bluuebunny/crossref_metadata_2025 huggingface dataset:
The proteomics of roadside hawk (Rupornis magnirostris), broad-snouted caiman (Caiman latirostris) and loggerhead sea turtle (Caretta caretta) tears
Authors: Raposo A. C. , Lebrilla C. B. , Portela R. W. , Goonatilleke E. , Neto F. A. Dórea , Oriá A. P.
Published: August 2020

Background

Tears play an important role in ocular surface protection, and help wild animals maintain visual acuity in the face of air and water friction. The proteomics of tears has only been described for mammals. The knowledge of the proteomics of wild animal tears can aid not only in the setting of normal standards for ocular disease studies in these animals, but also to base the search for new molecules to be used in ophthalmology therapeutics. We therefore set out to describe the proteomic profile of roadside hawk (Rupornis magnirostris), broad-snouted caiman (Caiman latirostris) and loggerhead sea turtle (Caretta caretta) tears. Tears were collected from healthy animals, their spectral profiles were obtained with an LTQ Orbitrap XL mass spectrometer, and the dataset was analyzed against reference taxa.

Results

For roadside hawk, 446 proteins were identified, the most abundant being albumin, transferrin, globulin and actin. For broad-snouted caiman and loggerhead sea turtle, 1358 and 163 proteins were identified, respectively. Uncharacterized proteins and transferrin were highly abundant in both species. The roadside hawk tear components and their properties were similar to those described for humans, but with a higher albumin concentration. Broad-snouted caiman tears presented a wide diversity of ontological functions, with an abundant presence of enzymatic compounds. In loggerhead sea turtle tears, the predominance of proteins with ion-transport functions was consistent with possible osmolality-maintenance mechanisms.

Conclusion

These data enhance our understanding of birds and reptiles’ tears microcomposition and may be used to base the discovery of new molecules with high biotechnological potential.
Loss of survival advantage for deficient mismatch repair in patients with advanced colorectal cancer may be caused by changes in prognostic value of CD8+T cell
Authors: Wang Bingyan , Li Fei , Guo Limei , Lu Siyi , Ma Junren , Ma Yanpeng , Meng Yan , Wang Junwei , Zhou Xin , Fu Wei
Published: August 2020

Background

Patients with stage II deficient mismatch repair (dMMR) show a better prognosis than patients with colorectal cancer (CRC) with proficient mismatch repair (pMMR). However, this beneficial effect is decreased in advanced stages of the disease. This study was conducted to investigate the prognostic value of dMMR in different stage and alterations in the tumor microenvironment.

Methods

This was a matched retrospective cohort study. Thirty-two patients with stage III&IV dMMR matched with 32 patients with stage I&II dMMR and 64 patients with pMMR were evaluated. Immunohistochemistry analysis was performed for the 64 patients with dMMR to explore the expression and prognostic effect of CD3, CD4, CD8, and PD-L1.

Results

Patients with stage III–IV dMMR showed no advantage in overall survival (OS) and disease-free survival (DFS) compared to patients with pMMR (P = 0.244, P = 0.667). No expression differences in CD3, CD4, CD8, and PD-L1 at the center of the tumor (CT) or invasive margin (IM) were found between patients with stage I&II and stage III&IV dMMR. High CD3 expression at the CT and high CD3 an CD4 expression at the IM improved both OS and DFS. High CD8 expression showed opposite prognostic value in patients with stage I&II and III&IV dMMR. A similar tendency was observed for PD-L1 expression.

Conclusion

Patients with stage III–IV dMMR showed no prognostic advantage over patients with pMMR. Expression of CD3, CD4, CD8, and PD-L1 was similar between stage I&II and III&IV dMMR CRC. High CD3 expression at the CT and high CD3 and CD4 expression at the IM can significantly improve patient prognosis. The opposite prognostic tendency of CD8 and PD-L1 for patients with stage I&II and III&IV dMMR may be relevant to CD8+T cell exhaustion and functional changes at inhibitory immune checkpoints.
Different surgical outcome and follow-up status between dMMR and pMMR colorectal cancer patients who fulfilled with Amsterdam-II criteria
Authors: Sun Ci-Yuan , Chiang Jy-Ming , Chen Tse-Ching , Hung Hsin-Yun , You Jeng-Fu
Published: August 2020

Background

Although hereditary non-polyposis colorectal cancer (HNPCC) could be subtyped into proficient or deficient mismatch repair gene expression (pMMR or dMMR), distinct clinical features between these two subgroups patients were rarely reported.

Methods

We retrospectively analyzed 175 hereditary non-polyposis colorectal cancer (HNPCC) patients between January 1995 and December 2012. Cox proportional hazards model was used to compare the differences between two subgroups.

Results

Significant differences of disease free survival (DFS) and overall survival (OS) exist between dMMR and pMMR. In addition to other factors including younger mean age of diagnosis for dMMR patients (48.6 years vs. 54.3 years), operation type (more extended colectomy for dMMR 35.8% vs. 14.5%), tumor location (right colon predominance for dMMR 61.7% vs. 27.3% and more rectum cases for pMMR 41.8% vs. 11.7%), tumor differentiation (more poor differentiation for dMMR 23.3% vs. 9.0%), N staging (more N0 cases for dMMR 70.8% vs. 50.9%), more frequently presence of extra-colonic tumors for dMMR (16.7% vs.1.8%), and lower recurrence rates (9.1% vs.35.3%). Significantly different cumulative incidences of developing metachronous colorectal cancer were observed with 6.18 for pMMR patients and 20.57 person-years for dMMR patients (p < 0.001).

Conclusions

Distinct clinicopathological features significantly exist between dMMR and pMMR subtypes patient, MMR status should be consider to tailor operation types and follow up surveillance between these two subgroups patients who all fulfilled with Amsterdam-II criteria.
An EGFR T790M-mutated lung adenocarcinoma undergoing large-cell neuroendocrine carcinoma transformation after osimertinib therapy: a case report
Authors: Miyazaki Shinichi , Kuno Yasumasa , Hayai Shunsaku , Teramachi Ryo , Yamashita Ryo , Saito Yusuke , Higuchi Kosuke , Nara Yoshiharu , Ikeda Takuya
Published: August 2020

Background

Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is selective for both epidermal growth factor receptor tyrosine kinase inhibitor–sensitizing and T790M resistance mutations. Almost all patients who initially respond to an epidermal growth factor receptor tyrosine kinase inhibitor subsequently report disease progression. Epidermal growth factor receptor–dependent resistance mechanisms, bypass pathway activation, and histological transformation have been reported with osimertinib therapy.

Case presentation

We report a case of a 64-year-old Asian man with epidermal growth factor receptor T790M-positive adenocarcinoma that transformed to epidermal growth factor receptor T790M-negative large-cell neuroendocrine carcinoma after osimertinib therapy. A prompt rebiopsy revealed a rare mechanism of resistance to epidermal growth factor receptor tyrosine kinase inhibitor, and subsequently treatment with carboplatin and etoposide was effective.

Conclusions

Despite the promising emergence of circulating tumoral DNA testing, this case report emphasizes the importance of rebiopsy of a progressive epidermal growth factor receptor–mutant tumor.
Correction to: Elbow flexion reconstruction after arm-sparing excision for high-grade triton sarcoma: a case report
Authors: Lupon Elise , Chevreau Christine , Lellouch Alexandre Gaston , Gangloff Dimitry , Meresse Thomas
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Different dietary starch sources alter the carcass traits, meat quality, and the profile of muscle amino acid and fatty acid in finishing pigs
Authors: Yu Miao , Li Zhenming , Rong Ting , Wang Gang , Liu Zhichang , Chen Weidong , Li Jiazhou , Li Jianhao , Ma Xianyong
Published: August 2020

Background

With increasing health awareness among consumers, the demand for healthier, tastier, higher quality and nutritional value pork is increasing. It has been shown that different dietary starch sources can alter the carcass traits and meat quality. However, research on the effects of different starch sources with clear different amylose/amylopectin ratio on the amino acid and fatty acid composition in Longissimus thoracis (L. thoracis) muscle of pigs is limited. This study aimed to investigate the effects of different dietary starch sources on carcass traits, meat quality, muscle amino acid and fatty acid composition, and the mRNA expression levels of genes involved in lipid metabolism and muscle fiber characteristics in finishing pigs. A total of 72 Duroc × Landrace × Large White barrows were randomly allocated to 3 different dietary treatment groups with 8 replicate pens/group and 3 pigs per pen. Tapioca starch (TS), corn starch (CS), and pea starch (PS), with amylose/amylopectin ratio of 0.11, 0.25, and 0.44, respectively, were used as their dietary starch sources for 40 days.

Results

Results showed that the PS diet significantly increased (P < 0.05) the final body weight, average daily gain, loin-eye area, and fat-free lean index compared with the TS diet, but significantly decreased (P < 0.05) the feed to gain ratio and backfat thickness. Compared with the TS diet, PS diet also increased (P < 0.05) the pH45 min, marbling scores, the content of intramuscular fat and inosine monophosphate in the L. thoracis, and decreased (P < 0.05) the drip loss and shear force. In addition, compared with the TS diet, PS diet increased (P < 0.05) the proportions of flavor amino acids, DHA, EPA, and n-3 polyunsaturated fatty acid (PUFA) in the L. thoracis compared with TS diet, but decreased (P < 0.05) the ratio of n-6/n-3 PUFA. Furthermore, compared with the TS diet, PS diet also upregulated (P < 0.05) the lipogenic genes (FAS, LPL, SCD, ACCα) and myosin heavy-chain (MyHC)-IIa mRNA expression levels compared with the TS diet, but downregulated (P < 0.05) the CPT1B and MyHC-IIb mRNA levels.

Conclusions

In conclusion, these results provided compelling evidence that the different dietary starch source altered the carcass traits, meat flavor and quality in finishing pigs, and consumption of a diet with higher amylose/amylopectin ratio results in the production of a healthy, higher quality, and nutritional value pork.
Environmental shaping of the bacterial and fungal community in infant bed dust and correlations with the airway microbiota
Authors: Gupta Shashank , Hjelmsø Mathis H. , Lehtimäki Jenni , Li Xuanji , Mortensen Martin S. , Russel Jakob , Trivedi Urvish , Rasmussen Morten A. , Stokholm Jakob , Bisgaard Hans , Sørensen Søren J.
Published: August 2020

Background

From early life, children are exposed to a multitude of environmental exposures, which may be of crucial importance for healthy development. Here, the environmental microbiota may be of particular interest as it represents the interface between environmental factors and the child. As infants in modern societies spend a considerable amount of time indoors, we hypothesize that the indoor bed dust microbiota might be an important factor for the child and for the early colonization of the airway microbiome. To explore this hypothesis, we analyzed the influence of environmental exposures on 577 dust samples from the beds of infants together with 542 airway samples from the Copenhagen Prospective Studies on Asthma in Childhood2010cohort.

Results

Both bacterial and fungal community was profiled from the bed dust. Bacterial and fungal diversity in the bed dust was positively correlated with each other. Bacterial bed dust microbiota was influenced by multiple environmental factors, such as type of home (house or apartment), living environment (rural or urban), sex of siblings, and presence of pets (cat and/or dog), whereas fungal bed dust microbiota was majorly influenced by the type of home (house or apartment) and sampling season. We further observed minor correlation between bed dust and airway microbiota compositions among infants. We also analyzed the transfer of microbiota from bed dust to the airway, but we did not find evidence of transfer of individual taxa.

Conclusions

Current study explores the influence of environmental factors on bed dust microbiota (both bacterial and fungal) and its correlation with airway microbiota (bacterial) in early life using high-throughput sequencing. Our findings demonstrate that bed dust microbiota is influenced by multiple environmental exposures and could represent an interface between environment and child.
Refraction wavefield migration
Authors: Shen Yang , Zhang Jie
Published: August 2020

Refraction methods are often applied to model and image near-surface velocity structures. However, near-surface imaging is very challenging, and no single method can resolve all of the land seismic problems across the world. In addition, deep interfaces are difficult to image from land reflection data due to the associated low signal-to-noise ratio. Following previous research, we have developed a refraction wavefield migration method for imaging shallow and deep interfaces via interferometry. Our method includes two steps: converting refractions into virtual reflection gathers and then applying a prestack depth migration method to produce interface images from the virtual reflection gathers. With a regular recording offset of approximately 3 km, this approach produces an image of a shallow interface within the top 1 km. If the recording offset is very long, the refractions may follow a deep path, and the result may reveal a deep interface. We determine several factors that affect the imaging results using synthetics. We also apply the novel method to one data set with regular recording offsets and another with far offsets; both cases produce sharp images, which are further verified by conventional reflection imaging. This method can be applied as a promising imaging tool when handling practical cases involving data with excessively weak or missing reflections but available refractions.
Photoplasticization Behavior and Photoinduced Pressure-Sensitive Adhesion Properties of Various Polymers Containing an Azobenzene-Doped Liquid Crystal
Authors: Koike Mioka , Aizawa Miho , Akamatsu Norihisa , Shishido Atsushi , Matsuzawa Yoko , Yamamoto Takahiro
Published: August 2020

Photochemical control of the hardness and fluidity of polymeric materials is applicable to the development of photoreversible adhesives. Here, we report that common polymers show photoplasticization behavior, which is the photoinduced reduction of the glass transition temperature, just by adding an azobenzene-doped liquid crystal (azo-doped LC). We found that the photoplasticization effect that occurred in amorphous polymers with an azo-doped LC was due to a microscopic phase separation of the azo-doped LC from the polymers. In contrast, we did not observe any photoplasticization behavior in crystalline polymers because of the macroscopic segregation of the azo-doped LC from the polymers and high rigidity of the crystalline regions of the polymers. Based on the photoplasticization effect, we successfully achieved photochemical induction of tackiness, which is a pressure-sensitive adhesion property. Furthermore, the maximum tack strength was enhanced upon photoirradiation of the polymers. We inferred that this behavior originated from an increase in the interaction between the samples and the test probe based on the change in polarity of the samples by the photoisomerization of azobenzene. We conclude that “photoplastic” polymers composed of common materials can be used for photoresponsive pressure-sensitive adhesives.
Recent advances in phenotypic drug discovery
Authors: Swinney David C. , Lee Jonathan A.
Published: August 2020

There is a great need for innovative new medicines to treat unmet medical needs. The discovery and development of innovative new medicines is extremely difficult, costly, and inefficient. In the last decade, phenotypic drug discovery (PDD) was reintroduced as a strategy to provide first-in-class medicines. PDD uses empirical, target-agnostic lead generation to identify pharmacologically active molecules and novel therapeutics which work through unprecedented drug mechanisms. The economic and scientific value of PDD is exemplified through game-changing medicines for hepatitis C virus, spinal muscular atrophy, and cystic fibrosis. In this short review, recent advances are noted for the implementation and de-risking of PDD (for compound library selection, biomarker development, mechanism identification, and safety studies) and the potential for artificial intelligence. A significant barrier in the decision to implement PDD is balancing the potential impact of a novel mechanism of drug action with an under-defined scientific path forward, with the desire to provide infrastructure and metrics to optimize return on investment, which a known mechanism provides. A means to address this knowledge gap in the future is to empower precompetitive research utilizing the empirical concepts of PDD to identify new mechanisms and pharmacologically active compounds.
Tempe extract reduces cell damage in the liver and kidneys after intensive physical exercise in rats
Authors: Suarsana I. Nyoman , Utama Iwan Harjono , Kardena I. Made
Published: August 2020

Background and Aim: Cells of the liver and kidneys are perpetually exposed to free radicals from endogenous and exogenous sources. High-intensity physical exercise can induce oxidative stress. This study aimed to determine the effects of tempe extract on cell damage in the liver and kidneys of rats after intensive physical exercise.

Materials and Methods: This study used five experimental groups: T0 (non-exercised control rats), T1 (rats made to exercise by swimming), and T2-T4 (rats made to exercise by swimming treated with 25, 50, and 100 mg/kg body weight tempe extract). The biochemical parameters that were analyzed included blood glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and creatinine levels. The morphology of liver and kidney tissues was histopathologically and immunohistochemically analyzed.

Results: Tempe extract treatment reduced cell damage in the liver and kidney tissues of rats, characterized by decreased expression of caspase-3. In addition, the ALT, AST, ALP, creatinine, and BUN levels of rats were significantly lower in tempe extract-treated rats than in rats after swimming exercise alone.

Conclusion: Tempe extract is capable of reducing cell damage and apoptosis in the liver and kidney cells of rats after intensive physical exercise and maintaining biochemical properties similar to the normal physiological state.
Production, immunogenicity, stability, and safety of a vaccine against Clostridium perfringens beta toxins
Authors: Saadh Mohamed J. , Sa'adeh Issam J. , Dababneh Moeen F. , Almaaytah Ammar M. , Bayan Mohammad F.
Published: August 2020

Background and Aim: The beta toxin is causing the most severe Clostridium perfringens-related diseases. This work was dedicated to developing a vaccine against beta toxin using C. perfringens type C (NCTC 3180).

Materials and Methods: The crude toxoid harvest contained 710 limits of flocculation (Lf)/mL. The vaccine was formulated. Each 1 mL of the final vaccine product contained at least 50 Lf/mL of beta toxoids, 0.2 mL 3% aluminum hydroxide gel (equivalent to 5.18 mg of aluminum), <0.001% W/V thiomersal, formaldehyde <0.05% W/V, and ∼0.7 mL phosphate-buffered saline (pH 7.2). The efficacy of the vaccine was evaluated by potency, stability, and safety tests.

Results: The vaccine demonstrated 24.36 IU/mL (standard deviation, ±0.56) and 14.74 IU/mL (±0.36) of neutralizing antibodies in rabbits and cattle, respectively. Indeed, these levels were above the minimum recommended by international protocols since the obtained antibody levels had 2.43- and 1.47-fold increase in both rabbits and cattle, respectively, over the minimum antitoxin level suggested by the United States Department of Agriculture. Interestingly, our formulation was capable of inducing 1.65-fold higher immune responses in rabbits than that stimulated in cattle (65% increase) with a significant difference (p<0.0001). The vaccine was stable up to 30 months. The vaccinated rabbits were suffered from a temporarily slight increase in temperatures in the first 10 h without any significant difference (p>0.05).

Conclusion: The research showed a procedure for the manufacturing process of the vaccine against C. perfringens beta toxins with a feasible quantity and the vaccine described here showed to be effective in eliciting levels of neutralizing antibodies higher than required by international standards. In addition, The vaccine was stable up to 30 months. Thus, it may represent an effective and safe for preventing C. perfringens-related diseases in rabbits and cattle, although further studies to prove its efficacy in the field on other farm animals are still needed.
Global Analysis of Cereal microProteins Suggests Diverse Roles in Crop Development and Environmental Adaptation
Authors: Bhati Kaushal Kumar , Kruusvee Valdeko , Straub Daniel , Chandran Anil Kumar Nalini , Jung Ki-Hong , Wenkel Stephan
Published: August 2020

MicroProteins are a class of small single-domain proteins that post-translationally regulate larger multidomain proteins from which they evolved or which they relate to. They disrupt the normal function of their targets by forming microProtein-target heterodimers through compatible protein-protein interaction (PPI) domains. Recent studies confirm the significance of microProteins in the fine-tuning of plant developmental processes such as shoot apical meristem maintenance and flowering time regulation. While there are a number of well-characterized microProteins in Arabidopsis thaliana, studies from more complex plant genomes are still missing. We have previously developed miPFinder, a software for identifying microProteins from annotated genomes. Here we present an improved version where we have updated the algorithm to increase its accuracy and speed, and used it to analyze five cereal crop genomes – wheat, rice, barley, maize and sorghum. We found 20,064 potential microProteins from a total of 258,029 proteins in these five organisms, of which approximately 2000 are high-confidence, i.e., likely to function as actual microProteins. Gene ontology analysis of these 2000 microProtein candidates revealed their roles in stress, light and growth responses, hormone signaling and transcriptional regulation. Using a recently developed rice gene co-expression database, we analyzed 347 potential rice microProteins that are also conserved in other cereal crops and found over 50 of these rice microProteins to be co-regulated with their identified interaction partners. Overall, our study reveals a rich source of biotechnologically interesting small proteins that regulate fundamental plant processes such a growth and stress response that could be utilized in crop bioengineering.
Anticoagulant Therapy for Patients with Coronavirus Disease 2019: Urgent Need for Enhanced Awareness
Authors: Komiyama Maki , Hasegawa Koji
Published: August 2020

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. SARS-CoV-2 binds to the angiotensin-converting enzyme 2 receptor, which is abundantly expressed in vascular endothelial cells and damages these cells. Besides pneumonia-induced respiratory failure, thrombotic cardiovascular complications are increasingly emerging as a major COVID-19 symptom. Multiple retrospective studies have strongly suggested that anticoagulant therapy improves the prognosis of people with COVID-19. However, validation of the safety and effectiveness of anticoagulant therapy for COVID-19 and greater awareness of this clinical therapeutic option are urgently needed.
Integration of GWAS Summary Statistics and Gene Expression Reveals Target Cell Types Underlying Kidney Function Traits
Authors: Li Yong , Haug Stefan , Schlosser Pascal , Teumer Alexander , Tin Adrienne , Pattaro Cristian , Köttgen Anna , Wuttke Matthias
Published: August 2020

Significance Statement

Genome-wide association studies (GWAS) are a powerful tool to identify genetic variants associated with CKD. However, knowledge of CKD-relevant target tissues and cell types important in the pathogenesis is incomplete. Integrating large-scale kidney function GWAS with gene expression datasets identified kidney and liver as the primary organs for kidney function traits. In the kidney, proximal tubule was the critical cell type for eGFR and urate, as well as for monogenic electrolyte or metabolic disease genes. Podocytes showed enrichment of genes implicated in glomerular disease. Compendia connecting traits, genes, and cell types allow further prioritization of genes in GWAS loci, enabling mechanistic studies.

Background

Genetic variants identified in genome-wide association studies (GWAS) are often not specific enough to reveal complex underlying physiology. By integrating RNA-seq data and GWAS summary statistics, novel computational methods allow unbiased identification of trait-relevant tissues and cell types.

Methods

The CKDGen consortium provided GWAS summary data for eGFR, urinary albumin-creatinine ratio (UACR), BUN, and serum urate. Genotype-Tissue Expression Project (GTEx) RNA-seq data were used to construct the top 10% specifically expressed genes for each of 53 tissues followed by linkage disequilibrium (LD) score–based enrichment testing for each trait. Similar procedures were performed for five kidney single-cell RNA-seq datasets from humans and mice and for a microdissected tubule RNA-seq dataset from rat. Gene set enrichment analyses were also conducted for genes implicated in Mendelian kidney diseases.

Results

Across 53 tissues, genes in kidney function–associated GWAS loci were enriched in kidney (P=9.1E-8 for eGFR; P=1.2E-5 for urate) and liver (P=6.8·10-5 for eGFR). In the kidney, proximal tubule was enriched in humans (P=8.5E-5 for eGFR; P=7.8E-6 for urate) and mice (P=0.0003 for eGFR; P=0.0002 for urate) and confirmed as the primary cell type in microdissected tubules and organoids. Gene set enrichment analysis supported this and showed enrichment of genes implicated in monogenic glomerular diseases in podocytes. A systematic approach generated a comprehensive list of GWAS genes prioritized by cell type–specific expression.

Conclusions

Integration of GWAS statistics of kidney function traits and gene expression data identified relevant tissues and cell types, as a basis for further mechanistic studies to understand GWAS loci.
Hnf4a Is Required for the Development of Cdh6-Expressing Progenitors into Proximal Tubules in the Mouse Kidney
Authors: Marable Sierra S. , Chung Eunah , Park Joo-Seop
Published: August 2020

Significance Statement

Proximal tubule cells are the most abundant cell type in the mammalian kidney, and they perform the bulk of the renal reabsorption function. Despite the importance of these cells in kidney function, the molecular mechanisms of proximal tubule development and maturation are not well understood. Experiments reveal that, in the developing mouse kidney, Cadherin-6-expressing cells act as proximal tubule progenitors and they require Hnf4a to further develop into mature proximal tubules. Genomic analyses show that Hnf4a directly regulates the expression of genes required for reabsorption, such as transmembrane transporter genes and metabolism genes. This study advances understanding of how kidney proximal tubule cells form during development.

Background

Hepatocyte NF 4α (Hnf4a) is a major regulator of renal proximal tubule (PT) development. In humans, a mutation inHNF4Aimpairs PT functions and is associated with Fanconi renotubular syndrome (FRTS). In mice, mosaic deletion ofHnf4ain the developing kidney reduces the population of PT cells, leading to FRTS-like symptoms. The molecular mechanisms underlying the role of Hnf4a in PT development remain unclear.

Methods

The gene deletion toolOsr2CreremovedHnf4ain developing nephrons in mice, generating a novel model for FRTS. Immunofluorescence analysis characterized the mutant phenotype, and lineage analysis tested whether Cadherin-6 (Cdh6)–expressing cells are PT progenitors. Genome-wide mapping of Hnf4a binding sites and differential gene analysis ofHnf4amutant kidneys identified direct target genes of Hnf4a.

Results

Deletion ofHnf4awithOsr2Creled to the complete loss of mature PT cells, lethal to theHnf4amutant mice. Cdh6high, lotus tetragonolobus lectin-low (LTLlow) cells serve as PT progenitors and demonstrate higher proliferation than Cdh6low, LTLhighdifferentiated PT cells. Additionally, Hnf4a is required for PT progenitors to differentiate into mature PT cells. Genomic analyses revealed that Hnf4a directly regulates the expression of genes involved in transmembrane transport and metabolism.

Conclusions

Hnf4a promotes the differentiation of PT progenitors into mature PT cells by regulating the expression of genes associated with reabsorption, the major function of PT cells.
Poetics of Relations: A Manifesto on Performance-Based Filmmaking
Authors: Stenke Verena , Pagnes Andrea
Published: August 2020

This video article expands upon the Poetics of Relations, the embodied research of VestAndPage (Verena Stenke and Andrea Pagnes), which informs their performance-based filmmaking theory and practice. Since 2010, the artist duo inquires into the pillars that constitute the cross-contamination of the two art forms of time-based live art and filmmaking. Their films have been produced geo-psychologically in a variety of locations around the world: from the remote regions of Chilean Patagonia and Tierra del Fuego to the Antarctica; from socio-cultural areas of conflict like Kashmir and North-West India to the volcanic island of Formentera; and during a month-long performance walk through Germany, Poland and the Russian exclave of Kaliningrad. Each of the films focuses upon a particular research and artistic subject. In this video article, their film projects are taken under the pinhole to look into what could constitute a manifesto of sorts in which the embodied research process identifies the essentials constituents of their practice, and elaborates on the integration of filming, story, time, space, character, action, objects, text, sound, effects, atmosphere, production and editing.
Orgullo loco y metáforas para una disidencia: un análisis lingüístico y simbólico
Authors: Correa-Urquiza Vidal Martín , Pié Balaguer Asun , Coll-Florit Marta , Hernández i Encuentra Eulàlia , Climent Salvador
Published: August 2020

El presente artículo expone un análisis lingüístico e interpretativo sobre el uso de la metáfora conceptual en el campo de la salud mental, tomando como campo de observación el uso de Twitter en la primera edición del Día del Orgullo Loco en España, celebrada el 20 de mayo de 2018. El objetivo es dar cuenta de los posicionamientos expresados por los activistas en primera persona. Los resultados muestran un cuestionamiento a las lógicas coercitivas producidas por la atención psiquiátrica, una problematización del modelo hegemónico en su conjunto, una denuncia a la opresión que implica el estigma, problemas de comunicación y demandas de mayor diálogo con los profesionales del campo de la salud mental. Este análisis nos ha permitido comprender el modo lingüístico de re-semantizar el campo de la salud mental, así como dar cuenta de las tensiones existentes entre las percepciones subjetivas de las personas diagnosticadas y las producciones del modelo médico hegemónico.
Kudüs Vakıflarında İstihdam: 18. Yüzyılda Vakıf Görevlilerinin Sosyo-Ekonomik ve Demografik Özellikleri
Authors: Eroğlu Memiş Şerife
Published: August 2020

Bu çalışma, Kudüs kenti vakıflarının 18. yüzyıldaki istihdam durumunu vakıf
görevlilerinin sosyo-ekonomik ve demografik özellikleri bakımından incelemeyi
amaçlamaktadır. Çalışma, Osmanlı merkezi yönetiminin vakıflara ilişkin uygulamaları
bağlamında, devlet iktidarı ve denetiminin taşradaki işleyişi ve varlık belirtileri
üzerinde durmaktadır. Dört kısımda oluşan incelemenin birinci kısmında Osmanlı
toplum yapısı içerisinde vakıf görevlilerinin konumu tespit edilerek, bu görevlilerin
tespit edilen unvan ve lakapları ve tarihsel süreç içerisindeki değişimlerine yer verilecektir.
Sonrasında, görevlilerin tevcih, azl ve görev süreleri yine ayrı bir başlık altında
incelenecektir. Bu bağlamda, Osmanlı merkezi yönetiminin yapılan bu atamalar konusundaki
etkisi ve denetimine ilişkin süreçler belirlenmeye çalışılacaktır. Kudüs’teki
vakıf görevlilerinin, kent nüfusu içerisindeki durumunu tespit etmeye çalıştığımız
üçüncü kısmı, vakıf görevlilerinin ücretlerinin incelendiği bölüm takip edecektir.
Bunların analizi ile Osmanlı merkezi yönetiminin bir taşra kentindeki otoritesini
sürdürmesini mümkün kılan istihdam politikalarına vakıf görevleri ve maaşlar üzerinden
ışık tutulmaya çalışılacaktır.
“All We Hope is a Generous Revival”: The Evangelization of the Ottoman Christians in Western Anatolia in the Nineteenth Century
Authors: Erol Merih
Published: August 2020

This article examines the American Board of Commissioners for Foreign
Missions’ activities in the 1870s and 80s at the Manisa and Smyrna/İzmir stations in
an attempt to evangelize Greeks and Armenians living in the region. The main body
of sources used in this study are the letters of the missionary Rev. Marcellus Bowen
(1874-1880) sent from Manisa to the headquarters of the ABCFM in Boston, and
the letters of Rev. George Constantine (1880-1889) sent from İzmir to the same
destination. These first-person narratives provide us with extremely rich material,
due to the fact that they comment on phenomena and events directly and immediately.
This article investigates a variety of themes, such as the efforts of the American
missionaries to adapt their missionary work to Smyrna’s multicultural and multinational
society; the missionaries’ decisions and arguments regarding which language
to use in their preachings or at religious services for the Greeks and Armenians of the
region; the means of persecution or opposition employed by the Greek Orthodox
high-ranked clergy in Smyrna/İzmir against the Protestant missionaries; and the conditions
under which foreigners could sell religious books or open / build schools and
churches in the Ottoman lands, and which intermediaries the missionaries appealed
to when they were challenged by the Ottoman authorities.
Sürdürülebilirlik Açısından Mermer Atıklarının Karayolu İnşaatında Değerlendirilmesi: Ekonomik Analiz Örneği
Authors: Yılmaz Altan
Published: August 2020

Günümüzde mineral agrega kullanım alanları büyük bir hızla artmakta olmasına rağmen doğal agrega kaynakları giderek azalmaktadır. Buna karşılık ülkemizdeki mermer fabrikalarının atıklarının büyük bir kısmı değerlendirilememekte, işletme sahalarında veya yakınlarındaki depo alanlarında depolanmaktadır. Mermer işleme tesislerinde ham blokların işlenmesi ile ortaya çıkan artık miktarı genellikle %30 - %45 civarında olmaktadır. Mermer atıklarının yığınlar halinde biriktirilmesi hem çevreye olumsuz etkileri olmakta hem de ekonomik olarak kayıplara sebep olmaktadır. Bu çalışmada atık mermer agregasının yol üstyapısında temel tabakalarında doğal agrega yerine alternatif kullanımı düşünülerek, doğal malzeme ile mukayeseli olarak ekonomik analizi yapılmıştır. Çalışmada öncelikle atık malzemelerin ve doğal agreganın birim maliyetleri belirlenmiştir. Maliyet analizinde sökme - kırma - eleme – sınıflandırma - yükleme ve nakliye maliyetleri arasında olası senaryolar dikkate alınmıştır. Yapılan maliyet hesabı neticesinde mermer atıklarının ham madde maliyeti olmaması sebebiyle, birim maliyeti doğal agreganın %50’si kadar çıkmıştır. Elde edilen birim maliyet farklarından hareketle, sonuç olarak mermer agregasının ekonomik olarak taşınabileceği belirli bir mesafe (Me) belirlenmiştir. Başa baş mesafesi olarak bulunan bu uzaklığın göz ardı edilemeyecek ölçüde olduğu tespit edilmiştir.
Volatility Modelling of the BRICS Stock Markets
Authors: Mukhodobwane Rosinah M , Sigauke Caston , Chagwiza Wilbert , Garira Winston
Published: August 2020

Volatility modelling is a key factor in equity markets for risk and portfolio management. This paper focuses on the use of a univariate generalized autoregressive conditional heteroscedasticity (GARCH) models for modelling volatility of the BRICS (Brazil, Russia, India, China and South Africa) stock markets. The study was conducted under the assumptions of seven error distributions that include the normal, skewed-normal, Student’s t, skewed-Student’s t, generalized error distribution (GED), skewed-GED and the generalized hyperbolic (GHYP) distribution. It was observed that using an ARMA(1, 1)-GARCH(1, 1) model, volatilities of the Brazilian Bovespa and the Russian IMOEX markets can both be well characterized (or described) by a heavy-tailed Student’s t distribution, while the Indian NIFTY market’s volatility is best characterized by the generalized hyperbolic (GHYP) distribution. Also, the Chinese SHCOMP and South African JALSH markets’ volatilities are best described by the skew-GED and skew-Student’s t distribution, respectively. The study further observed that the persistence of volatility in the BRICS markets does not follow the same hierarchical pattern under the error distributions, except under the skew-Student’s t and GHYP distributions where the pattern is the same. Under these two assumptions, i.e. the skew-Student’s t and GHYP, in a descending hierarchical order of magnitudes, volatility with persistence is highest in the Chinese market, followed by the South African market, then the Russian, Indian and Brazilian markets, respectively. However, under each of the five non-Gaussian error distributions, the Chinese market is the most volatile, while the least volatile is the Brazilian market.
Measurement Characteristics of the Most Common Used International Physical Activity Questionnaires for Adults Across EU-28 in National Language Versions: Systematic Review and Meta Analysis
Authors: Sember Vedrana , Meh Kaja , Sorić Maroje , Starc Gregor , Rocha Paulo , Jurak Gregor
Published: August 2020

This review and meta-analysis (PROSPERO registration number: CRD42020138845) critically evaluates test-retest reliability, concurrent validity and criterion validity of different physical activity (PA) levels of three most-common used international PA questionnaires (PAQs) in national language versions of EU-28: IPAQ-SF, GPAQ, and EHIS-PAQ. In total, 4969 abstracts were read, 287 full-text articles were identified as relvant to the study objectives, and 19 studies were included in the final meta-analysis. The studies’ results and quality were evaluated using the Quality Assessment of Physical Activity Questionnaires (QAPAQ) checklist. Results indicate that only five EU-28 countries validated national language versions of selected PAQs. Meta analysis revealed that assessment of moderate-to-vigourus PA (MVPA) is the most relevant PA level outcome, since no publication bias in any of measurement properties was detected while test-retest reliability was the moderately-high (rw=0.74), and moderate for both criterion (rw=0.41) and concurrent validity (rw=0.72). Reporting of methods and results of the studies was poor with overall moderate risk of bias with total score of 0.43. In conclusion, where only self-reporting is feasible, assessment of MVPA with selected PAQs in EU-28 adult population is recommended for policymaking.
Mathematical Description of Elastic Phenomena which Uses Caputo or Riemann-Liouville Fractional Order Partial Derivatives is Nonobjective
Authors: Balint Agneta M. , Balint Stefan , Birauas Silviu
Published: August 2020

In this paper it is shown that mathematical description of strain, constitutive law and dynamics obtained by direct replacement of integer order derivatives with Caputo or Riemann-Liouville fractional order partial derivatives, having integral representation on finite interval, in case of a guitar string, is nonobjective. The basic idea is that different observers, using this type of descriptions, obtain different results which cannot be reconciled, i.e. transformed into each other using only formulas that link the coordinates of the same point in two fixed orthogonal reference frames and formulas that link the numbers representing the same moment of time in two different choices of the origin of time measuring. This is not an academic curiosity! It is rather a problem: which one of the obtained results is correct?
IMPLEMENTASI PENGEMBANGAN ENTERPRENEURSHIP DALAM KURIKULUM PRODI PGMI INSTITUT PESANTREN MATHALI’UL FALAH PATI-JAWA TENGAH
Authors: Ulya Inayatul
Published: August 2020

One of the problems faced by countries emerging is the number of people living in poverty. Therefore, poverty reduction a priority in the implementation of economic development. For Indonesia, the reduction of poverty is one measure of the success of development. Considering the number of the world's population in poverty, it is natural for poverty become an international problem. It proved , the PBB has set Millennium Development Goals ( MDGs ), where one of the goal is to reduce poverty . as a high-level conference participants millenium of PBB, Indonesia seriously to reduce the number of poor people to reach 50 % by 2015. Poverty is a complex issue, so that countermeasures need approaches from various aspects, whether economic, political and socio-cultural. One of the solutions is through educational activities entrepreneurship in order to change the mental attitude of dependence and to develop a work ethic, which is expected to foster self-reliance. Through the implementation of entrepreneurship education is expected to raise the awareness that to eliminate poverty must be taken through the productive work carried out by their own. Then, Prodi PGMI of Institut Pesantren Mathali’ul Falah intends to develop entrepreneurship in the curriculum design and learning experiences so that graduates can survive in his life later
Dysplasia Epiphysealis Hemimelica (Trevor Disease) of the Patella
Authors: Vashisht Saurabh , Aggarwal Purnima , Bhagat Ranjeev , Garg Ankita , Gupta P. N. , Garg Sudhir Kumar
Published: August 2020

Case:

We report a rare case of dysplasia epiphysealis hemimelica in an 11-year-old male child involving the patella. The patient noticed swelling in the right knee 6 months before presentation. On evaluation, there was a mass lesion originating from superior pole of the patella extending into the suprapatellar pouch. On opening the knee joint, it was found to be mainly cartilaginous in nature. Surgical excision of the mass was carried out.

Conclusion:

Trevor disease should be considered in the differential diagnosis of a mass originating from the patella in children. The recommended treatment is complete excision of the mass.
Prognosis of Pregnancy-associated Breast Cancer: A Meta-analysis
Authors: SHAO Chunchun , YU Zhi gang , XIAO Juan , LIU Li yuan , HONG Fan zhen , ZHANG Yuan , JIA Hong ying
Published: August 2020

Background Pregnancy-associated breast cancer (PABC) is defined as breast cancer that is diagnosed during pregnancy and/or the postpartum period. Deﬁnitions of the duration of the postpartum period have been controversial, and this variability may lead to diverse results regarding prognosis. Moreover, evidence on the dose-response association between the time from the last pregnancy to breast cancer diagnosis and overall mortality has not been synthesized. Methods We systematically searched PubMed, Embase, and the Cochrane Library for observational studies on the prognosis of PABC published up to June 1, 2019. We estimated summary-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Subgroup analyses based on diagnosis time, PABC definition, geographic region, year of publication and estimation procedure for HR were performed. Additionally, dose-response analysis was conducted by using the variance weighted least-squares regression (VWLS) trend estimation. Results A total of 54 articles (76 studies) were included in our study. PABC was associated with poor prognosis for overall survival (OS), disease-free survival (DFS) and cause-specific survival (CSS), and the pooled HRs with 95% CIs were 1.45 (1.30-1.63), 1.39 (1.25-1.54) and 1.40 (1.17-1.68), respectively. The corresponding reference category was non-PABC patients. According to subgroup analyses, the varied definition of PABC led to diverse results. The dose-response analysis indicated a nonlinear association between the time from the last delivery to breast cancer diagnosis and the HR of overall mortality (P<0.001). Compared to nulliparous women, the mortality was almost 60% higher in women with PABC diagnosed at 12 months after the last delivery (HR=1.59, 95% CI 1.30-1.82), and the mortality was not significantly different at 70 months after the last delivery (HR=1.14, 95% CI 0.99-1.25). This finding suggests that the definition of PABC should be extended to include patients diagnosed up to approximately six years postpartum (70 months after the last delivery) to capture the increased risk. Conclusion This meta-analysis suggests that PABC is associated with poor prognosis, and the definition of PABC should be extended to include patients diagnosed up to approximately six years postpartum.
HIV/AIDS research in Africa and the Middle East: participation and equity in North-South collaborations and relationships.
Authors: González-Alcaide Gregorio , Menchi-Elanzi Marouane , Nacarapa Edy , Ramos-Rincón José-Manuel
Published: August 2020

Background HIV/AIDS has attracted considerable research attention since the 1980s. In the current context of globalization and the predominance of cooperative work, it is crucial to analyze the participation of the countries and regions where the infection is most prevalent. This study assesses the participation of African countries in publications on the topic, as well as the degree of equity or influence existing in North-South relations.Methods We identified all articles and reviews of HIV/AIDS indexed in the Web of Science Core Collection. We analyzed the scientific production, collaboration, and contributions from African and Middle Eastern countries to scientific activity in the region. The concept of leadership, measured through the participation as the first author of documents in collaboration was used to determine the equity in research produced through international collaboration. Results A total of 68,808 documents published from 2010 to 2017 were analyzed. Researchers from North America and Europe participated in 82.14% of the global scientific production on HIV/AIDS, compared to just 21.61% from Africa and the Middle East. Furthermore, the publications that did come out of these regions was concentrated in a small number of countries, led by South Africa (41% of the documents). Other features associated with HIV/AIDS publications from Africa include the importance of international collaboration from the USA, the UK, and other European countries (75%-93% of the documents) and the limited participation as first authors that is evident (30% to 36% of the documents). Finally, the publications to which African countries contributed had a notably different disciplinary orientation, with a predominance of research on public health, epidemiology, and drug therapy.Conclusions It is essential to foster more balance in research output, avoid the concentration of resources that reproduces the global North-South model on the African continent, and focus the research agenda on local priorities. To accomplish this, the global North should strengthen the transfer of research skills and seek equity in cooperative ties, favoring the empowerment of African countries. These efforts should be concentrated in countries with low scientific activity and high incidence and prevalence of the disease. It is also essential to foster intraregional collaborations between African countries.