bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Machine Learning Method for Mutational Analysis to Identifying Driver Genes in Breast Cancer
Authors: Taheri Golnaz , Habibi Mahnaz
Published: November 2022

Breast cancer has emerged as a severe public health issue and one of the main reasons for cancer-related mortality in women worldwide. Although the definitive reason for breast cancer is unknown, many genes and mutations in these genes associated with breast cancer have been identified using developed methods. The recurrence of a mutation in patients is a highly used feature for finding driver mutations. However, for various reasons, some mutations are more likely to arise than others. Sequencing analysis has demonstrated that cancer-driver genes perform across complicated pathways and networks, with mutations often arising in a modular pattern. In this work, we proposed a novel machine-learning method to study the functionality of genes in the networks derived from mutation associations, gene-gene interactions, and graph clustering for breast cancer analysis. These networks have revealed essential biological elements in the vital pathways, notably those that undergo low-frequency mutations. The statistical power of the clinical study is considerably increased when evaluating the network rather than just the effects of a single gene. The proposed method discovered key driver genes with various mutation frequencies. We investigated the function of the potential driver genes and related pathways. By presenting lower-frequency genes, we recognized breast cancer-related pathways that are less studied. In addition, we suggested a novel Monte Carlo-based algorithm to identify driver modules in breast cancer. We demonstrated our proposed modules’ importance and role in critical signaling pathways in breast cancer, and this evaluation for breast cancer-related driver modules gave us an inclusive insight into breast cancer development.
The WAVE complex drives the morphogenesis of the photoreceptor outer segment cilium
Authors: Spencer William J. , Schneider Nicholas F. , Skiba Nikolai P. , Arshavsky Vadim Y.
Published: November 2022

The photoreceptor outer segment is a modified cilium filled with hundreds of flattened “disc” membranes responsible for efficient light capture. To maintain photoreceptor health and functionality, outer segments are continuously renewed through the addition of new discs at their base. This process is driven by branched actin polymerization nucleated by the Arp2/3 complex. To induce actin polymerization, Arp2/3 requires a nucleation promoting factor. Here, we show that the nucleation promoting factor driving disc morphogenesis is the pentameric WAVE complex and identify all protein subunits of this complex. We further demonstrate that the knockout of one of them, WASF3, abolishes actin polymerization at the site of disc morphogenesis leading to formation of disorganized membrane lamellae emanating from the photoreceptor cilium instead of an outer segment. These data establish that, despite the intrinsic ability of photoreceptor ciliary membranes to form lamellar structures, WAVE-dependent actin polymerization is essential for organizing these membranes into a proper outer segment.
Effect of Surgically Acquired Neurological Deficits on Mortality Among Patients with Brain Metastases
Authors: Zheng Yilong , Lin Xie Sophie Jia , Teo Kejia , Weng Nga Vincent Diong , Yeo Tseng Tsai , Rui Lim Mervyn Jun
Published: November 2022

Purpose

To evaluate the association between surgically acquired neurological deficits and mortality among patients who underwent surgical resection of brain metastases.

Methods

Patients who underwent surgical resection of brain metastases at our institution between 2011 and 2019 were included. Surgically acquired neurological deficits were defined as dysarthria/aphasia, ataxia, hemiparesis, and visual field loss. A Cox proportional hazards model adjusting for potential confounders was constructed to evaluate whether surgically acquired neurological deficits were independently associated with a higher risk of overall mortality.

Results

A total of 153 patients were included in the analysis. 3.3% (5 patients) had a surgically acquired neurological deficit. On univariate time-to-event analysis, there was no statistically significant association between the development of a surgically acquired neurological deficit and mortality (HR=1.12; 95% CI=0.15, 8.24; p=0.910). On multivariate time-to-event analysis adjusting for potential confounders, there was also no statistically significant association between the development of a surgically acquired neurological deficit and mortality (HR=1.53; 95% CI=0.20, 11.9; p=0.683).

Conclusion

The development of a surgically acquired neurological deficit was not associated with overall mortality. Although this conclusion differs from other studies in the literature, the goal of surgical resection remains unchanged – to resect as much tumor as possible while still preserving neurological function.
Marker-free characterization of full-length transcriptomes of single live circulating tumor cells
Authors: Poonia Sarita , Goel Anurag , Chawla Smriti , Bhattacharya Namrata , Rai Priyadarshini , Lee Yi Fang , Yap Yoon Sim , West Jay , Bhagat Ali Asgar , Tayal Juhi , Mehta Anurag , Ahuja Gaurav , Majumdar Angshul , Ramalingam Naveen , Sengupta Debarka
Published: November 2022

The identification and characterization of circulating tumor cells (CTCs) are important for gaining insights into the biology of metastatic cancers, monitoring disease progression, and medical management of the disease. The limiting factor in the enrichment of purified CTC populations is their sparse availability, heterogeneity, and altered phenotypes relative to the primary tumor. Intensive research both at the technical and molecular fronts led to the development of assays that ease CTC detection and identification from peripheral blood. Most CTC detection methods based on single-cell RNA sequencing (scRNA-seq) use a mix of size selection, marker-based white blood cell (WBC) depletion, and antibodies targeting tumor-associated antigens. However, the majority of these methods either miss out on atypical CTCs or suffer from WBC contamination. We present unCTC, an R package for unbiased identification and characterization of CTCs from single-cell transcriptomic data. unCTC features many standard and novel computational and statistical modules for various analyses. These include a novel method of scRNA-seq clustering, named deep dictionary learning usingk-means clustering cost (DDLK), expression-based copy number variation (CNV) inference, and combinatorial, marker-based verification of the malignant phenotypes. DDLK enables robust segregation of CTCs and WBCs in the pathway space, as opposed to the gene expression space. We validated the utility of unCTC on scRNA-seq profiles of breast CTCs from six patients, captured and profiled using an integrated ClearCell FX and Polaris workflow that works by the principles of size-based separation of CTCs and marker-based WBC depletion.
Do Ṣukūk and Islamic indexes act as safe refuge to conventional stock markets? Evidence from Markov-switching CAPM approach
Authors: Bahloul Slah , Mathlouthi Fatma
Published: November 2022

Purpose

The objective of this paper is twofold. First, to study the safe-haven characteristic of the Islamic stock indexes and Ṣukūk during the crises time. Second, to evaluate this property in the last pandemic. This study employs the daily dataset from June 15, 2015, to June 15, 2020, for the most affected countries by the earlier disease.

Design/methodology/approach

This study uses the Markov-switching Capital Asset Pricing Model (CAPM) approach and the basic CAPM for the main analysis and the safe haven index (SHI) recently developed by Baur and Dimpfl (2021) for the robustness test.

Findings

Based on Baur and Lucey's (2010) definition, empirical findings indicate that Islamic stock indexes cannot be a refuge throughout the crisis regime for all selected conventional markets. However, Ṣukūk are a strong refuge in Brazilian, Russian and Malaysian markets. For the remainder countries, except Italy, the USA and Spain, the Ṣukūk index offers weak protection against serious conventional market downturns. Similar conclusions are obtained during the COVID-19 global crisis period. Finally, results are confirmed by using the SHI.

Originality/value

To the best of the authors’ knowledge, this paper is the first study that evaluates the safe haven effectiveness of the Islamic index and Ṣukūk using the SHI in the most impacted countries by the COVID-19 outbreak.
Evaluation of prisoner experiences during their engagement with the self-change programme
Authors: Kennedy Kara , McAlpine Stephan
Published: November 2022

Purpose

Previous difficulties were identified with the evaluation of violence interventions, resulting in gaps in the literature regarding the effectiveness of violence interventions. This study aims to contribute towards addressing the gap in the evaluation of violence interventions, by exploring the experience of prisoners who completed the self-change programme (SCP) during a 24-month period in HMP Shotts.

Design/methodology/approach

Five prisoners who completed the SCP at HMP Shotts were interviewed via a semi-structured interview to explore their experiences of engaging with this violence intervention. The data was analysed using interpretative phenomenological analysis (IPA), allowing the exploration and understanding of the subjective meanings of the experiences from the individual participants.

Findings

Interpretation of the data resulted in the identification of three superordinate themes that were relevant to participant experience: change as a process, supportive group environment and perceived outcomes.

Practical implications

These findings provide insight into prisoner experiences on SCP and contribute towards the evaluation of violence interventions. As prison-based interventions undergo a process of continued evaluation and re-accreditation, it is useful to understand the programme processes that enhance participant engagement and their learning experience, while also understanding the processes that may impede participant engagement and successful completion of violence interventions.

Originality/value

Although there has been substantial research conducted on violence interventions, this research has aimed to address some of the gaps and previous difficulties experienced within the evaluation of violence interventions.
GATA3 ameliorates melanocyte injuries in vitiligo through SIRT3‐mediated HMGB1 deacetylation
Authors: Nie Xiao‐Juan , Hao Bao‐Zhen , Zhang Ben‐Li , Li Yuan‐Yuan
Published: November 2022

Vitiligo is a skin depigmentation disorder. GATA3 expression is downregulated in vitiligo patients, and its role and regulatory mechanism in vitiligo are unclear. GATA3 and HMGB1 levels were detected by qRT‐PCR in peripheral blood cells of vitiligo patients and healthy controls, as well as H2O2‐treated PIG1 cells. Their expression correlation was assessed by Pearson analysis. qRT‐PCR, MTT assay, Ki67 immunostaining, flow cytometry, ELISA and Western blot were applied to determine GATA3 expression, cell survival, cell proliferation, cell apoptosis, melanin contents, and melanin‐related protein expressions. The cellular distributions of HMGB1 and its deacetylation levels were detected by Western blot. The binding of GATA3 to SIRT3 promoter and effects on SIRT3 expression and HMGB1 deacetylation was determined by dual‐luciferase assay, ChIP assay, and Western blot. GATA3 was decreased, and HMGB1 was increased in vitiligo. Pearson correlation assay showed that they were negatively correlated. H2O2 significantly inhibited cell survival, proliferation, melanin secretion, and melanin‐related protein expressions but remarkably increased cell apoptosis. GATA3 overexpression could distinctly reverse the effects of H2O2 through decreasing HMGB1 expression and retained HMGB1 in nuclear due to the decreased HMGB1 acetylation. GATA3 bound to the SIRT3 and subsequently decreased H2O2‐induced HMGB1 acetylation. Overexpressing HMGB1 or knockdown of SIRT3 could reverse the effects of GATA3 overexpression. GATA3 inhibited H2O2‐induced injury in PIG1 cells and enhanced melanin secretion by SIRT3‐regulated HMGB1 deacetylation, which might provide new evidence to treat vitiligo.
Animal tracing with sulfur isotopes: Spatial segregation and climate variability in Africa likely contribute to population trends of a migratory songbird
Authors: Brlík Vojtěch , Procházka Petr , Hansson Bengt , Stricker Craig A. , Yohannes Elizabeth , Powell Rebecca L. , Wunder Michael B.
Published: November 2022

Climatic conditions affect animals but range‐wide impacts at the population level remain largely unknown, especially in migratory species. However, studying climate–population relationships is still challenging in small migrants due to a lack of efficient and cost‐effective geographic tracking method.

Spatial distribution patterns of environmental stable isotopes (so called ‘isoscapes’) generally overcome these limitations but none of the currently available isoscapes provide a substantial longitudinal gradient in species‐rich sub‐Saharan Africa. In this region, sulphur (δ34S) has not been sufficiently explored on a larger scale.

We developed a δ34S isoscape to trace animal origins in sub‐Saharan Africa by coupling known‐origin samples from tracked migratory birds with continental remotely sensed environmental data building on environment–δ34S relationships using a flexible machine learning technique. Furthermore, we link population‐specific nonbreeding grounds with interannual climatic variation that might translate to breeding population trends.

The predicted δ34S isotopic map featured east–west and coast‐to‐inland isotopic gradients and was applied to predict nonbreeding grounds of three breeding populations of Eurasian Reed Warblers Acrocephalus scirpaceus with two distinct migratory phenotypes. Breeding populations as well as migratory phenotypes exhibited large‐scale segregation within the African nonbreeding range. These regions also differed substantially in the interannual climatic variation, with higher interannual variability in the eastern part of the range during 2001–2012. Over the same period, the eastern European breeding population seemed to have experienced a more steep decline in population size.

The link between migratory patterns and large‐scale climatic variability appears important to better understand population trajectories in many declining migratory animals. We believe animal tracing using sulphur isotopes will facilitate these efforts and offers manifold ecological and forensic applications in the biodiversity hotspot of sub‐Saharan Africa.
Emergency food aid and household food security during COVID‐19: Evidence from a field survey in Senegal
Authors: Diouf Awa , Ndiaye Mouhamadou Fallilou , Faye Cheikh
Published: November 2022

The effectiveness of food aid in reducing household food insecurity in developing countries has been extensively examined in previous studies. This study explores this issue in the context of COVID‐19, using the example of emergency food aid provided by the Senegalese government. Field survey data were collected from 4500 recipients and non‐recipients, and the matching method was used to examine whether there was a significant difference between the two groups. Several dimensions of food insecurity were explored through five indicators: the food consumption score and the coping strategies index from the World Food Programme and three indicators of simple, moderate and severe food insecurity based on the Food Insecurity Experience Scale of the US Food and Agriculture Organization (FAO). The results show that government aid has a negative and significant impact on the diversity and nutritional value of beneficiary households' diets. Nevertheless, this programme prevented the use of extreme coping strategies. Furthermore, government aid has a positive impact on food security as measured by negative experiences related to food access. Ultimately, despite low nutritional intake, the programme had a positive effect on recipients’ food access compared with non‐beneficiaries. Therefore, for future interventions, the government should promote local and more nutritious products to sustainably improve food security.
Exercise builds the scaffold of life: muscle extracellular matrix biomarker responses to physical activity, inactivity, and aging
Authors: Mavropalias Georgios , Boppart Marni , Usher Kayley M. , Grounds Miranda D. , Nosaka Kazunori , Blazevich Anthony J.
Published: November 2022

Skeletal muscle extracellular matrix (ECM) is critical for muscle force production and the regulation of important physiological processes during growth, regeneration, and remodelling. ECM remodelling is a tightly orchestrated process, sensitive to multi‐directional tensile and compressive stresses and damaging stimuli, and its assessment can convey important information on rehabilitation effectiveness, injury, and disease. Despite its profound importance, ECM biomarkers are underused in studies examining the effects of exercise, disuse, or aging on muscle function, growth, and structure. This review examines patterns of short‐ and long‐term changes in the synthesis and concentrations of ECM markers in biofluids and tissues, which may be useful for describing the time course of ECM remodelling following physical activity and disuse. Forces imposed on the ECM during physical activity critically affect cell signalling while disuse causes non‐optimal adaptations, including connective tissue proliferation. The goal of this review is to inform researchers, and rehabilitation, medical, and exercise practitioners better about the role of ECM biomarkers in research and clinical environments to accelerate the development of targeted physical activity treatments, improve ECM status assessment, and enhance function in aging, injury, and disease.
Microinclusive teaching in family science courses
Authors: Fitzpatrick Jacki
Published: November 2022

The purpose of this article is to provide a summary of microaggressive (MA) and microinclusive (MI) issues in college teaching. In MA communications, individuals/groups are treated as invisible or comparatively less desirable. MA can have a detrimental impact on its targets (to whom comments or behaviors are directed) as well as bystanders who witness the aggression. As part of ethics in family scholarship, it is worthwhile for faculty to consider MA and learn about more prosocial/supportive options, such as MI. This article provides a brief overview of MA, MI teaching, ethical approaches to MA/MI guidance, and MI teaching examples in one family science course. These issues are also relevant to coursework in other HDFS department programs or tracks (e.g., developmental, policy and practice, therapy, community education).
The impacts of highways on firm size distribution: Evidence from China
Authors: Zhou Jiangteng
Published: November 2022

This paper examines the impact of highway construction on the size distribution of manufacturing firms using Chinese firm and highway network data. I construct instrumental variables using historical and counterfactual road approaches to identify the causal effects of highway construction. I find that highway construction can increase firm size dispersion and market concentration. Areas near highways have a higher number of firms, more outsourcing activities, and more large firms; while areas further from highways have a higher share of new entry firms.
Perils of limiting the coverage of mandatory pay disclosure: The Korean experience
Authors: Ra Jinhyeok , Kim Woochan
Published: November 2022

In 2013, Korea adopted a mandatory pay disclosure rule applicable only to board members paid above a certain threshold (KRW 500 million, roughly equal to USD 5 million). In this study, we find evidence of Korean executives avoiding disclosure through director deregistration, that is, stepping down from the board, but retaining a non‐registered executive position in the same company. This tendency is stronger when deregistration cost is low (in case of family executives), and benefit is high (in case of high executive‐to‐worker pay ratios). We also find that family executives choose pay cuts over deregistration as means of avoidance when their income loss from pay cuts is relatively low. Last, we find that disclosure avoidance prompts negative share price reactions, leads to higher dividend payouts (in case of large pay cuts) and results in smaller board sizes (in case of family deregistration).
Commentary: Promoting positive mental health during pregnancy—reflections on Lähdepuro et al. (2023)
Authors: Henrichs Jens , Witteveen Anke B.
Published: November 2022

Lähdepuro et al. performed a sound large‐scale prospective pregnancy cohort study showing an association between positive maternal prenatal mental health and a reduced risk of developing clinically diagnosed childhood mental and behavioral disorders. Beneficial effects were also observed among the offspring of mothers experiencing mental health problems before and during pregnancy. The pathbreaking findings of Lähdepuro et al. set the stage for future research to shed more light on the so far almost unknown (neuro)biological mechanisms underlying the link between positive maternal prenatal mental health and child outcomes. More knowledge is needed about prenatal psychological and social factors enacting the potential of positive mental health as a resilience source buffering against maternal prenatal mental health problems and by this protecting subsequent child development. This also calls for further development, optimization, and evaluation of positive mental health‐enhancing interventions during pregnancy, especially for future mothers having mental health problems.
An exploratory study of a hands‐on naloxone training for rural clinicians and staff
Authors: Cody Shameka L. , Hines Cheryl B. , Glenn Christina J. , Sharp‐Marbury Rochelle , Newman Sharlene
Published: November 2022

Introduction

Since the COVID‐19 pandemic, an increase in fentanyl‐combined drugs has led to a surge in opioid overdose deaths in the United States. Higher opioid overdose mortality rates are problematic in rural communities, and there are few prevention, treatment, and recovery resources for individuals experiencing opioid use disorder.

Method

This exploratory project aimed to investigate a hands‐on naloxone training for rural clinicians and staff. Rural clinicians and staff at two behavioral health centers were recruited to participate in a 30‐min lecture and 30‐min hands‐on intranasal naloxone training using a low‐fidelity mannequin. A pre‐post opioid knowledge questionnaire, rubric based on the Substance Abuse and Mental Health Services Administration toolkit, and investigator‐generated survey were used to evaluate opioid knowledge and response, demonstration of intranasal naloxone administration, and participants' perceptions of the training. Enrollment characteristics were summarized using descriptive statistics and paired t‐tests were used to assess mean differences.

Results

Of the nine participants in the project, seven (87.5%) were female and six (75.0%) were Black. Four participants assumed a therapist role, attained a MS or MA degree, and had 5 or more years of experience working in healthcare. The total mean rubric score for all participants was 96.0 (SD = 8.8). No significant pre‐post mean differences among opioid knowledge, overdose risk, and overdose response categories were found, all p > 0.05. However, post‐intervention mean scores were slightly higher in all categories except overdose risk. Most participants (77.8%) responded that they felt comfortable handling an opioid situation and teaching the training to community members. Open‐ended responses indicated that participants liked the demonstrations, examples used, hands‐on nature of the training, and the presentation materials.

Conclusion

A hands‐on naloxone training is beneficial for training rural clinicians and staff to respond to opioid overdose. This training may be a promising solution to reduce response time between recognition of opioid symptoms and administration of the life‐saving medication, naloxone. Future studies should examine the efficacy of this training in larger samples with the inclusion of rural interdisciplinary teams, trusted community leaders, and family and friends of those impacted by opioid use disorder.

Clinical relevance

This innovative hands‐on naloxone training is designed for rural clinicians and residents who are most likely to witness individuals experiencing opioid toxicity. The primary goal is to reduce response time between recognition of signs and symptoms and administration of the life‐saving medication, Naloxone.
Associations Between Children's Depressive Symptoms, Life Events, and Family Factors Among School‐Aged Children
Authors: Talja Tiina , Rantanen Anja , Koivisto Anna‐Maija , Helenius Jenni , Joronen Katja
Published: November 2022

BACKGROUND

About 20‐30% of children worldwide report depressive symptoms. This study examined associations between children's depressive symptoms, life events, and family factors.

METHODS

Nationally representative data (n = 95,725) were drawn from the 2017 School Health Promotion Study in Finland. The respondents were 4th and 5th grade pupils (aged 10‐12) in primary schools and their parents/guardians (n = 33,726). Data were analyzed for child‐parent dyads (n = 32,181). Associations were studied using cross tabulation and logistic regression models.

RESULTS

Children's reports of poor self‐rated health, problems with family interactions, and the accumulation of life events were statistically significantly associated with depressive symptoms, also when controlling for sociodemographic factors. Financial situation and parent's depressed mood, both reported by parents, were associated with children's depressive symptoms when both were included in the regression model. However, this association disappeared when other predictors were added to the model.

CONCLUSION

The results make apparent the complex associations between children's depressive symptoms and family factors. Further research is needed on the discrepancies between parent and child experiences.
All roads lead to Rome: alternative biosynthetic routes in plant specialised metabolism
Authors: Davies Kevin M. , Andre Christelle M.
Published: November 2022

This article is a Commentary on T‐T. Zhu et al. (2023), 237: 515–531.
CIPK‐B is essential for salt stress signalling in Marchantia polymorpha
Authors: Tansley Connor , Houghton James , Rose Althea M. E. , Witek Bartosz , Payet Rocky D. , Wu Taoyang , Miller J. Benjamin
Published: November 2022

Calcium signalling is central to many plant processes, with families of calcium decoder proteins having expanded across the green lineage and redundancy existing between decoders. The liverwort Marchantia polymorpha has fast become a new model plant, but the calcium decoders that exist in this species remain unclear.

We performed phylogenetic analyses to identify the calcineurin B‐like (CBL) and CBL‐interacting protein kinase (CIPK) network of M. polymorpha. We analysed CBL‐CIPK expression during salt stress, and determined protein–protein interactions using yeast two‐hybrid and bimolecular fluorescence complementation. We also created genetic knockouts using CRISPR/Cas9.

We confirm that M. polymorpha has two CIPKs and three CBLs. Both CIPKs and one CBL show pronounced salt‐responsive transcriptional changes. All M. polymorpha CBL‐CIPKs interact with each other in planta. Knocking out CIPK‐B causes increased sensitivity to salt, suggesting that this CIPK is involved in salt signalling.

We have identified CBL‐CIPKs that form part of a salt tolerance pathway in M. polymorpha. Phylogeny and interaction studies imply that these CBL‐CIPKs form an evolutionarily conserved salt overly sensitive pathway. Hence, salt responses may be some of the early functions of CBL‐CIPK networks and increased abiotic stress tolerance required for land plant emergence.
Fire favors sexual precocity in a Mediterranean pine
Authors: Guiote Carmen , Pausas Juli G.
Published: November 2022

Wildfires are a natural disturbance in many ecosystems. Consequently, plant species have acquired traits that allow them to resist and regenerate in an environment with recurrent fires. A key trait in fire‐prone ecosystems is the age at first reproduction (maturity age); populations of non‐resprouting species cannot persist when the fire interval is shorter than this age. Maturity age is variable among individuals, so we hypothesized that short fire intervals select for early seed production (precocity). We selected 13 plots with different fire regimes in eastern Spain, all dominated byPinus halepensis(a non‐resprouting serotinous pine species). Then, we evaluated the age at first reproduction and the size of the canopy seed bank of each individual tree. Our results show a significant effect of fire regime on the onset of reproduction in this species, suggesting a selection towards higher precocity in populations subject to shorter fire intervals. Due to this higher precocity, pines stored more cones and therefore, increased their potential for reproduction post‐fire. We provide the first field evidence that fire can act as a driver of precocity. Being precocious in fire‐prone environments is adaptive because it increases the probability of having a significant seed bank when the next fire arrives.
The role of flexible bronchoscopy in the diagnostic pathway of children with unexplained peripheral eosinophilia
Authors: Hızal Mina , Eryilmaz Polat Sanem , Emiralioğlu Nagehan , Cinel Guzin , Yalcin Ebru , Dogru Deniz , Ozcelik Ugur , Kiper Nural
Published: November 2022

Background

Many possible underlying causes can be seen in children with unexplained peripheral eosinophilia (UPE) with suspected pulmonary involvement. Here, we aimed to demonstrate the clinical characteristics and diagnoses of children evaluated for UPE who underwent diagnostic bronchoscopy.

Methods

Thirty‐one children who underwent diagnostic bronchoscopy for UPE between 2006–2018 were included. Demographic characteristics, bronchoscopy findings and final diagnosis, and treatments were evaluated.

Results

The median age at the time of diagnosis was 5 (0.25–17.5) years. The final diagnoses of 26 patients were as follows: immunodeficiency (n = 6); hyper‐IgE syndromes (n = 4), DOCK8 deficiency + HES (idiopathic hypereosinophilic syndrome; n = 1), and severe combined immunodeficiency (n = 1), HES (n = 3), idiopathic chronic eosinophilic pneumonia (ICEP; n = 3), idiopathic pulmonary hemosiderosis (n = 1), B cell lymphoma (n = 1). In one child, an integrin α3 mutation + cytomegalovirus (CMV) pneumonia was detected. Congenital pneumonia was found in one patient, and parasitic infection in another. In two, eosinophilia was attributed to underlying asthma and atopy. In four, the underlying reasons could not be elucidated. Two children with HES and one with ICEP were lost to follow‐up. There was no significant relationship between the peripheral eosinophil count at the time of diagnosis and the percentage of bronchoalveolar lavage eosinophils (BAL). Bronchoscopy contributed to the management of 14 (53.9%) patients.

Conclusions

Bronchoscopy has potential diagnostic contribution in patients with UPE suspected of having pulmonary involvement. Numerous various underlying causes may be present in this patient group. There is no relation between peripheral eosinophil count and BAL eosinophil percentage.
How children tell a (prosocial) lie from an (ironic) joke: The role of shared knowledge
Authors: Aguert Marc
Published: November 2022

Understanding counterfactual utterances is a major challenge for children, because of the many ways in which they can be interpreted (pretence, errors, figures of speech, lies). In the present study, 7‐year‐olds and adults determined whether counterfactual utterances were prosocial lies or irony, depending on whether the counterfactuality was known only to the speaker (unshared knowledge) or to both interlocutors (shared knowledge). When the counterfactuality was shared by the interlocutors, both the 7‐year‐olds and the adults were less likely to interpret the speaker's counterfactual utterance as an attempted lie, and more likely to conclude that the speaker was being ironic. Adults were better than children at distinguishing irony from lies, but both age groups exhibited the same response pattern, namely a bias toward lying. This bias did not prevent the adults from deciding that the speaker was being ironic when the counterfactuality was shared, whereas children responded at chance level. In children, the association between task performance and theory‐of‐mind skills was nonsignificant, with a very small effect size. We discuss the possibility that, contrary to widespread belief, distinguishing irony from lies does not necessarily involve theory of mind (ToM).
Identification of HLA‐DPA1*01:03:01:57 and HLA‐DPA1*02:01:01:29 from a case–control study of atopic dermatitis
Authors: Damianos Georgios , Duke Jamie L. , Pagkrati Ioanna , Margolis David J. , Monos Dimitri S.
Published: November 2022

DPA1*01:03:01:57 and DPA1*02:01:01:29 differ by a single nucleotide from their closest references, DPA1*01:03:01:02 and DPA1*02:01:01:06.
Distinct mechanisms of CB1 and GABAB receptor presynaptic modulation of striatal indirect pathway projections to mouse globus pallidus
Authors: Sitzia Giacomo , Abrahao Karina Possa , Liput Daniel , Calandra Gian Marco , Lovinger David M.
Published: November 2022

Presynaptic modulation is a fundamental process regulating synaptic transmission. Striatal indirect pathway projections originate from A2A‐expressing spiny projection neurons (iSPNs), targeting the globus pallidus external segment (GPe) and control the firing of the tonically active GPe neurons via GABA release. It is unclear if and how the presynaptic G‐protein‐coupled receptors (GPCRs), GABAB and CB1 receptors modulate iSPN‐GPe projections. Here we used an optogenetic platform to study presynaptic Ca2+ and GABAergic transmission at iSPN projections, using a genetic strategy to express the calcium sensor GCaMP6f or the excitatory channelrhodopsin (hChR2) on iSPNs. We found that P/Q‐type calcium channels are the primary voltage‐gated Ca2+ channel (VGCC) subtype controlling presynaptic calcium and GABA release at iSPN‐GPe projections. N‐type and L‐type VGCCs also contribute to GABA release at iSPN‐GPe synapses. GABAB receptor activation resulted in a reversible inhibition of presynaptic Ca2+ transients (PreCaTs) and an inhibition of GABAergic transmission at iSPN‐GPe synapses. CB1 receptor activation did not inhibit PreCaTs but inhibited GABAergic transmission at iSPN‐GPe projections. CB1 effects on GABAergic transmission persisted in experiments where NaV and KV1 were blocked, indicating a VGCC‐ and KV1‐independent presynaptic mechanism of action of CB1 receptors. Taken together, presynaptic modulation of iSPN‐GPe projections by CB1 and GABAB receptors is mediated by distinct mechanisms.

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Key points

P/Q‐type are the predominant voltage‐gated Ca2+ channels controlling presynaptic Ca2+ and GABA release on the striatal indirect pathway projections.

GABAB receptors modulate iSPN‐GPe projections via a VGCC‐dependent mechanism.

CB1 receptors modulate iSPN‐GPe projections via a VGCC‐independent mechanism.
Thermodynamically Consistent Modified Lord–Shulman Generalized Thermoelasticity With Strain-Rate
Authors: Sarkar Indranil , Singh Gaurav
Published: November 2022

The analysis of thermoelastic wave propagation in continuum solids at micro/nano-seconds is especially significant for ultra-fast heating technologies, where strain relaxation effects will increase significantly. In most cases, it is commonly accompanied by a relatively small strain-rate; however, this is questionable in the environment of transient thermal wave propagation under the ultra-fast heating case. The present work is dedicated to constitutive modeling of a novel generalized thermoelasticity model by introducing an additional strain-rate term associated with a relaxation time parameter in the Lord–Shulman (LS) thermoelasticity with the aid of an extended thermodynamics framework. As an application, the newly developed model is applied to a one-dimensional half-space problem which is traction free at one end; a time-dependent thermal shock is imposed at the same end to analyze transient responses of thermodynamic field variables (temperature, displacement, strain, and stress). The inclusion of strain-rate in the LS model eliminates the probable propagating jump discontinuities of the strain and stress fields at the wavefront. The current work is expected to be useful in the mathematical modeling and numerical simulation of thermoelastic processes under an ultra-fast heating environment.
Conceptual Design of a Shape-Adaptive Structure With Tailored Structural Instability
Authors: Wheatcroft Ed , Shen Jiajia , Groh Rainer , Pirrera Alberto , Schenk Mark
Published: November 2022

A particular set of requirements is identified for the response of a passively actuated shape-adaptive structure. It is shown that neither conventional structures nor simple structural instabilities have suitable properties in order to meet these requirements. A novel solution is proposed which combines multiple structural instabilities to create a compound instability. This approach enables the shape-adaptive structure to achieve large output displacements only after a triggering input displacement is reached. First, this approach is investigated via an analytical bar-and-spring model, before a parametric sensitivity study demonstrates how the structural response of the model can be ‘tuned’ by varying its governing parameters. Next, a representative candidate structure with an analogous mechanical response is presented, and governing structural parameters are identified. It is found that there is an equivalent governing parameter across both models, and that this parameter can be used to tune the response of candidate structure in a way which mirrors the response of the bar-and-spring model. This analogy allows the simple bar-and-spring model to inform the design of its more complex counterpart, which can then achieve the desired functionality of the morphing structure.
High-Power SMA Bowling Ball Catapult
Authors: Molitor Philipp , Britz Rouven , Goergen Yannik , Motzki Paul
Published: November 2022

Today, Nickel-Titanium (NiTi)-based shape memory alloy (SMA) wires are already used in a wide range of commercial actuator applications. The combination of their unique properties, such as their high energy density as well as their biocompatibility provides a broad range of applications. The former in particular allows for designing light-weight actuator systems with high forces using small installation spaces. In systems like emergency brakes or switch disconnectors, which require high forces as well as high actuation speed, the high-power capability of NiTi actuators is exploited. The presented work discusses the development of a giant power catapult demonstrator, that combines the high-speed and high-force capability of SMA wires.

To illustrate the vast force, speed, and power potential of SMA wires, a bowling ball is launched from its resting position into the air using SMA wire bundles. For demonstration purposes a target altitude for the bowling ball of 500 mm is chosen, requiring a theoretical actuation force of F ≅ 920 N. To be able to launch the bowling ball to the desired height, an instantaneous energy release with an overall peak-power of P ≅ 0.5 MW is required.
Simulating Age Related Radial Pulses Using Magneto-Rheological Fluids
Authors: Eaton Miranda , Koo Jeong-Hoi , Yang Tae-Heon , Kim Young-Min
Published: November 2022

This study presents the design and test of a new pulse simulator capable of reproducing a wide range of radial pulses. It proposes to use a Magneto-Rheological (MR) fluid technology to shape radial pulse waveforms. The primary objective of this study is to demonstrate its feasibility of regenerating age-related human radial pulse waveforms using the proposed MR pulse simulator. The overall experimental set up includes a cam system, an MR device, an electromagnet, and sensors (laser displacement and pressure transducer). The cam system generates a base pulse waveform. This base pulse waveform is sent to an MR device which consists of a silicone tube (representing the radial artery) submerged in MR fluid. An electromagnet is placed beneath the MR fluid chamber which applies a specified magnetic field to control the MR fluid. This, in turn, enables the MR fluid to reshape the base pulse waveform to the desired pulse waveform. The mounted sensors collect data and measure the outputs for further analysis. Using this setup, a series of testing will be conducted by varying the input magnetic field with the pulse width modulation (PWM) control. PWM signals can be altered by changing the duty cycle and delay input to the electromagnet. These factors will affect the magnetic field, thus changing the MR fluid surrounding the silicone tube, and shaping the base pulse generated by the cam system. This study will then examine the pulse shaping performance of the MR device by comparing the reproduced radial pulses with those of in vivo radial pulses.
MFC Morphing Aileron Control With Intelligent Sensing
Authors: Haughn Kevin PT. , Gamble Lawren L. , Inman Daniel J.
Published: November 2022

Macro fiber composites (MFC) have proven useful as multifunctional material actuators for implementation in intelligent aerospace structures; however, due to nonlinear behaviors such as hysteresis and creep, incorporating sensor feedback is necessary to achieve sufficient control. In our work we use an antagonistic MFC unimorph system to produce a smooth trailing edge deflection in a morphing airfoil. In the past, piezoelectric flex sensors have been used to provide position feedback for the airfoil trailing edge, but these sensors also suffer from hysteresis. To achieve accurate position measurements from the flex sensors, we use time-series machine learning to model the relationship between flex voltage output and the true deflection. After testing offline, a long short-term memory (LSTM) neural network is implemented for inference on the hardware system and compared to a traditional linear model. True deflection information is obtained through external laser measurements, providing a context for comparing the accuracy of the mentioned state inference methods. Additionally, the sensor models are used in conjunction with a PD feedback controller to determine performance when controlling the aileron. Another difficulty in MFC actuator application is the change in performance under loading. Therefore, we perform final performance comparisons in a wind tunnel to simulate a realistic environment for the airfoil. We find the presented methods improve state inference performance over the traditional linear method, allowing for more accurate tip control under the aerodynamic loading.
Global Distribution of Carbohydrate Utilization Potential in the Prokaryotic Tree of Life
Authors: López-Mondéjar Rubén , Tláskal Vojtěch , da Rocha Ulisses Nunes , Baldrian Petr
Published: November 2022

This study expanded our knowledge of the phylogenetic distribution of carbohydrate-active enzymes across prokaryotic tree of life, including new phyla where the carbohydrate-active enzymes composition have not been described until now and demonstrated the potential for carbohydrate utilization of numerous yet uncultured phyla. Profiles of carbohydrate-active enzymes are largely habitat-specific and reflect local carbohydrate availability by selecting taxa with appropriate complements of these enzymes.
Hereditary thrombotic thrombocytopenic purpura (TTP) with co-occurring autosomal dominant polycystic kidney disease (ADPKD)
Authors: Dahlan Randah , Bablghaith Eman
Published: November 2022

Hereditary thrombotic thrombocytopenic purpura (TTP) and autosomal dominant polycystic kidney disease (ADPKD) are two distinct genetic diseases that may affect the kidneys through different mechanisms. ADPKD is a common genetic disorder that leads to exponential formation and growth of cysts replacing all segments of nephrons. Hereditary TTP is a rare autosomal recessive disorder that leads to the disseminated formation of arteriolar platelet-rich thrombi, which produce manifestations of various organs dysfunction. We present a case of a pregnant female with hereditary TTP co-occurring with ADPKD. To our knowledge, this is the first case in the literature describing the co-occurrence of ADPKD and hereditary TTP. We aim to describe the clinical course including the renal and the pregnancy outcomes, describe the consanguinity and family history, and try to explain the potential effect of one disease on the clinical course of the other.
Rare manifestation of hyperreactio luteinalis: when both the mother and baby girl are virilised
Authors: See Wing Shan Queenie , Seto Tin Yan Mimi , Poon Wing-Kit Grace , Tung Joanna Yuet-ling
Published: November 2022

Hyperreactio luteinalis is a benign, pregnancy-related condition with cystic enlargement of the ovaries and elevated androgen. However, only one-third of patients manifest as maternal virilisation and rarely does it cause fetal virilisation. Here, we report a virilised baby girl born to a virilised mother because of hyperreactio luteinalis. This case illustrates our management to maternal and fetal virilisation.
Pembrolizumab-induced acute right L5 neuritis unresponsive to steroids
Authors: Fitzpatrick Lachlan , Lwin Zarnie , Gericke Christian
Published: November 2022

We present a case of a patient with metastatic lung adenocarcinoma who developed severe right lower limb radicular pain in a L5-S1 dermatomal distribution 5 months into treatment with carboplatin, pemetrexed and pembrolizumab. MRI of the lumbar spine demonstrated contrast enhancement of the right L5 nerve root consistent with neuritis. The patient was treated with intravenous methylprednisolone 2 mg/kg/day for 3 days, followed by oral prednisolone 1 mg/kg/day with a slow wean over 6 weeks. There was no improvement and their performance status deteriorated to an Eastern Cooperative Oncology Group (ECOG) score of 3, representing capability of only limited self-care. We commenced induction therapy with intravenous immunoglobulin 2 g/kg over 5 days, which resulted in complete resolution of pain sustained for 3 weeks before recurrence of symptoms. We continued maintenance therapy with intravenous immunoglobulin 0.4 g/kg over 2 days at 4–5 weekly intervals, which led to resolution of symptoms and ECOG score to 1.