bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-methylation analysis in lung tissue identifies pathways for fetal origins of COPD
Authors: Kachroo Priyadarshini , Morrow Jarrett D. , Kho Alvin T. , Vyhlidal Carrie A. , Silverman Edwin K. , Weiss Scott T. , Tantisira Kelan G. , DeMeo Dawn L. 
Published: June 2020

COPD likely has developmental origins; however, the underlying molecular mechanisms are not fully identified. Investigation of lung tissue-specific epigenetic modifications such as DNA methylation using network approaches might facilitate insights linkingin uterosmoke (IUS) exposure and risk for COPD in adulthood.We performed genome-wide methylation profiling for adult lung DNA from 160 surgical samples and 78 fetal lung DNA samples isolated from discarded tissue at 8–18 weeks of gestation. Co-methylation networks were constructed to identify preserved modules that shared methylation patterns in fetal and adult lung tissues and associations with fetal IUS exposure, gestational age and COPD.Weighted correlation networks highlighted preserved and co-methylated modules for both fetal and adult lung data associated with fetal IUS exposure, COPD and lower adult lung function. These modules were significantly enriched for genes involved in embryonic organ development and specific inflammation-related pathways, including Hippo, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), Wnt, mitogen-activated protein kinase and transforming growth factor-β signalling. Gestational age-associated modules were remarkably preserved for COPD and lung function, and were also annotated to genes enriched for the Wnt and PI3K/AKT pathways.Epigenetic network perturbations in fetal lung tissue exposed to IUS and of early lung development recapitulated in adult lung tissue from ex-smokers with COPD. Overlapping fetal and adult lung tissue network modules highlighted putative disease pathways supportive of exposure-related and age-associated developmental origins of COPD.
Measures of lung function and their relationship with advanced glycation end-products
Authors: Zaigham Suneela , Persson Margaretha , Jujic Amra , Frantz Sophia , Borné Yan , Malinovschi Andrei , Wollmer Per , Engström Gunnar 
Published: June 2020

BackgroundAdvanced glycation end-products (AGEs) have been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). However, the association between AGE accumulation in the skin measured by skin autofluorescence (SAF) and lung function in healthy subjects has not been explored in detail. We use a population-based study of 50–64-year-olds to assess spirometry, diffusing capacity of the lung for carbon monoxide (DLCO) and impulse oscillometry (IOS) in relation to SAF.MethodsParticipants with information on SAF, lung function and potential confounding variables were included from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) cohort (spirometry, n=4111;DLCO, n=3889; IOS, n=3970). Linear regression was used to assess changes in lung function (as measured by spirometry (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC),DLCOand IOS (resistance measured at 5 (R5) and 20 Hz (R20),R5−R20, area of reactance, reactance measured at 5 Hz (X­5), and resonant frequency)) by a 1-sdincrease in SAF.ResultsFEV1, FVC andDLCOwere significantly and inversely associated with SAF after adjustment for potential confounding factors (per 1-sdincrease in SAF: FEV1−0.03 L (95% CI −0.04– −0.02 L), p<0.001; FVC −0.03 L (95% CI −0.05– −0.02 L), p<0.001;DLCO−0.07 mmol·min−1·kPa−1(95% CI −0.11– −0.03 mmol·min−1·kPa−1), p<0.001). This association was also found in nonsmokers and in non-COPD subjects. Pulmonary reactance (X5) but not pulmonary resistance (R5,R20andR5−R20) was significantly associated with SAF (per 1-sdincrease in SAF:X5−0.001 kPa·L−1·s (95% CI −0.003–0.00 kPa·L−1·s), p=0.042), which was mirrored in non-COPD patients but not in current nonsmokers.ConclusionsAGE accumulation, as measured by SAF, is significantly associated with lung function decrements indicative of changes in the lung parenchyma
Disequilibrium evolution of the Fructose-1,6-bisphosphatase gene family leads to their functional biodiversity in Gossypium species
Authors: Gě Qún , Cūi Yànli , Lǐ Jùnwén , Gōng Jǔwǔ , Lú Quánwěi , Lǐ Péngtāo , Shí Yùzhēn , Shāng Hǎihóng , Liú Àiyīng , Dèng Xiǎoyīng , Pān Jìngtāo , Chén Qúanjiā , Yuán Yǒulù , Gǒng Wànkuí 
Published: June 2020

Abstract
Background
Fructose-1,6-bisphosphatase (FBP) is a key enzyme in the plant sucrose synthesis pathway, in the Calvin cycle, and plays an important role in photosynthesis regulation in green plants. However, no systemic analysis of FBPs has been reported in Gossypium species.

Results
A total of 41 FBP genes from four Gossypium species were identified and analyzed. These FBP genes were sorted into two groups and seven subgroups. Results revealed that FBP family genes were under purifying selection pressure that rendered FBP family members as being conserved evolutionarily, and there was no tandem or fragmental DNA duplication in FBP family genes. Collinearity analysis revealed that a FBP gene was located in a translocated DNA fragment and the whole FBP gene family was under disequilibrium evolution that led to a faster evolutionary progress of the members in G. barbadense and in At subgenome than those in other Gossypium species and in the Dt subgenome, respectively, in this study. Through RNA-seq analyses and qRT-PCR verification, different FBP genes had diversified biological functions in cotton fiber development (two genes in 0 DPA and 1DPA ovules and four genes in 20–25 DPA fibers), in plant responses to Verticillium wilt onset (two genes) and to salt stress (eight genes).

Conclusion
The FBP gene family displayed a disequilibrium evolution pattern in Gossypium species, which led to diversified functions affecting not only fiber development, but also responses to Verticillium wilt and salt stress. All of these findings provide the foundation for further study of the function of FBP genes in cotton fiber development and in environmental adaptability.
Using the axillary reverse mapping technique to screen breast cancer patients with a high risk of lymphedema
Authors: Liu Siyao , Wang Nan , Gao Ping , Liu Peng , Yang Houpu , Xie Fei , Wang Siyuan , Liu Miao , Wang Shu 
Published: June 2020

AbstractBackgroundPreventing breast cancer-related lymphedema (BCRL) by preserving upper lymphatic drainage is still controversial. Our study aimed to use the axillary reverse mapping (ARM) technique in patients who underwent axillary surgery to analyse the correlation between postoperative residual ARM nodes and the occurrence of lymphedema, select candidates at high risk of developing lymphedema, and analyse the oncologic safety of ARM nodes.MethodsPatients undergoing sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) from October 2015 to February 2016 at the Peking University People’s Hospital Breast Center were prospectively recruited for the study. ARM was performed in all patients before surgery. ARM nodes were separated from SLNB and ALND specimens. Data were collected on the identification of ARM nodes before surgery, number of residual ARM nodes after surgery, nodal status, crossover rate, and correlation between residual ARM nodes and the occurrence of lymphedema.ResultsThe analysis included 78 patients. Of the 53 patients who underwent SLNB, crossover between ARM nodes and breast sentinel lymph nodes (SLNs) was seen in 22 specimens. The incidence of ARM node metastasis was 1.89% (1/53) and 25% (9/36) in the SLNB and ALND groups, respectively. The number of positive axillary lymph nodes was associated with the involvement of ARM nodes (P= 0.036). The incidence of residual ARM nodes was significantly higher in the SLNB group than in the ALND group (67.6% vs. 37.9%,P= 0.016). The incidence of lymphedema was significantly higher in the ALND group than in the SLNB group (33.3% vs. 5.4%,P= 0.003).ConclusionsFor SLNB, the ARM technique can help to resect SLNs more accurately. However, we do not recommend using the ARM technique to preserve ARM nodes in patients undergoing ALND due to oncologic safety issues. Nevertheless, we can predict patients undergoing axillary surgery who are more likely to have a high risk of lymphedema by assessing residual ARM nodes.Trial registrationThis study was registered onClinicalTrials.govin February 2016.The clinical trial registration number isNCT02691624.
Geographical variations of early age sexual initiation among reproductive-age women in Ethiopia: evidence from EDHS 2016
Authors: Nigatu Araya Mesfin , Birhanu Abraham Yeneneh , Endehabtu Berhanu Fikadie 
Published: June 2020

Abstract
Background
The early age of sexual initiation contribute a lot for various risks such as mistimed pregnancy followed by insecure termination, developing fistula and contracting sexually transmitted infections which are currently the major public health concerns for low-income countries. Therefore, the purpose of this study was to detect spatial clusters and identify factors associated with an early age sexual initiation of women in the reproductive age group.

Methods
We used a population-based nationwide representative Ethiopian Demographic and Health Survey (EDHS) 2016 data.. A total of 12,033 respondents of reproductive age (15–49 years) women who had at least one event of sexual intercourse was retrieved and included for the analysis. Spatial cluster detection and autocorrelation analysis were also done to explore the patterns of early age sexual initiation.

Results
The median age at first sexual intercourse among respondents was 16 (±3.3) years and more than half (66.2%) had their first sexual intercourse before the age of 18 years. The spatial variations of the age of sexual initiation was nonrandom and clustered with a Moran’s I = 0.413 (P-value < 0.001). In addition, five significant spatial clusters were also identified. Moreover, the probability of starting sex at an earlier age was associated with the respondent’s residence, marital status, educational attainment and wealth index.

Conclusion
This study found a higher proportion of an early age sexual initiation of women. Respondent’s residence, marital status, educational attainment and wealth index were significantly associated with early sexual initiation. The SaTScan analysis identified five statistical significant spatial clusters which indicate that there were geographical variations. Therefore, integrated interventions focusing on the identified high spot clustered areas are recommended to reduce early age sexual initiation.
Comparison of the protective effects of resveratrol and pterostilbene against intestinal damage and redox imbalance in weanling piglets
Authors: Zhang Hao , Chen Yanan , Chen Yueping , Ji Shuli , Jia Peilu , Li Yue , Wang Tian 
Published: June 2020

Abstract
Background
Evidence indicates that early weaning predisposes piglets to intestinal oxidative stress and increases the risk of intestinal dysfunction; however, there are minimal satisfactory treatment strategies for these conditions. This study investigated the potential of resveratrol and its analog, pterostilbene, as antioxidant protectants for regulating intestinal morphology, barrier function, and redox status among weanling piglets.

Methods
A total of 144 piglets were selected at 21 days of age and randomly allocated into one of four treatment groups, each of which included six replicates. Piglets in a sow-reared control group were suckling normally between ages 21 and 28 days, while those in weaned groups were fed a basal diet, supplemented with either 300 mg/kg of resveratrol or with 300 mg/kg of pterostilbene. Parameters associated with intestinal injury and redox status were analyzed at the end of the feeding trial.

Results
Early weaning disrupted the intestinal function of young piglets, with evidence of increased diamine oxidase activity and D-lactate content in the plasma, shorter villi, an imbalance between cell proliferation and apoptosis, an impaired antioxidant defense system, and severe oxidative damage in the jejunum relative to suckling piglets. Feeding piglets with a resveratrol-supplemented diet partially increased villus height (P = 0.056) and tended to diminish apoptotic cell numbers (P = 0.084) in the jejunum compared with those fed a basal diet. Similarly, these beneficial effects were observed in the pterostilbene-fed piglets. Pterostilbene improved the feed efficiency of weanling piglets between the ages of 21 and 28 days; it also resulted in diminished plasma diamine oxidase activity and D-lactate content relative to untreated weaned piglets (P < 0.05). Notably, pterostilbene restored jejunal antioxidant capacity, an effect that was nearly absent in the resveratrol-fed piglets. Pterostilbene reduced the malondialdehyde and 8-hydroxy-2´-deoxyguanosine contents of jejunal mucosa possibly through its regulatory role in facilitating the nuclear translocation of nuclear factor erythroid-2-related factor 2 and the expression levels of NAD(P)H quinone dehydrogenase 1 and superoxide dismutase 2 (P < 0.05).

Conclusions
The results indicate that pterostilbene may be more effective than its parent compound in alleviating early weaning-induced intestinal damage and redox imbalance among young piglets.
Study of a hysteresis window of FinFET and fully-depleted silicon-on-insulator (FDSOI) MOSFET with ferroelectric capacitor
Authors: Yoon Chankeun , Moon Seungjun , Shin Changhwan 
Published: June 2020

AbstractIn this work, the measured electrical characteristics of a fully depleted silicon-on-insulator (FDSOI) device and fin-shaped field-effect transistor (FinFET), whose gate electrode is connected in series to the bottom electrode of a ferroelectric capacitor (FE-FDSOI/FE-FinFET), are experimentally studied. The hysteretic property in input transfer characteristic of those devices is desirable for memory device applications, so that the understanding and modulating the hysteresis window is a key knob in designing the devices. It is experimentally observed that the hysteresis window of FE-FDSOI/FE-FinFET is decreased with (i) increasing the area of the ferroelectric capacitor and/or (ii) decreasing the gate area of baseline FET. The way how to control the hysteresis window of FE-FDSOI/FE-FinFET is proposed and discussed in detail.
Morphological changes in intraretinal microvascular abnormalities after anti-VEGF therapy visualized on optical coherence tomography angiography
Authors: Sorour Osama A. , Mehta Nihaal , Baumal Caroline R. , Ishibazawa Akihiro , Liu Keke , Konstantinou Eleni K. , Martin Sarah , Braun Phillip , Alibhai A. Yasin , Arya Malvika , Witkin Andre J. , Duker Jay S. , Waheed Nadia K. 
Published: June 2020

Abstract
Background
To examine the baseline morphological characteristics and alterations in intraretinal microvascular abnormalities (IRMAs) in response to anti-vascular endothelial growth factor (anti-VEGF) treatment, documented by optical coherence tomography angiography (OCTA) in diabetic eyes.

Methods
In this retrospective study, IRMAs were evaluated with multimodal imaging (fundus photography, fluorescein angiography, OCTA) in treatment-naïve diabetic eyes before and after anti-VEGF treatment for diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR) and compared to diabetic control eyes with similar diabetic retinopathy (DR) severity that did not receive anti-VEGF therapy. The morphological characteristics of IRMAs on enface OCTA imaging were graded by masked readers at baseline, then after anti-VEGF therapy in treated eyes or after observation in control eyes. Characterization of interval changes in an IRMA were based on the following parameters: branching, vessel caliber and area of adjacent capillary non-perfusion.

Results
The treated group included 45 IRMA foci from 15 eyes of 11 patients, while the control group included 27 IRMA foci from 15 eyes of 14 patients. Following anti-VEGF treatment, enface OCTA demonstrated that 14 foci of IRMA (31%) demonstrated regression with normalization of appearance of the capillary bed, 20 IRMAs (44%) remained unchanged, six IRMAs (13%) progressed with enlargement or development of new IRMAs and five IRMAs (11%) demonstrated complete obliteration defined as IRMA disappearance with advancing capillary drop-out. In the control group, 17 IRMA (63%) remained stable, 8 IRMAs (29.6%) progressed and 2 experienced total obliteration (7.4%). The difference in rank order between the two groups was statistically significant (p = 0.022).

Conclusions
In eyes with DR status post anti-VEGF therapy, foci of IRMAs have a variable course demonstrating one of four possible outcomes: regression, stability, progression or complete obliteration. In contrast, none of the untreated control diabetic eyes demonstrated regression of IRMAs, consistent with known progression of DR severity in high risk eyes. Morphologic evaluation of IRMAs with OCTA may help to monitor changes in retinal blood flow as well as the response to anti-VEGF treatment.
Improvement of a delayed swallowing reflex following treatment for advanced head and neck cancer
Authors: Ohkoshi Akira , Kato Kengo , Ogawa Takenori , Nakanome Ayako , Ishii Ryo , Katori Yukio 
Published: June 2020

Abstract
Background
The latency of the swallowing reflex is an important factor causing dysphagia in head and neck cancer patients. Although there are many reports comparing voluntary swallowing function before and after treatment, few studies have focused on the latency of the swallowing reflex, which is a risk factor for pneumonia due to silent aspiration. The aim of this retrospective study was to clarify the changes in the latency of the swallowing reflex before and after treatment.

Methods
The latency of the swallowing reflex was quantified using the time from the injection of 1 ml of distilled water into the pharynx through a nasal catheter to the onset of swallowing.

Results
The latency time of the swallowing reflex was significantly decreased 3 months after treatment compared to before treatment. A significant reduction was also observed in patients with pharyngeal cancer who underwent chemoradiation therapy.

Conclusions
This retrospective study showed that a delayed swallowing reflex improved with treatment in advanced head and neck cancer patients.

Trial registration
The Institutional Review Board of Tohoku University Hospital (Number 2014–1-274).
The role of integrated mental and community physical healthcare trusts in responding to the COVID-19 pandemic in the UK
Authors: Tracy Derek , Forrest Anna , Underwood Benjamin R. 
Published: June 2020

SummaryFor several decades, mental health services within the UK's National Health Service were provided by specialist mental health trusts. More recently many of these trusts have integrated community physical health services into their operations. We describe here how two integrated mental health trusts in England were able to make an enhanced response to the COVID-19 pandemic.
The social psychological impact of the COVID-19 pandemic on medical staff in China: A cross-sectional study
Authors: Dong Zai-Quan , Ma Jing , Hao Yan-Ni , Shen Xiao-Ling , Liu Fang , Gao Yuan , Zhang Lan 
Published: June 2020

Abstract

Background.
The COVID-19 outbreak required the significantly increased working time and intensity for health professionals in China, which may cause stress signs.

Methods.
From March 2–13 of 2020, 4,618 health professionals in China were included in an anonymous, self-rated online survey regarding their concerns on exposure to the COVID-19 outbreak. The questionnaires consisted of five parts: basic demographic information and epidemiological exposure; occupational and psychological impact; concerns during the episode; coping strategies; and the Huaxi Emotional-Distress Index (HEI).

Results.
About 24.2% of respondents experienced high levels of anxiety or/and depressive symptoms since the COVID-19 outbreak. Respondents who worried about their physical health and those who had COVID-19 infected friends or close relatives were more likely to have high HEI levels, than those without these characteristics. Further, family relationship was found to have an independent protective effect against high HEI levels. Their main concerns were that their families would not be cared for and that they would not be able to work properly. Compared to respondents with clear emotional problems, those with somewhat hidden emotional issues adopted more positive coping measures.

Conclusions.
About a quarter of medical staff experienced psychological problems during the pandemic of COVID-19. The psychological impact of stressful events was related to worrying about their physical health, having close COVID-19 infected acquaintances and family relationship issues. Therefore, the psychological supprot for medical staff fighting in the COVID-19 pandemic may be needed.
Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 Study.
Authors: Andre Thierry , Shiu Kai-Keen , Kim Tae Won , Jensen Benny Vittrup , Jensen Lars Henrik , Punt Cornelis J. A. , Smith Denis Michel , Garcia-Carbonero Rocio , Benavides Manuel , Gibbs Peter , De La Fouchardiere Christelle , Rivera Fernando , Elez Elena , Bendell Johanna C. , Le Dung T. , Yoshino Takayuki , Yang Ping , Farooqui Mohammed Zulfiqar Husain , Marinello Patricia , Diaz Luis A. 
Published: June 2020

LBA4 Background: KEYNOTE-177 (NCT02563002) is a phase 3, randomized open-label study evaluating the efficacy and safety of pembrolizumab (pembro) versus standard of care chemotherapy ± bevacizumab or cetuximab (chemo) as first-line therapy for patients (pts) with microsatellite-instability high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). We present results of the final PFS analysis. Methods: A total of 307 pts with MSI-H/dMMR mCRC as determined locally and ECOG PS 0 or 1 were randomly assigned 1:1 to first-line pembro 200 mg Q3W for up to 2 years or investigator’s choice of mFOLFOX6 or FOLFIRI Q2W ± bevacizumab or cetuximab (chemo chosen prior to randomization). Treatment continued until PD, unacceptable toxicity, pt/investigator decision to withdraw, or completion of 35 cycles (pembro only). Patients receiving chemo could crossover to pembro for up to 35 cycles after confirmed PD. Primary end points were PFS (RECIST v1.1, central review) and OS. Key secondary end points included ORR (RECIST v1.1, central review), and safety. The data cutoff date for this interim analysis was Feb 19, 2020. The study will continue without changes to evaluate OS. Results: At data cutoff, 153 pts were randomized to pembro and 154 to chemo. Median (range) study follow-up was 28.4 mo (0.2-48.3) with pembro vs 27.2 mo (0.8-46.6) with chemo. Pembro was superior to chemo for PFS (median 16.5 mo vs 8.2 mo; HR 0.60; 95% CI, 0.45-0.80; P=0.0002). The 12- and 24-mo PFS rates were 55.3% and 48.3% with pembro vs 37.3% and 18.6% with chemo. Confirmed ORR was 43.8% vs 33.1%; median (range) duration of response was not reached (2.3+ to 41.4+) with pembro vs 10.6 mo (2.8 to 37.5+) with chemo. Grade 3-5 treatment related adverse event (AE) rates were 22% vs 66% for pembro vs chemo. One pt in the chemo arm died due to a treatment-related AE. Conclusions: Pembro provided a clinically meaningful and statistically significant improvement in PFS versus chemo as first-line therapy for pts with MSI-H/dMMR mCRC, with fewer treatment-related AEs observed and should be the new standard of care for these pts. Clinical trial information: NCT02563002 .