bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of ubiquitin ligase E3A in polarized contact guidance and rescue strategies in UBE3A-deficient hippocampal neurons
Authors: Tonazzini Ilaria , Van Woerden Geeske M. , Masciullo Cecilia , Mientjes Edwin J. , Elgersma Ype , Cecchini Marco
Published: November 2019

Background

Although neuronal extracellular sensing is emerging as crucial for brain wiring and therefore plasticity, little is known about these processes in neurodevelopmental disorders. Ubiquitin protein ligase E3A (UBE3A) plays a key role in neurodevelopment. Lack of UBE3A leads to Angelman syndrome (AS), while its increase is among the most prevalent genetic causes of autism (e.g., Dup15q syndrome). By using microstructured substrates that can induce specific directional stimuli in cells, we previously found deficient topographical contact guidance in AS neurons, which was linked to a dysregulated activation of the focal adhesion pathway.

Methods

Here, we study axon and dendrite contact guidance and neuronal morphological features of wild-type, AS, and UBE3A-overexpressing neurons (Dup15q autism model) on micrograting substrates, with the aim to clarify the role of UBE3A in neuronal guidance.

Results

We found that loss of axonal contact guidance is specific for AS neurons while UBE3A overexpression does not affect neuronal directional polarization along microgratings. Deficits at the level of axonal branching, growth cone orientation and actin fiber content, focal adhesion (FA) effectors, and actin fiber–binding proteins were observed in AS neurons. We tested different rescue strategies for restoring correct topographical guidance in AS neurons on microgratings, by either UBE3A protein re-expression or by pharmacological treatments acting on cytoskeleton contractility. Nocodazole, a drug that depolymerizes microtubules and increases cell contractility, rescued AS axonal alignment to the gratings by partially restoring focal adhesion pathway activation. Surprisingly, UBE3A re-expression only resulted in partial rescue of the phenotype.

Conclusions

We identified a specific in vitro deficit in axonal topographical guidance due selectively to the loss of UBE3A, and we further demonstrate that this defective guidance can be rescued to a certain extent by pharmacological or genetic treatment strategies. Overall, cytoskeleton dynamics emerge as important partners in UBE3A-mediated contact guidance responses. These results support the view that UBE3A-related deficits in early neuronal morphogenesis may lead to defective neuronal connectivity and plasticity.
Differences in immune responses to Haemonchus contortus infection in the susceptible Ile de France and the resistant Santa Ines sheep under different anthelmintic treatments regimens
Authors: Albuquerque Ana Cláudia A. , Bassetto Cesar Cristiano , Almeida Fabiana A. , Hildersley Katie A. , McNeilly Tom N. , Britton Collette , Amarante Alessandro F. T.
Published: November 2019

Understanding the immunological basis of resistance to gastrointestinal nematode infections in livestock is important in order to develop novel methods of parasite control such as vaccination or genetic selection for parasite resistance. The present study aimed to investigate differences in immune response between parasite resistant Santa Ines and susceptible Ile de France sheep breeds to naturalHaemonchus contortusinfection. Parasitological parameters, humoral immunity, local and circulating cellular immune responses were evaluated in 19 Santa Ines and 19 Ile de France lambs undergoing different anthelmintic treatments regimens: suppressive treatments (SUP) or targeted selective treatments (TST) over a 5-month grazing period. Santa Ines lambs had significantly lowerHaemonchusfaecal egg count and worm burden compared to Ile de France regardless of treatment regime. In addition, circulating blood eosinophils count and parasite-specific IgG levels were significantly higher and more rapidly induced in Santa Ines lambs. Abomasal immune responses were generally greater in the resistant breed, which had significantly higher levels of parasite-specific IgA in mucus, and elevated number of globule leukocytes and CD3+ T cells within the abomasal mucosal. Furthermore, numbers of POU2F3+ epithelial cells, a tuft-cell specific transcription factor, were also elevated in the Santa Ines breed, suggesting that this breed is better able to initiate T-helper type 2 immune responses within the abomasum. In conclusion, the differential immunological responses detailed here are relevant to understanding resistance to gastrointestinal nematodes in other host breeds, as well as to resistance breeding as a sustainable control approach for parasitic infections.
Hsa_circ_0051079 functions as an oncogene by regulating miR-26a-5p/TGF-β1 in osteosarcoma
Authors: Zhang Zuojun , Zhao Ming , Wang Guojie
Published: November 2019

Background

Osteosarcoma is a most common bone malignant tumor which threatens children and adolescents. Circular RNAs (circRNAs) fundamentally play essential roles in the progress and development of human cancers by sponging with microRNAs (miRNAs). However, the role of circRNAs in osteosarcoma is not clear. The aim of the study was to investigate the roles and molecular mechanism of circRNAs in osteosarcoma.

Results

The data from qRT-PCR showed that circ_0051079 expression was higher in osteosarcoma cells and tissues compared to their normal controls. Meanwhile, bioinformatic analysis indicated that circ_0051079 was a sponge of miR-26a-5p, which was verified by luciferase activity assay. Subsequently, TGF-β1 was verified as a putative target mRNA of miR-26a-5p by luciferase assay. Cellular function assays were conducted and the findings revealed that circ_0051079/miR-26a-5p/TGF-β1 regulated osteosarcoma proliferation and metastasis.

Conclusion

The study demonstrated that circ_0051079 could act as an oncogene via regulating miR-26a-5p/TGF-β1 and a potential biomarker for osteosarcoma diagnose.
PRL2 serves as a negative regulator in cell adaptation to oxidative stress
Authors: Du Xinyue , Zhang Yang , Li Xiao , Li Qi , Wu Chenyun , Chen Guangjie , Guo XiaoKui , Weng Yongqiang , Wang Zhaojun
Published: November 2019

High levels of ROS cause oxidative stress, which plays a critical role in cell death. As a ROS effector protein, PRL2 senses ROS and controls phagocyte bactericidal activity during infection. Here we report PRL2 regulates oxidative stress induced cell death. PRL2 senses oxidative stress via highly reactive cysteine residues at 46 and 101. The oxidation of PRL2 causes protein degradation and supports pro-survival PDK1/AKT signal which in turn to protect cells against oxidative stress. As a result, PRL2 levels have a high correlation with oxidative stress induced cell death. In vivo experiments showed PRL2 deficient cells survive better in inflammatory oxidative environment and resist to ionizing radiation. Our finding suggests PRL2 serves as a negative regulator in cell adaptation to oxidative stress. Therefore, PRL2 could be targeted to modulate cell viability in inflammation or irradiation associated therapy.
New refinements for integral and sum forms of Hölder inequality
Authors: İşcan İmdat
Published: November 2019

In this paper, we establish new refinements for integral and sum forms of Hölder inequality. Many existing inequalities related to the Hölder inequality can be improved via newly obtained inequalities, which we illustrate by an application.
Noninvasive prenatal testing for chromosome aneuploidies and subchromosomal microdeletions/microduplications in a cohort of 42,910 single pregnancies with different clinical features
Authors: Chen Yibo , Yu Qi , Mao Xiongying , Lei Wei , He Miaonan , Lu Wenbo
Published: November 2019

Background

Since the discovery of cell-free DNA (cfDNA) in maternal plasma, it has opened up new approaches for non-invasive prenatal testing. With the development of whole-genome sequencing, small subchromosomal deletions and duplications could be found by NIPT. This study is to review the efficacy of NIPT as a screening test for aneuploidies and CNVs in 42,910 single pregnancies.

Methods

A total of 42,910 single pregnancies with different clinical features were recruited. The cell-free fetal DNA was directly sequenced. Each of the chromosome aneuploidies and the subchromosomal microdeletions/microduplications of PPV were analyzed.

Results

A total of 534 pregnancies (1.24%) were abnormal results detected by NIPT, and 403 pregnancies had underwent prenatal diagnosis. The positive predictive value (PPV) for trisomy 21(T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies (SCAs), and other chromosome aneuploidy was 79.23%, 54.84%, 13.79%, 33.04%, and 9.38% respectively. The PPV for CNVs was 28.99%. The PPV for CNVs ≤ 5 Mb is 20.83%, for within 5–10 Mb 50.00%, for > 10 Mb 27.27% respectively. PPVs of NIPT according to pregnancies characteristics are also different.

Conclusion

Our data have potential significance in demonstrating the usefulness of NIPT profiling not only for common whole chromosome aneuploidies but also for CNVs. However, this newest method is still in its infancy for CNVs. There is still a need for clinical validation studies with accurate detection rates and false positive rates in clinical practice.
Functional analysis of granulocyte and monocyte subpopulations in neonates
Authors: Hegge Ines , Niepel Ferry , Lange Anja , Vogelgesang Antje , Heckmann Matthias , Ruhnau Johanna
Published: November 2019

Background

Neonate immune cell functions lack full protection against pathogens. This could be either defect or protective mechanism against overshooting proinflammatory immune responses.

We here analysed the function of classical, pro- and anti-inflammatory monocytes and granulocytes from neonates in comparison with adults to investigate if suppressed functions of subpopulations are causative for the unique neonatal immune status. Therefore, reactive oxygen species (ROS) and surface activation markers were quantified in subpopulations.

Methods

In a prospective, longitudinal study granulocyte and monocyte subpopulations were analysed in healthy term infants (> 37 week;n = 13) in comparison with healthy young adults (n = 11). Percentage (%) of cells expressing surface marker (HLA-DR, CD11b, CD62L, CD32, Toll-Like-Receptor-2) and expression per cell, determined by mean fluorescence intensity (MFI), were measured by flow cytometry. ROS production was induced by fMLP, PMA andE. coliin term neonates (> 37 week;n = 13).

Results

Classical granulocytes were down- and proinflammatory granulocytes upregulated in neonates compared with adults. Percentage of TLR-2 expressing granulocytes was increased in neonates. Granulocytic ROS production depended on stimulation. The percentage of anti-inflammatory monocytes was increased, while classical monocytes were reduced in neonates. HLA-DR (%, MFI) showed reduction for all monocyte subpopulations, while CD32, CD11b, CD62L and TLR-2 were differently regulated in comparison with adults.

Conclusions

Differentially regulated granulocyte and monocyte subpopulations indicate a unique state of neonatal immunity to fight infections and prevent dysregulation. Further studies are needed to investigate the role of reduced granulocytic ROS formation and reduced monocytic HLA-DR in active disease.
Psychosocial support for parents of extremely preterm infants in neonatal intensive care: a qualitative interview study
Authors: Bry Anna , Wigert Helena
Published: November 2019

Background

Extremely premature infants (those born before 28 weeks’ gestational age) are highly immature, requiring months of care at a neonatal intensive care unit (NICU). For parents, their child’s grave medical condition and prolonged hospitalization are stressful and psychologically disruptive. This study aimed at exploring the needs of psychosocial support of parents of extremely premature infants, and how the NICU as an organization and its staff meets or fails to meet these needs.

Method

Sixteen open-ended interviews were conducted with 27 parents after their infant’s discharge from the NICU. Inductive content analysis was performed.

Results

Four themes were identified: Emotional support (with subthemes Empathic treatment by staff, Other parents as a unique source of support, Unclear roles of the various professions); Feeling able to trust the health care provider; Support in balancing time spent with the infant and other responsibilities; Privacy.

Parents of extremely premature infants needed various forms of emotional support at the NICU, including support from staff, professional psychological help and/or companionship with other patients’ parents. Parents were highly variable in their desire to discuss their emotional state with staff. The respective roles of nursing staff, social workers and psychologists in supporting parents emotionally and identifying particularly vulnerable parents appeared unclear. Parents also needed to be able to maintain a solid sense of trust in the NICU and its staff. Poor communication with and among staff, partly due to staff discontinuity, damaged trust. Parents struggled with perceived pressure from staff to be at the hospital more than they could manage and with the limited privacy of the NICU.

Conclusions

The complex and individual psychosocial needs of parents of extremely preterm infants present many challenges for the NICU and its staff. Increasing staffing and improving nurses’ competence in addressing psychosocial aspects of neonatal care would help both nurses and families. Clarifying the roles of different professions in supporting parents and developing their teamwork would lessen the burden on nurses. Communicating with parents about their needs and informing them early in their NICU stay about available support would be essential in helping them cope with their infant’s hospitalization.
Antihistamine effects and safety of fexofenadine: a systematic review and Meta-analysis of randomized controlled trials
Authors: Huang Cheng-zhi , Jiang Zhi-hui , Wang Jian , Luo Yue , Peng Hua
Published: November 2019

Background

As a new generation antihistamine, fexofenadine has been widely used in allergic diseases. However, there is still a lack of collective evidence regarding the antihistamine effects and safety profiles of fexofenadine relative to other antihistamine drugs and placebo. Therefore, we aimed to systematically evaluate the antihistamine effects and safety of fexofenadine.

Methods

An electronic literature search of randomized controlled trials (RCTs) was performed using Embase, Cochrane and PubMed from establishment to January 1st, 2018. RCTs comparing the antihistamine effects or safety (adverse events, sedative effects, and cognitive/psychomotor function) of fexofenadine with either other antihistamines or placebo for healthy subjects and patients with allergy were selected.

Results

Fifty-one studies of 14,551 participants met the inclusion criteria. When compared with the first-generation antihistamines, fexofenadine produced significantly lower adverse events frequency (OR = 0.446; 95% CI: 0.214 to 0.929, P = 0.031), significantly lower sedative effects frequency (OR = 0.265; 95% CI: 0.072 to 0.976, P = 0.046) and significantly less change of all cognitive/psychomotor function. When compared with the second-generation antihistamines, fexofenadine produced significantly marginal sedative effects (OR = 0.59; 95% CI, 0.38 to 0.93; P = 0.02) and significantly less change of most of the cognitive/psychomotor function. When compared with placebo, fexofenadine produced more significant antihistamine effects.

Conclusions

Fexofenadine has a positive antihistamine effect, which is probably no worse than the second-generation antihistamines. Fexofenadine probably has a favorable safety profile, which is more likely better than that of the first-generation antihistamines. There is lack of data to support that fexofenadine has a better overall safety profile compared to the second-generation antihistamines, however, some presently available evidence on sedative effects and certain aspects of cognitive/psychomotor function favors fexofenadine. Therefore, fexofenadine may be worthy of recommendation for safety related workers.
Reduction of the fluorine-18-labeled fluorodeoxyglucose dose for clinically dedicated breast positron emission tomography
Authors: Satoh Yoko , Sekine Tetsuro , Omiya Yoshie , Onishi Hiroshi , Motosugi Utaroh
Published: November 2019

Purpose

To determine the clinically acceptable level of reduction in the injected fluorine-18 (18F)-labeled fluorodeoxyglucose (18F-FDG) dose in dedicated breast positron emission tomography (dbPET).

Methods

A breast phantom with four spheres exhibiting various diameters (5, 7.5, 10, and 16 mm), a background 18F-FDG radioactivity of 2.28 kBq/mL, and a sphere-to-background radioactivity ratio of 8:1 was used. True dose-reduced dbPET images were obtained by data acquisition for 20 min in list mode at multiple time points over 7 h of radioactive decay. Simulated dose-reduced images were generated by reconstruction with a portion of the list mode acquisition data. True and simulated dose-reduced images were visually and quantitatively compared. On the basis of the phantom study, dbPET images for 32 breasts of 28 women with abnormal uptake were generated after simulated reduction of the injected 18F-FDG doses; these images were compared with those acquired using current clinical doses.

Results

There were no qualitative differences between true and simulated dose-reduced phantom images. The phantom study revealed that the minimal required dose was 12.5% for the detection of 5-mm spheres and 25% for precise semi-quantification of FDG in the spheres. The 7-min reconstruction with a 100% dose was defined as the reference for the clinical study. The image quality and lesion conspicuity were clinically acceptable for the 25% dose images. Lesion detectability on the 12.5% dose images was maintained despite image quality degradation.

Conclusions

In summary, 25% of the standard 18F-FDG dose for dbPET can provide a clinically acceptable image quality, while 12.5% of the standard dose results in acceptable quality in terms of lesion detection when lesions are located at a sufficient distance from the edge of the dbPET detector.
Correctable biliary atresia and cholangiocarcinoma: a case report of a 63-year-old patient
Authors: Nio Masaki , Wada Motoshi , Sasaki Hideyuki , Tanaka Hiromu , Hashimoto Masatoshi , Nakajima Yudai
Published: November 2019

Background

Although cancer occurrence following surgery for biliary atresia has gradually increased, the development of cholangiocarcinoma in a native liver survivor of biliary atresia is extremely rare.

Case presentation

A 3-month-old female patient with the correctable type of biliary atresia underwent a cystoduodenostomy. At 16 years of age, she underwent multiple surgeries including lysis of intestinal adhesions, ileostomy, and gastrojejunostomy at another hospital. At 54 years of age, she underwent lithotomy at the porta hepatis, resection of the residual cystic bile duct with gallbladder, and hepaticojejunostomy in Roux-en-Y fashion. As she approached the age of 63, her computed tomography scan showed no liver tumors. In the following year, she developed cholangiocarcinoma at the porta hepatis and underwent chemotherapy. However, the cancer progressed, and she died before she reached the age of 64 years.

Conclusions

Cholangiocarcinoma is extremely rare in patients with biliary atresia. However, physicians should follow up patients with biliary atresia as closely as possible, as malignant tumors secondary to biliary atresia may increase in number in the near future because of the growing number of long-term survivors with biliary atresia.
Impact of Endemic Infections on HIV Susceptibility in Sub-Saharan Africa
Authors: Yegorov Sergey , Joag Vineet , Galiwango Ronald M. , Good Sara V. , Okech Brenda , Kaul Rupert
Published: November 2019

Human immunodeficiency virus (HIV) remains a leading cause of global morbidity with the highest burden in Sub-Saharan Africa (SSA). For reasons that are incompletely understood, the likelihood of HIV transmission is several fold higher in SSA than in higher income countries, and most of these infections are acquired by young women. Residents of SSA are also exposed to a variety of endemic infections, such as malaria and various helminthiases that could influence mucosal and systemic immunology. Since these immune parameters are important determinants of HIV acquisition and progression, this review explores the possible effects of endemic infections on HIV susceptibility and summarizes current knowledge of the epidemiology and underlying immunological mechanisms by which endemic infections could impact HIV acquisition. A better understanding of the interaction between endemic infections and HIV may enhance HIV prevention programs in SSA.
Aflatoxin exposure in children age 6–12 years: a study protocol of a randomized comparative cross-sectional study in Kenya, East Africa
Authors: Wangia Ruth Nabwire , Githanga David Peter , Wang Jia-Sheng , Anzala Omu Aggrey
Published: November 2019

Background

Aflatoxins (AFs) are naturally occurring fungal metabolites produced by theAspergillaspecies of fungi. The staple food grain, maize (Zea mays), is highly susceptible to AF contamination. In Kenya, contamination of maize supplies by AFs is a recognized public health problem which has resulted in over 600 human deaths. Human exposure to AFs can occur in utero, via breast milk, through weaning foods, and throughout an individual’s lifetime. Recent epidemiological studies have shown that exposure to AFs in early life through diet is a contributing factor to immune suppression, micronutrient deficiency, possible vaccine interference, and impaired growth in children. However, these results remain inconsistent and inconclusive due to lack of randomized controlled studies.

Methods

A randomized school-based cross-sectional study was designed to study AF exposure levels and associated health effects in children between ages 6 and 12 years. Participants were recruited from primary schools within Siaya and Makueni Counties of Kenya, East Africa. The Joint Ethics Committee of the University of Nairobi and Kenyatta National Hospital in Kenya approved the research protocol and procedures for the study. Both parental consent and child assent were obtained before enrollment in the study. Parents were requested to provide household grain samples and fill out questionnaires detailing their sociodemographic information, household dietary patterns, farming practices, and knowledge of AF contamination. Blood samples were collected from children participants, and sera were prepared for analysis of AFB1-lysine which is one of the validated biomarkers for AF exposure.

Discussion

This protocol describes a school-based, cross-sectional study whose objective is to comparatively evaluate the role of AF exposure on adverse health outcomes in children. Specifically, effects of cumulative AF exposure on nutritional status, immune markers, and growth parameters will be assessed.

Trial registration

This study is not a clinical trial, rather a cross-sectional study aimed at providing baseline data on AF exposures in children who live in presumably high versus low AF exposure regions. Results from the study can be used to design interventions and/or prospective cohort studies aimed at studying adverse health effects associated with cumulative AF exposure through diets. The study reference number isP741/12/2017and registered with KNH-UoN Ethics and Research Committee.
Falsely high patient state index during cardiopulmonary bypass with intra-aortic balloon pumping: a case report
Authors: Iwata Shihoko , Sanuki Michiyoshi , Ozaki Makoto
Published: November 2019

Background

The patient state index (PSI) is a parameter of a four-channel electroencephalography (EEG)-derived variable used to assess the depth of anesthesia. A PSI value of 25–50 indicates adequate state of hypnosis, and a value of 100 indicates a fully awake state. Due to reduced interference from electronic devices like electrocautery, falsely high intraoperative PSI values are rarely reported. However, this case report cautions about falsely high PSI during cardiopulmonary bypass (CPB) with intra-aortic balloon pumping (IABP).

Case presentation

A 68-year-old man was scheduled for coronary artery bypass graft surgery with IABP. General anesthesia was maintained using sevoflurane. Initial PSI was between 30 and 50 before CPB. Propofol was administered during CPB, and IABP provided pulsatile flow. IABP was stopped soon after the initiation of CPB, and the ascending aorta was partially clamped to anastomose the saphenous vein graft to the ascending aorta. The PSI value decreased drastically, but with resumption of IABP, the value increased to approximately 80, despite increasing the dose of anesthetics. Meanwhile, the EEG waveform was nearly flat. After discontinuing CPB, the PSI value returned to being extremely low. There was no evidence of intraoperative awareness or instrument trouble.

After reviewing the anesthesia record, the high PSI value was almost consistent with ongoing IABP during CPB. We suspect that the oscillation noise created by IABP during CPB erroneously influences the PSI algorithm, resulting in a falsely high PSI.

Conclusions

Anesthesiologists should note that adherence to pEEG-derived values without discretion may cause errors when monitoring the depth of anesthesia.
Predictors of mortality among adult people living with HIV/AIDS on antiretroviral therapy at Suhul Hospital, Tigrai, Northern Ethiopia: a retrospective follow-up study
Authors: Misgina Kebede Haile , Weldu Meresa Gebremedhin , Gebremariam Tewodros Haile , Weledehaweria Negassie Berhe , Alema Haileslasie Berhane , Gebregiorgis Yosef Sibhatu , Tilahun Yonas Girma
Published: November 2019

Background

Ethiopia is striving to achieve a goal of “zero human immune deficiency virus/acquired immune deficiency syndrome (HIV/AIDS)-related deaths.” However, little has been documented on the factors that hamper the progress towards achieving this goal. Therefore, the ultimate aim of this study was to determine predictors of mortality among adult people living with HIV/AIDS on antiretroviral therapy (ART).

Methods

A retrospective follow-up study was employed on all adult HIV/AIDS patients who started ART between January 1 and December 30, 2010, at Suhul Hospital, Tigrai Region, Northern Ethiopia. Data were collected by trained fourth-year Public Health students using a checklist. Finally, the collected data were entered into SPSS version 16. Then after, Kaplan-Meier curves were used to estimate survival probability, the log-rank test was used for comparing the survival status, and Cox proportional hazards model were applied to determine predictors of mortality.

Results

The median follow-up period was 51 months (ranging between 1 and 60 months, inter-quartile range (IQR) = 14 months). At the end of follow-up, 37 (12.5%) patients were dead. The majority of these cumulative deaths, 19 (51.4%) and 29 (78.4%), occurred within 3 and 4 years of ART initiation respectively. Consuming alcohol (adjusted hazard ratio (AHR) = 2.23, 95% CI = 1.15, 4.32), low body weight (AHR = 2.38, 95% CI = 1.03, 5.54), presence of opportunistic infections (AHR = 2.18, 95% CI = 1.09, 4.37), advanced WHO clinical stage (AHR = 2.75, 95% CI = 1.36, 5.58), and not receiving isoniazid prophylactic therapy (AHR = 3.00, 95% CI = 1.33, 6.74) were found to be independent predictors of mortality.

Conclusion

The overall mortality was very high. Baseline alcohol consumption, low body weight, advanced WHO clinical stage, the presence of opportunistic infections, and not receiving isoniazid prophylactic therapy were predictors of mortality. Strengthening behavioral and nutritional counseling with close clinical follow-up shall be given much more emphasis in the ART care and support program.
Testing an active intervention to deter researchers’ use of questionable research practices
Authors: Bruton S. V. , Brown M. , Sacco D. F. , Didlake R.
Published: November 2019

Introduction

In this study, we tested a simple, active “ethical consistency” intervention aimed at reducing researchers’ endorsement of questionable research practices (QRPs).

Methods

We developed a simple, active ethical consistency intervention and tested it against a control using an established QRP survey instrument. Before responding to a survey that asked about attitudes towards each of fifteen QRPs, participants were randomly assigned to either a consistency or control 3–5-min writing task. A total of 201 participants completed the survey: 121 participants were recruited from a database of currently funded NSF/NIH scientists, and 80 participants were recruited from a pool of active researchers at a large university medical center in the southeastern US. Narrative responses to the writing prompts were coded and analyzed to assist post hoc interpretation of the quantitative data.

Results

We hypothesized that participants in the consistency condition would find ethically ambiguous QRPs less defensible and would indicate less willingness to engage in them than participants in the control condition. The results showed that the consistency intervention had no significant effect on respondents’ reactions regarding the defensibility of the QRPs or their willingness to engage in them. Exploratory analyses considering the narrative themes of participants’ responses indicated that participants in the control condition expressed lower perceptions of QRP defensibility and willingness.

Conclusion

The results did not support the main hypothesis, and the consistency intervention may have had the unwanted effect of inducing increased rationalization. These results may partially explain why RCR courses often seem to have little positive effect.
Pedestrian segmentation based on a spatio-temporally consistent graph-cut with optimal transport
Authors: Yu Yang , Makihara Yasushi , Yagi Yasushi
Published: November 2019

We address a method of pedestrian segmentation in a video in a spatio-temporally consistent way. For this purpose, given a bounding box sequence of each pedestrian obtained by a conventional pedestrian detector and tracker, we construct a spatio-temporal graph on a video and segment each pedestrian on the basis of a well-established graph-cut segmentation framework. More specifically, we consider three terms as an energy function for the graph-cut segmentation: (1) a data term, (2) a spatial pairwise term, and (3) a temporal pairwise term. To maintain better temporal consistency of segmentation even under relatively large motions, we introduce a transportation minimization framework that provides a temporal correspondence. Moreover, we introduce the edge-sticky superpixel to maintain the spatial consistency of object boundaries. In experiments, we demonstrate that the proposed method improves segmentation accuracy indices, such as the average and weighted intersection of union on TUD datasets and the PETS2009 dataset at both the instance level and semantic level.
A scoping review of non-communicable disease research capacity strengthening initiatives in low and middle-income countries
Authors: Haregu Tilahun Nigatu , Byrnes Allison , Singh Kavita , Sathish Thirunavukkarasu , Pasricha Naanki , Wickramasinghe Kremlin , Thankappan Kavumpurathu Raman , Oldenburg Brian
Published: November 2019

Introduction

As the epidemic of non-communicable diseases (NCDs) is rapidly developing in low and middle-income countries (LMICs), the importance of local research capacity and the role of contextually relevant research in informing policy and practice is of paramount importance. In this regard, initiatives in research capacity strengthening (RCS) are very important. The aim of this study was to review and summarize NCD research capacity strengthening strategies that have been undertaken in LMICs.

Methods

Using both systematic and other literature search, we identified and reviewed NCD-RCS initiatives that have been implemented in LMICs and reported since 2000. Information was extracted from published papers and websites related to these initiatives using a semi-structured checklist. We extracted information on program design, stakeholders involved, and countries of focus, program duration, targeted researchers, disease focus, skill/capacity areas involved and sources of funding. The extracted information was refined through further review and then underwent a textual narrative synthesis.

Results

We identified a number of different strategies used by research capacity strengthening programs and in the majority of initiatives, a combination of approaches was utilized. Capacity strengthening and training approaches were variously adapted locally and tailored to fit with the identified needs of the targeted researchers and health professionals. Most initiatives focused on individual level capacity and not system level capacity, although some undoubtedly benefited the research and health systems of LMICs. For most initiatives, mid-term and long-term outcomes were not evaluated. Though these initiatives might have enhanced research capacity in the immediate term, the sustainability of the results in the long-term remains unknown.

Conclusion

Most of NCD-RCS initiatives in LMICs focused on building individual capacity and only a few focused explicitly on institutional level capacity strengthening. Though many of the initiatives appear to have had promising short-term outcomes, evidence on their long-term impact and sustainability is lacking.
Quality of work life and factors associated with it among nurses in public hospitals, Iran
Authors: Raeissi Pouran , Rajabi Mohammad Reza , Ahmadizadeh Elahe , Rajabkhah Kourosh , Kakemam Edris
Published: November 2019

Background

There is an acute shortage of nurses worldwide including Iran. Quality of work life is important for nurses as it affects the safety and quality of care provided for patients as well as organizational factors. The aim of this study was to describe the status of quality of work life and to explore its predictors among nurses in Iran.

Methods

A cross-sectional study was conducted on 2391 nurses in 85 Iranian public hospitals, selected through the convenience sampling. Data were collected using demographic information and the quality of work life questionnaires.

Results

The mean score for total quality of work life was 2.58, indicating a low level of self-reported quality of work life, with 69.3% of nurses dissatisfied with their work life. The major influencing factors were inadequate and unfair payment, lack of solving staff problems by organization and poor management support, job insecurity, high job stress, unfair promotion policies, and inadequate involvement in the decision-making. Significant predictors in the multivariate analysis for lower quality of work life were male gender, being single, older age, having lower educational levels, and working in teaching hospitals.

Conclusion

The quality of nursing work life was at a low level and needs improvement interventions. The predictors identified allow for more targeted interventions. Nursing managers and policymakers should develop and implement successful strategies appropriately to improve the quality of work life. This includes the payments, organizational and managerial support, job security, fair promotion policies, and measures to reduce job stress.
How much does lumbar fusion change sagittal pelvic tilt in individuals receiving total hip arthroplasty?
Authors: Huang Gangyong , Zhao Guanglei , Chen Kangming , Wei Yibing , Wang Siqun , Xia Jun
Published: November 2019

Background

This study primarily aims to examine the effect of lumbar fusion on changes in sagittal pelvic tilt (SPT) in total hip arthroplasty (THA) patients.

Methods

We reviewed 19 hip osteoarthritic patients undergoing THA with or without lumbar fusion. The gender, age, primary disease, Deyo comorbidity score, and year of surgery were sorted and matched. All patients were followed up for at least 12 months. They were compared in terms of the SPT angle, Harris hip score (HHS) and complications.

Results

On average, the patients receiving lumbar fusion had a − 3.9 (95% CI − 7.7 to − 1.5) degrees of SPT before THA and − 2.7 (95% CI − 6.5 to 1.1) degrees postoperatively, and the THA patients without lumbar fusion averaged 2.5 (95% CI − 0.1 to 5.0) degrees and 4.2 (95% CI 2.0 to 6.4) degrees, respectively. In the lumbar fusion patients, the mean SPT was − 3.9 (95% CI − 9.9 to 2.0) degrees with L5S1 fusion and − 4.0(95% CI − 10.0 to 2.1) degrees without L5S1 fusion on the standing radiograph before THA (t = 0.01, P = 0.99). The mean SPT was − 1.2 (95% CI − 4.9 to 2.6) degrees with one- and two-segment fusion and − 10.0 (95% CI − 18.5 to 1.5) degrees with three- and four-segment fusion before THA (t = 2.60, P = 0.02). There was no statistically significant difference in cup inclination and cup anteversion after THA between the lumbar fusion and control groups. These patients in the two groups achieved a similar HHS 12 months after THA despite the fact that they had different SPT and HHS before THA.

Conclusion

Lumbar fusion appears to increase the posterior SPT by approximately 6 degrees in the patients undergoing THA. Lumbar fusion of more than two segments is a predictor of more posterior SPT changes, but fusion of L5S1 is not.
Telomerase reverse transcriptase gene amplification in hematological malignancies
Authors: Abdelrahman Amany H. , Eid Maha M. , Hassan Mirhane , Eid Ola M. , AbdelKader Rania M. A. , AlAzhary Nevin M. , Shahin Rasha Y. , Sallam Mohamed T.
Published: November 2019

Background

Telomere is a complex DNA–protein structure located at the end of all eukaryotic chromosomes. The major role of human telomerase is to catalyze the addition of telomeric repeat sequences TTAGGG onto chromosome ends for stabilization of telomere length in attaining cellular immortality and may therefore be a critical step in carcinogenesis. Expression of significant levels of telomerase can dramatically increase proliferative life span and promote cellular immortality, thereby contributing to the malignant phenotype. The purpose of this study is to investigate telomerase reverse transcriptase (TERT) gene amplification in hematological neoplasms, e.g., multiple myeloma (MM), B-non-Hodgkin lymphoma (B-NHL), and acute myeloid leukemia (AML), using FISH technique and to evaluate its potential use as a prognostic marker.

Results

TERT amplification was detected in all groups of the participant patients (15 MM, 15 B-NHL, and 15 AML patients), with higher incidence in AML patients (53.3%). A significant association between the pattern of presentation and telomerase amplification was detected in 88.9% of the relapsed patients who demonstrated amplification of TERT. TERT amplification shows a significant association with p53 deletion and a highly significant association with poor prognosis.

Conclusions

TERT gene amplification is significantly associated with hematological malignancies and may play a critical role in carcinogenesis; thus, elucidation of their regulatory mechanism is highly demanding. Higher amplification was found in relapsed cases than de novo cases which highlight its potential implication in clinical analysis and disease monitoring. Moreover, our results suggest the future use of TERT gene as a potential prognostic marker that may aid in treatment decision and chemotherapy.
Cognitive Construal-Consistent Instructor Language in the Undergraduate Biology Classroom
Authors: Betz Nicole , Leffers Jessica S. , Thor Emily E. Dahlgaard , Fux Michal , de Nesnera Kristin , Tanner Kimberly D. , Coley John D.
Published: November 2019

Researchers have identified patterns of intuitive thinking that are commonly used to understand and reason about the biological world. These cognitive construals (anthropic, teleological, and essentialist thinking), while useful in everyday life, have also been associated with misconceptions about biological science. Although construal-based thinking is pervasive among students, we know little about the prevalence of construal-consistent language in the university science classroom. In the current research, we characterized the degree to which construal-consistent language is present in biology students’ learning environments. To do so, we coded transcripts of instructor’s speech in 90 undergraduate biology classes for the presence of construal-consistent language. Classes were drawn from two universities with very different student demographic profiles and represented 18 different courses aimed at nonmajors and lower- and upper-division biology majors. Results revealed construal-consistent language in all 90 sampled classes. Anthropic language was more frequent than teleological or essentialist language, and frequency of construal-consistent language was surprisingly consistent across instructor and course level. Moreover, results were surprisingly consistent across the two universities. These findings suggest that construal-consistent language is pervasive in the undergraduate classroom and highlight the need to understand how such language may facilitate and/or interfere with students learning biological science.
Metabolomics Signatures in Type 2 Diabetes: A Systematic Review and Integrative Analysis
Authors: Sun Yue , Gao Hao-Yu , Fan Zhi-Yuan , He Yan , Yan Yu-Xiang
Published: November 2019

Objective

Metabolic signatures have emerged as valuable signaling molecules in the biochemical process of type 2 diabetes (T2D). To summarize and identify metabolic biomarkers in T2D, we performed a systematic review and meta-analysis of the associations between metabolites and T2D using high-throughput metabolomics techniques.

Methods

We searched relevant studies from MEDLINE (PubMed), Embase, Web of Science, and Cochrane Library as well as Chinese databases (Wanfang, Vip, and CNKI) inception through 31 December 2018. Meta-analysis was conducted using STATA 14.0 under random effect. Besides, bioinformatic analysis was performed to explore molecule mechanism by MetaboAnalyst and R 3.5.2.

Results

Finally, 46 articles were included in this review on metabolites involved amino acids, acylcarnitines, lipids, carbohydrates, organic acids, and others. Results of meta-analysis in prospective studies indicated that isoleucine, leucine, valine, tyrosine, phenylalanine, glutamate, alanine, valerylcarnitine (C5), palmitoylcarnitine (C16), palmitic acid, and linoleic acid were associated with higher T2D risk. Conversely, serine, glutamine, and lysophosphatidylcholine C18:2 decreased risk of T2D. Arginine and glycine increased risk of T2D in the Western countries subgroup, and betaine was negatively correlated with T2D in nested case-control subgroup. In addition, slight improvements in T2D prediction beyond traditional risk factors were observed when adding these metabolites in predictive analysis. Pathway analysis identified 17 metabolic pathways may alter in the process of T2D and metabolite-related genes were also enriched in functions and pathways associated with T2D.

Conclusions

Several metabolites and metabolic pathways associated with T2D have been identified, which provide valuable biomarkers and novel targets for prevention and drug therapy.
Bumpy and Smoother Pathways of Puberty Hormone Change: A Novel Way to Define Gonadal Hormone Trajectories in Adolescents
Authors: Steinbeck Katharine S , Garden Frances L , Cheng Hoi Lun , Luscombe Georgina M , Handelsman David J
Published: November 2019

Context

The study of gonadal hormone effects on adolescent wellbeing has been limited by logistical challenges. Urine hormone profiling offers new opportunities to understand the health and behavioral implications of puberty hormones.

Objective

To characterize pubertal change in urinary testosterone and estradiol among male and female adolescents, respectively.

Design

Three-year prospective cohort study.

Setting

Australian regional community.

Participants

282 (163 male) normally developing adolescents aged 11.8 ± 1.0 years at baseline.

Main outcome measure

Quarterly urine measurements of testosterone and estradiol (mass spectrometry); annual anthropometric assessment and Tanner stage (TS) self-report.

Results

Two-class sigmoidal and quadratic growth mixture models (centered on age at TS3) were identified as best-fit for describing testosterone (male) and estradiol (female) change. Classes 1 (male: 63%; female: 82%) and 2 (male: 37%; female: 18%) were respectively named the “stable” and “unstable” trajectories, characterized by different standard deviation of quarterly hormone change and magnitude of hormone peaks and troughs (all P < 0.001). Compared with class 1 (stable), class 2 males were taller at baseline (154 vs 151 cm), reported earlier and faster TS progression (P < 0.01), and showed higher serum testosterone levels at baseline and 3 years (P ≤ 0.01). Class 2 females exhibited smaller height and weight gains over the 3 years and had higher baseline serum estradiol (249 vs 98 pmol/L; P = 0.002) than class 1.

Conclusions

Adolescents showed 2 distinct urinary gonadal hormone trajectories, characterized by stability of change over time, which were not associated with consistent anthropometric differences. Results provide a methodology for studying gonadal hormone impacts on other aspects of biopsychosocial wellbeing. Identification of potential “at-risk” hormone groups would be important for planning supportive interventions.
Prevalence of Thyroid Incidentalomas from 1995 to 2016: A Single-Center, Retrospective Cohort Study
Authors: Drake Tyler , Gravely Amy , Westanmo Anders , Billington Charles
Published: November 2019

Background

Incidental detection of thyroid nodules on nonthyroid imaging may contribute to increased diagnosis of thyroid cancer. We investigated the prevalence of thyroid incidentalomas across imaging modalities among a predominately male veteran population.

Methods

Thyroid nodules were identified on nonthyroid-directed radiology reports using natural language processing. All reports from 1995 to 2016 for chest computed tomography (CT), carotid ultrasound (US), and neck magnetic resonance imaging (MRI) were reviewed. Individuals with multiple studies were included at their initial study and duplicates removed.

Results

A total of 25 763 carotid US, 23 526 chest CTs with contrast, 39 262 noncontrast chest CTs, and 9503 MRIs were reviewed. With duplicates removed, 14 642 carotid US, 12 923 chest CTs with contrast, 17 416 noncontrast chest CTs, and 6926 MRIs were included. Mean age was 66.2 years and 1834 were female (3.53%). Thyroid nodules were reported on 0.84% carotid US, 3.45% MRIs, 5.84% chest CTs with contrast, and 5.14% noncontrast chest CTs. Women had a higher rate of thyroid nodules on MRI (6.46% vs 3.20%, P = .003), chest CT with contrast (9.80% vs 5.72%, P = .007), and noncontrast chest CT (8.77% vs 5.02%, P = .002), but not on carotid US (1.99% vs 0.81%, P = .12). Incidentaloma prevalence increased with age on MRI, chest CT with or without contrast, but not on carotid US, and were more commonly reported from 2007 to 2016 compared to before 2007 across all modalities.

Conclusions

Thyroid incidentalomas are commonly reported, are more common among women, and increase with age. The rate of reported incidental thyroid nodules is increasing, likely contributing to the increase in thyroid cancer.