bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive feedback regulation between USP15 and ERK2 inhibits osteoarthritis progression through TGF-β/SMAD2 signaling
Authors: Wang Wenjuan , Zhu Yanhui , Sun Zhenyu , Jin Chen , Wang Xiang 
Published: February 2021

Abstract
Background: The transforming growth factor-β (TGF-β) signaling pathway plays an essential role in maintaining homeostasis in joints affected by osteoarthritis (OA). However, the specific mechanism of non-SMAD and classical SMAD signaling interactions is still unclear, which needs to be further explored.Methods: In ATDC5 cells, USP15 overexpression and knockout were performed using the transfected lentivirus USP15 and Crispr/Cas9. Western blotting and immunofluorescence staining were used to test p-SMAD2 and cartilage phenotype-related molecular markers. In rat OA models, immunohistochemistry, hematoxylin and eosin (HE)/Safranin-O fast green staining, and histology were used to examine the regulatory activity of USP15 in TGF-β/SMAD2 signaling and the cartilage phenotype. Then, ERK2 overexpression and knockout were performed. The expressions of USP15, p-SMAD2, and the cartilage phenotype were evaluated in vitro and in vivo. To address whether USP15 is required for ERK2 and TGF-β/SMAD2 signaling, we performed rescue experiments in vitro and in vivo. Immunoprecipitation and deubiquitination assays were used to examine whether USP15 could bind to ERK2 and affect the deubiquitination of ERK2. Finally, whether USP15 regulates the level of p-ERK1/2 was evaluated by western blotting, immunofluorescence staining, and immunohistochemistry in vitro and in vivo.Results: Our results indicated that USP15 stimulated TGF-β/SMAD2 signaling and the cartilage phenotype. Moreover, ERK2 required USP15 to influence TGF-β/SMAD2 signaling for regulating the cartilage phenotype in vivo and in vitro. And, USP15 can form a complex with ERK2 to regulate ubiquitination of ERK2. Interestingly, USP15 did not regulate the stability of ERK2 but increased the level of p-ERK1/2 to further enhance the TGF-β/SMAD2 signaling pathway.Conclusions: Taken together, our study revealed positive feedback regulation between USP15 and ERK2, which played a critical role in TGF-β/SMAD2 signaling to inhibit OA progression. Therefore, this specific mechanism can guide the clinical treatment of OA.
Suppression of hydraulic transients for desalination plants based on active control synthesis
Authors: Phuc Bui Duc Hong , You Sam-Sang , Kim Hwan-Seong , Lee Sang-Do 
Published: February 2021

AbstractThis paper proposes a control strategy to stabilize a reverse osmosis desalination system against hydraulic shocks with enhancing productivity and sustainability. First, the effects of hydraulic transients on water quality have been reviewed. The transient waves are approximated by sinusoidal functions so that their effects are incorporated into the controlled system as external disturbances. Next, the active control is implemented based on the adaptive super-twisting (STW) sliding mode control (SMC) algorithms. Then, the robust performance is guaranteed whenever the sliding variables reach the sliding surfaces in finite time despite disturbances. The STW SMC scheme is to eliminate the chattering problems for protecting the valves and to improve the convergence precision for water production. The control gains are adaptable to enable formation of an effective controller for dealing with large disturbances such as water hammer during desalination process. The simulation results reveal the superior performances on controlling water product, while eliminating shock waves. Especially, the effect of hydraulic shocks has been dramatically attenuated, hence the plant components are protected to avoid fracture. Finally, the robust stability and performance of the desalination plants are guaranteed against large disturbances to ensure the population with quality water as well as system sustainability.
Effect and mechanism of reduced membrane bioreactor fouling by powdered activated carbon
Authors: Zhang Yongji , Wang Xiaotong , Ye Hexiu , Zhou Lingling , Zhao Zhiling 
Published: February 2021

Abstract
Powered Activated Carbon – Membrane Bioreactors (PAC-MBRs) have been used with good results for slightly polluted water treatment. Our batch experiments showed that the transmembrane pressure of a PAC-MBR was 25% less than that of a MBR in one period of test, which indicated that PAC did help control the fouling in MBRs. Based on this observation, several mechanisms of membrane fouling of MBRs and PAC-MBRs were investigated to have some insight into how PAC brought a positive impact. The total resistances decreased by 60% and different resistances were redistributed after adding PAC. The dominant one changed from filtration resistance to cake resistance. These smaller cake resistances resulted from the PAC because, showing in the scanning electron microscopy pictures, it made the cake layer looser and rougher than that on a normal membrane. Meanwhile, the analysis of the membrane eluent showed that the addition of PAC changed the microbial species and its metabolites on the membrane and effectively reduced the adsorption of hydrophilic organic molecules on the membrane surface. Additionally, PAC prevented polypeptide compounds from being trapped inside the pores of membranes, so the cake on the PAC-MBR contaminated membrane surface was easier to scrape off. In the test of cleaning methods, alkaline cleaning removed the most organics from contaminated membranes to restore membrane performance.
Desenvolvimento de cerveja no estilo witbier adicionada de gengibre (Zingiber officinalis) e sua influência na fermentação
Authors: Reis Selvati Costa Barbara , Da Silva Gomes Yasmin , Costa Cazuza Celestina Alexandrina , Tashima Luana , Marcondes Rodrigues dos Santos Lígia 
Published: February 2021

A cerveja é composta por água, malte, lúpulo e levedura e passa pelos principais processos que são: moagem do malte, mosturação, fervura do mosto, fermentação e carbonatação. A witbier, estilo belga de alta fermentação, se caracteriza por ter aroma e sabor refrescante, que também é característica do gengibre. Essa especiaria possui benefícios terapêuticos antimicrobianos que pode afetar o crescimento celular das leveduras. O objetivo do trabalho foi produzir uma cerveja do estilo witbier adicionada de gengibre na Cervejaria Escola da Universidade de Vassouras (Vassouras, RJ) e analisar o crescimento de células de levedura, o teor alcóolico, o extrato. Também foi aplicado um teste sensorial de aceitação e intenção de compra. Para a produção da cerveja, o gengibre foi adicionado na etapa de fervura. A fermentação foi conduzida em fermentadores de 15 L com as concentrações de gengibre iguais a 0,0, 1,5 e 3,0 g/L. A fermentação terminou ao atingir 1,5°P. O teor alcóolico obtido foi entre 5 e 6,7 % para todas as amostras e o crescimento celular ficou entre 2,09 x106 e 4,4x106 células/mL. Além disso, foi observado que a adição de gengibre na cerveja, em especial na concentração de 3,0 g/L, retardou o crescimento celular, mas não o suficiente para impedir que todas fermentações chegassem ao mesmo patamar de extrato final, demonstrando que apesar das características antimicrobianas do gengibre, ele se mostrou uma matéria-prima capaz de ser utilizada para o estilo de cerveja produzido neste estudo.
In Vivo Evaluation of Inorganic Nanoparticle Complexes against CCL4 Induced Hepatotoxicity
Authors: Tabbasam Rabia , Khursid Sana , Ishaq Yasmeen , Malik Arif 
Published: February 2021

Background:
Combination of different chemotherapy drugs and nanoparticles as a carrier
has shown promising delivery system in cancer treatment. Doxorubicin is considered a potent anticancer
drug. However, its off-target activities and possible side effects make its use limited. Recently,
in the field of nanomedicine, different nanoconjugates have been developed as a unique platform
for the delivery of therapeutic drugs.

Objective:
The aim of present study was to evaluate the best possible combination for efficient delivery of DOX with combination of gold, silver and zinc oxide nanoparticles to target site against carbon tetrachloride induced rat hepatotoxicity.

Methods:
Effect of different conjugates administrated for 14 consecutive days was evaluated.

Results:
In comparison to DOX, Au:DOX, ZnoO:DOX and Ag:DOX showed less sign of liver fibrosis
as evaluated by serum enzymes and histopathological analysis. However, among all the conjugates,
Ag: DOX conjugate showed the most significant results. The serum alanine aminotransferase,
aspartate aminotransferase, alkaline phosphatase values were (111.2 ± 38.21, 323.2 ± 46.88
and 303.6 ± 73.80 respectively) very close to control group (72.2 ± 19.41, 368 ± 59.78 and 259.4 ±
61.54 respectively).

Conclusion:
Our results demonstrated that Ag: DOX may exhibit hepato-protective activity
against CCl4 induced liver damage.
Recent Progress in Small Molecular Inhibitors of DNA Gyrase
Authors: Man Ruo-Jun , Zhang Xu-Ping , Yang Yu-Shun , Jiang Ai-Qin , Zhu Hai-Liang 
Published: February 2021

Background:
In the past few decades, with the abuse of antibiotics, bacterial
resistance has enhanced constantly. More and more super species of bacteria, which are
seriously threatening human health, have been discovered. Developing novel antibacterial
agents to overcome the drug-resistance is an urgent duty. We all know that blocking
the information-transfer of bacterial DNA and RNA is one of the effective ways to inhibit
bacterial growth. Therefore, as the indispensable enzyme for DNA replication and transcription,
DNA gyrase is one of the important targets for bacterial inhibitors. Accordingly,
many inhibitors of DNA gyrase have also been developed.

Methods:
In this review, to highlight the recent progress in DNA gyrase inhibitors, the
study in this field over the past three years (2017-2019) was summarized and organized
based on their backbones or core moieties. Both of the subunits of DNA gyrase were taken
into consideration.

Results:
These DNA gyrase inhibitors have been classified based on their backbones or
core moieties. After the comparison of the divided 14 categories, we could achieve some
clues for future modification. In particular, we found that benzodiazepines and naphthalene
heterocycles were the most common structures in the drug design. On the other
hand, isopropyl and cyclopropyl have also been used in drug design, which provides
more inspiration for the investigations. Except for GSK2140944, which has entered the
phase III clinical trial stage, other compounds here were not fully promulgated with their
optimal pharmacokinetic activity.

Conclusion:
We briefly summed up the current situation and future challenges on this
topic. Through the discussion of the design strategies and drug effect, we hope that this
review can provide a focused direction for future researches.
Sofosbuvir/Ledipasvir for Treatment of Chronic Hepatitis C Infection in
Adult Patients with β- Thalassemia Major: A Real-Life Study
Authors: Elbedewy Tamer A. , Abd-Elsalam Sherief , Mostafa Sahar Mohamed , Abdellatif Raghda Samir , Fouad Amina , Youssef Mona , Abo-Amer Yousry Esam-Eldin , Elsebaey Mohamed A. 
Published: February 2021

Background & Aims:
Patients with thalassemia have a lifelong need for blood transfusion,
which makes them more risky to hepatitis C virus (HCV). Iron overload and chronic HCV are
considered risk factors for patients with thalassemia to develop liver insults. The aim of the present
study is to investigate the safety and efficacy of sofosbuvir/ledipasvir in the treatment of chronic
HCV infection in Egyptian adult patients with β- thalassemia major.

Methods:
A retrospective study included 53 patients with β-thalassemia major with chronic HCV
treated with sofosbuvir (400 mg) and ledipasvir (90 mg) as a single pill fixed-dose combination
once daily for 12 weeks. The effectiveness of the treatment was assessed by the sustained virologic
response (SVR) at 12 weeks after the end of the treatment.

Results:
SVR was achieved in 96.23% of patients. 47.17% of patients had minor side effects.
There was a significant reduction in ALT, AST, and serum ferritin 12 weeks post-therapy. There
was an insignificant change in hemoglobin level or blood transfusion requirement 12 weeks posttherapy.
There was no change in iron chelators doses throughout the study period.

Conclusion:
Sofosbuvir/ledipasvir regimen seems to be safe and highly effective in the treatment
of chronic HCV in patients with β-thalassemia major.
Extraction and Characterization of Fatty Acids from the Leaves and
Stems of Clinacanthus nutans Using Supercritical Carbon Dioxide and
Soxhlet Method
Authors: Ferdosh Sahena , Yunus Kamaruzzaman , Rashid Mohammad A. , Sarker Zaidul Islam 
Published: February 2021

Background:
The composition and bioactivity of natural plant extract strongly depend
on the extraction technique employed. Clinacanthus nutans Lindau (C. nutans) is a well-known
medicinal plant in South-East Asia that has been traditionally used for the treatment of various diseases.
Several conventional methods have been using for the extraction of bioactive compounds
from C. nutans. However, extraction of fatty acids using supercritical carbon dioxide was not reported
yet from this medicinal herbs.

Objective:
The main objective of the study is to examine the potential of supercritical carbon
dioxide (scCO2) extraction of fatty acids from leaves and stems of C. nutans.

Method:
Fatty acid compositions were determined from leaves and stems of C. nutans oil extracted
by scCO2 (temperature 45-65 °C, pressure 25-35 MPa) and compared to the results of Soxhlet extraction.

Results:
Supercritical CO2 extraction shows the highest oil recovery in both leaves (3.7%) and
stems (1.6%) at pressure 35 MPa, temperature 65°C and 2 ml/min flow rate, which was closer to
the yield of Soxhlet. The scCO2 yields presented a higher percentage of polyunsaturated fatty acids
(PUFA), especially linoleic acid (C18:2n-6). Palmitic acid ranging from 42%- 47% in leaves and
stems of C. nutans was found dominant saturated fatty acids (SFA) in both scCO2 and Soxhlet
method.

Conclusion:
The current results indicate that leaves and stems of C. nutans could be a potential
source of fatty acids, especially biologically active compounds.
Adoption of Digital Health Technologies in the Practice of Behavioral Health: Qualitative Case Study of Glucose Monitoring Technology
Authors: May Suepattra G , Huber Caroline , Roach Meaghan , Shafrin Jason , Aubry Wade , Lakdawalla Darius , Kane John M , Forma Felicia 
Published: February 2021

Background
Evaluation of patients with serious mental illness (SMI) relies largely on patient or caregiver self-reported symptoms. New digital technologies are being developed to better quantify the longitudinal symptomology of patients with SMI and facilitate disease management. However, as these new technologies become more widely available, psychiatrists may be uncertain about how to integrate them into daily practice. To better understand how digital tools might be integrated into the treatment of patients with SMI, this study examines a case study of a successful technology adoption by physicians: endocrinologists’ adoption of digital glucometers.

Objective
This study aims to understand the key facilitators of and barriers to clinician and patient adoption of digital glucose monitoring technologies to identify lessons that may be applicable across other chronic diseases, including SMIs.

Methods
We conducted focus groups with practicing endocrinologists from 2 large metropolitan areas using a semistructured discussion guide designed to elicit perspectives of and experiences with technology adoption. The thematic analysis identified barriers to and facilitators of integrating digital glucometers into clinical practice. Participants also provided recommendations for integrating digital health technologies into clinical practice more broadly.

Results
A total of 10 endocrinologists were enrolled: 60% (6/10) male; a mean of 18.4 years in practice (SD 5.6); and 80% (8/10) working in a group practice setting. Participants stated that digital glucometers represented a significant change in the treatment paradigm for diabetes care and facilitated more effective care delivery and patient engagement. Barriers to the adoption of digital glucometers included lack of coverage, provider reimbursement, and data management support, as well as patient heterogeneity. Participant recommendations to increase the use of digital health technologies included expanding reimbursement for clinician time, streamlining data management processes, and customizing the technologies to patient needs.

Conclusions
Digital glucose monitoring technologies have facilitated more effective, individualized care delivery and have improved patient engagement and health outcomes. However, key challenges faced by the endocrinologists included lack of reimbursement for clinician time and nonstandardized data management across devices. Key recommendations that may be relevant for other diseases include improved data analytics to quickly and accurately synthesize data for patient care management, streamlined software, and standardized metrics.
Utilización de PCR para la identificación de Piroplasmosis equina en un criadero de Jamundí (Colombia)
Authors: González Jiménez Indrid Marcela , Castro Castro Fernando Favian , Angarita Alonso Fredy Javier , Rivera Calderón Luis Gabriel 
Published: February 2021

Contextualización: la piroplasmosis equina es una enfermedad transmitida por garrapatas, causada por protozoarios de la especie Babesia caballi y Theileria equi. Los animales afectados presentan diferentes signos clínicos que incluyen anemia, fiebre, ictericia y depresión. Los equinos infectados con T. equi pueden ser portadores de manera vitalicia del parasito, mientras que aquellos que contraen B. caballi pueden diseminarlo por algunos años hasta finalmente quedar libres de la infección.
Vacío de investigación: en Colombia existen pocos estudios sobre el aislamiento e identificación de hemoparásitos en equinos mediante técnicas moleculares como reacción en cadena de la polimerasa. Dentro de estos parásitos se encuentran Babesia caballi y Theileria equi, agentes causantes de la Piroplasmosis una enfermedad de declaración obligatoria por la Organización Mundial de Sanidad Animal (OIE).
Propósito del estudio: el objetivo de este estudio fue identificar la Piroplasmosis equina mediante PCR en un criadero localizado en el municipio de Jamundí (Valle del Cauca).
Metodología: de un total de 20 ejemplares, divididos en dos grupos, (animales estabulados y animales en potrero), se colectó sangre periférica para realizar frotis teñidos con Wright. Además, se enviaron otras muestras al laboratorio para diagnóstico molecular.
Resultados y conclusiones: todas las muestras con Wright fueron negativas a hemoparásitos, sin embargo, por PCR convencional fue posible identificar piroplasmosis. La PCR fue un método sensible y confiable para diagnosticar la enfermedad en un individuo asintomático. Más estudios deben ser realizados en esta región sobre Babesia sp., para identificar sus posibles factores predisponentes y causales, así como para mejorar las medidas de prevención, control y tratamiento.
Evaluación de la exposición ocupacional a ruido en microempresas de madera de la ciudad de Neiva en el 2019
Authors: Romero Méndez Ingrith Marcela , Serrato Rojas Dinory , Bernal Medina Roberson Daniel , Cabrera Urriago Jhonathan 
Published: February 2021

Contextualización: la evaluación de la exposición a ruido es un componente indispensable en los programas de prevención de pérdida auditiva para reconocer trabajadores vulnerables, proponer medidas de control y/o evaluar las medidas implementadas.
Vacío de conocimiento: en Colombia, hay un número limitado de trabajos que abordan la exposición a ruido y las medidas de control de este.
Propósito del estudio: la exposición ocupacional a ruido en el área operativa de dos microempresas de la ciudad de Neiva fue evaluada mediante dosimetría y sonometría. Dichas empresas se dedican a la comercialización de madera aglomerada empleando máquinas especializadas como sierras verticales y enchapadoras.
Metodología: inicialmente se realizó una caracterización de las condiciones de trabajo, luego se realizaron las mediciones de ruido siguiendo la estrategia basada en la labor conforme la ISO 9612-2010.
Resultados y conclusiones: los niveles de presión sonora equivalente (73,0 y 82,4 dB (A)) encontrados a partir de sonometría se asemejan a los reportados en talleres de carpintería y fábricas de muebles. Los resultados de la dosimetría revelaron que los operarios de la sierra vertical y el de la enchapadora se exponen a diario a niveles de ruido entre 88,50 y 89,9 dB (A) que sobrepasan el valor límite permisible (85 dB) para un tiempo de exposición de 8 horas, como se estipula por la resolución 1792 de 1990. Sin embargo, los operarios de las microempresas de madera aglomerada evaluados no se encuentran sobreexpuestos a ruido gracias a la atenuación que brindan los protectores auditivos utilizados.
Rapid Changes in Serum Testosterone in Men With Newly Diagnosed Type 2 Diabetes With Intensive Insulin and Metformin
Authors: Hu Yun , Ding Bo , Shen Yun , Yan Reng-Na , Li Feng-Fei , Sun Rui , Jing Ting , Lee Kok-Onn , Ma Jian-Hua 
Published: February 2021

OBJECTIVE
To investigate the effect of metformin on testosterone levels in men with type 2 diabetes mellitus (T2DM).

RESEARCH DESIGN AND METHODS
Seventy men with newly diagnosed drug-naive T2DM and HbA1c &gt;9.0% (75 mmol/mol) were treated with intensive insulin pump therapy for 5 days to achieve glucose normalization. They were randomized to control (continued on intensive insulin only) and metformin (plus metformin) groups (1:1) for 1 month. Testosterone was measured at baseline, randomization, and after 1-month treatment.

RESULTS
Total, free, and bioavailable testosterone increased significantly within 5 days (all P &lt; 0.001). After 1 month, compared with the control group, the metformin group had lower total (12.7 vs. 15.3 nmol/L), free (0.20 vs. 0.24 nmol/L), and bioavailable (4.56 vs. 5.31 nmol/L) testosterone (all P &lt; 0.05).

CONCLUSIONS
In men with T2DM, 1-month oral metformin may decrease serum testosterone levels independent of blood glucose control. The effects of long-term metformin on testosterone in men need further study.
Komparasi Penyelesaian Perkara Pidana Kejahatan Genosida yang Terjadi di Rwanda dan Myanmar Ditinjau Dari Perspektif Hukum Pidana Internasional
Authors: Riski Wahyudi Anak Agung Ngurah , Budiana I Nyoman 
Published: February 2021

This study aims (1) to analyze and find out the efforts to resolve genocide disputes from the perspective of international criminal law, (2) to determine the comparison of resolving genocide disputes that occurred in Rwanda and Myanmar. This type of research uses normative legal research, namely literature study, rules and literature related to genocide, and uses an argumentative descriptive approach. The results of this study explain the efforts and comparisons of resolving genocide disputes that occurred in Rwanda and Myanmar from the perspective of international criminal law. Genocide is an international crime that aims to eliminate ethnicity, ethnicity, race and religion in a systematic and structured manner. Efforts to resolve disputes are carried out in an international criminal manner and are handled by the International Criminal Court. The International Criminal Court is the highest judicial institution, and has the authority to handle international cases. comparative law is a method of investigation with the aim of obtaining deeper knowledge about certain legal materials. Comparative law is not a set of rules and legal principles and is not a branch of law, but is a technique for dealing with foreign legal elements from a legal problem. Court. The International Criminal Court is the highest judicial institution, and has the authority to handle international cases