bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venetoclax alkalmazása myeloma multiplexben
Authors: Szita Virág Réka , Varga Gergely 
Published: April 2021

Összefoglaló. Bár az elmúlt évtizedben számos új gyógyszer került be
a myeloma multiplex kezelésének eszköztárába, a betegség az esetek nagy részében
továbbra is gyógyíthatatlan, ezért új hatóanyagok bevonására van szükség. A
venetoclax a bcl-2 antiapoptotikus fehérje gátlása révén ható új típusú
gyógyszermolekula, amelynek különböző hematológiai malignitásokban történő
alkalmazásáról az elmúlt években számos tanulmány készült. Myeloma multiplexben
való alkalmazása a hatásmechanizmusnak megfelelően a magas bcl-2/mcl-1, illetve
bcl-2/bcl-xl aránnyal rendelkező betegeknél előnyös, amely kedvező konstelláció
elsősorban a t(11;14) transzlokált betegeknél áll fenn. Bár korai tanulmányok
mutattak kedvező eredményeket más citogenetikai eltéréssel rendelkező betegeknél
is, a törzskönyvezési igénnyel indított nagy, randomizált 3. fázisú Bellini
klinikai vizsgálat a venetoclaxszal kezelt betegeknél ugyan a t(11;14)
csoportban nagyon kedvező eredményekre vezetett, de a nem t(11;14) betegeknél
többlethalálozást és OS-csökkenést mutatott ki. A vizsgálati eredmények
értelmében a venetoclax-alapú terápia myeloma multiplexben csak t(11;14)
betegeknek ajánlható. Az optimális alkalmazással és kombinációs partnerekkel
kapcsolatban további vizsgálatok szükségesek, mindazonáltal a venetoclax terápia
a myeloma multiplex személyre szabott kezelésének irányába tett első lépést
jelentheti.
Summary. Although recent decades introduced several new drugs to
multiple myeloma therapy, the disease is still considered incurable in most
cases and thus warrants the development of new agents. Venetoclax is a novel
type of drug inhibiting the antiapoptotic bcl-2 molecule whose use in varying
hematological malignancies has been evaluated by a multitude of studies in
recent years. Considering its mechanism of action, application in multiple
myeloma is possible in patients with high bcl-2/mcl-1 and bcl-2/bcl-xl ratios.
This favourable constellation is primarily found in patients with t(11;14)
translocations. Although early studies showed some promising results in patients
with different citogenetic makeup, the large randomized phase 3 Bellini study
which confirmed ventetoclax’s high effectivity in t(11;14) patients, proved
increased mortality and OS loss in the case of non-t(11;14) patients treated
with the drug. In light of these results, venetoclax based therapy may only be
recommended for t(11;14) myeloma patients. Further research is needed to
determine optimal application and combination partners, but venetoclax therapy
may be the first step towards personalized myeloma care.
Mély remisszióban lévő CML-es beteg hirtelen kezdetű pancytopeniája
Authors: Harasztdombi József , Lakatos Gergely , Szlávik János , Mikala Gábor 
Published: April 2021

Összefoglaló. A mély molekuláris remisszióban lévő CML-es betegnél
láz, izomfájdalmak alakultak ki, melyet jelentős kétvonalas cytopenia kísért.
Alapbetegségének blasztos transzfomációja mellett, az utazási anamnézisre
tekintettel a differenciáldiagnosztika trópusi betegségekre is kiterjedt.
Dengue-lázat diagnosztizáltunk, melyből a beteg szövődmény nélkül felépült.
Summary. A CML patient in deep molecular remission was admitted with
fever, muscle pain, followed by pronounced bilineage cytopenia. In addition to
possible blastic transformation, tropical diseases were also included in the
differential diagnosis, due to travel history. Dengue fever was diagnosed, and
the patient recovered without any complications.
A Patient Activities of Daily Living Scale for Amyotrophic Lateral Sclerosis
Authors: Herbelin Laura , Statland Jeffrey , Kimminau Kim , Waitman Russ , Heim Andrew , Dwyer Sally , Johnsen Kelli , Barohn Richard 
Published: April 2021

Background: Motor neuron disorders are rare, progressive neurodegenerative diseases which affect multiple domains of motor function. The ability to assess function from home using an electronic medical record (EMR) would facilitate pragmatic studies.
Objective: To develop a Patient Activity of Daily Living scale for Amyotrophic Lateral Sclerosis and other motor neuron disorders (PADL-ALS) to support large pragmatic trials.
Methods: The Greater Plains Collaborative Clinical Data Research Network (GPC) developed and tested the feasibility of using the PADL-ALS. We convened patient and caregiver focus groups and in-person meetings to recommend changes to the ALS Functional Rating Scale-Revised (ALSFRS-R), which clarified language and added questions about pseudobulbar affect, pain, and faith. Feasibility was determined by conducting a survey of participants identified using EMR-computable phenotypes and returned via patient-preferred modalities.
Results: Surveys were distributed to 1079 participants at nine GPC health systems. The survey response rate was 44.4% (range 12.9-57.66%): male to female ratio 1.56; 84% self-identified as a patient with ALS. Patient respondents used computers or tablets more frequently than caregivers responding on their behalf. The PADL-ALS correlated to clinic-performed ALSFRS-R within 4 weeks of survey completion (n=33, rho=0.93, Kansas only). The pseudobulbar affect question correlated to functional motor burden. Over 80% agreed to be contacted for future research opportunities.
Conclusion: We demonstrated the feasibility of determining functional burden with the PADL-ALS using an EMR-computable phenotype. Future directions include implementing the PADL-ALS to answer pragmatic questions about ALS care.
USE OF CYBER HATE IN THE ELECTORAL CAMPAIGNS BY THE MAINSTREAM POLITICAL PARTIES OF PAKISTAN
Authors: Siddiqua Ayesha 
Published: April 2021

Purpose of the study: The purpose of the study is to examine the use of cyber hate by the Pakistan’s mainstream political parties. The issue of poll rigging in Pakistan’s General Elections 2013 is examined through discourse analysis of the related tweets. The study also aims at comprehending the extent to which cyber ethics were violated during the digital electoral campaigns.
Methodology: Discourse Analysis of the tweets generated from the official Twitter handles of PTI and PMLN leaders was conducted to examine the use of cyber hate by the Pakistan’s mainstream political parties. Violation of cyber ethics was explored through the qualitative interviews of 8 purposively selected social media managers of PMLN, PPP, and PTI.
Main Findings: The findings indicated that party leadership/politicians used the elements of cyber hate which included abusive language, provocation, and character assassination against their opponents during the digital electoral campaign in general and regarding the poll rigging issue of Pakistan’s General Elections 2013 in specific. Resultantly the tweets using strong adjectives and metaphors on the political opponents were more frequently re-tweeted and attracted more favorites.
Applications of this study: The study can be helpful in various cross-disciplinary areas that focus on the examination of the usage and impact of social media and cyberspace as a medium for hate speech dissemination. The study can significantly contribute to areas related to cyber ethics, digital electoral campaigning, freedom of expression, and political opinion building.
Novelty/Originality of this study: The study’s originality lies in its attempt to unfold the foundations of digital electoral campaigning in Pakistan and how cyberhate was used as a pivotal tool for advancing the political narratives in a fragile democratic society.
The Societal Value of Vaccination in the Age of COVID-19
Authors: Bloom David E. , Cadarette Daniel , Ferranna Maddalena 
Published: April 2021

In recent years, academics and policymakers have increasingly recognized that the full societal value of vaccination encompasses broad health, economic, and social benefits beyond avoided morbidity and mortality due to infection by the targeted pathogen and limited health care costs. Nevertheless, standard economic evaluations of vaccines continue to focus on a relatively narrow set of health-centric benefits, with consequences for vaccination policies and public investments. The COVID-19 pandemic illustrates in stark terms the multiplicity and magnitude of harms that infectious diseases may inflict on society. COVID-19 has overtaxed health systems, disrupted routine immunization programs, forced school and workplace closures, impeded the operation of international supply chains, suppressed aggregate demand, and exacerbated existing social inequities. The obvious nature of the pandemic’s broad effects could conceivably convince more policymakers to identify and account for the full societal impacts of infectious disease when evaluating the potential benefits of vaccination. Such a shift could make a big difference in how we allocate societal resources in the service of population health and in how much we stand to gain from that spending.
COVID-19—The Case for Rethinking Health and Human Rights in Prisons
Authors: Pont Jörg , Enggist Stefan , Stöver Heino , Baggio Stéphanie , Gétaz Laurent , Wolff Hans 
Published: April 2021

This article considers health and human rights implications for people deprived of liberty during the COVID-19 crisis. The health risks of incarceration for individual and community health, particularly in overcrowded and underresourced prisons and detention centers, are well known, but with the COVID-19 pandemic have become a public health emergency. Physical distancing in prisons is hardly manageable, and protective means are poor or lacking. Emergency releases have been shown to be feasible in terms of public safety but lack sustainability in reducing the number of people living in detention, and, globally, only a small proportion of them have been released. Without controlling the infection inside prisons, global efforts to tackle the spread of the disease may fail. People living in detention are not only more vulnerable to infection with COVID-19 but they are also especially vulnerable to human rights violations induced by inappropriate restrictions under the pretext of infection control. Therefore, alternatives for detention should be promoted and the number of incarcerated people radically decreased. This article calls on policymakers and all professionals involved in public health and criminal justice not to waste the opportunities provided by the crisis but to act now.
Full-fledged gene-editing payload for AAV delivery built on guide RNA-remodeled miniature type V-F CRISPR
Authors: Kim Yong-Sam , Kim Do Yon , Lee Jeong Mi , Moon Su Bin , Chin Hyun Jung , Park Seyeon , Lim Youjung , Ko Jeong-Heon 
Published: April 2021

Abstract
The authors have requested that this preprint be removed from Research Square.
The Binding Characteristics of Sediment-Derived Dissolved Organic Matter with Ceftazidime: A Microstructural and Spectroscopic Correlation Study
Authors: Cai Xuewei , Qi Kemin , Zhang Xiaoli , Xie Xiaoyun , Wang Zhaowei 
Published: April 2021

Abstract
This research focused on the characterization of sediment-derived DOM (SDOM) extracted from sediment of Yellow River and the binding behaviors of ceftazidime (CAZ) with the presence of SDOM. The morphology, surface composition and structure of SDOM and the complexation between SDOM and CAZ in terms of component features, binding capacity and sequence were studied by multiple approaches. Results showed that SDOM was in situ autochthonous-dominated with a low weight-average molecular weight and aromaticity. The multiple morphological characteristics, high surface oxygen contents (53.49%) and more aliphatic of SDOM were further confirmed. Studies on SDOM-CAZ interaction suggested that the functional groups and chemical compositions of SDOM were susceptible to CAZ. In more detail, the aromatic protons and aliphatic protons of CAZ impacted significantly and the binding between CAZ and SDOM might relate to noncovalent. The protein-like fractions were considered to primary participant and the aromatics and amides as mainly active sites interaction with CAZ. These findings have significant implications on the environmental fate of cephalosporin antibiotics and that of sediment-derived DOM.
Effect of Laser surface texturing on coating adherence and tribological properties of CuNiIn and MoS2 coating
Authors: Bagade Vishal Uttamra , Duraiselvam Muthukannan , Sarangi Niranjan , K Parthiban 
Published: April 2021

Abstract
In aero gas turbine engine, copper nickel indium (CuNiIn) and molybdenum loaded disulphide (MoS2) duplex coating is applied on Ti6Al4V blades in bladed disk configuration of low pressure and high pressure compressor. Coating between blade and disk is provided to prevent fretting wear due to direct metal to metal contact of Ti6Al4V. Generally, grit blasting will be done for preparation of the surface before the application of coating. Laser surface texturing (LST) process can be explored by aero engine industry as a new surface preparation process for compressor blades. To compare two different surface preparation methods, Ti6Al4V surface is prepared by two different processes, conventional grit blasting as well as laser surface texturing (LST). LST with different elliptical and square patterns are created on Ti6Al4V. Surface topography is analyzed by SEM and WLI. CuNiIn is sprayed by atmospheric plasma spray (APS) and MoS2 on top of CuNiIn by painting and curing. Effects of surface preparation on coating adherence as well as on tribological properties are studied. The results showed that geometry and dimensions of LST pattern influences the coating adherence and wear performance. LST process can be optimized for better performance and explored as an alternative surface preparation process in industry for thermal spray coatings.
A Lean &amp; Green approach for the ecoefficiency assessment on construction sites: description and case study
Authors: Rezende Marilia de Oliveira , Saade Marcella Ruschi Mendes , Nunes Andréa Oliveira , Silva Vanessa Gomes da , Moris Virgínia Aparecida Silva , Silva Diogo Aparecido Lopes 
Published: April 2021

Abstract
Lean and Green seeks to increase added value and reduce waste generation, while also improving environmental sustainability performance in production activities. However, no studies were found exploring the potential results by combining Lean and Green with eco-efficiency assessments in the construction sector. Therefore, this paper aimed at proposing and testing a Lean and Green approach in three steps. Step 1 was based on the Value Stream Mapping application to calculate the Value Added of construction activities; step 2 focused on the Life Cycle Assessment of evaluated construction activities, and step 3 performed an eco-efficiency assessment of construction sites to guide decision-makers on selecting more lean and sustainable construction materials and strategies. A case study was developed for a 300m²-house construction considering two build options (reinforced concrete frame vs. light steel frame). The results affirm that light steel framing showed a Value Added 43% higher than the reinforced concrete in step 1, whilst having 8% less Global Warming Potential impacts in step 2. Step 3 concluded that light steel framing was 1.38 times more eco-efficient than the concrete structure. The proposed approach can be suitable for any building system evaluation in terms of construction technologies, materials, and/or production strategies and investigations towards more sustainable production.
Devosia Sediminis sp. nov., Isolated from Fubterranean Sediment.
Authors: Ma Fu , Zi Da Zhi , Li Wei , Wang Zhao Xuan , Lu Jun , Lv Jie 
Published: April 2021

Abstract
A novel Gram- negative, cream-colored, rod-shaped, aerobic, non-motile bacterium, designated MSA67T, was isolated from a subterranean sediment sample of the Mohe Basin in Northeast China. Strain MSA67T was detected to grow at 4–40°C (optimum, 28–30°C), pH 5.0–10.0 (optimum, pH 7.0) and in 0.0–8.0 % (w/v) NaCl (optimum, 2.0–3.0 %). Phylogenetic analysis based on 16S rRNA gene sequence revealed that strain MSA67T was a member of the genus Devosia, with the highest similarity with D. riboflavina IFO13584T (98.0 %) and D. chinhatensis IPL18T (97.0 %). The major cellular fatty acids are C16:0, C18:1ω7c 11-methyl and C18:1ω6c and/or C18:1ω7c. The major polar lipids are diphosphatidylglycerol, phosphatidylglycerol, glycolipids and three unidentified phospholipids. The major respiratory quinone is ubiquinone 10 (Q-10). The genomic size of strain MSA67T is 4.1 MB and DNA G + C content is 63.6 %. Based on genotypic, phenotypic and phylogenetic results, strain MSA67T is concluded to represent a novel species of the genus Devosia, for which the name Devosia sediminis sp. nov. is proposed. The type strain is MSA67T (= CGMCC 1.18467T = KCTC 82192T).
Knockdown of TRIM44 inhibits the progression of human epithelial ovarian cancer via the FOXM1-EZH2 signaling pathway
Authors: Meng Fanling , Ding Jing , Chen Xihai , Sui Lin , Hu Yuanlong , Liu Shuang , Shi Guangyue , He Yunlong , Ning Xin , Zhu Jiaqi , Zhao Ruixue , Ma Jing , Ren Sujing , Ma Rong , Huang Ning 
Published: April 2021

Abstract
Background. Tripartite motif‑containing protein 44 (TRIM44) was recently identified as a novel oncogene that is overexpressed in several types of human cancers. However, the biological functions of TRIM44 in epithelial ovarian cancer (EOC) remain unclear. Here, we aimed to investigate the role of TRIM44 in EOC and its clinical implications.Methods. The expression of TRIM44 in different ovarian cancer cell lines were detected by western blot. TRIM44 was knocked down by shRNA transfection. The in vitro proliferation, invasion, migration and apoptosis of ovarian cancer cells were detected by CCK8, colony formation assay, transwell filters, tube formation assay and flow cytometry analysis, respectively. The growth ability of xenograft tumors in vivo was examined by a nude mouse metastatic tumor model. Finally, we carried out gene chip analysis and IPA to analyze the potential gene network.Results. High expression of TRIM44 was observed in EOC tissues and cell lines. Knockdown of TRIM44 expression substantially suppressed the proliferation, migration, invasion and colony-forming ability of EOC cells in vitro and attenuated tumor growth in vivo. Mechanistic studies showed that silencing TRIM44 dramatically down regulated the expression of FOXM1, EZH2, CCNE2, CCND3 and BIRC5 in EOC cells, at least in part through inactivation of the FOXM1-EZH2 signaling pathway.Conclusion. Collectively, these data suggest that TRIM44 downregulation inhibits the progression of EOC cells through the suppression of the FOXM1-EZH2 signaling pathway. These results provide novel insight into the role of TRIM44 in tumorigenesis and suggest it could be a potential therapeutic target of ovarian carcinoma.
Establishment of An Orthotopic Prostate Cancer Xenograft Mouse Model Using Microscope-Guided Orthotopic Injection of LNCaP Cells Into The Dorsal Lobe of The Mouse Prostate
Authors: Liu Weiyong , Zhu Yunkai , Ye Lei , Zhu Yajuan , Wang Yuhao 
Published: April 2021

Abstract
Background: Orthotopic LNCaP xenograft mouse models closely mimic the progression of androgen-dependent prostate cancer in humans; however, orthotopic injection of LNCaP cells into the mouse prostate remains a challenge.Methods: Under the guidance of a stereoscopic microscope, the anatomy of the individual prostate lobes in male Balb/c athymic nude mice was investigated, and LNCaP cells were inoculated into the mouse dorsal prostate (DP) to generate orthotopic tumors that mimicked the pathophysiological process of prostate cancer in humans. Real-time ultrasound imaging was used to monitor orthotopic prostate tumorigenesis, contrast-enhanced ultrasonography (CEUS) was used to characterize tumor angiogenesis, and macroscopic and microscopic characteristics of tumors were described.Results: The DP had a trigonal bipyramid-shape and were located at the base of the seminal vesicles. After orthotopic inoculation, gray scale ultrasound imaging showed progressive changes in tumor echotexture, shape and location, and tumors tended to protrude into the bladder. After 8 weeks, the tumor take rate was 65% (n= 13/20 mice). On CEUS, signal intensity increased rapidly, peaked, and decreased gradually. Observations of gross specimens showed orthotopic prostate tumors were well circumscribed, round, dark brown, and soft, with a smooth outer surface and a glossy appearance. Microscopically, tumor cells were arranged in acini encircled by fibrous septa with variably thickened walls, mimicking human adenocarcinoma.Conclusions: This study describes a successful approach to establishing an orthotopic LNCaP xenograft Balb/c athymic nude mouse model. The model requires a thorough understanding of mouse prostate anatomy and proper technique. The model represents a valuable tool for the in vivo study of the biological processes involved in angiogenesis in prostate cancer and preclinical evaluations of novel anti-angiogenic therapies.
Mitofusin 1 and 2 regulation of mtDNA content is a critical determinant of glucose homeostasis
Authors: Sidarala Vaibhav , Zhu Jie , Pearson Gemma , Reck Emma , Kaufman Brett , Soleimanpour Scott 
Published: April 2021

Abstract
The dynamin-like GTPases Mitofusin 1 and 2 (Mfn1 and Mfn2) are essential for mitochondrial function, which has been principally attributed to their regulation of fission/fusion dynamics. Here, we report that Mfn1 and 2 are critical for glucose-stimulated insulin secretion (GSIS) primarily through control of mtDNA content. Whereas Mfn1 and Mfn2 individually were dispensable for glucose homeostasis, combined Mfn1/2 deletion in β-cells reduced mtDNA content, induced mitochondrial fragmentation, and impaired respiratory function, ultimately resulting in severe glucose intolerance. Importantly, gene dosage studies unexpectedly revealed that Mfn1/2 control of glucose homeostasis was dependent on maintenance of mtDNA content, rather than mitochondrial structure. Indeed, pharmacologic mitofusin agonists rescued islet mtDNA depletion due to mitofusin deficiency independent of changes on mitochondrial structure. Mfn1/2 maintain mtDNA content by regulating the expression of the crucial mitochondrial transcription factor Tfam, as Tfam overexpression ameliorated the reduction in mtDNA content and GSIS in Mfn1/2-deficient β-cells. Thus, the primary physiologic role of Mfn1 and 2 in β-cells is coupled to preservation of mtDNA content rather than mitochondrial architecture, and Mfn1 and 2 may be promising targets to overcome mitochondrial dysfunction and restore glucose control in diabetes.
Study on the Effect of Surface Subsidence Due to Tunneling Under Various Loading Conditions
Authors: KRISHNA SOMU S , Lokhande Ritesh D 
Published: April 2021

Abstract
The subsidence caused on the surface due to the construction of subsurface tunnels for various purposes in urban areas is a major concern for both the tunnel and the overlaid buildings. Seeing the importance of study, different models has been created keeping reference of commercial and residential buildings. The amount of surface deformation and the stresses so generated are calculated, which plays a paramount role before construction. These models are analyzed on circular and semicircular tunnels with various loading conditions and varying litho. In this paper, two software’s namely STAAD Pro and Rocscience were used for structural design and analysis respectively. The study gives the basic idea of behavior of these two shapes of tunnels with varying loading condition and strata which shows a path for predicting unforeseeable displacements in real life situations.