bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide identification of MAPK gene family members in Fagopyrum tataricum and their expression during development and stress responses
Authors: Yao Yingjun , Zhao Haixia , Sun Lei , Wu Wenjing , Li Chenglei , Wu Qi 
Published: February 2022

Abstract
Background
Mitogen-activated protein kinases (MAPKs) plays essential roles in the development, hormone regulation and abiotic stress response of plants. Nevertheless, a comprehensive study on MAPK family members has thus far not been performed in Tartary buckwheat.

Results
Here, we identified 16 FtMAPKs in the Fagopyrum tataricum genome. Phylogenetic analysis showed that the FtMAPK family members could be classified into Groups A, B, C and D, in which A, B and C members contain a Thr-Glu-Tyr (TEY) signature motif and Group D members contain a Thr-Asp-Tyr (TDY) signature motif. Promoter cis-acting elements showed that most ProFtMAPks contain light response elements, hormone response elements and abiotic stress response elements, and several ProFtMAPks have MYB-binding sites, which may be involved in the regulation of flavonoid biosynthesis-related enzyme gene expression. Synteny analysis indicated that FtMAPKs have a variety of biological functions. Protein interaction prediction suggested that MAPKs can interact with proteins involved in development and stress resistance. Correlation analysis further confirmed that most of the FtMAPK genes and transcription factors involved in the stress response have the same expression pattern. The transient transformation of FtMAPK1 significantly increased the antioxidant enzymes activity in Tartary buckwheat leaves. In addition, we also found that FtMAPK1 can respond to salt stress by up-regulating the transcription abundance of downstream genes.

Conclusions
A total of 16 MAPKs were identified in Tartary buckwheat, and the members of the MAPK family containing the TDY motif were found to have expanded. The same subfamily members have relatively conserved gene structures and similar protein motifs. Tissue-specific expression indicated that the expression of all FtMAPK genes varied widely in the roots, stems, leaves and flowers. Most FtMAPKs can regulate the expression of other transcription factors and participate in the abiotic stress response. Our findings comprehensively revealed the FtMAPK gene family and laid a theoretical foundation for the functional characterization of FtMAPKs.
Effects of different integrase strand transfer inhibitors on body weight in patients with HIV/AIDS: a network meta-analysis
Authors: Bai Ruojing , Lv Shiyun , Wu Hao , Dai Lili 
Published: February 2022

Abstract
Background
Global antiretroviral therapy has entered a new era. Integrase strand transfer inhibitor (INSTI) has become the first choice in acquired immunodeficiency syndrome (AIDS) treatment. Because INSTI has high antiviral efficacy, rapid virus inhibition, and good tolerance. However, INSTIs may increase the risk of obesity. Each INSTI has its unique impact on weight gain in patients with human immunodeficiency virus (HIV)/AIDS. This study systematically assessed different INSTIs in causing significant weight gain in HIV/AIDS patients by integrating data from relevant literature.

Methods
PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), and Wanfang databases were searched to find studies on the influence of different INSTIs in weight gain. Data on weight change were extracted, and a network meta-analysis was performed.

Results
Eight studies reported weight changes in HIV/AIDS patients were included. Results of the network meta-analysis showed that the weight gain of HIV/AIDS patients treated with Dolutegravir (DTG) was significantly higher than that of Elvitegravir (EVG) [MD = 1.13, (0.18–2.07)]. The consistency test results showed no overall and local inconsistency, and no significant difference in the results of the direct and indirect comparison was detected (p > 0.05). The rank order of probability was DTG (79.2%) > Bictegravir (BIC) (77.9%) > Raltegravir (RAL) (33.2%) > EVG (9.7%), suggesting that DTG may be the INSTI drug that causes the most significant weight gain in HIV/AIDS patients.

Conclusion
According to the data analysis, among the existing INSTIs, DTG may be the drug that causes the most significant weight gain in HIV/AIDS patients, followed by BIC.
Bilateral sequential theta burst stimulation in depressed veterans with service related posttraumatic stress disorder: a feasibility study
Authors: Vaithianathan Thelepa , Blair Mervin , Soares Vanessa , Rybak Yuri E. , Palaniyappan Lena , Richardson J Don , Burhan Amer M. 
Published: February 2022

AbstractBackgroundDepression comorbid with posttraumatic stress disorder (PTSD) can be disabling and treatment resistant. Preliminary evidence suggests that repetitive transcranial magnetic stimulation (rTMS), may have a role in helping these patients. There are only few published studies using different rTMS paradigms including bilateral intermittent theta burst (iTBS) and low frequency rTMS.MethodsIn this small cohort observation study, we examined the efficacy of bilateral sequential theta-burst stimulation (bsTBS) in 8 treatment resistant depression (TRD) military veterans with PTSD comorbidity stemming from military service experience.ResultsbsTBS was generally well tolerated and resulted in 25% and 38% remission and response rates on Depression scores respectively; 25% remission and response rate on PTSD scores.DiscussionThis study demonstrates preliminary feasibility and safety of bsTBS in TRD with comorbid military service related PTSD.We concluded that this paradigm might hold promise as a therapeutic tool to help patients with TRD co-morbid with military service related PTSD. Further adequately powered studies to compare rTMS treatment paradigms in this patient group are warranted.
Nonlinear causal effects of estimated glomerular filtration rate on myocardial infarction risks: Mendelian randomization study
Authors: Park Sehoon , Lee Soojin , Kim Yaerim , Cho Semin , Huh Hyeok , Kim Kwangsoo , Kim Yong Chul , Han Seung Seok , Lee Hajeong , Lee Jung Pyo , Joo Kwon Wook , Lim Chun Soo , Kim Yon Su , Kim Dong Ki 
Published: February 2022

Abstract
Background
Previous observational studies suggested that a reduction in estimated glomerular filtration rate (eGFR) or a supranormal eGFR value was associated with adverse cardiovascular risks. However, a previous Mendelian randomization (MR) study under the linearity assumption reported null causal effects from eGFR on myocardial infarction (MI) risks. Further investigation of the nonlinear causal effect of kidney function assessed by eGFR on the risk of MI by nonlinear MR analysis is warranted.

Methods
In this MR study, genetic instruments for log-eGFR based on serum creatinine were developed from European samples included in the CKDGen genome-wide association study (GWAS) meta-analysis (N=567,460). Alternate instruments for log-eGFR based on cystatin C were developed from a GWAS of European individuals that included the CKDGen and UK Biobank data (N=460,826). Nonlinear MR analysis for the risk of MI was performed using the fractional polynomial method and the piecewise linear method on data from individuals of white British ancestry in the UK Biobank (N=321,024, with 12,205 MI cases).

Results
Nonlinear MR analysis demonstrated a U-shaped (quadratic P value < 0.001) association between MI risk and genetically predicted eGFR (creatinine) values, as MI risk increased as eGFR declined in the low eGFR range and the risk increased as eGFR increased in the high eGFR range. The results were similar even after adjustment for clinical covariates, such as blood pressure, diabetes mellitus, dyslipidemia, or urine microalbumin levels, or when genetically predicted eGFR (cystatin C) was included as the exposure.

Conclusion
Genetically predicted eGFR is significantly associated with the risk of MI with a parabolic shape, suggesting that kidney function impairment, either by reduced or supranormal eGFR, may be causally linked to a higher MI risk.
Adolescent valuation of CARIES-QC-U: a child-centred preference-based measure of dental caries
Authors: Rogers H. J. , Sagabiel J. , Marshman Z. , Rodd H. D. , Rowen D. 
Published: February 2022

Abstract
Objectives
This study develops an adolescent value set for a child-centred dental caries-specific measure of oral health-related quality of life (OHRQoL) based upon CARIES-QC (Caries Impacts and Experiences Questionnaire for Children). This study develops a new approach to valuing child health by eliciting adolescent preferences and anchoring these onto the 1–0 full health-dead QALY (quality adjusted life year) scale using ordinal adult preferences.

Methods
Two online surveys were created to elicit preferences for the CARIES-QC classification system. The first comprised best–worst scaling (BWS) tasks for completion by adolescents aged 11–16 years. The second comprised discrete choice experiment tasks with a duration attribute (DCETTO) for completion by adults aged over 18 years. Preferences were modelled using the conditional logit model. Mapping regressions anchored the adolescent BWS data onto the QALY scale using adult DCETTO values, since the BWS survey data alone cannot generate anchored values.

Results
723 adolescents completed the BWS survey and 626 adults completed the DCETTO survey. The samples were representative of UK adolescent and adult populations. Fully consistent and robust models were produced for both BWS and DCETTO data. BWS preferences were mapped onto DCETTO values, resulting utility estimates for each health state defined by the classification system.

Conclusion
This is the first measure with predetermined scoring based on preferences to be developed specifically for use in child oral health research, and uses a novel technique to generate a value set using adolescent preferences. The estimates can be used to generate QALYs in economic evaluations of interventions to improve children’s oral health.
Comparison of six antibody assays and two combination assays for COVID-19
Authors: Yamamoto Masaki , Okazaki Kazuyuki , Kitai Yoko , Shinohara Koh , Yukawa Satomi , Noguchi Taro , Tanaka Michio , Matsumura Yasufumi , Nishiyama Yukiko , Nagao Miki 
Published: February 2022

Abstract
Introduction
In this work, six SARS-CoV-2-specific antibody assays were evaluated, namely, two pan-immunoglobulin (pan-Ig) assays [Roche Elecsys Anti-SARS-CoV-2 (named "Elecsys" in this study) and the PerkinElmer SuperFlex™ Anti-SARS-CoV-2 Ab Assay (SuperFlex_Ab)], two IgM assays [SuperFlex™ Anti-SARS-CoV-2 IgM Assay (SuperFlex_IgM) and YHLO iFlash-SARS-CoV-2 IgM (iFlash_IgM)], and two IgG assays [SuperFlex™ Anti-SARS-CoV-2 IgG Assay (SuperFlex_IgG) and iFlash-SARS-CoV-2 IgG (iFlash_IgG)]. Combination assays of SuperFlex™ (SuperFlex_any) and iFlash (iFlash_any) were also evaluated.

Methods
A total of 438 residual serum samples from 54 COVID-19 patients in the COVID-19 group and 100 samples from individuals without evidence of SARS-CoV-2 infection in the negative control group were evaluated.

Results
In the early stage of COVID-19 infection, within 14 days of symptom onset, the seropositive rate was lower than that of the late stage 15 days after onset (65.4% vs 99.6%). In the total period, the pan-Ig and IgG assays had higher sensitivity (90.8–95.3%) than the IgM assays (36.5–40.7%). SuperFlex_Ab and SuperFlex_any had higher sensitivity than Elecsys and SuperFlex_IgG (p < 0.05). The specificity of all the assays was 100%, except for SuperFlex_IgM (99.0%). The concordance rate between each assay was higher (96.4–100%) in the late stage than in the early stage (77.4–98.1%).

Conclusion
For the purpose of COVID-19 diagnosis, antibody testing should be performed 15 days after onset. For the purpose of epidemiological surveillance, highly sensitive assays should be used as much as possible, such as SuperFlex_Ab, iFlash_IgG and their combination. IgM assays were not suitable for these purposes.
Functions, mechanisms, and therapeutic implications of METTL14 in human cancer
Authors: Guan Qian , Lin Huiran , Miao Lei , Guo Huiqin , Chen Yongping , Zhuo Zhenjian , He Jing 
Published: February 2022

AbstractRNA modification plays a crucial role in many biological functions, and its abnormal regulation is associated with the progression of cancer. Among them, N6-methyladenine (m6A) is the most abundant RNA modification. Methyltransferase-like 14 (METTL14) is the central component of the m6A methylated transferase complex, which is involved in the dynamic reversible process of m6A modification. METTL14acts as both an oncogene and tumor suppressor gene to regulate the occurrence and development of various cancers. The abnormal m6A level induced by METTL14 is related to tumorigenesis, proliferation, metastasis, and invasion. To date, the molecular mechanism of METTL14 in various malignant tumors has not been fully studied. In this paper, we systematically summarize the latest research progress on METTL14 as a new biomarker for cancer diagnosis and its biological function in human tumors and discuss its potential clinical application. This study aims to provide new ideas for targeted therapy and improved prognoses in cancer.
Serum CCAT2 as a biomarker for adjuvant diagnosis and prognostic prediction of cervical cancer
Authors: Cao Xiaoli , Yao Juan , Jia Meiqun , Shen Xianjuan , Zhang Jinye , Ju Shaoqing 
Published: February 2022

AbstractGrowing evidence indicates that lncRNA colon cancer-associated transcript 2 (CCAT2) is associated with cancers. However, the clinical value of CCAT2 in cervical cancer (CC) remains unclear. In this study, serum CCAT2 level was detected by real-time quantitative PCR (RT-qPCR). Carbohydrate antigen 125 (CA125) and squamous-cell carcinoma antigen (SCC) were detected by electrochemiluminescence. A receiver operating characteristic (ROC) curve was utilized to estimate the diagnostic efficiency of CCAT2. Kaplan-Meier survival analysis and univariable and multivariable analyses were performed to assess the prognostic value of CCAT2. The relative expression level of CCAT2 in primary CC patients was significantly higher than that in cervical intraepithelial neoplasias (CIN) patients and healthy controls (both P < 0.001). CCAT2 relative expression was positively correlated with tumor Federation of Gynecology and Obstetrics (FIGO) stage, SCC-Ag and lymph node metastasis (LNM) (all P < 0.05). CCAT2 expression in recurrent/metastatic CC was significantly higher compared with primary CC (P < 0.0001) or operated CC (P < 0.0001) and during follow-up, CCAT2 expression was increased before surgery and decreased significantly after surgery (P < 0.0001). Furthermore, the overall survival rate of CC patients with high CCAT2 expression group markedly decreased as compared with that of low CCAT2 expression group (P = 0.026). Univariate analyses indicated that CCAT2 was a poor prognostic factor associated with overall survival (OS). Our study indicates that CCAT2 may be valuable in complementary diagnosis and monitoring of progression and prognosis of CC patients. Combined detection of CCAT2, CA125 and SCC can greatly improve the diagnostic efficiency of primary CC.
Usefulness of rapid molecular tests in pediatric respiratory tract infections
Authors: Nardi Simona , Carolis Lorella , Iannini Roberta , De Sandro Maria Vittoria , Solito Giovanna , Calafatti Matteo , Gizzi Camilla 
Published: February 2022

Abstract
Objective
To evaluate the role and the advantages of nasopharyngeal swabs in the detection of Influenza A and B viruses and Respiratory syncytial virus through a rapid test based upon a nucleic acid amplification reaction in order to avoid improper antibiotics use.

Design
Case-control retrospective study.

Setting
Emergency Room of “Sandro Pertini” General Hospital, Rome, Italy.

Participants
Children (< 14 years old) who consecutively arrived in the Emergency Department (ED) for respiratory tract infections, without obvious signs of bacterial respiratory tract infections and other comorbidities, in the maximal seasonal incidence period of November-to-March of every year between 2016 and 2020.

Methods
Medical records of children included in the study were retrospectively examined. Children were subdivided according to the following intervals: 2016–2017 and 2017–2018 (Group 1), 2018–2019 and 2019–2020 (Group 2). Children in Group 2 undertook a nasopharyngeal swab, while those in Group 1 did not undergo any specific diagnostic test.

Primary outcome
Avoidance of improper antibiotics administration.

Results
A total of 386 children were included in the study: 174 in Group 1, 212 in Group 2. The Odd Ratio (OR) of prescribing an antibiotic in the groups of children not being swabbed compared to those of children undertaking a swab was 9.21 (CI95% 5.6–15.2, p < 0.001). The overall percentage of hospitalizations, both in the short observation unit or in the pediatric unit, did not differ between the two groups.

Conclusions
Nasopharyngeal swabs for the detection of Influenza A and B viruses and Respiratory syncytial virus proved to be a useful means to a correct and timely diagnosis and allowed for a significant reduction in the prescription of antibiotic therapy.

Trial registration
Retrospectively registered.
Hypertrophic pyloric stenosis masked by kidney failure in a male infant with a contiguous gene deletion syndrome at Xp22.31 involving the steroid sulfatase gene: case report
Authors: Schierz Ingrid Anne Mandy , Giuffrè Mario , Cimador Marcello , D’Alessandro Maria Michela , Serra Gregorio , Favata Federico , Antona Vincenzo , Piro Ettore , Corsello Giovanni 
Published: February 2022

Abstract
Background
Contiguous gene deletion syndrome at Xp22.3 resulting in nullisomy in males or Turner syndrome patients typically encompasses the steroid sulfatase gene (STS) and contiguously located other genes expanding the phenotype. In large deletions, that encompass also the Kallmann syndrome 1 gene (KAL1), occasionally infantile hypertrophic pyloric stenosis (IHPS) and congenital anomalies of the kidney and urinary tract (CAKUT) have been reported.

Patient presentation
We report on a male newborn with family history in maternal uncle of renal abnormalities and short stature still without ichthyosiform dermatosis. The baby presented CAKUT with kidney failure and progressive vomiting. Renal bicarbonate loss masked hypochloremic and hypokalemic metabolic alkalosis classically present in IHPS and delayed its diagnosis. Antropyloric ultrasound examination and cystourethrography were diagnostic. After Fredet-Ramstedt extramucosal pyloromyotomy feeding and growing was regular and he was discharged home. Comparative whole-genome hybridization detected a maternal inherited interstitial deletion of 1.56 Mb on Xp22.31(6,552,712_8,115,153) × 0 involving the STS gene, but not the KAL1 gene.

Conclusions
Aberrant cholesterol sulfate storage due to STS deletion as the underlying pathomechanism is not limited to oculocutaneous phenotypes but could also lead to co-occurrence of both IHPS and kidney abnormalities, as we report. Thus, although these two latter pathologies have a high incidence in the neonatal age, their simultaneous association in our patient is resembling not a chance but a real correlation expanding the clinical spectrum associated with Xp22.31 deletions.
Incidence of acute respiratory infections in preschool children in an outpatient setting before and during Covid-19 pandemic in Lombardy Region, Italy
Authors: Mameli Chiara , Picca Marina , Buzzetti Roberto , Pace Maria Elisabetta , Badolato Raffaele , Cravidi Claudio , Zuccotti Gian Vincenzo , Marchisio Paola ,   for the Italian Society of Paediatrics Lombardy Section, Sala Marco , Di Cosimo Maria Elisabetta 
Published: February 2022

Abstract
Introduction
The incidence of acute respiratory tract infections (ARTIs) in children is difficult to estimate because they are typically treated in outpatient settings and the majority of epidemiological data originate from hospital settings and refer to the most severe illnesses. Therefore, the incidence of ARTIs in a real-world setting remains largely unexplored. Therefore, this study aims to estimate the incidence of ARTIs, upper respiratory tract infections (URTIs), and lower respiratory tract infections (LRTIs) in children aged 0–5 years in an outpatient setting.

Methods
This prospective cohort study was conducted in Lombardy, Italy, from October 1st, 2019, to March 31st, 2021, before and during the COVID-19 pandemic that began in March 2020. Caucasian healthy children aged 0–5 years were recruited from 69 Family Pediatricians (FP) and followed-up in an outpatient setting. Data were collected whenever a child was referred to FP and ARTI was diagnosed (Covid-19 related ARTI were excluded). The primary outcome was an estimate of the incidence of ARTIs. The incidence of ARTIs in different age groups and the effect of the COVID-19 pandemic on the incidence of ARTIs were secondary outcomes.

Results
We enrolled 484 children, 249 male (51.8%), mean age of 2.39 ± 1.68 years. The mean estimated incidence of ARTIs was 12.1/100 children × 30 days (95% CIs: 9.5–12.9), with the highest value observed in infants aged 1–12 months (24.9/100 children × 30 days; 95% CIs: 17.6–28.9). The mean estimated incidence of URTIs was higher than that of LRTIs (8.3 – CIs: 7.6–8.9 vs 3.8/100 children × 30 days – CIs: 6.4–4.3, respectively). The comparison of ARTIs, which occurred in the pre-pandemic winter, to those measured during the COVID-19 pandemic, revealed an impressive 82.1% drop in the incidence rate (CIs: 77.8–85.7).

Conclusions
This study showed that infants aged 1–12 months are more likely to develop ARTIs than older children and that COVID-19 pandemic has dramatically altered the epidemiology of ARTIs in children aged 0–5 years.
Retrospective longitudinal analysis of the effects of postnatal weight gain on the timing and tempo of puberty and menarche in a cohort of Italian girls
Authors: Ferrari Vittorio , Stefanucci Simona , Ferrari Marta , Ciofi Daniele , Stagi Stefano ,   on the behalf of the Tuscany Menarche Study Group, Milanesi Antonio , Cecchi Rossana , Fiore Rosalba , Pierattelli Monica , Pittari Angela Maria , Chiccoli Antonina , Becherucci Paolo , Cova Anna , Guidotti Tiziana , Balzer Elena , Citino Giovanni Scipione Gaetano , Bagni Paolo , Guarnieri Marzia , Pecchioli Roberto , Ascani Lara , Matteoni Donatella , Beacci Patrizia , Lelli Vanda , Breschi Cecilia , Fantacci Cristina , De Simone Anna , Gabbrielli Manuela 
Published: February 2022

Abstract
Objective
over the last few decades there has been a progressive decline in the average age of onset of pubertal development stages in both sexes. The increase in the prevalence of childhood obesity seems to play an important role in this phenomenon.

Design
we undertook a retrospective, longitudinal evaluation of the average age of thelarche and menarche to evaluate the relationship between BMI and weight change during the first years of life and the timing and tempo of puberty.

Methods
we evaluated data for 577 Italian girls born between 1995 and 2003. We collected the main auxological and clinical parameters, including age at B2 and at menarche, BMI SDS at B2 and menarche, gestational age and birth weight and Z-score change from birth weight (BW) to BMI at B2 and menarche.

Results
the mean age of B2 was 10.06 ± 1.03 years and the mean age of menarche was 12.08 ± 1.02 years. Age at B2 and menarche were inversely correlated with BMI SDS (p < 0.0001). Both age at menarche and at thelarche have an inverse relationship with the Z-score change from birth weight and BMI at menarche and thelarche respectively (p < 0.0001).

Conclusions
our data confirm a significant relationship between BMI and age of B2 and menarche. We observed a clear relationship among weight change during the first years of life, age at thelarche and menarche and the duration of puberty, demonstrating the importance of weight and weight gain in determining the timing and tempo of pubertal changes and growth.