bluuebunny/crossref_metadata_2025_split huggingface dataset:
mebipred: identifying metal-binding potential in protein sequence
Authors: Aptekmann A A , Buongiorno J , Giovannelli D , Glamoclija M , Ferreiro D U , Bromberg Y 
Published: May 2022

AbstractMotivationmetal-binding proteins have a central role in maintaining life processes. Nearly one-third of known protein structures contain metal ions that are used for a variety of needs, such as catalysis, DNA/RNA binding, protein structure stability, etc. Identifying metal-binding proteins is thus crucial for understanding the mechanisms of cellular activity. However, experimental annotation of protein metal-binding potential is severely lacking, while computational techniques are often imprecise and of limited applicability.Resultswe developed a novel machine learning-based method, mebipred, for identifying metal-binding proteins from sequence-derived features. This method is over 80% accurate in recognizing proteins that bind metal ion-containing ligands; the specific identity of 11 ubiquitously present metal ions can also be annotated. mebipred is reference-free, i.e. no sequence alignments are involved, and is thus faster than alignment-based methods; it is also more accurate than other sequence-based prediction methods. Additionally, mebipred can identify protein metal-binding capabilities from short sequence stretches, e.g. translated sequencing reads, and, thus, may be useful for the annotation of metal requirements of metagenomic samples. We performed an analysis of available microbiome data and found that ocean, hot spring sediments and soil microbiomes use a more diverse set of metals than human host-related ones. For human microbiomes, physiological conditions explain the observed metal preferences. Similarly, subtle changes in ocean sample ion concentration affect the abundance of relevant metal-binding proteins. These results highlight mebipred’s utility in analyzing microbiome metal requirements.Availability and implementationmebipred is available as a web server at services.bromberglab.org/mebipred and as a standalone package at https://pypi.org/project/mymetal/.Supplementary informationSupplementary data are available at Bioinformatics online.
NanoSplicer: accurate identification of splice junctions using Oxford Nanopore sequencing
Authors: You Yupei , Clark Michael B , Shim Heejung 
Published: May 2022

AbstractMotivationLong-read sequencing methods have considerable advantages for characterizing RNA isoforms. Oxford Nanopore sequencing records changes in electrical current when nucleic acid traverses through a pore. However, basecalling of this raw signal (known as a squiggle) is error prone, making it challenging to accurately identify splice junctions. Existing strategies include utilizing matched short-read data and/or annotated splice junctions to correct nanopore reads but add expense or limit junctions to known (incomplete) annotations. Therefore, a method that could accurately identify splice junctions solely from nanopore data would have numerous advantages.ResultsWe developed ‘NanoSplicer’ to identify splice junctions using raw nanopore signal (squiggles). For each splice junction, the observed squiggle is compared to candidate squiggles representing potential junctions to identify the correct candidate. Measuring squiggle similarity enables us to compute the probability of each candidate junction and find the most likely one. We tested our method using (i) synthetic mRNAs with known splice junctions and (ii) biological mRNAs from a lung-cancer cell-line. The results from both datasets demonstrate NanoSplicer improves splice junction identification, especially when the basecalling error rate near the splice junction is elevated.Availability and implementationNanoSplicer is available at https://github.com/shimlab/NanoSplicer and archived at https://doi.org/10.5281/zenodo.6403849. Data is available from ENA: ERS7273757 and ERS7273453.Supplementary informationSupplementary data are available at Bioinformatics online.
A decade of discovery: the stunning progress of premature ovarian insufficiency research in China
Authors: Wang Xiaoyan , Chen Zi-Jiang 
Published: May 2022

Abstract
Premature ovarian insufficiency (POI) is one of the key aspects of ovarian infertility. Due to early cession of ovarian function, POI imposes great challenges on the physiological and psychological health of women and becomes a common cause of female infertility. In the worldwide, there has been a special outpouring of concern for about 4 million reproductive-aged women suffering from POI in China. Driven by advances in new technologies and efforts invested by Chinses researchers, understanding about POI has constantly been progressing over the past decade. Here, we comprehensively summarize and review the landmark development and achievements from POI studies in China spanning 2011–2020, which aims to provide key insights from bench to bedside.
Multiomics analysis of male infertility
Authors: Wu Xiaolong , Zhou Liwei , Shi Jie , Cheng C Yan , Sun Fei 
Published: May 2022

AbstractInfertility affects 8–12% of couples globally, and the male factor is a primary cause in ~50% of couples. Male infertility is a multifactorial reproductive disorder, which can be caused by paracrine and autocrine factors, hormones, genes, and epigenetic changes. Recent studies in rodents and most notably in humans using multiomics approach have yielded important insights into understanding the biology of spermatogenesis. Nonetheless, the etiology and pathogenesis of male infertility are still largely unknown. In this review, we summarized and critically evaluated findings based on the use of advanced technologies to compare normal and obstructive azoospermic versus nonobstructive azoospermic men, including whole-genome bisulfite sequencing, single-cell RNA-seq, whole-exome sequencing, and transposase-accessible chromatin using sequencing. It is obvious that the multiomics approach is the method of choice for basic research and clinical studies including clinical diagnosis of male infertility.
Advances in haploid embryonic stem cell research
Authors: Liu Chao , Li Wei 
Published: May 2022

Abstract
Haploid embryonic stem cells are embryonic stem cells of a special type. Their nuclei contain one complete set of genetic material, and they are capable of self-renewal and differentiation. The emergence of haploid embryonic stem cells has aided research in functional genomics, genetic imprinting, parthenogenesis, genetic screening, and somatic cell nuclear transfer. This article reviews current issues in haploid stem cell research based on reports published in recent years and assesses the potential applications of these cells in somatic cell nuclear transfer, genome imprinting, and parthenogenesis.
Responsible governance of human germline genome editing in China
Authors: Peng Yaojin , Lv Jianwei , Ding Lulu , Gong Xia , Zhou Qi 
Published: May 2022

Abstract
Considerable improvements have been made to gene editing technology, which has been increasingly applied to research involving humans. Nevertheless, human heritable germline genome editing is associated with a series of potential ethical, legal, and social risks, which have generated major controversies and discussions worldwide, especially after the “gene-edited babies” incident. Influenced by this incident, China has realized the importance of ethical governance in the field of life science and technology, has accelerated legislative and policy efforts in this field, and has gradually moved toward the direction of “precautionary” ethical governance. Black letter analysis, big data public opinion analysis, and other research methods are used in this paper. This paper explores the scientific background, ethical debates, and latest developments regarding China’s regulatory framework for human germline gene editing after the “gene-edited babies” controversy and provides several recommendations on the future governance system of human germline gene editing in China. This paper argues that in recent years, the ethics governance of germline genome editing in China has been accelerated and great changes have been made. However, the regulatory system for germline genome editing requires further improvement in three aspects: coordination of legislation and agencies, establishment of an ethics review system at high levels, and public participation and education.
Longitudinal changes of white matter microstructure following traumatic brain injury in U.S. military service members
Authors: Yeh Ping-Hong , Lippa Sara. M. , Brickell Tracey A. , Ollinger John , French Louis M. , Lange Rael T. 
Published: May 2022

Abstract
The purpose of this study was to analyze quantitative diffusion tensor imaging measures across the spectrum of traumatic brain injury severity and evaluate their trajectories in military service members. Participants were 96 U.S. military service members and veterans who had sustained a mild traumatic brain injury [including complicated mild traumatic brain injury (n = 16) and uncomplicated mild traumatic brain injury (n = 68)], moderate-severe traumatic brain injury (n = 12), and controls (with or without orthopaedic injury, n = 39). All participants had been scanned at least twice, with some receiving up to five scans. Both whole brain voxel-wise analysis and tract-of-interest analysis were applied to assess the group differences of diffusion tensor imaging metrics, and their trajectories between time points of scans and days since injury. Linear mixed modelling was applied to evaluate cross-sectional and longitudinal diffusion tensor imaging metrics changes within and between groups using both tract-of-interest and voxel-wise analyses. Participants with moderate to severe traumatic brain injury had larger white matter disruption both in superficial subcortical and deep white matter, mainly over the anterior part of cerebrum, than those with mild traumatic brain injury, both complicated and uncomplicated, and there was no evidence of recovery over the period of follow-ups in moderate-severe traumatic brain injury, but deterioration was possible. Participants with mild traumatic brain injury had white matter microstructural changes, mainly in deep central white matter over the posterior part of cerebrum, with more spatial involvement in complicated mild traumatic brain injury than in uncomplicated mild traumatic brain injury and possible brain repair through neuroplasticity, e.g. astrocytosis with glial processes and glial scaring. Our results did not replicate ‘V-shaped’ trajectories in diffusion tensor imaging metrics, which were revealed in a previous study assessing the sub-acute stage of brain injury in service members and veterans following military combat concussion. In addition, non-traumatic brain injury controls, though not demonstrating any evidence of sustaining a traumatic brain injury, might have transient white matter changes with recovery afterward. Our results suggest that white matter integrity following a remote traumatic brain injury may change as a result of different underlying mechanisms at the microstructural level, which can have a significant consequence on the long-term well beings of service members and veterans. In conclusion, longitudinal diffusion tensor imaging improves our understanding of the mechanisms of white matter microstructural changes across the spectrum of traumatic brain injury severity. The quantitative metrics can be useful as guidelines in monitoring the long-term recovery.
Machine learning-based prediction of motor status in glioma patients using diffusion MRI metrics along the corticospinal tract
Authors: Shams Boshra , Wang Ziqian , Roine Timo , Aydogan Dogu Baran , Vajkoczy Peter , Lippert Christoph , Picht Thomas , Fekonja Lucius S. 
Published: May 2022

AbstractAlong tract statistics enables white matter characterization using various diffusion MRI metrics. These diffusion models reveal detailed insights into white matter microstructural changes with development, pathology and function. Here, we aim at assessing the clinical utility of diffusion MRI metrics along the corticospinal tract, investigating whether motor glioma patients can be classified with respect to their motor status. We retrospectively included 116 brain tumour patients suffering from either left or right supratentorial, unilateral World Health Organization Grades II, III and IV gliomas with a mean age of 53.51 ± 16.32 years. Around 37% of patients presented with preoperative motor function deficits according to the Medical Research Council scale. At group level comparison, the highest non-overlapping diffusion MRI differences were detected in the superior portion of the tracts’ profiles. Fractional anisotropy and fibre density decrease, apparent diffusion coefficient axial diffusivity and radial diffusivity increase. To predict motor deficits, we developed a method based on a support vector machine using histogram-based features of diffusion MRI tract profiles (e.g. mean, standard deviation, kurtosis and skewness), following a recursive feature elimination method. Our model achieved high performance (74% sensitivity, 75% specificity, 74% overall accuracy and 77% area under the curve). We found that apparent diffusion coefficient, fractional anisotropy and radial diffusivity contributed more than other features to the model. Incorporating the patient demographics and clinical features such as age, tumour World Health Organization grade, tumour location, gender and resting motor threshold did not affect the model’s performance, revealing that these features were not as effective as microstructural measures. These results shed light on the potential patterns of tumour-related microstructural white matter changes in the prediction of functional deficits.
The PxIxIT motif of the RCAN3 inhibits angiogenesis and tumor progression in Triple Negative breast cancer in immunocompetent mice
Authors: Biçer Atilla , López-Henares Patricia , Molero-Magariño Marta , Feu-Llauradó Andrea , Sabariego-Navarro Miguel , Bayod Sergi , Padilla Laura , Taco Mª Rosario , Larriba Sara , Pérez-Riba Mercè , Serrano-Candelas Eva 
Published: May 2022

Abstract
RCAN proteins are endogenous regulators of the calcineurin-cytosolic nuclear factor of activated T cells (CN-NFATc) pathway that bind CN through similar conserved motifs PxIxIT and LxVP of the NFATc family. RCAN1 and RCAN3 protein levels were reported to correlate with overall survival of breast cancer patients. We additionally provided supporting results about RCAN3 role on cancer showing that overexpression of the native PxIxIT sequence of RCAN3-derived R3 peptide (PSVVVH, EGFP-R3178–210) dramatically inhibits tumor growth and tumor angiogenesis in an orthotopic mouse model of Triple Negative Breast Cancer (TNBC) in nude mice. On the other hand, RCAN3 protein and its derived peptide EGFP-R3178–210 bind to CN and inhibit NFAT-mediated cytokine gene expression without affecting CN phosphatase activity suggesting that RCAN3 and EGFP-R3178–210 peptide have tumor suppressor and immunosuppressant activity. Due to the known relationship between tumor development and immune system, as well as the relevance of CN-NFATc in the regulation of the immune system, in the present study we decided to assess the effect of EGFP-R3178–210 peptide in an orthotopic syngeneic TNBC mouse model, in order to ensure that the role of RCAN3 as immunosuppressant do not override its tumor suppressor activity. Our results evidence that EGFP-R3178–210 peptide displays an inhibitory potential on tumor growth and tumor angiogenesis similar to those obtained in the previous orthotopic TNBC model. These results highlight the importance of the RCAN3 peptide as a tumor suppressor protein and totally complement our previous results, indicating that this antitumor activity role is maintained in the presence of a complete functional immune system.
Low G9a expression is a tumor progression factor of colorectal cancer via IL-8 promotion
Authors: Ichikawa Yoshitoshi , Takahashi Hidekazu , Chinen Yoshinao , Arita Asami , Sekido Yuki , Hata Tsuyoshi , Ogino Takayuki , Miyoshi Norikatsu , Uemura Mamoru , Yamamoto Hirofumi , Mizushima Tsunekazu , Doki Yuichiro , Eguchi Hidetoshi 
Published: May 2022

Abstract
The histone methyltransferase G9a is expressed in various types of cancer cells, including colorectal cancer (CRC) cells. Interleukin 8 (IL)-8, also known as C-X-C motif chemokine ligand 8 (CXCL8), is a chemokine that plays a pleiotropic function in the regulation of inflammatory responses and cancer development. Here, we examined the relationship between G9a and IL-8 and the clinical relevance of this association. We immunohistochemically analyzed 235 resected CRC samples to correlate clinical features. Samples with high G9a expression had better overall survival and relapse-free survival than those with low G9a expression. Univariate and multivariate analyses demonstrated that low G9a expression remained a significant independent prognostic factor for increased disease recurrence and decreased survival (P &lt; 0.05). G9a was expressed at high levels in commercially available CRC cell lines HCT116 and HT29. Knockdown of G9a by siRNA, shRNA or the G9a-specific inhibitor BIX01294 upregulated IL-8 expression. The number of spheroids was significantly increased in HCT116 cells with stably suppressed G9a expression, and the number of spheroids was significantly decreased in HCT116 cells with stably suppressed IL-8 expression. Thus, the suppression of IL-8 by G9a may result in a better prognosis in CRC cases with high G9a expression. Furthermore, G9a may suppress cancer stemness and increase chemosensitivity by controlling IL-8. Therefore, G9a is a potential novel marker for predicting CRC prognosis, and therapeutic targeting of G9a in CRC should be controversial.
Auditory cortical plasticity after cochlear implantation in asymmetric hearing loss is related to spatial hearing: a PET H215O study
Authors: Karoui Chadlia , Strelnikov Kuzma , Payoux Pierre , Salabert Anne-Sophie , James Chris J , Deguine Olivier , Barone Pascal , Marx Mathieu 
Published: May 2022

Abstract
In asymmetric hearing loss (AHL), the normal pattern of contralateral hemispheric dominance for monaural stimulation is modified, with a shift towards the hemisphere ipsilateral to the better ear. The extent of this shift has been shown to relate to sound localization deficits. In this study, we examined whether cochlear implantation to treat postlingual AHL can restore the normal functional pattern of auditory cortical activity and whether this relates to improved sound localization. The auditory cortical activity was found to be lower in the AHL cochlear implanted (AHL-CI) participants. A cortical asymmetry index was calculated and showed that a normal contralateral dominance was restored in the AHL-CI patients for the nonimplanted ear, but not for the ear with the cochlear implant. It was found that the contralateral dominance for the nonimplanted ear strongly correlated with sound localization performance (rho = 0.8, P &lt; 0.05). We conclude that the reorganization of binaural mechanisms in AHL-CI subjects reverses the abnormal lateralization pattern induced by the deafness, and that this leads to improved spatial hearing. Our results suggest that cochlear implantation enables the reconstruction of the cortical mechanisms of spatial selectivity needed for sound localization.
The role of rivaroxaban in eosinophilic myocarditis
Authors: Bodagh Carla , Sawh Chris , Garg Pankaj 
Published: May 2022

Abstract
This is a case of eosinophilic myocarditis which had large left-ventricular thrombus seen on echocardiography and cardiac magnetic resonance imaging which was successfully treated with a highly selective direct Factor Xa inhibitor—rivaroxaban.
‘Here comes the story of the Hurricane’: a case report of AL cardiac amyloidosis and myocardial bridging
Authors: Cappannoli Luigi , Ciliberti Giuseppe , Restivo Attilio , Palumbo Pierpaolo , D’Alò Francesco , Sanna Tommaso , Crea Filippo , D’Amario Domenico 
Published: May 2022

Abstract

Background
Cardiac amyloidosis (CA) is a rapidly progressive infiltrative cardiomyopathy, whose role is emerging as a not-so-rare disorder leading to heart failure (HF). Myocardial bridge (MB) is the most common inborn coronary artery variant, and its clinical relevance is still matter of debate. The exceptional coexistence of these two conditions could accelerate disease progression and worsen the already compromised clinical conditions.

Case summary
We present the case of a 76-year-old female patient experiencing relapsing HF decompensation and presenting to our centre with dyspnoea at rest and severe peripheral congestion. Echocardiogram showed severe concentric hypertrophy, severe biventricular contractile dysfunction, and third-degree diastolic dysfunction. Coronary angiography excluded epicardial atherosclerotic disease, though displaying a long intramyocardial course of left anterior descending artery. Physiological invasive test was achieved in terms of instantaneous wave-free ratio (iFR), both at baseline and after inotropic and chronotropic stimuli, and attested haemodynamic significance. Concurrently, the diagnostic flow chart for CA was accomplished, by means of both invasive (periumbilical fat biopsy, bone marrow aspiration) and non-invasive tests (99mTc-diphosphonate scintigraphy, serum-urine immunofixation) that confirmed the suspect of primary amyloidosis. Acute HF therapy was personalized according to the singularity of the case, avoiding both nitrates and beta-blockers, then first cycle of chemotherapy was started.

Discussion
Our clinical case shows a unique interaction between infiltrative cardiomyopathy and coronary artery abnormality. Amyloidosis can contribute to the ischaemic burden of the MB and this may, in turn, abbreviate the path to HF decompensation.
Effectiveness of methotrexate as a second-line treatment for cardiac sarcoidosis assessed via 18F-FDG PET: a case report
Authors: Dotare Taishi , Maeda Daichi , Matsue Yuya , Minamino Tohru 
Published: May 2022

Abstract

Background
Although methotrexate has been widely used as a second-line therapy for cardiac sarcoidosis (CS), it is not clear if it has a direct anti-inflammatory effect.

Case summary
A 65-year-old man presented to our hospital with symptomatic ventricular tachycardia (VT). After cardioversion, electrocardiography showed a first-degree atrioventricular block with a right bundle branch block, and transthoracic echocardiography revealed left ventricular dilatation. After extensive investigations, including fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET), the patient was diagnosed with CS according to the Japanese Circulation Society guidelines. After the implantation of a transvenous implantable cardioverter defibrillator, corticosteroid therapy was introduced at a starting dose of 30 mg/day. After corticosteroid therapy was tapered to a maintenance dose of 10 mg/day, he had an uneventful clinical course without symptoms for the 1st year after hospital discharge. However, symptomatic VT recurred and 18F-FDG PET showed abnormal patterns of cardiac FDG uptake. Although he was treated with corticosteroid therapy once more, which was gradually up-titrated to a dose of 20 mg/day over a 1-month period, myocardial uptake of 18F-FDG PET remained unchanged. As the patient was considered steroid refractory, second-line treatment with 6 mg/week of methotrexate was introduced, whereas maintaining the dose of corticosteroid therapy at 20 mg/day. After 1 month, 18F-FDG PET showed remarkable reduction in FDG uptake, and the patient had a good clinical course without further episodes of arrhythmia or other symptoms during an 8-month follow-up.

Discussion
Methotrexate may have a direct anti-inflammatory effect in patients with CS refractory to regular corticosteroid therapy.