bluuebunny/crossref_metadata_2025 huggingface dataset:
Two-year immunogenicity of a pre-exposure rabies vaccination administered as a two-dose schedule
Authors: Windels Laurie , Naneix-Laroche Véronique , Pasquier Christophe , Delobel Pierre , Parize Perrine , Martin-Blondel Guillaume
Published: February 2022

In a young and healthy population, immunogenicity at 2 years of a rabies pre-exposure prophylaxis in a two-dose intramuscular schedule is satisfying. This regimen may be appropriate in people occupationally exposed to RABV, or travelling to highly endemic countries, provided they receive two booster doses in case of exposure.
PUCHI represses early meristem formation in developing lateral roots of Arabidopsis thaliana
Authors: Bellande Kevin , Trinh Duy-Chi , Gonzalez Anne-Alicia , Dubois Emeric , Petitot Anne-Sophie , Lucas Mikaël , Champion Antony , Gantet Pascal , Laplaze Laurent , Guyomarc’h Soazig
Published: February 2022

Lateral root organogenesis is a key process in the development of a plant’s root system and its adaptation to the environment. During lateral root formation, an early phase of cell proliferation first produces a four-cell-layered primordium, and only from this stage onwards is a root meristem-like structure, expressing root stem cell niche marker genes, being established in the developing organ. Previous studies reported that the gene regulatory network controlling lateral root formation is organized into two subnetworks whose mutual inhibition may contribute to organ patterning. PUCHI encodes an AP2/ERF transcription factor expressed early during lateral root primordium development and required for correct lateral root formation. To dissect the molecular events occurring during this early phase, we generated time-series transcriptomic datasets profiling lateral root development in puchi-1 mutants and wild types. Transcriptomic and reporter analyses revealed that meristem-related genes were expressed ectopically at early stages of lateral root formation in puchi-1 mutants. We conclude that, consistent with the inhibition of genetic modules contributing to lateral root development, PUCHI represses ectopic establishment of meristematic cell identities at early stages of organ development. These findings shed light on gene network properties that orchestrate correct timing and patterning during lateral root formation.
When Brains Meet Buildings
Authors: Arbib Michael A.
Published: February 2022

Understanding our brains can enrich our understanding of the ways we act and interact in a complex world, and how our experience of the built environment helps shape who we are and yet can be shaped by us in turn. This book presents action-oriented perception, memory, and imagination as keys to unlocking the neuroscience of the experience and design of architecture, and explores what it might mean for buildings to have “brains.” It offers a conversation addressed not only to architects and scientists but also to all who share a fascination with the brains within them and the buildings around them. Analysis of famous buildings and of homely examples introduces concepts like aesthetics, affordances, atmosphere, construction, manual action, scripts, and wayfinding, and the search for their neural substrates. It explores how evolution shaped a language-ready brain that is also architecture-ready. Case studies of the Guggenheim Museum Bilbao and the Sydney Opera House introduce an account of how the brains and minds of architects operate, pursuing the idea that memory and imagination are interacting forms of mental construction, but that architectural design must eventually reach a form that can guide the physical construction of buildings. All these concerns set new challenges for collaboration between architects and neuroscientists, and for further research on the brains of humans and animals.
Cell Types in the Thalamus and Cortex
Authors: Martin Usrey W. , Murray Sherman S.
Published: February 2022

The dorsal thalamus and cerebral cortex contain a variety of cell types that form functional circuits. The two major cell types in the thalamus are glutamatergic relay cells with axons that project to the cortex and local GABAergic interneurons. A third group of cells that embryologically are part of the ventral thalamus but play a major role in thalamic circuits of the dorsal thalamus are the GABAergic cells of the thalamic reticular nucleus that integrate feedforward and feedback inputs and provide inhibition to relay cells. The cortex is also comprised of glutamatergic and GABAergic neurons. While some glutamatergic cells are strictly interneurons and others are projection neurons that also provide local input, GABAergic neurons are all interneurons. These cell types form circuits within the cortex that have stereotypical patterns of connectivity between the six cortical layers as well as with other cortical and subcortical structures, including, importantly, the thalamus. This chapter explores the cell types and connections of neurons in the thalamus and cortex.
Thalamic Circuitry
Authors: Martin Usrey W. , Murray Sherman S.
Published: February 2022

This chapter delves into details of thalamic circuitry, using the lateral geniculate nucleus as an initial model. Three major sources of input to relay cells exist: drivers (e.g., retinal input), a feedback from layer 6 of cortex, local GABAergic input from interneurons and cells of the thalamic reticular nucleus, and classic modulatory inputs from various brainstem sources. Surprisingly, driver input produces only about 5% of all synapses onto relay cells. The remaining inputs (layer 6 of cortex, local GABAergic, and brainstem modulatory) each contribute 30–40% of the synaptic input. The patterns of non-driver inputs are relatively consistent among thalamic nuclei and mammalian species. An unusual aspect of thalamic circuitry is the triadic synaptic arrangement, in which a terminal from the driving input synapses onto both a relay cell dendrite and onto a GABAergic dendritic terminal from an interneuron and the same interneuronal terminal synapses onto the same relay cell dendrite; the interneuronal process is thus both pre- and postsynaptic. Possible functions of the triadic circuitry are discussed. Also discussed are some quantitative differences in synaptic organization between first and higher order relays.
Thalamocortical Substrates of Attention
Authors: Martin Usrey W. , Murray Sherman S.
Published: February 2022

Selective attention is a cognitive process that allows an organism to direct processing resources to behaviorally relevant stimuli. Attention has clear benefits for survival, as attention improves reaction time as well as the discrimination of stimuli. Although most studies of attention have been focused on effects within the cortex, increasing evidence demonstrates attention affects thalamic processing and thalamocortical network activity. This chapter examines the influence of visual attention on the response properties of different classes of thalamic neurons and their network interactions within the thalamus and with the cortex. The neural mechanisms of attention also include evolutionarily older structures, and ideas are explored regarding the integration of older and more recent brain circuits for attention.
Corticothalamic Circuits Linking Sensation and Action
Authors: Martin Usrey W. , Murray Sherman S.
Published: February 2022

Anatomical data show that most or all driving inputs to thalamus arrive via branching axons, with many targets of the extrathalamic branches being motor centers in the brainstem and/or spinal cord. The interpretation of this is that the messages sent to thalamus for relay are exact copies of messages intended to create and/or influence a motor action. Such a copy can be regarded as an efference copy. This leads to the speculation that one of the differences in the messages sent via direct and transthalamic corticocortical pathways is that the latter can serve as efference copies to inform the target cortical areas of a motor message sent out by the afferent area. It is also suggested from an evolutionary perspective that efference copies exist at multiple levels—spinal, brainstem, and cortical—and that this idea implies that the central nervous system is challenged to deal effectively with all of these efference copies; how it does so remains to be determined.
Conclusions
Authors: Martin Usrey W. , Murray Sherman S.
Published: February 2022

This final chapter reflects on the topics, viewpoints, and speculation provided throughout the book. At the outset, the authors’ goal was to provide information essential for understanding and thinking about thalamocortical interactions and then to go one step further, to provide fresh perspective and new ideas that sometimes challenge current thinking. This chapter includes a list of several “take-away points to ponder” and a final discussion on “why do we have a thalamus?” The hope is that this book will stimulate further thinking and, hopefully, plant a few seeds for the generation of new and testable ideas that will further advance our understanding of thalamocortical interactions and their critical role in brain function.
Oesophageal tumours
Authors: Foley Kieran , Morgan Carys , Crosby Tom
Published: February 2022

Chapter 7 discusses oesophageal tumours, including clinical background, diagnosis and staging, planning, therapeutic assessment, and follow-up. Patients with oesophageal cancer have a poor prognosis because many present with advanced disease. Accurate multi-modality staging with computed tomography (CT), endoscopic ultrasound (EUS), and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) is vital for management decisions, in particular providing complementary information for radical radiotherapy planning. The role of radiological imaging to assess treatment response is an area of growing interest. The likelihood of disease recurrence following potentially curative therapy remains high but the benefit of post-treatment surveillance remains unproven.
Gastric tumours
Authors: Carroll Nicholas , Smyth Elizabeth C.
Published: February 2022

Chapter 8 discusses gastric tumours. Gastric adenocarcinoma is the fifth most common cancer globally and the third most common cause of cancer death. Although diagnosis is largely by endoscopy, imaging is integral to accurate staging and subsequent treatment decisions. The mobility and volume changes of the stomach can make interpretation of imaging difficult unless measures are taken to compensate for the differences in volume and relative collapse or distension of the mucosa and gastric wall. Other tumour types include lymphoma, stromal tumours, and metastases, but this chapter will focus on the imaging of adenocarcinoma. In addition there is a crossover between pure gastric tumours and tumours of the gastroesophageal junction. These are subclassified into Siewert types I, II, and III, the latter centred in the proximal stomach. The type III tumours are therefore staged and managed as gastric cancers.
Gastrointestinal stromal tumours
Authors: Choi Haesun
Published: February 2022

Gastrointestinal stromal tumour (GIST) is rare, but the most common tumour of non-epithelial origin in the GI tract. It was often misdiagnosed as leiomyomas and leiomyosarcomas, with a dismal prognosis until KIT receptor protein was identified in the tumour cells. GISTs are now thought to derive from a precursor of the interstitial cells of Cajal, which are normally present in the myenteric plexus, and are clearly distinct from other mesenchymal tumours. GISTs typically present with non-specific gastrointestinal symptoms and surgical resection is the only cure, but it most frequently presents with a large, non-resectable or marginally resectable mass. It is one of the solid tumours that took advantage of the early targeted agents, KIT tyrosine kinase receptor inhibitor, such as imatinib, with dramatic improvement of the survival. Prolonged survival with GISTs has been increasingly recognized and the role of imaging has become important not only for diagnosing and staging the tumours, but also for monitoring the tumours during and following treatments. This chapter will review the clinical presentation, diagnosis, current management, and role of imaging in management of GISTs.
Urological cancers
Authors: Choudhury Ananya , Hoskin Peter
Published: February 2022

Prostate cancer is the most common cancer in males. There have been significant advances in imaging over the past decade, leading to improvements in diagnosis, staging, response assessment, and patient follow-up. This chapter covers urological cancers, including prostate cancer, bladder cancer, upper urinary tract urothelial tumours, testicular cancer, penile cancer, renal cell carcinoma, and urethral cancer. The current gold standard in imaging is discussed, with a look at imaging modalities on the horizon which are likely to impact cancer treatment in the next few years. Ultrasound, cross-sectional and radioisotope imaging all have a place in the management of urological cancers and radiotherapy planning.
Imaging for common complications
Authors: Addley Helen , Hickman Katy , Ajithkumar Thankamma
Published: February 2022

Chapter 22 covers the imaging manifestations of common complications that arise from both the cancer disease process and the therapies used to treat cancer. We discuss how imaging plays a critical role in the detection, evaluation, and management of complications. Emergency conditions that develop in oncology patients secondary to the disease require timely imaging studies. These include conditions such as pulmonary embolism, superior vena cava obstruction, metastatic epidural spinal cord compression, abdominal emergencies including bowel obstruction, perforation, and bowel ischaemia, as well as the range of manifestations of sepsis. Complications also arise as a direct result of treatment, whether that be chemotherapy, radiotherapy, or immunotherapy. We will cover treatment related complications such as lung injury secondary to radiotherapy and chemotherapy, insufficiency fractures, and the range of complications associated with immunotherapy, including hepatitis, hypophysitis, colitis, and pneumonitis.
The role of the chaplain in palliative care
Authors: Handzo George , Puchalski Christina
Published: February 2022

Spirituality has been shown to be a key factor in how people understand illness and how they cope with suffering. It is especially important for people who have serious or chronic illness. Standards for palliative care include spiritual care as a required domain of palliative care. Models and recommendations have been developed to facilitate interprofessional spiritual care where all members of the team attend to the spiritual issues of patients with the professional chaplain being the expert in spiritual care in a generalist specialist model of care. Palliative care teams should have a professional chaplain with training in palliative care assigned. This chaplain functions as the spiritual care lead and the spiritual care specialist on the team.
Teaching
Authors: Goss Rachel , McMaster Emma , Rennie Stephanie
Published: February 2022

This chapter contains 15 different teaching sample cases for the Fellowship of the Royal College of Emergency Medicine (FRCEM) Objective Structured Clinical Examination (OSCE). In this chapter, candidates are provided with the opportunity to teach a variety of concepts such as examinations, practical procedures and skills, and theory of key concepts. There is a strong focus on teaching technique, communication skills, knowledge, and application of up-to-date guidelines. The cases reflect a range of common presentations that are pertinent to the Royal College of Emergency Medicine (RCEM) curriculum and that are seen in real-life Emergency Departments. Each case contains instructions for the candidate and the patient actor, as well as a sample mark scheme breakdown and a mark scheme. Key learning points are highlighted after each case.
Psychiatry Scenarios
Authors: Goss Rachel , McMaster Emma , Rennie Stephanie
Published: February 2022

Chapter 8 contains 6 different psychiatry sample cases for the FRCEM OSCE. In this chapter, candidates must be able to take a psychiatric history, assess mental state and capacity in the context of deliberate self-harm and mental disorder. This chapter also covers taking an alcohol history, assessing cognition using a MMSE. The cases reflect a range of common presentations that are pertinent to the RCEM curriculum and that are seen in real life Emergency Departments. Each case contains instructions for the candidate and the patient actor, as well as a sample mark scheme breakdown and mark scheme. Key learning points are highlighted after each case.
Management Scenarios
Authors: Goss Rachel , McMaster Emma , Rennie Stephanie
Published: February 2022

This chapter contains eight management sample cases for the Fellowship of the Royal College of Emergency Medicine (FRCEM) Objective Structured Clinical Examination (OSCE). This chapter provides candidates with a framework to approach senior management scenarios common in the emergency department. These include personnel- and patient-related situations. This will incorporate previously learnt communication skills. Candidates must incorporate communication skills, knowledge, and management skills to successfully negotiate the scenarios. The cases reflect a range of common presentations that are pertinent to the Royal College of Emergency Medicine (RCEM) curriculum and that are seen in real-life emergency departments. Each case contains instructions for the candidate and the patient actor, as well as a sample mark scheme breakdown and a mark scheme. Key learning points are highlighted.
The origin of star–gas misalignments in simulated galaxies
Authors: Casanueva Catalina I , Lagos Claudia del P , Padilla Nelson D , Davison Thomas A
Published: February 2022

We study the origin of misalignments between the stellar and star-forming gas components of simulated galaxies in the eagle simulations. We focus on galaxies with stellar masses ≥109 M⊙ at 0 ≤ z ≤ 1. We compare the frequency of misalignments with observational results from the SAMI survey and find that overall, eagle can reproduce the incidence of misalignments in the field and clusters, as well as the dependence on stellar mass and optical colour within the uncertainties. We study the dependence on kinematic misalignments with internal galaxy properties and different processes related to galaxy mergers and sudden changes in stellar and star-forming gas mass. We find that galaxy mergers happen in similar frequency in mis- and aligned galaxies, with the main difference being misaligned galaxies showing a higher tidal field strength and fraction of ex situ stars. We find that despite the environment being relevant in setting the conditions to misalign the star-forming gas, the properties internal to galaxies play a crucial role in determining whether the gas quickly aligns with the stellar component or not. Hence, galaxies that are more triaxial and more dispersion dominated display more misalignments because they are inefficient at realigning the star-forming gas towards the stellar angular momentum vector.
Practical galaxy morphology tools from deep supervised representation learning
Authors: Walmsley Mike , Scaife Anna M M , Lintott Chris , Lochner Michelle , Etsebeth Verlon , Géron Tobias , Dickinson Hugh , Fortson Lucy , Kruk Sandor , Masters Karen L , Mantha Kameswara Bharadwaj , Simmons Brooke D
Published: February 2022

Astronomers have typically set out to solve supervised machine learning problems by creating their own representations from scratch. We show that deep learning models trained to answer every Galaxy Zoo DECaLS question learn meaningful semantic representations of galaxies that are useful for new tasks on which the models were never trained. We exploit these representations to outperform several recent approaches at practical tasks crucial for investigating large galaxy samples. The first task is identifying galaxies of similar morphology to a query galaxy. Given a single galaxy assigned a free text tag by humans (e.g. ‘#diffuse’), we can find galaxies matching that tag for most tags. The second task is identifying the most interesting anomalies to a particular researcher. Our approach is 100 per cent accurate at identifying the most interesting 100 anomalies (as judged by Galaxy Zoo 2 volunteers). The third task is adapting a model to solve a new task using only a small number of newly labelled galaxies. Models fine-tuned from our representation are better able to identify ring galaxies than models fine-tuned from terrestrial images (ImageNet) or trained from scratch. We solve each task with very few new labels; either one (for the similarity search) or several hundred (for anomaly detection or fine-tuning). This challenges the longstanding view that deep supervised methods require new large labelled data sets for practical use in astronomy. To help the community benefit from our pretrained models, we release our fine-tuning code zoobot. Zoobot is accessible to researchers with no prior experience in deep learning.
The impact of AGN outflows on the surface habitability of terrestrial planets in the Milky Way
Authors: Ambrifi A , Balbi A , Lingam M , Tombesi F , Perlman E
Published: February 2022

It is well known that active galactic nuclei (AGNs) are accompanied by winds and outflows, some of which may reach weakly relativistic speeds of about 10 per cent the speed of light. Yet, in spite of their ubiquity, the impact of AGN outflows in modulating surface habitability of terrestrial planets on galactic scales, using the Milky Way as the basis for comparison, is poorly investigated and inadequately understood. In this work, we address this issue by focusing on two key mechanisms: AGN winds can heat atmospheres and drive the atmospheric escape, as well as stimulate the formation of nitrogen oxides and thence cause ozone depletion. By developing simple models, we estimate the maximal distance up to which these deleterious effects are rendered significant for Earth-like planets in the Milky Way, and thereby demonstrate that this value may extend to ≲ 1 kpc. In the case of quasars hosting larger supermassive black holes, such effects could actually influence the AGN host galaxy as a whole.
Cosmic ray production in superbubbles
Authors: Vieu T , Gabici S , Tatischeff V , Ravikularaman S
Published: February 2022

We compute the production of cosmic rays (CRs) in the dynamical superbubble (SB) produced by a cluster of massive stars. Stellar winds, supernova remnants, and turbulence are found to accelerate particles so efficiently that the non-linear feedback of the particles must be taken into account in order to ensure that the energy balance is not violated. High-energy particles do not scatter efficiently on the turbulence and escape quickly after each supernova explosion, which makes both their intensity inside the bubble and injection in the interstellar medium intermittent. On the other hand, the stochastic acceleration of low-energy particles hardens the spectra at GeV energies. Because CRs damp the turbulence cascade, this hardening is less pronounced when non-linearities are taken into account. Nevertheless, spectra with hard components extending up to 1–10 GeV and normalized to an energy density of 1–100 eV cm−3 are found to be typical signatures of CRs produced in SBs. Efficient shock reacceleration within compact clusters is further shown to produce hard, slightly concave spectra, while the presence of a magnetized shell is shown to enhance the confinement of CRs in the bubble and therefore the collective plasma effects acting on them. We eventually estimate the overall contribution of SBs to the Galactic CR content and show typical gamma-ray spectra expected from hadronic interactions in SB shells. In both cases, a qualitative agreement with observations is obtained.
Elucidation of complex respiratory chains: a straightforward strategy to monitor electron transfer between cytochromes
Authors: Morgado Leonor , Salgueiro Carlos A
Published: February 2022

Cytochromes are electron transfer (ET) proteins essential in various biological systems, playing crucial roles in the respiratory chains of bacteria. These proteins are particularly abundant in electrogenic microorganisms and are responsible for the efficient delivery of electrons to the cells’ exterior. The capability of sending electrons outside the cells open new avenues to be explored for emerging biotechnological applications in bioremediation, microbial electrosynthesis, and bioenergy fields. To develop these applications, it is critical to identify the different redox partners and to elucidate the stepwise ET along the respiratory paths. However, investigating direct ET events between proteins with identical features in nearly all spectroscopic techniques is extremely challenging. Nuclear magnetic resonance (NMR) spectroscopy offers the possibility to overcome this difficulty by analysing the alterations of the spectral signatures of each protein caused by electron exchange events. The uncrowded NMR spectral regions containing the heme resonances of the cytochromes display unique and distinct signatures in the reduced and oxidized states, which can be explored to monitor ET within the redox complex. In this study, we present a strategy for a fast and straightforward monitorization of ET between c-type cytochromes, using as model a triheme periplasmic cytochrome and a membrane-associated monoheme cytochrome from the electrogenic bacterium Geobacter sulfurreducens. The comparison between the 1D 1H NMR spectra obtained for samples containing the two cytochromes and for samples containing the individual proteins clearly demonstrated a unidirectional ET within the redox complex. This strategy provides a simple and straightforward means to elucidate complex biologic respiratory ET chains.
TRIM65 determines the fate of a novel subtype of pituitary neuroendocrine tumors via ubiquitination and degradation of TPIT
Authors: Yao Hong , Xie Wanqun , Dai Yuting , Liu Yanting , Gu Weiting , Li Jianfeng , Wu Liang , Xie Jing , Rui Weiwei , Ren Bohan , Xue Li , Cheng Yijun , Lin Shaojian , Li Changsheng , Tang Hao , Wang Yu , Lou Meiqing , Zhang Xiaobiao , Hu Ronggui , Shang Hanbing , Huang Jinyan , Wu Zhe Bao
Published: February 2022

Background

Pituitary neuroendocrine tumors (PitNETs) are common intracranial tumors that are classified into seven histological subtypes, including lactotroph, somatotroph, corticotroph, thyrotroph, gonadotroph, null cell, and plurihormonal PitNETs. However, the molecular characteristics of these types of PitNETs are not completely clear.

Methods

A total of 180 consecutive cases of PitNETs were collected to perform RNA sequencing. All subtypes of PitNETs were distinguished by unsupervised clustering analysis. We investigated the regulation of TPIT by TRIM65 and its effects on ACTH production and secretion in ACTH-secreting pituitary cell lines, as well as in murine models using biochemical analyses, confocal microscopy, and luciferase reporter assays.

Results

A novel subtype of PitNETs derived from TPIT lineage cells was identified as with normal TPIT transcription but with lowered protein expression. Furthermore, for the first time, TRIM65 was identified as the E3 ubiquitin ligase of TPIT. Depending on the RING domain, TRIM65 ubiquitinated and degraded the TPIT protein at multiple Lys sites. In addition, TRIM65-mediated ubiquitination of TPIT inhibited POMC transcription and ACTH production to determine the fate of the novel subtype of PitNETs in vitro and in vivo.

Conclusion

Our studies provided a novel classification of PitNETs and revealed that the TRIM65-TPIT complex controlled the fate of the novel subtype of PitNETs, which provides a potential therapy target for Cushing’s disease.
Prevalence of Menthol and Menthol Capsule Cigarette Use Among 11–16 Year Olds in Wales Prior to a Ban on Characterizing Flavors in Cigarettes: Findings From the 2019 Student Health and Wellbeing Survey
Authors: Moodie Crawford , Page Nicholas , Moore Graham
Published: February 2022

Introduction

The use of flavored cigarettes has increased in many countries because of the inclusion of one or more frangible flavor-changing capsules in the filter. Research suggests that these “capsule” cigarettes appeal most to youth, but little is known about how prevalent their use is among children.

Methods

A cross-sectional school survey was conducted between September and December 2019 with 11–16 year-olds (N = 119 388) from 198 secondary schools across Wales; the sample represented approximately two-thirds of all 11–16 year-olds in the country. The sample was asked about smoking behavior, with a quarter (N = 26 950) also asked about awareness of menthol cigarettes, and use of menthol and menthol capsule cigarettes if a current smoker (N = 1447).

Results

Current smoking prevalence was 5.7% among the entire sample and 5.9% among the analytical sample (those also asked about menthol and menthol capsule cigarettes). For the analytical sample, almost all current smokers (93.2%) were aware of menthol cigarettes, with three-fifths (60.5%) reporting having used menthol cigarettes in the past 30 days (42.3% capsule cigarettes, 18.2% noncapsule cigarettes). In comparison to nonmenthol smokers, those using menthol cigarettes (capsule and noncapsule) were more likely to be frequent smokers, with those using menthol capsule cigarettes more likely to have smoked for longer.

Conclusions

While past research suggests that flavored cigarettes appeal to youth, this study shows just how popular these products, and capsule cigarettes, in particular, were among young smokers in Wales. It also raises questions about why capsule cigarettes have received such limited public health attention.

Implications

That three in five 11–16 year-old smokers reported using menthol cigarettes in the past 30 days highlights how appealing these products are to young people, particularly capsule cigarettes, used by seventy percent of menthol smokers. Capsule cigarettes are one of the most successful tobacco product innovations in decades, even in countries with comprehensive bans on tobacco marketing and standardized packaging. The dearth of research on capsule cigarettes is a failure of global public health. Evaluation of the ban on characterizing flavors in the United Kingdom and across the European Union is critical.
Multicenter Real-World Study on Effectiveness and Early Discontinuation Predictors in Patients With Non-small Cell Lung Cancer Receiving Nivolumab
Authors: Pasello Giulia , Lorenzi Martina , Calvetti Lorenzo , Oliani Cristina , Pavan Alberto , Favaretto Adolfo , Palazzolo Giovanni , Giovanis Petros , Zustovich Fable , Bonetti Andrea , Bernardi Daniele , Mandarà Marta , Aprile Giuseppe , Crivellaro Giovanna , Sinigaglia Giusy , Tognazzo Sandro , Morandi Paolo , Bortolami Alberto , Marino Valentina , Bonanno Laura , Guarneri Valentina , Conte PierFranco
Published: February 2022

Background

Real-world (RW) evidence on nivolumab in pretreated patients with non-small cell lung cancer (NSCLC) by matching data from administrative health flows (AHFs) and clinical records (CRs) may close the gap between pivotal trials and clinical practice.

Methods

This multicenter RW study aims at investigating median time to treatment discontinuation (mTTD), overall survival (mOS) of nivolumab in pretreated patients with NSCLC both from AHF and CR; clinical-pathological features predictive of early treatment discontinuation (etd), budget impact (BI), and cost-effectiveness analysis were investigated; mOS in patients receiving nivolumab and docetaxel was assessed.

Results

Overall, 237 patients with NSCLC treated with nivolumab were identified from AHFs; mTTD and mOS were 4.2 and 9.8 months, respectively; 141 (59%) received at least 6 treatment cycles, 96 (41%) received < 6 (etd). Median overall survival in patients with and without etd were 3.3 and 19.6 months, respectively (P < .0001). Higher number, longer duration, and higher cost of hospitalizations were observed in etd cases. Clinical records were available for 162 patients treated with nivolumab (cohort 1) and 83 with docetaxel (cohort 2). Median time to treatment discontinuation was 4.8 and 2.6 months, respectively (P < .0001); risk of death was significantly higher in cohort 2 or cohort 1 with etd compared with cohort 1 without etd (P < .0001). Predictors of etd were body mass index <25, Eastern Cooperative Oncology Group performance status >1, neutrophile-to-lymphocyte ratio >2.91, and concomitant treatment with antibiotics and glucocorticoids. The incremental cost-effectiveness ratio of nivolumab was 3323.64 euros ($3757.37) in all patients and 2805.75 euros ($3171.47) for patients without etd. Finally, the BI gap (real-theoretical) was 857 188 euros ($969 050.18).

Conclusion

We defined predictors and prognostic-economic impact of nivolumab in etd patients.
Vulnerable Neotropical migratory songbird demonstrates flexibility in space use in response to rainfall change
Authors: Brunner Alicia R , Marra Peter P , Tonra Christopher M
Published: February 2022

Behavioral flexibility of individuals is essential if organisms are to ultimately adapt to climate change. As environmental conditions, such as precipitation patterns become increasingly variable, fine-scale spatiotemporal flexibility in space use may allow for individuals to track resources during periods of adverse or atypical conditions. Individual behavioral flexibility is observable over short timeframes and can therefore be used to assess resilience of a species to projected shifts in climate. The goal of our study was to determine if and how individuals modified their space and habitat use in response to rainfall-driven changes in resources throughout a period of atypical seasonal rainfall patterns. We used radio telemetry to estimate home ranges of nonbreeding Swainson’s Warblers (Limnothlypis swainsonii) in 2 time frames (bi-seasonally and bi-weekly) in Jamaica during dry and wet periods. We measured habitat structure and food (leaf litter arthropod) availability within each home range to determine possible predictors of space use change. Individuals modified the area and/or location of their home ranges with changes in precipitation, and those occupying more open habitats had greater changes in home range area as seasonal rainfall increased. As food increased following rain, individuals constricted their home ranges (bi-weekly) or shifted spatially (bi-seasonally) to a novel area with greater food availability. This suggests individuals are able to rapidly respond to how their environment changes, presumably adjusting to trade-offs between home range size and resource availability. This flexibility may be a key behavioral component in enduring long-term increasingly unpredictable environmental variability and may have population-level consequences. These responses are, however, mediated by habitat, suggesting the ability to respond to variable or poor conditions is not homogeneous across a population.
CamelliA-based simultaneous imaging of Ca2+ dynamics in subcellular compartments
Authors: Guo Jingzhe , He Jiangman , Dehesh Katayoon , Cui Xinping , Yang Zhenbiao
Published: February 2022

As a universal second messenger, calcium (Ca2+) transmits specific cellular signals via a spatiotemporal signature generated from its extracellular source and internal stores. Our knowledge of the mechanisms underlying the generation of a Ca2+ signature is hampered by limited tools for simultaneously monitoring dynamic Ca2+ levels in multiple subcellular compartments. To overcome the limitation and to further improve spatiotemporal resolutions, we have assembled a molecular toolset (CamelliA lines) in Arabidopsis (Arabidopsis thaliana) that enables simultaneous and high-resolution monitoring of Ca2+ dynamics in multiple subcellular compartments through imaging different single-colored genetically encoded calcium indicators. We uncovered several Ca2+ signatures in three types of Arabidopsis cells in response to internal and external cues, including rapid oscillations of cytosolic Ca2+ and apical plasma membrane Ca2+ influx in fast-growing Arabidopsis pollen tubes, the spatiotemporal relationship of Ca2+ dynamics in four subcellular compartments of root epidermal cells challenged with salt, and a shockwave-like Ca2+ wave propagating in laser-wounded leaf epidermis. These observations serve as a testimony to the wide applicability of the CamelliA lines for elucidating the subcellular sources contributing to the Ca2+ signatures in plants.
Overexpression of Arabidopsis nucleolar GTP-binding 1 (NOG1) proteins confers drought tolerance in rice
Authors: Pant Bikram D , Lee Seonghee , Lee Hee-Kyung , Krom Nick , Pant Pooja , Jang YoonJeong , Mysore Kirankumar S
Published: February 2022

As a major adverse environmental factor in most parts of the world, drought causes substantial crop yield losses. Rice (Oryza sativa) is one of the staple foods for more than one-half of the world’s population. Rice plants are sensitive to even mild drought stress and need almost twice the amount of water compared to wheat (Triticum aestivum) or maize (Zea mays). Arabidopsis (Arabidopsis thaliana) small GTPase Nucleolar GTP-binding protein 1 (AtNOG1) plays a role in biotic stress tolerance. Here, we created transgenic rice lines constitutively overexpressing AtNOG1-1 or AtNOG1-2. We also developed rice RNA interference (RNAi) lines that show downregulation of OsNOG1. AtNOG1-1 and AtNOG1-2 overexpressors showed enhanced drought tolerance without compromising grain yield, whereas OsNOG1-RNAi was more susceptible to drought when compared to wild-type plants. Analysis of physiological parameters showed increased cell sap osmolality, relative water content, and abscisic acid (ABA) level, but decreased leaf water loss in AtNOG1-1 or AtNOG1-2 overexpressor lines compared to the control. We found upregulation of several genes involved in ABA and jasmonic acid (JA) signaling, stomata regulation, osmotic potential maintenance, stress protection, and disease resistance in AtNOG1-1 and AtNOG1-2 overexpressor lines compared to the control. We elucidated the role of NOG1-2 and NOG1-1 in regulation of silica body formation around stomata to prevent transpirational water loss. These results provide an avenue to confer drought tolerance in rice.
GLYCINE-RICH RNA-BINDING PROTEIN 7 potentiates effector-triggered immunity through an RNA recognition motif
Authors: Sukarta Octavina C A , Zheng Qi , Slootweg Erik J , Mekken Mark , Mendel Melanie , Putker Vera , Bertran André , Brand Anouk , Overmars Hein , Pomp Rikus , Roosien Jan , Boeren Sjef , Smant Geert , Goverse Aska
Published: February 2022

The activity of intracellular plant nucleotide-binding leucine-rich repeat (NB-LRR) immune receptors is fine-tuned by interactions between the receptors and their partners. Identifying NB-LRR interacting proteins is therefore crucial to advance our understanding of how these receptors function. A co-immunoprecipitation/mass spectrometry screening was performed in Nicotiana benthamiana to identify host proteins associated with the resistance protein Gpa2, a CC-NB-LRR immune receptor conferring resistance against the potato cyst nematode Globodera pallida. A combination of biochemical, cellular, and functional assays was used to assess the role of a candidate interactor in defense. A N. benthamiana homolog of the GLYCINE-RICH RNA-BINDING PROTEIN7 (NbGRP7) protein was prioritized as a Gpa2-interacting protein for further investigations. NbGRP7 also associates in planta with the homologous Rx1 receptor, which confers immunity to Potato Virus X. We show that NbGRP7 positively regulates extreme resistance by Rx1 and cell death by Gpa2. Mutating the NbGRP7 RNA recognition motif (RRM) compromises its role in Rx1-mediated defense. Strikingly, ectopic NbGRP7 expression is likely to impact the steady-state levels of Rx1, which relies on an intact RRM. Our findings illustrate that NbGRP7 is a pro-immune component in effector-triggered immunity by regulating Gpa2/Rx1 function at a posttranscriptional level.
The BTB protein MdBT2 recruits auxin signaling components to regulate adventitious root formation in apple
Authors: Ji Xing-Long , Li Hong-Liang , Qiao Zhi-Wen , Zhang Jiu-Cheng , Sun Wei-Jian , You Chun-Xiang , Hao Yu-Jin , Wang Xiao-Fei
Published: February 2022

Ubiquitination is an important post-translational protein modification. Although BROAD-COMPLEX, TRAMTRACK AND BRIC A BRAC and TRANSCRIPTION ADAPTOR PUTATIVE ZINC FINGER domain protein 2 (BT2) is involved in many biological processes, its role in apple (Malus domestic) root formation remains unclear. Here, we revealed that MdBT2 inhibits adventitious root (AR) formation through interacting with AUXIN RESPONSE FACTOR8 (MdARF8) and INDOLE-3-ACETIC ACID INDUCIBLE3 (MdIAA3). MdBT2 facilitated MdARF8 ubiquitination and degradation through the 26S proteasome pathway and negatively regulated GRETCHEN HAGEN 3.1 (MdGH3.1) and MdGH3.6 expression. MdARF8 regulates AR formation through inducing transcription of MdGH3s (MdGH3.1, MdGH3.2, MdGH3.5, and MdGH3.6). In addition, MdBT2 facilitated MdIAA3 stability and slightly promoted its interaction with MdARF8. MdIAA3 inhibited AR formation by forming heterodimers with MdARF8 as well as other MdARFs (MdARF5, MdARF6, MdARF7, and MdARF19). Our findings reveal that MdBT2 acts as a negative regulator of AR formation in apple.
THE EFFECT OF OUT-OF-PLANE PATIENT SHIELDING ON CT RADIATION EXPOSURE AND TUBE CURRENT MODULATIONS: A PHANTOM STUDY ACROSS THREE VENDORS
Authors: Rautiainen Jari , Juntunen Mikael A K , Kotiaho Antti O
Published: February 2022

The aim of this study was to evaluate how out-of-plane patient shielding affects radiation exposure parameters and tube current modulation on different vendors’ computed tomography (CT) scanners. Helical CT scans were performed using two homogenous phantoms to mimic patient attenuation. Four CT scanners from three vendors were investigated by varying the distance of the patient shield from the border of the imaging volume. Scans were performed with a shield placed before and after the localizer. Changes in volume computed tomography dose index (CTDIvol), dose-length product (DLP) and tube current-time products were studied. Out-of-field lead shield increased the CTDIvol and DLP values for each scanner at least for one scan setting when the shield was present in the localizer. The most notable changes were recorded with >1.3 pitch values when the shield was closest to the scanned volume (2.5 cm), and the scan direction was towards the shield. The usage of patient shields in the localizer CT scans can disturb TCM even when placed 7.5 cm away from the edge of the scan.
Experiences of Discrimination, Institutional Responses to Seminal Race Events, and Depressive Symptoms in Black U.S. Medical Students
Authors: Milam Adam J. , Brown Italo , Edwards-Johnson Jennifer , McDougle Leon , Sousa Aron , Furr-Holden Debra
Published: February 2022

Purpose

To examine the relationship between experiences of discrimination, institutional responses to seminal race events, and depressive symptoms among Black medical students.

Method

This study collected data from a convenience sample of Black U.S. medical students via an anonymous electronic questionnaire in August 2020 that was distributed through the Student National Medical Association and Organization of Student Representatives listservs and an author’s social media accounts. It included questions on demographics, institutional responses to seminal race events, experiences of discrimination, and symptoms of depression. Path models were used to examine the relationship between experiences of discrimination, institutional responses to seminal race events, and depressive symptoms among Black medical students.

Results

Of the 750 students completing the survey, 733 (97.7%) were Black. Experiences of discrimination and a lack of institutional responses to seminal race events were associated with more depressive symptoms (b = 0.19, 95% CI: 0.11, 0.26; P < .001 and b = 0.12, 95% CI: 0.04, 0.20; P = .01). After controlling for gender and clinical diagnosis of depression or anxiety before medical school, there was a relationship between experiences of discrimination and institutional responses to seminal race events such that students who reported more experiences of discrimination were more likely to report that their institution did not respond to seminal race events (b = 0.41, 95% CI: 0.34, 0.48; P < .001). Experiences of discrimination moderated the relationship between institutional responses to seminal race events and depressive symptoms (i.e., the relationship between a lack of institutional responses to seminal race events and depressive symptoms was stronger among students who reported more frequent experiences of discrimination).

Conclusions

Institutions dedicated to supporting Black medical student wellness must be diligent in cultivating a culture intolerant of discrimination and deft in their responses to seminal race events in the larger culture.
Six Principles for Developing Leadership Training Ecosystems in Health Care
Authors: Winters Richard C. , Chen Ruth , Lal Sarrah , Chan Teresa M.
Published: February 2022

Leadership education in medicine is evolving to better meet the challenges of health care complexity, interprofessional practice, and threats from viruses and budget cuts alike. In this commentary, the authors build upon the findings of a scoping review by Matsas and colleagues, published in the same issue, and ask us to imagine what a learning ecosystem around leadership might look like. They subsequently engage in their own synthesis of leadership development literature and propose 6 key principles for medical educators and health care leaders to consider when designing leadership development within their educational ecosystems: (1) apply a conceptual framework; (2) scaffold development-oriented approaches; (3) accommodate individual levels of adult development; (4) integrate diversity of perspective; (5) interweave theory, practice, and reflection; and (6) recognize the broad range of leadership conceptualization.
Reviews of Literature in Nursing Research
Authors: Silva Amina Regina , Padilha Maria Itayra , Petry Stefany , Silva E Silva Vanessa , Woo Kevin , Galica Jacqueline , Wilson Rosemary , Luctkar-Flude Marian
Published: February 2022

Despite the availability of guidelines about the different types of review literature, the identification of the best approach is not always clear for nursing researchers. Therefore, in this article, we provide a comprehensive guide to be used by health care and nursing scholars while choosing among 4 popular types of reviews (narrative, integrative, scoping, and systematic review), including a descriptive discussion, critical analysis, and decision map tree. Although some review methodologies are more rigorous, it would be inaccurate to say that one is preferable over the others. Instead, each methodology is adequate for a certain type of investigation, nursing methodology research, and research paradigm.