bluuebunny/crossref_metadata_2025 huggingface dataset:
Greater Acute Concussion Symptoms Are Associated With Longer Recovery Times in NCAA Division III Collegiate Athletes
Authors: Iverson Grant L. , Terry Douglas P. , Maxwell Bruce , Zafonte Ross , Berkner Paul D. , Cook Nathan E.
Published: March 2022

We examined the association between the severity of acute concussion symptoms and time to return to school and to sports in National Collegiate Athletic Association (NCAA) Division III collegiate athletes. We hypothesized that students with the lowest burden of acute symptoms, measured in the first 72 h, would have the fastest return to school and sports and those with the highest burden of symptoms would have the slowest return to school and sports. This injury surveillance cohort included 808 athletes from 11 NCAA Division III colleges who sustained a concussion between 2014 and 2019. Athletic trainers documented time to return to school and to sports. Kruskal-Wallis tests with post-hoc planned comparison Mann-Whitney U tests were used to assess whether athletes took longer to return based on their acute symptom burden (Low, Medium, or High). Survival analysis (Kaplan Meier with log rank tests) was used to compare the recovery times based on acute symptom burden (censored at 28 days). Chi-square tests compared the proportion of those who had not yet returned to school or sports at various recovery benchmarks (i.e., 1 week, 10 days, 2 weeks, 3 weeks, 4 weeks) based on acute symptom burden. Women (median = 5 days) took slightly longer than men (median = 4 days) to return to school (p = 0.001; r = −0.11, small effect). Women and men did not differ on time to return to sports (p = 0.32, r = −0.04). A greater proportion with high acute symptoms remained out of school at 5 (odds ratio, OR = 4.53), 7 (OR = 4.98), and 10 (OR = 4.80) days compared to those with low acute symptoms. A greater proportion with high acute symptoms remained out of sports at 10 (OR = 4.11), 14 (OR = 3.46), and 21 (OR = 3.01) days compared to those with low acute symptoms. This study shows a strong association between having a high burden of acute post-concussion symptoms and having a slower return to school and sports in Division III collegiate athletes. Moreover, it also illustrates the converse: that those athletes with a low burden of acute symptoms have a faster return to school and sports.
Challenges and Opportunities of Real-World Data: Statistical Analysis Plan for the Optimise:MS Multicenter Prospective Cohort Pharmacovigilance Study
Authors: Waddingham Ed , Miller Aleisha , Dobson Ruth , Matthews Paul M.
Published: March 2022

Introduction

Optimise:MS is an observational pharmacovigilance study aimed at characterizing the safety profile of disease-modifying therapies (DMTs) for multiple sclerosis (MS) in a real world population. The study will categorize and quantify the occurrence of serious adverse events (SAEs) in a cohort of MS patients recruited from clinical sites around the UK. The study was motivated particularly by a need to establish the safety profile of newer DMTs, but will also gather data on outcomes among treatment-eligible but untreated patients and those receiving established DMTs (interferons and glatiramer acetate). It will also explore the impact of treatment switching.

Methods

Causal pathway confounding between treatment selection and outcomes, together with the variety and complexity of treatment and disease patterns observed among MS patients in the real world, present statistical challenges to be addressed in the analysis plan. We developed an approach for analysis of the Optimise:MS data that will include disproportionality-based signal detection methods adapted to the longitudinal structure of the data and a longitudinal time-series analysis of a cohort of participants receiving second-generation DMT for the first time. The time-series analyses will use a number of exposure definitions in order to identify temporal patterns, carryover effects and interactions with prior treatments. Time-dependent confounding will be allowed forviainverse-probability-of-treatment weighting (IPTW). Additional analyses will examine rates and outcomes of pregnancies and explore interactions of these with treatment type and duration.

Results

To date 14 hospitals have joined the study and over 2,000 participants have been recruited. A statistical analysis plan has been developed and is described here.

Conclusion

Optimise:MS is expected to be a rich source of data on the outcomes of DMTs in real-world conditions over several years of follow-up in an inclusive sample of UK MS patients. Analysis is complicated by the influence of confounding factors including complex treatment histories and a highly variable disease course, but the statistical analysis plan includes measures to mitigate the biases such factors can introduce. It will enable us to address key questions that are beyond the reach of randomized controlled trials.
Altered Spontaneous Brain Activity in Left-Behind Children: A Resting-State Functional MRI Study
Authors: Wang Yu , Lu Yi , Du Meimei , Hussein Nimo Mohamed , Li Lan , Wang Yu , Mao Chuanwan , Chen Tao , Chen Fangfang , Liu Xiaozheng , Yan Zhihan , Fu Yuchuan
Published: March 2022

Background

Parental migration has been associated with a higher risk of cognitive and behavioral abnormalities in left-behind children (LBC). This study aimed to explore the spontaneous brain activity in LBC and reveal the mechanisms underlying behavioral and cognitive abnormalities.

Methods

Involved LBC (n= 36) and non-LBC (n= 22) underwent resting-state functional MRI (fMRI) examination and cognitive and behavioral assessment. The fMRI-based amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were assessed to analyze the spontaneous brain activity pattern. The relationships among abnormal spontaneous brain activity, behavioral and cognitive deficits and altered family environment were assessed by partial correlation analysis.

Results

Compared with non-LBC, LBC exhibited increased amplitude of low-frequency fluctuations in the right lingual gyrus (LING), while a decreased ALFF was observed in the bilateral insula and right orbital part of the middle frontal gyrus (ORBmid) (two-tailed voxel-levelp< 0.01 and cluster-levelp<0.05, Gaussian Random Field (GRF) correction). The fALFF in LBC were significantly increased in the left cerebellum 9 (Cbe9) and right cerebellum Crus2 (CbeCru2), while it decreased in the right hippocampus and left superior temporal gyrus (STG) (two-tailed voxel-levelp< 0.01 and cluster-levelp< 0.05, GRF correction). The ALFF and fALFF values in abnormal brain regions were found to be correlated with the learning ability, except for the right insula, while the fALFF values of the left STG were positively correlated with the full-scale IQ scores (p< 0.05). Moreover, the ALFF and fALFF values in all abnormal brain regions correlated with the education level of caregivers (p< 0.05).

Conclusions

Our study provided empirical evidence that the lack of direct parental care during early childhood could affect brain function development involving cognition, behavior, and emotion. Our findings emphasized that intellectual and emotional cares are essential for LBC.
Acupuncture for the Treatment of Itch: Peripheral and Central Mechanisms
Authors: Tang Yi , Cheng Shirui , Wang Jin , Jin Yin , Yang Haodong , Lin Qihui , Xu Sanmei , Hui Lin , Yin Quanying , Yang Ying , Wu Xi
Published: March 2022

Despite the widespread clinical use of acupuncture in the treatment of pruritus caused by psoriasis, urticaria, uremic, and other diseases, insights into the mechanism of action of acupuncture are still emerging. For the above reasons, a beneficial effect of acupuncture on pruritus was not recommended or reported in recent clinical practice guidelines. Acupuncture is a kind of physical stimulation, which has the characteristics of multi-channel and multi-target effects. The biomechanical stimulation signal of acupuncture needling can be transformed into bioelectric and chemical signals; interfere with kinds of cells and nerve fibers in the skin and muscle; alter signaling pathways and transcriptional activity of cells, mediators, and receptors; and result in inhibition of peripheral and central transmission of pruritus. Available mechanistic data give insights into the biological regulation potency of acupuncture for pruritus and provide a basis for more in-depth and comprehensive mechanism research.
Feasibility and Long-Term Compliance to Continuous Positive Airway Pressure Treatment in Adults With Down Syndrome, a Genetic Form of Alzheimer’s Disease
Authors: Giménez Sandra , Farre Ariadna , Morente Fátima , Videla Laura , Gutiérrez Marta , Clos Susana , Fernández Ana , Blanco Marta , Altuna Miren , Pegueroles Jordi , Asensio Amparo , Benejam Bessy , Batista Mar , Barroeta Isabel , Fortuna Ana , Fortea Juan , Mayos Mercedes
Published: March 2022

Background

Down syndrome (DS) is a genetic form of Alzheimer’s disease (AD) with a high prevalence of obstructive sleep apnea (OSA). These characteristics place the DS population as an optimal model to study the relationship between sleep and AD and to design clinical trials of preventive sleep therapies for AD. Regrettably, OSA treatment with continuous positive airway pressure (CPAP) is often neglected in adults with DS. In both clinical practice and research trials, it is usually presumed that these patients will not adapt to or tolerate the therapy.

Study Objective

We aimed to evaluate the feasibility and long-term CPAP compliance in this population and their capacity to be enrolled in CPAP research studies.

Methods

We prospectively compared the CPAP compliance of 17 OSA patients with DS and 19 age and sex matched OSA euploid patients. CPAP management and follow-up schedules were prescribed according to the habitual clinical practice. We compared group differences in tolerance, objective, and subjective hours of nightly CPAP usage at the 1st, 3rd, 6th, 12th, 24th, and 36th month visits. Good compliance was defined as at least 4 h use per night. We also investigated predictive factors of long-term CPAP compliance.

Results

The percentage of DS subjects with good CPAP compliance (81.2 vs. 78.9%) and the objective CPAP use (5 vs. 6 h, p = 0.92) did not differ from the control group (CG). Subjective CPAP compliance was significantly higher in OSA patients with DS than in controls in all the follow-up visits (8 vs. 6.75 h, p = 0.001). The DS group had a significantly higher number of visits (9 vs. 5; p = 0.021) and mask changes (2.5 vs. 2; p = 0.05) than controls. Objective hours of CPAP use at the first follow-up visit predicted long-term CPAP compliance (p < 0.005).

Conclusion

CPAP treatment is feasible and has good long-term compliance in OSA patients with DS. It should be recommended to improve health and prevent comorbidities. The DS population is indeed suitable to participate in longitudinal preventive sleep clinical trials for AD.
AFF2 Is Associated With X-Linked Partial (Focal) Epilepsy With Antecedent Febrile Seizures
Authors: Zou Dongfang , Qin Bing , Wang Jie , Shi Yiwu , Zhou Peng , Yi Yonghong , Liao Jianxiang , Lu Xinguo
Published: March 2022

Objective

AFF2 mutations were associated with X-linked intellectual developmental disorder-109 and in males with autism spectrum disorder (ASD). The relationship between AFF2 and epilepsy has not been defined.

Method

Trios-based whole-exome sequencing was performed in a cohort of 372 unrelated cases (families) with partial (focal) epilepsy without acquired causes.

Results

Five hemizygous missense AFF2 mutations were identified in five males with partial epilepsy and antecedent febrile seizures without intellectual disability or other developmental abnormalities. The mutations did not present in the controls of general populations with an aggregate frequency significantly higher than that in the control populations. Previously, intellectual disability-associated AFF2 mutations were genomic rearrangements and CCG repeat expansion mutations mostly, whereas the mutations associated with partial epilepsy were all missense. Missense AFF2 mutations associated with epilepsy fell into the regions from N-terminal to the nuclear localization signal 1 (NLS1), while ASD-associated missense mutations fell in the regions from NLS1 to C-terminal.

Conclusion

AFF2 is potentially a candidate causative gene of X-link partial epilepsy with antecedent febrile seizures. The genotype–phenotype correlation and molecular sub-regional effect of AFF2 help in explaining the mechanisms underlying phenotypic variations.
Probiotic Intake and Inflammation in Patients With Chronic Kidney Disease: An Analysis of the CKD-REIN Cohort
Authors: Wagner Sandra , Merkling Thomas , Metzger Marie , Koppe Laetitia , Laville Maurice , Boutron-Ruault Marie-Christine , Frimat Luc , Combe Christian , Massy Ziad A. , Stengel Bénédicte , Fouque Denis
Published: March 2022

Background and Aims

Little is known about the effects of probiotics on inflammation in the context of chronic kidney disease (CKD). We investigated the association between probiotic intake and inflammation in patients with moderate-to-advanced CKD.

Methods

We performed a cross-sectional study of 888 patients with stage 3–5 CKD and data on serum C-reactive protein (CRP) levels and a concomitant food frequency questionnaire. We estimated the odds ratios (ORs) [95% confidence interval (CI)] for various CRP thresholds (>3, >4, >5, >6, and >7 mg/L) associated with three intake categories (no yoghurt, ordinary yoghurt, and probiotics from yoghurts or dietary supplements) and two frequency categories (daily or less than daily).

Results

The 888 study participants (median age: 70; men: 65%) had a median estimated glomerular filtration rate of 28.6 mL/min/1.73 m2 and a median [interquartile range] CRP level of 3.0 [1.6, 7.0] mg/L. Fifty-seven percent consumed ordinary yoghurt and 30% consumed probiotic yoghurt. The median intake frequency for yoghurt and probiotics was 7 per week. Relative to participants not consuming yoghurt, the ORs [95% CI] for CRP > 6 or >7 mg/L were significantly lower for participants consuming ordinary yoghurt (0.58 [0.37, 0.93] and 0.57 [0.35, 0.91], respectively) and for participants consuming probiotics (0.54 [0.33, 0.9] and 0.48 [0.28, 0.81], respectively), independently of age, sex, body mass index, CKD stage, cardiovascular disease, and fibre, protein and total energy intakes. The ORs were not significantly lower for CRP thresholds >3, >4, and >5 mg/L and were not significantly greater in daily consumers than in occasional consumers.

Conclusion

We observed independent associations between the consumption of yoghurt or probiotics and lower levels of inflammation in patients with CKD. There was no evidence of a dose-effect relationship.

Clinical Trial Registration

[https://www.clinicaltrials.gov/ct2/show/NCT03381950], identifier [NCT03381950].
Quality More Than Quantity: The Use of Carbohydrates in High-Fat Diets to Tackle Obesity in Growing Rats
Authors: Manzano Manuel , Giron Maria D. , Salto Rafael , Vilchez Jose D. , Reche-Perez Francisco J. , Cabrera Elena , Linares-Pérez Azahara , Plaza-Díaz Julio , Ruiz-Ojeda Francisco Javier , Gil Angel , Rueda Ricardo , López-Pedrosa Jose M.
Published: March 2022

Childhood obesity prevention is important to avoid obesity and its comorbidities into adulthood. Although the energy density of food has been considered a main obesogenic factor, a focus on food quality rather that the quantity of the different macronutrients is needed. Therefore, this study investigates the effects of changing the quality of carbohydrates from rapidly to slowly digestible carbohydrates on metabolic abnormalities and its impact on obesity in growing rats fed a high-fat diet (HFD). Growing rats were fed on HFD containing carbohydrates with different digestion rates: a HFD containing rapid-digesting carbohydrates (OBE group) or slow-digesting carbohydrates (ISR group), for 4 weeks and the effect on the metabolism and signaling pathways were analyzed in different tissues. Animals from OBE group presented an overweight/obese phenotype with a higher body weight gain and greater accumulation of fat in adipose tissue and liver. This state was associated with an increase of HOMA index, serum diacylglycerols and triacylglycerides, insulin, leptin, and pro-inflammatory cytokines. In contrast, the change of carbohydrate profile in the diet to one based on slow digestible prevented the obesity-related adverse effects. In adipose tissue, GLUT4 was increased and UCPs and PPARγ were decreased in ISR group respect to OBE group. In liver, GLUT2, FAS, and SRBP1 were lower in ISR group than OBE group. In muscle, an increase of glycogen, GLUT4, AMPK, and Akt were observed in comparison to OBE group. In conclusion, this study demonstrates that the replacement of rapidly digestible carbohydrates for slowly digestible carbohydrates within a high-fat diet promoted a protective effect against the development of obesity and its associated comorbidities.
Serum Homocysteine Level Is Positively Correlated With Serum Uric Acid Level in U.S. Adolescents: A Cross Sectional Study
Authors: Shi Yumeng , Wu Zuxiang , Wu Ji , Chen Zhiqiang , Li Ping
Published: March 2022

Background

Physiologically, the levels of homocysteine (Hcy) and serum uric acid (SUA) are closely related; however, clinical studies on the relationship between Hcy and SUA have drawn different conclusions and have not analyzed this association among adolescents. This study therefore aimed to evaluate the relationship between Hcy and SUA levels among adolescents.

Methods

In this study, we performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey for the period 1999–2006, which included 5,404 adolescents aged 12–19 years. An elevated SUA level was defined as ≥5.5 mg/dL. Multivariate logistic regression and multivariate linear regression models were also applied in this study.

Results

The mean concentrations of Hcy and SUA were 6.0 μmol/L and 5.0 mg/dL, respectively, and 33.6% of the participants had SUA levels of ≥5.5 mg/dL. There was a dose–response relationship between Hcy and SUA, and Hcy was linearly positively correlated with SUA. The β value [95% confidence interval (CI)] for SUA in the fully adjusted model was1.43 (95% CI: 1.18, 1.68). The multivariate logistic regression model showed that per 1 increment in log-transformed Hcy, the risk of elevated SUA levels increased by 8.80 times (odds ratio, 8.80, 95% CI: 4.25, 18.20). Subgroup analyses showed that the relationship between Hcy and SUA was significantly different according to sex, age, body mass index (BMI), and estimated glomerular filtration rate (eGFR) stratification (P for interaction <0.05).

Conclusion

Hcy levels were positively correlated with SUA levels and elevated SUA levels among U.S. teenagers, and this effect was more significant among boys aged ≥17 years and among people with lower BMI and eGFR.
Qualitative and Quantitative Analysis of Six Fatty Acid Amides in 11 Edible Vegetable Oils Using Liquid Chromatography–Mass Spectrometry
Authors: Li Zixiang , Dong Feng , Sun Yongzhi , Sun Zhaohui , Song Xinyu , Dong Yingran , Huang Xiaocai , Zhong Jiayi , Zhang Rui , Wang Maoqing , Sun Changhao
Published: March 2022

Fatty acid amides (FAAs) are endogenous lipid molecules that exhibit various physiological activities. FAAs are usually present at nanomolar levels in biological samples. In this study, a method for the qualitative and quantitative determination of six FAAs (linoleamide, linoleoyl ethanolamide, oleoyl ethanolamide, palmitic amide, oleamide, and octadecanamide) in edible vegetable oils was established. All six FAAs were detected in sesame, peanut, soybean (decolorized and non-decolorized), and blended oils; five in sunflower oil; four in rice oil; three in linseed and olive oils; and two in corn and canola oils. The total contents of FAAs were highest in sesame oil (104.88 ± 3.01 μg/mL), followed by peanut oil (34.96 ± 3.87 μg/mL), soybean oil (16.75 ± 1.27 μg/mL), and blended oil (13.33 ± 0.77 μg/mL), and the contents in the other edible vegetable oils were all <1.03 μg/mL. The concentrations of linoleoyl ethanolamide and oleoyl ethanolamide were highest in non-decolorized soybean oil, while the other four FAAs (linoleamide, palmitic amide, oleamide, and octadecanamide) showed the highest concentrations in sesame oil. The total contents of these FAAs in eight different oils were higher than those in biological fluids and tissue. Our study confirmed that edible vegetable oils are rich in FAAs, and provides reliable data for evaluating the nutritive value of vegetable oils.
Case Report: Molecular Profiling Assists in the Diagnosis and Treatment of Cancer of Unknown Primary
Authors: Yu Bo , Wang Qifeng , Liu Xin , Hu Silong , Zhou Liangping , Xu Qinghua , Sun Yifeng , Hu Xichun , Luo Zhiguo , Zhang Xiaowei
Published: March 2022

Background

For cancer of unknown primary (CUP), non-selective empiric chemotherapy is usually used. However, patients suffering from CUP are generally assumed to have a dismal prognosis with median overall survival of less than 1 year. Therefore, clinicians eagerly await the establishment of effective strategies for diagnosis and treatment. In recent years, the remarkable advances in next-generation sequencing (NGS) technology have enabled the wide usage of DNA/RNA sequencing to comprehensively analyze the molecular information of individual tumors and identify potential targets for patients’ diagnosis and treatment. Here, we describe a patient of CUP who was successfully diagnosed and treated with targeted therapy directed by comprehensive molecular profiling.

Case Presentation

A 61-year-old Asian woman with a painless, slow-growing mass lesion in the mesosternum underwent fluorodeoxyglucose-positron emission tomography/computed tomography and was found to have malignant metastatic tumors in the mesosternum. Conventional pathological examination of metastatic lesions could not conclude the primary origin of the tumors. The patient was diagnosed with CUP at first. Then, comprehensive molecular profiling was employed to identify the tumor origin and genetic alterations. A gene expression-based tissue origin assay was performed using a tissue biopsy sample. The test result suggested that the lesion tumors might be breast cancer metastasis. Furthermore, liquid biopsy-based circulating tumor DNA profiling detected an ERBB2 copy number amplification. Subsequent surgery and additional postoperative pathology analysis confirmed that the primary tumor site was indeed located in the right outer upper quadrant of the breast. After local surgical resection, the patient received 8 cycles of Docetaxel + Carboplatin + Trastuzumab + Pertuzumab (TCbHP) chemotherapy with subsequent human epidermal growth factor receptor 2 (HER2)-targeted maintenance therapy. Currently, the patient is on regular follow-up and has achieved disease control for up to 6 months.

Conclusion

Our findings suggest that molecular identification of the tumor origin and the detection of actionable molecular alterations may offer promise for improved diagnostic accuracy and important therapeutic implications for patients with the CUP syndrome.
Risk Factor Assessment of Lymph Node Metastasis in Patients With FIGO Stage IB1 Cervical Cancer
Authors: Xu Mu , Xie Xiaoyan , Cai Liangzhi , Xie Yongjin , Gao Qiao , Sun Pengming
Published: March 2022

Objectives

To assess the risk factors of lymph node metastasis (LNM) in patients with FIGO stage (2009) IB1 cervical cancer (CC).

Methods

Patients with FIGO stage IB1 CC who underwent radical resection between 2012 and 2018 were recruited. The risk factors for LNM were analysed. A recursive partitioning analysis (RPA) was used to divide the patients into risk groups and assess their risk of LNM.

Results

The 5-year overall survival rate was 91.72%, while 80.0% and 93.5% for patients with or without LNM (P<0.05). Multivariable logistic regression analysis showed that lymphovascular invasion (LVI), depth of invasion (DI), tumour size (TS), squamous cell carcinoma (SCC) antigen level were independent risk factors (all P<0.05). Patients were divided into low-risk (no LVI, DI <1/2, TS <2 cm), intermediate-risk (no LVI, DI <1/2, TS ≥2 cm; no LVI, DI ≥1/2, normal SCC level; LVI, DI <1/2, TS <2 cm), and high-risk (no LVI, DI ≥1/2, SCC level ≥1.5 ng/ml; LVI, TS <2 cm, DI ≥1/2; LVI, TS ≥2 cm) groups by RPA according to these four factors. The incidence of LNM among the three groups was 0.00%, 4.40%, and 24.10%, respectively (all P<0.001). The 5-year overall survival rates differed among the groups (98.2%, 92.7%, 83.0%, respectively, P=0.001).

Conclusions

LNM affects the prognosis of patients with FIGO stage IB1 CC. Lymphadenectomy may be avoided for patients in the low-risk group and recommended for those in the high-risk group. Whether dissection is performed in the intermediate-risk group depends on the lymph node biopsy results.
Prognostic Value of Lymph Node Evaluation in Stage II Small Bowel Adenocarcinoma: An Updated Analysis of Surveillance, Epidemiology, and End Results Database
Authors: Liu Zhen , Liu Kun , Gao Jiale , Jing Chao , Ma Yanhong , Zheng Shu , Shan Jianzhen
Published: March 2022

Background

Due to the lack of large-scale clinical trials, the treatment strategies of small bowel adenocarcinoma (SBA) are controversial, especially for stage II patients. According to the National Comprehensive Cancer Network (NCCN) guideline, few lymph nodes (LNs) examined (<5 for duodenum or <8 for jejunal/ileal primary location) are one of the high-risk features for stage II patients, for whom adjuvant chemotherapy is recommended. This consensus is originally drawn from data in the Surveillance, Epidemiology, and End Results Database (SEER) between 1988 and 2010. However, the surgical modalities and chemotherapy strategies changed a lot after 2004 for SBA patients. The previous data may not represent a true picture of current therapeutics. Thus, we reanalyzed the SEER database and updated the cutoff point of LN numbers resected with respect to cancer-specific survival (CSS) using the latest SEER information.

Methods

Patients diagnosed with stage II SBA and who underwent curative surgery between 2004 and 2018 were extracted from the SEER database. CSS was calculated using the Kaplan–Meier method and compared by log-rank test. Maximum survival differences based on total LNs examined for duodenal and jejunoileal tumors were determined separately with the cut-point analysis and maximum log-rank χ2 statistic. A nomogram model was constructed based on the multivariate Cox analysis to predict 5‐ and 10‐year CSS and was then validated with an internal cohort.

Results

A total of 935 stage II SBA patients met the inclusion criteria. The greatest difference in survival was found in patients who had removal of at least 5 LNs for duodenal and 12 LNs for jejunoileal tumors. Multivariate Cox analysis showed that age, T stage, histology grade, primary site, and LN numbers were independent prognostic factors for survival. The C index of nomogram model was 0.701 (95% CI, 0.661–0.741, p < 0.001).

Conclusions

The number of LNs harvested is an important prognostic factor for survival in stage II SBA patients. LN number examined <5 remains a high-risk factor for duodenum, but the cutoff point for jejunal/ileal tumors should rise from 8 to 12. Appropriate radical lymphadenectomy should be performed in stage II SBA surgery.
Transient Elastography in the Diagnosis of Pediatric Non-alcoholic Fatty Liver Disease and Its Subtypes
Authors: Yang Lin , Zhu Yafei , Zhou Lu , Yin Huimei , Lin Yan , Wu Guangsheng
Published: March 2022

Objective

To study the diagnosis efficacy of controlled attenuation parameters (CAP) and liver stiffness measurement (LSM) in the transient elastography of non-alcoholic fatty liver disease (NAFLD) and its subtypes in children with obesity.

Methods

Retrospectively analyze children with obesity in the Childhood Obesity Clinic of the Affiliated Hospital of Hangzhou Normal University from July 2020 to March 2021. The correlation between clinical data and NAFLD subtypes was analyzed, and included the relevant clinical data into the receiver operating characteristic curve for diagnosis and prediction.

Results

120 children aged between 6.1 and 17.8 years, with 70 males (58.33%), 50 females (41.67%), and a ratio of 1.4:1, were enrolled in the study. CAP and LSM correlated in all subtypes of NAFLD. The correlation was significant for diagnosing NAFLD in children with obesity when CAP > 258.00 dB/m and LSM > 4.65 kPa. It was also significant for NASH diagnosis when CAP > 276.00 dB/m and LSM > 5.15 kPa, while it was less significant for diagnosing NAFLD in children with obesity.

Conclusions

CAP and LSM have diagnostic efficacy for NAFLD and its subtypes in children with obesity, with optimal predictive values of CAP > 258.00 dB/m and LSM > 4.65 kPa for NAFLD in children with obesity, and CAP > 276.00 dB/m and LSM > 5.15 kPa for NASH in children with obesity.
A New Birthweight Reference by Gestational Age: A Population Study Based on the Generalized Additive Model for Location, Scale, and Shape Method
Authors: Wu Qiong , Zhang Hui-Yun , Zhang Li , Xu Yue-Qin , Sun Jin , Gao Nan-Nan , Qiao Xiu-Yun , Li Yan
Published: March 2022

Background

It is important to choose a suitable birthweight reference to assess newborns, especially those that are small for gestational age (SGA). Currently, there is no regional standard reference for the north of China or for Shandong province.

Methods

A total of 130,911 data records of singleton, live neonates born at 24–42 weeks of gestation were collected from 2016 to 2018 in Shandong province. A new birthweight-for-gestational age percentile reference was constructed based on the Generalized Additive Model for Location, Scale and Shape (GAMLSS) package in R version 3.5. The established gestational age weight curve was compared separately with the Fenton curve, INTERGROWTH−21st curve, and the Chinese Neonatal Network Standard curve of 2015.

Results

We established the reference values of birthweight by gestational age at the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles. Newborns had much heavier birthweights than those in the INTERGROWTH-21st and Fenton curves at most gestational ages. Although the newborns' birthweight references were closer to the Chinese Neonatal Network Standard except a few for gestational age, this study and INTERGROWTH-21st had similar birthweight curve shapes.

Conclusions

There are obvious differences among the criteria for newborn birthweights. Therefore, it is more accurate to assess newborns using the local birthweight reference.
Implementation of a Children's Safe Asthma Discharge Care Pathway Reduces the Risk of Future Asthma Attacks in Children–A Retrospective Quality Improvement Report
Authors: Kennedy Lesley , Gallagher Gillian , Maxwell Barbara , Bartholme Brigitte , Fitzsimons Andrew , Russell Catherine , Mallon Orla , Hughes Jenny L. , Beattie Susan , Vasi Veena , O'Donoghue Dara Bartholomew , Shields Michael David
Published: March 2022

Background

Many children attend Emergency Departments (ED) and Out of Hours (OoH) frequently for acute asthma. Follow up care is often suboptimal leaving these children at risk of a future attacks. We report on the development, implementation and evaluation of a safe asthma discharge care pathway (SADCP).

Methods

This is a retrospective report on the development, implementation and evaluation of outcomes of a SADCP. The pathway was based on the Teach-to-goal educational methodology that supported the mastery correct inhaler technique and ability to action the personalized asthma action plan (PAAP). Children with frequent asthma attacks were entered as they were discharged from the Emergency Department or ward. The first training session occurred within 1–3 weeks of the index asthma attack with 2 further sessions in the following 8 weeks. Children exiting the pathway were discharged either back to primary care or to a hospital clinic.

Results

81 children entered the pathway (median age 5 years) with 72 discharged from the ED and 9 from the medical wards of the Royal Belfast Hospital for Sick Children. At pathway entry 13% had correct inhaler technique, 10% had a Personalized Asthma Action Plan (PAAP), and 5% had >80% (45% >50%) repeat refill evidence of adherence to inhaled corticosteroid over the previous 12 months. On pathway exit all children demonstrated correct inhaler technique and were able to action their PAAP. One year later 51% and 95% had refill evidence of >80% and >50% adherence. Comparisons of the 12 months before and 12 months after exit from the pathway the median number of emergency ED or OoH asthma attendances and courses of oral corticosteroids reduced to zero with >75% having no attacks requiring this level of attention. Similar findings resulted when the SADCP was implemented in a district general hospital pediatric unit.

Conclusion

Implementing an asthma care pathway, using Teach-to-Goal skill training methods and frequent early reviews after an index asthma attack can reduce the future risk of asthma attacks in the next 6 to 12 months.
Mechanisms of Chemotherapy-Induced Neurotoxicity
Authors: Was Halina , Borkowska Agata , Bagues Ana , Tu Longlong , Liu Julia Y. H. , Lu Zengbing , Rudd John A. , Nurgali Kulmira , Abalo Raquel
Published: March 2022

Since the first clinical trials conducted after World War II, chemotherapeutic drugs have been extensively used in the clinic as the main cancer treatment either alone or as an adjuvant therapy before and after surgery. Although the use of chemotherapeutic drugs improved the survival of cancer patients, these drugs are notorious for causing many severe side effects that significantly reduce the efficacy of anti-cancer treatment and patients’ quality of life. Many widely used chemotherapy drugs including platinum-based agents, taxanes, vinca alkaloids, proteasome inhibitors, and thalidomide analogs may cause direct and indirect neurotoxicity. In this review we discuss the main effects of chemotherapy on the peripheral and central nervous systems, including neuropathic pain, chemobrain, enteric neuropathy, as well as nausea and emesis. Understanding mechanisms involved in chemotherapy-induced neurotoxicity is crucial for the development of drugs that can protect the nervous system, reduce symptoms experienced by millions of patients, and improve the outcome of the treatment and patients’ quality of life.
Molecular Mechanisms Underlying the Inhibition of Proliferation and Differentiation by Florfenicol in P19 Stem Cells: Transcriptome Analysis
Authors: Hu Dongfang , Zhang Bin , Suo Yu , Li Zhiyue , Wan Zhishuai , Zhao Weihua , Chen Lingli , Yin Zhihong , Ning Hongmei , Ge Yaming , Li Weiguo
Published: March 2022

Florfenicol (FLO), which is widely used in veterinary clinics and aquaculture, can disrupt the protein synthesis of bacteria and mitochondria and, thus, lead to antibacterial and toxic effects in plants, insects, and mammals. FLO was found to repress chicken embryonic development and induce early embryonic death previously, but the underlying mechanism is not fully understood. Clarifying the mechanism of FLO-induced embryonic toxicity is important to the research and development of new drugs and the rational use of FLO to ensure human and animal health and ecological safety. In this study, the effects of FLO on pluripotency, proliferation, and differentiation were investigated in P19 stem cells (P19SCs). We also identified differentially expressed genes and performed bioinformatics analysis to obtain hub genes and conducted some functional analysis. FLO inhibited the proliferation and pluripotency of P19SCs and repressed the formation of embryoid bodies derived from P19SCs. A total of 2,396 DEGs were identified using RNA-Seq in FLO-treated P19SCs, and these genes were significantly enriched in biological processes, such as angiogenesis, embryonic organ development, and morphogenesis of organs. Kyoto encyclopedia of genes and genome-based pathway analysis also showed that five relevant pathways, especially the canonical Wnt pathway, were engaged in FLO-induced toxicity of pluripotent stem cells. We further analyzed modules and hub genes and found the involvement of ubiquitin-mediated proteolysis, DNA replication, and cell cycle machinery in regulating the pluripotency and proliferation of FLO-treated P19SCs. In summary, our data suggest that FLO disrupts the signaling transduction of pathways, especially the canonical Wnt pathway, and further inhibits the expression of target genes involved in regulating DNA replication, cell cycle, and pluripotency. This phenomenon leads to the inhibition of proliferation and differentiation in FLO-treated P19SCs. However, further experiments are required to validate our findings and elucidate the potential mechanisms underlying FLO-induced embryonic toxicity.
The Efficacy and Safety of Sodium Bicarbonate Ringer’s Solution in Critically Ill Patients: A Retrospective Cohort Study
Authors: Bian Yi , Xu Tingting , Le Yue , Li Shusheng
Published: March 2022

Background: Sodium bicarbonate Ringer’s solution has been widely used in clinical practice in recent years. There are few clinical studies on the efficacy and safety of this fluid among critically ill patients until now.

Method: This retrospective cohort study included critically ill adult patients in the intensive care unit (ICU) of Tongji Hospital from 1 January 2019 to 31 December 2020. By reviewing exclusively the use of either sodium bicarbonate Ringer’s solution or saline for resuscitation or maintenance, the patients were included into two groups, respectively. The primary outcome was the major adverse kidney event within 30 days (MAKE30), including death, new receipt of renal replacement therapy, or persistent renal dysfunction. Safety outcomes were focused on arterial blood gas and plasma biochemical alterations, which might potentially be induced by the administration of bicarbonate Ringer’s solution.

Result: A total of 662 patients were included in the cohort. Compared to the saline group, the bicarbonate Ringer’s group had a significantly lower rate of the new receipt of renal replacement therapy [adjusted odds ratio (OR) = 0.591, 95% confidence interval (CI), 0.406 to 0.861; p = 0.006]. There was no significant difference between the two groups in 30-day mortality, final creatinine level ≥200% of baseline, and major adverse kidney event within 30 days. In subgroup analysis, the incidence of MAKE30 was higher in the bicarbonate Ringer’s group than that of the saline group among patients with cardiovascular disease. The patients in the bicarbonate Ringer’s group had a longer length of intensive care unit stay than patients in the saline group, but their new renal replacement therapy days were shorter. No major alterations were found in arterial blood gas and plasma biochemical during the follow-up period.

Conclusion: Compared to saline, sodium bicarbonate Ringer’s solution exhibited a potential renal function protective effect while causing no major alterations in arterial blood gas and plasma biochemistry. However, the application in patients with cardiovascular disease diagnosis at ICU admission should be cautious.
Hypoxia and Hypoxia-Inducible Factors in Lymphedema
Authors: Jiang Xinguo , Tian Wen , Kim Dongeon , McQuiston Alexander S. , Vinh Ryan , Rockson Stanley G. , Semenza Gregg L. , Nicolls Mark R.
Published: March 2022

Lymphedema is a chronic inflammatory disorder characterized by edema, fat deposition, and fibrotic tissue remodeling. Despite significant advances in lymphatic biology research, our knowledge of lymphedema pathology is incomplete. Currently, there is no approved pharmacological therapy for this debilitating disease. Hypoxia is a recognized feature of inflammation, obesity, and fibrosis. Understanding hypoxia-regulated pathways in lymphedema may provide new insights into the pathobiology of this chronic disorder and help develop new medicinal treatments.
MiR-130a-3p Alleviates Inflammatory and Fibrotic Phases of Pulmonary Fibrosis Through Proinflammatory Factor TNF-α and Profibrogenic Receptor TGF-βRII
Authors: Ding Yan , Hou Yapeng , Liu Yanhong , Yu Tong , Cui Yong , Nie Hongguang
Published: March 2022

Pulmonary fibrosis (PF) is a progressive disease characterized by extracellular matrix (ECM) deposition that destroys the normal structure of the lung parenchyma, which is classified into two successive inflammatory and fibrotic phases. To investigate the anti-inflammatory and anti-fibrotic roles of miR-130a-3p in mice with bleomycin (BLM)-induced PF and the underlying mechanism, we performed single-cell RNA-sequencing analysis, which demonstrated that BLM increased/decreased the percentage of macrophages and fibroblasts/epithelial cells in PF lungs, respectively. The differentially expressed genes were enriched in PPAR signaling pathway and lysosome, ECM–receptor interaction and ribosome, and metabolism reaction. Time-course studies demonstrated that the inflammation-related factors increased significantly at day 7 (inflammatory phase), whereas the fibrosis-related factors increased at day 28 (fibrotic phase) after BLM exposure. Meanwhile, miR-130a-3p could ameliorate pulmonary lesions by downregulating the secretion of inflammatory cytokines (IL-1β, IL-6, TNF-α, and TGF-β1) and the deposition of ECM (α-SMA, FN, HYP, and collagen) in the inflammatory and fibrotic phase, respectively. In the LPS-induced inflammatory cell model, the upregulation of miR-130a-3p was mainly achieved by the activation of the NF-κB signaling pathway, which suppressed the proinflammatory factor TNF-α. Comparatively, the TGF-β/Smad signaling pathway was inhibited by miR-130a-3p targeting TGF-βRII in the TGF-β1-deduced fibrotic cell model. The evidence supports that miR-130a-3p exerts an anti-inflammatory and anti-fibrotic effect in BLM-induced PF, implying a potential pharmacological agent in the therapy of PF patients.
Comparison of Vascular Function, Cardiometabolic Parameters, Hemorheological Function, and Cardiorespiratory Fitness Between Middle-Aged Korean Women With and Without Obesity—A Pilot Study
Authors: Park Hun-Young , Jung Won-Sang , Kim Sung-Woo , Jung Kyounghwa , Lim Kiwon
Published: March 2022

This study aimed to compare vascular function, cardiometabolic parameters, hemorheological function, and cardiorespiratory fitness in middle-aged Korean women according to obesity defined using body mass index (BMI). A total of 32 Korean women aged between 34 and 60 years (16 without obesity, mean age 46.31 ± 7.49 years and 16 with obesity, mean age 49.68 ± 6.69 years) participated in this study. Obesity was defined as BMI ≥ 25 kg/m2. The body composition, vascular function, cardiometabolic parameters, hemorheological function, and cardiorespiratory fitness of all participants were measured. Statistical differences in the dependent parameters between individuals with and without obesity were analyzed, and the correlations between BMI and the dependent variables were verified. The obese group showed significantly worse results (p < 0.05) for body composition (significantly higher weight, BMI, fat mass, and percent body fat), vascular function [significantly higher branchial ankle pulse wave velocity (baPWV) and lower flow-mediated vasodilation (FMD)], cardiometabolic parameters [significantly higher insulin and homeostatic model assessment for insulin resistance (HOMA-IR)], hemorheological function (significantly lower erythrocyte deformability and higher aggregation), and cardiorespiratory fitness [significantly lower maximal oxygen uptake (VO2max)] compared to the non-obese group. In addition, BMI showed a significant positive correlation (p < 0.05) with baPWV (r = 0.430); total cholesterol (r = 0.376), triglyceride (r = 0.411), low-density lipoprotein cholesterol (r = 0.462), and insulin (r = 0.477) levels; HOMA-IR (r = 0.443); and erythrocyte aggregation (r = 0.406), and a significant negative correlation (p < 0.05) with VO2max (r = −0.482) and FMD (r = −0.412). Our study confirmed that obesity is a major determinant for deterioration of vascular function, cardiometabolic parameters, hemorheological function, and cardiorespiratory fitness.
Determining the Effects of Differential Expression of GRKs and β-arrestins on CLR-RAMP Agonist Bias
Authors: Pearce Abigail , Redfern-Nichols Theo , Harris Matthew , Poyner David R. , Wigglesworth Mark , Ladds Graham
Published: March 2022

Signalling of the calcitonin-like receptor (CLR) is multifaceted, due to its interaction with receptor activity modifying proteins (RAMPs), and three endogenous peptide agonists. Previous studies have focused on the bias of G protein signalling mediated by the receptor and receptor internalisation of the CLR-RAMP complex has been assumed to follow the same pattern as other Class B1 G Protein-Coupled Receptors (GPCRs). Here we sought to measure desensitisation of the three CLR-RAMP complexes in response to the three peptide agonists, through the measurement of β-arrestin recruitment and internalisation. We then delved further into the mechanism of desensitisation through modulation of β-arrestin activity and the expression of GPCR kinases (GRKs), a key component of homologous GPCR desensitisation. First, we have shown that CLR-RAMP1 is capable of potently recruiting β-arrestin1 and 2, subsequently undergoing rapid endocytosis, and that CLR-RAMP2 and -RAMP3 also utilise these pathways, although to a lesser extent. Following this we have shown that agonist-dependent internalisation of CLR is β-arrestin dependent, but not required for full agonism. Overexpression of GRK2-6 was then found to decrease receptor signalling, due to an agonist-independent reduction in surface expression of the CLR-RAMP complex. These results represent the first systematic analysis of the importance of β-arrestins and GRKs in CLR-RAMP signal transduction and pave the way for further investigation regarding other Class B1 GPCRs.
Effects of Warming and Phosphorus Enrichment on the C:N:P Stoichiometry of Potamogeton crispus Organs
Authors: Dai Mingzhe , Wang Tao , Wang Yuyu , Xu Jun
Published: March 2022

The loss of submerged macrophytes from freshwater ecosystems is accelerating owing to the combined effects of eutrophication and climate change. Submerged macrophytes depend on spring clear water; however, increased water temperatures and excessive phosphorus (P) inputs often lead to the dominance of phytoplankton. It is still not clear how the stoichiometric characteristics of carbon (C), nitrogen (N), and P in different tissues of submerged macrophytes respond to P enrichment and temperature increases. In this study, we established 36 mesocosm ecosystems to explore the effects of warming and P addition on the leaf, turion, stem, and seed stoichiometry ofPotamogeton crispus. The results revealed that different functional plant organs show distinct responses to P addition and warming, which demonstrates the importance of evaluating the responses of different submerged macrophyte organs to environmental changes. In addition, interactive effects between P addition and warming were observed in the leaf, turion, and seed C:N:P stoichiometry, which highlights the importance of multifactorial studies. Our data showed that warming caused a decrease in the C content in most organs, with the exception of the stem; P addition increased the P content in most organs, with the exception of seed; N content in the turion and seed were influenced by interactive effects. Collectively, P addition could helpP. crispusto resist the adverse effects of high temperatures by aiding growth and asexual reproduction, and asexual propagules were found to be more sensitive to P enrichment than sexual propagules.