bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for protein leverage in a general population sample of children and adolescents
Authors: Saner Christoph , Senior Alistair M. , Zhang Hanyue , Eloranta Aino-Maija , Magnussen Costan G. , Sabin Matthew A. , Juonala Markus , Janner Marco , Burgner David P. , Schwab Ursula , Haapala Eero A. , Heitmann Berit L. , Simpson Stephen J. , Raubenheimer David , Lakka Timo A. 
Published: February 2023

Abstract
Background/Objectives
The strong regulation of protein intake can lead to overconsumption of total energy on diets with a low proportion of energy from protein, a process referred to as protein leverage. The protein leverage hypothesis posits that protein leverage explains variation in energy intake and potentially obesity in ecological settings. Here, we tested for protein leverage and the protein leverage hypothesis in children and adolescents.

Subjects/Methods
A population sample of children, mean (SD) age 7.6 (0.4) years (n = 422), followed up at age 9.8 (0.4) years (n = 387) and at age 15.8 (0.4) years (n = 229), participating for the Physical Activity and Nutrition in Children (PANIC) study. Exposures: 4-day food records-related proportional energy intake of proteins, fats, and carbohydrates. Outcomes: energy intake, body mass index (BMI) z-score and dual-energy X-ray absorptiometry-related energy expenditure.

Results
Proportional energy intake of proteins was inversely associated with energy intake following power functions at all 3 ages (mean [95%CI] strength of leverage of L = −0.36 [−0.47 to −0.25]; L = −0.26 [−0.37 to −0.15]; L = −0.25 [−0.38 to −0.13]; all P < 0.001). Mixture analysis indicated that variance in energy intake was associated primarily with the proportional intake of energy from proteins, not with either fats or carbohydrates. At all 3 ages, energy intake was not associated with BMI z-score but positively associated with energy expenditure (all P < 0.001).

Conclusions
This study provides evidence consistent with protein leverage in a population sample of children and adolescents. Increased energy intake on diets with lower protein content was counterbalanced by increased energy expenditure and therefore did not translate into increased adiposity.
Chondrule-like objects and Ca-Al-rich inclusions in Ryugu may potentially be the oldest Solar System materials
Authors: Nakashima Daisuke , Nakamura Tomoki , Zhang Mingming , Kita Noriko T. , Mikouchi Takashi , Yoshida Hideto , Enokido Yuma , Morita Tomoyo , Kikuiri Mizuha , Amano Kana , Kagawa Eiichi , Yada Toru , Nishimura Masahiro , Nakato Aiko , Miyazaki Akiko , Yogata Kasumi , Abe Masanao , Okada Tatsuaki , Usui Tomohiro , Yoshikawa Makoto , Saiki Takanao , Tanaka Satoshi , Nakazawa Satoru , Terui Fuyuto , Yurimoto Hisayoshi , Noguchi Takaaki , Yabuta Hikaru , Naraoka Hiroshi , Okazaki Ryuji , Sakamoto Kanako , Watanabe Sei-ichiro , Tachibana Shogo , Tsuda Yuichi 
Published: February 2023

AbstractChondrule-like objects and Ca-Al-rich inclusions (CAIs) are discovered in the retuned samples from asteroid Ryugu. Here we report results of oxygen isotope, mineralogical, and compositional analysis of the chondrule-like objects and CAIs. Three chondrule-like objects dominated by Mg-rich olivine are16O-rich and -poor with Δ17O (=δ17O – 0.52 × δ18O) values of ~ –23‰ and ~ –3‰, resembling what has been proposed as early generations of chondrules. The16O-rich objects are likely to be melted amoeboid olivine aggregates that escaped from incorporation into16O-poor chondrule precursor dust. Two CAIs composed of refractory minerals are16O-rich with Δ17O of ~ –23‰ and possibly as old as the oldest CAIs. The discovered objects (<30 µm) are as small as those from comets, suggesting radial transport favoring smaller objects from the inner solar nebula to the formation location of the Ryugu original parent body, which is farther from the Sun and scarce in chondrules. The transported objects may have been mostly destroyed during aqueous alteration in the Ryugu parent body.
The ULK3 kinase is a determinant of keratinocyte self-renewal and tumorigenesis targeting the arginine methylome
Authors: Goruppi Sandro , Clocchiatti Andrea , Bottoni Giulia , Di Cicco Emery , Ma Min , Tassone Beatrice , Neel Victor , Demehri Shadhmer , Simon Christian , Paolo Dotto G. 
Published: February 2023

AbstractEpigenetic mechanisms oversee epidermal homeostasis and oncogenesis. The identification of kinases controlling these processes has direct therapeutic implications. We show that ULK3 is a nuclear kinase with elevated expression levels in squamous cell carcinomas (SCCs) arising in multiple body sites, including skin and Head/Neck. ULK3 loss by gene silencing or deletion reduces proliferation and clonogenicity of human keratinocytes and SCC-derived cells and affects transcription impinging on stem cell-related and metabolism programs. Mechanistically, ULK3 directly binds and regulates the activity of two histone arginine methyltransferases, PRMT1 and PRMT5 (PRMT1/5), with ULK3 loss compromising PRMT1/5 chromatin association to specific genes and overall methylation of histone H4, a shared target of these enzymes. These findings are of translational significance, as downmodulating ULK3 by RNA interference or locked antisense nucleic acids (LNAs) blunts the proliferation and tumorigenic potential of SCC cells and promotes differentiation in two orthotopic models of skin cancer.
Methionine adenosyltransferase2A inhibition restores metabolism to improve regenerative capacity and strength of aged skeletal muscle
Authors: Rajabian Nika , Ikhapoh Izuagie , Shahini Shahryar , Choudhury Debanik , Thiyagarajan Ramkumar , Shahini Aref , Kulczyk Joseph , Breed Kendall , Saha Shilpashree , Mohamed Mohamed Alaa , Udin Susan B. , Stablewski Aimee , Seldeen Kenneth , Troen Bruce R. , Personius Kirkwood , Andreadis Stelios T. 
Published: February 2023

AbstractWe investigate the age-related metabolic changes that occur in aged and rejuvenated myoblasts using in vitro and in vivo models of aging. Metabolic and signaling experiments reveal that human senescent myoblasts and myoblasts from a mouse model of premature aging suffer from impaired glycolysis, insulin resistance, and generate Adenosine triphosphate by catabolizing methionine via a methionine adenosyl-transferase 2A-dependant mechanism, producing significant levels of ammonium that may further contribute to cellular senescence. Expression of the pluripotency factor NANOG downregulates methionine adenosyltransferase 2 A, decreases ammonium, restores insulin sensitivity, increases glucose uptake, and enhances muscle regeneration post-injury. Similarly, selective inhibition of methionine adenosyltransferase 2 A activates Akt2 signaling, repairs pyruvate kinase, restores glycolysis, and enhances regeneration, which leads to significant enhancement of muscle strength in a mouse model of premature aging. Collectively, our investigation indicates that inhibiting methionine metabolism may restore age-associated impairments with significant gain in muscle function.
North Atlantic oscillation controls multidecadal changes in the North Tropical Atlantic−Pacific connection
Authors: Ding Ruiqiang , Nnamchi Hyacinth C. , Yu Jin-Yi , Li Tim , Sun Cheng , Li Jianping , Tseng Yu‐Heng , Li Xichen , Xie Fei , Feng Juan , Ji Kai , Li Xumin 
Published: February 2023

AbstractBy exciting subtropical teleconnections, sea surface temperature (SST) anomalies in the North Tropical Atlantic (NTA) during boreal spring can trigger El Niño-Southern Oscillation (ENSO) events in the following boreal winter, thereby providing a precursor for ENSO predictability. However, this NTA−ENSO connection is not stationary, and it varies considerably over multidecadal timescales, which cannot be directly explained by the Atlantic multidecadal oscillation or the global warming trend. Here we show that multidecadal changes in the NTA−ENSO connection are principally controlled by multidecadal variability associated with the North Atlantic Oscillation (NAO). During the positive phase of the NAO, the amplification of the NTA impact on ENSO mainly arises from strengthening of the boreal spring mean precipitation over the equatorial Atlantic and enhancement of the persistence of NTA SST anomalies, which enhance the NTA influence by exciting stronger and more persistent subtropical teleconnections. Our findings show that multidecadal variability of the NAO is key to understanding the impacts of the NTA SST on the tropical Pacific Ocean.
Directed self-assembly of a xenogeneic vascularized endocrine pancreas for type 1 diabetes
Authors: Citro Antonio , Neroni Alessia , Pignatelli Cataldo , Campo Francesco , Policardi Martina , Monieri Matteo , Pellegrini Silvia , Dugnani Erica , Manenti Fabio , Maffia Maria Chiara , Valla Libera , Kemter Elisabeth , Marzinotto Ilaria , Olgasi Cristina , Cucci Alessia , Follenzi Antonia , Lampasona Vito , Wolf Eckhard , Piemonti Lorenzo 
Published: February 2023

AbstractIntrahepatic islet transplantation is the standard cell therapy for β cell replacement. However, the shortage of organ donors and an unsatisfactory engraftment limit its application to a selected patients with type 1 diabetes. There is an urgent need to identify alternative strategies based on an unlimited source of insulin producing cells and innovative scaffolds to foster cell interaction and integration to orchestrate physiological endocrine function. We previously proposed the use of decellularized lung as a scaffold for β cell replacement with the final goal of engineering a vascularized endocrine organ. Here, we prototyped this technology with the integration of neonatal porcine islet and healthy subject-derived blood outgrowth endothelial cells to engineer a xenogeneic vascularized endocrine pancreas. We validated ex vivo cell integration and function, its engraftment and performance in a preclinical model of diabetes. Results showed that this technology not only is able to foster neonatal pig islet maturation in vitro, but also to perform in vivo immediately upon transplantation and for over 18 weeks, compared to normal performance within 8 weeks in various state of the art preclinical models. Given the recent progress in donor pig genetic engineering, this technology may enable the assembly of immune-protected functional endocrine organs.
Single-cell atavism reveals an ancient mechanism of cell type diversification in a sea anemone
Authors: Babonis Leslie S. , Enjolras Camille , Reft Abigail J. , Foster Brent M. , Hugosson Fredrik , Ryan Joseph F. , Daly Marymegan , Martindale Mark Q. 
Published: February 2023

AbstractCnidocytes are the explosive stinging cells unique to cnidarians (corals, jellyfish, etc). Specialized for prey capture and defense, cnidocytes comprise a group of over 30 morphologically and functionally distinct cell types. These unusual cells are iconic examples of biological novelty but the developmental mechanisms driving diversity of the stinging apparatus are poorly characterized, making it challenging to understand the evolutionary history of stinging cells. Using CRISPR/Cas9-mediated genome editing in the sea anemoneNematostella vectensis, we show that a single transcription factor (NvSox2) acts as a binary switch between two alternative stinging cell fates. Knockout ofNvSox2causes a transformation of piercing cells into ensnaring cells, which are common in other species of sea anemone but appear to have been silenced inN. vectensis. These results reveal an unusual case of single-cell atavism and expand our understanding of the diversification of cell type identity.
Optogenetic stimulation of anterior insular cortex neurons in male rats reveals causal mechanisms underlying suppression of the default mode network by the salience network
Authors: Menon Vinod , Cerri Domenic , Lee Byeongwook , Yuan Rui , Lee Sung-Ho , Shih Yen-Yu Ian 
Published: February 2023

AbstractThe salience network (SN) and default mode network (DMN) play a crucial role in cognitive function. The SN, anchored in the anterior insular cortex (AI), has been hypothesized to modulate DMN activity during stimulus-driven cognition. However, the causal neural mechanisms underlying changes in DMN activity and its functional connectivity with the SN are poorly understood. Here we combine feedforward optogenetic stimulation with fMRI and computational modeling to dissect the causal role of AI neurons in dynamic functional interactions between SN and DMN nodes in the male rat brain. Optogenetic stimulation of Chronos-expressing AI neurons suppressed DMN activity, and decreased AI-DMN and intra-DMN functional connectivity. Our findings demonstrate that feedforward optogenetic stimulation of AI neurons induces dynamic suppression and decoupling of the DMN and elucidates previously unknown features of rodent brain network organization. Our study advances foundational knowledge of causal mechanisms underlying dynamic cross-network interactions and brain network switching.
A sub-wavelength Si LED integrated in a CMOS platform
Authors: Li Zheng , Xue Jin , de Cea Marc , Kim Jaehwan , Nong Hao , Chong Daniel , Lim Khee Yong , Quek Elgin , Ram Rajeev J. 
Published: February 2023

AbstractA nanoscale on-chip light source with high intensity is desired for various applications in integrated photonics systems. However, it is challenging to realize such an emitter using materials and fabrication processes compatible with the standard integrated circuit technology. In this letter, we report an electrically driven Si light-emitting diode with sub-wavelength emission area fabricated in an open-foundry microelectronics complementary metal-oxide-semiconductor platform. The light-emitting diode emission spectrum is centered around 1100 nm and the emission area is smaller than 0.14 μm2 (~$$\varnothing 400$$
∅
400
nm). This light-emitting diode has high spatial intensity of >50 mW/cm2 which is comparable with state-of-the-art Si-based emitters with much larger emission areas. Due to sub-wavelength confinement, the emission exhibits a high degree of spatial coherence, which is demonstrated by incorporating the light-emitting diode into a compact lensless in-line holographic microscope. This centimeter-scale, all-silicon microscope utilizes a single emitter to simultaneously illuminate ~9.5 million pixels of a complementary metal-oxide-semiconductor imager.
Site-specific encoding of photoactivity and photoreactivity into antibody fragments
Authors: Bridge Thomas , Wegmann Udo , Crack Jason C. , Orman Kate , Shaikh Saher A. , Farndon William , Martins Carlo , Saalbach Gerhard , Sachdeva Amit 
Published: February 2023

AbstractDesign of biomolecules that perform two or more distinct functions in response to light remains challenging. Here, we have introduced concurrent photoactivity and photoreactivity into an epidermal growth factor receptor (EGFR)-targeting antibody fragment, 7D12. This was achieved by site-specific incorporation of photocaged tyrosine (pcY) for photoactivity and p-benzoyl-ʟ-phenylalanine (Bpa) for photoreactivity into 7D12. We identified a position for installing Bpa in 7D12 that has minimal effect on 7D12–EGFR binding affinity in the absence of light. Upon exposure to 365-nm light, this Bpa-containing 7D12 mutant forms a covalent bond with EGFR in an antigen-specific manner. We then developed a method for site-specific incorporation of pcY and Bpa at two distinct sites in 7D12. Finally, we demonstrated that in the absence of light, this pcY- and Bpa-containing mutant of 7D12 does not bind to EGFR, but irradiation with 365-nm light activates (1) specific binding and (2) covalent bond formation with EGFR.
Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice
Authors: Reichart Daniel , Newby Gregory A. , Wakimoto Hiroko , Lun Mingyue , Gorham Joshua M. , Curran Justin J. , Raguram Aditya , DeLaughter Daniel M. , Conner David A. , Marsiglia Júlia D. C. , Kohli Sajeev , Chmatal Lukas , Page David C. , Zabaleta Nerea , Vandenberghe Luk , Liu David R. , Seidman Jonathan G. , Seidman Christine 
Published: February 2023

AbstractDominant missense pathogenic variants in cardiac myosin heavy chain cause hypertrophic cardiomyopathy (HCM), a currently incurable disorder that increases risk for stroke, heart failure and sudden cardiac death. In this study, we assessed two different genetic therapies—an adenine base editor (ABE8e) and a potent Cas9 nuclease delivered by AAV9—to prevent disease in mice carrying the heterozygous HCM pathogenic variant myosin R403Q. One dose of dual-AAV9 vectors, each carrying one half of RNA-guided ABE8e, corrected the pathogenic variant in ≥70% of ventricular cardiomyocytes and maintained durable, normal cardiac structure and function. An additional dose provided more editing in the atria but also increased bystander editing. AAV9 delivery of RNA-guided Cas9 nuclease effectively inactivated the pathogenic allele, albeit with dose-dependent toxicities, necessitating a narrow therapeutic window to maintain health. These preclinical studies demonstrate considerable potential for single-dose genetic therapies to correct or silence pathogenic variants and prevent the development of HCM.
Radiomics analysis of contrast-enhanced T1W MRI: predicting the recurrence of acute pancreatitis
Authors: Tang Lingling , Ma Lin , Chen Yuying , Hu Yuntao , Chen Xinyue , Huang Xiaohua , Liu Nian 
Published: February 2023

AbstractTo investigate the predictive value of radiomics based on T1-weighted contrast-enhanced MRI (CE-MRI) in forecasting the recurrence of acute pancreatitis (AP). A total of 201 patients with first-episode of acute pancreatitis were enrolled retrospectively (140 in the training cohort and 61 in the testing cohort), with 69 and 30 patients who experienced recurrence in each cohort, respectively. Quantitative image feature extraction was obtained from MR contrast-enhanced late arterial-phase images. The optimal radiomics features retained after dimensionality reduction were used to construct the radiomics model through logistic regression analysis, and the clinical characteristics were collected to construct the clinical model. The nomogram model was established by linearly integrating the clinically independent risk factor with the optimal radiomics signature. The five best radiomics features were determined by dimensionality reduction. The radiomics model had a higher area under the receiver operating characteristic curve (AUC) than the clinical model for estimating the recurrence of acute pancreatitis for both the training cohort (0.915 vs. 0.811, p = 0.020) and testing cohort (0.917 vs. 0.681, p = 0.002). The nomogram model showed good performance, with an AUC of 0.943 in the training cohort and 0.906 in the testing cohort. The radiomics model based on CE-MRI showed good performance for optimizing the individualized prediction of recurrent acute pancreatitis, which provides a reference for the prevention and treatment of recurrent pancreatitis.
Quitting smoking after a cancer diagnosis is associated with high-risk neutrophil-to-lymphocyte ratio among tobacco use-related cancer survivors
Authors: Lu You , Kwong Katherine , Wells James , Edwards Andrea , Chen Zhong , Tseng Tung-Sung , Zhang Kun 
Published: February 2023

AbstractQuitting smoking could potentially minimize the risk of a high neutrophil-to-lymphocyte ratio (NLR) among tobacco use-related (TUR) cancer survivors. A total of 1263 TUR cancer survivors aged 20 to 85 years old were investigated using data from the National Health and Nutritional Examination Survey 1999–2018. The primary outcome was the NLR, which was defined as having two levels: high-risk (≥ 3) and low-risk (< 3). The association between smoking cessation time and a high-risk NLR level was analyzed using weighted logistic regression models. Overall, the current smoking rate of TUR cancer survivors was found to be 21.7%. Older age (75 years above), gender and respiratory-related cancers are covariables associated with high risk of NLR levels for individual who identified as Non-Hispanic White (NHW). Non-Hispanic Black (NHB) (n = 27) who quit smoking after a cancer diagnosis were associated with the highest risk of a high NLR (OR 4.83, 95% CI 1.40–16.61, p = 0.01) compared to NHB nonsmokers (n = 139). These findings suggest that the risk of a high NLR level is strongly associated with the time of smoking cessation in NHB TUR cancer survivors. As a result, NHB TUR cancer survivors should quit smoking as soon as possible because the benefits of quitting smoking were observed over the 5 year period following smoking cessation.
The importance of cultural tailoring of communicators and media outlets in an influenza vaccination awareness campaign: a digital randomized trial
Authors: Habib G. L. , Yousuf H. , Bredius L. , Bindraban N. R. , Winter M. M. , Scherder E. J. A. , van der Linden S. , Narula J. , Hofstra L. 
Published: February 2023

AbstractThe COVID-19 pandemic has exposed the vulnerability of ethnic minorities again. Health inequity within ethnic minorities has been explained by factors such as higher prevalence of underlying disease, restricted access to care, and lower vaccination rates. In this study, we investigated the effect of cultural tailoring of communicators and media outlets, respectively, on vaccine willingness in an influenza vaccination campaign in the Netherlands. A total of 1226 participants were recruited from two culturally non-tailored media outlets (Dutch newspaper and Facebook), and one media outlet tailored to a large community in the Netherlands with Indian ancestry. The participants from all three media outlets were randomly exposed to a vaccination awareness video delivered by a physician with an Indian or Dutch background, followed by an online survey. Cultural tailoring compared to cultural non-tailoring of communicators showed no difference in improvement of vaccine willingness (13.9% vs. 20.7% increment, respectively, p = 0.083). However, the media outlet tailored to the community with Indian ancestry, resulted in a higher improvement of vaccine willingness compared to non-tailored media outlets (46.7% vs. 14.7% increment, respectively, p < 0.001, unadjusted OR = 5.096). These results suggest that cultural tailoring of media outlets may be critical to effectively reach out to ethnic minorities to help optimize vaccination rates and improve general health.
Exposure to nonnative-accented speech reduces listening effort and improves social judgments of the speaker
Authors: Rovetti Joseph , Sumantry David , Russo Frank A. 
Published: February 2023

AbstractPrior research has revealed a native-accent advantage, whereby nonnative-accented speech is more difficult to process than native-accented speech. Nonnative-accented speakers also experience more negative social judgments. In the current study, we asked three questions. First, does exposure to nonnative-accented speech increase speech intelligibility or decrease listening effort, thereby narrowing the native-accent advantage? Second, does lower intelligibility or higher listening effort contribute to listeners’ negative social judgments of speakers? Third and finally, does increased intelligibility or decreased listening effort with exposure to speech bring about more positive social judgments of speakers? To address these questions, normal-hearing adults listened to a block of English sentences with a native accent and a block with nonnative accent. We found that once participants were accustomed to the task, intelligibility was greater for nonnative-accented speech and increased similarly with exposure for both accents. However, listening effort decreased only for nonnative-accented speech, soon reaching the level of native-accented speech. In addition, lower intelligibility and higher listening effort was associated with lower ratings of speaker warmth, speaker competence, and willingness to interact with the speaker. Finally, competence ratings increased over time to a similar extent for both accents, with this relationship fully mediated by intelligibility and listening effort. These results offer insight into how listeners process and judge unfamiliar speakers.