bluuebunny/crossref_metadata_2025 huggingface dataset:
Fundamentals and contributions to validation of constructive computational methodologies: a focused survey
Authors: Li Yongzhe , Horváth Imre
Published: August 2019

Computational mechanisms (complex structures of functionally connected algorithms) are developed very frequently by both the academia and the industry for specific applications, but the transferability to other applications is seldom addressed and systematically tested. This raises the need for application validity of constructive computational methodologies (CCMs). First, this background research paper clarifies the fundamental concepts related to application validation. Applicability validation focusses on the indicators of appropriateness with regards to a particular purpose. Then, it surveys the various approaches of application validation based on the publications available in contemporary literature. Its main finding is that applicability validation of CCMs seems to be a stepchild of academic research. The same applies to the industrial exploration of the applicability of CCMs tailored to a narrow family of applications to a wider range of applications.
Intelligent Savings Equipment Design Based on Urban and Rual Empty Nest Elderly
Authors: Su Lin , Qi Na , Wei Xiaoying
Published: August 2019

China’s aging population and large base, which brings a lot of social problems. They have unique psychological and physical characteristics, which make them lonely in a social corner. They are the predecessors who have contributed their youth and wisdom to the construction of a better country. Therefore, we should extend our most sincere thanks and do our best to create a comfortable environment for them. What needs to be studied in this paper is the urban and rural empty nester who need more attention. They are a group separated from the intelligent age. In the Intelligent era, they have to use smart Banks. Therefore, it is particularly important to design a savings device that is more suitable for urban and rural empty nester. This is a qualitative research to design an intelligent savings device for urban and rural empty nester.
Spatiotemporal phase-shifting method for accurate phase analysis of fringe pattern
Authors: Ri Shien , Wang Qinghua , Xia Peng , Tsuda Hiroshi
Published: August 2019

High accurate phase analysis of waveforms as fringe patterns is essential for a wide range of scientific and engineering disciplines. However, precise phase analysis under extremely low signal-to-noise conditions is a challenging task for conventional phase-shifting methods. Here, a novel accurate phase recovering technique, called the spatiotemporal phase-shifting method (ST-PSM), is developed to measure the phase information robustly by utilizing two-dimensional intensity data in spatial- and temporal-domains simultaneously. Our simulation results indicated that ST-PSM had strong tolerance to random noise, and a self-neutralizing function to eliminate the periodical phase error due to the nonlinearity of detector, intensity saturation, vibration or phase-shifting error. The effectiveness was demonstrated experimentally from a non-contact shape measurement in fringe projection profilometry under extreme underexposure and overexposure recording conditions. Furthermore, by incorporating modern GPU parallel computing technology, a 4-step phase-shifted fringe pattern with 8 K image size can be calculated within one second. Due to its robustness and high accuracy with a fast calculation, therefore, we believe this technique has a significant impact on a variety of research and scientific fields.
Trees in cool climate cities may increase atmospheric carbon by altering building energy use
Authors: Erker Tedward , Townsend Philip A
Published: August 2019

Urban trees are a critical part of the ‘green infrastructure’ intended to make our growing cities more sustainable in an era of climate change. The potential for urban trees to modify microclimates and thereby reduce building energy use and the associated carbon emissions is a commonly cited ecosystem service used to justify million tree planting campaigns across the US. However, what we know of this ecosystem service comes primarily from unvalidated simulation studies. Using the first dataset of actual heating and cooling energy use combined with tree cover data, we show that contrary to the predictions of the most commonly used simulations, trees in a cool climate city increase carbon emissions from residential building energy use. This is driven primarily by near east (<20 m from building) tree cover. Further analysis of urban areas in the US shows that this is likely the case in cool climates throughout the country, encompassing approximately 39% of the US population and 62% of its area (56%, excluding Alaska). This work adds geographic nuance to our understanding of how urban shade trees affect the carbon budget, and it could have major implications for tree planting programs in cool climates.
ECHO: an application for detection and analysis of oscillators identifies metabolic regulation on genome-wide circadian output
Authors: De los Santos Hannah , Collins Emily J , Mann Catherine , Sagan April W , Jankowski Meaghan S , Bennett Kristin P , Hurley Jennifer M
Published: August 2019

Motivation

Time courses utilizing genome scale data are a common approach to identifying the biological pathways that are controlled by the circadian clock, an important regulator of organismal fitness. However, the methods used to detect circadian oscillations in these datasets are not able to accommodate changes in the amplitude of the oscillations over time, leading to an underestimation of the impact of the clock on biological systems.

Results

We have created a program to efficaciously identify oscillations in large-scale datasets, called the Extended Circadian Harmonic Oscillator application, or ECHO. ECHO utilizes an extended solution of the fixed amplitude oscillator that incorporates the amplitude change coefficient. Employing synthetic datasets, we determined that ECHO outperforms existing methods in detecting rhythms with decreasing oscillation amplitudes and in recovering phase shift. Rhythms with changing amplitudes identified from published biological datasets revealed distinct functions from those oscillations that were harmonic, suggesting purposeful biologic regulation to create this subtype of circadian rhythms.

Availability and implementation

ECHO’s full interface is available at https://github.com/delosh653/ECHO. An R package for this functionality, echo.find, can be downloaded at https://CRAN.R-project.org/package=echo.find.

Supplementary information

Supplementary data are available at Bioinformatics online.
Interdependent Neural Correlates of Reward and Punishment Sensitivity During Rewarded Action and Inhibition of Action
Authors: Le Thang M , Wang Wuyi , Zhornitsky Simon , Dhingra Isha , Zhang Sheng , Li Chiang-Shan R
Published: August 2019

Imaging studies have distinguished the brain correlates of approach and avoidance behaviors and suggested the influence of individual differences in trait sensitivity to reward (SR) and punishment (SP) on these neural processes. Theoretical work of reinforcement sensitivity postulates that SR and SP may interdependently regulate behavior. Here, we examined the distinct and interrelated neural substrates underlying rewarded action versus inhibition of action in relation to SR and SP as evaluated by the Sensitivity to Punishment and Sensitivity to Reward Questionnaire. Forty-nine healthy adults performed a reward go/no-go task with approximately 2/3 go and 1/3 no-go trials. Correct go and no-go responses were rewarded and incorrect responses were penalized. The results showed that SR and SP modulated rewarded go and no-go, respectively, both by recruiting the rostral anterior cingulate cortex and left middle frontal gyrus (rACC/left MFG). Importantly, SR and SP influenced these regional activations in opposite directions, thus exhibiting an antagonistic relationship as suggested by the reinforcement sensitivity theory. Furthermore, mediation analysis revealed that heightened SR contributed to higher rewarded go success rate via enhanced rACC/left MFG activity. The findings demonstrate interrelated neural correlates of SR and SP to support the diametric processes of behavioral approach and avoidance.
Deaf ACCESS: Adapting Consent Through Community Engagement and State-of-the-Art Simulation
Authors: Anderson Melissa L , Riker Timothy , Hakulin Stephanie , Meehan Jonah , Gagne Kurt , Higgins Todd , Stout Elizabeth , Pici-D’Ottavio Emma , Cappetta Kelsey , Wolf Craig Kelly S
Published: August 2019

One of the most understudied health disparity populations in the United States is the Deaf community, a sociolinguistic minority group of more than 500,000 individuals who communicate via American Sign Language. Research on Deaf health disparities is lacking due to inaccessible recruitment, sampling, and data collection procedures, as well as the fundamental disconnect between medical and cultural views of Deaf people. A potential starting place for addressing inaccessible research methods and mistrust of the biomedical research community is the careful reconsideration of the traditional informed consent process, often a Deaf individual’s first point of contact with the research world. Yet, most Deaf individuals experience obstacles to engaging in informed consent due to differences in language and development compared to hearing individuals. In response to these issues, our team led a three-phase, formative, community-engaged approach to adapt the informed consent process and train research staff in the updated method so that all required components are properly communicated and understood. The goals of our work were to promote Deaf engagement in research about the Deaf community, increase the number of Deaf individuals who participate in general population biomedical research, and generalize our findings to improve research accessibility for the general population.
Development of a Dementia-Focused End-of-Life Planning Tool: The LEAD Guide (Life-Planning in Early Alzheimer’s and Dementia)
Authors: Dassel Kara , Utz Rebecca , Supiano Katherine , Bybee Sara , Iacob Eli
Published: August 2019

Background and Objectives

To address the unique characteristics of Alzheimer’s disease and related dementias (ADRD) that complicate end-of-life (EOL), we created, refined, and validated a dementia-focused EOL planning instrument for use by healthy adults, those with early-stage dementia, family caregivers, and clinicians to document EOL care preferences and values within the current or future context of cognitive impairment.

Research Design and Methods

A mixed-method design with four phases guided the development and refinement of the instrument: (1) focus groups with early-stage ADRD and family caregivers developed and confirmed the tool content and comprehensiveness; (2) evaluation by content experts verified its utility in clinical practice; (3) a sample of healthy older adults (n = 153) and adults with early-stage ADRD (n = 38) completed the tool, whose quantitative data were used to describe the psychometrics of the instrument; and (4) focus groups with healthy older adults, family caregivers, and adults with early-stage ADRD informed how the guide should be used by families and in clinical practice.

Results

Qualitative data supported the utility and feasibility of a dementia-focused EOL planning tool; the six scales have high internal consistency (α = 0.66–0.89) and high test–rest reliability (r = .60–.90). On average, both participant groups reported relatively high concern for being a burden to their families, a greater preference for quality over length of life, a desire for collaborative decision-making process, limited interest in pursuing life-prolonging measures, and were mixed in their preference to control the timing of their death. Across disease progression, preferences for location of care changed, whereas preferences for prolonging life remained stable.

Discussion and Implications

The LEAD Guide (Life-Planning in Early Alzheimer’s and Dementia) has the potential to facilitate discussion and documentation of EOL values and care preferences prior to loss of decisional capacity, and has utility for healthy adults, patients, families, providers, and researchers.
Efficient discontinuous finite difference meshes for 3-D Laplace–Fourier domain seismic wavefield modelling in acoustic media with embedded boundaries
Authors: AlSalem H J , Petrov P , Newman G , Um E , Rector J
Published: August 2019

Simulation of acoustic wave propagation in the Laplace–Fourier (LF) domain, with a spatially uniform mesh, can be computationally demanding especially in areas with large velocity contrasts. To improve efficiency and convergence, we use 3-D second- and fourth-order velocity-pressure finite difference (FD) discontinuous meshes (DM). Our DM algorithm can use any spatial discretization ratio between meshes. We evaluate direct and iterative parallel solvers for computational speed, memory requirements and convergence. Benchmarks in realistic 3-D models and topographies show more efficient and stable results for DM with direct solvers than uniform mesh results with iterative solvers.
Large animal models contribute to the development of therapies for central and peripheral nervous system dysfunction in patients with lysosomal storage diseases
Authors: Gurda Brittney L , Vite Charles H
Published: August 2019

Lysosomal storage diseases (LSDs) are a group of 70 monogenic disorders characterized by the lysosomal accumulation of a substrate. As a group, LSDs affect ~1 in 5000 live births; however, each individual storage disease is rare, limiting the ability to perform natural history studies or to perform clinical trials. Perhaps in no other biomedical field have naturally occurring large animal (canine, feline, ovine, caprine, and bovine) models been so essential for understanding the fundamentals of disease pathogenesis and for developing safe and effective therapies. These models were critical for the development of hematopoietic stem cell transplantation in α- and β- mannosidosis, fucosidosis, and the mucopolysaccharidoses; enzyme replacement therapy for fucosidosis, the mucopolysaccharidoses, and neuronal ceroid lipofuscinosis; and small molecule therapy in Niemann–Pick type C disease. However, their most notable contributions to the biomedical field are in the development of gene therapy for LSDs. Adeno-associated viral vectors to treat nervous system disease have been evaluated in the large animal models of α-mannosidosis, globoid cell leukodystrophy, GM1 and GM2 gangliosidosis, the mucopolysaccharidoses, and neuronal ceroid lipofuscinosis. This review article will summarize the large animal models available for study as well as their contributions to the development of central and peripheral nervous system dysfunction in LSDs.
The Double-Edged Sword of Military Response to Societal Disruptions: A Systematic Review of the Evidence for Military Personnel as Pathogen Transmitters
Authors: Zemke Juliana N , Sanchez Jose L , Pang Junxiong , Gray Gregory C
Published: August 2019

Given their lack of immunity and increased exposure, military personnel have the potential to serve as carriers or reservoirs for infectious diseases into or out of the deployment areas, but, to our knowledge, the historical evidence for such transmission events has not previously been reviewed. Using PubMed, we performed a systematic review of published literature between 1955 and 2018, which documented evidence for military personnel transporting infectious pathogens into or out of deployment areas. Of the 439 articles screened, 67 were included for final qualitative and quantitative review. The data extracted from these articles described numerous instances in which thousands of military service members demonstrated potential or actual transmission and transportation of multiple diverse pathogens. These data underscore the immense importance preventive medical professionals play in mitigating such risk, how their public health efforts must be supported, and the importance of surveillance in protecting both military and civilian populations.
ZBTB7A promotes migration, invasion and metastasis of human breast cancer cells through NF-κB-induced epithelial–mesenchymal transition in vitro and in vivo
Authors: Mao Anyun , Chen Maojian , Qin Qinghong , Liang Zhijie , Jiang Wei , Yang Weiping , Wei Changyuan
Published: August 2019

It has been generally confirmed that zinc finger and BTB domain containing 7A (ZBTB7A) plays an important role in the occurrence and progression of malignant tumours, but the promotion or inhibition effect is related to tumour type. The mechanism between ZBTB7A and breast cancer is not well understood, so further research is needed. In this study, we first investigated the expression of ZBTB7A in tissue samples of clinical breast cancer patients, MDA-MB-231, MCF-7 and MCF-10A cells. Second, we overexpressed the ZBTB7A in MCF-7 cells and silenced the ZBTB7A in MDA-MB-231 cells using lentivirus transfection technology, respectively, and verified the effect of ZBTB7A on migration and invasion of breast cancer cell lines through in vitro cell function experiments, such as wound-healing assay, migration and invasion assay, quantitative real time reverse transcriptase (qRT-PCR) and western blot. Then, the correlation between the above influences, epithelial–mesenchymal transition (EMT) and NF-κB was analysed. Finally, in vivo tumour transplantation model in nude mice was established to verified the effect of ZBTB7A on metastasis of breast cancer MDA-MB-231 cells. In conclusion, ZBTB7A is highly expressed in cancer tissue, breast cancer cell line MDA-MB-231 and MCF-7. Meanwhile, the high expression of ZBTB7A may promote cell migration, invasion and tumour metastasis, which may be related to EMT events by regulating NF-κB.
Inflammatory profile dysregulation in nuclear workers occupationally exposed to low-dose gamma radiation
Authors: Aneva Nevena , Zaharieva Elena , Katsarska Olya , Savova Gergana , Stankova Katia , Djounova Jana , Boteva Rayna
Published: August 2019

Chronic inflammation is a common denominator linking a wide range of health conditions, including tissue response to radiation exposure. This pilot study investigates whether inflammatory cytokines—interleukins IL-6, −8, −10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor α (TNFα)—can be used as early biomarkers of radiation-induced adverse health effects in occupationally exposed individuals. The study included 33 workers externally exposed to gamma radiation from the nuclear industry with cumulated doses from 0.11 to 190 mSv and 42 non-exposed controls of comparable age and socio-economic status. IL-6, IL-8, MCP-1, TNFα and IL-10 were analyzed by enzyme-linked assay (ELISA) in blood plasma samples. Total antioxidant status (TAS) of blood plasma was determined by a colorimetric assay. The radiation-exposed and control groups measured significantly different levels of MCP-1, TNFα and IL-10. Seventy-five percent of radiation workers had either high MCP-1 levels or low IL-10 levels and 30% had all three cytokines dysregulated. Approximately 50% of workers showed upregulated antioxidant status, which appeared to compensate the pro-inflammatory cytokine shift in these individuals. In contrast, only 2% of the control subjects were found to have three dysregulated cytokines, and all of them measured within the normal TAS range. The present study may represent an important step towards the establishment of a reliable set of biomarkers for health-risk estimation in population cohorts exposed to low radiation doses.
The mass distribution of Galactic double neutron stars: constraints on the gravitational-wave sources like GW170817
Authors: Zhang Jianwei , Yang Yiyan , Zhang Chengmin , Yang Wuming , Li Di , Bi Shaolan , Zhang Xianfei
Published: August 2019

The merger event of double neutron star (DNS) system (GW170817) was detected by the gravitational-wave (GW) detectors (Advanced LIGO and Advanced Virgo) in 2017 for the first time, so their mass distribution has become a significant topic with the new round GW hunting (O3) in 2019. A few models (e.g. Gaussian, two-Gaussian, or mixture-Gaussian) were adopted to draw the mass distribution of observed Galactic DNS systems, however, there is no a confirmed model now due to the small size of DNS samples (N < 20). Here we focus on determining the most probable distribution ranges of DNS masses without model selection by assuming the neutron star masses to be uniformly distributed between the lower and upper bounds. We apply a Bayesian analysis and Markov chain Monte Carlo simulation to 15 Galactic DNS systems, and obtain that the component masses of DNS systems should mainly fall in the range of 1.165–1.590 M⊙, and the predominant ranges for the total mass, mass ratio, and chirp mass lie in 2.535–2.867 M⊙, 0.741–0.995, and 1.115–1.237 M⊙, respectively. Our results are in agreement with the properties of DNS in GW170817, whose 90 per cent credible intervals for the component masses, total masses, mass ratio, and chirp masses are 1.16–1.60 M⊙, $2.73_{-0.01}^{+0.04}\, \mathrm{ M}_\odot$, 0.73–1.00, and $1.186_{-0.001}^{+0.001}\, \mathrm{ M}_\odot$, respectively. The above similarity is an important indicator that reveals the source of GW170817 to be a DNS system from the galaxy NGC 4993, and our results can be tested by the forthcoming GW hunting O3.
The impact of the locally measured Hubble parameter on the mass of sterile neutrino
Authors: Ebadinejad M
Published: August 2019

We present a precise analysis to test hypothetical models involving sterile neutrinos beyond the standard flat-ΛCDM cosmology with the CMB observations from the Planck mission and BAO measurements. This analysis shows that adding the locally measured Hubble parameter H0  = 73.00 ± 1.75 km s−1 Mpc−1 to the data removes the need for the informative physical $m_{\mathrm{ sterile}}^{\mathrm{ thermal}}$ prior in CMB constraints of $m_{\nu ,\mathrm{ sterile}}^{\mathrm{ eff}}$. Under the constraints from the data containing the locally measured H0 we obtain an upper limit $m_{\nu ,\mathrm{ sterile}}^{\mathrm{ eff}} \lt 0.306$ eV scale mass for the massive sterile neutrino, and an upper limit Σmν < 0.214 eV scale mass for the three degenerate massive neutrino (95 per cent confidence level). We also obtain the value σ8  = $0.81^{+0.05}_{-0.06}$ (95 per cent confidence level), which is in compatibility with the constraints from Planck 2015 CMB data at the 1σ level. We find that introducing parameter $m_{\nu ,\mathrm{ sterile}}^{\mathrm{ eff}}$ to the model of cosmology reduces the σ8 value and moves it closer to the obtained value for this parameter from the KiDS-450 analysis. Our results show that the locally measured Hubble parameter can increase constraints on σ8 values.
Repair of base damage within break-induced replication intermediates promotes kataegis associated with chromosome rearrangements
Authors: Elango Rajula , Osia Beth , Harcy Victoria , Malc Ewa , Mieczkowski Piotr A , Roberts Steven A , Malkova Anna
Published: August 2019

Break induced replication (BIR) is a double strand break repair pathway that can promote genetic instabilities similar to those observed in cancer. Instead of a replication fork, BIR is driven by a migration bubble where asynchronous synthesis between leading and lagging strands leads to accumulation of single-stranded DNA (ssDNA) that promotes mutation. However, the details of the mechanism of mutagenesis, including the identity of the participating proteins, remain unknown. Using yeast as a model, we demonstrate that mutagenic ssDNA is formed at multiple positions along the BIR track and that Pol ζ is responsible for the majority of both spontaneous and damage-induced base substitutions during BIR. We also report that BIR creates a potent substrate for APOBEC3A (A3A) cytidine deaminase that can promote formation of mutation clusters along the entire track of BIR. Finally, we demonstrate that uracil glycosylase initiates the bypass of DNA damage induced by A3A in the context of BIR without formation of base substitutions, but instead this pathway frequently leads to chromosomal rearrangements. Together, the expression of A3A during BIR in yeast recapitulates the main features of APOBEC-induced kataegis in human cancers, suggesting that BIR might represent an important source of these hyper-mutagenic events.
Munc18-1-interacting protein 3 mitigates renal fibrosis through protection of tubular epithelial cells from apoptosis
Authors: Nasu Kahori , Kawakami Takahisa , Shinohara Akinari , Sakamoto Takeharu , Nangaku Masaomi
Published: August 2019

Background

Tubulointerstitial fibrosis is a hallmark of chronic kidney disease (CKD), and is initiated by tubular epithelial cell (TEC) injury. Hypoxia promotes tubular cell death, fibrosis and CKD progression. Munc18-1-interacting protein 3 (Mint3) is a molecule that activates hypoxia-inducible factors (HIFs) by binding and suppressing factor inhibiting HIF-1 (FIH). However, the role of Mint3 in tubulointerstitial fibrosis remains unknown.

Methods

We induced fibrosis of the kidney after unilateral ischemia–reperfusion injury (uIRI) in Mint3-knockout and littermate wild-type mice. The duration of ischemia was 23 min and the kidneys were harvested at 24 h and 7 days after ischemia–reperfusion. The function of Mint3 was further investigated by using mouse cortical tubular (MCT) cells, which were treated with Mint3 and/or FIH small interfering RNA and exposed to normoxia or hypoxia.

Results

Knockout of Mint3 did not affect the acute injury induced by uIRI, but exacerbated the tubulointerstitial fibrosis, accompanied by an increase in TEC apoptosis. Consistently, hypoxia-induced apoptosis of MCT cells was aggravated by Mint3 knockdown. Unexpectedly, the additional knockdown of FIH did not suppress the increase in apoptosis by Mint3 knockdown, demonstrating the irrelevance of the FIH/HIF pathway. Therefore, we next focused on nuclear factor (NF)-κB, which has an anti-apoptotic role. Indeed, not only the expression of the inhibitory NF-κB p50 but also the DNA-binding activity of p50/p50 homodimer was increased by knockdown of Mint3 in the TECs, along with the decreased expressions of the NF-κB-targeted anti-apoptotic genes. An increase in NF-κB p50 was also confirmed in Mint3-knockout kidneys.

Conclusions

Mint3 in epithelial cells protects the cells from apoptosis by up-regulating anti-apoptotic effects of NF-κB, leading to fibrosis suppression. This new pathophysiology of tubulointerstitial fibrosis could be a target of future therapy for CKD.
The Effect of Web-Based Preoperative and Postoperative Patient Care Education on Nursing Students
Authors: Durmaz Edeer Aylin , Vural Fatma , Turhan Damar Hale , Yasak Kübra , Damar Muhammet
Published: August 2019

This study examined the effect of Web-based preoperative and postoperative patient care education among undergraduate nursing students. This was an experimental, randomized controlled study. The study included 305 nursing students (experimental group: n = 155, control group: n = 150), who were assessed with the following instruments: the Preoperative and Postoperative Care Knowledge Test, Preoperative and Postoperative Care Skill Control List, Clinical Decision Making in Nursing Scale, and Nursing Student Clinical Performance Evaluation Scale. t Tests and χ
2 tests were used to evaluate the data. There was no statistically significant difference between the students' posttest knowledge levels, clinical performance assessment, or clinical decision-making scores. The experimental group was found to perform the skills of “check patient's documents and prophylactic antibiotics when going to surgery” (χ
2 = 4.88; P = .02), “controls the surgical safety checklist (before surgery) before going to surgery” (χ
2 = 10.41; P = .00), and “observes surgical site/dressing (χ
2 = 7.77; P = .00)” at a statistically significantly higher level. The education provided in the Web-based education was equivalent to that provided in traditional education. Thus, Web-based education appears to be a useful tool to educate student nurses in preoperative and postoperative patient care.
An Empirical Validation of the Within-subject Biospecimens Pooling Approach to Minimize Exposure Misclassification in Biomarker-based Studies
Authors: Vernet Céline , Philippat Claire , Agier Lydiane , Calafat Antonia M. , Ye Xiaoyun , Lyon-Caen Sarah , Hainaut Pierre , Siroux Valérie , Schisterman Enrique F. , Slama Rémy
Published: August 2019

Background:

Within-subject biospecimens pooling can theoretically reduce bias in dose–response functions from biomarker-based studies when exposure assessment suffers from classical-type error. However, collecting many urine voids each day is cumbersome. We evaluated the empirical validity of a within-subject pooling approach and compared several options to avoid sampling each void.

Methods:

In 16 pregnant women who collected a spot of each urine void over several nonconsecutive weeks, we compared concentrations of 10 phenols in daily, weekly, and pregnancy within-subject pools. We pooled either three or all daily samples. In a simulation study using these data, we quantified bias in dose–response functions when using one to 20 urine samples per subject to assess methylparaben (a compound with moderate within-subject variability) and bisphenol A (high variability) exposures.

Results:

Correlations between exposure estimates from pools of all and of only three voids per day were above 0.80 for all time windows and compounds, except for benzophenone-3 and triclosan in the daily time window (correlations, 0.57–0.68). With one spot sample to assess pregnancy exposure, correlations were all below 0.74. Using only one biospecimen led to attenuation bias in the dose–response functions of 29% (methylparaben) and 69% (bisphenol A); four samples for methylparaben and 18 for bisphenol A decreased bias to 10%.

Conclusions:

For nonpersistent chemicals, collecting and pooling three samples per day instead of all daily samples efficiently estimates exposures over a week or more. Collecting around 20 biospecimens can strongly limit attenuation bias for nonpersistent chemicals such as bisphenol A.
Perineal Talc Use, Douching, and the Risk of Uterine Cancer
Authors: O’Brien Katie M. , D’Aloisio Aimee A. , Shi Min , Murphy John D. , Sandler Dale P. , Weinberg Clarice R.
Published: August 2019

Background:

Perineal talc use and douching could affect the risk of uterine cancer through several possible pathways, including inflammation response, microbiota changes, or endocrine disruption. Two previous cohort studies of the association between talc use and uterine cancer have reported weak positive associations, but we know of no previous evaluations of the relationship between douching and uterine cancer.

Methods:

Using a large prospective cohort, we examined the relationship between incident uterine cancer and self-reported use of talc or douche using Cox proportional hazards models.

Results:

After excluding those with prior hysterectomy, 271 of 33,609 women reported incident uterine cancer (mean follow-up = 8.3 years in noncases; maximum 12.6 years). Overall, 26% of women reported ever using talc and 15% reported ever having douched. Ever talc use was associated with an increase in risk of uterine cancer (adjusted hazard ratio [HR] = 1.2; 95% confidence interval [CI] = 0.94, 1.6), with some evidence of a dose–response for frequency of talc use (P-for-trend = 0.07). Ever douching was not associated with uterine cancer risk (HR = 1.0; 95% CI = 0.72, 1.5), with no evidence of a frequency dose–response (P = 0.96). The estimates were similar when we restricted to invasive endometrial cancers, but not when we further restricted to endometroid adenocarcinomas.

Conclusion:

The positive association we observed between talc use and uterine cancer risk is consistent with findings from previous prospective cohort studies of endometrial cancer. The relationships between uterine cancer and both douching and talc use merit further consideration, particularly as both exposures are preventable.
Inhibitors of the Janus Kinases
Authors: Antonelli Elisabetta , Torti Gabriele , Bassotti Gabrio
Published: August 2019

Background:

The treatment of ulcerative colitis (UC) is based on conventional therapies (aminosalicylates, corticosteroids, and immunosuppressants) and when these are ineffective, biologic drugs. However, in a substantial portion of patients undergoing treatment with biologic agents there is primary or secondary loss of response. Thus, new therapeutic options are been actively explored; among these, there is interest in the Janus kinase (JAK) inhibitors, small molecules that can be administered orally.

Methods:

We carried out an extensive literature search concerning the effects of JAK inhibitors for the treatment of patients with UC.

Results:

Tofacitinib is the drug more extensively studied in this setting, and it was recently approved in Europe for the treatment of moderate to severe UC. The available data suggest that this drug can be effective in obtaining clinical and endoscopic remission in UC patients unresponsive to other treatments, even in those previously treated with biologic drugs. In addition, the drug was able to improve significantly the quality of life of these patients. There are still few data available for the treatment of UC with other JAK inhibitors.

Conclusions:

The JAK inhibitors, in particular tofacitinib, are a new class of orally administered drugs effective for the treatment of UC. However, more studies are needed to ascertain the safety of tofacitinib in the long term and whether other compounds of this class may be equally effective.
The Use of Capsule Endoscopy For Diagnosis of Iron Deficiency Anemia: A Retrospective Analysis
Authors: Stone James , Grover Kanika , Bernstein Charles N.
Published: August 2019

Background:

There was some ambiguity in the recent guidelines on the use of capsule endoscopy (CE) in cases of iron deficiency anemia (IDA).

Goal:

We aimed to examine the yield of CE in diagnosing the cause of IDA and to define clinical parameters that predict higher diagnostic yields.

Materials and Methods:

A total of 1351 individuals underwent CE in Winnipeg between 2005 and 2016. All studies were reported by 1 reading physician. Data included demographics and requested information on medication use, prior imaging studies, and hemoglobin and ferritin levels. In a total of 620 (46%) patients, CE was indicated for occult gastrointestinal bleeding or IDA. Positive findings on CE were separated into “definite” and “possible.” Multinomial regression analysis was used to determine the variables correlated with definite CE findings. A survey analysis was then used to assess how the study results impacted further management.

Results:

With regard to the 620 patients, the mean age was 62.9 years, mean hemoglobin level was 89 g/L, and median ferritin level was 9 μg/L. A total of 210 (33.9%) patients had positive findings (definite: 23%, possible: 10.8%). Vascular ectasias were the majority of definite findings (47.5%). Predictors of definite findings were age (relative risk ratio: 1.04; 95% confidence interval: 1.02-1.06) and male sex (relative risk ratio: 1.88; 95% confidence interval: 1.25-2.83). An overall 12.7% of positive studies required therapeutic intervention, with 65.8% undergoing further workup.

Conclusion:

We report a 33.9% positive yield, with 65.8% of patients undergoing further workup as a result of CE and 12.7% requiring therapeutic intervention. We conclude that CE plays an important role in the investigation of IDA and occult gastrointestinal bleeding and has important implications on further management.
A rare cutaneous phototoxic rash after vandetanib therapy in a patient with thyroid cancer
Authors: Yin Yue , Qiu Xin Ye , Zhang Yan Hua , Zhang Bin
Published: August 2019

Rationale:

Vandetanib is effective for treating symptomatic or progressive medullary thyroid cancer (MTC) in patients with unresectable locally advanced or metastatic disease, but its toxicity such as photosensitivity reactions should be considered. It is a rare adverse effect of this drug but might cause severe morbidity and even mortality.

Patient concerns:

A 26-year man with MTC developed phototoxic rashes on the sun-exposed areas of his shin after 15 days from the initiation of vandetanib treatment. Grade II skin toxicity was evaluated based on the Common Terminology Criteria for Adverse Events standard.

Diagnoses:

Drug-induced phototoxic rash.

Interventions:

The vandetanib dose was reduced by 30%, and the application of topical steroids and sunscreen was adopted.

Outcomes:

After dose reduction of vandetanib, the symptoms of vandetanib-induced phototoxic rash resolved, although residual pigmentation was observed.

Lessons:

Close attention should be paid to the adverse effect of vandetanib, phototoxic rash, and patients should be advised on the prevention and treatment measures.
Effect of coronary collateral circulation on the prognosis of elderly patients with acute ST-segment elevation myocardial infarction treated with underwent primary percutaneous coronary intervention
Authors: Chu Ai-Ai , Li Wei , Zhu You-Qi , Meng Xiao-Xue , Liu Guo-Yong
Published: August 2019

Investigate the effect of coronary collateral circulation (CCC) on the prognosis of elderly patients with acute ST-segment elevation myocardial infarction (STEMI) and acute total occlusion (ATO) of a single epicardial coronary artery.

Three hundred forty-six advanced-age patients (age ≥60 years) with STEMI and ATO who underwent primary percutaneous coronary intervention (PCI) were enrolled in this study. According to the Rentrop grades, the patients were assigned to the poor CCC group (Rentrop grade 0–1) and good CCC group (Rentrop grade 2–3).

Multivariate logistic regression analysis revealed that poor coronary collateral circulation was an independent factor for Killip class ≥2 (odds ratio [OR]: –1.559; 95% confidence interval [CI]: 1.346–2.378; P = .013), the use of an intra-aortic balloon pump (IABP) (OR: –1.302; 95% CI: 0.092–0.805; P = .019), and myocardial blush grade (MBG) 3 (OR: 1.516; 95% CI: 2.148–9.655; P < .001). We completed a 12-month follow-up, during which 52 patients (15.0%) were lost to follow-up and 19 patients (5.5%) died. Univariate analysis (Kaplan–Meier and log-rank tests) suggested that poor CCC had a significant effect on all-cause mortality (P = .046), while multivariate analysis (Cox regression analysis) indicated that CCC had no statistically significant effect on all-cause mortality (P = .089) after the exclusion of other confounding factors. After excluding the influence of other confounding factors, this study showed that the mortality rate increased by 26.9% within 1 year for every 1-hour increment of time of onset. The mortality rate in patients with Killip class ≥2 was 8.287 times higher than that in patients with Killip class 0 to 1. The mortality rate in patients over 75 years was 8.25 times higher than that in patients aged 60 to 75 years. The mortality rate in patients with myocardial blush grade 3 (MBG 3) was 5.7% higher than that in patients with MBG 0–2.

The conditions of CCC in the acute phase had no significant direct effect on all-cause mortality in patients, but those with good CCC had a higher rate of MBG 3 after primary PCI and a lower rate of Killip ≥2.
Post-treatment alpha-fetoprotein response predicts prognosis of patients with hepatocellular carcinoma
Authors: He Chao , Peng Wei , Liu Xiaojuan , Li Chuan , Li Xueting , Wen Tian-Fu
Published: August 2019

Background:

Post-treatment alpha-fetoprotein (AFP) response has been reported to be associated with prognosis of hepatocellular carcinoma (HCC) patients, but the results were not consistent. This meta-analysis aimed to explore the relationship between AFP response and clinical outcomes of HCC.

Methods:

PubMed, Embase, Medline and Cochrane library were searched for relevant articles published before March 20, 2019. The data were analyzed using RevMan5.3 software.

Results:

Twenty-nine articles with 4726 HCC patients were finally included for analysis. The pooled results showed that post-treatment AFP response was significantly associated with overall survival (OS) (hazard ratio (HR) = 0.41, 95% confidence interval (CI): 0.35–0.47, P <.001), progression free survival (PFS) (HR = 0.46, 95% CI: 0.39–0.54, P <.001) and recurrence free survival (RFS) (HR = 0.41, 95% CI: 0.29–0.56, P <.001) of HCC patients.

Conclusion:

post-treatment AFP response might be a useful prognostic marker for HCC patients.
Poor response to rivaroxaban in nephrotic syndrome with acute deep vein thrombosis
Authors: Li Yan , Chen Yikuan , Qi Xiaotong , Hu Bangqin , Du Qingqing , Qian Yan
Published: August 2019

Rationale:

Hypercoagulability can lead to thromboembolic events that are a life-threatening complication of nephrotic syndrome (NS). Conventional anticoagulants are first-line treatment in the presence of demonstrated thrombosis in NS. Direct-acting oral anticoagulants (DOACs) have provided useful alternatives for the prevention and treatment of thromboembolic events.

Patient concerns:

A 59-year-old male developed lower limbs deep vein thrombosis (DVT) during the early course of NS but presented poor response to oral therapeutic doses of rivaroxaban. The decision was made to switch from rivaroxaban to heparin and subsequently bridged to warfarin. The patient presented significant clinical symptom improvement.

Diagnosis:

NS with Lower limbs DVT.

Interventions:

Rivaroxaban was discontinued and switch to heparin and subsequently bridged to warfarin.

Outcomes:

Venography result of both lower limb vein showed the venous wall was smooth without obvious stenosis or obstruction. Edema of the patient's lower limbs gradually improved and disappeared.

Lessons:

The existing published data on the application of DOACs in NS are limited. DOACs have an immediate anticoagulant effect and have demonstrated safety and efficacy and required no routine monitoring, however, application of these agents in NS likely requires further investigation before widespread adoption.
Dynamic change of depression and anxiety after chemotherapy among patients with ovarian cancer
Authors: Liu Hongxia , Yang Linqing
Published: August 2019

Psychological state of patients with ovarian cancer is worthy of attention. We aimed to investigate the levels of anxiety and depression in patients with ovarian cancer. We also investigated the dynamic changes in anxiety and depression levels after chemotherapy.

A total of 228 females were included in this study. Among them, a total of 111 participants had ovarian cancer and 117 females who underwent a physical examination were selected as healthy controls. All patients enrolled were asked to fill in the Self-rating Depression Scale and the Self-rating Anxiety Scale. For patients with ovarian cancer, repeat questionnaires were measured after cycle 1 chemotherapy.

The depression score of patients with ovarian cancer was 45.90 ± 10.19, significantly higher than in controls (36.08 ± 9.06, P < .001). Similar results were observed in respect of anxiety score. The score of ovarian cancer patients was 39.53 ± 12.92, significantly higher than of controls (32.15 ± 7.44, P < .001). Multivariate analyses were conducted, and the results showed that young age was the independent risk factor associated with depression among patients with ovarian cancer, while young age and singleness were the independent risk factors associated with anxiety. Repeat questionnaires were measured after chemotherapy. Interestingly, we found depression scores decreased from 45.90 ± 10.19 to 36.29 ± 8.98 after chemotherapy (P < .001), while anxiety score increased from 39.53 ± 12.92 to 42.75 ± 9.96 after chemotherapy (P = .009). Multivariate analysis suggested that only higher income and higher baseline depression score were the independent and most relevant risk factors associated with depression remission after chemotherapy. For patients with anxiety remission, only higher baseline anxiety score was the independent risk factor associated with anxiety remission.

This study suggests that for patients with ovarian cancer, timely monitoring of the patient's psychological state, especially before and after chemotherapy treatment, is very important. Assessing the changes in the patient's psychological state, screening the population with risk factors, and prompt intervention by mobilizing social support may be effective in preventing depression and anxiety in such population.
Recurrent anti-GBM disease with T-cell large granular lymphocytic leukemia
Authors: Zhang Min , Guan Nan , Zhu Ping , Chen Tong , Liu Shaojun , Hao Chuanming , Xue Jun
Published: August 2019

Rationale:

Anti-glomerular basement membrane disease (anti-GBM disease) is a rare small vessel vasculitis caused by autoantibodies directed against the glomerular and alveolar basement membranes. Anti-GBM disease is usually a monophasic illness and relapse is rare after effective treatment. This article reports a case of coexistence of recurrent anti-GBM disease and T-cell large granular lymphocytic (T-LGL) leukemia.

Patient concerns:

A 37-year-old man presented with hematuria, edema, and acute kidney injury for 2 months.

Diagnosis:

Anti-GBM disease was diagnosed by renal biopsy, in which crescentic glomerulonephritis was observed with light microscopy, strong linear immunofluorescent staining for immunoglobulin G on the GBM and positive serum anti-GBM antibody. Given this diagnosis, the patient was treated with plasmapheresis, steroids, and cyclophosphamide for 4 months. The anti-GBM antibody titer was maintained to negative level but the patient remained dialysis-dependent. One year later, the patient suffered with a relapse of anti-GBM disease, after an extensive examination, he was further diagnosed T-LGL leukemia by accident.

Interventions:

The patient received cyclosporine A therapy for T-LGL leukemia.

Outcomes:

After treatment with cyclosporine A, serum anti-GBM antibody became undetectable. During the 16 months follow-up, anti-GBM titer remained normal and abnormal T-lymphocytes in the bone marrow and peripheral blood were also decreased.

Lessons:

T-LGL leukemia is an indolent lymphoproliferative disorder that represents a monoclonal expansion of cytotoxic T cells, which has been reported to be accompanied by some autoimmune diseases. This is the first report of coincidence of T-LGL leukemia and anti-GBM disease, and suggests there are some relationships between these 2 diseases. Clinical physicians should exclude hematological tumors when faced with recurrent anti-GBM disease.
Endovascular treatment of pulmonary sequestration with thoracic endograft
Authors: Chen Yu , Liu Bao , Shao Jiang , Liu Duan , Zheng Yuehong
Published: August 2019

Introduction:

Pulmonary sequestration (PS) is a rare congenital lung malformation. The classical treatment of the disease has been conventional surgery with resection of abnormal parenchyma. Recently, the endovascular embolization has been proposed for the treatment of this disease. Here we present 2 cases of PS successfully treated with thoracic endograft.

Patient concerns:

Two patients with abnormal consolidation in the left lower lobe were admitted in our hospital.

Diagnosis:

Chest computed tomography angiography (CTA) showed abnormal consolidation in the left lower lobe, which received systemic blood supply from the descending aorta in both patients. So the diagnosis of PS was confirmed.

Interventions:

Endovascular treatment with thoracic endograft was successfully performed.

Outcomes:

The patients recovered well and were completely free of symptoms. And the CTA follow-up showed the abnormal pulmonary parenchyma shrunk significantly.

Conclusions:

Endovascular treatment with thoracic endograft is a promising treatment option for PS.