bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraoperative incision irrigation with high-volume saline reduces surgical site infection for abdominal infections
Authors: Wang Jin , Lv Wen , Xu Shihai , Yang Chao , Du Bo , Zhong Yuanbo , Shi Fei , Shan Aijun
Published: July 2022

Purpose

Surgical site infection (SSI) remains one of the most common postoperative complications for patients with abdominal infections. This study aimed at investigating the effectiveness of high-volume normal saline (NS) irrigation in preventing postoperative SSI for patients with abdominal infections.

Methods

In this retrospective before-after clinical study, patients who underwent emergency laparotomy due to abdominal infections between Jan 2015 and Dec 2021 were included consecutively. A cohort of 207 patients with NS irrigation was compared to historical controls. A propensity score matching (PSM) with a 1:1 ratio was performed to reduce potential bias. The primary outcome was the 30-day SSI rate.

Results

Irrigation (n = 207) and control (n = 207) matched patients were statistically identical on baseline characteristics, perioperative, and intraoperative parameters. Irrigation patients had lower overall SSI rates (10.6% vs. 26.1%, p < 0.001), mainly due to reduction in superficial (4.3% vs. 17.9%) and deep (1.4% vs. 3.9%) SSIs, rather than space/organ SSIs (4.8% vs. 4.3%). Irrigation patients also had lower rates of incision seroma (4.8% vs. 11.6%, p = 0.012), shorter duration of antibiotics use (5.2 ± 1.7 d vs. 7.2 ± 2.0 d, p < 0.001), and unplanned readmission (1.0% vs. 8.7%, p < 0.001). Length of hospital stay showed a declining trend with irrigation intervention, while no significant difference was observed. Moreoever, logistic regression revealed that NS irrigationwas an independent protector against SSI (OR 0.309; 95% CI, 0.207–0.462; p < 0.001).

Conclusion

Intraoperative incision irrigation with high-volume NS is associated with a lower rate of SSI for patients with abdominal infections.
Gender discrimination in surgical oncology: An in-house appraisal
Authors: Pandrowala Saneya , Patkar Shraddha , Nair Deepa , Maheshwari Amita , Pramesh C. S. , Puri Ajay
Published: July 2022

Introduction

Gender discrimination (GD) though rarely blatant, may present indirectly within a surgical department in the form of subtle inequities, differing standards, and bias. GD encompasses a wide spectrum including academic development, surgical opportunities and sexual harassment.

Methods

We conducted an online survey to analyse the perceived incidence of GD in the surgical oncology department at a tertiary care cancer centre in India. The questionnaire consisted of 15 questions and was mailed to the entire department including trainees and faculty. Anonymity was maintained while collecting the data only of the participants' gender and whether they were faculty or trainee. Collated responses were analysed using proportions.

Results

The questionnaire was sent out to 200 recipients of whom 56% (112/200) responded via an online survey. Respondents included 84% of faculty (42/50) and 46.6% of trainees (70/150). GD was perceived by 28% of female trainees (7/25) as compared to 6.6% of male trainees (3/45), whereas amongst faculty, GD was perceived by 26.6% of female faculty (4/15) compared to 14.8% of male faculty (3/27). Approximately 13% of our trainees and 12% of our faculty mentioned that GD affected their professional performance or mental well-being. GD was experienced in terms of work experience and opportunities by a majority of trainees (13%) and faculty (9.5%). There was a significant lack of awareness about recourse to an institutional grievance committee by trainees (47%) compared to faculty (14%). About 7% of trainees and 12% of faculty acknowledged that they may have been responsible for intentional/unintentional GD.

Conclusion

Gender discrimination can present in subtle or overt fashion in surgical departments and requires active sustained efforts to allow both genders to feel equally empowered. Establishing a system to objectively evaluate gender equity while avoiding stereotyping for certain roles can help minimize GD.
Improved Whole Gamma Irradiated Avian Influenza Subtype H9N2 Virus Vaccine Using Trehalose and Optimization of Vaccination Regime on Broiler Chicken
Authors: Motamedi Sedeh Farahnaz , Khalili Iraj , Wijewardana Viskam , Unger Hermann , Shawrang Parvin , Behgar Mehdi , Moosavi Sayed Morteza , Arbabi Arash , Hosseini Sayedeh Maede
Published: July 2022

Gamma (γ)-radiation can target viral genome replication and preserve viral structural proteins compared to formalin inactivation. Thus, a stronger immunity could be induced after the inoculation of the irradiated virus. In this study, γ-irradiated low-pathogenic avian influenza virus-H9N2 (LPAIV-H9N2) was used to immunize the broiler chicken in two formulations, including γ-irradiated LPAIV-H9N2 with 20% Trehalose intranasally (IVT.IN) or γ-irradiated LPAIV-H9N2 plus Montanide oil adjuvant ISA70 subcutaneously (IV+ISA.SC) in comparison with formalin-inactivated LPAIV-H9N2 vaccine intranasally (FV.IN) or formalin-inactivated LPAIV-H9N2 plus ISA70 subcutaneously (FV+ISA.SC). Two vaccination regimes were employed; the first one was primed on day 1 and boosted on day 15 (early regime), and the second one was primed on day 11 and boosted on day 25 (late regime). A challenge test was performed with a live homologous subtype virus. Virus shedding was monitored by quantifying the viral load via RT-qPCR on tracheal and cloacal swabs. Hemagglutination inhibition (HI) antibody titration and stimulation index (SI) of the splenic lymphocyte proliferation were measured, respectively, by HI test and Cell Proliferation assay. Cytokine assay was conducted by the RT-qPCR on antigen-stimulated spleen cells. The results of the HI test showed significant increases in antibody titer in all vaccinated groups, but it was more evident in the IVT late vaccination regime, reaching 5.33 log2. The proliferation of stimulated spleen lymphocytes was upregulated more in the IVT.IN vaccine compared to other vaccines. The mRNA transcription levels of T-helper type 1 cytokines such as interferon-gamma (IFN-γ) and interleukin 2 (IL-2) were upregulated in all vaccinated groups at the late regime. Moreover, IL-6, a pro-inflammatory cytokine was upregulated as well. However, upregulation was more noticeable in the early vaccination than the late vaccination (p< 0.05). After the challenge, the monitoring of virus shedding for the H9 gene represented an extremely low viral load. The body weight loss was not significant (p > 0.05) among the vaccinated groups. In addition, the viral load of <100.5 TCID50/ml in the vaccinated chicken indicated the protective response for all the vaccines. Accordingly, the IVT vaccine is a good candidate for the immunization of broiler chicken via the intranasal route at late regime.
Numerical Solution for the Single-Impulse Flyby Co-Orbital Spacecraft Problem
Authors: Su Haoxiang , Dong Zhenghong , Liu Lihao , Xia Lurui
Published: July 2022

The traversal inspection of satellites in satellite constellations or geosynchronous orbits has been a focus of research. A large number of variable orbit requirements in the “single-to-single” mode severely affects the efficiency of inspections. To address this problem, this study investigated the problem of a single-impulse flyby co-orbiting two spacecraft and proposed a derivative-free numerical solution method that used the geometric relationship between the two intersections of the target and transfer orbits of the flyby problem in order to transform them into a nonlinear equation in a single variable for a given impulse time. The validity of the proposed method was verified using numerical examples. While the Lambert problem is one of the bases for solving the variable orbit problem, on-star intelligent control also raises the requirements for speed. To address this problem, this study also investigated the Lambert problem in a single-impulse flyby co-orbiting two spacecraft and determined the iterative initial value by constructing a quadratic interpolation equation between the inverse of the transfer time and the vertical component of the eccentric vector, the derivative-free quadratic interpolation cut-off method was proposed. Using 100,000 random tests showed that computational efficiency was improved by more than one order of magnitude compared with commonly used methods, with a calculation error of less than 10−6.
Performance of Nigerian Rice Farms from 2010 to 2019: A Stochastic Metafrontier Approach
Authors: Olasehinde Toba Stephen , Qiao Fangbin , Mao Shiping
Published: July 2022

Rice has become the most rapidly growing staple food crop in Nigeria. Despite the country favorable rice production ecology, there is still a huge gap between domestic rice production and consumption patterns. This study uses a two-step stochastic metafrontier model to estimate the performance of rice farms from 2010 to 2019, considering the differences between the North and South rice farms. The results indicate heterogeneity in production technology across farms located in different regions, and that both regions have low technical efficiency. However, Nigeria’s South rice farms were ranked better based on managerial issues rather than technological gaps. To attain self-sufficiency in rice production as proposed in its national plan, there is room for improvement of technical efficiency and output production at current production levels in the country’s rice farms.
Conservation Agricultural Practices Impact on Soil Organic Carbon, Soil Aggregation and Greenhouse Gas Emission in a Vertisol
Authors: Jayaraman Somasundaram , Sahu Meenakshi , Sinha Nishant K. , Mohanty Monoranjan , Chaudhary Ranjeet S. , Yadav Brijesh , Srivastava Lalit K. , Hati Kuntal M. , Patra Ashok K. , Dalal Ram C.
Published: July 2022

Conservation agriculture (CA), comprising of minimum soil disturbance and crop residue retention (>30%), with a diversified cropping system, has become increasingly popular around the world. It is recognized as a sustainable practice to improve soil health by augmenting key soil properties. However, scanty information exists about the effect of CA practices on soil organic carbon (SOC), aggregation and greenhouse gas emissions (GHG) in a vertisol. Thus, this study investigated the effect of CA practices on SOC, soil aggregation and GHG emission under soybean-wheat and maize-chickpea cropping systems in a vertisol in Central India. Treatment consisted of three different tillage practices, being conventional tillage (CT), reduced tillage (RT), and no tillage (NT) under four cropping systems viz., Soybean–Wheat, Soybean + Pigeon pea (2:1), Maize–Chickpea and Maize + Pigeon pea (1:1). Regardless of cropping system, the soil under NT and RT exhibited better aggregation (20.77 to 25.97% increase), and SOC (12.9 to 19.4% increase) compared to the CT practice in surface layers. The aggregate-associated C concentration increased with aggregate size, and it was highest with large macroaggregates and lowest with silt and clay fractions across different tillage and cropping systems. Higher SOC stock was recorded under NT (4.22 ± 0.133 Mg C/ha) compared to RT (3.84 ± 0.123 Mg C/ha) and CT (3.65 ± 0.04 Mg C/ha) practices at 0 to 5 cm depth. Thus, the adoption of CA practices reduced CO2 emissions, while also contributing to increases in SOC as well as improvement in soil structure.
Prediction of Cultivation Areas for the Commercial and an Early Flowering Wild Accession of Salvia hispanica L. in the United States
Authors: Hassani Mohammad , Piechota Thomas , Atamian Hagop S.
Published: July 2022

Salvia hispanica L., commonly known as chia, is a plant-based alternative to seafood and is rich in heart-healthy omega-3 fatty acid, protein, fiber, and antioxidants. In the Northern Hemisphere, chia flowering is triggered by the fall equinox (12-h light and dark, early October) and the seeds mature after approximately three months. Chia is sensitive to frost and end of season moisture which limits its cultivation to small areas in regions with temperate climate. The U.S. chia import has increased considerably over the years; however, chia is not widely cultivated in the United States. This study used the historical U.S. temperature and precipitation data as a first step to explore the potential of widescale chia cultivation. The 10th percentiles of 25 mm precipitation level as well as soft frost (32 °F: 0 °C) and hard frost (28 °F: −2.2 °C) were tabulated for the months of November and December. The results identified temperature as the main limiting factor for chia cultivation in the United States. The commercial chia variety (harvested in December) can be planted on approximately 10,000 km2 cropland (1,000,000 hectare) in the United States. The future development of early flowering variety (harvested in November) was demonstrated to open an additional 44,000 km2 (4,400,000 hectares) for chia cultivation in the United States. In conclusion, chia cultivation could provide economic benefits to U.S. farmers both by enriching the diversity within crop rotations aimed at reducing pest and pathogen populations and by its high economic value as an alternative specialty crop.
Genetic Parameters, Prediction of Gains and Intraspecific Hybrid Selection of Paspalum notatum Flügge for Forage Using REML/BLUP
Authors: Silveira Diógenes Cecchin , Machado Juliana Medianeira , Motta Eder Alexandre Minski da , Barbosa Marlon Risso , Simioni Carine , Weiler Roberto Luis , Mills Annamaria , Sampaio Rodrigo , Brunes André Pich , Dall’Agnol Miguel
Published: July 2022

Genetic improvement of native forage species is a sustainable alternative for maximizing livestock production. Paspalum notatum Flügge is the most important forage grass in the native grasslands of southern Brazil, with substantial potential available for further genetic improvement. The objective of this study was to quantify a range of genetic parameters and predict yield gains in a population of P. notatum intraspecific hybrids. Results indicated intraspecific hybrids of P. notatum had high magnitudes of heritability in the broad and average sense of genotype, plus high selective accuracy and genetic variation for all forage characteristics evaluated. This indicated REML/BLUP can contribute useful information for plant selection in future plant breeding programs. The genetic material studied showed high genetic variability for forage production. Analysis indicated hybrids 336, 332, 437, 132 and male parent ‘30N’ should be included in new crosses to increase the dry matter production of P. notatum. Parents need to be selected from different groups in order to maximize genetic variability and heterosis. In addition, these parents must be included in diallel crosses. The results obtained in this study provide important information for the future breeding of improved P. notatum cultivars for commercialization.
CFD Study of a Tunnel-Ventilated Compost-Bedded Pack Barn Integrating an Evaporative Pad Cooling System
Authors: Obando Vega Felipe Andrés , Montoya Ríos Ana Paola , Osorio Saraz Jairo Alexander , Andrade Rafaella Resende , Damasceno Flávio Alves , Barbari Matteo
Published: July 2022

Evaporative cooling is one of the most efficient techniques to reduce heat stress in cows in agricultural facilities. Additionally, compost-bedded pack barn has been shown to improve the welfare and production of cows. Two techniques were combined and analysed by developing a computational fluid dynamics (CFD) model of a tunnel-ventilated compost-bedded packed barn that integrated the heat and airflow dynamics of an evaporative pad cooling system. This allowed us to study the distribution of dry-bulb temperature, relative humidity and airflow velocity inside the barn based on the external environmental conditions, thickness of the pad, water temperature and specific manufacturer characteristics of the pad, providing optimal cooling pad location, size and operating conditions in the barn. Employing experimental data the CFD model was validated showing good agreement. The Equivalent Temperature Index for dairy Cattle (ETIC) was used to determine the level of stress of the cows considering the airflow velocity. It was found a moderate stress due to high relative humidity and low airflow velocity. From the predicted results, it was recommended to increase the airflow velocity above 3 m s−1 when simultaneously the external dry-bulb temperature and relative humidity exceed 30 °C and 55%, respectively, simultaneously. Additionally, installation of baffles at the pad outlet to drive the airflow to the floor was suggested to improve the drying of the compost-bedded closed to the pads, where a low airflow velocity region was established.
Main Factors Influencing the Gut Microbiota of Datong Yaks in Mixed Group
Authors: Qin Wen , Li Shuang , Wu Nan , Wen Zhouxuan , Xie Jiuxiang , Ma Hongyi , Zhang Shoudong
Published: July 2022

The Datong yak (Bos grunniens) is the first artificial breed of yaks in the world and has played an important role in the improvement of domestic yak quality on the Qinghai-Tibet Plateau. The Datong yak breeding farm in the Qinghai province of China is the main place for the breeding and feeding of Datong yaks. It hosts domestic Datong yaks and wild male yaks, mainly in mixed groups. Different managements have different effects on livestock. The gut microbiota is closely related to the health and immunity of Datong yaks, and mixed grouping can affect the composition and diversity of the gut microbiota of Datong yaks. To reveal the effects of mixed grouping on the gut microbiota of Datong yaks and wild yaks and identify the main dominant factors, we compared the gut microbial diversities of domestic males and females and wild males based on 16S rRNA V3–V4 regions using fresh fecal samples. The data showed significant differences in the gut microbial diversity of these three groups, and the α-diversity was the highest in wild males. Different factors influence the gut microbiota, and the main influencing factors were different in different groups, including sex differences, host genetics, and physical interactions. We also compared ecological assembly processes in the three groups. The results showed that mixed grouping contributed to the improvement of gut microbial diversity in domestic females. Our study provides effective and feasible suggestions for the feeding and management of the Datong yaks.
Analysis of Colostrum and Udder Skin Swabs from a Dairy Goat Herd in Germany regarding the Occurrence of Mycobacterium avium Subsp. paratuberculosis
Authors: Pickrodt Chris , Donat Karsten , Moog Udo , Köhler Heike
Published: July 2022

Oral intake of Mycobacterium avium subspecies paratuberculosis (MAP) in first days of life is considered to be the main route of infection for paratuberculosis. This can be related to a direct contact to contaminated feces or feeding of MAP containing colostrum. Colostrum is believed to become contaminated either by lactogenic shedding or introduction of MAP from environmental sources. In this pilot study, the presence of MAP in individual and bulk colostrum samples from a paratuberculosis-infected, vaccinated dairy goat herd in Germany and the effect of udder skin disinfection on the MAP load of colostrum were examined. In order to distinguish between lactogenic shedding and fecal contamination, 49 udder skin swabs were cultivated on solid medium whereas 29 swabs were additionally analyzed by qPCR. qPCR was applied on 110 individual colostrum samples collected from 55 goats, one before and one after disinfection with a mycobactericidal disinfectant, and 14 bulk colostrum samples. MAP DNA was detected in 10.3% (3/29) of the swab samples, but no viable MAP was cultivated from any sample. These results indicate a low-level MAP contamination of the udder skin and colostrum of milking goats suggesting a low risk of MAP transmission via these routes.
Pre-Partum Supplementation with Polyunsaturated Fatty Acids on Colostrum Characteristics and Lamb Immunity and Behavior after a Mild Post-Weaning Aversive Handling Period
Authors: Averós Xavier , Granado-Tajada Itsasne , Arranz Josune , Beltrán de Heredia Ignacia , González Laura , Ruiz Roberto , García-Rodríguez Aser , Atxaerandio Raquel
Published: July 2022

We studied the effect of pre-natal supplementation with n-3 α-linolenic acid (ALA) combined with a tannin-rich forage on colostrum composition and immunological quality and whether these changes had advantageous effects on lambs’ survival and stress reaction to a post-weaning stressor. Forty-eight Latxa ewes were fed during the last five weeks of pregnancy with two experimental diets: a control diet based on a neutral concentrate and forage (tall fescue hay; CO-FES), and a supplemented diet based on polyunsaturated (PUFA)-rich concentrate and tanniferous forage (sainfoin; ALA-SAIN). After parturition, twenty ewes had their blood and colostrum sampled, and their lambs were monitored until post-weaning. Lambs were afterwards subjected to (i) an aversive handling period (AHP) followed by a behavioral assessment and (ii) inflammatory and lymphocyte proliferation challenge. Feeding ALA-SAIN resulted in changes in colostrum fatty acid composition, specifically higher α-linoleic acid (p < 0.001), conjugate linoleic acid (p = 0.005), vaccenic acid (p = 0.006) and long-chain n-3 PUFA (p = 0.004). Pre-partum nutrition did not affect lamb immunoglobulin (Ig) G apparent efficacy absorption, but circulating IgG tended to be higher (p = 0.054) in ALA-SAIN lambs. ALA-SAIN lambs interacted more frequently with other lambs (p = 0.002), whereas ALA-SAIN females spent more time closer to other lambs (p < 0.001). Plasma cortisol was higher (p = 0.047) and plasma interleukin (IL)-2 lower (p = 0.003) in CO-FES lambs. This research highlights the importance of prenatal nutrition on the immune system stimulation and lambs’ behavior as a strategy to improve lambs’ health and welfare during early life.
Echocardiography and MALDI-TOF Identification of Myosin-Binding Protein C3 A74T Gene Mutations Involved Healthy and Mutated Bengal Cats
Authors: Demeekul Kanokwan , Sukumolanan Pratch , Panprom Chattida , Thaisakun Siriwan , Roytrakul Sittiruk , Petchdee Soontaree
Published: July 2022

This study aimed to identify the potential peptide candidates and expected proteins associated with MYBPC3-A74T gene mutations in Bengal cats and determine if peptidome profiles differ between healthy controls and cats with MYBPC3-A74T gene mutations. All animals were evaluated using echocardiography. DNA was isolated and followed by the screening test of MYBPC3 gene mutation. The MALDI-TOF mass spectrometry was conducted for analyzing the targeted peptide and protein patterns. The expected protein candidates were searched for within the NCBI database. Our results demonstrated that the MYBPC3-A74T gene mutation was dominant in Bengal cats but not in domestic shorthair cats. Correlations between baseline characteristics and echocardiographic parameters were discovered in Bengal cats. Mass spectrometry profiles of the candidate proteins were suspected to accompany the cat with the MYBPC3-A74T gene mutation, involving integral protein–membrane, organization of nucleus, DNA replication, and ATP-binding protein. Therefore, MYBPC3-A74T gene mutations occur frequently in Bengal cat populations. The high incidence of homozygotes for the mutation supports the causal nature of the MYBPC3-A74T mutation. In addition, peptidomics analysis was established for the first time under this condition to promise a complementary technique for the future clinical diagnosis of the MYBPC3-A74T mutation associated with physiological variables and cardiac morphology in cats.
Analytical Studies of Antimicrobial Peptides as Diagnostic Biomarkers for the Detection of Bacterial and Viral Pneumonia
Authors: Bakare Olalekan Olanrewaju , Gokul Arun , Keyster Marshall
Published: July 2022

Pneumonia remains one of the leading causes of infectious mortality and significant economic losses among our growing population. The lack of specific biomarkers for correct and timely diagnosis to detect patients’ status is a bane towards initiating a proper treatment plan for the disease; thus, current biomarkers cannot distinguish between pneumonia and other associated conditions such as atherosclerotic plaques and human immunodeficiency virus (HIV). Antimicrobial peptides (AMPs) are potential candidates for detecting numerous illnesses due to their compensatory roles as theranostic molecules. This research sought to generate specific data for parental AMPs to identify viral and bacterial pneumonia pathogens using in silico technology. The parental antimicrobial peptides (AMPs) used in this work were AMPs discovered in our previous in silico analyses using the HMMER algorithm, which were used to generate derivative (mutated) AMPs that would bind with greater affinity, in order to detect the bacterial and viral receptors using an in silico site-directed mutagenesis approach. These AMPs’ 3D structures were subsequently predicted and docked against receptor proteins. The result shows putative AMPs with the potential capacity to detect pneumonia caused by these pathogens through their binding precision with high sensitivity, accuracy, and specificity for possible use in point-of-care diagnosis. These peptides’ tendency to detect receptor proteins of viral and bacterial pneumonia with precision justifies their use for differential diagnostics, in an attempt to reduce the problems of indiscriminate overuse, toxicity due to the wrong prescription, bacterial resistance, and the scarcity and high cost of existing pneumonia antibiotics.
Galactosemia: Biochemistry, Molecular Genetics, Newborn Screening, and Treatment
Authors: Succoio Mariangela , Sacchettini Rosa , Rossi Alessandro , Parenti Giancarlo , Ruoppolo Margherita
Published: July 2022

Galactosemia is an inborn disorder of carbohydrate metabolism characterized by the inability to metabolize galactose, a sugar contained in milk (the main source of nourishment for infants), and convert it into glucose, the sugar used by the body as the primary source of energy. Galactosemia is an autosomal recessive genetic disease that can be diagnosed at birth, even in the absence of symptoms, with newborn screening by assessing the level of galactose and the GALT enzyme activity, as GALT defect constitutes the most frequent cause of galactosemia. Currently, galactosemia cannot be cured, but only treated by means of a diet with a reduced content of galactose and lactose. Although the diet is able to reverse the neonatal clinical picture, it does not prevent the development of long-term complications. This review provides an overview of galactose metabolism, molecular genetics, newborn screening and therapy of galactosemia. Novel treatments for galactosemia currently being investigated in (pre)clinical studies and potentially able to prevent long-term complications are also presented.
Clinically Relevant Dose of Pemafibrate, a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα), Lowers Serum Triglyceride Levels by Targeting Hepatic PPARα in Mice
Authors: Zhang Zhe , Diao Pan , Zhang Xuguang , Nakajima Takero , Kimura Takefumi , Tanaka Naoki
Published: July 2022

Pemafibrate (PEM) is a novel lipid-lowering drug classified as a selective peroxisome proliferator-activated receptor α (PPARα) modulator whose binding efficiency to PPARα is superior to that of fibrates. This agent is also useful for non-alcoholic fatty liver disease and primary biliary cholangitis with dyslipidemia. The dose of PEM used in some previous mouse experiments is often much higher than the clinical dose in humans; however, the precise mechanism of reduced serum triglyceride (TG) for the clinical dose of PEM has not been fully evaluated. To address this issue, PEM at a clinically relevant dose (0.1 mg/kg/day) or relatively high dose (0.3 mg/kg/day) was administered to male C57BL/6J mice for 14 days. Clinical dose PEM sufficiently lowered circulating TG levels without apparent hepatotoxicity in mice, likely due to hepatic PPARα stimulation and the enhancement of fatty acid uptake and β-oxidation. Interestingly, PPARα was activated only in the liver by PEM and not in other tissues. The clinical dose of PEM also increased serum/hepatic fibroblast growth factor 21 (FGF21) without enhancing hepatic lipid peroxide 4-hydroxynonenal or inflammatory signaling. In conclusion, a clinically relevant dose of PEM in mice efficiently and safely reduced serum TG and increased FGF21 targeting hepatic PPARα. These findings may help explain the multiple beneficial effects of PEM observed in the clinical setting.
CDI Exerts Anti-Tumor Effects by Blocking the FoxM1-DNA Interaction
Authors: Jang Woo Dae , Lee Mi Young , Mun Jihye , Lim Gyutae , Oh Kwang-Seok
Published: July 2022

The Forkhead box protein M1 (FoxM1) is an appealing target for anti-cancer therapeutics as this cell proliferation-associated transcription factor is overexpressed in most human cancers. FoxM1 is involved in tumor invasion, angiogenesis, and metastasis. To discover novel inhibitors that disrupt the FoxM1-DNA interaction, we identified CDI, a small molecule that inhibits the FoxM1–DNA interaction. CDI was identified through an assay based on the time-resolved fluorescence energy transfer response of a labeled consensus oligonucleotide that was bound to a recombinant FoxM1-dsDNA binding domain (FoxM1-DBD) protein and exhibited potent inhibitory activity against FoxM1-DNA interaction. CDI suppressed cell proliferation and induced apoptosis in MDA-MB-231 cells obtained from a breast cancer patient. Furthermore, it decreased not only the mRNA and protein expression of FoxM1 but also that of downstream targets such as CDC25b. Additionally, global transcript profiling of MDA-MB-231 cells by RNA-Seq showed that CDI decreases the expression of FoxM1-regulated genes. The docking and MD simulation results indicated that CDI likely binds to the DNA interaction site of FoxM1-DBD and inhibits the function of FoxM1-DBD. These results of CDI being a possible effective inhibitor of FoxM1-DNA interaction will encourage its usage in pharmaceutical applications.
Cellular and Humoral Responses Follow-up for 8 Months after Vaccination with mRNA-Based Anti-SARS-CoV-2 Vaccines
Authors: Gil-Manso Sergio , Carbonell Diego , Pérez-Fernández Verónica Astrid , López-Esteban Rocío , Alonso Roberto , Muñoz Patricia , Ochando Jordi , Sánchez-Arcilla Ignacio , Bellón Jose M , Correa-Rocha Rafael , Pion Marjorie
Published: July 2022

Vaccination against SARS-CoV-2 has become the main method of reducing mortality and severity of COVID-19. This work aims to study the evolution of the cellular and humoral responses conferred by two mRNA vaccines after two doses against SARS-CoV-2. On days 30 and 240 after the second dose of both vaccines, the anti-S antibodies in plasma were evaluated from 82 volunteers vaccinated with BNT162b2 and 68 vaccinated with mRNA-1273. Peripheral blood was stimulated with peptides encompassing the entire SARS-CoV-2 Spike sequence. IgG Anti-S antibodies (humoral) were quantified on plasma, and inflammatory cytokines (cellular) were measured after stimulation. We observed a higher response (both humoral and cellular) with the mRNA-1273 vaccine. Stratifying by age and gender, differences between vaccines were observed, especially in women under 48 and men over 48 years old. Therefore, this work could help to set up a vaccination strategy that could be applied to confer maximum immunity.
Techniques of Frameless Robot-Assisted Deep Brain Stimulation and Accuracy Compared with the Frame-Based Technique
Authors: Mei Shanshan , Yu Kaijia , Ren Zhiwei , Hu Yongsheng , Guo Song , Li Yongjie , Li Jianyu
Published: July 2022

Background: Frameless robot-assisted deep brain stimulation (DBS) is an innovative technique for leads implantation. This study aimed to evaluate the accuracy and precision of this technique using the Sinovation SR1 robot. Methods: 35 patients with Parkinson’s disease who accepted conventional frame-based DBS surgery (n = 18) and frameless robot-assisted DBS surgery (n = 17) by the same group of neurosurgeons were analyzed. The coordinate of the tip of the intended trajectory was recorded as xi, yi, and zi. The actual position of lead implantation was recorded as xa, ya, and za. The vector error was calculated by the formula of √(xi − xa)2 + (yi − ya)2 + (zi − za)2 to evaluate the accuracy. Results: The vector error was 1.52 ± 0.53 mm (range: 0.20–2.39 mm) in the robot-assisted group and was 1.77 ± 0.67 mm (0.59–2.98 mm) in the frame-based group with no significant difference between two groups (p = 0.1301). In 10.7% (n = 3) frameless robot-assisted implanted leads, the vector error was greater than 2.00 mm with a maximum offset of 2.39 mm, and in 35.5% (n = 11) frame-based implanted leads, the vector error was larger than 2.00 mm with a maximum offset of 2.98 mm. Leads were more posterior than planned trajectories in the robot-assisted group and more medial and posterior in the conventional frame-based group. Conclusions: Awake frameless robot-assisted DBS surgery was comparable to the conventional frame-based technique in the accuracy and precision for leads implantation.
Overall Survival Benefits of First-Line Treatments for Asian Patients with Advanced Epidermal Growth Factor Receptor-Mutated NSCLC Harboring Exon 19 Deletion: A Systematic Review and Network Meta-Analysis
Authors: Chan Sik-Kwan , Choi Horace Cheuk-Wai , Lee Victor Ho-Fun
Published: July 2022

(1) Background: Randomized controlled trials (RCTs) have explored various primary treatments for individuals diagnosed as having later-stage epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer. Nevertheless, the extent to which such treatments are efficacious, particularly with regard to overall survival (OS) rates of patients from Asia with exon 19 deletion (19del), has yet to be clarified. (2) Methods: A systematic review and frequentist network meta-analysis were conducted by obtaining pertinent studies from PubMed/MEDLINE Ovid, Embase, Cochrane Library, and trial registries, as well as various other sources. RCTs in which two or multiple treatments in the primary setting for patients from Asia with EGFR 19del were compared were included. This research has been recorded in the Prospective Register of Systematic Reviews (CRD 42022320833). (3) Results: A total of 2715 patients from Asia participated in 18 trials in which 12 different treatments were administered, which included: EGFR tyrosine kinase inhibitors (TKIs) (osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib), pemetrexed-based chemotherapy, pemetrexed-free chemotherapy, and combination treatments (gefitinib plus apatinib, erlotinib plus ramucirumab, erlotinib plus bevacizumab, and gefitinib plus pemetrexed-based chemotherapy). Such treatments were not significantly beneficial in terms of OS for patients from Asia who had 19del. It was demonstrated that erlotinib plus bevacizumab, ramucirumab plus erlotinib, and osimertinib consistently yielded the greatest benefits regarding progression-free survival benefit (P-scores = 94%, 84%, and 80%, respectively). Combination treatments resulted in increased toxicity, particularly gefitinib plus apatinib and erlotinib plus bevacizumab, causing the highest prevalence of grade ≥ 3 adverse events. Icotinib and osimertinib had the fewest grade ≥ 3 adverse events. Specific treatments were associated with a wide range of toxicity levels. (4) Conclusions: In patients from Asia with 19del, both EGFR-TKIs and treatments in which therapies were combined exhibited no OS benefits in comparison with standard chemotherapy treatments. Additional research is required to study TKIs’ resistance mechanisms and possible combined approaches for individuals harboring this common mutation.
Focal Adhesion Kinase Provides a Collateral Vulnerability That Can Be Leveraged to Improve mTORC1 Inhibitor Efficacy
Authors: Cuellar-Vite Leslie , Weber-Bonk Kristen L. , Abdul-Karim Fadi W. , Booth Christine N. , Keri Ruth A.
Published: July 2022

The PI3K/AKT/mTORC1 pathway is a major therapeutic target for many cancers, particularly breast cancer. Everolimus is an mTORC1 inhibitor used in metastatic estrogen receptor-positive (ER+) and epidermal growth factor receptor 2-negative (HER2-) breast cancer. However, mTORC1 inhibitors have limited efficacy in other breast cancer subtypes. We sought to discover collateral sensitivities to mTORC1 inhibition that could be exploited to improve therapeutic response. Using a mouse model of breast cancer that is intrinsically resistant to mTORC1 inhibition, we found that rapamycin alters the expression of numerous extracellular matrix genes, suggesting a potential role for integrins/FAK in controlling mTORC1-inhibitor efficacy. FAK activation was also inversely correlated with rapamycin response in breast cancer cell lines. Supporting its potential utility in patients, FAK activation was observed in >50% of human breast cancers. While blocking FAK in mouse models of breast cancer that are highly responsive to rapamycin had no impact on tumor growth, FAK inhibition sensitized rapamycin-resistant tumors to mTORC1 inhibition. These data reveal an innate dependency on FAK when mTORC1 signaling is lost in tumors that are resistant to mTORC1 inhibitors. They also suggest a precision medicine approach to improving mTORC1 inhibitor efficacy in resistant cancers by suppressing FAK signaling.
Immunophenotypic and Molecular Features of Acute Myeloid Leukemia with Plasmacytoid Dendritic Cell Differentiation Are Distinct from Blastic Plasmacytoid Dendritic Cell Neoplasm
Authors: Wang Wei , Xu Jie , Khoury Joseph D. , Pemmaraju Naveen , Fang Hong , Miranda Roberto N. , Yin C. Cameron , Hussein Siba El , Jia Fuli , Tang Zhenya , Hu Shimin , Konopleva Marina , Medeiros L. Jeffrey , Wang Sa A.
Published: July 2022

Acute myeloid leukemia (AML) with ≥2% plasmacytoid dendritic cells (pDC) has been recently described as AML with pDC differentiation (pDC-AML) characterized by pDC expansion with frequent RUNX1 mutations. In this study, we investigated a cohort of 53 pDC-AML cases representing about 3% of all AML cases. We characterized their immunophenotype and genetic profiles and compared these findings with blastic plasmacytoid dendritic cell neoplasm (BPDCN). pDC-differentiation/expansion was preferentially observed in AML with an immature myeloid or myelomonocytic immunophenotype, where myeloblasts were frequently positive for CD34 (98%), CD117 (94%), HLA-DR (100%) and TdT (79%), with increased CD123 (89%) expression. The median number of pDCs in pDC-AML was 6.6% (range, 2% to 26.3%) and their immunophenotype reminiscent of pDCs in early or intermediate stages of differentiation. The immunophenotype of pDCs in pDC-AML was different from BPDCN (n = 39), with major disparities in CD34 (96% vs. 0%), CD56 (8% vs. 97%) and TCL1 (12% vs. 98%) and significant differences in frequency of CD4, CD13, CD22, CD25, CD36, CD38, CD117 and CD303 expression. At the molecular level, the genetic landscapes of pDC-AML and BPDCN also differ, with RUNX1 mutations detected in 64% of pDC-AML versus 2% of BPDCN. Disparities in TET2 (21% vs. 56%), FLT3 (23% vs. 0%), DNMT3A (32% vs. 10%) and ZRSR2 (2% vs. 16%) (all p < 0.05) were also detected. The distinct immunophenotypic and mutation profiles of pDC-AML and BPDCN indicate that the neoplastic pDCs in pDC-AML and BPDCN derived from different subsets of pDC precursors.
Management of Nutritional Needs in Pediatric Oncology: A Consensus Statement
Authors: Fabozzi Francesco , Trovato Chiara Maria , Diamanti Antonella , Mastronuzzi Angela , Zecca Marco , Tripodi Serena Ilaria , Masetti Riccardo , Leardini Davide , Muratore Edoardo , Barat Veronica , Lezo Antonella , De Lorenzo Francesco , Caccialanza Riccardo , Pedrazzoli Paolo
Published: July 2022

Malnutrition, intended as both overnutrition and undernutrition, is a common problem in children with cancer, impacting quality of life as well as survival. In addition, nutritional imbalances during childhood can significantly affect proper growth. Nevertheless, there is currently a lack of a systematic approach to this issue in the pediatric oncology population. To fill this gap, we aimed to provide practice recommendations for the uniform management of nutritional needs in children with cancer. Twenty-one clinical questions addressing evaluation and treatment of nutritional problems in children with cancer were formulated by selected members from four Italian Association of Pediatric Hematology and Oncology (AIEOP) centers and from the Survivorship Care and Nutritional Support Working Group of Alliance Against Cancer. A literature search in PubMed was performed; during two consensus meetings, all recommendations were discussed and finalized using the nominal group technique. Members representing every institution voted on each recommendation. Finally, recommendations were approved by all authors.
Improved Delivery Performance of n-Butylidenephthalide-Polyethylene Glycol-Gold Nanoparticles Efficient for Enhanced Anti-Cancer Activity in Brain Tumor
Authors: Hsing Ming-Tai , Hsu Hui-Ting , Chang Chih-Hsuan , Chang Kai-Bo , Cheng Chun-Yuan , Lee Jae-Hwan , Huang Chien-Li , Yang Meng-Yin , Yang Yi-Chin , Liu Szu-Yuan , Yen Chun-Ming , Yang Shun-Fa , Hung Huey-Shan
Published: July 2022

n-butylidenephthalide (BP) has been verified as having the superior characteristic of cancer cell toxicity. Furthermore, gold (Au) nanoparticles are biocompatible materials, as well as effective carriers for delivering bio-active molecules for cancer therapeutics. In the present research, Au nanoparticles were first conjugated with polyethylene glycol (PEG), and then cross-linked with BP to obtain PEG-Au-BP nanodrugs. The physicochemical properties were characterized through ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) to confirm the combination of PEG, Au, and BP. In addition, both the size and structure of Au nanoparticles were observed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM), where the size of Au corresponded to the results of DLS assay. Through in vitro assessments, non-transformed BAEC and DBTRG human glioma cells were treated with PEG-Au-BP drugs to investigate the tumor-cell selective cytotoxicity, cell uptake efficiency, and mechanism of endocytic routes. According to the results of MTT assay, PEG-Au-BP was able to significantly inhibit DBTRG brain cancer cell proliferation. Additionally, cell uptake efficiency and potential cellular transportation in both BAEC and DBTRG cell lines were observed to be significantly higher at 2 and 24 h. Moreover, the mechanisms of endocytosis, clathrin-mediated endocytosis, and cell autophagy were explored and determined to be favorable routes for BAEC and DBTRG cells to absorb PEG-Au-BP nanodrugs. Next, the cell progression and apoptosis of DBTRG cells after PEG-Au-BP treatment was investigated by flow cytometry. The results show that PEG-Au-BP could remarkably regulate the DBTRG cell cycle at the Sub-G1 phase, as well as induce more apoptotic cells. The expression of apoptotic-related proteins in DBTRG cells was determined through Western blotting assay. After treatment with PEG-Au-BP, the apoptotic cascade proteins p21, Bax, and Act-caspase-3 were all significantly expressed in DBTRG brain cancer cells. Through in vivo assessments, the tissue morphology and particle distribution in a mouse model were examined after a retro-orbital sinus injection containing PEG-Au-BP nanodrugs. The results demonstrate tissue integrity in the brain (forebrain, cerebellum, and midbrain), heart, liver, spleen, lung, and kidney, as they did not show significant destruction due to PEG-Au-BP treatment. Simultaneously, the extended retention period for PEG-Au-BP nanodrugs was discovered, particularly in brain tissue. The above findings identify PEG-Au-BP as a potential nanodrug for brain cancer therapies.
Nanoparticle Black Ceramic Pigment Obtained by Hydrotalcite-like Compound Microwave Treatment
Authors: Oset María , Moya Alejandro , Paulo-Redondo Guillermo , Nebot-Díaz Isaac
Published: July 2022

Development of ceramic pigments with controlled particle sizes below 1 µm is essential for the preparation of ceramic inks used in inkjet digital decoration that is currently being applied in the ceramics sector. A black ceramic pigment based on NiCoCrFe composition has been prepared using thermal decomposition of hydrotalcite-like compounds. The stoichiometry ratio between different cations was studied to obtain the blackest pigment, giving Ni0,5Co0,5CrFeO4 the better cation ratio, also the thermal treatment, comparing traditional firing in an electric furnace with microwave treatment. Samples have been characterized by X-ray diffraction, Scanning Electron Microscopy and Lab colour measurement. Microwave treatment showed the best way to obtain a pigment with spinel-type structure and a homogeneous size distribution near to 150 nm, with a high intensity and colorimetric data, reducing drastically the temperature and energy consumption to obtain a black ceramic pigment suitable to be utilized in digital ceramic inks.
One-Step Hydrothermal Synthesis of 3D Interconnected rGO/In2O3 Heterojunction Structures for Enhanced Acetone Detection
Authors: San Xiaoguang , Zhang Yue , Zhang Lei , Wang Guosheng , Meng Dan , Cui Jia , Jin Quan
Published: July 2022

Acetone detection is of great significance for environmental monitoring or diagnosis of diabetes. Nevertheless, fast and sensitive detection of acetone at low temperatures remains challenging. Herein, a series of rGO-functionalized three-dimensional (3D) In2O3 flower-like structures were designed and synthesized via a facile hydrothermal method, and their acetone-sensing properties were systematically investigated. Compared to the pure 3D In2O3 flower-like structures, the rGO-functionalized 3D In2O3 flower-like structures demonstrated greatly improved acetone-sensing performance at relatively low temperatures. In particular, the 5-rGO/In2O3 sensor with an optimized decoration exhibited the highest response value (5.6) to 10 ppm acetone at 150 °C, which was about 2.3 times higher than that of the In2O3 sensor (2.4 at 200 °C). Furthermore, the 5-rGO/In2O3 sensor also showed good reproducibility, a sub-ppm-level detection limit (1.3 to 0.5 ppm), fast response and recovery rates (3 s and 18 s, respectively), and good long-term stability. The extraordinary acetone-sensing performance of rGO/In2O3 composites can be attributed to the synergistic effect of the formation of p-n heterojunctions between rGO and In2O3, the large specific surface area, the unique flower-like structures, and the high conductivity of rGO. This work provides a novel sensing material design strategy for effective detection of acetone.
An Integrated, Real-Time Convective PCR System for Isolation, Amplification, and Detection of Nucleic Acids
Authors: Miao Guijun , Guo Meng , Li Ke , Ye Xiangzhong , Mauk Michael G. , Ge Shengxiang , Xia Ningshao , Yu Duli , Qiu Xianbo
Published: July 2022

Convective PCR (CPCR) can perform rapid nucleic acid amplification by inducing thermal convection to continuously, cyclically driving reagent between different zones of the reactor for spatially separate melting, annealing, and extending in a capillary tube with constant heating temperatures at different locations. CPCR is promoted by incorporating an FTA membrane filter into the capillary tube, which constructs a single convective PCR reactor for both sample preparation and amplification. To simplify fluid control in sample preparation, lysed sample or wash buffer is driven through the membrane filter through centrifugation. A movable resistance heater is used to heat the capillary tube for amplification, and meanwhile, a smartphone camera is adopted to monitor in situ fluorescence signal from the reaction. Different from other existing CPCR systems with the described simple, easy-to-use, integrated, real-time microfluidic CPCR system, rapid nucleic acid analysis can be performed from sample to answer. A couple of critical issues, including wash scheme and reaction temperature, are analyzed for optimized system performance. It is demonstrated that influenza A virus with the reasonable concentration down to 1.0 TCID50/mL can be successfully detected by the integrated microfluidic system within 45 min.