bluuebunny/crossref_metadata_2025 huggingface dataset:
Fermented mulberry (Morus alba) leaves suppress high fat diet-induced hepatic steatosis through amelioration of the inflammatory response and autophagy pathway
Authors: Lee Mi Rim , Kim Ji Eun , Park Ji Won , Kang Mi Ju , Choi Hyeon Jun , Bae Su Ji , Choi Young Whan , Kim Kyung Mi , Hong Jin Tae , Hwang Dae Youn
Published: September 2020

Background

A novel extract of mulberry leaves fermented with Cordyceps militaris (EMfC) is reported to exert anti-obesity activity, although their molecular mechanism during hepatic steatosis has not verified.

Methods

To investigate the role of inflammation and autophagy during the anti-hepatic steatosis effects of EMfC, we measured alterations in the key parameters for inflammatory response and autophagy pathway in liver tissues of the high fat diet (HFD) treated C57BL/6N mice after exposure to EMfC for 12 weeks.

Results

Significant anti-hepatic steatosis effects, including decreased number of lipid droplets and expression of Klf2 mRNA, were detected in the liver of the HFD + EMfC treated group. The levels of mast cell infiltration, expression of two inflammatory mediators (iNOS and COX-2), and the MAPK signaling pathway were remarkably decreased in the liver of HFD + EMfC treated group as compared to the HFD + Vehicle treated group. Furthermore, a similar inhibitory effect was measured for the expression levels of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α and NF-κB. The expression level of members in the AKT/mTOR signaling pathway (a central regulator in autophagy) was recovered after treatment with EMfC, and autophagy-related proteins (Beclin and LC3-II) were remarkably decreased in the HFD + EMfC treated group compared to the HFD + Vehicle treated group. Moreover, the HFD + EMfC treated group showed decreased transcript levels of autophagy-regulated genes including Atg4b, Atg5, Atg7 and Atg12.

Conclusions

Taken together, findings of the present study provide novel evidences that the anti-hepatic steatosis of EMfC is tightly linked to the regulation of the inflammatory response and autophagy pathway in the liver tissue of HFD-induced obesity mice.
A network pharmacology study on analgesic mechanism of Yuanhu-Baizhi herb pair
Authors: Mi Bobin , Li Qiushi , Li Tong , Marshall Jessica , Sai Jiayang
Published: September 2020

Background

Millions of people are suffering from chronic pain conditions, such as headache, arthritis, cancer. Apart from western medicines, traditional Chinese medicines are also well accepted for pain management, especially in Asian countries. Yuanhu-Baizhi herb pair (YB) is a typical herb pair applied to the treatment of stomach pain, hypochondriac pain, headache, and dysmenorrhea, due to its effects on analgesia and sedation. This study is to identify potentially active compounds and the underlying mechanisms of YB in the treatment of pain.

Methods

Compounds in YB were collected from 3 online databases and then screened by bioavailability and drug likeness parameters. Swiss target prediction was applied to obtain targets information of the active compounds. Pain-related genes were conducted for Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Protein-protein interaction (PPI) networks of the genes were constructed using Cytoscape software. In addition, the hub genes were screened using maximal clique centrality (MCC) algorithm.

Results

In total, 31 compounds from Yuanhu were screened out with 35 putative target genes, while 26 compounds in Baizhi with 43 target genes were discovered. Hence, 78 potential target genes of YB were selected for further study. After overlap analysis of the 78 genes of YB and 2408 pain-associated genes, we finally achieved 34 YB-pain target genes, as well as 10 hub genes and 23 core compounds. Go enrichment and KEGG pathway analysis indicated that YB had a strong integration with neuro system, which might significantly contribute to antinociceptive effect.

Conclusion

Our data provide deep understanding of the pharmacological mechanisms of YB in attenuating pain. The discovery shed new light on the development of active compounds of YB for the treatment of pain.
Learning outcomes of a flipped classroom teaching approach in an adult-health nursing course: a quasi-experimental study
Authors: Fan Jun-Yu , Tseng Ying-Jung , Chao Li-Fen , Chen Shiah-Lian , Jane Sui-Whi
Published: September 2020

Background

New teaching strategies must be developed not only to enhance nurse’s competence but also to allow nurses to respond to the complex health care needs of today’s society. The purpose of this study was to explore the learning outcomes of a flipped classroom teaching approach in an adult-health nursing course for students in a two-year Bachelor of Science in Nursing program.

Methods

The study had a quasi-experimental design. An 18-week flipped classroom teaching approach was applied in an adult-health nursing course. In total, 485 nursing students enrolled in the study, with 287 in the experimental group and 198 in the control group. The Self-Evaluated Core Competencies Scale, Metacognitive Inventory for Nursing Students, Self-Directed Learning Readiness Scale, and self-designed learning satisfaction questionnaire were used to evaluate the students’ learning outcomes.

Results

The experimental group showed a statistically significant increase in the overall scores for self-evaluated core competencies, the “self-modification” subscale of the Metacognitive Inventory for Nursing Students, and in overall self-directed learning readiness; further, they also showed high levels of course satisfaction.

Conclusions

A flipped classroom teaching approach had a positive impact on student’s learning motivation and contributed to better learning outcomes in an adult-health nursing course. The flipped classroom combined with hybrid teaching methods is a suitable and effective learning strategy for a registered nurse (RN) to Bachelor of Science in Nursing (BSN) program to tackle today’s complex revolution in nursing curricula, and may enhance nursing students’ abilities to address numerous challenges.
A practical approach to the ethical use of memory modulating technologies
Authors: Tan Shawn Zheng Kai , Lim Lee Wei
Published: September 2020

Background

Recent advancements in neuroscientific techniques have allowed us to make huge progress in our understanding of memories, and in turn has paved the way for new memory modification technologies (MMTs) that can modulate memories with a degree of precision, which was not previously possible. With advancements in such techniques, new and critical ethical questions have emerged. Understanding and framing these ethical questions within the current philosophical theories is crucial in order to systematically examine them as we translate these techniques to the clinic.

Main body

In this paper, we discuss the ethical implications of modern neuroscience techniques that aim to disrupt or enhance memories. We attempt to frame the MMTs in the context of existing ethical philosophical theories to provide a cohesive analysis of the myriad of ethical quagmires that might emerge from such technologies. We argue the application of Aristotle’s Golden Mean and multiple accounts of authenticity are useful in approaching the ethical questions surrounding MMTs. We then propose a framework in which ethical considerations can be systematically examined. Lastly, we provide caveats and considerations for the use of this framework. Overall, we provide a practical approach for the ethical use of MMTs depending on the situation.

Conclusion

While at face value, our model appears to put severe limitations on the application of MMTs, we are not completely opposed to their use, but rather our framework guides the agent to consider the implications before making any decisions. Most importantly, we argue that the use of MMTs does not reduce the responsibility of the initial decision, and the agent must accept the post-MMT self as the new “true self” regardless of the outcome. As the developmental trajectory of MMTs suggests we are getting closer to practical clinical applications, ethical concerns across a wide range of disciplines need to be addressed to develop best strategies and policies when dealing with MMTs. If this can be achieved, we believe the ethical use of MMTs is not only possible but would also be of tremendous benefit to many people suffering from memory-related mental disorders.
Radiation recall pneumonitis induced by PD-1/PD-L1 blockades: mechanisms and therapeutic implications
Authors: Teng Feifei , Li Min , Yu Jinming
Published: September 2020

Background

The synergistic effect of radiotherapy (RT) in combination with immunotherapy has been shown in several clinical trials and case reports. The overlapping pulmonary toxicity induced by thoracic RT and programmed death 1/programmed death ligand-1 (PD-1/PD-L1) blockades is an important issue of clinical investigation in combination treatment. Thus far, the underlying mechanism of this toxicity remains largely unknown.

Main text

In this review, we discuss the unique pattern of radiation recall pneumonitis (RRP) induced by PD-1 blockade. The clinical presentation is different from common radiation pneumonitis (RP) or RRP induced by cytotoxic drugs. The immune checkpoint inhibitors may evoke an inflammatory reaction in patients’ previously irradiated fields, with infiltrating lymphocytes and potential involvement of related cytokines. All RRP patients have showed durable response to anti-PD-1/PD-L1. RRP is manageable; however, interruption of checkpoint blockades is necessary and immunosuppressive treatment should be started immediately. Further analyses of the predictive factors, including RT dosimetric parameters, tumor-infiltrating lymphocytes (TILs), and PD-L1 expression, are needed given the wide use of immune checkpoint inhibitors and high mortality from lung toxicity with the combination treatment.

Conclusion

Immune checkpoint inhibitors may evoke an RRP in the patients’ previously irradiated fields. Interactions between immune checkpoint inhibitors and radiotherapy should be studied further.
Mutation profiling in eight cases of vagal paragangliomas
Authors: Kudryavtseva Anna V. , Kalinin Dmitry V. , Pavlov Vladislav S. , Savvateeva Maria V. , Fedorova Maria S. , Pudova Elena A. , Kobelyatskaya Anastasiya A. , Golovyuk Alexander L. , Guvatova Zulfiya G. , Razmakhaev George S. , Demidova Tatiana B. , Simanovsky Sergey A. , Slavnova Elena N. , Poloznikov Andrey А. , Polyakov Andrey P. , Melnikova Nataliya V. , Dmitriev Alexey A. , Krasnov George S. , Snezhkina Anastasiya V.
Published: September 2020

Background

Vagal paragangliomas (VPGLs) belong to a group of rare head and neck neuroendocrine tumors. VPGLs arise from the vagus nerve and are less common than carotid paragangliomas. Both diagnostics and therapy of the tumors raise significant challenges. Besides, the genetic and molecular mechanisms behind VPGL pathogenesis are poorly understood.

Methods

The collection of VPGLs obtained from 8 patients of Russian population was used in the study. Exome library preparation and high-throughput sequencing of VPGLs were performed using an Illumina technology.

Results

Based on exome analysis, we identified pathogenic/likely pathogenic variants of the SDHx genes, frequently mutated in paragangliomas/pheochromocytomas. SDHB variants were found in three patients, whereas SDHD was mutated in two cases. Moreover, likely pathogenic missense variants were also detected in SDHAF3 and SDHAF4 genes encoding for assembly factors for the succinate dehydrogenase (SDH) complex. In a patient, we found a novel variant of the IDH2 gene that was predicted as pathogenic by a series of algorithms used (such as SIFT, PolyPhen2, FATHMM, MutationTaster, and LRT). Additionally, pathogenic/likely pathogenic variants were determined for several genes, including novel genes and some genes previously reported as associated with different types of tumors.

Conclusions

Results indicate a high heterogeneity among VPGLs, however, it seems that driver events in most cases are associated with mutations in the SDHx genes and SDH assembly factor-coding genes that lead to disruptions in the SDH complex.
Transcriptome analysis of peripheral whole blood identifies crucial lncRNAs implicated in childhood asthma
Authors: Zheng Peiyan , Huang Chen , Leng Dongliang , Sun Baoqing , Zhang Xiaohua Douglas
Published: September 2020

Background

Asthma is a chronic disorder of both adults and children affecting more than 300 million people heath worldwide. Diagnose and treatment for asthma, particularly in childhood asthma have always remained a great challenge because of its complex pathogenesis and multiple triggers, such as allergen, viral infection, tobacco smoke, dust, etc. It is thereby great significant to deeply investigate the transcriptome changes in asthmatic children before and after desensitization treatment, in order that we could identify potential and key mRNAs and lncRNAs which might be considered as useful RNA molecules for observing and supervising desensitization therapy for asthma, which might guide the diagnose and therapy in childhood asthma.

Methods

In the present study, we performed a systematic transcriptome analysis based on the deep RNA sequencing of ten asthmatic children before and after desensitization treatment, including identification of lncRNAs using a stringent filtering pipeline, differential expression analysis and network analysis, etc.

Results

First, a large number of lncRNAs were identified and characterized. Then differential expression analysis revealed 39 mRNAs and 15 lncRNAs significantly differentially expressed which involved in two biological processes and pathways. A co-expressed network analysis figured out a desensitization-treatment-related module which contains 27 mRNAs and 21 lncRNAs using WGCNA R package. Module analysis disclosed 17 genes associated to asthma at distinct level. Subsequent network analysis based on PCC figured out several key lncRNAs probably interacted to those key asthma-related genes, i.e., LINC02145, GUSBP2. Our functional investigation indicated that their functions might involve in immune, inflammatory response and apoptosis process.

Conclusions

Our study successfully discovered many key noncoding RNA molecules related to pathogenesis of asthma and relevant treatment, which may provide some clues for asthmatic diagnose and therapy in future.
A sporadic case of congenital aniridia caused by pericentric inversion inv(11)(p13q14) associated with a 977 kb deletion in the 11p13 region
Authors: Vasilyeva Tatyana A. , Marakhonov Andrey V. , Minzhenkova Marina E. , Markova Zhanna G. , Petrova Nika V. , Sukhanova Natella V. , Koshkin Philipp A. , Pyankov Denis V. , Kanivets Ilya V. , Korostelev Sergey A. , Krynskaya Irina A. , Shilova Nadezhda V. , Kutsev Sergey I. , Kadyshev Vitaly V. , Zinchenko Rena A.
Published: September 2020

Background

Because of the significant occurrence of “WAGR-region” deletions among de novo mutations detected in congenital aniridia, DNA diagnosis is critical for all sporadic cases of aniridia due to its help in making an early diagnosis of WAGR syndrome. Standard cytogenetic karyotype study is a necessary step of molecular diagnostics in patients with deletions and in the patients’ parents as it reveals complex chromosomal rearrangements and the risk of having another affected child, as well as to provide prenatal and/or preimplantation diagnostics.

Case presentation

DNA samples were obtained from the proband (a 2-year-old boy) and his two healthy parents. Molecular analysis revealed a 977.065 kb deletion that removed loci of the ELP4, PAX6, and RCN1 genes but did not affect the coding sequence of the WT1 gene. The deletion occurred de novo on the paternal allele. The patient had normal karyotype 46,XY and a de novo pericentric inversion of chromosome 11, inv(11)(p13q14).

Conclusions

We confirmed the diagnosis of congenital aniridia at the molecular level. For the patient, the risk of developing Wilms’ tumor is similar to that in the general population. The recurrence risk for sibs in the family is low, but considering the possibility of gonadal mosaicism, it is higher than in the general population.
Thrombospondin-1/CD47 signaling modulates transmembrane cation conductance, survival, and deformability of human red blood cells
Authors: Bissinger Rosi , Petkova-Kirova Polina , Mykhailova Olga , Oldenborg Per-Arne , Novikova Elena , Donkor David A. , Dietz Thomas , Bhuyan Abdulla Al Mamun , Sheffield William P. , Grau Marijke , Artunc Ferruh , Kaestner Lars , Acker Jason P. , Qadri Syed M.
Published: September 2020

Background

Thrombospondin-1 (TSP-1), a Ca2+-binding trimeric glycoprotein secreted by multiple cell types, has been implicated in the pathophysiology of several clinical conditions. Signaling involving TSP-1, through its cognate receptor CD47, orchestrates a wide array of cellular functions including cytoskeletal organization, migration, cell-cell interaction, cell proliferation, autophagy, and apoptosis. In the present study, we investigated the impact of TSP-1/CD47 signaling on Ca2+dynamics, survival, and deformability of human red blood cells (RBCs).

Methods

Whole-cell patch-clamp was employed to examine transmembrane cation conductance. RBC intracellular Ca2+levels and multiple indices of RBC cell death were determined using cytofluorometry analysis. RBC morphology and microvesiculation were examined using imaging flow cytometry. RBC deformability was measured using laser-assisted optical rotational cell analyzer.

Results

Exposure of RBCs to recombinant human TSP-1 significantly increased RBC intracellular Ca2+levels. As judged by electrophysiology experiments, TSP-1 treatment elicited an amiloride-sensitive inward current alluding to a possible Ca2+influx via non-selective cation channels. Exogenous TSP-1 promoted microparticle shedding as well as enhancing Ca2+- and nitric oxide-mediated RBC cell death. Monoclonal (mouse IgG1) antibody-mediated CD47 ligation using 1F7 recapitulated the cell death-inducing effects of TSP-1. Furthermore, TSP-1 treatment altered RBC cell shape and stiffness (maximum elongation index).

Conclusions

Taken together, our data unravel a new role for TSP-1/CD47 signaling in mediating Ca2+influx into RBCs, a mechanism potentially contributing to their dysfunction in a variety of systemic diseases.
Expression profile of SYNE3 and bioinformatic analysis of its prognostic value and functions in tumors
Authors: Liao Liwei , Zhang Longshan , Yang Mi , Wang Xiaoqing , Huang Weiqiang , Wu Xixi , Pan Hua , Yuan Lu , Huang Wenqi , Wu Yuting , Guan Jian
Published: September 2020

Background

Spectrin repeat containing nuclear envelope family member 3 (SYNE3) encodes an essential component of the linker of the cytoskeleton and nucleoskeleton (LINC) complex, namely nesprin-3. In a tumor, invasiveness and metastasis rely on the integrity of the LINC complex, while the role of SYNE3/nesprin-3 in cancer is rarely studied.

Methods

Here, we explored the expression pattern, prognostic value, and related mechanisms of SYNE3 through both experimental and bioinformatic methods. We first detected SYNE3 in BALB/c mice, normal human tissues, and the paired tumor tissues, then used bioinformatics databases to verify our results. We further analyzed the prognostic value of SYNE3. Next, we predicted miRNA targeting SYNE3 and built a competing endogenous RNA (ceRNA) network and a transcriptional network by analyzing data from the cancer genome atlas (TCGA) database. Interacting genes of SYNE3 were predicted, and we further performed GO and KEGG enrichment analysis on these genes. Besides, the relationship between SYNE3 and immune infiltration was also investigated.

Results

SYNE3 exhibited various expressions in different tissues, mainly located on nuclear and in cytoplasm sometimes. SYNE3 expression level had prognostic value in tumors, possibly by stabilizing nucleus, promoting tumor cells apoptosis, and altering tumor microenvironment. Additionally, we constructed a RP11-2B6.2-miR-149-5p-/RP11-67L2.2-miR-330-3p-SYNE3 ceRNA network and a SATB1-miR-149-5p-SYNE3 transcriptional network in lung adenocarcinoma to support the tumor-suppressing role of SYNE3.

Conclusions

Our study explored novel anti-tumor functions and mechanisms of SYNE3, which might be useful for future cancer therapy.
Effect of functional food ingredients on gut microbiota in a rodent diabetes model
Authors: Surono Ingrid S. , Wardana Ata Aditya , Waspodo Priyo , Saksono Budi , Verhoeven Jessica , Venema Koen
Published: September 2020

Background

The gut microbiota has been shown to be involved in the development and severity of type 2 diabetes. The aim of the present study was to test the effect of 4-week functional food ingredient feeding, alone or in combination, on the gut microbiota composition in diabetic rats.

Methods

Streptozotocin (STZ)-induced diabetic rats were treated for 4 weeks with (1) native taro starch, (2) modified taro-starch, (3) beet juice, (4) psicose, (5) the probiotic L. plantarum IS-10506, (6) native starch combined with beet juice, (7) native starch to which beet juice was adsorbed, (8) modified starch combined with beet juice or (9) modified starch to which beet juice was adsorbed, to modulate the composition of the gut microbiota. This composition was evaluated by sequencing the PCR amplified V3–V4 region of the 16S rRNA gene.

Results

The next-generation sequencing showed beneficial effects particularly of taro-starch feeding. Operational taxonomic units (OTUs) related to health (e.g. correlating with low BMI, OTUs producing butyrate) were increased in relative abundance, while OTUs generally correlated with disease (e.g. Proteobacteria) were decreased by feeding taro-starch.

Conclusion

The results of study show that a 4-week intervention with functional food ingredients, particularly taro-derived starch, leads to a more healthy gut microbiota in rats that were induced to be diabetic by induction with STZ.
Using the Red Cross wound classification to predict treatment needs in children with conflict-related limb injuries: a retrospective database study
Authors: van Gennip Lisanne , Haverkamp Frederike J. C. , Muhrbeck Måns , Wladis Andreas , Tan Edward C. T. H.
Published: September 2020

Background

The International Committee of the Red Cross (ICRC) implemented the Red Cross wound classification (RCWC) to quickly assess the severity of a wound in conflict settings. A subdivision into wound grades derived from the RCWC consists of grades 1, 2, and 3, and represents low, major, and massive energy transfer, respectively, to the injured tissue. The aim of this observational study is to assess whether the Red Cross wound grade of a pediatric patient’s wound correlates with patient outcomes.

Methods

All pediatric patients (age < 15 years) treated in an ICRC hospital between 1988 and 2014 for conflict-related penetrating extremity injuries were retroactively included. Correlations were assessed between wound grades and number of surgeries, blood transfusions, days hospitalized, and mortality. Stratification analyses were performed to evaluate potential effect modifiers.

Results

The study included 2463 pediatric patients. Pediatric patients with a higher wound grade received significantly more surgeries (grade 1 median 2; grade 3 median 3), more blood transfusions (grades 1 and 3 received 33.9 and 72.2 units per 100 patients, respectively), and were hospitalized longer (grade 1 median 15; grade 3 median 40 days). Mortality rates did not significantly differ. Stratification analyses did not reveal effect modifiers for the association between wound grades and patient outcomes.

Conclusion

The Red Cross wound grade of a pediatric patient’s extremity wound correlates independently with treatment needs. This simple wound grading system could support clinical decision-making and should be integrated into the clinical assessment of weapon-wounded pediatric patients in conflict settings.
Kappa opioid receptors in the central amygdala modulate spinal nociceptive processing through an action on amygdala CRF neurons
Authors: Ji Guangchen , Neugebauer Volker
Published: September 2020

The amygdala plays an important role in the emotional-affective aspects of behaviors and pain, but can also modulate sensory aspect of pain (“nociception”), likely through coupling to descending modulatory systems. Here we explored the functional coupling of the amygdala to spinal nociception. We found that pharmacological activation of neurons in the central nucleus of the amygdala (CeA) increased the activity of spinal dorsal horn neurons; and this effect was blocked by optogenetic silencing of corticotropin releasing factor (CRF) positive CeA neurons. A kappa opioid receptor (KOR) agonist (U-69,593) was administered into the CeA by microdialysis. KOR was targeted because of their role in averse-affective behaviors through actions in limbic brain regions. Extracellular single-unit recordings were made of CeA neurons or spinal dorsal horn neurons in anesthetized transgenic Crh-Cre rats. Neurons responded more strongly to noxious than innocuous stimuli. U-69,593 increased the responses of CeA and spinal neurons to innocuous and noxious mechanical stimulation of peripheral tissues. The facilitatory effect of the agonist was blocked by optical silencing of CRF-CeA neurons though light activation of halorhodopsin expressed in these neurons by viral-vector. The CRF system in the amygdala has been implicated in aversiveness and pain modulation. The results suggest that the amygdala can modulate spinal nociceptive processing in a positive direction through CRF-CeA neurons and that KOR activation in the amygdala (CeA) has pro-nociceptive effects.
The properties of MOF-Zn2(EBNB)2(BPY)2·2H2O and its basic study of loading methadone
Authors: Linxin Deng , Song Li , Xuehua Sun
Published: September 2020

The ligands of (E)-bis(p-3-nitrobenzoic acid) vinyl (C16H10N2O8) were synthesized in three steps, and then the MOF-Zn2(EBNB)2(BPY)2·2H2O was synthesized by solvothermal method. This structure was characterized by X-ray single crystal diffraction, SEM and TG. The drug loading and in vitro release of Zn2(EBNB)2(BPY)2·2H2O were also studied with Methadone as model drug. The results show that the highest loading amount of Zn2(EBNB)2(BPY)2·2H2O to Methadone was 0.256 g/g, and the drug delivery system was a two-phase mode. The results of in vitro cytotoxicity test show that Zn2(EBNB)2(BPY)2·2H2O has good biocompatibility.
Impact of abiotic factors, habitat type and urban wildlife on the ecology of hard ticks (Acari: Ixodidae) in urban and peri-urban habitats
Authors: Borşan Silvia-Diana , Toma-Naic Andra , Péter Áron , Sándor Attila D. , Peștean Cosmin , Mihalca Andrei-Daniel
Published: September 2020

Background

Ticks are increasingly acknowledged as significant vectors for a wide array of pathogens in urban environments with reports of abundant tick populations in recreational areas. The study aims to contribute to a better knowledge of the abiotic and biotic factors which impact the ecology of hard ticks in urban and peri-urban habitats in Romania.

Methods

Questing ticks were collected by flagging in seven recreational locations, from four types of habitats in Cluj-Napoca, Romania: parks; gardens; a cemetery; and peri-urban forests. Hedgehogs, birds and micromammals were also sampled and searched for ticks, using standard methods (i.e. torch-based searches, ornithological mist nets, snap-traps, etc.), while vegetation was evaluated on surveyed areas. Data on questing ticks were converted to abundance indices. Moodʼs median tests were used to assess the relationship between the abiotic and biotic factors and the abundance of questing ticks.

Results

Two species of questing ticks were found:Ixodes ricinus(96.8%) andHaemaphysalis punctata(3.2%).Ixodes ricinuswas also the predominant engorged tick collected from urban wildlife. ForI. ricinusthe highest mean total abundance index/location (total no. of ticks/100 m2) was recorded in the urban gardens (3.79, 95% CI: ± 1.59) and parks (2.68, 95% CI: ± 0.75), whereas the lowest mean total abundance index was noted in the peri-urban forests (0.06, 95% CI: ± 0.03) and the urban cemetery (0.04, 95% CI: ± 0.02). The adults and nymphs ofI. ricinusdisplayed a bimodal activity pattern, while the larvae showed a unimodal questing behaviour with an autumnal peak. Positive correlations were found between the mean total abundance index and the rise in the daily mean temperature and relative humidity, and between the global abundance of questing ticks and the presence of hedgehogs in the respective locations (P < 0.01).

Conclusions

Ticks were collected in all the recreational sites surveyed in Cluj-Napoca.Ixodes ricinuswas the dominant questing and engorged tick species. Several abiotic and biotic factors shape the ecology of ticks in Cluj-Napoca city, with climate and the local presence of suitable hosts being the most important.
Primary small cell type of non-Hodgkin lymphoma of the colon: a case report
Authors: Meir Eyal , Handler Chovav , Kaplan Uri , Kopelman Doron , Hatoum Ossama A.
Published: September 2020

Introduction

Primary lymphoma of the colon is exceedingly rare and comprises 0.2–1% of all colon tumors. The most common subtype of lymphoma in the colon is non-Hodgkin lymphoma. Symptoms are often nonspecific, and treatment varies between chemotherapy alone and a combination of surgery and chemotherapy.

Case presentation

We describe a case of a Ashkenazi Jew patient who presented in the typical way that carcinoma of the colon might present but turned out to have a very rare type of tumor in both its histology and its location.

Conclusion

There was apparent discordance between the relative bulkiness and gross appearance of the tumor with the unrevealing result of the biopsies, demanding a high level of suspicion as to the actual presence and possible type of such a tumor in the future.
Spectral discretization of time-dependent vorticity–velocity–pressure formulation of the Navier–Stokes equations
Authors: Abdelwahed Mohamed , Chorfi Nejmeddine
Published: September 2020

In this work, we propose a nonstationary Navier–Stokes problem equipped with an unusual boundary condition. The time discretization of such a problem is based on the backward Euler’s scheme. However, the variational formulation deduced from the nonstationary Navier–Stokes equations is discretized using the spectral method. We prove that the time semidiscrete problem and the full spectral discrete one admit at most one solution.
The effect of business cycle expectations on the German apprenticeship market: estimating the impact of Covid-19
Authors: Muehlemann Samuel , Pfeifer Harald , Wittek Bernhard H.
Published: September 2020

A firm’s expectation about the future business cycle is an important determinant of the decision to train apprentices, especially as German firms typically offer apprenticeships to either fill future skilled worker positions, or as a substitute for other types of labor. The current coronavirus crisis will have a strong and negative impact on the German economy, according to the current business cycle expectations of German firms. To the extent that the training decisions of firms depend on these perceptions, we expect a downward shift in firm demand for apprentices and consequently also a decrease in the equilibrium number of apprenticeship contracts. To assess the impact of changes in business cycle expectations, we analyze German data on the apprenticeship market at the state-level and at the occupation-level within states from 2007 to 2019. We apply first-differences regressions to account for unobserved heterogeneity across states and occupations, allowing us to identify the association between changes in two popular measures of business cycle expectations (the ifo Business Climate Index and the ifo Employment Barometer) and subsequent changes in the demand for apprentices, the number of new apprenticeship contracts, unfilled vacancies and unsuccessful applicants. We find that the German apprenticeship market prior to the current crisis can be characterized by excess demand for apprentices (although there are matching problems in some states, with both a high share of unfilled vacancies and a high share of unsuccessful applicants). Taking into account the most recent data on business cycle expectations up to June 2020, we estimate that the coronavirus-related decrease in firms’ expectations about the business cycle can be associated with a predicted 8% decrease in firm demand for apprentices and a 6% decrease in the number of new apprenticeship positions in Germany compared to 2019 (− 30,000 apprenticeship contracts; 95% confidence interval: ± 8000).
A guarded light pipe for direct visualization during primary scleral buckling on the Ngenuity platform
Authors: Agranat Joshua S. , Douglas Vivian P. , Douglas Konstantinos A. A. , Miller John B.
Published: September 2020

Background

Visualization during scleral buckling is traditionally achieved via indirect ophthalmoscopy. Recent advances have utilized the surgical microscope and a 25 gauge cannula-based endoillumination system, also known as a Chandelier lighting system. This report details an improved approach using a guarded 25 or 27 gauge light pipe and the Ngenuity digital three dimensional platform.

Methods

A standard Alcon light pipe is modified with a silicone guard to expose only 5 mm of the tip of the light pipe. The guard is created from the silicone that is already opened to secure the ends of the encircling band most often employed sleeve (e.g. 70, 270). This guarded light pipe is then inserted into the cannula as an alternative to a Chandelier lighting system.

Results

This is a technical report of a surgical visualization technique using a three dimensional digital visualization platform with a modified handheld vitrectomy light pipe.

Conclusion

The utilization of a guarded light pipe for visualization during primary scleral buckling is a promising, effective, and efficient technique. The three dimensional digital display allows for better educational impact and surgical communication with trainees and ancillary members of the surgical team.
A content analysis of internet information sources on medical cannabis
Authors: Kruger Daniel J. , Moffet Ilana M. , Seluk Liliah C. , Zammit Lara A.
Published: September 2020

Background

Medical cannabis users report that their knowledge regarding cannabis is predominantly from their own personal experiences and the Internet.

Objective

We summarize and describe information found through Internet searches on medical cannabis in English language websites.

Methods

We used terms related to medical cannabis in the Google search engine between November and December 2019. Resulting websites were catalogued and coded for content, including mentions of health and medical conditions, pharmacology, dosage, harmful or adverse effects, harm reduction techniques, cautions or warnings, products for sale, and credentials.

Results

We coded 344 web pages on 179 unique websites. Cannabis was mentioned for the treatment of 151 different medical and health conditions, only four of the twenty most frequently mentioned conditions have received substantial empirical support for cannabis or cannabinoid treatment. Information content varied widely across sites, only a small proportion of sites included information on pharmacology, dosage, risks, and other aspects that are requirements for pharmaceutical drugs. Information provided was only moderately related to conclusions in the emerging scientific literature.

Conclusions

Given the rise in cannabis use within the U.S. and the reliance on the Internet as a source of information, considerable efforts are needed to provide accurate on-line cannabis education to minimize harms and maximize benefits for individuals and society.
Unsupervised Resolution of Histomorphologic Heterogeneity in Renal Cell Carcinoma Using a Brain Tumor–Educated Neural Network
Authors: Faust Kevin , Roohi Adil , Leon Alberto J. , Leroux Emeline , Dent Anglin , Evans Andrew J. , Pugh Trevor J. , Kalimuthu Sangeetha N. , Djuric Ugljesa , Diamandis Phedias
Published: September 2020

PURPOSE

Applications of deep learning to histopathology have proven capable of expert-level performance, but approaches have largely focused on supervised classification tasks requiring context-specific training and deployment. More generalizable workflows that can be easily shared across subspecialties could help accelerate and broaden adoption. Here, we hypothesized that histology-optimized feature representations, generated by a convolutional neural network (CNN) during supervised learning, are transferable and can resolve meaningful differences in large-scale, discovery-type unsupervised analyses.

METHODS

We used a CNN, previously trained to recognize brain tumor histomorphologies, to extract 512 feature representations from > 550 digital whole-slide images (WSIs) of renal cell carcinomas (RCCs) from The Cancer Genome Atlas and other previously unencountered tumors. We use these extracted feature vectors to conduct unsupervised image-set clustering and analyze the clinical and biologic relevance of the intra- and interpatient subgroups generated.

RESULTS

Within individual WSIs, feature-based clustering could reliably segment tumor regions and other relevant histopathologic subpatterns (eg, adenosquamous and poorly differentiated regions). Across the larger RCC cohorts, clustering extracted features generated subgroups enriched for clinically relevant subtypes (eg, papillary RCC) and outcomes (eg, survival). Importantly, individual feature activation mapping highlighted salient subtype-specific patterns and features of malignancies (eg, nuclear grade, sarcomatous change) contributing to subgroupings. Moreover, some proposed clusters were enriched for recurring, human-based RCC-subtype misclassifications.

CONCLUSION

Our data support that CNNs, pretrained on large histologic datasets, can extend learned representations to novel scenarios and resolve clinically relevant intra- and interpatient tissue-pattern differences without explicit instruction or additional optimization. Repositioning of existing histology-educated networks could provide scalable approaches for image classification, quality assurance, and discovery of unappreciated patterns and subgroups of disease.
Disrupted Hypothalamo-Pituitary Axis in Association With Reduced SHH Underlies the Pathogenesis of NOTCH-Deficiency
Authors: Hamdi-Rozé Houda , Ware Michelle , Guyodo Hélène , Rizzo Aurélie , Ratié Leslie , Rupin Maïlys , Carré Wilfrid , Kim Artem , Odent Sylvie , Dubourg Christèle , David Véronique , de Tayrac Marie , Dupé Valérie
Published: September 2020

Context

In human, Sonic hedgehog (SHH) haploinsufficiency is the predominant cause of holoprosencephaly, a structural malformation of the forebrain midline characterized by phenotypic heterogeneity and incomplete penetrance. The NOTCH signaling pathway has recently been associated with holoprosencephaly in humans, but the precise mechanism involving NOTCH signaling during early brain development remains unknown.

Objective

The aim of this study was to evaluate the relationship between SHH and NOTCH signaling to determine the mechanism by which NOTCH dysfunction could cause midline malformations of the forebrain.

Design

In this study, we have used a chemical inhibition approach in the chick model and a genetic approach in the mouse model. We also reported results obtained from the clinical diagnosis of a cohort composed of 141 holoprosencephaly patients.

Results

We demonstrated that inhibition of NOTCH signaling in chick embryos as well as in mouse embryos induced a specific downregulation of SHH in the anterior hypothalamus. Our data in the mouse also revealed that the pituitary gland was the most sensitive tissue to Shh insufficiency and that haploinsufficiency of the SHH and NOTCH signaling pathways synergized to produce a malformed pituitary gland. Analysis of a large holoprosencephaly cohort revealed that some patients possessed multiple heterozygous mutations in several regulators of both pathways.

Conclusions

These results provided new insights into molecular mechanisms underlying the extreme phenotypic variability observed in human holoprosencephaly. They showed how haploinsufficiency of the SHH and NOTCH activity could contribute to specific congenital hypopituitarism that was associated with a sella turcica defect.
Pharmacodynamic Activity of the Novel Neurokinin-3 Receptor Antagonist SJX-653 in Healthy Men
Authors: Anderson Richard A , Cormier Jennifer , Thieroff-Ekerdt Ruth , Boyce Malcolm , van den Berg Frans , Grau Daniel , Turnquist David , Corzo Deya , Graham Philip
Published: September 2020

Context

SJX-653 is a novel neurokinin 3 receptor (NK3R) antagonist. The NK3 pathway is a central regulator of gonadotropin releasing hormone (GnRH) secretion and has also been implicated in the generation of hot flashes. Therefore, decreases of luteinizing hormone (LH) and testosterone in men serve as sensitive pharmacodynamic (PD) markers of central NK3 antagonism.

Objective

To characterize the safety, tolerability, pharmacokinetics, and pharmacodynamic activity of SJX-653 in healthy men.

Design

A randomized, placebo-controlled, double-blind, single ascending dose study.

Setting

Phase 1 unit.

Patients or Other Participants

Seven cohorts of 6 healthy men 18–45 years of age (4:2 randomization to SJX-653/placebo per cohort).

Intervention(s)

Single oral doses of 0.5–90 mg SJX-653.

Main Outcome Measure(s)

Safety assessments and serial pharmacokinetic (PK)/PD measurements.

Results

SJX-653 was well tolerated at all dose levels. Cmax and AUC0-24 increased in a dose-proportional manner. The terminal elimination half-life ranged between 9.8 and 12.5 hours independent of dose. A statistically significant, dose-dependent, reversible reduction of LH and testosterone was observed with near maximal effect after 15 mg and little to no effect at 4.5 mg. Maximal LH reduction was 70 ± 7% (mean ± sd) at 6 hours after 30 mg SJX-653 versus 10 ± 43% for placebo (P = 0.0006); maximal T reduction was of 68 ± 5% at 8 hours after 60 mg SJX-653 versus 18 ± 11% for placebo (P < 0.0001). The plasma IC50 for LH reduction was 33 ng/mL.

Conclusions

These data demonstrate clinical proof-of-mechanism for SJX-653 as a potent centrally-acting NK3R antagonist.
Surgical and Pharmacological Outcomes in Acromegaly: Real-Life Data From the Mexican Acromegaly Registry
Authors: Mercado Moisés , Abreu Coralys , Vergara-López Alma , González-Virla Baldomero , Espinosa-de-los-Monteros Ana-Laura , Sosa-Eroza Ernesto , Cadena-Obando Diego , Cuevas-Ramos Daniel , Portocarrero-Ortiz Lesly A , Pérez-Reyes Sara-Patricia , Mercado-Cherem Abraham , Ibarra-Salce Raúl , Talavera Juan O
Published: September 2020

Context

Acromegaly registries constitute a valuable source of therapeutic outcome information in real-life.

Objective

The objective of this work is to analyze surgical and pharmacological outcomes in the Mexican Acromegaly Registry (MAR).

Design and Methods

Data were extracted from the MAR informatic platform. Surgical remission was defined by a postoperative postglucose (GH) of less than 1 ng/mL and an insulin-like growth factor 1 (IGF-1) of less than 1.2 × upper limit of normal (ULN). Pharmacological remission was defined by a basal GH of less than 1 ng/mL and an IGF-1 of less than 1.2 × ULN.

Results

A total of 650 surgical outcomes were analyzed (94.6% transsphenoidal). Surgical remission was achieved in 40.15%, whereas 44.15% remained biochemically active. Persistently active disease after surgery was significantly associated with harboring an invasive macroadenoma, a basal GH of greater than 10 ng/mL, and/or an IGF-1 of greater than 2 × ULN at diagnosis on bivariate and multivariate analysis. The outcome of monotherapy with first-generation somatostatin analogs (SSAs) was evaluated in 267 patients (adjunctive in 65%), of whom 28.4% achieved remission. Persistently active disease was significantly associated with harboring an invasive macroadenoma as well as with pretreatment basal GH and IGF-1 levels of greater than 10 ng/mL and greater than 2 × ULN, respectively, on bivariate and multivariate analysis. Combined therapy with SSA and cabergoline was analyzed in 100 patients, of whom 19% achieved remission and 44% remained active; in this subset of patients, only a pretreatment IGF-1 of greater than 2 × ULN was significantly associated with persistent disease activity.

Conclusion

Surgical and pharmacological outcomes in acromegaly are highly dependent on tumor size/invasiveness as well as on the degree of hypersomatotropinemia.
A Manifesto for the Broken Machine
Authors: Sharma Sarah
Published: September 2020

This article reveals how conservative and alt-right understandings of technology are inextricably tied to how these ideologies conceptualize gender, race, and other forms of social difference. Feminists, the gender nonconforming, queer, nonwhite, and the rest of the non-abiding are cast off as broken technologies that need to be replaced and discarded. Using a techno-feminist approach, this article argues that rather than seek justice through inclusion or improvements in representation, there is a feminist politics up for grabs in this patriarchal formulation of feminists as broken machines. The piece offers a manifesto for the “Broken Machine,” revealing how power operates with a machinelike quality and can therefore offer feminism the possibility to refuse via the disruptive logics of broken technologies.
Tracking and forecasting milepost moments of the epidemic in the early-outbreak: framework and applications to the COVID-19
Authors: Wang Huiwen , Zhang Yanwen , Lu Shan , Wang Shanshan
Published: September 2020

Background: The outbreak of the 2019 novel coronavirus (COVID-19) has attracted global attention. In the early stage of the outbreak, the most important question concerns some meaningful milepost moments, including the time when the number of daily confirmed cases decreases, the time when the number of daily confirmed cases becomes smaller than that of the daily removed (recovered and death), and the time when the number of daily confirmed cases and patients treated in hospital, which can be called “active cases”, becomes zero. Unfortunately, it is extremely difficult to make right and precise prediction due to the limited amount of available data at the early stage of the outbreak. To address it, in this paper, we propose a flexible framework incorporating the effectiveness of the government control to forecast the whole process of a new unknown infectious disease in its early-outbreak.

Methods: We first establish the iconic indicators to characterize the extent of epidemic spread. Then we develop the tracking and forecasting procedure with mild and reasonable assumptions. Finally we apply it to analyze and evaluate the COVID-19 outbreak using the public available data for mainland China beyond Hubei Province from the China Centers for Disease Control (CDC) during the period of Jan 29th, 2020, to Feb 29th, 2020, which shows the effectiveness of the proposed procedure.

Results: Forecasting results indicate that the number of newly confirmed cases will become zero in the mid-early March, and the number of patients treated in the hospital will become zero between mid-March and mid-April in mainland China beyond Hubei Province.

Conclusions: The framework proposed in this paper can help people get a general understanding of the epidemic trends in countries where COVID-19 are raging as well as any other outbreaks of new and unknown infectious diseases in the future.