bluuebunny/crossref_metadata_2025 huggingface dataset:
An effective peptide vaccine strategy circumventing clonal MHC heterogeneity of murine myeloid leukaemia
Authors: Shin A-Ri , Lee Sang-Eun , Choi Haeyoun , Sohn Hyun-Jung , Cho Hyun-Il , Kim Tai-Gyu
Published: June 2020

Background

Therapeutic cancer vaccines are an attractive approach for treating malignant tumours, and successful tumour eradication depends primarily on controlling tumour immunosuppression status as well as heterogeneity of tumour cells driven by epigenetic alterations.

Methods

Peptide-loaded dendritic cell (DC) prime and non-infectious peptide booster heterologous immunisations were assessed for the immunogenicity of polo-like kinase-1 (PLK1)-derived peptides. Heterologous vaccination regimen targeting multiple shared tumour antigens simultaneously with PD-L1 blockade was assessed against murine myeloid leukaemia.

Results

A synthetic PLK1122 (DSDFVFVVL)-based heterologous vaccination generated large numbers of long-lasting antigen-specific CD8 T-cells eliciting therapeutic effects against various established tumours. The therapeutic efficacy of single antigen-targeting PLK1122-based vaccine with sufficient endurance of PD-L1 blockade toward C1498 leukaemia relied on the heterogeneous clonal levels of MHC-I and PD-L1 expression. A novel multi-peptide-based vaccination targeting PLK1 and survivin simultaneously along with PD1 blockade led to complete tumour eradication and long-term survival in mice with clonally heterologous C1498 myeloid leukaemia.

Conclusions

Our findings suggest that PLK1 could be an attractive immunotherapeutic target antigen for cancer immunotherapy, and that similar strategies would be applicable for the optimisation of cancer vaccines for the treatment of numerous viral diseases and malignant tumours.
Concurrent use of palbociclib and radiation therapy: single-centre experience and review of the literature
Authors: Beddok Arnaud , Xu Hao Ping , Henry Alexandre Arsène , Porte Baptiste , Fourquet Alain , Cottu Paul , Kirova Youlia
Published: June 2020

Palbociclib in combination with endocrine therapy increases progression-free survival in patients with ER-positive, HER2-negative advanced breast cancer (BC). In this study, we retrospectively evaluated safety in the first patient treated with concurrent use of palbociclib and radiation therapy (RT) in the Curie Institute. Between April 2017 and August 2019, 30 women with metastatic BC received locoregional and/or symptomatic irradiation at a metastatic site concurrently with palbociclib. The most common acute toxicities were radiodermatitis and neutropenia. Palbociclib had to be discontinued during RT in three locally treated patients who developed grade 3 radiodermatitis and febrile neutropenia, grade 2 dysphagia and metastatic disease progression, respectively. After a follow-up of at least 6 months, none of the patients had late toxicity. Concomitant administration of palbociclib with RT was reasonably well tolerated in our series of 30 patients. More prospective data with longer follow-up are needed to confirm these results.
A comprehensive population-based study comparing the phenotype and genotype in a pretherapeutic screen of dihydropyrimidine dehydrogenase deficiency
Authors: Pallet Nicolas , Hamdane Salma , Garinet Simon , Blons Hélène , Zaanan Aziz , Paillaud Elena , Taieb Julien , Laprevote Olivier , Loriot Marie-Anne , Narjoz Céline
Published: June 2020

Background

Pretherapeutic screening for dihydropyrimidine dehydrogenase (DPD) deficiency is recommended or required prior to the administration of fluoropyrimidine-based chemotherapy. However, the best strategy to identify DPD-deficient patients remains elusive.

Methods

Among a nationwide cohort of 5886 phenotyped patients with cancer who were screened for DPD deficiency over a 3 years period, we assessed the characteristics of both DPD phenotypes and DPYD genotypes in a subgroup of 3680 patients who had completed the two tests. The extent to which defective allelic variants of DPYD predict DPD activity as estimated by the plasma concentrations of uracil [U] and its product dihydrouracil [UH2] was evaluated.

Results

When [U] was used to monitor DPD activity, 6.8% of the patients were classified as having DPD deficiency ([U] > 16 ng/ml), while the [UH2]:[U] ratio identified 11.5% of the patients as having DPD deficiency (UH2]:[U] < 10). [U] classified two patients (0.05%) with complete DPD deficiency (> 150 ng/ml), and [UH2]:[U] < 1 identified three patients (0.08%) with a complete DPD deficiency. A defective DPYD variant was present in 4.5% of the patients, and two patients (0.05%) carrying 2 defective variants of DPYD were predicted to have low metabolism. The mutation status of DPYD displayed a very low positive predictive value in identifying individuals with DPD deficiency, although a higher predictive value was observed when [UH2]:[U] was used to measure DPD activity. Whole exon sequencing of the DPYD gene in 111 patients with DPD deficiency and a “wild-type” genotype (based on the four most common variants) identified seven heterozygous carriers of a defective allelic variant.

Conclusions

Frequent genetic DPYD variants have low performances in predicting partial DPD deficiency when evaluated by [U] alone, and [UH2]:[U] might better reflect the impact of genetic variants on DPD activity. A clinical trial comparing toxicity rates after dose adjustment according to the results of genotyping or phenotyping testing to detect DPD deficiency will provide critical information on the best strategy to identify DPD deficiency.
Syntenin-1 promotes colorectal cancer stem cell expansion and chemoresistance by regulating prostaglandin E2 receptor
Authors: Iwamoto Kazuya , Takahashi Hidekazu , Okuzaki Daisuke , Osawa Hideo , Ogino Takayuki , Miyoshi Norikatsu , Uemura Mamoru , Matsuda Chu , Yamamoto Hirofumi , Mizushima Tsunekazu , Mori Masaki , Doki Yuichiro , Eguchi Hidetoshi
Published: June 2020

Background

The protein syntenin-1 is expressed by a variety of cell types, and is upregulated in various malignancies, including melanoma, breast cancer and glioma. Although the mechanism by which elevated syntenin-1 expression contributes to cancer has been described, the exact pathway has not been elucidated.

Methods

To investigate the involvement of syntenin-1 in colorectal cancer (CRC), we performed immunohistochemical analysis of 139 CRC surgical specimens. We also examined syntenin-1 knockdown in CRC cell lines.

Results

High syntenin-1 expression was associated with less differentiated histologic grade and poor prognosis, and was an independent prognostic indicator in CRC. Syntenin-1 knockdown in CRC cells reduced the presence of cancer stem cells (CSCs), oxaliplatin chemoresistance and migration. DNA microarray analysis and quantitative real-time polymerase chain reaction showed decreased prostaglandin E2 receptor 2 (PTGER2) expression in syntenin-1-knockdown cells. PTGER2 knockdown in CRC cells yielded the same phenotype as syntenin-1 knockdown. Celecoxib, which has anti-inflammatory effects by targeting cyclooxygenase-2, reduced CSCs and decreased chemoresistance, while prostaglandin E2 (PGE2) had the opposite effect.

Conclusions

Our findings suggested that syntenin-1 enhanced CSC expansion, oxaliplatin chemoresistance and migration capability through regulation of PTGER2 expression. Syntenin-1 may be a promising new prognostic factor and target for anti-cancer therapies.
β-NaYF4:Yb,Er,Gd nanorods@1T/2H-MoS2 for 980 nm NIR-triggered photocatalytic bactericidal properties
Authors: Qiao Yan , Zhou Xionglin , Geng Hongchao , Sun Leilei , Zhen Deshuai , Cai Qingyun
Published: June 2020

Fabrication of β-NaYF4:Yb,Er,Gd@1T/2H-MoS2 nanocomposites for NIR-driven photocatalytic sterilization of Escherichia coli.
Novel synthesis of 0D, 1D and 2D nano-CsxWO3and their tunable optical-thermal response performance
Authors: Liu Guanghui , Kong Fandong , Xu Ju , Li Ruixing
Published: June 2020

0D, 1D and 2D nano-Cs0.3WO3were successfully synthesized in a controllable way, and their photoresponse properties were systematically investigated.
Under my Thumb?
Authors: Holzhauer Peter
Published: June 2020

Der Inhalt dieses Songs aus dem Jahre 1966 beschreibt die wechselseitigen
Abhängigkeiten und kleinen Grausamkeiten eines jungen Paares. Im gleichen
Jahr wurde während einer Live Performance dieses Stücks durch die
Rolling Stones im kalifornischen Altamont das gewaltsame Ende der vorher eher
beschaulichen Hippie-Ära eingeleitet. Durch den Mord eines Zuschauers durch
das „Security-Personal“ der Hells Angels erlangte dieser Song
traurige Berühmtheit. Begleitet sein Thema heute als Soundtrack unser
neues aktuelles Leben?
Stellenwert komplementärer Supportivtherapie bei
immunsupprimierten onkologischen Patienten – eine
Kasuistik
Authors: Holzhauer Peter , Gröber Uwe , Kisters Klaus
Published: June 2020

Die hochdosierte parenterale Applikation von Vitamin C ist eine von
zahlreichen komplementärmedizinischen Methoden, die häufig
zur Behandlung von tumorassoziierter Fatigue-Symptomatik und als
komplementäre Supportivtherapie – auch jetzt in der Phase
der Covid-19-Pandemie – zur Immunstimulation und als antivirale
Option eingesetzt wird. Die hier vorgestellte Kasuistik beschreibt neben
einer folgenreichen Wechselwirkung dieser medikamentösen supportiven
Therapie mit einem Hightech-Medizinprodukt auch moderne konventionelle
Therapieoptionen beim triple negativen Mammakarzinom. Dabei kommen
verschiedene immunrelevante Mikronährstoffe zum Einsatz, die
einerseits die moderne Checkpoint-Inhibition mit Atezolizumab
unterstützen, und andererseits eine möglichst optimale
Abwehrlage in der Phase der Pandemie gewährleisten sollen. Aktuelle
Daten wurden zu dieser Thematik gerade für Selen und Vitamin D
publiziert.
Genetische Untersuchungen beim Parkinson-Syndrom: Indikation und praktische Durchführung
Authors: Tönges Lars , Ip Chi Wang , Dresel Christian , Lingor Paul , Csoti Ilona , Kohl Zacharias , Winkler Jürgen , Klebe Stephan
Published: June 2020

Seit der Erstbeschreibung einer monogenetischen Ursache der Parkinson-Erkrankung sind mehr als 20 Jahre vergangen. Trotz der Fortschritte der molekulargenetischen Diagnostik wird diese immer noch sehr selten durchgeführt. Genetische Untersuchungen bei Patienten mit Parkinson-Syndromen werden allerdings zukünftig einen großen Stellenwert einnehmen. Dies ist nicht nur im Hinblick auf die Diagnosesicherung bei Parkinson-Patienten mit jungem Erkrankungsbeginn und / oder positiver Familienanamnese zu sehen, sondern auch im Rahmen der personalisierten Medizin mit neuen therapeutischen Möglichkeiten. Im Folgenden möchten wir einen Überblick über die Grundlagen der genetischen Diagnostik, die gesetzlichen Voraussetzungen, das Vorgehen für eine genetische Diagnostik und einen Ausblick in die Zukunft bei genetischen Parkinson-Erkrankungen geben.
Nebenwirkungen komplementär behandeln
Authors: Weis Nicole
Published: June 2020

In der supportiven Onkologie werden zunehmend Verfahren aus dem Bereich der
Naturheilkunde ergänzend eingesetzt, um Nebenwirkungen zu lindern.
Dieser Artikel gibt eine Übersicht der wichtigsten Symptome und
beschreibt anhand dessen komplementäre
Therapiemöglichkeiten, die sich in Studien beziehungsweise in der
Praxis bewährt haben.
Jod – unverzichtbar für die Gesundheit der Brust: Ein
neuer Ansatz zur Prävention und Therapie vom
Mammakarzinom
Authors: Kauffmann Kyra Daniela
Published: June 2020

Jod ist ein essentielles Spurenelement, das nicht nur eine Rolle im
Schilddrüsenstoffwechsel spielt. Ein Großteil des gesamten
Jodvorkommens im menschlichen Organismus findet sich in extrathyreoidalen
Geweben, vor allem in den Brustdrüsen. In der Schwangerschaft und
Stillzeit geht Jod eine Verbindung mit Lipiden ein, dabei entstehen
Jodlaktone. Diese beeinflussen die Wachstumsregulation und die Apoptose der
Brustdrüsenzellen.

Auch andere Jodverbindungen, wie Povidon-Jod oder die Lugolsche
Lösung zeigen sowohl in Tiersuchen, an Studien mit menschlichen
Brustkrebszelllinien sowie in klinischen Studien eine tumorzelltoxische
Wirkung. Vor dem Hintergrund dieser Forschungen ist eine ausreichende
Jodversorgung für Frauen hinsichtlich einer Primär- und auch
Sekundärprophylaxe von Brustkrebs grundsätzlich zu
empfehlen. Die Einnahmeempfehlungen der Ernährungsgesellschaften in
Bezug auf Jod sollten daher überarbeitet werden.
Immunrelevante Mikronährstoffe bei viralen
Atemwegsinfektionen
Authors: Gröber Uwe , Holzhauer Peter , Kisters Klaus
Published: June 2020

Ende 2019 nahm eine neue Coronavirus-Pandemie in der chinesischen Stadt Wuhan
in der Provinz Hubei ihren Lauf. Der klinische Verlauf der durch SARS-CoV-2
ausgelösten Lungenerkrankung Covid-19 ist unterschiedlich. Einige
Infizierte entwickeln nur leichte oder überhaupt keine Symptome. Bei
anderen kommt es rasch zu einem akuten Lungenversagen und zum Tod.
Über 80% der Covid-19-Erkrankungen treten bei
älteren Menschen (±70 Jahre) mit Grunderkrankungen auf, wie
KHK, Krebs, Diabetes mellitus oder zerebrovaskulären
Veränderungen (z. B. Demenz). Neben entsprechenden
Hygienemaßnahmen, dem individuellen Sozialverhalten, erfolgt derzeit
über die Medien kein Hinweis auf die physiologische Bedeutung
immunrelevanter Mikronährstoffe, mit der das Immunsystem gegen
virale Atemwegserkrankungen unterstützt und Begleitkomplikationen
verringert werden könnten. Deshalb sollte bei Covid-19-Patienten
grundsätzlich nicht nur der Makonährstoff-, sondern auch der
Mikronährstoff-Status labordiagnostisch objektiviert (z. B.
25(OH)D, Selen, Omega-3-Index) und gegebenenfalls gezielt kompensiert
werden.
Kurzzeitfasten unter Chemotherapie
Authors: Voiß Petra , Klose Petra , Kümmel Sherko ,   für die AGIMed der Arbeitsgemeinschaft Gynäkologische
                        Onkologie (AGO)
Published: June 2020

2016 erhielt der Japaner Yoshinori Ohsumi den Nobelpreis für die Entdeckung
der Mechanismen der Autophagie, des Selbstverdauungs- und Wiederverwertungsprozesses
der Zellen. Dieser Mechanismus trägt dazu bei, das Gleichgewicht zwischen
dem Abbau alter und der Produktion neuer Zellkomponenten herzustellen. Auch
krankhafte oder krankmachende Strukturen, eingedrungene Bakterien und Viren werden
so entsorgt. Eine fehlregulierte autophagische Aktivität kann umgekehrt zu
einem zellulären Desaster führen und sich in unterschiedlichsten
Krankheiten manifestieren.
CD8+CD28null T Lymphocytes are Associated with the Development of Atrial Fibrillation after Elective Cardiac Surgery
Authors: Kazem Niema , Sulzgruber Patrick , Thaler Barbara , Baumgartner Johanna , Koller Lorenz , Laufer Günther , Steinlechner Barbara , Hohensinner Philipp , Wojta Johann , Niessner Alexander
Published: June 2020

Background Postoperative atrial fibrillation (POAF) is assumed as a complex and multifactorial interaction of different pathogenic factors. Data suggests an inflammatory process as the main trigger of this specific type of atrial fibrillation. CD8+ T lymphocytes that lack the surface protein CD28 were found to be crucially involved in chronic inflammatory processes within the cardiovascular system. Of utmost interest, these so-called CD8+CD28null T cells are known to present with autoaggressive behavior and deleterious cytotoxic effects on human tissue.

Methods A total of 129 patients undergoing elective cardiac valve and/or coronary artery bypass graft surgery were enrolled. Fluorescence-activated cell sorting was performed to investigate lymphocyte subsets. Patients were stratified in two subgroups according to patients developing POAF (n = 60) and individuals free of POAF (n = 69).

Results Comparing patients developing POAF to individuals free of POAF, the fraction of CD8+ lymphocytes was significantly higher in individuals developing POAF (30.5% [POAF] vs. 25.7% [no-POAF]; p = 0.021). Interestingly, also the fraction of CD8+CD28null T lymphocytes was significantly higher in the POAF subgroup (66.7% [POAF] vs. 61.6% [non-POAF]; p = 0.043). Multivariate logistic regression proved that the fraction of CD8+CD28null cells is a strong and independent prognosticator for the development of POAF with an adjusted odds ratio per 1 standard deviation of 3.21 (95% confidence interval 1.01–10.18; p = 0.048).

Conclusion We found that cytotoxic CD8+CD28null T lymphocytes proved to be a strong and independent predictor for the development of POAF after elective cardiac surgery. Our results potentially indicate an autoimmune impact of this preexisting, highly cytotoxic T cell subset in the pathogenesis of POAF.
Dual Pathway Inhibition for Vascular Protection in Patients with Atherosclerotic Disease: Rationale and Review of the Evidence
Authors: Weitz Jeffrey Ian , Angiolillo Dominick J. , Geisler Tobias , Heitmeier Stefan
Published: June 2020

Despite advances in secondary prevention strategies in patients with cardiovascular disease, the residual risk of recurrent atherothrombotic events remains high. Dual-antiplatelet therapy is the standard of care for secondary prevention in patients with acute coronary syndrome (ACS), whereas single antiplatelet therapy, generally with aspirin, is the standard of care for secondary prevention in stable patients with coronary artery disease (CAD), peripheral artery disease (PAD), or cerebrovascular disease. However, atherosclerotic plaque disruption not only triggers platelet activation but also results in thrombin generation because of tissue factor exposure. Therefore, blocking both pathways by combining antiplatelet therapy with an anticoagulant, or dual pathway inhibition (DPI), has the potential to be more effective than inhibiting either pathway alone. The benefit of DPI has been demonstrated in the ATLAS ACS 2-TIMI 51, COMPASS, and VOYAGER PAD trials, where the combination of rivaroxaban vascular dose (2.5 mg twice daily) plus aspirin significantly reduced the risk of atherothrombotic events compared with aspirin across a broad range of patients, including those with recent ACS, those with chronic CAD and/or PAD, and patients with PAD who have undergone peripheral revascularization. This article provides the rationale for this regimen in more detail, including why the DPI regimen with the rivaroxaban vascular dose was developed for vascular protection in a broad spectrum of patients with atherosclerotic disease.
Surgical Decision-Making in Multivalvular Heart Disease: A Holistic Approach
Authors: Makhija Neeti , Malhotra Rohit , Magoon Rohan , Ramakrishnan Pradeep
Published: June 2020

Patients with multivalvular heart disease often presents a unique challenge with regard to the intraoperative decision-making in the form of choosing between a satisfactory valvular repair or a more definitive valve replacement. We describe a patient with multivalve involvement on antiretroviral therapy. Discussion presents a nuanced perspective on surgical decision-making in multi-valvular heart disease, wherein an effective communication between the surgeon and the echocardiographer is required for ensuring favorable postoperative outcomes.
Comparative Evaluation of Apical Sealing Ability of Different Obturation Techniques by Confocal Microscopy: An In Vitro Study
Authors: Arora Reetu , Kumar Yogesh , Jindal Neetu , Aggarwal Renu , Takhar Kavneet
Published: June 2020

Introduction The aim of obturation in the root canal is to completely seal the canal space to eliminate all the portals of entry and exit between root canal and periodontal space. Various techniques have been developed to achieve a hermetic seal.

Materials and Methods As many as 150 extracted human maxillary central incisors were taken for the study. Biomechanical preparation was done up to F5 protaper file. According to different obturation techniques, samples were divided into six groups, keeping 30 samples in experimental and 15 samples in control groups. Group I–Lateral Condensation, Group II–Thermafil, Group III–Beefill, Group IV–GuttaFlow, Group V–Positive Control group, Group VI–Negative Control group. After obturation, the samples were immersed in 2% Rhodamine-B dye for 24 hours. Each sample was longitudinally sectioned to examine under confocal laser scanning microscope.

Statistical Analysis The results were evaluated with ANOVA and posthoc Tukey honest significant difference (HSD) comparison test.

Results The mean values of dye penetration of different groups were Group I (Lateral Condensation) 1.51 ± 0.451, Group II (Thermafil) 0.918 ± 0.399, Group III (Beefill) 1.30 ± 0.559. Group IV (GuttaFlow) 0.655 ± 0.396, Group V (Positive Control group) 1.96 ±0.046, Group VI (Negative Control group) 0 ± 0. The lowest mean value of apical microleakage was found in GuttaFlow amongst all experimental groups.

Conclusion It can be concluded that the GuttaFlow obturating material exhibited better apical sealing ability with canal walls.
Labor and Delivery Outcomes with the Sequential Use of Misoprostol Followed by Cervical Foley Catheter
Authors: Hopkins Maeve K. , Hamm Rebecca F. , Srinivas Sindhu K. , Levine Lisa D.
Published: June 2020

Objective Studies demonstrate shorter time to delivery with concurrent use of misoprostol and cervical Foley catheter. However, concurrent placement may not be feasible. If misoprostol is used to start an induction, little is known regarding the benefit of sequentially using Foley catheter. We examine obstetrical outcomes in women with Foley catheter placed after misoprostol compared with those only requiring misoprostol.

Study Design Retrospective cohort study of singleton pregnancies, intact membranes, and an unfavorable cervix (Bishop score of ≤6 and dilation ≤2 cm) undergoing term induction May 2013 to June 2015. We compared obstetrical outcomes between women receiving misoprostol alone versus those that had a Foley catheter placed after misoprostol. Outcomes are mode of delivery, time to delivery, chorioamnionitis, admission to neonatal intensive care unit, and maternal morbidity. Chi-square and Fisher's exact tests were used for categorical variables, Mann–Whitney U-tests compared continuous variables.

Results Among 364 women, 281 began induction with misoprostol alone. A total of 135 (48%) subsequently had a Foley catheter placed. Characteristics were similar between the groups, although nulliparity and cervical dilation <1 cm at start of induction were more likely to have subsequent Foley catheter. Women with Foley catheter placement after misoprostol had a longer median time to delivery (15 vs. 11 hours, p < 0.001), twofold higher rate of cesarean (42 vs. 26%, odds ratio: 2.1, 95% confidence interval: 1.26–3.44, p = 0.004), and increased risk of neonatal intensive care unit (NICU) admission (21 vs. 11%, p = 0.024). There was a nonsignificant increased risk of chorioamnionitis (12 vs. 7%, p = 0.1) and maternal morbidity (15 vs. 8%, p = 0.08) in the misoprostol followed by Foley catheter group.

Conclusion In women receiving misoprostol for induction, nulliparas and those with dilation <1 cm are more likely to have subsequent Foley catheter placement. Sequential use of cervical Foley catheter after misoprostol is associated with longer labor, higher cesarean rate, and increased NICU admission. Requirement of Foley catheter after misoprostol confers higher risk and may guide counseling.

Key Points
Allicin suppresses growth and metastasis of gastric carcinoma: the key role of microRNA-383-5p-mediated inhibition of ERBB4 signaling
Authors: Lv Qing , Xia Qinghua , Li Jiang , Wang Zhiyong
Published: June 2020

Allicin is a natural product suppressing the progression of gastric carcinoma (GC). In the current study, the mechanism underlying the anti-GC effect of allicin was explored by focusing on the role of miR-383-5p/ERBB4 signaling. Two GC cell lines were treated with allicin and the effects on viability, apoptosis, migration, invasion, and miR-383-5p/ERBB4 activity in the cells were assessed. The interaction between allicin and miR-383-5p was further explored by inhibiting the miR-383-5p level. Allicin suppressed cell viability and induced apoptosis in both GC cell lines. The compound also inhibited migration and invasion of GC cells, which was associated with the up-regulation miR-383-5p and down-regulation of ERBB4. The inhibition of miR-383-5p by specific inhibitor blocked the anti-GC effect of allicin. Our results demonstrated that allicin contributed to the suppressed growth and metastasis potentials in GC cell lines. The effect was accompanied by an increased level of miR-383-5p and subsequent inhibition of ERBB4.
Aggregability of β(1→4)-linked glucosaminoglucan originating from a sulfur-oxidizing bacterium Thiothrix nivea
Authors: Takeda Minoru , Kondo Keiko , Tominaga Ryo , Mori Honomi , Kato Mana , Usami Ryoji , Murakami Tomoi , Ueda Kazuyoshi , Suzuki Ichiro , Katahira Masato
Published: June 2020

β-1,4-glucosaminoglucan (GG) was prepared from the sheath of a sulfur-oxidizing bacterium Thiothrix nivea. Recently, GG was found to be adsorbed by cellulose (paper) and is therefore potentially applicable as an aminating agent for cellulose. We attempted to increase the yield of GG using a fed-batch cultivation method. Furthermore, the behavior of GG molecules in water was theoretically and experimentally investigated. NMR analysis in combination with molecular dynamics calculation suggested that GG molecules tend to form soluble aggregates in water. It was experimentally revealed that the self-aggregation is enhanced by the addition of NaCl and reduced temperature. Adsorption of GG onto cellulose via hydrogen bonding was confirmed by molecular dynamics simulation. Adsorption was also promoted in the presence of NaCl but was inhibited by a reduction in temperature. Only 11% of the amino groups in the GG-treated paper was reactive, suggesting that GG molecules adsorbed by the paper were forming aggregates.
Actinomycins inhibit the production of the siderophore pyoverdines in the plant pathogen Pseudomonas cichorii SPC9018
Authors: Maenaka Risa , Tani Shuji , Hikichi Yasufumi , Kai Kenji
Published: June 2020

Pyoverdines, a group of peptide siderophores produced by Pseudomonas species, function not only in iron acquisition, but also in their virulence in hosts. Thus, chemical inhibition of pyoverdine production may be an effective strategy to control Pseudomonas virulence. In the plant pathogen Pseudomonas cichorii SPC9018 (SPC9018), pyoverdine production is required for virulence on eggplant. We screened microbial culture extracts in a pyoverdine-production inhibition assay of SPC9018 and found Streptomyces sp. RM-32 as a candidate-producer. We isolated two active compounds from RM-32 cultures, and elucidated their structures to be actinomycins X2 and D. Actinomycins X2 and D inhibited pyoverdine production by SPC9018 with IC50 values of 17.6 and 29.6 μM, respectively. Furthermore, pyoverdine production in other Pseudomonas bacteria, such as the mushroom pathogen P. tolaasii, was inhibited by the actinomycins. Therefore, these actinomycins may be useful as chemical tools to examine pyoverdine functions and as seed compounds for anti-Pseudomonas virulence agents.
Identification of copy number variation and population analysis of the sacred lotus (Nelumbo nucifera)
Authors: Zhang Qing , Zhang Xueting , Liu Jing , Mao Chaoyi , Chen Sha , Zhang Yujun , Leng Liang
Published: June 2020

The sacred lotus (Nelumbo nucifera) is widely cultured in East Asia for its horticultural, agricultural, and medicinal values. Although many molecular markers had been used to extrapolate population genetics of the sacred lotus, a study of large variations, such as copy number variation (CNV), are absent up to now. In this study, we applied whole-genome re-sequencing to 24 lotus accessions, and use read depth information to genotype and filter original CNV call. Totally 448 duplications and 4,267 deletions were identified in the final CNV set. Further analysis of population structure revealed that the population structure patterns revealed by CNV and SNP are largely consistent with each other. Our result indicated that deep sequencing followed by genotyping is a quick and straightforward way to mine out CNV from the population, and the CNV along with SNP could enable us to better comprehend the biology of the plant.
Sophocarpine exert protective effect against ox-LDL-induced endothelial damage via regulating NF-κB signaling pathway
Authors: Fang Hengrong , Bo Taizhu , Zi Xiaolong , Tan Dianxiang , Liu Xiaoping , Jiang Chonghui , Lei Gang , Deng Yufen , Cui Libao
Published: June 2020

Oxidized low-density lipoprotein (ox-LDL) was known to induce endothelial cell injury to the progression of atherosclerosis (AS). Sophocarpine (SPC), a compound of sophora alkaloids isolated from the plant Sophora alopecuroides, has been shown to exhibit various pharmacological activities. This study was designed to investigate the protective effect of SPC on ox-LDL-induced endothelial cells and explored its underlying mechanism. Our results show that SPC pre-incubation ameliorated ox-LDL-mediated HAECs cytotoxicity, DNA fragmentation, and apoptosis in a dose-dependent manner. Moreover, SPC significantly downregulated the mRNA or protein expression level of pro-inflammatory mediators (TGF-β, IL-6, IL-1β, TNF-α) and pro-inflammatory vascular adhesion molecules (VCAM-1, ICAM-1, and E-selectin). Mechanistically, SPC pre-treatment downregulated IκBα expression and inhibited translocation of NF-κB in ox-LDL-mediated HAECs, overexpression of NF-κB p65 counteracted the cytoprotective and anti-apoptotic effect of SPC, suggesting that its action is dependent on NF-κB signaling pathway. Collectively, SPC suppresses ox-LDL-induced HAECs injury by inhibiting the NF-κB signaling pathway.
Policy learning and crisis policy-making: quadruple-loop learning and COVID-19 responses in South Korea
Authors: Lee Sabinne , Hwang Changho , Moon M Jae
Published: June 2020

This study aims to analyze how the Korean government has been effective in taming COVID-19 without forced interruptions (i.e. lockdowns) of citizens’ daily lives. Extending the theory of organizational learning, we propose the quadruple-loop learning model, through which we examine how a government can find solutions to a wicked policy problem like COVID-19. The quadruple-loop learning model is applied to explain how the Korean government could effectively tame COVID-19 in the initial stage through its agile as well as adaptive approach based on effective interactions of backstage (time, target, and context) and frontstage of policy processes mainly focusing on the initial stage until the highest alert level was announced. Based on the Korean case, this study also examines critical factors to effective learning organizations such as leadership, information and transparency, as well as citizen participation and governance.
Rewilding the wildlife in Sangjiangyuan National Park, Qinghai-Tibetan Plateau
Authors: Zhao Xinquan , Xu Tianwei , Ellis Jacob , He Fuquan , Hu Linyong , Li Qi
Published: June 2020

The targets of China’s national park construction are to protect the authenticity and integrity of the ecosystems, and to achieve the harmonious development between humans and nature. Because of the high intensity of human activities, the authenticity of ecosystems has deviated over the past few decades. It is time to rewild the wildlife and restore the authenticity of these ecosystems. The status of rewilding wildlife in Sanjiangyuan National Park, indicating that the wildlife population, diversity and wildness have increased within the National Park. The wildlife population in the national park has been restored, with about 60,000 Tibetan antelope, 60,000 Tibetan gazelle, 36,000 Tibetan wild ass, 10,000 wild yak, and 10,000 white-lipped deer up to 2017. However, overgrazing existed on the alpine grassland with population increasing both of ungulates and livestock.
Long duration response in Parkinson’s disease: levodopa revisited
Authors: Poewe Werner , Espay Alberto J
Published: June 2020

This scientific commentary refers to ‘Natural history of motor symptoms in Parkinson’s disease and the long-duration response to levodopa’, by Cilia etal. (doi:10.1093/brain/awaa181).
Epic Regained: Phillis Wheatley’s Admonitory Poetics in the ‘Little Columbiad’
Authors: Toscano Pasquale S
Published: June 2020

Although many scholars have  discussed Phillis Wheatley’s subversive appropriation of the classics, they have been reluctant to locate a similar strain of subtle repudiation in her Revolutionary War poems. The present article reexamines these verses — ‘To His Excellency General Washington’ (1775), ‘On the Capture of General Lee’ (1776), and ‘On the Death of General Wooster’ (1778) — in light of the tradition of (neo)classical heroic poetry. I read them as a formally innovative epic, dispersed across three apparently ‘patriotic lyrics’ (Levernier (1993: 175)) and dubbed the ‘Little Columbiad’ for their personification of America. Wheatley signals that the triptych should be read as far more than a trio of occasional poems. She not only evokes elements of the epic tradition but also obfuscates the Lucanic heart of her piece within a Virgilian body. This deft juxtaposition of disparate epic registers and forms allows the poet to reprove revolutionary generals, comment upon the war, and decry a movement committed both to liberty and to slavery’s perpetuation. In playing the part of epic admonisher, Wheatley likewise spotlights the genre’s tendency to expose and dissect the flaws of leaders in even its most laudatory iterations. The ‘Little Columbiad’ therefore gives us an important opportunity to reevaluate its author’s pivotal position in the history of North American heroic poetry and epic reception, as well as to nuance regnant paradigms of the genre itself.
Unravelling sexual care in chronically ill patients: the perspective of GP practice nurses; Health Service Research
Authors: Barnhoorn Pieter C , Zuurveen Hannah R , Prins Inge C , van Ek Gaby F , den Oudsten Brenda L , den Ouden Marjolein E M , Putter Hein , Numans Mattijs E , Elzevier Henk W
Published: June 2020

Background

Assessment of sexual health is important in chronically ill patients, as many experience sexual dysfunction (SD). The general practice nurse (GPN) can play a crucial part in addressing SD.

Objective

The aim of this cross-sectional study was to examine to which extent GPNs discuss SD with chronically ill patients and what barriers may refrained them from discussing SD. Furthermore, we examined which factors had an association with a higher frequency of discussing SD.

Methods

A cross-sectional survey using a 48-item questionnaire was send to 637 GPNs across the Netherlands.

Results

In total, 407 GPNs returned the questionnaire (response rate 63.9%) of which 337 completed the survey. Two hundred and twenty-one responding GPNs (65.6%) found it important to discuss SD. More than half of the GPNS (n = 179, 53.3%) never discussed SD during a first consultation, 60 GPNs (18%) never discussed SD during follow-up consultations. The three most important barriers for discussing SD were insufficient training (54.7%), ‘reasons related to language and ethnicity’ (47.5%) and ‘reasons related to culture and religion’ (45.8%). More than half of the GPNs thought that they had not enough knowledge to discuss SD (n = 176, 54.8%). A protocol on addressing SD would significantly increase discussing during SD.

Conclusions

This study indicates that GPNs do not discuss SD with chronically ill patients routinely. Insufficient knowledge, training and reasons related to cultural diversity were identified as most important reasons for this practice pattern. Implementation of training in combination with guidelines on SD in the general practice could improve on the discussing of sexual health with chronic patients.
Seasonal effects of river flow on microbial community coalescence and diversity in a riverine network
Authors: Luo Xia , Xiang Xinyi , Yang Yuanhao , Huang Guoyi , Fu Kaidao , Che Rongxiao , Chen Liqiang
Published: June 2020

Terrestrial microbial communities may take advantage of running waters and runoff to enter rivers and mix with aquatic microorganisms. However, the environmental factors governing the interchange of the microbial community within a watercourse and its surrounding environment and the composition of the resulting community are often underestimated. The present study investigated the effect of flow rate on the mixing of water, soil, sediment and biofilm at four sites along the Lancang River and one branch of the river in winter and summer and, in turn, the resultant changes in the microbial community within each habitat. 16S rRNA gene-based Illumina high-throughput sequencing illustrated that bacterial communities were apparently distinct among biofilm, water, soil and sediment. Biofilms had the lowest richness, Shannon diversity and evenness indices compared with other habitats, and those three indices in all habitats increased significantly from winter to summer. SourceTracker analysis showed a significant coalescence between the bacterial communities of sediment, water and biofilm samples at lower flow rates. Additionally, the proportion of Betaproteobacteria in sediment and biofilms increased with a decrease in flow rate, suggesting the flow rate had a strong impact on microbial community composition and exchange among aquatic habitats. These results were further confirmed by a Mantel test and linear regression analysis. Microbial communities in all samples exhibited a significant but very weak distance–decay relationship (r = 0.093, P = 0.024). Turbidity played a much more important role on water bacterial community structure in summer (i.e. rainy season) (BIOENV, r = 0.92). Together, these results suggest that dispersal is an important factor affecting bacterial community structure in this system.
The tumor immune microenvironment transcriptomic subtypes of colorectal cancer for prognosis and development of precise immunotherapy
Authors: Tang Yun-Qiang , Chen Tu-Feng , Zhang Yan , Zhao Xiao-Chen , Zhang Yu-Zi , Wang Guo-Qiang , Huang Meng-Li , Cai Shang-Li , Zhao Jing , Wei Bo , Huang Jun
Published: June 2020

Background

Biomarkers based on immune context may guide prognosis prediction. T-cell inactivation, exclusion, or dysfunction could cause unfavorable tumor microenvironments, which affect immunotherapy and prognosis. However, none of the immuno-biomarkers reported to date can differentiate colorectal-cancer (CRC) patients. Thus, we aimed to classify CRC patients according to the levels of T-cell activation, exclusion, and dysfunction in the tumor microenvironment.

Methods

RNAseq data of 618 CRC patients from The Cancer Genome Atlas and microarray data of 316 CRC patients from Gene Expression Omnibus were analysed using the Tumor Immune Dysfunction and Exclusion algorithm. Unsupervised clustering was used to classify patients.

Results

Based on the expression signatures of myeloid-derived suppressor cells, cancer-associated fibroblasts, M2-like tumor-associated macrophages, cytotoxic T-lymphocytes, and PD-L1, all patients were clustered into four subtypes: cluster 1 had a high level of immune dysfunction, cluster 2 had a low level of immune activation, cluster 3 had intense immune exclusion, and cluster 4 had a high level of immune activation and a moderate level of both dysfunction and exclusion signatures. Compared with cluster 1, the hazard ratios and 95% confidential intervals for overall survival were 0.63 (0.35–1.13) for cluster 2, 0.55 (0.29–1.03) for cluster 3, and 0.30 (0.14–0.64) for cluster 4 in multivariate Cox regression. Similar immune clustering and prognosis patterns were obtained upon validation in the GSE39582 cohort. In subgroup analysis, immune clustering was significantly associated with overall survival among stage I/II patients, microsatellite stable/instability-low patients, and patients not treated with adjuvant therapy.

Conclusions

Our findings demonstrated that classifying CRC patients into different immune subtypes serves as a reliable prognosis predictor and may help to refine patient selection for personalized cancer immunotherapy.
The New Philippine Innovation Laws: A Response to the Call of MSMEs and Start-Ups
Authors: Ilas-Panganiban Divina , Mitra-Ventanilla Reena
Published: June 2020

Innovation is essential to driving national progress. As such, it has to be fostered, safeguarded and incentivized. In order for innovation and technological growth to flourish, it is necessary to have a robust intellectual property regime coupled with effective government policies. Developing countries face many challenges when it comes to harnessing innovation and creating the right environment that will support and nourish it. Extra attention should be given to small and medium-sized enterprises, as they are more likely to be at risk due to financing, productivity and regulatory burdens.

Although the Philippines has lagged behind in the area of innovation, recent national policies have been adopted to improve the country's position. The recent legislations, namely, the Philippine Innovation Act, the Innovative Startup Act and the Personal Property Security Act, are all aimed to create an environment that creates opportunities towards sustaining and incentivizing innovation. The Philippines designed a ‘whole of government’ approach, which seeks to effectively drive innovation across all areas of government policy and to better facilitate engagement of businesses, R&D entities and other relevant sectors in the community. These laws, however, are but the first steps in the right direction. Proper implementation, constant monitoring and fine-tuning are essential for a national innovation policy to succeed.
Convergence of a finite-volume scheme for a degenerate-singular cross-diffusion system for biofilms
Authors: Daus Esther S , Jüngel Ansgar , Zurek Antoine
Published: June 2020

An implicit Euler finite-volume scheme for a cross-diffusion system modeling biofilm growth is analyzed by exploiting its formal gradient-flow structure. The numerical scheme is based on a two-point flux approximation that preserves the entropy structure of the continuous model. Assuming equal diffusivities the existence of non-negative and bounded solutions to the scheme and its convergence are proved. Finally, we supplement the study by numerical experiments in one and two space dimensions.
Definition and Risks of Cytokine Release Syndrome in 11 Critically Ill COVID-19 Patients With Pneumonia: Analysis of Disease Characteristics
Authors: Wang Wenjun , Liu Xiaoqing , Wu Sipei , Chen Sibei , Li Yimin , Nong Lingbo , Lie Puyi , Huang Liyan , Cheng Linling , Lin Yongping , He Jianxing
Published: June 2020

Corona virus disease 2019 (COVID-19) patients with severe immune abnormalities are at risk of cytokine release syndrome (CRS). The definition, prevention, and treatment of symptoms of CRS in critically ill patients with COVID-19 are important problems. We report a single-center case series of 11 COVID-19 patients with acute respiratory distress syndrome from The First Affiliated Hospital of Guangzhou Medical University in China from 26 January 2020 to 18 February 2020. The termination date of follow-up was 19 February 2020. Eight patients were determined to have characteristics of CRS, including pulmonary inflammation, fever, and dysfunction of nonpulmonary organs. An increase in interleukin-6 in peripheral blood was the highest risk factor and an early indicator of CRS in COVID-19.
Intelligent Liver Function Testing: Working Smarter to Improve Patient Outcomes in Liver Disease
Authors: Macpherson Iain , Nobes Jennifer H , Dow Eleanor , Furrie Elizabeth , Miller Michael H , Robinson Emma M , Dillon John F
Published: June 2020

Chronic liver disease (CLD) is a significant health problem affecting millions of people worldwide. In Scotland, CLD is a major cause of premature mortality. Liver function tests (LFTs) are a panel of frequently requested blood tests which may indicate liver disease. However, LFTs commonly contain at least one abnormal result, and abnormalities are rarely investigated to the extent recommended by national guidelines. The intelligent Liver Function Testing (iLFT) pathway is a novel, automated system designed to improve early diagnosis of liver disease. Initial abnormal LFT results trigger a cascade of reflexive testing to help identify the cause of any liver dysfunction. Algorithms combine these results with demographic and clinical data (such as patient age, body mass index, and alcohol intake) and fibrosis estimates to produce an electronic diagnosis and management plan. The pilot trial demonstrated that iLFT increased diagnosis of liver disease whilst remaining cost-effective. As such, iLFT has been fully operational across our region (NHS Tayside, Scotland) since August 2018. In the first year, iLFT generated over 2000 diagnoses from 1824 patient samples with an abnormality in the initial LFTs. The majority of these patients could be safely managed in primary care. iLFT allows maximal value to be obtained from liver blood tests across biochemistry, virology, immunology, and hematology with only minor changes to working practices. ‘Intelligent’, algorithm-led testing pathways break down the barrier between clinical and laboratory medicine and offer solutions to many of the challenges experienced in modern healthcare systems.
Building for the future: the creation of a residency training track to foster innovation through clinical informatics in psychiatry
Authors: Vitiello Evan , Kane Michael , Hutto Alissa , Hall Austin
Published: June 2020

Early clinical informatics (CI) education provides an introduction to CI methodologies for resident physicians to apply within their boarded specialties. A specialty notably absent from the effort to train residents in CI is psychiatry. We present a novel means of integrating CI exposure into a structured educational track within a psychiatry residency training program. The clinical informatics track at the University of North Carolina Department of Psychiatry is a 3-year, longitudinal experience open to residents starting in postgraduate year 2. To our knowledge, this is the first track of its kind within a psychiatry residency training program.
Stakeholder bias in best practice advisories: an ethical perspective
Authors: Baird Aaron , Kibbe Bryan , Lesandrini Jason
Published: June 2020

Clinicians are increasingly being asked to heed and follow the guidance provided by “best practice advisories.” Such advisories, often in the form of electronic reminders or alerts, are meant to increase the efficiency and effectiveness of evidence-based medical practice. However, we argue that best practice advisories can sometimes be infused with stakeholder bias, even if inadvertently. We specifically argue that best practice advisory biases can occur when an advisory is not oriented to benefit patients at least as much or more than other stakeholders. To address this issue, we put forth the perspective that ethical consideration of biases is especially important in best practice advisory design and revision processes.