bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genetic heterogeneity and drug resistance mechanisms of relapsed refractory multiple myeloma
Authors: Vo Josh N. , Wu Yi-Mi , Mishler Jeanmarie , Hall Sarah , Mannan Rahul , Wang Lisha , Ning Yu , Zhou Jin , Hopkins Alexander C. , Estill James C. , Chan Wallace K. B. , Yesil Jennifer , Cao Xuhong , Rao Arvind , Tsodikov Alexander , Talpaz Moshe , Cole Craig E. , Ye Jing C. ,   Multiple Myeloma Research Consortium, Ailawadhi Sikander , Berdeja Jesus G. , Hofmeister Craig C. , Jagannath Sundar , Jakubowiak Andrzej , Krishnan Amrita , Kumar Shaji , Levy Moshe Yair , Lonial Sagar , Orloff Gregory J. , Siegel David , Trudel Suzanne , Usmani Saad Z. , Vij Ravi , Wolf Jeffrey L. , Zonder Jeffrey A. , Bergsagel P. Leif , Auclair Daniel , Cho Hearn Jay , Robinson Dan R. , Chinnaiyan Arul M. 
Published: June 2022

AbstractMultiple myeloma is the second most common hematological malignancy. Despite significant advances in treatment, relapse is common and carries a poor prognosis. Thus, it is critical to elucidate the genetic factors contributing to disease progression and drug resistance. Here, we carry out integrative clinical sequencing of 511 relapsed, refractory multiple myeloma (RRMM) patients to define the disease’s molecular alterations landscape. The NF-κB and RAS/MAPK pathways are more commonly altered than previously reported, with a prevalence of 45–65% each. In the RAS/MAPK pathway, there is a long tail of variants associated with the RASopathies. By comparing our RRMM cases with untreated patients, we identify a diverse set of alterations conferring resistance to three main classes of targeted therapy in 22% of our cohort. Activating mutations in IL6ST are also enriched in RRMM. Taken together, our study serves as a resource for future investigations of RRMM biology and potentially informs clinical management.
Deep learning to diagnose Hashimoto’s thyroiditis from sonographic images
Authors: Zhang Qiang , Zhang Sheng , Pan Yi , Sun Lin , Li Jianxin , Qiao Yu , Zhao Jing , Wang Xiaoqing , Feng Yixing , Zhao Yanhui , Zheng Zhiming , Yang Xiangming , Liu Lixia , Qin Chunxin , Zhao Ke , Liu Xiaonan , Li Caixia , Zhang Liuyang , Yang Chunrui , Zhuo Na , Zhang Hong , Liu Jie , Gao Jinglei , Di Xiaoling , Meng Fanbo , Zhang Linlei , Wang Yuxuan , Duan Yuansheng , Shen Hongru , Li Yang , Yang Meng , Yang Yichen , Xin Xiaojie , Wei Xi , Zhou Xuan , Jin Rui , Zhang Lun , Wang Xudong , Song Fengju , Zheng Xiangqian , Gao Ming , Chen Kexin , Li Xiangchun 
Published: June 2022

AbstractHashimoto’s thyroiditis (HT) is the main cause of hypothyroidism. We develop a deep learning model called HTNet for diagnosis of HT by training on 106,513 thyroid ultrasound images from 17,934 patients and test its performance on 5051 patients from 2 datasets of static images and 1 dataset of video data. HTNet achieves an area under the receiver operating curve (AUC) of 0.905 (95% CI: 0.894 to 0.915), 0.888 (0.836–0.939) and 0.895 (0.862–0.927). HTNet exceeds radiologists’ performance on accuracy (83.2% versus 79.8%; binomial test, p < 0.001) and sensitivity (82.6% versus 68.1%; p < 0.001). By integrating serologic markers with imaging data, the performance of HTNet was significantly and marginally improved on the video (AUC, 0.949 versus 0.888; DeLong’s test, p = 0.004) and static-image (AUC, 0.914 versus 0.901; p = 0.08) testing sets, respectively. HTNet may be helpful as a tool for the management of HT.
Structural and electrophysiological basis for the modulation of KCNQ1 channel currents by ML277
Authors: Willegems Katrien , Eldstrom Jodene , Kyriakis Efthimios , Ataei Fariba , Sahakyan Harutyun , Dou Ying , Russo Sophia , Van Petegem Filip , Fedida David 
Published: June 2022

AbstractThe KCNQ1 ion channel plays critical physiological roles in electrical excitability and K+recycling in organs including the heart, brain, and gut. Loss of function is relatively common and can cause sudden arrhythmic death, sudden infant death, epilepsy and deafness. Here, we report cryogenic electron microscopic (cryo-EM) structures ofXenopusKCNQ1 bound to Ca2+/Calmodulin, with and without the KCNQ1 channel activator, ML277. A single binding site for ML277 was identified, localized to a pocket lined by the S4-S5 linker, S5 and S6 helices of two separate subunits. Several pocket residues are not conserved in other KCNQ isoforms, explaining specificity. MD simulations and point mutations support this binding location for ML277 in open and closed channels and reveal that prevention of inactivation is an important component of the activator effect. Our work provides direction for therapeutic intervention targeting KCNQ1 loss of function pathologies including long QT interval syndrome and seizures.
Regulation of age-associated insulin resistance by MT1-MMP-mediated cleavage of insulin receptor
Authors: Guo Xuanming , Asthana Pallavi , Gurung Susma , Zhang Shuo , Wong Sheung Kin Ken , Fallah Samane , Chow Chi Fung Willis , Che Sijia , Zhai Lixiang , Wang Zening , Ge Xin , Jiang Zhixin , Wu Jiayan , Zhang Yijing , Wu Xiaoyu , Xu Keyang , Lin Cheng Yuan , Kwan Hiu Yee , Lyu Aiping , Zhou Zhongjun , Bian Zhao-Xiang , Wong Hoi Leong Xavier 
Published: June 2022

AbstractInsulin sensitivity progressively declines with age. Currently, the mechanism underlying age-associated insulin resistance remains unknown. Here, we identify membrane-bound matrix metalloproteinase 14 (MT1-MMP/MMP14) as a central regulator of insulin sensitivity during ageing. Ageing promotes MMP14 activation in insulin-sensitive tissues, which cleaves Insulin Receptor to suppress insulin signaling. MT1-MMP inhibition restores Insulin Receptor expression, improving insulin sensitivity in aged mice. The cleavage of Insulin Receptor by MT1-MMP also contributes to obesity-induced insulin resistance and inhibition of MT1-MMP activities normalizes metabolic dysfunctions in diabetic mouse models. Conversely, overexpression of MT1-MMP in the liver reduces the level of Insulin Receptor, impairing hepatic insulin sensitivity in young mice. The soluble Insulin Receptor and circulating MT1-MMP are positively correlated in plasma from aged human subjects and non-human primates. Our findings provide mechanistic insights into regulation of insulin sensitivity during physiological ageing and highlight MT1-MMP as a promising target for therapeutic avenue against diabetes.
Evaluating utility and feasibility of mismatch repair testing of colorectal cancer patients in a low-middle-income country
Authors: Elsayed Inas , Geraghty Robert , Mekki Salwa O. , Mohamedani Ahmed A. , Ahern Susan , Salim Omer E. H. , Khalil Balgis B. M. , Abdelrahim Sawsan , Suliman Suliman H. , Elhassan Moawia M. A. , Salah Salah O. , Salih Mohamed E. , Widatalla Abubakr H. , Abdelhamed Osman S. , Wang Xiaosheng , Ryan Éanna J. , Winter Des , Bakhiet Salih , Sheahan Kieran 
Published: June 2022

AbstractMolecular pathology services for colorectal cancer (CRC) in Sudan represent a significant unmet clinical need. In a retrospective cohort study involving 50 patients diagnosed with CRC at three major medical settings in Sudan, we aimed to outline the introduction of a molecular genetic service for CRC in Sudan, and to explore the CRC molecular features and their relationship to patient survival and clinicopathological characteristics. Mismatch repair (MMR) and BRAF (V600E) mutation status were determined by immunohistochemistry. A mismatch repair deficient (dMMR) subtype was demonstrated in 16% of cases, and a presumptive Lynch Syndrome (LS) diagnosis was made in up to 14% of patients. dMMR CRC in Sudan is characterized by younger age at diagnosis and a higher incidence of right-sided tumours. We report a high mortality in Sudanese CRC patients, which correlates with advanced disease stage, and MMR status. Routine MMR immunohistochemistry (with sequential BRAF mutation analysis) is a feasible CRC prognostic and predictive molecular biomarker, as well as a screening tool for LS in low-middle-income countries (LMICs).
Relationship between electroencephalographic data and comfort perception captured in a Virtual Reality design environment of an aircraft cabin
Authors: Ricci Giulia , De Crescenzio Francesca , Santhosh Sandhya , Magosso Elisa , Ursino Mauro 
Published: June 2022

AbstractSuccessful aircraft cabin design depends on how the different stakeholders are involved since the first phases of product development. To predict passenger satisfaction prior to the manufacturing phase, human response was investigated in a Virtual Reality (VR) environment simulating a cabin aircraft. Subjective assessments of virtual designs have been collected via questionnaires, while the underlying neural mechanisms have been captured through electroencephalographic (EEG) data. In particular, we focused on the modulation of EEG alpha rhythm as a valuable marker of the brain’s internal state and investigated which changes in alpha power and connectivity can be related to a different visual comfort perception by comparing groups with higher and lower comfort rates. Results show that alpha-band power decreased in occipital regions during subjects’ immersion in the virtual cabin compared with the relaxation state, reflecting attention to the environment. Moreover, alpha-band power was modulated by comfort perception: lower comfort was associated with a lower alpha power compared to higher comfort. Further, alpha-band Granger connectivity shows top-down mechanisms in higher comfort participants, modulating attention and restoring partial relaxation. Present results contribute to understanding the role of alpha rhythm in visual comfort perception and demonstrate that VR and EEG represent promising tools to quantify human–environment interactions.
Increased sleep duration and delayed sleep timing during the COVID-19 pandemic
Authors: Yuan Robin K. , Zitting Kirsi-Marja , Maskati Liyaan , Huang Jeff 
Published: June 2022

AbstractMany studies have examined how the 2019 Coronavirus Disease (COVID-19) has impacted sleep health. Early evidence suggests that lockdown policies worldwide have led to changes in sleep timing, duration, and quality; however, few studies have attempted to look at the longer-term effects across multiple countries in a large data set. This study uses self-reported data from 64,858 users of the Sleep As Android smartphone application from around the world over a 24-month period in 2019 to 2020. We found a significant but modest increase in time in bed (TIB), as well as a significant delay in sleep timing that was especially prominent on weekdays. While this effect persisted throughout the year, differences in sleep timing were more widespread and pronounced in the earlier months of the pandemic. We observed a small overall increase in TIB when comparing 2020 to 2019, but these changes depended on location and time of year, suggesting that sleep duration may have more closely tracked the progression of the pandemic in each country. Our findings suggest that pandemic-induced changes in lifestyle, such as remote work and lockdown policies, may have facilitated later sleep timing but that these changes may diminish as restrictions are lifted.
Magnesium stable isotope composition, but not concentration, responds to obesity and early insulin-resistant conditions in minipig
Authors: le Goff Samuel , Godin Jean-Philippe , Albalat Emmanuelle , Nieves José Manuel Ramos , Balter Vincent 
Published: June 2022

AbstractHypomagnesemia is frequently associated with type 2 diabetes and generally correlates with unfavorable disease progression, but the magnesium status in pre-diabetic conditions remains unclear. Here, the magnesium metabolism is scrutinized in a minipig model of obesity and insulin resistance by measuring variations of the metallome—the set of inorganic elements—and the magnesium stable isotope composition in six organs of lean and obese minipigs raised on normal and Western-type diet, respectively. We found that metallomic variations are most generally insensitive to lean or obese phenotypes. The magnesium stable isotope composition of plasma, liver, kidney, and heart in lean minipigs are significantly heavier than in obese minipigs. For both lean and obese minipigs, the magnesium isotope composition of plasma and liver were negatively correlated to clinical phenotypes and plasma lipoproteins concentration as well as positively correlated to hyperinsulinemic-euglycemic clamp output. Because the magnesium isotope composition was not associated to insulin secretion, our results suggest that it is rather sensitive to whole body insulin sensitivity, opening perspectives to better comprehend the onset of insulin-resistant diabetic conditions.
Guiding antiferromagnetic transitions in Ca$$_{2}$$RuO$$_{4}$$
Authors: Porter D. G. , Forte F. , Granata V. , Cannavacciuolo M. , Fittipaldi R. , Cuoco M. , Bombardi A. , Vecchione A. 
Published: June 2022

AbstractUnderstanding and controlling the transition between antiferromagnetic states having different symmetry content with respect to time-inversion and space-group operations are fundamental challenges for the design of magnetic phases with topologically nontrivial character. Here, we consider a paradigmatic antiferromagnetic oxide insulator, Ca$$_{2}$$

2

RuO$$_{4}$$

4

, with symmetrically distinct magnetic ground states and unveil a novel path to guide the transition between them. The magnetic changeover results from structural and orbital reconstruction at the transition metal site that in turn arise as a consequence of substitutional doping. By means of resonant X-ray diffraction we track the evolution of the structural, magnetic, and orbital degrees of freedom for Mn doped Ca$$_{2}$$

2

RuO$$_{4}$$

4

to demonstrate the mechanisms which drive the antiferromagnetic transition. While our analysis focuses on a specific case of substitution, we show that any perturbation that can impact in a similar way on the crystal structure, by reconstructing the induced spin–orbital exchange, is able to drive the antiferromagnetic reorganization.
Experimental and simulation study on aluminium alloy piston based on thermal barrier coating
Authors: Liu Yang , Lei Jilin , Niu Xiaoqiang , Deng Xiwen , Wen Jun , Wen Zhigao 
Published: June 2022

AbstractThermal barrier coatings (TBCs) have low thermal conductivity, effectively reducing the temperature of the metal matrix and improving thermal performance, knock resistance, and combustion performance of the piston. In this study, an off-road high-pressure common-rail diesel engine was chosen as the research object. Combined with the test results of the piston temperature field under the rated power and maximum torque conditions, a finite element simulation model of the thermal barrier coating piston was established. This model enabled the distribution characteristics and variation laws of the temperature field, stress, and deformation of the thermal barrier coating on the piston matrix to be analysed. The results show that the maximum temperature of the TBC piston is 12.2% and 13.73% lower than that of the aluminium alloy piston under the rated power and maximum torque conditions, respectively. The thermal stresses of the TBC piston at the top of the cavity were 25.9% and 26.8% lower than those of the aluminium piston, while the thermo-mechanical coupling stress of the TBC piston was slightly higher than that of the aluminium piston—1.2 MPa and 3.7 MPa in the bottom of the combustion chamber with geometric mutation, respectively. The radial thermal deformation of the TBC piston was 0.067 mm and 0.073 mm lower than that of the aluminium piston, with the radial thermo-mechanical coupling deformation also decreasing by 0.069 mm and 0.075 mm, respectively. The radial thermal deformation of the piston in the direction parallel to the pinhole axis was greater than that in the direction perpendicular to the pinhole axis; the difference in the magnitude of the change results in uneven thermal deformation of the piston.
Zinc nutritional status, mood states and quality of life in diarrhea-predominant irritable bowel syndrome: a case–control study
Authors: Rezazadegan Mahsa , Shahdadian Farnaz , Soheilipour Maryam , Tarrahi Mohammad Javad , Amani Reza 
Published: June 2022

AbstractZinc is an important trace element for structure, and regulation in the central nervous system, as well as the gut homeostasis. There are several mental disorders associated with zinc deficiency. The relationship between zinc nutritional status with mood states and quality of life (QoL) in diarrhea-predominant irritable bowel syndrome (IBS-D) has not been studied yet. This case–control study aimed to investigate the association between zinc nutritional status with mood states and QoL in IBS-D patients. Sixty-one newly diagnosed patients with IBS-D and 61 matched healthy controls were enrolled. Dietary zinc intakes and serum zinc levels were measured. Mood states and QoL were evaluated by validated questionnaires. Logistic regression was used to estimate the odds of IBS-D in relation to zinc deficiency. Decreased serum zinc levels were observed in the IBS-D group than in the controls (p = 0.001). There were higher scores of depression (p = 0.014), anxiety (p = 0.005), and stress (p = 0.001) among IBS-D patients. Moreover, overall QoL, physical and psychological health were lower in IBS-D patients compared to the controls (p < 0.001). “Food avoidance” had the lowest, while the “relationship” had the highest score among the patients (51.09 ± 26.80 and 78.14 ± 23.30, respectively). Dietary zinc intake was positively correlated with psychological health in the controls (r = 0.295, p = 0.022) and with body image in the patients (r = 0.266, p = 0.044). According to the logistic regression, zinc deficiency was not significantly associated with odds of IBS-D. Findings show that zinc deficiency may be associated with some parameters of IBS-D. Further clinical studies are needed to explore the causal relationship between zinc status and IBS pathogenesis.
Single-qubit reaped quantum state tomography
Authors: Choi Mahn-Soo 
Published: June 2022

AbstractQuantum state tomography is the experimental procedure of determining an unknown state. It is not only essential for the verification of resources and processors of quantum information but is also important in its own right with regard to the foundation of quantum mechanics. Standard methods have been elusive for large systems because of the enormous number of observables to be measured and the exponential complexity of data post-processing. Here, we propose a new scheme of quantum state tomography that requires the measurement of only three observables (acting jointly on the system and pointer) regardless of the size of the system. The system is coupled to a “pointer” of single qubit, and the wavefunction of the system is “reaped” onto the pointer upon the measurement of the system. Subsequently, standard two-state tomography on the pointer and classical post-processing are used to reconstruct the quantum state of the system. We also developed an efficient and scalable iterative maximum likelihood algorithm to estimate states from statistically incomplete data.
Comparative transcriptome analysis of Indian domestic duck reveals candidate genes associated with egg production
Authors: Bhavana Karippadakam , Foote Dustin J. , Srikanth Krishnamoorthy , Balakrishnan Christopher N. , Prabhu Vandana R. , Sankaralingam Shanmugam , Singha Hijam Surachandra , Gopalakrishnan Achamveetil , Nagarajan Muniyandi 
Published: June 2022

AbstractEgg production is an important economic trait and a key indicator of reproductive performance in ducks. Egg production is regulated by several factors including genes. However the genes involved in egg production in duck remain unclear. In this study, we compared the ovarian transcriptome of high egg laying (HEL) and low egg laying (LEL) ducks using RNA-Seq to identify the genes involved in egg production. The HEL ducks laid on average 433 eggs while the LEL ducks laid 221 eggs over 93 weeks. A total of 489 genes were found to be significantly differentially expressed out of which 310 and 179 genes were up and downregulated, respectively, in the HEL group. Thirty-eight differentially expressed genes (DEGs), includingLHX9, GRIA1, DBH, SYCP2L, HSD17B2, PAR6, CAPRIN2, STC2,andRAB27Bwere found to be potentially related to egg production and folliculogenesis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that DEGs were enriched for functions related to glutamate receptor activity, serine-type endopeptidase activity, immune function, progesterone mediated oocyte maturation and MAPK signaling. Protein–protein interaction network analysis (PPI) showed strong interaction between 32 DEGs in two distinct clusters. Together, these findings suggest a mix of genetic and immunological factors affect egg production, and highlights candidate genes and pathways, that provides an understanding of the molecular mechanisms regulating egg production in ducks and in birds more broadly.
Importance of underweight in childhood bacterial meningitis in Finland, Latin America and Angola
Authors: Roine Irmeli , Kallio Markku , Peltola Heikki , Pelkonen Tuula 
Published: June 2022

AbstractOur objective was to explore the importance of underweight on the course of childhood bacterial meningitis (BM) at different study sites, because prior studies showed discrepant results. Using directly comparable, prospective data from three continents, weight-for-age z-scores (WAZ) were determined by WHO Anthro programs in children with BM in Finland (N = 318), LatAm (N = 580), and Angola (N = 780) and compared with data describing the admission, course, and outcome of BM. WAZ < –1 indicates underweight; either mild (< –1 to –2), moderate (< –2 to –3), or severe (< –3). The mean WAZ (SD) was 0.17 (1.17), –0.42 (1.53), and –1.36 (1.44), and the prevalence of moderate-severe underweight 2.8%, 12.6%, and 31.3%, in Finland, LatAm, and Angola, respectively. In univariate analysis, LatAm and Angola showed an association between lower WAZ and poorer condition on admission, slower recovery, and more deaths. In Finland, infrequent underweight limited meaningful analysis. In multivariate analysis of different variables for increasing the odds of death, severe underweight had lower odds compared to disease severity in Angola, but highest in LatAm. Thus, the apparent discrepancy in underweights´ importance for increasing deaths varied from primary to more secondary according to locally more prominent risks.