bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of mirabegron in pediatric population: A systematic review
Authors: Nasution Ramlan , Husein Ali , Adhyatma Kharisma Prasetya
Published: September 2021

ABSTRACT

Introduction:

Mirabegron, a b3-adrenoceptor (b3-AR) agonist approved for the treatment of overactive bladder (OAB) symptoms in the adult population, is the first of a new class of compounds with a different mechanism of action. Mirabegron act during the bladder storage phase by relaxing the detrusor muscle thus increase bladder capacity without any significant impact on voiding. Although antimuscarinic agents are commonly used for daytime incontinence associated with overactive bladder and also for patient with congenital cause such as spina bifida, mirabegron could be an effective treatment option in children with neurogenic bladder, as shown in adult populations. In this systematic review, we aimed to evaluate the available literature regarding efficacy and safety of mirabegron in pediatric population.

Method:

This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.

Result:

The symptoms analyzed were frequency, urgency, nocturnal enuresis (NE) and daytime incontinence (DI). 37 (53%) out of 70 children were still receiving treatment at 6 months; 30 received mirabegron monotherapy, and 7 received combination therapy with anticholinergic (Solifenacin n = 4, Desmopressin n = 2, both n = 1). After six months, blood pressure monitoring and ECGs were normal in all patients. For patients on monotherapy, 6 of 17 (35%) had improvement in NE, 11 of 19 (58%) in DI, 12 of 20 (60%) in frequency, and 8 of 21 (38%) in urgency symptoms. For patients receiving combination therapy, 2 of 6 (33%) had improvement in NE, 2 of 4 in DI (50%), 2 of 4 (50%) in frequency, and 4 of 6 (67%) had improvement in urgency.

Conclusion:

The CV safety of mirabegron, the only clinically available β3-adrenoceptor agonist, appears to be good and comparable with that of antimuscarinic agents, the current first-line therapy for OAB. However, Further long-term data are desirable especially in patients with poorly controlled hypertension, arrhythmia, or cardiac heart failure.

Highlights
Role of peer support in competitive classroom climates: Focusing on the mediation effect of academic hatred in the JD-R model
Authors: Lee Minyoung , Lee Taerim , Lee Sang Min
Published: September 2021

This study aimed to verify the different effects of peer support on academic hatred depending on the levels of teachers’ academic pressure. Additionally, we examined the effects of academic hatred on academic burnout and engagement by applying the job demand-resources (JD-R) model. Data were collected from 43 classes at 8 high schools ( N = 1015, 94.2% response rate, 57.3% women) in South Korea. The results of a multigroup analysis were as follows: (1) peer support served as an important resource in classrooms experiencing high teachers’ academic pressures; (2) peer support directly affected academic burnout and engagement, and reduced academic hatred; and (3) reduced academic hatred served as a mediator for lower burnout rate and increased engagement.
From Recognition to Integration: Indigenous Autonomy, State Authority, and National Identity in the Philippines
Authors: MCMURRY NINA
Published: September 2021

How does the recognition of collective self-governance rights for indigenous communities affect national unity and state consolidation? In recent decades, many states have recognized such rights, devolving de jure control over land and local governance to indigenous institutions. Prominent perspectives in the state-building literature suggest that these policies are likely to threaten state consolidation by strengthening nonstate authorities at the expense of state authority and subnational identities at the expense of a national identity. Yet few studies have tested whether these policies have the consequences their critics claim. I address this gap, leveraging spatial and temporal variation in the granting of communal land titles to indigenous communities in the Philippines. Using difference-in-differences and panel designs, I find that titling increases both indigenous self-identification and compliance with the state. Results from an original survey experiment suggest that recognizing collective self-governance rights increases identification with the nation.
Cambrian and earliest Ordovician fauna and geology of the Sông Đà and adjacent terranes in Việt Nam (Vietnam)
Authors: Hughes Nigel C. , Peng Shanchi , Harper David A. T. , Myrow Paul M. , Phạm Ngân Kim , Wernette Shelly J. , Zhu Xuejian
Published: September 2021

Later Cambrian and earliest Ordovician trilobites and brachiopods spanning eight horizons from five localities within the Sông Mã, Hàm Rồng and Đông Sơn formations of the Thanh Hóa province of Việt Nam, constrain the age and faunal affinities of rocks within the Sông Đà terrane, one of several suture/fault-bounded units situated between South China to the north and Indochina to the south. ‘Ghost-like’ preservation in dolomite coupled with tectonic deformation leaves many of the fossils poorly preserved, and poor exposure precludes collecting within continuously exposed stratigraphic successions. Cambrian carbonate facies pass conformably into Lower Ordovician carbonate-rich strata that also include minor siliciclastic facies, and the recovered fauna spans several uppermost Cambrian and Lower Ordovician biozones. The fauna is of equatorial Gondwanan affinity, and comparable to that from South China, North China, Sibumasu and Australia. A new species of Miaolingian ‘ptychopariid’ trilobite,Kaotaia xuanensis, is described. Detrital zircon samples from Cambrian–Ordovician rocks of the North Việt Nam and Sông Đà terranes, and from Palaeozoic samples from the Trường Sơn sector of Indochina immediately to the south, contain a predominance of ages spanning the Neoproterozoic period and have a typical equatorial Gondwanan signature. We associate the Cambrian and Tremadocian of the Sông Đà terrane with areas immediately to the north of it, including the North Việt Nam terrane and the southern parts of Yunnan and Guangxi provinces of China.
John Robert Lawrence Allen FRS, FSA (25 October 1932–18 October 2020): a personal tribute
Authors: Shi John Z
Published: September 2021

John Robert Lawrence Allen (Fig. 1), an internationally distinguished sedimentologist, was born on 25 October 1932 in Birmingham, UK. He died in Thatcham, UK, on 18 October 2020, aged 87, after a short illness.
Are negative views of the self, world and future, mediators of the relationship between subjective social status and depressive symptoms?
Authors: Pössel Patrick , Wood Tyler , Roane Sarah J.
Published: September 2021

Background:

Elevated depressive symptoms are associated with impairments, reduced quality of life, and societal economic burden. A well-established stress-vulnerability model explaining depressive symptoms is Beck’s cognitive theory (Beck, 1976). An independent line of research demonstrated that a person’s perception of their status in comparison with others’ (subjective social status, SSS) is a stressor associated with depressive symptoms.

Aims:

Theory-driven research investigating the interplay of different factors associated with depressive symptoms opens the door to improve the lives of the affected individuals and to reduce the overall societal burden. This study’s aim was to examine if SSS can be integrated as a stressor into Beck’s theory, looking specifically at whether it impacts depressive symptoms through the individual components (self, world and future) of the cognitive triad.

Method:

In this cross-sectional study, 243 community college students (58.6% female; mean age 23.95 years) in the southern United States completed self-reports measuring SSS, negative views of the self, world and future, and depressive symptoms.

Results:

SSS is negatively associated with each view of the cognitive triad. SSS and views of the self and world are negatively associated with depressive symptoms. Mediation analyses displayed a significant direct effect between SSS and depressive symptoms, as well as two indirect effects via negative view of self and world.

Conclusions:

While further research is needed, therapists might benefit from our findings when tailoring their treatment to a client by considering their SSS and which negative view is particularly detrimental for this specific client.
The Caregiving System Scale
Authors: Colledani Daiana , Meneghini Anna M. , Mikulincer Mario , Shaver Phillip R.
Published: September 2021

Abstract. According to attachment theory, the propensity of human beings to care for others is governed by an inborn caregiving behavioral system that aims to promote welfare and reduce the distress of other people through effective provision of care. However, some individuals may develop non-optimal caregiving strategies, such as anxious hyperactivation and avoidant deactivation. These two non-optimal caregiving strategies can be evaluated in adults using the Caregiving System Scale (CSS). Recent findings suggested that the factor structure of the instrument may be more complex than was intended. The present work examines in-depth the factor structure of the CSS to provide a clearer understanding of the underlying dimensions. Gender invariance and the contribution of attachment orientations to CSS scores are also examined. Findings reveal that, whereas the CSS-deactivation subscale is unidimensional, the CSS-hyperactivation subscale is better represented by two distinct yet related constructs – caregiving-related worries/doubts and intrusive/coercive caregiving. Partial strict gender invariance is supported. The contribution of attachment orientations to non-optimal caregiving strategies is consistent with theoretical expectations. Results and future research directions are discussed in the final section.
Complementary and Catalytic Roles of Man‐Made VLF Waves and Natural Plasma Waves in the Loss of Radiation Belt Electrons
Authors: Li L. Y. , Wang Z. Y. , Yu J. , Cao J. B.
Published: September 2021

By simulating the energy and pitch angle diffusions of radiation belt electrons caused by ground‐based VLF transmitter waves, plasmaspheric hiss and lightning‐generated whistlers (LGWs), we quantitatively estimated the electron change rates caused by individual and multiple waves. We found that man‐made VLF waves and naturally generated hiss or LGWs play complementary and catalytic roles in the loss of radiation belt electrons. Man‐made VLF waves mainly reduce the hundreds of keV electrons in inner radiation belt (L < 2), but they alone cannot effectively remove the MeV electrons in slot region (L ∼ 2–3) because of unefficient diffusions at small pitch angles (<60°). On the contrary, natural hiss and LGWs do not affect the hundreds of keV electrons in the inner belt, but they are able to effectively reduce the hundreds of keV and MeV electrons at small pitch angles in the slot region. The loss of the small pitch electrons caused by hiss or LGWs offer a necessary phase space density gradient for the diffusion of large pitch angle MeV electrons (>60°) driven by man‐made VLF waves toward the loss cone. The combined diffusions by three types of the waves ultimately catalyze the loss of the large pitch angle MeV electrons in the slot region, and thus cause more electron losses in the wider energy and pitch angle ranges.
What is a ‘serious’ genetic condition? The perceptions of people living with genetic conditions
Authors: Boardman Felicity K. , Clark Corinna C.
Published: September 2021

Despite no consensus on the definition of ‘seriousness’, the concept is regularly used in policy and practice contexts to categorise conditions, determine access to genetic technologies and uses of selective pregnancy termination. Whilst attempts have been made to create taxonomies of genetic condition seriousness to inform clinical and policy decision-making, these have often relied on condition appraisals made by health and genetics professionals. The views of people with genetic conditions have been largely under-represented. This study explores the concept of seriousness through the perspectives of people with a range of ‘clinically serious’ conditions (fragile X conditions, spinal muscular atrophy, cystic fibrosis, haemophilia, thalassaemia). Attitudes towards suffering, quality of life (QoL) and selective pregnancy termination were elucidated from 45 in-depth qualitative interviews and 469 postal/online surveys. The majority of participants reported good health/wellbeing, and the capacity for good QoL, despite experiencing suffering with their condition. Notably, participants with later-onset conditions held more negative views of their health and QoL, and were more likely to view their condition as an illness, than those with early-onset conditions. These participants were more likely to see their condition as part of their identity. Whilst most participants supported prenatal screening, there was little support for selective termination. Moreover, social environment emerged as a critical mediator of the experience of the condition. The complex and rich insights of people living with genetic conditions might usefully be incorporated into future genetic taxonomies of ‘seriousness’ to ensure they more accurately reflect the lived reality of those with genetic conditions.
An immune response characterizes early Alzheimer’s disease pathology and subjective cognitive impairment in hydrocephalus biopsies
Authors: Huang Wenrui , Bartosch Anne Marie , Xiao Harrison , Maji Suvrajit , Youth Elliot H. H. , Flowers Xena , Leskinen Sandra , Tomljanovic Zeljko , Iodice Gail , Boyett Deborah , Spinazzi Eleonora , Menon Vilas , McGovern Robert A. , McKhann Guy M. , Teich Andrew F.
Published: September 2021

Early Alzheimer’s disease (AD) pathology can be found in cortical biopsies taken during shunt placement for Normal Pressure Hydrocephalus. This represents an opportunity to study early AD pathology in living patients. Here we report RNA-seq data on 106 cortical biopsies from this patient population. A restricted set of genes correlate with AD pathology in these biopsies, and co-expression network analysis demonstrates an evolution from microglial homeostasis to a disease-associated microglial phenotype in conjunction with increasing AD pathologic burden, along with a subset of additional astrocytic and neuronal genes that accompany these changes. Further analysis demonstrates that these correlations are driven by patients that report mild cognitive symptoms, despite similar levels of biopsy β-amyloid and tau pathology in comparison to patients who report no cognitive symptoms. Taken together, these findings highlight a restricted set of microglial and non-microglial genes that correlate with early AD pathology in the setting of subjective cognitive decline.
Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2
Authors: Sun Shihui , Gu Hongjing , Cao Lei , Chen Qi , Ye Qing , Yang Guan , Li Rui-Ting , Fan Hang , Deng Yong-Qiang , Song Xiaopeng , Qi Yini , Li Min , Lan Jun , Feng Rui , Guo Yan , Zhu Na , Qin Si , Wang Lei , Zhang Yi-Fei , Zhou Chao , Zhao Lingna , Chen Yuehong , Shen Meng , Cui Yujun , Yang Xiao , Wang Xinquan , Tan Wenjie , Wang Hui , Wang Xiangxi , Qin Cheng-Feng
Published: September 2021

There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory symptoms, and mortality. Our model exhibits age- and gender-related mortality akin to severe COVID-19. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three RBD mutations significantly enhance binding affinity to its endogenous receptor, ACE2. Cryo-electron microscopy analysis of human ACE2 (hACE2), or mouse ACE2 (mACE2), in complex with the RBD of MASCp36, at 3.1 to 3.7 Å resolution, reveals the molecular basis for the receptor-binding switch. N501Y and Q493H enhance the binding affinity to hACE2, whereas triple mutations at N501Y/Q493H/K417N decrease affinity and reduce infectivity of MASCp36. Our study provides a platform for studying SARS-CoV-2 pathogenesis, and unveils the molecular mechanism for its rapid adaptation and evolution.
Bardet-Biedl syndrome proteins modulate the release of bioactive extracellular vesicles
Authors: Volz Ann-Kathrin , Frei Alina , Kretschmer Viola , de Jesus Domingues António M. , Ketting Rene F. , Ueffing Marius , Boldt Karsten , Krämer-Albers Eva-Maria , May-Simera Helen L.
Published: September 2021

Primary cilia are microtubule based sensory organelles important for receiving and processing cellular signals. Recent studies have shown that cilia also release extracellular vesicles (EVs). Because EVs have been shown to exert various physiological functions, these findings have the potential to alter our understanding of how primary cilia regulate specific signalling pathways. So far the focus has been on lgEVs budding directly from the ciliary membrane. An association between cilia and MVB-derived smEVs has not yet been described. We show that ciliary mutant mammalian cells demonstrate increased secretion of small EVs (smEVs) and a change in EV composition. Characterisation of smEV cargo identified signalling molecules that are differentially loaded upon ciliary dysfunction. Furthermore, we show that these smEVs are biologically active and modulate the WNT response in recipient cells. These results provide us with insights into smEV-dependent ciliary signalling mechanisms which might underly ciliopathy disease pathogenesis.
Direct access to spirocycles by Pd/WingPhos-catalyzed enantioselective cycloaddition of 1,3-enynes
Authors: Li Long , Wang Shan , Luo Pengfei , Wang Ran , Wang Zheng , Li Xiaoguang , Deng Yuhua , Peng Fangzhi , Shao Zhihui
Published: September 2021

Spirocycles play an important role in drug discovery and development. The direct, catalytic, and enantioselective synthesis of spirocycles from readily available starting materials and in an atom economic manner remains a highly sought-after task in organic synthesis. Herein, an enantioselective Pd-hydride-catalyzed cycloaddition method for the synthesis of spirocyclic compounds directly from two classes of commonly available starting materials, 1,3-enynes and cyclic carbon−hydrogen (C−H) bonds, is reported. The reactions employ a chiral Pd/WingPhos catalyst to both suppress the formation of bis-allenyl by-products and control the stereoselectivity. 1,3-Enynes are used as dielectrophilic four-carbon units in the cycloaddition reactions, which also enables an enyne substrate-directed enantioselectivity switch with good levels of stereocontrol. The present spirocycle synthesis tolerates a broad range of functional groups of 1,3-enyne substrates, including alcohols, esters, nitriles, halides, and olefins. A variety of diverse cyclic nucleophiles, including pharmaceutically important heterocycles and carbocycles, can be flexibly incorporated with spiro scaffolds.
Biologically informed deep neural network for prostate cancer discovery
Authors: Elmarakeby Haitham A. , Hwang Justin , Arafeh Rand , Crowdis Jett , Gang Sydney , Liu David , AlDubayan Saud H. , Salari Keyan , Kregel Steven , Richter Camden , Arnoff Taylor E. , Park Jihye , Hahn William C. , Van Allen Eliezer M.
Published: September 2021

The determination of molecular features that mediate clinically aggressive phenotypes in prostate cancer remains a major biological and clinical challenge1,2. Recent advances in interpretability of machine learning models as applied to biomedical problems may enable discovery and prediction in clinical cancer genomics3–5. Here we developed P-NET—a biologically informed deep learning model—to stratify patients with prostate cancer by treatment-resistance state and evaluate molecular drivers of treatment resistance for therapeutic targeting through complete model interpretability. We demonstrate that P-NET can predict cancer state using molecular data with a performance that is superior to other modelling approaches. Moreover, the biological interpretability within P-NET revealed established and novel molecularly altered candidates, such as MDM4 and FGFR1, which were implicated in predicting advanced disease and validated in vitro. Broadly, biologically informed fully interpretable neural networks enable preclinical discovery and clinical prediction in prostate cancer and may have general applicability across cancer types.
Interindividual differences in attentional vulnerability moderate cognitive performance during sleep restriction and subsequent recovery in healthy young men
Authors: Mathew Gina Marie , Strayer Stephen M. , Ness Kelly M. , Schade Margeaux M. , Nahmod Nicole G. , Buxton Orfeu M. , Chang Anne-Marie
Published: September 2021

We investigated whether interindividual attentional vulnerability moderates performance on domain-specific cognitive tasks during sleep restriction (SR) and subsequent recovery sleep. Fifteen healthy men (M ± SD, 22.3 ± 2.8 years) were exposed to three nights of baseline, five nights of 5-h time in bed SR, and two nights of recovery sleep. Participants completed tasks assessing working memory, visuospatial processing, and processing speed approximately every two hours during wake. Analyses examined performance across SR and recovery (linear predictor day or quadratic predictor day2) moderated by attentional vulnerability per participant (difference between mean psychomotor vigilance task lapses after the fifth SR night versus the last baseline night). For significant interactions between day/day2 and vulnerability, we investigated the effect of day/day2 at 1 SD below (less vulnerable level) and above (more vulnerable level) the mean of attentional vulnerability (N = 15 in all analyses). Working memory accuracy and speed on the Fractal 2-Back and visuospatial processing speed and efficiency on the Line Orientation Task improved across the entire study at the less vulnerable level (mean − 1SD) but not the more vulnerable level (mean + 1SD). Therefore, vulnerability to attentional lapses after SR is a marker of susceptibility to working memory and visuospatial processing impairment during SR and subsequent recovery.
Real-time PCR assays for detection and quantification of early P. falciparum gametocyte stages
Authors: Gadalla Amal A. H. , Siciliano Giulia , Farid Ryan , Alano Pietro , Ranford-Cartwright Lisa , McCarthy James S. , Thompson Joanne , Babiker Hamza A
Published: September 2021

The use of quantitative qRT-PCR assays for detection and quantification of late gametocyte stages has revealed the high transmission capacity of the human malaria parasite, Plasmodium falciparum. To understand how the parasite adjusts its transmission in response to in-host environmental conditions including antimalarials requires simultaneous quantification of early and late gametocytes. Here, we describe qRT-PCR assays that specifically detect and quantify early-stage P. falciparum gametocytes. The assays are based on expression of known early and late gametocyte genes and were developed using purified stage II and stage V gametocytes and tested in natural and controlled human infections. Genes pfpeg4 and pfg27 are specifically expressed at significant levels in early gametocytes with a limit of quantification of 190 and 390 gametocytes/mL, respectively. In infected volunteers, transcripts of pfpeg4 and pfg27 were detected shortly after the onset of blood stage infection. In natural infections, both early (pfpeg4/pfg27) and late gametocyte transcripts (pfs25) were detected in 71.2% of individuals, only early gametocyte transcripts in 12.6%, and only late gametocyte transcripts in 15.2%. The pfpeg4/pfg27 qRT-PCR assays are sensitive and specific for quantification of circulating sexually committed ring stages/early gametocytes and can be used to increase our understanding of epidemiological processes that modulate P. falciparum transmission.
Discovery, optimization and biodistribution of an Affibody molecule for imaging of CD69
Authors: Persson Jonas , Puuvuori Emmi , Zhang Bo , Velikyan Irina , Åberg Ola , Müller Malin , Nygren Per-Åke , Ståhl Stefan , Korsgren Olle , Eriksson Olof , Löfblom John
Published: September 2021

Due to the wide scale of inflammatory processes in different types of disease, more sensitive and specific biomarkers are required to improve prevention and treatment. Cluster of differentiation 69 (CD69) is one of the earliest cell surface proteins expressed by activated leukocytes. Here we characterize and optimize potential new imaging probes, Affibody molecules targeting CD69 for imaging of activated immune cells. Analysis of candidates isolated in a previously performed selection from a Z variant E. coli library to the recombinant extracellular domain of human CD69, identified one cross-reactive Z variant with affinity to murine and human CD69. Affinity maturation was performed by randomization of the primary Z variant, followed by selections from the library. The resulting Z variants were evaluated for affinity towards human and murine CD69 and thermal stability. The in vivo biodistribution was assessed by SPECT/CT in rats following conjugation of the Z variants by a DOTA chelator and radiolabeling with Indium-111. A primary Z variant with a Kd of approximately 50 nM affinity to human and murine CD69 was identified. Affinity maturation generated 5 additional Z variants with improved or similar affinity. All clones exhibited suitable stability. Radiolabeling and in vivo biodistribution in rat demonstrated rapid renal clearance for all variants, while the background uptake and washout varied. The variant ZCD69:4 had the highest affinity for human and murine CD69 (34 nM) as well as the lowest in vivo background binding. In summary, we describe the discovery, optimization and evaluation of novel Affibody molecules with affinity for CD69. Affibody molecule ZCD69:4 is suitable for further development for imaging of activated immune cells.
Tuber yield and water efficiency of early potato varieties (Solanum tuberosum L.) cultivated under various irrigation levels
Authors: Jama-Rodzenska Anna , Janik Grzegorz , Walczak Amadeusz , Adamczewska-Sowinska Katarzyna , Sowinski Jozef
Published: September 2021

This study aims to determine the effects of differences in variety and irrigations levels on potato yield (appropriate humidity, temperature, shading the plants from the sun if necessary) on potato yield in greenhouse conditions. Functions of potato production with respect to water use were developed for five dates of measurements of plant growth, in relation to the various vegetation phases. On the basis of potato vegetation phases, the potato water demand was determined. An experiment was conducted using the randomized sub-block method. The first order factor were the two varieties of potato that were grown under drip irrigation with three water regimes as a second factor experiment: level 1 (pF 2.7), level 2 (pF 2.5) and level 3 (pF 2.2). The variety had a significant effect on the weight of potato tubers. The irrigation level had only a significant effect on the total potato biomass. The potato harvest date had a significant effect on both of the examined treatments. The growth dynamics of the aboveground part and potato tubers were the highest in conditions of constant level 1. Regardless of the variety studied, on level 3 caused a reduction in potato biomass production.The highest water consumption was observed during the tuber potato growth period to flowering. The values were varied from 0.39 l/pot day level 1 (in both investigated cultivars) to 0.99 l/ pot/day (humidity level 3 for Julinka cultivar) in July. The most intensive increase in water consumption was observed at the level 3. The average W index of the average daily water dose calculated for Denar cultivar amounted 0.40 l day−1 in the first period (O1) to 0.79 l day−1 in the fifth period (O5) and for Julinka cultivar 0.49 l day−1 (O1) to 0.92 l day−1 (O5). Stress due to water shortage and/or excessive levels of water in the soil negatively influenced the yield of potato tuber. Potato varieties reacted differently to soil water content.
Longitudinal assessment between lifestyle-related risk factors and a composite cardiovascular disease (CVD) risk index among adolescents in Malaysia
Authors: Thangiah Nithiah , Su Tin Tin , Chinna Karuthan , Jalaludin Muhammad Yazid , Mohamed Mohd Nahar Azmi , Majid Hazreen Abdul
Published: September 2021

The study aims to create a composite risk index of CVD among adolescents and examine the influence of demographic, socioeconomic and lifestyle-related risk factors on the composite risk index of biological CVD risk factors among adolescents in Malaysia. A Malaysian adolescent cohort of 1320 adolescents were assessed at 13, 15 and 17 years. Seven biological CVD risk factors with moderate correlation were identified, standardized and averaged to form a composite CVD risk index. Generalised estimating equation using longitudinal linear regression was used to examine the effects of changes in adolescent lifestyle-related risk factors on the composite CVD risk index over time. From the ages 13 to 17 years, physical fitness (β = − 0.001, 90% CI = − 0.003, 0.00002) and BMI (β = 0.051, 95% CI = 0.042, 0.060) were significant predictors of attaining high scores of CVD risk. Female (β = 0.118, 95% CI = 0.040, 0.197), Chinese (β = 0.122, 95% CI = 0.006, 0.239), Indians (β = − 0.114, 95% CI = − 0.216, − 0.012) and adolescents from rural schools (β = 0.066, 95% CI = − 0.005, 0.136) were also found to be considerably significant. A more robust and gender-specific intervention programme focusing on healthy lifestyle (including achieving ideal BMI and improving physical fitness) need to be implemented among school-going adolescents.
Improving the visual communication of environmental model projections
Authors: Bannister Hayley J. , Blackwell Paul G. , Hyder Kieran , Webb Thomas J.
Published: September 2021

Environmental and ecosystem models can help to guide management of changing natural systems by projecting alternative future states under a common set of scenarios. Combining contrasting models into multi-model ensembles (MMEs) can improve the skill and reliability of projections, but associated uncertainty complicates communication of outputs, affecting both the effectiveness of management decisions and, sometimes, public trust in scientific evidence itself. Effective data visualisation can play a key role in accurately communicating such complex outcomes, but we lack an evidence base to enable us to design them to be visually appealing whilst also effectively communicating accurate information. To address this, we conducted a survey to identify the most effective methods for visually communicating the outputs of an ensemble of global climate models. We measured the accuracy, confidence, and ease with which the survey participants were able to interpret 10 visualisations depicting the same set of model outputs in different ways, as well as their preferences. Dot and box plots outperformed all other visualisations, heat maps and radar plots were comparatively ineffective, while our infographic scored highly for visual appeal but lacked information necessary for accurate interpretation. We provide a set of guidelines for visually communicating the outputs of MMEs across a wide range of research areas, aimed at maximising the impact of the visualisations, whilst minimizing the potential for misinterpretations, increasing the societal impact of the models and ensuring they are well-placed to support management in the future.
Zinc(II) niflumato complex effects on MMP activity and gene expression in human endometrial cell lines
Authors: Rabajdová Miroslava , Špaková Ivana , Klepcová Zuzana , Smolko Lukáš , Abrahamovská Michaela , Urdzík Peter , Mareková Mária
Published: September 2021

Endometriosis is a chronic inflammatory disease which increasingly affects young women under 35 years of age and leads to subfertility even infertility. Analysis of the cytotoxic effect of zinc(II) niflumato complex with neocuproine ([Zn(neo)(nif)2] or Zn-Nif) on immortalized human endometriotic cell line (12Z) and on control immortalized human endometrial stromal cell line (hTERT) was performed using xCELLigence technology for approximately 72 h following the treatment with Zn-Nif as well as cell viability Trypan Blue Assay. 12Z cell line proliferated more slowly compared to unaffected cells, whereas hTERT cells did not show similar behavior after treatment. The complex probably reduces the effect of pro-inflammatory pathways due to the effect of NSAID, while presence of zinc might reduce the level of ROS and regulate ER2 levels and MMP activity. The observed effects and high selectivity for rapidly proliferating cells with increased inflammatory activity suggest a good prognosis of successful decrease of endometriosis stage with this complex.
Marine temperatures underestimated for past greenhouse climate
Authors: Vickers Madeleine L. , Bernasconi Stefano M. , Ullmann Clemens V. , Lode Stefanie , Looser Nathan , Morales Luiz Grafulha , Price Gregory D. , Wilby Philip R. , Hougård Iben Winther , Hesselbo Stephen P. , Korte Christoph
Published: September 2021

Understanding the Earth’s climate system during past periods of high atmospheric CO2 is crucial for forecasting climate change under anthropogenically-elevated CO2. The Mesozoic Era is believed to have coincided with a long-term Greenhouse climate, and many of our temperature reconstructions come from stable isotopes of marine biotic calcite, in particular from belemnites, an extinct group of molluscs with carbonate hard-parts. Yet, temperatures reconstructed from the oxygen isotope composition of belemnites are consistently colder than those derived from other temperature proxies, leading to large uncertainties around Mesozoic sea temperatures. Here we apply clumped isotope palaeothermometry to two distinct carbonate phases from exceptionally well-preserved belemnites in order to constrain their living habitat, and improve temperature reconstructions based on stable oxygen isotopes. We show that belemnites precipitated both aragonite and calcite in warm, open ocean surface waters, and demonstrate how previous low estimates of belemnite calcification temperatures has led to widespread underestimation of Mesozoic sea temperatures by ca. 12 °C, raising estimates of some of the lowest temperature estimates for the Jurassic period to values which approach modern mid-latitude sea surface temperatures. Our findings enable accurate recalculation of global Mesozoic belemnite temperatures, and will thus improve our understanding of Greenhouse climate dynamics.
Propagatory dynamics of nucleus-acoustic waves excited in gyrogravitating degenerate quantum plasmas electrostatically confined in curved geometry
Authors: Dasgupta Sayanti , Karmakar Pralay Kumar
Published: September 2021

A theoretic model to investigate the dynamics of the longitudinal nucleus-acoustic waves (NAWs) in gyrogravitating electrostatically confined degenerate quantum plasma (DQP) system in spherically symmetric geometry is constructed. The model setup consists of non-degenerate heavy nuclear species (HNS), lighter nuclear species (LNS), and quantum degenerate electronic species (DES). It specifically considers the influences of the Bohm potential, Coriolis rotation, viscoelasticity, and electrostatic confinement pressure (ECP, scaling quadratically in density). A standard normal spherical mode analysis gives a generalized dispersion relation (septic). It highlights the dependency of various atypical instability response on the equilibrium plasma parameters. A numerical illustrative platform portrays that the relative nuclear charge-to-mass coupling parameter ($$\beta$$
β
) acts as a destabilizing agency and the heavy-to-light nuclear charge density ratio ($$\mu$$
μ
) acts as a stabilizing agency in both the non-relativistic (NR) and ultra-relativistic (UR) limits. Another interesting conjuncture is that the Coriolis rotation introduces a destabilizing influence on the system in both the limits. The progressive analysis presented herein has correlations and consistencies in the dynamic growth backdrop of various compact astro objects and their circumvent atmospheres, such as white dwarfs, neutron stars, etc.
An increase in the posterior subarachnoid space accelerates the timing of syrinx resolution after foramen magnum decompression of type I Chiari malformation
Authors: Ohnishi Yuichiro , Fujiwara Sho , Takenaka Tomofumi , Kawamoto Saki , Iwatsuki Koichi , Kishima Haruhiko
Published: September 2021

Syrinx resolution has been associated with an increase in the size of the posterior subarachnoid space (pSAS) after foramen magnum decompression (FMD) for type I Chiari malformation (CM1). The present study investigated the influence of pSAS increase on syrinx resolution and symptom improvement after FMD. 32 patients with CM1 with syrinx were analyzed retrospectively. FMD was performed for the 24 patients with CM1 with syrinx. pSAS areas were measured on sagittal magnetic resonance images. Neurological symptoms were grouped into three clinical categories and scored. The rates of symptom improvement in the CM1 patients with syrinx after FMD was 19.7% ± 12.9%. The mean times to the improvement of neurological symptoms in CM1 patients with syrinx after FMD was 23.4 ± 50.2 months. There were no significant differences between the patients with and without improvement of syrinx after FMD with regard to the age, length of tonsillar herniation, BMI, and preoperative pSAS areas. The rate of increase in the pSAS areas was significantly higher in the group with syrinx improvement within 1 year (p < 0.0001). All patients with a > 50% rate of increase in the pSAS area showed syrinx improvement. Our results suggested that the increasing postoperative pSAS area accelerated the timing of syrinx resolution.
Long-term effect of continuous positive airway pressure therapy on blood pressure in patients with obstructive sleep apnea
Authors: Shirahama Ryutaro , Tanigawa Takeshi , Ida Yoshifumi , Fukuhisa Kento , Tanaka Rika , Tomooka Kiyohide , Lan Fan-Yun , Ikeda Ai , Wada Hiroo , Kales Stefanos N.
Published: September 2021

Obstructive sleep apnea (OSA) is a common cause of hypertension. Previous studies have demonstrated beneficial short-term effects of continuous positive airway pressure (CPAP) therapy on blood pressure. However, long-term antihypertensive effects of CPAP have not been properly verified. This study examined the longitudinal effect of CPAP therapy adherence on blood pressure among OSA patients. All patients diagnosed with OSA and undergoing subsequent CPAP therapy at a Kanagawa-area sleep clinic were clinically followed for 24 months to examine CPAP adherence, as well as longitudinal changes in blood pressure and body weight because it may become a confound factor for changes in blood pressure. The hours of CPAP usage were collected over the course of 30 nights prior to each follow-up visit (1st, 3rd, 6th, 12th, and 24th month). The relationship between CPAP adherence and blood pressure was analyzed using mixed-effect logistic regression models. A total of 918 OSA patients were enrolled in the study. We found a significant reduction in diastolic blood pressure among patients with good CPAP adherence during the 24-month follow-up period (β = − 0.13, p = 0.03), when compared to the group with poor CPAP adherence. No significant association was found between CPAP adherence and weight loss (β = − 0.02, p = 0.59). Long-term, good CPAP therapy adherence was associated with lower diastolic blood pressure without significant weight loss.
In vitro and in vivo comparative study of a novel 68Ga-labeled PSMA-targeted inhibitor and 68Ga-PSMA-11
Authors: Chen Huanyu , Cai Ping , Feng Yue , Sun Zhanliang , Wang Yinwen , Chen Yue , Zhang Wei , Liu Nan , Zhou Zhijun
Published: September 2021

68Ga-radiolabeled small molecules that specifically target prostate-specific membrane antigen (PSMA) have been extensively investigated, and some of these tracers have been used in the diagnosis of prostate cancer via 68Ga-positron emission tomography (68Ga-PET). Nevertheless, current 68Ga-labeled radiotracers show only fair detection rates for metastatic prostate cancer lesions, especially those with lower levels of prostate specific antigen (PSA), which often occurs in the biochemical recurrence of prostate cancer. The goal of this study was to design and synthesize a new PSMA-targeted radiotracer, 68Ga-SC691, with high affinity for prostate cancer cells and excellent pharmacokinetics. To this end, structural optimization was carried out on the bifunctional group, target motif, and linker while the high affinity targeting scaffold remained. To explore its potential in the clinic, a comparative study was further performed in vitro and in vivo between 68Ga-SC691 and 68Ga-PSMA-11, a clinically approved tracer for PSMA-positive prostate cancer. SC691 was radiolabeled to provide 68Ga-SC691 in 99% radiolabeling yield under mild conditions. High uptake and a high internalization ratio into LNCaP cells were observed in in vitro studies. In vivo studies showed that 68Ga-SC691 had favorable biodistribution properties and could specifically accumulate on PSMA-positive LNCaP xenografts visualized by micro-PET/CT. This radiotracer showed excellent PET imaging quality and comparable, if not higher, uptake in LNCaP xenografts than 68Ga-PSMA-11.
Detailed characterization of the transcriptome of single B cells in mantle cell lymphoma suggesting a potential use for SOX4
Authors: Valentin Hansen Simone , Høy Hansen Marcus , Cédile Oriane , Møller Michael Boe , Haaber Jacob , Abildgaard Niels , Guldborg Nyvold Charlotte
Published: September 2021

Mantle cell lymphoma (MCL) is a malignancy arising from naive B lymphocytes with common bone marrow (BM) involvement. Although t(11;14) is a primary event in MCL development, the highly diverse molecular etiology and causal genomic events are still being explored. We investigated the transcriptome of CD19+ BM cells from eight MCL patients at single-cell level. The transcriptomes revealed marked heterogeneity across patients, while general homogeneity and clonal continuity was observed within the patients with no clear evidence of subclonal involvement. All patients were SOX11+CCND1+CD20+. Despite monotypic surface immunoglobulin (Ig) κ or λ protein expression in MCL, 10.9% of the SOX11 + malignant cells expressed both light chain transcripts. The early lymphocyte transcription factor SOX4 was expressed in a fraction of SOX11 + cells in two patients and co-expressed with the precursor lymphoblastic marker, FAT1, in a blastoid case, suggesting a potential prognostic role. Additionally, SOX4 was found to identify non-malignant SOX11– pro-/pre-B cell populations. Altogether, the observed expression of markers such as SOX4, CD27, IgA and IgG in the SOX11+ MCL cells, may suggest that the malignant cells are not fixed in the differentiation state of naïve mature B cells, but instead the patients carry B lymphocytes of different differentiation stages.
Extremely low-energy ARPES of quantum well states in cubic-GaN/AlN and GaAs/AlGaAs heterostructures
Authors: Hajlaoui Mahdi , Ponzoni Stefano , Deppe Michael , Henksmeier Tobias , As Donat Josef , Reuter Dirk , Zentgraf Thomas , Springholz Gunther , Schneider Claus Michael , Cramm Stefan , Cinchetti Mirko
Published: September 2021

Quantum well (QW) heterostructures have been extensively used for the realization of a wide range of optical and electronic devices. Exploiting their potential for further improvement and development requires a fundamental understanding of their electronic structure. So far, the most commonly used experimental techniques for this purpose have been all-optical spectroscopy methods that, however, are generally averaging in momentum space. Additional information can be gained by angle-resolved photoelectron spectroscopy (ARPES), which measures the electronic structure with momentum resolution. Here we report on the use of extremely low-energy ARPES (photon energy ~ 7 eV) to increase depth sensitivity and access buried QW states, located at 3 nm and 6 nm below the surface of cubic-GaN/AlN and GaAs/AlGaAs heterostructures, respectively. We find that the QW states in cubic-GaN/AlN can indeed be observed, but not their energy dispersion, because of the high surface roughness. The GaAs/AlGaAs QW states, on the other hand, are buried too deep to be detected by extremely low-energy ARPES. Since the sample surface is much flatter, the ARPES spectra of the GaAs/AlGaAs show distinct features in momentum space, which can be reconducted to the band structure of the topmost surface layer of the QW structure. Our results provide important information about the samples’ properties required to perform extremely low-energy ARPES experiments on electronic states buried in semiconductor heterostructures.
A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies
Authors: Pode-Shakked Ben , Barel Ortal , Singer Amihood , Regev Miriam , Poran Hana , Eliyahu Aviva , Finezilber Yael , Segev Meirav , Berkenstadt Michal , Yonath Hagith , Reznik-Wolf Haike , Gazit Yael , Chorin Odelia , Heimer Gali , Gabis Lidia V. , Tzadok Michal , Nissenkorn Andreea , Bar-Yosef Omer , Zohar-Dayan Efrat , Ben-Zeev Bruria , Mor Nofar , Kol Nitzan , Nayshool Omri , Shimshoviz Noam , Bar-Joseph Ifat , Marek-Yagel Dina , Javasky Elisheva , Einy Reviva , Gal Moran , Grinshpun-Cohen Julia , Shohat Mordechai , Dominissini Dan , Raas-Rothschild Annick , Rechavi Gideon , Pras Elon , Greenbaum Lior
Published: September 2021

Exome sequencing (ES) is an important diagnostic tool for individuals with neurodevelopmental disorders (NDD) and/or multiple congenital anomalies (MCA). However, the cost of ES limits the test's accessibility for many patients. We evaluated the yield of publicly funded clinical ES, performed at a tertiary center in Israel, over a 3-year period (2018–2020). Probands presented with (1) moderate-to-profound global developmental delay (GDD)/intellectual disability (ID); or (2) mild GDD/ID with epilepsy or congenital anomaly; and/or (3) MCA. Subjects with normal chromosomal microarray analysis who met inclusion criteria were included, totaling 280 consecutive cases. Trio ES (proband and parents) was the default option. In 252 cases (90.0%), indication of NDD was noted. Most probands were males (62.9%), and their mean age at ES submission was 9.3 years (range 1 month to 51 years). Molecular diagnosis was reached in 109 probands (38.9%), mainly due to de novo variants (91/109, 83.5%). Disease-causing variants were identified in 92 genes, 15 of which were implicated in more than a single case. Male sex, families with multiple-affected members and premature birth were significantly associated with lower ES yield (p < 0.05). Other factors, including MCA and coexistence of epilepsy, autism spectrum disorder, microcephaly or abnormal brain magnetic resonance imaging findings, were not associated with the yield. To conclude, our findings support the utility of clinical ES in a real-world setting, as part of a publicly funded genetic workup for individuals with GDD/ID and/or MCA.