bluuebunny/crossref_metadata_2025 huggingface dataset:
Secondary polymer-induced particle aggregation and its rheological, electrical, and mechanical effects on PLA-based ternary composites
Authors: Kim Ji Hwan , Hong Joung Sook , Ahn Kyung Hyun
Published: January 2022

In order to fabricate electrically and mechanically reinforced biopolymer-based composites, we control the dispersion of the particles through the addition of a secondary polymer with high affinity to carbon black (CB) particles. The addition of a small amount of the secondary polymer induces the aggregation of CB particles beyond interfacial localization in a ternary composite. The aggregation and percolation network in poly(lactic acid) (PLA)-based ternary systems are investigated through a scaling analysis. According to rheological and geometric fractal analyses, the secondary polymer induces an aggregation of CB particles to form a percolation network because the induced-diffusion effect is stronger than the interaction between the particles, leading to a particle aggregate with a high-order structure. The modulus (G0′) of the CB/PLA binary composite has a scaling relationship with the particle volume fraction (φ), G0′∼φ1.92 (φc,G′=2.2%). In the CB/PLA binary composite, the addition of a small amount of secondary polymer having strong chemical affinity to CB changes the scaling relationship significantly depending on the type of the secondary polymer (G0′∼φ2.17∼2.53) with a lower percolation threshold (φc,G′) (φc,G′=0.96%). It also enhances the electrical percolation (electrical conductivity, σdc∼φ3.23∼3.78 φc,σ=1.50%−1.86% for ternary composites) with an increase in the exponent and a lower percolation threshold (φc,σ). The secondary polymer serves as a binder and causes the aggregates to be well dispersed, leading to a brittle-ductile transition and significant enhancement of the ductility.
Probing Anion Exchange Membrane Fuel Cell Cathodes by Varying Electrocatalysts and Electrode Processing
Authors: He Cheng , Yang-Neyerlin Ami C. , Pivovar Bryan S.
Published: January 2022

To date, several high-performing anion exchange membrane fuel cells (AEMFCs) have been demonstrated, but most these studies have focused on Pt containing cathodes with high loadings. Here, we explore and compare the performance and perform electrochemical diagnostics on three leading AEMFC cathode electrocatalysts: Pt/C, Ag/C, and Fe–N–C with electrodes that have been processed with either powder or dispersion-based ionomers using perfluorinated anion exchange polymers. Pt/C had the highest performance but also showed a strong dependence on ionomer type, with powder ionomer exhibiting much higher performance. These results were consistent with the observations for Ag/C but did not hold for the Fe–N–C catalyst where almost no change was observed between powder and dispersion-based ionomers. This is the first-time the impact of powder and dispersion ionomer with different classes of cathode electrocatalysts on the fuel cell performance have been compared, and the results have strong implications for the ability to achieve high performance at low loadings and for better understanding catalyst-ionomer interactions within AEMFCs.
Innovative Fabrication of Pd/Pd4S Based Highly Active Electrocatalysts for ORR in a Primary Zn-Air Battery
Authors: Yanhua Lei , Tan Ning , Tao Xinglong , Xia Jingxian , Huo Da , Ding MengChao , Zhang Yuliang , Wang Zengmei , Fan Baomin , Gao Guanhui
Published: January 2022

On account of their high theoretical energy density and minimal cost, Zn-air batteries have gotten a lot of interest as a viable energy storage technology. However, the problem of a high overpotential at the cathode because of the slow oxygen reduction reaction (ORR) kinetics persists. Developing an efficient cathode ORR catalyst and exceeding in performance in comparison to the existing and widely utilized Pt-based catalysts is still a formidable challenge. Herein, this study focuses on the design of a Pt-free catalyst, precisely, Pd/Pd4S based electrocatalysts to enhance ORR performance of cathode. The simple encapsulated structure containing nitrogen-doped carbon (N-doped C) coated Pd/Pd4S and CeO2 nanoparticles (Pd-Pd4S/CeO2/N-C) fabricated by a practical and trouble-free approach has a powerful electrochemical ability. Pd-Pd4S/CeO2/N-C displays a virtually identical limited current density to the commercial 20% Pt/C catalysts and better durability under alkaline conditions. Moreover, this work involves the subsequent utilization of Pd-Pd4S/CeO2/N-C in a primary Zn-air battery as the air electrode, where it manifested comparable current density and power density at 0.6 V as furnished by the Pt/C catalyst. Along with this, the primary Zn-air battery system comprising Pd-Pd4S/CeO2/N-C exhibited constant discharge comprising several hours, a specific capacity of 748 mAh gZn
−1, and stability at 10 mA cm−2.
Electrochemical Monitoring of Interaction of Temozolamide with DNA by Graphene Oxide Modified Single-Use Electrodes
Authors: Eksin Ece , Işın Deniz , Unal Didem Nur , Erdem Arzum
Published: January 2022

Graphene oxide (GO) modified single-use pencil graphite electrodes (PGEs) were used for electrochemical monitoring of surface confined interaction between Temozolamide (TMZ) and calf thymus double stranded DNA (ctdsDNA). First, the PGE surface was activated by EDC/NHS (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide) as covalent agents (CA). Then, modification of GO was done onto the surface of chemically activated PGE surface to obtain CA-GO-PGEs. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy studies were used to establish the interfacial electron transfer of the electrodes. The optimization of experimental conditions was carried out via CV technique followed by electrochemical examination of the interaction of TMZ with ctdsDNA.
A Meta-Analysis of Efficacy and Safety of PD-1/PD-L1 Inhibitors in Triple-Negative Breast Cancer
Authors: Wang Chaoyang
Published: January 2022

Objective. To evaluate the efficacy and safety of programmed cell death receptor-1 (PD-1)/programmed cell death-ligand protein-1 (PD-L1) inhibitors in triple-negative breast cancer (TNBC) to provide a treatment basis for TNBC. Methods. Published case-control studies on PD-1/PD-L1 inhibitors in the treatment of TNBC were retrieved from PubMed, Embase, and Cochrane Library databases, and collected data were processed by RevMan 5.4. Results. A total of 7 studies with 4340 study subjects were obtained, including 2092 PD-L1-negative cases, 1375 PD-L1-positive cases, and 847 PD-L1 unidentified cases. The use of PD-1/PD-L1 inhibitors showed no significant impact on patients’ progression-free survival (PFS) and overall survival (OS). The use of PD-1/PD-L1 inhibitors in the PD-L1-positive subgroup significantly improved patients’ PFS and OS. Treatment with PD-1/PD-L1 inhibitors presented no significant effect on the incidence of adverse events (AEs) but increased the risk of AE grade ≥3 and severe AEs (SAEs). Conclusion. PD-1/PD-L1 inhibitors are effective in the treatment of TNBC, which is strongly correlated with the expression of PD-L1; patient selection and clinical application require further investigation and verification.
Benchmark Problems for the Numerical Schemes of the Phase‐Field Equations
Authors: Hwang Youngjin , Lee Chaeyoung , Kwak Soobin , Choi Yongho , Ham Seokjun , Kang Seungyoon , Yang Junxiang , Kim Junseok
Published: January 2022

In this study, we present benchmark problems for the numerical methods of the phase‐field equations. To find appropriate benchmark problems, we first perform a linear stability analysis and then take a growth mode solution as the benchmark problem, which is closely related to the dynamics of the original governing equations. As concrete examples, we perform convergence tests of the numerical methods of the Allen–Cahn (AC) and Cahn–Hilliard (CH) equations using the proposed benchmark problems. The one‐ and two‐dimensional computational experiments confirm the accuracy and efficiency of the proposed scheme as the benchmark problems.
Vehicular Multilevel Data Arrangement-Based Intrusion Detection System for In-Vehicle CAN
Authors: Kim Wansoo , Lee Jungho , Lee Yousik , Kim Yoenjin , Chung Jingyun , Woo Samuel
Published: January 2022

Modern vehicles are equipped with various types of electrical/electronic (E/E) systems. Electronic control units (ECUs) are used to control various E/E systems in the vehicle. For efficient information exchange between ECUs, most vehicle manufacturers use the Controller Area Network (CAN) protocol. However, CAN has security vulnerabilities because it does not have an authentication or encryption method. Since attacks on in-vehicle networks affect the safety of drivers, it is essential to develop a technology to prevent attacks. The intrusion detection system (IDS) is one of the best ways to enhance network security. Unlike the traditional IDS for network security, IDS for the in-vehicle network requires a lightweight algorithm because of the limitation of the computing power of in-vehicle ECUs. In this paper, we propose a lightweight IDS algorithm for in-vehicle CAN based on the degree of change between successive data frames. In particular, the proposed method minimizes the load on the ECU by using the CAN data frame compression algorithm based on exclusive-OR operations as a tool for calculating the degree of change.
The Impact of Tobacco Use on COVID-19 Outcomes: A Systematic Review
Authors: Baker Jessica , Krishnan Nandita , Abroms Lorien C. , Berg Carla J. , Bittoun Renee
Published: January 2022

Introduction. Tobacco use increases risks for numerous diseases, including respiratory illnesses. We examined the literature to determine whether a history of tobacco use increases risks for adverse outcomes among COVID-19 patients. Methods. We conducted a systematic search of PubMed, LitCovid, Scopus, and Europe PMC (for preprints) using COVID-19 and tobacco-related terms. We included studies of human subjects with lab-confirmed COVID-19 infections that examined tobacco use history as an exposure and used multivariable analyses. The data was collected between March 31st, 2020, and February 20th, 2021. Outcomes included mortality, hospitalization, ICU admission, mechanical ventilation, and illness severity. Results. Among the 39 studies (33 peer-reviewed, 6 preprints) included, the most common outcome assessed was mortality (n = 32). The majority of these studies (17/32) found that tobacco use increased risk, one found decreased risk, and 14 found no association. Tobacco use was associated with increased risk of hospitalization in 7 of 10 studies, ICU admission in 6 of 9 studies, mechanical ventilation in 2 of 6 studies, and illness severity in 3 of 9 studies. One study found that tobacco use history increased risk of pulmonary embolism in COVID-19 patients. Tobacco use was found to compound risks associated with diabetes (n = 1), cancer (n = 2), and chronic liver disease (n = 1). Conclusion. There is strong evidence that tobacco use increases risks of mortality and disease severity/progression among COVID-19 patients. Public health efforts during the pandemic should encourage tobacco users to quit use and seek care early and promote vaccination and other preventive behaviors among those with a history of tobacco use.
lncRNA ROR and miR-125b Predict the Prognosis in Heart Failure Combined Acute Renal Failure
Authors: Xue Qianlong , Yang Lipeng , Wang Jia , Li Linlin , Wang Hui , He Ying
Published: January 2022

Objective. To elucidate the correlation between expression levels of long noncoding RNA (lncRNA) ROR and microRNA-125b (miR-125b) with the prognosis in heart failure (HF) patients combined acute renal failure (ARF). Methods. HF patients combined ARF (

n
=
90

) and healthy controls (

n
=
90

) in the same period were included in our hospital from April 2016 to December 2018. Every subject was followed up for 24 months. Serum levels of lncRNA ROR and miR-125b were detected, and their expression correlation was analyzed by Pearson correlation test. Receiver operating characteristic (ROC) curves were depicted for assessing the sensitivity and specificity of lncRNA ROR and miR-125b in diagnosing HF combined ARF. Results. lncRNA ROR was upregulated in serum of HF patients combined ARF, and its level was positively correlated to NYHA classification. miR-125b displayed an opposite trend. In serum samples of HF combined ARF, expression level of lncRNA ROR was negatively related to that of miR-125b. Diagnostic potentials of lncRNA ROR and miR-125b in HF combined ARF were confirmed by ROC curve analyses (lncRNA ROR:

AUC
=
0.9199

,

cutoff
 
value
=
5.595

,

sensitivity
=
92.22
%

, and

specificity
=
73.33
%

; miR-125b:

AUC
=
0.8509

,

cutoff
 
value
=
2.290

,

sensitivity
=
81.11
%

, and

specificity
=
74.44
%

). After 2-year follow-up, 16 cases were dead. Higher incidences of death and rehospitalization were observed in HF combined ARF cases expressing higher serum level of lncRNA ROR or lower level of miR-125b. Conclusions. Serum level of lncRNA ROR is upregulated, and miR-125b is downregulated in HF patients combined ARF. Their levels are linked to NYHA classification, which can be utilized as prognostic biomarkers in HF combined ARF.
Comparison of Approaches for Measuring Adherence and Persistence to Oral Oncologic Therapies in Patients Diagnosed with Metastatic Renal Cell Carcinoma
Authors: Chun Danielle S. , Hicks Blánaid , Hinton Sharon Peacock , Funk Michele Jonsson , Gooden Kyna , Keil Alexander P. , Tan Hung-Jui , Stürmer Til , Lund Jennifer L.
Published: January 2022

Background:

Adherence and persistence studies face several methodologic difficulties, including short-term mortality. We compared approaches to quantify adherence and persistence to first line (1L) oral targeted therapy (TT) in patients diagnosed with metastatic renal cell carcinoma (mRCC).

Methods:

Patients with mRCC ages 66 years or more who initiated TTs within 4 months of diagnosis were identified in the Surveillance, Epidemiology, and End Results Medicare-linked database (2007–2015). Adherence [proportion of days covered (PDC) >80%] was calculated using (i) PDC with a fixed 6-month denominator including then excluding patients who died within the 6 months and (ii) PDC with a denominator measuring time on treatment. Risk of nonpersistence was obtained by censoring death or treating death as a competing risk using cumulative incidence functions.

Results:

Among 485 patients with mRCC initiating a 1L oral TT (sunitinib, 64%; pazopanib, 25%; other, 11%), 40% died within 6 months. Adherence was higher after restricting to patients who survived (60%) compared with including those patients and assigning zero days covered after death (47%). Risk of nonpersistence was higher when censoring patients at death, 0.91 [95% confidence interval (CI), 0.88–0.94], compared with treating death as a competing risk, 0.75 (95% CI, 0.71–0.79).

Conclusions:

Different approaches to handling death resulted in different adherence and persistence estimates in the metastatic setting. Future studies should explicitly report the proportion of patient deaths over time and explore appropriate methods to account for death as competing risk.

Impact:

Use of several approaches can provide a more comprehensive picture of medication-taking behavior in the metastatic setting where death is a major competing risk.
Oncotype DX Risk Recurrence Score and Total Mortality for Early-Stage Breast Cancer by Race/Ethnicity
Authors: Moore Jaleesa , Wang Fei , Pal Tuya , Reid Sonya , Cai Hui , Bailey Christina E. , Zheng Wei , Lipworth Loren , Shu Xiao-Ou
Published: January 2022

Background:

Oncotype DX recurrence score (ODX RS) is a prognostic biomarker for early-stage, node-negative, estrogen receptor–positive (ER+) breast cancer. Whether test uptake, associated factors, and the test's prognostic values differ by race/ethnicity is unknown.

Methods:

From the National Cancer Database, 2010–2014, we identified 227,259 early-stage ER+, node-negative breast cancer cases. Logistic regression was used to examine ODX RS uptake and associated factors among non-Hispanic White (White), non-Hispanic Black (Black), Hispanic, and Asian American patients. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for overall mortality with ODX RS by race/ethnicity.

Results:

White patients were more likely to receive an ODX RS test compared with Black, Hispanic, and Asian American patients (36.7%, 32.8%, 31.6%, and 35.5%, respectively; P < 0.001). Disparities persisted after adjustments for demographics, clinical characteristics, and access-to-care, with rate ratios of 0.87 (95% CI, 0.85–0.88), 0.82 (95% CI, 0.80–0.85), and 0.89 (95% CI, 0.87–0.92), respectively, for Black, Hispanic, and Asian American compared with White patients. Black patients had higher proportions of high-risk scores (≥26) compared with White, Hispanic, and Asian American patients (19.1%, 14.0%, 14.2%, and 15.6%, respectively; P < 0.0001). ODX RS was predictive for total mortality across all races/ethnicities, particularly younger patients (<50). No significant race/ethnicity interactions were observed.

Conclusions:

Although ODX RS uptake and risk distribution varied by race/ethnicity, ODX RS was prognostic for mortality across groups.

Impact:

These findings emphasize the importance of developing strategies to increase ODX RS uptake among racial/ethnic minorities and call for more investigations on potential racial/ethnic differences in breast cancer biology.

See related commentary by Wang et al., p. 704
Assessing the Coverage of US Cancer Center Primary Catchment Areas
Authors: Leader Amy E. , McNair Christopher , Yurick Christina , Huesser Matthew , Schade Elizabeth , Stimmel Emily E. , Lerman Caryn , Knudsen Karen E.
Published: January 2022

Background:

Cancer centers are expected to engage communities and reduce the burden of cancer in their catchment areas. However, the extent to which cancer centers adequately reach the entire US population is unknown.

Methods:

We surveyed all members of the Association of American Cancer Institutes (N = 102 cancer centers) to document and map each cancer center's primary catchment area. Catchment area descriptions were aggregated to the county level. Catchment area coverage scores were calculated for each county and choropleths generated representing coverage across the US. Similar analyses were used to overlay US population density, cancer incidence, and cancer-related mortality compared with each county's cancer center catchment area coverage.

Results:

Roughly 85% of US counties were included in at least one cancer center's primary catchment area. However, 15% of US counties, or roughly 25 million Americans, do not reside in a catchment area. When catchment area coverage was integrated with population density, cancer incidence, and cancer-related mortality metrics, geographical trends in both over- and undercoverage were apparent.

Conclusions:

Geographic gaps in cancer center catchment area coverage exist and may be propagating cancer disparities. Efforts to ensure coverage to all Americans should be a priority of cancer center leadership.

Impact:

This is the first known geographic analysis and interpretation of the primary catchment areas of all US-based cancer centers and identifies key geographic gaps important to target for disparities reduction.

See related commentary by Lieberman-Cribbin and Taioli, p. 949
Impact of F
LT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naïve Acute Myeloid Leukemia
Authors: Konopleva Marina , Thirman Michael J. , Pratz Keith W. , Garcia Jacqueline S. , Recher Christian , Pullarkat Vinod , Kantarjian Hagop M. , DiNardo Courtney D. , Dail Monique , Duan Yinghui , Chyla Brenda , Potluri Jalaja , Miller Catherine L. , Wei Andrew H.
Published: January 2022

Purpose:

To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with FLT3-mutant acute myeloid leukemia.

Patients and Methods:

Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1–28) and azacitidine (75 mg/m2; days 1–7/28-day cycle). FLT3 mutation was analyzed centrally on pretreatment bone marrow aspirates.

Results:

In the biomarker evaluable population, FLT3 mutation was detected in 42 (15%) and 22 (19%) patients in the venetoclax + azacitidine and azacitidine groups. Composite complete remission [CRc; complete remission (CR) + CR with incomplete hematologic recovery (CRi)] rates (venetoclax + azacitidine/azacitidine) for FLT3-mutant patients were 67%/36%, median duration of remission (DoR) was 17.3/5.0 months, and median OS was 12.5/8.6 months. The CRc rates among FLT3 wild-type patients were 67%/25%, median DoR 18.4/13.4 months, and median OS 14.7/10.1 months. In patients treated with venetoclax + azacitidine, CRc in patients with FLT3-ITD and FLT3-TKD was 63% and 77% and median OS was 9.9 and 19.2 months, and in comutated FLT3-ITD + NPM1 patients, CRc was 70%, median DoR was not reached, and median OS was 9.1 months. There were no unexpected toxicities in the venetoclax + azacitidine group.

Conclusions:

When treated with venetoclax + azacitidine, patients with FLT3 mutations and FLT3 wild-type had similar outcomes. Future analyses in larger patient populations may further define the impact of venetoclax + azacitidine in patients harboring FLT3-ITD.

See related commentary by Perl and Vyas, p. 2719
Uma análise da psicodinâmica do trabalho de operadora de caixa de supermercado
Authors: Mélou Ana Carolina Secco de Andrade , Oliveira Paulo de Tarso Ribeiro de , Alvarenga Eric Campos , Lima Maria Lúcia Chaves
Published: January 2022

Trata-se de um estudo qualitativo com base na Psicodinâmica do Trabalho e que analisa o trabalho das operadoras de caixa de supermercado, investigando sua organização e a dinâmica prazer-sofrimento psíquico envolvida. Foram entrevistadas individualmente quinze mulheres, de quatro diferentes supermercados da cidade de Belém-PA, usando roteiro semiestruturado. O material foi examinado conforme a técnica de Análise de Núcleos de Sentido (ANS). Verificou-se uma rígida organização do trabalho das operadoras de caixa de supermercado, contendo poucas possibilidades de transformação do sofrimento em vivências de prazer. Há pouco espaço para as operadoras expressarem as dificuldades do trabalho, tais como: insatisfação com as chefias, falta de reconhecimento no trabalho, assédio sexual, constrangimentos praticados pela clientela e precariedade nas condições de trabalho. A submissão, a crença religiosa e o riso aparecem como estratégias coletivas de defesa para suportar as adversidades do cotidiano laboral.
Coaching interno: do discurso gerencialista ao sequestro da subjetividade
Authors: Castro Gustavo Henrique Carvalho de , Medeiros Bárbara Novaes , Dias Cledinaldo Aparecido , Siqueira Marcus Vinicius Soares
Published: January 2022

Este artigo analisa como a instrumentalização do coaching pelas organizações, enquanto prática gerencial, propicia a reprodução de preceitos gerencialistas que se alinham ao sequestro da subjetividade do trabalhador. Para tal, efetuaram-se entrevistas semiestruturadas com 11 gestores que conduziam tal intervenção no ambiente de trabalho. A interpretação dos dados fundamenta-se na Análise Crítica do Discurso, textualmente orientada (Fairclough, 2003). Embora o coaching no trabalho suscite reflexividade, tal postura encontra-se a serviço do ideal gerencialista, reafirmando o ideário social de culto ao desempenho, que propaga auto (e alta) responsabilização individual. O paradoxo é que a subjetividade – hiper solicitada para dar lugar a uma “subjetividade realizadora” –, foi representada discursivamente como entrave ao desenvolvimento pessoal, o qual é indissociado de anseios organizacionais. Por fim, discute-se o papel da resistência no bojo do referido processo de intervenção.
Identity Frame as the Anchor of Interstate Conflicts: The Case of the United States–North Korea Denuclearization Negotiation
Authors: Park Doyoun , Seo Yongseok
Published: January 2022

This study examines the fundamental causes of intractable conflict and deadlocked negotiation by centering on identity. The cognitive variables of identity are derived, and the causal layered analysis framework is used to analyze the influencing mechanism among cognitive layers. This research assumes that conflicts are influenced by interactions among key variables of the identity frame in the cognitive layer: “ingroup definition,” “outgroup definition,” and “conflict narrative.” The United States–North Korea denuclearization negotiation case is examined using this framework, seeking to understand how these factors influenced the conflict, policy initiatives and negotiations.
Hyaluronic Acid-Conjugated Nanoparticles for the Targeted Delivery of Cabazitaxel to CD44-Overexpressing Glioblastoma Cells
Authors: Chen Caili , Fan Rangrang , Wang Yuelong , Wang Lian , Huang Cheng , Zhou Liangxue , Xu Jianguo , Chen Haifeng , Guo Gang
Published: January 2022

In decades, the efficiency of glioma therapy is far from satisfaction due to the inability of most therapeutics to accumulate at the glioblastoma (GBM) site. Therefore, it is urgent to develop novel tumor-targeted delivery systems for more optimized and effective glioma treatment. In
this study, hyaluronic acid modified MPEG-PDLLA polymer (HAML) nanoparticles were used to encapsulate the cabazitaxel (Cab), creating Cab loaded HAML nanoparticles (Cab/HAML NPs) for glioma therapy both in vitro and in vivo. MTT assay and apoptotic study indicated Cab/HAML NPs
induced a significant cell growth inhibition and more apoptosis of C6 cells than free Cab in vitro. In vivo study showed that Cab/HAML NPs could significantly improve chemotherapeutic effect to C6 tumor-bearing rats compared with free Cab. The median survival rate of Cab/HAML NPs-treated
groups (30 days) was remarkably longer than the other groups treated with control (20 days), free Cab (19 days) and Cab/ML NPs (26 days). Immunohistochemical analysis revealed that Cab/HAML NPs improved Cab’s anti-tumor effect via improvement of tumor cell apoptosis, inhibition of tumor
cell proliferation and a significant decrease in tumor angiogenesis. Together, our study suggested that Cab/HAML NPs might show promise for application to glioma therapy.
A potential implication of UDP-glucuronosyltransferase 2B10 in the detoxification of drugs used in pediatric hematopoietic stem cell transplantation setting: an in silico investigation
Authors: Robin Shannon , Hassine Khalil Ben , Muthukumaran Jayaraman , Jurkovic Mlakar Simona , Krajinovic Maja , Nava Tiago , Uppugunduri Chakradhara Rao S. , Ansari Marc
Published: January 2022

Background

Sinusoidal occlusion syndrome (SOS) is a potentially severe complication following hematopoietic stem cell transplantation (HSCT) in pediatric patients. Treatment related risk factors such as intensity of conditioning, hepatotoxic co-medication and patient related factors such as genetic variants predispose individuals to develop SOS. The variant allele for SNP rs17146905 in UDP-glucuronosyl transferase 2B10 (UGT2B10) gene was correlated with the occurrence of SOS in an exome-wide association study. UGT2B10 is a phase II drug metabolizing enzyme involved in the N-glucuronidation of tertiary amine containing drugs.

Methods

To shed light on the functionality of UGT2B10 enzyme in the metabolism of drugs used in pediatric HSCT setting, we performed in silico screening against custom based library of putative ligands. First, a list of potential substrates for in silico analysis was prepared using a systematic consensus-based strategy. The list comprised of drugs and their metabolites used in pediatric HSCT setting. The three-dimensional structure of UGT2B10 was not available from the Research Collaboratory Structural Bioinformatics - Protein Data Bank (RCSB - PDB) repository and thus we predicted the first human UGT2B10 3D model by using multiple template homology modeling with MODELLER Version 9.2 and molecular docking calculations with AutoDock Vina Version 1.2 were implemented to quantify the estimated binding affinity between selected putative substrates or ligands and UGT2B10. Finally, we performed molecular dynamics simulations using GROMACS Version 5.1.4 to confirm the potential UGT2B10 ligands prioritized after molecular docking (exhibiting negative free binding energy).

Results

Four potential ligands for UGT2B10 namely acetaminophen, lorazepam, mycophenolic acid and voriconazole n-oxide intermediate were identified. Other metabolites of voriconazole satisfied the criteria of being possible ligands of UGT2B10. Except for bilirubin and 4-Hydroxy Voriconazole, all the ligands (particularly voriconazole and hydroxy voriconazole) are oriented in substrate binding site close to the co-factor UDP (mean ± SD; 0.72 ± 0.33 nm). Further in vitro screening of the putative ligands prioritized by in silico pipeline is warranted to understand the nature of the ligands either as inhibitors or substrates of UGT2B10.

Conclusions

These results may indicate the clinical and pharmacological relevance UGT2B10 in pediatric HSCT setting. With this systematic computational methodology, we provide a rational-, time-, and cost-effective way to identify and prioritize the interesting putative substrates or inhibitors of UGT2B10 for further testing in in vitro experiments.
Gene expression profiles in Malpighian tubules of the vector leafhopper Psammotettix striatus (L.) revealed regional functional diversity and heterogeneity
Authors: Yuan Feimin , Wei Cong
Published: January 2022

Background

Many leafhoppers are known as pests and disease vectors of economically important plants. Previous studies of the physiological functions of vector leafhoppers have mainly focused on the salivary glands and the alimentary tract that are deemed to be associated with digestion, host defense and phytoplasma and/or virus transmission. By contrast, the significance of Malpighian tubules (MTs) is less studied. To clarify the physiological function of MTs of the vector leafhopperPsammotettix striatusthat transmits phytoplasma triggering the wheat blue dwarf disease, we performed a transcriptome study onP. striatusMTs and compared gene expression profiles among different anatomical regions in the tubules (i.e., MT1+2, the anterior segment together with the sub-anterior segment; MT3, the inflated segment; and MT4, the distal segment).

Results

Transcriptome ofP. striatusMTs generate a total of 42,815 high-quality unigenes, among which highly expressed unigenes are mainly involved in organic solute transport, detoxification and immunity in addition to osmoregulation. Region-specific comparative analyses reveal that all these MT regions have functions in osmoregulation, organic solute transport and detoxification, but each region targets different substrates. Differential expression and regional enrichment of immunity-related effector activities and molecules involved in phagocytosis and the biosynthesis of antimicrobial peptides among different regions indicate that MT1+2 and MT4 have the ability to eliminate the invading pathogens. However, in MT3 which secrets brochosomes to the integument and eggs as physical barriers, disulfide-isomerase, acidic ribosomal protein P and many other unigenes were highly expressed, which can be attractive candidate genes for future studies of the biosynthesis and the origin of brochosomes.

Conclusions

Psammotettix striatusMTs perform multiple physiological functions as versatile organs than just excretory organs with osmoregulatory function. Heterogeneity of physiological functions among different MT regions is related to organic solute transport, detoxification, immunity and brochosome biosynthesis in addition to osmoregulation, and each region targets different substrates. These functions may be helpful forP. striatusto resist pathogens from habitats and to utilize a wider range of host plants, which may assist the transmission and spread of phytoplasmas. The results provide potential molecular targets for the exploit of chemical and/or gene-silencing insecticides.
MS275 as Class I HDAC inhibitor displayed therapeutic potential on malignant ascites by iTRAQ-based quantitative proteomic analysis
Authors: Du Li , Wang Dongyuan , Wei Xiuqi , Liu Chang , Xiao Zhuanglong , Qian Wei , Song Yuhu , Hou Xiaohua
Published: January 2022

Background

Malignant ascites is a manifestation of end stage events in a variety of cancers and is associated with significant morbidity. Epigenetic modulators play a key role in cancer initiation and progression, among which histone deacetylases (HDACs) are considered as one of the most important regulators for various cancer development, such as liver cancer, ovarian cancer, and pancreatic cancer et al. Thus, in this paper, we sought to explore the therapeutic effect of HDAC inhibitor on malignant ascites.

Methods

In this report, we tested the therapeutic effect of different isoform selective HDAC inhibitors (Class I HDACI MS275, Class IIa HDACI MC1568, pan-HDAC inhibitors SAHA) on malignant ascites in vitro and in vivo. We further used proteome analysis to find the potential mechanisms for malignant ascites therapy.

Results

Among the different isoform-selective HDAC inhibitors, the class I selective HDACI, MS275, exhibited preferential inhibition on various ascites cells. MS275 could induce cell cycle arrest in G0/G1 phase and promote apoptosis on ascites cells. Through proteome analysis, we found MS275 could downregulate proteins related to cell cycle progression, such as CDK4, CDC20, CCND1; MS275 could upregulate pro-apoptosis proteins such as PAPR1, LMNB2 and AIFM1; in addition, MS275 could change the expression of tumorigenic proteins related to the specific malignant ascites bearing tumors, such as TSP1 and CDK4 for bladder cancer. We then confirmed that abemaciclib (CDK4/6 selective inhibitor) could inhibit the proliferation of ascites cells, and the combination of abemaciclib and MS275 had synergistic anti-tumor effect. Finally, we found that MS275 could in vivo inhibit malignant ascites progression (ascites volume: 2.9 ± 1.0 mL vs 7.5 ± 1.2 mL, p < 0.01), tumor growth, and prolong 66% of the life-span when compared with the untreated group.

Conclusion

This present research revealed that the class I selective HDAC inhibitor, MS275, could effectively inhibit malignant ascites development and tumor growth via multiple pathways. These results indicated that HDACI could have great potential for clinical therapy of malignant ascites.
Disparities in use of skilled birth attendants and neonatal mortality rate in Guinea over two decades
Authors: Zegeye Betregiorgis , Ahinkorah Bright Opoku , Ameyaw Edward Kwabena , Budu Eugene , Seidu Abdul-Aziz , Olorunsaiye Comfort Z. , Yaya Sanni
Published: January 2022

Background

Maternal mortality remains high in sub-Saharan African countries, including Guinea. Skilled birth attendance (SBA) is one of the crucial interventions to avert preventable obstetric complications and related maternal deaths. However, within-country inequalities prevent a large proportion of women from receiving skilled birth attendance. Scarcity of evidence related to this exists in Guinea. Hence, this study investigated the magnitude and trends in socioeconomic and geographic-related inequalities in SBA in Guinea from 1999 to 2016 and neonatal mortality rate (NMR) between 1999 and 2012.

Methods

We derived data from three Guinea Demographic and Health Surveys (1999, 2005 and 2012) and one Guinea Multiple Indicator Cluster Survey (2016). For analysis, we used the 2019 updated WHO Health Equity Assessment Toolkit (HEAT). We analyzed inequalities in SBA and NMR using Population Attributable Risk (PAR), Population Attributable Fraction (PAF), Difference (D) and Ratio (R). These summary measures were computed for four equity stratifiers: wealth, education, place of residence and subnational region. We computed 95% Uncertainty Intervals (UI) for each point estimate to show whether or not observed SBA inequalities and NMR are statistically significant and whether or not disparities changed significantly over time.

Results

A total of 14,402 for SBA and 39,348 participants for NMR were involved. Profound socioeconomic- and geographic-related inequalities in SBA were found favoring the rich (PAR = 33.27; 95% UI: 29.85–36.68), educated (PAR = 48.38; 95% UI: 46.49–50.28), urban residents (D = 47.03; 95% UI: 42.33–51.72) and regions such as Conakry (R = 3.16; 95% UI: 2.31–4.00). Moreover, wealth-driven (PAF = -21.4; 95% UI: −26.1, −16.7), education-related (PAR = -16.7; 95% UI: −19.2, −14.3), urban-rural (PAF = -11.3; 95% UI: −14.8, −7.9), subnational region (R = 2.0, 95% UI: 1.2, 2.9) and sex-based (D = 12.1, 95% UI; 3.2, 20.9) inequalities in NMR were observed between 1999 and 2012. Though the pattern of inequality in SBA varied based on summary measures, both socioeconomic and geographic-related inequalities decreased over time.

Conclusions

Disproportionate inequalities in SBA and NMR exist among disadvantaged women such as the poor, uneducated, rural residents, and women from regions like Mamou region. Hence, empowering women through education and economic resources, as well as prioritizing SBA for these disadvantaged groups could be key steps toward ensuring equitable SBA, reduction of NMR and advancing the health equity agenda of “no one left behind.”
Factors associated with COVID-19 pandemic induced post-traumatic stress symptoms among adults living with and without HIV in Nigeria: a cross-sectional study
Authors: Folayan Morenike Oluwatoyin , Ibigbami Olanrewaju , ElTantawi Maha , Abeldaño Giuliana Florencia , Ara Eshrat , Ayanore Martin Amogre , Ellakany Passent , Gaffar Balgis , Al-Khanati Nuraldeen Maher , Idigbe Ifeoma , Ishabiyi Anthonia Omotola , Jafer Mohammed , Khan Abeedah Tu-Allah , Khalid Zumama , Lawal Folake Barakat , Lusher Joanne , Nzimande Ntombifuthi P. , Osamika Bamidele Emmanuel , Popoola Bamidele Olubukola , Quadri Mir Faeq Ali , Roque Mark , Shamala Anas , Al-Tammemi Ala’a B. , Yousaf Muhammad Abrar , Virtanen Jorma I. , Zuñiga Roberto Ariel Abeldaño , Okeibunor Joseph Chukwudi , Nguyen Annie Lu
Published: January 2022

Background

Nigeria is a country with high risk for traumatic incidences, now aggravated by the COVID-19 pandemic. This study aimed to identify differences in COVID-19 related post-traumatic stress symptoms (PTSS) among people living and not living with HIV; to assess whether PTSS were associated with COVID-19 pandemic-related anger, loneliness, social isolation, and social support; and to determine the association between PTSS and use of COVID-19 prevention strategies.

Methods

The data of the 3761 respondents for this analysis was extracted from a cross-sectional online survey that collected information about mental health and wellness from a convenience sample of adults, 18 years and above, in Nigeria from July to December 2020. Information was collected on the study’s dependent variable (PTSS), independent variables (self-reported COVID-19, HIV status, use of COVID-19 prevention strategies, perception of social isolation, access to emotional support, feelings of anger and loneliness), and potential confounder (age, sex at birth, employment status). A binary logistic regression model tested the associations between independent and dependent variables.

Results

Nearly half (47.5%) of the respondents had PTSS. People who had symptoms but were not tested (AOR = 2.20), felt socially isolated (AOR = 1.16), angry (AOR = 2.64), or lonely (AOR = 2.19) had significantly greater odds of reporting PTSS (p < 0.001). People living with HIV (AOR = 0.39), those who wore masks (AOR = 0.62) and those who had emotional support (AOR = 0.63), had lower odds of reporting PTSS (p < .05).

Conclusion

The present study identified some multifaceted relationships between post-traumatic stress, HIV status, facemask use, anger, loneliness, social isolation, and access to emotional support during this protracted COVID-19 pandemic. These findings have implications for the future health of those affected, particularly for individuals living in Nigeria. Public health education should be incorporated in programs targeting prevention and prompt diagnosis and treatment for post-traumatic stress disorder at the community level.
Added effect of 1% topical alendronate in intra-bony and inter-radicular defects as part of step II periodontal therapy: a systematic review with meta-analysis and trial sequential analysis
Authors: Arena Claudia , Caponio Vito Carlo Alberto , Zhurakivska Khrystyna , Lo Russo Lucio , Lo Muzio Lorenzo , Troiano Giuseppe
Published: January 2022

Background

This systematic review and meta-analysis aimed to investigate the role of alendronate combined with step 2 of periodontal therapy in reducing probing pocket depth, improving clinical attachment level, and reducing bone defect depth in intra-bony and inter-radicular defects.

Methods

RCTs with more than 6 months follow-up were included in this study. Risk of bias assessment was performed using the Cochrane collaboration tool. In addition, meta-analysis and trial sequential analysis were used to aggregate the available evidence.

Results

Seven studies met the inclusion criteria and were included in the systematic review. Topical application of alendronate during second step of periodontal therapy significantly improved PD and CAL.

Conclusion

Local application of alendronate may confer a beneficial effect when applied during step II of periodontal therapy even if long term studies are needed to confirm these results.

Clinical relevance

Considering the emerging role of host-inflammatory response in treatment of periodontitis and the antiresorptive and osteostimulative properties of bisphosphonates, several studies are focusing on the role of alendronate as an addition to non-surgical periodontal therapy.
Ethnobotanical study on wild edible plants used by Dulong people in northwestern Yunnan, China
Authors: Cheng Zhuo , Lu Xiaoping , Lin Fengke , Naeem Abid , Long Chunlin
Published: January 2022

Background

Dulong (Drung people) are one of the ethnic minorities of China, consisting of a small population living in remote and mountainous regions with limited facilities. Over the years, the Dulong have maintained their livelihood by collecting wild medicinal and edible plants. Therefore, through their experience and understanding, they had accumulated sufficient traditional knowledge about local plant resources. Since ancient times, wild edible plants have been essential to the food security of the Dulong people. However, there is almost no comprehensive report available on WEPs consumed by the Dulong people. The objectives of this study were to: (1) make a systematic study of WEPs used by Dulong people, (2) record traditional knowledge related to WEPs, (3) analyze multiple uses of WEPs, and (4) evaluate species with significant cultural significance to Dulong people.

Methods

Ethnobotanical survey including free listing, semi-structured interviews, key informant interviews and participatory observations was conducted in Dulongjiang Township, Gongshan County, Yunnan Province, Southwest China. A total of 127 informants were selected using the snowball method and information about WEPs, including vernacular name, food categories, parts used, mode of consumption, collection season, and other local uses were collected. The RFC and CFSI were calculated to identify the most culturally significant WEPs. One-way analysis of variance was performed to evaluate whether the four reference variables (gender, age, occupation, and education) significantly influenced the number of plant species mentioned by the respondents.

Results and discussion

A total of 148 species of WEPs consumed by the Dulong people belonging to 58 families were collected, including wild vegetables (71), wild fruits (52), staple food substitutes (15), spices (7), nuts (4), tea substitute (2), liquor making materials (3) oils and fats (3), and culinary coagulants (1). WEPs are used in a number of different ways, including as fuelwood, feed, and medicine. Food substitute plants accounted for the majority of the top 27 wild food plants identified by RFC and CFSI. It was observed that farmers have more knowledge of WEPs, and moderate education level informants reported less WEPs used.

Conclusion

The WEPs used by the Dulong people are diverse and abundant in the Dulongjiang region. In the future, WEPs such as Maianthemum atropurpureum, Caryota obtusa, Cardiocrinum giganteum, and Angiopteris esculenta with economic potential can be developed to provide a source of income for the residents. More studies of the nutritional value, chemical composition, and biological activities of WEPs are needed. The demands and development of local communities can be realized under the premise of protecting WEPs and the associated traditional knowledge. More attention should be paid to the value of WEP and underutilized plants during future rural development.
The WSES/SICG/ACOI/SICUT/AcEMC/SIFIPAC guidelines for diagnosis and treatment of acute left colonic diverticulitis in the elderly
Authors: Fugazzola Paola , Ceresoli Marco , Coccolini Federico , Gabrielli Francesco , Puzziello Alessandro , Monzani Fabio , Amato Bruno , Sganga Gabriele , Sartelli Massimo , Menichetti Francesco , Puglisi Gabriele Adolfo , Tartaglia Dario , Carcoforo Paolo , Avenia Nicola , Kluger Yoram , Paolillo Ciro , Zago Mauro , Leppäniemi Ari , Tomasoni Matteo , Cobianchi Lorenzo , Dal Mas Francesca , Improta Mario , Moore Ernest E. , Peitzman Andrew B. , Sugrue Michael , Agnoletti Vanni , Fraga Gustavo P. , Weber Dieter G. , Damaskos Dimitrios , Abu-Zidan Fikri M. , Wani Imtiaz , Kirkpatrick Andrew W. , Pikoulis Manos , Pararas Nikolaos , Tan Edward , Broek Richard Ten , Maier Ronald V. , Davies R. Justin , Kashuk Jeffry , Shelat Vishal G. , Mefire Alain Chicom , Augustin Goran , Magnone Stefano , Poiasina Elia , De Simone Belinda , Chiarugi Massimo , Biffl Walt , Baiocchi Gian Luca , Catena Fausto , Ansaloni Luca
Published: January 2022

Acute left colonic diverticulitis (ALCD) in the elderly presents with unique epidemiological features when compared with younger patients. The clinical presentation is more nuanced in the elderly population, having higher in-hospital and postoperative mortality. Furthermore, geriatric comorbidities are a risk factor for complicated diverticulitis. Finally, elderly patients have a lower risk of recurrent episodes and, in case of recurrence, a lower probability of requiring urgent surgery than younger patients. The aim of the present work is to study age-related factors that may support a unique approach to the diagnosis and treatment of this problem in the elderly when compared with the WSES guidelines for the management of acute left-sided colonic diverticulitis. During the 1° Pisa Workshop of Acute Care & Trauma Surgery held in Pisa (Italy) in September 2019, with the collaboration of the World Society of Emergency Surgery (WSES), the Italian Society of Geriatric Surgery (SICG), the Italian Hospital Surgeons Association (ACOI),
the Italian Emergency Surgery and Trauma Association (SICUT), the Academy of Emergency Medicine and Care (AcEMC) and the Italian Society of Surgical Pathophysiology (SIFIPAC), three panel members presented a number of statements developed for each of the four themes regarding the diagnosis and management of ALCD in older patients, formulated according to the GRADE approach, at a Consensus Conference where a panel of experts participated. The statements were subsequently debated, revised, and finally approved by the Consensus Conference attendees. The current paper is a summary report of the definitive guidelines statements on each of the following topics: diagnosis, management, surgical technique and antibiotic therapy.