bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipopolysaccharide induced systemic inflammation and heart rate variability in a term newborn piglet model
Authors: Pedersen Mette Vestergård , Renberg Ann Frida Videbæk , Christensen Julie Kehlet , Andersen Hannah Brogaard , Andelius Ted Carl Kejlberg , Kyng Kasper Jacobsen , Andersen Mads , Henriksen Tine Brink 
Published: July 2024

Abstract

Background
Early biomarkers are needed to improve diagnosis and support antibiotic stewardship in neonatal sepsis. Heart rate variability (HRV) is proposed as such a biomarker. However, there is a lack of studies in term newborns. Infusion of lipopolysaccharide (LPS) from Escherichia coli induces systemic inflammation comparable to sepsis in newborns. We aimed to study the effect of systemic LPS induced inflammation on HRV in term newborn piglets.

Methods
Baseline HRV was recorded for 1 h. This control period was compared to the hourly HRV for each piglet (n = 9) during 4 h of LPS infusion. For comparison, we used a mixed-effects regression model.

Results
Systemic inflammation induced by LPS was found to reduce HRV. Compared to baseline, most measures of HRV decreased to lower values compared to baseline at 2 h, 3 h, and 4 h after initiation of LPS infusion. Heart rate (HR) was increased at 2 h, 3 h, and 4 h. When adjusting for HR in the mixed-effects regression model all reductions in HRV were explained by the increase in HR.

Conclusions
Reduced HRV may be an early biomarker of neonatal sepsis. However, an increase in HR alone could be an already available, more accessible, and interpretable biomarker of sepsis in term neonates.

Impact

In a term newborn piglet model, systemic inflammation induced by lipopolysaccharide from Escherichia coli reduced heart rate variability measures and increased heart rate.

All reductions in heart rate variability were mediated by heart rate.

While heart rate variability may be a biomarker of sepsis in term newborns, changes in heart rate alone could be a more readily available biomarker.
Developing a phenotype risk score for tic disorders in a large, clinical biobank
Authors: Miller-Fleming Tyne W. , Allos Annmarie , Gantz Emily , Yu Dongmei , Isaacs David A. , Mathews Carol A. , Scharf Jeremiah M. , Davis Lea K. 
Published: July 2024

AbstractTics are a common feature of early-onset neurodevelopmental disorders, characterized by involuntary and repetitive movements or sounds. Despite affecting up to 2% of children and having a genetic contribution, the underlying causes remain poorly understood. In this study, we leverage dense phenotype information to identify features (i.e., symptoms and comorbid diagnoses) of tic disorders within the context of a clinical biobank. Using de-identified electronic health records (EHRs), we identified individuals with tic disorder diagnosis codes. We performed a phenome-wide association study (PheWAS) to identify the EHR features enriched in tic cases versus controls (n = 1406 and 7030; respectively) and found highly comorbid neuropsychiatric phenotypes, including: obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, and anxiety (p < 7.396 × 10−5). These features (among others) were then used to generate a phenotype risk score (PheRS) for tic disorder, which was applied across an independent set of 90,051 individuals. A gold standard set of tic disorder cases identified by an EHR algorithm and confirmed by clinician chart review was then used to validate the tic disorder PheRS; the tic disorder PheRS was significantly higher among clinician-validated tic cases versus non-cases (p = 4.787 × 10−151; β = 1.68; SE = 0.06). Our findings provide support for the use of large-scale medical databases to better understand phenotypically complex and underdiagnosed conditions, such as tic disorders.
ZDHHC1 downregulates LIPG and inhibits colorectal cancer growth via IGF2BP1 Palmitoylation
Authors: Zhang Qun , Du Zhouyuan , Zhou Wei , Li Wei , Yang Qinglin , Yu Haixin , Liu Tao 
Published: July 2024

AbstractAlteration in lipid metabolism is recognized as a hallmark feature of colorectal cancer (CRC). Protein S-palmitoylation plays a critical role in many different cellular processes including protein-lipid interaction. Zinc Finger DHHC-Type Containing 1 (ZDHHC1, also known as ZNF377) belongs to the palmitoyl-transferase ZDHHC family, and is a potential tumor suppressor. However, our knowledge of the functional roles of ZDHHC1 in CRC is limited. We discovered that ZDHHC1 expression was downregulated in CRC tissues and that low levels of ZDHHC1 were associated with unfavorable prognosis. Functional studies showed that ZDHHC1 inhibited CRC cell proliferation and invasion in vitro and in vivo. We also found that lipase G (LIPG) is negatively regulated by ZDHHC1 and plays a key role in CRC cell growth through lipid storage. Additionally, we demonstrated that ZDHHC1 functions as a IGF2BP1-palmitoylating enzyme that induces S-palmitoylation at IGF2BP1-C337, which results in downregulated LIPG expression via m6A modification. Mechanistic investigations revealed that the ZDHHC1/IGF2BP1/LIPG signaling axis is associated with inhibition of CRC cell growth. Our study uncovers the potential role of ZDHHC1 in CRC, including inhibition of CRC growth by reducing the stability of LIPG mRNA in an m6A dependent-manner by palmitoylation of IGF2BP1.
Glucocorticoid receptor controls atopic dermatitis inflammation via functional interactions with P63 and autocrine signaling in epidermal keratinocytes
Authors: Sevilla Lisa M. , Pons-Alonso Omar , Gallego Andrea , Azkargorta Mikel , Elortza Félix , Pérez Paloma 
Published: July 2024

AbstractAtopic dermatitis (AD), a prevalent chronic inflammatory disease with multifactorial etiology, features epidermal barrier defects and immune overactivation. Synthetic glucocorticoids (GCs) are widely prescribed for treating AD due to their anti-inflammatory actions; however, mechanisms are incompletely understood. Defective local GC signaling due to decreased production of endogenous ligand and/or GC receptor (GR) levels was reported in prevalent inflammatory skin disorders; whether this is a consequence or contributing factor to AD pathology is unclear. To identify the chromatin-bound cell-type-specific GR protein interactome in keratinocytes, we used rapid immunoprecipitation of endogenous proteins and mass spectrometry identifying 145 interactors that increased upon dexamethasone treatment. GR-interacting proteins were enriched in p53/p63 signaling, including epidermal transcription factors with critical roles in AD pathology. Previous analyses indicating mirrored AD-like phenotypes between P63 overexpression and GR loss in epidermis, and our data show an intricate relationship between these transcription factors in human keratinocytes, identifying TP63 as a direct GR target. Dexamethasone treatment counteracted transcriptional up-regulation of inflammatory markers by IL4/IL13, known to mimic AD, causing opposite shifts in GR and P63 genomic binding. Indeed, IL4/IL13 decreased GR and increased P63 levels in cultured keratinocytes and human epidermal equivalents (HEE), consistent with GR down-regulation and increased P63 expression in AD lesions vs normal skin. Moreover, GR knockdown (GRKD) resulted in constitutive increases in P63, phospho-P38 and S100A9, IL6, and IL33. Also, GRKD culture supernatants showed increased autocrine production of TH2-/TH1-/TH17-TH22-associated factors including IL4, CXCL10, CXCL11, and CXCL8. GRKD HEEs showed AD-like features including hyperplasia and abnormal differentiation, resembling phenotypes observed with GR antagonist or IL4/IL13 treatment. The simultaneous GR/P63 knockdown partially reversed constitutive up-regulation of inflammatory genes in GRKD. In summary, our data support a causative role for GR loss in AD pathogenesis via functional interactions with P63 and autocrine signaling in epidermal keratinocytes.
Dairy consumption and vitamin D concentration in adolescents with challenge-confirmed cow’s milk allergy during infancy
Authors: Piippo Sonja , Hauta-alus Helena , Viljanen Mirva , Savilahti Erkki , Kuitunen Mikael 
Published: July 2024

Abstract
Background/Objectives
Milk is an important source of dietary calcium and, if fortified, vitamin D. Cow’s milk allergy (CMA) is treated with a milk elimination diet. Although most children become tolerant by age 3 years, some continue dairy avoidance. It remains unclear whether adolescents with a history of CMA adopt similar milk consumption as their peers. We assessed dairy consumption and concentration of serum 25-hydroxyvitamin D (25(OH)D) in adolescents with either confirmed CMA or a negative CMA challenge in infancy (CMA-refuted group) and age-matched controls.

Subjects/Methods
This study is based on a previously reported randomized controlled trial from 1999 to 2002 on the treatment effect of probiotics on atopic eczema in participants aged <12 months (n = 230) with data on CMA status. We followed up these participants, aged 15–18 years, in 2017 (n = 104). A 20-item food frequency questionnaire assessed dairy consumption. An automated immunoassay measured 25(OH)D concentration.

Results
Median dairy product consumption did not differ between adolescents with CMA (449 g/d, n = 40), the CMA-refuted group (566 g/d, n = 36), and controls (235 g/d, n = 51) (P = 0.117). Median 25(OH)D concentrations were 76.0, 79.3, and 80.8 nmol/l, respectively (P = 0.844). Among participants, 93% were vitamin D sufficient (25(OH)D ≥ 50 nmol/l), with no differences between groups (P = 0.914).

Conclusion
Among adolescents with a history of CMA during infancy, our study found no reintroduction failure of milk and no difference in vitamin D insufficiency rate compared with peers. Current management of CMA seems to adequately minimize later nutritional disadvantages associated with a cow’s milk elimination diet.
Interplay of valley, layer and band topology towards interacting quantum phases in moiré bilayer graphene
Authors: Jeong Yungi , Park Hangyeol , Kim Taeho , Watanabe Kenji , Taniguchi Takashi , Jung Jeil , Jang Joonho 
Published: July 2024

AbstractIn Bernal-stacked bilayer graphene (BBG), the Landau levels give rise to an intimate connection between valley and layer degrees of freedom. Adding a moiré superlattice potential enriches the BBG physics with the formation of topological minibands — potentially leading to tunable exotic quantum transport. Here, we present magnetotransport measurements of a high-quality bilayer graphene–hexagonal boron nitride (hBN) heterostructure. The zero-degree alignment generates a strong moiré superlattice potential for the electrons in BBG and the resulting Landau fan diagram of longitudinal and Hall resistance displays a Hofstadter butterfly pattern with a high level of detail. We demonstrate that the intricate relationship between valley and layer degrees of freedom controls the topology of moiré-induced bands, significantly influencing the energetics of interacting quantum phases in the BBG superlattice. We further observe signatures of field-induced correlated insulators, helical edge states and clear quantizations of interaction-driven topological quantum phases, such as symmetry broken Chern insulators.
Pt nanoshells with a high NIR-II photothermal conversion efficiency mediates multimodal neuromodulation against ventricular arrhythmias
Authors: Wang Chenlu , Zhou Liping , Liu Chengzhe , Qiao Jiaming , Han Xinrui , Wang Luyang , Liu Yaxi , Xu Bi , Qiu Qinfang , Zhang Zizhuo , Wang Jiale , Zhou Xiaoya , Zeng Mengqi , Yu Lilei , Fu Lei 
Published: July 2024

AbstractAutonomic nervous system disorders play a pivotal role in the pathophysiology of cardiovascular diseases. Regulating it is essential for preventing and treating acute ventricular arrhythmias (VAs). Photothermal neuromodulation is a nonimplanted technique, but the response temperature ranges of transient receptor potential vanilloid 1 (TRPV1) and TWIK-related K+ Channel 1 (TREK1) exhibit differences while being closely aligned, and the acute nature of VAs require that it must be rapid and precise. However, the low photothermal conversion efficiency (PCE) still poses limitations in achieving rapid and precise treatment. Here, we achieve a nearly perfect blackbody absorption and a high PCE in the second near infrared (NIR-II) window (73.7% at 1064 nm) via a Pt nanoparticle shell (PtNP-shell). By precisely manipulating the photothermal effect, we successfully achieve rapid and precise multimodal neuromodulation encompassing neural activation (41.0–42.9 °C) and inhibition (45.0–46.9 °C) in a male canine model. The NIR-II photothermal modulation additionally achieves multimodal reversible autonomic modulation and confers protection against acute VAs associated with myocardial ischemia and reperfusion injury in interventional therapy.
Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging
Authors: Occean James R. , Yang Na , Sun Yan , Dawkins Marshall S. , Munk Rachel , Belair Cedric , Dar Showkat , Anerillas Carlos , Wang Lin , Shi Changyou , Dunn Christopher , Bernier Michel , Price Nathan L. , Kim Julie S. , Cui Chang-Yi , Fan Jinshui , Bhattacharyya Moitrayee , De Supriyo , Maragkakis Manolis , de Cabo Rafael , Sidoli Simone , Sen Payel 
Published: July 2024

AbstractDNA hydroxymethylation (5hmC), the most abundant oxidative derivative of DNA methylation, is typically enriched at enhancers and gene bodies of transcriptionally active and tissue-specific genes. Although aberrant genomic 5hmC has been implicated in age-related diseases, its functional role in aging remains unknown. Here, using mouse liver and cerebellum as model organs, we show that 5hmC accumulates in gene bodies associated with tissue-specific function and restricts the magnitude of gene expression changes with age. Mechanistically, 5hmC decreases the binding of splicing associated factors and correlates with age-related alternative splicing events. We found that various age-related contexts, such as prolonged quiescence and senescence, drive the accumulation of 5hmC with age. We provide evidence that this age-related transcriptionally restrictive function is conserved in mouse and human tissues. Our findings reveal that 5hmC regulates tissue-specific function and may play a role in longevity.
Bayesian blacksmithing: discovering thermomechanical properties and deformation mechanisms in high-entropy refractory alloys
Authors: Startt Jacob , McCarthy Megan J. , Wood Mitchell A. , Donegan Sean , Dingreville Rémi 
Published: July 2024

AbstractFinding alloys with specific design properties is challenging due to the large number of possible compositions and the complex interactions between elements. This study introduces a multi-objective Bayesian optimization approach guiding molecular dynamics simulations for discovering high-performance refractory alloys with both targeted intrinsic static thermomechanical properties and also deformation mechanisms occurring during dynamic loading. The objective functions are aiming for excellent thermomechanical stability via a high bulk modulus, a low thermal expansion, a high heat capacity, and for a resilient deformation mechanism maximizing the retention of the BCC phase after shock loading. Contrasting two optimization procedures, we show that the Pareto-optimal solutions are confined to a small performance space when the property objectives display a cooperative relationship. Conversely, the Pareto front is much broader in the performance space when these properties have antagonistic relationships. Density functional theory simulations validate these findings and unveil underlying atomic-bond changes driving property improvements.
Tailored molecular for ultra-stability and biocompatible pseudohalide metal-free perovskite towards X-ray detectors with record sensitivity
Authors: Lei Yutian , Yin Mengying , Shi Chang , Wu Lingxi , Peng Guoqiang , Xu Youkui , Wang Haoxu , Tang Rongbing , Li ZhenHua , Jin Zhiwen 
Published: July 2024

AbstractThe emerging pseudohalide metal-free perovskite (pseudohalide–MFPs) X-ray detector caters to the demands of timely mobile diagnosis owing to its lightweight, flexibility, and cost-effectiveness. However, the performance of these devices is severely limited by poor X-ray absorption, ultra-wide band gap, relative instability, and their unknown biotoxicity. Herein, we construct heavy atom covalent bonds (C–Br/Cl) on the A-site organic cation to reinforce component coordination to modulate X-ray absorption and band gap in pseudohalide–MFPs and further enhance its stability. Molecular dynamics simulations demonstrate that the introduction of halogen atoms can strengthen hydrogen bonding interactions, thereby improving the coordination between different components. The resultant (MDABCOBr)–NH4(BF4)3 (MDABCO = N-methyl-N’-diazabicyclo[2.2.2]octonium) single crystal significantly increases X-ray absorption cross-section and crystalline density (from 1.728 to 1.950 g cm−3), and synergistically realizes the band nature modulation (from 7.4 to 5.5 eV) and enhanced ionic migration inhibition (628 meV) with optimized stability. As such, our X-ray detectors realized a sensitivity of 2377 μC Gyair−1 cm−2, an ultralow detection limit of 50.1 nGyair s−1, and impressive operation stability. Moreover, cytotoxicity assay confirmed the compatibility of pseudohalide metal-free perovskite. Finally, within this framework, we successfully fabricate the (MDABCOBr)–NH4(BF4)3-based flexible device to create an ideal in vitro wearable X-ray detection.
Human tripartite cortical network model for temporal assessment of alpha-synuclein aggregation and propagation in Parkinson’s Disease
Authors: Kapucu Fikret Emre , Tujula Iisa , Kulta Oskari , Sukki Lassi , Ryynänen Tomi , Gram Hjalte , Vuolanto Valtteri , Vinogradov Andrey , Kreutzer Joose , Jensen Poul Henning , Kallio Pasi , Narkilahti Susanna 
Published: July 2024

AbstractPrevious studies have shown that aggregated alpha-synuclein (α-s) protein, a key pathological marker of Parkinson’s disease (PD), can propagate between cells, thus participating in disease progression. This prion-like propagation has been widely studied using in vivo and in vitro models, including rodent and human cell cultures. In this study, our focus was on temporal assessment of functional changes during α-s aggregation and propagation in human induced pluripotent stem cell (hiPSC)-derived neuronal cultures and in engineered networks. Here, we report an engineered circular tripartite human neuronal network model in a microfluidic chip integrated with microelectrode arrays (MEAs) as a platform to study functional markers during α-s aggregation and propagation. We observed progressive aggregation of α-s in conventional neuronal cultures and in the exposed (proximal) compartments of circular tripartite networks following exposure to preformed α-s fibrils (PFF). Furthermore, aggregated forms propagated to distal compartments of the circular tripartite networks through axonal transport. We observed impacts of α-s aggregation on both the structure and function of neuronal cells, such as in presynaptic proteins, mitochondrial motility, calcium oscillations and neuronal activity. The model enabled an assessment of the early, middle, and late phases of α-s aggregation and its propagation during a 13-day follow-up period. While our temporal analysis suggested a complex interplay of structural and functional changes during the in vitro propagation of α-s aggregates, further investigation is required to elucidate the underlying mechanisms. Taken together, this study demonstrates the technical potential of our introduced model for conducting in-depth analyses for revealing such mechanisms.
Observational threat learning influences costly avoidance behaviour in healthy humans
Authors: Mueller Madeleine , Cohen Oded , Shechner Tomer , Haaker Jan 
Published: July 2024

AbstractAvoidance is an essential behaviour for ensuring safety in uncertain and dangerous environments. One way to learn what is dangerous and must be avoided is through observational threat learning. This online study explored the behavioural implications of observed threat learning, examining how participants avoided or approached a learned threat and how this affected their movement patterns. Participants (n = 89) completed an observational threat learning task, rating their fear, discomfort, and physical arousal in response to conditioned stimuli. The retrieval of learned threat was reassessed 24 h later, followed by a reminder of the observed threat associations. Participants subsequently completed a computerised avoidance task, in which they navigated from a starting point to an endpoint by selecting one of two doors, each associated with either safety or danger, relying on observed information. Opting for the safe door entailed increased effort to attain the goal. Results demonstrated that observational threat learning influenced avoidance behaviour and decision-making dependent on baseline effort level. Participants tended to exhibit thigmotaxis, staying close to walls and taking extra steps to reach their goal. This behaviour indirectly mediated the number of steps taken. This study provides valuable insights into avoidance behaviour following observational threat learning in healthy humans.
The impact of tetrodotoxin (TTX) on the gut microbiome in juvenile tiger pufferfish, Takifugu rubripes
Authors: Wassel Mai A. , Makabe-Kobayashi Yoko , Iqbal Md Mehedi , Takatani Tomohiro , Sakakura Yoshitaka , Hamasaki Koji 
Published: July 2024

AbstractTetrodotoxin (TTX) is a potent neurotoxin that accumulates in Takifugu rubripes, commonly known as pufferfish, through the ingestion of TTX-bearing organisms as part of their food chain. Although researchers believe that pufferfish use TTX to relieve stress, data are not currently available on how TTX affects the gut microbiota of pufferfish. To address this gap, our study aimed to investigate whether administering TTX to fish could alter their gut microbiota and overall health under various salinity conditions, including 30.0 ppt, 8.5 ppt, and 1.7 ppt salinity, which represent full-strength, isosmotic, and low-salinity stress, respectively. We analyzed the effect of TTX ingestion on the community structure, core microbiome, and metabolic capabilities of the gut microbiome using high-throughput sequencing technologies. The predominant bacterial taxa within the gut microbiome were Firmicutes (21–85%), Campilobacterota (2.8–67%), Spirochaetota (0.5–14%), and Proteobacteria (0.7–9.8%), with Mycoplasma, uncultured Arcobacteraceae, Brevinema, Vibrio, Rubritalea, and uncultured Pirellulaceae as core genera. Our findings indicated that the impact of TTX on high-abundance genera at 30.0 ppt and 8.5 ppt salinity levels was negligible, indicating their stability and resilience to TTX ingestion. However, at 1.7 ppt, TTX-fed fish showed a significant increase in uncultured Arcobacteraceae. Furthermore, our analysis of TTX-fed fish revealed taxonomic alterations in low-abundance taxa, which altered the predicted functions of the gut microbiota at all salinity levels. These results suggest that TTX administration could cause subtle effects on the metabolic functions of gut microbial communities. Overall, our study provides insights into the complex relationship between a TTX-accumulating animal, T. rubripes, and its gut microbiota.