bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between the weight of schoolbags and low back pain among schoolchildren: A systematic review, meta‐analysis and individual patient data meta‐analysis
Authors: Calvo‐Muñoz Inmaculada , Kovacs Francisco M. , Roqué Marta , Seco‐Calvo Jesús
Published: August 2019

Background

The objective of this study was to determine whether carrying a heavy schoolbag is associated to a higher prevalence of low back pain (LBP).

Methods

A systematic review and meta‐analysis was conducted (PROSPERO, CRD42018077839). Observational studies analysing the relationship between schoolbag weight and LBP, were searched for in 20 electronic databases and 12 specialized journals until February 28th, 2019, without date or language restrictions. All studies which included ≥ 50 subjects aged 9 to 16, were reviewed. Methodological quality was assessed by two reviewers separately, using validated tools. A meta‐analysis and an individual patient data (IPD) meta‐analysis were conducted to examine the relationship between schoolbag weight and LBP. Certainty of evidence was assessed using an adapted GRADE methodology.

Results

5,524 citations were screened, 21 studies (18,296 subjects) were reviewed and 11 studies (9,188 subjects) were included in the meta‐analysis. The IPD meta‐analysis included 9,188 subjects from seven studies. Among the 21 studies reviewed, the mean score for methodological quality was 78.3 of 100. Only one study suggested an association between heavier schoolbags and LBP. Neither the meta‐analysis nor the IPD meta‐analysis found an association between carrying schoolbags weighing > 10% of bodyweight, and LBP. No differences based on age, gender or sport activity were found.

Discussion

Available evidence does not support that schoolbags weighing > 10% of bodyweight are associated with a higher prevalence of LBP among schoolchildren aged 9–16. The certainty of evidence is low. Further research is required on the relationship between schoolbag weight and LBP.

Significance

This systematic review, with a meta‐analysis and an IPD meta‐analysis, failed to find a link between schoolbags weighing ≥ 10% of body weight and LBP among schoolchildren aged 9 to 16. Further longitudinal studies, with large samples, long follow‐up periods, and rigorous methods taking into account duration of carry and the physical capacity of each subject, are required in this field.
Premorbid and concurrent predictors of TMD onset and persistence
Authors: Ohrbach Richard , Slade Gary D. , Bair Eric , Rathnayaka Nuvan , Diatchenko Luda , Greenspan Joel D. , Maixner William , Fillingim Roger B.
Published: August 2019

Background

Multiple risk factors predict temporomandibular disorders (TMD) onset, but temporal changes in risk factors and their contribution to risk of TMD have not been evaluated. The study aims were to (a) describe changes occurring in premorbid TMD risk factors when re‐measured at TMD onset and 6 months later, and (b) determine if measures of change improve accuracy in predicting TMD incidence compared to premorbid measures alone.

Methods

In this observational prospective cohort study at four university research clinics, 3,258 community‐based, 18‐ to 44‐year‐olds without TMD were enrolled. During the 3‐year median follow‐up, 260 incident cases of first‐onset TMD were identified, and 196 TMD‐free subjects were selected as matched controls. Six‐months later, 147 of 260 incident cases (56.6%) were re‐examined revealing 72 (49%) with ‘persistent TMD’ and 75 (51%) whose condition had resolved (‘transient TMD’). Virtually all (126) of the 127 re‐examined controls remained without TMD. Questionnaires and clinical measurements evaluated risk factors from clinical, health, psychological and behavioural and neurosensory domains.

Results

Most risk factors across all four domains increased with TMD onset, remained elevated in the persistent group and declined in the transient group (i.e., significant ANOVA interactions,p < .05). Accuracy in predicting first‐onset TMD, quantified as area under the receiver operating characteristic curve was 0.71 (95% CL 0.68, 0.73) using only premorbid measures of risk factors, which increased to 0.91 (95% CL 0.89, 0.94) after addition of change measures.

Conclusions

TMD pain onset and persistence appear to be determined by enduring characteristics of the person as well as mutually interactive with temporally evolving variables.

Significance

TMD is known to be a complex disorder, in which onset and persistence are associated with disease‐related variables in multiple domains, including environmental exposure, clinical, psychological, health status, and pain processing variables. Using a more dynamic approach in order to capture change across time, many aspects of those domains were found to worsen prior to the reporting of pain, with bidirectional influences between domains and pain emergence likely. TMD onset appears to represent the cumulative effect of multiple system dysregulation.
Risk factors for episodes of back pain in emerging adults. A systematic review
Authors: Øiestad Britt Elin , Hilde Gunvor , Tveter Anne Therese , Peat George G. , Thomas Martin J. , Dunn Kate M. , Grotle Margreth
Published: August 2019

Background and Objective

The transition from adolescence to adulthood is a sensitive period in life for health outcomes, including back pain. The objective was to synthesize evidence on risk factors for new episodes of back pain in emerging adults (18–29 years).

Methods

The protocol was registered in PROSPERO (CRD42016046635). We searched Medline; EMBASE; AMED and other databases up to September 2018 for prospective cohort studies that estimated the association between risk factor(s) and self‐reported back pain. Risk factors could be measured before or during the age range 18–29 years, and back pain could be measured during or after this age range, with at least 12 months between assessments. Risk factors assessed in ≥3 studies were summarized. Risk of bias was assessed using a 6‐item checklist.

Results

Forty‐nine studies were included with more than 150 different risk factors studied. Nine studies had low risk of bias, 26 had moderate and 14 had high risk of bias. Age, sex, height, body mass index (BMI), smoking, physical activity level, a history of back pain, job satisfaction and structural imaging findings were investigated in three or more studies. History of back pain was the only risk factor consistently associated with back pain after adjustment (nine studies).

Conclusion

There is moderate quality evidence that a history of back pain is a risk factor for back pain. There are inconsistent associations for age, sex, height, BMI, smoking and activity level. No associations were found between job satisfaction and structural imaging findings and back pain.

Significance

Emerging adulthood is a transitional period of life with changes in life style, potentially influencing future musculoskeletal health. This systematic review included 49 articles evaluating more than 150 potential risk factors for back pain, one of the most prevalent musculoskeletal disorders. No consistent results were found for life style factors such as physical activity level or BMI, both highlighted as important risk factors in previous literature. Importantly, a previous episode of back pain was a consistent risk factor for a new episode of back pain across several studies, and further investigation of risk factors for the first back pain episode is needed.
Metal Exposure Risk Assessment for Tree Sparrows at Different Life Stages via Diet from a Polluted Area in Northwestern China
Authors: Ai Shiwei , Yang Ying , Ding Jian , Yang Wenzhi , Bai Xiaojuan , Bao Xinkang , Ji Weihong , Zhang Yingmei
Published: August 2019

To estimate the risk of metal (Cu, Zn, Pb, and Cd) exposure of tree sparrows through food at different life stages (including nestling, juvenile, adult in summer, and adult in winter), metal daily intake (MDI), metal daily intake per unit of body weight (MDIBW), and exposure risks (hazard quotient and hazard index) of tree sparrows at different life stages from a polluted area, Baiyin, and a control area, Liujiaxia, were assessed. Metal daily intakes and MDIBWs of tree sparrows from Baiyin were higher than those from Liujiaxia, which can be attributed to higher metal concentrations of food sources in Baiyin than those in Liujiaxia. Metal daily intakes and MDIBWs of nestlings were higher than those of adults and juveniles. This difference is observed probably because nonphytophagous invertebrates, the predominant food fed to nestlings, possessed the highest metal concentrations. In addition, adults in summer had higher MDIs and MDIBWs than juveniles and adults in winter. This finding is probably observed because juveniles and adults in winter consumed a higher proportion of maize, which had the lowest metal concentrations. In addition, the biomagnification of 4 metals through the food chain increased the health risks of tree sparrows. Exposure risks of tree sparrows to metals were comparable to those of waterfowl and raptors, even when soil metals were below threshold. Environ Toxicol Chem 2019;38:2785–2796. © 2019 SETAC

Abstract

Diet of tree sparrows varies at different life stages, dominated by plant food (including cereal grains and grass seeds) as well as a small amount of invertebrates at the juvenile and adult stages, and including a higher proportion of invertebrates than plant food at the nestling stage. Tree sparrows from polluted areas had a higher heavy metal exposure risk, and nestlings had a higher heavy metal exposure level than juveniles and adults.
Reactions of polyphenols in pomegranate peel with nitrite under simulated stomach conditions
Authors: Xie Zhenjian , Li Xiaohong , Tang Renyong , Wang Guoze , Lu Yurong , Li Xuemei , Cheng Kun , Li Linzhi , He Qiang
Published: August 2019

Punicalagin and ellagic acid are the major polyphenols present in pomegranate peels. The contents of α‐punicalagin, β‐punicalagin, and ellagic acid in the pomegranate peels were approximately 75, 72, and 20 µM, respectively. The reactions of polyphenols in pomegranate peels with sodium nitrite under simulated stomach conditions were studied. The reactions decreased the polyphenolic contents of the pomegranate peels and accompanied the formation of nitroso compounds. The oxidation rates followed the order ellagic acid ＜α‐punicalagin ≈ β‐punicalagin. The results suggested that the reactions can occur in the stomach after a meal, while the pH changes from 2 to 4.5.
Meta‐MultiSKAT: Multiple phenotype meta‐analysis for region‐based association test
Authors: Dutta Diptavo , Gagliano Taliun Sarah A. , Weinstock Joshua S. , Zawistowski Matthew , Sidore Carlo , Fritsche Lars G. , Cucca Francesco , Schlessinger David , Abecasis Gonçalo R. , Brummett Chad M. , Lee Seunggeun
Published: August 2019

The power of genetic association analyses can be increased by jointly meta‐analyzing multiple correlated phenotypes. Here, we develop a meta‐analysis framework, Meta‐MultiSKAT, that uses summary statistics to test for association between multiple continuous phenotypes and variants in a region of interest. Our approach models the heterogeneity of effects between studies through a kernel matrix and performs a variance component test for association. Using a genotype kernel, our approach can test for rare‐variants and the combined effects of both common and rare‐variants. To achieve robust power, within Meta‐MultiSKAT, we developed fast and accurate omnibus tests combining different models of genetic effects, functional genomic annotations, multiple correlated phenotypes, and heterogeneity across studies. In addition, Meta‐MultiSKAT accommodates situations where studies do not share exactly the same set of phenotypes or have differing correlation patterns among the phenotypes. Simulation studies confirm that Meta‐MultiSKAT can maintain the type‐I error rate at the exome‐wide level of 2.5 × 10−6. Further simulations under different models of association show that Meta‐MultiSKAT can improve the power of detection from 23% to 38% on average over single phenotype‐based meta‐analysis approaches. We demonstrate the utility and improved power of Meta‐MultiSKAT in the meta‐analyses of four white blood cell subtype traits from the Michigan Genomics Initiative (MGI) and SardiNIA studies.
Ischemic preconditioning induces cortical microglial proliferation and a transcriptomic program of robust cell cycle activation
Authors: McDonough Ashley , Noor Shahani , Lee Richard V. , Dodge Ryan , Strosnider James S. , Shen Jasmine , Davidson Stephanie , Möller Thomas , Garden Gwenn A. , Weinstein Jonathan R.
Published: August 2019

Ischemic preconditioning (IPC) is an experimental phenomenon in which a subthreshold ischemic insult applied to the brain reduces damage caused by a subsequent more severe ischemic episode. Identifying key molecular and cellular mediators of IPC will provide critical information needed to develop novel therapies for stroke. Here we report that the transcriptomic response of acutely isolated preconditioned cortical microglia is dominated by marked upregulation of genes involved in cell cycle activation and cellular proliferation. Notably, this transcriptional response occurs in the absence of cortical infarction. We employed ex vivo flow cytometry, immunofluorescent microscopy, and quantitative stereology methods on brain tissue to evaluate microglia proliferation following IPC. Using cellular colocalization of microglial (Iba1) and proliferation (Ki67 and BrdU) markers, we observed a localized increase in the number of microglia and proliferating microglia within the preconditioned hemicortex at 72, but not 24, hours post‐IPC. Our quantification demonstrated that the IPC‐induced increase in total microglia was due entirely to proliferation. Furthermore, microglia in the preconditioned hemisphere had altered morphology and increased soma volumes, indicative of an activated phenotype. Using transgenic mouse models with either fractalkine receptor (CX3CR1)‐haploinsufficiency or systemic type I interferon signaling loss, we determined that microglial proliferation after IPC is dependent on fractalkine signaling but independent of type I interferon signaling. These findings suggest there are multiple distinct targetable signaling pathways in microglia, including CX3CR1‐dependent proliferation that may be involved in IPC‐mediated protection.
Correcting for Phylogenetic Autocorrelation in Species Sensitivity Distributions
Authors: Moore Dwayne RJ , Priest Colleen D , Galic Nika , Brain Richard A , Rodney Sara I
Published: August 2019

A species sensitivity distribution (SSD) is a cumulative distribution function of toxicity endpoints for a receptor group. A key assumption when deriving an SSD is that the toxicity data points are independent and identically distributed (iid). This assumption is tenuous, however, because closely related species are more likely to have similar sensitivities than are distantly related species. When the response of 1 species can be partially predicted by the response of another species, there is a dependency or autocorrelation in the data set. To date, phylogenetic relationships and the resulting dependencies in input data sets have been ignored in deriving SSDs. In this paper, we explore the importance of the phylogenetic signal in deriving SSDs using a case studies approach. The case studies involved toxicity data sets for aquatic autotrophs exposed to atrazine and aquatic and avian species exposed to chlorpyrifos. Full and partial data sets were included to explore the influences of differing phylogenetic signal strength and sample size. The phylogenetic signal was significant for some toxicity data sets (i.e., most chlorpyrifos data sets) but not for others (i.e., the atrazine data sets, the chlorpyrifos data sets for all insects, crustaceans, and birds). When a significant phylogenetic signal did occur, effective sample size was reduced. The reduction was large when the signal was strong. In spite of the reduced effective sample sizes, significant phylogenetic signals had little impact on fitted SSDs, even in the tails (e.g., hazardous concentration for 5th percentile species [HC5]). The lack of a phylogenetic signal impact occurred even when we artificially reduced original sample size and increased strength of the phylogenetic signal. We conclude that it is good statistical practice to account for the phylogenetic signal when deriving SSDs because most toxicity data sets do not meet the independence assumption. That said, SSDs and HC5s are robust to deviations from the independence assumption. Integr Environ Assess Manag 2019;00:1–13. © 2019 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)
Direct oral anticoagulants are effective and safe for the treatment of venous thromboembolism associated with gynecological cancers
Authors: Shimizu Aasa , Sawada Kenjiro , Shiomi Mayu , Kawano Mahiru , Matsumoto Yuri , Takiuchi Tsuyoshi , Kodama Michiko , Kobayashi Eiji , Hashimoto Kae , Mabuchi Seiji , Ueda Yutaka , Tomimatsu Takuji , Kimura Tadashi
Published: August 2019

Objective

To retrospectively review the efficacy and safety of novel direct oral anticoagulants (DOACs) and compare the results with those of vitamin K antagonists (VKA) when used in clinical practice to treat venous thromboembolism (VTE) because there is insufficient evidence regarding its use in patients with gynecological cancers.

Methods

A study was conducted of patients diagnosed with gynecological cancers at Osaka University Hospital between January 2010 and December 2017. The medical records of those who suffered from deep venous thrombosis (DVT) and/or pulmonary embolism (PE) were retrospectively reviewed.

Results

Among the 1698 cases of gynecological cancers, 107 (6.3%) cases were diagnosed as having VTE. A total of 34 (31.8%) patients presented DVT plus PE and 73 (68.2%) patients had DVT alone. Fifty‐four cases were treated with DOACs and 53 with VKA. Although 3 of the 53 patients (5.7%) in the VKA group developed recurrent VTE, only 1 (1.9%) patient in the DOAC group showed clinically relevant bleeding from a tumor penetrating the rectum. DOACs were non‐inferior to VKA with respect to the composite outcome, including recurrent venous thrombosis and relevant bleeding (hazard ratio 0.31, 95% confidence interval 0.03–3.12, P=0.363).

Conclusion

DOACs can be effectively and safely used in VTE patients with gynecological cancers.
Persistent depression after obstetric fistula repair
Authors: Stokes Mary J. , Wilkinson Jeffrey P. , Ganesh Prakash , Nundwe William , Pope Rachel J.
Published: August 2019

Objective

To measure depression over time using the Patient Health Questionnaire 9 (PHQ‐9) and identify characteristics associated with persistent depression.

Methods

A database of women undergoing obstetric fistula repair was used to examine associations between depression and variables such as demographics, type of fistula, and postoperative continence status.

Results

A total of 797 patients completed the PHQ‐9 at the initial preoperative assessment; 365 (45.8%) had a PHQ‐9 score of 5 or higher, indicating depression. Preoperatively, depression was associated with women aged 18–34 years, with no children, and with fistula for 5 years or less. Postoperatively, depression was associated with persistent incontinence. Over time, however, depression was rarely found among women returning for follow‐up.

Conclusion

Postoperative depression decreased over time in women who returned for follow‐up, either due to selection bias or due to improved adjustment to one's circumstances. This study underscores the need for ongoing follow‐up, especially for those not presenting for care or with persistent incontinence.
Genetic Screening in a Large Chinese Cohort of Childhood Onset Hypoparathyroidism by Next-Generation Sequencing Combined with TBX1-MLPA
Authors: Wang Yabing , Nie Min , Wang Ou , Li Yuepeng , Jiang Yan , Li Mei , Xia Weibo , Xing Xiaoping
Published: August 2019

At least 15 candidate genes have been implicated in hypoparathyroidism (HP). However, comprehensive screening of causative genes for HP is lacking. Here, we investigated the genotype spectrum in a large group of Chinese patients with childhood onset HP. A total of 173 patients with childhood onset HP were analyzed using targeted next-generation sequencing (NGS), including 15 candidate genes combined with multiplex ligation-dependent probe amplification (MLPA) of the TBX1 gene. Twenty-seven pathogenic or likely pathogenic mutations in five genes (TBX1, AIRE, GATA3, FAM111A, and CASR) including 13 novel variants in 23 patients, and 12 variants of uncertain clinical significance in five genes (GATA3, CASR, FAM111A, GCM2, and PTH) in 11 patients, were identified by NGS. Additionally, an entire gene deletion of TBX1 in 25 patients was found by TBX1-MLPA. Combined with clinical data, 26 (15.0%) cases of DiGeorge syndrome (OMIM #188400), nine (5.2%) autoimmune polyglandular syndrome type 1 (OMIM #240300), eight (4.6%) autosomal dominant hypocalcemia type 1 (OMIM #601198), four (2.3%) hypoparathyroidism-deafness-renal dysplasia syndrome (OMIM #146255), and one (0.6%) Kenny-Caffey syndrome type 2 (OMIM #127000) were verified. Among them, 16 of 26 (61.5%) DiGeorge syndrome cases were undiagnosed due to the lack of obvious clinical clues before genetic testing. The onset age of patients with mutations (median [interquartile range], 2.8 [0.1, 9.6] years) was significantly earlier than those without mutations (13.0 [8.8, 15.0] years) (p < 0.001). Family history, early onset age, especially prior to 5 years old, and extraparathyroid manifestations were clues for hereditary HP. The combined targeted NGS and TBX-1 MLPA were conveniently and effectively used for comprehensive genetic screening in this large Chinese cohort of childhood onset HP patients. Genetic defects were identified in 27.7% of early-onset HP patients, including four kinds of syndromic HP and one isolated HP. A total of 13 novel mutations were detected, which expands the mutation spectrum of hypoparathyroidism. © 2019 American Society for Bone and Mineral Research.
Hop2 Interacts with ATF4 to Promote Osteoblast Differentiation
Authors: Zhang Yang , Lin Tonghui , Lian Na , Tao Huan , Li Cong , Li Lingzhen , Yang Xiangli
Published: August 2019

Activating transcription factor 4 (ATF4) is a member of the basic leucine zipper (bZip) transcription factor family required for the terminal differentiation of osteoblasts. Despite its critical importance as one of the three main osteoblast differentiation transcription factors, regulators of osteoblast terminal maturation remain poorly defined. Here we report the identification of homologous pairing protein 2 (Hop2) as a dimerization partner of ATF4 in osteoblasts via the yeast two-hybrid system. Deletional mapping revealed that the Zip domain of Hop2 is necessary and sufficient to bind ATF4 and to enhance ATF4-dependent transcription. Ectopic Hop2 expression in preosteoblasts increased endogenous ATF4 protein content and accelerated osteoblast differentiation. Mice lacking Hop2 (Hop2−/−) have a normal stature but exhibit an osteopenic phenotype similar to the one observed in Atf4−/− mice, albeit milder, which is associated with decreased Osteocalcin mRNA expression and reduced type I collagen synthesis. Compound heterozygous mice (Atf4+/−:Hop2+/−) display identical skeletal defects to those found in Hop2−/− mice. These results indicate that Hop2 plays a previous unknown role as a determinant of osteoblast maturation via its regulation of ATF4 transcriptional activity. Our work for the first time reveals a function of Hop2 beyond its role in guiding the alignment of homologous chromosomes. © 2019 American Society for Bone and Mineral Research.
Retracted: AT1R knockdown confers cardioprotection against sepsis‐induced myocardial injury by inhibiting the MAPK signaling pathway in rats
Authors: Zhang Tao , Yin Yu‐Chao , Ji Xiang , Zhang Bo , Wu Sheng , Wu Xiao‐Zhe , Li Hong , Li Ya‐Dan , Ma Ya‐Ling , Wang Yu , Li Hai‐Tao , Zhang Bin , Wu Di
Published: August 2019

Myocardial dysfunction is an important manifestation of sepsis. In addition, inactivation of the mitogen‐activated protein kinase (MAPK) signaling pathway has been reported to be beneficial in sepsis. The current study used gene expression profiling to demonstrate the overexpression of angiotensin II type 1 receptor (AT1R) and activation of the MAPK signaling pathway in sepsis. In this study, we used a rat model of sepsis established by cecal ligation and puncture to explore the mechanism of AT1R silencing in relation to the MAPK signaling pathway on myocardial injury. Various parameters including blood pressure, heart rate, and cardiac function changes were observed. Enzyme‐linked immunosorbent assay was used to measure the concentration of cardiac troponin T (TnT), cardiac troponin I (cTnI), and creatine kinase isoenzyme muscle/brain (CK‐MB). Myocardial enzyme, tissue antioxidant capacity, mitochondria swelling, and membrane potential were also detected. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling staining was applied to measure cell apoptosis, and messenger RNA and protein levels of apoptosis‐related proteins (Fas ligand [Fasl], B‐cell CLL/lymphoma [Bcl‐2], p53) were also detected. Initially, sepsis rats exhibited decreased survival rate, but increased ejection fraction (EF), heart rate, and concentrations of TnT, cTnI, and CK‐MB. Furthermore, decreased AT1R expression inactivated the MAPK signaling pathway (shown as decreased extracellular signal–regulated kinase and cyclic adenosine 3′,5′‐monophosphate response element binding protein expression), decreased EF, heart rate, and concentrations of TnT, cTnI, and CK‐MB, but increased sepsis rat survival rate. Eventually, decreased AT1R expression inhibited myocardial cell apoptosis (shown as decreased apoptosis rate and p53 and Fasl expression as well as increased Bcl‐2 expression). These findings indicated that AT1R silencing plays an inhibitory role in sepsis‐induced myocardial injury by inhibiting the MAPK signaling pathway.
The application of lymphocyte*platelet and mean platelet volume/platelet ratio in influenza A infection in children
Authors: Fei Yang , Zhang Hongbo , Zhang Chi
Published: August 2019

Background

To explore the characteristics and regularity of complete blood count (CBC) changes among influenza A–positive child patients and to discover parameters that can help with the diagnosis and differential diagnosis.

Methods

One hundred and ninety‐one influenza A–positive children, two hundred and nineteen influenza A–negative children with influenza‐like symptoms, and two hundred and forty‐seven healthy children were included in this study. They were divided into three groups: influenza A–positive patient group, influenza A–negative patient group, and control group. Reverse transcriptase polymerase chain reaction testing and Sysmex XS‐800i hematology analyzer were used to obtain influenza A and CBC results, respectively. CBC along with parameters including lymphocyte‐to‐monocyte ratio (LMR), neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), mean platelet volume/platelet ratio (MPV/PLT), and lymphocyte*platelet (LYM*PLT) was calculated and recorded for each child. The differences in these parameters among different groups were tested with SPSS 15.0. The diagnostic values were also evaluated.

Results

The LYM and PLT of child patients with influenza A were significantly lower than those of both influenza A–negative patients with influenza‐like symptoms and healthy controls. Among all the parameters, LYM*PLT has the largest area under the curve and the highest diagnostic value, followed by MPV/PLT. Compared with using LMR or MPV/PLT, the diagnostic value of using LYM alone was, on the contrary, higher.

Conclusions

Low LYM*PLT and high MPV/PLT may indicate influenza A infection in children with influenza‐like symptoms, which can be a useful indicator for diagnosis and differentiation of influenza A infection.
Procalcitonin as a prognostic marker for sepsis based on SEPSIS‐3
Authors: Jekarl Dong Wook , Lee Seungok , Kim Myungshin , Kim Yonggoo , Woo Seon Hee , Lee Woon Jeong
Published: August 2019

Background

The revised definition of sepsis is life‐threatening organ dysfunction caused by a dysregulated host response to infection (SEPSIS‐3). The objective of this study was to evaluate procalcitonin (PCT) for the diagnosis and prognosis of sepsis using SEPSIS‐3.

Methods

We enrolled 248 patients, who were admitted to the emergency department with suspected bacterial infection from June 2016 to February 2017. Definite bacterial infection was defined by proven culture results, and probable bacterial infection was based on diagnostic modalities other than culture. The sequential organ failure assessment (SOFA) score of 2 points or more from the baseline was diagnosed as sepsis. PCT was measured by the AFIAS‐6 immunoassay system (Boditech Med Inc.) using whole blood. White blood cell (WBC), C‐reactive protein (CRP), and erythrocyte sedimentation rate (ERS) were evaluated.

Results

The final diagnosis was sepsis in 185 patients with infection of respiratory and genitourinary tract constituted 84.6%. The area under the receiver operating characteristic curve (AUROC) with 95% confidence interval (CI) was as follows: PCT, 0.682 (0.589‐0.765); CRP, 0.583 (0.487‐0.673); ESR, 0.540 (0.515‐0.699); and WBC, 0.611 (0.455‐0.633), respectively. In multivariate analysis, age, SOFA, and PCT (log scale) predicted non‐survivors with an odds ratio with 95% confidence interval of 1.055 (1.008‐1.105), 1.303 (1.142‐1.486), and 2.004 (1.240‐3.238), respectively. Among sepsis group, initial PCT was increased in non‐survivor (23.2 ng/dL) compared to survivor group (8.1 ng/dL) with statistical significance (P = .005).

Conclusions

PCT could support and predict the unfavorable prognosis of sepsis based on SEPSIS‐3, whereas diagnostic potential of PCT requires further evaluations.
Tumor‐derived exosomal miRNA‐320d as a biomarker for metastatic colorectal cancer
Authors: Tang Youyong , Zhao Yajing , Song Xingguo , Song Xianrang , Niu Limin , Xie Li
Published: August 2019

Background

To identify specific exosomal microRNAs (miRNAs) as serum biomarkers for prediction of metastasis in patients with colorectal cancer (CRC).

Materials and Methods

Serum exosomes were isolated from patients with metastatic CRC (n = 34) and non‐metastatic CRC (n = 108) by ultracentrifugation and characterized using transmission electron microscopy, qNano, and Western blot. Differential exosomal miRNAs were screened by sequencing and validated by qPCR in metastatic and non‐metastatic CRC patients.

Results

After sequence analysis, KEGG analysis showed that differential genes were associated with Rap1 signaling pathway and pathways in cancer, 6 upregulated exosomal miRNAs (miR‐224‐5p, miR‐548d‐5p, miR‐200a‐3p, miR‐320d, miR‐200b‐3p, and miR‐1246), and 3 downregulated exosomal miRNAs (novel_246, novel_301, and miR‐27a‐5p) were screened with fold change >1.5, among which miR‐320d was selected as the best candidate involved in CRC metastasis. Validation analysis revealed exosomal miR‐320d could significantly distinguish metastatic from non‐metastatic CRC patients (P = .019), with AUC of 0.633 for the diagnosis of patients with metastatic CRC. Besides, the combination of miR‐320d and CEA had an area under curve (AUC) of 0.804 for the diagnosis of patients with metastatic CRC.

Conclusion

Serum exosomal miR‐320d is a promising non‐invasive diagnostic biomarker for distinguishing metastatic from non‐metastatic CRC.
Type I collagen inhibits adipogenic differentiation via YAP activation in vitro
Authors: Liu Xiaoling , Long Xinyu , Gao Yanfang , Liu Weiwei , Hayashi Toshihiko , Mizuno Kazunori , Hattori Shunji , Fujisaki Hitomi , Ogura Takayuki , Onodera Satoshi , Wang Dan Ohtan , Ikejima Takashi
Published: August 2019

Extracellular matrix (ECM) has a marked influence on adipose tissue development. Adipose tissue formation is initiated with proliferation of preadipocytes and migration before undergoing further differentiation into mature adipocytes. Previous studies showed that collagen I (col I) provides a good substratum for 3T3‐L1 preadipocytes to grow and migrate. However, it remains unclear whether and how col I regulates adipogenic differentiation of preadipocytes. This study reports that lipid accumulation, representing in vitro adipogenesis of the 3T3‐L1 preadipocytes or the mouse primary adipocyte precursor cells derived from subcutaneous adipose tissue in the inguinal region is inhibited by the culture on col I, owing to downregulation of adipogenic factors. Previous study shows that col I enhances 3T3‐L1 cell migration via stimulating the nuclear translocation of yes‐associated protein (YAP). In this study, we report that downregulation of YAP is associated with in vitro adipogenesis of preadipocytes as well as with in vivo adipose tissue of high‐fat diet fed mice. Increased expression of YAP in the cells cultured on col I‐coated dishes is correlated with repression of adipogenic differentiation processes. The inactivation of YAP using YAP inhibitor, verteporfin, or YAP small‐interfering RNA enhanced adipogenic differentiation and reversed the inhibitory effect of col I. Activation of YAP either by the transfection of YAP plasmid or the silence of large tumor suppressor 1 (LATS1), an inhibitory kinase of YAP, inhibited adipogenic differentiation. The results indicate that col I inhibits adipogenic differentiation via YAP activation in vitro.
Metamizole (Dipyrone) and the Liver: A Review of the Literature
Authors: Lutz Mathias
Published: August 2019

Metamizole, also known as dipyrone, was introduced to the market nearly a century ago. Due to its excellent analgesic, antipyretic, and spasmolytic properties combined with its mostly favorable gastrointestinal tolerability, the drug was extensively applied worldwide during the first decades after its market introduction. Although rare, agranulocytosis is a well‐known adverse event of metamizole and led to its withdrawal from the market in a number of countries beginning in the 1960s. Nevertheless, metamizole is still a frequently used drug worldwide either legally (by prescription in some countries, over the counter in other countries) or without official approval (especially by immigrants knowing the drug from their home countries) or even illegally (due to its growing application as an adulterant in illicit drugs). Metamizole undergoes extensive metabolism in the liver and cases of potential metamizole‐associated hepatotoxicity have been described. Here, the literature is extensively reviewed for the first time regarding hepatic effects associated with the use of metamizole.
The relationship between sense of a life worth living and local self‐governance: A cross‐sectional study
Authors: Ohta Ryuichi , Sato Mikiya , Maeno Tetsuhiro
Published: August 2019

Background

Aging populations are facing increasing health problems, with social conditions often exacerbating such maladies. Although local self‐governance might effectively solve these problems, such civic participation can increase citizens’ mental and physical fatigue, which, in turn, may decrease their sense of leading productive lives.

Methods

This cross‐sectional study examined the relationship between citizens’ participation in and perceptions of local self‐governance and their sense of life worth living. The study was conducted in Unnan City, which is located in the southeastern part of Shimane Prefecture. A questionnaire measuring local self‐governance and participant backgrounds was distributed. Completed questionnaires were collected between March 1 and 31, 2018. A binomial logistic regression model was used.

Results

Of the distributed questionnaires, 38.5% (769/2000) were completed and returned. Responses from women and those over 65 years of age comprised 54.2% (417/769) and 35.1% (270/769) of the completed questionnaires, respectively. Analysis of the data using binomial logistic regression showed that age (≥65), health management, social interaction, learning habits, and interest in local self‐governance were significantly correlated with a sense of life worth living (odds ratio for the variables were 0.56 (P = .002), 2.58 (P < .001), 3.05 (P < .001), 2.51 (P < .001), and 1.61 (P = .009), respectively).

Conclusion

Promoting local self‐governance may lead to a better sense of life worth living for citizens of rural communities. Therefore, when assessing the effectiveness of local self‐governance regarding citizens’ sense of life worth living, their interest in local self‐governance should be taken into consideration.
Biocatalyzed Enantiomerically Pure Production of (S)‐Phenyl(thiophen‐2‐yl)methanol
Authors: Şahin Engin , Dertli Enes
Published: August 2019

Chiral aryl heteroaryl methanols are important precursors for the synthesis of pharmaceutically important molecules. The aims of this study were to use a biocatalyst that could efficiently bioreduce phenyl(thiophen‐2‐yl)methanone 1 to (S)‐phenyl(thiophen‐2‐yl)methanol 2, to identify the impact of the physicochemical factors that might affect the bioreduction by the biocatalyst, and to obtain multigram production of aryl heteroaryl secondary alcohol 2 with the biocatalyst under optimized conditions. Over the years, the (S)‐phenyl(thiophen‐2‐yl)methanol was synthesized on a small scale using a chemical catalyst without its enantiomerically pure form. In this study, Lactobacillus paracasei BD101 was used for the asymmetric reduction of phenyl(thiophen‐2‐yl)methanone to (S)‐phenyl(thiophen‐2‐yl)methanol in the large‐scale production. The asymmetric bioreduction conditions were systematically optimized, and the production of 3.77 g of (S)‐phenyl(thiophen‐2‐yl)methanol was carried out in enantiomerically pure form >99% enantiomeric excess (ee), >99% conversion, and 90% yield. This method obtained with this biocatalyst is a process that can be used industrially in terms of conversion, ee, and yield. This study provides guidance for the application of L. paracasei BD101 in the production of optically active aryl heteroaryl alcohols.
Overriding advance directives: A 20‐year legal and ethical overview
Authors: Banja John , Sumler Michele
Published: August 2019

Health professionals have been known to override patients’ advance directives. The most ethically problematic instances involve a directive's explicitly forbidding the administration of some life‐prolonging treatment like resuscitation or intubation with artificial ventilation. Sometimes the code team is unaware of the directive, but in other instances, the override is done knowingly and intentionally with clinicians later pleading that it was done “in the patient's best interests.” This article surveys a twenty‐year period extending back to 1997 when ethicists began to question the legitimacy of overriding advance directives despite clinicians believing they had compelling reasons to do so. A legal and ethical analysis of advance directive overrides is provided as no court to date has awarded damages to plaintiffs who alleged their loved one suffered “wrongful life” following a successful life‐prolonging intervention. A hypothetical scenario is especially discussed wherein a patient's DNR status is overridden because her cardiac arrest was caused by error whose effects might be reversible. The authors conclude with a strategy for mitigating certain vagaries associated with overriding advance directives, but suggest that until courts provide clinicians with clear guidelines and protections, violations of patients’ advance directives are likely to continue.
One‐year clinical outcomes of anticoagulation therapy among Japanese patients with atrial fibrillation: The Hyogo AF Network (HAF‐NET) Registry
Authors: Hyogo Kiyohiro , Yoshida Akihiro , Takeuchi Motoshi , Kiuchi Kunihiko , Fukuzawa Koji , Takami Mitsuru , Kobori Atsushi , Okajima Katsunori , Odake Michio , Okada Toshio , Shimane Akira , Kawahara Yasuhiro , Sekiya Junichi , Sano Hiroshi , Ichikawa Yasunori , Hirata Ken‐ichi ,   the HAF‐NET Registry Investigators
Published: August 2019

Background

Although anticoagulation therapy could reduce the risk of strokes in patients with atrial fibrillation (AF), large‐scale investigations in the direct oral anticoagulant (DOAC) and AF catheter ablation (CA) era are lacking.

Methods

This study was designed as a prospective, multicenter, observational study and a total of 2113 patients from 22 institutions were enrolled in the Hyogo area.

Results

The mean age and CHADS2 score were 70.1 ± 10.8 years old and 1.5 ± 1.1, respectively. The follow‐up period was 355 ± 43 days. CA was performed in 614 (29%) and DOACs were prescribed in 1118 (53%) patients. Ischemic strokes/systemic embolisms (SEs) and major bleeding occurred in 13 (0.6%) and 17 (0.8%) patients, respectively. New onset dementia, hospitalizations for cardiac events, and all‐cause death occurred in eight (0.4%), 60 (2.8%), and 29 (1.4%) patients, respectively. A multivariate analysis demonstrated that persistent AF and the body weight (BW) were associated with ischemic strokes/SEs and major bleeding, respectively (persistent AF: hazard ratio, 9.57; 95%CI, 1.2‐74.0; P = .03; BW: hazard ratio, 0.94; 95%CI, 0.90‐0.99; P = .02). AFCA history was associated with the cardiac events (hazard ratio, 0.44; 95%CI, 0.20‐0.99; P = .04). Age was associated with new onset dementia (hazard ratio, 1.1; 95%CI, 1.0‐1.2; P = .03).

Conclusions

In the DOAC and CA era, the incidence of ischemic strokes/SEs, major bleeding and cardiac events could be dramatically reduced in patients with AF. However, some unsolved issues of AF management still remain especially in elderly patients with persistent AF and a low BW.
Management ofMycobacterium aviumsubsp.paratuberculosisin dairy farms:Selection and evaluation of different DNA extraction methods from bovine and buffaloes milk and colostrum for the establishment of a safe colostrum farm bank
Authors: Gamberale Fabrizio , Pietrella Gabriele , Sala Marcello , Scaramella Paola , Puccica Silvia , Antognetti Valeria , Arrigoni Norma , Ricchi Matteo , Cersini Antonella
Published: August 2019

The aim of this study was to develop and validate different innovative DNA extraction methods to detectMycobacterium aviumsubsp.paratuberculosis (MAP)DNA from bovine and buffalo colostrum. Paratuberculosis is a chronic inflammatory infection of domestic and wild animals, especially ruminants, caused by MAP. The primary route of disease transmission is feces, but MAP can also be excreted in milk and colostrum. In 2015, the Italian Ministry of Health has issued a voluntary control plan of MAP in order to allow risk‐based certification of bovine and buffaloes farms. In addition to the annual diagnostic screening and to the clinical surveillance of animals the plan includes the adoption of biosecurity and management measures to progressively mitigate the incidence of MAP. To achieve this goal it is crucial to ensure the accuracy of the methods used to detect the presence of MAP in bovine and buffaloes milk and colostrum, in order to: (1) support a "safe colostrum farm‐bank" set‐up and thus prevent the main within‐farm MAP transmission route and (2) to allow the MAP‐free certification of milk products for export purposes. To achieve these goals, seven different DNA extraction protocols were identified from bibliography, out of which three methods were finally selected after the adoption of an evaluation procedure aimed at assessing the efficiency of extraction of DNA, the purity of DNA and the adaptability of the DNA amplification: NucleoSpin®Food Kit (Macherey‐Nagel), NucleoSpin®Food Kit (Macherey‐Nagel) combined with the magnetic beads, and QIAamp Cador Pathogen Mini kit (QIAGEN). In particular, the NucleoSpin®Food Kit (Macherey‐Nagel) and the QIAamp Cador Pathogen Mini kit (QIAGEN) were tested on bovine and buffalo colostrum, showing a LOD between 4 × 104(2.6 × 106 cfu/ml) and 4.08 (26.7 cfu/ml) IS900 target copies and a LOD between 5.3 × 105(4.1 × 106 cfu/ml) and 53 (4.1 × 103 cfu/ml) IS900 target copies, respectively.
Inertial self‐adaptive algorithm for solving split feasible problems with applications to image restoration
Authors: Suparatulatorn Raweerote , Charoensawan Phakdi , Poochinapan Kanyuta
Published: August 2019

We introduce a new self‐adaptive algorithm for applications to image restoration problems. In order to study an image restoration, we consider the algorithm that contains inertial effects and step sizes, which is independent from the norm of the bounded linear operator. With some control conditions, the strong convergence to the minimum norm solution of the algorithm is obtained. Convergence analysis of the proposed algorithm is also discussed. Moreover, numerical results of image restoration problems illustrate that the proposed algorithm is efficient and outperforms other ones.
A modality conversion approach to MV‐DRs and KV‐DRRs registration using information bottlenecked conditional generative adversarial network
Authors: Liu Cong , Lu Zheming , Ma Longhua , Wang Lang , Jin Xiance , Si Wen
Published: August 2019

Purpose

As affordable equipment, electronic portal imaging devices (EPIDs) are wildly used in radiation therapy departments to verify patients’ positions for accurate radiotherapy. However, these devices tend to produce visually ambiguous and low‐contrast planar digital radiographs under megavoltage x ray (MV‐DRs), which poses a tremendous challenge for clinicians to perform multimodal registration between the MV‐DRs and the kilovoltage digital reconstructed radiographs (KV‐DRRs) developed from the planning computed tomography. Furthermore, the existent of strong appearance variations also makes accurate registration beyond the reach of current automatic algorithms.

Methods

We propose a novel modality conversion approach to this task that first synthesizes KV images from MV‐DRs, and then registers the synthesized and real KV‐DRRs. We focus on the synthesis technique and develop a conditional generative adversarial network with information bottleneck extension (IB‐cGAN) that takes MV‐DRs and nonaligned KV‐DRRs as inputs and outputs synthesized KV images. IB‐cGAN is designed to address two main challenges in deep‐learning‐based synthesis: (a) training with a roughly aligned dataset suffering from noisy correspondences; (b) making synthesized images have real clinical meanings that faithfully reflects MV‐DRs rather than nonaligned KV‐DRRs. Accordingly, IB‐cGAN employs (a) an adversarial loss to provide training supervision at semantic level rather than the imprecise pixel level; (b) an IB to constrain the information from the nonaligned KV‐DRRs.

Results

We collected 2698 patient scans to train the model and 208 scans to test its performance. The qualitative results demonstrate realistic KV images can be synthesized allowing clinicians to perform the visual registration. The quantitative results show it significantly outperforms current nonmodality conversion methods by 22.37% (P = 0.0401) in terms of registration accuracy.

Conclusions

The modality conversion approach facilitates the downstream MV–KV registration for both clinicians and off‐the‐shelf registration algorithms. With this approach, it is possible to benefit the developing countries where inexpensive EPIDs are widely used for the image‐guided radiation therapy.