bluuebunny/crossref_metadata_2025 huggingface dataset:
The structural basis of odorant recognition in insect olfactory receptors
Authors: del Mármol Josefina , Yedlin Mackenzie , Ruta Vanessa
Published: January 2021

Olfactory systems must detect and discriminate an enormous diversity of chemicals in the environment. To contend with this challenge, diverse species have converged on a common strategy in which odorant identity is encoded through the combinatorial activation of large families of olfactory receptors (ORs), thus allowing a finite number of receptors to detect an almost infinite chemical world. Although most individual ORs are sensitive to a variety of odorants, the structural basis for such flexible chemical recognition remains unknown. Here, we combine cryo-electron microscopy with functional studies of receptor tuning to gain insight into the structural and mechanistic basis of promiscuous odorant recognition. We show that OR5 from the jumping bristletail,Machilis hrabei, assembles as a homo-tetrameric odorant-gated ion channel with broad chemical tuning. We elucidated the structure of OR5 in multiple gating states, alone and in complex with two of its agonists—the odorant eugenol and the insect repellent DEET. Both ligands bind to a common binding site located in the transmembrane region of each subunit, composed of a simple geometric arrangement of aromatic and hydrophobic residues. We reveal that binding is mediated by hydrophobic, non-directional interactions with residues distributed throughout the binding pocket, enabling the flexible recognition of structurally distinct odorants. Mutation of individual residues lining the binding pocket predictably altered OR5’s sensitivity to eugenol and DEET and broadly reconfigured the receptor’s tuning, supporting a model in which diverse odorants share the same structural determinants for binding. Together, these studies provide structural insight into odorant detection, shedding light onto the molecular recognition mechanisms that ultimately endow the olfactory system with its immense discriminatory capacity.
An Autoantigen Atlas from Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19
Authors: Wang Julia Y. , Zhang Wei , Roehrl Michael W. , Roehrl Victor B. , Roehrl Michael H.
Published: January 2021

COVID-19 is accompanied by a myriad of both transient and long-lasting autoimmune responses. Dermatan sulfate (DS), a glycosaminoglycan crucial for wound healing, has unique affinity for autoantigens (autoAgs) from apoptotic cells. DS-autoAg complexes are capable of stimulating autoreactive B cells and autoantibody production. Using DS affinity, we identified an autoantigenome of 408 proteins from human fetal lung fibroblast HFL11 cells, at least 231 of which are known autoAgs. Comparing with available COVID data, 352 proteins of the autoantigenome have thus far been found to be altered at protein or RNA levels in SARS-Cov-2 infection, 210 of which are known autoAgs. The COVID-altered proteins are significantly associated with RNA metabolism, translation, vesicles and vesicle transport, cell death, supramolecular fibrils, cytoskeleton, extracellular matrix, and interleukin signaling. They offer clues to neurological problems, fibrosis, smooth muscle dysfunction, and thrombosis. In particular, 150 altered proteins are related to the nervous system, including axon, myelin sheath, neuron projection, neuronal cell body, and olfactory bulb. An association with the melanosome is also identified. The findings from our study illustrate a strong connection between viral infection and autoimmunity. The vast number of COVID-altered proteins with propensity to become autoAgs offers an explanation for the diverse autoimmune complications in COVID patients. The variety of autoAgs related to mRNA metabolism, translation, and vesicles raises concerns about potential adverse effects of mRNA vaccines. The COVID autoantigen atlas we are establishing provides a detailed molecular map for further investigation of autoimmune sequelae of the pandemic.

Summary sentence

An autoantigenome by dermatan sulfate affinity from human lung HFL1 cells may explain neurological and autoimmune manifestations of COVID-19
Identification of LINE retrotransposons and long non-coding RNAs expressed in the octopus brain
Authors: Petrosino Giuseppe , Ponte Giovanna , Volpe Massimiliano , Zarrella Ilaria , Langella Concetta , Di Cristina Giulia , Finaurini Sara , Russo Monia T. , Basu Swaraj , Musacchia Francesco , Ristoratore Filomena , Pavlinic Dinko , Benes Vladimir , Ferrante Maria I. , Albertin Caroline , Simakov Oleg , Gustincich Stefano , Fiorito Graziano , Sanges Remo
Published: January 2021

Background

Transposable elements (TEs) widely contributed to the evolution of genomes allowing genomic innovations, generating germinal and somatic heterogeneity and giving birth to long non-coding RNAs (lncRNAs). These features have been associated to the evolution, functioning and complexity of the nervous system at such a level that somatic retrotransposition of long interspersed element (LINE) L1 has been proposed to be associated to human cognition. Among invertebrates, octopuses are fascinating animals whose nervous system reaches a high level of complexity achieving sophisticated cognitive abilities. The sequencing of the genome of theOctopus bimaculoidesrevealed a striking expansion of TEs which were proposed to have contributed to the evolution of its complex nervous system. We recently found a similar expansion also in the genome ofOctopus vulgaris. However a specific search for the existence of full-length transpositionally competent TEs has not been performed in this genus.

Results

Here we report the identification of LINE elements competent for retrotransposition inOctopus vulgarisandOctopus bimaculoidesand show evidence suggesting that they might be active driving germline polymorphisms among individuals and somatic polymorphisms in the brain. Transcription and translation measured for one of these elements resulted in specific signals in neurons belonging to areas associated with behavioral plasticity. We also report the transcription of thousands of lncRNAs and the pervasive inclusion of TE fragments in the transcriptomes of bothOctopusspecies, further testifying the crucial activity of TEs in the evolution of the octopus genomes.

Conclusions

The neural transcriptome of the octopus shows the transcription of thousands of putative lncRNAs and of a full lenght LINE element belonging to the RTE class. We speculate that a convergent evolutionary process involving retrotransposons activity in the brain has been important for the evolution of sophisticated cognitive abilities in this genus.
Molecular Dynamics Reveals the Effects of Temperature on Critical SARS-CoV-2 Proteins
Authors: Morgan Paul , Shu Chih-Wen
Published: January 2021

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a newly identified RNA virus that causes the serious infection Coronavirus Disease 2019 (COVID-19). The incidence of COVID-19 is still increasing worldwide despite the summer heat and cool winter. However, little is known about seasonal stability of SARS-CoV-2. Herein, we employ Molecular Dynamics (MD) simulations to explore the effect of temperature on four critical SARS-CoV-2 proteins. Our work demonstrates that the spike Receptor Binding Domain (RBD), Main protease (Mpro), and nonstructural protein 3 (macro X) possesses extreme thermos-stability when subjected to temperature variations rendering them attractive drug targets. Furthermore, our findings suggest that these four proteins are well adapted to habitable temperatures on earth and are largely insensitive to cold and warm climates. Furthermore, we report that the critical residues in SARS-CoV-2 RBD were less responsive to temperature variations as compared to the critical residues in SARS-CoV. As such, extreme summer and winter climates, and the transition between the two seasons, are expected to have a negligible effect on the stability of SARS-CoV-2 which will marginally suppress transmission rates until effective therapeutics are available world-wide.
Adverse effects of trimethoprim–sulfamethoxazole for the prophylaxis of Pneumocystis pneumonia in dermatology
Authors: Kokubu Hiraku , Kato Takeshi , Nishikawa Junko , Tanaka Toshihiro , Fujimoto Noriki
Published: January 2021

Trimethoprim–sulfamethoxazole (TMP/SMX) combination is used for the prophylaxis of Pneumocystis pneumonia (PCP). Although TMP/SMX is frequently used in dermatology for cases treated with corticosteroids and/or immunosuppressants, it is often difficult to continue the administration of TMP/SMX due to adverse events. There are only a few reported studies on the prophylaxis of PCP in dermatology. This is the first review focused on adverse events of TMP/SMX among patients with dermatological diseases compared with previous reports. In this study, we retrospectively investigated 132 cases treated with TMP/SMX and examined the adverse events. Adverse events occurred in 32 cases (24.2%) and the incidence in this study was higher than in previous reports. Thrombocytopenia occurred in 17 cases (12.5%), which was the most frequent adverse event. The possible causes of adverse events were that the standard dose of TMP/SMX may be excessive for most Japanese, in addition to the long administration period, and the concomitant use of corticosteroids and/or immunosuppressants in almost all cases. We must consider the risks of PCP and adverse events of TMP/SMX in each case. It is desirable to examine possible administration methods that can be continued by adjusting the dose and interval of TMP/SMX.
Human activities and weather drive contact rates of wintering elk
Authors: Janousek William M. , Graves Tabitha A. , Berman Ethan E. , Chong Geneva W. , Cole Eric K. , Dewey Sarah R. , Johnston Aaron N. , Cross Paul C.
Published: January 2021

Wildlife aggregation patterns can influence disease transmission. However, limited research evaluates the influence of anthropogenic and natural factors on aggregation. Many managers would like to reduce wildlife contact rates, driven by aggregation, to limit disease transmission. We develop a novel analytical framework to quantify how management activities such as supplemental feeding and hunting versus weather drive contact rates while accounting for correlated contacts. We apply the framework to the National Elk Refuge (NER), Wyoming, USA, where the probable arrival of chronic wasting disease (CWD) has magnified concerns.

We used a daily proximity index to measure contact rates among 68 global positioning system collared elk from 2016 to 2019. We modelled contact rates as a function of abiotic weather‐related effects, anthropogenic effects and aggregation from the prior day. The winter of 2017–2018 had greater natural forage availability and little snow, which led to a rare non‐feeding year on the NER and provided a unique opportunity to evaluate the effect of feeding on contact rates relative to other conditions.

Supplemental feeding was the strongest predictor of aggregation, and contact rates were 2.6 times larger while feeding occurred compared to the baseline rate (0.34 and 0.13, respectively). Snow‐covered area was the second strongest predictor of contact rates highlighting the importance of abiotic factors to elk aggregation, but this effect had half the strength of feeding. These results are the first to show, even in animals that congregate naturally, how greatly supplemental feeding amplifies aggregation. Contact rates were also 23% lower during times when elk hunting was active (0.10) compared to the baseline.

Synthesis and applications. Supplemental feeding increased contacts between elk well above the natural effects of weather, even after accounting for correlated movement expected in wintering ungulates. Similarly, differences in hunting season timing with adjacent areas led to an increase in contacts, suggesting an additional management option for reducing aggregation. The analytical framework presented supports the evaluation of temporally varying management actions that influence aggregation broadly and can be easily implemented whether the interest in changing aggregation is related to reduction of disease transmission, human–wildlife conflict or inter‐species competition.
The timing of leaf senescence relates to flowering phenology and functional traits in 17 herbaceous species along elevational gradients
Authors: Bucher Solveig Franziska , Römermann Christine
Published: January 2021

Leaf senescence is a major event in a plant's life history as autumn marks the end of the growing season. The optimal timing of leaf senescence is crucial to both minimise risks of low temperature events and to maximise carbon gain during the growing season. As abiotic conditions are currently changing at unprecedented rates, it is important to study how leaf senescence of different species is responding to these changes in order to forecast future growing season length and carbon sequestration potentials. In contrast to flowering phenology, data on autumn events are scarce and even more so for herbaceous than for woody plants, thus more information on this phenological stage is urgently needed.

We studied leaf senescence in 632 populations from 17 herbaceous species located along elevational gradients. We focussed on the beginning (5% of the population senesce, LS5) and peak (50% senesce, LS50) of leaf senescence. To see whether we can predict species‐specific changes, we studied the link between LS5 and LS50 and flowering phenology as well as leaf functional traits related to plant performance. We looked at first and last flowering day and flowering duration as well as the traits specific leaf area (SLA), leaf dry matter content (LDMC), area‐based leaf nitrogen and carbon content, carbon isotope discrimination (Δ13C) and the stomatal pore area index.

We found species‐specific slopes of the beginning of leaf senescence along the elevational gradient. The peak of leaf senescence was uniformly delayed with increasing elevation across all species. Flowering phenology as well as leaf functional traits had a close relationship with leaf senescence and thus can be used to forecast species‐specific responses to changes in abiotic conditions. High SLA and high leaf nitrogen were related to earlier senescence while high LDMC, high Δ13C and high stomatal pore area index were related to later senescence.

Synthesis. The link between senescence, flowering phenology and plant functional traits will help to fine‐tune predictions of future growing season length and ecosystem function. To date, most analyses are based on spring phenology and traits, for which data are more abundant than data on autumn senescence.
Impact of the supplemental nutritional assistance program on diet‐related disease morbidity among older adults
Authors: Booshehri Layla G. , Dugan Jerome
Published: January 2021

Objectives

To examine the health effects of the Supplemental Nutritional Assistance Program (SNAP) and the differential impact of SNAP across race/ethnicity among older adults.

Data Source/Study Setting

2008‐2013 Medical Expenditure Panel Survey, a nationally representative population‐based complex sample survey.

Study Design

A difference‐in‐regression‐discontinuity (DRD) design is used to assess the impacts of SNAP on diet‐related disease morbidity. The primary outcomes were the prevalence rate of hypertension, coronary heart disease, stroke, diabetes, and cancer. We also conducted supplemental analysis to examine potential co‐occurring trends in medical utilization.

Data Collection/Extraction Methods

Data are publicly available.

Principal Findings

In the full sample, SNAP eligibility was associated with a significant decline in diabetes (−3.71 percentage points [pp]; P < .05). Non‐Hispanic (NH) White respondents reported trends similar to the full sample; however, NH Black respondents reported large declines in hypertension (−13.95 pp; P < .01) and Hispanic respondents reported declines in the prevalence of angina (−6.94 pp; P < .05) and stroke (−4.48 pp; P < .05).

Conclusions

Supplemental Nutritional Assistance Program eligibility was associated with the reduced prevalence of diet‐related disease among older adults. These observed declines in the prevalence of diet‐related disease do not appear to be attributable to increased medical visits or spending on medical services and prescriptions.
Effects of periodontitis on postoperative pneumonia in patients with lung and esophageal cancer
Authors: Jia Chunling , Luan Yijun , Li Xibo , Zhang Xiaoying , Li Cuirong
Published: January 2021

Background

Few studies have been conducted on the relationship between chronic periodontitis and postoperative pneumonia (POP) in patients with lung and esophageal cancer. Furthermore, it remains controversial as to whether improving the periodontal condition of patients with lung and esophageal cancer before surgery reduces the incidence of POP. This retrospective study was conducted to assess the effects of periodontal therapy in patients with lung and esophageal cancer to prevent POP.

Methods

A total of 265 patients with lung or esophageal cancer complicated with chronic periodontitis who underwent open thoracotomy between July 2015 and June 2019 were selected and given the choice of being in the experimental or control group. A total of 141 participants in the experimental group received periodontal therapy, and 124 participants in the control group did not receive periodontal therapy. All clinical data of participants in both groups were retrospectively studied to determine the incidence of POP on the 30th day after discharge from hospital.

Results

Eight patients in the experimental and six in the control group, respectively, were excluded from the study. It was found that four of the 133 patients suffered from POP in the experimental group (incidence: 3.01%). A total of 18 of 118 patients in the control group had a pulmonary infection (incidence: 15.25%). POP incidence in the experimental group was significantly lower than that in the control group, and in the level analysis of different types of periodontitis, surgical methods, and diseases (p < 0.05).

Conclusions

Periodontal treatment is associated with a lower incidence of POP following lung and esophageal cancer surgery. Improving the periodontal condition of patients helps prevent POP. The presence of periodontitis is an important predisposing factor for POP in patients after open thoracotomy. Periodontal examination and therapy are recommended before the surgical treatment of lung or esophageal cancer.
The association between labour epidural case volume and the rate of accidental dural puncture
Authors: Sidhu N. S. , Cavadino A. , Ku H. , Kerckhoffs P. , Lowe M.
Published: January 2021

Accidental dural puncture is a recognised complication of labour epidural placement and can cause a debilitating headache. We examined the association between labour epidural case volume and accidental dural puncture rate in specialist anaesthetists and anaesthesia trainees. We performed a retrospective cohort study of labour epidural and combined spinal‐epidural nerve blocks performed between 1 July 2013 and 31 December 2017 at Waitemata District Health Board, Auckland, New Zealand. The mean (SD) annual number of obstetric epidural and combined spinal‐epidural procedures for high‐case volume specialists was 44.2 (15.0), and for low‐case volume specialists was 10.0 (6.8), after accounting for caesarean section combined spinal‐epidural procedures. Analysis of 7976 labour epidural and combined spinal‐epidural procedure records revealed a total of 92 accidental dural punctures (1.2%). The accidental dural puncture rate (95%CI) in high‐case volume specialists was 0.6% (0.4–0.9%) and in low‐case volume specialists 2.4% (1.4–3.9%), indicating probable skill decay. The odds of accidental dural puncture were 3.77 times higher for low‐ compared with high‐case volume specialists (95%CI 1.72–8.28, p = 0.001). Amongst trainees, novices had a significantly higher accidental dural puncture complication rate (3.1%) compared with registrars (1.2%), OR (95%CI) 0.39 (0.18–0.84), p = 0.016, or fellows (1.1%), 0.35 (0.16–0.76), p = 0.008. Accidental dural puncture complication rates decreased once trainees progressed past the ‘novice’ training stage.
How psychological contract breach affects long‐term mental and physical health: the longitudinal role of effort–reward imbalance
Authors: Griep Yannick , Bankins Sarah , Vander Elst Tinne , De Witte Hans
Published: January 2021

This study contributes to the research of employee health and well‐being by examining the longitudinal effects of psychological contract (PC) breach on employees’ health. We integrate Social Exchange and Conservation of Resources theories to position effort–reward imbalance (ERI) as the mediating mechanism. We also assessed the moderating role of perceived job control as a boundary condition through which employees could prevent PC breach and ERI from adversely affecting their health. Using three‐wave longitudinal survey data from 389 employees, we estimated a path model using each variable’s growth parameters (intercept and slope). We found support for our hypotheses regarding stable effects; we found positive associations between PC breach and physical and mental health complaints and a need for recovery through ERI perceptions. We further tested employees’ perceived control over the work environment as a boundary condition and found support for its role in attenuating the positive relationship between PC breach and ERI perceptions, but not for its moderating role in the ERI–health outcomes relationship. Our findings indicate that exposure to PC breach has a detrimental impact on employee health/well‐being via perceptions of ERI and allow us to unravel one of the cognitive mechanisms leading to potential employee ill‐health. We conclude with theoretical and practical implications.
Peer feedback or peer feedforward? Enhancing students’ argumentative peer learning processes and outcomes
Authors: Latifi Saeed , Noroozi Omid , Talaee Ebrahim
Published: January 2021

This study compared the effects of support for peer feedback, peer feedforward and their combination on students’ peer learning processes, argumentative essay quality and domain‐specific learning. Participants were 86 BSc students who were randomly divided over 43 dyads. These dyads, in a two‐factorial experimental design, were assigned to four conditions including: peer feedback (n = 22), peer feedforward (n = 22), mixed (n = 20) and control group (n = 22) conditions. An online peer feedback environment named EduTech was designed which allowed us to implement various types of support in the form of question prompts. In this online environment, students were asked to write an argumentative essay on a controversial topic, to engage in peer learning processes and to revise their essay. Overall, the results showed that students in the three experimental conditions (peer feedback, peer feedforward and their combination) benefited more than students in the control group condition (without any support) in term of peer learning processes, argumentative essay quality and domain‐specific learning. However, there was no significant difference among the three experimental conditions. This implies that peer feedforward can be as important as peer feedback in collaborative learning environments which is often neglected both in theory and practice.

Practitioner Notes

What is already known about this topic?

Writing argumentative essays is a common practice for higher education students in various disciplines which deal with controversial issues.

Writing argumentative essay requires solid argumentation strategies which makes it a challenging task for higher education students.

Additional instructional support is needed to help students write high‐quality argumentative essays.

What this paper adds?

Peer learning is a promising instructional strategy for improving students’ argumentative essay writing and learning.

Online support in the form of question prompts to guide students during peer learning can improve their argumentative essay writing and learning.

Next to the peer feedback, peer feedforward is also a promising instructional approach to support students’ argumentative essay writing and learning.

Implications for practice and/or policy

Given the positive effects of peer learning processes, the use of peer feedback and peer feedforward should be given more attention by teachers to support students write high‐quality argumentative essays for controversial issues.

Teachers and educational designers should not only provide opportunities for students to engage in peer feedback processes (how I am doing?) but also in peer feedforward processes (where to next?).
Phase 1 study of tazemetostat in Japanese patients with relapsed or refractory B‐cell lymphoma
Authors: Munakata Wataru , Shirasugi Yukari , Tobinai Kensei , Onizuka Makoto , Makita Shinichi , Suzuki Rikio , Maruyama Dai , Kawai Hidetsugu , Izutsu Koji , Nakanishi Tadashi , Shiba Sari , Hojo Seichiro , Ando Kiyoshi
Published: January 2021

Background

Tazemetostat is a selective and orally available inhibitor of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and epigenetic regulator of cellular differentiation programs. We carried out a phase I study of tazemetostat in Japanese patients with relapsed or refractory B‐cell non‐Hodgkin‐type lymphoma (B‐NHL) to evaluate its tolerability, safety, pharmacokinetics, and preliminary antitumor activity.

Methods

Tazemetostat was given orally at a single dose of 800 mg on the first day and 800 mg twice daily (BID: total 1600 mg/d) on following days in a 28‐day/cycle manner. Tazemetostat dose‐limiting toxicity (DLT) was evaluated up to the end of the first treatment cycle. Archival tumor tissues were analyzed for hotspot EZH2 mutations.

Results

As of 15 January 2018, seven patients (four follicular lymphoma [FL] and three diffuse large B‐cell lymphoma [DLBCL]) were enrolled. The median age was 73 (range, 59‐85) years, and the median number of prior chemotherapy regimens was three (range, one to five). No DLT was observed (one patient was not evaluable due to early disease progression). The common treatment‐related adverse events (AEs) were thrombocytopenia and dysgeusia (three patients each; 42.9%). No treatment‐related serious AEs were observed. The objective response rate was 57% (4/7 patients), including responses in three of four patients with FL and one of three patients with DLBCL. An EZH2 mutation was detected in one patient with FL responding to treatment.

Conclusions

Tazemetostat at 800 mg BID showed an acceptable safety profile and promising antitumor activity in Japanese patients with relapsed or refractory B‐NHL.
What Drove Housing Wealth Inequality in China?
Authors: Wan Guanghua , Wang Chen , Wu Yu
Published: January 2021

Although China is experiencing a deterioration in wealth distribution where housing is playing a dominant role, this issue has received scant research attention despite its importance. Combining four rounds of the China Household Finance Survey (CHFS) data, this paper measures and discusses wealth inequality in China, with a special emphasis on the contribution of housing. Our analysis reveals that housing is the largest contributor to wealth inequality, responsible for around 70 percent of total wealth inequality, and its contribution has been increasing over time. Our research efforts have focused on the housing wealth disparity, exploring its composition from alternative perspectives. The results show that housing wealth inequality has also been rising over time and an absolute majority of housing wealth inequality is due to within‐group gaps. Finally, we employ Wan's (2004) regression‐based decomposition methodology to quantify the contributions of different determinants to housing wealth disparity in China, and to demonstrate serious biases in the conventional approach that is often used to analyze housing wealth inequality.
The Role of the Real Estate Sector in the Structural Dynamics of the Chinese Economy: An Input–Output Analysis
Authors: Huang Yongming , Khan Jamal , Girardin Eric , Shad Umair
Published: January 2021

Market‐oriented housing reforms and the rapid urbanization process have led to spectacular growth in the Chinese real estate sector (RES). However, the changes in the role played by this sector in the structural dynamics of the Chinese economy have not been examined sufficiently. Accordingly, we analyze the intersectoral structural changes to the Chinese RES, its linkages with the rest of the economy, and its growth sources, using four Chinese input–output tables from 2002 to 2017. We depart from existing work on the RES by using the causative matrix approach and structural decomposition analysis, and obtain three main results. First, the RES, which received little non‐RES feedback during the 2002–2007 period, has subsequently received much more substantial feedback. Second, the impact of the RES on China's economic growth stems mainly from its forward linkages. Third, the growth in the RES has been driven mainly by domestic demand expansion. Our results highlight that the Chinese RES, which plays a key role in value chains, is highly dependent on its own final demand and a fall in its demand would impede economic development. An important implication of these results is that developing the national economy by stimulating the RES would not be as effective as developing the RES through stimulating the national economy.
Implications of addiction diagnosis and addiction beliefs for public stigma: A cross‐national experimental study
Authors: Rundle Samantha M. , Cunningham John A. , Hendershot Christian S.
Published: January 2021

Introduction

Stigmatisation of alcohol and other drug (AOD) use disorders poses a significant barrier to treatment access. A review by the World Health Organization concluded that addictive disorders were the most stigmatised health condition. Few studies have examined whether different etiological models of addiction (MOA) have implications for public stigma toward AOD disorders. The current study examined whether beliefs representative of five MOA predict public stigma levels and whether stigma differs for AOD use disorders relative to other health conditions.

Methods

Survey data were collected from Canada, the USA and Australia using an online data collection platform. Participants were randomised to one of four vignette manipulations describing an individual with an alcohol use disorder and/or other disorder. Participants' stigma toward the vignette character and beliefs related to five MOA (disease, moral, psychological, sociological, nature) were measured.

Results

Stigma ratings were significantly higher in the alcohol use disorder condition compared to other conditions. Two MOA accounted for significant variance in stigma ratings, where greater beliefs in the nature and psychological MOA predicted significantly lower levels of stigma toward alcohol use disorder. Contrary to predictions, beliefs in the disease MOA did not relate to lower stigma. Lastly, beliefs in the moral MOA partly accounted for geographical region differences (the USA vs. Canada) in public stigma.

Discussion and Conclusions

The current study provides further experimental support that AOD disorders are more stigmatised than others. Additionally, the findings suggest that MOA may relate differentially to perceived stigma, and that regional variability in such beliefs exists.
Bewertung der Wirksamkeit sub‐antimikrobieller Dosierungen von Doxycyclin bei Rosacea: Systematische Auswertung von klinischen Studien und Metaanalyse
Authors: Husein‐ElAhmed Husein , Steinhoff Martin
Published: January 2021

Hintergrund

Niedrig dosiertes Doxycyclin (sub‐antimicrobial dose doxycycline, SDD) ist eine antimikrobielle Substanz, die bei häufigen entzündlichen Hauterkrankungen zu einer Besserung des Krankheitsbildes zu führen scheint. Derzeit liegen nur wenige Daten zur allgemeinen Wirksamkeit, zur notwendigen Behandlungsdauer und zur optimalen Patientenauswahl bei Rosacea vor. Wir haben daher die Wirksamkeit sub‐antimikrobieller Dosen von Doxycyclin bei Rosacea papulopustulosa (RPP) untersucht. Gleichzeitig wollten wir herausarbeiten, welche Patienten für diesen Behandlungsansatz am besten geeignet sind.

Methoden

Im Zeitraum von Juli bis September 2019 wurde eine umfangreiche Literaturrecherche in fünf Datenbanken durchgeführt; der verwendete Suchbegriff war „rosacea” UND „doxycycline”.

Ergebnisse

Unsere Datenbankrecherche fand potenziell relevante Studien. Die allgemeine Metaanalyse fand keinen signifikanten Unterschied zwischen SDD und den Vergleichspräparaten (RR: 1,12; 95 %‐KI: 0,78–1,62; I2 = 86 %). Eine Subgruppenanalyse von Studien, in denen Doxycyclin mit Placebo verglichen wurde, ergab eine klare Überlegenheit von Doxycyclin (RR: 1,45; 95 %‐KI: 1,22–1,72; I2 = 31 %), die Subgruppenanalyse von Studien, bei denen aktive Medikationen miteinander verglichen wurden, zeigte hingegen keine Unterschiede zwischen den verschiedenen Behandlungsoptionen (RR: 0,52; 95 % KI: 0,17–1,63; I2 = 90 %).

Schlussfolgerung

Es gibt gute Belege dafür, dass SDD wirksamer ist als Placebo. Andere Medikamente wie etwa Minocyclin oder Isotretinoin zeigen jedoch im Vergleich zu SDD mindestens gleich gute Behandlungserfolge. Wir schließen aus unserer Analyse, dass die entzündungshemmenden Eigenschaften von SDD eher zur Behandlung leichter Formen der Rosacea geeignet sind, während bei mittelstarken oder stark ausgeprägten Formen die höheren (antimikrobiellen) Dosierungen von Doxycyclin besser geeignet sein dürften.
Therapy understanding and health related quality of life in stage III/IV melanoma patients treated with novel adjuvant therapies
Authors: Reschke Robin , Jäger Iris , Mehnert‐Theuerkauf Anja , Ziemer Mirjana
Published: January 2021

Objective

Our aims were to investigate the motivation for therapy, the understanding and valuation of potential treatment toxicities in melanoma patients offered adjuvant therapies.

Methods

Between September 2018 and September 2019 49 adjuvant patients with stage III and IV melanoma received a self‐created, pre‐treatment questionnaire. Furthermore, the patients were handed out the REPERES‐G, EQ‐5D‐3L and EORTC QLQ C‐30 questionnaires.

Results

Eight patients (18.3 %) decided against adjuvant therapy (mean age 71.6 years). Four of these had stage IIIA melanoma. The majority of patients (73.4 %) decided for adjuvant treatment with PD1‐inhibitors despite their potential high grade, persistent, irreversible or even fatal toxicities. About a third of patients with BRAF V600 mutated melanoma who decided for therapy chose targeted therapy (31.3 %). These patients were younger (mean age 49 years), still working and had families with children. The REPERES‐G questionnaire showed that our patients were generally satisfied with medical care. The average scores in the EQ‐5D‐3L and EORTC QLQ C‐30 questionnaires indicated good subjective general health.

Conclusions

Despite the associated toxicities as well as the required time and effort for a one‐year treatment the majority of patients decided for adjuvant treatments.
Angeborene kutane Neurofibrome bei Neurofibromatose Typ 1: Klinisch‐pathologische Merkmale in der frühen Kindheit
Authors: García‐Martínez Francisco Javier , Azorín Daniel , Duat‐Rodríguez Anna , Hernández‐Martín Ángela
Published: January 2021

Hintergrund und Zielsetzung

Klinisch‐pathologische Merkmale angeborener kutaner Neurofibrome, die sich bei Patienten mit Neurofibromatose Typ 1 (NF1) als große, unregelmäßig geformte „Café‐au‐lait“‐Flecken (CALM) präsentieren, sind noch nicht gut charakterisiert. Unser Ziel war, große „atypische“ CALM bei Kindern mit NF1 histopathologisch zu analysieren.

Patienten und Methoden

In dieser retrospektiven Beobachtungsstudie haben wir histopathologische und immunhistochemische Merkmale von 21 Biopsaten untersucht, die innerhalb der ersten Lebensmonate aus 18 großen hyperpigmentierten Flecken (mit oder ohne Hypertrichose) bei Kindern mit NF1 entnommen wurden.

Ergebnisse

Von den 21 Biopsaten zeigten zehn ein diffuses Neurofibrom, vier weitere hatten Charakteristika eines plexiformen Neurofibroms (PNF). Bei zwölf Proben fanden sich spindelförmige, linear angeordnete Zellen wie bei einem dünnen Nervenstrang mit abnormer Morphologie. Zwei dieser Läsionen wurden mit zunehmendem Alter erneut biopsiert und zeigten eine Transformation hin zu einem plexiformen Muster. In 17 Proben wurden vermehrt Zellen im interstitiellen Raum festgestellt, bei 16 waren die Zellen um ekkrine Drüsen konzentriert sowie bei zwölf Proben um Haarfollikel und Gefäßstrukturen. Alle diese Zellen exprimierten S100‐Protein und CD68, 15 Proben auch Melan‐A.

Schlussfolgerung

Die klinisch‐pathologischen Merkmale angeborener kutaner Neurofibrome liefern schon früh diagnostische Hinweise auf NF1 und sind hoch relevant für die Nachverfolgung der Patienten.
Can central banks run out of ammunition? The role of the money‐equities‐interaction channel in monetary policy
Authors: Congdon Tim
Published: January 2021

Many authorities claim that central banks ‘have run out of ammunition’, either because the central bank rate has dropped close to the zero lower bound or because of Keynes's liquidity trap. I argue first, that indefinitely large increases in the quantity of money remain possible even with the central bank rate close to zero, and, second, that increases in the quantity of money raise all asset prices, including the prices of quoted equities, not just bond prices. Bonds are an unimportant asset class in modern capitalist economies, relative to corporate equity and real estate. Meanwhile increases in equity prices always boost aggregate demand and output.
On the role of direct sunlight for egg‐laying behaviour: lessons and ideas from the Speckled wood
Authors: Braem Simon , Van Dyck Hans
Published: January 2021

1. Butterflies rely on suitable weather conditions for thermoregulation during active behaviour. While non‐sunny conditions are known to reduce time spent in active flight, detailed behavioural data on how variable microclimatic conditions affect decision making in specific behavioural contexts (e.g. habitat exploration, dispersal, mating, basking, oviposition) is often lacking.

2. We addressed the influence of direct sunlight on females of the Speckled wood butterfly (Pararge aegeria) that were motivated to oviposit. To test this, we observed gravid butterflies one by one in (1) a cage within a greenhouse, where temperature was kept high all the time, and (2) an outdoor cage under uncontrolled weather conditions.

3. Our results show that butterflies almost exclusively oviposit under direct sunlight. Surprisingly, results were similar in the warm within‐greenhouse cage, where activity remained high but oviposition never occurred during fully clouded conditions.

4. These results suggest that ovipositing butterflies require sunlight not only for thermoregulation. We hypothesise that direct sunlight benefits the ovipositing female by exposing more clearly the microclimatic variation of potential oviposition sites in the herbaceous layer of the vegetation. Heliophily during oviposition and pre‐oviposition exploration may apply to a range of microclimate‐sensitive species, particularly those living in microclimatically heterogeneous habitats. This warrants novel sensory ecological research, which will further improve our understanding of insect functional habitats.
Making the case for clinical mental health nurses to break their silence on the healing they create: A critical discussion
Authors: Hurley John , Lakeman Richard
Published: January 2021

This discursive paper aims to clarify what roles mental health nurses identify as being within their scope of practice in clinical settings. It also aims to highlight any consumer benefits arising from these roles. Role theory and its relationship with identity are critically discussed as a framework to explain how contemporary mental health nursing roles are poorly understood and undervalued within mental health services. In order to meet the aims of the paper literature written in the last five years by clinical mental health nurses reporting their roles, and outcomes of those roles were searched. This literature was then considered through the lens of social constructionism that premises truths are accessed and then constructed though relationship based language. Six core mental health nursing roles were identified across international settings. The MHN is a psychotherapist. The MHN is a consumer advocate. The MHN is a physical health therapist. The MHN is a psycho‐pharmacological therapist. The MHN is a relationship focussed therapist and finally the MHN is an aggression management therapist. While European and American nurses reported consumer benefit emerging from these roles those from Australia and the United Kingdom did not. The roles reported on were largely instrumental ones that offered little clarity towards the identity of our profession, nor its worth to consumers or funders of services. Mental health nurses will only have their true breadth of clinical capabilities recognized where there is a consistent construction emerging from clinicians in clinical settings on the efficacy of their clinical work.
Positive risk management: Staff perspectives in acute mental health inpatient settings
Authors: Just Daniela , Palmier‐Claus Jasper E. , Tai Sara
Published: January 2021

Aims

To explore inpatient staff's understanding and implementation of positive risk management.

Background

Risk management is an essential skill for staff working in acute mental health inpatient settings. National policies advocate the use of positive risk management as a form of collaborative, recovery‐focused risk management. However, little is known about how staff understand, operationalize, and use positive risk management in practice.

Design

Qualitative reflexive thematic analysis study.

Methods

The authors recruited a purposive sample of healthcare professionals working in acute inpatient settings (N = 16) in 2019 across three National Health Service Trusts in the North‐West of England. Participants completed semi‐structured interviews which were analysed using reflexive thematic analysis.

Results

The analysis generated three themes: (a) within staff barriers; (b) within service user barriers; and (c) delivery in practice.

Conclusion

Understanding and implementation of positive risk management was dependant on multiple factors, including staffs’ beliefs about mental health, levels of worry and anxiety, and amount of experience and seniority. Staff were more likely to use positive risk management with service users that they perceived as being trustworthy and less risky. Use of positive risk management was reliant on the support practitioners received, how able they were to view situations from multiple perspectives, and the degree to which they felt able to prioritize positive risk management.

Impact

Although staff expressed the desire and intention to practice positive risk management, the current study highlights challenges around operationalization and implementation. The authors discuss the clinical implications of the findings.
GHR is involved in gastric cell growth and apoptosis via PI3K/AKT signalling
Authors: Yan Hong‐Zhu , Wang Hua‐Feng , Yin Yueling , Zou Jue , Xiao Feng , Yi Li‐Na , He Ying , He Bo‐Sheng
Published: January 2021

Growth hormone receptor (GHR), the cognate receptor of growth hormone (GH), is a membrane bound receptor that belongs to the class I cytokine receptor superfamily. GH binding GHR induces cell differentiation and maturation, initiates the anabolism inside the cells and promotes cell proliferation. Recently, GHR has been reported to be associated with various types of cancer. However, the underlying mechanism of GHR in gastric cancer has not been defined. Our results showed that silence of GHR inhibited the growth of SGC‐7901 and MGC‐803 cells, and tumour development in mouse xenograft model. Flow cytometry showed that GHR knockout significantly stimulated gastric cancer cell apoptosis and caused G1 cell cycle arrest, which was also verified by Western blot that GHR deficiency induced the protein level of cleaved‐PARP, a valuable marker of apoptosis. In addition, GHR deficiency inhibited the activation of PI3K/AKT signalling pathway. On the basis of the results, that GHR regulates gastric cancer cell growth and apoptosis through controlling G1 cell cycle progression via mediating PI3K/AKT signalling pathway. These findings provide a novel understanding for the role of GHR in gastric cancer.
Transgenic overexpression of ITGB6 in intestinal epithelial cells exacerbates dextran sulfate sodium‐induced colitis in mice
Authors: Chen Haiyan , Chen Liubo , Wang Xin , Ge Xiaoxu , Sun Lifeng , Wang Zhanhuai , Xu Xiaoming , Song Yongmao , Chen Jing , Deng Qun , Xie Haiting , Chen Ting , Chen Yan , Ding Kefeng , Wu Jingjing , Wang Jian
Published: January 2021

Integrins, as a large family of cell adhesion molecules, play a crucial role in maintaining intestinal homeostasis. In inflammatory bowel disease (IBD), homeostasis is disrupted. Integrin αvβ6, which is mainly regulated by the integrin β6 subunit gene (ITGB6), is a cell adhesion molecule that mediates cell‐cell and cell‐matrix interactions. However, the role of ITGB6 in the pathogenesis of IBD remains elusive. In this study, we found that ITGB6 was markedly upregulated in inflamed intestinal tissues from patients with IBD. Then, we generated an intestinal epithelial cell‐specific ITGB6 transgenic mouse model. Conditional ITGB6 transgene expression exacerbated experimental colitis in mouse models of acute and chronic dextran sulphate sodium (DSS)‐induced colitis. Survival analyses revealed that ITGB6 transgene expression correlated with poor prognosis in DSS‐induced colitis. Furthermore, our data indicated that ITGB6 transgene expression increased macrophages infiltration, pro‐inflammatory cytokines secretion, integrin ligands expression and Stat1 signalling pathway activation. Collectively, our findings revealed a previously unknown role of ITGB6 in IBD and highlighted the possibility of ITGB6 as a diagnostic marker and therapeutic target for IBD.
Non‐coding RNAs in cardiomyocyte proliferation and cardiac regeneration: Dissecting their therapeutic values
Authors: Dong Xiaoxuan , Dong Xiuyun , Gao Feng , Liu Ning , Liang Tian , Zhang Feng , Fu Xuyang , Pu Linbin , Chen Jinghai
Published: January 2021

Cardiovascular diseases are associated with high incidence and mortality, contribute to disability and place a heavy economic burden on countries worldwide. Stimulating endogenous cardiomyocyte proliferation and regeneration has been considering as a key to repair the injured heart caused by ischaemia. Emerging evidence has proved that non‐coding RNAs participate in cardiac proliferation and regeneration. In this review, we focus on the observation and mechanism that microRNAs (or miRNAs), long non‐coding RNAs (or lncRNAs) and circular RNA (or circRNAs) regulate cardiomyocyte proliferation and regeneration to repair a damaged heart. Furthermore, we highlight the potential therapeutic role of some non‐coding RNAs used in stimulating CMs proliferation. Finally, perspective on the development of non‐coding RNAs therapy in cardiac regeneration is presented.