bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Risk Factors for Hepatotoxicity Induced by Immune Checkpoint Inhibitors
Authors: Cho Young Ah , Han Ji Min , Kang Sun Young , Kim Dong Chul , Youn Young Ju , Choi Kyung Hee , Gwak Hye Sun
Published: December 2020

Although hepatotoxicity induced by immune checkpoint inhibitors (ICPIs) can cause severe clinical complications, the risk factors associated with hepatotoxicity have rarely been investigated. The purpose of this study was to determine the potential risk factors for the incidence of hepatotoxicity and for time to ICPI-induced hepatotoxicity. Patients who received ICPIs (atezolizumab, nivolumab, pembrolizumab, and ipilimumab) were included in this retrospective 2-center study. Collected data included sex, age, body weight, body surface area, Eastern Cooperative Oncology Group performance status, underlying disease, liver metastasis, programmed cell death ligand-1 expression, interval from previous chemotherapy, and concomitant drug use. Among the 194 patients, patients who experienced hepatotoxicity after ICPI administration was 64.4% (n=125) in all grade and 10.8% (n=21) in grade III or higher. Multivariate analysis showed that patients aged 30–50 and 50–70 years had increased risks of hepatotoxicity by 4.9-fold (95% confidence interval, 1.3–18.0) and 2.7-fold (95% confidence interval, 1.3–5.5), respectively, compared with those older than 70 years. The use of acetaminophen increased the occurrence of hepatotoxicity by 2.1 times; the attributable risk was 53.2%. Male patients and patients younger than 65 years had around 1.5-fold increased hazard of time to reach hepatotoxicity. Patients treated with 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors had a 4.7-fold higher risk of grade III–IV hepatotoxicity compared with those without HMG-CoA reductase inhibitors; the attributable risk was 78.8%. In conclusion, close monitoring of liver function is recommended, especially in male patients, patients younger than 65 years old, and when there is concomitant use of hepatotoxic drugs including acetaminophen and HMG-CoA reductase inhibitors.
Nanoliposomal Irinotecan and Metronomic Temozolomide for Patients With Recurrent Glioblastoma
Authors: Elinzano Heinrich , Toms Steven , Robison Jordan , Mohler Alex , Carcieri Arieana , Cielo Deus , Donnelly Jennifer , Disano Dylan , Vatketich John , Baekey John , Sturtevant Ashlee , MacKinnon Kelsey , Wood Roxanne , Safran Howard
Published: December 2020

Background:

Liposomal formulations may improve the solubility and bioavailability of drugs potentially increasing their ability to cross the blood-brain barrier. We performed a phase I study to determine the maximum tolerated dose and preliminary efficacy of pegylated nanoliposomal irinotecan (nal-IRI)+metronomic temozolomide (TMZ) in patients with recurrent glioblastoma.

Patients and Methods:

Patients with glioblastoma who progressed after at least 1 line of therapy were eligible. All patients received TMZ 50 mg/m2/d until disease progression. Three dose levels of nal-IRI were planned, 50, 70, and 80 mg/m2, intravenously every 2 weeks. Patients were accrued in a 3+3 design. The study included a preliminary assessment after the first 13 evaluable patients. The trial would be terminated early if 0 or 1 responses were observed in these patients.

Results:

Twelve patients were treated over 2 dose levels (nal-IRI 50 and 70 mg/m2). At dose level 2, nal-IRI 70 mg/m2, 2 of 3 patients developed dose-limiting toxicities including 1 patient who developed grade 4 neutropenia and grade 3 diarrhea and anorexia and 1 patient with grade 3 diarrhea, hypokalemia fatigue, and anorexia. Accrual to dose level 1 was expanded to 9 patients. The Drug Safety Monitoring Board (DSMB) reviewed the data of the initial 12 patients—there were 0/12 responses (0%) and the median progression-free survival was 2 months and accrual was halted.

Conclusions:

The maximum tolerated dose of nal-IRI was 50 mg/m2 every 2 weeks with TMZ 50 mg/m2/d. The dose-limiting toxicities were diarrhea and neutropenia. No activity was seen at interim analysis and the study was terminated.
Clinical Trial Emulation by Matching Time-dependent Propensity Scores
Authors: Lenain Rémi , Boucquemont Julie , Leffondré Karen , Couchoud Cécile , Lassalle Mathilde , Hazzan Marc , Foucher Yohann
Published: December 2020

Background:

No study to our knowledge has examined the use of observational data to emulate a clinical trial whereby patients at the time of kidney transplant proposal are randomly assigned to an awaiting transplantation or transplantation group. The main methodologic issue is definition of the baseline for dialyzed patients assigned to awaiting transplantation, resulting in the inability to use common propensity score-based approaches. We aimed to use time-dependent propensity score to better appraise the benefit of transplantation.

Methods:

We studied 23,231 patients included in the French registry and on a transplant waiting list from 2005 to 2016. The main outcome was time to death. By matching on time-dependent propensity score, we obtained 10,646 pairs of recipients (transplantation group) versus comparable patients remaining on dialysis (awaiting transplantation group).

Results:

The baseline exposure, that is, pseudo-randomization, was matching time. Median follow-up time was 3.5 years. At 10 years’ follow-up, the restricted mean survival time was 8.8 years [95% confidence interval (CI) = 8.7, 8.9] in the transplantation group versus 8.2 years (95% CI = 8.1, 8.3) in the awaiting transplantation group. The corresponding life expectancy gain was 6.8 months (95% CI = 5.5, 8.2), and this corresponded to one prevented death at 10 years for 13 transplantations.

Conclusions:

Our study has estimated the life expectancy gain due to kidney transplantation. It confirms transplantation as the best treatment for end-stage renal disease. Furthermore, we demonstrated that this simple method should also be considered for estimating marginal effects of time-dependent exposures.
Laboring With the Heart
Authors: Gutiérrez Ángela , Young Maria-Elena De Trinidad , Dueñas Marisela , García Alma , Márquez Guadalupe , Chávez Maria-Elena , Ramírez Silvia , Rico Silvia , Bravo Rosana L.
Published: December 2020

Little is known about promotoras' professional experiences engaging in Latinx health promotion. In this promotora-led community-based participatory study, we purposively recruited and interviewed 30 Spanish-speaking promotoras who worked in Los Angeles County and who had at least 5 years of experience as promotoras. Using a constructivist grounded theory approach, findings revealed promotoras self-identified as health professionals who offered unique, insider perspectives. Challenges arose as employers viewed promotoras as volunteer lay health workers, while promotoras desired opportunities for professional growth. Motivation to continue working as promotoras stemmed from their commitment to Latinx communities. We provide recommendations to strengthen community-based capacity for advancing Latinx health.
Diabesity and Perinatal Mental Health: Evidence-based Recommendations for Screening and Intervention
Authors: STARK ELISABETH L. , MILLER EMILY S.
Published: December 2020

Perinatal mental illness, obesity, and diabetes mellitus are common complications of the perinatal period that are becoming ever more prevalent and frequently co-occur. This review seeks to examine the prevalence of comorbid obesity/diabetes (termed “diabesity”) and mental illness in the perinatal period and current understandings of the psychosocial and pathophysiological relationships between these diseases. We will present current guidelines for screening and make recommendations for adaptations of mental health treatment in patients with this comorbidity. Finally, we present future directions for research and clinical intervention.
Diabesity and Pregnancy: How Do We Get Our Patients Moving?
Authors: KOGUTT BENJAMIN K. , SZYMANSKI LINDA M.
Published: December 2020

Obesity and diabetes are 2 commonly encountered complications in pregnancy that adversely affect pregnancy outcomes, maternal health, and the health of the offspring, both short-term and long-term. It is well established that physical activity provides numerous health benefits, both during and outside of pregnancy. By participating in physical activity, many of the negative consequences of both obesity and diabetes may be mitigated. Physical activity guidelines recommend that all adults, including pregnant women, perform at least 150 minutes of moderate-intensity exercise weekly in order to obtain health benefits. More physical activity may be needed to achieve weight management goals.
Optical Coherence Tomography for the Investigation of Skin Adaptation in Lower-Limb Prosthesis Users
Authors: Swanson Eric C. , Friedly Janna L. , Wang Ruikang K. , Sanders Joan E.
Published: December 2020

Introduction

Mechanically induced skin breakdown is a significant problem for many lower-limb prosthesis users. It is known that skin can adapt to the mechanical stresses of prosthesis use thereby reducing the risk of breakdown, yet little is understood about the biology behind skin adaptation. This is a proof-of-concept study for the use of novel, noninvasive optical coherence tomography (OCT) imaging techniques to investigate skin adaptation.

Methods

Two OCT imaging-based tests were used to evaluate features of the skin that may be involved in adaptation to limb-socket interface stresses. The tests were used to assess the function and structure of the cutaneous microvasculature, respectively. Epidermal thickness was also quantified. Tests were run on three lower-limb prosthesis users in a region of the residual limb believed to be highly stressed within the prosthetic socket. The measurements were compared with measurements taken at a location-matched site on the contralateral limb.

Results

Two of three participants demonstrated a faster time-to-peak and larger peak magnitude reactive hyperemia response in their residual limb compared with their contralateral limb. Two of three participants also demonstrated a larger magnitude vessel density at maximum dilation in their residual limb versus contralateral limb. The epidermal thickness was greater in the residual limb versus contralateral limb for all participants.

Conclusions

This study demonstrated the utility of two novel OCT imaging techniques for investigating skin adaptation in users of lower-limb prostheses. If we are able to confirm these findings on a larger subject population, we will better understand the biology behind mechanically induced skin adaptation. These findings, along with the noninvasive OCT imaging methods introduced here, would have the potential to improve clinical practice by enabling the development of rehabilitation techniques and therapeutics to better strengthen skin, thereby reducing the incidence of harmful skin breakdown.
Characteristics Among Premenarchal Girls With Lichen Sclerosus
Authors: Wang Melinda , Arlen Angela M. , Vash-Margita Alla
Published: December 2020

Objectives

Lichen sclerosus (LS), a chronic inflammatory dermatosis localized in the anogenital region, is known to be associated with lower urinary tract symptoms (LUTS) in postmenopausal women; however, there is a paucity of data on prepubertal girls. We sought to characterize the relationship between LS, LUTS, and constipation among premenarchal girls.

Materials and Methods

We conducted a retrospective chart review of premenarchal girls presenting at the pediatric adolescent gynecology and pediatric urology clinics at our institution diagnosed with vulvar LS during a 4-year period. Demographics, clinical presentation, time from onset of urinary and/or bowel symptoms to LS diagnosis, and treatment response were assessed. Analysis was completed using median, range, and nonparametric statistical analysis where appropriate.

Results

Nineteen premenarchal girls with LS met inclusion criteria. The median age at LS diagnosis was 6.2 years (range = 3.3–13.3 yrs). Most girls (12/19, 63.2%) presented with LUTS during LS evaluation, and 11 (57.9%) of 19 patients had constipation. Pruritus and hypopigmentation were the most frequently encountered LS symptom and sign, respectively. Fourteen (73.7%) of the 19 girls had resolution/improvement of LS symptoms after LS treatment. Of the 12 patients with LUTS, 7 (58.3%) had resolution/improvement of LUTS symptoms, 3 (25.0%) had unchanged voiding symptoms, and 2 (16.7%) had unknown changes.

Conclusions

Although further studies are needed to better characterize the relationship between LUTS, constipation, and LS, our findings suggest that premenarchal subjects presenting with LUTS should be assessed for LS. Likewise, patients presenting with LS should be assessed for LUTS and constipation.
Are Nursing Interventions Effective in Improving Quality of Life in Cancer Survivors? A Systematic Review
Authors: Rodríguez-Matesanz Irati , Ambrosio Leire , Domingo-Oslé Marta , Elizondo-Rodríguez Nerea , La Rosa-Salas Virginia , Garcia-Vivar Cristina
Published: December 2020

Background

Cancer survivors (CSs) have needs that can negatively impact their quality of life (QoL). Oncology nurses play a key role in providing comprehensive care in cancer survivorship, although little is known about their impact on health outcomes.

Objective

The aim of this study was to determine the effectiveness of nursing interventions to improve QoL and satisfaction with care of CSs.

Methods

A systematic review was conducted. PubMed, CINAHL, PsycINFO, and Cochrane databases were searched for experimental studies. The Joanna Briggs Institute Checklist for Randomized Controlled Trials was used to verify the quality of the studies (Prospero reference: CRD42020148294).

Results

Of the 8 clinical trials eligible for inclusion, 5 demonstrated that interventions conducted by nurses improved the overall QoL or some of its domains in CSs. The included studies focused on short-term survival; no studies in long-term CSs were identified. Two studies assessed satisfaction with care of survivors, obtaining positive results.

Conclusions

Nursing interventions seem to improve the QoL of short-term CSs. However, because of the low number of studies identified, the findings of this systematic review should be interpreted with caution.

Implications for practice

Further studies are necessary to strengthen the implementation of effective nursing intervention in cancer practice. Research should particularly be conducted with long-term CSs as there is lack of data on this specific stage of cancer.
Evaluating the Benefit of Bereavement Mailings at a Large Pediatric Center
Authors: Edson JoEllen
Published: December 2020

The Boston Children’s Hospital Hematology/Oncology Bereavement Program has supported bereaved parents for three decades following the death of their child from cancer or blood disorder. An analysis of the current bereavement program as well as a review of up-to-date literature is crucial to maintaining and continuously improving the program. To evaluate the current practice, a 22-item Likert-type survey was mailed to 216 bereaved parents who utilized the bereavement program during a four-year period. Results from the program evaluation, particularly the qualitative remarks from bereaved parents, along with analysis of current literature underscore the value bereaved families find having at least one meaningful contact with their child’s healthcare team following the death.
Feasibility of an Intervention Study to Support Families When Their Loved One Has Life-sustaining Therapy Withdrawn
Authors: Scharf Barbara , Zhu Shijun , Tomlin Sarah , Cheon Jooyoung , Mooney-Doyle Kim , Baggs Judith Gedney , Weigand Debra
Published: December 2020

This investigation addressed family member perceptions of preparation for withdrawal of life-sustaining treatment in the intensive care unit. These families are at a high risk for psychosocial and physical sequelae. The quantitative results of this mixed methods study are reported. A control group received usual care and an educational booklet component of the intervention. The experimental group received the above plus exposure to comfort cart items and additional psychological support. Twenty-eight family members enrolled over a 13-month period. Sixty-one percent (10 intervention, 7 control) completed the follow-up. Fourteen family members (82%) recalled the booklet. Some family members reported moderate to severe depression (12.5%), anxiety (12.5%), and stress (12.6%). Satisfaction with care (83.7%-85.2%) and family member well-being (44.1) were within the norm. Short Form-36 physical component score was higher than the norm, and the mental component score was lower than the norm. This study demonstrated feasibility and acceptability of the interventions and follow-up questionnaires when families make the difficult decision to withdraw treatment. Strategies are suggested to strengthen statistical power.
The Decline of Salivary Adenocarcinoma Not Otherwise Specified as a Tumor Entity
Authors: Rooper Lisa M. , Mansour Mena , Yonescu Raluca , Oliai Bahram R. , Bishop Justin A. , Westra William H.
Published: December 2020

The classification of salivary gland carcinomas has become increasingly specific over the last decade with the definition of new tumor types, documentation of novel molecular and immunohistochemical findings, and development of more refined diagnostic criteria. In this setting, it is unclear how many salivary tumors still cannot be easily categorized—and whether such tumors represent undifferentiated malignancies or include additional definable entities. Relying largely on current classification schemes and contemporary immunohistochemical panels, we reassessed salivary tumors previously diagnosed as adenocarcinoma, not otherwise specified (ACA NOS) from 2 large academic medical centers. Fifty-seven ACA NOS (72%) could be reclassified as more specific entities including 31 salivary duct carcinomas (39%), 7 polymorphous adenocarcinomas (9%), 5 epithelial-myoepithelial carcinomas (6%), 4 myoepithelial carcinomas (5%), 4 secretory carcinomas (5%), 1 acinic cell carcinoma (1%), 1 basal cell adenocarcinoma (1%), 1 intraductal carcinoma (1%), and 1 clear cell carcinoma (1%) as well as 2 metastatic squamous cell carcinomas (3%). Of reclassified cases, 21 (37%) represented variant histologies within these categories. ACA NOS comprised 11% of salivary malignancies before reclassification, but only 4% after reclassification. The remaining 22 ACA NOS demonstrated heterogeneous features, with an association between histologic grade and clinical outcome. In effect, ACA NOS is becoming a bygone entity as modern classification schemes and ancillary techniques now permit more specific typing of a majority of these tumors, potentially facilitating more specific prognostication and treatment. Additional distinctive entities such as mucinous adenocarcinoma may still be definable within the ACA NOS category.
What Is on the Horizon for Novel Immunotherapies in Lung Cancer?
Authors: Garon Edward B. , Li Debory Yi
Published: December 2020

Programmed death (ligand) 1 checkpoint inhibitors have become standard treatment in patients with non–small cell lung cancer. Recently, combinations of nivolumab and ipilimumab have entered the clinic based on regulatory approval. Oftentimes, these checkpoint inhibitors are given in conjunction with chemotherapy. Through increased understanding of checkpoint evasion by cancer cells, many promising studies using combination therapies have continued to develop that aim to attack cancer cells by eliciting immunogenic responses through different modalities. Novel approaches include (1) using vaccines to trigger immune response, (2) combining multiple checkpoint inhibitors, (3) targeting inflammatory responses, (4) utilizing multitargeted tyrosine kinase inhibitors, (5) employing agonists of T-cell stimulators, and (6) applying specific biomarker antagonists to treat lung cancer patients. Herein, we discuss several studies that aim to answer what lies ahead in lung cancer treatment.
What Is the Standard First-Line Treatment for Advanced Non–Small Cell Lung Cancer?
Authors: Ricciuti Biagio , Awad Mark M.
Published: December 2020

The initial treatment regimens for advanced non–small cell lung cancer (NSCLC) have drastically evolved over the last 15 years with the rapid development of improved genomic sequencing technologies and the emergence of immune checkpoint inhibitors. Highly active oral kinase inhibitors are now approved for several molecularly defined subsets of NSCLC, including those harboring alterations in the EGFR, ALK, ROS1, BRAF, MET, RET, and NTRK genes, although acquired resistance to these targeted therapies remains a significant clinical challenge. In lung cancers lacking targetable mutations, programmed death 1/programmed death ligand 1 immune checkpoint inhibitors, used alone or in combination with cytotoxic T-lymphocyte-associated protein 4 inhibitors and/or cytotoxic chemotherapy, have led to meaningful improvements in overall survival. With many therapeutic options available to patients, here we review the recommended frontline treatment regimens for advanced NSCLC with and without targetable genomic drivers.
Harnessing the Immune System to Tackle Small Cell Lung Cancer
Authors: Newton Benjamin Robert , Chiang Anne C.
Published: December 2020

Immunotherapy has improved first-line therapy for small cell lung cancer and has activity in the relapsed setting as well. The immunobiology of small cell lung cancer poses challenges for immunotherapy, and efforts are underway to unlock to the potential of immunotherapy through the identification of meaningful disease subsets and the development of novel combination therapies.
Regular physical activity reduces the percentage of spinally projecting neurons that express mu-opioid receptors from the rostral ventromedial medulla in mice
Authors: Sluka Kathleen A. , Danielson Jessica , Rasmussen Lynn , Kolker Sandra J.
Published: December 2020

Introduction:

Regular physical activity/exercise is an effective nonpharmacological treatment for individuals with chronic pain. Central inhibitory mechanisms, involving serotonin and opioids, are critical to analgesia produced by regular physical activity. The rostral ventromedial medulla (RVM) sends projections to the spinal cord to inhibit or facilitate nociceptive neurons and plays a key role in exercise-induced analgesia.

Objective:

The goal of these studies was to examine if regular physical activity modifies RVM-spinal cord circuitry.

Methods:

Male and female mice received Fluoro-Gold placed on the spinal cord to identify spinally projecting neurons from the RVM and the nucleus raphe obscurus/nucleus raphe pallidus, dermorphin-488 into caudal medulla to identify mu-opioid receptors, and were immunohistochemically stained for either phosphorylated-N-methyl-d-aspartate subunit NR1 (p-NR1) to identify excitatory neurons or tryptophan hydroxylase (TPH) to identify serotonin neurons. The percentage of dermorphin-488-positive cells that stained for p-NR1 (or TPH), and the percentage of dermorphin-488-positive cells that stained for p-NR1 (or TPH) and Fluoro-Gold was calculated. Physically active animals were provided running wheels in their cages for 8 weeks and compared to sedentary animals without running wheels. Animals with chronic muscle pain, induced by 2 intramuscular injections of pH 4.0, were compared to sham controls (pH 7.2).

Results:

Physically active animals had less mu-opioid-expressing neurons projecting to the spinal cord when compared to sedentary animals in the RVM, but not the nucleus raphe obscurus/nucleus raphe pallidus. No changes were observed for TPH.

Conclusions:

These data suggest that regular exercise alters central facilitation so that there is less descending facilitation to result in a net increase in inhibition.
New Insights on Long-Term Hepatitis B Virus Responses in HIV–Hepatitis B virus Co-infected Patients: Implications for Antiretroviral Management in Hepatitis B virus-Endemic Settings
Authors: Dunn David , Price Huw , Vudriko Tobias , Kityo Cissy , Musoro Godfrey , Hakim James , Gilks Charles , Kaleebu Pontiano , Pillay Deenan , Gilson Richard ,   DART Virology Group
Published: December 2020

Background:

WHO treatment guidelines recommend tenofovir plus lamivudine or emtricitabine as the nucleoside reverse transcriptase inhibitor backbone in first-line regimens for HIV-infected adults. Lamivudine alone is not recommended, because of the risk of hepatitis B virus (HBV) resistance. We studied HBV responses in a large cohort of co-infected patients in a resource-limited setting.

Setting:

Clinical centers in Uganda and Zimbabwe.

Methods:

DART was a randomized trial of monitoring practices in HIV-infected adults starting antiretroviral therapy. Baseline samples were tested retrospectively for HBV serological markers and HBV DNA. Longitudinal HBV DNA testing at 48 weeks and the last available sample before HBV-relevant modification of antiretroviral therapy was performed on patients with detectable HBV DNA at baseline.

Results:

Two hundred twenty-four hepatitis B surface antigen-positive patients were followed for up to 4.8 years. Of the drugs with anti-HBV activity, 166 were prescribed lamivudine–tenofovir and 58 lamivudine alone. Ninety-eight percent (96/98) patients with baseline HBV DNA <6 log10 IU/mL achieved viral suppression at 48 weeks (HBV DNA <48 IU/mL), regardless of regimen, compared with 50%(26/52) for HBV DNA >6 log10 IU/mL. Of the 83 patients suppressed at 48 weeks and with follow-up data, only 7(8%) experienced viral rebound (range 200–3460 IU/mL). Of the 20 patients not suppressed at 48 weeks and with follow-up data, HBV DNA levels generally declined with lamivudine–tenofovir, but increased with lamivudine alone. Alanine transaminase flares were not observed in any patient who experienced viral rebound.

Conclusions:

The suppressive effect of lamivudine alone was highly durable (up to 5 years) in HIV–HBV co-infected patients with baseline HBV DNA <6 log10 IU/mL. It may be feasible to develop stratified approaches using lamivudine as the only drug with anti-HBV activity.
The Change in the Renal Pelvis Anterior-Posterior Diameter Between Prevoiding and Postvoiding Status, and Its Correlation With Vesicoureteral Reflux
Authors: Akdulum İsmail , Akyüz Melih , Gürün Enes , Öztürk Mehmet , Tabel Yilmaz , Siğirci Ahmet
Published: December 2020

In this study, our aim was to evaluate the significance of the change in renal pelvis anterior-posterior diameter (RPAPD) before and after micturition between vesicoureteral reflux (VUR)-positive and -negative patients to whom had voiding cystourethrography (VCUG) was performed.

In this study, 69 children, age ranging from 0 to 12 years, were included. Before the VCUG imaging, the RPAPD was measured first with a full bladder and then after urination via ultrasound (US). The differences between in RPAPD measurements were noted and values compared made among VUR-positive and -negative children. Data distribution was inhomogeneous, and the Wilcoxon Sign Rank test was utilized instead of Student t test. There was no statistically significant difference in prevoiding and postvoiding RPAPD in VUR (+) and VUR (−) patients (P = 0.672). There was no statistically significant relation between VUR and the presence of hydronephrosis (P = 0.126). Vesicoureteral reflux is more common in patients with urinary tract infections (UTI) (P = 0.001). There was no statistically significant relationship between prevoiding and postvoiding RPAPD change and VUR diagnosis (P = 0,164).

Ultrasound is the modality of choice for urinary system evaluation. Diagnosis of hydronephrosis via US is not sufficient in predicting VUR; however, indirect findings may reveal the diagnosis. A decrease in RPAPD in postvoiding US evaluation may not rule out the VUR diagnosis for this reason further imaging modalities, such as VCUG, should be taken into consideration for the patients with clinical suspicion.
An overview of shared technical challenges for magnetic and inertial fusion power plant development
Authors: Chapman I. T. , Walkden N. R.
Published: December 2020

Fusion energy is an area of active development and innovation worldwide, with many design concepts studied, each exhibiting a range of technical challenges. A significant portion of technical challenges will be unique for a given design concept; however, there are several overarching challenges that any design must address to some degree. These include tritium handling and the tritium cycle; materials and their survivability in the high-energy neutron environment of D-T fusion; neutronics and the validation of nuclear data; remote handling and maintenance activities; and integrated holistic approaches to fusion plant design. This paper provides an overview of these aspects for magnetic and inertial fusion approaches with a view to highlighting commonality and the benefits of shared knowledge that this may bring.

This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 2)’.
Sources and space–time distribution of the electromagnetic pulses in experiments on inertial confinement fusion and laser–plasma acceleration
Authors: Consoli F. , Andreoli P. L. , Cipriani M. , Cristofari G. , De Angelis R. , Di Giorgio G. , Duvillaret L. , Krása J. , Neely D. , Salvadori M. , Scisciò M. , Smith R. A. , Tikhonchuk V. T.
Published: December 2020

When high-energy and high-power lasers interact with matter, a significant part of the incoming laser energy is transformed into transient electromagnetic pulses (EMPs) in the range of radiofrequencies and microwaves. These fields can reach high intensities and can potentially represent a significative danger for the electronic devices placed near the interaction point. Thus, the comprehension of the origin of these electromagnetic fields and of their distribution is of primary importance for the safe operation of high-power and high-energy laser facilities, but also for the possible use of these high fields in several promising applications. A recognized main source of EMPs is the target positive charging caused by the fast-electron emission due to laser–plasma interactions. The fast charging induces high neutralization currents from the conductive walls of the vacuum chamber through the target holder. However, other mechanisms related to the laser–target interaction are also capable of generating intense electromagnetic fields. Several possible sources of EMPs are discussed here and compared for high-energy and high-intensity laser–matter interactions, typical for inertial confinement fusion and laser–plasma acceleration. The possible effects on the electromagnetic field distribution within the experimental chamber, due to particle beams and plasma emitted from the target, are also described.

This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 2)’.
AlphaTracker: A Multi-Animal Tracking and Behavioral Analysis Tool
Authors: Chen Zexin , Zhang Ruihan , Eva Zhang Yu , Zhou Haowen , Fang Hao-Shu , Rock Rachel R. , Bal Aneesh , Padilla-Coreano Nancy , Keyes Laurel , Tye Kay M. , Lu Cewu
Published: December 2020

The advancement of behavioral analysis in neuroscience has been aided by the development of computational tools1,2. Specifically, computer vision algorithms have emerged as a powerful tool to elevate behavioral research3,4. Yet fully automatic analysis of social behavior remains challenging in two ways. First, existing tools to track and analyze behavior often focus on single animals, not multiple, interacting animals. Second, many available tools are not developed for novice users and require programming experience to run. Here, we unveil a computer vision pipeline called AlphaTracker, which requires minimal hardware requirements and produces reliable tracking of multiple unmarked animals. An easy-to-use user interface further enables manual inspection and curation of results. We demonstrate the practical, real-time advantages of AlphaTracker through the study of multiple, socially-interacting mice.
Drawing the Borders of Olfactory Space
Authors: Mayhew Emily J. , Arayata Charles J. , Gerkin Richard C. , Lee Brian K. , Magill Jonathan M. , Snyder Lindsey L. , Little Kelsie A. , Yu Chung Wen , Mainland Joel D.
Published: December 2020

In studies of vision and audition, stimuli can be chosen to span the visible or audible spectrum; in olfaction, the axes and boundaries defining the analogous odorous space are unknown. As a result, the population of olfactory space is likewise unknown, and anecdotal estimates of 10,000 odorants have endured. The journey a molecule must take to reach olfactory receptors (OR) and produce an odor percept suggests some chemical criteria for odorants: a molecule must be 1) volatile enough to enter the air phase, 2) non-volatile and hydrophilic enough to sorb into the mucous layer coating the olfactory epithelium, 3) hydrophobic enough to enter an OR binding pocket, and 4) activate at least one OR. Here, we developed a simple and interpretable quantitative model that reliably predicts if a molecule is odorous or odorless based solely on the first three criteria. Applying our model to a database of all possible small organic molecules, we estimate that over 30 billion possible compounds are odorous, 6 orders of magnitude larger than current estimates of 10,000. With this model in hand, we can define the boundaries of olfactory space in terms of molecular volatility and hydrophobicity, enabling representative sampling of olfactory stimulus space.
Amilorides inhibit SARS-CoV-2 replication in vitro by targeting RNA structures
Authors: Zafferani Martina , Haddad Christina , Luo Le , Davila-Calderon Jesse , Yuan-Chiu Liang , Mugisha Christian Shema , Monaghan Adeline G. , Kennedy Andrew A. , Yesselman Joseph D. , Gifford Robert R. , Tai Andrew W. , Kutluay Sebla B. , Li Mei-Ling , Brewer Gary , Tolbert Blanton S. , Hargrove Amanda E.
Published: December 2020

The SARS-CoV-2 pandemic, and the likelihood of future coronavirus pandemics, has rendered our understanding of coronavirus biology more essential than ever. Small molecule chemical probes offer to both reveal novel aspects of virus replication and to serve as leads for antiviral therapeutic development. The RNA-biased amiloride scaffold was recently tuned to target a viral RNA structure critical for translation in enterovirus 71, ultimately uncovering a novel mechanism to modulate positive-sense RNA viral translation and replication. Analysis of CoV RNA genomes reveal many conserved RNA structures in the 5’-UTR and proximal region critical for viral translation and replication, including several containing bulge-like secondary structures suitable for small molecule targeting. Following phylogenetic conservation analysis of this region, we screened an amiloride-based small molecule library against a less virulent human coronavirus, OC43, to identify lead ligands. Amilorides inhibited OC43 replication as seen in viral plaque assays. Select amilorides also potently inhibited replication competent SARS-CoV-2 as evident in the decreased levels of cell free virions in cell culture supernatants of treated cells. Reporter screens confirmed the importance of RNA structures in the 5’-end of the viral genome for small molecule activity. Finally, NMR chemical shift perturbation studies of the first six stem loops of the 5’-end revealed specific amiloride interactions with stem loops 4, 5a, and 6, all of which contain bulge like structures and were predicted to be strongly bound by the lead amilorides in retrospective docking studies. Taken together, the use of multiple orthogonal approaches allowed us to identify the first small molecules aimed at targeting RNA structures within the 5’-UTR and proximal region of the CoV genome. These molecules will serve as chemical probes to further understand CoV RNA biology and can pave the way for the development of specific CoV RNA-targeted antivirals.
The gut hormone Allatostatin C regulates food intake and metabolic homeostasis under nutrient stress
Authors: Kubrak Olga , Jensen Line , Ahrentløv Nadja , Koyama Takashi , Malita Alina , Naseem Muhammad T. , Lassen Mette , Nagy Stanislav , Texada Michael J. , Halberg Kenneth A. , Rewitz Kim
Published: December 2020

The intestine is a central regulator of metabolic homeostasis. Dietary inputs are absorbed through the gut, which senses their nutritional value and relays hormonal information to other organs to coordinate systemic energy balance. However, the specific gut hormones that communicate energy availability to target organs to induce appropriate metabolic and behavioral responses are poorly defined. Here we show that the enteroendocrine cells (EECs) of theDrosophilagut sense nutrient stress via the intracellular TOR pathway, and in response secrete the peptide hormone allatostatin C (AstC). Gut-derived AstC induces secretion of glucagon-like adipokinetic hormone (AKH) via its receptor AstC-R2, a homolog of mammalian somatostatin receptors, to coordinate food intake and energy mobilization. Loss of gutAstCor its receptor in the AKH-producing cells impairs lipid and sugar mobilization during fasting, leading to hypoglycemia. Our findings illustrate a nutrient-responsive endocrine mechanism that maintains energy homeostasis under nutrient-stress conditions, a function that is essential to health and whose failure can lead to metabolic disorders.
Co-released Norepinephrine and Galanin Act on Different Timescales to Promote Stress-Induced Anxiety-Like Behavior
Authors: Tillage Rachel P. , Foster Stephanie L. , Lustberg Daniel , Liles L. Cameron , Weinshenker David
Published: December 2020

Background

Both the noradrenergic and galaninergic systems have been implicated in stress-related neuropsychiatric disorders, and these two neuromodulators are co-released from the stress-responsive locus coeruleus (LC); however, the individual contributions of LC-derived norepinephrine (NE) and galanin to behavioral stress responses are unclear. Here we aimed to disentangle the functional roles of co-released NE and galanin in stress-induced behavior.

Methods

We used foot shock, optogenetics, and behavioral pharmacology in wild-type (WT) mice and mice lacking either NE (Dbh-/-) or galanin (GalcKO-Dbh) specifically in noradrenergic neurons to isolate the roles of these co-transmitters in regulating anxiety-like behavior in the elevated zero maze (EZM) either immediately or 24 h following stress.

Results

Foot shock and optogenetic LC stimulation produced immediate anxiety-like behavior in WT mice, and the effects of foot shock persisted for 24 h. NE-deficient mice were resistant to the anxiogenic effects of acute stress and optogenetic LC stimulation, while mice lacking noradrenergic-derived galanin displayed typical increases in anxiety-like behavior. However, when tested 24 h after foot shock, bothDbh-/-andGalcKO-Dbhmice lacked normal expression of anxiety-like behavior. Pharmacological rescue of NE, but not galanin, in knockout mice during EZM testing was anxiogenic. In contrast, restoring galanin, but not NE, signaling during foot shock normalized stress-induced anxiety-like behavior 24 h later.

Conclusions

These results indicate that NE and noradrenergic-derived galanin play complementary, but distinguishable roles in behavioral responses to stress. NE is required for the expression of acute stress-induced anxiety, while noradrenergic-derived galanin mediates more persistent responses following a stressor.
Green human resource management, green organization identity and organizational citizenship behavior for the environment: the moderating effect of environmental values
Authors: Liu Zonghua , Mei Shiye , Guo Yulang
Published: December 2020

Purpose

Green human resource management (GHRM) is a new management philosophy and pattern that applies the concept of “green” to human resource management, which plays an important role in realizing environmental goals and obtaining competitive advantage. Based on 201 effective samples from 3 manufacturing enterprises, this study investigates the relationship between GRHM, green organization identity (GOI), environmental values and organizational citizenship behaviors for the environment (OCBEs). The results show that GRHM has a significant positive impact on OCBEs, and GOI plays an intermediary role in the relationship between GRHM and OCBEs, and environmental values moderate the impact of GRHM on GOI and OCBEs. The findings have important theoretical implications for enterprises to achieve green development strategy.

Design/methodology/approach

This study selects three manufacturing enterprises certified by the environmental management system ISO14001, which meet the environmental protection requirements of the Chinese Government, local communities and customers. Through interviews and referring to enterprise documents, the researchers find that the enterprises have set environmental protection standards such as energy consumption, solid waste emissions, water consumption and waste recycling. The enterprises surveyed have adopted the GRHM practice, such as green training for employees, encouraging employees to participate in green activities and so on. This study collects data in two ways: on-the-spot and entrustment questionnaire distribution. In the first stage, the data of GRHM and environmental values were collected. A total of 277 questionnaires were distributed and 264 were sent back, among them 252 were valid.

Findings

GRHM has a positive impact on OCBEs. GOI mediates the influence of GRHM on the OCBEs, and environmental values moderate the effect of GRHM on organizational identity and OCBEs.

Originality/value

This paper investigates the effect and mechanism of GRHM in China and provides theoretical guidance for enterprises to implement green management effectively.
Students' adoption of e-learning in emergency situation: the case of a Vietnamese university during COVID-19
Authors: Ho Nguyen Thi Thao , Sivapalan Subarna , Pham Hiep Hung , Nguyen Lan Thi Mai , Pham Anh Thi Van , Dinh Hung Viet
Published: December 2020

Purpose

By using a technology acceptance model (TAM) on survey results collected from two member schools of a Vietnamese educational institution, this study aims to uncover the key factors that affect students’ acceptance of e-learning during the Covid-19 period.

Design/methodology/approach

A bilingual questionnaire in English and Vietnamese was delivered. It was pre-tested on 30 participants before it was finalized. The authors first reviewed the measurement model and made adjustments to the theoretical TAM model. Then the adjusted TAM was used to investigate the relationships of the constructs in the model.

Findings

The results of the structural model show that computer self-efficacy (CSE) has a positive impact on perceived ease of use (PEOU). There is also a positive relationship between system interactivity (SI) and PEOU. Surprisingly, the authors documented that PEOU has no significant impact on students’ attitudes (ATT). The results show that SI can moderately affect ATT. Finally, it is noted that the social factor (SF) directly affects the student’s attitudes (ATT).

Research/limitations/implications

This study contains three limitations. First, as this study only focuses on undergraduate programs, readers should be careful in applying the findings and/or implications of this study to other education levels such as K-12, vocational training and postgraduate programs. Second, the findings are generated within the context of one type of e-learning, conducted via Google Meet. Therefore, future research is needed to provide further validation and comparison across other forms of e-learning. Finally, to further prevent the common bias problem, future research should use both five-point and seven-point Likert scales for the response options in the survey, as well as use negatively worded items. This will help prevent respondents from providing similar answers to all questions.

Originality/value

This study has both theoretical and practical implications. From a theoretical perspective, the study can provide a solid framework for similar studies. From a practical perspective, this study offers implications for governments and universities in the process of adopting e-learning, given that the Covid-19 pandemic is currently in its second and more dangerous wave.
Estimating green purchase behavior: an empirical study using integrated behavior model in Bangladesh
Authors: Siddique Md. Zillur Rahman , Saha Goutam , Kasem Aminur Rahman
Published: December 2020

Purpose

This paper aims to examine the exogenous effects of experiential attitude toward green (EAG), instrumental attitude toward green (IAG), injunctive norms on green (ING), descriptive norms about green (DNG), green perceived control (GPC) and green self-efficacy (GSE) on green purchase intention (GPI). Moreover, this paper also investigates the causal factors of green purchase behavior (GPB) considering green knowledge (GK), the salience of green behavior (SGB), environmental constraints (ECPG) and green habit (GH).

Design/methodology/approach

The research model was adopted to measure the green behavior of Bangladeshi consumers using an integrated behavior model (IBM). The data were randomly collected from 372 respondents and partial least squares structural equation modeling (PLS-SEM) approach was used to test the hypotheses.

Findings

PLS results imply that all independent variables (EAG; IAG; ING; DNG; GPC and GSE) impact GPI; and SGB, GH and GPI influence GPB. On the other hand, GK and ECPG have no significant effect on GPB.

Research limitations/implications

There may present a gap in the outcomes of the study to signify the generalizability because the survey was conducted in some cities of Bangladesh which may not represent the country as a whole.

Practical implications

This study anticipates the cause-effect relationship between GPI, GPB and their determinants. The results of the study can help marketers understand green consumer behavior and design appropriate strategies and tactics for new marketing challenges.

Originality/value

This research investigates green purchase behavior in a developing country. It empirically confirms the validity of IBM in assessing green behavior, especially for Bangladesh, a booming economy and suitable for investment. Although ample research explored green purchase behavior, green habit and saliency have not been considered in measuring green purchase behavior.
Conceptualising the interaction among organisational factors towards internal control quality
Authors: Alazzabi Waled Younes E. , Mustafa Hasri , Issa Mohamed
Published: December 2020

Purpose

This paper provides a theoretical foundation and conceptual framework to explain the interactions among risk management (RM), top management support (TMS), and internal audit activities (IAA) to achieve internal control quality (ICQ).

Design/methodology/approach

A review of the extant literature in RM, auditing and management control is conducted to develop and establish theoretical relationships.

Findings

In this work, interconnectedness among organisational factors is discussed by drawing on contingency theory to provide the theoretical logic and support the conceptual framework.

Research limitations/implications

Although this work illustrates the significance of the moderation effect of TMS and the mediation effect of IAA to link RM processes with the quality of internal controls, limitations exist, as the study is conceptual and lacks empirical evidence. The paper emphasises education and training on RM and internal audit to address emerging issues and arising challenges in RM and ICQ.

Originality/value

The paper extends the existing literature in the area of ICQ, which is discussed extensively in developed contexts. However, studies on ICQ in emerging economics, specifically the Middle East and North Africa region, which suffers from high levels of corruption, and asset misappropriation cases are limited. Hence, this work is important because it addresses under-researched issues in relation to ICQ in an attempt to develop a conceptual framework from the available and most effective organisational factors to attain better ICQ.