bluuebunny/crossref_metadata_2025 huggingface dataset:
Solar irrigation in sub-Saharan Africa: economic feasibility and development potential
Authors: Falchetta Giacomo , Semeria Francesco , Tuninetti Marta , Giordano Vittorio , Pachauri Shonali , Byers Edward
Published: August 2023

Irrespective of water resource abundance, agriculture in sub-Saharan Africa (SSA) is predominantly rainfed. Along with fertilization, irrigation could support smallholder farmers with stabilizing crop yields, increasing incomes, and achieving food security. A key barrier to irrigation uptake is inadequate rural electricity supply for pumping and distributing water, besides other infrastructure deficits. Here we devise a spatially explicit integrated modelling framework to show that over one third of unmet crop water requirements of 19 major crops in smallholder cropland of SSA could be supplied with standalone solar photovoltaic (PV) irrigation systems that can be paid back by farmers within 20 years. This accounts for 60 km3 yr−1 of blue irrigation water requirements distributed over 55 million ha of currently rainfed harvested area (about 40% of the total). Crucially, we identify 10 million ha with a profit potential >$100 ha−1 yr−1. To finance such distributed small-scale infrastructure deployment and operation, we estimate an average discounted investment requirement of $3 billion yr−1, generating potential profits of over $5 billion yr−1 from increased yields to the smallholder farmers, as well as significant food security and energy access co-benefits. We demonstrate the critical importance of business models and investment incentives, crop prices, and PV & battery costs in shaping the economic feasibility and profitability of solar irrigation. Yet, we find that without strong land and water resources management infrastructure and governance, a widespread deployment of solar pumps may drive an unsustainable exploitation of water sources and reduce environmental flows. Our analysis supports public and private stakeholders seeking to target investments along the water–energy–food–economy–sustainable development nexus.
Sacrificial scaffold-assisted direct ink writing of engineered aortic valve prostheses
Authors: Zhang Cheng , Hao Jiangtao , Shi Weiliang , Su Ya , Mitchell Kellen , Hua Weijian , Jin Wenbo , Lee Serena , Wen Lai , Jin Yifei , Zhao Danyang
Published: August 2023

Heart valve disease has become a serious global health problem, which calls for numerous implantable prosthetic valves to fulfill the broader needs of patients. Although current three-dimensional (3D) bioprinting approaches can be used to manufacture customized valve prostheses, they still have some complications, such as limited biocompatibility, constrained structural complexity, and difficulty to make heterogeneous constructs, to name a few. To overcome these challenges, a sacrificial scaffold-assisted direct ink writing approach has been explored and proposed in this work, in which a sacrificial scaffold is printed to temporarily support sinus wall and overhanging leaflets of an aortic valve prosthesis that can be removed easily and mildly without causing any potential damages to the valve prosthesis. The bioinks, composed of alginate, gelatin, and nanoclay, used to print heterogenous valve prostheses have been designed in terms of rheological/mechanical properties and filament formability. The sacrificial ink made from Pluronic F127 has been developed by evaluating rheological behavior and gel temperature. After investigating the effects of operating conditions, complex 3D structures and homogenous/heterogenous aortic valve prostheses have been successfully printed. Lastly, numerical simulation and cycling experiments have been performed to validate the function of the printed valve prostheses as one-way valves.
Probing nonperturbative third and fifth harmonic generation on silicon without and with thermal oxide layer
Authors: Seres J , Seres E , Céspedes E , Martinez-de-Olcoz L , Zabala M , Schumm T
Published: August 2023

We examine Si with and without additional SiO2 thin film coating as a candidate for producing powerful 3rd and 5th harmonics of Ti:sapphire laser pulses for future spectroscopic application. Polarization rotation experiments have been performed at different incident angles to determine the origin of the generated harmonics and a strong polarization-dependency of the harmonic signals was observed. A simplified tensor formalism is introduced to reproduce the measurements with high accuracy. Comparing the measurements with the Oh symmetry of the bulk crystal, the C2v structural symmetry for the uncoated Si sample and a C4v symmetry for the SiO2 coated sample, we conclude that the polarization anisotropies are determined by the surface/interface symmetries.
Simulation study of various factors affecting the performance of vertical organic field-effect transistors
Authors: Bisht Ramesh Singh , Kumar Pramod
Published: August 2023

Vertical organic field-effect transistors (VOFETs) can offer a short channel architecture that can further enhance the performance at low operating voltages, which makes it more viable for organic electronics applications. VOFETs can be prepared using low-cost techniques that reduce the high processing costs and can operate at high current densities and relatively high fRequencies. To further improve the performance, high current density, and operating frequency, the physics of charge carrier transport should be understood well with the simulation. The main problem with VOFET is the high off-current which is inevitable due to conduction from the source to the drain contact. Many efforts have been made to reduce the off-state current by the addition of an insulating layer on top of the source electrode, which further increases the processing complexity and cost of fabrication. Simulations based on device geometry, contact barriers, and organic semiconductor parameters are carried out to study the charge carrier transport in VOFET. The simulation results show that the most important factor, to enhance the performance is the device geometry or architecture, which requires a specific fill factor, a ratio of the exposed gate dielectric width to the total width of the device with the source electrode. The simulation results also show a different type of working physics of the basic VOFET architecture where the On/Off ratio and subthreshold swing are largely dependent on the initial negative gate field instead of the accumulated charge carriers at positive gate fields. Optimized VOFET architecture is then simulated for variation in contact barrier and semiconductor properties, which show further enhancement in performance.
Stochastic analysis of infinite particle systems—A new development in classical stochastic analysis and dynamical universality of random matrices
Authors: Osada Hirofumi
Published: August 2023

We examine the stochastic dynamics of infinite particle systems moving in

R

d

\mathbb {R}^{d}

. The classical stochastic analysis pursues the stochastic dynamics of a single particle. We explain how to extend the classical stochastic analysis when the object becomes an infinite particle system. The equilibrium states of a system of infinite number of particles resulting from random matrices have the logarithmic function as an interaction potential. Hence, we develop a theory that applies to interaction potentials having a dominating influence over long distances. As an application, we show that the universality of point processes related to random matrices holds for stochastic dynamics.
Rigorous numerics for fast-slow systems
Authors: Matsue Kaname
Published: August 2023

We show a series of results about rigorous numerics for dynamical systems generated by ordinary differential equations called fast-slow systems obtained through the author’s recent research. The contents of the present paper are mainly based on the results of Matsue [Topol. Methods Nonlinear Anal. 50 (2017), pp. 357–486].
Cohomology pairings of 3-manifolds and their diagrammatic computation
Authors: Nosaka Takefumi
Published: August 2023

We discuss some invariants of 3-dimensional manifolds, together with related topics. We also show some computations of the invariants, as results of the author.
Challenge Inoculum for Hepatitis C Virus Controlled Human Infection Model
Authors: Liang T Jake , Law John L M , Pietschmann Thomas , Ray Stuart C , Bukh Jens , Bull Rowena , Chung Raymond T , Tyrrell D Lorne , Houghton Michael , Rice Charles M
Published: August 2023

For any controlled human infection model (CHIM), a safe, standardized, and biologically relevant challenge inoculum is necessary. For hepatitis C virus (HCV) CHIM, we propose that human-derived high-titer inocula of several viral genotypes with extensive virologic, serologic, and molecular characterizations should be the most appropriate approach. These inocula should first be tested in human volunteers in a step-wise manner to ensure safety, reproducibility, and curability prior to using them for testing the efficacy of candidate vaccines.
Controlled Human Infection Model for Hepatitis C Virus Vaccine Development: Trial Design Considerations
Authors: Feld Jordan J , Bruneau Julie , Dore Gregory J , Ghany Marc G , Hansen Bettina , Sulkowski Mark , Thomas David L
Published: August 2023

The design of a clinical trial for a controlled human infection model (CHIM) to accelerate hepatitis C virus (HCV) vaccine development requires careful consideration. The design of a potential approach to HCV CHIM is outlined, involving initial sentinel cohorts to establish the safety and curability of the viral inoculum followed by larger cohorts to establish the spontaneous clearance rate for each inoculum. The primary endpoint would be HCV clearance by 24 weeks post-inoculation, recognizing that the prevention of chronic infection would be the primary goal of HCV vaccine candidates. Additional considerations are discussed, including the populations to be enrolled, the required monitoring approach, indications for antiviral therapy, and the required sample size for different CHIM approaches. Finally, safety considerations for CHIM participants are discussed.
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

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

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 < 0.001 and 46%, P = 0.001), PET (65%, P < 0.001 and 58%, P = 0.032), and CMR (72%, P < 0.001 and 33%, P < 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 < 0.001) and PET (67%, P < 0.001). Lastly, QFR exhibited a higher area under the receiver operating characteristic curve (0.89) than SPECT (0.57, P < 0.001), PET (0.66, P < 0.001), and CMR (0.60, P < 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

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

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

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

Objectives

To characterize a blaCMY variant associated with ceftazidime/avibactam resistance from a serially collected Escherichia coli isolate.

Methods

A 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 >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.

Results

WGS 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.

Conclusions

We 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

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

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.
Reevaluation of Sensitivity of Monilinia fructicola Isolates to the DMI Fungicide Propiconazole in the Southeastern United States and Investigation of the Genetic Element Mona
Authors: Gura William P. , Gelain Jhulia , Sikora Edward J. , Vinson Edgar L. , Brannen Phillip M. , Schnabel Guido
Published: August 2023

Sterol demethylation inhibitor (DMI) fungicides continue to be essential components for the control of brown rot of peach caused by Monilinia fructicola in the United States and worldwide. In the southeastern United States, resistance to DMIs had been associated with overexpression of the cytochrome P450 14α-demethylase gene MfCYP51 as well as the genetic element Mona, a 65 bp in length nucleotide sequence located upstream of MfCYP51 in resistant isolates. About 20 years after the first survey, we reevaluated sensitivity of M. fructicola from South Carolina and Georgia to propiconazole and also evaluated isolates from Alabama for the first time. A total of 238 M. fructicola isolates were collected from various commercial and two experimental orchards, and sensitivity to propiconazole was determined based on a discriminatory dose of 0.3 μg/ml. Results indicated 16.2, 89.2, and 72.4% of isolates from Alabama, Georgia, and South Carolina, respectively, were resistant to propiconazole. The detection of resistance in Alabama is the first report for the state. All resistant isolates contained Mona, but it was absent from most sensitive isolates. It was unclear if the resistance frequency had increased in South Carolina and Georgia. However, the resistance levels (as assessed by the isolate frequency in discriminatory dose-based relative growth categories) did not change notably, and no evidence of other resistance genotypes was found. Analysis of the upstream MfCYP51 gene region in the resistant isolate CF010 revealed an insertion sequence described for the first time in this report. Our study suggests that current fungicide spray programs have been effective against increasing resistance levels in populations of M. fructicola and suppressing development of new resistant genotypes of the pathogen.
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.
Codelivery of ERCC2 small interfering RNA and cisplatin with macrophage-derived mimetic nanovesicles for enhanced bladder cancer treatment
Authors: Zhou Qidong , Wu Hao , Miao Fengze , Cao Yirui , Liang Lifei , Huang Jiahua , Qian Zhiyu
Published: August 2023

Cisplatin-based chemotherapy plays a vital role in the management of muscle-invasive bladder cancer (MIBC); however, off-tumor toxicity and resistance often lead to cancer recurrence and eventual treatment failure. The loss of function of the nucleotide excision repair gene excision repair cross-complementing rodent repair deficiency gene 2 (ERCC2) in cancer cells correlates with sensitivity to cisplatin, while its overexpression causes cisplatin resistance. Small interfering RNA (siRNA) knockdown of ERCC2 combined with cisplatin treatment may improve therapeutic outcomes in patients with bladder cancer. Here, we aimed to develop macrophage-derived mimetic nanovesicles (MNVs) as a nanoplatform for the simultaneous delivery of cisplatin and ERCC2 siRNA for enhancing the efficacy of bladder cancer chemotherapy. The cellular uptake, gene down-regulation, tumor inhibition effects, and biosafety of the synthesized nanodrugs (MNV-Co) as a synergistic therapeutic strategy for MIBC were evaluated in vitro and in vivo. The results indicated high efficacy of MNV-Co against MIBC and low off-tumor toxicity. Furthermore, by down-regulating ERCC2 mRNA and protein levels, MNV-Co improved chemosensitivity, promoted cancer cell apoptosis, and effectively suppressed tumor growth. This study presents a potential approach for delivering cisplatin and ERCC2 siRNA concurrently to treat bladder cancer using a biomimetic nanosystem.
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.
Promising response of dabrafenib, trametinib, and osimertinib combination therapy for concomitant BRAF and EGFR-TKI resistance mutations
Authors: Chimbangu Clint Taonaishe , Ya Zhou , Xi Li , Jiayue Zhao , Xiao Meng , Ying Wang , Xingxu Yu , Liu Xiaomei
Published: August 2023

Despite the initial promise of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in effectively combating tumor growth, the majority of patients with advanced non-small cell lung cancers (NSCLCs) inevitably develop resistance to these treatments. An infrequent genetic mutation known as BRAFV600E has been identified as a contributing factor to the emergence of acquired resistance to EGFR-TKIs. Genetic alterations in BRAF, particularly V600E, contribute to resistance to osimertinib. However, a combination therapy involving osimertinib, dabrafenib (a BRAF inhibitor), and trametinib has shown effectiveness in overcoming BRAF V600E-mediated resistance in advanced lung adenocarcinoma. This treatment regimen holds promise for similar cases. In our case report, the combination of osimertinib, dabrafenib, and trametinib effectively overcame osimertinib resistance and resulted in sustained partial remission.
Development and Evaluation of a Mobile Application to Prevent Recurrent Stroke by Enhancing Self-management on Health Outcomes for Stroke Survivors
Authors: Jeong Young Ju , Kim Hee Sun , Kang Hyun Goo
Published: August 2023

This study aimed to develop a Mobile Application to Prevent Recurrent Stroke to prevent recurrent stroke by enhancing self-management and to evaluate its effects on stroke survivors' health outcomes. The Mobile Application to Prevent Recurrent Stroke was developed based on social cognitive theory and the model in order of analysis, design, development, implementation, and evaluation process. The Mobile Application to Prevent Recurrent Stroke consisted of health management contents such as information about stroke, its associated risk factors, and required skills to conduct self-management with tailored support and counseling. A quasi-experimental preintervention and postintervention design was used involving a total of 54 stroke survivors. The experimental group (n = 27) was provided the Mobile Application to Prevent Recurrent Stroke for 8 weeks, whereas the control group (n = 27) received an education booklet. The result revealed that medication adherence (P= .002), healthy eating habit (P< .001), physical activity (P< .001), and affected-side grip strength (P= .002) in the experimental group were significantly better than those in the control group. The systolic blood pressure (P= .020), diastolic blood pressure (P< .001), body mass index (P< .001), and waist circumference (P< .001) in the experimental group were significantly lower than those in the control group. Stroke survivors can easily use this Mobile Application to Prevent Recurrent Stroke to improve self-management. Nurses can provide tailored care based on the lifelogging data of stroke survivors to prevent recurrent stroke.
Nursing Diagnosis Accuracy in Nursing Education
Authors: Bertocchi Luca , Dante Angelo , La Cerra Carmen , Masotta Vittorio , Marcotullio Alessia , Caponnetto Valeria , Ferraiuolo Fabio , Jones Dorothy , Lancia Loreto , Petrucci Cristina
Published: August 2023

Computer-based technologies have been widely used in nursing education, although the best educational modality to improve documentation and nursing diagnostic accuracy using electronic health records is still under investigation. It is important to address this gap and seek an effective way to address increased accuracy around nursing diagnoses identification. Nursing diagnoses are judgments that represent a synthesis of data collected by the nurse and used to guide interventions and to achieve desirable patients' outcomes. This current investigation is aimed at comparing the nursing diagnostic accuracy, satisfaction, and usability of a computerized system versus a traditional paper-based approach. A total of 66 nursing students solved three validated clinical scenarios using the NANDA-International terminologies traditional paper-based approach and then the computer-based Clinical Decision Support System. Study findings indicated a significantly higher nursing diagnostic accuracy (P < .001) in solving cancer and stroke clinical scenarios, whereas there was no significant difference in acute myocardial infarction scenario. The use of the electronic system increased the number of correct diagnostic indicators (P < .05); however, the level of students' satisfaction was similar. The usability scores highlighted the need to make the electronic documentation systems more user-friendly.
Melanocytic neoplasms in neurofibromatosis type 1: a systematic review
Authors: Meyer Summer N. , Simmons Elanee , Studer Amy C. , Rauen Katherine A. , Kiurua Maija
Published: August 2023

Neurofibromatosis type 1 (NF1) is commonly mutated in melanoma, yet the risk of melanoma in individuals with NF1 is incompletely understood. We performed a systematic review to investigate the risk and characteristics of melanoma and melanocytic nevi in NF1 individuals. PubMed was searched for articles describing NF1 individuals with melanoma, or melanocytic nevi. Those with cutaneous and ocular melanomas were compared to the general population using Surveillance, Epidemiology, and End Results data. Fifty-three articles describing 188 NF1 patients were included (melanoma n = 82, melanocytic nevi n = 93, melanocytic nevi, and melanoma n = 13). Compared to the general population, NF1 patients with cutaneous melanomas had earlier melanoma diagnoses (49.1 vs. 58.6 years, P = 0.012), thicker tumors (3.7 vs. 1.2 mm, P = 0.006), and more frequent disease-specific deaths (27.3% vs. 8.6%, P = 0.005) with shorter survival (12.9 vs. 34.2 months, P = 0.011). Ocular melanomas made up 15.0% of all melanomas in NF1 patients versus 1.5% in the general population (P < 0.001). In pooling all population-based studies describing melanoma in NF1 populations, NF1 individuals had 2.55 higher odds of having melanoma compared to the general population. A nevus spilus was commonly reported among NF1 individuals with nevi (44.8%, 39/87). Our findings suggest that NF1 individuals may have a higher risk for developing melanomas and tend to have thicker melanomas and worse survival compared to the general population, highlighting the importance of cutaneous and ophthalmologic surveillance in NF1 patients. Our review also supports the association between NF1 and nevus spilus.
Short-term plasticity in the spinal nociceptive system
Authors: Cathenaut Lou , Schlichter Rémy , Hugel Sylvain
Published: August 2023

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

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

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.
Serum levels of endocannabinoids and related lipids in painful vs painless diabetic neuropathy: results from the Pain in Neuropathy Study
Authors: Bäckryd Emmanuel , Themistocleous Andreas , Stensson Niclas , Rice Andrew S. C. , Tesfaye Solomon , Bennett David L. , Gerdle Björn , Ghafouri Bijar
Published: August 2023

N-arachidonoylethanolamine (also known as anandamide) and 2-arachidonoylglycerol are activators of the cannabinoid receptors. The endocannabinoid system also includes structurally and functionally related lipid mediators that do not target cannabinoid receptors, such as oleoylethanolamide, palmitoylethanolamide, and stearoylethanolamide. These bioactive lipids are involved in various physiological processes, including regulation of pain. The primary aim of the study was to analyze associations between serum levels of these lipids and pain in participants in the Pain in Neuropathy Study, an observational, cross-sectional, multicentre, research project in which diabetic patients with painless or painful neuropathy underwent deep phenotyping. Our hypothesis was that painful neuropathy would be associated with higher levels of the 5 lipids compared with painless neuropathy. Secondary aims were to analyze other patient-reported outcome measures and clinical data in relationship to lipid levels. The lipid mediators were analyzed in serum samples using liquid chromatography tandem mass spectrometry (LC-MS/MS). Serum levels of anandamide were significantly higher in the painful group, but the effect size was small (Cohen d = 0.31). Using cluster analysis of lipid data, patients were dichotomized into a “high-level” endocannabinoid group and a “low-level” group. In the high-level group, 61% of patients had painful neuropathy, compared with 45% in the low-level group (P = 0.039). This work is of a correlative nature only, and the relevance of these findings to the search for analgesics targeting the endocannabinoid system needs to be determined in future studies.
Effects of machine perfusion strategies on different donor types in liver transplantation: a systematic review and meta-analysis
Authors: Liang Aijun , Cheng Weiye , Cao Peihua , Cai ShaoRu , Zhang Linya , Zhong Kebo , Nie Yu
Published: August 2023

Background:

Increasing use of extended-criteria donors (ECD) set higher requirements for graft preservation. Machine perfusion (MP) improves orthotopic liver transplantation (OLT) outcomes but its effects on different donor types remains unclear. Our aim was to assess the effects of hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), or normothermic regional perfusion (NRP) versus static cold storage (SCS) on different donor types.

Materials and Methods:

A literature search comparing the efficacy of MP versus SCS in PubMed, Cochrane and EMBASE database was conducted. Meta-analysis was performed to obtain pooled effects of MP on extended criteria donors (ECD), donation after circulatory death (DCD), donor after brainstem death.

Results:

39 studies were included (9 RCTs and 30 cohort studies). Compared with SCS, HMP significantly reduced the risk of non-anastomotic biliary stricture (NAS) (OR 0.43, 95%CI 0.26-0.72), major complications (OR 0.55, 95%CI 0.39-0.78), early allograft dysfunction (EAD) (OR 0.46, 95%CI 0.32-0.65) and improve one-year graft (OR 2.36, 95%CI 1.55-3.62) in ECD-OLT. HMP also reduced primary nonfunction (PNF) (OR 0.40, 95%CI 0.18-0.92) and acute rejection (OR 0.62, 95%CI 0.40-0.97). NMP only reduced major complications in ECD-OLT (OR 0.56, 95%CI 0.34-0.94), without favorable effects on other complications and survival. NRP lower the overall risk of NAS (OR 0.27, 95%CI 0.11-0.68), PNF (OR 0.43, 95%CI 0.22-0.85), EAD (OR 0.58, 95%CI 0.42-0.80) and meanwhile improved one-year graft survival (OR 2.40, 95%CI 1.65-3.49) in control DCD-OLT.

Conclusions:

HMP might currently be considered for marginal livers as it comprehensively improves ECD-OLT outcomes. NMP assists some outcomes in ECD-OLT but more evidence regarding NMP-ECD is warrant. NRP significantly improves DCD-OLT outcomes and is recommended where longer non-touch periods exist.