bluuebunny/crossref_metadata_2025 huggingface dataset:
Caenorhabditis ElegansJunctophilin has Tissue-Specific Functions and Regulates Neurotransmission with Extended-Synaptotagmin
Authors: Piggott Christopher A. , Wu Zilu , Nurrish Stephen , Xu Suhong , Kaplan Joshua M. , Chisholm Andrew D. , Jin Yishi
Published: November 2020

The junctophilin family of proteins tether together plasma membrane (PM) and endoplasmic reticulum (ER) membranes, and couple PM- and ER-localized calcium channels. Understandingin vivofunctions of junctophilins is of great interest for dissecting the physiological roles of ER-PM contact sites. Here, we show that the soleC. elegansjunctophilin JPH-1 localizes to discrete membrane contact sites in neurons and muscles and has important tissue-specific functions.jph-1null mutants display slow growth and development due to weaker contraction of pharyngeal muscles, leading to reduced feeding. In the body wall muscle, JPH-1 co-localizes with the PM-localized EGL-19 voltage-gated calcium channel and ER-localized UNC-68/RyR calcium channel, and is required for animal movement. We also find an unexpected cell non-autonomous effect ofjph-1in axon regrowth after injury. In neurons, JPH-1 co-localizes with the membrane contact site protein Extended-SYnaptoTagmin 2 (ESYT-2) and modulates neurotransmission. Interestingly,jph-1andesyt-2null mutants display mutual suppression in their response to aldicarb, suggesting that JPH-1 and ESYT-1 have antagonistic roles in neuromuscular synaptic transmission. Our genetic double mutant analysis also reveals thatjph-1functions in overlapping pathways with two PM-localized voltage-gated calcium channels,egl-19andunc-2,andunc-68/RyRfor animal health and development. Finally, we show thatunc-68/RyRis required for JPH-1 localization to ER-PM puncta. Our data demonstrate important roles for junctophilin in cellular physiology, and also provide insights into how junctophilin functions together with other calcium channelsin vivo.
Age-Associated Insolubility of Parkin in Human Midbrain is Linked to Redox Balance and Sequestration of Reactive Dopamine Metabolites
Authors: Tokarew Jacqueline M. , El-Kodsi Daniel N. , Lengacher Nathalie A. , Fehr Travis K. , Nguyen Angela P. , Shutinoski Bojan , O’Nuallain Brian , Jin Ming , Khan Jasmine M. , Ng Andy C. H. , Li Juan , Jiang Qiubo , Zhang Mei , Wang Liqun , Sengupta Rajib , Barber Kathryn R. , Tran An , Zandee Stephanie , Dong Xiajun , Scherzer Clemens R. , Prat Alexandre , Tsai Eve , Takanashi Masashi , Hattori Nobutaka , Chan Jennifer A. , Zecca Luigi , West Andrew B. , Holmgren Arne , Puente Lawrence , Shaw Gary S. , Toth Gergely , Woulfe John M. , Taylor Peggy , Tomlinson Julianna J. , Schlossmacher Michael G.
Published: November 2020

The mechanisms by which parkin protects the adult human brain from Parkinson disease remain incompletely understood. We hypothesized that parkin cysteines participate in redox reactions, which are reflected in its posttranslational modifications. We found that in human control brain, including theS. nigra, parkin is largely insoluble after age 40 years, which is linked to its oxidation,e.g.,at Cys95 and Cys253. In mice, oxidative stress increases posttranslational modifications at parkin cysteines and reduces its solubility. Oxidation of recombinant parkin also promotes insolubility and aggregate formation, but in parallel, lowers hydrogen peroxide (H2O2). This thiol-based redox activity is diminished by parkin point mutants,e.g.,p.C431F and p.G328E. Intriguingly, in parkin-deficient human brain H2O2concentrations are elevated. Inprkn-null mice, H2O2levels are dysregulated under oxidative stress conditions, such as acutely by MPTP-toxin exposure or chronically due to a second genetic hit. In dopamine toxicity studies, wild-type parkin, but not disease-linked mutants, protects human dopaminergic M17 cells, in part through lowering H2O2. Parkin also neutralizes reactive, electrophilic dopamine metabolites via adduct formation, which occurs foremost at primate-specific Cys95. Further, wild-type but not p.C95A-mutant parkin augments melanin formation. In sections of normal, adult human midbrain, parkin specifically co-localizes with neuromelanin pigment, frequently within LAMP-3/CD63+lysosomes. We conclude that oxidative modifications of parkin cysteines are associated with protective outcomes, which include the reduction of H2O2, conjugation of reactive dopamine metabolites, sequestration of radicals within insoluble aggregates, and increased melanin formation. The loss of these redox effects may augment oxidative stress in dopamine producing neurons of mutantPRKNallele carriers, thereby contributing to neurodegeneration.
Rapid benchmarking: the case of a multinational dairy company
Authors: Malik Rubab , Mann Robin , Knapman Rebecca
Published: November 2020

Purpose

The purpose of the study is to investigate and document a new approach to best practice benchmarking called rapid benchmarking. Rapid benchmarking is defined by the authors as an approach to dramatically shorten the typical length of time to conduct a successful best practice benchmarking project.

Design/methodology/approach

The methodology involved a case study exploration of a multinational dairy company's best practice benchmarking approach using structured interviews and data collection to examine the speed and results achieved through its benchmarking approach and whether it was justified in naming it as rapid benchmarking. A comparison of the speed of the dairy company's approach was undertaken against 24 other organisations that had utilised the same benchmarking methodology (TRADE Best Practice Benchmarking). In addition, a literature review was undertaken to search for other cases of rapid benchmarking and compare rapid benchmarking with other rapid improvement approaches.

Findings

The findings revealed that the approach used by the dairy company was unique, with best practices being identified and action plans signed off for deployment within a five-day period (far quicker than the average time of 211 days reported by other organisations). Key success factors for rapid benchmarking were found to be allocating five dedicated days for the benchmarking team to spend on the project, identifying the right team members for the project, obtaining sponsorship support for the project and providing intensive facilitation support through a benchmarking facilitator.

Research limitations/implications

Only one company was found to use a rapid benchmarking approach; therefore, the findings are from one case study. The depth of analysis presented was restricted due to commercial sensitivity.

Practical implications

The rapid benchmarking approach is likely to be of great interest to practitioners, providing them with a new way of finding solutions and best practices to address challenges that need to be solved quickly or with minimal expense. For organisations that have been using benchmarking for many years, the research will enable them to re-evaluate their own benchmarking approach and consider if rapid benchmarking could be used for some projects, particularly for internal benchmarking where it is easier to apply.

Originality/value

This research is the first to identify and document a rapid benchmarking approach and the first to provide a detailed analysis of the length of time it takes to undertake best practice benchmarking projects (and each stage of a benchmarking project).
Digitalization and migration: the role of social media and migrant networks in migration decisions. An exploratory study in Nigeria
Authors: Obi Chinedu , Bartolini Fabio , D’Haese Marijke
Published: November 2020

Purpose

This paper aims to explore the connectivity between social media use, access to migrant networks, information asymmetry and migration intentions.

Design/methodology/approach

The study was conducted using data from individuals living in Nigeria and analysed with a generalized structural equation model, which is rare for this kind of research.

Findings

The authors find a dual mediating role of the social media and the migrant networks in facilitating migration, i.e. reducing the threshold cost required to migrate and introducing a bias in terms of information asymmetry. While social media and access to migrant networks directly increase migration intentions, this changes when incomplete information is provided. People who use social media and their migrant networks for information are more likely to have information about destination countries than information on the transit risk.

Social implications

The study adds valuable insights for designing awareness campaigns aimed at reducing irregular migration.

Originality/value

This study contributes to the understanding of the intersection of migration and digitalization
Doctoral dissertations in supply chain management: a review of Chinese contributions from 1995 to 2019
Authors: Yang Lu , Huo Baofeng
Published: November 2020

Purpose

This study aims to investigate Chinese doctoral dissertations in supply chain management (SCM) by providing an overview of the evolution of this topic over the past 25 years.

Design/methodology/approach

This study reviews 1,945 doctoral dissertations in SCM from 39 Project 985 universities in China.

Findings

The annual number of SCM doctoral dissertations in China varied significantly over time, and the top producers are all strong players in the SCM field with long histories of research. The dissertations use multiple methods, of which mathematical, econometric modeling and simulation, and survey are the most frequently used. Most of the frequently used theories are borrowed from other disciplines. Traditional research topics are frequently investigated in Chinese doctoral dissertations in SCM, but the popular research topics differ by period.

Originality/value

This study has examined Chinese doctoral dissertations in SCM through a literature review. This study provides implications for research topics, methodological approaches, and theoretical lenses for future research. It also disseminates Chinese SCM knowledge to the global academic network to stimulate more SCM research.
Setting margins for margin buying in China: balancing the trade-off between liquidity and prudence
Authors: Hong Hui , Lee Chien-Chiang , Bian Zhicun
Published: November 2020

Purpose

The purpose of this paper is to propose a new dynamic margin setting method for margin buying in China and evaluate the validity of its performance with the current margin system adopted by stock exchanges in extreme episodes.

Design/methodology/approach

This paper adopts the dynamic conceptual model of Huang et al. (2012) (which is based on Figlewski (1984)) but incorporates Markov chain to describe the data generation process of stock price changes. By applying the model to margin buying contracts for the period of March 16, 2018, to May 2, 2018 (baseline study) and June 15, 2015, to July 27, 2015 (robustness test), the model’s superiority to the current margin system adopted by stock exchanges is also tested.

Findings

The paper has several important findings. First, the margins derived by this system vary with market conditions, rising (declining) when stock prices go down (up), and are generally lower than the requirements imposed by stock exchanges. Second, this margin system induces lower overall percentage of costs than that adopted by stock exchanges. Third, parameter estimation plays an important role on shaping empirical results.

Research limitations/implications

The primary limitation of this paper lies in the fact that it does not solve the issue of determining optimal parameters of the Markov chain model. On the implication of findings, policy-makers and regulators on supervising margin buying activities may need a tune-up on the current margin system which features static margin requirements. Dynamic margins that incorporate market factors are virtually useful to balance the trade-off between liquidity and prudence.

Originality/value

To the best of the authors’ knowledge, this study is the first of its kind to develop a dynamic margin setting method for margin buying in China, aiming to balance the trade-off between liquidity and prudence. It not only takes into account the uniqueness of Chinese markets but also allows for time variations in both initial and maintenance margins.
Improving programming skills: the use of learning style theory and the instant response supplement tool
Authors: Lai Chin-Feng , Jeng Yu-Lin , Huang Sheng-Bo
Published: November 2020

Purpose

In a programming course, students often need tutors' assistance to complete learning activities, as they lack enough background knowledge to complete tasks. A further problem is that without individual tutoring, the knowledge gap between students increases. Therefore, the authors have proposed an instant response learning supplement tool (IRLST) to support students' learning, in order to facilitate students' independent problem-solving skills.

Design/methodology/approach

The authors divided the students into two groups according to their learning styles: verbal and visual. The IRLST was used to collect and analyze the information on their usage and provide supplementary resources to facilitate their learning. The proposed system also analyzed the student usage, background knowledge and exam scores to assess their academic performance.

Findings

According to the results of statistical analysis, students' learning performance improved significantly, especially low-scoring students. Moreover, as compiler messages were not recognized, students tended to identify the same problems. Thus, it is suggested that teachers not only should focus on improving the students' syntax but also strengthening their background knowledge and debugging skills.

Research limitations/implications

There are two main limitations in this study: (1) as most of the students were in the visual learning group, the size of the groups was impacted, thus it was not possible to establish a control group; (2) one specific version of the IRLST system did not send reliable advice or supplementary content occasionally.

Originality/value

The IRLST developed in this study can be used to provide immediate supplementary resources to help students overcoming programming problems and developing problem-solving skills.
Visual contagion in prey defence signals can enhance honest defence
Authors: Dong Shihao , Tan Ken , Nieh James C.
Published: November 2020

The co‐evolutionary arms race between predators and their prey has led to complex signalling, especially in groups that benefit from the social transmission of alarm signals. In particular, pursuit deterrence signals can allow individuals and groups to indicate, at relatively low cost, that a predator's further approach is futile.

Pursuit deterrence signals are usually more effective if amplified, for example, by becoming contagious and rapidly spreading among prey without requiring individual prey to confirm predator presence. However, this can also lead to runaway false signalling.

We provide the first evidence of a contagious pursuit deterrence signal in social insects. The Asian honey bee Apis cerana, performs an I See You (ISY) signal that deters attacking hornets.

We show that these signals enhance defensive signalling by also attracting guard bees and that the visual movements of appropriate stimuli alone (hornets and ISY signalling bees, but not harmless butterflies) provide sufficient stimuli. Olfaction and other potential cues are not necessary. The ISY signal is visually contagious and is buffered from runaway false signals because it is specifically triggered and by likely selection for honesty within the highly cooperative bee colony.

These results expand our understanding of contagious signals and how they can be honestly maintained in highly cooperative collectives.
“Hangd for the True Faith”: Embodied Devotion in Early Modern English Carmelite Cloisters
Authors: Walker Claire
Published: November 2020

The annals of the English Carmelites of Antwerp document religious devotions which were intensely corporeal. Biographical sketches of individual sisters describe spiritual practices in which prayer and meditation, often enhanced by visual or bodily contact with devotional objects, fostered mystical encounters with Christ, saints, and martyrs. The Passion and the physical torment of holy figures who died for their faith infused the cloister's spirituality. At Antwerp, nuns encountered stories of suffering in devotional books and in hagiographical accounts of both the early Christian, and the more recent English, martyrs. They might also engage physically with Christ and saints through the cloister's relic collection and other objects of devotion. This article explores the religious milieu at Antwerp, considering the nuns' spiritual proclivity for suffering, which was inspired in part by their religious exile from England. It argues that a culture of martyrdom infused private devotional practices and shaped the convent's corporate identity.
Maximizing the acquisition of unique reads in noninvasive capture sequencing experiments
Authors: Fontsere Claudia , Alvarez‐Estape Marina , Lester Jack , Arandjelovic Mimi , Kuhlwilm Martin , Dieguez Paula , Agbor Anthony , Angedakin Samuel , Ayuk Ayimisin Emmanuel , Bessone Mattia , Brazzola Gregory , Deschner Tobias , Eno‐Nku Manasseh , Granjon Anne‐Céline , Head Josephine , Kadam Parag , Kalan Ammie K. , Kambi Mohamed , Langergraber Kevin , Lapuente Juan , Maretti Giovanna , Jayne Ormsby Lucy , Piel Alex , Robbins Martha M. , Stewart Fiona , Vergnes Virginie , Wittig Roman M. , Kühl Hjalmar S. , Marques‐Bonet Tomas , Hughes David A. , Lizano Esther
Published: November 2020

Noninvasive samples as a source of DNA are gaining interest in genomic studies of endangered species. However, their complex nature and low endogenous DNA content hamper the recovery of good quality data. Target capture has become a productive method to enrich the endogenous fraction of noninvasive samples, such as faeces, but its sensitivity has not yet been extensively studied. Coping with faecal samples with an endogenous DNA content below 1% is a common problem when prior selection of samples from a large collection is not possible. However, samples classified as unfavourable for target capture sequencing might be the only representatives of unique specific geographical locations, or to answer the question of interest. To explore how library complexity may be increased without repeating DNA extractions and generating new libraries, in this study we captured the exome of 60 chimpanzees (Pan troglodytes) using faecal samples with very low proportions of endogenous content (<1%). Our results indicate that by performing additional hybridizations of the same libraries, the molecular complexity can be maintained to achieve higher coverage. Also, whenever possible, the starting DNA material for capture should be increased. Finally, we specifically calculated the sequencing effort needed to avoid exhausting the library complexity of enriched faecal samples with low endogenous DNA content. This study provides guidelines, schemes and tools for laboratories facing the challenges of working with noninvasive samples containing extremely low amounts of endogenous DNA.
Long‐term outcomes of sentinel node identification using indocyanine green in patients with lung cancer
Authors: Kawakami Yukikiyo , Kondo Kazuya , Kawakita Naoya , Matsuoka Hisashi , Toba Hiroaki , Takizawa Hiromitsu , Yoshida Mitsuteru , Tangoku Akira
Published: November 2020

Background

Sentinel node (SN) biopsy is used in the management of numerous cancers to avoid unnecessary lymphadenectomy. This was a clinical exploration/feasibility study of a novel identification technique for SN biopsy using indocyanine green (ICG) fluorescence imaging during lung cancer surgery.

Methods

SN biopsy using ICG was performed on 22 patients who had cT1 or T2N0M0 lung cancer. ICG was injected just around the primary tumor. The fluorescence imaging system enabled visualization of the lymphatic vessels draining from the primary tumor toward the lymph nodes. Fluorescently labeled nodes were dissected, and patients were followed‐up for prognosis and recurrence to confirm the pattern of lymph node metastasis after surgery.

Results

SNs were successfully identified in 16 (72.7%) of 22 patients. A total of 13 of 16 patients had pathological N0 and three had SN metastasis. The median follow‐up time was 92.7 months. Only one patient had no SN metastasis at the postoperative pathological examination and lymph node metastasis during the follow‐up period. The accuracy rate was 93.8% (15/16) and the false‐negative rate was 7.7% (1/13).

Conclusions

SNs were identified by ICG fluorescence imaging, and this technique during lung cancer surgery had good identification and accuracy rates throughout the follow‐up period.

Key points

Significant findings of the study

We attempted to identify sentinel lymph nodes by indocyanine green in lung cancer surgery. The identification rate was 72.7%. The accuracy rate was 100% immediately after surgery, and 93.8% after follow‐up.

What this study adds

Sentinel node biopsy by indocyanine green may be useful for lymph node dissection during lung cancer surgery to avoid unnecessary lymphadenectomy.
Fetal Alcohol Exposure Alters BOLD Activation Patterns in Brain Regions Mediating the Interpretation of Facial Affect
Authors: Lindinger Nadine M. , Jacobson Joseph L. , Warton Christopher M.R. , Malcolm‐Smith Susan , Molteno Christopher D. , Dodge Neil C. , Robertson Frances , Meintjes Ernesta M. , Jacobson Sandra W.
Published: November 2020

Background

Although deficits in the interpretation of affective facial expressions have been described clinically and in behavioral studies of fetal alcohol spectrum disorders (FASD), effects of prenatal alcohol exposure on the neural networks that mediate affective appraisal have not previously been examined.

Methods

We administered a nonverbal event‐related fMRI affective appraisal paradigm to 64 children (mean age = 12.5 years; 18 with fetal alcohol syndrome (FAS) or partial FAS (PFAS), 18 nonsyndromal heavily exposed (HE), and 28 controls). Happy, sad, angry, fearful, and neutral faces and pixelated control images were presented sequentially in a randomized order. The child indicated whether the currently displayed face showed the same or different affect as the previous one.

Results

Data from whole‐brain analyses showed that all groups activated the appropriate face processing neural networks. Region of interest analyses indicated that, compared to HE and control children, the FAS/PFAS group exhibited greater blood oxygenation level–dependent (BOLD) signal changes when processing neutral faces than pixelated images in 2 regions that form part of the visual sensory social brain network, which plays an important role in the initial processing of facial affect. By contrast, BOLD signal when processing angry faces was weaker for the FAS/PFAS group in a region involved in the processing of facial identity and facial expressions and in a region involved in the recognition and selection of behavioral responses to aggressive behavior.

Conclusions

These findings of greater BOLD signal in the FAS/PFAS group in response to neutral faces suggest less efficient neural processing of more difficult to interpret emotions, and the weaker BOLD response to angry faces suggests altered processing of angry stimuli. Although behavioral performance did not differ in this relatively simple affective appraisal task, these data suggest that in children with FAS and PFAS, the appraisal of neutral affect and anger is likely to be more effortful in more challenging and dynamic social contexts.
Craving mediates the association between momentary pain and illicit opioid use during treatment for opioid‐use disorder: an ecological momentary assessment study
Authors: Mun Chung Jung , Finan Patrick H. , Epstein David H. , Kowalczyk William J. , Agage Daniel , Letzen Janelle E. , Phillips Karran A. , Preston Kenzie L.
Published: November 2020

Aim

To assess the role of momentary pain on opioid craving and illicit opioid use among individuals receiving opioid agonist treatment.

Design

Observational study using ecological momentary assessment.

Setting

The National Institute of Drug Abuse Intramural Research Program in the United States.

Participants

Fifty‐six adults who qualified for opioid agonist treatment.

Measurements

Participants completed randomly prompted assessments of pain severity, stress, negative mood, opioid craving and illicit opioid use for a mean of 66 days [standard deviation (SD) = 27]. Urine samples were collected two to three times/week throughout.

Findings

Almost 70% of participants reported moderate average pain severity in the past 24 hours at intake and 35% of participants reported chronic pain. There were no significant differences in percent of opioid‐positive urine samples (P = 0.73) and average level of opioid craving during the study period (P = 0.91) among opioid agonist treatment only patients versus opioid agonist treatment patients with chronic pain. However, momentary pain severity significantly predicted concurrent opioid craving [B = 0.02, 95% confidence interval (CI) = 0.01, 0.04], over and above stress and negative mood. Momentary opioid craving, in turn, significantly predicted illicit opioid use that was assessed in the next moment [odds ratio (OR) = 1.72, 95% CI = 1.12, 2.64), while controlling for autocorrelation and the effects of pain, negative mood and stress. Momentary opioid craving significantly mediated the prospective association between momentary pain and illicit opioid use (95% CI = 0.003, 0.032). Exploratory analysis revealed that momentary pain severity also significantly moderated the momentary association between stress and opioid craving (B = 0.02, 95% CI = 0.00, 0.04), such that when momentary pain severity increased, the association between the two intensified.

Conclusions

Among people receiving opioid agonist treatment, momentary pain appears to be indirectly associated with illicit opioid use via momentary opioid craving.
The rewarding recovery study: a randomized controlled trial of incentives for alcohol and drug abstinence with a rural American Indian community
Authors: McDonell Michael G. , Skalisky Jordan , Burduli Ekaterina , Foote Albert , Granbois Alexandria , Smoker Kenneth , Hirchak Katherine , Herron Jalene , Ries Richard K. , Echo‐Hawk Abigail , Barbosa‐Leiker Celestina , Buchwald Dedra , Roll John , McPherson Sterling M.
Published: November 2020

Aims

To test if contingency management (CM) interventions for alcohol and drug abstinence were associated with increased alcohol and drug abstinence among American Indian adults with alcohol dependence who also use drugs.

Design

In this 2 × 2 factorial randomized controlled trial, American Indian adults with alcohol dependence who also used drugs were randomized to four conditions: (1) incentives for submission of urine samples only (control condition), (2) CM incentives for alcohol abstinence, (3) CM incentives for drug abstinence or (4) CM incentives for abstinence from both alcohol and drugs.

Setting

A Northern Plains Reservation in the United States.

Participants

A total of 114 American Indian adults aged 35.8 years (standard deviation = 10.4); 49.1% were male.

Intervention and comparator

Participants received incentives if they demonstrated abstinence from alcohol (CM for alcohol, n = 30), abstinence from their most frequently used drug (CM for drugs, n = 27) or abstinence from both alcohol and their most frequently used drug (CM for alcohol and drugs, n = 32) as assessed by urine tests. Controls (n = 25) received incentives for submitting urine samples only.

Measurements

Primary outcomes were urine ethyl glucuronide (alcohol) and drug tests conducted three times per week during the 12‐week intervention period. Data analyses included listwise deletion and multiple imputation to account for missing data.

Findings

The three CM groups were significantly (P < 0.05) more likely to submit alcohol‐abstinent urine samples compared with the control condition, with odds ratios ranging from 2.4 to 4.8. The CM for drugs (OR = 3.2) and CM for alcohol and drugs (OR = 2.5) were significantly more likely to submit urine samples that indicated drug abstinence, relative to the control condition (P < 0.05). However, these differences were not significant in multiple imputation analyses (P > 0.05).

Conclusions

Contingency management (CM) incentives for abstinence were associated with increased alcohol abstinence in American Indian adults diagnosed with alcohol dependence who also used drugs, living on a rural reservation. The effect of CM incentives on drug abstinence was inconclusive.
Seasonal morphology and immunoreactivity of cytokeratin and atrial natriuretic peptide in dromedary camel poll glands
Authors: Ibrahim Zarroug Hassan , Al‐Kheraije Khalid Ali
Published: November 2020

Poll glands are characteristic feature of dromedary camels; although they yield a yellowish offensive secretion, especially during rutting (breeding) season, their function is not yet exactly specified. The present study shows the seasonal morphology and immunoreactivity of cytokeratin (CK) and atrial natriuretic peptide (ANP) in the camel poll gland; the result could clearly specify the role of the gland in camel reproduction. Poll glands are compound tubulo‐alveolar in structure. During rutting season, the secretory units showed wide lumina and simple squamous epithelium surrounded by myoepithelial cells; the lumina became narrower and the epithelium changed to simple cuboidal during non‐rutting season. Many glandular lobules showed abundant interlobular connective tissue with fewer and smaller secretory units during non‐rutting season compared to rutting season. Positive CK and ANP immunoreactivity was detected in the cytoplasm of epithelial cells of secretory units and ducts together with the myoepithelial cells and blood vessels. Although CK immunoreactivity was more intense during rutting season in comparison to non‐rutting season, there was no seasonal variation in ANP immunoreactivity. During both seasons, while the glandular capsule, connective tissue septa, interstitium showed negative CK immunoreactions, they reacted moderately to ANP. In conclusion, the poll gland undergoes annual structural and functional changes which are suggested to correlate with the male seasonal sexual behaviour. Further, the biological role of CK and ANP proteins together with their immunohistochemical expression in the camel poll gland suggests a stimulatory effect in the glandular secretory cells, and hence, they might modify camel sexual activity.
Annular atrophic lichen planus induced by anti‐HER2 antibodies
Authors: Chawla Sumir , Turner Nicholas , Terlizzo Monica , Heelan Kara
Published: November 2020

Pertuzumab and trastuzumab are monoclonal antibody inhibitors targeting human epidermal growth factor receptor 2 (HER‐2) and are increasingly being utilised in the management of HER2‐positive breast cancer, having been demonstrated to improve progression‐free survival in conjunction with docetaxel. We present a rare presentation of a lichenoid drug eruption, in an annular atrophic variant, in a 35‐year‐old woman after initiation of HER2‐inhibitor (pertuzumab and trastuzumab) therapy for metastatic breast cancer.
Public good, collective action and financial regulation
Authors: Ülgen Faruk
Published: November 2020

The economy‐wide liberalization reforms implemented from the 1980s onwards in major capitalist economies had deep impact on financial markets. Public financial regulation has been replaced by self‐regulation, financial innovations proliferated and gave rise to many diversified and complex speculative operations that financialized most economic decisions and actions. Recurrent instabilities and crises became common ground in advanced as well as in emerging market economies and converged on the global systemic crisis in 2007–08, notwithstanding the efficient market doctrine that kept supporting financial liberalization. This crisis raised concerns about the relevance of market‐based financial regulation with regard to the systemic viability of capitalist economies and brought forward the central role of financial regulatory framework in the sustainable working of open societies. This article considers financial stability as a collective action problem through the lens of the literature on the commons and public goods. It seeks to contribute to the development of a relevant paradigm of collective action in the provision of a particular public good, financial stability, through a particular public action, financial regulation. After recalling the broad outlines of the evolution of financial markets and the institutional environment in the last decades, the monetary and financial characteristics of a capitalist economy are presented. The monetary and financial structure turns out to be a public infrastructure. The criticalness of financial transactions for the whole economic society together with the non‐rivalrousness and non‐excludability of financial stability determine the very publicness of the latter. The continuity of financial relations fundamentally needs a viable financial system. However, this is a complex issue as it falls into the classical opposition “private vs public” and calls for a collective action framework consistent with the characteristics of a financialized economy. This article argues that financial stability cannot be ensured through individual‐decision‐based market relations because of the endogenous limits of individual actions and the systemic nature of instabilities they can provoke. A specific treatment of finance as a public utility and of financial stability as a public good is then required. The study on the organization and management of financial markets, namely financial governance issue, ultimately leads to consider financial regulation as a collective action problem that calls for a public supervision framework through an extra‐market macroregulation, apt to allow economy to work in a viable way.
Dual role of B7‐H6 as a novel prognostic marker in hepatocellular carcinoma
Authors: Qiu Hao , Gao Shangshang , Sun Ziling , Wang Jiamin
Published: November 2020

B7 homolog 6 (B7‐H6), a new member of the B7 family, is identified as an activating ligand for cytotoxicity triggering receptor 3 (NKp30) expressing on natural killer cells. The purpose of this study was to investigate the clinical significance of B7‐H6 in hepatocellular carcinoma (HCC). We evaluated B7‐H6 expression by immunohistochemistry in a cohort of 90 HCC tumors with clinical follow‐up, the potential relationship between the B7‐H6 expression and the clinicopathological characteristics of HCC patients was also analyzed. Stable B7‐H6 knockdown in hepatoma cell line was established to explore the function and mechanism of B7‐H6 in HCC. This study showed that high expression of B7‐H6 was significantly associated with smaller tumor size, single tumor number in HCC, but no significant association was found between B7‐H6 overexpression and other clinicopathological parameters. Moreover, Kaplan–Meier survival analysis showed that high expression of B7‐H6 was significantly correlated with better survival of HCC patients. Knockdown of B7‐H6 inhibited tumor cell proliferation and induced cell apoptosis. However, it also impaired the sensitivity of tumor cells to NK‐mediated lysis together with significantly decreased degranulation and IFN‐γ release of NK cells. These results indicated that B7‐H6 has a dual role in HCC. It could be an independent indicator for better survival of HCC and maybe a potential target for future cancer treatment.
Optimization of voriconazole therapy for treatment of invasive aspergillosis: Pharmacogenomics and inflammatory status need to be evaluated
Authors: Gautier‐Veyret Elodie , Thiebaut‐Bertrand Anne , Roustit Matthieu , Bolcato Léa , Depeisses Julie , Schacherer Mathilde , Schummer Gabriel , Fonrose Xavier , Stanke‐Labesque Françoise
Published: November 2020

Aims

Cytochrome 2C19 genotype‐directed dosing of voriconazole (VRC) reduces the incidence of insufficient VRC trough concentrations (Cmin) but does not account for CYP3A polymorphisms, also involved in VRC metabolism. This prospective observational study aimed to evaluate the utility of a genetic score combining CYP2C19 and CYP3A genotypes to predict insufficient initial VRC Cmin (<1 mg/L).

Methods

The genetic score was determined in hematological patients treated with VRC. The higher the genetic score, the faster the metabolism of the patient. The impact of the genetic score was evaluated considering initial VRC Cmin and all VRC Cmin (n = 159) determined during longitudinal therapeutic drug monitoring.

Results

Forty‐three patients were included, of whom 41 received VRC for curative indication. Thirty‐six patients had a genetic score ≥2, of whom 11 had an initial insufficient VRC Cmin. A genetic score ≥2 had a positive predictive value of 0.31 for having an initial insufficient VRC Cmin and initial VRC Cmin was not associated with the genetic score. The lack of association between the genetic score and VRC Cmin may be related to the inflammatory status of the patients (C‐reactive protein [CRP] levels: median [Q1‐Q3]: 43.0 [11.0‐110.0] mg/L), as multivariate analysis performed on all VRC Cmin identified CRP as an independent determinant of the VRC Cmin adjusted for dose (P < .0001).

Conclusion

The combined genetic score did not predict low VRC exposure in patients with inflammation, which is frequent in patients with invasive fungal infections. Strategies for the individualization of VRC dose should integrate the inflammatory status of patients in addition to pharmacogenetic variants.
A latent capture history model for digital aerial surveys
Authors: Borchers David L. , Nightingale Peter , Stevenson Ben C. , Fewster Rachel M.
Published: November 2020

We anticipate that unmanned aerial vehicles will become popular wildlife survey platforms. Because detecting animals from the air is imperfect, we develop a mark‐recapture line transect method using two digital cameras, possibly mounted on one aircraft, which cover the same area with a short time delay between them. Animal movement between the passage of the cameras introduces uncertainty in individual identity, so individual capture histories are unobservable and are treated as latent variables. We obtain the likelihood for mark‐recapture line transects without capture histories by automatically enumerating all possibilities within segments of the transect that contain ambiguous identities, instead of attempting to decide identities in a prior step. We call this method “Latent Capture‐history Enumeration” (LCE). We include an availability model for species that are periodically unavailable for detection, such as cetaceans that are undetectable while diving. External data are needed to estimate the availability cycle length, but not the mean availability rate, if the full availability model is employed. We compare the LCE method with the recently developed cluster capture‐recapture method (CCR), which uses a Palm likelihood approximation, providing the first comparison of CCR with maximum likelihood. The LCE estimator has slightly lower variance, more so as sample size increases, and close to nominal coverage probabilities. Both methods are approximately unbiased. We illustrate with semisynthetic data from a harbor porpoise survey.
Incorporating acalabrutinib, a selective next‐generation Bruton tyrosine kinase inhibitor, into clinical practice for the treatment of haematological malignancies
Authors: Danilov Alexey V. , Persky Daniel O.
Published: November 2020

Greater understanding of the mechanisms involved in the disease progression of haematological malignancies has led to the introduction of novel targeted therapies with reduced toxicity compared with chemotherapy‐based regimens, which has expanded the treatment options for patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). Ibrutinib is a first‐in‐class Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of patients with CLL/SLL or relapsed/refractory MCL. However, next‐generation BTK inhibitors have been developed with improved specificity and the potential to reduce the off‐target toxicity observed with ibrutinib. Acalabrutinib is a highly selective, next‐generation BTK inhibitor, which was granted accelerated approval by the US Food and Drug Administration in 2017 for the treatment of adult patients with MCL who have received at least one prior therapy. In November 2019, it was also granted approval for the treatment of adult patients with CLL/SLL on the basis of two phase 3 clinical trials. This review describes the current understanding of acalabrutinib according to clinical study data for the treatment of MCL and CLL/SLL and shares recommendations from our practice on how it should be used when treating patients in the clinic, including dosing, administration and management of adverse events.
Parental incarceration and children's oral health in the United States: Findings from the 2016‐2018 National Survey of Children's Health
Authors: Testa Alexander , Jackson Dylan B.
Published: November 2020

Objective

This study aimed to examine the association between parental incarceration and children's oral health in the United States and assess the degree to which household socioeconomic factors, children's healthcare insurance and oral healthcare utilization/preventive care explain this association.

Methods

Using data from the 2016‐2018 National Survey of Children's Health (NSCH; N = 99 962), a series of logistic regression models were used to investigate the association between parental incarceration and a variety of children's oral health conditions. The Karlson‐Holm‐Breen method was used to assess the degree to which household socioeconomic factors, children's healthcare insurance and oral healthcare utilization/preventive care visits reduced the association between parental incarceration and children's oral health.

Results

Results from logistic regression analyses demonstrated that net of control variables, children of incarcerated parents have significantly worse oral health including poor or fair teeth condition (OR = 2.71, 95% CI = 2.23‐3.29), toothaches (OR = 1.72, 95% CI = 1.36‐2.18), gum bleeding (2.12, 95% CI = 1.52‐2.94), cavities/tooth decay (OR = 1.50, 95% CI = 1.26‐1.77) and are more likely to have unmet dental care needs (OR = 1.78, 95% CI = 1.28‐2.46). Attenuation analyses demonstrated this relationship is partially explained by household material hardship and children's health insurance.

Conclusions

Parental incarceration is associated with worse oral health and unmet dental care needs. Household material hardship and children's health insurance partially attenuate this association. Efforts to expand oral health literacy to incarceration‐exposed parents, and policies that buffer against material hardship and inadequacies in children's health insurance may be useful for improving oral health of children whose parents have been incarcerated.
Selective forces acting on spinocerebellar ataxia type 3/Machado–Joseph disease recurrency: A systematic review and meta‐analysis
Authors: Sena Lucas Schenatto , dos Santos Pinheiro Jordânia , Saraiva‐Pereira Maria Luiza , Jardim Laura Bannach
Published: November 2020

Spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD) is a dominant neurodegenerative disease caused by the expansion of a CAG repeat tract in ATXN3. Anticipation and worsening of clinical picture in subsequent generations were repeatedly reported, but there is no indication that SCA3/MJD frequency is changing. Thus, we performed a systematic review and meta‐analysis on phenomena with potential effect on SCA3/MJD recurrency in populations: instability of CAG repeat transmissions, anticipation, fitness, and segregation of alleles. Transmission of the mutant allele was associated with an increase of 1.23 CAG repeats in the next generation, and the average change in age at onset showed an anticipation of 7.75 years per generation; but biased recruitments cannot be ruled out. Affected SCA3/MJD individuals had 45% more children than related controls. Transmissions from SCA3/MJD carriers showed that the expanded allele was segregated in 64% of their children. In contrast, transmissions from normal subjects showed that the minor allele was segregated in 54%. The present meta‐analysis concluded that there is a segregation distortion favoring the expanded allele, among children of carriers. Therefore, further studies on transmissions and anticipation phenomena as well as more observations about fertility are required to clarify these selective forces over SCA3/MJD.
Thermal effects of various drill materials during implant site preparation—Ceramic vs. stainless steel drills: A comparative in vitro study in a standardised bovine bone model
Authors: Tur Dino , Giannis Katharina , Unger Ewald , Mittlböck Martina , Rausch‐Fan Xiaohui , Strbac Georg D.
Published: November 2020

Objectives

The aim of this study was to evaluate thermal effects of ceramic and metal implant drills during implant site preparation using a standardised bovine model.

Material and Methods

A total of 320 automated intermittent osteotomies of 10‐ and 16‐mm drilling depths were performed using zirconium dioxide‐based and stainless steel drills. Various drill diameters (2.0/ 2.2, 2.8, 3.5, 4.2 mm ∅) and different cooling methods (without/ with external saline irrigation) were investigated at room temperature (21 ± 1°C). Temperature changes were recorded in real time using two custom‐built multichannel thermoprobes in 1‐ and 2‐mm distance to the osteotomy site. For comparisons, a linear mixed model was estimated.

Results

Comparing thermal effects, significantly lower temperatures could be detected with steel‐based drills in various drill diameters, regardless of drilling depth or irrigation method. Recorded temperatures for metal drills of all diameters and drilling depths using external irrigation were below the defined critical temperature threshold of 47°C, whereas ceramic drills of smaller diameters reached or exceeded the harmful temperature threshold at 16‐mm drilling depths, regardless of whether irrigation was applied or not. The results of this study suggest that the highest temperature changes were not found at the deepest point of the osteotomy site but were observed at subcortical and deeper layers of bone, depending on drill material, drill diameter, drilling depth and irrigation method.

Conclusions

This standardised investigation revealed drill material and geometry to have a substantial impact on heat generation, as well as external irrigation, drilling depth and drill diameter.