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Languages differ qualitatively in their numeral systems. At one extreme, some languages have a small set of number terms, which denote approximate or inexact numerosities; at the other extreme, many languages have forms for exact numerosities over a very large range, through a recursively defined counting system. Why do numeral systems vary as they do? Here, we use computational analyses to explore the numeral systems of 30 languages that span this spectrum. We find that these numeral systems all reflect a functional need for efficient communication, mirroring existing arguments in other semantic domains such as color, kinship, and space. Our findings suggest that cross-language variation in numeral systems may be understood in terms of a shared functional need to communicate precisely while using minimal cognitive resources.

Background: Mycoplasma pneumoniae (M. pneumoniae) is a significant contributor to community-acquired pneumonia among children. Since 1968, when a strain of M. pneumoniae resistant to macrolide antibiotics was initially reported in Japan, macrolide-resistant M. pneumoniae (MRMP) has been documented in many countries worldwide, with varying incidence rates. MRMP infections lead to a poor response to macrolide antibiotics, frequently resulting in prolonged fever, extended antibiotic treatment, increased hospitalization, intensive care unit admissions, and a significantly higher proportion of patients receiving glucocorticoids or second-line antibiotics. Since 2000, the global incidence of MRMP has gradually increased, especially in East Asia, which has posed a serious challenge to the treatment of M. pneumoniae infections in children and attracted widespread attention from pediatricians. However, there is still no global consensus on the diagnosis and treatment of MRMP in children., Methods: We organized 29 Chinese experts majoring in pediatric pulmonology and epidemiology to write the world's first consensus on the diagnosis and treatment of pediatric MRMP pneumonia, based on evidence collection. The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, CNKI, Medline, and the Cochrane Library. We used variations in terms for "macrolide-resistant", "Mycoplasma pneumoniae", "MP", "M. pneumoniae", "pneumonia", "MRMP", "lower respiratory tract infection", "Mycoplasma pneumoniae infection", "children", and "pediatric"., Results: Epidemiology, pathogenesis, clinical manifestations, early identification, laboratory examination, principles of antibiotic use, application of glucocorticoids and intravenous immunoglobulin, and precautions for bronchoscopy are highlighted. Early and rapid identification of gene mutations associated with MRMP is now available by polymerase chain reaction and fluorescent probe techniques in respiratory specimens. Although the resistance rate to macrolide remains high, it is fortunate that M. pneumoniae still maintains good in vitro sensitivity to second-line antibiotics such as tetracyclines and quinolones, making them an effective treatment option for patients with initial treatment failure caused by macrolide antibiotics., Conclusions: This consensus, based on international and national scientific evidence, provides scientific guidance for the diagnosis and treatment of MRMP in children. Further studies on tetracycline and quinolone drugs in children are urgently needed to evaluate their effects on the growth and development. Additionally, developing an antibiotic rotation treatment strategy is necessary to reduce the prevalence of MRMP strains., (© 2024. The Author(s).)

The mitochondrial genome (mtDNA) encodes essential machinery for oxidative phosphorylation and metabolic homeostasis. Tumor mtDNA is among the most somatically mutated regions of the cancer genome, but whether these mutations impact tumor biology is debated. We engineered truncating mutations of the mtDNA-encoded complex I gene, Mt-Nd5, into several murine models of melanoma. These mutations promoted a Warburg-like metabolic shift that reshaped tumor microenvironments in both mice and humans, consistently eliciting an anti-tumor immune response characterized by loss of resident neutrophils. Tumors bearing mtDNA mutations were sensitized to checkpoint blockade in a neutrophil-dependent manner, with induction of redox imbalance being sufficient to induce this effect in mtDNA wild-type tumors. Patient lesions bearing >50% mtDNA mutation heteroplasmy demonstrated a response rate to checkpoint blockade that was improved by ~2.5-fold over mtDNA wild-type cancer. These data nominate mtDNA mutations as functional regulators of cancer metabolism and tumor biology, with potential for therapeutic exploitation and treatment stratification., (© 2024. The Author(s).)

Tumor cell phenotypes and anti-tumor immune responses are shaped by local metabolite availability, but intratumoral metabolite heterogeneity (IMH) and its phenotypic consequences remain poorly understood. To study IMH, we profiled tumor/normal regions from clear cell renal cell carcinoma (ccRCC) patients. A common pattern of IMH transcended all patients, characterized by correlated fluctuations in the abundance of metabolites and processes associated with ferroptosis. Analysis of intratumoral metabolite-RNA covariation revealed that the immune composition of the microenvironment, especially the abundance of myeloid cells, drove intratumoral metabolite variation. Motivated by the strength of RNA-metabolite covariation and the clinical significance of RNA biomarkers in ccRCC, we inferred metabolomic profiles from the RNA sequencing data of ccRCC patients enrolled in 7 clinical trials, and we ultimately identifyied metabolite biomarkers associated with response to anti-angiogenic agents. Local metabolic phenotypes, therefore, emerge in tandem with the immune microenvironment, influence ongoing tumor evolution, and are associated with therapeutic sensitivity., Competing Interests: Declaration of interests R.R.K. is a consultant and/or on the Advisory Board of Eisai and reports receiving institutional research funding from Pfizer, Takeda, Novartis, Xencor, and Allogene Therapeutics. Y.-B.C. is a consultant for Inspirna, Inc. M.H.V. is a consultant and/or on the Advisory Board of Eisai, Exelixis, Merck, Calithera, Aveo, Genentech, Oncorena, Affimed, MICU Rx Aravive, onQuality, Astra Zeneca, and Mertelsmann Foundation. M.H.V. has received research funding from Pfizer, BMS, and Genentech. C.-H.L. has received research funding from AstraZeneca, BMS, Calithera, Eisai, Eli Lilly, Exelixis, and Merck. C.-H.L. is a consultant for Aadi, Aveo, BMS, Exelixis, Eisai, Merck, Pfizer, EMD Serono, and Cardinal Health. C.-H.L. has received honoraria from AiCME, IDEOlogy Health, Intellisphere, Medscape, MJH, and Research to Practice. M.G. was an employee and a shareholder of Illumina Inc. during the preparation of this study. M.G. is currently an employee and a shareholder of Roche. R.J.M. is a consultant and/or on the Advisory Board of AstraZeneca, Aveo, Calithera Biosciences, Eisai, Exelixis, Genentech/Roche, Incyte, Pfizer, and Merck. R.J.M. has received research funding from Aveo, Bristol Myers Squibb, Eisai, Exelixis, Genentech/Roche, Novartis, Pfizer, and Merck. A.A.H. is on the Advisory Board of Merck. E.R. is a consultant for Xontogeny, LLC., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the risk factors for airway mucus hypersecretion in childhood pneumonia infected by different pathogens. Method: A retrospective cohort included 968 children who were hospitalized for Mycoplasma pneumoniae pneumonia (MPP), respiratory syncytial virus (RSV) pneumonia, adenovirus pneumonia and underwent bronchoscopy in Respiratory Department of Children's Hospital of Chongqing Medical University from January 2019 to December 2021 was conducted. The children were divided into two groups distinguished by airway mucus secretion according to the airway mucus hypersecretion score which were scored according to the mucus secretion under the bronchoscope. The demographic characteristics, clinical characteristics, laboratory tests and disease severity of the two groups were compared. And the risk factors for the development of airway mucus hypersecretion in two groups were analyzed. Chi square test, Mann-Whithey U test and Fisher exact test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the influencing factors. Result: There were 559 males and 409 females in the 968 children, with an age of 4.0 (1.4, 6.0) years. Among the 642 children with MPP, 185 cases were in the hypersecretion group and 457 cases were in the non-hypersecretion group. There were 41 cases in the hypersecretion group and 160 cases in the non-hypersecretion group of 201 children with RSV pneumonia. In the 125 children with adenovirus pneumonia, there were 39 cases in the hypersecretion group and 86 cases in the non-hypersecretion group. In these children, the age of children in the hypersecretion group was older than that in the non-hypersecretion group (6.0 (4.0, 7.0) vs. 5.0 (3.0, 7.0) years old, 1.5 (0.5, 3.6) vs . 0.8 (0.4, 1.6) years old, 2.0 (1.2, 4.5) vs. 1.3 (0.8, 2.0) years old, U =35 295.00, 2 492.00, 1 101.00, all P <0.05). Through multivariate Logistic regression analysis it found that increased risk of airway mucus hypersecretion was present in childhood MPP with increase in peripheral blood white blood cell count ( OR =3.30, 95% CI 1.51-7.93, P =0.004) or increase in neutrophil ratio ( OR =2.24, 95% CI 1.16-4.33, P =0.016) or decrease in lymphocyte count ( OR =3.22, 95% CI 1.66-6.31, P <0.001) or decrease in serum albumin ( OR =2.00, 95% CI 1.01-3.98, P =0.047). The risk of airway mucus hypersecretion was increased in children with RSV pneumonia combined with elevated peripheral blood eosinophils ( OR =3.04, 95% CI 1.02-8.93, P =0.043). Meanwhile, airway mucus hypersecretion was associated with severe pneumonia ( OR =2.46, 95% CI 1.03-6.15, P =0.047) in children with RSV pneumonia. Older age was associated with increased risk of airway mucus hypersecretion in children with adenovirus pneumonia ( OR =1.02, 95% CI 1.00-1.04, P =0.026). In these children with occurrence of pulmonary rales, wheezes or sputum sounds ( OR =3.65, 95% CI 1.22-12.64, P =0.028) had an increased risk of airway mucus hypersecretion. Neutrophils in bronchoalveolar lavage fluid (BALF) demonstrated higher ratio in hypersecretion group from children with MPP (0.65 (0.43, 0.81) vs. 0.59 (0.34, 0.76), U =24 507.00, P <0.01), while the proportion of macrophages in BALF was lower (0.10 (0.05, 0.20) vs. 0.12 (0.06, 0.24), U =33 043.00, P <0.05). Nucleated cell count and neutrophil ratio in BALF were higher in hypersecretion group of children with RSV pneumonia (1 210 (442, 2 100)×10 6 vs . 490 (210, 1 510)×10 6 /L, 0.43 (0.26, 0.62) vs. 0.30 (0.13, 0.52), U =2 043.00, 2 064.00, all P <0.05). Conclusions: The increase in peripheral blood white blood cell count, neutrophil ratio and decrease in lymphocyte count, serum albumin in children with MPP is related to the development of airway mucus hypersecretion. In children with RSV pneumonia, the abnormal increase of eosinophils in peripheral blood has relationship with hypersecretion. The appearance of lung rale, wheezing, and sputum rale are associated with airway mucus hypersecretion in children with adenovirus pneumonia. In addition, local neutrophil infiltration in the respiratory tract is closely related to the occurrence of airway mucus hypersecretion caused by Mycoplasma pneumoniae and RSV infection.

Objective: To investigate the relationship between amino acid variations of respiratory syncytial virus (RSV) nonstructural protein (NS) 1 and the clinical characteristics. Method: A retrospective case review was conducted. From December 2018 to January 2020, a total of 81 cases of hospitalized children who were tested only positive for RSV by RT-PCR or PCR at the Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University were included in the study. The NS1 genes of RSV subtype A and subtype B were amplified by PCR and sequenced. The amino acid sequences were analyzed. The Chi-square test and Mann-Whitney rank sum test were used to compare the clinical characteristics and type Ⅰ interferon levels of children with or without NS1 variation in the variation and non-variation groups. Results: Among 81 cases, there were 58 males and 23 females. There were 11 cases in the variation group, the age of onset was 2.0 (1.0, 11.0) months, included 4 cases of subtype A (variant sites were: 2 cases for Lys33Gln, one case for Gly2Asp, Pro67Ser, Leu137Phe, respectively) and 7 cases of subtype B (variant sites were: two cases for Val121Ile, one case for Tyr30Cys, Val65Met, Asn85Ser, Ser118Asn, Asp124Asn, respectively). These variant sites all appeared at a very low frequency 0.08 (0.04, 0.29) % in the NCBI PROTEIN database. There were 70 cases in non-variation group, the onset age was 3.5 (1.0, 7.0) months. The proportion of dyspnea in the variation group was higher than that in the non-variation group (10/11 vs. 47% (33/70), χ 2 =7.31, P <0.01). Conclusions: There are some variant sites in nonstructural protein NS1 of RSV. Children may be prone to have dyspnea with NS1 variations.

Pneumonia complicated by preterm birth is related to adverse clinical sequelae from the neonatal period to childhood. Children with pneumonia during 2009-2021 were enrolled at the Children's Hospital of Chongqing Medical University. Altogether 20 respiratory pathogens were detected and compared. Among 8,206 children, 779 were in the preterm group with 246 of early-preterm and 533 of late preterm. The positive rates for all viral pathogens were comparable between the preterm group and the full-term group. For bacterial pathogens, higher positive rates for Escherichia coli and Klebsiella pneumoniae were observed in the preterm group. Severe pneumonia developed in 16.52% of all, which was higher in the preterm group than in the full-term group. A significantly higher rate of severe pneumonia was observed in the early-preterm group compared to the late-preterm group. Preterm birth has an impact on the detection of bacterial pathogens in children and is a risk factor for severe pneumonia., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Tumour metabolism is controlled by coordinated changes in metabolite abundance and gene expression, but simultaneous quantification of metabolites and transcripts in primary tissue is rare. To overcome this limitation and to study gene-metabolite covariation in cancer, we assemble the Cancer Atlas of Metabolic Profiles of metabolomic and transcriptomic data from 988 tumour and control specimens spanning 11 cancer types in published and newly generated datasets. Meta-analysis of the Cancer Atlas of Metabolic Profiles reveals two classes of gene-metabolite covariation that transcend cancer types. The first corresponds to gene-metabolite pairs engaged in direct enzyme-substrate interactions, identifying putative genes controlling metabolite pool sizes. A second class of gene-metabolite covariation represents a small number of hub metabolites, including quinolinate and nicotinamide adenine dinucleotide, which correlate to many genes specifically expressed in immune cell populations. These results provide evidence that gene-metabolite covariation in cellularly heterogeneous tissue arises, in part, from both mechanistic interactions between genes and metabolites, and from remodelling of the bulk metabolome in specific immune microenvironments., (© 2023. The Author(s).)

The mitochondrial genome encodes essential machinery for respiration and metabolic homeostasis but is paradoxically among the most common targets of somatic mutation in the cancer genome, with truncating mutations in respiratory complex I genes being most over-represented 1 . While mitochondrial DNA (mtDNA) mutations have been associated with both improved and worsened prognoses in several tumour lineages 1-3 , whether these mutations are drivers or exert any functional effect on tumour biology remains controversial. Here we discovered that complex I-encoding mtDNA mutations are sufficient to remodel the tumour immune landscape and therapeutic resistance to immune checkpoint blockade. Using mtDNA base editing technology 4 we engineered recurrent truncating mutations in the mtDNA-encoded complex I gene, Mt-Nd5 , into murine models of melanoma. Mechanistically, these mutations promoted utilisation of pyruvate as a terminal electron acceptor and increased glycolytic flux without major effects on oxygen consumption, driven by an over-reduced NAD pool and NADH shuttling between GAPDH and MDH1, mediating a Warburg-like metabolic shift. In turn, without modifying tumour growth, this altered cancer cell-intrinsic metabolism reshaped the tumour microenvironment in both mice and humans, promoting an anti-tumour immune response characterised by loss of resident neutrophils. This subsequently sensitised tumours bearing high mtDNA mutant heteroplasmy to immune checkpoint blockade, with phenocopy of key metabolic changes being sufficient to mediate this effect. Strikingly, patient lesions bearing >50% mtDNA mutation heteroplasmy also demonstrated a >2.5-fold improved response rate to checkpoint inhibitor blockade. Taken together these data nominate mtDNA mutations as functional regulators of cancer metabolism and tumour biology, with potential for therapeutic exploitation and treatment stratification., Competing Interests: Competing interests M.M., E.R. and P.A.G. are named inventors on patent applications resulting from this work filed by Cancer Research Horizons. P.A.G is a shareholder, and has been a consultant and Scientific Advisory Board member to Pretzel Therapeutics Inc.

Introduction: Allergic rhinitis (AR) in children is associated with various comorbidities, posing challenges for treatment and management. There have been few investigations of these multimorbidities in Chinese children with AR. Here, we investigated the prevalence of multimorbidities in children with moderate to severe AR and analyzed the influencing factors using real-world data., Methods: In total, 600 children who visited the outpatient clinic of our hospital and were diagnosed with moderate-severe AR were prospectively enrolled. All children underwent allergen detection and electronic nasopharyngoscopy. Parents or guardians completed a questionnaire that included age, sex, mode of delivery, feeding pattern, and familial history of allergy. The multimorbidities investigated included atopic dermatitis (AD), asthma, allergic conjunctivitis (AC), chronic rhinosinusitis (CRS), adenoid hypertrophy (AH), tonsil hypertrophy (TH), recurrent epistaxis, and recurrent respiratory tract infections (RRTIs)., Results: The AR multimorbidities reported in children were as follows: recurrent epistaxis (46.5%), AC (46.3%), AD (40.7%), asthma (22.5%), RRIs (21.3%), CRS (20.5%), AH (19.7%), and TH (12.5%). In univariate logistic regression analysis, age (&lt;6 years), birth mode, familial history of allergy, and single dust mite allergy were associated with AR multimorbidity (p &lt; 0.05). Multivariate logistic regression revealed that a familial history of allergy was an independent risk factor for AC (odds ratio [OR] = 1.539, 95% confidence interval [CI]: 1.104-2.145) and AH (OR = 1.506, 95% CI: 1.000-2.267) (p &lt; 0.05). Age (&lt;6 years) was independently associated with the risk of AD (OR = 1.405, 95% CI: 1.003-1.969) and RRTIs (OR = 1.869, 95% CI: 1.250-2.793) (p &lt; 0.05), cesarean section with AR and CRS risk (OR = 1.678, 95% CI: 1.100-2.561), and single dust mite allergy with asthma (OR = 1.590, 95% CI: 1.040-2.432) and CRS (OR = 1.600, 95% CI: 1.018-2.515) risk (p &lt; 0.05). Further, non-dust mite allergy was independently associated with AR and CRS (OR = 2.056, 95% CI: 1.084-3.899)., Conclusion: AR was found to be accompanied by different comorbidities, including both allergic and non-allergic comorbidities, complicating disease treatment. These findings demonstrated that age (&lt;6 years), familial history of allergy, types of allergens, and cesarean section were risk factors for different multimorbidities associated with AR., (© 2023 S. Karger AG, Basel.)

Telomerase reverse transcriptase (TERT) promoter (pTERT) mutation has often been described as a late event in gliomagenesis and it has been suggested as a prognostic biomarker in gliomas other than 1p19q codeleted tumors. However, the characteristics of isocitrate dehydrogenase (IDH) wild type (wt) (IDHwt), pTERTwt glioblastomas are not well known. We recruited 72 adult IDHwt, pTERTwt glioblastomas and performed methylation profiling, targeted sequencing, and fluorescence in situ hybridization (FISH) for TERT structural rearrangement and ALT (alternative lengthening of telomeres). There was no significant difference in overall survival (OS) between our cohort and a the Cancer Genome Atlas (TCGA) cohort of IDHwt, pTERT mutant (mut) glioblastomas, suggesting that pTERT mutation on its own is not a prognostic factor among IDHwt glioblastomas. Epigenetically, the tumors clustered into classic-like (11%), mesenchymal-like (32%), and LGm6-glioblastoma (GBM) (57%), the latter far exceeding the corresponding proportion seen in the TCGA cohort of IDHwt, pTERTmut glioblastomas. LGm6-GBM-clustered tumors were enriched for platelet derived growth factor receptor alpha (PDGFRA) amplification or mutation (p = 0.008), and contained far fewer epidermal growth factor receptor (EGFR) amplification (p < 0.01), 10p loss (p = 0.001) and 10q loss (p < 0.001) compared with cases not clustered to this group. LGm6-GBM cases predominantly showed ALT (p = 0.038). In the whole cohort, only 35% cases showed EGFR amplification and no case showed combined chromosome +7/-10. Since the cases were already pTERTwt, so the three molecular properties of EGFR amplification, +7/-10, and pTERT mutation may not cover all IDHwt glioblastomas. Instead, EGFR and PDGFRA amplifications covered 67% and together with their mutations covered 71% of cases of this cohort. Homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A)/B was associated with a worse OS (p = 0.031) and was an independent prognosticator in multivariate analysis (p = 0.032). In conclusion, adult IDHwt, pTERTwt glioblastomas show epigenetic clustering different from IDHwt, pTERTmut glioblastomas, and IDHwt glioblastomas which are pTERTwt may however not show EGFR amplification or +7/-10 in a significant proportion of cases. CDKN2A/B deletion is a poor prognostic biomarker in this group., (© 2022 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines., (Copyright © 2022. Production and hosting by Elsevier B.V.)

How malleable is alcohol consumption? Specifically, how much is alcohol consumption driven by the current environment versus individual characteristics? To answer this question, we analyze changes in alcohol purchases when consumers move from one state to another in the United States. We find that if a household moves to a state with a higher (lower) average alcohol purchases than the origin state, the household is likely to increase (decrease) its alcohol purchases right after the move. The current environment explains about two-thirds of the differences in alcohol purchases. The adjustment takes place both on the extensive and intensive margins., Competing Interests: Declaration of Competing Interest We declare that we have no relevant or material financial interests that relate to the research described in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Viral diarrhea is one of the leading causes of morbidity and mortality in children. This study was conducted to disclose the etiological cause and epidemiological features of viral diarrhea among children in China. From 2009 to 2021, active surveillance was performed on pediatric patients with acute diarrhea and tested for five enteric viruses. Positive detection was determined in 65.56% (3325/5072) patients and an age-specific infection pattern was observed. A significantly higher positive rate was observed in 12-23-month-old children for rotavirus (47.46%) and adenovirus (7.06%), while a significantly higher positive rate was observed for norovirus (37.62%) in 6-11-month-old patients, and for astrovirus (11.60%) and sapovirus (10.79%) in 24-47-month-old patients. A higher positive rate of rotavirus in girls and norovirus in boys was observed only among 6-11 months of patients. We also observed more norovirus among patients from rural areas in the 0-5- and 36-47-month groups and more rotavirus among those from rural areas in the 12-23-month group. Diarrhea severity was greater for rotavirus in the 6-23-month group and norovirus in the 6-11-month group. Coinfections were observed in 29.26% (973/3325) of positive patients, and were most frequently observed between rotavirus and others (89.31%). Our findings could help the prediction, prevention, and potential therapeutic approaches to viral diarrhea in children., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Objective: To investigate the effects of Streptococcus pneumoniae (Spn) colonization and the change of upper airway microbiome on the clinical manifestations in children with respiratory syncytial virus (RSV) infection. Methods: A retrospective cohort included 508 RSV-infected children with pneumonia and hospitalized in Respiratory Department of Children's Hospital of Chongqing Medical University from July 2009 to July 2018. A total of 508 cases of RSV-infected children (RSV non-sequencing group) were divided into 2 groups: children with Spn airway colonization (RSV+Spn group) and children without with Spn airway colonization (RSV group) according to the detection for virus and bacteria in nasopharyngeal aspirate, and these 2 groups were compared in terms of clinical manifestations by chi-square test in different age groups. In addition, in RSV pandemic season from November 2018 to February 2020, nasopharyngeal aspirates were collected from 20 children hospitalized in Respiratory Department of Children's Hospital of Chongqing Medical University and infected with RSV but without any positive detection of bacteria (RSV 16 S-sequencing group) and from children undergoing surgery without any sign of respiratory infection (control group). The difference of microbiome detected by 16 S RNA sequencing was compared using rank sum test between RSV 16 S-sequencing group and control group, and also between children with severe and mild pneumonia in RSV 16 S-sequencing group. Results: A total of 508 RSV non-sequencing group included 346 males and 162 females, and the visiting age was 6 (2, 12)  months. RSV group included 443 cases and RSV+Spn group included 65 cases. In the study 244 cases were aged <6 months and 264 cases were aged ≥6 months. In children aged ≥6 months of RSV non-sequencing group, the proportion of cases presenting fever over 38 ℃ and cases with severe pneumonia in RSV+Spn group were higher than those in RSV group (53.2% (25/47) vs. 34.6% (72/217), 38.3% (18/47) vs. 21.2% (46/217), χ²=5.70,6.15, both P <0.05). RSV 16 S-sequencing group included 16 males and 4 females and the visiting age was 3.0 (1.9, 8.0) months. Airway microbiome diversity in RSV 16 S-sequencing group was lower than that in control group (alpha index: 0.93 (0.42, 2.51) vs. 3.05 (2.88, 3.61), U =60.00, P =0.001). Conclusions: RSV infection is associated with the changes of the upper airway microbiome. When the balance of airway microbiome is broken and the presence of the dominant colonization of Spn follows, it may aggravate the severity of RSV infection in children aged ≥6 months.

The nervous system and the immune system are relatively independent but interactional, and neuro-immune regulation is very important for the respiratory system to resist external harmful stimuli and to maintain homeostasis. Neuro-immune interaction is involved in the occurrence and development of respiratory diseases, and is essential for monitoring and modulating inflammation and tissue repair. This article summaries the neuro-immune regulation of respiratory system and discusses its role in respiratory diseases, aiming to provide a theoretical basis for further understanding the crosstalk between the nervous and immune systems, to explore the underlying mechanism in respiratory diseases, and to provide new thoughts for the prevention and treatment of respiratory diseases.

Viral infection is clinically common and some viral diseases, such as the ongoing global outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have high morbidity and mortality. However, most viral infections are currently lacking in specific therapeutic agents and effective prophylactic vaccines, due to inadequate response, increased rate of drug resistance and severe adverse side effects. Therefore, it is urgent to find new specific therapeutic targets for antiviral defense among which "peptide-based therapeutics" is an emerging field. Peptides may be promising antiviral drugs because of their high efficacy and low toxic side effects. Vasoactive intestinal peptide (VIP) is a prospective antiviral peptide. Since its successful isolation in 1970, VIP has been reported to be involved in infections of SARS-CoV-2, human immune deficiency virus (HIV), vesicular stomatitis virus (VSV), respiratory syncytial virus (RSV), Zika virus (ZIKV) and cytomegalovirus (CMV). Additionally, given that viral attacks sometimes cause severe complications due to overaction of inflammatory and immune responses, the potent anti-inflammatory and immunoregulator properties of VIP facilitate it to be a powerful and promising candidate. This review summarizes the role and mechanisms of VIP in all reported viral infections and suggests its clinical potential as an antiviral therapeutic target.

Hürthle cell carcinomas (HCCs) display two exceptional genotypes: near-homoplasmic mutation of mitochondrial DNA (mtDNA) and genome-wide loss of heterozygosity (gLOH). To understand the phenotypic consequences of these genetic alterations, we analyzed genomic, metabolomic, and immunophenotypic data of HCC and other thyroid cancers. Both mtDNA mutations and profound depletion of citrate pools are common in HCC and other thyroid malignancies, suggesting that thyroid cancers are broadly equipped to survive tricarboxylic acid cycle impairment, whereas metabolites in the reduced form of NADH-dependent lysine degradation pathway were elevated exclusively in HCC. The presence of gLOH was not associated with metabolic phenotypes but rather with reduced immune infiltration, indicating that gLOH confers a selective advantage partially through immunosuppression. Unsupervised multimodal clustering revealed four clusters of HCC with distinct clinical, metabolomic, and microenvironmental phenotypes but overlapping genotypes. These findings chart the metabolic and microenvironmental landscape of HCC and shed light on the interaction between genotype, metabolism, and the microenvironment in cancer.

Objective: To address the limitations of existing methods and tools for evaluating clinical practice guidelines, we aimed to develop a comprehensive instrument focusing on the three main dimensions of guideline development: scientificity, transparency, applicability. We will use it to rank the guidelines according to the scores. We abbreviated it as STAR, and its reliability, validity and usability were also tested. Methods: A multidisciplinary expert working group was set up, including methodologists, statisticians, journal editors, medical professionals, and others. Scoping review, Delphi methods and hierarchical analysis were used to determine the final checklist of STAR. Results: The new instrument contained 11 domains and 39 items. Intrinsic reliability of each domain was indicated by Cronbach's α coefficient, with a average value of 0.646. The Cohen's kappa coefficients for methodological evaluators and clinical evaluators were 0.783 and 0.618. The overall content validity index was 0.905. The R 2 for the criterion validity analysis was 0.76. The average score for usability of the items was 4.6, and the mean time spent to evaluate each guideline was 20 minutes. Conclusion: The instrument has good reliability, validity and evaluating efficiency, and can be used for evaluating and ranking guidelines more comprehensively.

In castration-resistant prostate cancer (CRPC), the loss of androgen receptor (AR) dependence leads to clinically aggressive tumors with few therapeutic options. We used ATAC-seq (assay for transposase-accessible chromatin sequencing), RNA-seq, and DNA sequencing to investigate 22 organoids, six patient-derived xenografts, and 12 cell lines. We identified the well-characterized AR-dependent and neuroendocrine subtypes, as well as two AR-negative/low groups: a Wnt-dependent subtype, and a stem cell-like (SCL) subtype driven by activator protein-1 (AP-1) transcription factors. We used transcriptomic signatures to classify 366 patients, which showed that SCL is the second most common subtype of CRPC after AR-dependent. Our data suggest that AP-1 interacts with the YAP/TAZ and TEAD proteins to maintain subtype-specific chromatin accessibility and transcriptomic landscapes in this group. Together, this molecular classification reveals drug targets and can potentially guide therapeutic decisions.

Background: Childhood asthma has substantial effects on children's health. It is important to identify influencing factors in early life in the development of childhood asthma. We aim to evaluate the effects of early-life factors and indoor environmental exposure on childhood asthma in Chongqing, China., Method: We designed a case-control study to enrol children with asthma aged 3 to < 14 years old and controls in Chongqing, China. The "Children's Early Life and Indoor Environment Survey" was used to collect the early-life factors and indoor environmental exposure of foetuses in utero and of infants during the first 3 years of life. A multivariate logistic regression model was used to evaluate the association between independent variables and childhood asthma and the interaction of early-life factors and environmental exposure., Results: A total of 160 asthma cases and 247 controls were included in this study. The mean ages of the cases and controls were 5.53 ± 1.88 and 5.72 ± 2.34 years, respectively (P = 0.192). Early-life factors and indoor environmental exposure were independently associated with childhood asthma. Infectious diseases of the respiratory system in children under 3 years old [adjusted odds ratio (OR) = 5.76, 95% confidence interval (CI) 2.49-13.30], bedroom air conditioner use (adjusted OR = 4.61, 95% CI 1.45-14.64), and bedroom dampness/mould (adjusted OR = 2.98, 95% CI 1.54-5.75) ranked as the three most significant exposures associated with the risk of childhood asthma. Other factors associated with an increased risk of childhood asthma included second-hand smoke exposure in early life (adjusted OR = 1.93, 95% CI 1.24-3.00), neonatal pneumonia (adjusted OR = 1.90, 95% CI 1.05-3.42) and maternal allergic diseases during pregnancy (adjusted OR = 2.13, 95% CI 1.10-4.10). The interaction effects of child second-hand smoke exposure with other covariates were not found to be statistically significant., Conclusions: Early-life factors and indoor environmental exposure are closely related to childhood asthma in Chongqing, China. Further interventions and management in the early life of children should be considered to prevent and control childhood asthma in Chongqing and similar cities., (© 2022. Children's Hospital, Zhejiang University School of Medicine.)

Objective: To explore the relationship between the daily incidence of human respiratory syncytial virus (HRSV) and meteorological parameters in the main urban area of Chongqing. Methods: This study took 3 107 children hospitalized with acute lower respiratory tract infections from June 2009 to June 2019 in department of Respiratory medicine, Children's Hospital of Chongqing Medical University (CHCMU). Nasopharyngeal aspirate (NPA) was collected on the day of admission to detect HRSV and common respiratory virus; combined with the meteorological data of the main urban area of ​​Chongqing during the same period, the correlation and distribution lag nonlinear model analysis of the daily incidence of HRSV and meteorological parameters were carried out. Results: Among 3 107 children, HRSV positive accounted for 34.53% (1 073 cases), the age was 6 (3, 13) months, and males accounted for 64.31% (690 cases). The daily incidence of HRSV was negatively correlated with minimum temperature ( r =-0.220, P <0.001), maximum temperature ( r =-0.221, P <0.001), average temperature ( r =-0.221, P <0.001) and precipitation ( r =-0.052, P <0.001), and positively correlated with sunshine time ( r =0.011, P <0.001) and average relative humidity ( r =0.095, P <0.001). Compared with the reference temperature (20 ℃), when the lowest temperature of 6-10 ℃ lags for 4-8 d, the RR value of HRSV was 1.11-1.14, and when the lowest temperature of 5-19 ℃ lags for 5 d and 2-19 ℃ lags for 10 d, the RR values were 1.02-1.14 and 1.00-1.03. When the cumulative lag is 5, 10, 15 and 21 d, compared with the reference temperature (20 ℃), the RR (95% CI ) values at the lowest temperature of 10.4 ℃ were 1.93 (1.08-3.46), 3.49 (1.64-7.45), 5.00 (2.01-12.46) and 6.69 (2.18-20.48); the RR (95% CI ) values of the lowest temperature of 22.1 ℃ were 0.87 (0.77-0.98), 0.77 (0.66-0.90), 0.74 (0.62-0.89) and 0.68 (0.55-0.85). In the cumulative effect, compared with the reference temperature (20 ℃), the gender stratification showed that the maximum RR (95% CI ) values of the lowest temperature for boys and girls under different lag days were 7.24 (1.84-28.51) and 2.19 (1.07-4.46), the age stratification showed that the maximum RR (95% CI ) values of the lowest temperature for children<6 months old and children ≥6 months old under different lag days were 4.72 (1.05-21.23) and 11.98 (1.70-84.35) . Conclusions: In the main urban area of Chongqing, the daily incidence of HRSV in children is correlated with climatic parameters. Among them, the lowest temperature has a delayed and cumulative effect on HRSV infection. 6-10 ℃ has a greater impact on the incidence of HRSV when the lag is 4-8 days. The effect has a more obvious impact on the incidence of HRSV in boys and children ≥ 6 months.

Human parechoviruses (HPeVs) are important causes of infection in children. However, without a comprehensive and persistent surveillance, the epidemiology and clinical features of HPeV infection remain ambiguous. We performed a hospital-based surveillance study among three groups of pediatric patients with acute respiratory infection (Group 1), acute diarrhea (Group 2), and hand, foot and mouth disease (Group 3) in Chongqing, China, from 2009 to 2015. Among 10,212 tested patients, 707 (6.92%) were positive for HPeV, with the positive rates differing significantly among three groups (Group 1, 3.43%; Group 2, 14.94%; Group 3, 3.55%; P < 0.001). The co-infection with other pathogens was detected in 75.2% (531/707) of HPeV-positive patients. Significant negative interaction between HPeV and Parainfluenza virus (PIV) ( P = 0.046, OR = 0.59, 95% CI = 0.34-0.98) and positive interactions between HPeV and Enterovirus (EV) ( P = 0.015, OR = 2.28, 95% CI = 1.23-4.73) were identified. Among 707 HPeV-positive patients, 592 (83.73%) were successfully sequenced, and 10 genotypes were identified, with HPeV1 ( n = 396), HPeV4 ( n = 86), and HPeV3 ( n = 46) as the most frequently seen. The proportion of genotypes differed among three groups ( P < 0.001), with HPeV1 and HPeV4 overrepresented in Group 2 and HPeV6 overrepresented in Group 3. The spatial patterns of HPeV genotypes disclosed more close clustering of the currently sequenced strains than those from other countries/regions, although they were indeed mixed. Three main genotypes (HPeV1, HPeV3, and HPeV4) had shown distinct seasonal peaks, highlighting a bi-annual cycle of all HpeV and two genotypes (HPeV 1 and HPeV 4) with peaks in odd-numbered years and with peaks in even-numbered years HPeV3. Significantly higher HPeV1 viral loads were associated with severe diarrhea in Group 2 ( P = 0.044), while associated with HPeV single infection than HPeV-EV coinfection among HFMD patients ( P = 0.001). It's concluded that HPeV infection was correlated with wide clinical spectrum in pediatric patients with a high variety of genotypes determined. Still no clinical significance can be confirmed, which warranted more molecular surveillance in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Zhao, Chen, Yuan, Tang, Zhou, Ren, Lu, Wang, Zhang, Zhang, Fang, Zhou, Liu, Xu and Liu.)

Bacillus cereus YN917, obtained from a rice leaf with remarkable antifungal activity against Magnaporthe oryzae , was reported in our previous study. The present study deciphered the possible biocontrol properties. YN917 strain exhibits multiple plant growth-promoting and disease prevention traits, including production of indole-3-acetic acid (IAA), ACC deaminase, siderophores, protease, amylase, cellulase, and β-1,3-glucanase, and harboring mineral phosphate decomposition activity. The effects of the strain YN917 on growth promotion and disease prevention were further evaluated under detached leaf and greenhouse conditions. The results revealed that B. cereus YN917 can promote seed germination and seedling plant growth. The growth status of rice plants was measured from the aspects of rice plumule, radicle lengths, plant height, stem width, root lengths, fresh weights, dry weights, and root activity when YN917 was used as inoculants. YN917 significantly reduced rice blast severity under detached leaf and greenhouse conditions. Genome analysis revealed the presence of gene clusters for biosynthesis of plant promotion and antifungal compounds, such as IAA, tryptophan, siderophores, and phenazine. In summary, YN917 can not only be used as biocontrol agents to minimize the use of chemical substances in rice blast control, but also can be developed as bio-fertilizers to promote the rice plant growth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhou, Ren, Zu, Yu, Zhu, Li, Zhong and Liu.)

Background: For pediatric pneumonia, the meteorological and air pollution indicators have been frequently investigated for their association with viral circulation but not for their impact on disease severity., Methods: We performed a 10-year prospective, observational study in 1 hospital in Chongqing, China, to recruit children with pneumonia. Eight commonly seen respiratory viruses were tested. Autoregressive distributed lag (ADL) and random forest (RF) models were used to fit monthly detection rates of each virus at the population level and to predict the possibility of severe pneumonia at the individual level, respectively., Results: Between 2009 and 2018, 6611 pediatric pneumonia patients were included, and 4846 (73.3%) tested positive for at least 1 respiratory virus. The patient median age was 9 months (interquartile range, 4‒20). ADL models demonstrated a decent fitting of detection rates of R2 > 0.7 for respiratory syncytial virus, human rhinovirus, parainfluenza virus, and human metapneumovirus. Based on the RF models, the area under the curve for host-related factors alone was 0.88 (95% confidence interval [CI], .87‒.89) and 0.86 (95% CI, .85‒.88) for meteorological and air pollution indicators alone and 0.62 (95% CI, .60‒.63) for viral infections alone. The final model indicated that 9 weather and air pollution indicators were important determinants of severe pneumonia, with a relative contribution of 62.53%, which is significantly higher than respiratory viral infections (7.36%)., Conclusions: Meteorological and air pollution predictors contributed more to severe pneumonia in children than did respiratory viruses. These meteorological data could help predict times when children would be at increased risk for severe pneumonia and when interventions, such as reducing outdoor activities, may be warranted., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

RTK/RAS/RAF pathway alterations (RPAs) are a hallmark of lung adenocarcinoma (LUAD). In this study, we use whole-genome sequencing (WGS) of 85 cases found to be RPA(-) by previous studies from The Cancer Genome Atlas (TCGA) to characterize the minority of LUADs lacking apparent alterations in this pathway. We show that WGS analysis uncovers RPA(+) in 28 (33%) of the 85 samples. Among the remaining 57 cases, we observe focal deletions targeting the promoter or transcription start site of STK11 (n = 7) or KEAP1 (n = 3), and promoter mutations associated with the increased expression of ILF2 (n = 6). We also identify complex structural variations associated with high-level copy number amplifications. Moreover, an enrichment of focal deletions is found in TP53 mutant cases. Our results indicate that RPA(-) cases demonstrate tumor suppressor deletions and genome instability, but lack unique or recurrent genetic lesions compensating for the lack of RPAs. Larger WGS studies of RPA(-) cases are required to understand this important LUAD subset., Competing Interests: Declaration of interests M.M. is listed as the inventor on the patent for the EGFR mutation analysis for lung cancer diagnosis licensed to LabCorp; holds research support from Bayer, Janssen, and Ono; and serves as scientific advisory board chair for OrigiMed. P.W.L. serves on the scientific advisory boards of AnchorDx and Progenity. D.J.K. has research support from Revolution Medicines and Genentech and is a consultant to AADi., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Most mutations in cancer genomes occur in the non-coding regions with unknown impact on tumor development. Although the increase in the number of cancer whole-genome sequences has revealed numerous putative non-coding cancer drivers, their information is dispersed across multiple studies making it difficult to understand their roles in tumorigenesis of different cancer types. We have developed CNCDatabase, Cornell Non-coding Cancer driver Database (https://cncdatabase.med.cornell.edu/) that contains detailed information about predicted non-coding drivers at gene promoters, 5' and 3' UTRs (untranslated regions), enhancers, CTCF insulators and non-coding RNAs. CNCDatabase documents 1111 protein-coding genes and 90 non-coding RNAs with reported drivers in their non-coding regions from 32 cancer types by computational predictions of positive selection using whole-genome sequences; differential gene expression in samples with and without mutations; or another set of experimental validations including luciferase reporter assays and genome editing. The database can be easily modified and scaled as lists of non-coding drivers are revised in the community with larger whole-genome sequencing studies, CRISPR screens and further experimental validations. Overall, CNCDatabase provides a helpful resource for researchers to explore the pathological role of non-coding alterations in human cancers., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Summary: Large-scale sequencing projects, such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), have generated high throughput sequencing and molecular profiling data sets, but it is still challenging to identify potentially causal changes in cellular processes in cancer as well as in other diseases in an automated fashion. We developed the netboxr package written in the R programming language, which makes use of the NetBox algorithm to identify candidate cancer-related functional modules. The algorithm makes use of a data-driven, network-based approach that combines prior knowledge with a network clustering algorithm, obviating the need for and the limitation of independently curated functionally labeled gene sets. The method can combine multiple data types, such as mutations and copy number alterations, leading to more reliable identification of functional modules. We make the tool available in the Bioconductor R ecosystem for applications in cancer research and cell biology., Availability and Implementation: The netboxr package is free and open-sourced under the GNU GPL-3 license R package available at https://www.bioconductor.org/packages/release/bioc/html/netboxr.html., Competing Interests: The authors have declared that no competing interests exist.

Background: The influenza A virus is the most important human pathogen affecting respiratory tract in children and has been prevalent for more than a century., Objectives: To describe epidemiological and clinical features in hospitalized children with acute respiratory infection caused by a novel swine-origin influenza virus (S-OIV) and seasonal influenza virus A (IVA)., Material and Methods: A total of 1,074 nasopharyngeal aspirate (NPA) samples were collected from children hospitalized with acute respiratory tract infections. The RNAs of S-OIV and seasonal IVA in the samples were examined using real-time polymerase chain reaction (RT-PCR)., Results: The presence of IVA was detected in 105 samples (9.8%), including S-OIV in 15 samples (1.4%) and seasonal IVA in the remaining samples (8.4%). The incidence of both viral infections was lower in autumn and winter. The rates of severe pneumonia in patients with S-OIV and seasonal IVA were 6.7% and 15.6%, respectively. In total, 14 out of 90 seasonal IVA-positive cases were categorized as severe pneumonia and 1 out of 15 S-OIV-positive cases as severe bronchiolitis. Five samples were found to have single S-OIV infection among 15 S-OIV-positive cases, while other respiratory viruses were detected in the other 9 samples. Twenty-one samples were found to be single seasonal-IVA-positive among the 90 seasonal-IVA-positive cases. Underlying heart conditions (odds ratio (OR) = 13.60), wheezing (OR = 6.82) and co-infection with adenovirus (OR = 6.21) were risk factors for developing severe pneumonia in seasonal IVA patients., Conclusions: Children younger than 2 years appeared to be susceptible to both kinds of viral infection. Diagnoses of non-severe respiratory tract infection were mainly made for patients with S-OIV and IVA infection. Underlying heart conditions, wheezing and co-infection with adenovirus increase the risk of developing severe pneumonia in seasonal IVA patients.

The discovery of drivers of cancer has traditionally focused on protein-coding genes 1-4 . Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium 5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers 6,7 , raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.

Objective: To systematically evaluate the clinical effect of azithromycin (AZM) adjuvant therapy in children with bronchiolitis., Methods: Related databases were searched for randomized controlled trials (RCTs) on AZM adjuvant therapy in children with bronchiolitis published up to February 17, 2019. RevMan 5.3 was used to perform the Meta analysis., Results: A total of 14 RCTs were included, with 667 children in the intervention group and 651 in the control group. The pooled effect size showed that in the children with bronchiolitis, AZM adjuvant therapy did not shorten the length of hospital stay (MD=-0.29, 95%CI: -0.62 to 0.04, P=0.08) or oxygen supply time (MD=-0.33, 95%CI: -0.73 to 0.07, P=0.10), while it significantly shortened the time to the relief of wheezing (MD=-1.00, 95%CI: -1.72 to -0.28, P=0.007) and cough (MD=-0.48, 95%CI: -0.67 to -0.29, P<0.00001). The analysis of bacterial colonization revealed that AZM therapy significantly reduced the detection rates of Streptococcus pneumoniae (OR=0.24, 95%CI: 0.11-0.54, P=0.0006), Haemophilus (OR=0.28, 95%CI: 0.14-0.55, P=0.0002), and Moraxella catarrhalis (OR=0.21, 95%CI: 0.11-0.40, P<0.00001) in the nasopharyngeal region., Conclusions: AZM adjuvant therapy can reduce the time to the relief of wheezing and cough in children with bronchiolitis, but it has no marked effect on the length of hospital stay and oxygen supply time.

Recent studies have shown that mutations at non-coding elements, such as promoters and enhancers, can act as cancer drivers. However, an important class of non-coding elements, namely CTCF insulators, has been overlooked in the previous driver analyses. We used insulator annotations from CTCF and cohesin ChIA-PET and analyzed somatic mutations in 1,962 whole genomes from 21 cancer types. Using the heterogeneous patterns of transcription-factor-motif disruption, functional impact, and recurrence of mutations, we developed a computational method that revealed 21 insulators showing signals of positive selection. In particular, mutations in an insulator in multiple cancer types, including 16% of melanoma samples, are associated with TGFB1 up-regulation. Using CRISPR-Cas9, we find that alterations at two of the most frequently mutated regions in this insulator increase cell growth by 40%-50%, supporting the role of this boundary element as a cancer driver. Thus, our study reveals several CTCF insulators as putative cancer drivers., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Many studies find that women are more risk averse than men. Why does such a gender gap exist, and how malleable is this gender gap in risk aversion? The paper takes advantage of a rare setting in which children of the matrilineal Mosuo and the traditionally patriarchal Han attend the same schools in Yunnan, China to shed light on these questions. In particular, we exploit the fact that children would experience a shock in gender norms when they start to intermingle with children from other ethnic groups with the opposite gender norms at school. Using survey and field experiments, we elicit risk attitudes from Mosuo and Han elementary and middle school students. We find that, at the time when they first enter school, Mosuo and Han children exhibit opposite gender norms-Mosuo girls take more risks than Mosuo boys, while Han girls are more risk averse than Han boys, reflecting cultural differences. However, after Mosuo students spend more time with Han students, Mosuo girls become more and more risk averse. By age 11, Mosuo girls are also more risk averse than Mosuo boys. We also observe a shrinking gap in risk aversion for Han over time. Using random roommate assignment for boarding middle school students, we find Mosuo boys who have fewer Mosuo roommates behave more similarly to Han boys. This shows that risk preferences are shaped by culture and malleable in response to new environments., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Streptococcus pneumoniae (pneumococcus) is the most common respiratory pathogen worldwide. Nasopharyngeal carriage with S. pneumoniae is the major source of lower respiratory tract infection and horizontal spread among children. Investigating nasopharyngeal S. pneumoniae is crucial for clinicians to control pneumococcus disease. Here, we retrospectively analyzed clinical information of 5,960 hospitalized children, focusing on pneumonia children less than five years with positive nasopharyngeal pneumococcal cultures. Nasopharyngeal aspirates (NPAs) were collected between June 2009 and December 2016, which were outside the pneumococcal conjugate vaccine(PCV) period. NPAs were subjected to common bacterial culture and antibiotic susceptibility tests, and serotypes were identified by both multiplex PCR and DNA sequencing. Results clearly revealed that clinical manifestations of the children whose NPAs were S. pneumoniae culture positive were serious, especially in those less than twelve months old. Fifteen different serotypes of nasopharyngeal S. pneumoniae were detected, the most common ones being 19F (35.2%), 6A/B (23.8%), 19A (11.4%), 15B/C (9.3%) and 23F (7.8%). Eight serotypes, accounting for 85.5% of the isolates, corresponded to the PCV13 serotypes. Approximately one-third of all S. pneumoniae strains were susceptible to penicillin. Overall, we consider nasopharyngeal S. pneumoniae culture is beneficial in assessing the situations of pneumonia children. Moreover, PCV13 could be useful in preventing pneumococcal disease in Chongqing, China.

Tumor metabolism is reorganized to support proliferation in the face of growth-related stress. Unlike the widespread profiling of changes to metabolic enzyme levels in cancer, comparatively less attention has been paid to the substrates/products of enzyme-catalyzed reactions, small-molecule metabolites. We developed an informatic pipeline to concurrently analyze metabolomics data from over 900 tissue samples spanning seven cancer types, revealing extensive heterogeneity in metabolic changes relative to normal tissue across cancers of different tissues of origin. Despite this heterogeneity, a number of metabolites were recurrently differentially abundant across many cancers, such as lactate and acyl-carnitine species. Through joint analysis of metabolomic data alongside clinical features of patient samples, we also identified a small number of metabolites, including several polyamines and kynurenine, which were associated with aggressive tumors across several tumor types. Our findings offer a glimpse onto common patterns of metabolic reprogramming across cancers, and the work serves as a large-scale resource accessible via a web application (http://www.sanderlab.org/pancanmet)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Over the past 30 years, China has enjoyed rapid economic development along with urbanization at a massive scale that the world has not experienced before. Such development has also been associated with a rapid rise in the prevalence of allergic disorders. Because of the large childhood population in the country, the burden of childhood allergic disorders has become one of the major challenges in the healthcare system. Among the Chinese centers participating in the International Study of Asthma and Allergies in Childhood, the data clearly showed a continuing rise in the prevalence of asthma, allergic rhinitis, and atopic eczema. However, the discipline of pediatric allergy in mainland China is still in its infancy due to the lack of formal training program and subspecialty certification. Clinicians and researchers are increasingly interested in providing better care for patients with allergies by establishing pediatric allergy centers in different regions of the country. Many of them have also participated in national or international collaborative projects hoping to answer the various research questions related to the discipline of pediatric allergy and immunology. It is our hope that the research findings from China will not only improve the quality of care of affected children within this country but also the millions of patients with allergies worldwide., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)