bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIRT5-related desuccinylation modification of AIFM1 protects against compression-induced intervertebral disc degeneration by regulating mitochondrial homeostasis
Authors: Mao Jianxin , Wang Di , Wang Dong , Wu Qi , Shang Qiliang , Gao Chu , Wang Huanbo , Wang Han , Du Mu , Peng Pandi , Jia Haoruo , Xu Xiaolong , Wang Jie , Yang Liu , Luo Zhuojing 
Published: January 2023

AbstractMitochondrial dysfunction plays a major role in the development of intervertebral disc degeneration (IDD). Sirtuin 5 (SIRT5) participates in the maintenance of mitochondrial homeostasis through its desuccinylase activity. However, it is still unclear whether succinylation or SIRT5 is involved in the impairment of mitochondria and development of IDD induced by excessive mechanical stress. Our 4D label-free quantitative proteomic results showed decreased expression of the desuccinylase SIRT5 in rat nucleus pulposus (NP) tissues under mechanical loading. Overexpression of Sirt5 effectively alleviated, whereas knockdown of Sirt5 aggravated, the apoptosis and dysfunction of NP cells under mechanical stress, consistent with the more severe IDD phenotype of Sirt5 KO mice than wild-type mice that underwent lumbar spine instability (LSI) surgery. Moreover, immunoprecipitation-coupled mass spectrometry (IP-MS) results suggested that AIFM1 was a downstream target of SIRT5, which was verified by a Co-IP assay. We further demonstrated that reduced SIRT5 expression resulted in the increased succinylation of AIFM1, which in turn abolished the interaction between AIFM1 and CHCHD4 and thus led to the reduced electron transfer chain (ETC) complex subunits in NP cells. Reduced ETC complex subunits resulted in mitochondrial dysfunction and the subsequent occurrence of IDD under mechanical stress. Finally, we validated the efficacy of treatments targeting disrupted mitochondrial protein importation by upregulating SIRT5 expression or methylene blue (MB) administration in the compression-induced rat IDD model. In conclusion, our study provides new insights into the occurrence and development of IDD and offers promising therapeutic approaches for IDD.
HDAC7/c-Myc signaling pathway promotes the proliferation and metastasis of choroidal melanoma cells
Authors: Zhang Yimeng , Ding Peng , Wang Yuanyong , Shao Changjian , Guo Kai , Yang Hanyi , Feng Yingtong , Ning Jiayi , Pan Minghong , Wang Ping , Yan Xiaolong , Ma Zhiqiang , Han Jing 
Published: January 2023

AbstractChoroidal melanoma (CM) is the most common type of diagnosed uveal melanoma (UM), which is prone to metastasis and exhibits a poor prognosis. The molecular mechanisms underlying CM progression need further elucidation to research effective therapeutic strategies. Histone deacetylase 7 (HDAC7) is very important in regulating cancer progression, but the significance and effect of HDAC7 on CM progression are unclear. In the present study, we found that HDAC7 is overexpressed in CM tissues versus normal tissues. We built HDAC7 overexpressing CM cell lines to study the functions of HDAC7 in CM progression and verified that upregulation of HDAC7 promoted the proliferation and metastasis of CM cells, while pharmacological inhibition of HDAC7 suppressed both the proliferation and metastasis of CM cells. Furthermore, we found that the aforementioned cancer-promoting effect of HDAC7 was mediated by c-Myc. Targeted inhibition of c-Myc inhibited CM progression by interfering with the HDAC7/c-Myc signaling pathway. Our study highlighted the function of targeting the HDAC7/c-Myc signaling pathway to intervene in the pathological process of CM, which provides potential therapeutic strategies for CM treatment.
Crosstalk between G-quadruplex and ROS
Authors: Wu Songjiang , Jiang Ling , Lei Li , Fu Chuhan , Huang Jinhua , Hu Yibo , Dong Yumeng , Chen Jing , Zeng Qinghai 
Published: January 2023

AbstractThe excessive production of reactive oxygen species (ROS) can lead to single nucleic acid base damage, DNA strand breakage, inter- and intra-strand cross-linking of nucleic acids, and protein-DNA cross-linking involved in the pathogenesis of cancer, neurodegenerative diseases, and aging. G-quadruplex (G4) is a stacked nucleic acid structure that is ubiquitous across regulatory regions of multiple genes. Abnormal formation and destruction of G4s due to multiple factors, including cations, helicases, transcription factors (TFs), G4-binding proteins, and epigenetic modifications, affect gene replication, transcription, translation, and epigenetic regulation. Due to the lower redox potential of G-rich sequences and unique structural characteristics, G4s are highly susceptible to oxidative damage. Additionally, the formation, stability, and biological regulatory role of G4s are affected by ROS. G4s are involved in regulating gene transcription, translation, and telomere length maintenance, and are therefore key players in age-related degeneration. Furthermore, G4s also mediate the antioxidant process by forming stress granules and activating Nrf2, which is suggestive of their involvement in developing ROS-related diseases. In this review, we have summarized the crosstalk between ROS and G4s, and the possible regulatory mechanisms through which G4s play roles in aging and age-related diseases.
Dynamic chromatin landscape encodes programs for perinatal transition of cardiomyocytes
Authors: Zhang Jing , Ouyang Zhaohui , Xia Limei , Wang Qi , Zheng Feng , Xu Kun , Xing Yuexian , Wei Ke , Shi Shaolin , Li Chaojun , Yang Jingping 
Published: January 2023

AbstractThe perinatal period occurring immediately before and after birth is critical for cardiomyocytes because they must change rapidly to accommodate the switch from fetal to neonatal circulation after birth. This transition is a well-orchestrated process, and any perturbation leads to unhealthy cardiomyocytes and heart disease. Despite its importance, little is known about how this transition is regulated and controlled. Here, by mapping the genome-wide chromatin accessibility, transcription-centered long-range chromatin interactions and gene expression in cardiomyocytes undergoing perinatal transition, we discovered two key transcription factors, MEF2 and AP1, that are crucial for driving the phenotypic changes within the perinatal window. Thousands of dynamic regulatory elements were found in perinatal cardiomyocytes and we show these elements mediated the transcriptional reprogramming through an elegant chromatin high-order architecture. We recompiled transcriptional program of induced stem cell-derived cardiomyocytes according to our discovered network, and they showed adult cardiomyocyte-like electrophysiological expression. Our work provides a comprehensive regulatory resource of cardiomyocytes perinatal reprogramming, and aids the gap-filling of cardiac translational research.
Evaluation of standard-of-care intravitreal aflibercept treatment practices in patients with diabetic macular oedema in the UK: DRAKO study outcomes
Authors: Sivaprasad Sobha , Ghanchi Faruque , Kelly Simon P. , Kotagiri Ajay , Talks James , Scanlon Peter , McGoey Hellen , Nolan Andrew , Saddiq Moneeb , Napier Jackie , Morgan-Warren Peter 
Published: January 2023

Abstract
Background/Objectives
DRAKO (NCT02850263) was a 24-month, prospective, non-interventional, multi-centre cohort study enrolling patients with diabetic macular oedema (DMO) including central involvement. The study evaluated UK standard-of-care intravitreal aflibercept (IVT-AFL) treatment. This analysis describes the treatment pathway and service provision for the anti–vascular endothelial growth factor (VEGF) treatment-naïve (C1) and non-naïve patients (C2) who received prior anti-VEGF treatment for DMO other than IVT-AFL.

Methods
Mean changes in best-corrected visual acuity and central subfield thickness were measured and stratified by baseline factors, including ethnicity and administration of five initial monthly injections within predefined windows. Clinic visits were classified as treatment only (T1), monitoring assessment only (T2), combined visits (T3) or post-injection visits with no treatment or assessment (T4).

Results
Median time from decision to treat to treatment was 6 days. As a percentage of total visits, T1, T2, T3 and T4 were 7%, 42%, 48% and 3% for C1 and 11%, 39%, 48% and 2% for C2. Most IVT-AFL injections were administered by healthcare professionals (HCPs) other than doctors (C1, 57.4%; C2, 58.5%). The percentage of treatments associated with a procedure-related adverse event where at least 75% of injections were completed by the same injector role were similar for doctors and other HCPs (C1, 1.1% and 0.8%; C2, 0.7%, and 1.0%).

Conclusions
Results indicate that upon DMO diagnosis, patients were treated promptly, and most visits were combined (treatment and assessment) or monitoring only. Most IVT-AFL was administered by non-physicians with a similar treatment-related safety profile as IVT-AFL administered by physicians.
An integrated Mg battery-powered iontophoresis patch for efficient and controllable transdermal drug delivery
Authors: Zhou Yan , Jia Xiaoteng , Pang Daxin , Jiang Shan , Zhu Meihua , Lu Geyu , Tian Yaping , Wang Caiyun , Chao Danming , Wallace Gordon 
Published: January 2023

AbstractWearable transdermal iontophoresis eliminating the need for external power sources offers advantages for patient-comfort when deploying epidermal diseases treatments. However, current self-powered iontophoresis based on energy harvesters is limited to support efficient therapeutic administration over the long-term operation, owing to the low and inconsistent energy supply. Here we propose a simplified wearable iontophoresis patch with a built-in Mg battery for efficient and controllable transdermal delivery. This system decreases the system complexity and form factors by using viologen-based hydrogels as an integrated drug reservoir and cathode material, eliminating the conventional interface impedance between the electrode and drug reservoir. The redox-active polyelectrolyte hydrogel offers a high energy density of 3.57 mWh cm−2, and an optimal bioelectronic interface with ultra-soft nature and low tissue-interface impedance. The delivery dosage can be readily manipulated by tuning the viologen hydrogel and the iontophoresis stimulation mode. This iontophoresis patch demonstrates an effective treatment of an imiquimod-induced psoriasis mouse. Considering the advantages of being a reliable and efficient energy supply, simplified configuration, and optimal electrical skin-device interface, this battery-powered iontophoresis may provide a new non-invasive treatment for chronic epidermal diseases.
Extending the data collection from a clinical trial: The Extended Salford Lung Study research cohort
Authors: Meeraus Wilhelmine , Fu Qinggong , Mu George , Fry Mark , Frith Lucy , Pimenta Jeanne M. 
Published: January 2023

AbstractThe Extended Salford Lung Study (Ext-SLS) is an extension of the Salford Lung Studies (SLS) in asthma and chronic obstructive pulmonary disease (COPD) through retrospective and prospective collection of patient-level electronic health record (EHR) data. We compared the Ext-SLS cohort with the SLS intention-to-treat populations using descriptive analyses to determine if the strengths (e.g. randomization) of the clinical trial were maintained in the new cohort. Historical and patient-reported outcome data were captured from asthma-/COPD-specific questionnaires (e.g., Asthma Control Test [ACT]/COPD Assessment Test [CAT]). The Ext-SLS included 1147 participants (n = 798, SLS asthma; n = 349, SLS COPD). Of participants answering the ACT, 39% scored <20, suggesting poorly controlled asthma. For COPD, 61% of participants answering the CAT scored ≥21, demonstrating a high disease burden. Demographic/clinical characteristics of the cohorts were similar at SLS baseline. EHR data provided a long-term view of participants’ disease, and questionnaires provided information not typically captured. The Ext-SLS cohort is a valuable resource for respiratory research, and ongoing prospective data collection will add further value and ensure the Ext-SLS is an important source of patient-level information on obstructive airways disease.
Mono- and biallelic variant effects on disease at biobank scale
Authors: Heyne H. O. , Karjalainen J. , Karczewski K. J. , Lemmelä S. M. , Zhou W. ,   FinnGen, Havulinna A. S. , Kurki M. , Rehm H. L. , Palotie A. , Daly M. J. 
Published: January 2023

AbstractIdentifying causal factors for Mendelian and common diseases is an ongoing challenge in medical genetics1. Population bottleneck events, such as those that occurred in the history of the Finnish population, enrich some homozygous variants to higher frequencies, which facilitates the identification of variants that cause diseases with recessive inheritance2,3. Here we examine the homozygous and heterozygous effects of 44,370 coding variants on 2,444 disease phenotypes using data from the nationwide electronic health records of 176,899 Finnish individuals. We find associations for homozygous genotypes across a broad spectrum of phenotypes, including known associations with retinal dystrophy and novel associations with adult-onset cataract and female infertility. Of the recessive disease associations that we identify, 13 out of 20 would have been missed by the additive model that is typically used in genome-wide association studies. We use these results to find many known Mendelian variants whose inheritance cannot be adequately described by a conventional definition of dominant or recessive. In particular, we find variants that are known to cause diseases with recessive inheritance with significant heterozygous phenotypic effects. Similarly, we find presumed benign variants with disease effects. Our results show how biobanks, particularly in founder populations, can broaden our understanding of complex dosage effects of Mendelian variants on disease.
Octupole-driven magnetoresistance in an antiferromagnetic tunnel junction
Authors: Chen Xianzhe , Higo Tomoya , Tanaka Katsuhiro , Nomoto Takuya , Tsai Hanshen , Idzuchi Hiroshi , Shiga Masanobu , Sakamoto Shoya , Ando Ryoya , Kosaki Hidetoshi , Matsuo Takumi , Nishio-Hamane Daisuke , Arita Ryotaro , Miwa Shinji , Nakatsuji Satoru 
Published: January 2023

AbstractThe tunnelling electric current passing through a magnetic tunnel junction (MTJ) is strongly dependent on the relative orientation of magnetizations in ferromagnetic electrodes sandwiching an insulating barrier, rendering efficient readout of spintronics devices1–5. Thus, tunnelling magnetoresistance (TMR) is considered to be proportional to spin polarization at the interface1 and, to date, has been studied primarily in ferromagnets. Here we report observation of TMR in an all-antiferromagnetic tunnel junction consisting of Mn3Sn/MgO/Mn3Sn (ref. 6). We measured a TMR ratio of around 2% at room temperature, which arises between the parallel and antiparallel configurations of the cluster magnetic octupoles in the chiral antiferromagnetic state. Moreover, we carried out measurements using a Fe/MgO/Mn3Sn MTJ and show that the sign and direction of anisotropic longitudinal spin-polarized current in the antiferromagnet7 can be controlled by octupole direction. Strikingly, the TMR ratio (about 2%) of the all-antiferromagnetic MTJ is much larger than that estimated using the observed spin polarization. Theoretically, we found that the chiral antiferromagnetic MTJ may produce a substantially large TMR ratio as a result of the time-reversal, symmetry-breaking polarization characteristic of cluster magnetic octupoles. Our work lays the foundation for the development of ultrafast and efficient spintronic devices using antiferromagnets8–10.
The person-to-person transmission landscape of the gut and oral microbiomes
Authors: Valles-Colomer Mireia , Blanco-Míguez Aitor , Manghi Paolo , Asnicar Francesco , Dubois Leonard , Golzato Davide , Armanini Federica , Cumbo Fabio , Huang Kun D. , Manara Serena , Masetti Giulia , Pinto Federica , Piperni Elisa , Punčochář Michal , Ricci Liviana , Zolfo Moreno , Farrant Olivia , Goncalves Adriana , Selma-Royo Marta , Binetti Ana G. , Becerra Jimmy E. , Han Bei , Lusingu John , Amuasi John , Amoroso Loredana , Visconti Alessia , Steves Claire M. , Falchi Mario , Filosi Michele , Tett Adrian , Last Anna , Xu Qian , Qin Nan , Qin Huanlong , May Jürgen , Eibach Daniel , Corrias Maria Valeria , Ponzoni Mirco , Pasolli Edoardo , Spector Tim D. , Domenici Enrico , Collado Maria Carmen , Segata Nicola 
Published: January 2023

AbstractThe human microbiome is an integral component of the human body and a co-determinant of several health conditions1,2. However, the extent to which interpersonal relations shape the individual genetic makeup of the microbiome and its transmission within and across populations remains largely unknown3,4. Here, capitalizing on more than 9,700 human metagenomes and computational strain-level profiling, we detected extensive bacterial strain sharing across individuals (more than 10 million instances) with distinct mother-to-infant, intra-household and intra-population transmission patterns. Mother-to-infant gut microbiome transmission was considerable and stable during infancy (around 50% of the same strains among shared species (strain-sharing rate)) and remained detectable at older ages. By contrast, the transmission of the oral microbiome occurred largely horizontally and was enhanced by the duration of cohabitation. There was substantial strain sharing among cohabiting individuals, with 12% and 32% median strain-sharing rates for the gut and oral microbiomes, and time since cohabitation affected strain sharing more than age or genetics did. Bacterial strain sharing additionally recapitulated host population structures better than species-level profiles did. Finally, distinct taxa appeared as efficient spreaders across transmission modes and were associated with different predicted bacterial phenotypes linked with out-of-host survival capabilities. The extent of microorganism transmission that we describe underscores its relevance in human microbiome studies5, especially those on non-infectious, microbiome-associated diseases.
Modeling clinical and non-clinical determinants of intrapartum stillbirths in singletons in six public hospitals in the Greater Accra Region of Ghana: a case–control study
Authors: Vanotoo Linda , Dwomoh Duah , Laar Amos , Kotoh Agnes Millicent , Adanu Richard 
Published: January 2023

AbstractThe Greater Accra Region (GAR) of Ghana records 2000 stillbirths annually and 40% of them occur intrapartum. An understanding of the contributing factors will facilitate the development of preventive strategies to reduce the huge numbers of intrapartum stillbirths. This study identified determinants of intrapartum stillbirths in GAR. A retrospective 1:2 unmatched case–control study was conducted in six public hospitals in the Greater Accra Region of Ghana. A multivariable binary logistic regression model was used to quantify the effect of exposures on intrapartum stillbirth. The area under the receiver operating characteristics curve and the Brier scores were used to screen potential risk factors and assess the predictive performance of the regression models. The following maternal factors increased the odds of intrapartum stillbirths: pregnancy-induced hypertension (PIH) [adjusted Odds Ratio; aOR = 3.72, 95% CI:1.71–8.10,p < 0.001]; antepartum haemorrhage (APH) [aOR = 3.28, 95% CI: 1.33–8.10,p < 0.05] and premature rupture of membranes (PROM) [aOR = 3.36, 95% CI: 1.20–9.40,p < 0.05]. Improved management of PIH, APH, PROM, and preterm delivery will reduce intrapartum stillbirth. Hospitals should improve on the quality of monitoring women during labor. Auditing of intrapartum stillbirths should be mandatory for all hospitals and Ghana Health Service should include fetal autopsy in stillbirth auditing to identify other causes of fetal deaths. Interventions to reduce intrapartum stillbirth must combine maternal, fetal and service delivery factors to make them effective.
Features from the photoplethysmogram and the electrocardiogram for estimating changes in blood pressure
Authors: Finnegan Eoin , Davidson Shaun , Harford Mirae , Watkinson Peter , Tarassenko Lionel , Villarroel Mauricio 
Published: January 2023

AbstractThere is a growing emphasis being placed on the potential for cuffless blood pressure (BP) estimation through modelling of morphological features from the photoplethysmogram (PPG) and electrocardiogram (ECG). However, the appropriate features and models to use remain unclear. We investigated the best features available from the PPG and ECG for BP estimation using both linear and non-linear machine learning models. We conducted a clinical study in which changes in BP ($$\Delta$$ΔBP) were induced by an infusion of phenylephrine in 30 healthy volunteers (53.8% female, 28.0 (9.0) years old). We extracted a large and diverse set of features from both the PPG and the ECG and assessed their individual importance for estimating$$\Delta$$ΔBP through Shapley additive explanation values and a ranking coefficient. We trained, tuned, and evaluated linear (ordinary least squares, OLS) and non-linear (random forest, RF) machine learning models to estimate$$\Delta$$ΔBP in a nested leave-one-subject-out cross-validation framework. We reported the results as correlation coefficient ($$\rho _p$$ρp), root mean squared error (RMSE), and mean absolute error (MAE). The non-linear RF model significantly ($$p<0.05$$p<0.05) outperformed the linear OLS model using both the PPG and the ECG signals across all performance metrics. Estimating$$\Delta$$ΔSBP using the PPG alone ($$\rho _p$$ρp= 0.86 (0.23), RMSE = 5.66 (4.76) mmHg, MAE = 4.86 (4.29) mmHg) performed significantly better than using the ECG alone ($$\rho _p$$ρp= 0.69 (0.45), RMSE = 6.79 (4.76) mmHg, MAE = 5.28 (4.57) mmHg), all$$p < 0.001$$p<0.001. The highest ranking features from the PPG largely modelled increasing reflected wave interference driven by changes in arterial stiffness. This finding was supported by changes observed in the PPG waveform in response to the phenylephrine infusion. However, a large number of features were required for accurate BP estimation, highlighting the high complexity of the problem. We conclude that the PPG alone may be further explored as a potential single source, cuffless, blood pressure estimator. The use of the ECG alone is not justified. Non-linear models may perform better as they are able to incorporate interactions between feature values and demographics. However, demographics may not adequately account for the unique and individualised relationship between the extracted features and BP.
Peatland groundwater level in the Indonesian maritime continent as an alert for El Niño and moderate positive Indian Ocean dipole events
Authors: Sulaiman Albertus , Osaki Mitsuru , Takahashi Hidenori , Yamanaka Manabu D. , Susanto Raden Dwi , Shimada Sawahiko , Kimura Keiji , Hirano Takashi , Wetadewi Rahmawati Ihsani , Sisva Silsigia , Kato Tsuyoshi , Kozan Osamu , Kubo Hideyuki , Awaluddin Awaluddin , Tsuji Nobuyuki 
Published: January 2023

AbstractIn general, it is known that extreme climatic conditions such as El Niño and positive Indian Ocean Dipole (IOD+) cause prolonged drought in Indonesia's tropical peatlands so that groundwater levels (GWL) drop and peat is prone to fire. However, 27 years of GWL measurements in Central Kalimantan peat forests show the opposite condition, where the lowest GWL occurs several weeks before El Niño and after IOD+ reaches its peaks. We show that the dropped sea surface temperature anomaly induced by anomalously easterly winds along the southern Java-Sumatra occurs several weeks before the GWL drop to the lowest value. Local rainfall decreased, and GWL dropped sharply by 1.0 to 1.5 m, during the super El Niño events in 1997/98 and 2015, as well as remarkable events of IOD+ in 2019. It is suggested that the tropical peatland ecohydrological system (represented by the GWL), El Niño Southern Oscillation (ENSO), and IOD+ are teleconnected. Hence, monitoring GWL variability of peatland over the IMC is a possibility an alert for extreme climate events associated with El Niño and/or moderate IOD+.