bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting androgen receptor (AR) with antiandrogen Enzalutamide increases prostate cancer cell invasion yet decreases bladder cancer cell invasion via differentially altering the AR/circRNA-ARC1/miR-125b-2-3p or miR-4736/PPARγ/MMP-9 signals
Authors: Deng Gang , Wang Ronghao , Sun Yin , Huang Chi-Ping , Yeh Shuyuan , You Bosen , Feng Changyong , Li Gonghui , Ma Shenglin , Chang Chawnshang 
Published: June 2021

AbstractAndrogen-deprivation therapy (ADT) via targeting androgens/androgen receptor (AR) signals may suppress cell proliferation in both prostate cancer (PCa) and bladder cancer (BCa), yet its impact on the cell invasion of these two urological cancers remains unclear. Here we found targeting androgens/AR with either the recently developed antiandrogen Enzalutamide (Enz) or AR-shRNAs led to increase PCa cell invasion, yet decrease BCa cell invasion. Mechanistic dissection revealed that suppressing androgens/AR signals could result in differential alterations of the selective circular RNAs (circRNAs) as a result of differential endogenous AR transcription. A negative autoregulation in PCa, yet a positive autoregulation in BCa, as a result of differential binding of AR to different androgen-response elements (AREs) and a discriminating histone H3K4 methylation, likely contributes to this outcome between these two urological tumors. Further mechanistic studies indicated that AR-encoded circRNA-ARC1 might sponge/alter the availability of the miRNAs miR-125b-2-3p and/or miR-4736, to impact the metastasis-related PPARγ/MMP-9 signals to alter the PCa vs. BCa cell invasion. The preclinical study using the in vivo mouse model confirms in vitro cell lines data, showing that Enz treatment could increase PCa metastasis, which can be suppressed after suppressing circRNA-ARC1 with sh-circRNA-ARC1. Together, these in vitro/in vivo results demonstrate that antiandrogen therapy with Enz via targeting AR may lead to either increase PCa cell invasion or decrease BCa cell invasion. Targeting these newly identified AR/circRNA-ARC1/miR-125b-2-3p and/or miR-4736/PPARγ/MMP-9 signals may help in the development of new therapies to better suppress the Enz-altered PCa vs. BCa metastasis.
Conventional glaucoma implants and the new MIGS devices: a comprehensive review of current options and future directions
Authors: Pereira Inês C. F. , van de Wijdeven Rosanne , Wyss Hans M. , Beckers Henny J. M. , den Toonder Jaap M. J. 
Published: June 2021

AbstractGlaucoma is a progressive optic neuropathy that is the second leading cause of preventable blindness worldwide, after cataract formation. A rise in the intraocular pressure (IOP) is considered to be a major risk factor for glaucoma and is associated with an abnormal increase of resistance to aqueous humour outflow from the anterior chamber. Glaucoma drainage devices have been developed to provide an alternative pathway through which aqueous humour can effectively exit the anterior chamber, thereby reducing IOP. These devices include the traditional aqueous shunts with tube-plate design, as well as more recent implants, such as the trabeculectomy-modifying EX-PRESS® implant and the new minimally invasive glaucoma surgery (MIGS) devices. In this review, we will describe each implant in detail, focusing on their efficacy in reducing IOP and safety profile. Additionally, a critical and evidence-based comparison between these implants will be provided. Finally, we will propose potential developments that may help to improve the performance of current devices.
Variants in BANK1 are associated with lupus nephritis of European ancestry
Authors: Bolin Karin , Imgenberg-Kreuz Juliana , Leonard Dag , Sandling Johanna K. , Alexsson Andrei , Pucholt Pascal , Haarhaus Malena Loberg , Almlöf Jonas Carlsson , Nititham Joanne , Jönsen Andreas , Sjöwall Christopher , Bengtsson Anders A. , Rantapää-Dahlqvist Solbritt , Svenungsson Elisabet , Gunnarsson Iva , Syvänen Ann-Christine , Lerang Karoline , Troldborg Anne , Voss Anne , Molberg Øyvind , Jacobsen Søren , Criswell Lindsey , Rönnblom Lars , Nordmark Gunnel 
Published: June 2021

AbstractThe genetic background of lupus nephritis (LN) has not been completely elucidated. We performed a case-only study of 2886 SLE patients, including 947 (33%) with LN. Renal biopsies were available from 396 patients. The discovery cohort (Sweden, n = 1091) and replication cohort 1 (US, n = 962) were genotyped on the Immunochip and replication cohort 2 (Denmark/Norway, n = 833) on a custom array. Patients with LN, proliferative nephritis, or LN with end-stage renal disease were compared with SLE without nephritis. Six loci were associated with LN (p < 1 × 10−4, NFKBIA, CACNA1S, ITGA1, BANK1, OR2Y, and ACER3) in the discovery cohort. Variants in BANK1 showed the strongest association with LN in replication cohort 1 (p = 9.5 × 10−4) and proliferative nephritis in a meta-analysis of discovery and replication cohort 1. There was a weak association between BANK1 and LN in replication cohort 2 (p = 0.052), and in the meta-analysis of all three cohorts the association was strengthened (p = 2.2 × 10−7). DNA methylation data in 180 LN patients demonstrated methylation quantitative trait loci (meQTL) effects between a CpG site and BANK1 variants. To conclude, we describe genetic variations in BANK1 associated with LN and evidence for genetic regulation of DNA methylation within the BANK1 locus. This indicates a role for BANK1 in LN pathogenesis.
Impact of changing guidelines on genetic testing and surveillance recommendations in a contemporary cohort of breast cancer survivors with family history of pancreatic cancer
Authors: Wang Annie , Everett Jessica N. , Chun Jennifer , Cen Cindy , Simeone Diane M. , Schnabel Freya 
Published: June 2021

AbstractChanging practice guidelines and recommendations have important implications for cancer survivors. This study investigated genetic testing patterns and outcomes and reported family history of pancreatic cancer (FHPC) in a large registry population of breast cancer (BC) patients. Variables including clinical and demographic characteristics, FHPC in a first or second-degree relative, and genetic testing outcomes were analyzed for BC patients diagnosed between 2010 and 2018 in the NYU Langone Health Breast Cancer Database. Among 3334 BC patients, 232 (7%) had a positive FHPC. BC patients with FHPC were 1.68 times more likely to have undergone genetic testing (p < 0.001), but 33% had testing for BRCA1/2 only and 44% had no genetic testing. Pathogenic germline variants (PGV) were identified in 15/129 (11.6%) BC patients with FHPC, and in 145/1315 (11.0%) BC patients without FHPC. Across both groups, updates in genetic testing criteria and recommendations could impact up to 80% of this cohort. Within a contemporary cohort of BC patients, 7% had a positive FHPC. The majority of these patients (56%) had no genetic testing, or incomplete testing by current standards, suggesting under-diagnosis of PC risk. This study supports recommendations for survivorship care that incorporate ongoing genetic risk assessment and counseling.
Multiplexed engineering glycosyltransferase genes in CHO cells via targeted integration for producing antibodies with diverse complex-type N-glycans
Authors: Nguyen Ngan T. B. , Lin Jianer , Tay Shi Jie , Mariati  , Yeo Jessna , Nguyen-Khuong Terry , Yang Yuansheng 
Published: June 2021

AbstractTherapeutic antibodies are decorated with complex-type N-glycans that significantly affect their biodistribution and bioactivity. The N-glycan structures on antibodies are incompletely processed in wild-type CHO cells due to their limited glycosylation capacity. To improve N-glycan processing, glycosyltransferase genes have been traditionally overexpressed in CHO cells to engineer the cellular N-glycosylation pathway by using random integration, which is often associated with large clonal variations in gene expression levels. In order to minimize the clonal variations, we used recombinase-mediated-cassette-exchange (RMCE) technology to overexpress a panel of 42 human glycosyltransferase genes to screen their impact on antibody N-linked glycosylation. The bottlenecks in the N-glycosylation pathway were identified and then released by overexpressing single or multiple critical genes.
Overexpressing B4GalT1 gene alone in the CHO cells produced antibodies with more than 80% galactosylated bi-antennary N-glycans. Combinatorial overexpression of B4GalT1 and ST6Gal1 produced antibodies containing more than 70% sialylated bi-antennary N-glycans. In addition, antibodies with various tri-antennary N-glycans were obtained for the first time by overexpressing MGAT5 alone or in combination with B4GalT1 and ST6Gal1. The various N-glycan structures and the method for producing them in this work provide opportunities to study the glycan structure-and-function and develop novel recombinant antibodies for addressing different therapeutic applications.
High fructose and streptozotocin induced diabetic impairments are mitigated by Indirubin-3-hydrazone via downregulation of PKR pathway in Wistar rats
Authors: Udumula Mary Priyanka , Mangali Sureshbabu , Kalra Jaspreet , Dasari Deepika , Goyal Srashti , Krishna Vandana , Bollareddy Srivarsha Reddy , Sriram Dharamrajan , Dhar Arti , Bhat Audesh 
Published: June 2021

AbstractMetabolic disorders are becoming more common in young population due to increased consumption of carbohydrate rich diet, lack of physical activity and stress. Fructose is used as a sweetener in many carbonated beverages and is a known inducer of oxidative stress and hypertension. Up-regulation of the double-stranded RNA-dependent protein kinase (PKR) causes impairment in insulin signaling pathway and metabolic dysfunctions in type 2 diabetes mellitus. In the present study we investigated the role of PKR and associated pathways in high fructose (HF) and streptozotocin (STZ) induced diabetes and whether indirubin-3-hydrazone (IHZ), a novel PKR inhibitor can reverse the HF and STZ induced diabetic impairments in Wistar rats. Diabetes was induced by feeding rats 20% high fructose in drinking water for 6 weeks and by giving a single dose of STZ (35 mg/kg., i.p) at the end of week 5. Glucose and lipid levels were measured by using assay kits. Expression of PKR and its downstream genes were determined by immunohistochemistry, qRT-PCR and western blotting techniques. Histo-pathological studies were performed using H&E staining. Fibrosis was detected in insulin sensitive tissues and organs using Sirius red and Masson’s trichrome staining and apoptosis by TUNEL assay. HF and STZ induced hyperglycemia, fibrosis, oxidative stress, and inflammation in liver, pancreas, skeletal muscle and adipose tissue are mediated via PKR pathway and its downstream effectors, and these effects were attenuated by PKR inhibitor IHZ. Thus, inhibition of PKR can protect insulin sensitive organs and tissues from HF induced diabetic impairments via the inhibition of c-Jun N-terminal kinase (JNK) pathway.
Predictors of blood glucose change and vascular complication of type 2 diabetes mellitus patients in Felege Hiwot Referral Hospital, North West Ethiopia
Authors: Shita Nigusie Gashaye , Muluneh Essey Kebede 
Published: June 2021

AbstractVascular complication results in serious physical damages which may lead to the death of Type 2 diabetes mellitus patients. Studying the determinant factors of changes in blood glucose level and duration of time to the development of vascular complications helps to save the lives of citizens. A retrospective cohort study was conducted among type 2 diabetes mellitus (T2DM) patients enrolled between December 2011 and December 2012 at Felege Hiwot Referral Hospital. A total of 159 T2DM patients were included in the study. Joint modelling of longitudinal and survival analysis was employed to identify predictors of Blood Glucose Change and Vascular Complication of Type 2 Diabetes Mellitus Patients. The prevalence of vascular complication in Type 2 diabetes patients was 23.3%. Half of these patients developed an avascular complication after 24 months from the onset of the follow-up. The significant predictors of shorter time to development of vascular complication were positive proteinuria (adjusted hazard ratio (AHR) = 1.62, CI: 1.08–2.41), increase in the level of serum creatinine (AHR = 4.12, CI: 1.94–8.74), cholesterol ≥ 200 mg/dl (AHR = 1.54, CI: 1.01–2.35), and log (fasting blood glucose) (AHR = 1.453, CI: 1.004–2.104). The predictors of progression of fasting blood glucose were duration of treatment (CL: − 0.015, − 0.0001), hypertension (CL: 0.018, 0.098), baseline fasting blood glucose level 126–139 and 140-199 mg/dl (CI: − 0.40, − 0.31) and (CI: − 0.24, − 0.17), respectively. Male T2DM patients, patients with more visits to the hospital and patients who required one oral agent had a relatively lower progression of blood sugar level. Type 2 diabetes mellitus patients having higher cholesterol level, positive proteinuria, higher fasting blood sugar and a lesser number of hospital visits had a higher risk of developing a complication.
An affinity-matured human monoclonal antibody targeting fusion loop epitope of dengue virus with in vivo therapeutic potency
Authors: Kotaki Tomohiro , Kurosu Takeshi , Grinyo-Escuer Ariadna , Davidson Edgar , Churrotin Siti , Okabayashi Tamaki , Puiprom Orapim , Mulyatno Kris Cahyo , Sucipto Teguh Hari , Doranz Benjamin J. , Ono Ken-ichiro , Soegijanto Soegeng , Kameoka Masanori 
Published: June 2021

AbstractDengue virus (DENV), from the genus flavivirus of the family flaviviridae, causes serious health problems globally. Human monoclonal antibodies (HuMAb) can be used to elucidate the mechanisms of neutralization and antibody-dependent enhancement (ADE) of DENV infections, leading to the development of a vaccine or therapeutic antibodies. Here, we generated eight HuMAb clones from an Indonesian patient infected with DENV. These HuMAbs exhibited the typical characteristics of weak neutralizing antibodies including high cross-reactivity with other flaviviruses and targeting of the fusion loop epitope (FLE). However, one of the HuMAbs, 3G9, exhibited strong neutralization (NT50 < 0.1 μg/ml) and possessed a high somatic hyper-mutation rate of the variable region, indicating affinity-maturation. Administration of this antibody significantly prolonged the survival of interferon-α/β/γ receptor knockout C57BL/6 mice after a lethal DENV challenge. Additionally, Fc-modified 3G9 that had lost their in vitro ADE activity showed enhanced therapeutic potency in vivo and competed strongly with an ADE-prone antibody in vitro. Taken together, the affinity-matured FLE-targeting antibody 3G9 exhibits promising features for therapeutic application including a low NT50 value, potential for treatment of various kinds of mosquito-borne flavivirus infection, and suppression of ADE. This study demonstrates the therapeutic potency of affinity-matured FLE-targeting antibodies.
A novel approach for nitrogen diagnosis of wheat canopies digital images by mobile phones based on histogram
Authors: Qi Xin , Zhao Yanan , Huang Yufang , Wang Yang , Qin Wei , Fu Wen , Guo Yulong , Ye Youliang 
Published: June 2021

AbstractThe accurate and nondestructive assessment of leaf nitrogen (N) is very important for N management in winter wheat fields. Mobile phones are now being used as an additional N diagnostic tool. To overcome the drawbacks of traditional digital camera diagnostic methods, a histogram-based method was proposed and compared with the traditional methods. Here, the field N level of six different wheat cultivars was assessed to obtain canopy images, leaf N content, and yield. The stability and accuracy of the index histogram and index mean value of the canopy images in different wheat cultivars were compared based on their correlation with leaf N and yield, following which the best diagnosis and prediction model was selected using the neural network model. The results showed that N application significantly affected the leaf N content and yield of wheat, as well as the hue of the canopy images and plant coverage. Compared with the mean value of the canopy image color parameters, the histogram could reflect both the crop coverage and the overall color information. The histogram thus had a high linear correlation with leaf N content and yield and a relatively stable correlation across different growth stages. Peak b of the histogram changed with the increase in leaf N content during the reviving stage of wheat. The histogram of the canopy image color parameters had a good correlation with leaf N content and yield. Through the neural network training and estimation model, the root mean square error (RMSE) and the mean absolute percentage error (MAPE) of the estimated and measured values of leaf N content and yield were smaller for the index histogram (0.465, 9.65%, and 465.12, 5.5% respectively) than the index mean value of the canopy images (0.526, 12.53% and 593.52, 7.83% respectively), suggesting a good fit for the index histogram image color and robustness in estimating N content and yield. Hence, the use of the histogram model with a smartphone has great potential application in N diagnosis and prediction for wheat and other cereal crops.
A novel anti‐Doppler SEI algorithm based on the vector diagram decomposition
Authors: Zha Xiong , Li Tianyun , Qiu Zhaoyang , Feng Yiwei 
Published: June 2021

AbstractIn practical applications, communication emitters are often carried by low orbit satellites aircraft, ships, and other moving carriers. Doppler phenomenon usually exists due to the relative motion between the emitter and the receiver, which seriously affects the identification performance. Given this situation, a method based on the signal vector decomposition and the multi‐feature fusion is proposed. By normalizing and demodulating the target signal, the signal vector diagram is decomposed into four parts. We present a multi‐feature fusion model with varying features extracted from each diagram by a deep learning network. Experimental results show that the proposed method is effective in the presence of Doppler effect.
A quantitative research on the level of disturbance to secondary signal ports of electronic voltage transformers under the operation of gas‐insulated switchgear
Authors: Wang Qi , Fu Chao , Chu Fanwu , Tong Yue , Wang Xiaozhou , Ye Guoxiong , Wu Xiong 
Published: June 2021

AbstractThe collectors of electronic transformers has the problem of electromagnetic incompatibility under the operation of disconnecting switches, which limits their wide application in smart grids. To evaluate the maximum level of disturbance that collectors are able to withstand in the stochastic process of switching operation, this work introduces a quantitative approach based on limited test measurements, which can quantify the level of disturbance in the signal acquisition ports of electronic voltage transformers (EVT) in different gas‐insulated switchgears (GIS). Based on large numbers of experimental statistical data of the true type simulation experimental platform, the Spearman rank correlation coefficient is used to prove that the amplitude of the disturbance voltage pulse at the secondary side port and the breakdown voltage between the primary side fracture approximately satisfy a linear relationship. Subsequently, the quantile regression model is used to quantify and verify the maximum disturbance level of the secondary side port. Moreover, a solution is proposed to tackle the difficulty in obtaining the breakdown voltage at breaks in the GIS substation field applicatvion, under which the quantified maximum disturbance voltage deviation of secondary ports is only −4.34% by comparison. The research work can further explore the practical value of the measured data in a few tests under GIS substation field conditions and provide references for the subsequent revision of EVT‐related standards.
Therapie des Lymphödems
Authors: Brenke Rainer 
Published: June 2021

ZusammenfassungDie Therapie des Lymphödems gestaltet sich immer individuell – in Abhängigkeit vom jeweiligen Befund. Noch immer ist die Komplexe Physikalische Entstauungstherapie (KPE) die Therapie der Wahl beim Lymphödem. Kernstück ist die Manuelle Lymphdrainage, die auch bei verwandten Krankheitsbildern zum Einsatz kommen kann. Ergänzt wird diese Methode durch Kompression, Bewegung und Hautpflege.Der Beitrag gibt einen Überblick zur KPE. Im abschließenden Ausblick wird der Stellenwert weiterer Therapiemöglichkeiten wie chirurgische Optionen, Medikamente, Ernährung, Lymphtaping, Tiefenoszillation u. a. erläutert.
Fast-Track-Rehabilitation nach Ösophagektomie
Authors: Schroeder Wolfgang , Mallmann Christoph , Babic Benjamin , Bruns Christiane , Fuchs Hans Friedrich 
Published: June 2021

ZusammenfassungDas multimodale und interprofessionelle Konzept der Fast-Track-Rehabilitation (Synonym: „enhanced recovery after surgery“, ERAS) ist bei der transthorakalen Ösophagektomie grundsätzlich umsetzbar, weist aber im Gegensatz zur Fast-Track-Chirurgie anderer onkologischer Prozeduren 2 wesentliche Besonderheiten auf. Aufgrund der hohen Komorbidität der Patienten mit Ösophaguskarzinom ist das Fast-Track-Konzept ein Teilaspekt des perioperativen Managements und von der präoperativen Konditionierung einzelner Organdysfunktionen (Prähabilitation) nicht zu trennen. Da die gastrale Rekonstruktion eine hohe Prävalenz eines „delayed gastric conduit emptying“ (DGCE) bedingt, ist postoperativ ein frühzeitiger und kalorisch adäquater, oraler Kostaufbau nur eingeschränkt durchführbar. Einen allgemein akzeptierten Algorithmus zum postoperativen Ernährungsmanagement und zur Prophylaxe/Therapie des DGCE gibt es gegenwärtig nicht. Die in spezialisierten Zentren bereits niedrige Mortalität
wird durch das Fast-Track-Programm nicht beeinflusst. Ob die postoperative Morbidität mit diesem Konzept gesenkt wird, kann durch die gegenwärtige Studienlage nicht abschließend beantwortet werden. Nach modifizierter Fast-Track-Rehabilitation ist eine Entlassung aus der stationären Behandlung ab dem 8. postoperativen Tag bei unkompliziertem Verlauf möglich.
Gitelman Syndrome in Pregnancy: A Clinical Challenge
Authors: Ergani Seval Yilmaz , Orgul Gokcen , Tolunay Harun Egemen , Arici Mustafa , Yucel Aykan , Uygur Dilek 
Published: June 2021

Abstract
Purpose Disease progress may be affected by pregnancy-related changes, and
underlying conditions may also affekt pregnancy outcomes in women with Gitelman
syndrome (GS). Case presentation A 35-year-old woman with GS (gravida 2 para 1)
was referred to our hospital to start routine antenatal care follow-up at 6
weeks of gestation. At the age of 31, she had been diagnosed with GS after her
first uneventful pregnancy. Upon early admission, her serum Mg+level was
0.51 mmol/L and her serum K+level
2.7 mmol/L with normal kidney function tests. She was already
taking oral combined potassium citrate and potassium bicarbonate supplementation
once a day before pregnancy. At the eighth gestational week, the medication was
changed to an oral potassium color sachet of 1.5 gram per day until labor
because of the insufficient dosage to maintain optimum potassium levels. She was
also taking 365 milligrams of oral magnesium oxide twice a day before and during
pregnancy. In the third trimester of the pregnancy, her serum Mg+level
was 0.48 mmol/L and serum K+level
2.8 mmol/L. Because of the previous uterine surgery history, she
underwent an elective cesarean operation at 39 weeks’ gestation under
spinal anesthesia and delivered a healthy 3090-gram female
infant.
Conclusion Increased need for potassium and magnesium supplementation
should be the critical considerations when managing pregnant patients with
GS.