bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ascending Growth is Associated with Offspring Adiposity in Pregnancies Complicated with Obesity or Gestational Diabetes
Authors: Huvinen Emilia , Tuomaala Anna-Kaisa , Bergman Paula H , Meinilä Jelena , Tammelin Tuija , Kulmala Janne , Engberg Elina , Koivusalo Saila B 
Published: February 2021

Abstract

Context
Early growth is associated with childhood adiposity, but the influence of lifestyle remains unknown.

Objective
This work aimed to investigate the association of growth profiles from high-risk pregnancies with adiposity at age 5 years, taking into account lifestyle and several antenatal/postnatal exposures.

Methods
This prospective cohort study

included
609 children born during the Finnish Gestational Diabetes Prevention Study (RADIEL), recruiting women with body mass index (BMI) greater than or equal to 30 and/or prior gestational diabetes mellitus (GDM) (2008-2013). Altogether 332 children attended the 5-year follow-up (2014-2017). Main outcome measures included growth profiles based on ponderal index (PI = weight/height3), investigated using latent class mixed models. Adiposity was assessed with anthropometrics and body composition (InBody720).

Results
We identified 3 growth profiles: ascending (n = 82), intermediate (n = 351), and descending (n = 149). Children with ascending growth had a higher body fat percentage, ISO-BMI, and waist circumference (P &lt; .05) at age 5 years. Ascending (β 4.09; CI, 1.60-6.58) and intermediate (β 2.27; CI, 0.50-4.03) profiles were associated with higher fat percentage, even after adjustment for age, sex, gestational age, diet, physical activity, education, and prepregnancy BMI. Similar associations existed with ISO-BMI. After adjusting for age and education, ascending growth was associated with prepregnancy BMI (odds ratio [OR] 1.06; CI, 1.01-1.12), primiparity (OR 3.07; CI, 1.68-5.62), cesarean delivery (OR 2.23; CI, 1.18-4.21), and lifestyle intervention (OR 2.56; CI, 1.44-4.57). However, meeting the intervention goals and exclusive breastfeeding for 3 months or more were associated with lower odds of ascending growth.

Conclusion
Accelerated early growth was associated with higher adiposity in 5-year-old children from high-risk pregnancies, even when adjusted for lifestyle. Reducing cesarean deliveries and promoting breastfeeding may be beneficial for postnatal growth.
Hes1 overexpression leads to expansion of embryonic neural stem cell pool and stem cell reservoir in the postnatal brain
Authors: Ohtsuka Toshiyuki , Kageyama Ryoichiro 
Published: February 2021

ABSTRACT
Neural stem cells (NSCs) gradually alter their characteristics during mammalian neocortical development, resulting in the production of various neurons and glial cells, and remain in the postnatal brain as a source of adult neurogenesis. Notch-Hes signaling is a key regulator of stem cell properties in the developing and postnatal brain, and Hes1 is a major effector that strongly inhibits neuronal differentiation and maintains NSCs. To manipulate Hes1 expression levels in NSCs, we generated transgenic (Tg) mice using the Tet-On system. In Hes1-overexpressing Tg mice, NSCs were maintained in both embryonic and postnatal brains, and generation of later-born neurons was prolonged until later stages in the Tg neocortex. Hes1 overexpression inhibited the production of Tbr2+ intermediate progenitor cells but instead promoted the generation of basal radial glia-like cells in the subventricular zone (SVZ) at late embryonic stages. Furthermore, Hes1-overexpressing Tg mice exhibited the expansion of NSCs and enhanced neurogenesis in the SVZ of adult brain. These results indicate that Hes1 overexpression expanded the embryonic NSC pool and led to the expansion of the NSC reservoir in the postnatal and adult brain.
Retinoic acid production, regulation and containment through Zic1, Pitx2c and Cyp26c1 control cranial placode specification
Authors: Dubey Aditi , Yu Jianshi , Liu Tian , Kane Maureen A. , Saint-Jeannet Jean-Pierre 
Published: February 2021

ABSTRACT
All paired sensory organs arise from a common precursor domain called the pre-placodal region (PPR). In Xenopus, Zic1 non-cell autonomously regulates PPR formation by activating retinoic acid (RA) production. Here, we have identified two Zic1 targets, the RA catabolizing enzyme Cyp26c1 and the transcription factor Pitx2c, expressed in the vicinity of the PPR as being crucially required for maintaining low RA levels in a spatially restricted, PPR-adjacent domain. Morpholino- or CRISPR/Cas9-mediated Cyp26c1 knockdown abrogated PPR gene expression, yielding defective cranial placodes. Direct measurement of RA levels revealed that this is mediated by a mechanism involving excess RA accumulation. Furthermore, we show that pitx2c is activated by RA and required for Cyp26c1 expression in a domain-specific manner through induction of FGF8. We propose that Zic1 anteriorly establishes a program of RA containment and regulation through activation of Cyp26c1 and Pitx2c that cooperates to promote PPR specification in a spatially restricted domain.
Case Report: Voriconazole induced refractory hyperkalemia and adrenal insufficiency
Authors: Tariq Ezza Fatima , Irshad Yusra , Khan Usman A. , Shoaib Muhammad , Asif Hajra 
Published: February 2021

Voriconazole, an azole drug, inhibits cytochrome P450 dependent lanosterol 14-alpha-demethylase. It is a potent anti-fungal agent. Adverse effects include neurotoxicity, cardiac arrhythmias, electrolyte disturbances and adrenal insufficiency. Hyperkalemia is a rare adverse effect that has been described, but is not well reported, in the literature. We present a case of intractable hyperkalemia resulting from voriconazole use. A 47-year-old male presented with worsening shortness of breath, requiring mechanical ventilation within 24 hours of presentation. Diagnosis of acute respiratory distress syndrome was made. Empirical treatment with broad-spectrum antibacterial coverage resulted in no improvement. Voriconazole was added for anti-fungal coverage, causing treatment resistant hyperkalemia necessitating continuous renal replacement therapy (CRRT). Renal function remained normal. Stopping voriconazole restored normal potassium levels. CRRT was discontinued. Hyperkalemia caused by voriconazole occurs in less than 2% of cases. It is a potentially life-threatening side effect. Physicians should be aware of this association and seek alternative treatment when necessary.
Whole-exome sequencing of de novo genetic variants in a Chinese family with a sporadic case of congenital nonsyndromic hearing loss
Authors: Hu Sijing , Zhang Hao , Liu Yunqiang , Liu Mohan , Li Jingjing , Liao Shunyao 
Published: February 2021

Background: We examined the genetic variants of a Chinese family with a 22-month-old infant with sporadic non-syndromic sensorineural hearing loss (NSHL). Methods: The whole-exome sequence data in the family, especially the de novo variants presented in the patient, were analyzed and the effect of the disease-causing genetic variants on the protein expression level and cellular localization were examined by cell-based functional assay. Results: The infant had no known NSHL-causing variants, except two compound heterozygous variants in connexin26 gene GJB2; one was the c.79G>A, c.341A>G haplotype from the asymptomatic mother which was benign, and the other was a de novo pathogenic c.262G>C (p.A88P). In vitro, GJB2 with c.262G>C was weakly expressed and displayed a punctate distribution in the cytoplasm and cytomembrane, while wild type GJB2 was robustly expressed in the cytomembrane. We deduced that the de novo pathogenic GJB2 c.262G>C exacerbated loss-of-function in the context of leaky variants c.79G>A, c.341A>G in the patient. Interestingly, further analysis of exome sequences revealed that the occurrence of de novo pathogenic variants in the infant was frequent. Among the total~47,000 variants, 143 were de novo in the patient, whereas among all 74 variants predicted to be pathogenic/likely pathogenic, 21 were heterozygous and two were homozygous de novo. The occurrence rate of de novo deleterious variants was much higher (31.1%, 23/74) than that in total (0.34%, 143/47,000). It is notable that most genes with de novo deleterious variants were environment-sensitive, such as GJB2, MNK1, MNK2, MUC4, RAD21 and DNA copy number variations. Conclusions: The full picture of genetic variants in the exome might help us to interpret the NSHL-causing variants. More research is needed into the causes of de novo deleterious variants and gene-environment interactions in congenital NSHL.
The international Perinatal Outcomes in the Pandemic (iPOP) study: protocol
Authors: Stock Sarah J. , Zoega Helga , Brockway Meredith , Mulholland Rachel H. , Miller Jessica E. , Been Jasper V. , Wood Rachael , Abok Ishaya I. , Alshaikh Belal , Ayede Adejumoke I. , Bacchini Fabiana , Bhutta Zulfiqar A. , Brew Bronwyn K. , Brook Jeffrey , Calvert Clara , Campbell-Yeo Marsha , Chan Deborah , Chirombo James , Connor Kristin L. , Daly Mandy , Einarsdóttir Kristjana , Fantasia Ilaria , Franklin Meredith , Fraser Abigail , Håberg Siri Eldevik , Hui Lisa , Huicho Luis , Magnus Maria C. , Morris Andrew D. , Nagy-Bonnard Livia , Nassar Natasha , Nyadanu Sylvester Dodzi , Iyabode Olabisi Dedeke , Palmer Kirsten R. , Pedersen Lars Henning , Pereira Gavin , Racine-Poon Amy , Ranger Manon , Rihs Tonia , Saner Christoph , Sheikh Aziz , Swift Emma M. , Tooke Lloyd , Urquia Marcelo L. , Whitehead Clare , Yilgwan Christopher , Rodriguez Natalie , Burgner David , Azad Meghan B. ,   iPOP Study Team
Published: February 2021

Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread “natural experiment” of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic.
Individual-level variations in malaria susceptibility and acquisition of clinical protection
Authors: Valletta John Joseph , Addy John W.G. , Reid Adam J. , Ndungu Francis M. , Bediako Yaw , Mwacharo Jedida , Said Khadija , Musyoki Jennifer , Ngoi Joyce Mwongeli , Wambua Joshua , Otieno Edward , Berriman Matt , Bejon Philip , Marsh Kevin , Langhorne Jean , Newbold Chris I. , Recker Mario 
Published: February 2021

After decades of research, our understanding of when and why individuals infected with Plasmodium falciparum develop clinical malaria is still limited. Correlates of immune protection are often sought through prospective cohort studies, where measured host factors are correlated against the incidence of clinical disease over a set period of time. However, robustly inferring individual-level protection from these population-level findings has proved difficult due to small effect sizes and high levels of variance underlying such data. In order to better understand the nature of these inter-individual variations, we analysed the long-term malaria epidemiology of children ≤12 years old growing up under seasonal exposure to the parasite in the sub-location of Junju, Kenya. Despite the cohort’s limited geographic expanse (ca. 3km x 10km), our data reveal a high degree of spatial and temporal variability in malaria prevalence and incidence rates, causing individuals to experience varying levels of exposure to the parasite at different times during their life. Analysing individual-level infection histories further reveal an unexpectedly high variability in the rate at which children experience clinical malaria episodes. Besides exposure to the parasite, measured as disease prevalence in the surrounding area, we find that the birth time of year has an independent effect on the individual’s risk of experiencing a clinical episode. Furthermore, our analyses reveal that those children with a history of an above average number of episodes are more likely to experience further episodes during the upcoming transmission season. These findings are indicative of phenotypic differences in the rates by which children acquire clinical protection to malaria and offer important insights into the natural variability underlying malaria epidemiology.
Understanding the pathogenesis of heart failure
Authors: Easa Jamshid , Chappell Jacob , Warriner David 
Published: February 2021

Heart failure is a complex clinical syndrome. Jamshid Easa, Jacob Chappell and David Warriner explain the pathogenesis behind the most common form of this condition Heart failure a complex clinical syndrome due to impairment of ventricular filling or contraction, resulting in a constellation of physical symptoms and signs, primarily due to salt and water retention. In this clinically focused review of the pathophysiology, we will summarise the main consequences of the most common type, left ventricular failure; knowledge of which is essential for those working in general practice due to the high prevalence of heart failure in the community and to aid understanding of the various pharmacotherapies that work to act on the pathological mechanisms.
Supporting people with dementia during the COVID-19 pandemic
Authors: Nazarko Linda 
Published: February 2021

People with dementia have experienced great disruption to their lives due to the pandemic. Linda Nazarko highlights the way individuals have been affected and how the practice nurse can support them People with dementia and their caregivers have been severely affected by the COVID-19 pandemic. Isolation, a reduction in formal and informal support, and disruption to routine have contributed to feelings of loneliness and anxiety in people with dementia and their caregivers. The pandemic has led to staff shortages in health and social care, changes of care workers and a reduction in the level of support provided. These changes have affected the physical and mental health of people with dementia and increased their reliance on primary care. Practice nurses have a key role to play in supporting affected individuals.
A randomized clinical trial of low dose single antibiotic-loaded cement versus high dose dual antibiotic-loaded cement in patients receiving a hip hemiarthroplasty after fracture: A protocol for the WHiTE 8 COPAL study
Authors: Agni Nickil Ramesh , Costa Matthew L. , Achten Juul , O’Connor Heather , Png May Ee , Peckham Nicholas , Dutton Susan J. , Wallis Stephanie , Milca Svetlana , Reed Mike 
Published: February 2021

Aims Patients receiving cemented hemiarthroplasties after hip fracture have a significant risk of deep surgical site infection (SSI). Standard UK practice to minimize the risk of SSI includes the use of antibiotic-loaded bone cement with no consensus regarding type, dose, or antibiotic content of the cement. This is the protocol for a randomized clinical trial to investigate the clinical and cost-effectiveness of high dose dual antibiotic-loaded cement in comparison to low dose single antibiotic-loaded cement in patients 60 years and over receiving a cemented hemiarthroplasty for an intracapsular hip fracture. Methods The WHiTE 8 Copal Or Palacos Antibiotic Loaded bone cement trial (WHiTE 8 COPAL) is a multicentre, multi-surgeon, parallel, two-arm, randomized clinical trial. The pragmatic study will be embedded in the World Hip Trauma Evaluation (WHiTE) (ISRCTN 63982700). Participants, including those that lack capacity, will be allocated on a 1:1 basis stratified by recruitment centre to either a low dose single antibiotic-loaded bone cement or a high dose dual antibiotic-loaded bone cement. The primary analysis will compare the differences in deep SSI rate as defined by the Centers for Disease Control and Prevention within 90 days of surgery via medical record review and patient self-reported questionnaires. Secondary outcomes include UK Core Outcome Set for hip fractures, complications, rate of antibiotic prescription, resistance patterns of deep SSI, and resource use (more specifically, cost-effectiveness) up to four months post-randomization. A minimum of 4,920 patients will be recruited to obtain 90% power to detect an absolute difference of 1.5% in the rate of deep SSI at 90 days for the expected 3% deep SSI rate in the control group. Conclusion The results of this trial will provide evidence regarding clinical and cost-effectiveness between low dose single and high dose dual antibiotic-loaded bone cement, which will inform policy and practice guidelines such as the National Institute for Health and Care Excellence guidance on management of hip fractures. Cite this article: Bone Jt Open 2021;2(2):72–78.
1.3  GHz E-O bandwidth GaN-based micro-LED for multi-gigabit visible light communication
Authors: Wang Lei , Wei Zixian , Chen Chien-Ju , Wang Lai , Fu H. Y. , Zhang Li , Chen Kai-Chia , Wu Meng-Chyi , Dong Yuhan , Hao Zhibiao , Luo Yi 
Published: February 2021

The data rate of a visible light communication (VLC) system is basically determined by the electrical-to-optical (E-O) bandwidth of its light-emitting diode (LED) source. In order to break through the intrinsic limitation of the carrier recombination rate on E-O bandwidth in conventional c-plane LEDs based on InGaN quantum wells, a blue micro-LED with an active region of nano-structured InGaN wetting layer is designed, fabricated, and packaged to realize a high-speed VLC system. The E-O bandwidth of the micro-LED can reach up to 1.3 GHz. Based on this high-speed micro-LED, we demonstrated a data rate of 2 Gbps with a bit error rate (BER) of

1.2
×

10

−
3

with simple on-off keying signal for a 3-m real-time VLC. In addition, a 4-Gbps VLC system using quadrature phase shift keying-orthogonal frequency-division multiplexing with a BER of

3.2
×

10

−
3

is also achieved for the same scenario. Among all the point-to-point VLC systems based on a single-pixel LED, this work has the highest distance-bandwidth product of 3 GHz·m and the highest distance-rate product of 12 Gbps·m.
Observation of transition between multimode Q-switching and spatiotemporal mode locking
Authors: Liu Kewei , Xiao Xiaosheng , Yang Changxi 
Published: February 2021

We report experimental observation of multimode

Q

-switching and spatiotemporal mode locking in a multimode fiber laser. A typical steady

Q

-switching state is achieved with a 1.88 μs pulse duration, a 70.14 kHz repetition rate, and a 215.8 mW output power, corresponding to the single pulse energy of 3.08 μJ. We find weak spatial filtering is essential to obtain stable

Q

-switched pulses, in contrast to the relatively stronger spatial filtering for spatiotemporal mode locking. Furthermore, a reversible transition process, as well as a critical bistable state, between multimode

Q

-switching and spatiotemporal mode locking, is achieved with specific spatial coupling and waveplates sets. We believe the results will not only contribute to understanding the complicated nonlinear dynamics in multimode, fiber-based platforms, but also benefit the development of promising high-pulse energy lasers.
High-speed silicon photonic Mach–Zehnder modulator at 2 μm
Authors: Wang Xi , Shen Weihong , Li Wenxiang , Liu Yingjie , Yao Yong , Du Jiangbing , Song Qinghai , Xu Ke 
Published: February 2021

Recently, 2-μm wave band has gained increasing interest due to its potential application for next-generation optical communication. But the development of 2-μm optical communications is substantially hampered by the modulation speed due to the device bandwidth constraints. Thus, a high-speed modulator is highly demanded at 2 μm. Motivated by this prospect, we demonstrate a high-speed silicon Mach–Zehnder modulator for a 2-μm wave band. The device is configured as a single-ended push–pull structure with waveguide electrorefraction via the free carrier plasma effect. The modulator was fabricated via a multiproject wafer shuttle run at a commercial silicon photonic foundry. The modulation efficiency of a single arm is measured to be

1.6

V
·
cm

. The high-speed characterization is also performed, and the modulation speed can reach 80 Gbit/s with 4-level pulse amplitude modulation (PAM-4) formats.