bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Validation of a Radiomics Nomogram Using Computed Tomography for Differentiating Immune Checkpoint Inhibitor-Related Pneumonitis From Radiation Pneumonitis for Patients With Non-Small Cell Lung Cancer
Authors: Qiu Qingtao , Xing Ligang , Wang Yu , Feng Alei , Wen Qiang 
Published: April 2022

BackgroundThe combination of immunotherapy and chemoradiotherapy has become the standard therapeutic strategy for patients with unresected locally advance-stage non-small cell lung cancer (NSCLC) and induced treatment-related adverse effects, particularly immune checkpoint inhibitor-related pneumonitis (CIP) and radiation pneumonitis (RP). The aim of this study is to differentiate between CIP and RP by pretreatment CT radiomics and clinical or radiological parameters.MethodsA total of 126 advance-stage NSCLC patients with pneumonitis were enrolled in this retrospective study and divided into the training dataset (n =88) and the validation dataset (n = 38). A total of 837 radiomics features were extracted from regions of interest based on the lung parenchyma window of CT images. A radiomics signature was constructed on the basis of the predictive features by the least absolute shrinkage and selection operator. A logistic regression was applied to develop a radiomics nomogram. Receiver operating characteristics curve and area under the curve (AUC) were applied to evaluate the performance of pneumonitis etiology identification.ResultsThere was no significant difference between the training and the validation datasets for any clinicopathological parameters in this study. The radiomics signature, named Rad-score, consisting of 11 selected radiomics features, has potential ability to differentiate between CIP and RP with the empirical and α-binormal-based AUCs of 0.891 and 0.896. These results were verified in the validation dataset with AUC = 0.901 and 0.874, respectively. The clinical and radiological parameters of bilateral changes (p &lt; 0.001) and sharp border (p = 0.001) were associated with the identification of CIP and RP. The nomogram model showed good performance on discrimination in the training dataset (AUC = 0.953 and 0.950) and in the validation dataset (AUC = 0.947 and 0.936).ConclusionsCT-based radiomics features have potential values for differentiating between patients with CIP and patients with RP. The addition of bilateral changes and sharp border produced superior model performance on classifying, which could be a useful method to improve related clinical decision-making.
Decreased Vessel Density in Retinal Capillary Plexus and Thinner Ganglion Cell Complex Associated With Cognitive Impairment
Authors: Yang Kai , Cui Lele , Chen Xueyu , Yang Chuang , Zheng Jingwei , Zhu Xiaoxuan , Xiao Yunfan , Su Binbin , Li Chunmei , Shi Keai , Lu Fan , Qu Jia , Li Ming 
Published: April 2022

BackgroundTo determine the association of the retinal capillary plexus (RCP) and ganglion cell complex (GCC) with cognitive impairment using optical coherence tomography angiography (OCTA).MethodsA cross-sectional, community-based study utilizing data from the participants enrolled between August 2019 and January 2020 in the Jidong Eye Cohort Study. We assessed the vessel density in RCP and GCC thickness using OCTA, and cognitive testing using the Montreal Cognitive Assessment (MoCA). Cognitive impairment in this study was defined as MoCA score &lt; 24. We used multivariable analysis to evaluate the association of RCP and GCC with cognitive impairment after adjusting for confounders.ResultsThis study analyzed 1555 participants. The mean age of participants was 52.3 (8.4) years, and 861 (55.4%) were women. Cognitive impairment was observed in 268 (17.2%) participants. The adjusted odds ratio (OR) with 95% confidence interval (95% CI) for parafovea vessel density in the deep RCP with cognitive impairment was 1.20 (1.03–1.39). For vessel area and length density surrounding foveal avascular zone with cognitive impairment, the ORs with 95% CIs were 1.23 (1.07–1.41) and 1.30 (1.13–1.49), respectively. For thickness in the superior GCC with cognitive impairment, the OR with 95% CI was 1.16 (1.01–1.32).ConclusionLower vessel density in the RCP and thinner GCC were associated with cognitive impairment. Our results suggest that alterations in the RCP and GCC could provide further evidence when assessing the cognitive function and may even be potentially useful biomarkers in the detection of cognitive impairment.
The Potential Mechanism Behind Native and Therapeutic Collaterals in Moyamoya
Authors: Bao Xiang-Yang , Fan Yan-Na , Wang Qian-Nan , Wang Xiao-Peng , Yang Ri-Miao , Zou Zheng-Xing , Zhang Qian , Li De-Sheng , Duan Lian , Yu Xin-Guang 
Published: April 2022

Background and PurposeTo explore the genetic basis and molecular mechanism of native arteriogenesis and therapeutic synangiosis in moyamoya disease (MMD).MethodsAn angiography-based study using patients from a prospective trial of encephaloduroarteriosynangiosis (EDAS) surgery was performed. The spontaneous collaterals grades were evaluated according to the system described by a new grading system. Blood samples were collected from all the recruited patients before EDAS and during the second hospitalization 3 months post-EDAS. We performed Boolean analysis using a combination of specific cell surface markers of CD34briCD133+CD45dimKDR+. Genotyping of p.R4810K was also performed. The correlation of age, sex, initial symptoms at diagnosis, collateral grade, Suzuki stages, the RNF213 genotype, time to peak (TTP), and endothelial progenitor cell (EPC) count with good collateral circulation was evaluated.ResultsEighty-five patients with MMD were included in this study. The mutation rate of RNF213 p.R4810K in our study was 25.9% (22/85). The heterozygous mutations were occurred significantly more frequently in the cases that were presented with infarction, worse neurological status, severe posterior cerebral artery (PCA) stenosis, and longer TTP delay. Further, the heterozygous mutations occurred significantly more frequently in the poor collateral stage group. Lower grades were significantly correlated with severe ischemia symptoms, worse neurological status, and a longer TTP delay. The post-operative angiographic findings showed that a good Matsushima grade was correlated with heterozygous mutations, a lower collateral stage, and a longer TTP delay. The CD34briCD133+CD45dimKDR+ cell count in patients 3 months post-EDAS was significantly higher as compared to the count before EDAS in the good Matsushima grade group. However, this change was not observed in the poor Matsushima grade group.ConclusionsThese data imply that mutations of RNF213 p.R4810K affect the establishment of spontaneous collateral circulation, and EPCs are involved in the process of formation of new EDAS collaterals.
Temporal Dispersion and Duration of the Distal Compound Muscle Action Potential Do Not Distinguish Diabetic Sensorimotor Polyneuropathy From Chronic Inflammatory Demyelinating Polyneuropathy
Authors: Alcantara Monica , Ngo Mylan , de la Cruz James , Menon Deepak , Barnett-Tapia Carolina , Katzberg Hans , Bril Vera 
Published: April 2022

ObjectiveTo investigate the contribution of duration and temporal dispersion (TD) of the distal compound muscle action potential (CMAP) in discriminating chronic inflammatory demyelinating polyneuropathy (CIDP) from diabetic sensorimotor polyneuropathy (DSP) and from CIDP+DSP.MethodsWe performed a retrospective review of patients diagnosed with CIDP, DSP and CIDP+DSP (responsive to immunotherapy) and examined differences in CMAP duration and TD at baseline.ResultsWe included 59 subjects: 17 CIDP, 21 DSP and 21 CIDP+DSP. Of these, 16 (94.1%) CIDP, 18 (85.7%) CIDP+DSP and 1 (4.7%) DSP fulfilled the 2010 EFNS/PNS criteria for definite CIDP. There was no difference in CMAP duration or TD in all nerves (compound outcome) or in individual motor nerves. Patients with CIDP/CIDP+DSP had more conduction blocks, slower conduction velocities and more prolonged F wave latencies than those with DSP.ConclusionMeasures of CMAP duration and TD were not helpful in distinguishing CIDP, DSP or CIDP+DSP patients; however, parameters such as F-wave latencies, conduction blocks or the number of demyelinating parameters were useful in this separation.SignificanceThere are no definite nerve conduction criteria to distinguish patients with CIDP+DSP from DSP alone. Further studies focusing on measures of demyelination may provide stronger evidence to guide treatment decisions in CIDP + DSP patients.
Long Noncoding RNA MALAT1 and Colorectal Cancer: A Propensity Score Analysis of Two Prospective Cohorts
Authors: Li Heng , Zhang Yuxue , Liu Yanlong , Qu Zhangyi , Liu Yupeng , Qi Jiping 
Published: April 2022

BackgroundPrevious researches have shown that the aberrant expression of Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) in tumour tissues may serve as a biomarker for colorectal cancer (CRC) prognosis. However, these previous studies have small sample sizes and lacked validation from independent external populations. We therefore aimed to clarify the prognostic value of MALAT1 expression status in CRC patients using a large cohort and validate the findings with another large external cohort.MethodsThe prognostic association between MALAT1 expression status and CRC outcomes was evaluated initially in a prospective cohort in China (n=164) and then validated in an external TCGA population (n=596). In the initial cohort, MALAT1 expression levels were quantified by quantitative reverse transcriptase polymerase chain reaction. Propensity score (PS) adjustment method was used to control potential confounding biases. The prognostic significance was reported as PS-adjusted hazard ratio (HR) and corresponding 95% confidence interval (CI).ResultsThere was no statistically significant association between MALAT1 expression status and CRC patient overall survival (OS) or disease free survival (DFS) in both initial cohort and external validation cohort populations. When combining these populations together, the results did not change materially. The summarized HRPS-adjusted were 1.010 (95% CI, 0.752-1.355, P=0.950) and 1.170 (95% CI, 0.910-1.502, P=0.220) for OS and DFS, respectively.ConclusionsMALAT1 expression status is not associated with prognostic outcomes of CRC patients. However, additional larger population studies are needed to further validate these findings.
Aggressiveness of Differentiated Thyroid Carcinoma in Pediatric Patients Younger Than 16 years: A Propensity Score-Matched Analysis
Authors: Kim Soo Young , Yun Hyeok Jun , Chang Hojin , Kim Seok-Mo , Jeon Soyoung , Lee Sujee , Lee Yong Sang , Chang Hang-Seok , Park Cheong Soo 
Published: April 2022

BackgroundThe biological behavior of thyroid cancer in children has been known to be different from that in adults. We sought to understand the differences between DTC presentation in pediatric (&lt;16 years) and adult patients, to guide better prognosis and clinical treatments.MethodsThis retrospective study included 48 pediatric patients younger than 16 years who underwent initial thyroid surgery and were diagnosed with DTC between January 1992 and December 2014 at Yonsei University in Seoul, South Korea. For a 1:4 propensity score-matched analysis, adult patients with matched sex and cancer size were included.ResultsThe mean age was 12.54 ± 3.01 years. Total thyroidectomy (70.8%) without lateral lymph node dissection (47.9%) was the most commonly performed surgery. Central (73.9%) and lateral neck node metastases (62.5%) were common; distant metastasis was observed in 2 (4.2%) patients and recurrence occurred in 11 (22.9%). In propensity score-matched analysis, central lymph node metastasis and lateral neck node metastasis were significantly more frequent in pediatric patients. Symptoms were more common in the pediatric group than in the adult group (p &lt; 0.001). In stratified cox regression, pediatric patients were more likely to experience recurrence [HR 5.339 (1.239–23.007)]. In stratified log-rank analysis, recurrence-free survival was significantly different between the adult and pediatric groups (p = 0.0209).ConclusionDTC in the pediatric group revealed more aggressive patterns than in the adult group with the same cancer size. Central lymph node metastasis and lateral neck node metastasis were more frequent. Stratified log-rank analysis revealed that recurrence was significantly higher in pediatric patients than in matched adult patients.
Epidemiology and Outcomes of Neonatal Hemophagocytic Lymphohistiocytosis
Authors: Balakumar Niveditha , Sendi Prithvi , Totapally Balagangadhar R. 
Published: April 2022

ObjectivesNeonatal hemophagocytic lymphohistiocytosis (HLH) is a rare entity. The objective of the study was to describe the prevalence, clinical characteristics, interventions and outcomes of neonates diagnosed with HLH in the United States.MethodsA retrospective analysis of 2009, 2012, and 2016 Kids' Inpatient Database was performed. Neonates discharged/died with a diagnosis of HLH were identified and analyzed.ResultsAmong 11,130,055 discharges, 76 neonates had a diagnosis of HLH. Fifty-two percent (95% CI: 38.6–63.6) were males and 54% (95% CI: 39.7–68.5) were white. Herpes simplex infection was present in 16% (95% CI: 9.2–28.1). 24.4% (95% CI: 14.5–37.9) received chemotherapy, 11.5% (95% CI: 5.2–23.6) IVIG and 3.6% (95% CI: 0.8–14.4) allogenic hemopoietic stem cell transplantation. Organ dysfunction was commonly seen and severe sepsis was documented in 26.6% (95% CI: 16.4–39.9). Median LOS was 16 (IQR 7–54) days. The mortality was 42% (95% CI: 30.8–55).ConclusionsHLH is a rare diagnosis and carries a high mortality in neonates. Herpes simplex virus is the most common infection associated with neonatal HLH. HLH should be considered in the differential diagnosis in neonates presenting with multi-organ dysfunction or sepsis.
Anti-infective Medicines Use in Children and Neonates With Pre-existing Kidney Dysfunction: A Systematic Review
Authors: Minotti Chiara , Barbieri Elisa , Doni Denis , Impieri Cristina , Giaquinto Carlo , Donà Daniele 
Published: April 2022

BackgroundDosing recommendations for anti-infective medicines in children with pre-existing kidney dysfunction are derived from adult pharmacokinetics studies and adjusted to kidney function. Due to neonatal/pediatric age and kidney impairment, modifications in renal clearance and drug metabolism make standard anti-infective dosing for children and neonates inappropriate, with a risk of drug toxicity or significant underdosing. The aim of this study was the systematic description of the use of anti-infective medicines in pediatric patients with pre-existing kidney impairment.MethodsA systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The EMBASE, Medline and Cochrane databases were searched on September 21st, 2021. Studies in all languages reporting data on pre-defined outcomes (pharmacokinetics-PK, kidney function, safety and efficacy) regarding the administration of anti-infective drugs in children up to 18 years with pre-existing kidney dysfunction were included.Results29 of 1,792 articles were eligible for inclusion. There were 13 case reports, six retrospective studies, nine prospective studies and one randomized controlled trial (RCT), reporting data on 2,168 pediatric patients. The most represented anti-infective class was glycopeptides, with seven studies on vancomycin, followed by carbapenems, with five studies, mostly on meropenem. Antivirals, aminoglycosides and antifungals counted three articles, followed by combined antibiotic therapy, cephalosporins, lipopeptides with two studies, respectively. Penicillins and polymixins counted one study each. Nine studies reported data on patients with a decreased kidney function, while 20 studies included data on kidney replacement therapy (KRT). Twenty-one studies reported data on PK. In 23 studies, clinical outcomes were reported. Clinical cure was achieved in 229/242 patients. There were four cases of underdosing, one case of overdosing and 13 reported deaths.ConclusionThis is the first systematic review providing evidence of the use of anti-infective medicines in pediatric patients with impaired kidney function or requiring KRT. Dosing size or interval adjustments in pediatric patients with kidney impairment vary according to age, critical illness status, decreased kidney function and dialysis type. Our findings underline the relevance of population PK in clinical practice and the need of developing predictive specific models for critical pediatric patients.
Factors Influencing Background Incidence Rate Calculation: Systematic Empirical Evaluation Across an International Network of Observational Databases
Authors: Ostropolets Anna , Li Xintong , Makadia Rupa , Rao Gowtham , Rijnbeek Peter R. , Duarte-Salles Talita , Sena Anthony G. , Shaoibi Azza , Suchard Marc A. , Ryan Patrick B. , Prieto-Alhambra Daniel , Hripcsak George 
Published: April 2022

Objective: Background incidence rates are routinely used in safety studies to evaluate an association of an exposure and outcome. Systematic research on sensitivity of rates to the choice of the study parameters is lacking.Materials and Methods: We used 12 data sources to systematically examine the influence of age, race, sex, database, time-at-risk, season and year, prior observation and clean window on incidence rates using 15 adverse events of special interest for COVID-19 vaccines as an example. For binary comparisons we calculated incidence rate ratios and performed random-effect meta-analysis.Results: We observed a wide variation of background rates that goes well beyond age and database effects previously observed. While rates vary up to a factor of 1,000 across age groups, even after adjusting for age and sex, the study showed residual bias due to the other parameters. Rates were highly influenced by the choice of anchoring (e.g., health visit, vaccination, or arbitrary date) for the time-at-risk start. Anchoring on a healthcare encounter yielded higher incidence comparing to a random date, especially for short time-at-risk. Incidence rates were highly influenced by the choice of the database (varying by up to a factor of 100), clean window choice and time-at-risk duration, and less so by secular or seasonal trends.Conclusion: Comparing background to observed rates requires appropriate adjustment and careful time-at-risk start and duration choice. Results should be interpreted in the context of study parameter choices.
Idiopathic Pulmonary Fibrosis Mortality Risk Prediction Based on Artificial Intelligence: The CTPF Model
Authors: Wu Xuening , Yin Chengsheng , Chen Xianqiu , Zhang Yuan , Su Yiliang , Shi Jingyun , Weng Dong , Jiang Xing , Zhang Aihong , Zhang Wenqiang , Li Huiping 
Published: April 2022

Background: Idiopathic pulmonary fibrosis (IPF) needs a precise prediction method for its prognosis. This study took advantage of artificial intelligence (AI) deep learning to develop a new mortality risk prediction model for IPF patients.Methods: We established an artificial intelligence honeycomb segmentation system that segmented the honeycomb tissue area automatically from 102 manually labeled (by radiologists) cases of IPF patients’ CT images. The percentage of honeycomb in the lung was calculated as the CT fibrosis score (CTS). The severity of the patients was evaluated by pulmonary function and physiological feature (PF) parameters (including FVC%pred, DLco%pred, SpO2%, age, and gender). Another 206 IPF cases were randomly divided into a training set (n = 165) and a verification set (n = 41) to calculate the fibrosis percentage in each case by the AI system mentioned previously. Then, using a competing risk (Fine–Gray) proportional hazards model, a risk score model was created according to the training set’s patient data and used the validation data set to validate this model.Result: The final risk prediction model (CTPF) was established, and it included the CT stages and the PF (pulmonary function and physiological features) grades. The CT stages were defined into three stages: stage I (CTS≤5), stage II (5 &lt; CTS&lt;25), and stage III (≥25). The PF grades were classified into mild (a, 0–3 points), moderate (b, 4–6 points), and severe (c, 7–10 points). The AUC index and Briers scores at 1, 2, and 3 years in the training set were as follows: 74.3 [63.2,85.4], 8.6 [2.4,14.8]; 78 [70.2,85.9], 16.0 [10.1,22.0]; and 72.8 [58.3,87.3], 18.2 [11.9,24.6]. The results of the validation sets were similar and suggested that high-risk patients had significantly higher mortality rates.Conclusion: This CTPF model with AI technology can predict mortality risk in IPF precisely.
Lower FSH With Normal Fertility in Male Mice Lacking Gonadotroph Kisspeptin Receptor
Authors: Ma Yaping , Awe Olubusayo , Radovick Sally , Yang Xiaofeng , Divall Sara , Wolfe Andrew , Wu Sheng 
Published: April 2022

The kisspeptin receptor, crucial for hypothalamic control of puberty and reproduction, is also present in the pituitary gland. Its role in the pituitary gland is not defined. Kisspeptin signaling via the Kiss1r could potentially regulate reproductive function at the level of pituitary gonadotrope. Using Cre/Lox technology, we deleted the Kiss1r gene in pituitary gonadotropes (PKiRKO). PKiRKO males have normal genital development (anogenital distance WT: 19.1 ± 0.4 vs. PKiRKO: 18.5 ± 0.4 mm), puberty onset, testes cell structure on gross histology, normal testes size, and fertility. PKiRKO males showed significantly decreased serum FSH levels compared to WT males (5.6 ± 1.9 vs. 10.2 ± 1.8 ng/ml) with comparable LH (1.1 ± 0.2 vs. 1.8 ± 0.4 ng/ml) and testosterone levels (351.8 ± 213.0 vs. 342.2 ± 183.0 ng/dl). PKiRKO females have normal puberty onset, cyclicity, LH and FSH levels and fertility. Overall, these findings indicate that absence of pituitary Kiss1r reduces FSH levels in male mice without affecting testis function. PKiRKO mice have normal reproductive function in both males and females.