bluuebunny/crossref_metadata_2025_split huggingface dataset:
Holding residential property on inter vivos trusts in Singapore: transfers to trustees
Authors: Ooi Vincent 
Published: September 2022

Abstract
As a response to the “missing beneficial owner” problem highlighted by the Zhao Hui Fang case, amendments have been made to Singapore’s stamp duty regime. ABSD will now be levied at 35% on transfers of residential property to trustees, with a remission available if certain conditions are met. These conditions effectively mean that residential property held on inter vivos trusts in Singapore must be given to beneficiaries without conditions or powers of revocation or variation. This has major ramifications for succession planning, since such restrictions largely defeat the purpose of using a trust to hold property in the first place.
Holding residential property on inter vivos trusts in Singapore: transfers of equity interests
Authors: Ooi Vincent 
Published: September 2022

Abstract
Following amendments to the ACD regime in Singapore, transferring equity interests to and from a trust with no beneficial owners will attract ACD, as will the exercise of a power of appointment by a trustee to grant equity interests to a beneficiary. Renunciation of interests in a bare trust will also attract ACD. Together with the introduction of ABSD (Trust), it is now impractical to use trusts to hold residential properties for succession planning purposes. Remaining options are to gift the properties without any strings attached or bequeath the properties in a will and risk subsequent changes to death taxation.
EU private law injustices
Authors: Hesselink Martijn W 
Published: September 2022

Abstract
This article offers a critique of injustices in European private law. It explains why the EU should be held morally responsible for the injustices created or supported by its private law. In particular, it demonstrates for several core elements of EU private law that they are unjust, because they cannot be justified with non-rejectable reasons, and insofar lead to domination by EU private law. This is the case, especially, for EU private law’s consumerism, its Eurocentrism, its constitutionalized market-functionalism, its doctrinal and judicial expert government, and its blindness towards intersectional domination. The article also critically discusses, and rejects, various theories offering blueprints for an ideal European private law system. Instead, it argues for the priority of democratic justice and for an urgent focus on salient injustices in EU private law’s theory and practice.
Drug-Related Adverse Events Necessitating Treatment Discontinuation in Pediatric Inflammatory Bowel Disease Patients
Authors: Salzmann Medea , von Graffenried Thea , Righini-Grunder Franziska , Braegger Christian , Spalinger Johannes , Schibli Susanne , Schoepfer Alain , Nydegger Andreas , Pittet Valérie , Sokollik Christiane ,   the Swiss IBD Cohort Study Group
Published: September 2022

Objectives:
Inflammatory bowel disease (IBD) requires long-term drug therapy in most patients, posing a risk for adverse drug events with the need for discontinuation. In this study, we investigated adverse events (AE) necessitating drug discontinuation in pediatric and adolescent IBD patients.

Methods:
We used data prospectively collected from IBD patients below the age of 18 enrolled in the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS), namely demographic variables, medical characteristics, drug treatments, and related AE. We analyzed the frequency, type, and risk factors for AE necessitating drug discontinuation.

Results:
A total of 509 pediatric IBD patients fulfilled the inclusion criteria of which 262 (51.5%) were diagnosed with Crohn disease (CD), 206 (40.5%) with ulcerative colitis (UC), and 41 (8%) with IBD-unclassified (IBD-U). In total, 132 (25.9%) presented with at least 1 drug-related AE that required drug cessation. Immunomodulators [methotrexate 29/120 (24.2%), azathioprine 57/372 (15.3%)] followed by tumor necrosis factor (TNF)-alpha antagonists [adalimumab 8/72 (11.1%), infliximab 22/227 (9.7%)] accounted for the highest proportions of AE necessitating treatment discontinuation. Treatment schemes with at least 3 concomitant drugs significantly amplified the risk for development of drug-related AE [odds ratio = 2.50, 95% confidence interval (1.50–4.17)] in all pediatric IBD patients.

Conclusions:
Drug-related AE necessitating discontinuation are common in pediatric and adolescent IBD patients. Caution needs to be taken in the case of concomitant drug use.
Evaluation of the Relationship Between Head Trauma and Attention-Deficit/Hyperactivity Disorder in Primary School Children Admitted to the Emergency Department
Authors: Beyoglu Resad , Erdur Bulent 
Published: September 2022

Objective
Head trauma causes a significant number of deaths as well as temporary and permanent disabilities every year. In this study, the prevalence of attention-deficit/hyperactivity disorder (ADHD) in primary school children who visited the emergency department (ED) for mild head trauma and the role of ADHD in mild head trauma of this age group were investigated.

Methods
It was performed with 134 children of primary school age (6–12 years) who were admitted to the ED with mild head trauma and 134 children (control group) who presented with complaints other than head trauma. Turgay DSM-IV–Based Child and Adolescent Behavioral Disorders Screening and Rating Scale (T-DSM-IV-S) was used to evaluate the children for suspected ADHD. According to this scale, some children were referred to the child and adolescent psychiatry department (CAPD) for further evaluation. At the CAPD outpatient clinics, the children who were referred from the ED were examined in detail according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, for possible diagnosis of ADHD. After evaluation of their sociodemographic characteristics and the ADHD test scores that were recorded, the diagnosis of ADHD in these children was established or ruled out.

Results
It was observed that 41 of the 134 children (30.60%) who presented to the ED with mild head trauma and 12 of the 134 children (8.96%) in the control group were diagnosed with ADHD (P = 0.0001). When ADHD is corrected for sex, 29 of the 41 cases (70.7%) diagnosed with ADHD were boys and 12 (29.3%) were girls (P = 0.000). According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, when the patients who had been diagnosed with ADHD were grouped according to the ages of the children, no statistically significant difference was found between the groups in terms of ADHD (P = 0.097).

Conclusions
The prevalence of ADHD has been found to be higher in children of primary school age who present to the ED with mild head trauma. Hence, it can be deduced that the diagnosis of childhood ADHD increases the risk of presenting to the ED with head trauma. We believe that it is very important to keep the possible diagnosis of ADHD in mind and to refer that cases to the CAPD in case of high clinical suspicion, especially in primary school boys who are admitted to the ED with mild head trauma. We believe that in this way, morbidity and mortality due to head trauma in this age group can be significantly reduced.
A potential transition from a concentrated to a generalized HIV epidemic: the case of Madagascar
Authors: Alonso David , Vallès Xavier 
Published: September 2022

AbstractHIV expansion is controlled by a range of interrelated factors, including the natural history of HIV infection and socio-economical and structural factors. However, how they dynamically interact in particular contexts to drive a transition from concentrated HIV epidemics in vulnerable groups to generalized epidemics is poorly understood. We developed a compartmental dynamic model using available data from Madagascar, a country with a contrasting concentrated epidemic, to explore the interaction between these factors with special consideration of commercial and transactional sex as HIV-infection drivers. The model predicts sigmoidal-like prevalence curves with turning points within years 2020-2022, and prevalence reaching stabilization by 2033 within 9 to 24% in the studied (10 out of 11) cities, similar to high-prevalence regions in Southern Africa. Circumcision could have slowed down HIV propagation, but, given the key interplay between risky behaviors associated to young women and acute infections prevalence, mediated by transactional sex, the protective effect of circumcision is currently insufficient to contain the expansion of the disease in Madagascar. These results suggest that Madagascar may be experiencing a silent transition from a concentrated to a generalized HIV epidemic. This case-study model could help to understand how this HIV epidemic transition occurs.
Constitutively active Lyn kinase causes a cutaneous small vessel vasculitis and liver fibrosis syndrome
Authors: de Jesus Adriana A. , Chen Guibin , Yang Dan , Brdicka Tomas , Ruth Natasha , Bennin David , Cebecauerova Dita , Malcova Hana , Freeman Helen , Martin Neil , Svojgr Karel , Paso Murray , Bhuyan Farzana , Alehashemi Sara , Rastegar Andre , Uss Kat , Kardova Lela , Marrero Bernadette , Duric Iris , Omoyinmi Ebun , Peldova Petra , Lee Chyi-Chia Richard , Kleiner David E. , Hadigan Colleen M. , Hewitt Stephen M. , Pittaluga Stefania , Carmona-Rivera Carmelo , Calvo Katherine R. , Shah Nirali , Balascakova Miroslava , Fink Danielle , Kotalova Radana , Parackova Zuzana , Peterkova Lucie , Kuzilkova Daniela , Campr Vit , Sramkova Lucie , Biancotto Angelique , Brooks Stephen R. , Manes Cameron , Meffre Eric , Harper Rebecca L. , Kuehn Hyesun , Kaplan Mariana J. , Brogan Paul , Rosenzweig Sergio D. , Merchant Melinda , Deng Zuoming , Huttenlocher Anna , Moir Susan , Kuhns Doug , Boehm Manfred , Kramarzova Karolina Skvarova , Goldbach-Mansky Raphaela 
Published: September 2022

SummaryNeutrophilic inflammation is a hallmark of many monogenic autoinflammatory diseases; pathomechanisms that regulate extravasation of damaging immune cells into surrounding tissues are poorly understood. We identified three unrelated boys with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation. Two patients developed liver fibrosis in their first year of life. Next-generation sequencing identified two de novo truncating variants in the Src-family tyrosine kinase, LYN, p.Y508*, p.Q507* and a de novo missense variant, p.Y508F, that result in constitutive activation of Lyn kinase. Functional studies reveal increased expression of ICAM-1 on induced patient-derived endothelial cells (iECs) and of β2-integrins on neutrophils that increase neutrophil adhesion and vascular transendothelial migration (TEM). Treatment with TNF inhibition improved systemic inflammation; and liver fibrosis resolved on treatment with the Src kinase inhibitor dasatinib. These findings reveal a critical role for Lyn kinase in modulating inflammatory signals, regulating microvascular permeability and neutrophil recruitment, and in promoting hepatic fibrosis.
Polygenic Susceptibility to Hypertension is Associated with Worse Cognitive Performance in Middle-Aged Persons without Dementia
Authors: Rivier Cyprien , Szejko Natalia , Renedo Daniela , Noche Rommell , Acosta Julian N. , Both Cameron P. , Payabvash Seyedmehdi , De Havenon Adam , Sheth Kevin N. , Gill Thomas M. , Falcone Guido J. 
Published: September 2022

ABSTRACTBackgroundMounting evidence indicates that hypertension leads to higher risk of cognitive decline and dementia. Hypertension is a highly heritable trait and a higher polygenic susceptibility to hypertension (PSH) is known to be associated with higher risk of dementia. We tested the hypothesis that a higher PSH leads to worse cognitive performance in middle-aged persons without dementia.MethodsWe conducted a nested, cross-sectional, genetic study within the UK Biobank, a large population study that enrolled middle-aged Britons. Study participants with a history of dementia or stroke were excluded. We categorized participants as having low (≤20th percentile), intermediate (>20th and <80th percentile), or high (≥80th percentile) PSH according to results of 2 polygenic risk scores for systolic and diastolic blood pressure (BP), generated with genomic data on 732 genetic risk variants for these traits. Cognitive performance was evaluated via 5 simple tests: Pairs Memory, Reaction Time, Numeric Memory, Prospective Memory and Fluid Intelligence. A general cognitive ability score was calculated as the first principal component of a principal component analysis that included the results of these 5 tests. Primary analyses focused on Europeans and secondary analyses included all race/ethnic groups.ResultsOut of 409,551 study participants of European ancestry with available genomic data, 42,080 (10.3%) completed all 5 tests. Multivariable regression models using systolic BP-related genetic variants indicated that, compared to study participants with low PSH, those with intermediate and high PSH had reductions of 3.9% (beta -0.039, SE 0.012) and 6.6% (beta - 0.066, SE 0.014), respectively, in their general cognitive ability score (test for trend p <0.001). Secondary analyses including all race/ethnic groups (n=48,118) and using diastolic BP-related genetic variants yielded similar results (both instances, p<0.05). Analyses evaluating each cognitive test separately indicated that Reaction Time, Numeric Memory and Fluid Intelligence drove the association of PSH with the general cognitive ability score (all individual tests, p<0.05).ConclusionsAmong non-demented, community-dwelling, middle-aged Britons, a higher PSH is associated with worse cognitive performance. These findings suggest the genetic predisposition to hypertension influence brain health in persons who have not yet developed dementia.
Adolescent Anxiety and TikTok. An exploratory study
Authors: Zheluk Andrey , Anderson Judith , Dineen – Griffin Sarah 
Published: September 2022

ABSTRACTINTRODUCTIONSocial media is ubiquitous in adolescents’ lives. TikTok is a medium primarily used by adolescents and young adults under 30 years. TikTok is thus an appropriate social media platform with which to examine discussions of anxiety among this age cohort. In this exploratory mixed-methods study we aimed to evaluate the scope of anxiety content available on TikTok in English in December 2021, and to further develop methods for analysing TikTok content.METHODWe analysed a data set of 147 TikToks with the hashtag #anxiety. The data set consisted both of metadata and TikTok videos. This data set represented 18% of all TikToks featuring the hashtag #anxiety in December 2021. We examined the following research questions (RQs). RQ1: What are the creator identities reflected in the final data set in this study?; RQ2: What are the metadata characteristics of the TikToks in the final data set?; RQ3: What are the anxiety content themes in the final data set?; and RQ4: What are the characteristics of the data set based on an anxiety management reference checklist?RESULTSInfluencers were the most frequent creator identity in our data set. Influencers comprised 85.5% of the 147 TikToks in our final data set. We coded 79 (54%) female and 45 male (31%) influencers. We found male influencers created the most played (mean 81 147 062), and most liked (mean 1 510 585) TikToks. We found content themes varied by influencer gender. Notable finding were: the greater use of humour by males (22.7% males; n=10, and females 12.7%; n=10); and inspiration (38.6%; males n=17; and 13.9%; females n=11). Among female influencers, we identified self-disclosure as the most common theme (n= 40 and 50.6% compared with n=11 and 25% male influencers). Overall, we found limited references to evidence-based anxiety self-care content in our final data set.DISCUSSIONWe suggest that the TikToks in our data set were primarily directed at raising awareness of and de-stigmatising anxiety symptoms. TikTok anxiety content may be viewed by adolescents for emotional self-regulation, beyond evidence-based health information seeking. Self-disclosure on TikTok may also provide symptomatic relief to adolescents with anxiety. We suggest that gender is a salient consideration when considering TikTok content.CONCLUSIONSOur content findings are broadly consistent with previous research into adolescent use of social media. This research also provides methodological insights for researchers and clinicians seeking to understand TikTok, and to develop engaging content targeted at the specific concerns and preferences of adolescent TikTok consumers.
m6A-ELISA, a simple method for quantifyingN6-methyladenosine from mRNA populations
Authors: Ensinck Imke , Sideri Theodora , Modic Miha , Capitanchik Charlotte , Toolan-Kerr Patrick , van Werven Folkert J. 
Published: September 2022

AbstractN6-methyladenosine (m6A) is a widely studied and abundant RNA modification. The m6A mark regulates the fate of RNAs in various ways, which in turn, drives changes in cell physiology, development, and disease pathology. Over the last decade, numerous methods have been developed to map and quantify m6A sites genomewide through deep sequencing. Alternatively, m6A levels can be quantified from a population of RNAs using techniques such as liquid chromatography-mass spectrometry or thin layer chromatography. However, many methods for quantifying m6A levels involve extensive protocols and specialized data analysis, and often only a few samples can be handled in a single experiment. Here, we developed a simple method for determining m6A levels in mRNA populations from various sources based on enzyme-linked immunosorbent-based assay (m6A-ELISA). We have optimized various steps of m6A-ELISA such as sample preparation and the background signal resulting from the primary antibody. We validated the method using mRNA populations from budding yeast and mouse embryonic stem cells. The full protocol takes less than a day, requiring only 25 ng of mRNA. The m6A-ELISA protocol is therefore quick, cost-effective, and scalable, making it a valuable tool for determining relative m6A levels in samples from various sources that could be adapted to detect other mRNA modifications.
A Purinergic Mechanism Underlying Metformin Regulation of Hyperglycemia
Authors: Senfeld J. , Peng Q. , Shi Y. , Qian S. , Shen J. 
Published: September 2022

AbstractMetformin, created in 1922, has been the first-line medication treating type 2 diabetes mellitus for almost 70 years; however, its mechanism of action has been heavily debated, partly because most prior studies used supratherapeutic concentrations exceeding 1mM. Here we report that at a clinically relevant concentration of 10 μM, metformin blocks high glucose-stimulated ATP secretion from hepatocytes mediating its antihyperglycemic action. Following glucose administration, mice demonstrate increased circulating ATP concentrations, which are prevented by metformin. Extracellular ATP through P2Y2 receptors (P2Y2R) compromises insulin-induced AKT activation and increases hepatic glucose production. In addition, metformin-dependent improvement in glucose tolerance is abolished in P2Y2R-null mice. Thus, removing the target of extracellular ATP, P2Y2R, mimics the effects of metformin, revealing a novel purinergic antidiabetic mechanism for metformin.One-Sentence SummaryMetformin abolishes high glucose-stimulated ATP secretion, preventing purinergic mechanism-mediated hepatic insulin resistance and glucose production.
Activation of SARS-CoV-2 by trypsin-like proteases in the clinical specimens of patients with COVID-19
Authors: Igarashi Emiko , Shimada Takahisa , Yazawa Shunsuke , Saga Yumiko , Itamochi Masae , Inasaki Noriko , Hasegawa Sumiyo , Morinaga Yoshitomo , Oishi Kazunori , Tani Hideki 
Published: September 2022

AbstractSARS-CoV-2 enters host cells through the angiotensin converting enzyme 2 (ACE2) receptor and/or transmembrane protease, serine 2 (TMPRSS2). Serine proteases, such as TMPRSS2 and trypsin, promote viral entry.In this study, we investigated whether proteases increased SARS-CoV-2 infectivity using pseudotyped viruses and clinical specimens from patients with COVID-19. First, we investigated how trypsin increased infectivity using the pseudotyped virus. Our findings revealed that trypsin increased infectivity after the virus was adsorbed on the cells, but no increase in infectivity was observed when the virus was treated with trypsin. We examined the effect of trypsin on SARS-CoV-2 infection in clinical specimens and found that the infectivity of the SARS-CoV-2 delta variant increased 36,000-fold after trypsin treatment. By contrast, the infectivity of SARS-CoV-2 omicron variant increased to less than 20-fold in the clinical specimens. Finally, infectivity of clinical specimens containing culture supernatants of Fusobacterium necrophorum was increased from several- to 10-fold. Because SARS-CoV-2 infectivity increases in the oral cavity, which may contain anaerobic bacteria, keeping the oral cavities clean may help prevent SARS-CoV-2 infection.ImportanceIn this study, we examined whether trypsin-like proteases increased the infectivity of SARS-CoV-2. We found that trypsin-like proteases increased the infectivity of both the pseudotyped viruses and the live virus in the clinical specimens. The increase in infectivity was significantly higher for the delta than the omicron variant. A large amount of protease in the oral cavity during SARS-CoV-2 infection is expected to increase infectivity. Therefore, keeping the oral cavity clean is important for preventing infection.
The Arabidopsis SHORTROOT network coordinates shoot apical meristem development with auxin dependent lateral organ initiation
Authors: Bahafid Elmehdi , Bradtmöller Imke , Thies Ann Marlene , Nguyen Thi Thuy Oanh Nicole , Gutierrez Crisanto , Desvoyes Bénédicte , Stahl Yvonne , Blilou Ikram , Simon Rüdiger 
Published: September 2022

AbstractUnlike animals, plants have the capacity to produce new organs post-embryonically throughout their entire life cycle. This is due to stem cells present in the shoot and the root apical meristems (SAM and RAM, respectively). In the SAM, stem cells are located in the central zone (CZ) where they divide slowly. Stem cell daughters are displaced laterally and enter the peripheral zone (PZ). Here, their mitotic activity increases, and lateral organ primordia (LOP) are formed. How the spatial arrangement of these different domains is initiated and controlled during SAM growth and development, and how sites of LOP are determined in the PZ is not yet completely understood.In the RAM, the GRAS family transcription factor SHORTROOT (SHR) acts as a master regulator of signalling pathways that maintain the root stem cell niche and control formation of ground tissue layers. We hypothesized that SHR could perform a similar role in the SAM, and found that SHR, together with its target transcription factors SCARECROW (SCR), SCARECROW-LIKE23 (SCL23) and JACKDAW (JKD), controls shoot meristem size by regulating cell division rates, and promotes formation of lateral organs. SHR, SCR, SCL23 and JKD are expressed in very distinct patterns in the SAM. Where these expression domains overlap, they can physically interact to activate expression of the key cell cycle regulator CYCLIND6;1 (CYCD6;1) and thereby promote the formation of new cell layers.In the PZ, upregulation of SHR expression at sites of organ initiation depends on the phytohormone auxin, acting through the auxin response factor MONOPTEROS (MP) and auxin response elements in the SHR promoter. In the CZ, the SHR-target SCL23 physically interacts with WUS, a key regulator of stem cell maintenance, and both SCL23 and WUS expression are subject to negative feedback regulation from stem cells through the CLAVATA signalling pathway. Together, our findings illustrate how SHR-dependent transcription factor complexes act in different domains of the shoot meristem to mediate cell division and auxin dependent organ initiation in the PZ, and coordinate this activity with stem cell maintenance in the CZ of the SAM.