bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylation of the serotonin reuptake transporter gene and non-motor symptoms in dystonia patients
Authors: Timmers Elze R. , Plösch Torsten , Smit Marenka , Hof Ingrid H. , Verkaik-Schakel Rikst Nynke , Tijssen Marina A. J. , de Koning Tom J. , Niezen-Koning Klary E. 
Published: December 2022

Abstract
Background
Dystonia is a rare movement disorder, in which patients suffer from involuntary twisting movements or abnormal posturing. Next to these motor symptoms, patients have a high prevalence of psychiatric comorbidity, suggesting a role for serotonin in its pathophysiology. This study investigates the percentage of DNA methylation of the gene encoding for the serotonin reuptake transporter (SLC6A4) in dystonia patients and the associations between methylation levels and presence and severity of psychiatric symptoms.

Methods
Patients with cervical dystonia (n = 49), myoclonus dystonia (n = 41) and dopa-responsive dystonia (DRD) (n = 27) and a group of healthy controls (n = 56) were included. Psychiatric comorbidity was evaluated with validated questionnaires. Methylation levels of 20 CpG sites situated 69 to 213 base pairs upstream of the start codon of SLC6A4 were investigated. Methylation in dystonia patients was compared to healthy controls, correcting for age, and correlated with psychiatric comorbidity.

Results
Bootstrapped quantile regression analysis showed that being a dystonia patient compared to a healthy control significantly explains the methylation level at two CpG sites (CpG 24: pseudo-R2 = 0.05, p = 0.04, CpG 32: pseudo-R2 = 0.14, p = 0.03). Subgroup analysis revealed that being a DRD patient significantly explained a part of the variance of methylation levels at two CpG sites (CpG 21: pseudo-R2 = 0.03, p = 0.00, CpG 24: pseudo-R2 = 0.06, p = 0.03). Regression analysis showed that methylation level at CpG 38 significantly explained a small proportion of the variance of severity score for anxiety (R2 = 0.07, p = 0.04) and having a diagnosis of depression (Nagelkerke R2: 0.11, p = 0.00). Genotype of the 5-HTTLPR polymorphism had no additional effect on these associations.

Conclusions
This study showed an association between percentage of methylation at several specific sites of the promoter region of SLCA64 and (dopa-responsive) dystonia patients compared to healthy controls. Furthermore, methylation levels were associated with severity of anxiety and presence of a depressive disorder in the dystonia group. This study suggests alterations in the serotonergic metabolism in dystonia patients, and its relation with the non-motor symptoms.
Five-year remission without disease progression in a patient with relapsed/refractory multiple myeloma with extramedullary disease treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study: a case report
Authors: Wang Bai-Yan , Zhao Wan-Hong , Chen Yin-Xia , Cao Xing-Mei , Yang Yun , Zhang Yi-Lin , Wang Fang-Xia , Zhang Peng-Yu , Lei Bo , Gu Liu-Fang , Wang Jian-Li , Bai Ju , Xu Yan , Wang Xu-Geng , Zhang Rui-Li , Wei Li-Li , Zhuang Qiu-Chuan , Fan Frank , Zhang Wang-Gang , He Ai-Li , Liu Jie 
Published: December 2022

Abstract
Background
Multiple myeloma remains incurable despite treatment advancements over the last 20 years. LCAR-B38M Cells in Treating Relapsed/Refractory Multiple Myeloma was a phase 1, first-in-human, investigator-initiated study in relapsed/refractory multiple myeloma conducted at four sites in China. The study used LCAR-B38M chimeric antigen receptor-T cells expressing two B-cell maturation antigen-targeting single-domain antibodies designed to confer avidity, and a CD3ζ signaling domain with a 4-1BB costimulatory domain to optimize T-cell activation and proliferation. This chimeric antigen receptor construct is identical to ciltacabtagene autoleucel. In the LEGEND-2 study (n = 57, Xi’an site), overall response rate was 88%; median (95% CI) progression-free survival and overall survival were 19.9 (9.6–31.0) and 36.1 (26.4–not evaluable) months, respectively; and median follow-up was 25 months. This case study reports on a patient with relapsed/refractory multiple myeloma (λ light chain type) who was treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study (Xi’an site); he had received five prior lines of treatment and had extensive extramedullary lesions.

Case presentation
The patient, a 56-year-old Asian male, received cyclophosphamide (500 mg daily × 3 days) as lymphodepletion therapy and a total dose of 0.5 × 106 chimeric antigen receptor + T cells/kg split into three infusions (days 1, 24, and 84 from June to August 2016). He experienced grade 2 cytokine release syndrome after the first infusion; all symptoms resolved with treatment. No cytokine release syndrome occurred following the second and third infusions. His λ light chain levels decreased and normalized 20 days after the first infusion, and extramedullary lesions were healed as of January 2018. He has sustained remission for 5 years and received no other multiple myeloma treatments after LCAR-B38M chimeric antigen receptor T cell infusion. As of 30 October 2020, the patient is still progression-free and has maintained minimal residual disease-negative (10–4) complete response status for 52 months.

Conclusions
This case provides support that treatment with LCAR-B38M chimeric antigen receptor T cells can result in long-term disease remission of 5 or more years without disease progression in a heavily pretreated patient with extensive extramedullary disease and no other treatment options.
Lapatinib and lapatinib plus trastuzumab therapy versus trastuzumab therapy for HER2 positive breast cancer patients: an updated systematic review and meta-analysis
Authors: Yuan Ye , Liu Xumei , Cai Yi , Li Wenyuan 
Published: December 2022

Abstract
Introduction
Trastuzumab, as the gold standard for HER2-positive BC treatment, was the first-line HER2 targeted drug. However, some studies reported patients benefited more from lapatinib and lapatinib plus trastuzumab therapy than standard trastuzumab therapy. This study presents an update of a systematic review and meta-analysis involving comparison of lapatinib and lapatinib plus trastuzumab therapy versus trastuzumab therapy.

Aim
We determined whether trastuzumab plus lapatinib or lapatinib therapy is not inferior to trastuzumab therapy in HER2-positive breast cancer patients.

Methods
Relevant trials were searched in CNKI, Wanfang, VIP, Sinomed, PubMed, Embase, and Cochrane CENTRAL databases from inception until October 25, 2021. Primary outcomes were OS, DFS/EFS, and PFS while secondary outcomes were pCR (ypT0/is ypN0), pCR (ypT0/is ypN0/+), ORR, DCR, rate of BCS, RFS, cardiac toxicities, and other toxicities.

Results
Thirteen randomized controlled trials were included in this study. Trastuzumab combined with lapatinib therapy was found to be superior to standard trastuzumab therapy alone with regard to overall survival, disease-free survival/event-free survival, pathologic complete response (ypT0/is ypN0), pathologic complete response (ypT0/is ypN0/+), recurrence-free survival, higher incidences of diarrhea, and rash/skin toxicity. Lapatinib therapy was established to be inferior to trastuzumab therapy in overall survival, progression-free survival, disease-free survival/event-free survival, pathologic complete response (ypT0/is ypN0) and pathologic complete response (ypT0/is ypN0/+), diarrhea, and rash/skin toxicity and had a low incidence of left ventricular ejection fraction decline.

Conclusions
The efficacy of trastuzumab combined with lapatinib therapy is superior to standard trastuzumab therapy alone; however, it has more non-cardiac grade III/IV toxicities. Moreover, the efficacy of lapatinib therapy is inferior to that of standard trastuzumab therapy alone.
Awareness regarding antimicrobial resistance and confidence to prescribe antibiotics in dentistry: a cross-continental student survey
Authors: Bajalan Aya , Bui Tiina , Salvadori Gabriela , Marques Dalton , Schumacher Alison , Rösing Cassiano Kuchenbecker , Dahle Ulf Reidar , Petersen Fernanda Cristina , Ricomini-Filho Antônio Pedro , Nicolau Belinda Farias , Junges Roger 
Published: December 2022

Abstract
Background
The antimicrobial resistance (AMR) crisis is a major global threat and one of its biggest drivers is the overuse of antibiotics in humans. Dentists are responsible for 5–10% antibiotic prescriptions worldwide and recent data suggest that knowledge and prescribing practices need improvement.

Methods
A cross-sectional web-survey was sent to dental students from six universities in Norway, Canada, and Brazil. Topics addressed covered awareness, confidence to prescribe antibiotics, and education needs. Data were presented descriptively and statistical testing was employed to compare group means when applicable.

Results
In total, 562 responses were collected across the three countries with a response rate of 28.6%. ‘Antibiotic resistance’ was among the highest priorities (scale 1–10) with an average of 8.86 (SEM ± 0.05), together with ‘Gender inequality’ (8.68 ± 0.07) and ‘Climate change’ (8.68 ± 0.07). Only 28.8% thought that Dentistry was engaged in national/international campaigns promoting awareness on the topic and 8.9% stated to have heard about the ‘One Health’ concept. Final year dental students showed an average confidence to prescribe antibiotics of 7.59 (± 0.14). Most students demonstrated interest in receiving additional education on all topics listed, with the three most pressing being ‘antibiotic prescription for treatment of infections’ (82.9%), ‘drug interactions’ (80.9%), and ‘spread of antibiotic resistance’ (79.6%). A trend was observed between higher awareness regarding the topic and higher confidence to prescribe.

Conclusions
There is a need to revisit dental education on antibiotic resistance with a global perspective and to create more stewardship initiatives that promote awareness on the topic.
Perceived social support and college student engagement: moderating effects of a grateful disposition on the satisfaction of basic psychological needs as a mediator
Authors: Xin Zhongyi 
Published: December 2022

Abstract
Background
Previous research has examined the role of support provided by the workplace in promoting employee engagement. This study aimed to extend this research to the academic environment by testing a proposed model of the relationship between perceived social support and student engagement and its underlying mechanisms, with the latter involving the satisfaction of basic psychological needs and a grateful disposition.

Methods
A total of 622 Chinese college students were selected by convenience sampling. I adopted the Perceived Social Support Scale, Basic Needs Satisfaction in General Scale, Gratitude Questionnaire, and Utrecht Work Engagement Scale-Student to collect their responses. The data were analyzed by using a moderated mediation model with SPSS and the Process 4.0 macro.

Results
The results showed that the satisfaction of basic psychological needs played a mediating role in the association between perceived social support and student engagement, while a grateful disposition played a moderating role. The moderating mediation model further revealed that this effect was more robust for students with a higher grateful disposition than for those with a lower level.

Conclusion
Perceived social support can significantly and positively predict student engagement through the satisfaction of their basic psychological needs. Students with a high grateful disposition benefit more than those with a low grateful disposition from using social support, as well as can use the received social support fully in order to meet their psychological needs and promote academic engagement.
Comparison of sparse Gabor-based methods for detection of microseismic events
Authors: Bui Hanh , van der Baan Mirko , Sacchi Mauricio D. 
Published: December 2022

Event detection and selection is a challenging and time-consuming step in microseismic data processing because signals often are embedded in noisy recordings. Automated triggering-based algorithms can detect many potential events in the data. However, their precision rates often are low, thus requiring substantial manual labor to select desired events of interest. This study investigates two time-frequency methods which combine signal enhancement with automated event detection and selection, namely, (1) the sparse Gabor transform and (2) the neighboring block thresholding. Both methods use thresholding in the time-frequency domain to increase signal enhancement, followed by an energy detection criterion, leading to improved event detection with higher precision rates. However, the neighboring block thresholding causes amplitude fidelity issues and we observe changes in the relative and maximum amplitudes of the waveforms reconstructed from the thresholded coefficients. Conversely, the sparse Gabor transform attenuates the noise significantly while preserving the signals. Thus, this time-frequency method is suitable for enhanced event detection and subsequent processing, including magnitude estimation and moment tensor inversion.
EVRENSELCİ DİKOTOMİ BAĞLAMINDA ARI HAAN DESTANI
Authors: ÖZPINAR Berna , KOÇAK Aynur 
Published: December 2022

Türkler kendine özgü bir hikmet oluşturabilmiş milletlerdendir. Hikmet ise kolektif tefekkürün en yüce eseridir. Hikmetin bir açıdan dünya görüşü olması onu bir yönüyle kozmogoni ile ilişkilendirmektedir.
Türk düşüncesi dünyayı bir bütün olarak algılamakta, evreni oluşturan tüm varlıkları bütünün parçaları olarak saymaktadır. Bununla birlikte Türk düşüncesinde Dünya, Yer ve Göğün birleşiminden oluşur. İkisi zıt karakterde olsalar da birbirine uyum sağlayarak birlik oluştururlar. İkisi birbirine denktir, biri diğerinden üstün değildir. Yer ve Göğün oluşturduğu bu sistem evrenselci dikotomi, evrensel iki ilke, iki ilkeli sistem gibi adlarla anılır.
Türk düşüncesinin en temel anlayışı olan evrenselci dikotomi, zıtlıklar içinde uyumu ve birliği oluşturacak şekilde Türk yaşamının her alanında etkisini gösterir. Anlatılar da buna dahildir. Türk mitolojik anlatılarının olay örgüsü içinde yer alan semboller, görünürdeki konunun derinlerinde evrensel iki ilkeyi barındırmaktadır. İki ilkenin varlığı ancak semboller çözümlendiğinde ortaya çıkmaktadır ve anlatıların temeli bu sisteme oturmaktadır. Bu çalışmada Tuva Türklerine ait, arkaik özellikleri barındıran Arı Haan Destanı’ndaki sembollerin çözümlenmesi yapılarak ve destan evrenselci dikotomi bağlamında incelenecektir.
Bridging as Metaphor- A Systems Thinking Approach for Exploring Transboundary Risk
Authors: Locklear Kathleen 
Published: December 2022

This paper provides a novel approach for understanding transboundary risk, including ‘grand challenges’ such as climate change. Discussion begins with an exploration of the origins of transboundary risk as a byproduct of globalization. Thereafter, the concept of ‘bridging’ is used in order to conceptualize the spread of transboundary risk across traditional physical boundaries, including geographic borders. Building upon prior theory, systems thinking and complexity are used as conceptual lenses for understanding the dynamics of transboundary risk. Scenario planning is offered as a means for envisioning and addressing the challenges presented by transboundary risk. The result of this discussion is a holistic, systems view of transboundary risk which stands in contrast to traditional, reductionist perspectives of risk. As such, the paper concludes by proposing a set of epistemological questions that emerge as a result of this shift.
Sanctions are Costly for Citizens but Beneficial for Autocrats: A Political-Economic Perspective
Authors: Eichenberger Reiner , Stadelmann David 
Published: December 2022

Abstract
Economic sanctions negatively affect the target country’s economic potential. As a type of enforced protectionism, sanctions shift the relative power in the target country between its citizens and its (autocratic) government. This shift tends to favor autocrats as their power over the limited means of production increases and as they control the remaining international exchange opportunities. Resistance against autocratic governments would require collective action by citizens or an organized political opposition, but the autocrats’ relative gain in power due to sanctions increases their likelihood of staying in power. Internationally, an economically weakened country may present less of an external military threat. However, as the stabilization of a target regime is a likely outcome of sanctions, sanctioned regimes remain an international threat. Therefore, we also discuss potential alternatives to sanctions as policy tools.
A critical review on application of organic, inorganic and hybrid nanophotocatalytic assemblies for photocatalysis of methyl orange dye in aqueous medium
Authors: Din Muhammad Imran , Khalid Rida , Hussain Zaib , Arshad Muhammad , Khan Safyan A. 
Published: December 2022

Abstract
Methyl orange (MO) is a highly carcinogenic and harmful contaminant, which has been extensively reported for its detrimental impact on human and aquatic life. The photodegradation of MO into less toxic products has gained much attention over the past few decades. Herein we have reviewed the recent advancement in designing of nanomaterials (NMs) stabilized on different fabricating assemblies and their application in photocatalysis of MO dye. These photocatalytic systems possess various advantages and disadvantages. Graphene-based supported materials on different NMs are highly reported photocatalysts for photocatalysis of MO dye. Recent advancement, parameters affecting photocatalytic studies, kinetics and photocatalytic mechanism of MO have been thoroughly explained in this review. Future outcomes are also provided for extending the development of scientific research in this field.
Current advances in stem cell therapy in the treatment of multiple sclerosis
Authors: Zolfaghari Baghbadorani Parnian , Rayati Damavandi Amirmasoud , Moradi Samira , Ahmadi Meysam , Bemani Peyman , Aria Hamid , Mottedayyen Hossein , Rayati Damavandi Amirhossein , Eskandari Nahid , Fathi Farshid 
Published: December 2022

Abstract
Multiple sclerosis (MS) is an inflammatory disease related to the central nervous system (CNS) with a significant global burden. In this illness, the immune system plays an essential role in its pathophysiology and progression. The currently available treatments are not recognized as curable options and, at best, might slow the progression of MS injuries to the CNS. However, stem cell treatment has provided a new avenue for treating MS. Stem cells may enhance CNS healing and regulate immunological responses. Likewise, stem cells can come from various sources, including adipose, neuronal, bone marrow, and embryonic tissues. Choosing the optimal cell source for stem cell therapy is still a difficult verdict. A type of stem cell known as mesenchymal stem cells (MSCs) is obtainable from different sources and has a strong immunomodulatory impact on the immune system. According to mounting data, the umbilical cord and adipose tissue may serve as appropriate sources for the isolation of MSCs. Human amniotic epithelial cells (hAECs), as novel stem cell sources with immune-regulatory effects, regenerative properties, and decreased antigenicity, can also be thought of as a new upcoming contender for MS treatment. Overall, the administration of stem cells in different sets of animal and clinical trials has shown immunomodulatory and neuroprotective results. Therefore, this review aims to discuss the different types of stem cells by focusing on MSCs and their mechanisms, which can be used to treat and improve the outcomes of MS disease.
The existence of a triangle when its three elements are known
Authors: Mazėtis Edmundas , Melničenko Grigorijus 
Published: December 2022

The problem of the existence of a triangle with respect to three given elements in some cases can be very difficult. For example, Brokard's problem about the existence of a triangle, given its three bisectors [1], has a long history [3] and solved only in 1994 [10]. We include in the number of elements: three sides, three angles, three heights, three medians, three bisectors, radii of the circumscribed and inscribed circles, and perimeter. In total, there are 186 different problems of the existence of a triangle with three given elements and for 116 problems are given sufficient conditions (for some sufficient and necessary conditions of existence) when a triangle can be construct by a compass and a ruler, and the remaining 70 problems when it is impossible to construct a triangle by a compass and a ruler. The authors list these 70 problems and indicate for which of them the necessary and sufficient conditions for the uniqueness of the existence of a triangle with three prescribed elements have found.
In vitro effect of bioscaffolds on viability and insulin‑producing function of human islets of Langerhans
Authors: Ponomareva A. S. , Baranova N. V. , Miloserdov I. A. , Sevastianov V. I. 
Published: December 2022

The culture of islets of Langerhans with bioscaffolds – extracellular matrix (ECM) mimetics – can provide a native microenvironment suitable for islets. This is one of the main conditions for creating a pancreatic tissue equivalent.Objective: to compare the secretory capacity of viable human pancreatic islets in monoculture (control group) and cultured in the presence of two bioscaffolds: biopolymer collagen-based hydrogel scaffold (experimental group 1) and tissue-specific scaffold from decellularized deceased donor pancreas (experimental group 2).Materials and methods. Islets of Langerhans were isolated from the caudal pancreas using a collagenase technique. The viability of cultured islets was accessed by vital fluorescence staining, while secretory capacity was evaluated by enzyme-linked immunosorbent assay (ELISA).Results. Pancreatic islets cultured with bioscaffolds showed no signs of degradation and fragmentation, they remained viable throughout the entire period of observation (7 days). The monoculture of islets showed significant destructive changes during this period. Basal insulin levels in experimental groups 1 and 2 increased by 18.8% and 39.5% on day 1 of culture compared to the control group, by 72.8% and 102.7% on day 4 of incubation, and by 146.4% and 174.6% on day 7, respectively. The insulin secretion level of islets with tissue-specific scaffolds was 17.4% higher than that when cultured with biopolymer collagen-based scaffolds.Conclusion. Biopolymer and tissue-specific ECM mimetics contribute not only to preservation of the viability of isolated islets of Langerhans but also maintain their insulin secretion capacity for 7 days at a higher level in comparison with monoculture. The experiments revealed that the use of a tissue-specific scaffold for the creation of a pancreatic tissue equivalent has slight potential advantage over biopolymer scaffold.