bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement and calculation method of substation grounding system parameters based on CDEGS
Authors: Hu Yuan , Wu Peng , Gong Fangchao , Cao Jin , Xu Xiaolin , Zhang Shuai , Wang Ning , Li Yan , Zhao Penghui
Published: April 2022

Indoor substations are often located in areas with intensive power consumption, and its grounding design has become a very important task. In this paper, the whole process of grounding design is studied from the grounding resistance measurement obtained in the early geological exploration to the final grounding resistance, touch voltage and step voltage verification to ensure the accuracy of the design. According to the design parameters of grounding performance, the simulation calculation based on CDEGS software is adopted and optimized, which improves the design accuracy. Taking a 110kV actual substation as an example, the simulation results are accurate and reliable, which shows that the research method of grounding design based on CDEGS software can effectively improve the design quality.
Research on transient dynamic behavior and stress of reciprocating compressor valve under air volume regulation
Authors: Shu Yue , Xiao Jun , Liu Zhilong , Li Fengyu
Published: April 2022

By establishing the motion equation of the air valve under the condition of air volume adjustment, the motion law of the air valve in the process of expansion, compression, suction and exhaust of the reciprocating compressor under different loads is calculated, and the reciprocating compressor with stepless air volume adjustment is used. The compressor unit verifies the calculation results. The maximum stress of the valve plate under different loads is analyzed, and the results show that in the ideal state where the fork pressure disappears instantaneously, the adjustment method of the partial stroke pressure opening suction valve has a greater influence on the stress concentration of the valve plate than the normal condition; in the partial stroke pressure opening suction valve adjustment method, the free retraction speed and stress of the valve plate will increase as the compressor load decreases.
Spatial asynchrony in environmental and economic benefits of stream restoration
Authors: Zhang Ruoyu , Newburn David , Rosenberg Andrew , Lin Laurence , Groffman Peter , Duncan Jonathan , Band Lawrence
Published: April 2022

Stream restoration is widely used to mitigate the degradation of urban stream channels, protect infrastructure, and reduce sediment and nutrient loadings to receiving waterbodies. Stabilizing and revegetating riparian areas can also provide recreational opportunities and amenities, and improve quality of life for nearby residents. In this project, we developed indices of an environmental benefit (potential nitrate load reduction, a priority in the Chesapeake Bay watershed) and economic benefit (household willingness to pay, WTP) of stream restoration for all low order stream reaches in three main watersheds in the Baltimore metro region. We found spatial asynchrony of these benefits such that their spatial patterns were negatively correlated. Stream restoration in denser urban, less wealthy neighborhoods have high WTP, but low potential nitrate load reduction, while suburban and exurban, wealthy neighborhoods have the reverse trend. The spatial asynchrony raises challenges for decision makers to balance economic efficiency, social equity, and specific environmental goals of stream restoration programs.
Meeting U.S. greenhouse gas emissions goals with the international air pollution provision of the clean air act
Authors: Yuan Mei , Barron Alexander R , Selin Noelle E , Picciano Paul D , Metz Lucy E , Reilly John M , Jacoby Henry D
Published: April 2022

We explore economic, distributional and health consequences of U.S. greenhouse gas emissions objectives that could be achieved using Section 115 of the Clean Air Act (international air pollution), which has only recently received detailed legal analysis as a potential U.S. climate policy tool. Under it a national emissions target could be allocated among the states. This illustrative analysis considers 45% and 50% reductions of energy and industry-related CO2 emissions by 2030, below 2005 levels, via a model rule. Different approaches (based on legal precedent) for the interstate allocation are considered, along with alternative rates of technology improvement. The detail needed to analyze this approach is provided by MIT’s U.S. Regional Energy Policy model (30 individual states and multi-state regions), with its electricity sector replaced by the U.S. National Renewable Energy Laboratory’s Renewable Energy Development System (ReEDS). Air quality benefits are estimated using modeling tools developed by academic researchers and the U.S. Environmental Protection Agency. Three-quarters of emissions reductions in 2030 come in the electric sector, while reductions elsewhere illustrate the efficiency advantage of a multi-sector policy. With all states participating in allowance trading, the resulting national emissions price is lower than in older assessments. The difference is due to lower growth expectations, recent state policies, falling costs of low carbon technologies, and an improved representation of electric system flexibility by the ReEDS model. Even ignoring climate and air quality benefits, economic welfare grows at near the baseline rate for all regions regardless of the interstate allocation approach. When states distribute allowance revenue to residents on an equal per-capita basis, the policy is welfare improving to the lowest income quintile in all regions. Aggregation of control costs, the mortality effects of reduced particulates, and the value of avoided climate damages yields positive national net benefits in all cases.
Climate warming outweighs vegetation greening in intensifying flash droughts over China
Authors: Zhang Miao , Yuan Xing , Otkin Jason A , Ji Peng
Published: April 2022

The increasing occurrence of flash droughts with rapid onsets poses a great threat to food security and ecosystem productivity. While temporal trends in flash droughts have been extensively studied, the contributions of climate warming, vegetation greening, and the physiological effect of rising CO2 to trends in flash drought characteristics remain unclear. Here we show there are significant increasing trends in flash drought frequency, duration, and intensity for most of China during 1961–2016. Warmer temperatures and vegetation greening increase evapotranspiration and decrease soil moisture, and explain 89% and 54% of the increasing frequency of flash drought respectively. Rising CO2 concentrations reduce stomatal conductance, which acts to decelerate the increasing drought frequency trend by 18%, whereas the physiological effects of rising CO2 on flash drought duration and intensity are smaller. Warming also outweighs vegetation greening for the increasing trends of flash drought duration and intensity over most of China, except North China. Our study highlights the role of climate warming in increasing the risk of flash droughts.
Contrasting climate and carbon-cycle consequences of fossil-fuel use versus deforestation disturbance
Authors: Jayakrishnan K U , Bala Govindasamy , Cao Long , Caldeira Ken
Published: April 2022

Carbon dioxide emissions from deforestation disturbance (e.g. clear-cutting, forest fires) are in the same units as carbon dioxide emissions from fossil fuels. However, if the forest is allowed to regrow, there is a large difference between climate effects of that forest disturbance and climate effects of fossil CO2. In this study, using a set of idealized global climate-carbon model simulations with equal amounts of CO2 emissions, we show that on century to millennial timescales the response of the climate system to fossil-fuel burning versus deforestation disturbance are vastly different. We performed two 1000 year simulations where we add abrupt emissions of about 600 PgC to the preindustrial state as a consequence of either fossil fuel use or deforestation disturbance with vegetation regrowth. In the fossil fuel simulations, after 1000 years, about 20% of the initial atmospheric CO2 concentration perturbation remains in the atmosphere and the climate is about 1 °C warmer compared to preindustrial state. In contrast, in the case of deforestation with regrowth, after 1000 years, atmospheric CO2 concentration returns close to preindustrial values, because deforested land will typically recover its carbon over the decades and centuries in the absence of further human intervention. These results highlight the differences in the degree of long-term commitment associated with fossil-fuel versus deforestation emissions.
Uncertainties in quantum measurements: a quantum tomography
Authors: Balachandran A P , Calderón F , Nair V P , Pinzul Aleksandr , Reyes-Lega A F , Vaidya S
Published: April 2022

The observables associated with a quantum system S form a non-commutative algebra

A

S

. It is assumed that a density matrix ρ can be determined from the expectation values of observables. But

A

S

admits inner automorphisms

a
↦
u
a

u

−
1

,
a
,
u
∈

A

S

,

u

*

u
=
u

u

*

=
1

, so that its individual elements can be identified only up to unitary transformations. So since Tr ρ(uau*) = Tr(u*ρu)a, only the spectrum of ρ, or its characteristic polynomial, can be determined in quantum mechanics. In local quantum field theory, ρ cannot be determined at all, as we shall explain. However, abelian algebras do not have inner automorphisms, so the measurement apparatus can determine mean values of observables in abelian algebras

A

M

⊂

A

S

(M for measurement, S for system). We study the uncertainties in extending

ρ

|

A

M

to

ρ

|

A

S

(the determination of which means measurement of

A

S

) and devise a protocol to determine

ρ

|

A

S

≡
ρ

by determining

ρ

|

A

M

for different choices of

A

M

. The problem we formulate and study is a generalization of the Kadison–Singer theorem. We give an example where the system S is a particle on a circle and the experiment measures the abelian algebra of a magnetic field B coupled to S. The measurement of B gives information about the state ρ of the system S due to operator mixing. Associated uncertainty principles for von Neumann entropy are discussed in the appendix, adapting the earlier work by Białynicki-Birula and Mycielski (1975 Commun. Math. Phys.
44 129) to the present case.
Control of frustrated double ionization channels with the carrier-envelope phase of few-cycle linearly polarized laser pulses
Authors: Xu Tong-Tong , Zhang Lian-Lian , Gong Wei-Jiang
Published: April 2022

Using a three-dimensional classical method, we theoretically explore the frustrated double ionization (FDI) of Ar atoms under few-cycle linearly polarized laser pulses with different carrier-envelope phases (CEPs). Our calculated spectra are similar to the recent experimentally observed two peeks in the electron momentum distribution (Larimian et al 2020 Phys. Rev. Res.
2 013021). The dependence of FDI on laser CEPs is investigated, and the result reveals that the two different pathways of FDI can be controlled by CEPs. The information on which pathway leads to FDI is encoded in the electron-electron energy distribution shortly after recollision and momentum distribution at the ionization time after recollision.
Nanofocusing performance of plasmonic probes based on gradient permittivity materials
Authors: Wang Dongxue , Zhang Ze , Wang Jianwei , Ma Ke , Gao Hua , Wang Xi
Published: April 2022

Probe is the core component of an optical scanning probe microscope such as scattering-type scanning near-field optical microscopy (s-SNOM). Its ability of concentrating and localizing light determines the detection sensitivity of nanoscale spectroscopy. In this paper, a novel plasmonic probe made of a gradient permittivity material (GPM) is proposed and its nanofocusing performance is studied theoretically and numerically. Compared with conventional plasmonic probes, this probe has at least two outstanding advantages: first, it does not need extra structures for surface plasmon polaritons excitation or localized surface plasmon resonance, simplifying the probe system; second, the inherent nanofocusing effects of the conical probe structure can be further reinforced dramatically by designing the distribution of the probe permittivity. As a result, the strong near-field enhancement and localization at the tip apex improve both spectral sensitivity and spatial resolution of a s-SNOM. We also numerically demonstrate that a GPM probe as well as its enhanced nanofocusing effects can be realized by conventional semiconductor materials with designed doping distributions. The proposed novel plasmonic probe promises to facilitate subsequent nanoscale spectroscopy applications.
An astigmatic transform of a fractional-order edge dislocation
Authors: Kotlyar Victor V , Abramochkin Eugeny G , Kovalev Alexey A , Nalimov Anton G
Published: April 2022

In this work, it is theoretically and numerically demonstrated that an astigmatic transformation of a νth-order edge dislocation (shaped as a zero-intensity straight line) of a coherent light field—where ν =n + α is a real positive number, n is integer, and 0 <α <1 is fractional—produces n optical elliptic vortices (screw dislocations) with topological charge (TC) −1, which are arranged on a straight line perpendicular to the edge dislocation and found at Tricomi function zeros. We also reveal that at a distance from the said optical vortices (OV), an extra OV with charge −1 is born on the same straight line, which departs to the periphery with α tending to zero, or gets closer to the n OVs with α tending to 1. Additionally, we find that a countable number of OVs (intensity nulls) with charge −1 are produced at the field periphery and arranged on diverging hyperbolic curves equidistant from the straight line of the n main intensity nulls. These additional OVs, which we term as ‘escort’, either approach the beam center, accompanying the extra ‘companion’ OV if 0 <α <0.5, or depart to the periphery, whereas the ‘companion’ keeps close to the main OVs if 0.5 <α <1. At α =0 or α = 1, the ‘escort’ OVs are shown to be at infinity. At fractional ν, the TC of the whole optical beam is theoretically shown to be infinite. Numerical simulation results are in agreement with the theoretical findings.
Effects of asna fibre reinforced with epoxy resin with and without steel wire mesh and simulation of car bumper
Authors: Elumalai P V , Dhineshbabu N R , Varsala Pragna , Anjani Devi S , Sitaramamurty Adduri S S M , Saleel C Ahamed , Hasan Nasim
Published: April 2022

The utilization of natural fiber composites has been increased in replacing various parts in the automobile sector made up of synthetic fiber due to its degradability nature and environment friendliness. In this work, the naturally available Asna fiber was processed and the composites were prepared without and with steel wire mesh in various volume fractions (vf) of the fiber. In the present experimental investigation, the influence of different composite on the thermal, mechanical, and water absorption characteristics. Various properties such as tensile, flexural and impact strength were tested for the multiple composites. Subsequently, a simulation model of a car front bumper was prepared using ANSYS to test it while defining the determined properties of the composites. The test results showed that when vf was increased from 0.4 to 0.5%, the tensile and flexural were decreased by 0.72% and 59%, respectively, whereas impact strength was increased by 5.9% for the composite without wire mesh. The tensile and flexural strengths were decreased by 18.2%, whereas impact strength was increased by 1.6% for 0.5 vf of the composite when steel wire mesh was added to the composite. The investigation of composite’s thermal behavior showed that when the temperature range comes within 330 °C–370 °C, the composites started decomposing. Various images were captured using Scanning Electron Microscope to investigate the fibers’ dispersion in epoxy polymers and its interfacial bonding. The simulation results showed that the bumper made up of the composite with wire mesh provides a better impact strength as compared to other composites and steel.
Surface modification of plasma spraying Al2O3–13 wt% TiO2 coating by laser remelting technique
Authors: Zhou Yan , Xu Lifeng , Zheng Haizhong , Wang Dongsheng
Published: April 2022

An Al2O3–13 wt% TiO2 composite ceramic coating was prepared on the TiAl alloy surface by plasma spraying and laser remelting combined technique. The morphology, microstructure, and phase composition of the prepared coating were analyzed by scanning electron microscopy, energy disperse spectroscopy, and x-ray diffraction. The bonding strength, microhardness, wear resistance, erosion resistance, and thermal shock resistance of the coating were also tested. Results demonstrated that after processing by laser remelting, the particles on the ceramic coating surface were refined, lamellar structure disappeared, and density increased. A remelting layer basically without crack and other defects was gained. Due to laser remelting, the metastable-phase γ-Al2O3 was converted into stable-phase α-Al2O3. Influenced by the low thermal conductivity of ceramic materials, remelting of the whole ceramic layer is impossible to realize during laser remelting. The remelted ceramic coating formed the isometric crystal remelting zone with small grain size, sintering zone, and lamellar residual plasma spraying zone. The bonding strength and microhardness of the coating improved significantly after laser remelting, and the wear resistance, erosion resistance, and thermal shock resistance were significantly superior to those of the original plasma spraying layer. Laser remelting specimens still represented typical brittle erosion characteristics. Cracks initiated and expanded on near surface, finally leading to breakage of the remelting layer, mainly manifested by grain peeling. With respect to thermal shock failure mode, the corner peeling is the major failure mode of the ceramic coating after plasma spraying. Differently, corner peeling and considerable local peelings were found at the center of the ceramic coating after laser remelting. The influences of laser remelting on the thermal shock performances of the coating are mainly manifested as the decreased initial failure resistance, decelerated crack expansion, and changes in failure modes of the coating.
Influence of Cu content on the microstructure and mechanical property of Ti3SiC2/Cu composites
Authors: Ma Shuai , Zhang Rui , Liu Fuyan , Chen Biao , Wu Chenlong
Published: April 2022

Ti3SiC2/Cu composites with different Cu content were prepared by spark plasma sintering (SPS) process in vacuum and the effect of Cu content on the microstructure and mechanical property was investigated. The axial displacement, temperature and current of the composites during the sintering process were recorded and discussed. The phase compositions of the original Ti3SiC2 and Cu powder before and after ball-milling, and the as-produced composites were studied by XRD analysis. The surface morphology and fracture surface of the composites were investigated by SEM. The influence of Cu content on the relative density, hardness and compressive strength of the composites was inquired. The results discovered that the phase composition of Ti3SiC2/Cu composites varied with the content of Cu. The phase composition of the Ti3SiC2/5 vol% Cu composite was composed of Ti3SiC2, Ti5Si3 and Cu3Si, while that of Ti3SiC2/10 vol% Cu composite and Ti3SiC2/15 vol% Cu composite contained TiC, besides Ti3SiC2, Ti5Si3 and Cu3Si. Moreover, the relative density of all Ti3SiC2/Cu composites was relatively high (≥93%). With the increase of Cu content, the axial displacement, hardness and compressive strength of the Ti3SiC2/Cu composites increased. Conclusively, the Ti3SiC2/Cu composite with 15 vol% Cu exhibited better mechanical properties.
The impact of a magnetic ion on the thermoelectric properties of copper-rich quaternary selenides
Authors: Aldowiesh Alaa , Mangelis Panagiotis , Vaqueiro Paz , Powell Anthony V
Published: April 2022

A series of copper-based p-type chalcogenide semiconductors, Cu2+x

BGe1−x
Se4 (B = Zn, Fe; 0 ⩽ x ⩽ 0.15), was prepared by high-temperature methods, to explore the impact of replacement of the closed-shell ion, Zn2+, with the magnetically active, Fe2+ cation. Powder x-ray diffraction in conjunction with Rietveld refinement reveals that zinc-containing materials are described in the kesterite-type structure (space group:

I

4
ˉ

) and contain trace amounts of secondary phases, whereas in the iron analogues, described in the stannite-type structure (space group: I

4
ˉ

2
m

), single-phase behaviour persists to x = 0.1. Excess copper ions lead to the formation of holes and the electrical resistivity of both series is reduced from that of the stoichiometric end members. In the case of the iron-containing materials, this is shown to be due to an increase in the hole mobility, µ. This decrease in resistivity offsets the observed reduction in Seebeck coefficient and both series exhibit an improvement in thermoelectric performance. The lower electrical resistivity of the iron-containing materials, leads to higher figures-of-merit, compared to those of the zinc-containing materials at the same level of copper excess. The maximum figure-of-merit, ZT = 0.3 is attained for Cu2.075FeGe0.925Se4 at the comparatively low temperature of 575 K. This is an increase of ca. 62% from that of the end member phase and ca. 67% higher than that of the zinc analogue at the same level of substitution.
Evaluation of “Spin” in the Abstracts of Systematic Reviews and Meta-Analyses of Therapeutic Interventions Published in High-Impact Plastic Surgery Journals: A Systematic Review
Authors: Gallo Lucas , Yuan Morgan , Gallo Matteo , Chin Brian , Huynh Minh N Q , McRae Mark , McRae Matthew , Coroneos Christopher J , Thoma Achilleas , Voineskos Sophocles H
Published: April 2022

Background

“Spin” is a form of reporting bias where there is a misappropriated presentation of study results, often overstating efficacy, or understating harms. Abstracts of systematic reviews (SRs) in other clinical domains have been demonstrated to employ spin, which may lead to clinical recommendations not justified by the literature.

Objectives

The authors sought to determine the prevalence of spin strategies in abstracts of plastic surgery SRs.

Methods

A literature search was conducted in MEDLINE, Embase, and CENTRAL to identify all SRs published in the top 5 plastic surgery journals from 2015 to 2021. Screening, data extraction, and spin analysis were performed by 2 independent reviewers. Data checking of the spin analysis was performed by a plastic surgery resident with graduate-level training in clinical epidemiology.

Results

From an initial search of 826 SRs, 60 SRs and meta-analyses were included in this study. Various types of spin were identified in 73% of SR abstracts (n = 44). “Conclusion claims the beneficial effect of the experimental treatment despite high risk of bias in primary studies” was the most prevalent type of spin and was identified in 63% of SRs (n = 38). There were no significant associations between the presence of spin and study characteristics.

Conclusions

This study found that 73% of abstracts in plastic surgery SRs contain spin. Although systemic reviews represent the highest level of evidence, readers should be aware of types of “spin” when interpreting results and incorporating recommendations into patient care.
GASS-Metal: identifying metal-binding sites on protein structures using genetic algorithms
Authors: Paiva Vinícius A , Mendonça Murillo V , Silveira Sabrina A , Ascher David B , Pires Douglas E V , Izidoro Sandro C
Published: April 2022

Metals are present in >30% of proteins found in nature and assist them to perform important biological functions, including storage, transport, signal transduction and enzymatic activity. Traditional and experimental techniques for metal-binding site prediction are usually costly and time-consuming, making computational tools that can assist in these predictions of significant importance. Here we present Genetic Active Site Search (GASS)-Metal, a new method for protein metal-binding site prediction. The method relies on a parallel genetic algorithm to find candidate metal-binding sites that are structurally similar to curated templates from M-CSA and MetalPDB. GASS-Metal was thoroughly validated using homologous proteins and conservative mutations of residues, showing a robust performance. The ability of GASS-Metal to identify metal-binding sites was also compared with state-of-the-art methods, outperforming similar methods and achieving an MCC of up to 0.57 and detecting up to 96.1% of the sites correctly. GASS-Metal is freely available at https://gassmetal.unifei.edu.br. The GASS-Metal source code is available at https://github.com/sandroizidoro/gassmetal-local.
CHERRY: a Computational metHod for accuratE pRediction of virus–pRokarYotic interactions using a graph encoder–decoder model
Authors: Shang Jiayu , Sun Yanni
Published: April 2022

Prokaryotic viruses, which infect bacteria and archaea, are key players in microbial communities. Predicting the hosts of prokaryotic viruses helps decipher the dynamic relationship between microbes. Experimental methods for host prediction cannot keep pace with the fast accumulation of sequenced phages. Thus, there is a need for computational host prediction. Despite some promising results, computational host prediction remains a challenge because of the limited known interactions and the sheer amount of sequenced phages by high-throughput sequencing technologies. The state-of-the-art methods can only achieve 43% accuracy at the species level. In this work, we formulate host prediction as link prediction in a knowledge graph that integrates multiple protein and DNA-based sequence features. Our implementation named CHERRY can be applied to predict hosts for newly discovered viruses and to identify viruses infecting targeted bacteria. We demonstrated the utility of CHERRY for both applications and compared its performance with 11 popular host prediction methods. To our best knowledge, CHERRY has the highest accuracy in identifying virus–prokaryote interactions. It outperforms all the existing methods at the species level with an accuracy increase of 37%. In addition, CHERRY’s performance on short contigs is more stable than other tools.
Characterizing HIV-Preventive, Plasma Tenofovir Concentrations—A Pooled Participant-level Data Analysis From Human Immunodeficiency Virus Preexposure Prophylaxis Clinical Trials
Authors: Garcia-Cremades Maria , Vučićević Katarina , Hendrix Craig W , Jayachandran Priya , Jarlsberg Leah , Grant Robert , Celum Connie L , Martin Michael , Baeten Jared M , Marrazzo Jeanne , Anderson Peter , Choopanya Kachit , Vanichseni Suphak , Glidden David V , Savic Radojka M
Published: April 2022

Background

Daily dosing of tenofovir disoproxil fumarate, with or without emtricitabine, has high efficacy in preventing human immunodeficiency virus (HIV) infection when individuals are adherent. The target protective plasma concentration of tenofovir (TFV), however, is not fully understood. The aim of this study is to estimate the protective TFV plasma concentration.

Methods

Participant data from TFV-based daily oral and topical active arms of phase 3 trials (iPrEx, VOICE, and Partners PrEP) were pooled (n = 2950). Individual specific risk scores (low and high risk) of acquiring HIV, based on an earlier placebo analysis, were created. Longitudinal TFV pharmacokinetics (PK), HIV outcome, individual risk scores and the effect of sex at birth data were integrated and analyzed using non-linear mixed effects models.

Results

Around 50% of the individuals were estimated to be adherent, which differed from self-reported adherence (∼90%) and large variation between longitudinal adherence patterns were identified. Following oral administration, the estimated protective TFV trough concentration was substantially higher in high-risk females (45.8 ng/mL) compared with high-risk males (16.1 ng/mL) and to low-risk individuals (∼7.5 ng/mL). Dosing simulations indicated that high-risk women require full adherence to maintain protective levels.

Conclusions

Using the largest PK-HIV outcome database to date, we developed a population adherence-PK-risk-outcome model. Our results indicate that high-risk females need higher levels of plasma TFV to achieve HIV protection compared with males. HIV protection exceeds 90% in all populations if daily adherence is achieved.
Low Body Mass Index at Treatment Initiation and Rifampicin-Resistant Tuberculosis Treatment Outcomes: An Individual Participant Data Meta-Analysis
Authors: Campbell Jonathon R , Chan Edward D , Falzon Dennis , Trajman Anete , Keshavjee Salmaan , Leung Chi C , Miller Ann C , Monedero-Recuero Ignacio , Rodrigues Denise S , Seo Haesook , Baghaei Parvaneh , Udwadia Zarir , Viiklepp Piret , Bastos Mayara , Menzies Dick
Published: April 2022

Background

The impact of low body mass index (BMI) at initiation of rifampicin-resistant tuberculosis (RR-TB) treatment on outcomes is uncertain. We evaluated the association between BMI at RR-TB treatment initiation and end-of-treatment outcomes.

Methods

We performed an individual participant data meta-analysis of adults aged ≥18 years with RR-TB whose BMI was documented at treatment initiation. We compared odds of any unfavorable treatment outcome, mortality, or failure/recurrence between patients who were underweight (BMI <18.5 kg/m2) and not underweight. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using logistic regression, with matching on demographic, clinical, and treatment-related factors. We evaluated effect modification by human immunodeficiency virus (HIV) status and other variables using likelihood ratio tests. We also estimated cumulative incidence of mortality during treatment stratified by HIV.

Results

Overall, 5148 patients were included; 1702 (33%) were underweight at treatment initiation. The median (interquartile range) age was 37 years (29 to 47), and 455 (9%) had HIV. Compared with nonunderweight patients, the aOR among underweight patients was 1.7 (95% CI, 1.4–1.9) for any unfavorable outcome, 3.1 (2.4–3.9) for death, and 1.6 (1.2–2.0) for failure/recurrence. Significant effect modification was found for World Health Organization region of treatment. Among HIV-negative patients, 24-month mortality was 14.8% (95% CI, 12.7%–17.3%) for underweight and 5.6% (4.5%–7.0%) for not underweight patients. Among patients with HIV, corresponding values were 33.0% (25.6%–42.6%) and 20.9% (14.1%–27.6%).

Conclusions

Low BMI at treatment initiation for RR-TB is associated with increased odds of unfavorable treatment outcome, particularly mortality.
Expression Patterns and Corepressor Function of Retinoic Acid-induced 2 in Prostate Cancer
Authors: Besler Katharina , Węglarz Aleksandra , Keller Laura , von Amsberg Gunhild , Bednarz-Knoll Natalia , Offermann Anne , Stoupiec Sara , Eltze Elke , Semjonow Axel , Boettcher Lena , Schneegans Svenja , Perner Sven , Hauch Siegfried , Todenhöfer Tilman , Peine Sven , Pantel Klaus , Wikman Harriet , Werner Stefan
Published: April 2022

Background

Revealing molecular mechanisms linked to androgen receptor activity can help to improve diagnosis and treatment of prostate cancer. Retinoic acid-induced 2 (RAI2) protein is thought to act as a transcriptional coregulator involved in hormonal responses and epithelial differentiation. We evaluated the clinical relevance and biological function of the RAI2 protein in prostate cancer.

Methods

We assessed RAI2 gene expression in the Cancer Genome Atlas prostate adenocarcinoma PanCancer cohort and protein expression in primary tumors (n = 199) by immunohistochemistry. We studied RAI2 gene expression as part of a multimarker panel in an enriched circulating tumor cell population isolated from blood samples (n = 38) of patients with metastatic prostate cancer. In prostate cancer cell lines, we analyzed the consequences of androgen receptor inhibition on RAI2 protein expression and the consequences of RAI2 depletion on the expression of the androgen receptor and selected target genes.

Results

Abundance of the RAI2 protein in adenocarcinomas correlated with the androgen receptor; keratins 8, 18, and 19; and E-cadherin as well as with an early biochemical recurrence. In circulating tumor cells, detection of RAI2 mRNA significantly correlated with gene expression of FOLH1, KLK3, RAI2, AR, and AR-V7. In VCaP and LNCaP cell lines, sustained inhibition of hormone receptor activity induced the RAI2 protein, whereas RAI2 depletion augmented the expression of MME, STEAP4, and WIPI1.

Conclusions

The RAI2 protein functions as a transcriptional coregulator of the androgen response in prostate cancer cells. Detection of RAI2 gene expression in blood samples from patients with metastatic prostate cancer indicated the presence of circulating tumor cells.
5: LOCAL ENDOSCOPIC RESECTION IS INFERIOR TO GASTRECTOMY FOR EARLY CLINICAL STAGE T1A AND T1B GASTRIC ADENOCARCINOMA: A PROPENSITY-MATCHED STUDY
Authors: Kamarajah S , Markar S , Phillips A , Salti G , Dahdaleh F
Published: April 2022

Background and aim

The role of ER in the management of subsets of clinical T1N0 gastric adenocarcinoma remains controversial. The aim of this study was to evaluate the outcome of endoscopic resection (ER) versus gastrectomy in node negative cT1a and cT1b gastric adenocarcinoma.

Methods

Data from the National Cancer Database (2010–2015), was used to identify patients with clinical T1aN0 (n = 2,927; ER, n = 1,157; gastrectomy, n = 1,770) and T1bN0 (n = 2,915; ER, n = 474; gastrectomy, n = 2,441) gastric adenocarcinoma. Propensity score matching (PSM) and Cox multivariable analyses were used to account for treatment selection bias.

Results

ER for cT1a and cT1b cancers was performed more frequently over time. Rates of node-positive disease in patients with cT1a and cT1b gastric adenocarcinoma were 5% and 18%, respectively. In the matched cohort, gastrectomy was associated with increased survival compared to ER for cT1a cancers (HR: 0.79, 95% CI: 0.66–0.95, P = 0.013), and corresponding 5-year survival for gastrectomy and ER were 72% and 66% (P = 0.013), respectively. For cT1b cancers, gastrectomy had a significantly longer survival compared to ER (HR: 0.77, 95% CI: 0.63–0.93, P = 0.008) and the corresponding 5-year survival for gastrectomy and ER were 60% and 50% (P = 0.013), respectively.

Conclusion

This study demonstrates ER inferior long-term survival for clinical T1aN0 and T1bN0 gastric adenocarcinoma, despite current recommendations for ER in cT1 gastric cancers. Future research should seek to identify the subset of T1a and T1b cancers at low risk of nodal metastasis and thus would maximally benefit from ER.
7: NEOADJUVANT CHEMORADIOTHERAPY OR CHEMOTHERAPY ALONE FOR OESOPHAGEAL CANCER: POPULATION-BASED COHORT STUDY
Authors: Kamarajah S , Phillips A , Ferri L , Hofstetter W , Markar S
Published: April 2022

Background and aim

Although both neoadjuvant chemoradiotherapy (nCRT) and chemotherapy (nCT) are used as neoadjuvant treatment for oesophageal cancer, it is unknown if one provides a survival advantage over the other particularly with respect to histological subtype. This study aimed to compare prognosis following nCRT and nCT in patients undergoing oesophagectomy for oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC).

Methods

Data from the National Cancer Database (2006 to 2015) were used to identify patients with OAC (n = 11,167; nCRT 9,972 (89%), nCT 1,195 (11%)) and OSCC (n = 2,367; nCRT 2 m155 (91%), nCT 212 (9%)). Propensity score matching and Cox multivariable analyses were used to account for treatment selection biases.

Results

In the matched cohort for OAC, nCRT provided higher rates of complete pathological response (35% vs. 21%, P < 0.001) and margin-negative resections (90% vs. 86%, P < 0.001). However, nCRT had similar survival to nCT (Hazard ratio (HR):1.04, 95% confidence interval (CI):0.95–1.14). The corresponding 5-year survival for nCRT and nCT were 36% and 37% (P = 0.1), respectively. For OSCC, nCRT had higher rates of complete pathological response (51% vs. 30%, P < 0.001) and margin-negative resections (93% vs. 82%, P < 0.001). nCRT had a statistically significant overall survival benefit (HR: 0.78, 95% CI: 0.62–0.97). The 5-year survival for nCRT and nCT were 45% versus 38% (P = 0.026), respectively.

Conclusion

Despite pathological benefits including primary tumour response from nCRT, there was no prognostic benefit to nCRT compared to nCT for OAC suggesting both modalities are equally acceptable. However, for OSCC, nCRT followed by surgery appears to remain the optimal treatment approach.
128: DECIPHERING THE IMMUNOLOGICAL DETERMINANTS OF RESPONSE TO NEOADJUVANT CHEMO-RADIATION IN ESOPHAGEAL ADENOCARCINOMA
Authors: Arbore G , Albarello L , Bucci G , Punta M , Bilello V , Bonfiglio S , Fanti L , Cossu A , Tonon G , Rosati R , Casorati G , Dellabona P
Published: April 2022

Background and aim

The standard therapy for esophageal adenocarcinoma (EAC) is pre-operative neoadjuvant chemo-radiation (NACR) and surgery. Less that 30% of patients achieve a pathological complete response (pCR) and increased 5-year survival after NACR. Understanding the mechanisms of response to NACR is pivotal to better stratify patients and inform the design of more efficacious therapies. Cancer progression partly depends on defective immune surveillance, and the presence of tumor infiltrating T lymphocytes (TILs) is associated with better prognosis of several malignancies. We hypothesize that NACR induces immunogenic cell death that stimulates immune responses against tumor neoantigens (TNAs), derived from cancer somatic mutations, in the responders. We thus compared responders and non-responders for tumor immune contexture, immune molecular pathways, circulating immune markers and TNAs-specific T cells responses.

Methods

Pre-NACR tumor biopsies prospectively collected from consecutive EAC patients were subjected to DNA whole exome and RNA sequencing, high dimensional (HD) multiparametric flow cytometry and immune contexture analysis by histology and by proteome digital spatial profiling (n = 53 targets), while their peripheral blood mononuclear cells and plasma collected pre- and post- NACR were analyzed by HD flow cytometry and cytokine multiplexing assay respectively.

Results

Treatment-naïve EACs of NACR responders showed higher TNA load and enriched immune signatures compared to non-responders. Moreover, pre-treatment EACs of responders demonstrate augmented effector T cell infiltration and reduced Treg cells and M2-like pro-tumoral macrophages. High M2-like macrophages score associated with lower overall survival. Increased frequencies of circulating myeloid suppressor populations were detected both at baseline and after NACR in non-responder patients. These observations were associated with circulating levels of n = 30 cytokines/chemokines and with spatial expression of immune markers in tumor biopsies.

Conclusion

Collectively, these results support pre-existing immune-mediated mechanisms of anti-tumor response stimulated by NACR in the fraction of responder EAC patients, suggesting possible ways to stratify patients and direct them to more tailored neoadjuvant and/or adjuvant treatments, possibly in combination with personalized immunotherapy approaches.
176: YAP/TAZ ACTIVATION IS A MECHANISM OF TUMOR PROGRESSION IN THE POORLY COHESIVE GASTRIC CANCER PHENOTYPE
Authors: Sacco M , Bencivenga M , Torroni L , Tomezzoli A , Castelli C , Alloggio M , Verlato G , Giacopuzzi S , Iglesias M , Pera M , De Manzoni G , Melisi D
Published: April 2022

Background and aim

Poorly Cohesive Gastric Cancer (PC-GC), according with the latest WHO classification, has a poor prognosis and its relative incidence is increasing. Disregulation of the Hippo pathway and/or activation of YAP/TAZ signaling pathway are emerging as central determinants for tumor initiation, progression and chemoresistance. The role of YAP/TAZ in human GC has not been defined to date. We hypothesized that RhoA-YAP/TAZ axis is a mechanisms of tumor progression in PC-GC, influencing prognosis.

Methods

We retrospectively analysed 131 PC-GC patients, treated at two European surgical centres from 2004 to 2014. YAP/TAZ nuclear expression was analysed with immunohistochemistry. Both YAP and TAZ nuclear expression was coded as ‘negative’ (complete absence of nuclear reactivity) or ‘any positive’ (both low and high nuclear expression).

Results

21 patients showed absence of nuclear reactivity YAP−/TAZ-, while 110 showed any positivity: YAP+ (85/133 = 63.9%), TAZ+ (93/131 = 69.9%). Pathological tumor stage were significantly earlier in YAP−/TAZ- patients; 38% of YAP−/TAZ- were pT1–2 compared with only 17% of cases showing any expression (P = 0.041). Patients without nuclear YAP/TAZ expression were pN0 in 55% of cases compared with 26% of cases with any positive nuclear reaction (P = 0.020). In negative group 5-year OS was 57% compared with 29% in any positive group (P = 0.030). 5-year survival was the highest in YAP−/TAZ- group, intermediate when only one of the two biomarkers was expressed, and the lowest in YAP+/TAZ+ group (P = 0.010).

Conclusion

Nuclear negativity to both YAP and TAZ identify a subgroup of PC-GC with more favourable prognosis. Higher clinic-pathological stage and a worse OS was associated to YAP/TAZ positive patients supporting the involvement of this pathway in the progression of PC gastric carcinoma. Our results provide new insights into the role of YAP/TAZ signalling cascade as a mechanism of cancer progression in sporadic PC-GC.
177: A 5-YEAR SINGLE CENTER EXPERIENCE IN ROBOTIC SURGERY FOR ESOPHAGEAL ACHALASIA IN A TERTIARY CENTER, WITH PERI-OPERATIVE TAILORED PROTOCOLS
Authors: Voltarel G , Guerzoni G , Zenzaro M , Beber A , Veltri A , Casella F , Giacopuzzi S
Published: April 2022

Background and aim

Esophageal achalasia is a rare benign disease with heavy impact on daily life. Laparoscopic Heller-myotomy as the gold standard surgical treatment. In recent years the robot-assisted (DaVinci, Intuitive Surgical Inc., CA) technique became widely used for its reported advantages in terms of vision, precision and motion. The aim of the study was to evaluate the supposed advantages of robot-assisted Heller myotomy compared to the standard laparoscopic approach in a single center experience.

Methods

We included the patients who underwent standard laparoscopic and robot-assisted Heller-myotomy with Dor fundoplicatio in the last 5 years in the Upper-GI division of the University Hospital of Verona. We assessed if the robot-assisted Heller-Dor myotomy was simplified in terms of the ease of the myotomy, especially on the gastric side and the following fundoplicatio, on the sharpness of the endoscope and on the precision of the movements. We also compared the operative times with the two techniques, and the overall morbidity and mortality rates, also with the introduction of new peri-operative protocols for standardized and enhanced recovery.

Results

We included 40 patients who underwent Heller-Dor, robot-assisted Heller-Dor approach was performed in 17 patients and standard laparoscopic approach in 23 patients. Based on the surgeons experience and judgment, robot-assisted Heller-myotomy seems to be easier than the laparoscopic procedure in terms of sharpness of vision, freedom of motion and consequently precision in the single-fibers dissection of the muscularis. The operative times were comparable between the robot-assisted procedures and the laparoscopic approach, as were morbidity and mortality rates; in-hospital stay was also similar in the two groups, with a slight decrease in the last 6 months, after the introduction of new post-operative protocols for enhanced recovery with mandatory contrast swallow on POD1.

Conclusion

Our study suggests that robot-assisted Heller-myotomy for achalasia is a valid alternative to the traditional laparoscopic approach, for the improvement of surgical precision and myotomy outcome, with apparently no deterioration of safety and surgical complications, in particular with dedicate personnel and standardized recovery protocols. It also suggests that the learning curve is negligible if supported by an adequate number of patients per-year, as in a tertiary center.
Timing of cardiac surgery during pregnancy: a patient-level meta-analysis
Authors: van Steenbergen Gijs J , Tsang Queeny H Y , van der Heijden Olivier W.H. , Vart Priya , Rodwell Laura , Roos-Hesselink Jolien W , van Kimmenade Roland R J , Li Wilson W L , Verhagen Ad F T M
Published: April 2022

Aims

To investigate the association between the timing of cardiac surgery during pregnancy and both maternal and foetal outcomes.

Methods and results

Studies published up to 6 February 2021 on maternal and/or foetal mortality after cardiac surgery during pregnancy that included individual patient data were identified. Maternal and foetal mortality was analysed per trimester for the total population and stratified for patients who underwent caesarean section (CS) prior to cardiac surgery (Caesarean section (CaeSe) group) vs. patients who did not (Cardiac surgery (CarSu) group). Multivariable logistic regression analysis was performed to evaluate predictors of both maternal and foetal mortality. In total, 179 studies were identified including 386 patients of which 120 underwent CS prior to cardiac surgery. Maternal mortality was 7.3% and did not differ significantly among trimesters of pregnancy (P = 0.292) nor between subgroup CaeSe and CarSu (P = 0.671). Overall foetal mortality was 26.5% and was lowest when cardiac surgery was performed during the third trimester (10.3%, P < 0.01). CS prior to surgery was significantly associated with a reduced risk of foetal mortality in a multivariable model [odds ratio 0.19, 95% confidence interval [0.06–0.56)]. Trimester was not identified as an independent predictor for foetal nor maternal mortality.

Conclusion

Maternal mortality after cardiac surgery during pregnancy is not associated with the trimester of pregnancy. Cardiac surgery is associated with high foetal mortality but is significantly lower in women where CS is performed prior to cardiac surgery. When the foetus is viable, CS prior to cardiac surgery might be safe. When CS is not feasible, trimester stage does not seem to influence foetal mortality.