bluuebunny/crossref_metadata_2025 huggingface dataset:
Greater stem growth, woody allocation, and aboveground biomass in Paleotropical forests than in Neotropical forests
Authors: Taylor Philip G. , Cleveland Cory C. , Soper Fiona , Wieder William R. , Dobrowski Solomon Z. , Doughty Christopher E. , Townsend Alan R.
Published: February 2019

Forest dynamics and tree species composition vary substantially between Paleotropical and Neotropical forests, but these broad biogeographic regions are treated uniformly in many land models. To assess whether these regional differences translate into variation in productivity and carbon (C) storage, we compiled a database of climate, tree stem growth, litterfall, aboveground net primary production (ANPP), and aboveground biomass across tropical rainforest sites spanning 33 countries throughout Central and South America, Asia, and Australasia, but excluding Africa due to a paucity of available data. Though the sum of litterfall and stem growth (ANPP) did not differ between regions, both stem growth and the ratio of stem growth to litterfall were higher in Paleotropical forests compared to Neotropical forests across the full observed range of ANPP. Greater C allocation to woody growth likely explains the much larger aboveground biomass estimates in Paleotropical forests (~29%, or ~80 Mg DW/ha, greater than in the Neotropics). Climate was similar in Paleo‐ and Neotropical forests, thus the observed differences in C likely reflect differences in the evolutionary history of species and forest structure and function between regions. Our analysis suggests that Paleotropical forests, which can be dominated by tall‐statured Dipterocarpaceae species, may be disproportionate hotspots for aboveground C storage. Land models typically treat these distinct tropical forests with differential structures as a single functional unit, but our findings suggest that this may overlook critical biogeographic variation in C storage potential among regions.
The thioredoxin‐1 and glutathione/glutaredoxin‐1 systems redundantly fuel murine B‐cell development and responses
Authors: Muri Jonathan , Thut Helen , Heer Sebastian , Krueger Caroline C. , Bornkamm Georg W. , Bachmann Martin F. , Kopf Manfred
Published: February 2019

Antioxidant systems maintain cellular redox homeostasis. The thioredoxin‐1 (Trx1) and the glutathione (GSH)/glutaredoxin‐1 (Grx1) systems are key players in preserving cytosolic redox balance. In fact, T lymphocytes critically rely on reducing equivalents from the Trx1 system for DNA biosynthesis during metabolic reprogramming upon activation. We here show that the Trx1 system is also indispensable for development and functionality of marginal zone (MZ) B cells and B1 cells in mice. In contrast, development of conventional B cells, follicular B‐cell homeostasis, germinal center reactions, and antibody responses are redundantly sustained by both antioxidant pathways. Proliferating B2 cells lacking Txnrd1 have increased glutathione (GSH) levels and upregulated cytosolic Grx1, which is barely detectable in expanding thymocytes. These results suggest that the redox capacity driving proliferation is more robust and flexible in B cells than in T cells, which may have profound implications for the therapy of B and T‐cell neoplasms.
Advances in catalytic conversion of methane and carbon dioxide to highly valuable products
Authors: Cai Xiaojiao , Hu Yun Hang
Published: February 2019

Two typical processes have been developed for the conversion of methane and carbon dioxide to higher valuable products: dry reforming of methane (DRM) and CO2‐oxidative coupling of methane (CO2‐OCM). Numerous articles reviewed progresses in either DRM or CO2‐OCM, but no one covers both processes. In this review article, we systematically evaluated progresses in both DRM and CO2‐OCM processes for conversion of methane and CO2 to highly valuable products. Critical issues, which are carbon deposition and high energy cost for DRM and the contradiction between large activity and high selectivity for CO2‐OCM, were emphasized. Strategies to develop effective catalysts were evaluated, including the enhancement of metal‐support interactions, the introduction of promotors, the formation of solid solutions, and the construction of core‐shell structures. Plasma and photocatalysis were discussed as new promising technologies for DRM and CO2‐OCM.
Targeted deletion of β1‐syntrophin causes a loss of Kir4.1 from Müller cell endfeet in mouse retina
Authors: Rao Shreyas B. , Katoozi Shirin , Skauli Nadia , Froehner Stanley C. , Ottersen Ole Petter , Adams Marvin E. , Amiry‐Moghaddam Mahmood
Published: February 2019

Proper function of the retina depends heavily on a specialized form of retinal glia called Müller cells. These cells carry out important homeostatic functions that are contingent on their polarized nature. Specifically, the Müller cell endfeet that contact retinal microvessels and the corpus vitreum show a tenfold higher concentration of the inwardly rectifying potassium channel Kir4.1 than other Müller cell plasma membrane domains. This highly selective enrichment of Kir4.1 allows K+ to be siphoned through endfoot membranes in a special form of spatial buffering. Here, we show that Kir4.1 is enriched in endfoot membranes through an interaction with β1‐syntrophin. Targeted disruption of this syntrophin caused a loss of Kir4.1 from Müller cell endfeet without affecting the total level of Kir4.1 expression in the retina. Targeted disruption of α1‐syntrophin had no effect on Kir4.1 localization. Our findings show that the Kir4.1 aggregation that forms the basis for K+ siphoning depends on a specific syntrophin isoform that colocalizes with Kir4.1 in Müller endfoot membranes.
Could We Be Marsupials? Very Premature Babies and Artificial Wombs
Authors: Davis Dena S.
Published: February 2019

It is often pointed out that one cannot be “a little bit pregnant,” but pregnancy’s borders are no longer so crisp. At Children’s Hospital of Philadelphia, scientists have created an artificial womb in which “extremely premature” lambs were nurtured for four weeks, enough to make them ready to meet the world. The goal is to advance this technology until it is available for very premature human infants. At present, we put preemies into neonatal intensive care units, which are extremely stressful for the babies and their families, and the things we do to try to support them often cause serious damage. If successful, the artificial womb could be a terrific technology. The implications are remarkable. Would humans become somewhat like marsupials? Now, one is either born or not. Would this technology create a new, intermediate stage? What would this mean ethically and legally?
Requests for PAD and the Assessment of Capacity
Authors: Strouse Thomas B.
Published: February 2019

I was asked to evaluate M by her medical oncologist, Dr. T. As a psychiatrist, I was to perform the duties of a mental health specialist in the care of this fifty‐eight‐year‐old woman with metastatic breast cancer who had requested physician aid in dying. Dr. T had no specific concerns, but she was adhering to the letter of the law by referring the patient to me—a “mental health specialist”—because, according to the patient’s medical history, there was “evidence of a mental disorder.” That evidence was comprised of depression treated in the remote past.

Some years before California passed its End of Life Options Act in 2015, M had begun talking with Dr. T about the circumstances under which she might no longer want to be alive and might even choose to take active steps to end her life. She had fairly specific and durable criteria for knowing “when the time had come.” In our interview, she asserted very clearly that the time had not come but that, with the law now active, she hoped to have access to a lethal prescription in case it did.
The Strange Tale of Three Identical Strangers: Cinematic Lessons in Bioethics
Authors: Moore Bryanna , Garrett Jeremy R. , McNolty Leslie Ann , Murano Maria Cristina
Published: February 2019

Tim Wardle’s 2018 documentary film Three Identical Strangers is an exploration of identity, family, and loss. It’s also about nature versus nurture and the boundaries of ethically permissible research, particularly research involving children. The film tells the story of identical triplets who were separated soon after birth in 1961. A different family adopted each boy, without being told that their son had two identical brothers. The adoption agency responsible for finding the families was collaborating with a group of researchers working on a study about … something. Three Identical Strangers details the boys’ fight to obtain information about the study and for closure. But while the film may have received rave reviews, it left us feeling uneasy. We came away with two sets of questions, one having to do with the story that the film documents and the second with the ethics of filmmaking itself.
Deep Ethical Learning: Taking the Interplay of Human and Artificial Intelligence Seriously
Authors: Ho Anita
Published: February 2019

From predicting medical conditions to administering health behavior interventions, artificial intelligence technologies are being developed to enhance patient care and outcomes. However, as Mélanie Terrasse and coauthors caution in an article in this issue of the Hastings Center Report, an overreliance on virtual technologies may depersonalize medical interactions and erode therapeutic relationships. The increasing expectation that patients will be actively engaged in their own care, regardless of the patients’ desire, technological literacy, and economic means, may also violate patients’ autonomy and exacerbate access. Moreover, since AI design is both a technical and social process, algorithms may mirror human biases, calling into question the vision of AI technologies surpassing human judgment and avoiding prejudices in decision‐making. The best answer to these problems is to develop AI health technologies as part of a culture of health care quality improvement, responding to existing needs while being proactive about potential technical and ethical problems that can arise from the technologies’ design and implementation.
Ethical Use of Social Media Data: Beyond the Clinical Context
Authors: Hammack Catherine M.
Published: February 2019

In “Social Media, e‐Health, and Medical Ethics,” in this issue of the Hastings Center Report, Mélanie Terrasse, Moti Gorin, and Dominic Sisti address and suggest recommendations for several ethical issues central to the systematic ethical analysis of the effects of social media on clinical practice, health services research, and public health. The topic is as timely as it is important: social media data collected by device and web applications are constantly increasing and might have both individual and public health benefits. The authors focus their analysis primarily on the health care context. Yet the implications of the intersection of social media data and research warrant focused consideration, as even the most thorough ethical analysis in the clinical context is not necessarily directly applicable in the research context. While many ethical issues are present in both settings, the research context poses new challenges and calls for consideration of distinct factors. In particular, because the legal framework is less protective in research, critical ethical analysis of the research‐specific issues and considerations is essential to the ethical conduct of research using social media data as well as to the design and operation of social media device and web applications themselves.
Treatment of advanced gastrointestinal cancer with genetically modified autologous mesenchymal stem cells: Results from the phase 1/2 TREAT‐ME‐1 trial
Authors: von Einem Jobst Christian , Guenther Christine , Volk Hans‐Dieter , Grütz Gerald , Hirsch Daniela , Salat Christoph , Stoetzer Oliver , Nelson Peter J. , Michl Marlies , Modest Dominik P. , Holch Julian W. , Angele Martin , Bruns Christiane , Niess Hanno , Heinemann Volker
Published: February 2019

TREAT‐ME‐1, a Phase 1/2 open‐label multicenter, first‐in‐human, first‐in‐class trial, evaluated the safety, tolerability and efficacy of treatment with genetically modified autologous mesenchymal stromal cells (MSC), MSC_ apceth_101, in combination with ganciclovir in patients with advanced gastrointestinal adenocarcinoma. Immunological and inflammatory markers were also assessed. All patients (3 in Phase 1; 7 in Phase 2) received three treatment cycles of MSC_apceth_101 at one dose level on Day 0, 7, and 14 followed by ganciclovir administration according to the manufacturer's instructions for 48─72 h after MSC_apceth_101 injection. Ten patients were treated with a total dose of 3.0 x 106 cells/kg MSC_apceth_101. 36 adverse events and six serious adverse events were reported. Five patients achieved stable disease (change in target lesions of −2 to +28%). For all patients, the median time to progression was 1.8 months (95% CI: 0.5, 3.9 months). Median overall survival could not be estimated as 8/10 patients were still alive at the end of the study (1 year) and therefore censored. Post‐study observation of patients showed a median overall survival of 15.6 months (ranging from 2.2─27.0 months). Treatment with MSC_apceth_101 and ganciclovir did not induce a consistent increase or decrease in levels of any of the tumor markers analyzed. No clear trends in the immunological markers assessed were observed. MSC_apceth_101 in combination with ganciclovir was safe and tolerable in patients with advanced gastrointestinal adenocarcinoma, with preliminary signs of efficacy in terms of clinical stabilization of disease.
CA125 over‐release behavior following a 75‐g oral glucose test as a predictive biomarker of multidrug resistance in patients with ovarian cancer
Authors: He Yifeng , Gu Zhuowei , Zhu Qiujing , Chen Mo , He Chenghui , Huang Yuting , Li Qing , Di Wen
Published: February 2019

Multidrug resistance is a major cause of death in patients with ovarian cancer. To improve patient survival, we developed a novel, noninvasive and convenient tool, the 75‐gram oral glucose (75gOG)‐stimulated CA125 test, to monitor cancer chemoresistance in real time. Our in vitro proof‐of‐principal experiments revealed that post‐75gOG glucose and insulin peaks can synergistically increase cancer‐derived CA125 levels, and the increase in CA125 secretion (ΔCA125) is correlated with the overactivation of the insulin receptor (IR)‐PI3K‐Akt axis and increases (ΔIC50s) in cisplatin/taxol IC50s. Correspondingly, among the 93 patients enrolled, post‐75gOG CA125 over‐release (i.e., enhanced ΔCA125) behavior was associated with overexpression of the IR‐PI3K‐Akt pathway and its downstream components, namely, IR, pAkt, pS6 and GLUT4, in cancer specimens. Furthermore, both pre‐ and postsurgical 75gOG CA125 tests demonstrated that CA125 over‐release showed excellent prediction efficacy on the chemoresistance potential of ovarian cancer; notably, the former indicated the need for an optimal debulking surgery, and the latter suggested the use of IR‐PI3K‐Akt inhibitors. Both test results possess independent prognostic significance for the 2‐year progression‐free survival (PFS) and overall survival (OS) of patients. The odds ratios and corresponding 95% confidence intervals (95% CIs) were 2.680 (95% CI: 1.393–5.156) for patients with CA125 over‐release behavior evidenced by a presurgical 75gOG CA125 test or 3.822 (95% CI: 1.942–7.522) for that evidenced by a postsurgical test in PFS; and 3.320 (95% CI: 1.508–7.309) for patients with CA125 over‐release behavior evidenced by a presurgical test or 5.212 (95% CI: 2.241–12.121) for that evidenced by a postsurgical test in OS.
Radiation‐induced sarcoma after radiation therapy for prostate adenocarcinoma
Authors: Wakabayashi Kohei , Konishi Kenta , Komatsu Tetsuya , Ishiba Ryo , Ota Naofumi , Ito Toshiki , Aki Ryota , Tsuchida Takashi , Miyake Hideaki , Nakamura Katsumasa
Published: February 2019

Introduction

Radiation therapy is widely used for prostate cancer, but radiation‐induced sarcomas have been rarely reported.

Case presentation

A 77‐year‐old Japanese male was diagnosed with prostate cancer and received a combined androgen blockade and radiation therapy (total dose of 76 Gy). Five years after the radiation therapy, testicular pain and dysuria appeared. Computed tomography showed a soft tissue dense mass with invasion to the right subpubic ramus and prostate, mainly to the perineum. A needle biopsy revealed the pathological features of high‐grade sarcoma. The patient was diagnosed with radiation‐induced sarcoma based on the cancer's occurrence in the vicinity of the radiation field.

Conclusion

Although irradiation is one of the important treatments for prostate cancer, the risk of radiation‐induced malignancy should be considered.
The Prerna Girls’ Education Initiative in India: Scaling Literacy to Reach for the Sky
Authors: Sahni Urvashi
Published: February 2019

This department focuses on literacy leaders, including school and instructional leaders, teachers, and external partners, who are working to improve outcomes for adolescent and adult learners in a wide range of education settings. Columns investigate the challenges and complexities inherent in such work and share lessons learned, impactful strategies and approaches, and promising pathways forward.
Nanocurcumin: A novel strategy in treating ankylosing spondylitis by modulating Th17 cells frequency and function
Authors: Hajialilo Mehrzad , Dolati Sanam , Abdolmohammadi‐Vahid Samaneh , Ahmadi Majid , Kamrani Amin , Eghbal‐Fard Shadi , Ghassembaglou Arezou , Valizadeh Amir , Shenas Mohammad Hossein Musavi , Aghebati‐Maleki Leili , Kafil Hossein Samadi , Mehdizadeh Amir , Yousefi Mehdi
Published: February 2019

Ankylosing spondylitis (AS) is a chronic rheumatic disease which mainly affects the axial skeleton and sacroiliac joints. T‐helper 17 (Th17) cells have been reportedly involved in AS pathogenesis. Nanocurcumin is considered to be beneficial, as an anti‐inflammatory compound, in AS patients treatment. In this study, Th17‐related immunological parameters were evaluated in AS patients. Transcription factors messenger RNA (mRNA) expression level, cytokines, and related microRNAs (miRNAs) were measured by real‐time polymerase chain reaction. Additionally, Th17 frequency and cytokines secretion were evaluated by flow cytometry and enzyme‐linked immunosorbent assay tests, respectively. The frequency of Th17 was higher in AS patients. Gained data from nanocurcumin group also demonstrated that retinoic acid‐related orphan receptor γ (RORγt) and interleukin‐17 (IL‐17) mRNA expression levels were significantly decreased (P = 0.0001 and 0.0006, respectively), as the decrease also happened in Th17‐associated miRNAs including miR‐141, miR‐155, and miR‐200 (
P = 0.04,
P = 0.02, and
P < 0.0001, respectively). Posttreatment data of miR‐155 and miR‐200 in the nanocurcumin and placebo groups also showed a higher expression level in the placebo group compared with nanocurcumin‐treated patients. Some clinical symptoms of AS patients were also improved at the end of the treatment process. The results of this study showed the potential ability of nanocurcumin to regulate Th17 cells activity in AS patients. This study provided further evidence on the function and underlying mechanism of nanocurcumin helping better treatment of AS.
Macrophage colony‐stimulating factor pretreatment of bone marrow progenitor cells regulates osteoclast differentiation based upon the stage of myeloid development
Authors: Yang Xuehui , Pande Shivangi , Scott Cameron , Friesel Robert
Published: February 2019

Osteoclasts (OCs) are large, multinucleated bone resorbing cells originating from the bone marrow myeloid lineage, and share a common progenitor with macrophages and dendritic cells. Bone marrow cells (BMCs) are a common source for in vitro osteoclastogenesis assays but are a highly heterogeneous mixture of cells. Protocols for in vitro osteoclastogenesis vary considerably thus hindering interpretation and comparison of results between studies. Macrophage colony‐stimulating factor (M‐CSF) pretreatment is commonly used to expand OC progenitors (OCPs) in BMC cultures before in vitro differentiation. However, the failure of osteoclastogenesis of M‐CSF primed bone marrow myeloid blasts has been reported. In this study, we used a simple method of differential adherence to plastic to enrich OCP from mouse BMCs. We found that M‐CSF pretreatment of plastic‐adherent BMCs (adBMCs) increased the number of CD11b‐F4/80+ macrophages and decreased the number of CD11b+ monocytes resulting in decreased OC formation. M‐CSF pretreatment of purified c‐Kit+ progenitors weakly inhibited OC formation, whereas M‐CSF pretreatment of purified c‐Kit‐CD11b+ progenitors promoted the formation of large OC. M‐CSF pretreatment increased the proliferation of both purified c‐Kit+ and c‐Kit‐CD11b+ cells and increased the percentage of CD11b‐F4/80+ cells from c‐Kit+ progenitors. In addition, M‐CSF pretreatment increased the percentage of CD11b+ F4/80− cells from purified c‐Kit‐CD11b+ cells. M‐CSF pretreatment increased the percentage of CD14 + CD16 + intermediate monocytes and subsequent OC formation from human 2adBMCs, and increased OC formation of purified CD14 + cells. Together, these results indicate that in vitro OCP expansion in the presence of M‐CSF and bone marrow stromal cells is dependent upon the developmental stage of myeloid cells, in which M‐CSF favors macrophage differentiation of multipotent progenitors, promotes monocyte maturation and supports differentiation of late‐stage OCP cells.
Circulating lncRNA ITSN1‐2 is upregulated, and its high expression correlates with increased disease severity, elevated inflammation, and poor survival in sepsis patients
Authors: Zeng Qingwei , Wu Jingdong , Yang Shijiang
Published: February 2019

Background

This study aimed to assess the correlation of long noncoding (lnc) RNA intersectin (ITSN) 1‐2 expression with disease risk, severity, inflammation, and survival in sepsis patients.

Methods

Three hundred and nine intensive care unit (ICU)‐treated sepsis patients and 300 healthy controls were consecutively recruited in this study. Blood samples were collected from all sepsis patients within 24 hours after admitted to ICU and from healthy controls at the time of health screening, and the expression of lncRNA ITSN1‐2 in plasma was detected by quantitative polymerase chain reaction. Disease severity was assessed by physicians using acute physiology and chronic health evaluation (APACHE) II score on day 1 after ICU admission. Additionally, the plasma inflammatory cytokines (including tumor necrosis factor α (TNF‐α), interleukin 1β (IL‐1β), IL‐6, IL‐8, IL‐10, and IL‐17) were measured by enzyme‐linked immunosorbent assay (ELISA) kits.

Results

lncRNA ITSN1‐2 was highly expressed in sepsis patients compared to healthy controls and could differentiate sepsis patients from healthy controls with area under the curve (AUC) 0.777 (95% CI: 0.740‐0.813). lncRNA ITSN1‐2 expression was positively correlated with APACHE II score, C‐reactive protein (CRP), TNF‐α, IL‐6, and IL‐8 levels, but negatively correlated with IL‐10 level. In addition, lncRNA ITSN1‐2 was highly expressed in non‐survivors compared to survivors and could distinguish survivors from non‐survivors in sepsis patients with AUC 0.654 (95% CI: 0.581‐0.726).

Conclusion

Circulating lncRNA ITSN1‐2 is upregulated, and its high expression associates with increased disease severity and inflammation as well as poor prognosis in sepsis patients.
Detection of Ureaplasma spp. serovars in genital tract of infertile males
Authors: Song Tiejun , Liu Zhiwei , Zhang Ying , Han Yetao , Huang Jun
Published: February 2019

Background

The colonization of Ureaplasma species in genital tract is related with male infertility. However, it has been postulated based upon limited study that virulence is related to serotype specificity. The aim of this study was to determine the distribution of Ureaplasma serovars in genital tract of infertile males and analyze their role in male infertility.

Methods

A total of 358 urethral swabs samples were obtained from infertile males. The culture of Ureaplasma species were performed using a commercially available Mycoplasma IST 2 kit. Serovars were determined by real‐time polymerase chain reaction (real‐time PCR).

Results

A total of 92 (25.7%) infertile males were positive for Ureaplasma spp; among them, Ureaplasma parvum (UPA) was detected in 73 (79.3%) isolates, and Ureaplasma urealyticum (UUR) was detected in 19 (20.7%) isolates. Serovars 1, 6, or in combination accounted for 63.0% (46/73) of UPA isolates. Serovar 9 (alone and in combination of other serovars) was the most common serovar in UUR (47.4%, 9/19). Multiple serovars were detected in 21 (22.8%) isolates, and serovars 4, 5, 7, and 12 were not detected in any sample.

Conclusion

The distribution of 14 Ureaplasma serovars in genital tract of infertile males was identified for the first time by real‐time PCR assay. UPA serovars 1 and 6, and UUR serovar 9 are the most common serovars colonization in urogenital tract of infertile males.
Sample‐to‐cutoff ratios using Architect HIV Ag/Ab Combo: The influence with the results of supplemental tests and optimal cutoff value to predict HIV infection
Authors: Wang Linchuan , Wang Jing‐Yuan , Tian Xu‐Dong , Ruan Jin‐xiong , Yu Yan , Yan Fang
Published: February 2019

Background

The Architect HIV Ag/Ab Combo has excellent performance for HIV screening; however, the false‐positive rate (FPR) was high in low HIV prevalence setting.

Objectives

The purpose of this study was to analyze the influence of sample‐to‐cutoff (s/co) ratios by Architect HIV Ag/Ab Combo with the results of confirmatory test and explore the potential utility of s/co to predict HIV infection.

Methods

A retrospective review on Architect HIV Ag/Ab Combo reactive results was performed at a teaching hospital in Xi'an. The s/co values in different groups, that is, true positives (TP) and false positives (FP), different Western blotting (WB) bands among WB‐positive cases, were compared. The receiver operating characteristic curve (ROC) analysis was used to determine the optimal cutoff value for predicting HIV infection.

Results

During the study period, 219 out of 84 702 patients were reactive by ARCHITECT with a 0.0992% of HIV prevalence and a 56.25% of FPR. The mean s/co ratios in TP were significantly higher than that in FP (458.15 vs 3.11, P < 0.0001). Among the WB‐positive cases, the s/co ratios increased significantly with the increase in the number of bands, P = 0.0065. The optimal cutoff (24.44) by ROC analysis can provide the highest sum of sensitivity (100%) and specificity (100%) with no FP results.

Conclusions

For Architect HIV Ag/Ab Combo, the FPR is reduced when s/co ratios increase, and the s/co ≥24.44 may be reliable to predict HIV infection.
Study on the diagnosis of gout with xanthine and hypoxanthine
Authors: Wang Yu , Deng Miao , Deng Binge , Ye Liming , Fei Xiaofan , Huang Zhigang
Published: February 2019

Background

Hyperuricemia is the only biochemical index in the classification of acute gouty arthritis in American Rheumatism Association 1977 and the main basis of clinical diagnosis for most doctors. However, nearly half of the time gout occurs without hyperuricemia, especially in an acute attack，which leads to an urgent need to find a new substitute diadynamic criteria of gout. Xanthine and hypoxanthine, as precursors of uric acid, have been reported to be high in gout patients with hyperuricemia and presumed to be gout biomarkers.

Objectives

To further explore the possibility of xanthine and hypoxanthine to be gout biomarkers as substitutes for uric acid.

Methods

A reversed‐phase HPLC‐UV method was employed for simultaneous quantitative detection of uric acid (UA), xanthine (X), and hypoxanthine (HX) in gout patients’ (with and without hyperuricemia) and healthy persons’ serum.

Results

The xanthine and hypoxanthine concentrations in gout patients with hyperuricemia and without hyperuricemia are higher than in healthy persons with a P < 0.001.

Conclusions

This study supplements previous researches by confirming that xanthine and hypoxanthine are significantly elevated in gout patients’ serum especially in patients’ with normouricemia, which supported xanthine and hypoxanthine may have clinical application for the diagnosis of gout.
Rumination moderates the role of meaning in the development of prolonged grief symptomatology
Authors: Milman Evgenia , Neimeyer Robert A. , Fitzpatrick Marilyn , MacKinnon Christopher J. , Muis Krista R. , Cohen S. Robin
Published: February 2019

Objective:

To address the etiology of prolonged grief disorder (PGD) by examining whether rumination moderates the role of meaning‐making in mediating the impact of PGD risk factors.

Method:

A survey assessing PGD risk factors (low social support, insecure attachment, violent loss, neuroticism, and loss of a spouse), meaning, and rumination was administered 2–12 months postloss among adults across North America and Europe (mean age = 44.3, 71.9% female). At a 7–10 months follow‐up, symptoms of PGD were assessed (n = 171).

Results:

When measuring meaning with the Grief and Meaning Reconstruction Inventory, the moderated mediation pathway was significant for each PGD‐risk factor. However, when measuring meaning with the Integration of Stressful Life Experiences‐Short Form, the pathway was significant for every risk factors except violent loss.

Conclusions:

Rumination appears to moderate meaning‐making in the development of PGD symptomatology. These findings highlight rumination as a target for intervention with at‐risk grievers.
Bicultural stress, coping, and psychological functioning among Mexican‐descent and White college students
Authors: Piña‐Watson Brandy , Romero Andrea J. , Navarro Rachel L. , Ojeda Lizette
Published: February 2019

Objective

The present study investigates associations between bicultural stress, coping, and responses to stress (RTS) in relation to depressive symptoms and self‐esteem for Mexican‐descent and non‐Latinx White college students.

Method

With a sample of 268 Mexican‐descent and non‐Latinx White college students, two multiple‐mediation path models and two moderation models are examined.

Results

The hypothesized mediation models were both supported indicating higher bicultural stress is associated with higher reporting of engaged and disengaged forms of coping and RTS. Engaged coping was associated with mental health resiliency while disengaged coping and RTS contributed to vulnerability. Disengaged and secondary engaged coping were mediators in the depressive symptoms and self‐esteem models. In terms of moderation, disengaged coping and RTS were both moderators in the bicultural stress–depressive symptoms relationships.

Conclusions

College students' reactions to bicultural stress may either promote mental health resiliency through engaged strategies or increase vulnerability through disengaged coping and involuntary RTS.
Role of the novel gene BZW2 in the development of hepatocellular carcinoma
Authors: Jin Xin , Liao Mingmei , Zhang Lihua , Yang Manyi , Zhao Jinfeng
Published: February 2019

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in adults. Basic leucine zipper and W2 domains 2 (BZW2) is a member of the basic‐region leucine zipper (bZIP) superfamily of transcription factors. Here, we found that BZW2 expression was substantially increased in both human HCC tissues and cell lines, which was correlated with the clinical progression of patients with HCC. Silence of BZW2 in HCC cells by infecting with the lentivirus for delivering BZW2 shRNA (short hairpin RNA), prohibits cell progression, as determined by the suppressed cell proliferation, clonality, invasion, and increased cell apoptosis. Furthermore, overexpression of BZW2 promotes drug resistance of HCC cells, as shown by the attenuated suppression of cell viability and invasion following rapamycin (RAPA) treatment. Mechanistically, overexpression (or silence) of BZW2 in HCC cells significantly stimulates (or decreases) the activation of the PI3K/AKT/mTOR signaling pathway, which is responsible for HCC progression. Thus, increased BZW2 expression in HCC can induce HCC progression and drug resistance via stimulating the PI3K/AKT/mTOR pathway, which may represent a new therapeutic target for HCC.
Hepatocyte growth factor plays a dual role in tendon‐derived stem cell proliferation, migration, and differentiation
Authors: Han Peilin , Cui Qingbo , Lu Wenjun , Yang Shulong , Shi Manyu , Li Zhou , Gao Peng , Xu Bo , Li Zhaozhu
Published: February 2019

Heterotopic ossification is common in tendon healing after trauma, but the detailed mechanisms remain unknown. Tendon‐derived stem cells (TDSCs) are a type of progenitor cell found in the tendon niche, and their incorrect differentiation after trauma may lead to tendon calcification. The expression of hepatocyte growth factor (HGF) presents drastic fluctuations in serum/tissue after trauma and was found to activate quiescent stellate cells and contribute to wound healing; however, its potential role in TDSCs remains elusive. In this study, TDSCs isolated from rats were cultured in media containing HGF with or without a signaling inhibitor, and the proliferation, migration, and differentiation ability of TDSCs were measured to determine the role and mechanism of HGF in TDSCs. We showed that HGF promotes TDSC proliferation and migration but inhibits TDSC osteogenic differentiation ability. HGF activated‐HGF/c‐Met, mitogen‐activated protein kinase (MAPK)/extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2), and phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT) signaling, which was positively correlated with TDSCs proliferation and migration but negatively related to TDSC osteogenic differentiation ability. The phosphorylation of Smad1/5/8 was also negatively related to HGF/c‐Met, MAPK/ERK1/2, and PI3K/AKT signaling, which demonstrated that the inhibition of osteogenic differentiation was dependent on BMP/Smad1/5/8 signaling. Overall, we showed that HGF could promote TDSCs proliferation and migration and inhibit osteogenic differentiation in vitro, suggesting a potential role for HGF as a cytokine treatment of tendon trauma.
Comparison of student team dynamics between nonflipped and flipped versions of a large‐enrollment sophomore design engineering course
Authors: Baughman Jacqulyn , Hassall Lesya , Xu Xiaowei
Published: February 2019

Background

This study examined the differences between team dynamics in nonflipped and flipped versions of a multisection team‐ and project‐based sophomore engineering design course.

Purpose/Hypothesis

We hypothesized that team dynamics in nonflipped and flipped course settings may reveal differences in student perceptions of team conflict, peer assessment, and team member satisfaction as well as possible relationships among these three variables.

Design/Method

Students in both nonflipped and flipped settings completed a web‐based Comprehensive Assessment of Team Member Effectiveness (CATME) SMARTER Teamwork survey. A series of ANCOVAs and path analyses were conducted to gain insights into team dynamics in both course environments.

Results

Although no significant differences in team conflict were found, significantly higher levels of team member satisfaction and peer assessment rates were detected in the flipped course. The path analysis revealed relationships among team conflict, team member satisfaction, and peer assessment in both course versions. Differences in relationships among the unidimensional levels of team conflict and the other two variables were found between the nonflipped and flipped versions.

Conclusions

The primary pedagogical implication of this research points to the affordance of the flipped course setting in providing sufficient time for student members to become cohesive teams. As part of the student experience, engineering educators are encouraged to allow time for team formation and development in addition to content learning. Instructors should provide guidance that helps teams and individuals understand themselves and others as well as create workflows to support their learning and team management.
Morphology and distribution of antennal sensilla in egg parasitoid, Ooencyrtus nezarae (Hymenoptera: Encyrtidae)
Authors: Roh Gwang Hyun , Lee Yeon Jeong , Zhu Junwei J. , Park Chung Gyoo
Published: February 2019

Morphology of antennal sensilla and their distribution were investigated in adults of Ooencyrtus nezarae, an egg parasitoid of Riptortus pedestris, using scanning electron microscopy. Male antennae was found to be significantly greater in overall length than female antennae. The antenna of O. nezarae was composed of the radicula, scape, pedicel, funicle and clava in both sexes, with seven types of sensilla identified: sensillum trichodea; s. finger‐like; s. placoidea; s. chaetica; s. basiconica; s. coeloconica, and s. campaniform. They occur in varying number and distribution along the antennae. Two sensillum types were further categorized into additional subtypes, with two subtypes in s. trichodea and three in s. chaetica. Among all characterized sensilla, s. trichodea subtype 1 and s. placoidea were multiporous, indicating that the primary function of these sensilla is olfactory. Sensillum trichodea was the most abundant sensillum type on the antennae of both sexes. Sexual dimorphism was only observed from the subtype 1 sensilla of s. trichodea in males and the subtype 3 sensilla of s. chaetica in females. The morphological information established in our study may provide useful information for further investigations in sensory physiological function of each morphological type of sensilla and their related behavior in this egg parasitoid.
Antimalarial drugs and their metabolites are potent Zika virus inhibitors
Authors: Han Yingshan , Pham Hanh T. , Xu Hongtao , Quan Yudong , Mesplède Thibault
Published: February 2019

Studies aimed at repurposing existing drugs revealed that some antimalarial compounds possess anti‐Zika virus (anti‐ZIKV) activity. Here, we further tested 14 additional antimalarial drugs and their metabolites or analogs for anti‐ZIKV activity using a phenotypic screening approach. We identified four compounds with varying anti‐ZIKV activity, including a metabolite of amodiaquine termed desethylamodiaquine (DAQ) and N‐desethylchloroquine (DECQ), a metabolite of chloroquine, which both exhibited low micromolar effective concentrations against three different ZIKV strains. Two other compounds termed dihydroartemisinin (DHA) and quinidine (QD) exhibited only partial inhibition of ZIKV replication. Characterization of the inhibitory mechanisms of DAQ and DECQ showed that both drugs target the entry step as well as postentry events of the viral replication cycle. These hits represent attractive starting points for future optimization of new anti‐ZIKV drug candidates derived from antimalarial drugs and their analogs.
Performance of a simple reanalysis proxy for U.S. cloud‐to‐ground lightning
Authors: Tippett Michael K. , Lepore Chiara , Koshak William J. , Chronis Themis , Vant‐Hull Brian
Published: February 2019

The product of convective available potential energy (CAPE) and precipitation rate has previously been used as a proxy for cloud‐to‐ground (CG) lightning flash counts in climate change applications. Here, the ability of this proxy, denoted CP, to represent the climatology and variability of CG lightning flash counts over the contiguous United States (CONUS) during the period 2003–2016 is assessed. CP values computed using the North American Regional Reanalysis are compared with negative and positive polarity CG flash counts from the National Lightning Detection Network. Overall, the proxy performs better on shorter time scales (daily and monthly) than on longer time scales (annual and semi‐annual). Proxy performance tends to be worse during the warm season (May–October), when most lightning occurs, and better during the cool season (November–April). The correlation of annually accumulated CONUS CP with CG flash counts is not statistically significant because of poor warm‐season performance. Cool season negative CG flash counts are well correlated with CONUS CP values. Positive CG flash counts (∼7% of all CG flashes) are well correlated with annual values of CONUS CP. The relatively strong relations between CP and CG flash counts in some regions and times of the year at daily resolution provide a benchmark for more complex proxies and suggest that proxy‐based extended‐ and long‐range prediction of lightning activity may be feasible to the extent that precipitation rate and CAPE can be predicted.
Nearly half of children, teens with MH disorders not receiving treatment
Authors: Canady Valerie A.
Published: February 2019

Half of the estimated children with a treatable mental health condition did not receive treatment from a mental health professional, according to new research providing national and state‐level estimates of the prevalence of mental health disorders and care in children. The research letter was published online Feb. 11 in JAMA Pediatrics.
APA policy calls spanking harmful discipline for children
Authors: Canady Valerie A.
Published: February 2019

A new resolution adopted by the American Psychological Association (APA) noted that scientific evidence demonstrates that physical discipline of children by parents and other caregivers can harm children's mental health and possibly increase their propensity toward aggressive behavior. Instead, alternative forms of discipline that are associated with more positive outcomes for children — such as reasoning, time out, taking away privileges, warnings and ignoring misbehavior — are recommended, officials stated in a release.
Heterogeneously integrated resonant waveguide grating structure on magneto‐active elastomeric sponge
Authors: Ray Chaudhuri Ritesh , Rostami Azmand Hojjat , Song Youngsik , Seo Sang‐Woo
Published: February 2019

In this article, we employ thin‐film resonant waveguide grating structure on magneto‐active elastomeric sponge using a delamination‐assisted transfer process. Periodic nanostructured polymer layer was successfully separated from its host substrate and transferred onto a spongy elastomeric structure embedded with magnetic nanoparticles as a magneto‐optical sensor. The fabricated magnetic sensor shows potential sensing enhancement from optical resonance characteristics. Based on a post‐integration scheme, the presented approach can be applied to various nonplanar structures, which opens new avenues for low‐cost novel sensing applications.
Single‐shot measurement of solids and liquids T1 values by a small‐angle flip‐flop pulse sequence
Authors: Cucinelli Neto Roberto Pinto , Rodrigues Elton Jorge da Rocha , Tavares Maria Inês Bruno
Published: February 2019

We propose the small‐angle flip‐flop (SAFF) pulse sequence as an alternative procedure for the rapid measurement of the 1H spin–lattice relaxation time in the laboratory frame (T1) of solid and liquid substances, in a time‐domain NMR experiment. Based on the original flip‐flop pulse sequence, this technique allows the fast estimation of T1 values of samples that require minutes to hours of acquisition time if traditional pulse sequences are employed. We have applied SAFF to different substances, with T1 ranging from microseconds up to seconds, including natural clays, polymers, and organic and inorganic solvents. We also demonstrate the potential of the pulse sequence in the real‐time monitoring of dynamic processes, such as the conformational changes of polymeric materials during heating. The results we obtained with SAFF are comparable with those acquired with the inversion‐recovery pulse sequence, with the addition of several benefits. This pulse sequence obeys steady‐state and magnetization‐conserving principles, making it possible to dismiss the need for relaxation delay times of the order of 5T1. SAFF has shown high sensitivity in the resolution of individual components of T1 in multiexponential systems and can be easily integrated to well‐established pulse sequences, such as Magic Sandwich Echo and Carr–Purcell–Meiboom–Gill, for the single‐shot determination of T1 and T2 or T2*.
Detection of the effects and potential interactions of FSH, VEGFA, and 2‐methoxyestradiol in follicular angiogenesis, growth, and atresia in mouse ovaries
Authors: Zhang Jinbi , Zhang Jun , Gao Beibei , Xu Yinxue , Liu Honglin , Pan Zengxiang
Published: February 2019

Ovarian follicular development is a complex process that requires codevelopment of the perifollicular vascular network, which is closely regulated by angiogenic factors, gonadotropins, sex steroids, and their metabolites. To detect the effects of vascular endothelial growth factor 120 (VEGF120), follicle‐stimulating hormone (FSH), and 2‐methoxyestradiol (2ME2) on follicular angiogenesis during development and atresia, we treated sexually immature and mature female mice with VEGF120, FSH, 2ME2, and FSH receptor (FSHR) antagonist singly or in combination via intraperitoneal injection. The number of follicles and their perifollicular angiogenesis and atresia rates at different developmental stages were examined in paraffin sections after hematoxylin and eosin staining. The results showed that the exogenous factors have specific and precise effects on developmental, angiogenesis, and atresia processes in follicles of different sizes in mature and immature mice. Perifollicular angiogenesis was regulated by VEGFA and closely related to follicular development and atresia. 2ME2 affected angiogenesis through VEGFA and might regulate atresia directly. FSH might control VEGFA function via both transcriptional and posttranscriptional mechanisms because FSHR was required for achieving VEGFA functions at all the follicular development stages. The present study presents insights into the mechanisms of FSH, 2ME2, and VEGFA in follicular development and disorders and provides a foundation for the development of new therapeutic strategies.
Team orienteering with uncertain rewards and service times with an application to phlebotomist intrahospital routing
Authors: Jin Huan , Thomas Barrett W.
Published: February 2019

This study focuses on the intrahospital routing of phlebotomists at the University of Iowa Hospitals and Clinics (UIHC). Phlebotomists are responsible for drawing specimens from patients based on doctors' orders. The results of the analysis of these specimens play an important role in determining patient treatment. However, the demand for phlebotomists is likely to outpace supply over the next few years. Therefore, it is important to improve the efficiency of phlebotomists. In this paper, we formulate the phlebotomist intrahospital routing problem as a team orienteering problem with stochastic rewards and service times. The rewards and service times are particularly interesting as they are the result of a queueing process. We present an a priori solution approach and derive a method for efficiently sampling the value of a solution, a value that cannot be determined analytically. Finally, we demonstrate that our proposed approach outperforms the current practice at UIHC.
A C0 interior penalty discontinuous Galerkin Method for fourth‐order total variation flow. II: Existence and uniqueness
Authors: Bhandari Chandi , Hoppe Ronald H.W. , Kumar Rahul
Published: February 2019

We prove the existence and uniqueness of a solution of a C0 Interior Penalty Discontinuous Galerkin (C0 IPDG) method for the numerical solution of a fourth‐order total variation flow problem that has been developed in part I of the paper. The proof relies on a nonlinear version of the Lax‐Milgram Lemma. It requires to establish that the nonlinear operator associated with the C0 IPDG approximation is Lipschitz continuous and strongly monotone on bounded sets of the underlying finite element space.