bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative genomic profiling identifies targetable brain metastasis drivers in non-small cell lung cancer
Authors: Nicos Marcin , Harbers Luuk , Patrucco Enrico , Kramer-Drauberg Maximilian , Zhang Xiaolu , Voena Claudia , Kowalczyk Anna , Bozyk Aleksandra , Peksa Rafal , Jarosz Bozena , Szumilo Justyna , Simonetti Michele , Zuk Monika , Wasag Bartosz , Reszka Katarzyna , Duchnowska Renata , Milanowski Janusz , Chiarle Roberto , Bienko Magda , Krawczyk Pawel , Jassem Jacek , Ambrogio Chiara , Crosetto Nicola
Published: February 2022

Brain metastases (BM) severely impact the prognosis and quality of life of patients with non-small cell lung cancer (NSCLC). To identify targetable drivers of NSCLC-BM, we profiled somatic copy number alterations (SCNAs) in 51 matched pairs of primary NSCLC and BM samples from 33 patients with lung adenocarcinoma (LUAD) and 18 patients with lung squamous cell carcinoma (LUSC). BM consistently had a higher burden of SCNAs compared to the matched primary tumors, and SCNAs were typically homogeneously distributed within BM, as revealed by multi-region SCNA profiling in 15 BM samples, suggesting that BM do not undergo extensive evolution once formed. By comparing focal SCNAs in matched NSCLC-BM pairs, we identified BM driving alterations affecting multiple cancer genes, including several targetable genes such as CDK12, DDR2, ERBB2, and NTRK1, which we validated in an independent cohort of 84 BM samples. We explored the metastatic potential of CDK12 and DDR2 in vitro and in vivo and found that overexpression of either gene alone in murine lung cancer cells causes the induction of key genes involved in epithelial-mesenchymal transition. Finally, we performed whole-exome sequencing of 40 NSCLC-BM pairs and identified BM driver mutations in multiple cancer genes, including several genes involved in epigenome editing and 3D genome organization, such as EP300, CTCF, and STAG2, which we validated by targeted sequencing of an independent cohort of 115 BM samples. Our study represents the most comprehensive genomic characterization of LUAD and LUSC BM available to date, uncovering potentially targetable NSCLC-BM drivers and inspiring the design of novel precision treatment strategies for NSCLC patients.
Characterization of almond scion/rootstock communication in cultivar and rootstock tissues through a RNA-Seq approach
Authors: Grimplet Jérôme , Montesinos Álvaro , Rubio-Cabetas María José
Published: February 2022

Background: Rootstock genotype determines multiple aspects of the scion development, including the scion three-dimensional structure, or tree architecture. Thus, rootstock choice is an important factor in the establishment of new almond (Prunus amygdalus (L.) Batsch, syn P. dulcis (Mill.)) planting systems, which demand cultivars whose vigor and shape adapt to these new requirements. However, if the rootstock genotype is able to alter scion development, it is likely that the scion genotype affects the rootstock performance. Results: We carried out a transcriptomic analysis of the scion/rootstock interaction in young trees, focusing on the scion effect in the rootstock molecular response. Two commercial almond cultivars were grafted onto two hybrid rootstocks, resulting in four combinations, whose gene expression in both scion and rootstock tissue was analyzed via RNA-Seq. We observed that, in fact, the scion genotype has an impact on the rootstock expression profile, affecting the expression of genes associated with hormonal regulation, root development and light signaling. Conclusions: Scion/rootstock communication has a pivotal role in the development of both scion and rootstock, accentuating the importance of a correct choice when establishing new almond orchards.
Development of an Optimal Time for Learning Questionnaire in Chinese University Students
Authors: LIU Lingshan , LV Hongyuan , LU Yifan , WANG Chu , CHAI Hao , RIMOL Lars M. , Wang Wei
Published: February 2022

Background
Autonomous learning is crucial for students’ academic achievements, however, there lacks a structure-validated questionnaire to measure the optimal time for autonomous learning with different learning contents.
Methods
Based on the previous investigations, we have designed a matrix of 49 items based on seven learning contents and seven time periods of a day to measure the optimal time for autonomous learning and invited 305 Chinese university students to answer the matrix.
Results
Through both exploratory and confirmatory factor analyses, we have developed an Optimal Time for Learning Questionnaire with a satisfactory model structure of five factors (7, 6, 6, 6, 5 items per factor respectively) namely Noon, Late Night, Nightfall, Morning and Afternoon. The internal reliabilities of these factors were acceptable, and their inter-correlations were significant, albeit in low or medium levels.
Conclusions
The Optimal time for Learning Questionnaire may help students find their optimal learning efficiency individually.
Melatonin attenuates inflammation, oxidative stress, and DNA damage in mice with nonalcoholic steatohepatitis induced by a methionine- and choline-deficient diet.
Authors: Miguel Fabiano Moraes , Picada Jaqueline Nascimento , Silva Juliana Bondan da , Schemitt Elizângela Gonçalves , Colares Josieli Raskopf , Hartmann Renata Minuzzo , Marroni Cláudio Augusto , Marroni Norma Possa
Published: February 2022

Nonalcoholic steatohepatitis (NASH) is a disease with a high incidence worldwide, but its diagnosis and treatment are poorly managed. In this study, NASH pathophysiology and DNA damage biomarkers were investigated in mice with NASH treated and untreated with melatonin (MLT). C57BL/6 mice were fed a methionine- and choline-deficient (MCD) diet for four weeks to develop NASH. Melatonin was administered at 20 mg/kg during the last two weeks. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured, and hepatic tissue was dissected for histological analysis, evaluation of lipoperoxidation, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as nuclear factor-erythroid 2 (Nrf2), tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS), and tumor necrosis factor alpha (TGF-β) expression by immunohistochemistry. DNA damage was evaluated using Comet assay, while a micronucleus test in bone marrow was performed to assess the genomic instability associated with the disease. Melatonin decreased AST and ALT, liver inflammatory processes, balloonization and fibrosis in mice with NASH, decreasing TNF-α, iNOS, and TGF-β, as well as oxidative stress, shown by reducing lipoperoxidation, and intensifying Nrf2 expression. The SOD and GPx activities were increased while CAT was decreased by treatment with MLT. Although the micronucleus frequency was not increased in mice with NASH, a protective effect on DNA was observed with MLT treatment in blood and liver tissues using Comet assay. As conclusions, MLT slows down the progression of NASH, reducing hepatic oxidative stress and inflammatory processes, inhibiting DNA damage via anti-inflammatory and antioxidant actions.
Anatomical Study Of Sites And Footprints Of Tibial Posterior Tendon Attachment
Authors: Uchiyama Inori , Edama Mutsuaki , Yokota Hirotake , Hirabayashi Ryo , Sekine Chie , Maruyama Sae , Syagawa Mayuu , Togashi Ryoya , Yamada Yuki , Kageyama Ikuo
Published: February 2022

Background: The purpose of this study was to clarify variations in the tibialis posterior tendon (TPT) attachment site using a large sample and to quantify the contribution of each attachment site by examining the surface area of the attachment region.Methods: We examined 100 feet from 50 Japanese cadavers. The TPT of attachment to the the navicular bone (NB), medial cuneiform bone [1], and lateral cuneiform bone (LCB) was set as the main attachment site (Type I). Type II was defined as one extra attachment site in addition to those of Type I, meaning attachment to a total of four sites. Classification up to Type VII was seen according to the number of additional attachment sites. Furthermore, surface area was measured using a 3-dimensional scanner to make the foot sample three-dimensional. Surface area was then calculated using 3-dimensional software.Results: Attachment to the NB, MCB, and LCB was present in all specimens. Attachment to the intermediate cuneiform bone was seen in 25 feet (25%), and to the cuboid bone in 66%. Among 1st–5th metatarsal bones, 4th metatarsal bone was the most attached, at 95%. The TPT attachment to the NB, MCB, and LCB were comprising 75.1% of total attachment surface area. The ratio of the NB, MCB and LCB in each type was about 90% in Types II and III, and 70–80% in Types IV–VII.Conclusion: Attachment of the TPT to the NB, MCB, and LCB may thus contribute to stability of the foot arch.
Graphene quantum dots rescue angiogenic retinopathy via blocking STAT3/Periostin/ERK signaling
Authors: Zhao Na , Gui Xiao , Fang Qian , Zhang Rui , Zhu Weiye , Zhang Haorui , Li Qing , Zhou Yukun , Zhao Jiawei , Cui Xiao , Gao Guangping , Tang Huipeng , Shen Ni , Chen Taoyong , Song Hongyuan , Shen Wei
Published: February 2022

Background: Pathological retinal angiogenesis resulting from a variety of ocular diseases including oxygen induced retinopathy, diabetic retinopathy and ocular vein occlusion, is one of the major reasons for vision loss, yet the therapeutic option is limited. Multiple nanoparticles have been reported to alleviate angiogenic retinopathy. However, the adverse effect cannot be ignored due to the relatively large scale. Graphene quantum dots (GQDs) have shown potential in drug delivery and have been proved biocompatible. In this study, Graphene quantum dots are extensively investigated for their application in angiogenic retinopathy therapy. Results: We showed that GQDs were biocompatible nanomaterials in vitro and in vivo. The nanoparticles have a dose-dependent inhibitory effect on proliferation, migration, tube formation and sprouting of human umbilical vein endothelial cells (HUVECs). Further data show that GQDs could inhibit pathological retinal neovascularization in an oxygen-induced retinopathy (OIR) model. The data of RNA sequencing suggested that periostin is involved in this process. GQDs inhibit the expression of periostin via STAT3, and further regulated cell cycle-related protein levels through ERK pathway. The signaling pathway was conformed in vivo using OIR mouse model. Conclusions: The present study indicated that GQDs could be a biocompatible anti-angiogenic nanomedicine in the treatment of pathological retinal neovascularization via disrupting periostin/ERK pathway and subsequent cell cycle.
Decreased miR-17-92 Cluster Correlates With the Senescent Features and Disrupted Oxidative Homeostasis, and the Impaired Therapeutic Efficacy of Adipose Tissue-derived Mesenchymal Stem Cells
Authors: Cen Yelei , Qi Jinjin , Chen Liang , Liu Yanning , Lou Guohua
Published: February 2022

Background: Aging and replicative cellular senescence is associated with the reduced therapeutic potential of mesenchymal stem cells (MSCs) on variety of diseases. This study aimed to determine the mechanism in regulating MSC senescence and further explore a modification strategy to reverse the senescence-associated cell dysfunction for improving the therapeutic efficacy of MSCs on acute liver failure (ALF).Methods: Adipose tissue-derived MSCs from old-aged mice (oAMSCs) or young mice were intravenously administrated into the mice with lipopolysaccharide and D-galactosamine (LPS/GalN)-exposure and their effects were evaluated by serumbiochemical and liver histological analysis. SA-β-gal staining, expression analysis on p21, p16 and senescence-associated secretory phenotype markers, and reactive oxygen species (ROS) generation assay were used for determine the senescent features in aged AMSCs and replicative senescent AMSCs. MiRNA expression assay, small interfering RNA and miRNA transfection, and thioredoxin (TRX) activity assay were performed for further elucidate the mechanisms in AMSC senescence. MiRNA-modified AMSCs were used for determine whether cellular miR-17-92 cluster level can as an index to evaluate the therapeutic potential of AMSCs on ALF.Results: oAMSCs displayed senescent phenotypes and showed reduced therapeutic efficacy on LPS/GalN-induced ALF, as determined by reduced hepatic necrosis and serum liver function indicators, and inflammatory cytokine levels. Then we found that the miR-17-92 cluster, especially miR-17 and miR-20a, was obviously decreased in oAMSCs and replicative senescent AMSCs. The decreased miR-17-92 level was consistent with the declined oncogene c-Myc level during AMSC senescence and may mediate c-Myc stemness addiction. Further experiments revealed that miR-17-92 could modulate AMSC senescence by affecting the expression of classic senescence protein p21 and also the oxidative homeostasis in AMSCs through TXNIP-mediated TRX activity regulation. Furthermore, modification of AMSCs with the above two key miRNAs in miR-17-92 cluster could reverse the senescent features of oAMSCs and remodeling the therapeutic potential of senescent AMSCs on ALF.Conclusions: c-Myc-regulated miR-17-92 contributes to the increased p21 expression and dysregulated redox system during AMSC senescence. The cellular miR-17-92 cluster level can be used both as an index for evaluating and as a modification target for improving the therapeutic potential of AMSCs.
A report of short term spontaneous regression of herniated lumbar disc.
Authors: UNNITHAN AJAYA KUMAR AYYAPPAN
Published: February 2022

A 58-year lady presented with backache, left leg pain, and weakness for 3 months. A magnetic resonance imaging ( MRI) scan of lumbosacral spine, taken three months back, showed L3-4 disc extrusion and canal stenosis. She had improvement with conservative treatment. But she had recurrence of symptoms 10 days back. Straight leg raising test was positive at 40 degree on left side. Dorsiflexion was grade 4 on left side. Sensations of touch and vibration were reduced in L4 dermatomal region. A repeat MRI scan was done to plan surgery. The disc extrusion at L3-4 had shrunk. She was given gabapentin, methylcobolamine, and physiotherapy. She improved over 1 week. Spontaneous regression of herniated lumbar discs over a course of time is documented in literature. But the concomitant relief of symptoms is not seen always. The reports of regression within 3 months are a few. Kim ES et al reported about the peroperative identification of regression of an extruded disc fragment, during microdiscectomy 2 months after the magnetic resonance imgaging(MRI). So it is better to do a repeat imaging before planning surgery for a patient with a prior diagnosis of disc herniation. Thus an unnecessary surgery can be avoided.
Analytical modeling of side grinding of orthogonal laminated SiCf/SiC composites based on effective elastic properties
Authors: Zhang Zikang , Yuan Songmei , Gao Xiaoxing , Xu Weiwei , Zhang Jiaqi , An Wenzhao
Published: February 2022

SiCf/SiC composites have been applied in numerous fields because of their outstanding properties like high specific strength and high specific modulus. However, defects can be produced during grinding because the composites are hard and brittle. Moreover, the fabrication process of laminated SiCf/SiC composites is complicated and unstable, resulting in large differences in their elastic properties. Therefore, the effective elastic properties of composites needs to be obtained through theoretical analysis. In this study, the anisotropy of orthogonal laminated SiCf/SiC composites and the fracture removal mechanism of the brittle material were both considered to develop a more accurate model. The effective elastic constants of the laminated composites were calculated using a macromechanical analysis. The grinding process was divided into the ductile, ductile-to-brittle transition, and brittle stages for analysis by the critical cutting depth. The modeling development was based on the interaction between the diamond grains and workpiece. Substituting the effective elastic constants into the model, the predicted value is consistent well with the experimental value. The cutting force value presents a non-linear decreasing trend with increasing spindle speed but increases linearly with increasing feed rate and cutting width. The spindle speed and cutting width have more influence on the cutting force than the feed rate. Increasing the spindle speed and decreasing the feed rate and cutting width can reduce the cutting force. The model can be applied to adequately evaluate the effective elastic properties of laminated SiCf/SiC composites and effectively improve the grinding processes and machining efficiency in future applications.
Relationship between Undernutrition and Periodontal Diseases among a sample of Yemeni Population: A Cross-Sectional Study
Authors: Al-Kalisi Milad , Al-Hajri Manal , Al-Rai Sarah
Published: February 2022

Undernutrition is an inadequate supply of energy and nutrients. Periodontal diseases (PDs) are defined as a broad form of chronic inflammatory disease of the gingiva, bone and ligaments supporting the teeth. This study aimed to reveal the relationship between undernutrition, using body mass index (BMI) and serum albumin level (Alb), and PDs in a sample of Yemeni population. A cross-sectional study was conducted at dental teaching clinics at the Faculty of Dentistry, Sana’a University. Of the 1920 patients attended to clinics, only 229 matched the study criteria. Oral examination was performed to assess the periodontal clinical parameters measurements. BMI and Alb was measured. Participants of both genders were involved with slight increase in males (n = 134, 58.5%) and most of the study sample was at the age group of (18–35) (n = 209, 91.3%). Regarding to habits, only (n = 43, 18.2%) of patients were smokers and about half of participants (n = 136, 59.4%) were khat chewers. Most of cases had a mild undernutrition according to BMI (n = 139, 60.7%) and normal Alb level (n = 213, 93%). Regarding the periodontal diagnosis, most of the participants were diagnosed with gingivitis (n = 186, 81.2%). BMI and albumin level were non significantly associated with PDs. PDs were statistically significant with the participant’s age, gender, level of education and smoking (P ≤ 0.05). Whereas, BMI, khat chewing, and Albumin level were non-significant factors of periodontal diseases among Yemeni participants (P > 0.05). In both genders, variables such as age of the patients, smoking, khat chewing and PDs were non-significantly associated with BMI. This study showed that the majority of the participants had diagnosed with gingivitis but there was not an association between PDs and undernutrition This paper is presented on research square URL:// https://www.researchsquare.com/article/rs-429796/v1 with DOI: 10.21203/rs.3.rs-429796/v1
Selection of Cape Gooseberry Based on Physical Variables of Their Fruit
Authors: de Oliveira Job Teixeira , da Cunha Fernando França , de Oliveira Rubens Alves , Pina Catariny Cabral Aleman
Published: February 2022

Path coefficient analysis has been widely used to understand production better and determine the relationships between fruit and their constituents. This study evaluated the correlations between mass and other physical characteristics, and contributes to selecting cape gooseberry fruit. The attributes assessed were the total mass of the cape gooseberry fruit (TM) (fruit mass with husk), fruit mass (FM) (fruit mass without husk), husk mass (HM), husk length (HL), the largest transverse husk diameter (LD), fruit diameter (FD), and color of the husk (CH). Using path analysis, it was possible to verify directly that, among the physical components of the study, TM and FD have a direct and positive influence on FM. Fruit mass had a direct and negative correlation with HM, indicating that fruit with the heaviest husk (and green color) have not yet reached full maturation, nor reached their greatest mass. This result suggests that TM is strongly indirectly influenced by the HL, husk diameter, HM, and FD.
Trabajo social y ambiente, un escenario para la innovación y la intervención pertinente
Authors: Castrillón Nancy Lorena , Posada Muñoz Eliana María
Published: February 2022

Esta ponencia, es una reflexión del proceso vivido por el semillero de investigación: Ambiente Planeación, Desarrollo y Trabajo Social, durante el periodo 2018-2020-1, desde las investigaciones: Prácticas y saberes de intervención en el escenario ambiental, desde la experiencia de los departamentos de Antioquia y Caldas; y, Aprendizajes para la intervención del Trabajo Social a partir de las prácticas y saberes de los movimientos y organizaciones sociales en el marco de la justicia medio ambiental en Antioquia. Estas experiencias contextualizan al semillero para reconocer la importancia del trabajo social  ante las problemáticas ambientales contemporáneas, por ende, la necesidad de incluir en la formación académica y profesional, el tema ambiental; dado el constante deterioro al medio ambiente requiere intervenciones eficaces desde la particularidad de los contextos, para propiciar espacios de participación con las comunidades afectadas, desde las cuales se apueste por el fortalecimiento del tejido social.
A földrajzi mobilitás változó mintázatai: Átmeneti elvándorlás, tartós letelepedés és cirkuláris migráció a magyar állampolgárok körében
Authors: Ligeti Anna Sára
Published: February 2022

A migrációt gyakran egyirányú és tartós folyamatként leíró statisztikák egyre kevésbé képesek lépést tartani az ezredfordulót követő globális léptékű, gyorsan változó trendekkel. A ki- és visszavándorlások mérésére használt adminisztratív adatok longitudinális megközelítésű vizsgálatán keresztül azonban lehetőségünk nyílik a magyar állampolgárok migrációs történetének nyomon követésére, az ismétlődő, cirkuláris mozgások azonosítására, valamint a külföldön töltött idő mérésére is. Az adatok alapján a 2010-es évek mobilitási mintázatai egyszerre jellemezhetők tartós külföldi letelepedésekkel és időszakos mozgásokkal. Az évtized során a magyar állampolgárok körében egyre jelentősebbé váltak a “likvid” migrációs mintázatok térnyerését jelző rövidtávú és ismétlődő vándorlások, melyek elsősorban nem a magasabb társadalmi-gazdasági státuszú, hanem az ipari és szolgáltatói szektorban dolgozók időszakos munkavállalási stratégiáit jellemzik. Az évtized elején, a kivándorlások intenzív szakaszában távozók fele máig nem tért vissza, a külföldön élő magyarok számának folyamatos növekedése pedig az évtized második felétől kezdve lehetővé tette a folyamatos visszaáramlásokat a hosszabb idő óta külföldön élők köréből is. Ezzel párhuzamosan az évtized végére Nagy-Britannia sokat vesztett népszerűségéből a kivándorlók között, így mostanra Németország és Ausztria tekinthetők a legfőbb célországoknak.
Book Review: Affect, Narratives and Politics of Southeast Asian Migration by Carlos M. Piocos III
Authors:   Department of Cultural Studies,  Lingnan University, Calabias Jose Kervin Cesar B.
Published: February 2022

Carlos Piocos’s ground-breaking book, Affect, Narratives and Politics of Southeast Asian Migration published earlier this year by Routledge, provides an in-depth analysis of the intimate labour(ed) landscape of Filipina and Indonesian migrant workers in Hong Kong and Singapore, and how their (im)mobilities are not just hastened and aggravated by the neoliberal framework of global labor and the policies of their sending and receiving nation-states, but also in terms of the emotionality that circulates within the global care chains network. Piocos specifically turns our attention to the “felt” politics that emanate from films and fictions of and by Southeast Asian migrant workers and how these cultural productions create an affective economy that, according to him, is not just “sticky” as feminist critic Sarah Ahmed describes, but demonstrates varying viscosities of “thickening and thinning out,” reflecting a “messiness” of feelings that do not necessarily coalesce in these texts (p. 10).
Book Review: Feminist Translation Studies: Local and Transnational Perspectives edited by Olga Castro and Emek Ergun
Authors:   Department of English, University of Macau, Macau, FONG John Chi Chon
Published: February 2022

Currently, there are hardly any works that explicitly claim the political title “feminist” or “activist” while fully exploring feminist translation. Without necessarily embracing and recognizing the transgressive or reactionary processes of translation in feminist movements and activisms, existing collections generally explore the “connections between gender and translation or women and translation” (p. 2). This essay collection suggests that the important role of translation in the trans/formation of feminist politics requires more analytical recognition. Hence, the authors put the “F word” back into the discussion in their chapters, focusing on the roles of translation in the development of feminisms.
Book Review: Twenty-First-Century Children’s Gothic: from the Wanderer to Nomadic Subject by Chloé Germaine Buckley
Authors:   Ocean University of China, Yifan Zhao
Published: February 2022

Children’s literature has long intertwined with Gothic motifs, yet contrasting with the profound Gothic inheritance of children’s literature, the relevant research remains to be a relatively new direction, which has gained increasing popularity only in recent years. As the newest monograph in the field, Twenty-First-Century Children’s Gothic: from the Wanderer to Nomadic Subject brings out an exciting outlook to children’s Gothic studies, tracing through a range of children’s Gothic fictions between 2000 and 2015. Following Braidotti’s account of nomadic subjectivity, the book’s author Dr Chloé Germaine Buckley concludes that the theme of homelessness is a major concern for post-millennial children’s Gothic, which does not lead to despair but positive possibilities to new lives, regarding homelessness as nomadism—a concept echoing with the nomadic ethics of Deleuze’s philosophy, which expresses a process ontology that values change and motion over stability (Braidotti, 2013, p. 344).
N1-Methylnicotinamide: Is it Time to Consider it as a Dietary Supplement for
Athletes?
Authors: Nejabati Hamid Reza , Ghaffari-Novin Mahsa , Fathi-Maroufi Nazila , Faridvand Yousef , Holmberg Hans-Christer , Hansson Ola , Nikanfar Saba , Nouri Mohammad
Published: February 2022

Exercise is considered to be a “medicine” due to its modulatory roles in metabolic disorders, such as
diabetes and obesity. The intensity and duration of exercise determine the mechanism of energy production by
various tissues of the body, especially by muscles, in which the requirement for adenosine triphosphate (ATP)
increases by as much as 100-fold. Naturally, athletes try to improve their exercise performance by dietary
supplementation with, e.g., vitamins, metabolites, and amino acids. MNAM, as a vitamin B3 metabolite, reduces
serum levels and liver contents of triglycerides and cholesterol, and induces lipolysis. It stimulates gluconeogenesis
and prohibits liver cholesterol and fatty acid synthesis through the expression of sirtuin1 (SIRT1).
It seems that MNAM is not responsible for the actions of NNMT in the adipose tissues as MNAM inhibits the
activity of NNMT in the adipose tissue and acts as an inhibitor of its activity. NNMT-MNAM axis is more
activated in the muscles of individuals undergoing the high-volume-low-intensity exercise and caloric
restriction. Therefore, MNAM could be an important myokine during exercise and fasting where it provides the
required energy for muscles through the induction of lipolysis and gluconeogenesis in the liver and adipose
tissues, respectively. Increased levels of MNAM in exercise and fasting led us to propose that the consumption
of MNAM during training, especially endurance training, could boost exercise capacity and improve performance.
Therefore, in this review, we shed light on the potential of MNAM as a dietary supplement in sports
medicine.
Drug Delivery Systems for Cancer Treatment: A Review of Marine-derived Polysaccharides
Authors: Atmaca Harika , Oguz Ferdi , Ilhan Suleyman
Published: February 2022

Cancer is a disease characterized by uncontrolled cell proliferation and the spread of cells to other
tissues and remains one of the worldwide problems waiting to be solved. There are various treatment strategies
for cancer, such as chemotherapy, surgery, radiotherapy, and immunotherapy, although it varies according to its
type and stage. Many chemotherapeutic agents have limited clinical use due to lack of efficacy, off-target toxicity,
metabolic instability, or poor pharmacokinetics. One possible solution to this high rate of clinical failure is
to design drug delivery systems that deliver drugs in a controlled and specific manner and are not toxic to normal
cells. Marine systems contain biodiversity, including components and materials that can be used in biomedical
applications and therapy. Biomaterials such as chitin, chitosan, alginate, carrageenan, fucoidan, hyaluronan,
agarose, and ulvan obtained from marine organisms have found use in DDSs today. These polysaccharides are
biocompatible, non-toxic, biodegradable, and cost-effective, making them ideal raw materials for increasingly
complex DDSs with a potentially regulated release. In this review, the contributions of polysaccharides from
the marine environment to the development of anticancer drugs in DDSs will be discussed.
Anti-HIV Aptamers: Challenges and Prospects
Authors: Serumula William , Fernandez Geronimo , Gonzalez Victor M. , Parboosing Raveen
Published: February 2022

:

Human Immunodeficiency Virus (HIV) infection continues to be a significant health burden
in many countries around the world. Current HIV treatment through a combination of different
antiretroviral drugs (cART) effectively suppresses viral replication, but drug resistance and crossresistance
are significant challenges. This has prompted the search for novel targets and agents,
such as nucleic acid aptamers. Nucleic acid aptamers are oligonucleotides that attach to the target
sites with high affinity and specificity. This review provides a target-by-target account of research
into anti-HIV aptamers and summarises the challenges and prospects of this therapeutic strategy,
specifically in the unique context of HIV infection.
Clozapine-induced Myocarditis: Pathophysiologic Mechanisms and Implications
for Therapeutic Approaches
Authors: Rabkin Simon W. , Tang Jacky K. K.
Published: February 2022

Clozapine, a superior treatment for treatment-resistant schizophrenia can cause poten-tially life-threatening myocarditis and dilated cardiomyopathy. While the occurrence of this condi-tion is well known, its molecular mechanisms are unclear and may be multifactorial. Putative mech-anisms warrant an in-depth review not only from the perspective of toxicity but also for understand-ing the molecular mechanisms of the adverse cardiac effects of clozapine and the development of novel therapeutic approaches. Clozapine-induced cardiac toxicity encompasses a diverse set of pathways, including (i) immune modulation and proinflammatory processes encompassing an IgE-mediated (type I hypersensitivity) response and perhaps a cytokine release syndrome (ii) catechol-aminergic activation (iii) induction of free radicals and oxidative stress (iv) activation of cardiomy-ocyte cell death pathways, including apoptosis, ischemia through impairment in coronary blood flow via changes in endothelial production of NO and vasoconstriction induced by norepinephrine as well as other factors released from cardiac mast cells. (v) In addition, an extensive examination of the effects of clozapine on non-cardiac cellular proteins demonstrates that clozapine can impair enzymes involved in cellular metabolism, such as pyruvate kinase, mitochondrial malate dehydro-genase, and other proteins, including α-enolase, triosephosphate isomerase and cofilin, which might explain clozapine-induced reductions in myocardial energy generation for cell viability as well as contractile function. Pharmacologic antagonism of these cellular protein effects may lead to the development of strategies to antagonize the cardiac damage induced by clozapine
An Overview of Biotechnological Applications in Ayurveda: Amalgamation
of Modern Techniques and Science
Authors: Chauhan Ashutosh , Semwal Deepak Kumar , Joshi Sunil Kumar
Published: February 2022

Health trends are constantly evolving, and so are health systems. No health system is perfect, hence the needed complement. Therefore, Western medicine (WM) practitioners are looking for traditional medicine (TM) and vice versa, as WM has an edge in an emergency while TM has in chronic diseases. However, the purpose of both systems is similar, which is a relief, despite different philosophies and methodologies. Globally, acceptance of TM by the scientific community is limited due to the lack of scientific evidence of benefits and efficiency, despite its potential. Ayurveda is one kind of the oldest TM systems of the world, serving humankind without changing a little, despite changes in geography, environment, weather conditions, and soil composition, which result in new diseases. Hence, the challenge of good health is arising. Therefore, there is a need to carry out research that would apply in its own way and satisfy the tenets of biomedical research too. The best way of doing this is multidisciplinary research by involving technology and Ayurvedic experts. Biotechnology can offer techniques from diagnosis to treatment of disease through substances of natural origin, including plants, animals and minerals. The present review is merely an overview of the possibilities which may be applied in Ayurveda in the present scenario. Ayurveda is the “science of life, and biotechnology is like “the service provider.” Therefore, biotechnology has all those techniques to serve Ayurveda up to the maximum and humankind at large. Even it may give rise to a new approach by combining Ayurveda and biotechnology.
Regional Politics: Penetrating Indigenous Rights in Regional Expansion in Nagari Salareh Aia, Palembayan District, Agam Regency, West Sumatra Province in 2020
Authors: Ishak Ishak , Ernanda Oksa
Published: February 2022

Abstract: The regional expansion was carried out to facilitate access to public services. The implementation of regional expansion was initially carried out in defining territorial boundaries. In the demarcation of this territory, there are protests due to the lack of involvement of indigenous peoples. As residents of the original domicile, the indigenous peoples fight for their land ownership rights, which are involved in the regional expansion plan. It happened in the expansion of the Nagari Salareh Aia area, Palembayan District, Agam Regency. After the enactment of Regent Regulation No. 15 of 2017 regarding the preparation of Nagari guardians. There were many protests against the boundaries set by the government through these instruments. Researchers try to explore this phenomenon through social law by examining aspects of regional politics, in this case, the rights of indigenous peoples, social capital in conflict resolution, and an assessment of the impact of these two issues in resolving regional division conflicts. Through a set of studies and discussions, it was found that the government and the community must work together and make decisions that do not ignore regional wisdom. Through this synergy, it was hoped that regional expansion would be conducted appropriately, which can provide benefits to the community and regional government.
PRÁTICA EDUCATIVA: ENTRE O ESSENCIALISMO E A PRÁXIS
Authors: Bandeira Hilda Maria Martins , Ibiapina Ivana Maria Lopes de Melo
Published: February 2022

A prática educativa é utilizada com frequência na literatura como equivalente à pedagógica, à docente e à práxis. Este artigo pretende analisar a prática educativa a partir de sua interação com a educação da Grécia Clássica e a influência iluminista e romântica de Rousseau, bem como sua contribuição para compreensão na tripla dimensão da prática educativa. Parte da premissa de que a prática educativa é multidimensional e de que prática pedagógica e prática docente são modalidades daquela. Os resultados deste estudo bibliográfico de tese de doutorado focalizam que a prática educativa se desenvolve e se atualiza conforme as necessidades do contexto sócio-histórico, e que a práxis entendida como relação intrínseca entre teoria e prática constitui a possibilidade emergente da prática transformadora.
Urban Air Pollution and Emergency Department Visits for Cardiac and Respiratory Diseases
Authors:   Health Canada, 251 Sir Frederick Banting Driveway, Ottawa, Canada, Szyszkowicz Mieczyslaw , Angelis Nicholas de ,   Carleton University, 1125 Colonel By Drive, Ottawa, Canada
Published: February 2022

Air pollution affects various aspects of human health. Here, the associations between the number of emergency department visits for circulatory and respiratory problems and ambient air pollution in Toronto, Canada, in the period between April 2004 and December 2015 were studied. The health data were linked with urban air pollution data and weather factors. The conditional Poisson regression models were built for 18 strata (sex, age group, season), 8 exposure factors (air pollutants, indexes), and their 15 lags (0-14 days). Circulatory problems: the associations were intensified in the cold period (October - March) and were associated with the air quality health index (AQHI). The estimated relative risks for all patients in the cold period, for an increase of the AQHI by 1, at lags 0, 1, and 2 were 1.017 and 95% confidence interval (1.010, 1.024), 1.014 (1.007, 1.021), and 1.009 (1.002, 1.016). Respiratory problems: the analogous results for ozone and its increase by 12.8 ppb at lags 3, 4, and 5 were 1.052 (1.033, 1.161), 1.039 (1.020, 1.121), and 1.027 (1.008, 1.082). It was observed that exposure to certain air pollutants (nitrogen dioxide, ozone, and the AQHI index) are associated with increased emergency department visits in both cardiac and respiratory health problems.
Evaluation of mHealth Apps for Diverse, Low-Income Patient Populations: Framework Development and Application Study
Authors: Sharma Shreya , Gergen Barnett Katherine , Maypole John (Jack) , Grochow Mishuris Rebecca
Published: February 2022

Background

The use of mobile technology or smartphones has grown exponentially in the United States, allowing more individuals than ever internet access. This access has been especially critical to households earning less than US $30,000, the majority of whom indicate that smartphones are their main source of internet access. The increasing ubiquity of smartphones and virtual care promises to offset some of the health disparities that cut through the United States. However, disparities cannot be addressed if the medical information offered though smartphones is not accessible or reliable.

Objective

This study seeks to create a framework to review the strengths and weaknesses of mobile Health (mHealth) apps for diverse, low-income populations.

Methods

Focusing on smoking cessation, diabetes management, and medication adherence as models of disease management, we describe the process for selecting, evaluating, and obtaining patient feedback on mHealth apps.

Results

The top 2 scoring apps in each category were QuitNow! and Smoke Free-Quit Smoking Now for smoking cessation, Glucosio and MyNetDiary for diabetes management, and Medisafe and MyMeds for medication adherence.

Conclusions

We believe that this framework will prove useful for future mHealth app development, and clinicians and patient advisory groups in connecting culturally, educationally, and socioeconomically appropriate mHealth apps with low-income, diverse communities and thus work to bridge health disparities.
Attentional Harms and Digital Inequalities
Authors: Hartford Anna , Stein Dan J
Published: February 2022

Recent years have seen growing public concern about the effects of persuasive digital technologies on public mental health and well-being. As the draws on our attention reach such staggering scales and as our ability to focus our attention on our own considered ends erodes ever further, the need to understand and articulate what is at stake has become pressing. In this ethical viewpoint, we explore the concept of attentional harms and emphasize their potential seriousness. We further argue that the acknowledgment of these harms has relevance for evolving debates on digital inequalities. An underdiscussed aspect of web-based inequality concerns the persuasions, and even the manipulations, that help to generate sustained attentional loss. These inequalities are poised to grow, and as they do, so will concerns about justice with regard to the psychological and self-regulatory burdens of web-based participation for different internet users. In line with calls for multidimensional approaches to digital inequalities, it is important to recognize these potential harms as well as to empower internet users against them even while expanding high-quality access.
Student-Run Online Journal Club Initiative During a Time of Crisis: Survey Study
Authors: Ozkara Burak Berksu , Karabacak Mert , Alpaydin Duygu Demet
Published: February 2022

Background

Since the closure of university campuses due to COVID-19 in spring 2020 necessitated a quick transition to online courses, medical students were isolated from hospitals and universities, negatively impacting their education. During this time, medical students had no opportunity to participate in academic discussions and were also socially isolated. Furthermore, medical doctors and professors of medical schools were given additional responsibilities during the pandemic because they were the frontliners in the fight against COVID-19. As a result, they did not have enough time to contribute effectively to medical student education.

Objective

This paper describes the establishment of the Cerrahpasa Neuroscience Society Journal Clubs, a group of entirely student-run online journal clubs at Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa.

Methods

The website, mass emailing, and social media accounts were used to announce the online journal clubs. Only medical students were eligible to apply. Journal clubs included psychiatry, neuroradiology, neurosurgery, neurology, and neuroscience. Following the last journal club meeting, a questionnaire created by the society’s board was distributed to the participants. SPSS Statistics (version 26) was used for statistical analysis.

Results

Since March 15, 2021, synchronous online journal club meetings have been held every 2 weeks on a weekday using Google Meet, Microsoft Teams, or Zoom. Meetings of each journal club lasted approximately 1 hour on average. Interstudent interaction across multiple institutions was achieved since a total of 45 students from 11 different universities attended the meetings on a regular basis. Students on the society’s board served as academic mentors for the clubs. The clubs received excellent feedback from participants, with an overall contentment score of 4.32 out of 5.

Conclusions

By establishing these clubs, we have created a venue for academic discussions, which helps to reduce the negative impact of the pandemic on education. In addition, we believe it greatly aided students in staying in touch with their peers, thereby reducing the sense of isolation. We realize that traditional journal clubs are run by faculty; however, we believe that this experience demonstrated that medical students could run a journal club on their own since the feedback from participants was excellent. Additionally, as a medical student, being a journal club academic mentor is a challenging responsibility; however, having this responsibility significantly improved our academic mentors’ leadership abilities.
Predicting Changes in Depression Severity Using the PSYCHE-D (Prediction of Severity Change-Depression) Model Involving Person-Generated Health Data: Longitudinal Case-Control Observational Study
Authors: Makhmutova Mariko , Kainkaryam Raghu , Ferreira Marta , Min Jae , Jaggi Martin , Clay Ieuan
Published: February 2022

Background

In 2017, an estimated 17.3 million adults in the United States experienced at least one major depressive episode, with 35% of them not receiving any treatment. Underdiagnosis of depression has been attributed to many reasons, including stigma surrounding mental health, limited access to medical care, and barriers due to cost.

Objective

This study aimed to determine if low-burden personal health solutions, leveraging person-generated health data (PGHD), could represent a possible way to increase engagement and improve outcomes.

Methods

Here, we present the development of PSYCHE-D (Prediction of Severity Change-Depression), a predictive model developed using PGHD from more than 4000 individuals, which forecasts the long-term increase in depression severity. PSYCHE-D uses a 2-phase approach. The first phase supplements self-reports with intermediate generated labels, and the second phase predicts changing status over a 3-month period, up to 2 months in advance. The 2 phases are implemented as a single pipeline in order to eliminate data leakage and ensure results are generalizable.

Results

PSYCHE-D is composed of 2 Light Gradient Boosting Machine (LightGBM) algorithm–based classifiers that use a range of PGHD input features, including objective activity and sleep, self-reported changes in lifestyle and medication, and generated intermediate observations of depression status. The approach generalizes to previously unseen participants to detect an increase in depression severity over a 3-month interval, with a sensitivity of 55.4% and a specificity of 65.3%, nearly tripling sensitivity while maintaining specificity when compared with a random model.

Conclusions

These results demonstrate that low-burden PGHD can be the basis of accurate and timely warnings that an individual’s mental health may be deteriorating. We hope this work will serve as a basis for improved engagement and treatment of individuals experiencing depression.