bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Utility of Peripheral Blood Leucocyte Ratios as Biomarkers in Neonatal Sepsis: A Systematic Review and Meta-Analysis
Authors: Zhang Juanjuan , Zeng Jun’an , Zhang Liangjuan , Yu Xiping , Guo Jinzhen , Li Zhankui 
Published: July 2022

BackgroundEarly stage diagnosis of neonatal sepsis (NS) remains a major roadblock due to non-specific symptoms and the absence of precise laboratory index tests. The full blood count is a relatively cheap, universal, and rapid diagnostic test.MethodThis study assessed the diagnostic accuracies of immature-to-total neutrophil ratio (ITR), immature-to-mature neutrophil ratio (IMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) used in the diagnosis of NS. Included studies were retrieved by searching four major databases and relevant references, and reviewed based on the inclusion/exclusion criteria. Pooled sensitivities and specificities were calculated, I2 was utilized to test for heterogeneity, and the source was investigated via meta-regression analysis.ResultsFinally, 38 studies passed the eligibility criteria. A total of thirty-one studies (6,221 neonates) included data on the ITR, eight studies (1,230 neonates) included data on the IMR, seven studies (751 neonates) included data on the NLR, and two studies (283 neonates) included data on the PLR. The summary sensitivity estimates with 95% confidence interval (CI) for the ITR, IMR, NLR, and PLR tests were, respectively, 0.74 (95% CI: 0.66–0.80), 0.74 (95% CI: 0.54–0.88), 0.73 (95% CI: 0.68–0.78), and 0.81 (95% CI: 0.55–1.00). The summary specificity values for the ITR, IMR, NLR, and PLR tests were 0.83 (95% CI: 0.77–0.87), 0.89 (95% CI: 0.80–0.94), 0.69 (95% CI: 0.57–0.79), and 0.93 (95% CI: 0.81–1.00), respectively. The area under the summary receiver operating characteristic curves for the ITR, IMR, and NLR tests were 0.85 (95% CI: 0.82–0.88), 0.91 (95% CI: 0.88–0.93), and 0.75 (95% CI: 0.71–0.79). The PLR could not be evaluated because only two studies included pertinent data.ConclusionThe NLR test might not be sufficiently accurate in precisely diagnosing NS. The ITR and IMR tests alone can improve the accuracy of NS diagnosis, but the marked heterogeneity and the limited number of studies prevented us from reaching any definitive conclusions. Thus, further studies are warranted to validate these findings.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021247850].
Evaluation of the neonatal sequential organ failure assessment and mortality risk in neonates with respiratory distress syndrome: A retrospective cohort study
Authors: Shi Shanshan , Guo Jie , Fu Minqiang , Liao Lihua , Tu Jiabin , Xiong Jialing , Liao Quanwang , Chen Weihua , Chen Kaihong , Liao Ying 
Published: July 2022

BackgroundRespiratory distress syndrome (RDS) is one of the leading causes of neonatal death in the neonatal intensive care unit (NICU). Previous studies have suggested that the development of neonatal RDS may be associated with inflammation and lead to organ dysfunction. The neonatal sequential organ failure assessment (nSOFA) scoring system is an operational definition of organ dysfunction, but whether it can be used to predict mortality in neonates RDS is unknown. The aim of this study was to clarify the performance of the nSOFA score in predicting mortality in patients with neonatal RDS, with the aim of broadening the clinical application of the nSOFA score.MethodsNeonates with RDS were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Cox proportional hazards model were used to assess the association between nSOFA score and mortality. Propensity score matched analysis were used to assess the robustness of the analytical results.ResultsIn this study of 1,281 patients with RDS of which 57.2% were male, death occurred in 40 cases (3.1%). Patients with high nSOFA scores had a higher mortality rate of 10.7% compared with low nSOFA scores at 0.3%. After adjusting for confounding, multivariate Cox proportional risk analysis showed that an increase in nSOFA score was significantly associated with increased mortality in patients with RDS [adjusted Hazards Ratio (aHR): 1.48, 95% Confidence Interval (CI): 1.32–1.67; p &lt; 0.001]. Similarly, the High nSOFA group was significantly associated with higher mortality in RDS patients (aHR: 19.35, 95% CI: 4.41–84.95; p &lt; 0.001) compared with the low nSOFA group.ConclusionThe nSOFA score was positively associated with the risk of mortality in cases of neonatal RDS in the NICU, where its use may help clinicians to quickly and accurately identify high risk neonates and implement more aggressive intervention.
Relationship between sleep disorders and attention-deficit–hyperactivity disorder in children
Authors: Yin Huimei , Yang Dong , Yang Lin , Wu Guangsheng 
Published: July 2022

ObjectiveTo explore the correlation between sleep disorders and attention-deficit–hyperactivity disorder (ADHD) in children.MethodsWe studied 100 Chinese children (70 boys and 30 girls; mean age, 8.77 ± 2.39 years). Parents completed the Children's Sleep Disturbance Scale (SDSC) and the Swanson Nolan and Pelham Version IV Scale (SNAP-IV) questionnaires. SNAP-IV and SDSC scores were compared in children with and without sleep disorders and ADHD.ResultsThere were significant differences in SDSC scores, Arousal Disorder (AD) scores, and Sleep Breathing Disorder (SBD) scores between children with and without ADHD (P &lt; 0.05). The sleep disorder group had higher SNAP-IV scores than the non-sleep disorder group (P &lt; 0.05). Children with sleep disorders showed higher ADHD symptom values (inattention, hyperactivity/impulsivity, and oppositional defiance) than children without sleep disorders (P &lt; 0.01). There was a moderate correlation between SDSC scores and SNAP-IV scores (r = 0.486, P &lt; 0.05). Using SNAP-IV scores as the dependent variable, multiple linear regression analysis was applied, and a statistically significant effect of AD and Sleep–Wake Transition Disorder (SWTD) scores on SNAP-IV scores was found (P &lt; 0.05). The area under the curve (95% CI) of the SDSC score for predicting sleep disorders with ADHD was 0.714 (0.606, 0.821; P = 0.0005).ConclusionChildren with ADHD are prone to sleep disorders. The higher the ADHD symptom score, the more sleeping problems. Sleep disorders can also cause or exacerbate ADHD symptoms, and the ADHD symptom score correlates with sleep disorder severity. We can reduce the severity of attention-deficit–hyperactivity in children with ADHD by improving their sleep with behavioral sleep interventions.
Phenotypes of Cornelia de Lange syndrome caused by non-cohesion genes: Novel variants and literature review
Authors: Shangguan Huakun , Chen Ruimin 
Published: July 2022

BackgroundCornelia de Lange syndrome (CdLS) is a genetic disorder caused by variants in cohesion genes including NIPBL, SMC1A, SMC3, RAD21, and HDAC8. According to the 2018 consensus statement, a patient with clinical scored ≥ 11 points could be diagnosed as CdLS. However, some variants in non-cohesion genes rather than cohesion genes can manifest as phenotypes of CdLS.ObjectivesThis study describes six variants of non-cohesion genes (KDM6A, KMT2D, KMT2A ANKRD11, and UBE2A), and assesses the reliability of 11-points scale criteria in the clinical diagnosis of CdLS.MethodsWhole-exome sequencing (WES) was performed on six patients with features of CdLS. Phenotypic and genotypic spectra of 40 previously reported patients with features of CdLS caused by non-cohesion genes variants and 34 previously reported patients with NIPBL variants were summarized. Clinical score comparison among patients with NIPBL variants versus those with variants in non-cohesin genes was performed.ResultsVariants in non-cohesion genes were found in six patients [KMT2A (n = 2), KMT2D, ANKRD11, KDM6A, and UBE2A]. Of them, four variants (KMT2A c.7789C &gt; T, ANKRD11 c.1757_1776del, KDM6A c.655-1G &gt; A, and UBE2A c.439C &gt; T) were novel. Combining with previously reported cases, 46 patients with phenotypes of CdLS caused by variants in 20 non-cohesion genes are now reported. From this total cohort, the average clinical score of patients in ANKRD11 cohort, SETD5 cohort, and AFF4 cohort was statistically lower than those in NIPBL cohort (8.92 ± 1.77 vs. 12.23 ± 2.58, 7.33 ± 2.52 vs. 12.23 ± 2.58, 5.33 ± 1.53 vs. 12.23 ± 2.58; p &lt; 0.05). The average clinical score of KMT2A cohort, EP300 cohort, and NIPBL cohort had not significantly different from (11 ± 2.19 vs. 12.23 ± 2.58, 10 ± 4.58 vs. 12.23 ± 2.58; p &gt; 0.05).ConclusionWe described 4 novel variants of non-cohesion genes in six Chinese patients with phenotypes of CdLS. Of note, three genes (KMT2D, KDM6A, and UBE2A) causing features of CdLS have never been reported. The proposed clinical criteria for CdLS needed to be updated and refined, insofar as WES was necessary to confirm the diagnosis of CdLS. Our study expanded the spectra of non-cohesion genetic variations in patients with features of CdLS.
Camostat Mesylate Versus Lopinavir/Ritonavir in Hospitalized Patients With COVID-19—Results From a Randomized, Controlled, Open Label, Platform Trial (ACOVACT)
Authors: Karolyi M. , Pawelka E. , Omid S. , Koenig F. , Kauer V. , Rumpf B. , Hoepler W. , Kuran A. , Laferl H. , Seitz T. , Traugott M. , Rathkolb V. , Mueller M. , Abrahamowicz A. , Schoergenhofer C. , Hecking M. , Assinger A. , Wenisch C. , Zeitlinger M. , Jilma B. , Zoufaly A. 
Published: July 2022

Background: To date, no oral antiviral drug has proven to be beneficial in hospitalized patients with COVID-19.Methods: In this randomized, controlled, open-label, platform trial, we randomly assigned patients ≥18 years hospitalized with COVID-19 pneumonia to receive either camostat mesylate (CM) (considered standard-of-care) or lopinavir/ritonavir (LPV/RTV). The primary endpoint was time to sustained clinical improvement (≥48 h) of at least one point on the 7-category WHO scale. Secondary endpoints included length of stay (LOS), need for mechanical ventilation (MV) or death, and 29-day mortality.Results: 201 patients were included in the study (101 CM and 100 LPV/RTV) between 20 April 2020 and 14 May 2021. Mean age was 58.7 years, and 67% were male. The median time from symptom onset to randomization was 7 days (IQR 5–9). Patients in the CM group had a significantly shorter time to sustained clinical improvement (HR = 0.67, 95%-CI 0.49–0.90; 9 vs. 11 days, p = 0.008) and demonstrated less progression to MV or death [6/101 (5.9%) vs. 15/100 (15%), p = 0.036] and a shorter LOS (12 vs. 14 days, p = 0.023). A statistically nonsignificant trend toward a lower 29-day mortality in the CM group than the LPV/RTV group [2/101 (2%) vs. 7/100 (7%), p = 0.089] was observed.Conclusion: In patients hospitalized for COVID-19, the use of CM was associated with shorter time to clinical improvement, reduced need for MV or death, and shorter LOS than the use of LPV/RTV. Furthermore, research is needed to confirm the efficacy of CM in larger placebo-controlled trials.Systematic Review Registration: [https://clinicaltrials.gov/ct2/show/NCT04351724, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001302-30/AT], identifier [NCT04351724, EUDRACT-NR: 2020–001302-30].
Treatment of COVID-19 Pneumonia and Acute Respiratory Distress With Ramatroban, a Thromboxane A2 and Prostaglandin D2 Receptor Antagonist: A Four-Patient Case Series Report
Authors: Ogletree Martin L. , Chander Chiang Kate , Kulshrestha Rashmi , Agarwal Aditya , Agarwal Ashutosh , Gupta Ajay 
Published: July 2022

Hypoxemia in COVID-19 pneumonia is associated with hospitalization, mechanical ventilation, and mortality. COVID-19 patients exhibit marked increases in fatty acid levels and inflammatory lipid mediators, predominantly arachidonic acid metabolites, notably thromboxane B2&gt;&gt; prostaglandin E2&gt; prostaglandin D2. Thromboxane A2increases pulmonary capillary pressure and microvascular permeability, leading to pulmonary edema, and causes bronchoconstriction contributing to ventilation/perfusion mismatch. Prostaglandin D2-stimulated IL-13 production is associated with respiratory failure, possibly due to hyaluronan accumulation in the lungs. Ramatroban is an orally bioavailable, dual thromboxane A2/TP and prostaglandin D2/DP2 receptor antagonist used in Japan for allergic rhinitis. Four consecutive outpatients with COVID-19 pneumonia treated with ramatroban exhibited rapid relief of dyspnea and hypoxemia within 12–36 h and complete resolution over 5 days, thereby avoiding hospitalization. Therefore, ramatroban as an antivasospastic, broncho-relaxant, antithrombotic, and immunomodulatory agent merits study in randomized clinical trials that might offer hope for a cost-effective pandemic treatment.
The Cost-Effectiveness of Tislelizumab Plus Chemotherapy for Locally Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer
Authors: Luo Xia , Zhou Zhen , Zeng Xiaohui , Liu Qiao 
Published: July 2022

Objective: To investigate the cost-effectiveness of adding Chinese-developed anti-PD-1 antibody tislelizumab to first-line pemetrexed-platinum chemotherapy in (1) a study population of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (nsqNSCLC) and without known sensitizing EGFR mutations or ALK rearrangements and (2) its subgroups from the perspective of Chinese healthcare system.Material and Methods: Separate Markov models were constructed for the entire study population and its subgroups; 10,000 patients with locally advanced or metastatic nsqNSCLC and without driver gene mutations were simulated in the first-line tislelizumab plus pemetrexed-platinum (TPP) arm and first-line pemetrexed-platinum (PP) arm, respectively. Transition probabilities were extracted from the RATIONALE 304 trial. Public health state utilities and costs were obtained from published literature, public national databases, and local general hospitals. The main outputs were incremental cost-effectiveness ratios (ICERs). The ICERs were compared to a willingness-to-pay threshold of $35,663 per quality-adjusted life-years (QALYs) to determine the cost-effective treatment. Sensitivity analyses were employed to assess the uncertainty in the model.Results: For the entire patient population, first-line TPP versus PP use increased the effectiveness by 0.99 QALYs and healthcare costs by $28,749, resulting in an ICER of $28,749/QALY that was lower than the prespecified WTP threshold. For patient subgroups, first-line TPP conferred the greatest survival benefit in patients with PD-L1 expression ≥50%, followed by patients with liver metastasis and those who are current or former smokers. Overall, the ICERs for the first-line TPP versus PP ranged from $27,018/QALYs to $33,074/QALYs, which were consistently below the WTP threshold.Conclusion: For Chinese patients with locally advanced or metastatic nsqNSCLC who had no known sensitizing EGFR mutations or ALK rearrangements, adding the Chinese-developed anti-PD-1 antibody tislelizumab to the first-line pemetrexed-platinum chemotherapy was cost-effective regardless of their baseline characteristics.
Saturated Fatty Acid-Induced Endoplasmic Reticulum Stress and Insulin Resistance Are Prevented by Imoxin in C2C12 Myotubes
Authors: Eo Hyeyoon , Valentine Rudy J 
Published: July 2022

In obesity, plasma free fatty acids (FFAs) levels are elevated due to enlarged adipose tissue mass. Saturated fatty acids can induce prolonged ER stress and insulin resistance. Double-stranded RNA-dependent Protein Kinase (PKR) is activated under stress conditions in skeletal muscle. The current study aimed to investigate the effect of imoxin (IMX), a selective PKR inhibitor, on palmitate-induced ER stress and insulin resistance in C2C12 myotubes. Cells were treated with 5 μM imoxin and exposed to 0.5 mM bovine serum albumin (BSA)-conjugated PA for 24 h. A subset of cells was stimulated with 50 nM insulin for the last 15 min. Glucose uptake was monitored and protein levels involved in ER stress and insulin signaling were measured by Western blotting. Palmitate stimulated PKR phosphorylation, which was prevented by imoxin. Moreover, imoxin reduced protein levels of ER stress-related markers including glucose-regulating protein 78 (GRP78), CCAAT-enhancer-binding protein homologous protein (CHOP), activating transcription factor 6 (ATF6) and spliced X-box binding protein 1 (XBP-1s) which were induced by palmitate. Furthermore, imoxin ameliorated palmitate-induced suppression of phospho-insulin receptor beta (p-IRβ) and Akt phosphorylation in myotubes. In addition, imoxin promoted glucose uptake in response to insulin under palmitate exposure. Furthermore, imoxin reduced phospho-c-Jun N-terminal kinase (p-JNK) induced by palmitate treatment. These findings suggest that imoxin may protect against saturated fatty acid-induced ER stress and insulin resistance in skeletal muscle, which are potentially mediated by PKR.
Organic zinc with moderate chelation strength enhances zinc absorption in the small intestine and expression of related transporters in the duodenum of broilers
Authors: Hu Yun , Wang Chuanlong , Wu Wei , Qu Yicheng , Zhang Weiyun , Li Ding , Zhu Ling , Gao Feiyu , Wu Bingxin , Zhang Liyang , Cui Xiaoyan , Li Tingting , Geng Yanqiang , Luo Xugang 
Published: July 2022

Our previous study demonstrated that the absorption of zinc (Zn) from the organic Zn proteinate with moderate chelation strength was significantly higher than that of Zn from the inorganic Zn sulfate in the in situ ligated duodenal segment of broilers, but the underlying mechanisms are unknown. The present study aimed to determine the effect of organic Zn with moderate chelation strength and inorganic Zn on the Zn absorption in the small intestine and the expression of related transporters in the duodenum of broilers. The Zn-deficient broilers (13 days old) were fed with the Zn-unsupplemented basal diets (control) containing 25.72 and 25.64 mg Zn/kg by analysis or the basal diets supplemented with 60 mg Zn/kg as the Zn sulfate or the Zn proteinate with moderate chelation strength (Zn-Prot M) for 26 days. The results showed that the plasma Zn contents from the hepatic portal vein of broilers at 28 days and 39 days of age were increased (p &lt; 0.05) by Zn addition and greater (p &lt; 0.05) in the Zn-Prot M than in the Zn sulfate. On d 28, Zn addition upregulated (p &lt; 0.05) mRNA expression of zinc transporter 1 (ZnT1), Zrt-irt-like protein 5 (ZIP5), y + L-type amino transporter 2 (y + LAT2) and b0,+-type amino acid transporter (rBAT), zinc transporter 4 (ZnT4) protein expression, and zinc transporter 9 (ZnT9) mRNA and protein expression in the duodenum. Moreover, ZnT9 mRNA expression, ZnT4, ZIP5, and rBAT protein expression, zinc transporter 7 (ZnT7), and y + LAT2 mRNA and protein expression in the duodenum of broilers on 28 days were higher (p &lt; 0.05) in the Zn-Prot M than in the Zn sulfate. On d 39, supplemental Zn increased (p &lt; 0.05) peptide-transporter 1 (PepT1) mRNA expression and y + LAT2 protein expression, while the mRNA expression of ZnT7 and Zrt-irt-like protein 3 (ZIP3) were higher (p &lt; 0.05) for the Zn-Prot M than for the Zn sulfate in the duodenum. It was concluded that the Zn-Prot M enhanced the Zn absorption in the small intestine partially via upregulating the expression of ZnT4, ZnT7, ZnT9, ZIP3, ZIP5, y + LAT2, and rBAT in the duodenum of broilers.
Communal coping and its association with marital relations and psychological outcomes among healthcare professionals during the COVID-19 pandemic
Authors: Alimoradi Zainab , Soleimani Mohammad Ali , Keramtkar Maryam , Bahrami Nasim , Griffiths Mark D. 
Published: July 2022

BackgroundCommunal coping is a type of interdependency in which couples dealing with a health threat share assessment of a threat and respond together to the stress. The present study investigated communal coping in the COVID-19 pandemic and its association with psychological and relational outcomes among healthcare professionals.MethodsIn the present cross-sectional survey study, 242 healthcare professionals from hospitals and health centers were recruited via convenience sampling between August and October 2020. Communal coping with working conditions during the COVID-19 pandemic, dyadic adjustment, psychological distress, and fear of COVID-19 along with demographic and professional characteristics were assessed via an online survey.ResultsMultivariable linear regression showed that dyadic adjustment (β = 0.73), psychological distress (β = 0.16), fear of COVID-19 (β = 0.11), and support gap (β = −0.04) were significant independent variables associated with communal coping among healthcare professionals.ConclusionHealthcare professionals coped communally within the family in dealing with working conditions during the COVID-19 pandemic. Dyadic adjustment was the strongest predictor of communal coping among healthcare professionals.
Correlates of suicidal ideation in rural Chinese junior high school left-behind children: A socioecological resilience framework
Authors: Zhou Yu-ming , Mak Leona , Zhao Chun-xia , He Fan , Huang Xiao-na , Tian Xiao-bo , Yi-zheng  , Sun Jing 
Published: July 2022

IntroductionSuicide is one of the top five causes of adolescent mortality around the world. The socioecological resilience framework in explaining the risk factors and protective factors for suicidal ideation in left-behind children (LBC) has not been well explored. The current study aims to compare the prevalence of suicidal ideation in LBC and non-LBC, and explore its correlations with resilience factors among LBC.MethodologyThis study was part of an epidemiological survey conducted by UNICEF exploring mental health outcomes in left-behind children. We implemented a cross-sectional study collecting data from 11 provinces and 1 municipal, with 5,026 participants (3,359 LBC, 1,667 controls) in year one junior high school living in impoverished areas of rural China. Data on suicidal ideation, self-harm, resilience factors including health-risk behaviors, psychological wellbeing as it was measured by the Strengths and Difficulties Questionnaire, peer relationship within the school environment, and family support were collected.ResultsOverall prevalence of suicidal ideation among LBC was 7.2% which is significantly different from 5.5% reported by NLBC (χ2 = 4.854, p = 0.028). LBC reported a higher prevalence of self-harm (16.4%) than NLBC (13.0%; χ2 = 10.232, p = 0.001), but there was no difference in the prevalence of suicide plan, suicide attempt or help-seeking. LBC had significantly poorer psychological feeling, and greater emotional and behavioral difficulties peer relationship in the school environment than controls. In the multiple logistic regression, history of self-harm was the greatest predictor for suicidal ideation among LBC (OR = 2.078, 95% CI: 1.394–3.100, p &lt; 0.001). Health risk behavior including previous smoking attempt, poor psychological feeling, and emotional and behavior difficulties, and poor peer relationship within school environment, were also significant risk factors for suicidal ideation among LBC.ConclusionThe prevalence of suicidal ideation and self-harm was greater among left-behind than non-left-behind children. Our results show resilience factors including previous self-harm, emotional and behavioral problems, smoking, and poor peer relationship are significantly associated with suicidal ideation in left-behind adolescents.