deliver extremist content has been an active area of research. However, it is unclear whether the algorithm may exhibit political leanings toward either the Left or Right. To fill this gap, we constructed archetypal users across six personas in the US political context, ranging from Far Left to Far Right. Utilizing these users, we performed a controlled experiment in which they consumed over eight months worth of videos and were recommended over 120,000 unique videos. We find that while the algorithm pulls users away from political extremes, this pull is asymmetric, with users being pulled away from Far Right content stronger than from Far Left. Furthermore, we show that the recommendations made by the algorithm skew left even when the user does not have a watch history. Our results raise questions on whether the recommendation algorithms of social media platforms in general, and YouTube, in particular, should exhibit political biases, and the wide-reaching societal and political implications that such biases could entail.
Comparison of Infant Length Measurements Using Tape Measure Versus Length Board
Authors: Ribeiro Denise Scalercio , Sasinski Juliet , Hackett Heather , Manalo Catherine , Choi Jaehee , Miller Pamela S. 
Published: August 2023

Background:
For infants requiring intensive care, infant length is a primary gauge of nutrition and forms the basis for important future treatment decisions. However, existing evidence demonstrates discrepancies in infant length measurements between tape measure and length board.

Purpose:
To compare the accuracy and reliability of infant length measurements using tape measure (standard practice) and length board in a neonatal intensive care unit (NICU) at a public academic medical center.

Methods:
Using a single-group, quasi-experimental, repeated-measures design, 108 infants (35.58 ± 3.68 weeks, male 59%, 2124.83 ± 881.69 g) admitted to the NICU were prospectively enrolled. Clinical nurses measured infants weekly per unit-based protocol using tape measures. Study team measured length using length boards within 24 hours of tape measurement. Primary outcome was infant length. Length measurements were converted to sex-specific Fenton or WHO growth percentiles. Linear mixed-effects regression, κ coefficient, intraclass correlation coefficient, and positive predictive value were calculated.

Findings/Results:
The main effect of measurement conditions and time was significant. Predicted length was 0.38 cm lower for length board than for tape measure over time. Weighted κ coefficient and intraclass correlation coefficient indicated good to excellent agreement. More than 37% of infants shifted to a new percentile category based on both measurements. Positive predictive value of length board at time 1 was 63%.

Implications for Practice:
Length board measurements are reliable for accurate classification of an infant's growth curve to influence diagnosis and future plan of care.

Implications for Research:
Future research warrants replication using a longitudinal design across multiple sites.
Anti-cancer effectiveness of a novel ceramide analog on chemo-sensitive and chemo-resistant breast cancers
Authors: Ponnapakkam Tulasi , Saulsberry Tyjah , Hill-Odom Miriam , Beamon Teresa , Hooks Royce , Goyal Navneet , Shaik Shahensha , Anbalagan Muralidharan , Foroozesh Maryam 
Published: August 2023

Introduction
Ceramides are known to show anti-cancer activity. A novel ceramide analog, (S,E)-3-hydroxy-2-(2-hydroxybenzylidene)amino-N-tetradecylpropanamide (analog 315) was developed as part of a larger study focused on finding more effective breast cancer treatments.

Objective
To assess whether analog 315 shows any or a combination of the following effects in breast cancer cells in vitro: inhibiting proliferation, inducing apoptosis, and altering protein expression. Also, to determine whether it inhibits chemo-resistant breast cancer tumor growth in vivo mouse model.

Methods

In vitro cell proliferation and apoptosis after treatment with analog 315 were assessed in three breast cancer cell lines (MCF-7, MCF-7TN-R, and MDA-MB-231) and reported. Protein expression was assessed by microarray assay. For the in vivo studies, chemo-resistant breast cancer cells were used for tumor development in two groups of mice (treated and control). Analog 315 (25 mg/kg/day) or control (dimethyl sulfoxide) was administered intraperitoneally for 7 days. Effects of analog 315 on inhibiting the growth of chemo-resistant breast cancer tumors after treatment are reported.

Results
Analog 315 reduced MCF-7TN-R chemo-resistant tumor burden (volume and weight) in mice. Liver metastasis was observed in control mice, but not in the treated animals. Ki-67, a proliferation marker for breast cancer cells, increased significantly (P < 0.05) in control tumor tissue. In vitro studies showed that analog 315 inhibited cell proliferation, altered protein expression and induced apoptosis in all three breast cancer cell lines studied, of which the effects on MCF-7TN-R cells were the most significant.

Conclusion
Analog 315 reduced tumor growth in chemo-resistant breast cancer, inhibited cell proliferation, altered protein expression, and induced apoptosis in all three cell lines studied.
Short-term plasticity in the spinal nociceptive system
Authors: Cathenaut Lou , Schlichter Rémy , Hugel Sylvain 
Published: August 2023

Abstract
Somatosensory information is delivered to neuronal networks of the dorsal horn (DH) of the spinal cord by the axons of primary afferent neurons that encode the intensity of peripheral sensory stimuli under the form of a code based on the frequency of action potential firing. The efficient processing of these messages within the DH involves frequency-tuned synapses, a phenomenon linked to their ability to display activity-dependent forms of short-term plasticity (STP). By affecting differently excitatory and inhibitory synaptic transmissions, these STP properties allow a powerful gain control in DH neuronal networks that may be critical for the integration of nociceptive messages before they are forwarded to the brain, where they may be ultimately interpreted as pain. Moreover, these STPs can be finely modulated by endogenous signaling molecules, such as neurosteroids, adenosine, or GABA. The STP properties of DH inhibitory synapses might also, at least in part, participate in the pain-relieving effect of nonpharmacological analgesic procedures, such as transcutaneous electrical nerve stimulation, electroacupuncture, or spinal cord stimulation. The properties of target-specific STP at inhibitory DH synapses and their possible contribution to electrical stimulation-induced reduction of hyperalgesic and allodynic states in chronic pain will be reviewed and discussed.
Thalamic neurometabolite alterations in chronic low back pain: a common phenomenon across musculoskeletal pain conditions?
Authors: Weerasekera Akila , Knight Paulina C. , Alshelh Zeynab , Morrissey Erin J. , Kim Minhae , Zhang Yi , Napadow Vitaly , Anzolin Alessandra , Torrado-Carvajal Angel , Edwards Robert R. , Ratai Eva-Maria , Loggia Marco L. 
Published: August 2023

Abstract
Recently, we showed that patients with knee osteoarthritis (KOA) demonstrate alterations in the thalamic concentrations of several metabolites compared with healthy controls: higher myo-inositol (mIns), lower N-acetylaspartate (NAA), and lower choline (Cho). Here, we evaluated whether these metabolite alterations are specific to KOA or could also be observed in patients with a different musculoskeletal condition, such as chronic low back pain (cLBP). Thirty-six patients with cLBP and 20 healthy controls were scanned using 1H-magnetic resonance spectroscopy (MRS) and a PRESS (Point RESolved Spectroscopy) sequence with voxel placement in the left thalamus. Compared with healthy controls, patients with cLBP demonstrated lower absolute concentrations of NAA (P = 0.0005) and Cho (P < 0.05) and higher absolute concentrations of mIns (P = 0.01) when controlling for age, as predicted by our previous work in KOA. In contrast to our KOA study, mIns levels in this population did not significantly correlate with pain measures (eg, pain severity or duration). However, exploratory analyses revealed that NAA levels in patients were negatively correlated with the severity of sleep disturbance (P < 0.01), which was higher in patients compared with healthy controls (P < 0.001). Additionally, also in patients, both Cho and mIns levels were positively correlated with age (P < 0.01 and P < 0.05, respectively). Altogether, these results suggest that thalamic metabolite changes may be common across etiologically different musculoskeletal chronic pain conditions, including cLBP and KOA, and may relate to symptoms often comorbid with chronic pain, such as sleep disturbance. The functional and clinical significance of these brain changes remains to be fully understood.
Paradoxical heat sensation as a manifestation of thermal hypesthesia: a study of 1090 patients with lesions of the somatosensory system
Authors: Vollert Jan , Fardo Francesca , Attal Nadine , Baron Ralf , Bouhassira Didier , Enax-Krumova Elena K. , Freynhagen Rainer , Hansson Per , Jensen Troels S. , Kersebaum Dilara , Maier Christoph , Pogatzki-Zahn Esther , Rice Andrew S.C. , Sachau Juliane , Schaldemose Ellen L. , Segerdahl Märta , Sendel Manon , Tölle Thomas R. , Finnerup Nanna B. , Treede Rolf-Detlef 
Published: August 2023

Abstract
Paradoxical heat sensation (PHS) is the perception of warmth when the skin is cooled. Paradoxical heat sensation rarely occurs in healthy individuals but more frequently in patients suffering from lesions or disease of the peripheral or central nervous system. To further understand mechanisms and epidemiology of PHS, we evaluated the occurrence of PHS in relation to disease aetiology, pain levels, quantitative sensory testing parameters, and Neuropathic Pain Symptom Inventory (NPSI) items in patients with nervous system lesions. Data of 1090 patients, including NPSI scores from 404 patients, were included in the analysis. We tested 11 quantitative sensory testing parameters for thermal and mechanical detection and pain thresholds, and 10 NPSI items in a multivariate generalised linear model with PHS, aetiology, and pain (yes or no) as fixed effects. In total, 30% of the neuropathic patients reported PHS in contrast to 2% of healthy individuals. The frequency of PHS was not linked to the presence or intensity of pain. Paradoxical heat sensation was more frequent in patients living with polyneuropathy compared with central or unilateral peripheral nerve lesions. Patients who reported PHS demonstrated significantly lower sensitivity to thermal perception, with lower sensitivity to normally painful heat and cold stimuli. Neuropathic Pain Symptom Inventory scores were lower for burning and electric shock–like pain quality for patients with PHS. Our findings suggest that PHS is associated with loss of small thermosensory fibre function normally involved in cold and warm perception. Clinically, presence of PHS could help screening for loss of small fibre function as it is straightforward to measure or self-reported by patients.