bluuebunny/crossref_metadata_2025 huggingface dataset:
Archetypal Analysis of Injury in Kidney Transplant Biopsies Identifies Two Classes of Early AKI
Authors: Halloran Philip F. , Böhmig Georg A. , Bromberg Jonathan , Einecke Gunilla , Eskandary Farsad A. , Gupta Gaurav , Myslak Marek , Viklicky Ondrej , Perkowska-Ptasinska Agnieszka , Madill-Thomsen Katelynn S. ,   The INTERCOMEX Investigators
Published: April 2022

All transplanted kidneys are subjected to some degree of injury as a result of the donation-implantation process and various post-transplant stresses such as rejection. Because transplants are frequently biopsied, they present an opportunity to explore the full spectrum of kidney response-to-wounding from all causes. Defining parenchymal damage in transplanted organs is important for clinical management because it determines function and survival. In this study, we classified the scenarios associated with parenchymal injury in genome-wide microarray results from 1,526 kidney transplant indication biopsies collected during the INTERCOMEX study. We defined injury groups by using archetypal analysis (AA) of scores for gene sets and classifiers previously identified in various injury states. Six groups and their characteristics were defined in this population: No injury, minor injury, two classes of acute kidney injury (“AKI,” AKI1, and AKI2), chronic kidney disease (CKD), and CKD combined with AKI. We compared the two classes of AKI, namely, AKI1 and AKI2. AKI1 had a poor function and increased parenchymal dedifferentiation but minimal response-to-injury and inflammation, instead having increased expression of PARD3, a gene previously characterized as being related to epithelial polarity and adherens junctions. In contrast, AKI2 had a poor function and increased response-to-injury, significant inflammation, and increased macrophage activity. In random forest analysis, the most important predictors of function (estimated glomerular filtration rate) and graft loss were injury-based molecular scores, not rejection scores. AKI1 and AKI2 differed in 3-year graft survival, with better survival in the AKI2 group. Thus, injury archetype analysis of injury-induced gene expression shows new heterogeneity in kidney response-to-wounding, revealing AKI1, a class of early transplants with a poor function but minimal inflammation or response to injury, a deviant response characterized as PC3, and an increased risk of failure. Given the relationship between parenchymal injury and kidney survival, further characterization of the injury phenotypes in kidney transplants will be important for an improved understanding that could have implications for understanding native kidney diseases (ClinicalTrials.gov #NCT01299168).
Macular Changes Observed on Optical Coherence Tomography Angiography in Patients Infected With Human Immunodeficiency Virus Without Infectious Retinopathy
Authors: Du Kui-Fang , Huang Xiao-Jie , Chen Chao , Kong Wen-Jun , Xie Lian-Yong , Dong Hong-Wei , Wei Wen-Bin
Published: April 2022

Purpose

As the human immunodeficiency virus (HIV) pandemic is far from over, whether there are subclinical macular changes in HIV-positive patients is something that should not be overlooked. We aimed to apply optical coherence tomography angiography (OCTA) to assess the macular structure and microvasculature changes in patients with HIV without infectious retinopathy.

Methods

HIV-positive and -negative participants were included and classified into three groups: HIV-negative, HIV-positive, and HIV-positive with microvasculopathy. OCTA parameters regarding macular structure and microvasculature were analyzed.

Results

Compared with the HIV-negative group, the superficial retinal vessel density (VD) in the parafovea sectors and the whole Early Treatment of Diabetic Retinopathy Study (ETDRS) grid and the choroidal vascularity index (CVI) in the whole ETDRS grid were significantly decreased in the HIV-positive and HIV-positive with microvasculopathy groups (p < 0.05). No differences were found in OCTA parameters between the HIV-positive and HIV-positive with microvasculopathy groups. Retinal, retinal nerve fiber layer-ganglion cell layer-inner plexiform layer (RNFL-GCL-IPL), RNFL, GCL-IPL, and INL thickness showed a negative association with the duration of HIV diagnosis or antiretroviral therapy (ART) (all p < 0.05). All OCTA microvasculature parameters showed no association with HIV-related clinical variables (all p > 0.05).

Conclusions

Subclinical macular changes existed in HIV-infected patients without clinical infectious retinopathy. Substructures from inner retinal layers might be associated with HIV infection or ART duration.
MDGNN: Microbial Drug Prediction Based on Heterogeneous Multi-Attention Graph Neural Network
Authors: Pi Jiangsheng , Jiao Peishun , Zhang Yang , Li Junyi
Published: April 2022

Human beings are now facing one of the largest public health crises in history with the outbreak of COVID-19. Traditional drug discovery could not keep peace with newly discovered infectious diseases. The prediction of drug-virus associations not only provides insights into the mechanism of drug–virus interactions, but also guides the screening of potential antiviral drugs. We develop a deep learning algorithm based on the graph convolutional networks (MDGNN) to predict potential antiviral drugs. MDGNN is consisted of new node-level attention and feature-level attention mechanism and shows its effectiveness compared with other comparative algorithms. MDGNN integrates the global information of the graph in the process of information aggregation by introducing the attention at node and feature level to graph convolution. Comparative experiments show that MDGNN achieves state-of-the-art performance with an area under the curve (AUC) of 0.9726 and an area under the PR curve (AUPR) of 0.9112. In this case study, two drugs related to SARS-CoV-2 were successfully predicted and verified by the relevant literature. The data and code are open source and can be accessed from https://github.com/Pijiangsheng/MDGNN.
Dissecting the Effect of Berberine on the Intestinal Microbiome in the Weaned Piglets by Metagenomic Sequencing
Authors: Hu Hong , Xu Kexing , Wang Kunping , Zhang Feng , Bai Xi
Published: April 2022

This study aimed to investigate the microbial structure and function in the rectum of weaned piglets with berberine supplementation. Twelve healthy 21-day-old Duorc × (Landrace × Large White) weaned piglets (similar body weight) were evenly divided into control and berberine groups and were fed a basal diet supplemented with 0 and 0.1% berberine, respectively. After 21 days, metagenomic sequencing analysis was performed to detect microbial composition and function in the rectum of weaned piglets. Results showed that there were 10,597,721,931–14,059,392,900 base pairs (bp) and 10,186,558,171–15,859,563,342 bp of clean data in the control and berberine groups, respectively. The Q20s of the control and berberine groups were 97.15 to 97.7% and 96.26 to 97.68%, respectively. The microorganisms in the berberine group had lower (p < 0.05) Chao1, alternating conditional expectation, Shannon, and Simpson indices at the species levels than those in the control group. Analysis of similarity showed that there were significant differences (p < 0.01) between the control and berberine groups at the genus and species levels of the gut microorganisms. Dietary berberine significantly increased (p < 0.05) the abundance of Subdoligranulum variabile, but decreased (p < 0.05) the abundance of Prevotella copri compared with the control group. Carbohydrate-active enzymes analysis revealed that the levels of polysaccharide lyases and carbohydrate esterases were lower (p < 0.05) in the berberine group than that in the control group. Linear discriminant analysis effect size analysis showed that berberine supplementation could induce various significant Kyoto Encyclopedia of Genes and Genomes pathways, including carbohydrate metabolism, environmental information processing, and microbial metabolism in diverse environments. In conclusion, our findings suggest that berberine could improve the composition, abundance, structure, and function of gut microbiome in the weaned piglets, potentially providing a suitable approach for the application of berberine in human and animal health.
Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders
Authors: Williams Monray E. , Cloete Ruben
Published: April 2022

HIV-1 is responsible for a spectrum of neurocognitive deficits defined as HIV-associated neurocognitive disorders (HAND). The HIV transactivator of transcription (Tat) protein plays a key role in the neuropathophysiology of HAND. The Tat protein functions by transactivation of viral genes through its interaction with the transactivation response (TAR) RNA element. Subtype-specific Tat protein signatures including C31S, R57S and Q63E present in Tat subtype C has previously been linked to a lowered neuropathophysiology compared to Tat subtype B. In this study, we attempted to understand the molecular mechanism by which Tat subtype-specific variation, particularly, C31S, R57S, and Q63E influence the Tat-TAR interaction. We performed molecular modeling to generate accurate three-dimensional protein structures of the HIV-1 Tat subtypes C and B using the Swiss model webserver. Thereafter, we performed a molecular docking of the TAR RNA element to each of the Tat subtypes B and C protein structures using the HDOCK webserver. Our findings indicate that Tat subtype B had a higher affinity for the TAR RNA element compared to Tat subtype C based on a higher docking score of −187.37, a higher binding free energy value of −9834.63 ± 216.17 kJ/mol, and a higher number of protein–nucleotide interactions of 26. Furthermore, Tat subtype B displayed more flexible regions when bound to the TAR element and this flexibility could account for the stronger affinity of Tat subtype B to TAR. From the Tat signatures linked to neuropathogenesis, only R57/R57S are involved in Tat-TAR interaction. Due to the lack of electrostatic interactions observed between Tat subtype C and TAR, weaker affinity is observed, and this may contribute to a lower level of neuropathophysiology observed in subtype C infection.
The Important Double-Edged Role of Astrocytes in Neurovascular Unit After Ischemic Stroke
Authors: Han Guangyuan , Song Lijuan , Ding Zhibin , Wang Qing , Yan Yuqing , Huang Jianjun , Ma Cungen
Published: April 2022

In recent years, neurovascular unit (NVU) which is composed of neurons, astrocytes (Ast), microglia (MG), vascular cells and extracellular matrix (ECM), has become an attractive field in ischemic stroke. As the important component of NVU, Ast closely interacts with other constituents, which has been playing double-edged sword roles, beneficial or detrimental after ischemic stroke. Based on the pathophysiological changes, we evaluated some strategies for targeting Ast in treating ischemic stroke. The present review is focused on the roles of Ast in NVU and its complex signaling molecular network after ischemic stroke, which may be a prospective approach to the treatment of ischemic diseases in central nervous system.
Segregation of Multimodal Inputs Into Discrete Midbrain Compartments During an Early Critical Period
Authors: Weakley Jacob M. , Kavusak Erin K. , Carroll Julianne B. , Gabriele Mark L.
Published: April 2022

The lateral cortex of the inferior colliculus (LCIC) is a multimodal subdivision of the midbrain inferior colliculus (IC) that plays a key role in sensory integration. The LCIC is compartmentally-organized, exhibiting a series of discontinuous patches or modules surrounded by an extramodular matrix. In adult mice, somatosensory afferents target LCIC modular zones, while auditory afferents terminate throughout the encompassing matrix. Recently, we defined an early LCIC critical period (birth: postnatal day 0 to P12) based upon the concurrent emergence of its neurochemical compartments (modules: glutamic acid decarboxylase, GAD+; matrix: calretinin, CR+), matching Eph-ephrin guidance patterns, and specificity of auditory inputs for its matrix. Currently lacking are analogous experiments that address somatosensory afferent shaping and the construction of discrete LCIC multisensory maps. Combining living slice tract-tracing and immunocytochemical approaches in a developmental series of GAD67-GFP knock-in mice, the present study characterizes: (1) the targeting of somatosensory terminals for emerging LCIC modular fields; and (2) the relative separation of somatosensory and auditory inputs over the course of its established critical period. Results indicate a similar time course and progression of LCIC projection shaping for both somatosensory (corticocollicular) and auditory (intracollicular) inputs. While somewhat sparse and intermingling at birth, modality-specific projection patterns soon emerge (P4–P8), coincident with peak guidance expression and the appearance of LCIC compartments. By P12, an adult-like arrangement is in place, with fully segregated multimodal afferent arrays. Quantitative measures confirm increasingly distinct input maps, exhibiting less projection overlap with age. Potential mechanisms whereby multisensory LCIC afferent systems recognize and interface with its emerging modular-matrix framework are discussed.
DREADDs in Epilepsy Research: Network-Based Review
Authors: Mueller John-Sebastian , Tescarollo Fabio Cesar , Sun Hai
Published: April 2022

Epilepsy can be interpreted as altered brain rhythms from overexcitation or insufficient inhibition. Chemogenetic tools have revolutionized neuroscience research because they allow “on demand” excitation or inhibition of neurons with high cellular specificity. Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are the most frequently used chemogenetic techniques in epilepsy research. These engineered muscarinic receptors allow researchers to excite or inhibit targeted neurons with exogenous ligands. As a result, DREADDs have been applied to investigate the underlying cellular and network mechanisms of epilepsy. Here, we review the existing literature that has applied DREADDs to understand the pathophysiology of epilepsy. The aim of this review is to provide a general introduction to DREADDs with a focus on summarizing the current main findings in experimental epilepsy research using these techniques. Furthermore, we explore how DREADDs may be applied therapeutically as highly innovative treatments for epilepsy.
Social-Cognitive Network Connectivity in Preterm Children and Relations With Early Nutrition and Developmental Outcomes
Authors: Sato Julie , Vandewouw Marlee M. , Safar Kristina , Ng Dawn V. Y. , Bando Nicole , O’Connor Deborah L. , Unger Sharon L. , Pang Elizabeth , Taylor Margot J.
Published: April 2022

Infants born very low birth weight (VLBW, < 1,500 g) are at a heightened risk for structural brain abnormalities and social-cognitive deficits, which can impair behavioural functioning. Resting-state fMRI, reflecting a baseline level of brain activity and underlying social-cognitive processes, has also been reported to be altered in children born VLBW. Yet very little is known about the functional networks underlying social cognition using magnetoencephalography (MEG) and how it relates to neonatal factors and developmental outcomes. Thus, we investigated functional connectivity at rest in VLBW children and the associations with early nutrition and IQ and behavioural problems. We collected resting-state MEG recordings and measures of IQ and social-cognitive behaviour, as well as macronutrient/energy intakes during initial hospitalisation in 5-year-old children born VLBW (n = 37) compared to full-term (FT; n = 27) controls. We examined resting-state network differences controlling for sex and age at scan. Functional connectivity was estimated using the weighted phase lag index. Associations between functional connectivity with outcome measures and postnatal nutrition were also assessed using regression analyses. We found increased resting-state functional connectivity in VLBW compared to FT children in the gamma frequency band (65–80 Hz). This hyper-connected network was primarily anchored in frontal regions known to underlie social-cognitive functions such as emotional processing. In VLBW children, increased functional connectivity was related to higher IQ scores, while reduced connectivity was related to increased behavioural problems at 5 years of age. These within-group associations were found in the slower frequency bands of theta (4–7 Hz) and alpha (8–12 Hz), frequently linked to higher-order cognitive functions. We also found significant associations between macronutrient (protein and lipid) and energy intakes during the first postnatal month with functional connectivity at preschool-age, highlighting the long-term impacts of postnatal nutrition on preterm brain development. Our findings demonstrate that at preschool-age, VLBW children show altered resting-state connectivity despite IQ and behaviour being in the average range, possibly reflecting functional reorganisation of networks to support social-cognitive and behavioural functioning. Further, our results highlight an important role of early postnatal nutrition in the development of resting-state networks, which in turn may improve neurodevelopmental outcomes in this vulnerable population.
Ki67 Immunohistochemical Expression Level ≥70%, Bulky Presentation ≥7.5 cm, Meningeal Lymphomatosis, and Interim PET ΔSUVmax After 4 Treatment Cycles <71% as Parts of a Practical Scoring System to Predict Progression-Free Survival and Overall Survival in Diffuse Large B-Cell Lymphoma
Authors: Rebière Vincent , Maajem Meriem , Le Calloch Ronan , Raj Leela , Le Bris Anne-Sophie , Malou Mohamed , Salmon François , Quintin-Roué Isabelle , Tempescul Adrian , Bourhis David , Samaison Laura , Saad Hussam , Salaun Pierre-Yves , Berthou Christian , Ianotto Jean-Christophe , Abgral Ronan , Eveillard Jean-Richard
Published: April 2022

Currently, prognostic models in diffuse large B-cell lymphoma (DLBCL) fail to closely reflect patients' biological, clinical, and survival heterogeneity. We, therefore, assessed the impact of clinical, biological, immunohistochemical (IHC), baseline (0), and interim (after 2 and 4 treatment cycles) PET (PET0, PET2, and PET4) data not yet included in any scoring system on DLBCL outcome. The analysis was conducted on 89 previously untreated adult patients of the Finistere Observatory Cohort (O.Ly.Fin) with documented DLBCL, recruited between January 2010 and December 2017, with progression-free survival (PFS) and overall survival (OS) as primary and secondary endpoints, respectively. Seventy-eight patients were treated with rituximab, cyclophosphamide, hydroxyadriamycin, vincristine, and prednisone (R-CHOP), while 11 received R-dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and hydroxyadriamycin (EPOCH). Patients were followed up until June 20, 2020. On multivariate analysis, Ki67 ≥ 70% on IHC (K), bulky presentation ≥7.5 cm (B), meningeal lymphomatosis (M), and PET0–PET4 ΔSUVmax <71% (P4) were identified as strong independent predictors of PFS, and all variables but bulky disease also strongly and independently predicted OS. Using these 4 parameters, we designed a scoring model named KBMP4 stratifying patients into low- (0 parameter), intermediate- (1 or 2), and high-risk (≥3) subgroups by the Kaplan–Meier analysis. At a median follow-up of 43 months, PFS and OS were both 100% in the low-risk subgroup, 71.4 and 90.5%, respectively, in the intermediate-risk subgroup, and 0 and 55.5%, respectively, in the high-risk subgroup. Use of the KBMP4 model in clinical practice may improve accuracy in prognostic prediction and treatment decisions in de novo DLBCL patients.
Efficacy and Safety of Lactobacillus reuteri CCFM1040 in Allergic Rhinitis and Asthma: A Randomized, Placebo-Controlled Trial
Authors: Li Lingzhi , Fang Zhifeng , Lee Yuan-kun , Zhao Jianxin , Zhang Hao , Peng Huaiming , Zhang Yulong , Lu Wenwei , Chen Wei
Published: April 2022

The coexistence of allergic rhinitis (AR) and asthma reinforces the concept of “one airway, one disease,” which has prompted the exploration for a single intervention to treat both diseases. Lactobacillus reuteri CCFM1040 (CCFM1040) was found to be an inhibitor of the common pathogenesis of AR and asthma in our previous studies. This study presented a randomized, placebo-controlled trial to investigate the clinical effects of CCFM1040 on both diseases. The total symptom score (TSS), the quality of life (QoL), and the modulation in the gut microbiota of patients with AR, the Asthma Control and Test (ACT) of patients with asthma, and the safety of both AR and asthma were measured. In patients with AR, CCFM1040 numerically decreased TSS, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), 3 nasal scores in TSS (nasal congestion, watery eyes, and rhinorrhea), and sleep and significantly improved (P = 0.014) non-nose/eye symptoms. The ACT score was numerically increased in patients with asthma (from partially controlled to well-controlled). Significant microbial (from class level to genus level) and metabolic differences (P < 0.05) were found in patients with AR. No adverse reactions were observed. No effect on the blood and urine routine indexes. CCFM1040 has a potential benefit on both diseases. Further studies based on these findings will help to optimize the management of AR and asthma.
Drp1 Regulated Mitochondrial Hypofission Promotes the Invasion and Proliferation of Growth Hormone-Secreting Pituitary Adenomas via Activating STAT3
Authors: Zhang Yin , Zhang Lei , Fan Kexia , Gou Yajun , Zang Zhenle , Ding Xiao , Yang Hui , Li Song
Published: April 2022

The invasiveness and high proliferation rate of growth hormone-secreting pituitary adenomas (GHPAs) are closely related to poor prognosis in patients. We previously reported that abnormal glycolysis participates in this process; however, the role of mitochondria in the invasion and proliferation of GHPAs remains unknown. In the current study, stereological methods were first used to quantitatively calculate the number and morphology of mitochondria. The results revealed that the numbers, volumes and membrane areas of mitochondria were decreased in invasive GHPAs (IGHPAs) samples compared to noninvasive GHPAs (NIGHPAs) samples. Furthermore, significantly downregulated mRNA and protein levels of dynamin-related protein 1 (Drp1) were detected in IGHPAs, but no notable changes in fusion related molecules (Mfn1, Mfn2 and OPA1) were detected, suggesting that the abnormal mitochondrial dynamics in IGHPAs are characterized by hypofission. Mitochondrial hypofission caused by Mdivi-1, a specific Drp1 inhibitor, enhanced the invasion and proliferation of GH3 cell lines and primary cells from patients with GHPAs in vitro and in vivo, while overexpression of Drp1 reversed these processes. Mechanistically, mitochondrial hypofission might activate signal transducer and activator of transcription 3 (STAT3). Specifically, elevated nuclear pSTAT3Y705 may promote GH3 cell invasion by upregulating the activity of matrix metalloproteinase 2/9, and elevated mitochondrial pSTAT3S727 may promote GH3 cell proliferation by inhibiting the mitochondria-dependent apoptotic pathway. Taken together, our findings suggest that mitochondrial hypofission induced by Drp1 might strengthen the invasion and proliferation of GHPA tumor cells by activating STAT3, providing us with a new perspective on how mitochondria regulate the development of IGHPAs.
Predicting Bone Metastasis Risk Based on Skull Base Invasion in Locally Advanced Nasopharyngeal Carcinoma
Authors: Wu Bo , Guo Yu , Yang Hai-hua , Gao Qian-gang , Tian Ye
Published: April 2022

Objective

To develop and validate a bone metastasis prediction model based on skull base invasion (SBI) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC).

Methods

This retrospective cohort study enrolled 290 patients with LA-NPC who received intensity-modulated radiation therapy in two hospitals from 2010 to 2020. Patient characteristics were grouped by SBI and hospital. Both unadjusted and multivariate-adjusted models were used to determine bone metastasis risk based on SBI status. Subgroup analysis was performed to investigate heterogeneity using a forest graph. Cox proportional hazard regression analysis was used to screen for risk factors of bone metastasis-free survival (BMFS). A nomogram of BMFS based on SBI was developed and validated using C-index, receiver operating characteristic curve, calibration curves, and decision curve analysis after Cox proportional hazard regression analysis.

Results

The incidence of bone metastasis was 14.83% (43/290), 20.69% (24/116), and 10.92% (19/174) in the overall population, SBI-positive group, and SBI-negative group, respectively. In the unadjusted model, SBI was associated with reduced BMFS [HR 2.43 (1.32–4.47), P = 0.004], and the results remained stable after three continuous adjustments (P <0.05). No significant interaction was found in the subgroup analyses (P for interaction >0.05). According to Cox proportional hazard regression analysis and clinical value results, potential risk factors included SBI, Karnofsky performance status, TNM stage, induction chemotherapy, concurrent chemoradiotherapy, and adjuvant chemotherapy. Using a training C-index of 0.80 and a validation C-index of 0.79, the nomogram predicted BMFS and demonstrated satisfactory prognostic capability in 2, 3, and 5 years (area under curve: 83.7% vs. 79.6%, 81.7% vs. 88.2%, and 79.0% vs. 93.8%, respectively).

Conclusion

Skull base invasion is a risk factor for bone metastasis in patients with LA-NPC. The SBI-based nomogram model can be used to predict bone metastasis and may assist in identifying LA-NPC patients at the highest risk of bone metastasis.
Circular RNA and Its Roles in the Occurrence, Development, Diagnosis of Cancer
Authors: Zhang Yue , Zhang Xinyi , Xu Yumeng , Fang Shikun , Ji Ying , Lu Ling , Xu Wenrong , Qian Hui , Liang Zhao Feng
Published: April 2022

Circular RNAs (circRNAs) are non-coding single-stranded covalently closed circular RNA, mainly produced by reverse splicing of exons of precursor mRNAs (pre-mRNAs). The characteristics of high abundance, strong specificity, and good stability of circRNAs have been discovered. A large number of studies have reported its various functions and mechanisms in biological events, such as the occurrence and development of cancer. In this review, we focus on the classification, characterization, biogenesis, functions of circRNAs, and the latest advances in cancer research. The development of circRNAs as biomarkers in cancer diagnosis and treatment also provides new ideas for studying circRNAs research.
Radiomics Nomogram Based on Multiple-Sequence Magnetic Resonance Imaging Predicts Long-Term Survival in Patients Diagnosed With Nasopharyngeal Carcinoma
Authors: Liu Kai , Qiu Qingtao , Qin Yonghui , Chen Ting , Zhang Diangang , Huang Li , Yin Yong , Wang Ruozheng
Published: April 2022

Purpose

Although the tumor–node–metastasis staging system is widely used for survival analysis of nasopharyngeal carcinoma (NPC), tumor heterogeneity limits its utility. In this study, we aimed to develop and validate a radiomics model, based on multiple-sequence magnetic resonance imaging (MRI), to estimate the probability of overall survival in patients diagnosed with NPC.

Methods

Multiple-sequence MRIs, including T1-weighted, T1 contrast, and T2-weighted imaging, were collected from patients diagnosed with NPC. Radiomics features were extracted from the contoured gross tumor volume of three sequences from each patient using the least absolute shrinkage and selection operator with the Cox regression model. The optimal Rad score was determined using 12 of the 851 radiomics features derived from the multiple-sequence MRI and its discrimination power was compared in the training and validation cohorts. For better prediction performance, an optimal nomogram (radiomics nomogram-MS) that incorporated the optimal Rad score and clinical risk factors was developed, and a calibration curve and a decision curve were used to further evaluate the optimized discrimination power.

Results

A total of 504 patients diagnosed with NPC were included in this study. The optimal Rad score was significantly correlated with overall survival in both the training [C-index: 0.731, 95% confidence interval (CI): 0.709–0.753] and validation cohorts (C-index: 0.807, 95% CI: 0.782–0.832). Compared with the nomogram developed with only single-sequence MRI, the radiomics nomogram-MS had a higher discrimination power in both the training (C-index: 0.827, 95% CI: 0.809–0.845) and validation cohorts (C-index: 0.836, 95% CI: 0.815–0.857). Analysis of the calibration and decision curves confirmed the effectiveness and utility of the optimal radiomics nomogram-MS.

Conclusions

The radiomics nomogram model that incorporates multiple-sequence MRI and clinical factors may be a useful tool for the early assessment of the long-term prognosis of patients diagnosed with NPC.
Neonatal Acute Kidney Injury
Authors: Coleman Cassandra , Tambay Perez Anita , Selewski David T. , Steflik Heidi J.
Published: April 2022

Acute kidney injury (AKI) is a common occurrence in the neonatal intensive care unit (NICU). In recent years, our knowledge of the incidence and impact of neonatal AKI on outcomes has expanded exponentially. Neonatal AKI has been shown to be associated with adverse outcomes including increased length of mechanical ventilation, prolonged length of stay, and rise in mortality. There has also been increasing work suggesting that neonates with AKI are at higher risk of chronic kidney disease (CKD). In the past, AKI had been defined multiple ways. The utilization of the neonatal modified Kidney Disease: Improving Global Outcomes (KDIGO) criteria as the standard definition for neonatal AKI in research and clinical care has driven the advances in our understanding of neonatal AKI over the last 10 years. This definition has allowed researchers and clinicians to better understand the incidence, risk factors, and outcomes associated with neonatal AKI across populations through a multitude of single-center studies and the seminal, multicenter Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study. As the impacts of neonatal AKI have become clear, a shift in efforts toward identifying those at highest risk, protocolizing AKI surveillance, improving prevention and diagnosis, and expanding kidney support therapy (KST) for neonates has occurred. These efforts also include improving risk stratification (identifying high risk populations, including those with nephrotoxic medication exposure) and diagnostics (novel biomarkers and diagnostic tools). Recent work has also shown that the targeted use of methylxanthines may prevent AKI in a variety of high-risk populations. One of the most exciting developments in neonatal AKI is the advancement in technology to provide KST to neonates with severe AKI. In this comprehensive review we will provide an overview of recent work and advances in the field of neonatal AKI. This will include a detailed review of (1) the definition of neonatal AKI, (2) the epidemiology, risk factors, and outcomes associated with neonatal AKI, (3) improvements in risk stratification and diagnostics, (4) mitigation and treatment, (5) advancements in the provision of KST to neonates, and (6) the incidence and risk of subsequent CKD.
Chemotherapy Combined With Surgery in a Case With Metanephric Adenoma
Authors: Hu Shaohua , Zhao Zhenli , Wan Zhisheng , Bu Weizhen , Chen Songqiang , Lu Yiqun
Published: April 2022

Background

Metanephric adenoma is an extremely rare renal neoplasm, especially in pediatrics. Chemotherapy combined with surgery in metanephric adenoma has not been reported.

Methods

We describe a case of metanephric adenoma in a child less than 2 years old, which were treated by chemotherapy combined with surgery.

Results

Nephron sparing surgery was performed after regular chemotherapy, and the pathological result was metanephric adenoma.

Conclusion

Pediatric metanephric adenoma is extremely rare; the clinical manifestations and imaging examinations lack specificity. Nephron sparing surgery is recommended as the preferred treatment for metanephric adenoma. Long-term follow-up and more in-depth molecular genetic research are still needed to determine the benign or malignant of metanephric adenoma and whether chemotherapy drugs have an effect on it.
Thymoquinone’s Antiviral Effects: It is Time to be Proven in the Covid-19 Pandemic Era and its Omicron Variant Surge
Authors: Abdelrahim Maen , Esmail Abdullah , Al Saadi Noor , Zsigmond Eva , Al Najjar Ebtesam , Bugazia Doaa , Al-Rawi Hadeel , Alsaadi Ayat , Kaseb Ahmed O.
Published: April 2022

The COVID-19 pandemic has impacted every country in the world. With more than 400 million cases and more than 5.5 million deaths. The FDA either approved or authorized the emergency use for three vaccines against COVID-19. The treatment options of COVID-19 are very limited. Multiple complementary and alternative medicine modalities were suggested to be efficacious in the treatment of COVID-19 such as Thymoquinone. The effects of Thymoquinone have been examined and multiple studies indicate a promising beneficial effect. However, the current body of research is limited in terms of its scope, quality, and quantity. While higher-quality studies are required, physicians do not routinely recommend the use of marketed supplements of natural products, including Thymoquinone for COVID-19. Given the numerous suggested positive effects of Thymoquinone, including anti-inflammatory and antimicrobial properties, additional research is required to confirm or refute these promising benefits. Complementary and alternative medicine is an area that requires additional evidence-based practice and research to confirm effects observed in clinical practice.
Metformin Use on Incidence and Oncologic Outcomes of Bladder Cancer Patients With T2DM: An Updated Meta-Analysis
Authors: Liu Chen-Qian , Sun Jian-Xuan , Xu Jin-Zhou , Qian Xiao-Yuan , Hong Sen-Yuan , Xu Meng-Yao , An Ye , Xia Qi-Dong , Hu Jia , Wang Shao-Gang
Published: April 2022

Background: The incidence rate and mortality of bladder cancer are increasing year by year. Interestingly, the commonly used metabolic regulatory drug metformin has been reported to have anti-tumor effect in recent years. Nevertheless, it keeps unclear whether the usage of metformin is beneficial or unbeneficial in treating bladder cancer. Thus, a meta-analysis was conducted to explore the long-term effect of metformin on the incidence of bladder cancer and OS, PFS, DSS and RFS in bladder cancer patients with T2DM.

Method: We aim to collect evidence of the association between the usage of metformin and the incidence and treatment outcome of bladder cancer. We searched PubMed, Embase, Ovid Medline and Cochrane Library up to February 2021 to get effective literature reporting the effects of metformin in bladder cancer. The main outcomes were the protective effects of metformin on the incidence, overall survival (OS), recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS) of bladder cancer. And OR (odds ratio) and HR (hazard ratio) with their 95%CI were pooled. Two independent researchers assessed the quality of included studies using the Newcastle-Ottawa Scale (NOS).

Results: We involved 12 studies meeting the inclusion criteria, including a total of 1,552,773 patients. The meta-analysis showed that use of metformin could decrease the incidence (OR = 0.45, 95%CI = 0.37–0.56; p < 0.01) and prolong recurrence-free-survival (HR = 0.56, 95%CI = 0.41–0.76; p = 0.91) of bladder cancer. However, there were no significant protective effects in the overall survival (HR = 0.93, 95%CI = 0.67–1.28, p = 0.05), disease-specific-survival (HR = 0.73, 95%CI = 0.47–1.16; p = 0.01), and progression-free-survival (HR = 0.78, 95%CI = 0.53–1.15, p = 0.34).

Conclusion: The results revealed that the usage of metformin could reduce the incidence of bladder cancer and prolong the prognosis of bladder cancer in T2DM patients, respectively. More prospective studies are needed to prove the protective role of metformin on bladder cancer.
Physical Activity in Late Prepuberty and Early Puberty Is Associated With High Bone Formation and Low Bone Resorption
Authors: Rempe Jakob , Rosengren Björn E. , Jehpsson Lars , Swärd Per , Dencker Magnus , Karlsson Magnus K.
Published: April 2022

Background

Physical activity (PA) increases bone mass, especially in late prepuberty and early puberty, but it remains unclear if and how PA affects both bone formation and bone resorption.

Materials and Methods

We included 191 boys and 158 girls aged 7.7 ± 0.6 (mean ± SD) in a population-based PA intervention study. The intervention group (123 boys and 94 girls) received daily physical education (PE) in school (40 min/day; 200 min/week) from study start and during the nine compulsory school years in Sweden. The controls (68 boys and 64 girls) received the national standard of 1–2 classes PE/week (60 min/week). During the intervention, blood samples were collected at ages 9.9 ± 0.6 (n = 172; all in Tanner stages 1–2) and 14.8 ± 0.8 (n = 146; all in Tanner stages 3–5) and after termination of the intervention at age 18.8 ± 0.3 (n = 93; all in Tanner stage 5) and 23.5 ± 0.7 (n = 152). In serum, we analyzed bone formation markers [bone-specific alkaline phosphatase (bALP), osteocalcin (OC), and N-terminal propeptide of collagen type 1 (PINP)] and bone resorption markers [C-terminal telopeptide cross links (CTX) and tartrate-resistant acid phosphatase (TRAcP 5b)]. Linear regression was used to compare age and sex-adjusted mean differences between intervention children and controls in these markers.

Results

Two years after the intervention was initiated (at Tanner stages 1–2), we found higher serum levels of bALP and OC, and lower serum levels of TRAcP 5b in the intervention compared with the control group. The mean difference (95% CI) was for bALP: 13.7 (2.1, 25.3) μg/L, OC: 9.1 (0.1, 18.1) μg/L, and TRAcP 5b: −2.3 (−3.9, −0.7) U/L. At Tanner stages 3–5 and after the intervention was terminated, bone turnover markers were similar in the intervention and the control children.

Conclusion

Daily school PA in the late prepubertal and early pubertal periods is associated with higher bone formation and lower bone resorption than school PA 1–2 times/week. In late pubertal and postpubertal periods, bone formation and resorption were similar. Termination of the intervention is not associated with adverse bone turnover, indicating that PA-induced bone mass benefits gained during growth may remain in adulthood.
Expression of CCL2, FOS, and JUN May Help to Distinguish Patients With IgA Nephropathy From Healthy Controls
Authors: Zhou Xue , Wang Ning , Zhang Yuefeng , Yu Pei
Published: April 2022

Background

IgA nephropathy (IgAN), the most common type of glomerulonephritis worldwide, can only be diagnosed mainly by renal biopsy owing to lack of effective biomarkers. It is urgent to explore and identify the potential diagnostic biomarkers through assessing the gene expression profiles of patients with IgAN.

Methods

Two datasets were obtained from the Gene Expression Omnibus (GEO) database, including GSE115857 (55 IgAN, 7 living healthy donors) and GSE35487 (25 IgAN, 6 living healthy donors), then underwent differentially expressed genes (DEGs) and function enrichment analyses utilizing R packages. The common gene list was screened out between DEGs and immune-associated genes by Venn diagram, then performed gene-gene interaction, protein-protein interaction (PPI) and function enrichment analyses. Top three immune-associated hub genes were selected by Maximal Clique Centrality (MCC) method, then the expression and diagnostic value of these hub genes were determined. Consensus clustering algorithm was applied to conduct the unsupervised cluster analysis of the immune-associated hub gene list in IgAN. Finally, the Nephroseq V5 tool was applied to identify the expression level of CCL2, FOS, JUN in kidney diseases, as well as the correlation between CCL2, FOS, JUN expression and renal function in the patients with IgAN.

Results

A total of 129 DEGs were obtained through comparing IgAN with healthy controls via the GSE115857 and GSE35487 datasets. Then, we screened out 24 immune-associated IgAN DEGs. CCL2, JUN, and FOS were identified as the top three hub genes, and they were all remarkably downregulated in IgAN. More importantly, CCL2, JUN, and FOS had a high accuracy [area under the curve (AUC) reached almost 1] in predicting IgAN, which could easily distinguish between IgAN patients and healthy individuals. Three distinct subgroups of IgAN were determined based on 24 immune-associated DEGs, with significant differences in the expression of CCL2, JUN, and FOS genes. Finally, CCL2, FOS, JUN were manifested a meaningful association with proteinuria, glomerular filtration rate (GFR), and serum creatinine level.

Conclusion

In summary, our study comprehensively uncovers that CCL2, JUN, and FOS may function as promising biomarkers for diagnosis of IgAN.
UCHL1 Regulates Lipid and Perilipin 2 Level in Skeletal Muscle
Authors: Antony Ryan , Aby Katherine , Gao Hongbo , Eichholz Mary , Srinivasan Rekha , Li Yifan
Published: April 2022

Ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that was originally found in neurons. We found that UCHL1 is highly expressed in slow oxidative skeletal muscles, but its functions remain to be fully understood. In this study, we observed that UCHL1 protein levels in skeletal muscle and C2C12 myotubes were downregulated by fasting or glucose starvation respectively. Skeletal muscle selective knockout (smKO) of UCHL1 resulted in a significant reduction of lipid content in skeletal muscle and improved glucose tolerance. UCHL1 smKO did not significantly change the levels of key proteins involved in oxidative metabolism such as SDHA, Akt, or PDH. Interestingly, while the levels of the major lipases and lipid transporters were unchanged, perilipin 2 was significantly downregulated in UCHL1 smKO muscle. Consistently, in C2C12 myotubes, UCHL1 siRNA knockdown also reduced perilipin 2 protein level. This data suggests that UCHL1 may stabilize perilipin 2 and thus lipid storage in skeletal muscle.
Preliminary Assessment of Individual Zone of Optimal Functioning Model Applied to Music Performance Anxiety in College Piano Majors
Authors: Yao Zijin , Li Yue
Published: April 2022

Individual zone of optimal functioning (IZOF) is a psychological model studied and applied to quantify athletes’ anxiety and predicts their achievement in sports competitions. This study aimed to determine the application of the IZOF model to evaluate music performance anxiety (MPA) in pianists because the causes of anxiety in athletes and musicians may be similar. A total of 30 college-level piano-major students were included in the study, and the anxiety level in performance was scored by the Competitive State Anxiety Inventory-2 questionnaire. In the first phase, participants recalled and self-scored the four important performances in the past year. Notably, seven piano teachers scored the performances. Both results were combined to identify the individual IZOF zone. Each student showed different anxiety scores for cognitive state anxiety (CA), somatic state anxiety (SA), and self-confidence (SC). In the second phase, all participants scored their anxiety level 1 day before the final performance, and the same judges evaluated the performance immediately afterward. A total of 60% of the participants who had at least two subscales inside the IZOF received performance scores greater than 90. In conclusion, the IZOF model provides information for both piano teachers and pianists to help review their anxiety intensity and predict their performance scores to some extent.
Investigation of the Influence of Artificial Intelligence Markup Language-Based LINE ChatBot in Contextual English Learning
Authors: Chien Yu-Cheng , Wu Ting-Ting , Lai Chia-Hung , Huang Yueh-Min
Published: April 2022

This study is intended to create an innovative contextual English learning environment making use of the widely used communication software, LINE ChatBot, based on the Artificial Intelligence Markup Language (AIML), in order to improve speaking and listening ability among learners. A total of 73 students were invited to participate in learning activities involving a 4-week English conversation exercise including both speaking and listening. Additionally, in order to explore the influence of competition on language acquisition, we added competition characteristics to the learning activities in the experimental group to enhance learning motivation and learning outcomes. The results showed that with the help of the LINE ChatBot contextual learning environment, the performance of both groups of students was slightly enhanced, but no significant differences were found. Meanwhile, extrinsic motivation in both the experimental and control group was improved if they spoke anonymously. That is, the contextual learning environment based on the LINE ChatBot significantly improved the learners’ English speaking and listening ability. In addition, the results showed that the addition of a competition element effectively enhanced the learners’ intrinsic motivation to learn English on the LINE ChatBot.
Spinal Cord Injury at Birth, Expected Medical and Health Complexity in Chronic Injury Guided Anew by Activity-Based Restorative Therapy: Case Report
Authors: Leon Machado Laura , Noonan Kathryn , Bickel Scott , Singh Goutam , Brothers Kyle , Calvery Margaret , Behrman Andrea L.
Published: April 2022

As infancy is characterized by rapid physical growth and critical periods of development, disruptions due to illness or disease reveal vulnerability associated with this period. Spinal cord injury (SCI) has devastating consequences at any age, but its onset neonatally, at birth, or within the first year of life multiplies its impact. The immediate physical and physiological consequences are obvious and immense, but the effects on the typical trajectory of development are profound. Activity-based restorative therapies (ABRT) capitalize on activity-dependent plasticity of the neuromuscular system below the lesion and when provided to children with SCI aim to improve the child’s neuromuscular capacity, health and quality of life. This is a report of an infant with a cervical SCI at birth resulting in paralysis of leg and trunk muscles and paresis of arm and hands who was enrolled in an ABRT program at 3 years of age. After 59 sessions of ABRT, the child demonstrated significant improvements in trunk control and arm function, as well as social and emotional development. Despite the chronicity of injury and low expectations for improvement with therapeutic interventions, ABRT had a positive impact on the child’s physical capacity and provided benefits across multiple developmental domains.
Visualizing Commognitive Responsibility Shift in Collaborative Problem-Solving During Computer-Supported One-to-One Math Tutoring
Authors: Lu Jijian , Tuo Pan , Feng Ruisi , Stephens Max , Zhang Mohan , Shen Zhonghua
Published: April 2022

The aim of this study is to use a commognitive responsibility framework to visualize responsibility shift in collaborative problem solving (CPS) during computer-supported one-to-one tutoring. Commognitive responsibility shift means that individuals’ cognitive responsibility shift can be reflected by the discourse in communication. For our sample, we chose a 15-year-old Chinese boy and his mathematics teacher with 6 years of teaching experience, both of whom have experienced computer-supported learning and teaching mathematics, respectively. We collected four tutoring videos (each 60–90 min; in total, more than 330 min) online, and a 45-min interview video from the teacher. We found that the third type of commognitive responsibility shift in both the teacher’s and student’s CPS behavior online is not only teacher–student comparison but also alternating-led, which includes teacher–student-led (TS) and student–teacher-led (ST).