bluuebunny/crossref_metadata_2025 huggingface dataset:
Vesicle transport and growth dynamics in Aspergillus niger: Microscale modeling of secretory vesicle flow and centerline extraction from confocal fluorescent data
Authors: Kunz Philipp J. , Barthel Lars , Meyer Vera , King Rudibert
Published: June 2020

In this paper, we present a mathematical model to describe filamentous fungal growth based on intracellular secretory vesicles (SVs), which transport cell wall components to the hyphal tip. Vesicular transport inside elongating hyphae is modeled as an advection–diffusion–reaction equation with a moving boundary, transformed into fixed coordinates, and discretized using a high‐order weighted essentially nonoscillatory discretization scheme. The model describes the production and the consumption of SVs with kinetic functions. Simulations are subsequently compared against distributions of SVs visualized by enhanced green fluorescent protein in young Aspergillus niger hyphae after germination. Intensity profile data are obtained using an algorithm scripted in ImageJ that extracts mean intensity distributions from 3D time‐lapse confocal measurement data. Simulated length growth is in good agreement with the experimental data. Our simulations further show that a decrease of effective vesicle transport velocity towards the tip can explain the observed tip accumulation of SVs.
Biomass soft sensor for aPichia pastorisfed‐batch process based on phase detection and hybrid modeling
Authors: Brunner Vincent , Siegl Manuel , Geier Dominik , Becker Thomas
Published: June 2020

A common control strategy for the production of recombinant proteins inPichia pastorisusing the alcohol oxidase 1 (AOX1) promotor is to separate the bioprocess into two main phases: biomass generation on glycerol and protein production via methanol induction. This study reports the establishment of a soft sensor for the prediction of biomass concentration that adapts automatically to these distinct phases. A hybrid approach combining mechanistic (carbon balance) and data‐driven modeling (multiple linear regression) is used for this purpose. The model parameters are dynamically adapted according to the current process phase using a multilevel phase detection algorithm. This algorithm is based on the online data of CO2in the off‐gas (absolute value and first derivative) and cumulative base feed. The evaluation of the model resulted in a mean relative prediction error of 5.52% andR²of .96 for the entire process. The resulting model was implemented as a soft sensor for the online monitoring of theP. pastorisbioprocess. The soft sensor can be used for quality control and as input to process control systems, for example, for methanol control.
Implementation of Measurement‐Based Care in a Child Partial Hospital Program
Authors: Barnes Sarah E. , Steiguer Abby de , Gelman Daniella , Parade Stephanie
Published: June 2020

The routine collection and use of patient data throughout treatment, commonly referred to as measurement‐based care (MBC), holds promise as an effective, evidence‐based practice that has the potential to greatly improve the quality of usual care if implementation were more widespread (Scott & Lewis, 2015). Indeed, nearly two decades of research in behavioral health care settings has demonstrated the value of MBC as a mechanism for improving treatment outcomes and services (see Gondek et al., 2016, for a review). A person‐centered approach to care, MBC facilitates patient engagement and shared decision‐making, which can in turn enhance better outcomes and higher quality of care. Given the potential of MBC to improve the quality of care and demonstrate the value of services to stakeholders, The Joint Commission outlines three standards related to MBC within behavioral health care settings. Though the standards themselves (discussed in more detail below) are relatively straightforward, several practical implications and questions are raised in each.
Targeted school violence: Timely research needed for prevention
Authors: Paccione‐Dyszlewski Margaret
Published: June 2020

As an elementary school student in New York City in the late 1950s, I remember participating in Federal Civil Defense Association atomic bomb air‐raid drills. These were the days of air‐raid sirens, Bert the Turtle, and duck and cover.
Effect of abiotic stress on bioactive compound production in germinated brown rice
Authors: Nascimento Lucas Ávila do , Avila Bianca Pio , Colussi Rosana , Elias Moacir Cardoso
Published: June 2020

Background and objectives

The objective of this study was to evaluate the effect of germination and various abiotic stresses on the technological, nutritional, and sensorial characteristics of brown rice. The seeds were soaked at 40°C and 30% humidity. The soaked seeds were allowed to germinate at 30°C for 36 hr in BOD chamber. The soaked rice grains were subjected to stress conditions in the last 4 hr of germination using saline (SBR/S), low temperature (4°C) (SBR/C), or a combination of saline and low temperature (SBR/B) and, after, it was analyzed the effect of germination and those abiotic stresses on the technological, nutritional, and sensorial characteristics of brown rice by the color parameters, texture profile, γ‐aminobutyric acid content, protein, and starch digestibilities.

Findings

The sprouted grains (SBR) were darker than the brown rice. The germinated rice grains exposed to cold stress were more resistant to crushing and chewing compared to grains exposed to salinity stress and those exposed to both cold and salinity stresses. Germination enhanced the γ‐aminobutyric acid (GABA) content and starch digestibility. The GABA content increased further, whereas the protein digestibility decreased in the germinated grains upon exposure to abiotic stresses.

Conclusions

The best conditions for germination and alternative processes that can help them to intensify the nutritional value of germinated grains must be elucidated. The results of this study were satisfactory for the nutritional and technological parameters, and thus, exposure of germinated grains to abiotic stress can be an alternative method for enriched rice production.

Significance and novelty

Color and texture parameters change with germination and vary according to abiotic stresses. For the same reason, the content of GABA is increased. Protein digestibility is reduced, differently about the starch digestibility.
A case of secretory carcinoma of the submandibular gland with unusual immunohistochemical staining
Authors: Karabachev Alexander , Aulet Ricardo , Sajisevi Mirabelle , Ciolino Allison
Published: June 2020

Mammaglobin negative secretory carcinoma may be overlooked. It is important to assess the possibility of diagnosis when histology is suggestive and immunohistochemical staining for S‐100 is positive even when staining for mammaglobin is negative.
Start‐Up Study on Biohydrogen from Palm Oil Mill Effluent in a Pilot‐Scale Reactor
Authors: Akhbari Azam , Chuen Onn Chiu , Zinatizadeh Ali Akbar , Ibrahim Shaliza
Published: June 2020

A start‐up study for biohydrogen production from palm oil mill effluent (POME) is carried out in a pilot‐scale up‐flow anaerobic sludge blanket fixed‐film reactor (UASFF). A substrate with a chemical oxygen demand (COD) of 30 g L−1 is used, starting with molasses solution for 30 days and followed by a 10% v/v increment of POME/molasses ratio. At 100% POME, a hydrogen content of 80%, hydrogen production rate of 36 L H2 per day, and maximum COD removal of 48.7% are achieved. Bio‐kinetic coefficients of Monod, first‐order, Grau second‐order, and Stover‐Kincannon kinetic models are calculated to describe the performance of the system. The steady‐state data with 100% POME shows that Monod and Stover‐Kincannon models with bio‐kinetic coefficients of half‐velocity constant (Ks) of 6000 mg COD L−1, microbial decay rate (Kd) of 0.0015 per day, growth yield constant (Y) of 0.786 mg volatile suspended solids (VSS)/mg COD, specific biomass growth rate (μmax) of 0.568 per day, and substrate consumption rate of (Umax) 3.98 g/L day could be considered as superior models with correlation coefficients (R2) of 0.918 and 0.989, respectively, compared to first‐order and Grau's second‐order models with coefficients of K1 1.08 per day, R2 0.739, and K2s 1.69 per day, a = 7.0 per day, b = 0.847.
Influence of Protein Modification and Glycosylation in the Catalytic Hydrogen Evolution Reaction of Avidin and Neutravidin: An Electrochemical Analysis
Authors: Izadi Nasim , Černocká Hana , Trefulka Mojmír , Ostatná Veronika
Published: June 2020

To investigate glycans’ influence on the behavior of glycoproteins on charged surfaces, avidin and its nonglycosylated and neutralized version neutravidin were studied by label‐free chronopotentiometric stripping (CPS) analysis and alternating current voltammetry combined with a mercury electrode. Despite neutravidin's and avidin's similar size and structure, their CPS responses differed due to the different amounts of catalytically active free amino groups of lysine and arginine residues. Acetylation of the proteins resulted in the suppression of their CPS responses by almost four times for avidin and by about 50 % for neutravidin, respectively. On the other hand, the presence of glycans in the acetylated avidin induced about 30 % higher chronopotentiometric response compared to the acetylated neutravidin. We suggest that the presence, size and composition of the glycans influenced the CPS signal due to differences in the orientation at a charged surface. The obtained results can be utilized in glycoprotein research.
Root and axillary shoot development of hairy vetch stem cuttings and cessation of flower development under a short photoperiod
Authors: Wiering Nicholas , Gardner Gary , Sheaffer Craig C. , Ehlke Nancy J.
Published: June 2020

Clonal propagation is a valuable tool for plant breeders to maintain heterozygous genotypes in crop species that are not amenable to self‐pollination or apomixis. An example is the drought‐tolerant forage and N‐fixing cover crop hairy vetch (Vicia villosa Roth), which primarily outcrosses and is developed into composite cultivars by plant breeders. The ability to obtain clones of desirable genotypes in breeding nurseries would enable the maintenance of heterozygous genotypes for genetic study or the ability to reconstitute a true synthetic cultivar. We developed an efficient method of clonal propagation from stem cuttings to maintain genotypes in a vegetative state for a minimum of 2 yr, even when obtained from flowering parental plants. The long‐term viability of such clones is unknown, however. We determined that hairy vetch, which flowers under long days, exhibits a form of partial flowering where vegetative meristems are maintained during conditions that induce flowering. Clones obtained from flowering parents would resume reproductive growth and eventually senesce if kept in inductive conditions. However, if clones were grown under a continuous 6‐h photoperiod, reproductive development would cease and vegetative growth would resume indefinitely.
T‐cell activation and immune memory enhancement induced by irreversible electroporation in pancreatic cancer
Authors: He Chaobin , Huang Xin , Zhang Yu , Lin Xiaojun , Li Shengping
Published: June 2020

Background

Irreversible electroporation is shown to induce immune changes in pancreatic cancer while the histology evidences are still lacking. The aim of this study is to show the immune changes in histology and explore whether irreversible electroporation (IRE) can induce immunogenic cell death (ICD) of tumor cells and activate specific immune responses.

Methods

Subcutaneous and orthotopic pancreatic cancer models were established and used to evaluate the effect of immune modulation of IRE. The infiltration of T cells was assessed in several tissue samples before and after IRE. Abscopal effect was then assessed by comparing the tumor growth of subcutaneous tumors after in situ ablation with IRE or exposure to tumor culture supernatant (TSN) of IRE‐treated Pan02. The expression of damage‐associated molecular patterns (DAMPs) of tumor cells after IRE was detected in vitro.

Results

IRE could significantly suppress the tumor growth and increase the infiltration of CD8+ T cells. After ablation with IRE or stimulation with TSN of Pan02 treated by IRE, the growth of untreated tumor was suppressed and the effector CD8+ T cells and memory T cells increased significantly in mice. Additionally, the inhibition effect of tumor growth increased along with the increasing strength levels of electroporation. IRE induced ICD of tumor cells by increasing the synthesis and secretion of DAMPs.

Conclusions

IRE induced local immunomodulation by increasing specific T cells infiltration. Through enhancing specific immune memory, IRE not only led a complete tumor regression in suit, but also induced abscopal effect, suppressing the growth of the latent lesions.
Oxidative stress induces monocyte‐to‐myofibroblast transdifferentiation through p38 in pancreatic ductal adenocarcinoma
Authors: Huang Xin , He Chaobin , Hua Xin , Kan Anna , Mao Yize , Sun Shuxin , Duan Fangting , Wang Jun , Huang Peng , Li Shengping
Published: June 2020

Background

Cancer‐associated fibroblasts (CAFs) are among the most prominent cells during the desmoplastic reaction in pancreatic ductal adenocarcinoma (PDAC). However, CAFs are heterogeneous and the precise origins are not fully elucidated. This study aimed to explore whether monocytes can transdifferentiate into fibroblasts in PDAC and evaluate the clinical significance of this event.

Methods

CD14+ monocytes were freshly isolated from human peripheral blood. Immunofluorescence, reverse transcription‐quantitative PCR, western blot, flow cytometry and enzyme‐linked immunosorbent assay were used to detect the expression of αSMA, fibronectin, and other relevant molecules. In addition, latex beads with a mean particle size of 2.0 µm were used to assess the phagocytic capacity. Moreover, RNA sequencing (RNA‐seq) was performed to identify the differences induced by H2O2 and the underlying mechanisms.

Results

Immunofluorescence identified αSMA and fibroblast‐specific protein 1 expression by tumor‐associated macrophages in PDAC. The in vitro experiment revealed that oxidative stress (H2O2 or radiation) induced monocyte‐to‐myofibroblast transdifferentiation (MMT), as identified by upregulated αSMA expression at both the RNA and protein levels. In addition, compared with freshly isolated monocytes, human monocyte‐derived macrophages increased fibronectin expression. RNA‐seq analysis identified p53 activation and other signatures accompanying this transdifferentiation; however, the p53 stabilizer nutlin‐3 induced αSMA expression through reactive oxygen species generation but not through the p53 transcription/mitochondria‐dependent pathway, whereas the p38 inhibitor SB203580 could partially inhibit αSMA expression. Finally, MMT produced a unique subset of CAFs with reduced phagocytic capacity that could promote the proliferation of pancreatic cancer cells.

Conclusions

Oxidative stress in the tumor microenvironment could induce MMT in PDAC, thus inducing reactive stroma, modulating immunosuppression, and promoting tumor progression. Reducing oxidative stress may be a promising future therapeutic regimen.
COVID‐19 critical illness pathophysiology driven by diffuse pulmonary thrombi and pulmonary endothelial dysfunction responsive to thrombolysis
Authors: Poor Hooman D. , Ventetuolo Corey E. , Tolbert Thomas , Chun Glen , Serrao Gregory , Zeidman Amanda , Dangayach Neha S. , Olin Jeffrey , Kohli‐Seth Roopa , Powell Charles A.
Published: June 2020

Patients with severe COVID‐19 disease have been characterized as having the acute respiratory distress syndrome (ARDS). Critically ill COVID‐19 patients have relatively well‐preserved lung mechanics despite severe gas exchange abnormalities, a feature not consistent with classical ARDS but more consistent with pulmonary vascular disease. Many patients with severe COVID‐19 also demonstrate markedly abnormal coagulation, with elevated d‐dimers and higher rates of venous thromboembolism. We present four cases of patients with severe COVID‐19 pneumonia with severe respiratory failure and shock, with evidence of markedly elevated dead‐space ventilation who received tPA. All showed post treatment immediate improvements in gas exchange and/or hemodynamics. We suspect that severe COVID‐19 pneumonia causes respiratory failure via pulmonary microthrombi and endothelial dysfunction. Treatment for COVID‐19 pneumonia may warrant anticoagulation for milder cases and thrombolysis for more severe disease.
Next‐generation sequencing in residual liquid‐based cytology specimens for cancer genome analysis
Authors: Yamaguchi Tomomi , Akahane Toshiaki , Harada Ohi , Kato Yasutaka , Aimono Eriko , Takei Hidehiro , Tasaki Takashi , Noguchi Hirotsugu , Nishihara Hiroshi , Kamata Hajime , Tanimoto Akihide
Published: June 2020

Background

Cancer genome profiling of cytology specimens using next‐generation sequencing (NGS) requires adequate and good‐quality DNA. Genomic examination of cytology samples was conventionally performed on cell block (CB) or smear specimens than on residual liquid‐based cytology (LBC) specimens, which are high‐quality DNA sources even after long‐term storage.

Methods

We estimated tumor fractions of 37 residual LBC specimens, including 30 fine needle aspiration (FNA) samples from the thyroid (12 papillary thyroid carcinomas and two malignant lymphomas), lymph node (13 metastatic carcinomas and one malignant lymphoma), and breast cancer (one phyllodes tumor and one invasive ductal carcinoma), two pancreatic carcinoma samples, and five liquid (ascites, pleural effusion, and cerebrospinal fluid) samples. The DNA was extracted from all samples and subjected to NGS using a customized cancer gene panel comprising 28 cancer‐related genes.

Results

NGS analysis revealed somatic mutations corresponding to pathological diagnosis with adequate variant allele frequency (VAF) in 24 LBC specimens, which had significantly higher tumor fraction (72.5% ± 4.9%). Ten cases, including the five fluid samples, had very small tumor fractions (7.5% ± 2.3%) to obtain sufficient VAF. Other two samples had high tumor fractions but showed very low VAF, indicating the presence of fusion genes. The remaining one sample yielded no DNA recovery.

Conclusion

The residual LBC specimens collected by FNA from the thyroid gland and lymph node were verified to carry high tumor fraction and could serve as an alternate source for molecular testing to screen and diagnose cancers without the use of CB or smears.
Tool for genomic selection and breeding to evolutionary adaptation: Development of a 100K single nucleotide polymorphism array for the honey bee
Authors: Jones Julia C. , Du Zhipei G. , Bernstein Richard , Meyer Monique , Hoppe Andreas , Schilling Elmar , Ableitner Martin , Juling Katrin , Dick Regina , Strauss Anja S. , Bienefeld Kaspar
Published: June 2020

High‐throughput high‐density genotyping arrays continue to be a fast, accurate, and cost‐effective method for genotyping thousands of polymorphisms in high numbers of individuals. Here, we have developed a new high‐density SNP genotyping array (103,270 SNPs) for honey bees, one of the most ecologically and economically important pollinators worldwide. SNPs were detected by conducting whole‐genome resequencing of 61 honey bee drones (haploid males) from throughout Europe. Selection of SNPs for the chip was done in multiple steps using several criteria. The majority of SNPs were selected based on their location within known candidate regions or genes underlying a range of honey bee traits, including hygienic behavior against pathogens, foraging, and subspecies. Additionally, markers from a GWAS of hygienic behavior against the major honey bee parasite Varroa destructor were brought over. The chip also includes SNPs associated with each of three major breeding objectives—honey yield, gentleness, and Varroa resistance. We validated the chip and make recommendations for its use by determining error rates in repeat genotypings, examining the genotyping performance of different tissues, and by testing how well different sample types represent the queen's genotype. The latter is a key test because it is highly beneficial to be able to determine the queen's genotype by nonlethal means. The array is now publicly available and we suggest it will be a useful tool in genomic selection and honey bee breeding, as well as for GWAS of different traits, and for population genomic, adaptation, and conservation questions.
Breaking barriers? Ethnicity and socioeconomic background impact on early career progression in the fields of ecology and evolution
Authors: Wanelik Klara M. , Griffin Joanne S. , Head Megan L. , Ingleby Fiona C. , Lewis Zenobia
Published: June 2020

The academic disciplines of Science, Technology, Engineering and Mathematics (STEM) have long suffered from a lack of diversity. While in recent years there has been some progress in addressing the underrepresentation of women in STEM subjects, other characteristics that have the potential to impact on equality of opportunity have received less attention. In this study, we surveyed 188 early career scientists (ECRs), defined as within 10 years of completing their PhD, in the fields of ecology, evolutionary biology, behaviour, and related disciplines. We examined associations between ethnicity, age, sexual orientation, sex, socioeconomic background, and disability, with measures of career progression, namely publication record, number of applications made before obtaining a postdoc, type of contract, and number of grant applications made. We also queried respondents on perceived barriers to progression and potential ways of overcoming them. Our key finding was that socioeconomic background and ethnicity were associated with measures of career progression. While there was no difference in the number of reported first‐authored papers on PhD completion, ethnic minority respondents reported fewer other‐authored papers. In addition, ECRs from a lower socioeconomic background were more likely to report being in teaching and research positions, rather than research‐only positions, the latter being perceived as more prestigious by some institutions. We discuss our findings in the context of possible inequality of opportunity. We hope that this study will stimulate wider discussion and help to inform strategies to address the underrepresentation of minority groups in the fields of ecology and evolution, and STEM subjects more widely.
Alkylation of α‐Oxo‐Compounds through C(sp3)‐H Functionalization of 2‐Methyl Quinolines Under Catalyst‐ and Solvent‐Free Conditions
Authors: Rao Yadavalli Subba , Latha Dandugula Sneha , Devunuri Nagaraju , Almansour Abdulrahman I. , Arumugam Natarajan , Yaragorla Srinivasarao
Published: June 2020

Highly facile approach of chemoselective alkylation of α‐oxo compounds such as α‐keto amides, α‐keto esters, isatins, and cyclic‐α‐diketones is developed through C(sp3)‐H functionalization of 2‐methyl quinolines under solvent and catalyst‐free conditions. Further, we complemented the efficacy of this green synthetic protocol by demonstrating the broad substrate diversity, gram‐scale synthesis, and new synthetic transformations of the obtained products.
Prediction of flotation efficiency of metal sulfides using an original hybrid machine learning model
Authors: Cook Rachel , Monyake Keitumetse Cathrine , Hayat Muhammad Badar , Kumar Aditya , Alagha Lana
Published: June 2020

Froth flotation process is extensively used for selective separation of base metal sulfides from uneconomic mineral resources. Reliable prediction of process outcomes (metal recovery and grade) is vital to ensure peak performance. This work employs an innovative hybrid machine learning (ML) model—constructed by combining the random forest model and the firefly algorithm—to predict froth flotation efficiency of galena and chalcopyrite in relation to various experimental process parameters. The hybrid model's prediction performance was rigorously evaluated, and compared against four different standalone ML models. The outcomes of this study illustrate that the hybrid ML model has the prediction ability to process outcomes with high‐fidelity, while consistently outperforming the standalone ML models.
Fire and climate change: conserving seasonally dry forests is still possible
Authors: Stephens Scott L , Westerling A LeRoy , Hurteau Matthew D , Peery M Zachariah , Schultz Courtney A , Thompson Sally
Published: June 2020

The destructive wildfires that occurred recently in the westernUSstarkly foreshadow the possible future of forest ecosystems and human communities in the region. With increases in the area burned by severe wildfire in seasonally dry forests expected to result from climate change, judicious, science‐based fire and restoration strategies will be essential for improving the resilience of forest ecosystems. We argue that fire use treatments (including prescribed fires and managed wildfires) as well as restoration thinning strategies, rather than conflicting with existing environmental objectives, will provide numerous co‐benefits, including enhanced biodiversity, increased water availability, greater long‐term and more sustainable carbon storage, improved forest resilience and adaptation to climate change, and reduced air pollution. Timber production, however, may have to be better aligned with fire management goals to achieve these co‐benefits. Taking immediate actions today to promote positive ecological outcomes in seasonally dry forests should be a primary focus of management, particularly in the westernUS.
Evaluation of yield and experiences of age‐related molecular investigation for heritable and nonheritable causes of mismatch repair deficient colorectal cancer to identify Lynch syndrome
Authors: Vos Janet R. , Fakkert Ingrid E. , Spruijt Liesbeth , Willems Riki W. , Langenveld Sera , Mensenkamp Arjen R. , Leter Edward M. , Nagtegaal Iris D. , Ligtenberg Marjolijn J. L. , Hoogerbrugge Nicoline ,   FINAL Group
Published: June 2020

Universal mismatch repair deficiency (dMMR) testing of colorectal cancer (CRC) is promoted as routine diagnostics to prescreen for Lynch syndrome. We evaluated the yield and experience of age‐related molecular investigation for heritable and nonheritable causes of dMMR in CRC below age 70 to identify Lynch Syndrome. In a prospective cohort of 3602 newly diagnosed CRCs below age 70 from 19 hospitals, dMMR, MLH1 promoter hypermethylation, germline MMR gene and somatic MMR gene testing was assessed in daily practice. Yield was evaluated using data from the Dutch Pathology Registry (PALGA) and two regional genetic centers. Experiences of clinicians were evaluated through questionnaires. Participating clinicians were overwhelmingly positive about the clinical workflow. Pathologists routinely applied dMMR‐testing in 84% CRCs and determined 10% was dMMR, largely due to somatic MLH1 hypermethylation (66%). Of those, 69% with dMMR CRC below age 70 without hypermethylation were referred for genetic testing, of which 55% was due to Lynch syndrome (hereditary) and 43% to somatic biallelic pathogenic MMR (nonhereditary). The prevalence of Lynch syndrome was 18% in CRC < 40, 1.7% in CRC age 40‐64 and 0.7% in CRC age 65‐69. Age 65‐69 represents most cases with dMMR, in which dMMR due to somatic causes (13%) is 20 times more prevalent than Lynch syndrome. In conclusion, up to age 65 routine diagnostics of (non‐)heritable causes of dMMR CRCs effectively identifies Lynch syndrome and reduces Lynch‐like diagnoses. Above age 64, the effort to detect one Lynch syndrome patient in dMMR CRC is high and germline testing rarely needed.
Primary conization overcomes the risk of developing local recurrence following laparoscopic radical hysterectomy in early stage cervical cancer
Authors: Bogani Giorgio , Ditto Antonino , Chiappa Valentina , Pinelli Ciro , Sonetto Cristina , Raspagliesi Francesco
Published: June 2020

Objective

To investigate whether primary conization might overcome the risk of local dissemination in patients undergoing laparoscopic radical hysterectomy.

Methods

Consecutive data of 262 patients with early stage cervical cancer were retrieved: 88 women had conization followed by radical hysterectomy. A propensity‐matched comparison (1:1) was carried out in order to compare laparoscopy and open surgery. Accumulating data highlighted that minimally invasive surgery has been associated with higher recurrence rates and worse overall survival than open surgery in women with early stage cervical cancer.

Results

Data of 35 paired patients (total 70 patients) were analyzed. No between‐group differences in baseline, disease, and pathological variables were observed. Patients undergoing laparoscopy correlated with lower blood loss (50 [range 30–100] vs 150 [range 50–500] mL; P<0.001) and shorter length of stay (3 ± 0.8 vs 5.4 ± 1.4 days; P<0.001) compared to open surgery. One local recurrence was observed per group (P=1.00). Type of surgical approach did not influence site of recurrence (P=1.00) or survival outcomes, in terms of 10‐year disease‐free (P=0.549, log‐rank test) and overall survivals (P=0.615, log‐rank test).

Conclusions

The data show that primary conization might overcome the risk of local recurrence after laparoscopic radical hysterectomy in early stage cervical cancer. Further prospective evidence is needed.
Malaria in the third trimester and maternal‐perinatal outcome
Authors: Nkwabong Elie , Mayane Diane N. , Meka Esther , Essiben Felix
Published: June 2020

Objective

To evaluate maternal and perinatal outcomes in cases of third‐trimester malaria (TTM).

Methods

A parity‐matched comparative cohort study was carried out between December 1, 2018, and April 30, 2019, in three university teaching hospitals in Yaoundé (Cameroon). Women with and without TTM were followed up till delivery. The variables analyzed included maternal and gestational ages at delivery, the regimen of intermittent preventive treatment, usage of insecticide‐treated net, history of malaria recorded during pregnancy, birth and placenta weights, Apgar score, and early neonatal outcomes. Fisher exact test, t‐test, and logistic regression were used for comparison. P<0.05 was considered statistically significant.

Results

Of 3063 pregnant women, 130 (4.2%) had TTM. Adverse outcomes associated with TTM were maternal anemia (relative risk [RR] 10, 95% confidence interval [CI] 4.91–20.34), intrauterine fetal demise (RR 7.50, 95% CI 1.47–38.06), preterm delivery (RR 4.50, 95% CI 2.37–8.51), low birth weight (adjusted RR 2.88, 95% CI 1.34–6.19), neonatal asphyxia especially if delivery occurred during parenteral treatment (RR 5.18, 95% CI 2.56–10.48), transfer of the newborn to the neonatal intensive care unit (RR 4.38, 95% CI 2.59–7.42), and intrapartum or early neonatal death (RR 4.18, 95% CI 1.48–11.74).

Conclusion

TTM was associated with adverse perinatal outcome especially if labor started during parenteral treatment.
Gene-Metabolite Network Linked to Inhibited Bioenergetics in Association With Spaceflight-Induced Loss of Male Mouse Quadriceps Muscle
Authors: Chakraborty Nabarun , Waning David L , Gautam Aarti , Hoke Allison , Sowe Bintu , Youssef Dana , Butler Stephan , Savaglio Michael , Childress Paul J , Kumar Raina , Moyler Candace , Dimitrov George , Kacena Melissa A , Hammamieh Rasha
Published: June 2020

Prolonged residence of mice in spaceflight is a scientifically robust and ethically ratified model of muscle atrophy caused by continued unloading. Under the Rodent Research Program of the National Aeronautics and Space Administration (NASA), we assayed the large-scale mRNA and metabolomic perturbations in the quadriceps of C57BL/6j male mice that lived in spaceflight (FLT) or on the ground (control or CTR) for approximately 4 weeks. The wet weights of the quadriceps were significantly reduced in FLT mice. Next-generation sequencing and untargeted mass spectroscopic assays interrogated the gene-metabolite landscape of the quadriceps. A majority of top-ranked differentially suppressed genes in FLT encoded proteins from the myosin or troponin families, suggesting sarcomere alterations in space. Significantly enriched gene-metabolite networks were found linked to sarcomeric integrity, immune fitness, and oxidative stress response; all inhibited in space as per in silico prediction. A significant loss of mitochondrial DNA copy numbers in FLT mice underlined the energy deprivation associated with spaceflight-induced stress. This hypothesis was reinforced by the transcriptomic sequencing–metabolomics integrative analysis that showed inhibited networks related to protein, lipid, and carbohydrate metabolism, and adenosine triphosphate (ATP) synthesis and hydrolysis. Finally, we discovered important upstream regulators, which could be targeted for next-generation therapeutic intervention for chronic disuse of the musculoskeletal system. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
Long‐term consequences of the 2020 coronavirus pandemics: Historical global‐macro context
Authors: Tokic Damir
Published: June 2020

The COVID‐19 pandemics is likely to accelerate the trends of de‐globalization and de‐dollarization. Over the long term, the major financial consequence is likely to be the accelerated trend of rising inflation and long‐term interest rates. More broadly, the post‐pandemic environment will likely encompass difficult longer‐term economic and geopolitical challenges. Alternatively, the COVID‐19 pandemics also creates an opportunity for building a new trend of more sustainable globalization.
Searching new structures of beryllium‐doped in small‐sized magnesium clusters: Be2MgnQ (Q = 0, −1; n = 1–11) clusters DFT study
Authors: Zeng Lu , Deng Ping‐Ji , Bi Jie , Zhu Ben‐Chao
Published: June 2020

Using CALYPSO method to search new structures of neutral and anionic beryllium‐doped magnesium clusters followed by density functional theory (DFT) calculations, an extensive study of the structures, electronic and spectral properties of Be2MgnQ (Q = 0, −1; n = 2–11) clusters is performed. Based on the structural optimization, it is found that the Be2MgnQ (Q = 0, −1) clusters are shown by tetrahedral‐based geometries at n = 2–6 and tower‐like‐based geometries at n = 7–11. The calculations of stability indicate that Be2Mg5Q=0, Be2Mg5Q=−1, and Be2Mg8Q=−1 clusters are “magic” clusters with high stability. The NCP shows that the charges are transferred from Mg atoms to Be atoms. The s‐ and p‐orbitals interactions of Mg and Be atoms are main responsible for their NEC. In particular, chemical bond analysis including molecular orbitals (MOs) and chemical bonding composition for magic clusters to further study their stability. The results confirmed that the high stability of these clusters is due to the interactions between the Be atom and the Mg5 or Mg8 host. Finally, theoretical calculations of infrared and Raman spectra of the ground state of Be2MgnQ (Q = 0, −1; n = 1–11) clusters were performed, which will be absolutely useful for future experiments to identify these clusters.
Single‐cell RNA analysis on ACE2 expression provides insights into SARS‐CoV‐2 potential entry into the bloodstream and heart injury
Authors: Guo Jieyu , Wei Xiangxiang , Li Qinhan , Li Liliang , Yang Zhaohua , Shi Yu , Qin Yue , Zhang Xinyue , Wang Xinhong , Zhi Xiuling , Meng Dan
Published: June 2020

Coronavirus disease‐2019 (COVID‐19) is a global pandemic with high infectivity and pathogenicity, accounting for tens of thousands of deaths worldwide. Recent studies have found that the pathogen of COVID‐19, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), shares the same cell receptor angiotensin converting enzyme II (ACE2) as SARS‐CoV. The pathological investigation of COVID‐19 deaths showed that the lungs had characteristics of pulmonary fibrosis. However, how SARS‐CoV‐2 spreads from the lungs to other organs has not yet been determined. Here, we performed an unbiased evaluation of cell‐type‐specific expression of ACE2 in healthy and fibrotic lungs, as well as in normal and failed adult human hearts, using published single‐cell RNA‐seq data. We found that ACE2 expression in fibrotic lungs mainly locates in arterial vascular cells, which might provide a route for bloodstream spreading of SARS‐CoV‐2. Failed human hearts have a higher percentage of ACE2‐expressing cardiomyocytes, and SARS‐CoV‐2 might attack cardiomyocytes through the bloodstream in patients with heart failure. Moreover, ACE2 was highly expressed in cells infected by respiratory syncytial virus or Middle East respiratory syndrome coronavirus and in mice treated by lipopolysaccharide. Our findings indicate that patients with pulmonary fibrosis, heart failure, and virus infection have a higher risk and are more susceptible to SARS‐CoV‐2 infection. The SARS‐CoV‐2 might attack other organs by getting into the bloodstream. This study provides new insights into SARS‐CoV‐2 blood entry and heart injury and might propose a therapeutic strategy to prevent patients from developing severe complications.
JunB can enhance the transcription of IL‐8 in oral squamous cell carcinoma
Authors: Tsunoda Mariko , Fukasawa Mai , Nishihara Anna , Takada Leo , Asano Masatake
Published: June 2020

Proteasome inhibitor MG132 was shown to enhance the secretion of interleukin 8 (IL‐8) by various cells. The enhancement is regulated by the transcription factor activator protein‐1 (AP‐1) at the transcriptional level. AP‐1 is a dimer formed by AP‐1 family proteins. The purpose of the present study was to explore the combinations of the AP‐1 family proteins that contribute to MG132‐driven IL‐8 secretion. Oral squamous cell carcinoma‐derived cell lines, Ca9‐22 and HSC3, were used to demonstrate their response to MG132. IL‐8 secretion was augmented by MG132 in both cell lines. c‐Jun expression was detected in both the cell lines, whereas c‐Fos expression was detected only in the HSC3. The influence of MG132 stimulation on c‐Jun and c‐Fos expression was further examined by western blot analysis. c‐Jun expression was increased by MG132 stimulation, whereas c‐Fos expression was not detected even after MG132 stimulation. As JunB is reported to inhibit the transcriptional activity of the AP‐1 complex, we speculated that the c‐Jun homodimer should contribute to IL‐8 enhancement. Expression vectors encoding wild type and c‐Jun mutants, M17 and M22‐23, respectively, were constructed and transfected into the Ca9‐22 cells. In contrast to our expectations, MG132‐induced IL‐8 secretion was significantly reduced in all the transfectants suggesting that other c‐Jun members might form homodimers with c‐Jun and contribute to IL‐8 enhancement. Transfection of the cells with c‐Jun or JunB small hairpin RNA (shRNA) reduced IL‐8 secretion up to 50% and 65% of the control shRNA transfectant. Furthermore, cotransfection of both shRNA almost completely inhibited the IL‐8 secretion. These results indicate that JunB not only inhibits but also enhances the transcription of c‐Jun targets in combination with c‐Jun.
Low shear stress regulates vascular endothelial cell pyroptosis through miR‐181b‐5p/STAT‐3 axis
Authors: Xu Xiangshan , Yang Yang , Wang Guofeng , Yin Yu , Han Shuo , Zheng Donghan , Zhou Shaobo , Zhao Yuanyuan , Chen Yong , Jin Yuanzhe
Published: June 2020

Low shear stress and pyroptosis both play an important role in the onset and development of atherosclerosis (AS). MicroRNAs (miRNAs) are a kind of short (18–22) nucleotide sequences that can bind to the 3′‐untranslated region (3′‐UTR) of messenger RNA, thereby regulating programmed cell death including pyroptosis. However, the function of miRNAs in cells subjected to shear stress conditions is unknown. Therefore, we conducted the current study to demonstrate the effect of low shear stress on pyroptosis and the underlying mechanism. Human umbilical vein endothelial cells (HUVECs) stimulated by undisturbed shear stress (5 dynes/cm2) were the experimental group while HUVECs without shear stress treatment were the control group in our experiments. We observed that shear stress can suppress mechanosensitive miR‐181b‐5p expression, accompanying the elevated expression of NLRP3 inflammasome‐dependent pyroptosis. Introduction of miR‐181b‐5p could alleviate NLRP3 inflammasome‐dependent pyroptosis. Luciferase assay showed specific binding of miR‐181b‐5p to the 3′‐UTR of signal transduction and transcriptional activation factor 3 (STAT‐3) gene. Inhibition of STAT‐3 gene expression at the posttranscriptional level results in the alleviation of NLRP3 inflammasome‐dependent pyroptosis. Besides, the silencing of STAT‐3 reduced anti‐miR‐181b‐5p‐mediated HUVEC pyroptosis via regulating NLRP3 inflammasome activation. Given the role of mechanosensitive miR‐181b‐5p and STAT‐3 in the shear stress‐induced pyroptosis, regulation of their expression levels may be a promising strategy to control AS.
What are the consequences of Methylphenidate exposure for maternally separated rats?
Authors: Mohtashami Borzadaran Fatemeh , Esmaeilpour Khadijeh , Joushi Sara , Rajizadeh Mohammad Amin , Sheibani Vahid , ur Rehman Naeem , Sepehri Gholamreza
Published: June 2020

Methylphenidate (MPH) abuse is prevalent among youth. Drug abuse results in pain perception. We sought to investigate whether Maternal separation (MS) prone to MPH addiction. The next question was whether MPH abusers with MS differ in pain perception. We investigated the impact of MS on addiction and drug reward as well as pain perception following 5 days of MPH injection in males and females rats. Initially, rats underwent MS protocol of 3 hr daily for 21 days. Conditioned place preference (CPP) test was an attempt to investigate whether MS rats experience more reward with MPH. The protocol consisted of 10 min habituation on Day 1, conditioning on Day 2–Day 6 (5 mg per kg MPH injection in drug compartment and saline in saline compartment with 4 hr gap between injections) and 10 min test on Day 7. Furthermore, using another group, differences in pain perception were investigated after 5 days of daily MPH injection with 5 mg per kg. Sensory pain sensitivity was tested on PND 39 using tail flick and hotplate in MS and control groups with and without MPH exposure. Results indicated that female rats are equally prone to addiction in CPP. On the other hand, MS males experience a higher reward in CPP. In tail flick test, female MS rats exposed to MPH show a lower sensory pain threshold with similar MPH exposure. Experiencing MPH similarly declined hotplate pain perception in MS and controls in the females. Males, on the other hand, did not show any difference in sensory pain tests. According to results one can argue MS is detrimental. MS males experience more reward with MPH, females are equally addiction prone and MS females experience more pain in tail flick. On the other hand pain threshold can decline in hotplate test for both control and MS females that received MPH.
Clinicopathological characteristics of intraductal papillary neoplasm of the bile duct: a Japan‐Korea collaborative study
Authors: Kubota Keiichi , Jang Jin‐Young , Nakanuma Yasuni , Jang Kee‐Taek , Haruyama Yasuo , Fukushima Noriyoshi , Furukawa Toru , Hong Seung‐Mo , Sakuraoka Yuhki , Kim Haeryoung , Matsumoto Takatsugu , Lee Kyung Bun , Zen Yoh , Kim Jaeri , Miyazaki Masaru , Choi Dong Wook , Heo Jin Seok , Endo Itaru , Hwang Shin , Nakamura Masafumi , Han Ho‐Seong , Uemoto Shinji , Park Sang Jae , Hong Eun Kyung , Nanashima Atsushi , Kim Dong‐Sik , Kim Joo Young , Ohta Tetsuo , Kang Koo Jeong , Fukumoto Takumi , Nah Yang Won , Seo Hyung Il , Inui Kazuo , Yoon Dong‐Sup , Unno Michiaki
Published: June 2020

Background

The prevalent location and incidence of intraductal papillary neoplasm of the bile duct (IPNB) and invasive carcinoma associated with them have varied markedly among studies due to differences in diagnostic criteria and tumor location.

Methods

IPNBs were classified into two types: Type 1 IPNB, being histologically similar to intraductal papillary mucinous neoplasm of the pancreas, and Type 2 IPNB, having a more complex histological architecture with irregular papillary branching or foci of solid‐tubular components. Medical data were evaluated.

Results

Among 694 IPNB patients, 520 and 174 had Type 1 and Type 2, respectively. The levels of AST, ALT, ALP, T. Bil, and CEA were significantly higher in patients with Type 2 than in those with Type 1. Type 1 IPNB was more frequently located in the intrahepatic bile duct than Type 2, whereas Type 2 was more frequently located in the distal bile duct than Type 1 IPNB (P < 0.001). There were significant differences in 5‐year cumulative survival rates (75.2% vs 50.9%; P < 0.0001) and 5‐year cumulative disease‐free survival rates (64.1% vs 35.3%; P < 0.0001) between the two groups.

Conclusion

Type 1 and Type 2 IPNBs differ in their clinicopathological features and prognosis. This classification may help to further understand IPNB.
Safety of a new spray‐type adhesion barrier (AdSpray®) in liver surgery
Authors: Okubo Satoshi , Shindoh Junichi , Kobayashi Yuta , Hashimoto Masaji
Published: June 2020

Background

Although adhesion barriers are increasingly used in liver surgery, there are no sufficient data yet in support of their safety.

Methods

Data of 104 consecutive patients in whom a spray‐type adhesion barrier (AdSpray®) was used after hepatectomy were compared with those of 94 control subjects in whom no adhesion barriers were used, and the risk factors for major morbidity after hepatectomy were investigated.

Results

The incidence of major morbidity was not significantly different between the AdSpray group and the control group (17% vs 15%, P = .645), although multivariate analyses revealed that the use of AdSpray was associated with an increased risk of abdominal abscess (odds ratio [OR], 4.42; P = .043). Similar tendency was also confirmed after propensity score adjustment to account for the potential selection bias. A sub‐group analysis revealed that incidence of abscess formation decreased as operators' experience in the used of AdSpray increased, and multivariate analysis identified preoperative chemotherapy (OR, 3.96; P = .043) as being independent predictors of abscess formation after the use of AdSpray.

Conclusions

AdSpray use was not associated with global incidence of major morbidity after liver surgery, although surgeon's experience would be needed for adequate use of AdSpray to minimize the risk of postoperative abscess formation.
Trends in the use of implantable cardioverter‐defibrillator and cardiac resynchronization therapy device in advancing age: Analysis of the Japan cardiac device treatment registry database
Authors: Yokoshiki Hisashi , Shimizu Akihiko , Mitsuhashi Takeshi , Ishibashi Kohei , Kabutoya Tomoyuki , Yoshiga Yasuhiro , Kohno Ritsuko , Abe Haruhiko , Nogami Akihiko ,   Members of the Implantable Cardioverter-Defibrillator (ICD) Committee of the Japanese Heart Rhythm Society
Published: June 2020

Background

Trends of de novo implantation of cardiac implantable electronic devices (CIEDs) including implantable cardioverter‐defibrillator (ICD) and cardiac resynchronization therapy with a defibrillator (CRT‐D) or pacemaker (CRT‐P) in advancing age are unknown.

Methods

Analysis of data from the Japan cardiac device treatment registry (JCDTR) with an implantation date between January 2006 and December 2016 was performed focusing on advancing age of ≧75 years.

Results

The cohort included 17 564 ICD, 9470 CRT‐D and 1087 CRT‐P recipients for de novo implantation. The rate of patients ≧75 years of age increased from 17.1% to 20.5% in ICD implantation (P = .052), from 19.7% to 30.0% in CRT‐D implantation (P < .0001), and from 40.0% to 64.0% in CRT‐P implantation (P = .17). There was an apparent increase in the percentage of nonischemic patients aged ≧75 years receiving ICD (10.9% in 2006 to 16.4% in 2016, P = .0008) and CRT‐D (17.1% in 2006 to 27.8% in 2016, P = .0001). The implantation for primary prevention ICD (P = .059) and CRT‐D (P = .012) was also associated with a temporal increase in the percentage of patients aged ≧75 years.

Conclusions

Proportion of patients ≧75 years of age for de novo CIED implantation gradually increased from 2006 to 2016, presumably because of the growing number of nonischemic cardiomyopathy and heart failure patients requiring primary prevention of sudden cardiac death.