bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical Activity During Pregnancy and Preterm Birth: Findings From the 2015 Pelotas (Brazil) Birth Cohort Study
Authors: Müller Werner de Andrade , Mielke Grégore Iven , da Silva Inácio Crochemore M. , Silveira Mariangela F. , Domingues Marlos Rodrigues 
Published: September 2020

Background: Physical activity (PA) during pregnancy is associated with several benefits in maternal and child outcomes, and its relationship with preterm birth is still conflicting. This study aims to examine the associations between PA during pregnancy and occurrence of preterm birth. Methods: PA was assessed by questionnaire (for each trimester) and accelerometry (second trimester) in women enrolled in a birth cohort study that started during pregnancy and included births that occurred between January 1 and December 31, 2015. Gestational age was based on the last menstrual period and ultrasonography. All deliveries before 37 weeks of gestation were considered preterm births. A Poisson regression model was used to measure associations controlling for potential confounders. Results: PA information was available for 4163 women and 13.8% of births were preterm. A total of 15.8% of women were engaged in PA during pregnancy. Multivariate analysis showed that only PA performed in the third trimester of pregnancy (prevalence ratio = 0.58; 95% confidence interval, 0.36–0.96) was associated with the outcome. Conclusions: PA performed in the third trimester of pregnancy was associated with a protection to preterm birth. Pregnant women should be counseled to engage in PA to lower the risk of premature delivery.
Influence of Insulin Resistance on the Association Between Physical Activity and Heart Rate Variability: The Toon Health Study
Authors: Saito Isao , Maruyama Koutatsu , Kato Tadahiro , Takata Yasunori , Tomooka Kiyohide , Kawamura Ryoichi , Uesugi Yuichi , Naito Yoshihiko , Osawa Haruhiko , Tanigawa Takeshi 
Published: September 2020

Background: Autonomic activity is possibly influenced by physical activity (PA). However, it remains unclear whether this association is modified by insulin resistance. Methods: This population-based study between 2009 and 2012 included 2016 men and women aged 30–79 years. The PA was assessed using a validated questionnaire based on sleep, occupation, transportation, household characteristics, and leisure-time PA. Heart rate (HR) and heart rate variability (HRV) in the sitting position were determined from 5-minute recordings of pulse waves detected by a fingertip sensor. The HRV was calculated as frequency (standard deviation of normal-to-normal [NN] intervals [SDNN]), root mean square of successive differences (RMSSD), and percentage differences between normal NN intervals >50 milliseconds [pNN50]) and time domains. Insulin resistance was evaluated using the homeostasis model assessment index (HOMA-IR). Results: HR, RMSSD, and pNN50 were related to the total and moderate/vigorous PA tertiles in models that included HOMA-IR. The partial regression coefficient of total PA per 1-SD increase was .05 (P = .019) for log-transformed RMSSD and 1.86 (P = .001) for pNN50. No interactive associations were observed between PA and HOMA-IR. Conclusions: Low total PA was associated with increased HR and low levels of RMSSD and pNN50, reflecting parasympathetic modulation that was not modified by insulin resistance.
Temporal Changes in Outer Surface Proteins A and C of the Lyme Disease-Associated Spirochete,
Borrelia burgdorferi
, during the Chain of Infection in Ticks and Mice
Authors: Schwan Tom G. , Piesman Joseph 
Published: September 2020

ABSTRACT

The Lyme disease-associated spirochete,
Borrelia burgdorferi
, is maintained in enzootic cycles involving
Ixodes
ticks and small mammals. Previous studies demonstrated that
B. burgdorferi
expresses outer surface protein A (OspA) but not OspC when residing in the midgut of unfed ticks. However, after ticks feed on blood, some spirochetes stop making OspA and express OspC. Our current work examined the timing and frequency of OspA and OspC expression by
B. burgdorferi
in infected
Ixodes scapularis
nymphs as they fed on uninfected mice and in uninfected
I. scapularis
larvae and nymphs as they first acquired spirochetes from infected mice. Smears of midguts from previously infected ticks were prepared at 12- or 24-h intervals following attachment through repletion at 96 h, and spirochetes were stained for immunofluorescence for detection of antibodies to OspA and OspC. As shown previously, prior to feeding spirochetes in nymphs expressed OspA but not OspC. During nymphal feeding, however, the proportion of spirochetes expressing OspA decreased, while spirochetes expressing OspC became detectable. In fact, spirochetes rapidly began to express OspC, with the greatest proportion of spirochetes having this protein at 48 h of attachment and then with the proportion decreasing significantly by the time that the ticks had completed feeding. In vitro cultivation of the spirochete at different temperatures showed OspC to be most abundant when the spirochetes were grown at 37°C. Yet, the synthesis of this protein waned with continuous passage at this temperature. Immunofluorescence staining of spirochetes in smears of midguts from larvae and nymphs still attached or having completed feeding on infected mice demonstrated that OspA but not OspC was produced by these spirochetes recently acquired from mice. Therefore, the temporal synthesis of OspC by spirochetes only in feeding ticks that were infected prior to the blood meal suggests that this surface protein is involved in transmission from tick to mammal but not from mammal to tick.
Psychological interventions for chronic non-specific low back pain: protocol of a systematic review with network meta-analysis
Authors: Ho Emma , Ferreira Manuela , Chen Lingxiao , Simic Milena , Ashton-James Claire , Comachio Josielli , Hayden Jill , Ferreira Paulo 
Published: September 2020

IntroductionPsychological factors such as fear avoidance beliefs, depression, anxiety, catastrophic thinking and familial and social stress, have been associated with high disability levels in people with chronic low back pain (LBP). Guidelines endorse the integration of psychological interventions in the management of chronic LBP. However, uncertainty surrounds the comparative effectiveness of different psychological approaches. Network meta-analysis (NMA) allows comparison and ranking of numerous competing interventions for a given outcome of interest. Therefore, we will perform a systematic review with a NMA to determine which type of psychological intervention is most effective for adults with chronic non-specific LBP.Methods and analysisWe will search electronic databases (MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS and CINAHL) from inception until 22 August 2019 for randomised controlled trials comparing psychological interventions to any comparison interventions in adults with chronic non-specific LBP. There will be no restriction on language. The primary outcomes will include physical function and pain intensity, and secondary outcomes will include health-related quality of life, fear avoidance, intervention compliance and safety. Risk of bias will be assessed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2) tool and confidence in the evidence will be assessed using the Confidence in NMA (CINeMA) framework. We will conduct a random-effects NMA using a frequentist approach to estimate relative effects for all comparisons between treatments and rank treatments according to the mean rank and surface under the cumulative ranking curve values. All analyses will be performed in Stata.Ethics and disseminationNo ethical approval is required. The research will be published in a peer-reviewed journal.PROSPERO registration numberCRD42019138074.
Role of cumulative biological risk in mediating socioeconomic disparities in cognitive function in the elderly: a mediation analysis
Authors: Akrivos Jimmy , Zhu Carolyn Wei , Haroutunian Vahram 
Published: September 2020

ObjectivesTo evaluate whether allostatic load (AL), a measure of cumulative biological risk, fully or partially mediates observed socioeconomic status (SES) differences in cognitive function in the elderly.DesignCross-sectional mediation analysis.SettingCommunity-dwelling US elderly who participated in the National Health and Nutrition Examination Survey (NHANES).ParticipantsThe NHANES uses a complex, multistage, probability sampling design to select a nationally representative sample. Of the 4976 elderly (60 years or older) who were selected, 3234 agreed to participate in the household and medical exam interviews (65% response rate).Primary and secondary outcome measuresPerformance on the Digit Symbol Substitution Test (DSST)—a measure of cognitive function.ResultsRelative to participants with the lowest level of education or family income, participants who were college graduates (β=24.4, 95% CI 22 to 26.8, p<0.0001) or in the highest income quartile (β=17.3, 95% CI 15.2 to 19.4, p<0.0001) had the highest DSST scores and the least AL burden (β=−0.72, 95% CI −0.98 to −0.47 and β=−0.82, 95% CI −1 to −0.57; p<0.0001, respectively). Although, AL was significantly negatively associated with cognitive performance (β = −1, 95% CI −1.4 to −0.5, p<0.0001), it mediated at most 4.5% of the SES effect on DSST performance.ConclusionsThe findings suggest that AL, as measured by a summary index of parameters for cardiovascular function, metabolism and chronic inflammation, is not a significant mediator of SES-related differences in cognitive function in the elderly. Further efforts are required to elucidate the exact physiological pathways and mechanisms through which SES impacts cognitive function in late life.
Cohort profile: he East London Health and Care Partnership Data Repository: using novel integrated data to support commissioning and research
Authors: Ronaldson Amy , Chandakas Evangelos , Kang Qiongwen , Brennan Katie , Akande Aminat , Ebyarimpa Irene , Wyllie Eleanor , Howard George , Fradgley Richard , Freestone Mark , Bhui Kamaldeep 
Published: September 2020

PurposeThe East London Health and Care Partnership (ELHCP) Data Repository was established to support commissioning decisions in London. This dataset comprises routine clinical data for the general practitioner (GP)-registered populations of two London boroughs, Tower Hamlets and City and Hackney, and provides a rich source of demographic, clinical and health service use data of relevance to clinicians, commissioners, researchers and policy makers. This paper describes the dataset in its current form, its representativeness and data completeness.ParticipantsThere were 351 749 and 344 511 members of the GP-registered population in the two boroughs, respectively, for the financial year 2017/2018. Demographic information and prevalence data were available for 9 mental health and 15 physical health conditions. Prevalence rates from the cohort were compared with local and national data. In order to illustrate the health service use data available in the dataset, emergency department use across mental health conditions was described. Information about data completeness was provided.Findings to dateThe ELHCP Data Repository provides a rich source of information about a relatively young, urban, ethnically diverse, population within areas of socioeconomic deprivation. Prevalence data were in line with local and national statistics with some exceptions. Physical health conditions were more common in those with mental health conditions, reflecting that comorbidities are the norm rather than the exception. This has implications for integrated care. Data completeness for risk factors (eg, blood pressure, cholesterol) was high in patients with long-term conditions.Future plansThe data are being further cleaned and evaluated using imputation, Bayesian and economic methods, principally focusing on specific cohorts, including type II diabetes, depression and personality disorder. Data continue to be collected for the foreseeable future to support commissioning decisions, which will also enable more long-term prospective analysis as data become available at the end of each financial year.
Permeability of the blood-brain barrier through the phases of ischaemic stroke and relation with clinical outcome: protocol for a systematic review
Authors: Bernardo-Castro Sara , Donato Helena , Ferreira Lino , Sargento-Freitas João 
Published: September 2020

IntroductionIschaemic stroke is the most prevalent type of stroke and is characterised by a myriad of pathological events triggered by a vascular arterial occlusion. Disruption of the blood-brain barrier (BBB) is a key pathological event that may lead to fatal outcomes. However, it seems to follow a multiphasic pattern that has been associated with distinct biological substrates and possibly contrasting outcomes. Addressing the BBB permeability (BBBP) along the different phases of stroke through imaging techniques could lead to a better understanding of the disease, improved patient selection for specific treatments and development of new therapeutic modalities and delivery methods. This systematic review will aim to comprehensively summarise the existing evidence regarding the evolution of the BBBP values during the different phases of an acute ischaemic stroke and correlate this event with the clinical outcome of the patient.Methods and analysisWe will conduct a computerised search on Medline, EMBASE, Cochrane Central Register of Controlled Trials, Scopus and Web of Science. In addition, grey literature and ClinicalTrials.gov will be scanned. We will include randomised controlled trials, cohort, cross-sectional and case-controlled studies on humans that quantitatively assess the BBBP in stroke. Retrieved studies will be independently reviewed by two authors and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias of the selected studies. If possible, data will be combined in a quantitative meta-analysis following the guidelines provided by Cochrane Handbook for Systematic Reviews of Interventions. We will assess cumulative evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach.Ethics and disseminationEthical approval is not needed. All data used for this work are publicly available. The result obtained from this work will be published in a peer-reviewed journal and disseminated in relevant conferences.PROSPERO registration numberCRD42019147314.
Determinants of neonatal jaundice among neonates admitted to five referral hospitals in Amhara region, Northern Ethiopia: an unmatched case-control study
Authors: Bizuneh Asmamaw Demis , Alemnew Birhan , Getie Addisu , Wondmieneh Adam , Gedefaw Getnet 
Published: September 2020

BackgroundNeonatal jaundice is associated with a significant risk of neonatal morbidity and mortality. It is a major cause of hospital neonatal intensive care unit admission and readmissions during the neonatal period. Hence, the study aimed to identify the determinant factors of neonatal jaundice among neonates admitted at five referral hospitals in Amhara region, Northern Ethiopia.MethodA hospital-based unmatched case-control study design was employed, on 447 neonates (149 cases and 298 controls) at referral hospitals in Amhara region, Northern Ethiopia, from 1 March to 30 July 2019. Consecutive sampling method was used to select both the cases and controls. The collected data were entered into Epi data V.4.2 and then exported into SPSS window V.24 for analysis. Bivariable and multivariable analysis were carried out by using binary logistic regression. A p value of <0.05 was considered as significant difference between cases and controls for the exposure variable of interest.ResultsThe median (±IQR) age of neonate at the time of admission and gestational age were 3±2 days and 38 (±3) weeks, respectively. Prolonged duration of labour (adjusted OR (AOR)=2.45, 95% CI 1.34 to 4.47), being male sex (AOR=3.54, 95% CI 1.99 to 6.29), low birth weight (AOR=5.06, 95% CI 2.61 to 9.82), birth asphyxia (AOR=2.88, 95% CI 1.38 to 5.99), sepsis (AOR=2.49, 95% CI 1.22 to 5.11) and hypothermia (AOR=2.88, 95% CI 2.63 to 14.02) were the determinant factors for neonatal jaundice.ConclusionsProlonged duration of labour, hypothermia, sepsis, birth asphyxia, low birth weight and sex of neonate were independent determinants of neonatal jaundice. Early recognition and management of identified modifiable determinants are the recommended interventions.
CD122-Selective IL2 Complexes Reduce Immunosuppression, Promote Treg Fragility, and Sensitize Tumor Response to PD-L1 Blockade
Authors: Drerup Justin M. , Deng Yilun , Pandeswara Sri Lakshmi , Padrón Álvaro S. , Reyes Ryan M. , Zhang Xinyue , Mendez Jenny , Liu Aijie , Clark Curtis A. , Chen Wanjiao , Conejo-Garcia José R. , Hurez Vincent , Gupta Harshita , Curiel Tyler J. 
Published: September 2020

AbstractThe IL2 receptor (IL2R) is an attractive cancer immunotherapy target that controls immunosuppressive T regulatory cells (Treg) and antitumor T cells. Here we used IL2Rβ-selective IL2/anti-IL2 complexes (IL2c) to stimulate effector T cells preferentially in the orthotopic mouse ID8agg ovarian cancer model. Despite strong tumor rejection, IL2c unexpectedly lowered the tumor microenvironmental CD8+/Treg ratio. IL2c reduced tumor microenvironmental Treg suppression and induced a fragile Treg phenotype, helping explain improved efficacy despite numerically increased Tregs without affecting Treg in draining lymph nodes. IL2c also reduced Treg-mediated, high-affinity IL2R signaling needed for optimal Treg functions, a likely mechanism for reduced Treg suppression. Effector T-cell IL2R signaling was simultaneously improved, suggesting that IL2c inhibits Treg functions without hindering effector T cells, a limitation of most Treg depletion agents. Anti-PD-L1 antibody did not treat ID8agg, but adding IL2c generated complete tumor regressions and protective immune memory not achieved by either monotherapy. Similar anti-PD-L1 augmentation of IL2c and degradation of Treg functions were seen in subcutaneous B16 melanoma. Thus, IL2c is a multifunctional immunotherapy agent that stimulates immunity, reduces immunosuppression in a site-specific manner, and combines with other immunotherapies to treat distinct tumors in distinct anatomic compartments.Significance:These findings present CD122-targeted IL2 complexes as an advancement in cancer immunotherapy, as they reduce Treg immunosuppression, improve anticancer immunity, and boost PD-L1 immune checkpoint blockade efficacy in distinct tumors and anatomic locations.
Osimertinib, an Irreversible Next-Generation EGFR Tyrosine Kinase Inhibitor, Exerts Antitumor Activity in Various Preclinical NSCLC Models Harboring the Uncommon EGFR Mutations G719X or L861Q or S768I
Authors: Floc'h Nicolas , Lim Sangbin , Bickerton Sue , Ahmed Afshan , Orme Jonathan , Urosevic Jelena , Martin Matthew J. , Cross Darren A.E. , Cho Byoung Chul , Smith Paul D. 
Published: September 2020

Abstract

Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI–sensitizing and EGFR T790M–resistance mutations with lower activity against wild-type EGFR and has demonstrated efficacy in non–small cell lung cancer (NSCLC) CNS metastases. The sensitizing mutations, the in-frame deletions in exon 19 and the L858R point mutation in exon 21, represent between 80% and 90% of all EGFR mutations. The remaining 10% to 20% are referred to as uncommon activating mutations and are a diverse group of mutations in exons 18 to 21 within the kinase domain of the EGFR gene. Excluding those found as insertion mutations in exon 20, the uncommon mutations involving codons G719, S768, and L861 are the most prevalent.

Although the efficacy of EGFR-TKIs for the common EGFR mutations is well established, much less is known about rare EGFR mutations, such as exon 20 insertions, G719X, L861Q, S768I, as most of the data consist of single case reports or small case series.

Using available patient-derived xenografts (PDX) and cell lines derived from two of these PDXs that harbor the G719X mutation, we have evaluated in vitro and in vivo the preclinical activity of osimertinib. We report osimertinib inhibits signaling pathways and cellular growth in G719X-mutant cell lines in vitro and demonstrate sustained tumor growth inhibition of PDX harboring the G719X mutation alone or in combination with L861Q and S768I.

Together, these data support clinical testing of osimertinib in patients with uncommon EGFR NSCLC.
Cancer Immunoprevention: Challenges and Potential Opportunities for Use of Immune Checkpoint Inhibitors
Authors: Mohammed Altaf , Shoemaker Robert H. , Sei Shizuko 
Published: September 2020

Abstract
Cancer immunoprevention is achieved through promoting antitumor immune surveillance to block tumor formation and progression. Following the success of prophylactic vaccines against human papillomavirus (HPV) in preventing HPV-associated cancer, immunopreventive cancer vaccines targeting tumor antigens have been increasingly evaluated against cancers of noninfectious origin. While advances in cancer immunotherapy with immune checkpoint inhibitors (ICI) have clearly shown that the host immune system can mount effective antitumor immunity against tumor antigens when immune checkpoints are optimally blocked, the use of ICIs in the prevention setting has not been widely explored because of concerns of ICI-associated adverse events. In this issue of Cancer Prevention Research, Chung and colleagues demonstrate that the human cirrhotic liver harbors neoantigens, which accumulate further as the disease progresses to hepatocellular carcinoma (HCC), suggesting that cirrhotic liver may be susceptible to ICI therapy. Utilizing an established mouse model of carcinogen-induced liver fibrosis and HCC, they show that intermittent intervention by ICI, anti-mouse PD-1 (CD279) antibody, can prevent the progression of the precancerous stage of cirrhosis to HCC accompanied by increased T-cell infiltrates in the liver parenchyma. Importantly, there were no overt ICI-associated toxicities in the treated mice, indicating that safe dosing regimens could be established. This work is both significant and timely, opening the door to future studies, where the utility of ICI therapy can be further investigated not only in cirrhosis but other high-risk precancerous conditions. In this perspective, we discuss the implications of their findings, and the challenges and potential opportunities for use of ICIs for cancer immunoprevention.
See related article by Chung et al., p. 911
Automatic recognition of the digital modulation types using the artificial neural networks
Authors: Hreshee Saad S. 
Published: September 2020

As digital communication technologies continue to grow and evolve, applications for this steady development are also growing. This growth has generated a growing need to look for automated methods for recognizing and classifying the digital modulation type used in the communication system, which has an important effect on many civil and military applications. This paper suggests a recognizing system capable of classifying multiple and different types of digital modulation methods (64QAM, 2PSK, 4PSK, 8PSK, 4ASK, 2FSK, 4FSK, 8FSK). This paper focuses on trying to recognize the type of digital modulation using the artificial neural network (ANN) with its complex algorithm to boost the performance and increase the noise immunity of the system.
This system succeeded in recognizing all the digital modulation types under the current study without any prior information. The proposed system used 8 signal features that were used to classify these 8 modulation methods. The system succeeded in achieving a recognition ratio of at least 68% for experimental signals on a signal to noise ratio (SNR = 5dB) and 89.1% for experimental signals at (SNR = 10dB) and 91% for experimental signals at (SNR = 15dB) for a channel with Additive White Gaussian Noise (AWGN).