bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pulmonary metatranscriptome prior to pediatric HCT identifies post-HCT lung injury
Authors: Zinter Matt S. , Lindemans Caroline A. , Versluys Birgitta A. , Mayday Madeline Y. , Sunshine Sara , Reyes Gustavo , Sirota Marina , Sapru Anil , Matthay Michael A. , Kharbanda Sandhya , Dvorak Christopher C. , Boelens Jaap J. , DeRisi Joseph L. 
Published: December 2020

Abstract
Lung injury after pediatric allogeneic hematopoietic cell transplantation (HCT) is a common and disastrous complication that threatens long-term survival. To develop strategies to prevent lung injury, novel tools are needed to comprehensively assess lung health in HCT candidates. Therefore, this study analyzed biospecimens from 181 pediatric HCT candidates who underwent routine pre-HCT bronchoalveolar lavage (BAL) at the University Medical Center Utrecht between 2005 and 2016. BAL fluid underwent metatranscriptomic sequencing of microbial and human RNA, and unsupervised clustering and generalized linear models were used to associate microbiome gene expression data with the development of post-HCT lung injury. Microbe-gene correlations were validated using a geographically distinct cohort of 18 pediatric HCT candidates. The cumulative incidence of post-HCT lung injury varied significantly according to 4 pre-HCT pulmonary metatranscriptome clusters, with the highest incidence observed in children with pre-HCT viral enrichment and innate immune activation, as well as in children with profound microbial depletion and concomitant natural killer/T-cell activation (P &lt; .001). In contrast, children with pre-HCT pulmonary metatranscriptomes containing diverse oropharyngeal taxa and lacking inflammation rarely developed post-HCT lung injury. In addition, activation of epithelial-epidermal differentiation, mucus production, and cellular adhesion were associated with fatal post-HCT lung injury. In a separate validation cohort, associations among pulmonary respiratory viral load, oropharyngeal taxa, and pulmonary gene expression were recapitulated; the association with post-HCT lung injury needs to be validated in an independent cohort. This analysis suggests that assessment of the pre-HCT BAL fluid may identify high-risk pediatric HCT candidates who may benefit from pathobiology-targeted interventions.
Malaria and COVID-19: unmasking their ties
Authors: Hussein Mogahed Ismail Hassan , Albashir Ahmed Abdalazim Dafallah , Elawad Omer Ali Mohamed Ahmed , Homeida Anmar 
Published: December 2020

AbstractThe incidence and mortality of COVID-19, according to the World Health Organization reports, shows a noticeable difference between North America, Western Europe, and South Asia on one hand and most African countries on the other hand, especially the malaria-endemic countries. Although this observation could be attributed to limited testing capacity, mitigation tools adopted and cultural habits, many theories have been postulated to explain this difference in prevalence and mortality. Because death tends to occur more in elders, both the role of demography, and how the age structure of a population may contribute to the difference in mortality rate between countries were discussed. The variable distribution of the ACEI/D and the ACE2 (C1173T substitution) polymorphisms has been postulated to explain this variable prevalence. Up-to-date data regarding the role of hydroxychloroquine (HCQ) and chloroquine (CQ) in COVID-19 have been summarized. The article also sheds lights on how the similarity of malaria and COVID-19 symptoms can lead to misdiagnosis of one disease for the other or overlooking the possibility of co-infection. As the COVID-19 pandemic threatens the delivery of malaria services, such as the distribution of insecticide-treated nets (ITNs), indoor residual spraying, as well as malaria chemoprevention there is an urgent need for rapid and effective responses to avoid malaria outbreaks.
Tumour-infiltrating lymphocytes as a prognostic and tamoxifen predictive marker in premenopausal breast cancer: data from a randomised trial with long-term follow-up
Authors: Lundgren Christine , Bendahl Pär-Ola , Ekholm Maria , Fernö Mårten , Forsare Carina , Krüger Ute , Nordenskjöld Bo , Stål Olle , Rydén Lisa 
Published: December 2020

Abstract
Background
Tumour-infiltrating lymphocytes (TILs) are of important prognostic and predictive value in human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) and triple-negative breast cancer (TNBC), but their clinical relevance in oestrogen receptor-positive/HER2-negative (ER+/HER2−) remains unknown. The primary study aim was to analyse the prognostic effect of TILs on the BC-free interval (BCFi) in premenopausal patients stratified by BC subtypes. The secondary aim was to investigate if TILs are predictive of tamoxifen (TAM) benefit.

Methods
Archival tissues from primary breast tumours were collected from patients from the SBII:2pre trial, in which 564 premenopausal women were randomised to 2 years of adjuvant TAM or no systemic treatment, regardless of hormone receptor status. TILs were scored on whole tissue sections from 447 patients with available ER status. Tumours were divided into ER+/HER2−, HER2+ and TNBC subtypes by immunohistochemistry and in situ hybridisation. The prognostic value of TILs was analysed in systemically untreated patients (n = 221); the predictive information was investigated in the ER+ subgroup (n = 321) by cumulative incidence curves and Cox regression analyses. The median follow-up was 28 years.

Results
High (≥ 50%) infiltration of TILs was a favourable prognostic factor in terms of BCFi (univariable analysis: hazard ratioBCFi (HRBCFi) 0.40; 95% confidence interval (CI) 0.22–0.71; P = 0.002). Similar effects were observed across all BC subtypes. The effect of adjuvant TAM was stronger in patients with ER+ tumours and TILs < 50% (HRBCFi 0.63; 95% CI 0.47–0.84; P = 0.002) than in patients with high immune infiltration (≥ 50%) (HRBCFi 0.84; 95% CI (0.24–2.86); P = 0.77). However, evidence for differential effects of TAM in categories of TILs, i.e. interaction, was weak.

Conclusions
We demonstrate a long-term favourable prognostic value of high infiltration of TILs in a cohort of premenopausal BC patients and the positive prognostic effect was extended to the ER+/HER2− subgroup. A beneficial effect of TAM in ER+ patients was observed in patients with tumours of low TIL infiltration, but evidence for a treatment predictive effect was weak.

Trial registration
This trial is registered in the ISRCTN database, trial ID: ISRCTN12474687.
Immunity and the carotid body: implications for metabolic diseases
Authors: Conde Silvia V. , Sacramento Joana F. , Martins Fatima O. 
Published: December 2020

AbstractNeuro-immune communication has gained enormous interest in recent years due to increasing knowledge of the way in which the brain coordinates functional alterations in inflammatory and autoimmune responses, and the mechanisms of neuron-immune cell interactions in the context of metabolic diseases such as obesity and type 2 diabetes. In this review, we will explain how this relationship between the nervous and immune system impacts the pro- and anti-inflammatory pathways with specific reference to the hypothalamus-pituitary-adrenal gland axis and the vagal reflex and will explore the possible involvement of the carotid body (CB) in the neural control of inflammation. We will also highlight the mechanisms of vagal anti-inflammatory reflex control of immunity and metabolism, and the consequences of functional disarrangement of this reflex in settlement and development of metabolic diseases, with special attention to obesity and type 2 diabetes. Additionally, the role of CB in the interplay between metabolism and immune responses will be discussed, with specific reference to the different stimuli that promote CB activation and the balance between sympathetic and parasympathetic in this context. In doing so, we clarify the multivarious neuronal reflexes that coordinate tissue-specific responses (gut, pancreas, adipose tissue and liver) critical to metabolic control, and metabolic disease settlement and development. In the final section, we will summarize how electrical modulation of the carotid sinus nerve may be utilized to adjust these reflex responses and thus control inflammation and metabolic diseases, envisioning new therapeutics horizons.
Development of a fast-hardening retarding high-early-strength concrete with low-alkalinity sulphoaluminate cement and practical application
Authors: Sha Zhijun , Long Xiang , Feng Jiahui , Jiang Haibo , Wang Tianlong 
Published: December 2020

AbstractTo widen bridges, a usual method is to cast joint connections between new and old bridge decks without traffic interruption. The traffic vibrations have negative influence on the quality of joint connections. Shortening the construction time can alleviate the impact on the traffics, a fast-hardening retarding high-early-strength concrete (FRHC) for the connections is in need. In this study, low-alkalinity sulphoaluminate cement (LASC) concrete was modified to gain these characteristics. Based on FRHC concrete, four slab specimens including a monolithic concrete slab and three joint FRHC slabs were cast to investigate their flexural behaviors. With proper splicing details in joint connections, the joint FRHC specimens behaved approximately similar to the monolithic specimen. Combing the laboratory tests and engineering practice, the newly developed FRHC mixture succeeded in fast-hardening, retarding and high-early strength and the joint connections filled with FRHC have a good flexural performance.
Accuracy of dopaminergic imaging as a biomarker for mild cognitive impairment with Lewy bodies
Authors: Roberts Gemma , Donaghy Paul C. , Lloyd Jim , Durcan Rory , Petrides George , Colloby Sean J. , Lawley Sarah , Ciafone Joanna , Hamilton Calum A. , Firbank Michael , Allan Louise , Barnett Nicola , Barker Sally , Olsen Kirsty , Howe Kim , Ali Tamir , Taylor John-Paul , O'Brien John , Thomas Alan J. 
Published: December 2020

BackgroundDopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain.AimsTo provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies.MethodWe conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard.ResultsAt latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52–77%), specificity 88% (76–95%) and accuracy 76% (68–84%), with positive likelihood ratio 5.3.ConclusionsIt is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.
Microsatellite Instability in Patients With Stage III Colon Cancer Receiving Fluoropyrimidine With or Without Oxaliplatin: An ACCENT Pooled Analysis of 12 Adjuvant Trials
Authors: Cohen Romain , Taieb Julien , Fiskum Jack , Yothers Greg , Goldberg Richard , Yoshino Takayuki , Alberts Steven , Allegra Carmen , de Gramont Aimery , Seitz Jean-Francois , O'Connell Michael , Haller Daniel , Wolmark Norman , Erlichman Charles , Zaniboni Alberto , Lonardi Sara , Kerr Rachel , Grothey Axel , Sinicrope Frank A. , André Thierry , Shi Qian 
Published: December 2020

PURPOSE: In patients with stage III colon cancer (CC) whose tumors demonstrate microsatellite instability (MSI), the efficacy of adjuvant fluoropyrimidine (FP) with or without oxaliplatin has not been clearly demonstrated and the prognostic value of MSI remains uncertain. MATERIALS AND METHODS: Individual patient data from the ACCENT database were used to evaluate the effect of FP with or without oxaliplatin on disease-free survival (DFS) and overall survival (OS) among patients with MSI stage III CC and the prognostic value of MSI in patients treated with FP plus oxaliplatin, by stratified Cox models adjusted for demographic and clinicopathological factors. RESULTS: MSI status was available for 5,457 patients (609 MSI, 11.2%; 4848 microsatellite stable [MSS], 88.8%) from 12 randomized clinical trials (RCTs). Oxaliplatin significantly improved OS of MSI patients from the two RCTs testing FP with or without oxaliplatin (n = 185; adjusted hazard ratio [aHR] = 0.52, 95% CI, 0.28 to 0.93). Among the 4,250 patients treated with FP plus oxaliplatin (461 MSI and 3789 MSS), MSI was associated with better OS in the N1 group compared with MSS (aHR = 0.66; 95% CI, 0.46 to 0.95) but similar survival in the N2 population (aHR = 1.13; 95% CI, 0.86 to 1.48; P interaction = .029). The main independent prognosticators of MSI patients treated with FP plus oxaliplatin were T stage (aHR = 2.09; 95% CI, 1.29 to 3.38) and N stage (aHR = 3.57; 95% CI, 2.32 to 5.48). Similar results were observed for DFS in all analyses. CONCLUSION: Adding oxaliplatin to FP improves OS and DFS in patients with MSI stage III CC. Compared with MSS, MSI patients experienced better outcomes in the N1 group but similar survival in the N2 group.
Randomized Trial of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF-Mutant Metastatic Colorectal Cancer (SWOG S1406)
Authors: Kopetz Scott , Guthrie Katherine A. , Morris Van K. , Lenz Heinz-Josef , Magliocco Anthony M. , Maru Dipen , Yan Yibing , Lanman Richard , Manyam Ganiraju , Hong David S. , Sorokin Alexey , Atreya Chloe E. , Diaz Luis A. , Allegra Carmen , Raghav Kanwal P. , Wang Stephen E. , Lieu Christopher H. , McDonough Shannon L. , Philip Philip A. , Hochster Howard S. 
Published: December 2020

PURPOSE BRAF V600E mutations are rarely associated with objective responses to the BRAF inhibitor vemurafenib in patients with metastatic colorectal cancer (CRC). Blockade of BRAF V600E by vemurafenib causes feedback upregulation of EGFR, whose signaling activities can be impeded by cetuximab. METHODS One hundred six patients with BRAF V600E-mutated metastatic CRC previously treated with one or two regimens were randomly assigned to irinotecan and cetuximab with or without vemurafenib (960 mg PO twice daily). RESULTS Progression-free survival, the primary end point, was improved with the addition of vemurafenib (hazard ratio, 0.50, P = .001). The response rate was 17% versus 4% ( P = .05), with a disease control rate of 65% versus 21% ( P < .001). A decline in circulating tumor DNA BRAF V600E variant allele frequency was seen in 87% versus 0% of patients ( P < .001), with a low incidence of acquired RAS alterations at the time of progression. RNA profiling suggested that treatment benefit did not depend on previously established BRAF subgroups or the consensus molecular subtype. CONCLUSION Simultaneous inhibition of EGFR and BRAF combined with irinotecan is effective in BRAF V600E-mutated CRC.
Path-dependent course of epidemic: Are two phases of quarantine better than one?
Authors: Nimmagadda Varun , Kogan Oleg , Khain Evgeniy 
Published: December 2020

Abstract
The importance of a strict quarantine has been widely debated during the COVID-19 epidemic even from the purely epidemiological point of view. One argument against strict lockdown measures is that once the strict quarantine is lifted, the epidemic comes back, and so the cumulative number of infected individuals during the entire epidemic will stay the same. We consider an SIR model on a network and follow the disease dynamics, modeling the phases of quarantine by changing the node degree distribution. We show that the system reaches different steady states based on the history: the outcome of the epidemic is path-dependent despite the same final node degree distribution. The results indicate that the two-phase route to the final node degree distribution (a strict phase followed by a soft phase) is always better than one phase (the same soft one) unless all the individuals have the same number of connections at the end (the same degree); in the latter case, the overall number of infected is indeed history-independent. The modeling also suggests that the optimal procedure of lifting the quarantine consists of releasing nodes in the order of their degree - highest first.
Circulating Exosomes From Patients With Graves’ Disease Induce an Inflammatory Immune Response
Authors: Cui Xuejiao , Huang Mingshi , Wang Shiwei , Zhao Na , Huang Ting , Wang Zhenzhen , Qiao Jing , Wang Shuo , Shan Zhongyan , Teng Weiping , Li Yushu 
Published: December 2020

Abstract
Exosomes are extracellular vesicles that can participate in autoimmune diseases. The purpose of this study was to explore whether circulating exosomes are involved in Graves’ disease (GD) pathogenesis. In this study, serum exosomes were extracted from 26 healthy controls (HC-EXO), 26 GD patients (GD-EXO), and 7 Graves’ ophthalmopathy patients (GO-EXO). For each group, the total protein content was detected, and thyrotropin receptor, insulin-like growth factor 1 receptor (IGF-1R), heat shock protein 60 (HSP60), and cluster of differentiation (CD) 63 expression were analyzed by Western blotting (WB). Healthy volunteer-derived peripheral blood mononuclear cells (PBMCs) and HC-EXO or GD-EXO were cocultured for 24 h, and immunofluorescence was used to observe the locations of the exosomes and toll-like receptor (TLR) 2/3. CD11c+TLR2+ and CD11c+TLR3+ cell percentages were determined by flow cytometry. Myeloid differentiation factor 88 (MyD88), toll/interleukin (IL)-1 receptor domain-containing adaptor inducing interferon-β (TRIF) and p-P65 expression were analyzed by WB. IL-6 and IL-1β supernatant levels were detected using enzyme-linked immunosorbent assay. The results showed that the total protein concentration was similar among GD-EXO, GO-EXO, and HC-EXO. IGF-1R and HSP60 expression was significantly higher in GD-EXO and GO-EXO than in HC-EXO. After coculturing PBMCs with GD-EXO or HC-EXO for 24 h, GD-EXO could bind to TLR2/3. GD-EXO significantly increased CD11c+TLR2+ and CD11c+TLR3+ cell percentages; MyD88, TRIF, and p-P65 protein expression; and IL-6 and IL-1β levels. In conclusion, we first demonstrated that GD-EXO and GO-EXO highly expressed IGF-1R and HSP60. GD-EXO may induce an inflammatory response through the TLR/NF-κB signaling pathway and be involved in the pathogenesis of GD.
Protein kinase Cα regulates the nucleocytoplasmic shuttling of KRIT1
Authors: De Luca Elisa , Perrelli Andrea , Swamy Harsha , Nitti Mariapaola , Passalacqua Mario , Furfaro Anna Lisa , Salzano Anna Maria , Scaloni Andrea , Glading Angela J. , Retta Saverio Francesco 
Published: December 2020

ABSTRACT
KRIT1 is a scaffolding protein that regulates multiple molecular mechanisms, including cell–cell and cell–matrix adhesion, and redox homeostasis and signaling. However, rather little is known about how KRIT1 is itself regulated. KRIT1 is found in both the cytoplasm and the nucleus, yet the upstream signaling proteins and mechanisms that regulate KRIT1 nucleocytoplasmic shuttling are not well understood. Here, we identify a key role for protein kinase C (PKC) in this process. In particular, we found that PKC activation promotes the redox-dependent cytoplasmic localization of KRIT1, whereas inhibition of PKC or treatment with the antioxidant N-acetylcysteine leads to KRIT1 nuclear accumulation. Moreover, we demonstrated that the N-terminal region of KRIT1 is crucial for the ability of PKC to regulate KRIT1 nucleocytoplasmic shuttling, and may be a target for PKC-dependent regulatory phosphorylation events. Finally, we found that silencing of PKCα, but not PKCδ, inhibits phorbol 12-myristate 13-acetate (PMA)-induced cytoplasmic enrichment of KRIT1, suggesting a major role for PKCα in regulating KRIT1 nucleocytoplasmic shuttling. Overall, our findings identify PKCα as a novel regulator of KRIT1 subcellular compartmentalization, thus shedding new light on the physiopathological functions of this protein.
The budding yeast Start repressor Whi7 differs in regulation from Whi5, emerging as a major cell cycle brake in response to stress
Authors: Méndez Ester , Gomar-Alba Mercè , Bañó M. Carmen , Mendoza Manuel , Quilis Inma , Igual J. Carlos 
Published: December 2020

ABSTRACT
Start is the main decision point in the eukaryotic cell cycle at which cells commit to a new round of cell division. It involves the irreversible activation of a transcriptional programme through the inactivation of Start transcriptional repressors: the retinoblastoma family in mammals, or Whi5 and its recently identified paralogue Whi7 (also known as Srl3) in budding yeast. Here, we provide a comprehensive comparison of Whi5 and Whi7 that reveals significant qualitative differences. Indeed, the expression, subcellular localization and functionality of Whi7 and Whi5 are differentially regulated. Importantly, Whi7 shows specific properties in its association with promoters not shared by Whi5, and for the first time, we demonstrate that Whi7, and not Whi5, can be the main contributor to Start inhibition such as it occurs in the response to cell wall stress. Our results help to improve understanding of the interplay between multiple differentially regulated Start repressors in order to face specific cellular conditions.
Research Progress on Photocatalytic Reduction of Cr(VI) in Polluted Water
Authors: Yuan Gaoqian , Li Faliang , Li Kezhuo , Liu Jie , Li Junyi , Zhang Shaowei , Jia Quanli , Zhang Haijun 
Published: December 2020

Abstract
More and more wastewater containing hexavalent chromium (Cr(VI)), which causes increasingly threatening environmental events including death of plants or organisms, soil inactivation and canceration of human organs, has been caused by rapid industrial growth. Various methods, such as photocatalytic reduction, physical adsorption, electrochemical and photoelectrochemical approaches have been proposed to detoxify/remove Cr(VI) contained in wastewater. Quite significantly, photocatalytic Cr(VI) reduction grabs increasing attention with many advantages, including environmental friendliness, no sludge, low secondary pollution risk, high utilization of solar energy and low dosage of chemical reagents. For the purpose of improving the Cr(VI) removal efficiency during the photocatalytic reduction process, various kinds of catalysts were developed. In this mini-review, the photocatalytic reduction of Cr(VI) by ion doping photocatalysts, faceted photocatalysts, and heterostructure photocatalysts are briefly introduced. Furthermore, some suggestions for modifying photocatalysts to enhance their photocatalytic performance on Cr(VI) reduction are put forward.