bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotype imputation methods for whole and complex genomic regions utilizing deep learning technology
Authors: Naito Tatsuhiko , Okada Yukinori 
Published: January 2024

AbstractThe imputation of unmeasured genotypes is essential in human genetic research, particularly in enhancing the power of genome-wide association studies and conducting subsequent fine-mapping. Recently, several deep learning-based genotype imputation methods for genome-wide variants with the capability of learning complex linkage disequilibrium patterns have been developed. Additionally, deep learning-based imputation has been applied to a distinct genomic region known as the major histocompatibility complex, referred to as HLA imputation. Despite their various advantages, the current deep learning-based genotype imputation methods do have certain limitations and have not yet become standard. These limitations include the modest accuracy improvement over statistical and conventional machine learning-based methods. However, their benefits include other aspects, such as their “reference-free” nature, which ensures complete privacy protection, and their higher computational efficiency. Furthermore, the continuing evolution of deep learning technologies is expected to contribute to further improvements in prediction accuracy and usability in the future.
Are probiotics effective in reducing the metabolic side effects of psychiatric medication? A scoping review of evidence from clinical studies
Authors: Mötteli Sonja , Vetter Stefan , Colla Michael , Hotzy Florian 
Published: January 2024

AbstractThe psychopharmacological treatment of patients with schizophrenia or depression is often accompanied by serious side effects. In particular, the clinical findings of weight gain are worrying, as this side effect can lead to various medical sequelae in the future. However, the treatment of metabolic changes in psychiatric patients is often neglected or unsuccessful. An improved knowledge of possible therapeutic approaches is needed. The aim of this study was to provide an overview of the utilisation and effectiveness of probiotics in reducing weight gain in patients with severe mental illness. A scoping review of studies published until 15 June 2022 was conducted to identify studies using probiotics in people with schizophrenia or depression. We systematically searched the databases EMBASE, PubMed (MEDLINE), Web of Science and SCOPUS with a predefined search string. In addition, reference lists of relevant publications were examined for additional studies. The studies were assessed by two reviewers. The primary outcomes were weight-related measurements. The secondary outcomes were metabolic blood parameters and gut microbiota. Four studies ultimately met the inclusion criteria. Two studies in which probiotics were administered did not find significant effects on pharmacologically induced weight gain. The other two studies examined the effects of synbiotics (a combination of probiotics and prebiotics). Interestingly, less weight gain was observed in individuals with this combined intervention. Adjustments in diet can be helpful and are generally well-accepted interventions in the fight against pharmacologically induced weight gain. The clinical use of probiotics and prebiotics (or synbiotics) as dietary interventions may represent a promising additional strategy in this regard. However, the few studies available showed no clear conclusions.
USP30 inhibition induces mitophagy and reduces oxidative stress in parkin-deficient human neurons
Authors: Okarmus Justyna , Agergaard Jette Bach , Stummann Tina C. , Haukedal Henriette , Ambjørn Malene , Freude Kristine K. , Fog Karina , Meyer Morten 
Published: January 2024

AbstractUbiquitination of mitochondrial proteins plays an important role in the cellular regulation of mitophagy. The E3 ubiquitin ligase parkin (encoded by PARK2) and the ubiquitin-specific protease 30 (USP30) have both been reported to regulate the ubiquitination of outer mitochondrial proteins and thereby mitophagy. Loss of E3 ligase activity is thought to be pathogenic in both sporadic and inherited Parkinson’s disease (PD), with loss-of-function mutations in PARK2 being the most frequent cause of autosomal recessive PD. The aim of the present study was to evaluate whether mitophagy induced by USP30 inhibition provides a functional rescue in isogenic human induced pluripotent stem cell-derived dopaminergic neurons with and without PARK2 knockout (KO). Our data show that healthy neurons responded to CCCP-induced mitochondrial damage by clearing the impaired mitochondria and that this process was accelerated by USP30 inhibition. Parkin-deficient neurons showed an impaired mitophagic response to the CCCP challenge, although mitochondrial ubiquitination was enhanced. USP30 inhibition promoted mitophagy in PARK2 KO neurons, independently of whether left in basal conditions or treated with CCCP. In PARK2 KO, as in control neurons, USP30 inhibition balanced oxidative stress levels by reducing excessive production of reactive oxygen species. Interestingly, non-dopaminergic neurons were the main driver of the beneficial effects of USP30 inhibition. Our findings demonstrate that USP30 inhibition is a promising approach to boost mitophagy and improve cellular health, also in parkin-deficient cells, and support the potential relevance of USP30 inhibitors as a novel therapeutic approach in diseases with a need to combat neuronal stress mediated by impaired mitochondria.
ZBTB7B is a permissive regulator of hepatocellular carcinoma initiation by repressing c-Jun expression and function
Authors: Zhu Yue , Wang Qinqin , Xie Xinyu , Ma Cuihong , Qiao Yuemei , Zhang Yu , Wu Yanjun , Gao Yuan , Jiang Jing , Liu Xin , Chen Jianfeng , Li Chen , Ge Gaoxiang 
Published: January 2024

AbstractHepatocarcinogenesis is a multi-step process. However, the regulators of hepatocellular carcinoma (HCC) initiation are understudied. Adult liver-specific gene expression was globally downregulated in HCC. We hypothesize that adult liver-specific genes, especially adult liver-enriched transcription factors may exert tumor-suppressive functions in HCC. In this study, we identify ZBTB7B, an adult liver-enriched transcription factor as a permissive regulator of HCC initiation. ZBTB7B is highly expressed in hepatocytes in adult livers, compared to fetal livers. To evaluate the functions of ZBTB7B in hepatocarcinogenesis, we performed hepatocyte-specific ZBTB7B knockout in hydrodynamic oncogene transfer-induced mouse liver cancer models. Hepatocyte-specific knockout of ZBTB7B promotes activated Akt and N-Ras-induced HCC development. Moreover, ZBTB7B deficiency sensitizes hepatocytes to a single oncogene Akt-induced oncogenic transformation and HCC initiation, which is otherwise incompetent in inducing HCC. ZBTB7B deficiency accelerates HCC initiation by down-regulating adult liver-specific gene expression and priming livers to a fetal-like state. The molecular mechanism underlying ZBTB7B functions in hepatocytes was investigated by integrated transcriptomic, phosphoproteomic, and chromatin immunoprecipitation-sequencing analyses. Integrative multi-omics analyses identify c-Jun as the core signaling node in ZBTB7B-deficient liver cancer initiation. c-Jun is a direct target of ZBTB7B essential to accelerated liver cancer initiation in ZBTB7B-deficient livers. Knockdown of c-Jun expression or dominant negative c-Jun expression delays HCC development in ZBTB7B-deficient livers. In addition, ZBTB7B competes with c-Jun for chromatin binding. Ectopic ZBTB7B expression attenuates the tumor-promoting functions of c-Jun. Expression of ZBTB7B signature, composed of 140 genes co-regulated by ZBTB7B and c-Jun, is significantly downregulated in early-stage HCCs compared to adjacent normal tissues, correlates to liver-specific gene expression, and is associated with good prognosis in human HCC. Thus, ZBTB7B functions as a permissive regulator of HCC initiation by directly regulating c-Jun expression and function.
Mitochondrial stress activates YAP/TAZ through RhoA oxidation to promote liver injury
Authors: Kwon Ari , Lee Na Young , Yu Jae-Hyun , Choi Myeung Gi , Park Jeongwoo , Koo Ja Hyun 
Published: January 2024

AbstractYes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1; also known as TAZ) are the main effectors of the Hippo pathway and their dysregulation contributes to diseases in tissues including the liver. Although mitochondria are capable of transmitting signals to change transcriptomic landscape of diseased hepatocytes, such retrograde signaling and the related nuclear machinery are largely unknown. Here, we show that increased YAP activity is associated with mitochondrial stress during liver injury; and this is required for secondary inflammation, promoting hepatocyte death. Mitochondrial stress inducers robustly promoted YAP/TAZ dephosphorylation, nuclear accumulation, and target gene transcription. RNA sequencing revealed that the majority of mitochondrial stress transcripts required YAP/TAZ. Mechanistically, direct oxidation of RhoA by mitochondrial superoxide was responsible for PP2A-mediated YAP/TAZ dephosphorylation providing a novel physiological input for the Hippo pathway. Hepatocyte-specific Yap/Taz ablation suppressed acetaminophen-induced liver injury and blunted transcriptomic changes associated with the pathology. Our observations uncover unappreciated pathway of mitochondrial stress signaling and reveal YAP/TAZ activation as the mechanistic basis for liver injury progression.
Episodic ataxia type 2 with a novel missense variant (Leu602Arg) in CACNA1A
Authors: Miura Shiroh , Watanabe Emina , Senzaki Kensuke , Hiruki Shigeyoshi , Matsumoto Sayaka , Morikawa Takuya , Uchiyama Yusuke , Kurata Seiji , Ochi Masayuki , Ohyagi Yasumasa , Shibata Hiroki 
Published: January 2024

Abstract
Autosomal dominant episodic ataxia type 2 (EA2) is caused by variants in CACNA1A. We examined a 20-year-old male with EA symptoms from a Japanese family with hereditary EA. Cerebellar atrophy was not evident, but single photon emission computed tomography showed cerebellar hypoperfusion. We identified a novel nonsynonymous variant in CACNA1A, NM_001127222.2:c.1805T>G (p.Leu602Arg), which is predicted to be functionally deleterious; therefore, this variant is likely responsible for EA2 in this pedigree.
Rare mosaic variant of GJA1 in a patient with a neurodevelopmental disorder
Authors: Shimomura Rina , Yanagishita Tomoe , Ishiguro Kumiko , Shichiji Minobu , Sato Takatoshi , Shimojima Yamamoto Keiko , Nagata Miho , Ishihara Yasuki , Miyashita Yohei , Ishigaki Keiko , Nagata Satoru , Asano Yoshihiro , Yamamoto Toshiyuki 
Published: January 2024

Abstract

GJA1 is the causative gene for oculodentodigital dysplasia (ODDD). A novel de novo GJA1 variant, NM 000165:c263C > T [p.P88L], was identified in a mosaic state in a patient with short stature, seizures, delayed myelination, mild hearing loss, and tooth enamel hypoplasia. Although the patient exhibited severe neurodevelopmental delay, other clinical features of ODDD, including limb anomalies, were mild. This may be due to differences in the mosaic ratios in different organs.
Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development
Authors: Shah Amil M. , Myhre Peder L. , Arthur Victoria , Dorbala Pranav , Rasheed Humaira , Buckley Leo F. , Claggett Brian , Liu Guning , Ma Jianzhong , Nguyen Ngoc Quynh , Matsushita Kunihiro , Ndumele Chiadi , Tin Adrienne , Hveem Kristian , Jonasson Christian , Dalen Håvard , Boerwinkle Eric , Hoogeveen Ron C. , Ballantyne Christie , Coresh Josef , Omland Torbjørn , Yu Bing 
Published: January 2024

AbstractHeart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with diverse age, geography, and HF ascertainment to identify circulating proteins and protein networks associated with HF development. Parallel analyses in Atherosclerosis Risk in Communities study participants in mid-life and late-life and in Trøndelag Health Study participants identified 37 proteins consistently associated with incident HF independent of traditional risk factors. Mendelian randomization supported causal effects of 10 on HF, HF risk factors, or left ventricular size and function, including matricellular (e.g. SPON1, MFAP4), senescence-associated (FSTL3, IGFBP7), and inflammatory (SVEP1, CCL15, ITIH3) proteins. Protein co-regulation network analyses identified 5 modules associated with HF risk, two of which were influenced by genetic variants that implicated trans hotspots within the VTN and CFH genes.
Gas diffusion enhanced electrode with ultrathin superhydrophobic macropore structure for acidic CO2 electroreduction
Authors: Sun Mingxu , Cheng Jiamin , Yamauchi Miho 
Published: January 2024

AbstractCarbon dioxide (CO2) electroreduction reaction (CO2RR) offers a promising strategy for the conversion of CO2 into valuable chemicals and fuels. CO2RR in acidic electrolytes would have various advantages due to the suppression of carbonate formation. However, its reaction rate is severely limited by the slow CO2 diffusion due to the absence of hydroxide that facilitates the CO2 diffusion in an acidic environment. Here, we design an optimal architecture of a gas diffusion electrode (GDE) employing a copper-based ultrathin superhydrophobic macroporous layer, in which the CO2 diffusion is highly enhanced. This GDE retains its applicability even under mechanical deformation conditions. The CO2RR in acidic electrolytes exhibits a Faradaic efficiency of 87% with a partial current density $$( {j}_{{{{\rm{C}}}}_{2+}})$$

(

j

C

2
+

)

of −1.6 A cm−2 for multicarbon products (C2+), and $$ {j}_{{{{{{\rm{C}}}}}}_{2+}}$$

j

C

2
+

of −0.34 A cm−2 when applying dilute 25% CO2. In a highly acidic environment, C2+ formation occurs via a second order reaction which is controlled by both the catalyst and its hydroxide.
Replicating shear-mediated self-assembly of spider silk through microfluidics
Authors: Chen Jianming , Tsuchida Arata , Malay Ali D. , Tsuchiya Kousuke , Masunaga Hiroyasu , Tsuji Yui , Kuzumoto Mako , Urayama Kenji , Shintaku Hirofumi , Numata Keiji 
Published: January 2024

AbstractThe development of artificial spider silk with properties similar to native silk has been a challenging task in materials science. In this study, we use a microfluidic device to create continuous fibers based on recombinant MaSp2 spidroin. The strategy incorporates ion-induced liquid-liquid phase separation, pH-driven fibrillation, and shear-dependent induction of β-sheet formation. We find that a threshold shear stress of approximately 72 Pa is required for fiber formation, and that β-sheet formation is dependent on the presence of polyalanine blocks in the repetitive sequence. The MaSp2 fiber formed has a β-sheet content (29.2%) comparable to that of native dragline with a shear stress requirement of 111 Pa. Interestingly, the polyalanine blocks have limited influence on the occurrence of liquid-liquid phase separation and hierarchical structure. These results offer insights into the shear-induced crystallization and sequence-structure relationship of spider silk and have significant implications for the rational design of artificially spun fibers.
Evolution of optimal growth temperature in Asgard archaea inferred from the temperature dependence of GDP binding to EF-1A
Authors: Lu Zhongyi , Xia Runyue , Zhang Siyu , Pan Jie , Liu Yang , Wolf Yuri I. , Koonin Eugene V. , Li Meng 
Published: January 2024

AbstractThe archaeal ancestor of eukaryotes apparently belonged to the phylum Asgardarchaeota, but the ecology and evolution of Asgard archaea are poorly understood. The optimal GDP-binding temperature of a translation elongation factor (EF-1A or EF-Tu) has been previously shown to correlate with the optimal growth temperature of diverse prokaryotes. Here, we reconstruct ancestral EF-1A sequences and experimentally measure the optimal GDP-binding temperature of EF-1A from ancient and extant Asgard archaea, to infer the evolution of optimal growth temperatures in Asgardarchaeota. Our results suggest that the Asgard ancestor of eukaryotes was a moderate thermophile, with an optimal growth temperature around 53 °C. The origin of eukaryotes appears to coincide with a transition from thermophilic to mesophilic lifestyle during the evolution of Asgard archaea.
Synthesis of inter-[60]fullerene conjugates with inherent chirality
Authors: Hashikawa Yoshifumi , Okamoto Shu , Murata Yasujiro 
Published: January 2024

AbstractCoalescence of [60]fullerenes potentially produces hypothetical nanocarbon assemblies with non-naturally occurring topologies. Since the discovery of [60]fullerene in 1985, coalesced [60]fullerene oligomers have only been observed as transient species by transmission electron microscopy during an oligomerization process under a high electron acceleration voltage. Herein, we showcase the rational synthesis of covalent assemblies consisting of inherently chiral open-[60]fullerenes. The crystallographic analyses unveiled double-caged structures of non-conjugated and conjugated inter-[60]fullerene hybrids, in which the two [60]fullerene cages are bounds to each other through a covalent linkage. The former one further assembles via a heterochiral recognition so that four carbon cages are arranged in a tetrahedral manner both in solution and solid state. Reflecting radially-conjugated double π-surface nature, the inter-[60]fullerene conjugate exhibits strong electronic communication in its reduced states, intense absorption behavior, and chiroptical activity with a dissymmetry factor of 0.21 (at 674 nm) which breaks the record for known chiral organic molecules.
The phosphatase DUSP22 inhibits UBR2-mediated K63-ubiquitination and activation of Lck downstream of TCR signalling
Authors: Shih Ying-Chun , Chen Hsueh-Fen , Wu Chia-Ying , Ciou Yi-Ru , Wang Chia-Wen , Chuang Huai-Chia , Tan Tse-Hua 
Published: January 2024

AbstractDUSP22 is a dual-specificity phosphatase that inhibits T cell activation by inactivating the kinase Lck. Here we show that the E3 ubiquitin ligase UBR2 is a positive upstream regulator of Lck during T-cell activation. DUSP22 dephosphorylates UBR2 at specific Serine residues, leading to ubiquitin-mediated UBR2 degradation. UBR2 is also modified by the SCF E3 ubiquitin ligase complex via Lys48-linked ubiquitination at multiple Lysine residues. Single-cell RNA sequencing analysis and UBR2 loss of function experiments showed that UBR2 is a positive regulator of proinflammatory cytokine expression. Mechanistically, UBR2 induces Lys63-linked ubiquitination of Lck at Lys99 and Lys276 residues, followed by Lck Tyr394 phosphorylation and activation as part of TCR signalling. Inflammatory phenotypes induced by TCR-triggered Lck activation or knocking out DUSP22, are attenuated by genomic deletion of UBR2. UBR2-Lck interaction and Lck Lys63-linked ubiquitination are induced in the peripheral blood T cells of human SLE patients, which demonstrate the relevance of the UBR2-mediated regulation of inflammation to human pathology. In summary, we show here an important regulatory mechanism of T cell activation, which finetunes the balance between T cell response and aggravated inflammation.
An updated PREDICT breast cancer prognostic model including the benefits and harms of radiotherapy
Authors: Grootes Isabelle , Wishart Gordon C. , Pharoah Paul David Peter 
Published: January 2024

AbstractPREDICT Breast (www.breast .predict.nhs.uk) is a prognostication tool for early invasive breast cancer. The current version was based on cases diagnosed in 1999–2003 and did not incorporate the benefits of radiotherapy or the harms associated with therapy. Since then, there has been a substantial improvement in the outcomes for breast cancer cases. The aim of this study was to update PREDICT Breast to ensure that the underlying model is appropriate for contemporary patients. Data from the England National Cancer Registration and Advisory Service for invasive breast cancer cases diagnosed 2000–17 were used for model development and validation. Model development was based on 35,474 cases diagnosed and registered by the Eastern Cancer Registry. A Cox model was used to estimate the prognostic effects of the year of diagnosis, age at diagnosis, tumour size, tumour grade and number of positive nodes. Separate models were developed for ER-positive and ER-negative disease. Data on 32,408 cases from the West Midlands Cancer Registry and 100,551 cases from other cancer registries were used for validation. The new model was well-calibrated; predicted breast cancer deaths at 5-, 10- and 15-year were within 10 per cent of the observed validation data. Discrimination was also good: The AUC for 15-year breast cancer survival was 0.809 in the West Midlands data set and 0.846 in the data set for the other registries. The new PREDICT Breast model outperformed the current model and will be implemented in the online tool which should lead to more accurate absolute treatment benefit predictions for individual patients.
Hong-Ou-Mandel interference of single-photon-level pulses stored in independent room-temperature quantum memories
Authors: Gera Sonali , Wallace Chase , Flament Mael , Scriminich Alessia , Namazi Mehdi , Kim Youngshin , Sagona-Stophel Steven , Vallone Giuseppe , Villoresi Paolo , Figueroa Eden 
Published: January 2024

AbstractQuantum repeater networks require independent absorptive quantum memories capable of storing and retrieving indistinguishable photons to perform high-repetition entanglement swapping operations. The ability to perform these coherent operations at room temperature is of prime importance for the realization of scalable quantum networks. We perform Hong-Ou-Mandel (HOM) interference between photonic polarization states and single-photon-level pulses stored and retrieved from two sets of independent room-temperature quantum memories. We show that the storage and retrieval of polarization states from quantum memories does not degrade the HOM visibility for few-photon-level polarization states in a dual-rail configuration. For single-photon-level pulses, we measure the HOM visibility with various levels of background in a single polarization, single-rail QM, and investigate its dependence on the signal-to-background ratio. We obtain an HOM visibility of 43%, compared to the 48% no-memory limit of our set-up. These results allow us to estimate a 33% visibility for polarization qubits under the same conditions. These demonstrations lay the groundwork for future applications using large-scale memory-assisted quantum networks.
Twice hidden string order and competing phases in the spin-1/2 Kitaev–Gamma ladder
Authors: Sørensen Erik S. , Kee Hae-Young 
Published: January 2024

AbstractFinding the Kitaev spin liquid in candidate materials involves understanding the entire phase diagram, including other allowed interactions. One of these interactions, called the Gamma (Γ) interaction, causes magnetic frustration and its interplay with the Kitaev (K) interaction is crucial to comprehend Kitaev materials. Due to the complexity of the combined KΓ model, quasi-one-dimensional models have been investigated. While several disordered phases are found in the 2-leg ladder, the nature of the phases are yet to be determined. Here we focus on the disordered phase near the antiferromagnetic Γ limit (denoted by AΓ phase) next to the ferromagnetic Kitaev phase. We report a distinct non-local string order parameter characterizing the AΓ phase, different from the string order parameter in the Kitaev phase. This string order parameter becomes evident only after two unitary transformation, referred to as a twice hidden string order parameter. The related entanglement spectrum, edge states, magnetic field responses, and the symmetry protecting the phase are presented, and its relevance to the two-dimensional Kitaev materials is discussed. Two newly identified disordered phases in the phase diagram of KΓ ladder is also reported.