bluuebunny/crossref_metadata_2025 huggingface dataset:
POCKET BOOK KEANEKARAGAMAN MANGROVE DI KAWASAN TELUK SEPANG SEBAGAI MEDIA BELAJAR TAKSONOMI TUMBUHAN II
Authors: Agnestia Selvina , Kasrina Kasrina , Yani Ariefa Primair
Published: May 2021

Penelitian ini bertujuan untuk mengetahui kelayakan buku saku (pocket book) yang dikembangkan berdasarkan hasil dari identifikasi spesies mangrove dalam matakuliah Taksonomi Tumbuhan II. Pada penelitian ini menggunakan metode Penelitian dan Pengembangan (Research and Development). Teknik pengumpulan data pada penelitian ini adalah angket (kuisioner). Instrumen yang digunakan adalah lembar angket untuk dua orang validator (satu validator media ajar dan satu validator materi ajar), dan uji keterbacaan buku saku dilakukan kepada mahasiswa Pendidikan Biologi UNIB. Berdasarkan hasil uji validasi buku saku yang dilakukan oleh validator media ajar dengan presentase 81,25 % dan uji validasi yang dilakukan oleh validator materi ajar dengan presentase 93,75 %. Kedua skor tersebut mendapatkan presentase 87,5 % (Sangat Valid). Sementara dari hasil uji keterbacaan terhadap mahasiswa diperoleh persentase sebesar 86,3 % (Sangat Valid). Berdasarkan hasil uji validitas dan keterbacaan tersebut, buku saku yang dikembangkan, layak digunakan sebagai media ajar dalam Mata kuliah Taksonomi Tumbuhan II. Buku saku dapat memudahkan dalam penggunaannya yang mudah dibawa serta dengan isi buku saku yang lengkap beserta gambar yang jelas.Kata Kunci : Buku saku, Mangrove, Teluk Sepang
Modern Iranian Female Identity in Farhad Hassanzadeh's Hasti
Authors: Ghane Fateme , Nojoumian Amir Ali
Published: May 2021

Iranian women's first attempt at changing their social conditions dates back to the Qajar era, continuing up to the present time. In recent years, the traditional discourse on women in Iran has changed significantly, resulting in ongoing revisions concerning modern Iranian female gender identity. Yet, this new conception of identity has not been reflected in official Iranian media. Similarly, children's books usually depict women and girls mostly within pre-established ideological frameworks. However, a seminal publication project acted as a game-changer in 2010. ‘Today's Young Adult Fiction’, commissioned by the Institute for the Intellectual Development of Children and Young Adults, invited many children's and adolescents' novelists to contribute to a collection of novels with a new outlook. Among the published books, some writers narrated women's issues and struggles in the guise of young adult literature. Hasti (2013), a novel by Farhad Hassanzadeh, comes from this project, emerging as an exemplar of protest against gender stereotypes. We argue that Hassanzadeh's book has been influenced by radical changes in gender identity in Iran's recent years, and in turn, this novel, among other literary and artistic works, may raise awareness and affect the process of change in Iranian society.
Hukuk Mesleklerinde Kadınlar
Authors: Balcı Emine
Published: May 2021

Kitap, Hacettepe Üniversitesi’nde Siyaset Bilimi bilim dalında bir doktora tezi olarak hazırlanmış ve 2018 yılında Yetkin Yayınları tarafından basılmıştır. Toplumsal cinsiyet eşitsizliğinin bir yansıması olarak profesyonel mesleklerde kadın temsilindeki eşitsizliğin hukuk mesleklerinde de görüldüğü, hukuk uygulayıcılarının cinsiyeti bakımından temsilde adaletsizliğin olduğu ve bu adaletsiz durumun cinsiyetçi önyargılar temeline dayandığı argümanıyla bu eserde Türkiye’deki hukukçu kadınların hukuk mesleklerindeki temsili analiz edilmiştir.
Long Noncoding RNA lnc-TSSK2-8 Activates Canonical Wnt/β-Catenin Signaling Through Small Heat Shock Proteins HSPA6 and CRYAB
Authors: Fa Jingjing , Zhang Xiaoqing , Zhang Xiaoping , Qi Ming , Zhang Xingyu , Fu Qihua , Xu Zhuoming , Gao Yunqian , Wang Bo
Published: May 2021

Congenital heart defects (CHDs) are the most common birth defects worldwide. 22q11.2 deletion syndrome is the most common microdeletion disorder that has been frequently associated with conotruncal malformations. By now, the dosage-sensitive gene TBX1 has been adopted as the major pathogenic gene responsible for 22q11.2 deletion, which is regulated by canonical Wnt/β-catenin signaling pathway in heart outflow tract development. Here, we report the long noncoding RNA (lncRNA) lnc-TSSK2-8, which is encompassed in the 22q11.2 region, that can activate canonical Wnt/β-catenin signaling by protecting β-catenin from degradation, which could result from decreased ubiquitination. Such effects were mediated by two short heat shock proteins HSPA6 and α-β-crystallin (CRYAB), whose expression was regulated by lnc-TSSK2-8 through a competing endogenous RNA (ceRNA) mechanism. In clinical practice, the pathogenesis of copy number variation (CNV) was always attributed to haploinsufficiency of protein-coding genes. Here, we report that the 22q11.2 lncRNA lnc-TSSK2-8 significantly activated canonical Wnt/β-catenin signaling, which has major roles in cardiac outflow tract development and should act upstream of TBX1. Our results suggested that lncRNAs should contribute to the etiology of CNV-related CHD.
Replication Fork Reversal and Protection
Authors: Qiu Shan , Jiang Guixing , Cao Liping , Huang Jun
Published: May 2021

During genome replication, replication forks often encounter obstacles that impede their progression. Arrested forks are unstable structures that can give rise to collapse and rearrange if they are not properly processed and restarted. Replication fork reversal is a critical protective mechanism in higher eukaryotic cells in response to replication stress, in which forks reverse their direction to form a Holliday junction-like structure. The reversed replication forks are protected from nuclease degradation by DNA damage repair proteins, such as BRCA1, BRCA2, and RAD51. Some of these molecules work cooperatively, while others have unique functions. Once the stress is resolved, the replication forks can restart with the help of enzymes, including human RECQ1 helicase, but restart will not be considered here. Here, we review research on the key factors and mechanisms required for the remodeling and protection of stalled replication forks in mammalian cells.
Highly Efficient Semi-Continuous Extraction and In-Line Purification of High β-O-4 Butanosolv Lignin
Authors: Zijlstra Douwe Sjirk , de Korte Joren , de Vries Ernst P. C. , Hameleers Lisanne , Wilbers Erwin , Jurak Edita , Deuss Peter Joseph
Published: May 2021

Innovative biomass fractionation is of major importance for economically competitive biorefineries. Lignin is currently severely underutilized due to the use of high severity fractionation methodologies that yield complex condensed lignin that limits high-value applicability. Mild lignin fractionation conditions can lead to lignin with a more regular C-O bonded structure that has increased potential for higher value applications. Nevertheless, such extraction methodologies typically suffer from inadequate lignin extraction efficiencies and yield. (Semi)-continuous flow extractions are a promising method to achieve improved extraction efficiency of such C-O linked lignin. Here we show that optimized organosolv extraction in a flow-through setup resulted in 93–96% delignification of 40 g walnut shells (40 wt% lignin content) by applying mild organosolv extraction conditions with a 2 g/min flowrate of a 9:1 n-butanol/water mixture with 0.18 M H2SO4 at 120°C in 2.5 h. 85 wt% of the lignin (corrected for alcohol incorporation, moisture content and carbohydrate impurities) was isolated as a powder with a high retention of the β-aryl ether (β-O-4) content of 63 linking motifs per 100 C9 units. Close examination of the isolated lignin showed that the main carbohydrate contamination in the recovered lignin was butyl-xyloside and other butoxylate carbohydrates. The work-up and purification procedure were investigated and improved by the implementation of a caustic soda treatment step and phase separation with a continuous integrated mixer/separator (CINC). This led to a combined 75 wt% yield of the lignin in 3 separate fractions with 3% carbohydrate impurities and a very high β-O-4 content of 67 linking motifs per 100 C9 units. Analysis of all the mass flows showed that 98% of the carbohydrate content was removed with the inline purification step, which is a significant improvement to the 88% carbohydrate removal for the traditional lignin precipitation work-up procedure. Overall we show a convenient method for inline extraction and purification to obtain high β-O-4 butanosolv lignin in excellent yields.
The Effects of Sampling and Storage Conditions on the Metabolite Profile of the Marine Sponge Geodia barretti
Authors: Erngren Ida , Smit Eva , Pettersson Curt , Cárdenas Paco , Hedeland Mikael
Published: May 2021

Geodia barretti is a deep-sea marine sponge common in the north Atlantic and waters outside of Norway and Sweden. The sampling and subsequent treatment as well as storage of sponges for metabolomics analyses can be performed in different ways, the most commonly used being freezing (directly upon collection or later) or by storage in solvent, commonly ethanol, followed by freeze-drying. In this study we therefore investigated different sampling protocols and their effects on the detected metabolite profiles in liquid chromatography-mass spectrometry (LC-MS) using an untargeted metabolomics approach. Sponges (G. barretti) were collected outside the Swedish west coast and pieces from three sponge specimens were either flash frozen in liquid nitrogen, frozen later after the collection cruise, stored in ethanol or stored in methanol. The storage solvents as well as the actual sponge pieces were analyzed, all samples were analyzed with hydrophilic interaction liquid chromatography as well as reversed phase liquid chromatography with high resolution mass spectrometry using full-scan in positive and negative ionization mode. The data were evaluated using multivariate data analysis. The highest metabolite intensities were found in the frozen samples (flash frozen and frozen after sampling cruise) as well as in the storage solvents (methanol and ethanol). Metabolites extracted from the sponge pieces that had been stored in solvent were found in very low intensity, since the majority of metabolites were extracted to the solvents to a high degree. The exception being larger peptides and some lipids. The lowest variation between replicates were found in the flash frozen samples. In conclusion, the preferred method for sampling of sponges for metabolomics was found to be immediate freezing in liquid nitrogen. However, freezing the sponge samples after some time proved to be a reliable method as well, albeit with higher variation between the replicates. The study highlights the importance of saving ethanol extracts after preservation of specimens for biology studies; these valuable extracts could be further used in studies of natural products, chemosystematics or metabolomics.
Genetic Manipulation of Ticks: A Paradigm Shift in Tick and Tick-Borne Diseases Research
Authors: Nuss Andrew , Sharma Arvind , Gulia-Nuss Monika
Published: May 2021

Ticks are obligate hematophagous arthropods that are distributed worldwide and are one of the most important vectors of pathogens affecting humans and animals. Despite the growing burden of tick-borne diseases, research on ticks has lagged behind other arthropod vectors, such as mosquitoes. This is largely because of challenges in applying functional genomics and genetic tools to the idiosyncrasies unique to tick biology, particularly techniques for stable genetic transformations. CRISPR-Cas9 is transforming non-model organism research; however, successful germline editing has yet to be accomplished in ticks. Here, we review the ancillary methods needed for transgenic tick development and the use of CRISPR/Cas9, the most promising gene-editing approach, for tick genetic transformation.
Subsequent Fertility in Women Treated for Caesarean Scar Pregnancy With Hysteroscopy: A 5-Year Follow-Up Descriptive Study in a Tertiary Hospital
Authors: Sun Xinyi , Liu Yang , Tang Yunhui , Yu Hongying , Zhao Min , Chen Qi
Published: May 2021

Objective

The outcomes of subsequent pregnancies and fertility in women with a history of caesarean scar pregnancy have not been well described. In this study, we followed up 149 women with a history of caesarean scar pregnancy and analysed the effect on their fertility.

Methods

149 women with a history of caesarean scar pregnancy were followed up for five years. Of them, 53 women had unprotected sexual intercourse attempting to become pregnant again. Data including clinical parameters and treatment options at the time of diagnosis of caesarean scar pregnancy, and the outcomes in subsequent pregnancy were collected. In addition, a questionnaire about the menstrual cycle after treatment was voluntarily completed by these women.

Results

Of the 53 women, 46 (84%) women had a subsequent pregnancy, while seven (14%) women did not. There was no association between the clinical parameters in previous caesarean scar pregnancy or treatment and future fertility. From the questionnaire, there was no difference seen in the length of the menstrual cycle and menses between the two groups. However, a higher number of women with light menstrual bleeding were seen in women without a subsequent pregnancy (67%), compared with women who did (28%). In addition, six women (13%) who had a subsequent pregnancy experienced foetus death in the first trimester.

Conclusion

We reported that 14% of women with a history of cesarean scar pregnancy did not have a subsequent pregnancy, after unprotected sexual intercourse for more than two years. Light menstrual bleeding after treatment may be associated with this adverse effect. Our findings need to be further investigated with large sample size.
Birch as a Model Species for the Acclimation and Adaptation of Northern Forest Ecosystem to Changing Environment
Authors: Oksanen Elina
Published: May 2021

Northern forest ecosystems are exposed to rapid climate change, i.e., climate warming, extended growing seasons, increasing greenhouse gases, and changes in precipitation and water availability, accompanied by increasing pressure of herbivores and pathogens. Silver birch (Betula pendulaRoth) is an important deciduous trees species in the boreal zone, with extensive distribution across Eurasia. Silver birch is an excellent model system for the adaptation of northern trees to climate change due to recent advances in genomics, high genetic variation, and intensive studies with different abiotic and biotic stress factors. In this paper, the current understanding about the responses and acclimation mechanisms of birch to changing environment is presented, based on Fennoscandian studies. Several complementary experiments in laboratory, semi-field and natural field conditions have shown that warming climate and increasing CO2is expected to increase the growth and biomass of birch, but the risk of herbivore damage will increase with negative impact on carbon sink strength. Deleterious impacts of high humidity, soil drought and increasing ozone has been clearly demonstrated. All these environmental changes have led to metabolic shifts or changes in carbon/nutrient balance which may have further ecological impacts. However, high plasticity and genotypic variation predict excellent acclimation capacity in rapidly changing environment and a rich genetic pool for sustainable forestry. Because the trees and forest ecosystems are exposed to multiple environmental factors simultaneously, it is necessary to continue research with multiple-stress interaction studies.
Mesopelagic Scattering Layer Behaviors Across the Clarion-Clipperton Zone: Implications for Deep-Sea Mining
Authors: Perelman Jessica N. , Firing Eric , van der Grient Jesse M. A. , Jones Benjamin A. , Drazen Jeffrey C.
Published: May 2021

The Clarion-Clipperton Zone (CCZ) is a 4 million km2 area in the eastern Central Pacific Ocean exhibiting large variability in environmental parameters, particularly oxygen and primary production, that is being targeted for deep-sea polymetallic nodule mining. This remote region’s pelagic biology is very poorly sampled, including for micronekton and zooplankton that provide essential ecosystem services such as carbon flux and support for commercial fisheries. We built a baseline of deep scattering layer (DSL) depths and vertical migration behaviors, proxies for mesopelagic micronekton and zooplankton communities, using shipboard acoustic Doppler current profiler datasets. Acoustic data (38 kHz, 75 kHz) were compiled from research cruises passing near or through the CCZ (2004–2019), and environmental data (mean midwater oxygen partial pressure, surface chlorophyll-a, and sea surface height anomaly) were assembled from the World Ocean Atlas and satellite oceanographic datasets. Our results suggest that midwater oxygen, associated with the Eastern Tropical Pacific Oxygen Minimum Zone (OMZ), is the strongest predictor of daytime DSL depths and the proportions of midwater populations that undergo vertical migration in this region. We used these relationships to predict micronekton and zooplankton behaviors across the CCZ, including licensed mining exploration areas and no-mining reserves. While the OMZ encompasses most licensed exploration areas, the current network of reserves lies outside of the core OMZ and ultimately may not represent or protect the pelagic OMZ fauna at highest risk from mining impacts. This research will further assist in developing resource exploitation regulations by the International Seabed Authority, and will provide mesopelagic baseline information for monitoring changes that may occur in the CCZ once industrial-scale mining begins.
Diel Transcriptional Oscillations of a Plastid Antiporter Reflect Increased Resilience of Thalassiosira pseudonana in Elevated CO2
Authors: Valenzuela Jacob J. , Ashworth Justin , Cusick Allison , Abbriano Raffaela M. , Armbrust E. Virginia , Hildebrand Mark , Orellana Mónica V. , Baliga Nitin S.
Published: May 2021

Acidification of the ocean due to high atmospheric CO2 levels may increase the resilience of diatoms causing dramatic shifts in abiotic and biotic cycles with lasting implications on marine ecosystems. Here, we report a potential bioindicator of a shift in the resilience of a coastal and centric model diatom Thalassiosira pseudonana under elevated CO2. Specifically, we have discovered, through EGFP-tagging, a plastid membrane localized putative Na+(K+)/H+ antiporter that is significantly upregulated at >800 ppm CO2, with a potentially important role in maintaining pH homeostasis. Notably, transcript abundance of this antiporter gene was relatively low and constant over the diel cycle under contemporary CO2 conditions. In future acidified oceanic conditions, dramatic oscillation with >10-fold change between nighttime (high) and daytime (low) transcript abundances of the antiporter was associated with increased resilience of T. pseudonana. By analyzing metatranscriptomic data from the Tara Oceans project, we demonstrate that phylogenetically diverse diatoms express homologs of this antiporter across the globe. We propose that the differential between night- and daytime transcript levels of the antiporter could serve as a bioindicator of a shift in the resilience of diatoms in response to high CO2 conditions in marine environments.
Economic Study of 2-Stage Exchange in Patients With Knee or Hip Prosthetic Joint Infection Managed in a Referral Center in France: Time to Use Innovative(s) Intervention(s) at the Time of Reimplantation to Reduce the Risk of Superinfection
Authors: Serrier Hassan , Julien Christell , Batailler Cécile , Mabrut Eugénie , Brochier Corinne , Thevenon Sylvie , Maynard-Muet Marianne , Henry Agnes , Lustig Sébastien , Huot Laure , Ferry Tristan ,   The Lyon BJI Study group
Published: May 2021

Objective: Chronic prosthetic joint infections (PJI) are serious complications in arthroplasty leading to prosthesis exchange and potential significant costs for health systems, especially if a subsequent new infection occurs. This study assessed the cost of chronic PJI managed with 2-stage exchange at the Lyon University Hospital, CRIOAc Lyon reference center, France. A threshold analysis was then undertaken to determine the reimbursement tariff of a hypothetical preventive device usable at the time of reimplantation, which possibly enables health insurance to save money according to the risk reduction of subsequent new infection. This analysis was also performed for a potential innovative device already available on the market, a dual antibiotic loaded bone cement used to fix cemented prosthesis that releases high concentrations of gentamicin and vancomycin locally (G+V cement).

Method: Patients >18 years, admitted for a hip or knee chronic PJI managed with 2-stage exchange, between January 1, 2013, and December 31, 2015, were retrospectively identified. Following, resource consumption in relation to inpatient hospital stay, hospitalization at home, rehabilitation care, outpatient antibiotic treatments, imaging, laboratory analysis, and consultations were identified and collected from patient records and taken into account in the evaluation. Costs were assessed from the French health insurance perspective over the 2 years following prosthesis reimplantation.

Results: The study included 116 patients (median age 67 y; 47% hip prosthesis). Mean cost of chronic PJI was estimated over the 2 years following prosthesis reimplantation at €21,324 for all patients, and at €51,697 and €15,745 for patients with (n = 18) and without (n = 98) a subsequent new infection after reimplantation, respectively. According to the threshold analysis the reimbursement tariff (i) should not exceed €2,820 for a device which can reduce the risk of a new infection by 50% and (ii) was between €2,988 and €3,984 if the G + V cement can reduce the risk of a new infection by 80% (this reduction risk is speculative and has to be confirmed by clinical trials).

Conclusion: This study revealed that chronic PJI requiring a 2-stage revision is costly, with significant costs in relation to the reimplantation procedure (about 15 k€). However, following reimplantation the rate of subsequent new infection remained high, and the cost of reimplantation following a new infection is considerable, reaching 50k€ per patient. These first cost estimates of managing chronic PJI with 2-stage exchange in France underline the economic interest of preventing new infections.
Age-Dependent Remodeling in Infrapatellar Fat Pad Adipocytes and Extracellular Matrix: A Comparative Study
Authors: Stocco Elena , Belluzzi Elisa , Contran Martina , Boscolo-Berto Rafael , Picardi Edgardo , Guidolin Diego , Fontanella Chiara Giulia , Olivotto Eleonora , Filardo Giuseppe , Borile Giulia , Romanato Filippo , Ramonda Roberta , Ruggieri Pietro , Favero Marta , Porzionato Andrea , De Caro Raffaele , Macchi Veronica
Published: May 2021

The infrapatellar fat pad (IFP) is actively involved in knee osteoarthritis (OA). However, a proper description of which developmental modifications occur in the IFP along with age and in absence of joint pathological conditions, is required to adequately describe its actual contribution in OA pathophysiology. Here, two IFP sources were compared: (a) IFP from healthy young patients undergoing anterior-cruciate ligament (ACL) reconstruction for ACL rupture (n = 24); (b) IFP from elderly cadaver donors (n = 23). After histopathological score assignment to confirm the absence of inflammatory features (i.e., inflammatory infiltrate and increased vascularity), the adipocytes morphology was determined; moreover, extracellular matrix proteins were studied through histology and Second Harmonic Generation approach, to determine collagens content and orientation by Fast Fourier Transform and OrientationJ. The two groups were matched for body mass index. No inflammatory signs were observed, while higher area, perimeter, and equivalent diameter and volume were detected for the adipocytes in the elderly group. Collagen III displayed higher values in the young group and a lower total collagen deposition with aging was identified. However, collagen I/III ratio and the global architecture of the samples were not affected. A higher content in elastic fibers was observed around the adipocytes for the ACL-IFPs and in the septa cadaver donor-IFPs, respectively. Age affects the characteristics of the IFP tissue also in absence of a pathological condition. Variable mechanical stimulation, depending on age-related different mobility, could be speculated to exert a role in tissue remodeling.
Effects of Obligate Heterofermentative Lactic Acid Bacteria Alone or in Combination on the Conservation of Sugarcane Silage
Authors: Gomes Ana Luiza Mendonça , Bueno Antônio Vinicius Iank , Osmari Milene Puntel , Machado Juliana , Nussio Luiz Gustavo , Jobim Clóves Cabreira , Daniel João Luiz Pratti
Published: May 2021

Our objective was to determine the effects of two strains of obligate heterofermentative bacteria, alone or in combination, on the fermentation profile, gas production kinetics, chemical composition, and aerobic stability of sugarcane silage. A plot of sugarcane was manually harvested, mechanically chopped and treated with: distilled water (5 mL kg–1; Control),Lentilactobacillus hilgardiiCNCM I-4785 [3 × 105colony-forming units (cfu) g–1; LH],Lentilactobacillus buchneriNCIMB 40788 (3 × 105cfu g–1; LB), and LH+LB (1.5 × 105cfu g–1of each strain). Treated forages were packed into 1.96-L gas-tight silos (0.40 porosity) and stored at 25 ± 1.5°C for 70 days (4 replicates per treatment). All heterolactic inoculants were effective to increase acetic acid concentration and inhibit yeast metabolism, as treated silages had lower formation of ethanol, ethyl esters and gas during fermentation. Lower fungal development spared soluble carbohydrates, consequently resulting in silages with higherin vitrodigestibility. Nevertheless,L. buchneriwas the most effective strain to extend the aerobic stability of sugarcane silage (based on both temperature and pH rise). The use ofL. buchnerialone or in combination withL. hilgardii, applied at 3 × 105cfu g–1, is a feasible strategy to inhibit yeast metabolism and increase the nutritional quality of sugarcane silage.
Investigating the Mechanism of Sodium Binding to SERT Using Direct Simulations
Authors: Szöllősi Dániel , Stockner Thomas
Published: May 2021

The serotonin transporter (SERT) terminates neurotransmission by transporting serotonin from the synapse into the pre-synaptic nerve terminal. Altered SERT function leads to several neurological diseases including depression, anxiety, mood disorders, and attention deficit hyperactivity disorders (ADHD). Accordingly SERT is the target for their pharmacological treatments, but also targeted by multiple drugs of abuse. Transport of serotonin by SERT is energized by the transmembrane electrochemical gradient of sodium. We used extensive molecular dynamics simulations to investigate the process of sodium binding to SERT, which is the first step in the transport cycle that leads to serotonin uptake. Comparing data from 51 independent simulations, we find a remarkably well-defined path for sodium entry and could identify two transient binding sites, while observing binding kinetics that are comparable to experimental data. Importantly, the structure and dynamics of the sodium binding sites indicate that sodium binding is accompanied by an induced-fit mechanism that leads to new conformations and reduces local dynamics.
Accuracy of Support-Vector Machines for Diagnosis of Alzheimer's Disease, Using Volume of Brain Obtained by Structural MRI at Siriraj Hospital
Authors: Vichianin Yudthaphon , Khummongkol Anutr , Chiewvit Pipat , Raksthaput Atthapon , Chaichanettee Sunisa , Aoonkaew Nuttapol , Senanarong Vorapun
Published: May 2021

Background: The determination of brain volumes using visual ratings is associated with an inherently low accuracy for the diagnosis of Alzheimer's disease (AD). A support-vector machine (SVM) is one of the machine learning techniques, which may be utilized as a classifier for various classification problems. This study exploratorily investigated the accuracy of SVM classification models for AD subjects using brain volume and various clinical data as features.

Methods: The study was designed as a retrospective chart review. A total of 201 eligible subjects were recruited from the Memory Clinic at Siriraj Hospital, Thailand. Eighteen cases were excluded due to incomplete MRI data. Subjects were randomly assigned to a training group (AD = 46, normal = 46) and testing group (AD = 45, normal = 46) for SVM modeling and validation, respectively. The results in terms of accuracy and a receiver operating characteristic curve analysis are reported.

Results: The highest accuracy for brain volumetry (62.64%) was found using the hippocampus as a single feature. A combination of clinical parameters as features provided accuracy ranging between 83 and 90%. However, a combination of brain volumetry and clinical parameters as features to the SVM models did not improve the accuracy of the result.

Conclusions: In our study, the use of brain volumetry as SVM features provided low classification accuracy with the highest accuracy of 62.64% using the hippocampus volume alone. In contrast, the use of clinical parameters [Thai mental state examination score, controlled oral word association tests (animals; and letters K, S, and P), learning memory, clock-drawing test, and construction-praxis] as features for SVM models provided good accuracy between 83 and 90%.
Synergistic Effect of Statins and Abiraterone Acetate on the Growth Inhibition of Neuroblastoma via Targeting Androgen Receptor
Authors: Hu Zengchun , Cheng Chuandong , Wang Yue , Chen Tianrui , Tu Junhong , Niu Chaoshi , Xing Rong , Wang Yang , Xu Yinghui
Published: May 2021

Neuroblastoma is the most common extracranial neuroendocrine tumor in childhood. Although many studies have tried to find effective treatments, there are still numerous limitations in current clinical targeted therapy. So, it is important to find new therapeutic targets and strategies from a new perspective. Our previous study reported that the androgen receptor (AR) promotes the growth of neuroblastoma in vitro and in vivo. Based on documentary investigation, we postulated that the AR–SCAP–SREBPs-CYP17/HMGCR axis may regulate cholesterol and androgens synthesis and form a positive enhancement loop promoting NB progression. Clinical samples and Oncomine database analysis proved the activation of AR–SCAP–SREBPs-CYP17/HMGCR axis in neuroblastoma. The combination of inhibitors of HMGCR (statins) and CYP17A1 (abiraterone acetate) showed synergistic effect that significantly inhibited the proliferation and migration with decreased expression of related genes detected in vitro and in vivo suggesting the dual-targeted therapy had the potential to inhibit the progression of neuroblastoma in spite of its MYCN status. This study provides new ideas for clinical treatment of neuroblastoma with efficacy and reduced toxicity.
Combining 68Ga-PSMA-PET/CT-Directed and Elective Radiation Therapy Improves Outcome in Oligorecurrent Prostate Cancer: A Retrospective Multicenter Study
Authors: Kirste Simon , Kroeze Stephanie G. C. , Henkenberens Christoph , Schmidt-Hegemann Nina-Sophie , Vogel Marco M. E. , Becker Jessica , Zamboglou Constantinos , Burger Irene , Derlin Thorsten , Bartenstein Peter , Ruf Juri , la Fougère Christian , Eiber Matthias , Christiansen Hans , Combs Stephanie E. , Müller Arndt-Christian , Belka Claus , Guckenberger Matthias , Grosu Anca-Ligia
Published: May 2021

Background

In case of oligo-recurrent prostate cancer (PC) following prostatectomy, 68Ga-PSMA-PET/CT can be used to detect a specific site of recurrence and to initiate metastasis-directed radiation therapy (MDT). However, large heterogeneities exist concerning doses, treatment fields and radiation techniques, with some studies reporting focal radiotherapy (RT) to PSMA-PET/CT positive lesions only and other studies using elective RT strategies. We aimed to compare oncological outcomes and toxicity between PET/CT-directed RT (PDRT) and PDRT plus elective RT (eRT; i.e. prostate bed, pelvic or paraaortal nodes) in a large retrospective multicenter study.

Methods

Data of 394 patients with oligo-recurrent 68Ga-PSMA-PET/CT-positive PC treated between 04/2013 and 01/2018 in six different academic institutions were evaluated. Primary endpoint was biochemical-recurrence-free survival (bRFS). bRFS was analyzed using Kaplan–Meier survival curves and log rank testing. Uni- and multivariate analyses were performed to determine influence of treatment parameters.

Results

In 204 patients (51.8%) RT was directed only to lesions seen on 68Ga-PSMA-PET/CT (PDRT), 190 patients (48.2%) received PDRT plus eRT. PDRT plus eRT was associated with a significantly improved 3-year bRFS compared to PDRT alone (53 vs. 37%; p = 0.001) and remained an independent factor in multivariate analysis (p = 0.006, HR 0.29, 95% CI 0.12–0.68). This effect was more pronounced in the subgroup of patients who were treated with PDRT and elective prostate bed radiotherapy (ePBRT) with a 3-year bRFS of 61% versus 22% (p <0.001). Acute and late toxicity grade ≥3 was 0.8% and 3% after PDRT plus eRT versus no toxicity grade ≥3 after PDRT alone.

Conclusions

In this large cohort of patients with oligo-recurrent prostate cancer, elective irradiation of the pelvic lymphatics and the prostatic bed significantly improved bRFS when added to 68Ga-PSMA-PET/CT-guided focal radiotherapy. These findings need to be evaluated in a randomized controlled trial.
Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio
Authors: van Gisbergen Marike W. , Zwilling Emma , Dubois Ludwig J.
Published: May 2021

To meet the anabolic demands of the proliferative potential of tumor cells, malignant cells tend to rewire their metabolic pathways. Although different types of malignant cells share this phenomenon, there is a large intracellular variability how these metabolic patterns are altered. Fortunately, differences in metabolic patterns between normal tissue and malignant cells can be exploited to increase the therapeutic ratio. Modulation of cellular metabolism to improve treatment outcome is an emerging field proposing a variety of promising strategies in primary tumor and metastatic lesion treatment. These strategies, capable of either sensitizing or protecting tissues, target either tumor or normal tissue and are often focused on modulating of tissue oxygenation, hypoxia-inducible factor (HIF) stabilization, glucose metabolism, mitochondrial function and the redox balance. Several compounds or therapies are still in under (pre-)clinical development, while others are already used in clinical practice. Here, we describe different strategies from bench to bedside to optimize the therapeutic ratio through modulation of the cellular metabolism. This review gives an overview of the current state on development and the mechanism of action of modulators affecting cellular metabolism with the aim to improve the radiotherapy response on tumors or to protect the normal tissue and therefore contribute to an improved therapeutic ratio.
World Cancer Day 2021 - Perspectives in Pediatric and Adult Neuro-Oncology
Authors: Sulman Erik P. , Eisenstat David D.
Published: May 2021

Significant advances in our understanding of the molecular genetics of pediatric and adult brain tumors and the resulting rapid expansion of clinical molecular neuropathology have led to improvements in diagnostic accuracy and identified new targets for therapy. Moreover, there have been major improvements in all facets of clinical care, including imaging, surgery, radiation and supportive care. In selected cohorts of patients, targeted and immunotherapies have resulted in improved patient outcomes. Furthermore, adaptations to clinical trial design have facilitated our study of new agents and other therapeutic innovations. However, considerable work remains to be done towards extending survival for all patients with primary brain tumors, especially children and adults with diffuse midline gliomas harboring Histone H3 K27 mutations and adults with isocitrate dehydrogenase (IDH) wild-type, O6 guanine DNA-methyltransferase gene (MGMT) promoter unmethylated high grade gliomas. In addition to improvements in therapy and care, access to the advances in technology, such as particle radiation or biologic therapy, neuroimaging and molecular diagnostics in both developing and developed countries is needed to improve the outcome of patients with brain tumors.
Radiation Therapy for Chemotherapy Refractory Gingival Myeloid Sarcoma
Authors: Lee Daniel Y. , Baron Jonathan , Wright Christopher M. , Plastaras John P. , Perl Alexander E. , Paydar Ima
Published: May 2021

Gingival myeloid sarcoma (MS) refractory to induction chemotherapy is a rare clinical entity and can be treated with palliative radiation therapy (RT). However, there are few previously published reports of RT approaches for the treatment of gingival MS. We present a single institution retrospective observational study of adult patients treated with palliative RT for chemotherapy refractory gingival MS. A total of six patients diagnosed with gingival MS in the setting of relapsed or refractory acute myeloid leukemia treated with palliative RT were identified, with a median age of 66 (range 52–77). Patients were treated with radiation doses ranging from 5 to 20 Gy in 2–10 fractions. Two patients had adequate follow-up time to assess treatment response. One patient who was simulated with PET/CT experienced a local complete response, while the other patient required retreatment 2 months after initial treatment and experienced an eventual local partial response. Three patients experienced radiation mucositis, with one patient experiencing grade 5 toxicity attributed to concomitant treatment with the radiosensitizer hydroxyurea. We believe that this study can provide a practical reference point for other clinicians given the rarity of gingival MS requiring palliative radiation therapy as a clinical entity.
Micro-Ureteroscopy as a Treatment of Renal Pelvis Lithiasis in Young Children
Authors: Parente Alberto , Ortiz Ruben , Fernández-Bautista Beatriz , Burgos Laura , Angulo José Maria
Published: May 2021

Aim: Miniaturization of endoscopic instruments has allowed to improve the efficacy of kidney stone treatment in young children. Aim of the study is to evaluate the usefulness of microureteroscopy with 4.85F sheath in the treatment of renal stones in children.

M&M: We present 4 cases of microureteroscopy in 3 younger than 3 years patients with renal pelvic stones. Lithiasis was unilateral in 2 female patients and bilateral in 1 male patient. Microureteroscopy was performed using a MicroPerc set 4.85F sheath, without placing a safety guide or dilating the meatus in 3 procedures. The lithotripter system used was Ho:YAG Laser with 200-μm fiber in all cases.

Results: Mean operating time was 100 ± 16 min. There were no intraoperative complications. In all procedures, complete pulverization of the lithiasis was achieved, except in the coraliform lithiasis in which 5 mm residual lithiasis remained in the lower calyx. All patients were discharged 24 h after the intervention.

Conclusion: Microureteroscopy can be considered a new alternative for treatment of selected cases of renal pelvic stones in infants and children.
Netherton Syndrome in Children: Management and Future Perspectives
Authors: Barbati Federica , Giovannini Mattia , Oranges Teresa , Lodi Lorenzo , Barni Simona , Novembre Elio , Baldo Ermanno , Cristofolini Mario , Stagi Stefano , Ricci Silvia , Mori Francesca , Filippeschi Cesare , Azzari Chiara , Indolfi Giuseppe
Published: May 2021

Netherton syndrome (NS) is a genetic, multisystemic disease classically distinguished by a triad of clinical manifestations: congenital ichthyosiform erythroderma, hair shaft abnormalities, and immune dysregulation. Due to the complex pathogenesis of the disease, there are no specific therapies currently accessible for patients with NS. An early diagnosis is crucial to start the correct management of these patients. A multidisciplinary approach, including specialists in immunology, allergology, and dermatology, is necessary to set up the best therapeutic pathway. We conducted a review with the aim to summarize the different therapeutic strategies currently accessible and potentially available in the future for children with NS. However, given the limited data in the literature, the best-tailored management should be decided upon the basis of the specific clinical characteristics of the patients with this rare clinical condition. Further comprehension of the pathophysiology of the disease could lead to more efficacious specific therapeutic options, which could allow a change in the natural history of NS.
Heterocyclic Compounds: Pharmacology of Pyrazole Analogs From Rational Structural Considerations
Authors: Costa Rafael Fernades , Turones Larissa Córdova , Cavalcante Keilah Valéria Naves , Rosa Júnior Ismael Aureliano , Xavier Carlos Henrique , Rosseto Lucimar Pinheiro , Napolitano Hamilton Barbosa , Castro Patrícia Ferreira da Silva , Neto Marcos Luiz Ferreira , Galvão Gustavo Mota , Menegatti Ricardo , Pedrino Gustavo Rodrigues , Costa Elson Alves , Martins José Luis Rodrigues , Fajemiroye James Oluwagbamigbe
Published: May 2021

Low quality of life and life-threatening conditions often demand pharmacological screening of lead compounds. A spectrum of pharmacological activities has been attributed to pyrazole analogs. The substitution, replacement, or removal of functional groups on a pyrazole ring appears consistent with diverse molecular interactions, efficacy, and potency of these analogs. This mini-review explores cytotoxic, cytoprotective, antinociceptive, anti-inflammatory, and antidepressant activities of some pyrazole analogs to advance structure-related pharmacological profiles and rational design of new analogs. Numerous interactions of these derivatives at their targets could impact future research considerations and prospects while offering opportunities for optimizing therapeutic activity with fewer adverse effects.
Constitutive Endocytosis of the Neuronal Glutamate Transporter Excitatory Amino Acid Transporter-3 Requires ARFGAP1
Authors: Saha Kusumika , Yang Jae-Won , Hofmaier Tina , Venkatesan SanthoshKannan , Steinkellner Thomas , Kudlacek Oliver , Sucic Sonja , Freissmuth Michael , Sitte Harald H.
Published: May 2021

The eukaryotic endocytic pathway regulates protein levels available at the plasma membrane by recycling them into specific endosomal compartments. ARFGAP1 is a component of the coat protein I (COPI) complex but it also plays a role in promoting adapter protein-2 (AP-2) mediated endocytosis. The excitatory amino acid transporter-3 (EAAT3) mediates the reuptake of glutamate from the synaptic cleft to achieve rapid termination of synaptic transmission at glutamatergic synapses. In this study, we identified two interacting proteins of EAAT3 by mass spectrometry (MS) ARFGAP1 and ARF6. We explored the role of ARFGAP1 and ARF6 in the endocytosis of EAAT3. Our data revealed that ARFGAP1 plays a role in the recycling of EAAT3, by utilizing its GTPase activating protein (GAP) activity and ARF6 acting as the substrate. ARFGAP1 promotes cargo sorting of EAAT3 via a single phenylalanine residue (F508) located at the C-terminus of the transporter. ARFGAP1-promoted AP-2 dependent endocytosis is abolished upon neutralizing F508. We utilized a heterologous expression system to identify an additional motif in the C-terminus of EAAT3 that regulates its endocytosis. Impairment in endocytosis did not affect somatodendritic targeting in cultured hippocampal neurons. Our findings support a model where endocytosis of EAAT3 is a multifactorial event regulated by ARFGAP1, occurring via the C-terminus of the transporter, and is the first study to examine the role of ARFGAP1 in the endocytosis of a transport protein.
Parent-Adolescent Communication and Early Adolescent Depressive Symptoms: The Roles of Gender and Adolescents’ Age
Authors: Zhang Qiongwen , Pan Yangu , Zhang Lei , Lu Hang
Published: May 2021

Positive parent-adolescent communication has been found to be negatively related to adolescent depressive symptoms; however, few studies have investigated the moderating effects of adolescent gender and age on this relationship, especially during early adolescence in China. The present study investigated the joint moderating effects of adolescent gender and age on the linkage of father-adolescent and mother-adolescent communication with adolescents’ depressive symptoms. A total of 11,455 Chinese junior high school students (Mage = 14.15 years, SD = 1.22 years; 49.86% boys; Ngrade7 = 5712, Ngrade9 = 5743) completed ad hoc questionnaires of parent-adolescent communication and depressive symptoms. Multiple linear regression analyses were conducted. Results indicated that gender and age jointly moderated the association between parental communication and adolescent depressive symptoms. Specifically, for girls, the negative effects of both father-adolescent and mother-adolescent communication on depressive symptoms were stronger in 9th grade students than in 7th grade students, while for boys, the negative effects were not different between 7th grade students and 9th grade students. These findings suggest that in China, the protective effects of positive parent-adolescent communication on adolescents’ depressive symptoms may be most salient among senior-grade girls in junior high school.
Effect of Cognitive Variables on the Reading Ability of Spanish Children at Age Seven
Authors: González-Valenzuela María José , López-Montiel Dolores , Díaz-Giráldez Félix , Martín-Ruiz Isaías
Published: May 2021

The objective of this study is to determine the contribution made by knowledge of letters, phonological awareness, phonological memory, and alphanumeric and non-alphanumeric rapid automatized naming at the ages of six and seven to the ability of Spanish children to read words at 7 years of age. A total of 116 Spanish-speaking school children took part in the study, from schools located in an average socio-cultural setting, without special educational needs. The reading ability of these pupils was evaluated at the age of seven, and cognitive variables were assessed at 6 and 7 years of age. Descriptive-exploratory analyses, bivariate analyses, and multivariate regressions were performed. The results show that cognitive variables measured at these ages contribute differently to the ability to read words at 7 years of age. Rapid naming does not seem to influence word reading; knowledge of letters no longer influences word reading as children grow older; and phonological awareness and phonological memory maintain their contribution to the explanation of word reading. These results indicate that reading in Spanish depends on different cognitive variables and that this relationship varies according to age. The findings have key educational implications in terms of teaching reading skills and the prevention of specific learning difficulties in Spanish Primary Education.