bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eocene Terrane Accretion in Northern Cascadia Recorded by Brittle Left‐Lateral Slip on the San Juan Fault
Authors: Harrichhausen Nicolas , Morell Kristin D. , Regalla Christine , Lynch Emerson M. , Leonard Lucinda J. 
Published: October 2022

AbstractThe San Juan fault (SJF), on southern Vancouver Island, Canada, juxtaposes the oceanic Wrangellia and Pacific Rim terranes in the northern Cascadia forearc, and has been suggested to play a role in multiple Mesozoic‐Cenozoic terrane accretion events. However, direct observations of the SJF's kinematics have not been documented and its exact role in accommodating strain arising from terrane accretion is unknown. To test if, how, and when the SJF accommodated accretion‐related strain, we use geologic mapping, kinematic inversion of fault‐plane slickenlines, and dating of marine sediments to constrain the timing and direction of brittle slip of the SJF.P‐ andT‐axes from kinematic inversions indicate predominantly left‐lateral slip. Left‐lateral brittle faulting cross‐cuts ∼51 Ma magmatic intrusions and foliation, providing a maximum age of brittle deformation. The fault zone is non‐conformably overlain by a >300 m‐thick sequence of clastic marine shelf and slope sediments that are not left‐laterally offset. A strontium isotope age of foraminifers helps constrain the depositional age of the sediments to late Eocene–early Oligocene, bracketing left‐lateral slip to the Eocene. Eocene left‐lateral slip is temporally and kinematically consistent with regional southwest‐northeast compression during accretion of the Siletzia ocean island plateau, suggesting brittle slip on the SJF accommodated strain resulting from the accretion of this terrane. This result does not support hypotheses that brittle slip along the SJF directly accommodated earlier accretion of the Pacific Rim terrane to Wrangellia, instead it offsets the older accretionary boundary between these two terranes.
MEKK4-mediated Phosphorylation of HOXA10 at Threonine 362 facilitates embryo adhesion to the endometrial epithelium
Authors: Zhang Mei , Zhang Qun , Cao Zhiwen , Cai Xinyu , Liu Jingyu , Jiang Yue , Zhu Yingchun , Zhou Jidong , Yu Lina , Zhen Xin , Hu Yali , Yan Guijun , Sun Haixiang 
Published: October 2022

AbstractEmbryo adhesion is a very important step in the embryo implantation process. Homeobox A10 (HOXA10), a key transcriptional factor of endometrial receptivity, is indispensable for embryo adhesion. However, how to control the activation status of HOXA10 remains elusive. Here, we found that Mitogen-activated protein kinase kinase kinase 4 (MEKK4) was associated with HOXA10 and directly phosphorylated HOXA10 at threonine 362. This MEKK4-mediated phosphorylation enhanced HOXA10-mediated transcriptional responses and adhesion between the embryo and endometrial epithelium. Specific deletion or kinase inactivation of MEKK4 in endometrial epithelial cells attenuates adhesion between embryo and epithelium. Therefore, the identification of MEKK4 as a novel physiological positive regulator of HOXA10 activation provides mechanistic insights to improve embryo implantation success. Moreover, when Thr362 was mutated to alanine (T362A) to mimic its dephosphorylation, the protein stability and transcriptional regulation of HOXA10 were decreased. In addition, HOXA10 -promoted embryo adhesion was weakened after the mutation of Thr362, suggesting that the phosphorylation of HOXA10 at this site may be a new indicator for evaluating endometrial receptivity and judging the ‘implantation window’.
Old drugs, new tricks: leveraging known compounds to disrupt coronavirus-induced cytokine storm
Authors: Richman Spencer , Lyman Cole , Nesterova Anastasia , Yuryev Anton , Morris Matthew , Cao Hongbao , Cheadle Chris , Skuse Gary , Broderick Gordon 
Published: October 2022

AbstractA major complication in COVID-19 infection consists in the onset of acute respiratory distress fueled by a dysregulation of the host immune network that leads to a run-away cytokine storm. Here, we present an in silico approach that captures the host immune system’s complex regulatory dynamics, allowing us to identify and rank candidate drugs and drug pairs that engage with minimal subsets of immune mediators such that their downstream interactions effectively disrupt the signaling cascades driving cytokine storm. Drug–target regulatory interactions are extracted from peer-reviewed literature using automated text-mining for over 5000 compounds associated with COVID-induced cytokine storm and elements of the underlying biology. The targets and mode of action of each compound, as well as combinations of compounds, were scored against their functional alignment with sets of competing model-predicted optimal intervention strategies, as well as the availability of like-acting compounds and known off-target effects. Top-ranking individual compounds identified included a number of known immune suppressors such as calcineurin and mTOR inhibitors as well as compounds less frequently associated for their immune-modulatory effects, including antimicrobials, statins, and cholinergic agonists. Pairwise combinations of drugs targeting distinct biological pathways tended to perform significantly better than single drugs with dexamethasone emerging as a frequent high-ranking companion. While these predicted drug combinations aim to disrupt COVID-induced acute respiratory distress syndrome, the approach itself can be applied more broadly to other diseases and may provide a standard tool for drug discovery initiatives in evaluating alternative targets and repurposing approved drugs.
Current stress minimization for isolated dual active bridge DC–DC converter
Authors: Rashwan Ahmed , Ali Ahmed I. M. , Senjyu Tomonobu 
Published: October 2022

AbstractThis paper presents a new phase-shift modulation for isolated dual active bridge (DAB) direct current–direct current (DC–DC) converter. The proposed technique aims to minimize the maximum current stress of the converter, which could directly increase the efficiency and reduce the device losses. This modulation technique controls the converter power through only two phase-shift angles or two degrees of freedom; one phase shift is used between the legs of its first bridge and the other one between the legs of the second bridge. Although the traditional single-phase shift (SPS) technique has only one degree of freedom, it suffers from many drawbacks in terms of high current stress and reverse circulating power flow, which decrease the converter efficiency. On the other hand, increasing the number of phase-shift angles can enhance the system performance but also increase the control complexity. Thus, a comparative analysis between the proposed modulation technique and the traditional SPS was conducted; the new method showed better performance in terms of current stress reduction, along with implementation simplicity.
Clustering of trauma patients based on longitudinal data and the application of machine learning to predict recovery
Authors: Stoitsas Kostas , Bahulikar Saurabh , de Munter Leonie , de Jongh Mariska A. C. , Jansen Maria A. C. , Jung Merel M. , van Wingerden Marijn , Van Deun Katrijn 
Published: October 2022

AbstractPredicting recovery after trauma is important to provide patients a perspective on their estimated future health, to engage in shared decision making and target interventions to relevant patient groups. In the present study, several unsupervised techniques are employed to cluster patients based on longitudinal recovery profiles. Subsequently, these data-driven clusters were assessed on clinical validity by experts and used as targets in supervised machine learning models. We present a formalised analysis of the obtained clusters that incorporates evaluation of (i) statistical and machine learning metrics, (ii) clusters clinical validity with descriptive statistics and medical expertise. Clusters quality assessment revealed that clusters obtained through a Bayesian method (High Dimensional Supervised Classification and Clustering) and a Deep Gaussian Mixture model, in combination with oversampling and a Random Forest for supervised learning of the cluster assignments provided among the most clinically sensible partitioning of patients. Other methods that obtained higher classification accuracy suffered from cluster solutions with large majority classes or clinically less sensible classes. Models that used just physical or a mix of physical and psychological outcomes proved to be among the most sensible, suggesting that clustering on psychological outcomes alone yields recovery profiles that do not conform to known risk factors.
Quinoline–imidazole/benzimidazole derivatives as dual-/multi-targeting hybrids inhibitors with anticancer and antimicrobial activity
Authors: Diaconu Dumitrela , Antoci Vasilichia , Mangalagiu Violeta , Amariucai-Mantu Dorina , Mangalagiu Ionel I. 
Published: October 2022

AbstractTwo new classes of hybrid quinoline–imidazole/benzimidazole derivatives (the hybrid QIBS salts and QIBC cycloadducts) were designed and synthesized to evaluate their anticancer and antimicrobial activity. The strategy adopted for synthesis is straight and efficient, in four steps: N-acylation, N-alkylation, quaternization and a Huisgen 3 + 2 cycloaddition. The in vitro single-dose anticancer assay of forty six hybrid quinoline-benzimidazole compounds reveal that one QIBS salt (11h), has an excellent quasi nonselective activity against all type of cancer cell with an excellent PGI in the area of 90–100% and very good lethality. Three others quinoline–imidazole/benzimidazole hybrids (8h, 12h, 12f) has an excellent selective activity against some cancer cell lines: breast cancer MDA-MB-468 and Leukemia HL-60 TB). The five-dose assay screening confirms that compound 11h possesses excellent anti-proliferative activity, with GI50 in the range of nano-molar, against some cancer cell lines: Leukemia HL-60 TB, Leukemia K-526, Leukemia RPMI-8226, Breast cancer MDA-MB-468, Lung cancer HOP-92 and Ovarian cancer IGROV1. The antibacterial assay indicates that three hybrid QIBS salts (12f, 12c, 12d) have an excellent activity against Gram-negative bacteria E. coli (superior to control Gentamicin) while against Gram-positive bacteria S. aureus only one compound 8i (R2 = -CF3) exhibits a significant activity (superior to control Gentamicin). The MIC assay indicates that two other compounds (11h, 12h) are biologically active to a very low concentration, in the range of nano-molar. We believe that all these excellent assets related to anticancer and antibacterial activities, make from our hybrid quinoline–imidazole/benzimidazole compounds bearing a phenyl group (R2 = –C6H5) in the para (4)-position of the benzoyl moiety a good candidate for future drug developing.
Single-cell transcriptomic profiling for inferring tumor origin and mechanisms of therapeutic resistance
Authors: Lin Maoxuan , Sade-Feldman Moshe , Wirth Lori , Lawrence Michael S. , Faden Daniel L. 
Published: October 2022

AbstractHead and Neck Squamous Cell Carcinoma (HNSCC) is an aggressive epithelial cancer with poor overall response rates to checkpoint inhibitor therapy (CPI) despite CPI being the recommended treatment for recurrent or metastatic HNSCC. Mechanisms of resistance to CPI in HNSCC are poorly understood. To identify drivers of response and resistance to CPI in a unique patient who was believed to have developed three separate HNSCCs, we performed single-cell RNA-seq (scRNA-seq) profiling of two responding lesions and one progressive lesion that developed during CPI. Our results not only suggest interferon-induced APOBEC3-mediated acquired resistance as a mechanism of CPI resistance in the progressing lesion but further, that the lesion in question was actually a metastasis as opposed to a new primary tumor, highlighting the immense power of scRNA-seq as a clinical tool for inferring tumor origin and mechanisms of therapeutic resistance.
Listening Effort and Speech Perception Performance Using Different Facemasks
Authors: Mendel Lisa Lucks , Pousson Monique A. , Shukla Bhanu , Sander Kara , Larson Brooke 
Published: October 2022

Purpose:
The aim of this study was to assess the effect of eight different facemasks on speech perception and listening effort in listeners with normal hearing (NH) and hearing loss by manipulating both mask type and background noise levels.

Method:
Forty adults listened to Quick Speech-in-Noise Test sentences recorded by a female talker through eight different facemasks including a baseline condition with no mask. Listeners were tested in the sound field positioned 6 ft from the loudspeaker. Signal-to-noise ratio (SNR) loss and listening effort were measured.

Results:
Listeners with NH exhibited a mild SNR loss, whereas those with hearing loss experienced a moderate SNR loss. Scores for the mild hearing loss group were significantly poorer (higher) than those with slight hearing loss. Speech perception performance was best in the no mask, KN95, and surgical mask conditions and poorest in the cloth mask and cloth mask plus face shield conditions for all groups. As listening effort decreased, speech perception increased for all groups.

Conclusions:
The impact of different types of facemasks on speech perception in noise was demonstrated in this study indicating that as the SNR was reduced, listening effort increased and speech perception performance decreased for listeners with NH and slight/mild hearing loss. No mask, KN95, and surgical masks had the least impact on performance, whereas cloth masks posed a significant detriment to communication. If communication is to occur in a background of noise while wearing masks, a KN95 mask and an SNR of at least +15 dB is recommended regardless of hearing status.
Travel mode choice prediction based on personalized recommendation model
Authors: Lai Zhilin , Wang Jing , Zheng Junjie , Ding Yuxing , Wang Cheng , Zhang Huizhen 
Published: October 2022

AbstractThe accurate prediction of individual travel mode in the city is necessary for the development of urban traffic intelligence. Through deep analysis on distribution of travel modes, policy makers can make proper policies to improve traffic conditions. With the development of sensing techniques and telecommunication technologies, it is easy to collect travel data of individuals and use some popular models to detect travel modes. However, existing methods are limited to aggregation analysis and these models suggest that travelers' preference mainly depend on the characteristics of travelers, little is known considering to extract individual travel preference from individual historical trips. Due to collect the user information is expensive and time‐consuming, one of the difficult tasks facing the prediction of travel mode by traditional methods is the lack of user's profile. What is more, data of different travel modes are always imbalanced. Accordingly, the paper proposes a model Balance Multi Travel Mode Deep Learning Prediction (BMTM‐DLP) for individual travel mode prediction inspired by the idea of recommender system. For the first time, the theory of recommender system is introduced into the field of individual travel mode choice prediction and we take advantage of the model to extract individual travel preference for travel mode prediction. Further, the focal loss function module is introduced into the model to reduce the impact of unbalanced categories. Experiments show that the model performs well on both datasets LPMC and XSCR, achieving 92.2% and 82.8% prediction accuracy in respective. It showed that the proposed model performed well in individual travel mode prediction.
The Therapeutic Role of Rho Kinase Inhibitor, Fasudil, on Pulmonary Hypertension; a Systematic Review and Meta-Analysis
Authors: Abedi Farshad , Omidkhoda Navid , Arasteh Omid , Ghavami Vahid , Hosseinzadeh Hossein 
Published: October 2022

AbstractBackground Pulmonary hypertension (PH) is a pathophysiological disorder, which involves multiple clinical conditions such as the upregulation of the Rho/ROCK signaling pathway. On the other hand, fasudil as a Rho kinase inhibitor has been investigated in the treatment of PH in some clinical studies.Objectives The present systematic review and meta-analysis aimed to evaluate the human clinical trials regarding the efficacy of fasudil in the management of PH.Methods Databases were searched with pre-defined search terms, up to December 2021. Efficacy measures were such as mean pulmonary arterial pressure (mPAP), systolic PAP (sPAP), pulmonary vascular resistance (PVR), systolic vascular resistance (SVR) and cardiac index (CI).Results A total of 12 studies involving 575 PH patients were included in our research. Eight short-term trials and four mid-term trials were found (no clinical trials on the long-term effects). Short-term trials had a before-after study design and measuring pulmonary hemodynamic parameters’ intervention revealed a statistically significant improvement of mPAP, sPAP, PVR, SVR, and CI in the meta-analysis of five eligible studies. Three mid-term trials also revealed improvement in some pulmonary hemodynamic parameters with fasudil and in another mid-term trial, fasudil significantly decreased rehospitalization and mortality in PH patients. No serious adverse effects with fasudil were reported in these trials.Conclusion Fasudil therapy is efficacious and probably safe in the improvement of some hemodynamics in PH patients along short and mid-term periods. However, long-term randomized controlled trials comparing fasudil with placebo and other treatments are warranted for confirmation of these benefits.
Assoziation schneller Reaktionen der Genexpression mit Änderungen der 3D-Chromatinkonformation in veränderter Schwerkraft
Authors: Thiel Cora S. , Vahlensieck Christian , Ullrich Oliver 
Published: October 2022

ZUSAMMENFASSUNGDie molekularen Prinzipien bei der Transduktion von Schwerkraftänderungen in zelluläre Antwort- und Anpassungsprozesse sind bisher weitgehend unbekannt. Wir konnten in humanen Jurkat-T-Zellen zeigen, dass Gene bei veränderter Schwerkraft in Clusterstrukturen („gravity-responsive chromosomal regions“, GRCRs) differenziell reguliert werden. Durch Kombination mit Hochdurchsatz-Chromatin-Konformationsanalysen (Hi-C) konnte eine hochsignifikante Assoziation von GRCRs mit strukturellen 3D-Chromatinveränderungen identifiziert werden, die vor allem auf den kleinen Chromosomen (chr16–chr22) kolokalisieren. Wir fanden weiterhin Hinweise auf einen mechanistischen Zusammenhang zwischen Spleißprozessen und differenzieller Genexpression bei veränderter Schwerkraft. Somit haben wir erste Belege dafür gefunden, dass Änderungen der Schwerkraft in den Zellkern übertragen werden und dort 3D-Chromosomen-Konformationsänderungen hervorrufen, die mit einer schnellen Transkriptionsantwort verbunden sind. Wir vermuten, dass die schnelle genomische Antwort auf veränderte Gravitationskräfte in der Organisation des Chromatins spezifisch codiert ist.
Correlação entre posicionamento do cage e lordose lombar em fusão transforaminal minimamente invasiva (TLIF)
Authors: Vialle Emiliano Neves , Ramos Guilherme Zandavalli , Hinojosa Fabian Lopez , Guiroy Alfredo , Rocha Luiz Gustavo Dal'Oglio da , Arruda André de Oliveira 
Published: October 2022

Resumo
Objetivo Avaliar os resultados radiográficos e comparar a lordose pós-operatória em técnica de artrodese intersomática lombar transforaminal (TLIF, na sigla em inglês), considerando como variável o posicionamento do dispositivo intersomático (cage) em relação ao espaço discal.
Métodos Análise retrospectiva radiográfica de pacientes cirúrgicos, em nível único, por doença lombar degenerativa, aplicando-se TLIF e instrumentação pedicular posterior. Os pacientes foram divididos, conforme a posição do cage, em 2 grupos: 1. TLIF-A – cages na posição anterior do espaço discal; e 2. TLIF-P, cages na posição posterior do espaço discal (considerando-se o platô vertebral superior da vértebra inferior incluída na instrumentação, cages que ocuparam a superfície correspondente a 50% anterior da linha média, compuseram o grupo TLIF-A; opostamente, cages em posicionamento posterior compuseram o grupo TLIF-P). Procedeu-se à avaliação dos exames radiográficos ortostáticos em perfil no pré- e pós-operatórios, com a tomada das seguintes medidas: lordose lombar (LL) (ângulo L1–S1); lordose segmentar (LS) (L4–S1) e lordose segmentar do cage (LSC).
Resultados Cem pacientes foram incluídos de 2011 a 2018, sendo 44 homens e 46 mulheres, com idade média de 50.5 anos (27–76 anos). Um total de 43 cages foram classificados como “anteriores” (TLIF-A) e 57, “posteriores” (TLIF-P); considerando o grupo TLIF- A, os resultados pós-operatórios médios foram: LL 50.7°, LS 34.9° e LSC 21.6°; para o grupo TLIF-P, comparativamente: LL 42.3° (p < 0,01), LS 30.7° (p < 0,05) e LSC 18.8° (p > 0,05).
Conclusão: O posicionamento anterior do cage em relação ao espaço discal correlaciona-se a melhora da lordose lombar e segmentar na radiografia em comparação com o posicionamento posterior do implante.
Severity Scoring Cutoff for MLPA and Its Diagnostic Yield in 332 North Indian Children with Developmental Delay
Authors: Srivastava Priyanka , Kaur Parminder , Daniel Roshan , Chaudhry Chakshu , Kaur Anit , Seth Saurabh , Kumari Divya , Kaur Anupriya , Panigrahi Inusha 
Published: October 2022

AbstractChromosomal aberrations/rearrangements are the most common cause of intellectual disability (ID), developmental delay (DD), and congenital malformations. Traditionally, karyotyping has been the investigation of choice in such cases, with the advantage of being cheap and easily accessible, but with the caveat of the inability to detect copy number variations of sizes less than 5 Mb. Chromosomal microarray can solve this problem, but again the problems of expense and poor availability are major challenges in developing countries. The purpose of this study is to find the utility of multiplex ligation-dependent probe amplification (MLPA) as a middle ground, in a resource-limited setting. We also attempted to establish an optimum cutoff for the de Vries score, to enable physicians to decide between these tests on a case-to-case basis, using only clinical data. A total of 332 children with DD/ID with or without facial dysmorphism and congenital malformations were studied by MLPA probe sets P245. Assessment of clinical variables concerning birth history, facial dysmorphism, congenital malformations, and family history was done. We also scored the de Vries scoring for all the patients to find a suitable cutoff for MLPA screening. In our study, the overall detection rate of MLPA was 13.5% (45/332). The majority of patients were DiGeorge's syndrome with probe deletion in 22q11.21 in 3.3% (11/332) followed by 15q11.2 del in 3.6% (12/332, split between Angelman's and Prader–Willi's syndromes). Also, 3.0% (10/332) of patients were positive for Williams–Beuren's syndrome 7q11.23, 1.8% (6/332) for Wolf–-Hirschhorn's syndrome 4p16.3, 1.2% (4/332) for 1p36 deletion, and 1% for each trichorhinophalangeal syndrome type I 8q23.3 duplication syndrome and cri du chat syndrome. The optimum cutoff of de Vries score for MLPA testing in children with ID and/or dysmorphism came out to be 2.5 (rounded off to 3) with a sensitivity of 82.2% and specificity of 66.7%. This is the largest study from India for the detection of chromosomal aberrations using MLPA common microdeletion kit P245. Our study suggests that de Vries score with a cutoff of 3 or more can be used to offer MLPA as the first tier test for patients with unexplained ID, with or without facial dysmorphism and congenital malformations.